Wang Z

References (285)

Title : Biotransformation activities of fungal strain apiotrichum sp. IB-1 to ibuprofen and naproxen - Peng_2024_Arch.Microbiol_206_232
Author(s) : Peng L , Yun H , Ji J , Zhang W , Xu T , Li S , Wang Z , Xie L , Li X
Ref : Arch Microbiol , 206 :232 , 2024
Abstract : Ibuprofen (IBU) and naproxen (NPX), as widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs), are largely produced and consumed globally, leading to frequent and ubiquitous detection in various aqueous environments. Previously, the microbial transformation of them has been given a little attention, especially with the isolated fungus. A yeast-like Apiotrichum sp. IB-1 has been isolated and identified, which could simultaneously transform IBU (5 mg/L) and NPX (2.5 mg/L) with maximum efficiencies of 95.77% and 88.31%, respectively. For mono-substrate, the transformation efficiency of IB-1 was comparable to that of co-removal conditions, higher than most of isolates so far. IBU was oxidized mainly through hydroxylation (m/z of 221, 253) and NPX was detoxified mainly via demethylation (m/z of 215) as shown by UPLC-MS/MS results. Based on transcriptome analysis, the addition of IBU stimulated the basic metabolism like TCA cycle. The transporters and respiration related genes were also up-regulated accompanied with higher expression of several dehydrogenase, carboxylesterase, dioxygenase and oxidoreductase encoding genes, which may be involved in the transformation of IBU. The main functional genes responsible for IBU and NPX transformation for IB-1 should be similar in view of previous studies, which needs further confirmation. This fungus would be useful for potential bioremediation of NSAIDs pollution and accelerate the discovery of functional oxidative genes and enzymes different from those of bacteria.
ESTHER : Peng_2024_Arch.Microbiol_206_232
PubMedSearch : Peng_2024_Arch.Microbiol_206_232
PubMedID: 38658486

Title : Comparison Study of Two Fumonisin-Degrading Enzymes for Detoxification in Piglets - Wang_2024_Toxins.(Basel)_16_3
Author(s) : Wang Z , Lv Z , Czabany T , Nagl V , Krska R , Wang X , Han B , Tao H , Liu J , Wang J
Ref : Toxins (Basel) , 16 :3 , 2024
Abstract : Fumonisins (FBs), particularly fumonisin B1 (FB1) and fumonisin B2 (FB2) produced mainly by Fusarium verticillioide and Fusarium proliferatum, are common contaminants in animal feed and pose a serious threat to both animal and human health. The use of microbial enzymes to efficiently and specifically convert fumonisins into non-toxic or low-toxic metabolites has emerged as the most promising approach. However, most of the available enzymes have only been evaluated in vitro and lack systematic evaluation in vivo. In this study, the detoxification efficacy of two carboxylesterases, FumD (FUMzyme((a))) and FumDSB, was evaluated comparatively in piglets. The results show that feeding piglets 4.4 mg/kg FBs-contaminated diets for 32 days did not significantly affect the average daily gain, organ indices, and immunoglobulins of the piglets. However, a significant reduction (21.2%) in anti-inflammatory cytokine interleukin-4 was observed in the FBs group, and supplementation with FUMzyme((a)) and FumDSB significantly increased interleukin-4 by 62.1% and 28.0%, respectively. In addition, FBs-contaminated diets resulted in a 3-fold increase in the serum sphinganine/sphingosine (Sa/So) ratio, which is a specific biomarker that has been used to accurately reflect fumonisin levels. The serum Sa/So ratio was significantly reduced by 48.8% after the addition of FUMzyme((a)), and was insignificantly reduced by 8.2% in the FumDSB group. These results suggested that FUMzyme was more effective than FumDSB in mitigating FBs toxicity in piglets by down-regulating the Sa/So ratio.
ESTHER : Wang_2024_Toxins.(Basel)_16_3
PubMedSearch : Wang_2024_Toxins.(Basel)_16_3
PubMedID: 38276527
Gene_locus related to this paper: sphmc-FumD , 9sphn-a0a101vlk1

Title : The pathogenic mutations of APOA5 in Chinese patients with hyperlipidemic acute pancreatitis - Liu_2024_Lipids.Health.Dis_23_44
Author(s) : Liu Y , Dai S , Qin S , Zhou J , Wang Z , Yin G
Ref : Lipids Health Dis , 23 :44 , 2024
Abstract : BACKGROUND AND AIMS: To study the role of gene mutations in the development of severe hypertriglyceridemia (HTG) in patients with hyperlipidemic acute pancreatitis (HLAP), especially different apolipoprotein A5 (APOA5) mutations. METHODS: Whole-exome sequencing was performed on 163 patients with HLAP and 30 patients with biliary acute pancreatitis (BAP). The pathogenicity of mutations was then assessed by combining clinical information, predictions of bioinformatics programs, information from multiple gene databases, and residue location and conservation. The pathogenic mutations of APOA5 were visualized using the software. RESULTS: 1. Compared with BAP patients, pathogenic mutations of APOA5 were frequent in HLAP patients; among them, the heterozygous mutation of p.G185C was the most common. 2. All six pathogenic mutations of APOA5 identified in this study (p.S35N, p.D167V, p.G185C, p.K188I, p.R223C, and p.H182fs) were positively correlated with severe HTG; they were all in the important domains of apolipoprotein A-V (apoA-V). Residue 223 is strictly conserved in multiple mammals and is located in the lipoprotein lipase (LPL)-binding domain (Pro215-Phe261). When Arg 223 is mutated to Cys 223, the positive charge of this residue is reduced, which is potentially destructive to the binding function of apoA-V to LPL. 3. Four new APOA5 mutations were identified, namely c.563A > T, c.667C > T, c.788G > A, and c.544_545 insGGTGC. CONCLUSIONS: The pathogenic mutations of APOA5 were specific to the patients with HLAP and severe HTG in China, and identifying such mutations had clinical significance in elucidating the etiology and subsequent treatment.
ESTHER : Liu_2024_Lipids.Health.Dis_23_44
PubMedSearch : Liu_2024_Lipids.Health.Dis_23_44
PubMedID: 38331899

Title : Long noncoding RNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote lung carcinogenesis - Wang_2024_Environ.Int_185_108494
Author(s) : Wang PS , Liu Z , Sweef O , Xie J , Chen J , Zhu H , Zeidler-Erdely PC , Yang C , Wang Z
Ref : Environ Int , 185 :108494 , 2024
Abstract : Hexavalent chromium [Cr(VI)] is a common environmental pollutant and chronic exposure to Cr(VI) causes lung cancer in humans, however, the mechanism of Cr(VI) carcinogenesis has not been well understood. Lung cancer is the leading cause of cancer-related death, although the mechanisms of how lung cancer develops and progresses have been poorly understood. While long non-coding RNAs (lncRNAs) are found abnormally expressed in cancer, how dysregulated lncRNAs contribute to carcinogenesis remains largely unknown. The goal of this study is to investigate the mechanism of Cr(VI)-induced lung carcinogenesis focusing on the role of the lncRNA ABHD11 antisense RNA 1 (tail to tail) (ABHD11-AS1). It was found that the lncRNA ABHD11-AS1 expression levels are up-regulated in chronic Cr(VI) exposure-transformed human bronchial epithelial cells, chronically Cr(VI)-exposed mouse lung tissues, and human lung cancer cells as well. Bioinformatics analysis revealed that ABHD11-AS1 levels are up-regulated in lung adenocarcinomas (LUADs) tissues and associated with worse overall survival of LUAD patients but not in lung squamous cell carcinomas. It was further determined that up-regulation of ABHD11-AS1 expression plays an important role in chronic Cr(VI) exposure-induced cell malignant transformation and tumorigenesis, and the stemness of human lung cancer cells. Mechanistically, it was found that ABHD11-AS1 directly binds SART3 (spliceosome associated factor 3, U4/U6 recycling protein). The interaction of ABHD11-AS1 with SART3 promotes USP15 (ubiquitin specific peptidase 15) nuclear localization. Nuclear localized USP15 interacts with pre-mRNA processing factor 19 (PRPF19) to increase CD44 RNA alternative splicing activating beta-catenin and enhancing cancer stemness. Together, these findings indicate that lncRNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote cell malignant transformation and lung carcinogenesis.
ESTHER : Wang_2024_Environ.Int_185_108494
PubMedSearch : Wang_2024_Environ.Int_185_108494
PubMedID: 38364571

Title : Soil microbiome of shiro reveals the symbiotic relationship between Tricholoma bakamatsutake and Quercus mongolica - Guo_2024_Front.Microbiol_15_1361117
Author(s) : Guo H , Liu W , Xie Y , Wang Z , Huang C , Yi J , Yang Z , Zhao J , Yu X , Sibirina LA
Ref : Front Microbiol , 15 :1361117 , 2024
Abstract : Tricholoma bakamatsutake is a delicious and nutritious ectomycorrhizal fungus. However, its cultivation is hindered owing to limited studies on its symbiotic relationships. The symbiotic relationship between T. bakamatsutake and its host is closely related to the shiro, a complex network composed of mycelium, mycorrhizal roots, and surrounding soil. To explore the symbiotic relationship between T. bakamatsutake and its host, soil samples were collected from T. bakamatsutake shiro (Tb) and corresponding Q. mongolica rhizosphere (CK) in four cities in Liaoning Province, China. The physicochemical properties of all the soil samples were then analyzed, along with the composition and function of the fungal and bacterial communities. The results revealed a significant increase in total potassium, available nitrogen, and sand in Tb soil compared to those in CK soil, while there was a significant decrease in pH, total nitrogen, total phosphorus, available phosphorus, and silt. The fungal community diversity in shiro was diminished, and T. bakamatsutake altered the community structure of its shiro by suppressing other fungi, such as Russula (ectomycorrhizal fungus) and Penicillium (phytopathogenic fungus). The bacterial community diversity in shiro increased, with the aggregation of mycorrhizal-helper bacteria, such as Paenibacillus and Bacillus, and plant growth-promoting bacteria, such as Solirubrobacter and Streptomyces, facilitated by T. bakamatsutake. Microbial functional predictions revealed a significant increase in pathways associated with sugar and fat catabolism within the fungal and bacterial communities of shiro. The relative genetic abundance of carboxylesterase and gibberellin 2-beta-dioxygenase in the fungal community was significantly increased, which suggested a potential symbiotic relationship between T. bakamatsutake and Q. mongolica. These findings elucidate the microbial community and relevant symbiotic environment to better understand the relationship between T. bakamatsutake and Q. mongolica.
ESTHER : Guo_2024_Front.Microbiol_15_1361117
PubMedSearch : Guo_2024_Front.Microbiol_15_1361117
PubMedID: 38601932

Title : Microneedle-mediated nose-to-brain drug delivery for improved Alzheimer's disease treatment - Ruan_2024_J.Control.Release__
Author(s) : Ruan S , Li J , Ruan H , Xia Q , Hou X , Wang Z , Guo T , Zhu C , Feng N , Zhang Y
Ref : J Control Release , : , 2024
Abstract : Conventional transnasal brain-targeted drug delivery strategies are limited by nasal cilia clearance and the nasal mucosal barrier. To address this challenge, we designed dissolving microneedles combined with nanocarriers for enhanced nose-to-brain drug delivery. To facilitate transnasal administration, a toothbrush-like microneedle patch was fabricated with hyaluronic acid-formed microneedles and tannic acid-crosslinked gelatin as the base, which completely dissolved in the nasal mucosa within seconds leaving only the base, thereby releasing the loaded cyclodextrin-based metal-organic frameworks (CD-MOFs) without affecting the nasal cilia and nasal microbial communities. As nanocarriers for high loading of huperzine A, these potassium-structured CD-MOFs, reinforced with stigmasterol and functionalized with lactoferrin, possessed improved physical stability and excellent biocompatibility, enabling efficient brain-targeted drug delivery. This delivery system substantially attenuated H(2)O(2)- and scopolamine-induced neurocyte damage. The efficacy of huperzine A on scopolamine- and D-galactose & AlCl(3)-induced memory deficits in rats was significantly improved, as evidenced by inhibiting acetylcholinesterase activity, alleviating oxidative stress damage in the brain, and improving learning function, meanwhile activating extracellular regulated protein kinases-cyclic AMP responsive element binding protein-brain derived neurotrophic factor pathway. Moreover, postsynaptic density protein PSD-95, which interacts with two important therapeutic targets Tau and beta-amyloid in Alzheimer's disease, was upregulated. This fruitful treatment was further shown to significantly ameliorate Tau hyperphosphorylation and decrease beta-amyloid by ways including modulating beta-site amyloid precursor protein cleaving enzyme 1 and a disintegrin and metalloproteinase 10. Collectively, such a newly developed strategy breaks the impasse for efficient drug delivery to the brain, and the potential therapeutic role of huperzine A for Alzheimer's disease is further illustrated.
ESTHER : Ruan_2024_J.Control.Release__
PubMedSearch : Ruan_2024_J.Control.Release__
PubMedID: 38219911

Title : A polylactic acid degrading lipase from Bacillus safensis: Characterization and structural analysis - Wang_2024_Int.J.Biol.Macromol_268_131916
Author(s) : Wang Y , Zhang W , Wang Z , Lyu S
Ref : Int J Biol Macromol , 268 :131916 , 2024
Abstract : A polylactic acid degrading triacylglycerol lipase (TGL) was identified from Bacillus safensis based on genome annotation and validated by real-time quantitative PCR. TGL displayed optimal activity at pH 9.0 and 55 degreesC. It maintained stability at pH 9.0 and temperatures 45 degreesC. The activity of TGL was found to benefit from the presence of potassium sodium ions, and low concentrations of Triton X-100. The TGL could erode the surface of polylactic acid films and increase its hydrophilicity. The hydrolysis products of polylactic acid by TGL were lactate monomer and dimer. TGL contains a classical catalytic triad structure of lipase (Ser77, Asp133, and His156) and an Ala-X-Ser-X-Gly sequence. Compared with some lipases produced by the same genus Bacillus, TGL is highly conserved in its amino acid sequence, mainly reflected in the amino acid residues that exercise the enzyme activity, including the catalytic activity center and the substrate binding sites.
ESTHER : Wang_2024_Int.J.Biol.Macromol_268_131916
PubMedSearch : Wang_2024_Int.J.Biol.Macromol_268_131916
PubMedID: 38679264

Title : Concentration-dependent effects of lithium on Daphnia magna: Life-history profiles and integrated biomarker response implementation - Chen_2024_Sci.Total.Environ__169866
Author(s) : Chen W , Zhang P , Ye L , Yao J , Wang Z , Liu J , Qin X
Ref : Sci Total Environ , :169866 , 2024
Abstract : The growing use of lithium (Li) in industrial and energy applications and increasing demand worldwide has inevitably resulted in its wide dispersal, representing a significant threat to aquatic systems. Unfortunately, as a ubiquitous emerging contaminant, the comprehensive toxicological information regarding Li at multifarious levels is limited. To diminish this gap, this work was focused to explore Li-induced cascading effects on Daphnia magna as a key species in freshwater ecosystems. Specifically, the organisms were chronically exposed to gradient Li concentrations with emphasis on characterizing life-history traits from individual to population scale, primarily as observed by a markedly concentration-dependent decrease along exposure gradients. In parallel, a robust set of biomarkers relating to energy reserves, antioxidant and biotransformation enzymes, cellular damage, ionoregulation and neurotoxicity were assayed for further understanding potential underlying mechanisms. As a result, biomarker alterations were characterized by significant decreases in energy storage and enzymatic profiles of antioxidant and biotransformation systems, not only triggering an imbalance between reactive oxygen species (ROS) generation and elimination under Li exposure, but compromising the fecundity fitness of phenotypical costs. In contrast, malondialdehyde (MDA) levels were remarkably enhanced as a consequence of inefficient antioxidant and biotransformation capacity leading to lipid peroxidation (LPO). Additionally, Li exerted a dose-dependent biphasic effect on the activities of superoxide dismutase (SOD), Na(+),K(+)-ATPase and acetylcholinesterase (AChE) by interfering with inherent balance. In terms of responsive patterns and dose-effect trends, the integrated biomarker response indices (IBRv2) and star plots were consistent with the differences in biomarker profiles, not only presenting comprehensively biological effects in a visualized form, but signaling the importance of progressive induced changes in an integrative way. Overall, these findings highlighted the need for elucidating Li-produced impacts from a comprehensive perspective, providing valuable insights into better understanding the toxicity of Li in relation to aquatic ecosystem functioning and ecological relevance.
ESTHER : Chen_2024_Sci.Total.Environ__169866
PubMedSearch : Chen_2024_Sci.Total.Environ__169866
PubMedID: 38190914

Title : Acetylcholinesterase is regulated by exposure of ultraviolet B in skin keratinocytes: A potential inducer of cholinergic urticaria - Wu_2024_Faseb.j_38_e23641
Author(s) : Wu Q , Xia Y , Guo MS , Au TY , Yuen GKW , Kong I , Wang Z , Lin Y , Dong TTX , Tsim KWK
Ref : Faseb j , 38 :e23641 , 2024
Abstract : Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.
ESTHER : Wu_2024_Faseb.j_38_e23641
PubMedSearch : Wu_2024_Faseb.j_38_e23641
PubMedID: 38690717

Title : Improvement of plant resistance to geminiviruses via protein de-S-acylation - Zhao_2024_Stress.Biol_4_23
Author(s) : Zhao Y , Li Z , Wang Z , Huang L , Li G , Liu X , Yuan M , Huang W , Ling L , Yang C , He Z , Lai J
Ref : Stress Biol , 4 :23 , 2024
Abstract : Geminiviruses are an important group of viruses that infect a variety of plants and result in heavy agricultural losses worldwide. The homologs of C4 (or L4) in monopartite geminiviruses and AC4 (or AL4) in bipartite geminiviruses are critical viral proteins. The C4 proteins from several geminiviruses are the substrates of S-acylation, a dynamic post-translational modification, for the maintenance of their membrane localization and function in virus infection. Here we initiated a screening and identified a plant protein ABAPT3 (Alpha/Beta Hydrolase Domain-containing Protein 17-like Acyl Protein Thioesterase 3) as the de-S-acylation enzyme of C4 encoded by BSCTV (Beet severe curly top virus). Overexpression of ABAPT3 reduced the S-acylation of BSCTV C4, disrupted its plasma membrane localization, inhibited its function in pathogenesis, and suppressed BSCTV infection. Because the S-acylation motifs are conserved among C4 from different geminiviruses, we tested the effect of ABAPT3 on the C4 protein of ToLCGdV (Tomato leaf curl Guangdong virus) from another geminivirus genus. Consistently, ABAPT3 overexpression also disrupted the S-acylation, subcellular localization, and function of ToLCGdV C4, and inhibited ToLCGdV infection. In summary, we provided a new approach to globally improve the resistance to different types of geminiviruses in plants via de-S-acylation of the viral C4 proteins and it can be extendedly used for suppression of geminivirus infection in crops.
ESTHER : Zhao_2024_Stress.Biol_4_23
PubMedSearch : Zhao_2024_Stress.Biol_4_23
PubMedID: 38662136
Gene_locus related to this paper: arath-At5g14390

Title : Molecular simulations guide immobilization of lipase on nest-like ZIFs with regulatable hydrophilic\/hydrophobic surface - Zhong_2024_J.Colloid.Interface.Sci_667_199
Author(s) : Zhong L , Wang Z , Ye X , Cui J , Jia S
Ref : J Colloid Interface Sci , 667 :199 , 2024
Abstract : The catalytic performance of immobilized lipase is greatly influenced by functional support, which attracts growing interest for designing supports to achieve their promotive catalytic activity. Many lipases bind strongly to hydrophobic surfaces where they undergo interfacial activation. Herein, the behavioral differences of lipases with distinct lid structures on interfaces of varying hydrophobicity levels were firstly investigated by molecular simulations. It was found that a reasonable hydrophilic/hydrophobic surface could facilitate the lipase to undergo interfacial activation. Building on these findings, a novel "nest"-like superhydrophobic ZIFs (ZIFN) composed of hydrophobic ligands was prepared for the first time and used to immobilize lipase from Aspergillus oryzae (AOL@ZIFN). The AOL@ZIFN exhibited 2.0-folds higher activity than free lipase in the hydrolysis of p-Nitrophenyl palmitate (p-NPP). Especially, the modification of superhydrophobic ZIFN with an appropriate amount of hydrophilic tannic acid can significantly improve the activity of the immobilized lipase (AOL@ZIFN-TA). The AOL@ZIFN-TA exhibited 30-folds higher activity than free lipase, and still maintained 82% of its initial activity after 5 consecutive cycles, indicating good reusability. These results demonstrated that nanomaterials with rational arrangement of the hydrophilic/hydrophobic surface could facilitate the lipase to undergo interfacial activation and improve its activity, displaying the potential of the extensive application.
ESTHER : Zhong_2024_J.Colloid.Interface.Sci_667_199
PubMedSearch : Zhong_2024_J.Colloid.Interface.Sci_667_199
PubMedID: 38636222

Title : Cobalt oxyhydroxide nanosheet-modulated ratiometric fluorescence platform for the selective detection of malachite green in fish - Zhang_2024_Mikrochim.Acta_191_119
Author(s) : Zhang Y , Shi YE , Wang S , Song Q , Li W , Wang Z
Ref : Mikrochim Acta , 191 :119 , 2024
Abstract : A ratiometric fluorescence platform was developed based on the cobalt oxyhydroxide (CoOOH) nanosheet-modulated fluorescence response of blue emissive copper nanoclusters (Cu NCs) and yellow emissive o-phenylenediamine (OPD). CoOOH nanosheets showed dual function of strong absorption and oxidation ability, which can effectively quench the blue fluorescence of Cu NCs, with an excitation and emission peak maximum at 390 and 450 nm, respectively , and transfer the OPD into yellow fluorescence products, with an excitation and emission peak maximum at 390 and 560 nm, respectively. Upon introducing butyrylcholinesterase (BChE) and its substrates, CoOOH nanosheets were decomposed into Co(2+), and malachite green (MG) showed strong inhibition ability to this process. This resulted in the obvious difference on the ratio of blue and yellow fluorescence recorded on the system in the presence and absence of MG, which was utilized for the quantitative detection of MG, with a limit of detection of 0.140 microM and a coefficient of variation of 3.5%. The fluorescence ratiometric assay showed excellent detection performances in practical sample analysis.
ESTHER : Zhang_2024_Mikrochim.Acta_191_119
PubMedSearch : Zhang_2024_Mikrochim.Acta_191_119
PubMedID: 38300297

Title : Interface chemistry affected the digestion fate of ketogenic diet based on medium- and long-chain triglycerides - Li_2024_Food.Res.Int_180_114059
Author(s) : Li X , Cheng Y , Xu Z , Lin X , Xu B , Wang Z , Li P , Nian B
Ref : Food Res Int , 180 :114059 , 2024
Abstract : Ketogenic diet, characterized by high fat and low carbohydrate content, is gradually becoming a new perspective in the human diet; however, the mechanism of digestion of ketogenic diet remains unknown. In this study, we explored the oil-water interface to elucidate the digestion of a ketogenic diet based on typical representative medium- and long-chain triglycerides. The free fatty acids (FFAs) release indicated that glycerol trioctanoate with a shorter carbon chain (FFA = 920.55 +/- 10.17 micromol) was significantly more digestible than glycerol tripalmitate (851.36 +/- 9.48 micromol) and glycerol tristearate (805.81 +/- 10.03 micromol). Particle size analysis revealed that the length of the carbon chain increased the size of triglycerides, resulting in a decreased contact area with lipase. The interfacial phenomenon indicated that the longer the carbon chain of triglycerides, the greater the reduction in binding capacity with salt ions in the digestive solution. Fluorescence spectroscopy analysis showed that the length of the carbon chain induced the displacement of the lipase peak, suggesting that the carbon chain length could alter the structure of lipase. Molecular dynamics simulation showed that the longer the carbon chain of triglycerides, the easier it was to loosen the structure of lipase. Bond energy analysis showed that the carbon chain length of triglycerides was positively correlated with the bond energy strength of the ester bonding. In conclusion, this study emphasizes that the ketogenic diet should primarily consist of shorter carbon chain triglycerides because carbon chain length can alter the digestion of triglycerides. This provides a new perspective on the quest for more effective ketogenic diet, in line with the current view of healthy diet.
ESTHER : Li_2024_Food.Res.Int_180_114059
PubMedSearch : Li_2024_Food.Res.Int_180_114059
PubMedID: 38395552

Title : Enzymatic synthesis of branched chain fatty acid-enriched structured triacylglycerols via esterification with glycerol - Huang_2023_Food.Chem_429_136943
Author(s) : Huang Y , Li H , Wang Z , Fu Y , Chen Y , Wang X
Ref : Food Chem , 429 :136943 , 2023
Abstract : While branched-chain fatty acids (BCFA)-enriched triacylglycerols (TAG) has various health benefits, its preparation has not been reported. This study aimed to synthesize high-purity BCFA-enriched structured TAG. First, BCFA was enriched from lanolin through saponification, calcification, and urea complexation. Next, BCFA-enriched TAG was synthesized by enzymatic esterification of BCFA and glycerol. Then, lipases were screened by molecular docking and practical experiments, which suggested that Lipozyme 435 was the best lipase for esterification since it had the lowest binding energy. Structured TAG containing 92.23% BCFA was synthesized under conditions optimized by single-factor experiments. Furthermore, molecular distillation was adapted to remove excess fatty acids and small molecule impurities. Finally, high-purity BCFA-enriched structured lipid containing 70.26% TAG was obtained. Overall, this study successfully developed a method for synthesizing BCFA-enriched structured TAG, which holds great promise for applications in value-added foods.
ESTHER : Huang_2023_Food.Chem_429_136943
PubMedSearch : Huang_2023_Food.Chem_429_136943
PubMedID: 37517224

Title : Strigolactone regulates adventitious root formation via the MdSMXL7-MdWRKY6-MdBRC1 signaling cascade in apple - Fan_2023_Plant.J_113_772
Author(s) : Fan X , Li Y , Deng CH , Wang S , Wang Z , Wang Y , Qiu C , Xu X , Han Z , Li W
Ref : Plant J , 113 :772 , 2023
Abstract : Propagation through stem cuttings is a popular method worldwide for species such as fruit tree rootstocks and forest trees. Adventitious root (AR) formation from stem cuttings is crucial for effective and successful clonal propagation of apple rootstocks. Strigolactones (SLs) are newly identified hormones involved in AR formation. However, the regulatory mechanisms underpinning this process remain elusive. In the present study, weighted gene co-expression network analysis, as well as rooting assays using stable transgenic apple materials, revealed that MdBRC1 served as a key gene in the inhibition of AR formation by SLs. We have demonstrated that MdSMXL7 and MdWRKY6 synergistically regulated MdBRC1 expression, depending on the interactions of MdSMXL7 and MdWRKY6 at the protein level downstream of SLs as well as the direct promoter binding on MdBRC1 by MdWRKY6. Furthermore, biochemical studies and genetic analysis revealed that MdBRC1 inhibited AR formation by triggering the expression of MdGH3.1 in a transcriptional activation pathway. Finally, the present study not only proposes a component, MdWRKY6, that enables MdSMXL7 to regulate MdBRC1 during the process of SL-controlled AR formation in apple, but also provides prospective target genes to enhance AR formation capacity using CRISPR (i.e. clustered regularly interspaced short palindromic repeats) technology, particularly in woody plants.
ESTHER : Fan_2023_Plant.J_113_772
PubMedSearch : Fan_2023_Plant.J_113_772
PubMedID: 36575587

Title : Alcoholic Setdb1 suppression promotes hepatosteatosis in mice by strengthening Plin2 - Zhang_2023_Metabolism__155656
Author(s) : Zhang Y , Li Y , Liu Y , Wang H , Chen Y , Zhang B , Song M , Song L , Ding Q , Qiu J , Fan M , Qu L , Wang Z
Ref : Metabolism , :155656 , 2023
Abstract : BACKGROUND AND AIMS: Hepatosteatosis is one of the early features of alcoholic liver disease (ALD) and pharmaceutical or genetic interfering of the development of hepatosteatosis will efficiently alleviate the progression of ALD. Currently, the role of histone methyltransferase Setdb1 in ALD is not yet well understood. METHOD: Lieber-De Carli diet mice model and NIAAA mice model were constructed to confirm the expression of Setdb1. The hepatocyte-specific Setdb1-knockout (Setdb1-HKO) mice was established to determine the effects of Setdb1 in vivo. Adenovirus-Setdb1 were produced to rescue the hepatic steatosis in both Setdb1-HKO and Lieber-De Carli mice. The enrichment of H3k9me3 in the upstream sequence of Plin2 and the chaperone-mediated autophagy (CMA) of Plin2 were identified by ChIP and co-IP. Dual-luciferase reporter assay was used to detect the interaction of Setdb1 3'UTR and miR216b-5p in AML12 or HEK 293 T cells. RESULTS: We found that Setdb1 was downregulated in the liver of alcohol-fed mice. Setdb1 knockdown promoted lipid accumulation in AML12 hepatocytes. Meanwhile, hepatocyte-specific Setdb1-knockout (Setdb1-HKO) mice exhibited significant lipid accumulation in the liver. Overexpression of Setdb1 was performed with an adenoviral vector through tail vein injection, which ameliorated hepatosteatosis in both Setdb1-HKO and alcoholic diet-fed mice. Mechanistically, downregulated Setdb1 promoted the mRNA expression of Plin2 by desuppressing H3K9me3-mediated chromatin silencing in its upstream sequence. Pin2 acts as a critical membrane surface-associated protein to maintain lipid droplet stability and inhibit lipase degradation. The downregulation of Setdb1 also maintained the stability of Plin2 protein through inhibiting Plin2-recruited chaperone-mediated autophagy (CMA). To explore the reasons for Setdb1 suppression in ALD, we found that upregulated miR-216b-5p bound to the 3'UTR of Setdb1 mRNA, disturbed its mRNA stability, and eventually aggravated hepatic steatosis. CONCLUSIONS: Setdb1 suppression plays an important role in the progression of alcoholic hepatosteatosis via elevating the expression of Plin2 mRNA and maintaining the stability of Plin2 protein. Targeting hepatic Setdb1 might be a promising diagnostic or therapeutic strategy for ALD.
ESTHER : Zhang_2023_Metabolism__155656
PubMedSearch : Zhang_2023_Metabolism__155656
PubMedID: 37419179

Title : The phospholipase effector Tle1(Vc) promotes Vibrio cholerae virulence by killing competitors and impacting gene expression - Liu_2023_Gut.Microbes_15_2241204
Author(s) : Liu M , Wang H , Liu Y , Tian M , Wang Z , Shu RD , Zhao MY , Chen WD , Fu Y
Ref : Gut Microbes , 15 :2241204 , 2023
Abstract : Vibrio cholerae utilizes the Type VI secretion system (T6SS) to gain an advantage in interbacterial competition by delivering anti-prokaryotic effectors in a contact-dependent manner. However, the impact of T6SS and its secreted effectors on physiological behavior remains poorly understood. In this study, we present Tle1(Vc), a phospholipase effector in atypical pathogenic V. cholerae E1 that is secreted by T6SS via its interaction with VgrG1(E1). Tle1(Vc) contains a DUF2235 domain and belongs to the Tle1 (type VI lipase effector) family. Bacterial toxicity assays, lipase activity assays and site-directed mutagenesis revealed that Tle1(Vc) possessed phospholipase A(1) activity and phospholipase A(2) activity, and that Tle1(Vc)-induced toxicity required a serine residue (S356) and two aspartic acid residues (D417 and D496). Cells intoxication with Tle1(Vc) lead to membrane depolarization and alter membrane permeability. Tli1(tox-), a cognate immunity protein, directly interacts with Tle1(Vc) to neutralize its toxicity. Moreover, Tle1(Vc) can kill multiple microorganisms by T6SS and promote in vivo fitness of V. cholerae through mediating antibacterial activity. Tle1(Vc) induces bacterial motility by increasing the expression of flagellar-related genes independently of functional T6SS and the tit-for-tat (TFT) response, where Pseudomonas aeruginosa uses its T6SS-H1 cluster to counterattack other offensive attackers. Our study also demonstrated that the physical puncture of E1 T6SS can induce a moderate TFT response, which is essential to the Tle1(Vc)-mediated strong TFT response, maximizing effector functions. Overall, our study characterized the antibacterial mechanism of phospholipase effector Tle1(Vc) and its multiple physiological significance.
ESTHER : Liu_2023_Gut.Microbes_15_2241204
PubMedSearch : Liu_2023_Gut.Microbes_15_2241204
PubMedID: 37526354

Title : Identifying Sex-Specific Serum Patterns of Alzheimer's Mice through Deep TMT Profiling and a Concentration-Dependent Concatenation Strategy - Dey_2023_J.Proteome.Res__
Author(s) : Dey KK , Yarbro JM , Liu D , Han X , Wang Z , Jiao Y , Wu Z , Yang S , Lee D , Dasgupta A , Yuan ZF , Wang X , Zhu L , Peng J
Ref : J Proteome Res , : , 2023
Abstract : Alzheimer's disease (AD) is the most prevalent form of dementia, disproportionately affecting women in disease prevalence and progression. Comprehensive analysis of the serum proteome in a common AD mouse model offers potential in identifying possible AD pathology- and gender-associated biomarkers. Here, we introduce a multiplexed, nondepleted mouse serum proteome profiling via tandem mass-tag (TMTpro) labeling. The labeled sample was separated into 475 fractions using basic reversed-phase liquid chromatography (RPLC), which were categorized into low-, medium-, and high-concentration fractions for concatenation. This concentration-dependent concatenation strategy resulted in 128 fractions for acidic RPLC-tandem mass spectrometry (MS/MS) analysis, collecting -5 million MS/MS scans and identifying 3972 unique proteins (3413 genes) that cover a dynamic range spanning at least 6 orders of magnitude. The differential expression analysis between wild type and the commonly used AD model (5xFAD) mice exhibited minimal significant protein alterations. However, we detected 60 statistically significant (FDR < 0.05), sex-specific proteins, including complement components, serpins, carboxylesterases, major urinary proteins, cysteine-rich secretory protein 1, pregnancy-associated murine protein 1, prolactin, amyloid P component, epidermal growth factor receptor, fibrinogen-like protein 1, and hepcidin. The results suggest that our platform possesses the sensitivity and reproducibility required to detect sex-specific differentially expressed proteins in mouse serum samples.
ESTHER : Dey_2023_J.Proteome.Res__
PubMedSearch : Dey_2023_J.Proteome.Res__
PubMedID: 37910662

Title : DAGLbeta is the principal synthesizing enzyme of 2-AG and promotes aggressive intrahepatic cholangiocarcinoma via AP-1\/DAGLbeta\/miR4516 feedforward circuitry - Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
Author(s) : Ma M , Zeng G , Tan B , Zhao G , Su Q , Zhang W , Song Y , Liang J , Xu B , Wang Z , Chen J , Hou M , Yang C , Yun J , Huang Y , Lin Y , Chen D , Han Y , DeMorrow S , Liang L , Lai J , Huang L
Ref : American Journal of Physiology Gastrointest Liver Physiol , : , 2023
Abstract : The endocannabinoid system (ECS) is dysregulated in various liver diseases. Previously we had shown that the major endocannabinoid 2-arachidonoyl glycerol (2-AG) promoted tumorigenesis of intrahepatic cholangiocarcinoma (ICC). However, biosynthesis regulation and clinical significance of 2-AG remain elusive. In present study we quantified 2-AG by gas chromatography/mass spectrometry (GC/MS) and showed that 2-AG was enriched in ICC patients' samples as well as in thioacetamide-induced orthotopic rat ICC model. Moreover, we found that diacylglycerol lipase beta (DAGLbeta) was the principal synthesizing enzyme of 2-AG which significantly upregulated in ICC. DAGLbeta promoted tumorigenesis and metastasis of ICC in vitro and in vivo, and positively correlated with clinical stage and poor survival in ICC patients. Functional studies showed that AP-1 (heterodimers of c-Jun and FRA1) directly binded to the promoter and regulated transcription of DAGLbeta, which can be enhanced by lipopolysaccharide (LPS). miR-4516 was identified as the tumor-suppressing miRNA of ICC which can be significantly suppressed by LPS, 2-AG or ectopic DAGLbeta overexpression. FRA1 and STAT3 were targets of miR-4516 and overexpression of miRNA-4516 significantly suppressed expression of FRA1, SATA3 and DAGLbeta. Expression of miRNA-4516 was negatively correlated with FRA1, SATA3 and DAGLbeta in ICC patients' samples. Our findings identify DAGLbeta as the principal synthesizing enzyme of 2-AG in ICC. DAGLbeta promotes oncogenesis and metastasis of ICC and is transcriptionally regulated by a novel AP-1/DAGLbeta/miR4516 feedforward circuitry.
ESTHER : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedSearch : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedID: 37366545
Gene_locus related to this paper: human-DAGLB

Title : Bidirectional selection of the functional properties and environmental friendliness of organophosphorus (OP) pesticide derivatives: Design, screening, and mechanism analysis - Wang_2023_Sci.Total.Environ__163043
Author(s) : Wang Z , Pu Q , Li Y
Ref : Sci Total Environ , :163043 , 2023
Abstract : Organophosphorus pesticides (OPs) are widely used in agricultural production, but the resulting pollution and drug resistance have sparked widespread concern. Therefore, this paper built a model to design OP substitute molecules with high functionality and environmental friendliness, as well as conducted various human health and ecological environment evaluations, synthetic accessibility screening, and easy detection screening. The functionality of the two OP substitute molecules, DIM-100 and DIM-164, increased by 22.79 % and 22.18 %, respectively, and the environmental friendliness increased by 18.07 % and 24.02 %, respectively. The human health risk and ecological, environmental risks were significantly reduced. Both molecules are easy to synthesize, and their detection sensitivity is 9.85 % and 11.24 % higher than that of the target molecule, respectively. Furthermore, significant changes in the distribution of electrons and holes near the C8 and S1 atoms of the OP substitute molecule resulted in easier breakage of the C8-S1 bond, enhancing its photodegradation ability. The charge transfer ability between the atoms of the molecule (as increasing the electron-withdrawing group led to an increase in charge of the P atom) and the volume of the cholinesterase active pocket both affect the functionality of the DIM substitute molecule. That is, the volume of the cholinesterase active pocket of the bee is smaller than that of the brown planthopper and is more affected by the volume of the OP molecule. Furthermore, the mutual verification analysis of the bidirectional selectivity effect of OP substitute molecules between the BayesianRidge model and the 3D-QS(A(2) + (3))R model reveals that the overall charge transfer degree of DIM substitute molecules is the main reason for the increase in the bidirectional selectivity effect.
ESTHER : Wang_2023_Sci.Total.Environ__163043
PubMedSearch : Wang_2023_Sci.Total.Environ__163043
PubMedID: 36963678

Title : Salicylic acid attenuates brassinosteroid signaling via protein de-S-acylation - Liu_2023_Embo.j__e112998
Author(s) : Liu X , Chen Z , Huang L , Ouyang Y , Wang Z , Wu S , Ye W , Yu B , Zhang Y , Yang C , Lai J
Ref : EMBO j , :e112998 , 2023
Abstract : Brassinosteroids (BRs) are important plant hormones involved in many aspects of development. Here, we show that BRASSINOSTEROID SIGNALING KINASEs (BSKs), key components of the BR pathway, are precisely controlled via de-S-acylation mediated by the defense hormone salicylic acid (SA). Most Arabidopsis BSK members are substrates of S-acylation, a reversible protein lipidation that is essential for their membrane localization and physiological function. We establish that SA interferes with the plasma membrane localization and function of BSKs by decreasing their S-acylation levels, identifying ABAPT11 (ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN 17-LIKE ACYL PROTEIN THIOESTERASE 11) as an enzyme whose expression is quickly induced by SA. ABAPT11 de-S-acylates most BSK family members, thus integrating BR and SA signaling for the control of plant development. In summary, we show that BSK-mediated BR signaling is regulated by SA-induced protein de-S-acylation, which improves our understanding of the function of protein modifications in plant hormone cross talk.
ESTHER : Liu_2023_Embo.j__e112998
PubMedSearch : Liu_2023_Embo.j__e112998
PubMedID: 37211868
Gene_locus related to this paper: arath-AT5G20520

Title : Improving Visual Working Memory with Cholinergic Deep Brain Stimulation - Bava_2023_Brain.Sci_13_
Author(s) : Bava JM , Wang Z , Bick SK , Englot DJ , Constantinidis C
Ref : Brain Sci , 13 : , 2023
Abstract : Acetylcholine is a critical modulatory neurotransmitter for cognitive function. Cholinergic drugs improve cognitive performance and enhance neuronal activity in the sensory and association cortices. An alternative means of improving cognitive function is through the use of deep brain stimulation. Prior animal studies have demonstrated that stimulation of the nucleus basalis of Meynert through DBS improves cognitive performance on a visual working memory task to the same degree as cholinesterase inhibitors. Additionally, unlike current pharmacological treatments for neurocognitive disorders, DBS does not lose efficacy over time and adverse effects are rare. These findings suggest that DBS may be a promising alternative for treating cognitive impairments in neurodegenerative disorders such as Alzheimer's disease. Thus, further research and human trials should be considered to assess the potential of DBS as a therapeutic treatment for these disorders.
ESTHER : Bava_2023_Brain.Sci_13_
PubMedSearch : Bava_2023_Brain.Sci_13_
PubMedID: 37371395

Title : Enzyme-mediated Ru@UiO-66@MnO(2) NSs\/thiamine-based ratiometric fluorescence sensor for visual detection of organophosphorus pesticide residues - Tong_2023_Food.Chem_429_136945
Author(s) : Tong F , Yang Z , Wang Z , Liu W , Jiang W , Zhu L , Wang L , Zheng M , Hou R , Zhou Y , Liu Y
Ref : Food Chem , 429 :136945 , 2023
Abstract : In view of the potential hazards of organophosphorus pesticides (OPs), this paper constructed a ratiometric fluorescent probe utilizing a functionalized metal-organic framework to detect OPs. Ru(bpy)(3)Cl(2) was encapsulated inside UiO-66 as a reference signal, and MnO(2) nanosheets (MnO(2) NSs) were grown on the surface to obtain Ru@UiO-66@MnO(2) NSs. Acetylcholinesterase catalyzed the decomposition of acetylcholine into reductive thiocholine, which consumed MnO(2) NSs, thus restoring the Ru@UiO-66 fluorescence. Due to the enzymatic inhibition of OPs and the redox reaction between MnO(2) NSs and thiamine, this probe emitted blue fluorescence in the presence of OPs. The probe achieved linear responses to dichlorvos and chlorpyrifos with LODs of 9.99 x 10(-6) microg mL(-1) and 9.99 x 10(-5) microg mL(-1). The probe exhibited a satisfactory recovery rate for OPs in green tea. Furthermore, a hydrogel detection platform was developed by embedding the probe into sodium alginate. Overall, this work provides a visual approach to detect OPs in agricultural products.
ESTHER : Tong_2023_Food.Chem_429_136945
PubMedSearch : Tong_2023_Food.Chem_429_136945
PubMedID: 37487398

Title : Design, Synthesis, and Proof of Concept of Balanced Dual Inhibitors of Butyrylcholinesterase (BChE) and Histone Deacetylase 6 (HDAC6) for the Treatment of Alzheimer's Disease - Wang_2023_ACS.Chem.Neurosci__
Author(s) : Wang L , Sun T , Wang Z , Liu H , Qiu W , Tang X , Guo H , Yang P , Chen Y , Sun H
Ref : ACS Chem Neurosci , : , 2023
Abstract : Concomitant inhibition of butyrylcholinesterase (BChE) and histone deacetylase 6 (HDAC6) is supposed to be effective in the treatment of Alzheimer's disease (AD). Inspired by our previous efforts in designing BChE inhibitors, herein, selective BChE and HDAC6 dual inhibitors were successfully identified through the fusion of the core pharmacophoric moiety of BChE and HDAC6 inhibitors. After the structure-activity relationship (SAR) studies, two compounds (24g and 29a) were confirmed to have superior inhibitory activity against BChE (the IC(50) against hBChE are 4.0 and 1.8 nM, respectively) and HDAC6 (the IC(50) against HDAC6 are 8.9 and 71.0 nM, respectively). These two compounds showed prominently neuroprotective effects in vitro, potent reactive oxygen species (ROS) scavenging effects, and effective metal ion (Fe(2+) and Cu(2+)) chelation. In addition, they exhibited pronounced inhibition of phosphorylated tau and a moderate immunomodulatory effect, with a lack of neurotoxicity at the cellular level. In vivo studies showed that both 24g and 29a ameliorated the cognitive impairment in an Abeta(1-42)-induced mouse model at a low dosage (2.5 mg/kg). Our data demonstrated that BChE/HDAC6 dual inhibitors could establish the basis for a potential new symptomatic and disease-modifying strategy to treat AD.
ESTHER : Wang_2023_ACS.Chem.Neurosci__
PubMedSearch : Wang_2023_ACS.Chem.Neurosci__
PubMedID: 37561893

Title : Pyridostigmine ameliorates pristane-induced arthritis symptoms in Dark Agouti rats - Zeng_2023_Scand.J.Rheumatol__1
Author(s) : Zeng M , Issotina Zibrila A , Li X , Liu X , Wang X , Zeng Z , Wang Z , He Y , Meng L , Liu J
Ref : Scand J Rheumatol , :1 , 2023
Abstract : OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder. Pyridostigmine (PYR), an acetylcholinesterase (AChE) inhibitor, has been shown to reduce inflammation and oxidative stress in several animal models for inflammation-associated conditions. The present study aimed to investigate the effects of PYR on pristane-induced (PIA) in Dark Agouti (DA) rats. METHOD: DA rats were intradermally infused with pristane to establish the PIA model, which was treated with PYR (10 mg/kg/day) for 27 days. The effects of PYR on synovial inflammation, oxidative stress, and gut microbiota were evaluated by determining arthritis scores, H&E staining, quantitative polymerase chain reaction, and biochemical assays, as well as 16S rDNA sequencing. RESULTS: Pristane induced arthritis, with swollen paws and body weight loss, increased arthritis scores, synovium hyperplasia, and bone or cartilage erosion. The expression of pro-inflammatory cytokines in synovium was higher in the PIA group than in the control group. PIA rats also displayed elevated levels of malondialdehyde, nitric oxide, superoxide dismutase, and catalase in plasma. Moreover, sequencing results showed that the richness, diversity, and composition of the gut microbiota dramatically changed in PIA rats. PYR abolished pristane-induced inflammation and oxidative stress, and corrected the gut microbiota dysbiosis. CONCLUSION: The results of this study support the protective role of PYR in PIA in DA rats, associated with the attenuation of inflammation and correction of gut microbiota dysbiosis. These findings open new perspectives for pharmacological interventions in animal models of RA.
ESTHER : Zeng_2023_Scand.J.Rheumatol__1
PubMedSearch : Zeng_2023_Scand.J.Rheumatol__1
PubMedID: 37339380

Title : Enzymatic enrichment of acylglycerols rich in n - 3 polyunsaturated fatty acids by selective methanolysis: Optimization and kinetic studies - Jiang_2023_J.Food.Sci__
Author(s) : Jiang C , Wang Z , Huang Y , Wang X , Chang M
Ref : J Food Sci , : , 2023
Abstract : n - 3 Polyunsaturated fatty acids (n - 3 PUFA) have special physiological effect, but their contents in natural oils may not meet the growing demand. Lipase-catalyzed selective methanolysis could be used to produce acylglycerols rich in n - 3 PUFA. To explore the kinetics of enzymatic methanolysis, factors affecting the reaction, including reaction system, water content, substrate molar ratio, temperature, lipase loading, and reaction time, were first investigated in the view of optimizing the reaction. Then the effects of triacylglycerol concentrations and methanol concentrations on initial reaction rate were studied. Finally, the key kinetic parameters of methanolysis were determined subsequently. The results showed that under optimal conditions, the n - 3 PUFA content in acylglycerols increased from 39.88% to 71.41%, and the n - 3 PUFA yield was 73.67%. The reaction followed a Ping-Pong Bi Bi mechanism with inhibition by methanol. The kinetic analysis indicated the lipase could selectively remove saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) in acylglycerols. The inhibition constant of methanol to the n - 3 PUFA (K(iM) , 0.30 mmol/L) was lower than that to the SFA and MUFA (219.64 and 79.71 mmol/L). The combined effects of the fatty acid selectivity of Candida antarctica lipase A and methanol inhibition resulted in an enrichment of n - 3 PUFA in acylglycerols. Overall, the methanolysis reaction catalyzed by the lipase A is a prospective enrichment method. PRACTICAL APPLICATION: This study demonstrated that enzymatic selective methanolysis is a prospective enrichment method to produce acylglycerols rich in n - 3 PUFA. This method is highly efficient, environment-friendly, and simple. n - 3 PUFA concentrates have been widely applied in the food, health-care food, and pharmaceutical industries.
ESTHER : Jiang_2023_J.Food.Sci__
PubMedSearch : Jiang_2023_J.Food.Sci__
PubMedID: 37219384

Title : High-efficiency depolymerization\/degradation of polyethylene terephthalate plastic by a whole-cell biocatalyst - Fang_2023_3.Biotech_13_138
Author(s) : Fang Y , Chao K , He J , Wang Z , Chen Z
Ref : 3 Biotech , 13 :138 , 2023
Abstract : Polyethylene terephthalate (PET) is the most abundantly produced plastic due to its excellent performance, but is also the primary source of poorly degradable plastic pollution. The development of environment-friendly PET biodegradation is attracting increasing interest. The leaf-branch compost cutinase mutant ICCG (F243I/D238C/S283C/Y127G) exhibits the best hydrolytic activity and thermostability of all known PET hydrolases. However, its superior PET degradation is highly dependent on its preparation as a purified enzyme, which critically reduces its industrial utility. Herein, we report the use of rational design and combinatorial mutagenesis to develop a novel ICCG mutant RITK (D53R/R143I/D193T/E208K) that demonstrated excellent whole-cell biocatalytic activity. Whole cells expressing RITK showed an 8.33-fold increase in biocatalytic activity compared to those expressing ICCG. Thermostability was also improved. After reacting at 85 degreesC for 3 h, purified RITK exhibited a 12.75-fold increase in depolymerization compared to ICCG. These results will greatly enhance the industrial utility of PET hydrolytic enzymes and further the progress of PET recycling. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-023-03557-4.
ESTHER : Fang_2023_3.Biotech_13_138
PubMedSearch : Fang_2023_3.Biotech_13_138
PubMedID: 37124986

Title : Green biosynthesis of DHA-phospholipids in tailor-made supersaturated DHA aqueous solution and catalytic mechanism study - Zhang_2023_Food.Chem_431_137164
Author(s) : Zhang T , Wang J , Zhao Y , Wang Z , Hu D , Liu Y , Zhang X , Li H , Zhao B , Li B
Ref : Food Chem , 431 :137164 , 2023
Abstract : Docosahexaenoic acid-phospholipids (DHA-PLs) were prepared via lipase-mediated transesterification of DHA donor and phosphatidylcholine (PC) in a purely aqueous solution. Pre-existing carriers would play the role as "artificial interfaces" to adsorb water-insoluble PC and made them disperse in water. DHA donors were concentrated by a pH-responsive method and presented as supersaturated salt solutions. 153 triacylglycerol lipase structures were analyzed and screened in silico. Transesterification was carried out to further evaluate the six lipase candidates. Lipase B from Candida antarctica (CALB) was the best biocatalyst with 34.8% of DHA incorporation and 80.0% of PLs yields (involving 38.1% PC and 41.9% sn-1 lyso-PC). Toxic organic solvents were avoided. Six possible microunits of our aqueous system consisting of three PLs donors (PC, lyso-PC, sn-glycero-3-PC) and two DHA donors (DHA and DHA salts), were simulated by molecular dynamics (MD) to illustrate the enzymatic mechanism based on diffusional channels, competitive bindings, and enzymatic structures.
ESTHER : Zhang_2023_Food.Chem_431_137164
PubMedSearch : Zhang_2023_Food.Chem_431_137164
PubMedID: 37607420

Title : Influence of Cry1Ab protein on growth and development of a predatory spider, Pardosa pseudoannulata, from protective perspectives - He_2023_Ecotoxicol.Environ.Saf_269_115799
Author(s) : He Y , Lv B , Chao Y , Tang YE , Wang J , Wang Z , Peng YD
Ref : Ecotoxicology & Environmental Safety , 269 :115799 , 2023
Abstract : The expression of Cry proteins in genetically modified rice varieties safeguards the crop from lepidopteran pests. These proteins have the potential to be transferred through the food chain to arthropods like planthoppers and predatory spiders, triggering defensive responses in these unintended organisms. Hence, we hypothesized that Cry protein might influence the growth and development of spiders by altering protective enzyme activities. The results showed that Cry1Ab protein could accumulate in tissues and subcellular organelles of Pardosa pseudoannulata from Nilaparvata lugens. Cry1Ab protein exposure prolonged the developmental duration in the 5th and 7th instar spiderlings but induced no alterations of other growth indicators, such as body length, median ocular area, and survival rate. In addition, Cry1Ab protein exerted no adverse impacts on several detoxifying enzymes (i.e., superoxide dismutase, catalase, glutathione peroxidase, and acetylcholine esterase) in muscle, midgut, ganglia, and hemolymph at subcellular components (i.e., microsome and cytoplasm). To further explore the effects of Cry1Ab protein on the spiderlings, we performed an integrated transcriptome analysis on spiderlings exposed to Cry1Ab protein. The results showed that Cry1Ab protein might prolong the development duration of P. pseudoannulata via the altered cuticle metabolism (e.g., chitin metabolic process and structural constituent of cuticle). In addition, the gene expression profile associated with detoxifying enzymes and three stress-responsive pathways (JAK/STAT, JNK/SAPK, and Hippo pathways) also displayed no significant alterations under Cry1Ab exposure. Collectively, this integrated analysis generates multidimensional insights to assess the effects of Cry1Ab protein on non-target spiders and demonstrates that Cry1Ab protein exerts no toxicity in P. pseudoannulata.
ESTHER : He_2023_Ecotoxicol.Environ.Saf_269_115799
PubMedSearch : He_2023_Ecotoxicol.Environ.Saf_269_115799
PubMedID: 38070414

Title : Identification of the first selective bioluminescent probe for real-time monitoring of carboxylesterase 2 in vitro and in vivo - Chen_2023_Analyst__
Author(s) : Chen Z , Yu J , Sun K , Song J , Chen L , Jiang Y , Wang Z , Chen Y , Zhao T , Miao Z , Huang T , Chen M , Zhao Y , Hai A , Qi Q , Feng P , Li M , Ke B
Ref : Analyst , : , 2023
Abstract : Carboxylesterase (CES), a main hydrolysis enzyme family in the human body, plays a crucial role in drug metabolism. Among them, CES1 and CES2 are the primary subtypes, and each exhibits distinct distribution and functions. However, convenient and non-invasive methods for distinguishing them and the real-time monitoring of CES2 are relatively rare, hindering the further understanding of physiological functions and underlying mechanisms. In this study, we have designed, synthesized, and evaluated the first selective bioluminescent probe (CBP 1) for CES2 with high sensitivity, high specificity and rapid reactivity. This probe offers a promising approach for the real-time detection of CES2 and its dynamic fluctuations both in vitro and in vivo.
ESTHER : Chen_2023_Analyst__
PubMedSearch : Chen_2023_Analyst__
PubMedID: 36661088 || 38078792

Title : Spatial distribution differences of cholinesterase in healthy Chinese under the influence of geographical environmental factors - Yang_2023_Environ.Sci.Pollut.Res.Int__
Author(s) : Yang W , Ge M , Wang Z , Li T
Ref : Environ Sci Pollut Res Int , : , 2023
Abstract : The main targets of this were to screen the factors that may influence the distribution of cholinesterase (CHE) reference value in healthy people, and further explored the geographical distribution differences of CHE reference value in China. In this study, we collected the CHE data of 17,601 healthy people from 173 cities in China to analyse the correlation between CHE and 22 geography secondary indexes through spearman regression analysis. Six indexes with significant correlation were extracted, and a ridge regression model was built, and the country's urban CHE reference value of healthy Chinese was predicted. By using the disjunctive kriging method, we obtained the geographical distribution of CHE reference values for healthy people in China. The reference value of CHE for healthy Chinese was significantly correlated with the 6 secondary indexes, namely, latitude ( degrees), altitude (m), annual average temperature ( degreesC), annual average relative humidity (%) and annual precipitation (mm), and topsoil sand gravel percentage (% wt). The geographical distribution of CHE values of healthy Chinese showed a trend of being higher in southeast China and lower in northwest. This study lays a foundation for further research on the mechanism of different influencing factors on the reference value of CHE index. A ridge regression model composed of significant influencing factors has been established to provide the basis for formulating reference criteria for the treatment factors of the liver damage diseases and liver cancer using CHE reference values in different regions.
ESTHER : Yang_2023_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Yang_2023_Environ.Sci.Pollut.Res.Int__
PubMedID: 36800095

Title : Biochemical characterization and molecular modification of a zearalenone hydrolyzing enzyme Zhd11D from Phialophora attinorum - Wang_2023_Enzyme.Microb.Technol_170_110286
Author(s) : Wang Z , Luo F , Jiang S , Selvaraj JN , Zhou Y , Zhang G
Ref : Enzyme Microb Technol , 170 :110286 , 2023
Abstract : ZEN lactone hydrolase (ZHD) can hydrolyze zearalenone (ZEN) to less or non-toxic product, providing an environment-friendly way for food or feeds-containing ZENs detoxification. Here, a newly identified ZHD from Phialophora attinorum, annotated as Zhd11D, was characterized to exhibit highest activity against ZEN at pH 8.0 and 35 degC with a specific activity of 304.7 U/mg, which was far higher than most of the reported ZHDs. A nonspecific protein engineering method was introduced through fusing a segment of amphiphilic short peptide S1 at the N-terminus of Zhd11D, resulting in both improved activity (1.5-fold) and thermostability (2-fold at 40 degC). Biochemical analysis demonstrated that self-aggregation caused by intermolecular interactions between S1 contributed to the improvement of the enzymatic properties of Zhd11D. Additionally, S1-Zhd11D showed a higher hydrolysis rate of ZEN than Zhd11D in peanut oil.
ESTHER : Wang_2023_Enzyme.Microb.Technol_170_110286
PubMedSearch : Wang_2023_Enzyme.Microb.Technol_170_110286
PubMedID: 37499311

Title : Green biosynthesis of rare DHA-phospholipids by lipase-catalyzed transesterification with edible algal oil in solvent-free system and catalytic mechanism study - Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
Author(s) : Zhang T , Li B , Wang Z , Hu D , Zhang X , Zhao B , Wang J
Ref : Front Bioeng Biotechnol , 11 :1158348 , 2023
Abstract : Docosahexaenoic acid (DHA)-enriched phosphatidylcholine (PC) has received significant scientific attention due to the health benefits in food and pharmaceutical products. In this work, the edible algal oil rich in DHA-triacylglycerol (DHA-TAG) without pretreatment was first used as the DHA donor for the transesterification of phospholipids (PLs) to prepare three kinds of rare PLs, including DHA-PC, DHA-phosphatidylethanolamine (DHA-PE), and DHA-phosphatidylserine (DHA-PS). Here, 153 protein structures of triacylglycerol lipase (EC 3.1.1.3) were virtually screened and evaluated by transesterification. PLA1 was the best candidate due to a higher DHA incorporation. Results showed that the transesterification of PC with DHA-TAG at 45 degreesC and 0.7% water content (without additional water addition) could produce DHA-PC with 39.1% DHA incorporation at 30 min. The different DHA donors, including forms of fatty acid, methyl ester, and triglycerides, were compared. Molecular dynamics (MD) was used to illustrate the catalytic mechanism at the molecular level containing the diffusions of substrates, the structure-activity relationship of PLA1, and the effect of water content.
ESTHER : Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
PubMedSearch : Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
PubMedID: 37064237

Title : Ultrasensitive Fluorescence Platform Based on AgNPs In Situ-Incorporated Zr-MOFs for the Detection of Organophosphorus Pesticides - Wang_2023_ACS.Appl.Mater.Interfaces__
Author(s) : Wang L , Pan Y , Wang Z , Wang Y , Wei X
Ref : ACS Appl Mater Interfaces , : , 2023
Abstract : Organophosphorus pesticides (OPPs) are extensively used in agricultural production, and the contamination caused by their residues has raised significant concerns regarding potential threats to human health. Herein, a novel fluorescence nanoprobe based on an enzyme-mediated silver nanoparticle-modified metal organic framework (AgNPs@PCN-224) was successfully prepared for the rapid detection of OPPs. Initially, AgNPs@PCN-224 were synthesized by reducing silver nitrate (AgNO(3)) using sodium borohydride (NaBH(4)) embedded into luminescent PCN-224. This triggered the inner filter effect, leading to fluorescence quenching. Meanwhile, under the catalysis of acetylcholinesterase (AChE) and choline oxidase (CHO), acetylcholine (ATCh) was decomposed to hydrogen peroxide (H(2)O(2)), which could destroy AgNPs to form Ag(+) released from PCN-224 for fluorescence recovery. Instead, fenitrothion, an OPP, inhibited AChE activity, allowing the quenched fluorescence to be reactivated. Under the current optimum conditions, the fluorescence intensity had a good correlation (Y = -728.5370X + 2178.4248, R(2) = 0.9869) over a dynamic range of fenitrothion concentrations from 0.1 to 500 ng/mL, with an LOD of 0.037 ng/mL. In addition, the anti-interference ability and robustness of the proposed sensor was verified for the monitoring of fenitrothion in tea with recoveries of 87.67-103.72% and the relative standard deviations (RSD) < 5.43%, indicating that the system has excellent prospects for OPP determination in practical applications. Furthermore, this work provides a universal platform for screening other enzyme inhibitors to detect OPPs.
ESTHER : Wang_2023_ACS.Appl.Mater.Interfaces__
PubMedSearch : Wang_2023_ACS.Appl.Mater.Interfaces__
PubMedID: 37676637

Title : Plasma membrane association and resistosome formation of plant helper immune receptors - Wang_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2222036120
Author(s) : Wang Z , Liu X , Yu J , Yin S , Cai W , Kim NH , El Kasmi F , Dangl JL , Wan L
Ref : Proc Natl Acad Sci U S A , 120 :e2222036120 , 2023
Abstract : Intracellular plant immune receptors, termed NLRs (Nucleotide-binding Leucine-rich repeat Receptors), confer effector-triggered immunity. Sensor NLRs are responsible for pathogen effector recognition. Helper NLRs function downstream of sensor NLRs to transduce signaling and induce cell death and immunity. Activation of sensor NLRs that contain TIR (Toll/interleukin-1receptor) domains generates small molecules that induce an association between a downstream heterodimer signalosome of EDS1 (EnhancedDisease Susceptibility 1)/SAG101 (Senescence-AssociatedGene 101) and the helper NLR of NRG1 (NRequired Gene 1). Autoactive NRG1s oligomerize and form calcium signaling channels largely localized at the plasma membrane (PM). The molecular mechanisms of helper NLR PM association and effector-induced NRG1 oligomerization are not well characterized. We demonstrate that helper NLRs require positively charged residues in their N-terminal domains for phospholipid binding and PM association before and after activation, despite oligomerization and conformational changes that accompany activation. We demonstrate that effector activation of a TIR-containing sensor NLR induces NRG1 oligomerization at the PM and that the cytoplasmic pool of EDS1/SAG101 is critical for cell death function. EDS1/SAG101 cannot be detected in the oligomerized NRG1 resistosome, suggesting that additional unknown triggers might be required to induce the dissociation of EDS1/SAG101 from the previously described NRG1/EDS1/SAG101 heterotrimer before subsequent NRG1 oligomerization. Alternatively, the conformational changes resulting from NRG1 oligomerization abrogate the interface for EDS1/SAG101 association. Our data provide observations regarding dynamic PM association during helper NLR activation and underpin an updated model for effector-induced NRG1 resistosome formation.
ESTHER : Wang_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2222036120
PubMedSearch : Wang_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2222036120
PubMedID: 37523563

Title : Sensitive detection of butyrylcholinesterase activity based on a stimuli-responsive fluorescence reaction - Pang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_299_122886
Author(s) : Pang Y , Ma Z , Song Q , Wang Z , Shi YE
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 299 :122886 , 2023
Abstract : A fluorogenic reaction between the chelate of Mn(II)-citric acid and terephthalic acid (PTA) was discovered, which was carried out through heating the aqueous mixture of Mn(2+), citric acid and PTA. Detailed investigations indicated the reaction products were 2-hydroxyterephthalic acid (PTA-OH), which was attributed to the reaction between PTA and OH, formed by the triggering of Mn(II)-citric acid in the presence of dissolved O(2). PTA-OH showed a strong blue fluorescence, peaked at 420 nm, and the fluorescence intensity presented a sensitive response to pH of the reaction system. Based on these mechanisms, the fluorogenic reaction was used for the detection of butyrylcholinesterase activity, achieving a detection limit of 0.15 U/L. The detection strategy was successfully applied in human serum samples, and it was also extended for the detection of organophosphorus pesticides and radical scavengers. Such a facile fluorogenic reaction and its stimuli-responsive properties offered an effective tool for designing detection pathways in the fields of clinical diagnosis, environmental monitoring and bioimaging.
ESTHER : Pang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_299_122886
PubMedSearch : Pang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_299_122886
PubMedID: 37210854

Title : Characteristics of CXE family of Salvia miltiorrhiza and identification of interactions between SmGID1s and SmDELLAs - Li_2023_Plant.Physiol.Biochem_206_108140
Author(s) : Li Y , Pang Q , Li B , Fu Y , Guo M , Zhang C , Tian Q , Hu S , Niu J , Wang S , Wang D , Wang Z
Ref : Plant Physiol Biochem , 206 :108140 , 2023
Abstract : Carboxylesterase (CXE) is a class of hydrolases that contain an alpha/beta folding domain, which plays critical roles in plant growth, development, and stress responses. Based on the genomic and transcriptomic data of Salvia miltiorrhiza, the SmCXE family was systematically analyzed using bioinformatics. The results revealed 34 SmCXE family members in S. miltiorrhiza, and the SmCXE family could be divided into five groups (Group I, Group II, Group III, Group IV, and Group V). Cis-regulatory elements indicated that the SmCXE promoter region contained tissue-specific and development-related, hormone-related, stress-related, and photoresponsive elements. Transcriptome analysis revealed that the expression levels of SmCXE2 were highest in roots and flowers (SmCXE8 was highest in stems and SmCXE19 was highest in leaves). Further, two GA receptors SmCXE1 (SmGID1A) and SmCXE2 (SmGID1B) were isolated from the SmCXE family, which are homologous to other plants. SmGID1A and SmGID1B have conserved HGGSF motifs and active amino acid sites (Ser-Asp-Val/IIe), which are required to maintain their GA-binding activities. SmGID1A and SmGID1B were significantly responsive to gibberellic acid (GA(3)) and methyl jasmonate (MeJA) treatment. A subcellular assay revealed that SmCXE1 and SmCXE2 resided within the nucleus. SmGID1B can interact with SmDELLAs regardless of whether GA(3) exists, whereas SmGID1A can only interact with SmDELLAs in the presence of GA(3). A Further assay showed that the GRAS domain mediated the interactions between SmGID1s and SmDELLAs. This study lays a foundation for further elucidating the role of SmCXE in the growth and development of S. miltiorrhiza.
ESTHER : Li_2023_Plant.Physiol.Biochem_206_108140
PubMedSearch : Li_2023_Plant.Physiol.Biochem_206_108140
PubMedID: 38134738
Gene_locus related to this paper: salmi-SmCXE1 , salmi-SmCXE2 , salmi-SmCXE3 , salmi-SmCXE4 , salmi-SmCXE5 , salmi-SmCXE6 , salmi-SmCXE7 , salmi-SmCXE8 , salmi-SmCXE9 , salmi-SmCXE10 , salmi-SmCXE11 , salmi-SmCXE12 , salmi-SmCXE13 , salmi-SmCXE14 , salmi-SmCXE15 , salmi-SmCXE16 , salmi-SmCXE17 , salmi-SmCXE18 , salmi-SmCXE19 , salmi-SmCXE20 , salmi-SmCXE21 , salmi-SmCXE22 , salmi-SmCXE23 , salmi-SmCXE24 , salmi-SmCXE25 , salmi-SmCXE26 , salmi-SmCXE27 , salmi-SmCXE28 , salmi-SmCXE29 , salmi-SmCXE30 , salmi-SmCXE31 , salmi-SmCXE32 , salmi-SmCXE33 , salmi-SmCXE34

Title : Hormetic effects of EGC and EGCG on CES1 activity and its rescue from oxidative stress in rat liver S9 - Luo_2023_Chem.Biol.Interact__110612
Author(s) : Luo X , Lu F , Yin Z , Zhou Z , Wang Z , Zhang H
Ref : Chemico-Biological Interactions , :110612 , 2023
Abstract : Carboxylesterase 1 (CES1) is a hydrolytic enzyme that plays an important role in the activation or deactivation of many therapeutic agents, thus affecting their pharmacokinetic and pharmacodynamic outcomes. Using rat liver S9 as an enzyme source and enalapril as a CES1 substrate, the present study examined effects of a number of flavonoids on the formation of enalaprilat (the active form of enalapril) produced by CES1-mediated hydrolysis. While a majority of flavonoids tested showed inhibition on CES1, an unexpected hormetic effect was observed for epigallocatechin (EGC) and epigallocatechin gallate (EGCG), i.e., stimulatory effect at low concentrations and enzyme inhibition at high concentrations. Further experiments revealed that oxidative stress caused by hydrogen peroxide, arachidonic acid plus iron, and oxidized low density lipoproteins (oxLOL) reduced CES1 activity in rat liver S9 and the loss of CES1 enzyme activity could be rescued largely by EGC or EGCG. In contrast, such effects were minimal in human liver S9, probably due to the presence of a higher ratio of reduced vs oxidized forms of glutathione. The above findings suggest that the polyphenolic nature of EGC or EGCG might be responsible for rescuing CES1 activity under oxidative stress. Because of the importance of CES1 in drug activation or deactivation and rat liver S9 as a versatile in vitro system used for drug metabolism studies and drug safety assessment, caution should be exercised to avoid potential biases for data interpretation and decision making when CES1 activity in rat liver S9 is evaluated with dependency on experimental conditions.
ESTHER : Luo_2023_Chem.Biol.Interact__110612
PubMedSearch : Luo_2023_Chem.Biol.Interact__110612
PubMedID: 37353134

Title : Oxymatrine-mediated prevention of amyloid beta-peptide-induced apoptosis on Alzheimer's model PC12 cells: in vitro cell culture studies and in vivo cognitive assessment in rats - Zhu_2023_Inflammopharmacology__
Author(s) : Zhu Y , Wang Z , Gao C , Zhang L , Sui R
Ref : Inflammopharmacology , : , 2023
Abstract : Alzheimer's disease (AD) is a major neurological disease affecting elderly individuals worldwide. Existing drugs only reduce the symptoms of the disease without addressing the underlying causes. Commonly, Abeta25-35 peptide aggregation is the main reason for AD development. Recently, the discovery of multiple protein-targeting molecules has provided a new strategy for treating AD. This study demonstrates the neuroprotective potential of oxymatrine against multiple mechanisms, such as acetylcholinesterase, mitochondrial damage, and beta-amyloid-induced cell toxicity. The in vitro cell culture studies showed that oxymatrine possesses significant potential to inhibit acetylcholine esterase and promotes antioxidant, antiapoptotic effects while preventing Abeta25-35 peptide aggregation in PC12 cells. Furthermore, oxymatrine protects PC12 cells against Abeta25-35-induced cytotoxicity and down-regulates the reactive oxygen species generation. The in vivo acute toxicological studies confirm the safety of oxymatrine without causing organ damage or death in animals. Overall, this study provided evidence that oxymatrine is an efficient neuroprotective agent, with a potential to be a multifunctional drug for Alzheimer's disease treatment. These findings present a reliable and synergistic approach for treating AD.
ESTHER : Zhu_2023_Inflammopharmacology__
PubMedSearch : Zhu_2023_Inflammopharmacology__
PubMedID: 37515653

Title : Gut microbiome helps honeybee (Apis mellifera) resist the stress of toxic nectar plant (Bidens pilosa) exposure: Evidence for survival and immunity - Tang_2023_Environ.Microbiol__
Author(s) : Tang Q , Li W , Wang Z , Dong Z , Li X , Li J , Huang Q , Cao Z , Gong W , Zhao Y , Wang M , Guo J
Ref : Environ Microbiol , : , 2023
Abstract : Honeybee (Apis mellifera) ingestion of toxic nectar plants can threaten their health and survival. However, little is known about how to help honeybees mitigate the effects of toxic nectar plant poisoning. We exposed honeybees to different concentrations of Bidens pilosa flower extracts and found that B. pilosa exposure significantly reduced honeybee survival in a dose-dependent manner. By measuring changes in detoxification and antioxidant enzymes and the gut microbiome, we found that superoxide dismutase, glutathione-S-transferase and carboxylesterase activities were significantly activated with increasing concentrations of B. pilosa and that different concentrations of B. pilosa exposure changed the structure of the honeybee gut microbiome, causing a significant reduction in the abundance of Bartonella (p < 0.001) and an increase in Lactobacillus. Importantly, by using Germ-Free bees, we found that colonization by the gut microbes Bartonella apis and Apilactobacillus kunkeei (original classification as Lactobacillus kunkeei) significantly increased the resistance of honeybees to B. pilosa and significantly upregulated bee-associated immune genes. These results suggest that honeybee detoxification systems possess a level of resistance to the toxic nectar plant B. pilosa and that the gut microbes B. apis and A. kunkeei may augment resistance to B. pilosa stress by improving host immunity.
ESTHER : Tang_2023_Environ.Microbiol__
PubMedSearch : Tang_2023_Environ.Microbiol__
PubMedID: 37291689

Title : Integrative analysis uncovers response mechanism of Pirata subpiraticus to chronic cadmium stress - Dai_2022_Environ.Sci.Pollut.Res.Int__
Author(s) : Dai OL , Lei ZY , Peng YD , Wang Z
Ref : Environ Sci Pollut Res Int , : , 2022
Abstract : Soil cadmium (Cd) pollution is global environmental pollution and adversely affects paddy field organisms. Wolf spider grants a new insight to evaluate the toxicity triggered by Cd, yet the impact of chronic Cd exposure on the spider and its molecular mechanism remains unclear. The present study found that the wolf spider Pirata subpiraticus fed with Cd-accumulated flies for 5 weeks presented lower catalase, peroxidase, and acetylcholinesterase activities and higher malonaldehyde content than the control spiders (p < 0.05). An in-depth transcriptomic analysis yielded a total of 5995 differentially expressed genes (DEGs, with 3857 up-regulated and 2138 down-regulated genes) from the comparison, and 19 DEGs encoding three enzymatic indicators were down-regulated. Further enrichment analysis indicated that Cd stress could inhibit the expression of cuticle and chitin-encoding genes via the down-regulation of several key enzymes, such as chitin synthase, glutamine-fructose-6-phosphate transaminase, and chitinase. In addition, our findings suggested that hedgehog and FoxO signaling pathways might play an essential role in regulating survival, cell cycle, and autophagy process in spiders, which were primarily down-regulated under Cd stress. An intensely interactive network displayed that Cd exposure could repress key biological processes in P. subpiraticus, particularly peptide metabolic process and peptide biosynthetic process. To sum up, this integrative investigation confirmed an effective bioindicator for assessing Cd-induced toxicity; provided a mass of genes, proteins, and enzymes for further validation; and granted novel perspectives to uncover the molecular responses of spiders to Cd pollution.
ESTHER : Dai_2022_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Dai_2022_Environ.Sci.Pollut.Res.Int__
PubMedID: 35864398

Title : Karrikin Receptor KAI2 Coordinates Salt Tolerance Mechanisms in Arabidopsis thaliana - Mostofa_2022_Plant.Cell.Physiol__
Author(s) : Mostofa MG , Abdelrahman M , Rahman MM , Tran CD , Nguyen KH , Watanabe Y , Itouga M , Li W , Wang Z , Mochida K , Tran LP
Ref : Plant Cell Physiol , : , 2022
Abstract : Plants activate a myriad of signaling cascades to tailor adaptive responses under environmental stresses, such as salinity. While the roles of exogenous karrikins (KARs) in salt stress mitigation are well comprehended, genetic evidence of KAR signaling during salinity responses in plants remains unresolved. Here, we explored the functions of the possible KAR receptor KARRIKIN INSENSITIVE2 (KAI2) in Arabidopsis thaliana resistance to salt stress by investigating comparative responses of wild-type (WT) and kai2 mutant plants under a gradient of NaCl. Defect in KAI2 functions resulted in delayed and inhibited cotyledon opening in kai2 seeds compared with WT seeds, suggesting that KAI2 played an important role in enhancing seed germination under salinity. Salt-stressed kai2 plants displayed more phenotypic aberrations, biomass reduction, water loss and oxidative damage than WT plants. kai2 shoots accumulated significantly more Na+, and thus had a lower K+/Na+ ratio, than WT, indicating a severe ion-toxicity in salt-stressed kai2 plants. Accordingly, kai2 plants displayed lower expression of the genes associated with Na+ homeostasis, such as SALT OVERLY SENSITIVE (SOS) 1, SOS2, HIGH AFFINITY POTASSIUM TRANSPORTER 1;1 (HKT1;1) and CATION-HYDROGEN EXCHANGER 1 (NHX1) than WT plants. WT plants maintained a better status of glutathione level, glutathione-related redox status and antioxidant enzyme activities relative to kai2 plants, implying KAI2's function in oxidative stress mitigation in response to salinity. kai2 shoots had lower expression levels of the genes involved in the biosynthesis of strigolactones, salicylic acid and jasmonic acid, and the signaling of abscisic acid and strigolactones than those of WT plants, indicating interactive functions of KAI2 signaling with other hormone signaling in modulating plant responses to salinity. Collectively, these results underpin the likely roles of KAI2 in alleviation of salinity effects in plants by regulating several physiological and biochemical mechanisms involved in ionic and osmotic balance, oxidative stress tolerance and hormonal crosstalk.
ESTHER : Mostofa_2022_Plant.Cell.Physiol__
PubMedSearch : Mostofa_2022_Plant.Cell.Physiol__
PubMedID: 35997763

Title : From Function to Metabolome: Metabolomic Analysis Reveals the Effect of Probiotic Fermentation on the Chemical Compositions and Biological Activities of Perilla frutescens Leaves - Wang_2022_Front.Nutr_9_933193
Author(s) : Wang Z , Jin X , Zhang X , Xie X , Tu Z , He X
Ref : Front Nutr , 9 :933193 , 2022
Abstract : This study aimed to investigate the impact of probiotic fermentation on the active components and functions of Perilla frutescens leaves (PFL). PFL was fermented for 7 days using six probiotics (Lactobacillus Plantarum SWFU D16, Lactobacillus Plantarum ATCC 8014, Lactobacillus Rhamnosus ATCC 53013, Streptococcus Thermophilus CICC 6038, Lactobacillus Casei ATCC 334, and Lactobacillus Bulgaricus CICC 6045). The total phenol and flavonoid contents, antioxidant abilities, as well as alpha-glucosidase and acetylcholinesterase inhibition abilities of PFL during the fermentation process were evaluated, and its bioactive compounds were further quantified by high-performance liquid chromatography (HPLC). Finally, non-targeted ultra-HPLC-tandem mass spectroscopy was used to identify the metabolites affected by fermentation and explore the possible mechanisms of the action of fermentation. The results showed that most of the active component contents and functional activities of PFL exhibited that it first increased and then decreased, and different probiotics had clearly distinguishable effects from each other, of which fermentation with ATCC 53013 for 1 day showed the highest enhancement effect. The same trend was also confirmed by the result of the changes in the contents of 12 phenolic acids and flavonoids by HPLC analysis. Further metabolomic analysis revealed significant metabolite changes under the best fermentation condition, which involved primarily the generation of fatty acids and their conjugates, flavonoids. A total of 574 and 387 metabolites were identified in positive ion and negative ion modes, respectively. Results of Spearman's analysis indicated that some primary metabolites and secondary metabolites such as flavonoids, phenols, and fatty acids might play an important role in the functional activity of PFL. Differential metabolites were subjected to the KEGG database and 97 metabolites pathways were obtained, of which biosyntheses of unsaturated fatty acids, flavonoid, and isoflavonoid were the most enriched pathways. The above results revealed the potential reason for the differences in metabolic and functional levels of PFL after fermentation. This study could provide a scientific basis for the further study of PFL, as well as novel insights into the action mechanism of probiotic fermentation on the chemical composition and biological activity of food/drug.
ESTHER : Wang_2022_Front.Nutr_9_933193
PubMedSearch : Wang_2022_Front.Nutr_9_933193
PubMedID: 35898707

Title : Fluorescence-activated droplet sorting of PET degrading microorganisms - Qiao_2022_J.Hazard.Mater_424_127417
Author(s) : Qiao Y , Hu R , Chen D , Wang L , Wang Z , Yu H , Fu Y , Li C , Dong Z , Weng YX , Du W
Ref : J Hazard Mater , 424 :127417 , 2022
Abstract : Enzymes that can decompose synthetic plastics such as polyethylene terephthalate (PET) are urgently needed. Still, a bottleneck remains due to a lack of techniques for detecting and sorting environmental microorganisms with vast diversity and abundance. Here, we developed a fluorescence-activated droplet sorting (FADS) pipeline for high-throughput screening of PET-degrading microorganisms or enzymes (PETases). The pipeline comprises three steps: generation and incubation of droplets encapsulating single cells, picoinjection of fluorescein dibenzoate (FDBz) as the fluorogenic probe, and screening of droplets to obtain PET-degrading cells. We characterized critical factors associated with this method, including specificity and sensitivity for discriminating PETase from other enzymes. We then optimized its performance and compatibility with environmental samples. The system was used to screen a wastewater sample from a PET textile mill. We successfully obtained PET-degrading species from nine different genera. Moreover, two putative PETases from isolates Kineococcus endophyticus Un-5 and Staphylococcus epidermidis Un-C2-8 were genetically derived, heterologously expressed, and preliminarily validated for PET-degrading activities. We speculate that the FADS pipeline can be widely adopted to discover new plastic-degrading microorganisms and enzymes in various environments and may be utilized in the directed evolution of degrading enzymes using synthetic biology.
ESTHER : Qiao_2022_J.Hazard.Mater_424_127417
PubMedSearch : Qiao_2022_J.Hazard.Mater_424_127417
PubMedID: 34673397

Title : Tanshinone IIA regulates glycogen synthase kinase-3beta-related signaling pathway and ameliorates memory impairment in APP\/PS1 transgenic mice - Peng_2022_Eur.J.Pharmacol__174772
Author(s) : Peng X , Chen L , Wang Z , He Y , Ruganzu JB , Guo H , Zhang X , Ji S , Zheng L , Yang W
Ref : European Journal of Pharmacology , :174772 , 2022
Abstract : Our previous findings indicated that tanshinone IIA (tan IIA), a natural component extracted from the root and rhizome of danshen, significantly attenuated beta-amyloid accumulation, neuroinflammation, and endoplasmic reticulum stress, as well as improved learning and memory deficits in APP/PS1 transgenic mouse model of Alzheimer's disease (AD). However, whether tan IIA can ameliorate tau pathology and the underlying mechanism in APP/PS1 mice remains unclear. In the current study, tan IIA (15 mg/kg and 30 mg/kg) or saline was intraperitoneally administered to the 5-month-old APP/PS1 mice once daily for 4 weeks. The open-field test, novel object recognition test, Y-maze test, and Morris water maze test were performed to assess the cognitive function. Nissl staining, immunohistochemistry, TUNEL, and western blotting were conducted to explore tau hyperphosphorylation, neuronal injury, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt)/glycogen synthase kinase-3beta (GSK-3beta) signaling pathway. The activity of GSK-3beta, acetylcholinesterase (AChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), and the level of malondialdehyde (MDA) were measured using commercial kits. Our results revealed that tan IIA treatment significantly ameliorated behavioral deficits and improved spatial learning and memory ability of APP/PS1 mice. Additionally, tan IIA markedly attenuated tau hyperphosphorylation and prevented neuronal loss and apoptosis in the parietal cortex and hippocampus. Simultaneously, tan IIA reversed cholinergic dysfunction and reduced oxidative stress. Furthermore, tan IIA activated the PI3K/Akt signaling pathway and suppressed GSK-3beta. Taken together, the above findings suggested that tan IIA improves cognitive decline and tau pathology may through modulation of PI3K/Akt/GSK-3beta signaling pathway.
ESTHER : Peng_2022_Eur.J.Pharmacol__174772
PubMedSearch : Peng_2022_Eur.J.Pharmacol__174772
PubMedID: 35090935

Title : Phytochemical Composition, Antioxidant Activity, alpha-Glucosidase and Acetylcholinesterase Inhibitory Activity of Quinoa Extract and Its Fractions - Chen_2022_Molecules_27_2420
Author(s) : Chen X , He X , Sun J , Wang Z
Ref : Molecules , 27 :2420 , 2022
Abstract : This study is aimed to evaluate the chemical compositions and biological activities of quinoa, a novel and excellent food crop. Quinoa extract and its fractions were prepared by ethanol extraction and liquid-liquid extraction, including ethanol crude extract, and petroleum ether, chloroform, ethyl acetate (EAF), and n-butanol and water fractions. The total phenolic and flavonoid contents, antioxidant activities, alpha-glucosidase and acetylcholinesterase inhibitory abilities of the extract and fractions were further determined. Based on these foundations, the chemical composition of the EAF fraction exhibiting the strongest functional activity was analyzed by ultra-performance liquid chromatography-mass spectrometry. The results showed the EAF fraction had the highest phenolic and flavonoid contents, and the highest antioxidant activities, as well as the strongest alpha-glucosidase and acetylcholinesterase inhibitory abilities, which is even better than the positive control. The phytochemical composition of the EAF fraction indicated that 661 and 243 metabolites were identified in positive and negative ion modes, which were classified into superclass, class and subclass levels, respectively. Phenolic acids and flavonoids were the major bioactive compounds in the EAF fraction. This study found that quinoa, especially its ethyl acetate fraction, had the potential for the development of natural antioxidants, acetylcholinesterase inhibitors, and hypoglycemic agents.
ESTHER : Chen_2022_Molecules_27_2420
PubMedSearch : Chen_2022_Molecules_27_2420
PubMedID: 35458616

Title : Biodegradation of highly crystallized poly(ethylene terephthalate) through cell surface codisplay of bacterial PETase and hydrophobin - Chen_2022_Nat.Commun_13_7138
Author(s) : Chen Z , Duan R , Xiao Y , Wei Y , Zhang H , Sun X , Wang S , Cheng Y , Wang X , Tong S , Yao Y , Zhu C , Yang H , Wang Y , Wang Z
Ref : Nat Commun , 13 :7138 , 2022
Abstract : The process of recycling poly(ethylene terephthalate) (PET) remains a major challenge due to the enzymatic degradation of high-crystallinity PET (hcPET). Recently, a bacterial PET-degrading enzyme, PETase, was found to have the ability to degrade the hcPET, but with low enzymatic activity. Here we present an engineered whole-cell biocatalyst to simulate both the adsorption and degradation steps in the enzymatic degradation process of PETase to achieve the efficient degradation of hcPET. Our data shows that the adhesive unit hydrophobin and degradation unit PETase are functionally displayed on the surface of yeast cells. The turnover rate of the whole-cell biocatalyst toward hcPET (crystallinity of 45%) dramatically increases approximately 328.8-fold compared with that of purified PETase at 30 degreesC. In addition, molecular dynamics simulations explain how the enhanced adhesion can promote the enzymatic degradation of PET. This study demonstrates engineering the whole-cell catalyst is an efficient strategy for biodegradation of PET.
ESTHER : Chen_2022_Nat.Commun_13_7138
PubMedSearch : Chen_2022_Nat.Commun_13_7138
PubMedID: 36414665
Gene_locus related to this paper: idesa-peth

Title : Characterization of pectin methylesterase gene family and its possible role in juice sac granulation in navel orange (Citrus sinensis Osbeck) - Li_2022_BMC.Genomics_23_185
Author(s) : Li Z , Wu L , Wang C , Wang Y , He L , Wang Z , Ma X , Bai F , Feng G , Liu J , Jiang Y , Song F
Ref : BMC Genomics , 23 :185 , 2022
Abstract : BACKGROUND: Citrus is one of the most important fresh fruit crops worldwide. Juice sac granulation is a physiological disorder, which leads to a reduction in soluble solid concentration, total sugar, and titratable acidity of citrus fruits. Pectin methylesterase (PME) catalyzes the de-methylesterification of homogalacturonans and plays crucial roles in cell wall modification during plant development and fruit ripening. Although PME family has been well investigated in various model plants, little is known regarding the evolutionary property and biological function of PME family genes in citrus. RESULTS: In this study, 53 non-redundant PME genes were identified from Citrus sinensis genome, and these PME genes were divided into four clades based on the phylogenetic relationship. Subsequently, bioinformatics analyses of gene structure, conserved domain, chromosome localization, gene duplication, and collinearity were performed on CsPME genes, providing important clues for further research on the functions of CsPME genes. The expression profiles of CsPME genes in response to juice sac granulation and low-temperature stress revealed that CsPME genes were involved in the low temperature-induced juice sac granulation in navel orange fruits. Subcellular localization analysis suggested that CsPME genes were localized on the apoplast, endoplasmic reticulum, plasma membrane, and vacuole membrane. Moreover, yeast one-hybrid screening and dual luciferase activity assay revealed that the transcription factor CsRVE1 directly bound to the promoter of CsPME3 and activated its activity. CONCLUSION: In summary, this study conducts a comprehensive analysis of the PME gene family in citrus, and provides a novel insight into the biological functions and regulation patterns of CsPME genes during juice sac granulation of citrus.
ESTHER : Li_2022_BMC.Genomics_23_185
PubMedSearch : Li_2022_BMC.Genomics_23_185
PubMedID: 35249536

Title : Novel pathogenic variant combination in LPL causing familial chylomicronemia syndrome in an Asian family and experimental validation in vitro: a case report - Shi_2022_Transl.Pediatr_11_1717
Author(s) : Shi H , Wang Z
Ref : Transl Pediatr , 11 :1717 , 2022
Abstract : BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder, typically caused by biallelic pathogenic variants in the lipoprotein lipase (LPL) gene. Lipoprotein lipase, encoded by the LPL gene, catalyzes the hydrolysis of triglycerides, and its deficiency or dysfunction can lead to chylomicronemia and potentially fatal recurrent acute pancreatitis. CASE DESCRIPTION: Here, we report an Asian child with FCS due to compound heterozygous LPL variants. The 4-year-old patient presented with splenomegaly and severe hypertriglyceridemia, specifically chylomicronemia which resulted in abnormal coagulation measured by a turbidity-based assay. Based on the clinical features and family history, the diagnosis of FCS was suspected, and confirmed by the identification of compound heterozygous variants in the LPL gene (c.461A>G; p.His154Arg and c.788T>A; p.Leu263Gln) in the patient, inheriting one from each parent. According to the clinical and genetic findings, the patient was diagnosed with FCS. In vitro experimental validation found that the LPL p.H154R variant reduced the expression of lipoprotein lipase and decreased its lipolytic activity, while the LPL p.L263Q variant mainly impaired its lipolytic activity. CONCLUSIONS: FCS was molecularly diagnosed using whole exome sequencing in the case presented. When interpreting abnormal coagulation profiles measured by turbidity-based assay, the possibility of lipemic blood (or chylomicronemia) should be considered and the presence of this phenomenon might indicate the diagnosis of FCS. In vitro experiments showed that the two LPL variants impaired lipoprotein lipase expression and/or function making them likely to be pathogenic.
ESTHER : Shi_2022_Transl.Pediatr_11_1717
PubMedSearch : Shi_2022_Transl.Pediatr_11_1717
PubMedID: 36345447
Gene_locus related to this paper: human-LPL

Title : Improvement of methanol tolerance and catalytic activity of Rhizomucor miehei lipase for one-step synthesis of biodiesel by semi-rational design - Tian_2022_Bioresour.Technol__126769
Author(s) : Tian M , Yang L , Lv P , Wang Z , Fu J , Miao C , Li Z , Li L , Liu T , Du W , Luo W
Ref : Bioresour Technol , :126769 , 2022
Abstract : Exploiting highly active and methanol-resistant lipase is of great significance for biodiesel production. A semi-rational directed evolution method combined with N-glycosylation is reported, and all mutants exhibiting higher catalytic activity and methanol tolerance than the wild type (WT). Mutant N267 retained 64% activity after incubation in 50% methanol for 8 h, which was 48% greater than that of WT. The catalytic activity of mutants N267 and N167 was 30- and 71- fold higher than that of WT. Molecular dynamics simulations of N267 showed that the formation of new strong hydrogen bonds between glycan and the protein stabilized the structure of lipase and improved its methanol tolerance. N267 achieved biodiesel yields of 99.33% (colza oil) and 81.70% (waste soybean oil) for 24 h, which was much higher than WT (51.6% for rapeseed oil and 44.73% for wasted soybean oil). The engineered ProRML mutant has high potential for commercial biodiesel production.
ESTHER : Tian_2022_Bioresour.Technol__126769
PubMedSearch : Tian_2022_Bioresour.Technol__126769
PubMedID: 35092821

Title : Pseudo toxicity abatement effect of norfloxacin and copper combined exposure on Caenorhabditis elegans - Liu_2022_Chemosphere_287_132019
Author(s) : Liu L , He S , Tang M , Zhang M , Wang C , Wang Z , Sun F , Yan Y , Li H , Lin K
Ref : Chemosphere , 287 :132019 , 2022
Abstract : The coexistence of antibiotics and heavy metals may result in complex ecotoxicological effects on living organisms. In this work, the combined toxic effects of norfloxacin (NOR) and copper (Cu) on Caenorhabditis elegans (C. elegans) were investigated due to the highly possible co-pollution tendency. The results indicated that locomotion behaviors (frequency of head thrash and body bend) of C. elegans were more sensitive as the exposure time of NOR or Cu prolonged. Meanwhile, the physiological indexes (locomotion behaviors, body length) of C. elegans were more sensitive to the combined pollution that with lower Cu dosage (0.0125 microM), in prolonged exposure experiments. In addition, the toxic effects of NOR-Cu on physiological indexes of C. elegans seemed to be alleviated during prolonged exposure when Cu was 1.25 microM. Similarly, the ROS production and apoptosis level almost unchanged with the addition of NOR compared with Cu (1.25 microM) exposure groups, but both significantly higher than the control groups. Furthermore, compared with Cu (0.0125 microM and 1.25 microM) exposure experiments, the addition of NOR had resulted in the genetic expression decrease of hsp-16.1, hsp-16.2, hsp-16.48, and the oxidative stress in C. elegans seems to be alleviated. However, the significantly decreased of ape-1 and sod-3 expression indicated the disruption of ROS defense mechanism. The irregular change in ace-1 and ace-2 gene expressions in NOR-Cu (0.0125 microM) would result in the locomotion behaviors disorders of C. elegans, and this also explains why C. elegans are more sensitive to the combination of NOR and lower concentration of Cu.
ESTHER : Liu_2022_Chemosphere_287_132019
PubMedSearch : Liu_2022_Chemosphere_287_132019
PubMedID: 34450372

Title : Recent advance on carbamate-based cholinesterase inhibitors as potential multifunctional agents against Alzheimer's disease - Zhang_2022_Eur.J.Med.Chem_240_114606
Author(s) : Zhang H , Wang Y , Li X , Wang S , Wang Z
Ref : Eur Journal of Medicinal Chemistry , 240 :114606 , 2022
Abstract : Alzheimer's disease (AD), as the fourth leading cause of death among the elderly worldwide, has brought enormous challenge to the society. Due to its extremely complex pathogeneses, the development of multi-target directed ligands (MTDLs) becomes the major strategy for combating AD. Carbamate moiety, as an essential building block in the development of MTDLs, exhibits structural similarity to neurotransmitter acetylcholine (ACh) and has piqued extensive attention in discovering multifunctional cholinesterase inhibitors. To date, numerous preclinical studies demonstrate that carbamate-based cholinesterase inhibitors can prominently increase the level of ACh and improve cognition impairments and behavioral deficits, providing a privileged strategy for the treatment of AD. Based on the recent research focus on the novel cholinesterase inhibitors with multiple biofunctions, this review aims at summarizing and discussing the most recent studies excavating the potential carbamate-based MTDLs with cholinesterase inhibition efficacy, to accelerate the pace of pleiotropic cholinesterase inhibitors for coping AD.
ESTHER : Zhang_2022_Eur.J.Med.Chem_240_114606
PubMedSearch : Zhang_2022_Eur.J.Med.Chem_240_114606
PubMedID: 35858523

Title : Discovery of pyrrole derivatives as acetylcholinesterase-sparing butyrylcholinesterase inhibitor - Sun_2022_Front.Pharmacol_13_1043397
Author(s) : Sun S , Shi T , Peng Y , Zhang H , Zhuo L , Peng X , Li Q , Wang M , Wang S , Wang Z
Ref : Front Pharmacol , 13 :1043397 , 2022
Abstract : Inspired by the crucial roles of (hetero)aryl rings in cholinesterase inhibitors and the pyrrole ring in new drug discovery, we synthesized 19 pyrrole derivatives and investigated their cholinesterase inhibitory activity. As a result, compounds 3o, 3p, and 3s with a 1,3-diaryl-pyrrole skeleton showed high selectivity toward BChE over AChE with a best IC(50) value of 1.71 +/- 0.087smicroM, which were comparable to donepezil. The pharmaceutical potential of these structures was further predicted and compounds 3o and 3p were proved to meet well with the Lipinsky's five rules. In combination of the inhibition kinetic studies with the results of molecular docking, we concluded that compound 3p inhibited BChE in a mixed competitive mode. This research has proved the potential of the 1,3-diaryl-pyrrole skeleton as a kind of selective BChE inhibitor.
ESTHER : Sun_2022_Front.Pharmacol_13_1043397
PubMedSearch : Sun_2022_Front.Pharmacol_13_1043397
PubMedID: 36561337

Title : Fosthiazate exposure induces oxidative stress, nerve damage, and reproductive disorders in nontarget nematodes - Liu_2022_Environ.Sci.Pollut.Res.Int_30_12522
Author(s) : Liu S , Wu Q , Zhong Y , He Z , Wang Z , Li R , Wang M
Ref : Environ Sci Pollut Res Int , 30 :12522 , 2022
Abstract : As a forceful nematicide, fosthiazate has been largely applied in the management of root-knot nematodes and other herbivorous nematodes. However, the toxicity of fosthiazate to nontarget nematodes is unclear. To explore the toxicity and the mechanisms of fosthiazate in nontarget nematodes, Caenorhabditis elegans was exposed to 0.01-10 mg/L fosthiazate. The results implied that treatment with fosthiazate at doses above 0.01 mg/L could cause injury to the growth, locomotion behavior, and reproduction of the nematodes. Moreover, L1 larvae were more vulnerable to fosthiazate exposure than L4 larvae. Reactive oxygen species (ROS) production and lipofuscin accumulation were fairly increased in 1 mg/L fosthiazate-exposed nematodes. Treatment with 0.1 mg/L fosthiazate significantly inhibited the activity of acetylcholinesterase (p < 0.01). Furthermore, subacute exposure to 10 mg/L fosthiazate strongly influenced the expression of genes related to oxidative stress, reproduction, and nerve function (e.g., gst-1, sod-1, puf-8, wee-1.3, and ace-1 genes). These findings suggested that oxidative stress, reproduction and nerve disorders could serve as key endpoints of toxicity induced by fosthiazate. The cyp-35a family gene was the main metabolic fosthiazate in C. elegans, and the cyp-35a5 subtype was the most sensitive, with a change in expression level of 2.11-fold compared with the control. These results indicate that oxidative stress and neurological and reproductive disorders played fundamental roles in the toxicity of fosthiazate in C. elegans and may affect the abundance and function of soil nematodes.
ESTHER : Liu_2022_Environ.Sci.Pollut.Res.Int_30_12522
PubMedSearch : Liu_2022_Environ.Sci.Pollut.Res.Int_30_12522
PubMedID: 36112285

Title : Construction of a Novel Lipase Catalytic System Based on Hybrid Membranes with Interwoven Electrospun Polyacrylic Acid and Polyvinyl Pyrrolidone Gel Fibers - Wang_2022_Gels_8_
Author(s) : Wang Z , Lin S , Zhang Q , Li J , Yin S
Ref : Gels , 8 : , 2022
Abstract : Efficient lipase catalysis requires sufficient oil-water interface engineered through structural design. Inspired by the architectural features of fabrics, a novel lipase-membrane catalytic system with interwoven polyacrylic acid (PAA) gel fibers and polyvinyl pyrrolidone (PVP) gel fibers was developed in this study by using double-needle electrospinning and gelation. It has been demonstrated that PAA/PVP hybrid gel fiber membranes (HGFMs) have a high swelling capacity for both water and oil phases, which created numerous discontinuous oil-water contact surface units in limited space of HGFMs, consequently forming effective interfacial catalytic systems. Volume competition between the water and oil phases suggests that balancing the proportions of these phases is very important for effective construction of oil-water interfaces and conditioning catalysis. Regulation of multiple factors of PAA/PVP HGFMs resulted in a catalytic efficiency of up to 2.1 times that of a macroscopic 'oil-up/water-down' system (room temperature, pH = 7), and 2.9 times when three membranes are superimposed, as well as excellent pH and temperature stability. HGFMs were stacked to build a high-performing catalytic performance reactor. We expect that this study will be a beneficial exploration for expanding the lipase catalytic system.
ESTHER : Wang_2022_Gels_8_
PubMedSearch : Wang_2022_Gels_8_
PubMedID: 36547336

Title : Activated autophagy-lysosomal pathway in dairy cows with hyperketonemia is associated with lipolysis of adipose tissues - Yu_2022_J.Dairy.Sci__
Author(s) : Yu H , Fan M , Chen X , Jiang X , Loor JJ , Aboragah A , Zhang C , Bai H , Fang Z , Shen T , Wang Z , Song Y , Li X , Liu G , Du X
Ref : J Dairy Sci , : , 2022
Abstract : Activated autophagy-lysosomal pathway (ALP) can degrade virtually all kinds of cellular components, including intracellular lipid droplets, especially during catabolic conditions. Sustained lipolysis and increased plasma fatty acids concentrations are characteristic of dairy cows with hyperketonemia. However, the status of ALP in adipose tissue during this physiological condition is not well known. The present study aimed to ascertain whether lipolysis is associated with activation of ALP in adipose tissues of dairy cows with hyperketonemia and in calf adipocytes. In vivo, blood and subcutaneous adipose tissue (SAT) biopsies were collected from nonhyperketonemic (nonHYK) cows [blood beta-hydroxybutyrate (BHB) concentration <1.2 mM, n = 10] and hyperketonemic (HYK) cows (blood BHB concentration 1.2-3.0 mM, n = 10) with similar days in milk (range: 3-9) and parity (range: 2-4). In vitro, calf adipocytes isolated from 5 healthy Holstein calves (1 d old, female, 30-40 kg) were differentiated and used for (1) treatment with lipolysis inducer isoproterenol (ISO, 10 microM, 3 h) or mammalian target of rapamycin inhibitor Torin1 (250 nM, 3 h), and (2) pretreatment with or without the ALP inhibitor leupeptin (10 microg/mL, 4 h) followed by ISO (10 microM, 3 h) treatment. Compared with nonHYK cows, serum concentration of free fatty acids was greater and serum glucose concentration, DMI, and milk yield were lower in HYK cows. In SAT of HYK cows, ratio of phosphorylated hormone-sensitive lipase to hormone-sensitive lipase, and protein abundance of adipose triacylglycerol lipase were greater, but protein abundance of perilipin 1 (PLIN1) and cell death-inducing DNA fragmentation factor-alpha-like effector c (CIDEC) was lower. In addition, mRNA abundance of autophagy-related 5 (ATG5), autophagy-related 7 (ATG7), and microtubule-associated protein 1 light chain 3 beta (MAP1LC3B), protein abundance of lysosome-associated membrane protein 1, and cathepsin D, and activity of beta-N-acetylglucosaminidase were greater, whereas protein abundance of sequestosome-1 (p62) was lower in SAT of HYK cows. In calf adipocytes, treatment with ISO or Torin1 decreased protein abundance of PLIN1, and CIDEC, and triacylglycerol content in calf adipocytes, but increased glycerol content in the supernatant of calf adipocytes. Moreover, the mRNA abundance of ATG5, ATG7, and MAP1LC3B was upregulated, the protein abundance of lysosome-associated membrane protein 1, cathepsin D, and activity of beta-N-acetylglucosaminidase were increased, whereas the protein abundance of p62 was decreased in calf adipocytes treated with ISO or Torin1 compared with control group. Compared with treatment with ISO alone, the protein abundance of p62, PLIN1, and CIDEC, and triacylglycerol content in calf adipocytes were higher, but the glycerol content in the supernatant of calf adipocytes was lower in ISO and leupeptin co-treated group. Overall, these data indicated that activated ALP is associated with increased lipolysis in adipose tissues of dairy cows with hyperketonemia and in calf adipocytes.
ESTHER : Yu_2022_J.Dairy.Sci__
PubMedSearch : Yu_2022_J.Dairy.Sci__
PubMedID: 35688731

Title : Insights into acylation mechanisms: co-expression of serine carboxypeptidase-like acyltransferases and their non-catalytic companion paralogs - Yao_2022_Plant.J_111_117
Author(s) : Yao S , Liu Y , Zhuang J , Zhao Y , Dai X , Jiang C , Wang Z , Jiang X , Zhang S , Qian Y , Tai Y , Wang Y , Wang H , Xie DY , Gao L , Xia T
Ref : Plant J , 111 :117 , 2022
Abstract : Serine carboxypeptidase-like acyltransferases (SCPL-ATs) play a vital role in the diversification of plant metabolites. Galloylated flavan-3-ols highly accumulate in tea (Camellia sinensis), grape (Vitis vinifera), and persimmon (Diospyros kaki). To date, the biosynthetic mechanism of these compounds remains unknown. Herein, we report that two SCPL-AT paralogs are involved in galloylation of flavan-3-ols: CsSCPL4, which contains the conserved catalytic triad S-D-H, and CsSCPL5, which has the alternative triad T-D-Y. Integrated data from transgenic plants, recombinant enzymes, and gene mutations showed that CsSCPL4 is a catalytic acyltransferase, while CsSCPL5 is a non-catalytic companion paralog (NCCP). Co-expression of CsSCPL4 and CsSCPL5 is likely responsible for the galloylation. Furthermore, pull-down and co-immunoprecipitation assays showed that CsSCPL4 and CsSCPL5 interact, increasing protein stability and promoting post-translational processing. Moreover, phylogenetic analyses revealed that their homologs co-exist in galloylated flavan-3-ol- or hydrolyzable tannin-rich plant species. Enzymatic assays further revealed the necessity of co-expression of those homologs for acyltransferase activity. Evolution analysis revealed that the mutations of the CsSCPL5 catalytic residues may have taken place about 10 million years ago. These findings show that the co-expression of SCPL-ATs and their NCCPs contributes to the acylation of flavan-3-ols in the plant kingdom.
ESTHER : Yao_2022_Plant.J_111_117
PubMedSearch : Yao_2022_Plant.J_111_117
PubMedID: 35437852
Gene_locus related to this paper: dioka-dkSCPL1 , camsi-SCPL5 , camsi-SCPL4

Title : Evaluation of Antioxidative and Neuroprotective Activities of Total Flavonoids From Sea Buckthorn (Hippophae rhamnoides L.) - Wang_2022_Front.Nutr_9_861097
Author(s) : Wang Z , Wang W , Zhu C , Gao X , Chu W
Ref : Front Nutr , 9 :861097 , 2022
Abstract : The aim of this study was to investigate the antioxidative and neuroprotective activities of total flavonoids from sea buckthorn (Hippophae rhamnoides L.) (TFH). Results indicated that TFH possessed DPPH radicals, hydroxyl radicals and superoxide anions scavenging activities. The neuroprotective potential was assessed with acetylcholinesterase (AChE) and monoamine oxidase A (MAO-A). The inhibition rates of AChE and MAO-A by 50 microg/ml TFH were 75.85 and 51.22%, respectively. The in vivo antioxidative and neuroprotective potential of TFH were explored in Caenorhabditis elegans. In the longevity assay, TFH (50 microg/ml) significantly increased the lifespan of wild-type C. elegans (29.40%). In the hydrogen peroxide-induced oxidative stress challenge, the antioxidant capacity of TFH-treated wild-type C. elegans was significantly enhanced. The C. elegans mutant strain CL4176 was used to study the neuroprotective effect of TFH in vivo. Results showed that TFH significantly delayed paralysis in C. elegans CL4176. Our study suggested total flavonoids from sea buckthorn (Hippophae rhamnoides L.) had the potential as an antioxidative and neuroprotective agent to extend aging and treat neurodegenerative diseases.
ESTHER : Wang_2022_Front.Nutr_9_861097
PubMedSearch : Wang_2022_Front.Nutr_9_861097
PubMedID: 35799585

Title : Highly Selective Detection of Paraoxon in Food Based on the Platform of Cu Nanocluster\/MnO(2) Nanosheets - Liu_2022_Nanomaterials.(Basel)_12_
Author(s) : Liu S , Zhang P , Miao Y , Li C , Shi YE , Liu J , Lv YK , Wang Z
Ref : Nanomaterials (Basel) , 12 : , 2022
Abstract : Selective and sensitive identification of paraoxon residue in agricultural products is greatly significant for food safety but remains a challenging task. Herein, a detection platform was developed by integrating Cu nanoclusters (Cu NCs) with MnO(2) nanosheets, where the fluorescence of Cu NCs was effectively quenched. Upon introducing butyrylcholinesterase and butyrylcholine into the system, their hydrolysate, thiocholine, leads to the decomposition of the platform through a reaction between the MnO(2) nanosheets and thiol groups on thiocholine. The electron-rich groups on thiocholine can further promote the fluorescence intensity of Cu NCs through host-guest interactions. Adding paraoxon results in the failure of fluorescence recovery and further promotion, which could be utilized for the quantitative detection of paraoxon, and a limit of detection as low as 0.22 ng/mL can be achieved. The detection platform shows strong tolerance to common interference species, which endows its applications for the detection of paraoxon in vegetables and fruit. These presented results not only open a new door for the functionalization of metal nanoclusters but also offer an inspiring strategy for analytic techniques in nanomedicine and environmental science.
ESTHER : Liu_2022_Nanomaterials.(Basel)_12_
PubMedSearch : Liu_2022_Nanomaterials.(Basel)_12_
PubMedID: 35564138

Title : Plin5 Bidirectionally Regulates Lipid Metabolism in Oxidative Tissues - Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
Author(s) : Zhang X , Xu W , Xu R , Wang Z , Wang P , Peng K , Li M , Li J , Tan Y , Wang X , Pei H
Ref : Oxid Med Cell Longev , 2022 :4594956 , 2022
Abstract : Cytoplasmic lipid droplets (LDs) can store neutral lipids as an energy source when needed and also regulate the key metabolic processes of intracellular lipid accumulation, which is associated with several metabolic diseases. The perilipins (Plins) are a family of proteins that associate with the surface of LDs. As a member of Plins superfamily, perilipin 5 (Plin5) coats LDs in cardiomyocytes, which is significantly related to reactive oxygen species (ROS) production originated from mitochondria in the heart, consequently determining the progression of diabetic cardiomyopathy. Plin5 may play a bidirectional function in lipid metabolism which is in a state of dynamic balance. In the basic state, Plin5 inhibited the binding of comparative gene identification-58 (CGI-58) to adipose triglyceride lipase (ATGL) by binding CGI-58, thus inhibiting lipolysis. However, when the body is under stress (such as cold, fasting, exercise, and other stimuli), protein kinase A (PKA) phosphorylates and activates Plin5, which then causes Plin5 to release the binding site of CGI-58 and ATGL, prompting CGI-58 to bind to ATGL and activate ATGL activity, thus accelerating the lipolysis process, revealing the indispensable role of Plin5 in lipid turnover. Here, the purpose of this review is to summarize the present understanding of the bidirectional regulation role of Plin5 in oxidative tissues and to reveal its potential role in diabetic cardiomyopathy protection.
ESTHER : Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
PubMedSearch : Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
PubMedID: 35401929

Title : Nanobodies as binding-chaperones stabilize the recombinant Bombyx mori acetylcholinesterase and protect the enzyme activity in pesticide detection - Cai_2022_Enzyme.Microb.Technol_155_109992
Author(s) : Cai J , Romao E , Wu G , Li J , Li L , Wang Z , Li Y , Yang J , Shen Y , Xu Z , Muyldermans S , Wang H
Ref : Enzyme Microb Technol , 155 :109992 , 2022
Abstract : In our previous study, the recombinant type II acetylcholinesterase from Bombyx mori (rBmAChE) presented outstanding sensitivity to pesticides, which exhibited great potential in pesticides detection. However, the poor stability of rBmAChE and also the unclear mechanism of its sensitivity hindered the applications in on-site testing of pesticides residues. In this study, we constructed an immune nanobody library, in which we obtained 48 rBmAChE-specific nanobodies. Among them, Nb4 and Nb9 were verified as the most prominent enhancers of the enzyme activity and stabilizers under thermal stress, which indicated their usage as protective reagents for rBmAChE. The simultaneously addition of the two Nbs enhanced the thermal-stability of rBmAChE against exposure to 50-70 degreesC, and also remained 100% residual activity after 30 days storage at - 20 degreesC or 4 degreesC, whereas 80% and 62% at - 80 degreesC and 25 degreesC. The homologous modeling and docking of Nb4 and Nb9 to rBmAChE indicated the stabilization of Nb4 to the peripheral anion site (PAS) of rBmAChE while Nb9 protected the C-terminal structure. Substrate docking demonstrated the importance of electrostatic attraction during catalytic process, that might be enhanced by Nbs. As a result, Nb4 and Nb9 were proved to have great potential on rBmAChE applications due to their regulation on enzyme activity and protection against thermal-inactivation and long-term storage of rBmAChE.
ESTHER : Cai_2022_Enzyme.Microb.Technol_155_109992
PubMedSearch : Cai_2022_Enzyme.Microb.Technol_155_109992
PubMedID: 35114480

Title : N-glycosylation as an effective strategy to enhance characteristics of Rhizomucor miehei lipase for biodiesel production - Tian_2022_Enzyme.Microb.Technol_160_110072
Author(s) : Tian M , Wang Z , Fu J , Lv P , Liang C , Li Z , Yang L , Liu T , Li M , Luo W
Ref : Enzyme Microb Technol , 160 :110072 , 2022
Abstract : The construction of methanol-resistant lipases with high catalytic activity is world-shattering for biodiesel production. A semi-rational method has been constructed to enhance the properties of Rhizomucor miehei lipase with propeptide (ProRML) by introducing N-glycosylation sites in the Loop structure. The enzyme activities of the mutants N288 (1448.89 +/- 68.64 U/mg) and N142 (1073.68 +/- 33.87 U/mg) increased to 56.09 and 41.56 times relative to that of wild type ProRML (WT, 25.83 +/- 0.73 U/mg), respectively. After incubation in 50 % methanol for 2.5 h, the residual activities of N314 and N174-1 were 95 % and 85%, which were higher than the WT (27 %). Additionally, the biodiesel yield of all mutants was increased after a one-time addition of methanol for 24 h. Among them, N288 increased the quantity of biodiesel from colza oil from 9.49 % to 88 %, and N314 increased the amount of biodiesel from waste soybean oil from 8.44% to 70%. This study provides an effective method to enhance the properties of lipase and improve its application potential in biodiesel production.
ESTHER : Tian_2022_Enzyme.Microb.Technol_160_110072
PubMedSearch : Tian_2022_Enzyme.Microb.Technol_160_110072
PubMedID: 35689964

Title : Biodegradation of polybutylene adipate-co-terephthalate by Priestia megaterium, Pseudomonas mendocina, and Pseudomonas pseudoalcaligenes following incubation in the soil - Wei_2022_Chemosphere__135700
Author(s) : Wei S , Zhao Y , Zhou R , Lin J , Su T , Tong H , Wang Z
Ref : Chemosphere , :135700 , 2022
Abstract : Soil that contained polybutylene adipate-co-terephthalate (PBAT) was incubated with Priestia megaterium, Pseudomonas mendocina, and Pseudomonas pseudoalcaligenes to improve the biodegradative process of this polymer. The mixture of Pr. megaterium and Ps. mendocina was highly effective at biodegrading the PBAT, and after eight weeks of soil incubation, approximately 84% of the PBAT film weight was lost. Mixtures of the other two species also positively affected the synergistic degradation of PBAT film in the soil, but the mixture of three species had a negative effect. The residual PBAT film microstructure clearly demonstrated the degradation of PBAT, and the degree of degradation was related to the different species. Cleavage of the PBAT film ester bond after soil microbial action affected its properties. The incubation of PBAT in soil that contained these species affected soil dehydrogenase and soil lipase in particular. The secretion of lipase by these species could play an important role in the degradation of PBAT in the soil.
ESTHER : Wei_2022_Chemosphere__135700
PubMedSearch : Wei_2022_Chemosphere__135700
PubMedID: 35850225

Title : Hydrolysis Mechanism of Carbamate Methomyl by a Novel Esterase PestE: A QM\/MM Approach - Wang_2022_Int.J.Mol.Sci_24_
Author(s) : Wang Z , Zhang Q , Wang G , Wang W , Wang Q
Ref : Int J Mol Sci , 24 : , 2022
Abstract : Methomyl is one of the most important carbamates that has caused potential hazardous effects on both human beings and the environment. Here, we systematically investigated the hydrolysis mechanism of methomyl catalyzed by esterase PestE using molecular dynamics simulations (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. The hydrolysis mechanism involves two elementary steps: () serine-initiated nucleophilic attack and () C-O bond cleavage. Our work elicits the atomic level details of the hydrolysis mechanism and free energy profiles along the reaction pathway. The Boltzmann-weighted average potential barriers are 19.1 kcal/mol and 7.5 kcal/mol for steps and , respectively. We identified serine-initiated nucleophilic attack as the rate determining-step. The deep learning-based k(cat) prediction model indicated that the barrier of the rate-determining step is 15.4 kcal/mol, which is in good agreement with the calculated results using Boltzmann-weighted average method. We have elucidated the importance of the protein-substrate interactions and the roles of the key active site residues during the hydrolysis process through noncovalent interactions analysis and electrostatic potential (ESP) analysis. The results provide practical value for achieving efficient degradation of carbamates by hydrolases.
ESTHER : Wang_2022_Int.J.Mol.Sci_24_
PubMedSearch : Wang_2022_Int.J.Mol.Sci_24_
PubMedID: 36613879

Title : An efficient multi-enzyme cascade platform based on mesoporous metal-organic frameworks for the detection of organophosphorus and glucose - Cao_2022_Food.Chem_381_132282
Author(s) : Cao X , Guo Y , Zhao M , Li J , Wang C , Xia J , Zou T , Wang Z
Ref : Food Chem , 381 :132282 , 2022
Abstract : An efficient colorimetric detection platform based on multi-enzyme cascade has been developed for detection of organophosphorus. Firstly, the dual-enzyme platform was prepared and applied for sensitive glucose detection (detection limit 0.32 microM). And then three enzymes, including acetylcholinesterase, horseradish peroxidase and choline oxidase were encapsulated in cruciate flower-like zeolitic imidazolate framework-8 (CF-ZIF-8) through one-step co-precipitation to construct detection platform with acetylcholine chloride as substrate. The acephate inhibited the activity of acetylcholinesterase, obstructed the cascade reaction and reduced the production of H(2)O(2), resulting in the changes of color intensity for the colorimetric detection. With suitable size and porous structure, CF-ZIF-8 provided a good microenvironment for guaranteeing the activity and spatial proximity of enzymes. The multi-enzyme platform displayed great performances with the detection limit of 0.23 nM for acephate. It was applied to the detection of acephate in Chinese cabbage and romaine, verifying the practicability of this platform.
ESTHER : Cao_2022_Food.Chem_381_132282
PubMedSearch : Cao_2022_Food.Chem_381_132282
PubMedID: 35176684

Title : Esterase-Activated Precipitating Strategy to Achieve Highly Specific Detection and Long-Term Imaging of Calcium Ions by Aggregation-Induced Phosphorescence Probe - Wang_2022_Anal.Chem__
Author(s) : Wang Z , Xiong Z , Liu W , Zhu Q , Zhang X , Ding Y , Huang C , Feng H , Zhang K , Zhu E , Qian Z
Ref : Analytical Chemistry , : , 2022
Abstract : Spatial and temporal monitoring of bioactive targets such as calcium ions is vitally significant for their essential roles in physiological and biochemical functions. Herein, we proposed an esterase-activated precipitating strategy to achieve highly specific identification and long-term bioimaging of calcium ions via lighting up the calcium ions by precipitation using a water-soluble aggregation-induced phosphorescence (AIP) probe. The designed probe CaP2 has an AIP behavior and can be efficiently aggregated by calcium ions through the coupling coordination of carboxylic acid and cyanide groups, which enables it to light up Ca(2+) by precipitating-triggered phosphorescence. Four hydrophilic groups of tetraethylene glycol were introduced to endow the resulting probe CaP3 with extraordinary water solubility as well as excellent cellular penetration. Only when the probe CaP3 penetrates inside the live cells the existing esterase in cells can activate the probe to be transformed active CaP2 probe selectively binding with calcium ion in the surroundings. The probe was used to further evaluate the imaging of intracellular calcium ions in model organisms. The excellent imaging performance of CaP3 in Arabidopsis thaliana seedling roots demonstrates that CaP3 has the excellent capability of monitoring calcium ions in live-cell imaging, and furthermore CaP3 exhibits much better photostability and thereby greater potential in long-term imaging. This work established a general esterase-activated precipitating strategy to achieve specific detection and bioimaging in situ triggered by esterase in live cells, and established a water-soluble aggregation-induced phosphorescence probe with high selectivity to achieve specific sensing and long-term imaging of calcium ions in live cells.
ESTHER : Wang_2022_Anal.Chem__
PubMedSearch : Wang_2022_Anal.Chem__
PubMedID: 35315662

Title : A preliminary study of the chemical composition and bioactivity of Bombax ceiba L. flower and its potential mechanism in treating type 2 diabetes mellitus using ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry and network pharmacology analysis - Yin_2022_Front.Nutr_9_1018733
Author(s) : Yin K , Yang J , Wang F , Wang Z , Xiang P , Xie X , Sun J , He X , Zhang X
Ref : Front Nutr , 9 :1018733 , 2022
Abstract : This study aimed to preliminary investigate the phytochemistry, bioactivity, hypoglycemic potential, and mechanism of action of Bombax ceiba L. flower (BCF), a wild edible and food plant in China. By using methanol extraction and liquid-liquid extraction, the crude extract (CE) of BCF and its petroleum ether (PE), dichloromethane (DCM), ethyl acetate (EtOAc), n-butanol (n-BuOH), and aqueous (AQ) fractions were obtained, and their chemical components and biological activities were evaluated. Further high-performance liquid chromatography (HPLC) analysis was carried out to identify and quantify the active constituents of BFC and its five fractions, and the phytochemical composition of the best-performing fraction was then analyzed by ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC/Q-TOF-MS). Finally, a network pharmacology strategy based on the chemical profile of this fraction was applied to speculate its main hypoglycemic mechanism. Results revealed the excellent biological activities of BCF, especially the EtOAc fraction. In addition to the highest total flavonoid content (TFC) (367.72 microg RE/mg E) and total phenolics content (TPC) (47.97 microg GAE/mg E), EtOAc showed the strongest DPPH scavenging ability (IC(50) value = 29.56 microg/mL), ABTS (+) scavenging ability (IC(50) value = 84.60 microg/mL), and ferric reducing antioxidant power (FRAP) (889.62 microg FeSO(4)/mg E), which were stronger than the positive control BHT. EtOAc also exhibited the second-best alpha-glucosidase inhibitory capacity and second-best acetylcholinesterase (AChE) inhibitory capacity with the IC(50) values of 2.85 and 3.27 mg/mL, respectively. Also, EtOAc inhibited HepG2, MCF-7, Raw264.7, and A549 cell with IC(50) values of 1.08, 1.62, 0.77, and 0.87 mg/mL, which were the second or third strongest in all fractions. Additionally, HPLC analysis revealed significant differences in the compounds' abundance between different fractions. Among them, EtOAc had the most detected compounds and the highest content. According to the results of UPLC/Q-TOF-MS, 38 compounds were identified in EtOAc, including 24 phenolic acids and 6 flavonoids. Network pharmacological analysis further confirmed 41 potential targets of EtOAc in the treatment of type 2 diabetes, and intracellular receptor signaling pathways, unsaturated fatty acid, and DNA transcription pathways were the most possible mechanisms. These findings suggested that BCF was worthwhile to be developed as an antioxidant and anti-diabetic food/drug.
ESTHER : Yin_2022_Front.Nutr_9_1018733
PubMedSearch : Yin_2022_Front.Nutr_9_1018733
PubMedID: 36313078

Title : Effects of Fatty-Type and Lean-Type on Growth Performance and Lipid Droplet Metabolism in Pekin Ducks - Zhuang_2022_Animals.(Basel)_12_
Author(s) : Zhuang Z , Yang T , Jia W , Bai M , Bai H , Wang Z , Chen G , Jiang Y , Chang G
Ref : Animals (Basel) , 12 : , 2022
Abstract : The reasons for differences in lipid depositions between fatty-type (F-T) and lean-type (L-T) ducks remain unknown. The present study aimed to compare the growth performance, lipid deposition, and gene expression related to lipid droplet formation in F-T and L-T Pekin ducks. One-day-old, 140 each L-T and F-T male ducks were selected and distributed separately into 20 replicate cages. All ducks were fed commercial diets up to 35 d of age. F-T ducks had a higher average daily gain from 21 to 28 d of age. On 35-day-old, F-T ducks had higher serum levels of high- and low-density lipoprotein cholesterol, cholesterol, albumin, and hydroxybutyrate dehydrogenase activity than L-T ducks. F-T ducks had higher abdominal fat and subcutaneous fat percentages than those in L-T ducks. Liver histological examination showed that L-T ducks contained more lipid droplets in the liver, which gradually decreased with increasing age. The average adipocyte area and diameter of abdominal fat and subcutaneous fat in the F-T and L-T ducks increased with age and were higher in F-T ducks than those in L-T ducks. Furthermore, the gene expression of perilipin 1, perilipin 2, angiopoietin-like protein 4, adipose triglyceride lipase, alpha/beta-hydrolase domain-containing protein 5 (ABHD5), and serine/threonine kinase 17a in the liver, abdominal fat, and subcutaneous fat of F-T ducks was higher than that in L-T ducks, and it increased with age. Compared to L-T ducks, F-T ducks had higher expression of ABHD5 in the abdominal fat and subcutaneous fat and lower expression in the liver. Thus, F-T ducks displayed lower hepatic lipid deposition and a higher percentage of abdominal fat and subcutaneous fat, suggesting that F-T ducks had higher lipid storage capacity due to increased gene expression related to lipid droplets.
ESTHER : Zhuang_2022_Animals.(Basel)_12_
PubMedSearch : Zhuang_2022_Animals.(Basel)_12_
PubMedID: 36077988

Title : Comprehensive Enantioselectivity Evaluation of Insecticidal Activity and Mammalian Toxicity of Fenobucarb - He_2022_J.Agric.Food.Chem__
Author(s) : He Z , Li C , Xia W , Wang Z , Li R , Zhang Y , Wang M
Ref : Journal of Agricultural and Food Chemistry , : , 2022
Abstract : To comprehensively evaluate the efficiency and risk of the chiral pesticide fenobucarb, the bioactivity, toxicity, and environmental behavior of fenobucarb (FNC) enantiomers were investigated. The results showed that R-FNC possesses 1.8-2.7 times more bioactivity than S-FNC but 1.3-3.0 times lower toxicity than S-FNC against four nontarget organisms: Chlorella pyrenoidosa, HepG2, and Danio rerio and its embryos. The corresponding enzyme inhibitory activity showed consistent results; the acetylcholinesterase inhibitory activity of target organisms was ordered as R-FNC > rac-FNC > S-FNC, while the reduction in catalase activity after exposure to R-FNC was 2.5 times that after exposure to S-FNC in zebrafish. The enantioselective bioactivity mechanism of FNC enantiomers was further explored in silico. No significant enantioselective degradation was found in soils or rat liver microsomes. In sum, R-FNC possesses higher insecticidal activity and lower toxicity. The development of R-FNC as a commercial agrochemical is beneficial for reducing pesticide inputs.
ESTHER : He_2022_J.Agric.Food.Chem__
PubMedSearch : He_2022_J.Agric.Food.Chem__
PubMedID: 35451821

Title : From tryptamine to the discovery of efficient multi-target directed ligands against cholinesterase-associated neurodegenerative disorders - Wu_2022_Front.Pharmacol_13_1036030
Author(s) : Wu J , Zhang H , Wang Y , Yin G , Li Q , Zhuo L , Chen H , Wang Z
Ref : Front Pharmacol , 13 :1036030 , 2022
Abstract : A novel class of benzyl-free and benzyl-substituted carbamylated tryptamine derivatives (CDTs) was designed and synthesized to serve as effective building blocks for the development of novel multi-target directed ligands (MTDLs) for the treatment of neurological disorders linked to cholinesterase (ChE) activity. The majority of them endowed butyrylcholinesterase (BuChE) with more substantial inhibition potency than acetylcholinesterase (AChE), according to the full study of ChE inhibition. Particularly, hybrids with dibenzyl groups (2b-2f, 2j, 2o, and 2q) showed weak or no neuronal toxicity and hepatotoxicity and single-digit nanomolar inhibitory effects against BuChE. Through molecular docking and kinetic analyses, the potential mechanism of action on BuChE was first investigated. In vitro H(2)O(2)-induced HT-22 cells assay demonstrated the favorable neuroprotective potency of 2g, 2h, 2j, 2m, 2o, and 2p. Besides, 2g, 2h, 2j, 2m, 2o, and 2p endowed good antioxidant activities and COX-2 inhibitory effects. This study suggested that this series of hybrids can be applied to treat various ChE-associated neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as promising building blocks for further structure modification to develop efficient MTDLs.
ESTHER : Wu_2022_Front.Pharmacol_13_1036030
PubMedSearch : Wu_2022_Front.Pharmacol_13_1036030
PubMedID: 36518670

Title : Tannic acid reduced apparent protein digestibility and induced oxidative stress and inflammatory response without altering growth performance and ruminal microbiota diversity of Xiangdong black goats - Wang_2022_Front.Vet.Sci_9_1004841
Author(s) : Wang Z , Yin L , Liu L , Lan X , He J , Wan F , Shen W , Tang S , Tan Z , Yang Y
Ref : Front Vet Sci , 9 :1004841 , 2022
Abstract : The present study was performed to evaluate the impacts of tannic acid (TA) supplementation at different levels on the growth performance, physiological, oxidative and immunological metrics, and ruminal microflora of Xiangdong black goats. Twenty-four goats were randomly assigned to four dietary treatments: the control (CON, basal diet), the low-dose TA group [TAL, 0.3 % of dry matter (DM)], the mid-dose TA group (TAM, 0.6 % of DM), and the high-dose TA group (TAH, 0.9 % of DM). Results showed that the growth performance was unaffected (P > 0.05) by adding TA, whilst the 0.3 % and 0.6 % TA supplementation significantly decreased (P < 0.05) the apparent digestibility of crude protein (CP) and ruminal NH(3)-N concentration, and raised (P < 0.05) the level of total volatile fatty acid (TVFA) in rumen. The increments of alanine aminotransferase (ALT), triglyceride (TG), cortisol (CORT), total antioxidant capacity (T-AOC), interleukin (IL)-1beta, IL-6, and serumamyloid A (SAA), and decrements of globulin (GLB), immunoglobulin G (IgG), cholinesterase (CHE), glutathione reductase (GR), creatinine (CRE), growth hormone (GH), high-density lipoprotein cholesterol (HDLC), and insulin-like growth factor 1 (IGF-1) to different extents by TA addition were observed. Although the Alpha and Beta diversity of rumen bacterial community remained unchanged by supplementing TA, the relative abundance of the predominant genus Prevotella_1 was significantly enriched (P < 0.05) in TAL. It could hence be concluded that the TA supplementation in the present trial generally decreased CP digestion and caused oxidative stress and inflammatory response without influencing growth performance and ruminal microbiota diversity. More research is needed to explore the premium dosage and mechanisms of effects for TA addition in the diet of goats.
ESTHER : Wang_2022_Front.Vet.Sci_9_1004841
PubMedSearch : Wang_2022_Front.Vet.Sci_9_1004841
PubMedID: 36187804

Title : Carbamate-based N-Substituted tryptamine derivatives as novel pleiotropic molecules for Alzheimer's disease - Zhang_2022_Bioorg.Chem_125_105844
Author(s) : Zhang H , Wang Y , Liu D , Li J , Feng Y , Lu Y , Yin G , Li Z , Shi T , Wang Z
Ref : Bioorg Chem , 125 :105844 , 2022
Abstract : A novel series of carbamate-based N-substituted tryptamine derivatives were designed and synthesized based on functional group combination strategy, and possessed both cholinesterase inhibition and neuroprotective effects. After systematically evaluating the cholinesterase inhibitory activity of 24 synthesized compounds, compound 6H6, bearing n-heptyl residue as carbamate moiety, was highlighted due to its great BChE-selective inhibition (eeAChE IC(50) > 100 microM; eqBChE IC(50) = 7 nM), neuronal protection, antioxidation and anti-neuroinflammation efficacy. Cytotoxicity and acute toxicity assays confirmed the safety-efficacy profiles of compound 6H6. Besides, pharmacokinetic properties and blood-brain barrier (BBB) permeability of compound 6H6 were favorable and suitable for further study in vivo. The behavioral tests revealed that compound 6H6 could remarkably improve the scop-induced ethological changes and memory impairment, suggesting compound 6H6, as an attractive pleiotropic molecule, had great promise in treating Alzheimer's disease.
ESTHER : Zhang_2022_Bioorg.Chem_125_105844
PubMedSearch : Zhang_2022_Bioorg.Chem_125_105844
PubMedID: 35594720

Title : Discovery of carbamate-based N-salicyloyl tryptamine derivatives as novel pleiotropic agents for the treatment of Alzheimer's disease - Wang_2022_Bioorg.Chem_127_105993
Author(s) : Wang Y , Zhang H , Liu D , Li X , Long L , Peng Y , Qi F , Jiang W , Wang Z
Ref : Bioorg Chem , 127 :105993 , 2022
Abstract : In this work, based on the potential anti-AD molecule previously studied by our group, we continue to introduce different substituents at different positions to improve both drug-like properties and on target activities. 33 N-salicyloyl tryptamine-carbamate hybrids were designed, synthesized and evaluated as cholinesterase inhibitors. H327 was the most potent BChE inhibitor (eqBChE IC(50) = 0.057 +/- 0.005 microM), and showed threefold improved inhibitory potency than the positive drug rivastigmine (eqBChE IC(50) = 0.19 +/- 0.001 microM). In addition, H327 as a pseudo-irreversible BChE inhibitor was endowed with neuroprotective, antioxidative and anti-neuroinflammatory properties. Cytotoxicity and acute toxicity tests confirmed the safety of compound H327. The pharmacokinetics study showed that compound H327 had a longer T(1/2) time and higher bioavailability than the lead compound 1 g. Compound H327 was able to cross the blood-brain barrier (BBB) in vivo. Moreover, the behavioral tests showed that compound H327 could significantly improve scopolamine-induced cognitive impairment in vivo. Overall, these results demonstrated that compound H327 is a promising multi-target agent for the treatment of AD.
ESTHER : Wang_2022_Bioorg.Chem_127_105993
PubMedSearch : Wang_2022_Bioorg.Chem_127_105993
PubMedID: 35834980

Title : Design, synthesis, and biological evaluation of carbamate derivatives of N-salicyloyl tryptamine as multifunctional agents for the treatment of Alzheimer's disease - Liu_2022_Eur.J.Med.Chem_229_114044
Author(s) : Liu D , Zhang H , Wang Y , Liu W , Yin G , Wang D , Li J , Shi T , Wang Z
Ref : Eur Journal of Medicinal Chemistry , 229 :114044 , 2022
Abstract : In this study, we designed, synthesized, and evaluated a series of carbamate derivatives of N-salicyloyl tryptamine as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). After screening the acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitory activities, target compound 1g stood out as a mixed type reversible dual inhibitor of AChE and BChE. In addition, molecular docking studies were conducted to explore the actions on AChE and BChE. The results showed that 1g could decrease the level of pro-inflammatory cytokines NO, iNOS, IL-6, TNF-alpha, and ROS, increase the level of anti-inflammatory cytokines IL-4, and inhibit the aggregation of Abeta(1-42). Moreover, the administration of 1g suppressed the activity of AChE in the brain. In a word, the compound 1g is effective for improving learning and memory behavior, blood-brain barrier permeation, pharmacokinetics, ChE inhibition, and anti-neuroinflammation. It may be considered as a promising multi-functional therapeutic agent for further investigation for the treatment of AD.
ESTHER : Liu_2022_Eur.J.Med.Chem_229_114044
PubMedSearch : Liu_2022_Eur.J.Med.Chem_229_114044
PubMedID: 34923430

Title : Enantioselective Metabolic Mechanism and Metabolism Pathway of Pydiflumetofen in Rat Liver Microsomes: In Vitro and In Silico Study - Wang_2022_J.Agric.Food.Chem_70_2520
Author(s) : Wang Z , Li R , Wu Q , Duan J , Tan Y , Sun X , Chen R , Shi H , Wang M
Ref : Journal of Agricultural and Food Chemistry , 70 :2520 , 2022
Abstract : Pydiflumetofen (PYD) has been used worldwide. However, the enantioselective fate of PYD within mammals is not clear. Thus, the enantioselective metabolism and its potential mechanisms of PYD were explored via in vitro and in silico. Consistent results were observed between metabolism and enzyme kinetics experiments, with S-PYD metabolizing faster than R-PYD in rat liver microsomes. Moreover, CYP3A1 and carboxylesterase 1 were found to be major enzymes participating in the metabolism of PYD. Based on the computational results, S-PYD bound with CYP3A1 and carboxylesterase 1 more tightly with lower binding free energy than R-PYD, explaining the mechanism of enantioselective metabolism. Nine phase I metabolites of PYD were identified, and metabolic pathways of PYD were speculated. This study is the first to clarify the metabolism of PYD in mammals, and further research to evaluate the toxicological implications of these metabolites will help in assessing the risk of PYD.
ESTHER : Wang_2022_J.Agric.Food.Chem_70_2520
PubMedSearch : Wang_2022_J.Agric.Food.Chem_70_2520
PubMedID: 35184556

Title : Ferulic acid regulates miR-17\/PTEN axis to inhibit LPS-induced pulmonary microvascular endothelial cells apoptosis through activation of PI3K\/Akt pathway - Zhang_2022_J.Toxicol.Sci_47_61
Author(s) : Zhang Q , Wang Z , Zhu J , Peng Z , Tang C
Ref : Journal of Toxicological Sciences , 47 :61 , 2022
Abstract : Acute lung injury (ALI) is mainly mediated by the damage of pulmonary microvascular endothelial cells (PMVECs). LPS is one of the pathogenic factors leading to microcirculatory abnormalities of ALI. Ferulic acid (FA) exhibits therapeutic eects against various diseases. During lipopolysaccharide-induced acute respiratory distress syndrome, FA, when given beforehand, could depress inflammation and oxidative stress. However, the concrete role and underlying mechanism of FA in ALI have not been well characterized. Ten microg/mL Lipopolysaccharide (LPS) was used to treat rat PMVECs for 24 hr. qRT-PCR was used to detect the level of miR-17 and phosphatase and tensin homolog deleted on chromosome ten (PTEN). Western blot was used to analyze the associated proteins in the PI3K/Akt pathway, and the apoptosis-related proteins. Flow cytometric analysis was performed to detect the apoptosis of PMVECs. MTT assay was constructed to detect the cell viability. Luciferase assay was conducted to detect the target gene of miR-17 and PTEN. A cell model for in vitro studying the role of FA in ALI was established using PMVECs. Our data demonstrate that FA up-regulates miR-17 and declines apoptosis induced by LPS. FA inhibits apoptosis mediated by up-regulating miR-17. Furthermore, we found miR-17 targeted PTEN negatively. FA inhibits cleaved caspase-3 and Bax expression through the PI3K/Akt pathway mediated by up-regulating miR-17. Over-expression of PTEN could contribute to the similar expression trend of the PI3K/Akt signal pathway protein compared to miR-17 inhibitor transfected cells. FA inhibits PMVECs apoptosis induced by LPS via miR-17/PTEN to further regulate the activation of the PI3K/Akt pathway in ALI. We anticipate that our data will provoke additional studies for ALI clinical therapy.
ESTHER : Zhang_2022_J.Toxicol.Sci_47_61
PubMedSearch : Zhang_2022_J.Toxicol.Sci_47_61
PubMedID: 35110471

Title : Biodegradation of polyester polyurethane by the marine fungus Cladosporium halotolerans 6UPA1 - Zhang_2022_J.Hazard.Mater_437_129406
Author(s) : Zhang K , Hu J , Yang S , Xu W , Wang Z , Zhuang P , Grossart HP , Luo Z
Ref : J Hazard Mater , 437 :129406 , 2022
Abstract : Lack of degradability and the accumulation of polymeric wastes increase the risk for the health of the environment. Recently, recycling of polymeric waste materials becomes increasingly important as raw materials for polymer synthesis are in short supply due to the rise in price and supply chain disruptions. As an important polymer, polyurethane (PU) is widely used in modern life, therefore, PU biodegradation is desirable to avoid its accumulation in the environment. In this study, we isolated a fungal strain Cladosporium halotolerans from the deep sea which can grow in mineral medium with a polyester PU (Impranil DLN) as a sole carbon source. Further, we demonstrate that it can degrade up to 80% of Impranil PU after 3 days of incubation at 28 degC by breaking the carbonyl groups (1732 cm(-1)) and C-N-H bonds (1532 cm(-1) and 1247 cm(-1)) as confirmed by Fourier-transform infrared (FTIR) spectroscopy analysis. Gas chromatography-mass spectrometry (GC-MS) analysis revealed polyols and alkanes as PU degradation intermediates, indicating the hydrolysis of ester and urethane bonds. Esterase and urease activities were detected in 7 days-old cultures with PU as a carbon source. Transcriptome analysis showed a number of extracellular protein genes coding for enzymes such as cutinase, lipase, peroxidase and hydrophobic surface binding proteins A (HsbA) were expressed when cultivated on Impranil PU. The yeast two-hybrid assay revealed that the hydrophobic surface binding protein ChHsbA1 directly interacts with inducible esterases, ChLip1 (lipase) and ChCut1 (cutinase). Further, the KEGG pathway for "fatty acid degradation" was significantly enriched in Impranil PU inducible genes, indicating that the fungus may use the degradation intermediates to generate energy via this pathway. Taken together, our data indicates secretion of both esterase and hydrophobic surface binding proteins by C. halotolerans plays an important role in Impranil PU absorption and subsequent degradation. Our study provides a mechanistic insight into Impranil PU biodegradation by deep sea fungi and provides the basis for future development of biotechnological PU recycling.
ESTHER : Zhang_2022_J.Hazard.Mater_437_129406
PubMedSearch : Zhang_2022_J.Hazard.Mater_437_129406
PubMedID: 35753302

Title : Recent advance on pleiotropic cholinesterase inhibitors bearing amyloid modulation efficacy - Zhang_2022_Eur.J.Med.Chem_242_114695
Author(s) : Zhang H , Peng Y , Zhuo L , Wang Y , Zeng G , Wang S , Long L , Li X , Wang Z
Ref : Eur Journal of Medicinal Chemistry , 242 :114695 , 2022
Abstract : Due to the hugely important roles of neurotransmitter acetylcholine (ACh) and amyloid-beta (Abeta) in the pathogenesis of Alzheimer's disease (AD), the development of multi-target directed ligands (MTDLs) focused on cholinesterase (ChE) and Abeta becomes one of the most attractive strategies for combating AD. To date, numerous preclinical studies toward multifunctional conjugates bearing ChE inhibition and anti-Abeta aggregation have been reported. Noteworthily, most of the reported multifunctional cholinesterase inhibitors are carbamate-based compounds due to the initial properties of carbamate moiety. However, because their easy hydrolysis in vivo and the instability of the compound-enzyme conjugate, the mechanism of action of these compounds is rare. Thus, non-carbamate compounds are of great need for developing novel cholinesterase inhibitors. Besides, given that Abeta accumulation begins to occur 10-15 years before AD onset, modulating Abeta is ineffective only in inhibiting its aggregation but not eliminate the already accumulated Abeta if treatment is started when the patient has been diagnosed as AD. Considering the limitation of current Abeta accumulation modulators in ameliorating cognitive deficits and ineffectiveness of ChE inhibitors in blocking disease progression, the development of a practically valuable strategy with multiple pharmaceutical properties including ChE inhibition and Abeta modulation for treating AD is indispensable. In this review, we focus on summarizing the scaffold characteristics of reported non-carbamate cholinesterase inhibitors with Abeta modulation since 2020, and understanding the ingenious multifunctional drug design ideas to accelerate the pace of obtaining more efficient anti-AD drugs in the future.
ESTHER : Zhang_2022_Eur.J.Med.Chem_242_114695
PubMedSearch : Zhang_2022_Eur.J.Med.Chem_242_114695
PubMedID: 36044812

Title : Point-of-care testing of butyrylcholinesterase activity through modulating the photothermal effect of cuprous oxide nanoparticles - Ma_2021_Mikrochim.Acta_188_392
Author(s) : Ma J , Ma L , Cao L , Miao Y , Dong J , Shi YE , Wang Z
Ref : Mikrochim Acta , 188 :392 , 2021
Abstract : Butyrylcholinesterase (BChE) is an important indicator for clinical diagnosis of liver dysfunction, organophosphate toxicity, and poststroke dementia. Point-of-care testing (POCT) of BChE activity is still a challenge, which is a critical requirement for the modern clinical diagnose. A portable photothermal BChE assay is proposed through modulating the photothermal effects of Cu(2)O nanoparticles. BChE can catalyze the decomposition of butyrylcholine, producing thiocholine, which further reduce and coordinate with CuO on surface of Cu(2)O nanoparticle. This leads to higher efficiency of formation of Cu(9)S(8) nanoparticles, through the reaction between Cu(2)O nanoparticle and NaHS, together with the promotion of photothermal conversion efficiency from 3.1 to 59.0%, under the excitation of 1064 nm laser radiation. An excellent linear relationship between the temperature change and the logarithm of BChE concentration is obtained in the range 1.0 to 7.5 U/mL, with a limit of detection of 0.076 U/mL. In addition, the portable photothermal assay shows strong detection robustness, which endows the accurate detection of BChE in human serum, together with the screening and quantification of organophosphorus pesticides. Such a simple, sensitive, and robust assay shows great potential for the applications to clinical BChE detection and brings a new horizon for the development of temperature based POCT.
ESTHER : Ma_2021_Mikrochim.Acta_188_392
PubMedSearch : Ma_2021_Mikrochim.Acta_188_392
PubMedID: 34697648

Title : Acetylcholinesterase inhibition with Pyridostigmine attenuates hypertension and neuroinflammation in the paraventricular nucleus in rat model for Preeclampsia - Issotina_2021_Int.Immunopharmacol__108365
Author(s) : Issotina Zibrila A , Li Y , Wang Z , Zhao G , Liu H , Leng J , Ahasan Ali M , Ampofo Osei J , Kang YM , Liu J
Ref : Int Immunopharmacol , :108365 , 2021
Abstract : Preeclampsia (PE) is characterized by hypertension, autonomic imbalance and inflammation. The subfornical organ (SFO) reportedly relays peripheral inflammatory mediator's signals to the paraventricular nucleus (PVN), a brain autonomic center shown to mediate hypertension in hypertensive rat but not yet in PE rat models. Additionally, we previously showed that Pyridostigmine (PYR), an acetylcholinesterase inhibitor, attenuated placental inflammation and hypertension in PE models. In this study, we investigated the effect of PYR on the activities of these brain regions in PE model. PYR (20 mg/kg/day) was administered to reduced uterine perfusion pressure (RUPP) Sprague-Dawley rat from gestational day (GD) 14 to GD19. On GD19, the mean arterial pressure (MAP) was recorded and samples were collected for analysis. RUPP rats exhibited increased MAP (P = 0.0025), elevated circulating tumor necrosis factor-alpha (TNF-alpha, P = 0.0075), reduced baroreflex sensitivity (BRS), increased neuroinflammatory markers including TNF-alpha, interleukin-1beta (IL-1beta), microglial activation (P = 0.0039), oxidative stress and neuronal excitation within the PVN and the SFO. Changes in MAP, in molecular and cellular expression induced by RUPP intervention were improved by PYR. The ability of PYR to attenuate TNF-alpha mediated central effect was evaluated in TNF-alpha-infused pregnant rats. TNF-alpha infusion-promoted neuroinflammation in the PVN and SFO in dams was abolished by PYR. Collectively, our data suggest that PYR improves PE-like symptoms in rat by dampening placental ischemia and TNF-alpha-promoted inflammation and pro-hypertensive activity in the PVN. This broadens the therapeutical potential of PYR in PE.
ESTHER : Issotina_2021_Int.Immunopharmacol__108365
PubMedSearch : Issotina_2021_Int.Immunopharmacol__108365
PubMedID: 34815190

Title : Ultrasensitive detection of butyrylcholinesterase activity based on self-polymerization modulated fluorescence of sulfur quantum dots - Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
Author(s) : Chen M , Zhang J , Chang J , Li H , Zhai Y , Wang Z
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 269 :120756 , 2021
Abstract : Butyrylcholinesterase (BChE) is an important clinical diagnosing index for liver dysfunction and organophosphate toxicity. However, the current assays for BChE activity are suffering from the relative poor detection sensitivity. In this work, an ultrasensitive fluorescence assay for BChE activity was developed based on the self-polymerization modulated fluorescence of sulfur quantum dots (S-dots). The luminescence of S-dots can be quenched by the self-polymerized dopamine. The hydrolysate of substrates, thiocholine, under the catalysis of BChE can reduce dopamine, which results in the inhibition of self-polymerization and the fluorescence recovery of S-dots. BChE can be quantitatively detected by recording the recovered fluorescence of S-dots, and a linear relationship is observed between the ratio of fluorescence and the concentration of BChE in the range from 0.01 to 10 U/L. A limit of detection as low as 0.0069 U/L calculated, which is the lowest number so far. The assay also shows excellent selectivity towards various interference species and acetylcholinesterase. These features allowed the direct detection of BChE activity in human serum, demonstrating the great practical applications of our assay.
ESTHER : Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
PubMedSearch : Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
PubMedID: 34952437

Title : The impact of ABCB1 and CES1 polymorphisms on dabigatran pharmacokinetics and pharmacodynamics in patients with atrial fibrillation - Ji_2021_Br.J.Clin.Pharmacol_87_2247
Author(s) : Ji Q , Zhang C , Xu Q , Wang Z , Li X , Lv Q
Ref : British Journal of Clinical Pharmacology , 87 :2247 , 2021
Abstract : AIMS: Our study aimed to determine the impact of genetic polymorphisms of ABCB1 and CES1 on the pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran in patients with nonvalvular atrial fibrillation (NVAF). METHODS: We conducted a prospective study and enrolled NVAF patients treated with dabigatran. Blood samples were obtained from each patient and used for genotyping and determination of plasma dabigatran concentration (PDC) and coagulation parameters including activated partial thromboplastin time (APTT) and thrombin time. Patients' demographics and clinical outcomes from scheduled follow-up visits were all recorded. Statistical analysis was performed to identify the impact of genetic polymorphisms on the PK/PD and bleeding risk of dabigatran. RESULTS: A total of 198 patients were included in analysis. For the ABCB1 polymorphisms rs4148738 and rs1045642, no significant association was found with dabigatran PK/PD. For the CES1 polymorphism rs8192935, the minor allele(C) was associated with increased trough PDCs (ANOVA: P < .001; CC vs. TT genotype, P < .001; CT vs. TT genotype, P = .014) and with APTT values at trough level (P = .015). For the CES1 polymorphism rs2244613, the minor allele(A) carriers had higher levels of trough PDC than noncarriers (ANOVA: P < .001; AA vs. CC genotype, P < .001; CA vs. CC genotype, P = .004) and increased risk for minor bleeding (P = .034; odds ratio = 2.71, 95% confidence interval 1.05-7.00). CONCLUSION: Our study indicated that the minor allele(C) on the CES1 SNP rs8192935 was associated with PDCs and APTT values at trough level. The minor allele(A) on the CES1 SNP rs2244613 was associated with increased trough PDCs and higher risk for minor bleeding in NVAF patients treated with dabigatran.
ESTHER : Ji_2021_Br.J.Clin.Pharmacol_87_2247
PubMedSearch : Ji_2021_Br.J.Clin.Pharmacol_87_2247
PubMedID: 33179295

Title : The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model - Wang_2021_Am.J.Sports.Med__363546520988680
Author(s) : Wang Z , Chen Y , Xiao H , Li S , Zhang T , Hu J , Lu H , Xie H
Ref : Am J Sports Med , :363546520988680 , 2021
Abstract : BACKGROUND: How to improve rotator cuff healing remains a challenge. Little is known about the effect of the parasympathetic transmitter acetylcholine (ACh) and the acetylcholinesterase inhibitor pyridostigmine (PYR), both of which have anti-inflammatory properties, in the healing process of rotator cuff injury. HYPOTHESIS: ACh and PYR could enhance bone-tendon interface healing in a murine model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 160 C57BL/6 mice underwent unilateral rotator cuff repair surgery. Fibrin gel (FG) was used as a drug carrier. The mice were randomly assigned to 4 groups with 40 mice per group: FG group (received FG alone), 10(-5) M ACh group (received FG containing 10(-5) M ACh), 10(-6) M ACh group (received FG containing 10(-6) M ACh), and PYR group (received FG containing 25 microg of PYR). Ten mice in each group were euthanized at 2, 4, 8, and 12 weeks postoperatively. Histologic, immunohistochemical, and biomechanical evaluations were performed for analysis. RESULTS: Histologically, fibrocartilage-like tissue was shown at the repaired site. The proteoglycan content of the 10(-5) M ACh group was significantly increased compared with the FG group at 4 weeks. M2 macrophages were identified at the repaired site for all groups at 2 and 4 weeks. At 8 weeks, M2 macrophages withdrew back to the tendon in the FG group, but a number of M2 macrophages were retained at the repaired sites in the ACh and PYR groups. Biomechanically, failure load and stiffness of the ACh and PYR groups were significantly higher than those of the FG group at 4 weeks. The stiffness of the ACh and PYR groups was significantly increased compared with the FG group at 8 weeks (P < .001 for all). At 12 weeks, most of the healing properties of the ACh and PYR groups were not significantly different compared with the FG group. CONCLUSION: ACh and PYR enhanced the early stage of bone-tendon insertion healing after rotator cuff repair. CLINICAL RELEVANCE: These findings imply that ACh and PYR could serve as potential therapeutic strategies for rotator cuff healing.
ESTHER : Wang_2021_Am.J.Sports.Med__363546520988680
PubMedSearch : Wang_2021_Am.J.Sports.Med__363546520988680
PubMedID: 33592162

Title : A novel lipase from Aspergillus oryzae WZ007 catalyzed synthesis of brivaracetam intermediate and its enzymatic characterization - Li_2021_Chirality_33_62
Author(s) : Li Q , Zhang M , Li X , Zhang Y , Wang Z , Zheng J
Ref : Chirality , 33 :62 , 2021
Abstract : Brivaracetam is a structural derivative of the chiral drug levetiracetam and has been approved for the adjuvant treatment of partial epilepsy. As a new antiepileptic drug, it is widely used in a variety of epilepsy models. In this study, a novel lipase M16 derived from Aspergillus oryzae WZ007 was cloned, expressed, and used for chiral resolution. Lipase M16 has a high enantioselectivity to the racemic substrate (R,S)-methyl 2-propylsuccinate 4-tert-butyl ester, and the intermediate (R)-2-propylsuccinic acid 4-tert-butyl ester of brivaracetam was obtained efficiently. Under optimal conditions, the enantiomeric excess of substrate was up to 99.26%, and the e.e.(p) was 96.23%. The conversion and apparent E value were 50.63% and 342.48, respectively. This study suggests a new biocatalytic resolution via lipase M16 for preparing the brivaracetam chiral intermediate and its potential application in the pharmaceutical industry.
ESTHER : Li_2021_Chirality_33_62
PubMedSearch : Li_2021_Chirality_33_62
PubMedID: 33274501

Title : Rapid screening for natural lipase inhibitors from Alisma orientale combining high-performance thin-layer chromatography-bioautography with mass spectrometry - Yang_2021_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1170_122599
Author(s) : Yang F , Gu L , Han Z , Wang Z
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 1170 :122599 , 2021
Abstract : Lipase inhibitors are an attractive class of hypolipidemic compounds, which inhibit the activity of human pancreatic lipase, thereby preventing the absorption of triglycerides in vivo. As a library of promising lead compounds for drug development, traditional Chinese medicine (TCM) has gained growing attention in quick discovery and identification of enzyme inhibitors of natural-origin. The purpose of this work was to discover unknown lipase inhibitors from Alisma orientale by the activity oriented analysis method thin-layer chromatography-bioautography, then use electrospray ionization mass spectrometry technology via the elution based TLC-MS interface to identify their structures. As a result, eleven natural lipase inhibitors from Alisma orientale extracts were identified based on molecular mass and fragment ions obtained by HPTLC-MS, and further confirmed by a series of complementary means including UV spectra, (1)H NMR characteristic proton signals and polarity of compounds, eleven lipase inhibitors were tentatively assigned as triterpenoids: alisol B (m/z 495.50 [M + Na](+)), alisol B 23-acetate (m/z 537.58 [M + Na](+)), 11-deoxy-alisol B (m/z 479.50 [M + Na](+)), 11-deoxy-alisol B 23-acetate (m/z 521.50 [M + Na](+)), alisol A/epialisol A (m/z 513.50 [M + Na](+)), 16-oxo-11-deoxy-alisol A (m/z 511.50 [M + Na](+)), 16-oxo-alisol A (527.50 [M + Na] (+)), alisol C (m/z 509.58 [M + Na](+)), alisol C 23-acetate (m/z 551.50 [M + Na](+)), alisol M 23-acetate (m/z 567.50 [M + Na](+)), and alismanol Q/neoalisol (m/z 493.42 [M + Na](+)). The integrated approach is an efficient method for rapid screening lipase inhibitors from complex plant extracts and provides a reasonable and favorable basis for the identification and separation of other enzymatic system and other important compounds with therapeutic values.
ESTHER : Yang_2021_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1170_122599
PubMedSearch : Yang_2021_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1170_122599
PubMedID: 33713950

Title : Phytochemical Composition, Antioxidant Activity, and Enzyme Inhibitory Activities (alpha-Glucosidase, Xanthine Oxidase, and Acetylcholinesterase) of Musella lasiocarpa - Li_2021_Molecules_26_
Author(s) : Li R , Ru Y , Wang Z , He X , Kong KW , Zheng T , Zhang X
Ref : Molecules , 26 : , 2021
Abstract : In this study, we aimed to investigate the chemical components and biological activities of Musella lasiocarpa, a special flower that is edible and has functional properties. The crude methanol extract and its four fractions (petroleum ether, ethyl acetate, n-butanol, and aqueous fractions) were tested for their total antioxidant capacity, followed by their alpha-glucosidase, acetylcholinesterase, and xanthine oxidase inhibitory activities. Among the samples, the highest total phenolic and total flavonoid contents were found in the ethyl acetate (EtOAc) fraction (224.99 mg GAE/g DE) and crude methanol extract (187.81 mg QE/g DE), respectively. The EtOAc fraction of Musella lasiocarpa exhibited the strongest DPPH. scavenging ability, ABTS.(+) scavenging ability, and alpha-glucosidase inhibitory activity with the IC(50) values of 22.17, 12.10, and 125.66 microg/mL, respectively. The EtOAc fraction also showed the strongest ferric reducing antioxidant power (1513.89 mg FeSO(4)/g DE) and oxygen radical absorbance capacity ability (524.11 mg Trolox/g DE), which were higher than those of the control BHT. In contrast, the aqueous fraction demonstrated the highest acetylcholinesterase inhibitory activity (IC(50) = 10.11 microg/mL), and the best xanthine oxidase inhibitory ability (IC(50) = 5.23 microg/mL) was observed from the crude methanol extract as compared with allopurinol (24.85 microg/mL). The HPLC-MS/MS and GC-MS analyses further revealed an impressive arsenal of compounds, including phenolic acids, fatty acids, esters, terpenoids, and flavonoids, in the most biologically active EtOAc fraction. Taken together, this is the first report indicating the potential of Musella lasiocarpa as an excellent natural source of antioxidants with possible therapeutic, nutraceutical, and functional food applications.
ESTHER : Li_2021_Molecules_26_
PubMedSearch : Li_2021_Molecules_26_
PubMedID: 34361630

Title : Yeast cell surface display of bacterial PET hydrolase as a sustainable biocatalyst for the degradation of polyethylene terephthalate - Chen_2021_Methods.Enzymol_648_457
Author(s) : Chen Z , Xiao Y , Weber G , Wei R , Wang Z
Ref : Methods Enzymol , 648 :457 , 2021
Abstract : Enzymatic hydrolysis of polyethylene terephthalate (PET) is considered to be an environmentally friendly method for the recycling of plastic waste. Recently, a bacterial enzyme named IsPETase was found in Ideonella sakaiensis with the ability to degrade amorphous PET at ambient temperature suggesting its possible use in recycling of PET. However, applying the purified IsPETase in large-scale PET recycling has limitations, i.e., a complicated production process, high cost of single-use, and instability of the enzyme. Yeast cell surface display has proven to be an effectual alternative for improving enzyme degradation efficiency and realizing industrial applications. This chapter deals with the construction and application of a whole-cell biocatalyst by displaying IsPETase on the surface of yeast (Pichia pastoris) cells.
ESTHER : Chen_2021_Methods.Enzymol_648_457
PubMedSearch : Chen_2021_Methods.Enzymol_648_457
PubMedID: 33579416
Gene_locus related to this paper: idesa-peth

Title : Molecular response uncovers neurotoxicity of Pardosa pseudoannulata exposed to cadmium pressure - Lv_2021_Environ.Pollut_280_117000
Author(s) : Lv B , Wang J , He Y , Zeng Z , Tang YE , Li N , Chen LJ , Wang Z , Song QS
Ref : Environ Pollut , 280 :117000 , 2021
Abstract : Cadmium (Cd) is a widely distributed heavy metal in south of China. Growing evidence indicates that systemic exposure to Cd, particularly the long-term exposure, may cause neurotoxic effects. Nevertheless, mechanisms underlying Cd neurotoxicity remain not completely understood. In this report, we investigated the neural alterations in the spider Pardosa pseudoannulata (Bosenberg and Strand, 1906) exposed to long-term Cd (LCd) and short-term Cd (SCd) pressure. Cd stress lowered foraging ability and prey consuming time in the spiders. In addition, enzymatic analysis results indicated that Cd exposure reduced the level of acetylcholinesterase at subcellular level. We then identified differentially expressed genes (DEGs) in the Cd exposed spiders using pairwise comparisons and found that a large number of DEGs were related to neurotransmitter receptors and ion transport and binding proteins. Notably, LCd exposure harbored more altered genes in ion transporter activity comparing with SCd exposure. From six K-means clusters, 53 putative transcriptional factors (TFs) belonging to 21 families were characterized, and ZBTB subfamily displayed the most distinctive alterations in the characterized genes, which is assumed to play a key role in the regulation of ion transmembrane process under Cd stress. A protein-to-protein interaction network constructed by the yielded DEGs also showed that ion and receptor binding activities were affected under long-term Cd exposure. Four key modules from the network indicated that Cd may further down-regulate energy metabolism pathway in spiders. Collectively, this comprehensive analysis provides multi-dimensional insights to understand the molecular response of spiders to Cd exposure.
ESTHER : Lv_2021_Environ.Pollut_280_117000
PubMedSearch : Lv_2021_Environ.Pollut_280_117000
PubMedID: 33784568

Title : Ratiometric sensing of butyrylcholinesterase activity based on the MnO(2) nanosheet-modulated fluorescence of sulfur quantum dots and o-phenylenediamine - Ma_2021_Mikrochim.Acta_188_294
Author(s) : Ma Z , Li P , Jiao M , Shi YE , Zhai Y , Wang Z
Ref : Mikrochim Acta , 188 :294 , 2021
Abstract : Butyrylcholinesterase (BChE) can modulate the expression level of cholinesterase, which emerges as an important clinical diagnose index. However, the currently reported assays for BChE are suffering from the problem of interferences. A ratiometric fluorescence assay was developed based on the MnO(2) nanosheet (NS)-modulated fluorescence of sulfur quantum dots (S-dots) and o-phenylenediamine (OPD). MnO(2) NS can not only quench the fluorescence of blue emissive S-dots, but also enhance the yellow emissive OPD by catalyzing its oxidation reactions. Upon introducing BChE and substrate into the system, their hydrolysate can reduce MnO(2) into Mn(2+), leading to the fluorescence recovery of S-dots and failure of OPD oxidation. BChE activity can be quantitatively detected by recording the change of fluorescence signals in the blue and yellow regions. A linear relationship is observed between the ratio of F(435)/F(560) and the concentration of BChE in the range 30 to 500 U/L, and a limit of detection of 17.8 U/L has been calculated. The ratiometric fluorescence assay shows an excellent selectivity to acetylcholinesterase and tolerance to various other species. The method developed provides good detection performances in human serum medium and for screening of inhibitors.
ESTHER : Ma_2021_Mikrochim.Acta_188_294
PubMedSearch : Ma_2021_Mikrochim.Acta_188_294
PubMedID: 34363549

Title : Improved methanol tolerance of Rhizomucor miehei lipase based on Nglycosylation within the alpha-helix region and its application in biodiesel production - Tian_2021_Biotechnol.Biofuels_14_237
Author(s) : Tian M , Yang L , Wang Z , Lv P , Fu J , Miao C , Li M , Liu T , Luo W
Ref : Biotechnol Biofuels , 14 :237 , 2021
Abstract : BACKGROUND: Liquid lipases are widely used to convert oil into biodiesel. Methanol-resistant lipases with high catalytic activity are the first choice for practical production. Rhizomucor miehei lipase (RML) is a single-chain alpha/beta-type protein that is widely used in biodiesel preparation. Improving the catalytic activity and methanol tolerance of RML is necessary to realise the industrial production of biodiesel. RESULTS: In this study, a semi-rational design method was used to optimise the catalytic activity and methanol tolerance of ProRML. After N-glycosylation modification of the alpha-helix of the mature peptide in ProRML, the resulting mutants N218, N93, N115, N260, and N183 increased enzyme activity by 66.81, 13.54, 10.33, 3.69, and 2.39 times than that of WT, respectively. The residual activities of N218 and N260 were 88.78% and 86.08% after incubation in 50% methanol for 2.5 h, respectively. In addition, the biodiesel yield of all mutants was improved when methanol was added once and reacted for 24 h with colza oil as the raw material. N260 and N218 increased the biodiesel yield from 9.49% to 88.75% and 90.46%, respectively. CONCLUSIONS: These results indicate that optimising N-glycosylation modification in the alpha-helix structure is an effective strategy for improving the performance of ProRML. This study provides an effective approach to improve the design of the enzyme and the properties of lipase mutants, thereby rendering them suitable for industrial biomass conversion.
ESTHER : Tian_2021_Biotechnol.Biofuels_14_237
PubMedSearch : Tian_2021_Biotechnol.Biofuels_14_237
PubMedID: 34911574

Title : Transesterification of Indazole-3-Carboxamide Synthetic Cannabinoids: Identification of Metabolite Biomarker for Diagnosing Co-Abuse of 5F-MDMB-PINACA and Alcohol - Wang_2021_J.Anal.Toxicol__
Author(s) : Wang Z , Fong CY , Goh EML , Moy HY , Chan ECY
Ref : J Anal Toxicol , : , 2021
Abstract : Concurrent use of alcohol with synthetic cannabinoids (SCs) has been widely recorded among drug abusers. The susceptibilities of three indazole-3-carboxamide type SCs with methyl ester moiety, 5F-MDMB-PINACA, 5F-MMB-PINACA and MMB-FUBINACA, to transesterification in the presence of ethanol warranted further investigation in view of probable augmented toxicity. In vitro metabolite identification experiments were firstly performed using human liver microsomes (HLM) to characterize the novel metabolites of the three parent SCs in the presence of ethanol. Formation of transesterified metabolite, hydrolyzed metabolite and several oxidative metabolites in HLM in the presence of alcohol were further determined for each parent SC and the respective ethyl ester analogue, 5F-EDMB-PINACA, 5F-EMB-PINACA and EMB-FUBINACA, to quantitatively elucidate transesterification and hydrolysis activities. Our results suggested that all three SCs undergo carboxylesterase-mediated transesterification to their respective ethyl ester analogue in the presence of ethanol, which was incubation time- and ethanol concentration-dependent. Each ethyl ester metabolite was sequentially and readily metabolized to novel oxidative metabolites with the intact ethyl ester moiety and the same hydrolyzed metabolite as derived from its parent SC. A smaller extent of transesterification was non-enzymatically driven. Notably, we proposed 5F-EDMB-PINACA oxidative defluorination metabolite as the biomarker for diagnosing the potential co-abuse of 5F-MDMB-PINACA and alcohol. Due to the comparable pharmacological activities between each SC and its ethyl ester metabolite, augmented toxicity associated with co-abuse of SCs and alcohol is probable and deserves further investigation.
ESTHER : Wang_2021_J.Anal.Toxicol__
PubMedSearch : Wang_2021_J.Anal.Toxicol__
PubMedID: 34918103

Title : Perilla frutescens Leaf Extract and Fractions: Polyphenol Composition, Antioxidant, Enzymes (alpha-Glucosidase, Acetylcholinesterase, and Tyrosinase) Inhibitory, Anticancer, and Antidiabetic Activities - Wang_2021_Foods_10_
Author(s) : Wang Z , Tu Z , Xie X , Cui H , Kong KW , Zhang L
Ref : Foods , 10 : , 2021
Abstract : This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid-liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 microg GAE/mg DE) and flavonoid content (455.22 microg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful alpha-glucosidase inhibitory ability with the IC(50) value of 190.03 microg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC(50) values of 37.92 and 13.43 microg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent.
ESTHER : Wang_2021_Foods_10_
PubMedSearch : Wang_2021_Foods_10_
PubMedID: 33546380

Title : Dipeptidyl peptidase IV is required for endometrial carcinoma cell proliferation and tumorigenesis via the IL-6\/STAT3 pathway - Yang_2021_J.Obstet.Gynaecol.Res__
Author(s) : Yang X , Zhu Y , Shi Q , Zhao X , Huang Y , Yao F , Zhang Y , Wang Z
Ref : J Obstet Gynaecol Res , : , 2021
Abstract : AIM: To study the functions and signaling pathways controlled by dipeptidyl peptidase IV (DPPIV) in endometrial carcinoma (EC). METHODS: DPPIV expression in EC cells was detected by flow cytometry, reverse transcription-polymerase chain reaction analysis and Western blot. Interleukin-6 (IL-6) expression in the supernatant was measured by enzyme-linked immunosorbent assay. The protein levels of signal transducers and activators of transcription-3 (STAT3), phosphorylate STAT3, cellular Myc, and vascular endothelial growth factor in EC cells were measured by Western blot. Colony formation assays were used to assess the clonogenicity of EC cells. Ki67 immunostaining and cell counting were used to test the proliferative ability of EC cells. Nude mouse tumorigenicity assay was used to confirm DPPIV promotes the tumorigenicity of EC cells. A cell counting kit-8 assay was used to determine the half-maximal inhibitory concentration of sitagliptin. RESULTS: Overexpression of DPPIV in EC cells with low DPPIV expression promoted cell proliferation in vitro (p < 0.01) and enhanced tumorigenicity in vivo (p < 0.05). Conversely, knocking down DPPIV expression in EC cells with high DPPIV expression inhibited cell proliferation (p < 0.01) and in vivo tumorigenicity (p < 0.01). DPPIV promoted EC cell proliferation via activation of IL-6/STAT3 signaling pathway, and that IL-6 could trigger a positive feedback loop that increased DPPIV expression (p < 0.01). Furthermore, the DPPIV inhibitor reduced STAT3 expression (p < 0.01) and inhibited growth of EC cells (p < 0.001). CONCLUSION: DPPIV enhances the properties that allow tumorigenesis in EC via IL-6 and STAT3 signaling.
ESTHER : Yang_2021_J.Obstet.Gynaecol.Res__
PubMedSearch : Yang_2021_J.Obstet.Gynaecol.Res__
PubMedID: 33969570

Title : Pyridostigmine ameliorates preeclamptic features in pregnant rats by inhibiting tumour necrosis factor-alpha synthetsis and antagonizing tumour necrosis factor-alpha-related effects - Issotina_2021_J.Hypertens__
Author(s) : Issotina Zibrila A , Wang Z , Ali MA , Osei JA , Sun Y , Zafar S , Liu K , Li C , Kang Y , Liu J
Ref : J Hypertens , : , 2021
Abstract : OBJECTIVE: Preeclampsia is a hypertensive disorder of pregnancy marked by an excessive inflammatory response. The anti-inflammatory effect of pyridostigmine (PYR) was previously reported; however, its role in hypertensive pregnancies remains unclear. We hypothesized that PYR could attenuate increased blood pressure and other pathological features in preeclampsia models. METHODS: The expression of tumour necrosis factor (TNF)-alpha was evaluated in normal and preeclampsia pregnant women. PYR (20mg/kg) was administered daily to reduced uterine perfusion pressure (RUPP) and TNF-alpha (150ng/day) infused rats from gestation day 14 to GD19. In a cell culture experiment, the effect of acetylcholine (ACh) on TNF-alpha-stimulated primary human umbilical endothelial cells (HUVEC) was assessed. RESULTS: Preeclampsia women had higher placental TNF-alpha expression than normal pregnant women. Mean arterial pressure (MAP) in the RUPP group was higher than in the Sham group. PYR inhibited serum and placental acetylcholinesterase activity in rats, and reduced MAP, placental oxidative stress, apoptosis and inflammation in the RUPP group but not in the Sham group. In addition, PYR significantly attenuated the TNF-alpha-induced increase in MAP, placental oxidative stress and apoptosis. Moreover, TNF-alpha decreased cell viability and increased the number of TUNEL-positive nuclei of HUVEC, which could largely be abolished by ACh treatment. CONCLUSION: Collectively, PYR ameliorated hypertension and other preeclampsia-like symptoms in rat models of preeclampsia not only by inhibiting the synthesis of TNF-alpha but also by acting against TNF-alpha-induced detrimental effects directly, which is worthy of further investigation and may be used as a potential agent for preeclampsia management.
ESTHER : Issotina_2021_J.Hypertens__
PubMedSearch : Issotina_2021_J.Hypertens__
PubMedID: 34232157

Title : Behaviors and biochemical responses of macroinvertebrate Corbicula fluminea to polystyrene microplastics - Fu_2021_Sci.Total.Environ_813_152617
Author(s) : Fu L , Xi M , Nicholaus R , Wang Z , Wang X , Kong F , Yu Z
Ref : Sci Total Environ , 813 :152617 , 2021
Abstract : Microplastic, a well-documented emerging contaminant, is widespread in aquatic environments resulting from the production and fragmentation of large plastics items. The knowledge about the chronic toxic effects and behavioral toxicity of microplastics, particularly on freshwater benthic macroinvertebrates, is limited. In this study, adult Asian clams (Corbicula fluminea) were exposed to gradient microplastic solutions for 42 days to evaluate behavioral toxicity and chronic biotoxicity. The results showed that microplastics caused behavior toxicity, oxidative stress, and tissue damage in high-concentration treatments. Siphoning, breathing, and excretion was significantly inhibited (p < 0.05) at high-concentration treatments, suggesting that high-concentration microplastics induced behavioral toxicity in C. fluminea. Malondialdehyde content, superoxide dismutase, catalase, and glutathione reductase activities were significantly enhanced (p < 0.05) and the acetylcholinesterase was significantly inhibited (p < 0.05) throughout the exposure period in high-concentration treatments. Enzymes associated with energy supply were significantly higher at high-concentration microplastics treatments on D7 and D21. However, they recovered to a normal level on D42. The instability of the enzymes indicated that high-concentration microplastics induced oxidative stress and disorder in neurotransmission and energy supply. The gills of C. fluminea in treatments underwent cilia degeneration, which indicated that microplastics caused tissue damage in the gills. The analysis of integrated biomarker response values revealed that high-concentration microplastics led to long-term effects on the health of C. fluminea. In conclusion, continuous exposure to microplastics (10 mg L(-1)) would damage physical behavior and the antioxidant system of C. fluminea.
ESTHER : Fu_2021_Sci.Total.Environ_813_152617
PubMedSearch : Fu_2021_Sci.Total.Environ_813_152617
PubMedID: 34963588

Title : [Propeptide-mediated protein folding: mechanism and its impact on lipase] - Tian_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_88
Author(s) : Tian M , Zhang J , Luo W , Wang Z , Fu J , Huang S , Lu P
Ref : Sheng Wu Gong Cheng Xue Bao , 37 :88 , 2021
Abstract : The formation of most proteins consists of two steps: the synthesis of precursor proteins and the synthesis of functional proteins. In these processes, propeptides play important roles in assisting protein folding or inhibiting its activity. As an important polypeptide chain coded by a gene sequence in lipase gene, propeptide usually functions as an intramolecular chaperone, assisting enzyme molecule folding. Meanwhile, some specific sites on propeptide such as glycosylated sites, have important effect on the activity, stability in extreme environment, methanol resistance and the substrate specificity of the lipase. Studying the mechanism of propeptide-mediated protein folding, as well as the influence of propeptide on lipases, will allow to regulate lipase by alternating the propeptide folding behavior and in turn pave new ways for protein engineering research.
ESTHER : Tian_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_88
PubMedSearch : Tian_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_88
PubMedID: 33501792

Title : Design and synthesis of novel tacrine-dipicolylamine dimers that are multiple-target-directed ligands with potential to treat Alzheimer's disease - Zhang_2021_Bioorg.Chem_116_105387
Author(s) : Zhang P , Wang Z , Mou C , Zou J , Xie Y , Liu Z , Benjamin Naman C , Mao Y , Wei J , Huang X , Dong J , Yang M , Wang N , Jin H , Liu F , Lin D , Liu H , Zhou F , He S , Zhang B , Cui W
Ref : Bioorg Chem , 116 :105387 , 2021
Abstract : Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an beta-amyloid (Abeta) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Abeta(1-42) aggregation in vitro, and 13a exhibited nanomolar level inhibition. Molecular docking analysis suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Abeta(1-42) pentamers. Moreover, 13a effectively attenuated Abeta(1-42) oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments. All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD.
ESTHER : Zhang_2021_Bioorg.Chem_116_105387
PubMedSearch : Zhang_2021_Bioorg.Chem_116_105387
PubMedID: 34628225

Title : Tralopyril affects locomotor activity of zebrafish (Danio rerio) by impairing tail muscle tissue, the nervous system, and energy metabolism - Chen_2021_Chemosphere_286_131866
Author(s) : Chen X , Zheng J , Teng M , Zhang J , Qian L , Duan M , Cheng Y , Zhao W , Wang Z , Wang C
Ref : Chemosphere , 286 :131866 , 2021
Abstract : Tralopyril (TP), an antifouling biocide, is widely used to prevent heavy biofouling, and can have potential risks to aquatic organisms. In this study, the effect of TP on locomotor activity and related mechanisms were evaluated in zebrafish (Danio rerio) larvae. TP significantly reduced locomotor activity after 168 -h exposure. Adverse modifications in tail muscle tissue, the nervous system, and energy metabolism were also observed in larvae. TP caused thinning of the muscle bundle in the tail of larvae. In conjunction with the metabolomics results, changes in dopamine (DA) and acetylcholine (ACh), acetylcholinesterase (AChE) activity, and the expression of genes involved in neurodevelopment, indicate that TP may disrupt the nervous system in zebrafish larvae. The change in metabolites (e.g., glucose 6-phosphate, cis-Aconitic acid, acetoacetyl-CoA, coenzyme-A and 3-Oxohexanoyl-CoA) involved in carbohydrate and lipid metabolism indicates that TP may disrupt energy metabolism. TP exposure may inhibit the locomotor activity of zebrafish larvae by impairing tail muscle tissue, the nervous system, and energy metabolism.
ESTHER : Chen_2021_Chemosphere_286_131866
PubMedSearch : Chen_2021_Chemosphere_286_131866
PubMedID: 34391112

Title : Deficiency of TMEM53 causes a previously unknown sclerosing bone disorder by dysregulation of BMP-SMAD signaling - Guo_2021_Nat.Commun_12_2046
Author(s) : Guo L , Iida A , Bhavani GS , Gowrishankar K , Wang Z , Xue JY , Wang J , Miyake N , Matsumoto N , Hasegawa T , Iizuka Y , Matsuda M , Nakashima T , Takechi M , Iseki S , Yambe S , Nishimura G , Koseki H , Shukunami C , Girisha KM , Ikegawa S
Ref : Nat Commun , 12 :2046 , 2021
Abstract : Bone formation represents a heritable trait regulated by many signals and complex mechanisms. Its abnormalities manifest themselves in various diseases, including sclerosing bone disorder (SBD). Exploration of genes that cause SBD has significantly improved our understanding of the mechanisms that regulate bone formation. Here, we discover a previously unknown type of SBD in four independent families caused by bi-allelic loss-of-function pathogenic variants in TMEM53, which encodes a nuclear envelope transmembrane protein. Tmem53(-/-) mice recapitulate the human skeletal phenotypes. Analyses of the molecular pathophysiology using the primary cells from the Tmem53(-/-) mice and the TMEM53 knock-out cell lines indicates that TMEM53 inhibits BMP signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of BMP2-activated Smad proteins. Pathogenic variants in the patients impair the TMEM53-mediated blocking effect, thus leading to overactivated BMP signaling that promotes bone formation and contributes to the SBD phenotype. Our results establish a previously unreported SBD entity (craniotubular dysplasia, Ikegawa type) and contribute to a better understanding of the regulation of BMP signaling and bone formation.
ESTHER : Guo_2021_Nat.Commun_12_2046
PubMedSearch : Guo_2021_Nat.Commun_12_2046
PubMedID: 33824347
Gene_locus related to this paper: human-TMEM53

Title : An Evolving Technology That Integrates Classical Methods with Continuous Technological Developments: Thin-Layer Chromatography Bioautography - Wang_2021_Molecules_26_
Author(s) : Wang M , Zhang Y , Wang R , Wang Z , Yang B , Kuang H
Ref : Molecules , 26 : , 2021
Abstract : Thin-layer chromatography (TLC) bioautography is an evolving technology that integrates the separation and analysis technology of TLC with biological activity detection technology, which has shown a steep rise in popularity over the past few decades. It connects TLC with convenient, economic and intuitive features and bioautography with high levels of sensitivity and specificity. In this study, we discuss the research progress of TLC bioautography and then establish a definite timeline to introduce it. This review summarizes known TLC bioautography types and practical applications for determining antibacterial, antifungal, antitumor and antioxidant compounds and for inhibiting glucosidase, pancreatic lipase, tyrosinase and cholinesterase activity constitutes. Nowadays, especially during the COVID-19 pandemic, it is important to identify original, natural products with anti-COVID potential compounds from Chinese traditional medicine and natural medicinal plants. We also give an account of detection techniques, including in situ and ex situ techniques; even in situ ion sources represent a major reform. Considering the current technical innovations, we propose that the technology will make more progress in TLC plates with higher separation and detection technology with a more portable and extensive scope of application. We believe this technology will be diffusely applied in medicine, biology, agriculture, animal husbandry, garden forestry, environmental management and other fields in the future.
ESTHER : Wang_2021_Molecules_26_
PubMedSearch : Wang_2021_Molecules_26_
PubMedID: 34361800

Title : Biodegradation of erythromycin by Delftia lacustris RJJ-61 and characterization of its erythromycin esterase - Ren_2021_J.Basic.Microbiol_61_55
Author(s) : Ren J , Wang Z , Deng L , Niu D , Fan B , Huhe T , Li Z , Zhang J , Li C
Ref : J Basic Microbiol , 61 :55 , 2021
Abstract : The residual erythromycin in fermentation waste can pollute the environment and threaten human health. However, there are no effective approaches to remedy this issue. In this study, an erythromycin-degrading bacterium named RJJ-61 was isolated and identified as a strain of Delftia lacustris based on morphological and phylogenetic analyses. The degradation ability of this strain was also evaluated; it could degrade 45.18% of erythromycin at 35 degreesC in 120h. Furthermore, the key degradation gene ereA was cloned from strain RJJ-61 and expressed in Escherichia coli BL21; the molecular weight of the expressed protein was ~45kDa. The enzyme activity of EreA was 108.0mUml(-1) at 35 degreesC and pH 7.0. Finally, the EreA protein was used to degrade erythromycin from mycelial dregs and 50% diluted solution, and the removal rates in them were 41.42% and 69.78%, respectively. In summary, D. lacustris RJJ-61 is a novel erythromycin-degrading strain that has great potential to remove erythromycin pollutants from the environment.
ESTHER : Ren_2021_J.Basic.Microbiol_61_55
PubMedSearch : Ren_2021_J.Basic.Microbiol_61_55
PubMedID: 33332633

Title : Electro-Acupuncture Improve the Early Pattern Separation in Alzheimer's Disease Mice via Basal Forebrain-Hippocampus Cholinergic Neural Circuit - Li_2021_Front.Aging.Neurosci_13_770948
Author(s) : Li L , Li J , Dai Y , Yang M , Liang S , Wang Z , Liu W , Chen L , Tao J
Ref : Front Aging Neurosci , 13 :770948 , 2021
Abstract : OBJECTIVES: To explore the effect of electro-acupuncture (EA) treatment on pattern separation and investigate the neural circuit mechanism involved in five familial mutations (5 x FAD) mice. METHODS: Five familial mutations mice were treated with EA at Baihui (DU20) and Shenting (DU24) acupoints for 30 min each, lasting for 4 weeks. Cognitive-behavioral tests were performed to evaluate the effects of EA treatment on cognitive functions. (1)H-MRS, Nissl staining, immunohistochemistry, and immunofluorescence were performed to examine the cholinergic system alteration. Thioflavin S staining and 6E10 immunofluorescence were performed to detect the amyloid-beta (Abeta). Furthermore, hM4Di designer receptors exclusively activated by designer drugs (DREADDs) virus and long-term clozapine-N-oxide injection were used to inhibit the medial septal and vertical limb of the diagonal band and dentate gyrus (MS/VDB-DG) cholinergic neural circuit. Cognitive-behavioral tests and immunofluorescence were performed to investigate the cholinergic neural circuit mechanism of EA treatment improving cognition in 5 x FAD mice. RESULTS: Electro-acupuncture treatment significantly improved spatial recognition memory and pattern separation impairment, regulated cholinergic system via reduction neuron loss, upregulation of choline/creatine, choline acetyltransferase, vesicular acetylcholine transporter, and downregulation of enzyme acetylcholinesterase in 5 x FAD mice. Abeta deposition was reduced after EA treatment. Subsequently, the monosynaptic hM4Di DREADDs virus tracing and inhibiting strategy showed that EA treatment activates the MS/VDB-DG cholinergic neural circuit to improve the early pattern separation. In addition, EA treatment activates this circuit to upregulating M1 receptors positive cells and promoting hippocampal neurogenesis in the dentate gyrus (DG). CONCLUSION: Electro-acupuncture could improve the early pattern separation impairment by activating the MS/VDB-DG cholinergic neural circuit in 5 x FAD mice, which was related to the regulation of the cholinergic system and the promotion of neurogenesis by EA treatment.
ESTHER : Li_2021_Front.Aging.Neurosci_13_770948
PubMedSearch : Li_2021_Front.Aging.Neurosci_13_770948
PubMedID: 35185516

Title : Responses of Asian clams (Corbicula fluminea) to low concentration cadmium stress: Whether the depuration phase restores physiological characteristics - Wang_2021_Environ.Pollut_284_117182
Author(s) : Wang Z , Kong F , Fu L , Li Y , Li M , Yu Z
Ref : Environ Pollut , 284 :117182 , 2021
Abstract : The effect of low concentration Cd stress on bivalves is unclear. In this study, Asian clams (Corbicula fluminea) were continuously exposed to 0, 0.05, 0.10, and 0.20 mg/L Cd for 14 d (exposure phase) and to artificial freshwater for 7 d (depuration phase). A total of 16 variables were measured to explore the toxic effects on C. fluminea. All physiological characteristics were significantly inhibited in the treatments (p < 0.05), and the negative effects of Cd did not return to normal levels in the short term. Tissue damage was found in the feet and gills of C. fluminea in all the treatments. On the 7th day (D7), enzyme activity in all the treatments was significantly higher (p < 0.05) than in the control group. Acetylcholinesterase, superoxide dismutase, and catalase activities were enhanced on D14 in all the treatments. However, only glutathione S-transferase activity was significantly higher in all the treatments (p < 0.05) than in the control group on D21. The instability of the enzymes indicated that the adaptability of C. fluminea became stronger throughout the experiment. In each group, the maximum bioaccumulation of Cd followed the order: 0.20 mg/L > 0.05 mg/L > 0.10 mg/L, which might be caused by the filtration capacity of C. fluminea in the 0.05-mg/L group, which was higher than that of the 0.10-mg/L group. Thus, low Cd concentrations effect the physiological characteristics, tissue health, and antioxidant system of C. fluminea and may require a long recovery time to be restored to normal levels.
ESTHER : Wang_2021_Environ.Pollut_284_117182
PubMedSearch : Wang_2021_Environ.Pollut_284_117182
PubMedID: 33901982

Title : Enhanced activity of Rhizomucor miehei lipase by directed saturation mutation of the propeptide - Tian_2021_Enzyme.Microb.Technol_150_109870
Author(s) : Tian M , Huang S , Wang Z , Fu J , Lv P , Miao C , Liu T , Yang L , Luo W
Ref : Enzyme Microb Technol , 150 :109870 , 2021
Abstract : The propeptide is a short sequence that facilitates protein folding. In this study, four highly active Rhizomucor miehei lipase (RML) mutants were obtained through saturation mutagenesis at three propeptide positions: Ser8, Pro35, and Pro47. The enzyme activities of mutants P35 N, P47 G, P47 N, and S8E/P35S/P47A observed at 40 degreesC, and pH 8.0 were 10.19, 7.53, 6.15, and 8.24 times of that wild-type RML, respectively. The S8E/P35S/P47A mutant showed good thermostability. After incubation at 40 degreesC for 1 h, 98.98 % of its initial activity remained, whereas wild-type RML retained only 78.76 %. This result indicated that the enhancement of hydrophilicity of 35- and 47- amino-acid residues could promote the interaction between the propeptide and the mature peptide and the enzyme activity and expression level. Highly conserved sites had a more significant impact on enzyme performance than did other sites, similar to the Pro35 and Pro47 mutants showed in this study. This study provides a new idea for protein modification: enzyme performance can be improved through propeptide regulation.
ESTHER : Tian_2021_Enzyme.Microb.Technol_150_109870
PubMedSearch : Tian_2021_Enzyme.Microb.Technol_150_109870
PubMedID: 34489029

Title : Identification of Candidate Carboxylesterases Associated With Odorant Degradation in Holotrichia parallela Antennae Based on Transcriptome Analysis - Yi_2021_Front.Physiol_12_674023
Author(s) : Yi J , Wang S , Wang Z , Wang X , Li G , Zhang X , Pan Y , Zhao S , Zhang J , Zhou JJ , Wang J , Xi J
Ref : Front Physiol , 12 :674023 , 2021
Abstract : Insects rely on their olfactory systems in antennae to recognize sex pheromones and plant volatiles in surrounding environments. Some carboxylesterases (CXEs) are odorant-degrading enzymes (ODEs), degrading odorant signals to protect the olfactory neurons against continuous excitation. However, there is no report about CXEs in Holotrichia parallela, one of the most major agricultural underground pests in China. In the present study, 20 candidate CXEs were identified based on transcriptome analysis of female and male antennae. Sequence alignments and phylogenetic analysis were performed to investigate the characterization of these candidate CXEs. The expression profiles of CXEs were compared by RT-qPCR analysis between olfactory and non-olfactory tissues of both genders. HparCXE4, 11, 16, 17, 18, 19, and 20 were antenna-biased expressed genes, suggesting their possible roles as ODEs. HparCXE6, 10, 11, 13, and 16 showed significantly higher expression profiles in male antennae, whereas HparCXE18 was expressed more in female antennae. This study highlighted candidate CXE genes linked to odorant degradation in antennae, and provided a useful resource for further work on the H. parallela olfactory mechanism and selection of target genes for integrative control of H. parallela.
ESTHER : Yi_2021_Front.Physiol_12_674023
PubMedSearch : Yi_2021_Front.Physiol_12_674023
PubMedID: 34566671

Title : Physiological and transcriptomic changes of zebrafish (Danio rerio) embryos-larvae in response to 2-MIB exposure - Zhou_2021_J.Hazard.Mater_416_126142
Author(s) : Zhou W , Li X , Wang Y , Wang J , Zhang J , Wei H , Peng C , Wang Z , Li G , Li D
Ref : J Hazard Mater , 416 :126142 , 2021
Abstract : 2-Methylisoborneol (2-MIB), a natural odorous substance, is widely distributed in water environment, but there is a paucity of information concerning its systemic toxicity. Herein, we investigated the effects of 2-MIB exposure on developmental parameters, locomotive behavior, oxidative stress, apoptosis and transcriptome of zebrafish. Zebrafish embryos exposed to different concentrations (0, 0.5, 5 and 42.8 microg/L) of 2-MIB showed no changes in mortality, hatchability, and malformation rate, but the body length of zebrafish larvae was significantly increased in a dose-dependent manner, and accompanied by the changes of growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis genes. Moreover, the swimming activity of zebrafish larvae increased, which may be due to the increase of acetylcholinesterase (AChE) activity. Meanwhile, 2-MIB caused oxidative stress and apoptosis in zebrafish larvae by altering the NF-E2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing assay showed that the phototransduction signaling pathway was significantly enriched, and most of the genes in this pathway exhibited enhanced expression after exposure to 2-MIB. These findings provide an important reference for risk assessment and early warning to 2-MIB exposure.
ESTHER : Zhou_2021_J.Hazard.Mater_416_126142
PubMedSearch : Zhou_2021_J.Hazard.Mater_416_126142
PubMedID: 34492931

Title : Co-Expression of a Thermally Stable and Methanol-Resistant Lipase and Its Chaperone from Burkholderia cepacia G63 in Escherichia coli - Zhang_2021_Appl.Biochem.Biotechnol_193_717
Author(s) : Zhang J , Tian M , Chen X , Lv P , Luo W , Wang Z , Xu J
Ref : Appl Biochem Biotechnol , 193 :717 , 2021
Abstract : Biodiesel biosynthesis with enzymatic transesterification is considered green, sustainable, and environmentally friendly method. Lipase from Burkholderia cepacia G63 has excellent catalytic properties in biodiesel production. Lipase chaperones promote secretion and folding of enzymes, thereby enhancing enzymatic activity. In the current study, heterologous co-expression of lipase (lipA) and chaperone (lipB) was achieved in Escherichia coli through codon optimization. The enzymatic activity of purified and renatured lipAB was 2080.23 +/- 19.18 U/g at 50 degreesC and pH 8.0. Moreover, lipAB showed increased resistance to pH and temperature changes, and lipAB retained stable catalytic properties after treatment with metal ions, organic solvents, and surfactants, namely Mg(2+), methanol, and Triton-100X. Besides, using recombinant lipase lipAB as catalysts, biodiesel was synthesized using rapeseed oil under 50 degreesC for 72 h with a yield of 90.23%. Thus, the current study confirmed that co-expression of lipase and its chaperone is an effective strategy to enhance enzyme activity and improve the biochemical profile, meanwhile, showing that lipAB is a promising biocatalyst for biodiesel production.
ESTHER : Zhang_2021_Appl.Biochem.Biotechnol_193_717
PubMedSearch : Zhang_2021_Appl.Biochem.Biotechnol_193_717
PubMedID: 33184764

Title : Congenital myasthenic syndrome in China: genetic and myopathological characterization - Zhao_2021_Ann.Clin.Transl.Neurol__
Author(s) : Zhao Y , Li Y , Bian Y , Yao S , Liu P , Yu M , Zhang W , Wang Z , Yuan Y
Ref : Ann Clin Transl Neurol , : , 2021
Abstract : OBJECTIVE: We aimed to summarize the clinical, genetic, and myopathological features of a cohort of Chinese patients with congenital myasthenic syndrome, and follow up on therapeutic outcomes. METHODS: The clinical spectrum, mutational frequency of genes, and pathological diagnostic clues of various subtypes of patients with congenital myasthenic syndrome were summarized. Therapeutic effects were followed up. RESULTS: Thirty-five patients from 29 families were recruited. Ten genes were identified: GFPT1 (27.6%), AGRN (17.2%), CHRNE (17.2%), COLQ (13.8%), GMPPB (6.9%), CHAT, CHRNA1, DOK7, COG7, and SLC25A1 (3.4% each, respectively). Sole limb-girdle weakness was found in patients with AGRN (1/8) and GFPT1 (7/8) mutations, whereas distal weakness was all observed in patients with AGRN (6/8) mutations. Tubular aggregates were only found in patients with GFPT1 mutations (5/6). The patients with GMPPB mutations (2/2) had decreased alpha-dystroglycan. Acetylcholinesterase inhibitor therapy resulted in no response or worsened symptoms in patients with COLQ mutations, a diverse response in patients with AGRN mutations, and a good response in patients with other subtypes. Albuterol therapy was effective or harmless in most subtypes. Therapy effects became attenuated with long-term use in patients with COLQ or AGRN mutations. INTERPRETATION: The genetic distribution of congenital myasthenic syndrome in China is distinct from that of other ethnic origins. The appearance of distal weakness, selective limb-girdle myasthenic syndrome, tubular aggregates, and decreased alpha-dystroglycan were indicative of the specific subtypes. Based on the follow-up findings, we suggest cautious evaluation of the long-term efficacy of therapeutic agents in congenital myasthenic syndrome.
ESTHER : Zhao_2021_Ann.Clin.Transl.Neurol__
PubMedSearch : Zhao_2021_Ann.Clin.Transl.Neurol__
PubMedID: 33756069

Title : Early Use of Blood Purification in Severe Epstein-Barr Virus-Associated Hemophagocytic Syndrome - Huang_2020_Pediatrics__
Author(s) : Huang P , Huang C , Xu H , Lu J , Tian R , Wang Z , Chen Y
Ref : Pediatrics , : , 2020
Abstract : Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a common type of hemophagocytic lymphohistiocytosis (HLH) that exhibits high rates of morbidity and fatalities. Multiorgan failure caused by Epstein-Barr virus (EBV)-induced hypercytokinemia is one of the main reasons for early deaths. Blood purification techniques have been successfully applied in previously treated hypercytokinemia. However, there were insufficient studies to support the combination of plasma exchange (PE) and continuous renal replacement therapy (CRRT) in treating patients with severe EBV-HLH. In this article, we have summarized the effects of early incorporation of PE and CRRT, together with HLH-2004 chemoimmunotherapy, in 8 pediatric patients with severe EBV-HLH. Early use of PE and CRRT appeared to be well tolerated, and no serious side effects and early deaths were observed. After PE and CRRT procedures, cytokine levels were reduced to normal values, except for soluble interleukin 2 receptor, and significant reductions in EBV DNA, serum ferritin, aspartate transaminase, total bilirubin, total bile acid, lactate dehydrogenase, and body temperature values and increases in the neutrophil count in addition to hemoglobin, albumin, and cholinesterase values were observed. Furthermore, through continuous HLH-2004 treatment regimens, lower limits of detection were exhibited for EBV DNA levels, and all other observational indicator levels were restored to normal. Finally, 7 patients achieved and maintained complete remission for 15 to 24 months, culminating in August 2019. Therefore, it is our suggestion that early incorporation of PE and CRRT with chemoimmunotherapy might be a safe and effective treatment for patients with severe EBV-HLH.
ESTHER : Huang_2020_Pediatrics__
PubMedSearch : Huang_2020_Pediatrics__
PubMedID: 32430444

Title : Neuroprotective Effects of the Sonic Hedgehog Signaling Pathway in Ischemic Injury through Promotion of Synaptic and Neuronal Health - Yin_2020_Neural.Plast_2020_8815195
Author(s) : Yin S , Bai X , Xin D , Li T , Chu X , Ke H , Han M , Chen W , Li X , Wang Z
Ref : Neural Plast , 2020 :8815195 , 2020
Abstract : Cerebral ischemia is a common cerebrovascular condition which often induces neuronal apoptosis, leading to brain damage. The sonic hedgehog (Shh) signaling pathway has been reported to be involved in ischemic stroke, but the underlying mechanisms have not been fully elucidated. In the present study, we demonstrated that expressions of Shh, Ptch, and Gli-1 were significantly downregulated at 24 h following oxygen-glucose deprivation (OGD) injury in neurons in vitro, effects which were associated with increasing numbers of apoptotic cells and reactive oxygen species generation. In addition, expressions of synaptic proteins (neuroligin and neurexin) were significantly downregulated at 8 h following OGD, also associated with concomitant neuronal apoptosis. Treatment with purmorphamine, a Shh agonist, increased Gli-1 in the nucleus of neurons and protected against OGD injury, whereas the Shh inhibitor, cyclopamine, produced the opposite effects. Activation of Shh signals promoted CREB and Akt phosphorylation; upregulated the expressions of BDNF, neuroligin, and neurexin; and decreased NF-kappaB phosphorylation following OGD. Notably, this activation of Shh signals was accompanied by improved neurobehavioral responses along with attenuations in edema and apoptosis at 48 h postischemic insult in rats. Taken together, these results demonstrate that activation of the Shh signaling pathway played a neuroprotective role in response to ischemic exposure via promotion of synaptic and neuronal health.
ESTHER : Yin_2020_Neural.Plast_2020_8815195
PubMedSearch : Yin_2020_Neural.Plast_2020_8815195
PubMedID: 32802036

Title : Tricresyl phosphate isomers exert estrogenic effects via G protein-coupled estrogen receptor-mediated pathways - Ji_2020_Environ.Pollut_264_114747
Author(s) : Ji X , Li N , Ma M , Rao K , Yang R , Wang Z
Ref : Environ Pollut , 264 :114747 , 2020
Abstract : Tricresyl phosphates (TCPs), as representative aromatic organophosphate flame retardants (OPFRs), have received much attention due to their potential neurotoxicity and endocrine-disrupting effects. However, the role of estrogen receptor alpha (ERalpha) and G protein-coupled estrogen receptor (GPER) in their estrogen disrupting effects remains poorly understood. Therefore, in this study, three TCP isomers, tri-o-cresyl phosphate (ToCP), tri-m-cresyl phosphate (TmCP) and tri-p-cresyl phosphate (TpCP), were examined for their activities on ERalpha by using two-hybrid yeast assay, and action on GPER by using Boyden chamber assay, cAMP production assay, calcium mobilization assay and molecular docking analysis. The results showed that three TCP isomers were found to act as ERalpha antagonists. Conversely, they had agonistic activity on GPER to promote GPER-mediated cell migration of MCF7 cells and SKBR3 cells. Both ToCP and TpCP activated GPER-mediated cAMP production and calcium mobilization, whereas TmCP had different mode of action, it only triggered GPER-mediated calcium mobilization, as evidenced by using the specific GPER inhibitor (G15) and GPER overexpressing experiments. Molecular docking further revealed that the way of interaction of TmCP and TpCP with GPER was different from that of ToCP with GPER, and higher activity of ToCP in activating GPER-mediated pathways might be associated with the alkyl substitution at the ortho position of the aromatic ring. Our results, for the first time, found a new target, GPER, for TCPs exerting their estrogen-disrupting effects, and demonstrated complex estrogen-disrupting effects of three TCP isomers involved their opposite activities toward ERalpha and GPER.
ESTHER : Ji_2020_Environ.Pollut_264_114747
PubMedSearch : Ji_2020_Environ.Pollut_264_114747
PubMedID: 32559878

Title : Development of a practical prediction scoring system for severe acute organophosphate poisoning - Dong_2020_J.Appl.Toxicol__
Author(s) : Dong N , Liu J , Wang Z , Gao N , Pang L , Xing J
Ref : J Appl Toxicol , : , 2020
Abstract : Acute organophosphorus poisoning (AOPP) is a serious public health issue, especially in the rural areas. This study was designed to establish a scoring system to assess the risk of cases with severe AOPP. A retrospective cohort study was conducted at two independent hospitals. The derivation cohort included 444 patients with AOPP and the validation cohort included 274 patients. A risk score for patients with severe AOPP was developed. The rates of severe AOPP cases were 20.7% and 20.1% in the derivation and validation cohorts, respectively. A scoring system for severe AOPP risk was developed that included: (1) age >50 years, (2) white blood cell count of >15 x 10(9) /L, (3) plasma cholinesterase of <360 U/L, (4) plasma albumin of <35 g/L, (5) blood pH <7.3, and (6) lactic acid >3.0 mmol/L. The predicted score in severe cases of AOPP had good accuracy in both the derivation (area under the receiver operating characteristic curve [AUC] 0.88, 95% confidence interval [CI], 0.85-0.92) and validation cohorts (AUC 0.83, 95% CI, 0.77-0.90). A practical bedside prediction scoring system was developed for patients with severe AOPP. The routine use of this scoring system could rapidly assist in identifying patients at higher risk who require more intensive care or transfer to a larger better-equipped hospital.
ESTHER : Dong_2020_J.Appl.Toxicol__
PubMedSearch : Dong_2020_J.Appl.Toxicol__
PubMedID: 32030807

Title : Predicting the Effects of CYP2C19 and Carboxylesterases on Vicagrel, a Novel P2Y12 Antagonist, by Physiologically Based Pharmacokinetic\/Pharmacodynamic Modeling Approach - Liu_2020_Front.Pharmacol_11_591854
Author(s) : Liu S , Wang Z , Tian X , Cai W
Ref : Front Pharmacol , 11 :591854 , 2020
Abstract : Vicagrel, a novel acetate derivative of clopidogrel, exhibits a favorable safety profile and excellent antiplatelet activity. Studies aim at identifying genetic and non-genetic factors affecting vicagrel metabolic enzymes Cytochrome P450 2C19 (CYP2C19), Carboxylesterase (CES) 1 and 2 (CES1 and CES2), which may potentially lead to altered pharmacokinetics and pharmacodynamics, are warranted. A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating vicagrel and its metabolites was constructed, verified and validated in our study, which could simultaneously characterize its sequential two step metabolism and clinical response. Simulations were then performed to evaluate the effects of CYP2C19, CES1 and CES2 genetic polymorphisms as well as inhibitors of these enzymes on vicagrel pharmacokinetics and antiplatelet effects. Results suggested vicagrel was less influenced by CYP2C19 metabolic phenotypes and CES1 428 G > A variation, in comparison to clopidogrel. No pharmacokinetic difference in the active metabolite was also noted for volunteers carrying different CES2 genotypes. Omeprazole, a CYP2C19 inhibitor, and simvastatin, a CES1 and CES2 inhibitor, showed weak impact on the pharmacokinetics and pharmacodynamics of vicagrel. This is the first study proposing a dynamic PBPK/PD model of vicagrel able to capture its pharmacokinetic and pharmacodynamic profiles simultaneously. Simulations indicated that genetic polymorphisms and drug-drug interactions showed no clinical relevance for vicagrel, suggesting its potential advantages over clopidogrel for treatment of cardiovascular diseases. Our model can be utilized to support further clinical trial design aiming at exploring the effects of genetic polymorphisms and drug-drug interactions on PK and PD of this novel antiplatelet agent.
ESTHER : Liu_2020_Front.Pharmacol_11_591854
PubMedSearch : Liu_2020_Front.Pharmacol_11_591854
PubMedID: 33424602

Title : Toxicological effects of nano- and micro-polystyrene plastics on red tilapia: Are larger plastic particles more harmless? - Ding_2020_J.Hazard.Mater_396_122693
Author(s) : Ding J , Huang Y , Liu S , Zhang S , Zou H , Wang Z , Zhu W , Geng J
Ref : J Hazard Mater , 396 :122693 , 2020
Abstract : Nanoplastics (NPs) and microplastics (MPs) are a heterogeneous class of pollutants with diverse sizes in aquatic environments. To evaluate the hazardous effects of N/MPs with different sizes, the accumulation, oxidative stress, cytochrome P450 (CYP) enzymes, neurotoxicity, and metabolomics changes were investigated in the red tilapia exposed to three sizes of polystyrene (PS) N/MPs (0.3, 5, and 70-90mum). After 14-d exposures, the largest particles (70-90mum) showed the highest accumulation levels in most cases. Exposures to PS-MPs (5 and 70-90mum) caused a more severe oxidative stress in red tilapia than PS-NPs. The activity of CYP3A-related enzyme was obviously inhibited by PS-NPs, whereas the CYP enzymes in the liver may not be sensitive to MP exposures. In the brain, only 5mumPS-MPs significantly inhibited the acetylcholinesterase activity. After exposures, the treatments with 0.3, 5, and 70-90mum N/MPs resulted in 31, 40, and 23 significantly differentially expressed metabolites, respectively, in which the pathway of tyrosine metabolism was significantly affected by all the three PS-N/MP exposures. Overall, the PS particles within the mum size posed more severe stress to red tilapia. Our results suggest that the toxicity of N/MPs may not show a simply monotonic negative correlation with their sizes.
ESTHER : Ding_2020_J.Hazard.Mater_396_122693
PubMedSearch : Ding_2020_J.Hazard.Mater_396_122693
PubMedID: 32353735

Title : Hybrid Aspen Expressing a Carbohydrate Esterase Family 5 Acetyl Xylan Esterase Under Control of a Wood-Specific Promoter Shows Improved Saccharification - Wang_2020_Front.Plant.Sci_11_380
Author(s) : Wang Z , Pawar PM , Derba-Maceluch M , Hedenstrom M , Chong SL , Tenkanen M , Jonsson LJ , Mellerowicz EJ
Ref : Front Plant Sci , 11 :380 , 2020
Abstract : Fast-growing broad-leaf tree species can serve as feedstocks for production of bio-based chemicals and fuels through biochemical conversion of wood to monosaccharides. This conversion is hampered by the xylan acetylation pattern. To reduce xylan acetylation in the wood, the Hypocrea jecorina acetyl xylan esterase (HjAXE) from carbohydrate esterase (CE) family 5 was expressed in hybrid aspen under the control of the wood-specific PtGT43B promoter and targeted to the secretory pathway. The enzyme was predicted to deacetylate polymeric xylan in the vicinity of cellulose due to the presence of a cellulose-binding module. Cell-wall-bound protein fractions from developing wood of transgenic plants were capable of releasing acetyl from finely ground wood powder, indicative of active AXE present in cell walls of these plants, whereas no such activity was detected in wild-type plants. The transgenic lines grew in height and diameter as well as wild-type trees, whereas their internodes were slightly shorter, indicating higher leaf production. The average acetyl content in the wood of these lines was reduced by 13%, mainly due to reductions in di-acetylated xylose units, and in C-2 and C-3 mono-acetylated xylose units. Analysis of soluble cell wall polysaccharides revealed a 4% reduction in the fraction of xylose units and an 18% increase in the fraction of glucose units, whereas the contents of cellulose and lignin were not affected. Enzymatic saccharification of wood from transgenic plants resulted in 27% higher glucose yield than for wild-type plants. Brunauer-Emmett-Teller (BET) analysis and Simons' staining pointed toward larger surface area and improved cellulose accessibility for wood from transgenic plants compared to wood from wild-type plants, which could be achieved by HjAXE deacetylating xylan bound to cellulose. The results show that CE5 family can serve as a source of enzymes for in planta reduction of recalcitrance to saccharification.
ESTHER : Wang_2020_Front.Plant.Sci_11_380
PubMedSearch : Wang_2020_Front.Plant.Sci_11_380
PubMedID: 32322259

Title : Lipase catalysis of alpha-linolenic acid-rich medium- and long-chain triacylglycerols from perilla oil and medium-chain triacylglycerols with reduced by-products - Huang_2020_J.Sci.Food.Agric_100_4565
Author(s) : Huang Z , Cao Z , Guo Z , Chen L , Wang Z , Sui X , Jiang L
Ref : J Sci Food Agric , 100 :4565 , 2020
Abstract : BACKGROUND: Medium- and long- chain triacylglycerols (MLCTs) are functional structural lipids that can provide the human body with essential fatty acids and a faster energy supply. This study aimed to prepare MLCTs rich in alpha-linolenic by enzymatic interesterification of perilla oil and medium-chain triacylglycerols (MCTs), catalyzed by Lipozyme RM IM, Lipozyme TL IM, Lipozyme 435, and Novozyme 435 respectively. RESULTS: The effects of lipase loading, concentration of MCTs, reaction temperature, and reaction time on the yield of MLCTs were investigated. It was found that the reaction achieved more than a 70% yield of MLCTs in triacylglycerols under the conditions of 400 g kg(-1) MCTs and 60 g kg(-1) lipase loading after equilibrium. A novel two-stage deodorization was also applied to purify the interesterification products. The triacylglycerols reach over 97% purity in the products with significant removal (P < 0.05) of the free fatty acids, and the trans fatty acids were strictly controlled at below 1%. There was more than 40% alpha-linolenic in the purified products, with long-chain fatty acids mostly occupying the desired sn-2 position in acylglycerols, which are more active in hydrolysis. CONCLUSION: A series of novel alpha-linolenic acid-rich medium- and long-chain triacylglycerols was prepared. Under appropriate reaction conditions, the yield of MLCTs in triacylglycerols was above 70%. A novel two-stage deodorization can be used to promote the elimination of free fatty acids and limit the generation of trans fatty acids.
ESTHER : Huang_2020_J.Sci.Food.Agric_100_4565
PubMedSearch : Huang_2020_J.Sci.Food.Agric_100_4565
PubMedID: 32419135

Title : Rv3091, An Extracellular Patatin-Like Phospholipase in Mycobacterium tuberculosis, Prolongs Intracellular Survival of Recombinant Mycolicibacterium smegmatis by Mediating Phagosomal Escape - Cui_2020_Front.Microbiol_11_2204
Author(s) : Cui Z , Dang G , Song N , Cui Y , Li Z , Zang X , Liu H , Wang Z , Liu S
Ref : Front Microbiol , 11 :2204 , 2020
Abstract : Patatin-like phospholipases (PLPs) are important virulence factors of many pathogens. However, there are no prevailing studies regarding PLPs as a virulence factor of Mycobacterium tuberculosis (Mtb). Analysis of Rv3091, a putative protein of Mtb, shows that it belongs to the PLPs family. Here, we cloned and expressed the rv3091 gene in Mycobacterium smegmatis and, subsequently, conducted protein purification and characterization. We show that it possesses phospholipase A(1), phospholipase A(2), and lipase activity. We confirm the putative active site residues, namely, Ser214 and Asp407, using site directed mutagenesis. The Rv3091 is an extracellular protein that alters the colony morphology of M. smegmatis. The presence of Rv3091 enhances the intracellular survival capability of M. smegmatis in murine peritoneal macrophages. Additionally, it promotes M. smegmatis phagosomal escape from macrophages. Moreover, Rv3091 significantly increased the survival of M. smegmatis and aggravated lesions in C57BL/6 J murine lungs in vivo. Taken together, our results indicate that Rv3091 as an extracellular PLP that is critical to the pathogenicity of mycobacterium as it allows mycobacterium to utilize phospholipids for its growth and provides resistance to phagosome killing, resulting in its enhanced intracellular survival.
ESTHER : Cui_2020_Front.Microbiol_11_2204
PubMedSearch : Cui_2020_Front.Microbiol_11_2204
PubMedID: 33042041

Title : Immobilization of Lipozyme TL 100L for methyl esterification of soybean oil deodorizer distillate - Zheng_2020_3.Biotech_10_51
Author(s) : Zheng J , Wei W , Wang S , Li X , Zhang Y , Wang Z
Ref : 3 Biotech , 10 :51 , 2020
Abstract : An immobilization method for binding cross-linked enzyme aggregates of Lipozyme TL 100L on macroporous resin NKA (CLEA-TLL@NKA) was developed in this study. The esterification activity of CLEA-TLL@NKA reached 6.4 U/mg. The surface structure of immobilized lipase was characterized by scanning electron microscopy. Methyl esterification reaction of soybean oil deodorizer distillate (SODD) was catalyzed by CLEA-TLL@NKA, which the conversion rate reached 98% and its activity retained over 90% after 20 batches of reaction. Compared with the commercial enzyme Lipozyme TLIM, half-life (t 1/2) of CLEA-TLL@NKA increased by 25 times and the catalytic activity increased by approximate 10 times. Thus, CLEA-TLL@NKA had high catalytic activity, good operational stability, and potential industrial application in the field of oil processing.
ESTHER : Zheng_2020_3.Biotech_10_51
PubMedSearch : Zheng_2020_3.Biotech_10_51
PubMedID: 32002342
Gene_locus related to this paper: humla-1lipa

Title : Directed evolution of Aspergillus oryzae lipase for the efficient resolution of (R,S)-ethyl-2-(4-hydroxyphenoxy) propanoate - Zhang_2020_Bioprocess.Biosyst.Eng_43_2131
Author(s) : Zhang M , Li Q , Lan X , Li X , Zhang Y , Wang Z , Zheng J
Ref : Bioprocess Biosyst Eng , 43 :2131 , 2020
Abstract : Aspergillus oryzae lipase (AOL) is a potential biocatalyst for industrial application. In this study, a mutant lipase AOL-3(F38N/V230R) was screened through two rounds of directed evolution, resulting in a fourfold increase in lipase activity, and threefold in catalytic efficiency (k(cat)/K(m)), while maintaining its excellent stereoselectivity. AOL-3(F38N/V230R) enzyme activity was maximum at pH 7.5 and also at 40 degreesC. And compared with wild-type AOL-3, AOL-3(F38N/V230R) preferentially hydrolyzed the fatty acid ethyl ester carbon chain length from C4 to C6-C10. In the same catalytic reaction conditions, the conversion of (R,S)-ethyl-2-(4-hydroxyphenoxy) propanoate ((R,S)-EHPP) by AOL-3(F38N/V230R) can be increased 169.7% compared to the original enzyme. The e.e.(s) of (R,S)-EHPP achieved 99.4% and conversion about 50.2% with E value being 829.0. Therefore, AOL-3(F38N/V230R) was a potential biocatalyst for obtaining key chiral compounds for aryloxyphenoxy propionate (APP) herbicides.
ESTHER : Zhang_2020_Bioprocess.Biosyst.Eng_43_2131
PubMedSearch : Zhang_2020_Bioprocess.Biosyst.Eng_43_2131
PubMedID: 32959146
Gene_locus related to this paper: aspor-TGLA

Title : Patatin primary structural properties and effects on lipid metabolism - Wu_2020_Food.Chem__128661
Author(s) : Wu J , Wu Q , Yang D , Zhou M , Xu J , Wen Q , Cui Y , Bai Y , Xu S , Wang Z , Wang S
Ref : Food Chem , :128661 , 2020
Abstract : Patatin, the major protein found in potatoes, was purified and shows several isoforms. The essential amino acid content of patatin was ashighas 76%, indicating that it is a valuable protein source. Patatin was an O-linked glycoprotein that contained fucose monosaccharides, as well as mannose, rhamnose, glucose, galactose, xylose, and arabinose. Patatin had a fucosylated glycan structural feature, which strongly bound AAL (Aleuria aurantia Leukoagglutinin), a known fucose binding lectin. Moreover, thelipid metabolism regulatory effects of patatin on the fat catabolism, fat absorption, and inhibition of lipase activity were measured after high-fat feeding of zebrafish larvae. Results revealed that 37.0 g/mL patatin promoted 23% lipid decomposition metabolism. Meanwhile patatin could inhibite lipase activity and fat absorption, whose effects accounted for half that of a positive control drug. Our findings suggest that patatin, a fucosylated glycoprotein, could potentially be used as a naturalactiveconstituent with anti-obesity effects.
ESTHER : Wu_2020_Food.Chem__128661
PubMedSearch : Wu_2020_Food.Chem__128661
PubMedID: 33272761

Title : Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer's Disease - Shen_2020_Front.Pharmacol_11_595254
Author(s) : Shen Y , Zhang B , Pang X , Yang R , Chen M , Zhao J , Wang J , Wang Z , Yu Z , Wang Y , Li L , Liu A , Du G
Ref : Front Pharmacol , 11 :595254 , 2020
Abstract : Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three in vitro cell models were applied to evaluate the neuroprotective effects of potential lead compounds in XXMD. Through the China Natural Products Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, Traditional Chinese Medicine (TCM)-Database @Taiwan and literature, a total of 1481 compounds in XXMD were finally collected. After ADME/T properties filtering, 908 compounds were used for the further study. Based on the prediction data, the constituents in XXMD formula could interact with 41 AD-related targets. Among them, cyclooxygenase-2 (COX-2), estrogen receptor alpha (ERalpha) and AChE were the major targets. The constituents in XXMD were found to have the potential to treat AD through multiple AD-related targets. 62 constituents in it were found to interact with more than or equal to 10 AD-related targets. The prediction results were further validated by in vitro biology experiment, resulting in several potential anti-AD multitarget-directed ligands (MTDLs), including two AChE inhibitors with the IC(50) values ranging from 4.83 to 10.22 microM. Moreover, fanchinoline was furtherly found to prevent SH-SY5Y cells from the cytotoxicities induced by sodium nitroprusside, sodium dithionate and potassium chloride. In conclusion, XXMD was found to have the potential to treat AD by targeting multiple AD-related targets and canonical pathways. Fangchinoline and dauricine might be the potential lead compounds in XXMD for the treatment of AD.
ESTHER : Shen_2020_Front.Pharmacol_11_595254
PubMedSearch : Shen_2020_Front.Pharmacol_11_595254
PubMedID: 33390981

Title : Ultrasensitive detection of butyrylcholinesterase activity based on the inner filter effect of MnO(2) nanosheets on sulfur nanodots - Li_2020_Analyst_145_5206
Author(s) : Li T , Gao Y , Li H , Zhang C , Xing Y , Jiao M , Shi YE , Li W , Zhai Y , Wang Z
Ref : Analyst , 145 :5206 , 2020
Abstract : Butyrylcholinesterase (BChE) activity is an important index for a variety of diseases. In this work, a "turn-on" assay is proposed based on controlling the inner filter effect (IFE) of MnO(2) nanosheets (NSs) on sulfur nanodots (S-dots). The fluorescence of S-dots is effectively quenched by the MnO(2) NSs, due to the wide overlap of the emission spectrum of S-dots and absorption spectrum of MnO(2) NSs, together with the superior light absorption capability of MnO(2) NSs. BChE can catalyze acetylthiocholine and produce thiocholine, which effectively decomposes the MnO(2) NSs into Mn(2+), resulting in the disappearance of the IFE and recovery of fluorescence of S-dots. Two-stage linear relationships between the ratio of fluorescence intensity and concentration of BChE are observed from 0.05 to 10 and from 10 to 500 U L(-1). A limit of detection of 0.035 U L(-1) is achieved, which is the best performance so far. The as-proposed assay is robust enough for practical detection in human serum, and it can avoid interference from its sister enzyme (acetylcholinesterase) and glutathione at the micromolar level. The presented results provide a clue for the functionalization of S-dots, and offer a powerful tool as an analytic technique for nanomedicine and environmental science.
ESTHER : Li_2020_Analyst_145_5206
PubMedSearch : Li_2020_Analyst_145_5206
PubMedID: 32578586

Title : Efficient biodegradation of highly crystallized polyethylene terephthalate through cell surface display of bacterial PETase - Chen_2020_Sci.Total.Environ_709_136138
Author(s) : Chen Z , Wang Y , Cheng Y , Wang X , Tong S , Yang H , Wang Z
Ref : Sci Total Environ , 709 :136138 , 2020
Abstract : Polyethylene terephthalate (PET) is one of the most widely used plastics in the world. Accumulation of the discarded PET in the environment is creating a global environmental problem. Recently, a bacterial enzyme named PETase was found to have the novel ability to degrade the highly crystallized PET. However, the enzymatic activity of native PETase is still low limiting its possible use in recycling of PET. In this study, we developed a whole-cell biocatalyst by displaying PETase on the surface of yeast (Pichia pastoris) cell to improve its degradation efficiency. Our data shows that PETase could be functionally displayed on the yeast cell with enhanced pH and thermal stability. The turnover rate of the PETase-displaying yeast whole-cell biocatalyst towards highly crystallized PET dramatically increased about 36-fold compared with that of purified PETase. Furthermore, the whole-cell biocatalyst showed stable turnover rate after seven repeated use and under some chemical/solvent conditions, and its ability to degrade different commercial highly crystallized PET bottles. Our results reveal that PETase-displaying whole-cell biocatalyst affords a promising route for efficient biological recycling of PET.
ESTHER : Chen_2020_Sci.Total.Environ_709_136138
PubMedSearch : Chen_2020_Sci.Total.Environ_709_136138
PubMedID: 31887523

Title : MnO(2) switch-bridged DNA walker for ultrasensitive sensing of cholinesterase activity and organophosphorus pesticides - Li_2020_Biosens.Bioelectron_169_112605
Author(s) : Li W , Rong Y , Wang J , Li T , Wang Z
Ref : Biosensors & Bioelectronics , 169 :112605 , 2020
Abstract : Cholinesterases (ChEs) are important indicators of neurological disease, hepatocellular carcinoma, and organophosphate poisoning. In this work, a MnO(2) switch-bridged DNA walker was developed for ultrasensitive sensing of ChEs activity. The fuel strands loaded MnO(2) switch was designed to bridge the hydrolysis activity of ChEs and the running of the DNA walker. Under the action of ChE, the substrate butyrylcholine is first catalytically hydrolyzed to thiocholine, which then mediates MnO(2) nanosheet reduction to Mn(2+), releasing the fuel strands into solution. The fuel strands as substitute targets then trigger the continuous operation of DNA walker with the aid of Mn(2+), generating detectable fluorescence responses. The detection of ChE activity is converted to DNA detection in this method. Benefited from the robust operation and amplification effect of DNA walker, a wide linear range between the BChE activity and fluorescence intensity of nearly six orders of magnitude (1000-0.005 U/mL) and a limit of detection as low as 0.0008 U/mL are achieved. This allows the direct determination of BChE activity in clinical serum samples without any pretreatments. Moreover, the proposed method has remarkable capabilities for inhibitor (organophosphorus pesticide) screening and quantification, and organophosphorus pesticide detection in real samples is also achieved. Therefore, the MnO(2) switch-bridged DNA walker represents a powerful tool for ultrasensitive sensing of ChEs and organophosphorus pesticides, and has great application potential in clinical diagnosis, therapeutics, and drug screening.
ESTHER : Li_2020_Biosens.Bioelectron_169_112605
PubMedSearch : Li_2020_Biosens.Bioelectron_169_112605
PubMedID: 32947079

Title : A Dual-Protein Cascade Reaction for the Regioselective Synthesis of Quinoxalines - Li_2020_Org.Lett__
Author(s) : Li F , Tang X , Xu Y , Wang C , Wang Z , Li Z , Wang L
Ref : Org Lett , : , 2020
Abstract : In this work, an efficient dual-protein (lipase and hemoglobin) system was successfully constructed for the regioselective synthesis of quinoxalines in water. A set of quinoxalines were obtained in high yields under optimal reaction conditions. This dual-protein method exhibited a regioselectivity higher than those of previously reported methods. This study not only provides a green and mild strategy for the synthesis of quinoxalines but also expands the application of lipase and hemoglobin in organic synthesis.
ESTHER : Li_2020_Org.Lett__
PubMedSearch : Li_2020_Org.Lett__
PubMedID: 32337998

Title : High-efficiency expression of the thermophilic lipase from Geobacillus thermocatenulatus in Escherichia coli and its application in the enzymatic hydrolysis of rapeseed oil - Zhang_2020_3.Biotech_10_523
Author(s) : Zhang J , Tian M , Lv P , Luo W , Wang Z , Xu J
Ref : 3 Biotech , 10 :523 , 2020
Abstract : Long-chain fatty acids are widely used in food and chemical industries, and the enzymatic preparation of fatty acids is considered an environmentally friendly process. In the present study, long-chain fatty acids were prepared by the enzymatic hydrolysis of rapeseed oil with a genetically engineered lipase. Because thermophilic lipase has strong stability at higher temperatures, it was more suitable for the industrial production of long-chain fatty acids. Therefore, the thermophilic lipase BTL2 from Geobacillus thermocatenulatus was efficiently expressed in E. coli BL21(DE3) cells with an enzyme activity of 39.50 U/mg followed by gene codon optimisation. Experimental results showed that the recombinant lipase BTL2 exhibited excellent resistance to certain organic solvents (n-hexane, benzene, ethanol, and butanol). The metal cation Ca(2+) and the non-ionic surfactant Triton-100X enhanced enzyme activity by 7.36% and 56.21% respectively. Moreover, the acid value of the liberated long-chain fatty acids by hydrolysing rapeseed oil was approximately 161.64 mg KOH/g at 50 degreeC in 24 h, the hydrolytic conversion rate was 91.45%, and the productivity was approximately 6.735 mg KOH/g h. These results suggested that the recombinant lipase BTL2 has excellent hydrolytic performance for rapeseed oil and showed great potential for the enzymatic preparation of long-chain fatty acids.
ESTHER : Zhang_2020_3.Biotech_10_523
PubMedSearch : Zhang_2020_3.Biotech_10_523
PubMedID: 33194527

Title : Cadmium exposure alters expression of protective enzymes and protein processing genes in venom glands of the wolf spider Pardosa pseudoannulata - Lv_2020_Environ.Pollut_268_115847
Author(s) : Lv B , Yang HL , Peng YD , Wang J , Zeng Z , Li N , Tang YE , Wang Z , Song QS
Ref : Environ Pollut , 268 :115847 , 2020
Abstract : Cadmium (Cd) pollution is currently the most serious type of heavy metal pollution throughout the world. Previous studies have shown that Cd elevates the mortality of paddy field spiders, but the lethal mechanism remains to be explored profoundly. In the present study, we measured the activities of protective enzymes (acetylcholinesterase, glutathione peroxidase, phenol oxidase) and a heavy metal chelating protein (metallothionein) in the pond wolf spider Pardosa pseudoannulata after Cd exposure. The results indicated that Cd initially increased the enzyme activities and protein concentration of the spider after 10- and 20-day exposure before inhibiting them at 30-day exposure. Further analysis showed that the enzyme activities in the cephalothorax were inhibited to some extent. Since the cephalothorax region contains important venom glands, we performed transcriptome sequencing (RNA-seq) analysis of the venom glands collected from the spiders after long-term Cd exposure. RNA-seq yielded a total of 2826 differentially expressed genes (DEGs), and most of the DEGs were annotated into the process of protein synthesis, processing and degradation. Furthermore, a mass of genes involved in protein recognition and endoplasmic reticulum (ER) -associated protein degradation were down-regulated. The reduction of protease activities supports the view that protein synthesis and degradation in organelles and cytoplasm were dramatically inhibited. Collectively, our outcomes illustrate that Cd poses adverse effects on the expression of protective enzymes and protein, which potentially down-regulates the immune function in the venom glands of the spiders via the alteration of protein processing and degradation in the ER.
ESTHER : Lv_2020_Environ.Pollut_268_115847
PubMedSearch : Lv_2020_Environ.Pollut_268_115847
PubMedID: 33130443

Title : Rhizoma Coptidis for Alzheimer's Disease and Vascular Dementia: A Literature Review - Wang_2020_Curr.Vasc.Pharmacol_18_358
Author(s) : Wang Z , Yang Y , Liu M , Wei Y , Liu J , Pei H , Li H
Ref : Curr Vasc Pharmacol , 18 :358 , 2020
Abstract : BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are major types of dementia, both of which cause heavy economic burdens for families and society. However, no currently available medicines can control dementia progression. Rhizoma coptidis, a Chinese herbal medicine, has been used for >2000 years and is now gaining attention as a potential treatment for AD and VaD. METHODS: We reviewed the mechanisms of the active ingredients of Rhizoma coptidis and Rhizoma coptidis-containing Chinese herbal compounds in the treatment of AD and VaD. We focused on studies on ameliorating the risk factors and the pathological changes of these diseases. RESULTS: The Rhizoma coptidis active ingredients include berberine, palmatine, coptisine, epiberberine, jatrorrhizine and protopine. The most widely studied ingredient is berberine, which has extensive therapeutic effects on the risk factors and pathogenesis of dementia. It can control blood glucose and lipid levels, regulate blood pressure, ameliorate atherosclerosis, inhibit cholinesterase activity, Abeta generation, and tau hyperphosphorylation, decrease neuroinflammation and oxidative stress and alleviate cognitive impairment. Other ingredients (such as jatrorrhizine, coptisine, epiberberine and palmatine) also regulate blood lipids and blood pressure; however, there are relatively few studies on them. Rhizoma coptidis-containing Chinese herbal compounds like Huanglian-Jie-Du-Tang, Huanglian Wendan Decoction, Banxia Xiexin Decoction and Huannao Yicong Formula have anti-inflammatory and antioxidant stress activities, regulate insulin signaling, inhibit gamma-secretase activity, neuronal apoptosis, tau hyperphosphorylation, and Abeta deposition, and promote neural stem cell differentiation, thereby improving cognitive function. CONCLUSION: The "One-Molecule, One-Target" paradigm has suffered heavy setbacks, but a "multitarget- directed ligands" strategy may be viable. Rhizoma coptidis active ingredients and Rhizoma coptidiscontaining Chinese herbal compounds have multi-aspect therapeutic effects on AD and VaD.
ESTHER : Wang_2020_Curr.Vasc.Pharmacol_18_358
PubMedSearch : Wang_2020_Curr.Vasc.Pharmacol_18_358
PubMedID: 31291876

Title : A novel lipase from Aspergillus oryzae catalyzed resolution of (R,S)-ethyl 2-bromoisovalerate - Wu_2020_Chirality_32_231
Author(s) : Wu P , Zhang M , Zhang Y , Wang Z , Zheng J
Ref : Chirality , 32 :231 , 2020
Abstract : In this study, a novel lipase M5 derived from Aspergillus oryzae WZ007 was prone to exhibit high hydrolytic activity and stereoselectivity towards racemic substrate (R,S)-ethyl 2-bromoisovalerate. (R)-ethyl 2-bromoisovalerate was obtained by enzymatic resolution, which is the key chiral intermediate for highly efficient enantiomerically fluvalinate. The results showed that the enzymatic reaction was carried out in 120mM racemic substrate for 3 hours, the enantiomeric excess reached 98.6%, the conversion was 51.7%, and E value above 120. Therefore, the novel lipase M5 has the ability to efficiently produce (R)-ethyl 2-bromoisovalerate, which greatly reduces the industrial production cost of the highly efficient counterpart of fluvalinate.
ESTHER : Wu_2020_Chirality_32_231
PubMedSearch : Wu_2020_Chirality_32_231
PubMedID: 31856428
Gene_locus related to this paper: aspor-q2ue03

Title : Kinetics and Mechanism of Solvent Influence on the Lipase-Catalyzed 1,3-Diolein Synthesis - Wang_2020_ACS.Omega_5_24708
Author(s) : Wang Z , Dai L , Liu D , Liu H , Du W
Ref : ACS Omega , 5 :24708 , 2020
Abstract : 1,3-Diacylglycerol preparation has roused increasing attention in recent years as the 1,3-diacylglycerol-rich oils can suppress the deposition of visceral fat and prevent the body weight increasing. Lipozyme TL IM-mediated esterification of oleic acid with monoolein was effective for 1,3-diacylglycerol production. During the esterification process, the solvent shows obvious influence on the diolein synthesis as well as the 1,3-diolein production. This work investigated the related kinetics and mechanism of the solvent effect on the esterification and Lipozyme TL IM performance. The results indicated that both the esterification rate constant and the acyl migration rate constant positively correlated with the logP of the solvent, while the site specificity of lipase has negative correlation with solvent logP. The acylation toward the 2-position of 1-monoolein was more sensitive to the solvent logP compared to the 1-position of glycerides. Molecular dynamics simulation revealed that solvents with different logP influenced the structure of Lipozyme TL IM including RMSD, hydrogen bond, and radial distribution function to a large extent, which subsequently led to the catalytic activity and selectivity variation of the lipase.
ESTHER : Wang_2020_ACS.Omega_5_24708
PubMedSearch : Wang_2020_ACS.Omega_5_24708
PubMedID: 33015488

Title : Preparation of porous materials by selective enzymatic degradation: effect of in vitro degradation and in vivo compatibility - Shi_2020_Sci.Rep_10_7031
Author(s) : Shi K , Ma Q , Su T , Wang Z
Ref : Sci Rep , 10 :7031 , 2020
Abstract : Poly(butylene succinate) (PBS) and poly(lactic acid) (PLA) were melt-blended and formed into a film by hot press forming. The film was selectively degraded by cutinase and proteinase K to form a porous material. The porous materials were characterized with respect to their pore morphology, pore size, porosity and hydrophilicity. The porous materials were investigated in vitro degradation and in vivo compatibility. The results show that the pore size of the prepared porous materials could be controlled by the proportion of PBS and the degradation time. When the PBS composition of PBS/PLA blends was changed from 40 wt% to 50 wt%, the mean pore diameter of the porous materials significantly increased from 6.91 microm to 120 microm, the porosity improved from 81.52% to 96.90%, and the contact angle decreased from 81.08 degrees to 46.56 degrees . In vitro degradation suggests that the PBS-based porous materials have a good corrosion resistance but the PLA-based porous materials have degradability in simulated body fluid. Subcutaneous implantation of the porous materials did not cause intense inflammatory response, which revealed good compatibility. The results of hematoxylin and eosin and Masson's trichrome staining assays demonstrated that the porous materials promote chondrocyte production. Porous materials have great potential in preparing implants for tissue engineering applications.
ESTHER : Shi_2020_Sci.Rep_10_7031
PubMedSearch : Shi_2020_Sci.Rep_10_7031
PubMedID: 32341461
Gene_locus related to this paper: fusso-cutas

Title : DL0410 attenuates oxidative stress and neuroinflammation via BDNF\/TrkB\/ERK\/CREB and Nrf2\/HO-1 activation - Zhang_2020_Int.Immunopharmacol_86_106729
Author(s) : Zhang B , Zhao J , Wang Z , Xu L , Liu A , Du G
Ref : Int Immunopharmacol , 86 :106729 , 2020
Abstract : Oxidative stress and neuroinflammation have been deeply associated with Alzheimer's disease. DL0410 is a novel acetylcholinesterase inhibitor with potential anti-oxidative effects in AD-related animal models, while the specific mechanism has not been fully clarified. In this study, DL0410 was predicted to be related to the modification of cell apoptosis, oxidation-reduction process, inflammatory response and ERK1/ERK2 cascade by in silico target fishing and GO enrichment analysis. Then the possible protective effects of DL0410 were evaluated by hydrogen peroxide (H2O2)-induced oxidative stress model and lipopolysaccharides (LPS)-induced neuroinflammation model H2O2 decreased the viability of SH-SY5Y cells, induced malondialdehyde (MDA) accumulation, mitochondrial membrane potential (Deltapsim) loss and cell apoptosis, which could be reversed by DL0410 dose-dependently, indicating that DL0410 protected SH-SY5Y cells against H2O2-mediated oxidative stress. Western blot analysis showed that DL0410 increased the H2O2-triggered down-regulated TrkB, ERK and CREB phosphorylation and the expression of BDNF. In addition, TrkB inhibitor ANA-12, ERK inhibitor SCH772984 and CREB inhibitor 666-15 eliminated the inhibition of DL0410 on MDA accumulation and Deltapsim loss. Furthermore, DL0410 attenuates inflammatory responses and ROS production in LPS-treated BV2 cells, which is responsible for Nrf2 and HO-1 up-regulation. The present study demonstrates that DL0410 is a potential activator of the BDNF/TrkB/ERK/CREB and Nrf2/HO-1 pathway and may be a potential candidate for regulating oxidative stress and neuroinflammatory response in the brain. Together, the results showed that DL0410 is a promising drug candidate for treating AD and possibly other nervous system diseases associated with oxidative stress and neuroinflammation.
ESTHER : Zhang_2020_Int.Immunopharmacol_86_106729
PubMedSearch : Zhang_2020_Int.Immunopharmacol_86_106729
PubMedID: 32645628

Title : Direct, selective and ultrasensitive electrochemical biosensing of methyl parathion in vegetables using Burkholderia cepacia lipase@MOF nanofibers-based biosensor - Wang_2019_Talanta_197_356
Author(s) : Wang Z , Ma B , Shen C , Cheong LZ
Ref : Talanta , 197 :356 , 2019
Abstract : Methyl parathion is one of the most widely used pesticides in agricultural practices. It caused accumulation of acetylcholine and over-stimulation of receptors in synapses which eventually led to damage of the nervous system. Present study developed a direct, sensitive, rapid and reliable method for methyl parathion residues detection in vegetable samples. MOF nanofibers which demonstrated stable framework structure, good thermal/chemical stability, good electrochemical behavior, high porosity, surface area and pore volume was synthesized and used for fabrication of Burkholderia cepacia lipase (BCL)@MOF nanofibers biosensors. BCL@MOF nanofibers/chitosan/GCE biosensor demonstrated high sensitivity for methyl detection with a wide linear range (0.1-38microM) and low limit of detection 0.067microM. During the 3 weeks storage stability test at 4 degrees C, the fabricated biosensor demonstrated good reusability and excellent stability for methyl parathion detection with retainment of more than 80% of its initial response. When applied for detection of methyl parathion residues in vegetable samples, the BCL@MOF nanofibers/chitosan/GCE biosensors demonstrated good recovery rates.
ESTHER : Wang_2019_Talanta_197_356
PubMedSearch : Wang_2019_Talanta_197_356
PubMedID: 30771947

Title : Neuroligin 3 Regulates Dendritic Outgrowth by Modulating Akt\/mTOR Signaling - Xu_2019_Front.Cell.Neurosci_13_518
Author(s) : Xu J , Du YL , Xu JW , Hu XG , Gu LF , Li XM , Hu PH , Liao TL , Xia QQ , Sun Q , Shi L , Luo JH , Xia J , Wang Z
Ref : Front Cell Neurosci , 13 :518 , 2019
Abstract : Neuroligins (NLs) are a group of postsynaptic cell adhesion molecules that function in synaptogenesis and synaptic transmission. Genetic defects in neuroligin 3 (NL3), a member of the NL protein family, are associated with autism. Studies in rodents have revealed that mutations of NL3 gene lead to increased growth and complexity in dendrites in the central nervous system. However, the detailed mechanism is still unclear. In our study, we found that deficiency of NL3 led to morphological changes of the pyramidal neurons in layer II/III somatosensory cortex in mice, including enlarged somata, elongated dendritic length, and increased dendritic complexity. Knockdown of NL3 in cultured rat neurons upregulated Akt/mTOR signaling, resulting in both increased protein synthesis and dendritic growth. Treating neurons with either rapamycin to inhibit the mTOR or LY294002 to inhibit the PI3K/Akt activity rescued the morphological abnormalities resulting from either NL3 knockdown or knockout (KO). In addition, we found that the hyperactivated Akt/mTOR signaling associated with NL3 defects was mediated by a reduction in phosphatase and tensin (PTEN) expression, and that MAGI-2, a scaffold protein, interacted with both NL3 and PTEN and could be a linker between NL3 and Akt/mTOR signaling pathway. In conclusion, our results suggest that NL3 regulates neuronal morphology, especially dendritic outgrowth, by modulating the PTEN/Akt/mTOR signaling pathway, probably via MAGI-2. Thereby, this study provides a new link between NL3 and neuronal morphology.
ESTHER : Xu_2019_Front.Cell.Neurosci_13_518
PubMedSearch : Xu_2019_Front.Cell.Neurosci_13_518
PubMedID: 31849609

Title : Mechanism-based pharmacokinetics-pharmacodynamics studies of harmine and harmaline on neurotransmitters regulatory effects in healthy rats: Challenge on monoamine oxidase and acetylcholinesterase inhibition - Jiang_2019_Phytomedicine_62_152967
Author(s) : Jiang B , Meng L , Zou N , Wang H , Li S , Huang L , Cheng X , Wang Z , Chen W , Wang C
Ref : Phytomedicine , 62 :152967 , 2019
Abstract : BACKGROUND: beta-Carboline alkaloid harmine (HAR) and harmaline (HAL) are monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitors. However, whether HAR and HAL inhibit MAO or AChE selectively and competitively is unclear. PURPOSE: The purpose of this study was to investigate the potential competition inhibition of HAR and HAL on MAO and AChE in brain endothelial cells (RBE4) and in healthy rats to provide a basis for the application of the inhibitors in the treatment of patients with depression and with Parkinson's disease or Alzheimer's disease. STUDY DESIGN/METHODS: The transport properties of HAR and HAL by using blood-brain barrier models constructed with RBE4 were systematically investigated. Then, the modulation effects of HAR and HAL on CNS neurotransmitters (NTs) in healthy rat brains were determined by a microdialysis method coupled with LC-MS/MS. The competition inhibition of HAR and HAL on MAO and AChE was evaluated through real time-PCR, Western blot analysis, and molecular docking experiments. RESULTS: Results showed that HAL and HAR can be detected in the blood and striatum 300min after intravenous injection (1mg/kg). Choline (Ch), gamma-aminobutyric acid (GABA), glutamate (Glu), and phenylalanine (Phe) levels in the striatum decreased in a time-dependent manner after the HAL treatment, with average velocities of 1.41, 0.73, 3.86, and 1.10 (ng/ml)/min, respectively. The Ch and GABA levels in the striatum decreased after the HAR treatment, with average velocities of 1.16 and 0.22ng/ml/min, respectively. The results of the cocktail experiment using the human liver enzyme indicated that the IC50 value of HAL on MAO-A was 0.10 +/- 0.08microm and that of HAR was 0.38 +/- 0.21microm. Their IC50 values on AChE were not obtained. These findings indicated that HAL and HAR selectively acted on MAO in vitro. However, RT-PCR and Western blot analysis results showed that the AChE mRNA and protein expression decreased in a time-dependent manner in RBE4 cells after the HAR and HAL treatments. CONCLUSION: NT analysis results showed that HAL and HAR selectively affect AChE in vivo. HAL and HAR may be highly and suitably developed for the treatment of Alzheimer's disease.
ESTHER : Jiang_2019_Phytomedicine_62_152967
PubMedSearch : Jiang_2019_Phytomedicine_62_152967
PubMedID: 31154274

Title : Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors - Park_2019_Nat.Struct.Mol.Biol_26_1151
Author(s) : Park YJ , Walls AC , Wang Z , Sauer MM , Li W , Tortorici MA , Bosch BJ , DiMaio F , Veesler D
Ref : Nat Struct Mol Biol , 26 :1151 , 2019
Abstract : The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often lethal respiratory illness in humans, and no vaccines or specific treatments are available. Infections are initiated via binding of the MERS-CoV spike (S) glycoprotein to sialosides and dipeptidyl-peptidase 4 (the attachment and entry receptors, respectively). To understand MERS-CoV engagement of sialylated receptors, we determined the cryo-EM structures of S in complex with 5-N-acetyl neuraminic acid, 5-N-glycolyl neuraminic acid, sialyl-Lewis(X), alpha2,3-sialyl-N-acetyl-lactosamine and alpha2,6-sialyl-N-acetyl-lactosamine at 2.7-3.0 A resolution. We show that recognition occurs via a conserved groove that is essential for MERS-CoV S-mediated attachment to sialosides and entry into human airway epithelial cells. Our data illuminate MERS-CoV S sialoside specificity and suggest that selectivity for alpha2,3-linked over alpha2,6-linked receptors results from enhanced interactions with the former class of oligosaccharides. This study provides a structural framework explaining MERS-CoV attachment to sialoside receptors and identifies a site of potential vulnerability to inhibitors of viral entry.
ESTHER : Park_2019_Nat.Struct.Mol.Biol_26_1151
PubMedSearch : Park_2019_Nat.Struct.Mol.Biol_26_1151
PubMedID: 31792450

Title : Traditional Chinese Medicine Shenmayizhi Decoction Ameliorates Memory And Cognitive Impairment Induced By Scopolamine Via Preventing Hippocampal Cholinergic Dysfunction In Rats - Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
Author(s) : Wu Q , Cao Y , Liu M , Liu F , Brantner AH , Yang Y , Wei Y , Zhou Y , Wang Z , Ma L , Wang F , Pei H , Li H
Ref : Neuropsychiatr Dis Treat , 15 :3167 , 2019
Abstract : Purpose: Clinical trials have illustrated that Shenmayizhi decoction (SMYZ) could improve the cognitive functions in patients with dementia. However, the mechanism needs to be explored. Methods: Fifty adult male rats (Wistar strain) were divided into five groups equally and randomly, including control, model, and SMYZ of low dose, medium dose and high dose. Rats in each group received a daily gavage of respective treatment. Rats in control and model group were administrated by the same volume of distilled water. Memory impairment was induced by intraperitoneal administration of scopolamine (0.7 mg/kg) for 5 continuous days. Four weeks later, Morris water maze (MWM) was performed to evaluate the spatial memory in all rats. Then, rats were sacrificed and the hippocampus was removed for further tests. Furthermore, Western blot analysis was employed to assess the levels of acetylcholine M1 receptor (M1), acetylcholine M2 receptor (M2), acetylcholinesterase (AChE) and cholineacetyltransferase (ChAT). AChE and ChAT activities were determined. Results: The SMYZ decoction significantly improved behavioral performance of rats in high dose. The SMYZ decoction in three doses exhibited anti-acetylcholinesterase activity. In addition, a high dose of SMYZ promoted ChAT activity. Moreover, a high dose of SMYZ increased the level of ChAT and declined the level of AChE assessed by Western blotting. Besides, an increased level of M1 receptor was found after treatment. Conclusion: Shenmayizhi decoction could mitigate scopolamine-induced cognitive deficits through the preventative effect on cholinergic system dysfunction.
ESTHER : Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
PubMedSearch : Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
PubMedID: 31814724

Title : Discovery of delta-sultone-fused pyrazoles for treating Alzheimer's disease: Design, synthesis, biological evaluation and SAR studies - Xu_2019_Eur.J.Med.Chem_181_111598
Author(s) : Xu Y , Zhang Z , Jiang X , Chen X , Wang Z , Alsulami H , Qin HL , Tang W
Ref : Eur Journal of Medicinal Chemistry , 181 :111598 , 2019
Abstract : A class of novel delta-sulfonolactone-fused pyrazole scaffold was prepared via sulfur (VI) fluoride exchange (SuFEx) chemistry using aryl sulfonyl fluorides and pyrazolones. Enzyme screening revealed their cholinesterase inhibitory activity, among them, compounds 4a, 5a and 5d were identified as highly selective submicromolar BuChE inhibitors (IC50=0.20, 0.46 and 0.42muM, respectively), which exhibited nontoxicity, lipophilicity and remarkable neuroprotective activity. Kinetic studies showed that BuChE inhibition of compounds 5a and 5d was reversible, mixed-type and non-competitive inhibition against BuChE (Ki=145nM and 60nM, respectively). Compound 5d can be accommodated into hBuChE via pi-S interaction and hydrophobic interactions. The title compounds are potentially symptomatic treatment in progressive Alzheimer's disease.
ESTHER : Xu_2019_Eur.J.Med.Chem_181_111598
PubMedSearch : Xu_2019_Eur.J.Med.Chem_181_111598
PubMedID: 31415981

Title : Surface functionalization of graphene oxide by amino acids for Thermomyces lanuginosus lipase adsorption - Zhou_2019_J.Colloid.Interface.Sci_546_211
Author(s) : Zhou W , Zhuang W , Ge L , Wang Z , Wu J , Niu H , Liu D , Zhu C , Chen Y , Ying H
Ref : J Colloid Interface Sci , 546 :211 , 2019
Abstract : Graphene oxide (GO) with oxygen containing functional groups can be selectively modified by small biomolecules to achieve heterogeneous surface properties. To achieve a hyper-enzymatic activity, the surface functionality of GO should be tailored to the orientation adsorption of the Thermomyces lanuginosus (TL) lipase, and the active center can be covered by a relatively hydrophobic helical lid for protection. In this work, amino acids were used to interact with GO through reduction reaction, hydrophobic forces, electrostatic forces, or hydrogen bonding to alter the surface hydrophobicity and charge density. Characterization of the structure and surface properties confirmed that the GO samples decorated with phenylalanine (Phe) and glutamic acid (Glu) exhibited superior hydrophobicity than other modifications, whereas tryptophan (Trp) and cysteine (Cys) provided weaker reduction effects on GO. Moreover, the zeta potential of the samples modified by amino acids of lysine (Lys) and arginine (Arg) is higher than other modified samples. The adsorption amount of lipase on Glu-GO reached 172mg/g and the relative enzymatic activity reached up to 200%. The thermodynamic data and the Freundlich isotherm model fitting showed that the lipase adsorption process on modified samples was spontaneous, endothermic and entropy increase.
ESTHER : Zhou_2019_J.Colloid.Interface.Sci_546_211
PubMedSearch : Zhou_2019_J.Colloid.Interface.Sci_546_211
PubMedID: 30921675

Title : High-level expression and characterization of a stereoselective lipase from Aspergillus oryzae in Pichia pastoris - Zheng_2019_Protein.Expr.Purif_155_1
Author(s) : Zheng JY , Lan X , Li XJ , Huang LJ , Zhang YJ , Wang Z
Ref : Protein Expr Purif , 155 :1 , 2019
Abstract : Pichia pastoris expression is a mature and efficient eukaryotic expression system. In this work, Aspergillus oryzae lipase (AOL, with the molecular mass of 28 kDa), which can perform highly stereoselective hydrolysis of (R, S)-methyl 2-(4-hydroxyphenoxy) propanoate, was expressed in P. pastoris X-33. The specific activity of AOL was 432 U/mg, which was obtained by fed-batch cultivation in a 5 L bioreactor using a methanol feeding strategy. After fermentation, the supernatant was concentrated by ultrafiltration with a 10 kDa cut-off membrane and purified with DEAE-Sepharose FF ion-exchange chromatography and phenyl Seflnose 6 FF hydrophobic interaction chromatography. The purified lipase activity reached 5509 U/mg. AOL showed high activity toward short-chain triacylglyceride (C(4)), and the optimum temperature and pH were 40 degreesC and 8.0, respectively. The purified enzyme activity was inhibited by Zn(2+) and Cu(2+). Moreover, the K(m) and V(max) values were 1 mM and 32.89 mmol/min, respectively.
ESTHER : Zheng_2019_Protein.Expr.Purif_155_1
PubMedSearch : Zheng_2019_Protein.Expr.Purif_155_1
PubMedID: 30389593
Gene_locus related to this paper: aspor-TGLA

Title : Single and joint oxidative stress-related toxicity of sediment-associated cadmium and lead on Bellamya aeruginosa - Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
Author(s) : Liu X , Chen Q , Ali N , Zhang J , Wang M , Wang Z
Ref : Environ Sci Pollut Res Int , 26 :24695 , 2019
Abstract : The biotoxicity of heavy metals in sediments toward benthic organisms has evoked great concern for the health of freshwater ecosystems. This study applied a sediment toxicity testing protocol to investigate the single and joint toxicity of cadmium (Cd) and lead (Pb) on Bellamya aeruginosa. B. aeruginosa were exposed to different concentrations of Cd (5, 25, and 100 mg/kg), Pb (20, 100, and 400 mg/kg), and their different concentration combinations. A suite of biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), metallothionein (MT), malondialdehyde (MDA), and acetylcholinesterase (AChE), were measured after 7, 14, 21, and 28 days of exposure to evaluate their oxidative stress status. Cell apoptosis of soft tissue was also determined after exposure. Results revealed that these endpoints represented sensitive biomarkers for the characterization of the oxidative stress response induced by these metals. Specifically, a decrease of SOD and GPx and an increase of MDA were indicative of the potential failure of the antioxidant defense system in neutralizing the reactive oxygen species (ROS) generated in the exposure of the Pb-treated group. The integrated biomarker response (IBR) index revealed the most significant sub-lethal toxicity for Pb-spiked sediments, leading to the highest rate of cell apoptosis (70.8%). Exposure to Cd resulted in a time- and dose-dependent effect on MT levels, which suggested active detoxification of this metal. Exposure to the mixture resulted in amelioration of Pb toxicity, likely due to the competitive binding of Cd to active enzyme, with the result of an observed antagonistic interaction. This study indicated that B. aeruginosa represents a good biomonitor for assessing Cd and Pb contamination of sediments, and laid the foundation for their potential risk assessments in freshwater ecosystems.
ESTHER : Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
PubMedSearch : Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
PubMedID: 31240645

Title : Visual detection of mixed organophosphorous pesticide using QD-AChE aerogel based microfluidic arrays sensor - Hu_2019_Biosens.Bioelectron_136_112
Author(s) : Hu T , Xu J , Ye Y , Han Y , Li X , Wang Z , Sun D , Zhou Y , Ni Z
Ref : Biosensors & Bioelectronics , 136 :112 , 2019
Abstract : In this paper, we present a simple strategy to fabricate a sensitive fluorescence microfluidic sensor based on quantum dots (QDs) aerogel and acetylcholinesterase enzyme (AChE) for organophosphate pesticides (OPs) detection The detection is based on the change of fluorescence intensity of QDs aerogel, which will be partly quenched as a consequence of the hydrolytic reaction of acetylthiocholine (ATCh) catalyzed by the AChE, and then the fluorescence of QDs aerogel is recovered due to decreasing of the enzymatic activity in the presence of OPs. The QDs-AChE aerogel based microfluidic arrays sensor provided good sensitivity for rapid detection of OPs with a detection limit of 0.38 pM, while the detection range is from 10(-5) to 10(-12)M. Due to the result of random orientations of AChE in the 3D porous aerogel nano-structure, the sensor presents similar calibration curves to difference pesticides, which promises the ability of the sensor to monitor total OPs of mixture. This determination sensor shows a low detection limit, wide linear range, and highly accurate determination of total OPs and carbamate content. Finally, we show the proposed sensor can be used to monitor of simple OPs and mixture in spiked fruit samples. This novel QDs-AChE aerogel sensor has an extremely high sensitivity and large detection range, it is a promising tool for accurate, rapid and cost-effective detection of various OP residues on agricultural products.
ESTHER : Hu_2019_Biosens.Bioelectron_136_112
PubMedSearch : Hu_2019_Biosens.Bioelectron_136_112
PubMedID: 31054518

Title : Different EPHX1 methylation levels in promoter area between carbamazepine-resistant epilepsy group and carbamazepine-sensitive epilepsy group in Chinese population - Lv_2019_BMC.Neurol_19_114
Author(s) : Lv Y , Zheng X , Shi M , Wang Z , Cui L
Ref : BMC Neurol , 19 :114 , 2019
Abstract : BACKGROUND: Epigenetics underlying refractory epilepsy is poorly understood. DNA methylation may affect gene expression in epilepsy patients without affecting DNA sequences. Herein, we investigated the association between Carbamazepine-resistant (CBZ-resistant) epilepsy and EPHX1 methylation in a northern Han Chinese population, and conducted an analysis of clinical risk factors for CBZ-resistant epilepsy. METHODS: Seventy-five northern Han Chinese patients participated in this research. 25 cases were CBZ-resistant epilepsy, 25 cases were CBZ-sensitive epilepsy and the remaining 25 cases were controls. Using a CpG searcher was to make a prediction of CpG islands; bisulfite sequencing PCR (BSP) was applied to test the methylation of EPHX1. We then did statistical analysis between clinical parameters and EPHX1 methylation. RESULTS: There was no difference between CBZ-resistant patients, CBZ-sensitive patients and healthy controls in matched age and gender. However, a significant difference of methylation levels located in NC_000001.11 (225,806,929.....225807108) of the EPHX1 promoter was found in CBZ-resistant patients, which was much higher than CBZ-sensitive and controls. Additionally, there was a significant positive correlation between seizure frequency, disease course and EPHX1 methylation in CBZ-resistant group. CONCLUSION: Methylation levels in EPHX1 promoter associated with CBZ-resistant epilepsy significantly. EPHX1 methylation may be the potential marker for CBZ resistance prior to the CBZ therapy and potential target for treatments.
ESTHER : Lv_2019_BMC.Neurol_19_114
PubMedSearch : Lv_2019_BMC.Neurol_19_114
PubMedID: 31164100

Title : Enzymatic hydrolysis of polyester: Degradation of poly(epsilon-caprolactone) by Candida antarctica lipase and Fusarium solani cutinase - Shi_2020_Int.J.Biol.Macromol_144_183
Author(s) : Shi K , Jing J , Song L , Su T , Wang Z
Ref : Int J Biol Macromol , 144 :183 , 2019
Abstract : Poly(epsilon-caprolactone) (PCL) particles were melt-pressed into films using a hot press and then subjected to degradation by lipase from Candida antarctica and cutinase from Fusarium solani, respectively. The differences in weight loss, degradation modes, thermal stability, and crystallization were investigated after degradation by two kinds of enzymes. The result showed that mass loss of PCL films degraded by lipase was higher than that degraded by cutinase at the same enzyme concentrations. The degradation mode of PCL films is layered for cutinase degradation and penetrated for lipase degradation. Crystallinity of PCL had no obvious decrease after degradation by cutinase, but it markedly decreased after lipase-degradation. PCL films occurred one-step decomposition during heating and the cutinase-degraded products had similar thermal stability. Whereas the thermal stability of lipase-degraded PCL decreased significantly and the weight loss of the PCL occurred in several steps with increasing lipase hydrolysis time.
ESTHER : Shi_2020_Int.J.Biol.Macromol_144_183
PubMedSearch : Shi_2020_Int.J.Biol.Macromol_144_183
PubMedID: 31843602

Title : Bioaccumulation, behavior changes and physiological disruptions with gender-dependent in lizards (Eremias argus) after exposure to glufosinate-ammonium and l-glufosinate-ammonium - Zhang_2019_Chemosphere_226_817
Author(s) : Zhang L , Chen L , Meng Z , Zhang W , Xu X , Wang Z , Qin Y , Deng Y , Liu R , Zhou Z , Diao J
Ref : Chemosphere , 226 :817 , 2019
Abstract : Reptiles, the most diverse taxon of terrestrial vertebrates, might be particularly vulnerable to soil pollution. Reptiles especially lizards have been rarely evaluated in ecotoxicological studies, and there is a very limited report for effects of soil pesticide contaminants on lizards. In this study, male and female lizards (Eremias argus) were exposed to Glufosinate-ammonium (GLA) and l- Glufosinate-ammonium (L-GLA) for 60 days. Slower sprint speed, higher frequency of turning back and reduced brain index were observed in treatment groups. The accumulation of GLA in the brain of lizard was higher than that of L-GLA. Moreover, the activities of neurotoxicity-related enzymes and biomarkers of oxidative stress were also investigated. In summary, the neurotoxic effects of lizards have been observed after exposure to GLA and L-GLA. Based on the result of the Integrated Biomarker Response (IBR), males were more sensitive to contaminants than females. On the other hand, the neurotoxic pathways by GLA and L-GLA triggered were slightly different: GLA mainly acted on glutamine synthetase (GS), acetylcholinesterase (AchE) and Catalase (CAT) and L-GLA aimed at AchE, Na(+)/K(+)-ATPase, Superoxide dismutase (SOD) and Malondialdehyde (MDA). In summary, the accumulation of GLA and L-GLA in lizard's brain induced neurotoxicity by altering the levels of enzymes related to nervous system and antioxidant activity and further resulted in the decrease of brain index and locomotor performance.
ESTHER : Zhang_2019_Chemosphere_226_817
PubMedSearch : Zhang_2019_Chemosphere_226_817
PubMedID: 30965253

Title : Fabrication and Properties of a Bio-Based Biodegradable Thermoplastic Polyurethane Elastomer - Wang_2019_Polymers.(Basel)_11_
Author(s) : Wang Z , Yan J , Wang T , Zai Y , Qiu L , Wang Q
Ref : Polymers (Basel) , 11 : , 2019
Abstract : Using the melt polycondensation of five bio-based aliphatic monomers (succinic acid, sebacic acid, fumaric acid, 1,3-propanediol, and 1,4-butanediol), we first synthesized the more flexible and biodegradable polyester diols (BPD) with an average molecular weight of 3825. Then, the BPD was polymerized with excessive 4,4'-diphenylmethane diisocyanate (MDI). Finally, the molecular chain extender of 1,4-butanediol (BDO) was used to fabricate the biodegradable thermoplastic polyurethane elastomer (BTPU), comprising the soft segment of BPD and the hard segment polymerized by MDI and BDO. Atomic force microscope (AFM) images showed the two-phase structure of the BTPU. The tensile strength of the BTPU containing 60% BPD was about 30 MPa and elongation at break of the BTPU was over 800%. Notably, the BTPU had superior biodegradability in lipase solution and the biodegradation weight loss ratio of the BTPU containing 80% BPD reached 36.7% within 14 days in the lipase solution.
ESTHER : Wang_2019_Polymers.(Basel)_11_
PubMedSearch : Wang_2019_Polymers.(Basel)_11_
PubMedID: 31269638

Title : Subchronic effects of dietary selenium yeast and selenite on growth performance and the immune and antioxidant systems in Nile tilapia Oreochromis niloticus - Chen_2019_Fish.Shellfish.Immunol_97_283
Author(s) : Chen H , Li J , Yan L , Cao J , Li D , Huang GY , Shi WJ , Dong W , Zha J , Ying GG , Zhong H , Wang Z , Huang Y , Luo Y , Xie L
Ref : Fish Shellfish Immunol , 97 :283 , 2019
Abstract : Selenium is an essential element but toxic at high levels in animals. The effects of Se on growth performance and the immune system in Nile tilapia remain inconclusive. In this study, Nile tilapia Oreochromis niloticus was fed on selenium yeast (Se(Y))- and selenite (Se(IV))-enriched feed at 0, 3, 6, and 12 mug/g (dry wt) for 45 and 90 d. The growth, bioaccumulation, biochemical markers related to antioxidant, immunological, nervous and digestive systems were evaluated in various fish tissues (liver, intestine, kidney, muscle, brain, spleen, gills). The results showed that the accumulation of Se(Y) was 1.3-2 folds of Se(IV) in most tissues. The growth of tilapia was enhanced by both Se(Y) and Se(IV) at 3 mug/g after 90 d, with Se(Y) better than Se(IV) in tilapia feed. After 45 d, the levels of lipid peroxidation, the activity of the antioxidant enzymes, and the transcriptional levels of the immune related genes (IL-1beta, IFN-gamma and TNF-alpha) and stress proteins (HSP70 and MT) were enhanced in all treatments, except that of MT in the 12 mug/g Se(Y) group. In addition, both Se species inhibited the activity of acetylcholinesterase (AChE) in the brain and one digestive enzyme alpha-glucosidase (alpha-Glu) in the intestine at 12 mug/g. However, after 90 d, the effects on most biochemical markers were less pronounced, implying a possible acclimation after prolonged duration. The results demonstrate Se is beneficial to O. niloticus at low levels and toxic at elevated levels. The immunostimulation by Se might be greatly weakened after long term feeding Se-enriched feed. This study helps to better understand the effects of Se on the antioxidant and immune systems and to establish the optimal Se levels in the feed and duration for O. niloticus.
ESTHER : Chen_2019_Fish.Shellfish.Immunol_97_283
PubMedSearch : Chen_2019_Fish.Shellfish.Immunol_97_283
PubMedID: 31863904

Title : Liver function and energy metabolism in hepatocellular carcinoma developed in patients with hepatitis B-related cirrhosis - Ren_2019_Medicine.(Baltimore)_98_e15528
Author(s) : Ren M , Li J , Xue R , Wang Z , Coll SL , Meng Q
Ref : Medicine (Baltimore) , 98 :e15528 , 2019
Abstract : Energy metabolism in patients with Hepatocellular carcinoma (HCC) accompanying by hepatitis B cirrhosis is unknown.To compare the differences in liver functions and energy metabolism between patients with hepatitis B-related cirrhosis and patients with HCC.This was a retrospective study of patients with hepatitis B-related cirrhosis (LC group, n = 75) and patients with HCC accompanying by hepatitis B cirrhosis (HCC group, n = 80) treated in Beijing You'an Hospital between January 2013 and June 2017. The resting energy expenditure (REE), respiratory quotient (RQ), carbohydrate oxidation rate (CHO%), fat oxidation rate (FAT%), and protein oxidation rate (PRO%) were measured using a metabolic cart. Liver function, renal function, blood coagulation, etc. were collected.Compared to the LC group, patients with HCC had normal metabolism, but RQ (0.83 +/- 0.07 vs 0.85 +/- 0.08, P = .073) and CHO% (35.5% vs 49%, P = .013) were lower and FAT% was higher (41% vs 33%, P = .030). Compared with patients with LC group, albumin (ALB), gamma-glutamyltranspeptadase (GGT), alkaline phosphatase (AKP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and prothrombin time activity (PTA) were elevated in the HCC group, while total bilirubin (TB), total bile acid (TBA), and international normalized ratio (INR) were reduced (P < .05). Cholinesterase (CHE) was positively correlated with RQ, CHO, and CHO% (P < .05), while negatively correlated with FAT and FAT% (P < .05). AKP was negatively correlated with RQ, CHO, and CHO% (P < .05), while positively correlated with FAT and FAT% (P < .05). TBA was negatively correlated with RQ and CHO (P < .05), while positively correlated with FAT (P < .05).HCC leads to increased liver synthetic function and improve the liver functions of patients with LC, at least to some extent, but the nutritional metabolism was poor.
ESTHER : Ren_2019_Medicine.(Baltimore)_98_e15528
PubMedSearch : Ren_2019_Medicine.(Baltimore)_98_e15528
PubMedID: 31083199

Title : Musa balbisiana genome reveals subgenome evolution and functional divergence - Wang_2019_Nat.Plants_5_810
Author(s) : Wang Z , Miao H , Liu J , Xu B , Yao X , Xu C , Zhao S , Fang X , Jia C , Wang J , Zhang J , Li J , Xu Y , Ma W , Wu Z , Yu L , Yang Y , Liu C , Guo Y , Sun S , Baurens FC , Martin G , Salmon F , Garsmeur O , Yahiaoui N , Hervouet C , Rouard M , Laboureau N , Habas R , Ricci S , Peng M , Guo A , Xie J , Li Y , Ding Z , Yan Y , Tie W , D'Hont A , Hu W , Jin Z
Ref : Nat Plants , 5 :810 , 2019
Abstract : Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars.
ESTHER : Wang_2019_Nat.Plants_5_810
PubMedSearch : Wang_2019_Nat.Plants_5_810
PubMedID: 31308504
Gene_locus related to this paper: musam-m0tuu7 , musam-a0a804kav5

Title : Purification and characterization of a thermoalkaliphilic esterase from Bacillus cereus WZZ006 for enantioselective resolution of indoxacarb intermediate - Zhang_2019_Int.J.Biol.Macromol_140_358
Author(s) : Zhang H , Xia Y , Zhou M , Zheng J , Wang Z , Zhang Y
Ref : Int J Biol Macromol , 140 :358 , 2019
Abstract : An intracellular esterase (BCE) from Bacillus cereus WZZ006 was purified to homogeneity with an 89.5-fold purification, specific activity of 1.79U/mg, and 26.7% recovery. The estimated molecular weight of BCE was 96kDa which was analyzed by SDS-PAGE and MALDI-TOF-MS. Activity staining denotes that BCE has an unexplored new carboxyl esterase characteristic. BCE enzyme activity was maximum at pH8.5 and also at 50 degrees C with pNP-caproate as a substrate. This indicates that the studied BCE as a thermoalkaliphilic esterase. The kinetic properties like Km, Vmax, kcat and kcat/Km value for BCE was found to be 0.98mM, 0.03mM/min, 69.47min(-1) and 70.89mM(-1)min(-1), respectively. Synthesis of (S)-5-chloro-1-oxo-2,3-dihydro-2-hydroxy-1H-indole-2-carboxylic acid methyl ester ((S)-CODHCM) by BCE can be shortened to 3h compared to 36h with whole-cell catalysis. The e.e.s achieved was 93.83%, and conversion around 52.78% with E being 39.95. These features render BCE as a promising biocatalyst for the synthesis of a key chiral intermediate for indoxacarb.
ESTHER : Zhang_2019_Int.J.Biol.Macromol_140_358
PubMedSearch : Zhang_2019_Int.J.Biol.Macromol_140_358
PubMedID: 31430490

Title : Toxicity and possible mechanisms of action of honokiol from Magnolia denudata seeds against four mosquito species - Wang_2019_Sci.Rep_9_411
Author(s) : Wang Z , Perumalsamy H , Wang X , Ahn YJ
Ref : Sci Rep , 9 :411 , 2019
Abstract : This study was performed to determine the toxicity and possible mechanism of the larvicidal action of honokiol, extracted from Magnolia denudata seeds, and its 10 related compounds against third-instar larvae of insecticide-susceptible Culex pipiens pallens, Aedes aegypti, and Aedes albopictus and Anopheles sinensis resistant to deltamethrin and temephos. Honokiol (LC50, 6.13-7.37 mg/L) was highly effective against larvae of all of the four mosquito species, although the toxicity of the compound was lower than that of the synthetic larvicide temephos. Structure-activity relationship analyses indicated that electron donor and/or bulky groups at the ortho or para positions of the phenol were required for toxicity. Honokiol moderately inhibited acetylcholinesterase and caused a considerable increase in cyclic AMP levels, indicating that it might act on both acetylcholinesterase and octopaminergic receptors. Microscopy analysis clearly indicated that honokiol was mainly targeted to the midgut epithelium and anal gills, resulting in variably dramatic degenerative responses of the midgut through sequential epithelial disorganization. Honokiol did not affect the AeCS1 mRNA expression level in Ae. aegypti larvae, but did enhance expression of the genes encoding vacuolar-type H(+)-ATPase and aquaporin 4, indicating that it may disturb the Na(+), Cl(-) and K(+) co-transport systems. These results demonstrate that honokiol merits further study as a potential larvicide, with a specific target site, and as a lead molecule for the control of mosquito populations.
ESTHER : Wang_2019_Sci.Rep_9_411
PubMedSearch : Wang_2019_Sci.Rep_9_411
PubMedID: 30674912

Title : Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways - Li_2019_Biol.Res_52_10
Author(s) : Li W , Yu X , Zhu C , Wang Z , Zhao Z , Li Y , Zhang Y
Ref : Biol Res , 52 :10 , 2019
Abstract : BACKGROUND: Non-canonical Wnt pathways play important roles in liver fibrosis. Notum is a newly discovered inhibitor to Wnt proteins. This study was to investigate anti-fibrotic effects of Notum. METHODS: 53 patients with hepatitis B virus (HBV) infection as well as a cell co-culture system of LX-2 and Hep AD38 cells were engaged in this study. Clinical, biological and virological data of each patient were analyzed. Cell viability was detected at different time points. mRNA and protein levels of NFATc1 (Nuclear factor of activated T-cells), Jnk, alpha-SMA, Col1A1 and TIMP-1 were detected both in LX-2 and liver tissue. Protein levels of NFATc1 and Jnk in liver tissue and their correlations with fibrosis score were analyzed. RESULTS: Hepatitis B virus replication up-regulated Wnt5a induced NFATc1 and Jnk activity in Hep AD38. Notum suppressed NFATc1, Jnk and fibrosis genes expression, reduced cell viability in co-cultured LX-2 cells induced by HBV. Interestingly, Patients with HBV DNA > 5log copies/ml had higher mRNA levels of NFATc1 and fibrosis genes than patients with HBV DNA < 5log copies/ml. Most importantly, protein expressions of NFATc1 and pJnk have positive correlations with liver fibrosis scores in HBV-infected patients. CONCLUSIONS: Our data showed that Notum inhibited HBV-induced liver fibrosis through down-regulating Wnt 5a mediated non-canonical pathways. This study shed light on anti-fibrotic treatment.
ESTHER : Li_2019_Biol.Res_52_10
PubMedSearch : Li_2019_Biol.Res_52_10
PubMedID: 30871618
Gene_locus related to this paper: human-NOTUM

Title : Aryl-phosphorus-containing flame retardants induce oxidative stress, the p53-dependent DNA damage response and mitochondrial impairment in A549 cells - Yuan_2019_Environ.Pollut_250_58
Author(s) : Yuan S , Han Y , Ma M , Rao K , Wang Z , Yang R , Liu Y , Zhou X
Ref : Environ Pollut , 250 :58 , 2019
Abstract : Aryl phosphorus-containing flame retardants (aryl-PFRs) have been frequently detected with increasingly used worldwide as one of alternatives for brominated flame retardants. However, information on their adverse effects on human health and ecosystem is insufficient, with limited study on their molecular mode of action insvitro. In this study, the cytotoxicity, DNA damage, mitochondrial impairment and the involved molecular mechanisms of certain frequently detectable aryl-PFRs, including 2-ethylhexyldiphenyl phosphate (EHDPP), methyl diphenyl phosphate (MDPP), bisphenol-A bis (diphenyl phosphate) (BDP), isodecyl diphenyl phosphate (IDPP), cresyl diphenyl phosphate (CDP) and the structurally similar and widely used organophosphorus pesticide chlorpyrifos (CPF), were evaluated in A549 cells using high-content screening (HCS) system. Aryl-PFRs showed different lethal concentration 50 (LC50) values ranging from 97.94 to 546.85 microM in A549 cells using CCK-8 assay. EHDPP, IDPP, CDP, MDPP and CPF demonstrated an ability to induce DNA damage, evidenced by increased DNA content and S phase-reducing cell cycle arrest effect using fluorophore dye cocktail assay. Additionally, the selected aryl-PFRs induced mitochondrial impairment by the increasing mitochondrial mass and decreasing mitochondrial membrane potential. Moreover, BDP, MDPP, and CDP, which contain short alkyl chains showed their potential oxidative stress with intracellular ROS and mitochondrial superoxide overproduction from an initially relatively low concentration. Additionally, based on the promotion of firefly luminescence in p53-transfected A549 cells, p53 activation was found to be involved in aryl-PFRs-induced DNA damage. Further real-time PCR results showed that all selected aryl-PFRs triggered p53/p21/gadd45beta-, and p53/p21/mdm2-mediated cell cycle pathways, and the p53/bax mediated apoptosis pathway to induce DNA damage and cytotoxic effects. These results suggest that aryl-PFRs (e.g., BDP, MDPP, CDP) cause oxidative stress-mediated DNA damage and mitochondrial impairment, and p53-dependent pathway was involved in the aryl-PFRs-induced DNA damage and cell cycle arrest. In conclusion, this study improves the understanding of PFRs-induced adverse outcomes and the involved molecular mechanism.
ESTHER : Yuan_2019_Environ.Pollut_250_58
PubMedSearch : Yuan_2019_Environ.Pollut_250_58
PubMedID: 30981936

Title : Tricellular junction proteins promote disentanglement of daughter and neighbour cells during epithelial cytokinesis - Wang_2018_J.Cell.Sci_131_
Author(s) : Wang Z , Bosveld F , Bellache Y
Ref : Journal of Cell Science , 131 : , 2018
Abstract : In epithelial tissue, new cell-cell junctions are formed upon cytokinesis. To understand junction formation during cytokinesis, we explored de novo formation of tricellular septate junctions (TCJs) in Drosophila epithelium. We found that upon midbody formation, the membranes of the two daughter cells and of the neighbouring cells located below the adherens junction (AJ) remain entangled in a 4-cell structure apposed to the midbody. The septate junction protein Discs-Large and components of the TCJ, Gliotactin and Anakonda accumulate in this 4-cell structure. Subsequently, a basal movement of the midbody parallels the detachment of the neighbouring cell membranes from the midbody, the disengagement of the daughter cells from their neighbours and the reorganisation of TCJs between the two daughter cells and their neighbouring cells. While the movement of midbody is independent of the Alix and Shrub abscission regulators, the loss of Gliotactin or Anakonda function impedes both the resolution of the connection between the daughter-neighbour cells and midbody movement. TCJ proteins therefore control an additional step of cytokinesis necessary for the disentanglement of the daughter cells from their neighbours during cytokinesis.
ESTHER : Wang_2018_J.Cell.Sci_131_
PubMedSearch : Wang_2018_J.Cell.Sci_131_
PubMedID: 29739875

Title : Selective enzymatic degradation and porous morphology of poly(butylene succinate)\/poly(lactic acid) blends - Shi_2018_Int.J.Biol.Macromol_126_436
Author(s) : Shi K , Bai Z , Su T , Wang Z
Ref : Int J Biol Macromol , 126 :436 , 2018
Abstract : Poly(butylene succinate) (PBS) and poly(lactic acid) (PLA) were melt-blended in different proportions and selectively degraded by cutinase and proteinase K, respectively. The selective enzymatic degradation process was systematically investigated. The degraded PBS/PLA blends were analyzed via scanning electron microscopy, Fourier-transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry. The results of the weight loss of PBS/PLA blends degraded by cutinase and proteinase K suggested that PLA hindered the cutinase-catalyzed degradation of PBS, whereas the addition of PBS in the blends accelerated the degradation of PLA within a specific PBS/PLA ratio. The change in crystallinity after degradation was closely related to the different way of degradation. The characterization of PBS/PLA blends after degradation showed that selective enzymatic degradation could not completely degrade PBS or PLA component. After degradation, the pores formed by proteinase K were more uniform and larger than those formed by cutinase. This work provides a new insight into the selective enzymatic degradation processes of the porous materials, which will be used in tissue engineering or oil-water separation in the future.
ESTHER : Shi_2018_Int.J.Biol.Macromol_126_436
PubMedSearch : Shi_2018_Int.J.Biol.Macromol_126_436
PubMedID: 30586586

Title : Molluscicidal activity of Solidago canadensis L. extracts on the snail Pomacea canaliculata Lam - Shen_2018_Pestic.Biochem.Physiol_149_104
Author(s) : Shen X , Wang Z , Liu L , Zou Z
Ref : Pestic Biochem Physiol , 149 :104 , 2018
Abstract : Extracts from the aerial parts of Solidago canadensis L. were evaluated for molluscicidal activity against Pomacea canaliculata Lam. using an immersion bioassay method. The petroleum ether fraction of the ethanolic extract (PEEE) from S. canadensis exhibited strong molluscicidal activity. The PEEE mode of action in the hepatopancreas tissue of P. canaliculata was tested at several concentrations. Biochemical parameters, namely, soluble sugar content, protein, malondialdehyde (MDA), acetylcholinesterase (AChE) activity, alanine aminotransferase (ALT), and aspartate transaminase (AST) were significantly decreased or increased after exposure to PEEE for 48 h (p<0.05). Histological assessment results showed that hepatopancreas tissue structure was destroyed by exposure to PEEE. Gas chromatography-mass spectrometry analysis (GC-MS) was used to identify 15 compounds that could contribute to the molluscicidal efficacy of the PEEE. Molluscicidal assay, biochemical tests and histological assessments suggest that the PEEE from S. canadensis has potential utility as a molluscicide.
ESTHER : Shen_2018_Pestic.Biochem.Physiol_149_104
PubMedSearch : Shen_2018_Pestic.Biochem.Physiol_149_104
PubMedID: 30033006

Title : Structure-guided Discovery of Dual-recognition Chemibodies - Cheng_2018_Sci.Rep_8_7570
Author(s) : Cheng AC , Doherty EM , Johnstone S , DiMauro EF , Dao J , Luthra A , Ye J , Tang J , Nixey T , Min X , Tagari P , Miranda LP , Wang Z
Ref : Sci Rep , 8 :7570 , 2018
Abstract : Small molecules and antibodies each have advantages and limitations as therapeutics. Here, we present for the first time to our knowledge, the structure-guided design of "chemibodies" as small molecule-antibody hybrids that offer dual recognition of a single target by both a small molecule and an antibody, using DPP-IV enzyme as a proof of concept study. Biochemical characterization demonstrates that the chemibodies present superior DPP-IV inhibition compared to either small molecule or antibody component alone. We validated our design by successfully solving a co-crystal structure of a chemibody in complex with DPP-IV, confirming specific binding of the small molecule portion at the interior catalytic site and the Fab portion at the protein surface. The discovery of chemibodies presents considerable potential for novel therapeutics that harness the power of both small molecule and antibody modalities to achieve superior specificity, potency, and pharmacokinetic properties.
ESTHER : Cheng_2018_Sci.Rep_8_7570
PubMedSearch : Cheng_2018_Sci.Rep_8_7570
PubMedID: 29765112
Gene_locus related to this paper: ratno-dpp4

Title : Complex role of titanium dioxide nanoparticles in the trophic transfer of arsenic from Nannochloropsis maritima to Artemia salina nauplii - Yang_2018_Aquat.Toxicol_198_231
Author(s) : Yang F , Zeng L , Luo Z , Wang Z , Huang F , Wang Q , Drobne D , Yan C
Ref : Aquat Toxicol , 198 :231 , 2018
Abstract : Increasing concern has been focused on the potential risks associated with the trophic transfer to aquatic organisms of ambient contaminants in the presence of titanium dioxide nanoparticles (nano-TiO2). This study investigated the influence of nano-TiO2 on the trophic transfer of arsenic (As) from the microalgae Nannochloropsis maritima to the brine shrimp Artemia salina nauplii. We found that nano-TiO2 could significantly facilitate As sorption on N. maritima within an exposure period of 24h, and this sorption subsequently led to higher As trophic transfer from the algae to A. salina according to trophic transfer factors (TTFAs+nano-TiO2>TTFAs). However, after 48h of depuration, the retention of As in A. salina fed As-nano-TiO2-contaminated algae was even lower than that in A. salina fed As-contaminated algae at the same exposure concentrations. This result indicates that the increased food chain transfer of As in the presence of nano-TiO2 can be explained by adsorption of As onto nano-TiO2 in contaminated food (algae), but the bioavailability of As in A. salina is reduced after the introduction of nanoparticles. Although the stress enzyme activities of superoxide dismutase (SOD) and acetylcholinesterase (AChE) in A. salina at a lower As concentration treatment in the presence of nano-TiO2 were not significantly changed, they increased with higher exposure concentrations of As with or without nano-TiO2. Our study highlighted the complex role of nanomaterials in the transfer of ambient contaminants via trophic chains and the potential of nano-TiO2 to reduce the bioavailability of As via trophic transfer to saltwater zooplankton.
ESTHER : Yang_2018_Aquat.Toxicol_198_231
PubMedSearch : Yang_2018_Aquat.Toxicol_198_231
PubMedID: 29558708

Title : Treatment of secondary brain injury by perturbing postsynaptic density protein-95-NMDA receptor interaction after intracerebral hemorrhage in rats - Wang_2018_J.Cereb.Blood.Flow.Metab__271678X18762637
Author(s) : Wang Z , Chen Z , Yang J , Yang Z , Yin J , Duan X , Shen H , Li H , Chen G
Ref : Journal of Cerebral Blood Flow & Metabolism , :271678X18762637 , 2018
Abstract : Postsynaptic density protein-95 (PSD95) plays important roles in the formation, differentiation, remodeling, and maturation of neuronal synapses. This study is to estimate the potential role of PSD95 in cognitive dysfunction and synaptic injury following intracerebral hemorrhage (ICH). The interaction between PSD95 and NMDA receptor subunit NR2B-neurotransmitter nitric oxide synthase (nNOS) could form a signal protein complex mediating excitatory signaling. Besides NR2B-nNOS, PSD95 also can bind to neurexin-1-neuroligin-1 to form a complex and participates in maintaining synaptic function. In this study, we found that there were an increase in the formation of PSD95-NR2B-nNOS complex and a decrease in the formation of neurexin-1-neuroligin-1-PSD95 complex after ICH, and this was accompanied by increased neuronal death and degeneration, and behavior dysfunction. PSD95 inhibitor Tat-NR2B9c effectively inhibited the interaction between PSD95 and NR2B-nNOS, and promoted the formation of neurexin-1-nueuroligin-1-PSD95 complex. In addition, Tat-NR2B9c treatment significantly reduced neuronal death and degeneration and matrix metalloproteinase 9 activity, alleviated inflammatory response and neurobehavioral disorders, and improved the cognitive and learning ability of ICH rats. Inhibition of the formation of PSD95-NR2B-nNOS complex can rescue secondary brain injury and behavioral cognitive impairment after ICH. PSD95 is expected to be a target for improving the prognosis of patients with ICH.
ESTHER : Wang_2018_J.Cereb.Blood.Flow.Metab__271678X18762637
PubMedSearch : Wang_2018_J.Cereb.Blood.Flow.Metab__271678X18762637
PubMedID: 29513122

Title : A Novel esterase from Pseudochrobactrum asaccharolyticum WZZ003: Enzymatic properties toward model substrate and catalytic performance in chiral fungicide intermediate synthesis - Cheng_2018_Process.Biochem_69_92
Author(s) : Cheng F , Zheng J , Wu G , Zhang Y , Wang Z
Ref : Process Biochemistry , 69 :92 , 2018
Abstract : Only a few esterases have been used for the synthesis of optically pure fungicide. For example, (R)-metalaxyl synthesized using esterase-involved bioreaction displays fungicide activity, whereas (S)-enantiomer is redundant. However, the biosynthesis of (R)-metalaxyl is currently hampered by the lower activity, selectivity and thermostability of esterase. Therefore, to obtain a better biocatalyst, several esterase genes were cloned from Pseudochrobactrum asaccharolyticum WZZ003. The esterase PAE07, among eight enzymes, was selected because it exhibited the highest hydrolysis activity toward (R,S)-DMPM. The DNA and amino acid sequence analysis suggested that PAE07 is a new member of lipolytic enzyme family V. The enzymatic properties of PAE07 toward (R,S)-DMPM and model substrate (p-nitrophenyl acetate) were investigated. PAE07 was found to be a highly active esterase with excellent enantioselectivity. The reaction conditions including temperatureand pH were optimized, and the effects of metal ions, organic solvents and detergents were also investigated. Results indicated that PAE07 is a competitive candidate for (R)-metalaxyl manufacturing.
ESTHER : Cheng_2018_Process.Biochem_69_92
PubMedSearch : Cheng_2018_Process.Biochem_69_92
PubMedID:
Gene_locus related to this paper: 9hyph-a0a2r3sty9

Title : Enzymatic degradation of poly(butylene succinate) with different molecular weights by cutinase - Pan_2018_Int.J.Biol.Macromol_111_1040
Author(s) : Pan W , Bai Z , Su T , Wang Z
Ref : Int J Biol Macromol , 111 :1040 , 2018
Abstract : Poly(butylene succinate) (PBS) films with different molecular weights were enzymatically degraded by cutinase. Changes in the properties of the films before and after enzymatic degradation were studied through scanning electron microscopy, differential scanning calorimetry, thermogravimetry, X-ray powder diffraction, proton nuclear magnetic resonance, and gel-permeation chromatography analysis. The weight loss of the films initially decreased and then increased with increasing molecular weight. Crystallinity was inversely proportional to weight loss and tended to decrease with prolonged degradation time. Crystalline and amorphous regions were simultaneously degraded. The thermal stability of PBS films decreased after enzymatic degradation. PBS was the main component of the enzymatically degraded polymers. The molecular weights of the films did not considerably change before and after degradation by cutinase.
ESTHER : Pan_2018_Int.J.Biol.Macromol_111_1040
PubMedSearch : Pan_2018_Int.J.Biol.Macromol_111_1040
PubMedID: 29366885

Title : Kinetic resolution of N-acetyl-DL-alanine methyl ester using immobilized Escherichia coli cells bearing recombinant esterase from Bacillus cereus - Zheng_2018_Chirality_30_907
Author(s) : Zheng J , Lan X , Huang L , Zhang Y , Wang Z
Ref : Chirality , 30 :907 , 2018
Abstract : D-alanine is widely used in medicine, food, additives, cosmetics, and other consumer items. Esterase derived from Bacillus cereus WZZ001 exhibits high hydrolytic activity and stereoselectivity. In this study, we expressed the esterase gene in Escherichia coli BL21 (DE3). We analyzed the biocatalytic resolution of N-acetyl-DL-alanine methyl ester by immobilized whole E. coli BL21 (DE3) cells, which were prepared through embedding and cross-linking. We analyzed biocatalytic resolution under the optimal conditions of pH of 7.0, temperature of 40 degrees C and substrate concentration of at 700 mM with an enantiomeric excess of 99.99% and e.e.p of 99.50%. The immobilized recombinant B. cereus esterase E. coli BL21 (DE3) cells exhibited excellent reusability and retained 86.04% of their initial activity after 15 cycles of repeated reactions. The immobilized cells are efficient and stable biocatalysts for the preparation of N-acetyl-D-alanine methyl esters.
ESTHER : Zheng_2018_Chirality_30_907
PubMedSearch : Zheng_2018_Chirality_30_907
PubMedID: 29676476

Title : Neurotrophins and cholinergic enzyme regulated by calpain-2: New insights into neuronal apoptosis induced by polybrominated diphenyl ether-153 - Zhang_2018_Toxicol.Lett_291_29
Author(s) : Zhang H , Yang X , Li X , Zhang Z , Hou L , Wang Z , Niu Q , Wang T
Ref : Toxicol Lett , 291 :29 , 2018
Abstract : Polybrominated diphenyl ether-153 (BDE-153) has been demonstrated to induce neuronal apoptosis in rat cerebral cortex and primary neurons. Neurotrophins and cholinergic enzymes play critical roles in the neuronal survival, maintenance, synaptic plasticity and learning memory, however, their roles in neuronal apoptosis following the BDE-153 treatment remain unclear. In this study, we firstly explored the possible predominant pathway underlying the neuronal apoptotic induced by the BDE-153 treatment in rat cerebral cortex, by measuring expression levels (mRNA and protein) of p53, caspase-3, 8, 9, calpain-1, and calpain-2, detected the levels (protein contents and mRNA) of neurotrophins including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), and measured acetylcholinesterase (AchE) and choline acetyltransferase (ChaT) activities in rat cerebral cortex and primary neurons following BDE-153 treatment with or without pretreatment with inhibitors. Results showed that the neuronal apoptosis induced by BDE-153 was dependent on p53, and dependent on more calpain-2 than caspase-3 in the cerebral cortex of rats. Following the BDE-153 treatment, the protein contents and mRNA levels of BDNF, GDNF, NGF, NT-3, and NT-4, as well as the AchE and ChaT activities were significantly decreased in the cerebral cortex and primary neurons when compared to the untreated group. When pretreated primary neurons with calpain inhibitor PD150606 or cyclin-dependent kinase (cdk5, the downstream complex of calpain) inhibitor Roscovitine, the neurotrophins contents and activities of ChaT and AchE were reverted, along with the improvement of neuron survival compared with BDE-153 treatment alone. We conclude that neurotrophins and cholinergic enzymes were regulated by the calpain-2 activation and its downstream cdk5 pathway, and which was involved in the neuronal apoptosis induced by the BDE-153 treatment.
ESTHER : Zhang_2018_Toxicol.Lett_291_29
PubMedSearch : Zhang_2018_Toxicol.Lett_291_29
PubMedID: 29621559

Title : Protective and Detoxifying Enzyme Activity and ABCG Subfamily Gene Expression in Sogatella furcifera Under Insecticide Stress - Zhou_2018_Front.Physiol_9_1890
Author(s) : Zhou C , Yang H , Wang Z , Long GY , Jin DC
Ref : Front Physiol , 9 :1890 , 2018
Abstract : Sogatella furcifera, an important migratory pest of rice, has substantial detrimental effects on rice production. To clarify the mechanism whereby S. furcifera responds to insecticide stress, we measured the activity of its protective [superoxide dismutase (SOD); peroxidase (POD); catalase (CAT)] and detoxifying [carboxylesterase (CarE); glutathione S-transferase (GST); mixed-function oxidase (MFO)] enzymes and the expression levels of its ATP-binding cassette subfamily G (ABCG) transporter genes in response to sublethal concentrations (LC10 and LC25) of the insecticides thiamethoxam, buprofezin, and abamectin. On the bases of the transcriptome data and the ABCG genes of Laodelphax striatellus, we obtained 14 full-length ABCG sequences for S. furcifera. RT-qPCR results showed that 13, 12, and 9 sfABCG genes were upregulated in the presence of thiamethoxam, buprofezin, and abamectin, respectively, at LC10. Moreover, 13 and 7 sfABCG genes were upregulated following treatment with thiamethoxam and abamectin, respectively, at LC25. Enzyme activity assays showed that although thiamethoxam, buprofezin, and abamectin induced GST, CarE, CAT, POD, and SOD activity, they did so at different concentrations and exposure times. The activity of MFO was generally inhibited with prolonged exposure to the three insecticides, with the inhibitory effect being most significant at 72 h. These results indicate that S. furcifera differs in its response to different types or concentrations of insecticides. Taken together, our results lay the foundations for gaining a deeper understanding of the mechanisms underlying the adaptation of S. furcifera to different types of insecticides, which would be of considerable significance for the development of effective pest management strategies.
ESTHER : Zhou_2018_Front.Physiol_9_1890
PubMedSearch : Zhou_2018_Front.Physiol_9_1890
PubMedID: 30670985

Title : Genome assembly with in vitro proximity ligation data and whole-genome triplication in lettuce - Reyes-Chin-Wo_2017_Nat.Commun_8_14953
Author(s) : Reyes-Chin-Wo S , Wang Z , Yang X , Kozik A , Arikit S , Song C , Xia L , Froenicke L , Lavelle DO , Truco MJ , Xia R , Zhu S , Xu C , Xu H , Xu X , Cox K , Korf I , Meyers BC , Michelmore RW
Ref : Nat Commun , 8 :14953 , 2017
Abstract : Lettuce (Lactuca sativa) is a major crop and a member of the large, highly successful Compositae family of flowering plants. Here we present a reference assembly for the species and family. This was generated using whole-genome shotgun Illumina reads plus in vitro proximity ligation data to create large superscaffolds; it was validated genetically and superscaffolds were oriented in genetic bins ordered along nine chromosomal pseudomolecules. We identify several genomic features that may have contributed to the success of the family, including genes encoding Cycloidea-like transcription factors, kinases, enzymes involved in rubber biosynthesis and disease resistance proteins that are expanded in the genome. We characterize 21 novel microRNAs, one of which may trigger phasiRNAs from numerous kinase transcripts. We provide evidence for a whole-genome triplication event specific but basal to the Compositae. We detect 26% of the genome in triplicated regions containing 30% of all genes that are enriched for regulatory sequences and depleted for genes involved in defence.
ESTHER : Reyes-Chin-Wo_2017_Nat.Commun_8_14953
PubMedSearch : Reyes-Chin-Wo_2017_Nat.Commun_8_14953
PubMedID: 28401891
Gene_locus related to this paper: lacsa-a0a2j6jnd3 , lacsa-a0a2j6l6y4 , lacsa-a0a2j6mjs5 , lacsa-a0a2j6mk82 , lacsa-a0a2j6k5z4 , lacsa-a0a2j6mk08 , lacsa-a0a2j6mhc5 , lacsa-a0a2j6m8d0 , lacsa-a0a2j6mdb6 , lacsa-a0a2j6mdh6 , lacsa-a0a2j6jnf0 , lacsa-a0a2j6mji4 , lacsa-a0a2j6ke81 , lacsa-a0a2j6jip3 , lacsa-a0a2j6jir5 , lacsa-a0a2j6ksa7 , lacsa-a0a2j6l4a3

Title : Efficient kinetic resolution of (+\/-)-menthol by a lipase from Thermomyces lanuginosus - De Yan_2017_Biotechnol.Appl.Biochem_64_87
Author(s) : De Yan H , Li Q , Wang Z
Ref : Biotechnol Appl Biochem , 64 :87 , 2017
Abstract : A lipase from Thermomyces lanuginosus (Lipozyme TL IM) exhibited high enantioselectivity for kinetic resolution of (+/-)-menthol in organic solvent. The various reaction parameters affecting the conversion and enantioselectivity were studied. The optimum reaction conditions for the transesterification reaction were found with vinyl acetate in the solvent of methyl tert-butyl ether with a vinyl acetate:(+/-)-menthol molar ratio of 5:1 and an enzyme concentration of 200 g/L at 30 degreeC. In these conditions, (-)-menthyl acetate with 99.3% enantiomeric excess was obtained, whereas the conversion was 34.7% with the reaction time of 12 H at the substrate concentration of 0.5 M. In addition, the enzyme allowed the substrate loading to be increased up to 1.5 M without the decrease of the enantioselectivity. These results indicated that Lipozyme TL IM was a promising biocatalyst in the resolution of (+/-)-menthol.
ESTHER : De Yan_2017_Biotechnol.Appl.Biochem_64_87
PubMedSearch : De Yan_2017_Biotechnol.Appl.Biochem_64_87
PubMedID: 26549685
Gene_locus related to this paper: humla-1lipa

Title : In vivo metabolism of organophosphate flame retardants and distribution of their main metabolites in adult zebrafish - Wang_2017_Sci.Total.Environ_590-591_50
Author(s) : Wang G , Chen H , Du Z , Li J , Wang Z , Gao S
Ref : Sci Total Environ , 590-591 :50 , 2017
Abstract : Understanding the metabolism of chemicals as well as the distribution and depuration of their main metabolites in tissues are essential for evaluating their fate and potential toxicity in vivo. Herein, we investigated the metabolism of six typical organophosphate (OP) flame retardants (tripropyl phosphate (TPRP), tri-n-butyl phosphate (TNBP), tris(2-butoxyethyl) phosphate (TBOEP), tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tri-p-cresyl phosphate (p-TCP)) in adult zebrafish in laboratory at three levels (0, 1/150 LC50 (environmentally relevant level), and 1/30 LC50 per OP analog). Twenty main metabolites were detected in the liver of OPs-exposed zebrafish using high resolution mass spectrometry (Q-TOF). The reaction pathways involving scission of the ester bond (hydrolysis), cleavage of the ether bond, oxidative hydroxylation, dechlorination, and coupling with glucuronic acid were proposed, and were further confirmed by the frontier electron density and point charge calculations. Tissue distribution of the twenty metabolites revealed that liver and intestine with the highest levels of metabolites were the most active organs for OPs biotransformation among the studied tissues of intestine, liver, roe, brain, muscle, and gill, which showed the importance of hepatobiliary system (liver-bile-intestine) in the metabolism and excretion of OPs in zebrafish. Fast depuration of metabolites from tissues indicated that the formed metabolites might be not persistent in fish, and easily released into water. This study provides comprehensive information on the metabolism of OPs in the tissue of zebrafish, which might give some hints for the exploration of their toxic mechanism in aquatic life.
ESTHER : Wang_2017_Sci.Total.Environ_590-591_50
PubMedSearch : Wang_2017_Sci.Total.Environ_590-591_50
PubMedID: 28292737

Title : Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern - Huo_2017_Sci.Rep_7_4422
Author(s) : Huo YY , Li S , Huang J , Rong Z , Wang Z , Li Z , Ji R , Kuang S , Cui HL , Li J , Xu XW
Ref : Sci Rep , 7 :4422 , 2017
Abstract : Lysophospholipase_carboxylesterase (LPCE) has highly conserved homologs in many diverse species ranging from bacteria to humans, as well as substantial biological significance and potential therapeutic implications. However, its biological function and catalytic mechanism remain minimally investigated because of the lack of structural information. Here, we report the crystal structure of a bacterial esterase PE8 belonging to the LPCE family. The crystal structure of PE8 was solved with a high resolution of 1.66 A. Compared with other homologs in the family, significant differences were observed in the amino acid sequence, three-dimensional structure, and substrate-binding pattern. Residue Arg79 undergoes configuration switching when binding to the substrate and forms a unique wall, leading to a relatively closed cavity in the substrate-binding pocket compared with the relatively more open and longer clefts in other homologs. Moreover, the mutant Met122Ala showed much stronger substrate affinity and higher catalytic efficiency because less steric repulsion acted on the substrates. Taken together, these results showed that, in PE8, Arg79 and Met122 play important roles in substrate binding and the binding pocket shaping, respectively. Our study provides new insight into the catalytic mechanism of LPCE, which may facilitate the development of structure-based therapeutics and other biocatalytic applications.
ESTHER : Huo_2017_Sci.Rep_7_4422
PubMedSearch : Huo_2017_Sci.Rep_7_4422
PubMedID: 28667306
Gene_locus related to this paper: pelhb-g4rfi7

Title : De novo transcriptome and expression profile analyses of the Asian corn borer (Ostrinia furnacalis) reveals relevant flubendiamide response genes - Cui_2017_BMC.Genomics_18_20
Author(s) : Cui L , Rui C , Yang D , Wang Z , Yuan H
Ref : BMC Genomics , 18 :20 , 2017
Abstract : BACKGROUND: The Asian corn borer (ACB), Ostrinia furnacalis (Guenee), has become the most damaging insect pest of corn in Asia. However, the lack of genome or transcriptome information heavily hinders our further understanding of ACB in every aspect at a molecular level and on a genome-wide scale. Here, we used the Ion Torrent Personal Genome Machine (PGM) Sequencer to explore the ACB transcriptome and to identify relevant genes in response to flubendiamide, showing high selective activity against ACB.
RESULTS: We obtained 35,430 unigenes, with an average length of 716 bp, representing a dramatic expansion of existing cDNA sequences available for ACB. These sequences were annotated with Non-redundant Protein (Nr), Gene Ontology (GO), Clusters of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to better understand their functions. A total of 31 cytochrome P450 monooxygenases (P450s), 27 carboxyl/cholinesterases (CCEs) and 19 glutathione S-transferases (GSTs) were manually curated to construct phylogenetic trees, and 25 unigenes encoding target proteins (acetylcholinesterase, nicotinic acetylcholine receptor, gamma-aminobutyric acid receptor, glutamate-gated chloride channel, voltage-gated sodium channel and ryanodine receptor) were identified. In addition, we compared and validated the differentially expressed unigenes upon flubendiamide treatment, revealing that the genes for detoxification enzymes (P450s and esterase), calcium signaling pathways and muscle control pathways (twitchin and tropomyosin), immunoglobulin (hemolin), chemosensory protein and heat shock protein 70 were significantly overexpressed in response to flubendiamide, while the genes for cuticular protein, protease and oxidoreductase showed much lower expression levels. CONCLUSION: The obtained transcriptome information provides large genomic resources available for further studies of ACB. The differentially expressed gene data will elucidate the molecular mechanisms of ACB in response to the novel diamide insecticide, flubendiamide. In particular, these findings will facilitate the identification of the genes involved in insecticide resistance and the development of new compounds to control the ACB.
ESTHER : Cui_2017_BMC.Genomics_18_20
PubMedSearch : Cui_2017_BMC.Genomics_18_20
PubMedID: 28056803

Title : Depletion of juvenile hormone esterase extends larval growth in Bombyx mori - Zhang_2017_Insect.Biochem.Mol.Biol_81_72
Author(s) : Zhang Z , Liu X , Shiotsuki T , Wang Z , Xu X , Huang Y , Li M , Li K , Tan A
Ref : Insect Biochemistry & Molecular Biology , 81 :72 , 2017
Abstract : Two major hormones, juvenile hormone (JH) and 20-hydroxyecdysone (20E), regulate insect growth and development according to their precisely coordinated titres, which are controlled by both biosynthesis and degradation pathways. Juvenile hormone esterase (JHE) is the primary JH-specific degradation enzyme that plays a key role in regulating JH titers, along with JH epoxide hydrolase (JHEH) and JH diol kinase (JHDK). In the current study, a loss-of-function analysis of JHE in the silkworm, Bombyx mori, was performed by targeted gene disruption using the transgenic CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/RNA-guided Cas9 nucleases) system. Depletion of B. mori JHE (BmJHE) resulted in the extension of larval stages, especially the penultimate and ultimate larval stages, without deleterious effects to silkworm physiology. The expression of JHEH and JHDK was upregulated in mutant animals, indicating the existence of complementary routes in the JH metabolism pathway in which inactivation of one enzyme will activate other enzymes. RNA-Seq analysis of mutant animals revealed that genes involved in protein processing in the endoplasmic reticulum and in amino acid metabolism were affected by BmJHE depletion. Depletion of JHE and subsequent delayed JH metabolism activated genes in the TOR pathway, which are ultimately responsible for extending larval growth. The transgenic Cas9 system used in the current study provides a promising approach for analysing the actions of JH, especially in nondrosophilid insects. Furthermore, prolonging larval stages produced larger larvae and cocoons, which is greatly beneficial to silk production.
ESTHER : Zhang_2017_Insect.Biochem.Mol.Biol_81_72
PubMedSearch : Zhang_2017_Insect.Biochem.Mol.Biol_81_72
PubMedID: 28057597

Title : Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice - Liu_2017_J.Ethnopharmacol_204_95
Author(s) : Liu W , Zhu Y , Wang Y , Qi S , Ma C , Li S , Jiang B , Cheng X , Wang Z , Xuan Z , Wang C
Ref : J Ethnopharmacol , 204 :95 , 2017
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear. AIM OF THE STUDY: The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches. MATERIALS AND
METHODS: The acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid fraction (ALK) and flavonoid fraction (FLA) from APP were evaluated in normal male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks. The levels of biomarkers, enzyme activity and protein expression of cholinergic system were determined in brain tissues.
RESULTS: The AChE activity was significantly decreased and the content of neurotransmitter acetylcholine (ACh) was significantly increased in normal mice cortex and hippocampus by treatment with donepezil at dosage of 8mg/kg, EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), and the AChE activity and the content of ACh were not significantly changed in cortex and hippocampus after treatment with FLA at dosages of 10, 30, 90mg/kg (P>0.05). In the MWM task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by treatment with EXT at dosages of 550, 1650mg/kg and ALK at dosages of 30, 90mg/kg (P<0.05). Moreover, the activity and protein expression of AChE was significantly decreased and the content of neurotransmitter ACh was significantly increased in cerebral cortex of scopolamine-induced mice by treatment with EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), compared with scopolamine-treated group.
CONCLUSIONS: EXT and ALK from APP exert beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. APP is an effective traditional folk medicine and the ALK fraction is proved to be the main effective components for the treatment of forgetfulness. The ALK may be valuable source for lead compounds discovery and drug development for treatment of memory impairment such as in Alzheimer's disease.
ESTHER : Liu_2017_J.Ethnopharmacol_204_95
PubMedSearch : Liu_2017_J.Ethnopharmacol_204_95
PubMedID: 28442406

Title : Screening of a natural compound library identifies emodin, a natural compound from Rheum palmatum Linn that inhibits DPP4 - Wang_2017_PeerJ_5_e3283
Author(s) : Wang Z , Yang L , Fan H , Wu P , Zhang F , Zhang C , Liu W , Li M
Ref : PeerJ , 5 :e3283 , 2017
Abstract : Historically, Chinese herbal medicines have been widely used in the treatment of hyperglycemia, but the mechanisms underlying their effectiveness remain largely unknown. Here, we screened a compound library primarily comprised of natural compounds extracted from herbs and marine organisms. The results showed that emodin, a natural compound from Rheum palmatum Linn, inhibited DPP4 activity with an in vitro IC50 of 5.76 microM without inhibiting either DPP8 or DPP9. A docking model revealed that emodin binds to DPP4 protein through Glu205 and Glu206, although with low affinity. Moreover, emodin treatment (3, 10 and 30 mg/kg, P.O.) in mice decreased plasma DPP4 activity in a dose-dependent manner. Our study suggests that emodin inhibits DPP4 activity and may represent a novel therapeutic for the treatment of type 2 diabetes.
ESTHER : Wang_2017_PeerJ_5_e3283
PubMedSearch : Wang_2017_PeerJ_5_e3283
PubMedID: 28507818

Title : In Vitro Metabolism of Oprozomib, an Oral Proteasome Inhibitor: Role of Epoxide Hydrolases and Cytochrome P450s - Wang_2017_Drug.Metab.Dispos_45_712
Author(s) : Wang Z , Fang Y , Teague J , Wong H , Morisseau C , Hammock BD , Rock DA
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 45 :712 , 2017
Abstract : Oprozomib is an oral proteasome inhibitor currently under investigation in patients with hematologic malignancies or solid tumors. Oprozomib elicits potent pharmacological actions by forming a covalent bond with the active site N-terminal threonine of the 20S proteasome. Oprozomib has a short half-life across preclinical species and in patients due to systemic clearance via metabolism. Potential for drug-drug interactions (DDIs) could alter the exposure of this potent therapeutic; therefore, a thorough investigation of pathways responsible for metabolism is required. In the present study, the major drug-metabolizing enzyme responsible for oprozomib metabolism was identified in vitro. A diol of oprozomib was found to be the predominant metabolite in human hepatocytes, which formed via direct epoxide hydrolysis. Using recombinant epoxide hydrolases (EHs) and selective EH inhibitors in liver microsomes, microsomal EH (mEH) but not soluble EH (sEH) was found to be responsible for oprozomib diol formation. Coincubation with 2-nonylsulfanyl-propionamide, a selective mEH inhibitor, resulted in a significant decrease in oprozomib disappearance (>80%) with concurrent complete blockage of diol formation in human hepatocytes. On the contrary, a selective sEH inhibitor did not affect oprozomib metabolism. Pretreatment of hepatocytes with the pan-cytochrome P450 (P450) inhibitor 1-aminobenzotriazole resulted in a modest reduction ( approximately 20%) of oprozomib metabolism. These findings indicated that mEH plays a predominant role in oprozomib metabolism. Further studies may be warranted to determine whether drugs that are mEH inhibitors cause clinically significant DDIs with oprozomib. On the other hand, pharmacokinetics of oprozomib is unlikely to be affected by coadministered P450 and sEH inhibitors and/or inducers.
ESTHER : Wang_2017_Drug.Metab.Dispos_45_712
PubMedSearch : Wang_2017_Drug.Metab.Dispos_45_712
PubMedID: 28428366

Title : De Novo Genome and Transcriptome Assembly of the Canadian Beaver (Castor canadensis) - Lok_2017_G3.(Bethesda)_7_755
Author(s) : Lok S , Paton TA , Wang Z , Kaur G , Walker S , Yuen RK , Sung WW , Whitney J , Buchanan JA , Trost B , Singh N , Apresto B , Chen N , Coole M , Dawson TJ , Ho K , Hu Z , Pullenayegum S , Samler K , Shipstone A , Tsoi F , Wang T , Pereira SL , Rostami P , Ryan CA , Tong AH , Ng K , Sundaravadanam Y , Simpson JT , Lim BK , Engstrom MD , Dutton CJ , Kerr KC , Franke M , Rapley W , Wintle RF , Scherer SW
Ref : G3 (Bethesda) , 7 :755 , 2017
Abstract : The Canadian beaver (Castor canadensis) is the largest indigenous rodent in North America. We report a draft annotated assembly of the beaver genome, the first for a large rodent and the first mammalian genome assembled directly from uncorrected and moderate coverage (< 30 x) long reads generated by single-molecule sequencing. The genome size is 2.7 Gb estimated by k-mer analysis. We assembled the beaver genome using the new Canu assembler optimized for noisy reads. The resulting assembly was refined using Pilon supported by short reads (80 x) and checked for accuracy by congruency against an independent short read assembly. We scaffolded the assembly using the exon-gene models derived from 9805 full-length open reading frames (FL-ORFs) constructed from the beaver leukocyte and muscle transcriptomes. The final assembly comprised 22,515 contigs with an N50 of 278,680 bp and an N50-scaffold of 317,558 bp. Maximum contig and scaffold lengths were 3.3 and 4.2 Mb, respectively, with a combined scaffold length representing 92% of the estimated genome size. The completeness and accuracy of the scaffold assembly was demonstrated by the precise exon placement for 91.1% of the 9805 assembled FL-ORFs and 83.1% of the BUSCO (Benchmarking Universal Single-Copy Orthologs) gene set used to assess the quality of genome assemblies. Well-represented were genes involved in dentition and enamel deposition, defining characteristics of rodents with which the beaver is well-endowed. The study provides insights for genome assembly and an important genomics resource for Castoridae and rodent evolutionary biology.
ESTHER : Lok_2017_G3.(Bethesda)_7_755
PubMedSearch : Lok_2017_G3.(Bethesda)_7_755
PubMedID: 28087693
Gene_locus related to this paper: cascn-a0a250y2s0 , cascn-a0a250y135 , cascn-a0a250y1i6 , cascn-a0a250y2u8 , cascn-a0a250xy53 , ursma-a0a384cw87 , cascn-a0a250y6h8

Title : Efficient kinetic resolution of (RS)-1-phenylethanol by a mycelium-bound lipase from a wild-type Aspergillus oryzae strain - Yan_2017_Biotechnol.Appl.Biochem_64_251
Author(s) : Yan HD , Wang Z , Qian JQ
Ref : Biotechnol Appl Biochem , 64 :251 , 2017
Abstract : A mycelium-bound lipase from Aspergillus oryzae (AOL) exhibited excellent enantioselectivity for kinetic resolution of (RS)-1-phenylethanol ((RS)-1-PE) in organic solvent. The various reaction parameters affecting the conversion and enantioselectivity were studied, including type of acyl donor, solvent, molar ratio, temperature, enzyme amount, and substrate concentration. The optimum reaction conditions were found to be transesterification with vinyl acetate at 30 degrees C in methyl tert-butyl ether with a vinyl acetate: (RS)-1-PE molar ratio of 1:1 and an enzyme concentration of 60 g/L. At the optimum reaction conditions, the conversion could reach above 46% with >99% enantiomeric excess of the product, (R)-1-phenylethyl acetate, when the substrate concentration was below 1.4 M. The enzyme displayed an excellent enantioselectivity with an E-value of >200 and a strong tolerance for high substrate concentration of up to 1.8 M. Those results indicated that AOL was a promising biocatalyst in the kinetic resolution of (RS)-1-PE.
ESTHER : Yan_2017_Biotechnol.Appl.Biochem_64_251
PubMedSearch : Yan_2017_Biotechnol.Appl.Biochem_64_251
PubMedID: 26854002

Title : Evolution of Digestive Enzymes and RNASE1 Provides Insights into Dietary Switch of Cetaceans - Wang_2016_Mol.Biol.Evol_33_3144
Author(s) : Wang Z , Xu S , Du K , Huang F , Chen Z , Zhou K , Ren W , Yang G
Ref : Molecular Biology Evolution , 33 :3144 , 2016
Abstract : Although cetaceans (whales, porpoises, and dolphins) have multi-chambered stomachs, feeding habits of modern cetaceans have dramatically changed from herbivorous to carnivorous. However, the genetic basis underlying this dietary switch remains unexplored. Here, we present the first systematic investigation of 10 digestive enzymes genes (i.e., CYP7A1, CTRC, LIPC, LIPF, PNLIP, PGC, PRSS1, SI, SLC5A1, and TMPRSS15) of representative cetaceans, and the evolutionary trajectory of RNASE1 in cetartiodactylans. Positive selections were detected with proteinases (i.e., CTRC, PRSS1, and TMPRSS15) and lipases (i.e., CYP7A1, LIPF, and PNLIP) suggesting that cetaceans have evolved an enhanced digestion capacity for proteins and lipids, the major nutritional components of their prey (fishes and invertebrates). In addition, it was found that RNASE1 gene duplicated after the cetartiodactylan speciation and two independent gene duplication events took place in Camelidae and Ruminantia. Positive selection was detected with RNASE1 of Camelidae and Bovidae, suggesting enhanced digestive efficiency in the ruminants. Remarkably, even though the ancestors of cetaceans were terrestrial artiodactyls that are herbivorous, modern cetaceans lost the pancreatic RNASE1 copy with digestive function, which is in accordance with the dietary change from herbivorous to carnivorous. In sum, this is the first study that provides new insights into the evolutionary mechanism of dietary switch in cetaceans.
ESTHER : Wang_2016_Mol.Biol.Evol_33_3144
PubMedSearch : Wang_2016_Mol.Biol.Evol_33_3144
PubMedID: 27651393
Gene_locus related to this paper: souch-a0a1d8i1n4

Title : Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM - Miao_2016_Nat.Commun_7_11716
Author(s) : Miao H , Ou J , Peng Y , Zhang X , Chen Y , Hao L , Xie G , Wang Z , Pang X , Ruan Z , Li J , Yu L , Xue B , Shi H , Shi C , Liang H
Ref : Nat Commun , 7 :11716 , 2016
Abstract : Metabolic reprogramming in stromal cells plays an essential role in regulating tumour growth. The metabolic activities of tumour-associated macrophages (TAMs) in colorectal cancer (CRC) are incompletely characterized. Here, we identify TAM-derived factors and their roles in the development of CRC. We demonstrate that ABHD5, a lipolytic co-activator, is ectopically expressed in CRC-associated macrophages. We demonstrate in vitro and in mouse models that macrophage ABHD5 potentiates growth of CRC cells. Mechanistically, ABHD5 suppresses spermidine synthase (SRM)-dependent spermidine production in macrophages by inhibiting the reactive oxygen species-dependent expression of C/EBPvarepsilon, which activates transcription of the srm gene. Notably, macrophage-specific ABHD5 transgene-induced CRC growth in mice can be prevented by an additional SRM transgene in macrophages. Altogether, our results show that the lipolytic factor ABHD5 suppresses SRM-dependent spermidine production in TAMs and potentiates the growth of CRC. The ABHD5/SRM/spermidine axis in TAMs might represent a potential target for therapy.
ESTHER : Miao_2016_Nat.Commun_7_11716
PubMedSearch : Miao_2016_Nat.Commun_7_11716
PubMedID: 27189574

Title : Nonenzymatic all-solid-state coated wire electrode for acetylcholine determination in vitro - He_2016_Biosens.Bioelectron_85_679
Author(s) : He C , Wang Z , Wang Y , Hu R , Li G
Ref : Biosensors & Bioelectronics , 85 :679 , 2016
Abstract : A nonenzymatic all-solid-state coated wire acetylcholine electrode was investigated. Poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT/PSS) as conducting polymer was coated on one end of a gold wire (0.5mm in diameter). The acetylcholine selective membrane containing heptakis(2,3,6-tri-Omicron-methyl)-beta-cyclodextrin as an ionophore covered the conducting polymer layer. The electrode could work stably in a pH range of 6.5-8.5 and a temperature range of 15-40 degrees C. It covered an acetylcholine concentration range of 10(-5)-10(-1)M with a slope of 54.04+/-1.70mV/decade, while detection limit was 5.69+/-1.06microM. The selectivity, dynamic response, reproducibility and stability were evaluated. The electrode could work properly in the rat brain homogenate to detect different concentrations of acetylcholine.
ESTHER : He_2016_Biosens.Bioelectron_85_679
PubMedSearch : He_2016_Biosens.Bioelectron_85_679
PubMedID: 27254787

Title : Bioactive alpha-pyrone meroterpenoids from mangrove endophytic fungus Penicillium sp - Ding_2016_Nat.Prod.Res__1
Author(s) : Ding B , Wang Z , Huang X , Liu Y , Chen W , She Z
Ref : Nat Prod Res , :1 , 2016
Abstract : Five alpha-pyrone meroterpenoids, including one new 3-epiarigsugacin E (1) and four known compounds, arisugacin D (2), arisugacin B (3), territrem C (4) and terreulactone C (5) were obtained from the marine fungus Penicillium sp. SK5GW1L. Their structures were identified by MS and NMR experiments, and the absolute configuration of compound 1 was further confirmed by low temperature (150 K) single crystal X-ray diffraction with Cu Kalpha radiation. Compounds 3, 4 and 5 showed strong inhibitory activities against acetylcholinesterase (AchE) with IC50 values of 3.03, 0.23 and 0.028 muM, respectively.
ESTHER : Ding_2016_Nat.Prod.Res__1
PubMedSearch : Ding_2016_Nat.Prod.Res__1
PubMedID: 27067533

Title : Dual functional cholinesterase and MAO inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of homoisoflavonoid derivatives - Wang_2016_J.Enzyme.Inhib.Med.Chem_31_389
Author(s) : Wang Y , Sun Y , Guo Y , Wang Z , Huang L , Li X
Ref : J Enzyme Inhib Med Chem , 31 :389 , 2016
Abstract : Because of the complexity of Alzheimer's disease (AD), the multi-target-directed ligand (MTDL) strategy is expected to provide superior effects for the treatment of AD, instead of the classic one-drug-one-target strategy. In this context, we focused on the design, synthesis and evaluation of homoisoflavonoid derivatives as dual acetyl cholinesterase (AChE) and monoamine oxidase (MAO-B) inhibitors. Among all the synthesized compounds, compound 10 provided a desired balance of AChE and hMAO-B inhibition activities, with IC50 value of 3.94 and 3.44 muM, respectively. Further studies revealed that compound 10 was a mixed-type inhibitor of AChE and an irreversible inhibitor of hMAO-B, which was also confirmed by molecular modeling studies. Taken together, the data indicated that 10 was a promising dual functional agent for the treatment of AD.
ESTHER : Wang_2016_J.Enzyme.Inhib.Med.Chem_31_389
PubMedSearch : Wang_2016_J.Enzyme.Inhib.Med.Chem_31_389
PubMedID: 25798687

Title : Involvement of Three Esterase Genes from Panonychus citri (McGregor) in Fenpropathrin Resistance - Shen_2016_Int.J.Mol.Sci_17_
Author(s) : Shen XM , Liao CY , Lu XP , Wang Z , Wang JJ , Dou W
Ref : Int J Mol Sci , 17 : , 2016
Abstract : The citrus red mite, Panonychus citri (McGregor), is a major citrus pest with a worldwide distribution and an extensive record of pesticide resistance. However, the underlying molecular mechanism associated with fenpropathrin resistance in this species have not yet been reported. In this study, synergist triphenyl phosphate (TPP) dramatically increased the toxicity of fenpropathrin, suggesting involvement of carboxylesterases (CarEs) in the metabolic detoxification of this insecticide. The subsequent spatiotemporal expression pattern analysis of PcE1, PcE7 and PcE9 showed that three CarEs genes were all over-expressed after insecticide exposure and higher transcripts levels were observed in different field resistant strains of P. citri. Heterologous expression combined with 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT) cytotoxicity assay in Spodoptera frugiperda (Sf9) cells revealed that PcE1-, PcE7- or PcE9-expressing cells showed significantly higher cytoprotective capability than parental Sf9 cells against fenpropathrin, demonstrating that PcEs probably detoxify fenpropathrin. Moreover, gene silencing through the method of leaf-mediated dsRNA feeding followed by insecticide bioassay increased the mortalities of fenpropathrin-treated mites by 31% (PcE1), 27% (PcE7) and 22% (PcE9), respectively, after individual PcE gene dsRNA treatment. In conclusion, this study provides evidence that PcE1, PcE7 and PcE9 are functional genes mediated in fenpropathrin resistance in P. citri and enrich molecular understanding of CarEs during the resistance development of the mite.
ESTHER : Shen_2016_Int.J.Mol.Sci_17_
PubMedSearch : Shen_2016_Int.J.Mol.Sci_17_
PubMedID: 27548163

Title : Characterization of a Desiccation Stress Induced Lipase Gene from Brassica napus L. - Zhang_2016_J.Agr.Sci.Tech_18_1129
Author(s) : Zhang H , Zhou J , Zheng X , Zhang Z , Wang Z , Tan X
Ref : J Agr Sci Tech , 18 :1129 , 2016
Abstract : Lipases are known to have important functions in many physiological processes in plants. Here, we cloned a lipase gene via Rapid Amplification of cDNA Ends (RACE) technique from Brassica napus L., designated as BnDIL1 (B. napus Desiccation-Induced Lipase 1). The lipase enzyme activity was confirmed by estimating the lipase activity and reduced lipids content in Saccharomyces cerevisiae (pep4) transformant. Two B. napus lines with different oil contents were employed to examine the transcription profiles of BnDIL1 during the processes of seed morphogenesis, maturation, dormancy, pregermination and germination. The transcription level of lipid degradation pathway was enhanced during the processes of seed maturation, dormancy, pregermination and germination, and was higher in seeds of low oil-contents line than that of high oil-contents line. However, BnDIL1 was significantly activated when seed desiccation started. Both slow desiccation and -fast desiccation- treatments on seedlings dramatically activated the transcription of BnDIL1, while only -slow desiccation- stress, which would induce the cell apoptosis, significantly activated the transcription of lipid degradation gene. This result demonstrated that BnDIL1 in B. napus was desiccation stress dependent gene rather than fatty acids degradation gene.
ESTHER : Zhang_2016_J.Agr.Sci.Tech_18_1129
PubMedSearch : Zhang_2016_J.Agr.Sci.Tech_18_1129
PubMedID:

Title : Chemical Constituents of Plants from the Genus Phlegmariurus - Yang_2016_Chem.Biodivers_13_269
Author(s) : Yang Y , Wang Z , Wu J , Chen Y
Ref : Chem Biodivers , 13 :269 , 2016
Abstract : Phlegmariurus is a genus of ca. 200 species in the family Huperziaceae. Up to now, six species of the Phlegmariurus genus have been chemically investigated, and 89 compounds, including Lycopodium alkaloids possessing diverse structures and serratane-type triterpenes, have been isolated. These compounds show potent bioactivities, such as acetylcholinesterase inhibitory and cytotoxic activities.
ESTHER : Yang_2016_Chem.Biodivers_13_269
PubMedSearch : Yang_2016_Chem.Biodivers_13_269
PubMedID: 26916276

Title : Conifer flavonoid compounds inhibit detoxification enzymes and synergize insecticides - Wang_2016_Pestic.Biochem.Physiol_127_1
Author(s) : Wang Z , Zhao Z , Cheng X , Liu S , Wei Q , Scott IM
Ref : Pestic Biochem Physiol , 127 :1 , 2016
Abstract : Detoxification by glutathione S-transferases (GSTs) and esterases are important mechanisms associated with insecticide resistance. Discovery of novel GST and esterase inhibitors from phytochemicals could provide potential new insecticide synergists. Conifer tree species contain flavonoids, such as taxifolin, that inhibit in vitro GST activity. The objectives were to test the relative effectiveness of taxifolin as an enzyme inhibitor and as an insecticide synergist in combination with the organophosphorous insecticide, Guthion (50% azinphos-methyl), and the botanical insecticide, pyrethrum, using an insecticide-resistant Colorado potato beetle (CPB) Leptinotarsa decemlineata (Say) strain. Both taxifolin and its isomer, quercetin, increased the mortality of 1(st) instar CPB larvae after 48h when combined with Guthion, but not pyrethrum. Taxifolin had greater in vitro esterase inhibition compared with the commonly used esterase inhibitor, S, S, S-tributyl phosphorotrithioate (DEF). An in vivo esterase and GST inhibition effect after ingestion of taxifolin was measured, however DEF caused a greater suppression of esterase activity. This study demonstrated that flavonoid compounds have both in vitro and in vivo esterase inhibition, which is likely responsible for the insecticide synergism observed in insecticide-resistant CPB.
ESTHER : Wang_2016_Pestic.Biochem.Physiol_127_1
PubMedSearch : Wang_2016_Pestic.Biochem.Physiol_127_1
PubMedID: 26821651

Title : Biocatalytic Resolution of Rac-alpha-Ethyl-2-Oxo-Pyrrolidineacetic Acid Methyl Ester by Immobilized Recombinant Bacillus cereus Esterase - Zheng_2016_Appl.Biochem.Biotechnol_178_1471
Author(s) : Zheng JY , Liu YY , Luo WF , Zheng RC , Ying XX , Wang Z
Ref : Appl Biochem Biotechnol , 178 :1471 , 2016
Abstract : A new esterase-producing strain (Bacillus cereus WZZ001) which exhibiting high hydrolytic activity and excellent enantioselectivity on rac-alpha-ethyl-2-oxo-pyrrolidineacetic acid methyl ester (R, S-1) has been isolated from soil sample by our laboratory. In this study, the stereoselective hydrolysis of (R, S-1) was performed using the recombinant Bacillus cereus esterase which expressed in Escherichia coli BL21 (DE3). Under the optimized conditions of pH 8.0, 35 degrees C, and concentration of substrate 400 mM, a successful enzymatic resolution was achieved with an e.e. s of 99.5 % and conversion of 49 %. Immobilization considerably increased the reusability of the recombinant esterase; the immobilized enzyme showed excellent reusability during 6 cycles of repeated 2 h reactions at 35 degrees C. Thereby, it makes the recombinant B. cereus esterase a usable biocatalyst for industrial application.
ESTHER : Zheng_2016_Appl.Biochem.Biotechnol_178_1471
PubMedSearch : Zheng_2016_Appl.Biochem.Biotechnol_178_1471
PubMedID: 26695776

Title : Dietary methionine level influences growth and lipid metabolism via GCN2 pathway in cobia (Rachycentron canadum) - Wang_2016_Aquaculture_454_148
Author(s) : Wang Z , Mai K , Xu W , Zhang Y , Liu Y , Ai Q
Ref : Aquaculture , 454 :148 , 2016
Abstract : This study investigated the effect of dietary methionine level on growth and lipid metabolism via the general control nonderepressible2 kinase (GCN2) pathway in cobia (Rachycentron canadum). Cobia were fed diets with six levels of methionine (0.62%, 0.84%, 1.02%, 1.15%, 1.25% and 1.42% of dry diet) with a constant cystine level (0.42% dry diet). The feeding experiment began in September 2013 and ended in December 2013; during the experiment, cobia were fed ad libitum twice daily (7:00 and 18:00h) for 10weeks. Cobia fed the diet with 1.02% methionine showed elevated weight gain (WG) and feed efficiency ratio (FER) compared with those fed the other diets (P<0.05). The content of liver lipid, total triglyceride, and total cholesterol were first enhanced significantly with increasing dietary methionine level from 0.62% to 1.02%, and then decreased markedly with higher levels of dietary methionine level (1.02% to 1.42%). Crude lipid was markedly elevated when the dietary methionine level was 1.02%, and then plateaued with higher dietary methionine level. The expression of genes associated with hepatic lipid synthesis (sterol regulatory element binding protein-1, peroxisome proliferator activated receptor , fatty acid synthetase, and stearoyl-CoA desaturase-1) were markedly up-regulated in fish fed the diet containing 1.02% methionine, whereas the transcriptional levels of lipolytic genes (peroxisome proliferator activated receptor , carnitine acyl transferase-1, and lipase lipoprotein lipase) were elevated in fish fed the methionine-deficient diet (0.62%; P<0.05). The expression of insulin-like growth factor-I (IGF-I) was suppressed by the methionine-deficient diet, whereas the hepatic mRNA expression levels of genes related to amino acid responses (AAR), i.e., GCN2, activating transcription factor 4 (ATF4), CCAAT enhancer binding protein (C/EBP), and asparagine synthetase (ASNS), were significantly up-regulated. In conclusion, the dietary methionine requirement of cobia was estimated to be 1.04% and 1.15% of dry matter (2.23% and 2.45% dietary protein) on the basis of WG and FER, respectively. Results of this study suggested that methionine deficiency could suppress growth, decrease lipid content, and inhibit expression of IGF-I and some genes related to lipid synthesis in cobia; these changes might be regulated by inducing the expression of genes related to the GCN2 pathway (GCN2, ATF4, C/EBP, and ASNS). Statement of relevance The present study was conducted to investigate the effect of dietary methionine on growth performance, plasma biochemical indexes, lipid content and gene expression involved in lipid metabolism and GCN2 pathway in cobia (Rachycentron canadum). Our findings have showed that methionine deficiency could suppress growth, decrease lipid content and inhibit expressions of IGF-I and some lipid synthesis related genes of cobia, which may be regulated by inducing the mRNA expressions of GCN2 pathway related genes (GCN2, ATF4, C/EBP and ASNS). The results are reliable and of both theoretical and practical importance. The work described has not been submitted elsewhere for publication, in whole or in part, and all the authors listed have approved the manuscript that is enclosed. I have read and have abided by the statement of ethical standards for manuscripts submitted to Aquaculture.
ESTHER : Wang_2016_Aquaculture_454_148
PubMedSearch : Wang_2016_Aquaculture_454_148
PubMedID:

Title : Targeting neurotrophic factors and their receptors, but not cholinesterase or neurotransmitter, in the neurotoxicity of TDCPP in Chinese rare minnow adults (Gobiocypris rarus) - Yuan_2016_Environ.Pollut_208_670
Author(s) : Yuan L , Li J , Zha J , Wang Z
Ref : Environ Pollut , 208 :670 , 2016
Abstract : Organophosphate flame retardants (OPFRs) have been detected at high concentrations in various environmental and biotic samples, but little is known about their toxicity. In this study, the potential neurotoxicity of three OPFRs (TCEP, TDCPP, and TPP) and Chlorpyrifos (CPF, an organophosphate pesticide) were compared in Chinese rare minnow using an acute toxicity test and a 21-day fish assay. The acute test demonstrated significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by CPF. Although significant AChE inhibition at high concentration of TPP was also observed, none of the OPFRs had effects similar to CPF on these enzymes, indicating that their acute toxicities to Chinese rare minnow may be unrelated to cholinesterase inhibition. In addition, the 21-day fish assay with TDCPP demonstrated no significant effects on cholinesterase activities or neurotransmitter levels. Nonetheless, this OPFR exhibited widespread effects on the neurotrophic factors and their receptors (e.g., ntf3, ntrk1, ntrk2, ngfr, and fgf2, fgf11, fgf22, fgfr4), indicating that TDCPP or other OPFRs may elicit neurological effects by targeting neurotrophic factors and their receptors in Chinese rare minnow.
ESTHER : Yuan_2016_Environ.Pollut_208_670
PubMedSearch : Yuan_2016_Environ.Pollut_208_670
PubMedID: 26552522

Title : Enzymatic degradation of poly(butylene succinate) by cutinase cloned from Fusarium solani - Hu_2016_Polym.Degrad.Stab_134_211
Author(s) : Hu X , Gao Z , Wang Z , Su T , Yang L , Li P
Ref : Polymer Degradation and Stability , 134 :211 , 2016
Abstract : A gene encoding cutinase from Fusarium solani was cloned and overexpressed in Pichia pastoris. The recombinant cutinase with a molecular weight of 24 kDa was then purified to homogeneity. The enzyme presents degradation capacity for poly(butylene succinate) (PBS) and exhibits the optimum pH and temperature of 8.0 and 50 C, respectively. Enzyme activity is enhanced by K+ and Na+ and inhibited by Zn2+,Fe2+ ,Mn2+, and Co2+. The inhibitions of different chemicals on recombinant enzyme activity were examined. EDTA and b-mercaptoethanol exert significant inhibitory effect. The degradation of PBS films in the presence of the recombinant enzyme was further studied. Results showed that enzymatic degradation is a rapid process, and the PBS fi lms were degraded completely after approximately 6 h. The characteristics of PBS films after degradation were analyzed. With the extension of degradation time, the surfaces of PBS films became rougher and holes appeared with a gradually increasing trend. Differential scanning calorimetry and scanning electron microscopy analyses revealed that both amorphous and crystalline regions of PBS were degraded by the recombinant enzyme. Wide-angle X-ray diffractometer also indicated the crystallinity of PBS has a gradual downward trend with the extension of degradation time. Gel permeation chromatography showed the molecular weight of PBS has no obvious change before and after degradation.
ESTHER : Hu_2016_Polym.Degrad.Stab_134_211
PubMedSearch : Hu_2016_Polym.Degrad.Stab_134_211
PubMedID:
Gene_locus related to this paper: fusso-cutas

Title : Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis - Wang_2015_Hepatology_61_870
Author(s) : Wang C , Zhao Y , Gao X , Li L , Yuan Y , Liu F , Zhang L , Wu J , Hu P , Zhang X , Gu Y , Xu Y , Wang Z , Li Z , Zhang H , Ye J
Ref : Hepatology , 61 :870 , 2015
Abstract : Abnormal metabolism of nonesterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), an LD-binding protein, regulates the storage and hydrolysis of TG in LD. However, its roles and underlying mechanisms in the liver remain unknown. Here we found that Plin5 expression was increased in steatotic livers. Using Plin5 knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller-sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. Plin5-deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression and activity of PPARalpha stimulated by the increased NEFA levels. Meanwhile, Plin5-deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically, we found that Plin5 blocks adipose triglyceride lipase (ATGL)-mediated lipolysis by competitively binding to comparative gene identification-58 (CGI-58) and disrupting the interaction between CGI-58 and ATGL. CONCLUSION: Plin5 is an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis. This provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity.
ESTHER : Wang_2015_Hepatology_61_870
PubMedSearch : Wang_2015_Hepatology_61_870
PubMedID: 25179419

Title : In vitro and in vivo metabolism and inhibitory activities of vasicine, a potent acetylcholinesterase and butyrylcholinesterase inhibitor - Liu_2015_PLoS.One_10_e0122366
Author(s) : Liu W , Shi X , Yang Y , Cheng X , Liu Q , Han H , Yang B , He C , Wang Y , Jiang B , Wang Z , Wang C
Ref : PLoS ONE , 10 :e0122366 , 2015
Abstract : Vasicine (VAS), a potential natural cholinesterase inhibitor, exhibited promising anticholinesterase activity in preclinical models and has been in development for treatment of Alzheimer's disease. This study systematically investigated the in vitro and in vivo metabolism of VAS in rat using ultra performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. A total of 72 metabolites were found based on a detailed analysis of their 1H- NMR and 13C NMR data. Six key metabolites were isolated from rat urine and elucidated as vasicinone, vasicinol, vasicinolone, 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, 9-oxo-1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, and 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-beta-D-glucuronide. The metabolic pathway of VAS in vivo and in vitro mainly involved monohydroxylation, dihydroxylation, trihydroxylation, oxidation, desaturation, sulfation, and glucuronidation. The main metabolic soft spots in the chemical structure of VAS were the 3-hydroxyl group and the C-9 site. All 72 metabolites were found in the urine sample, and 15, 25, 45, 18, and 11 metabolites were identified from rat feces, plasma, bile, rat liver microsomes, and rat primary hepatocyte incubations, respectively. Results indicated that renal clearance was the major excretion pathway of VAS. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of VAS and its main metabolites were also evaluated. The results indicated that although most metabolites maintained potential inhibitory activity against AChE and BChE, but weaker than that of VAS. VAS undergoes metabolic inactivation process in vivo in respect to cholinesterase inhibitory activity.
ESTHER : Liu_2015_PLoS.One_10_e0122366
PubMedSearch : Liu_2015_PLoS.One_10_e0122366
PubMedID: 25849329

Title : The high-resolution crystal structure of human LCAT - Piper_2015_J.Lipid.Res_56_1711
Author(s) : Piper DE , Romanow WG , Gunawardane RN , Fordstrom P , Masterman S , Pan O , Thibault ST , Zhang R , Meininger D , Schwarz M , Wang Z , King C , Zhou M , Walker NP
Ref : J Lipid Res , 56 :1711 , 2015
Abstract : LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. Here we report the 2.65 A crystal structure of the human LCAT protein. Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. The crystal structure reveals that LCAT has an alpha/beta hydrolase core with two additional subdomains that play important roles in LCAT function. Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. Mapping the naturally occurring mutations onto the structure provides insight into how they may affect LCAT enzymatic activity.
ESTHER : Piper_2015_J.Lipid.Res_56_1711
PubMedSearch : Piper_2015_J.Lipid.Res_56_1711
PubMedID: 26195816
Gene_locus related to this paper: human-LCAT

Title : Potent AChE and BChE inhibitors isolated from seeds of Peganum harmala Linn by a bioassay-guided fractionation - Yang_2015_J.Ethnopharmacol_168_279
Author(s) : Yang Y , Cheng X , Liu W , Chou G , Wang Z , Wang C
Ref : J Ethnopharmacol , 168 :279 , 2015
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Peganum harmala Linn are traditionally used as folk medical herb in Uighur medicine in China to treat disorders of hemiplegia and amnesia. Previously studies have proved that dominating alkaloids in P. harmala show significant inhibitory activities on the cholinesterase. AIM OF THE STUDY: The aim of the present study is to isolate trace ingredients from seeds of P. harmala and evaluate its inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). MATERIALS AND
METHODS: For sake of screening effective cholinesterase inhibitors, trace compounds were isolated from seeds of P. harmala through a bioassay-guided fractionation and their structures were determined via detailed spectral analysis. The inhibitory activities on AChE and BChE were assessed using an improved Ellman method by UPLC-ESI-MS/MS to determine the common final product choline.
RESULTS: The activity-guided fractionation led to the isolation of two new alkaloids 2-aldehyde-tetrahydroharmine (10), 2-carboxyl-3,4-dihydroquinazoline (19), one syringin structure analog 1-O-beta-D-xylopyranose sinapyl alcohol (22), and along with 19 known compounds. Compounds acetylnorharmine (6), harmic acid methy ester (7), harmine N-oxide (13), 6-methoxyindoline (14), syringin (21) were first found from genus Peganum and compounds 3-hydroxylated harmine (4), 1-hydroxy-7-methoxy-beta-carboline (5) were new natural products. The results showed that the 2-aldehyde-tetrahydroharmine (10) has a potential inbibitive effect on both AChE and BChE with IC50 values of 12.35+/-0.24 and 5.51+/-0.33microM, respectively. Deoxyvasicine (15) and vasicine (16) showed the strongest BChE inhibitory activity with IC50 values of 0.04+/-0.01 and 0.1+/-0.01microM. The analysis of the structure-activity relationship indicated that the saturation of pyridine ring and the presence of substitution at indole ring, C-1, C-3, C-7 and N-2, for beta-carbolines, were essential for effective inhibition of both AChE and BChE and the five-membered ring between C-2 and N-3 as well as the substituent groups sited at C-4 and C-9, for quinazolines, were important to both the AChE/BChE-inhibitory activity.
CONCLUSIONS: Bioassay-guided fractionation has led to the isolation of AChE and BChE inhibitors from the seeds of P. harmala. These results are in agreement with the traditional uses of the seeds of P. harmala.
ESTHER : Yang_2015_J.Ethnopharmacol_168_279
PubMedSearch : Yang_2015_J.Ethnopharmacol_168_279
PubMedID: 25862961

Title : Characterization of large structural genetic mosaicism in human autosomes - Machiela_2015_Am.J.Hum.Genet_96_487
Author(s) : Machiela MJ , Zhou W , Sampson JN , Dean MC , Jacobs KB , Black A , Brinton LA , Chang IS , Chen C , Chen K , Cook LS , Crous Bou M , De Vivo I , Doherty J , Friedenreich CM , Gaudet MM , Haiman CA , Hankinson SE , Hartge P , Henderson BE , Hong YC , Hosgood HD, 3rd , Hsiung CA , Hu W , Hunter DJ , Jessop L , Kim HN , Kim YH , Kim YT , Klein R , Kraft P , Lan Q , Lin D , Liu J , Le Marchand L , Liang X , Lissowska J , Lu L , Magliocco AM , Matsuo K , Olson SH , Orlow I , Park JY , Pooler L , Prescott J , Rastogi R , Risch HA , Schumacher F , Seow A , Setiawan VW , Shen H , Sheng X , Shin MH , Shu XO , VanDen Berg D , Wang JC , Wentzensen N , Wong MP , Wu C , Wu T , Wu YL , Xia L , Yang HP , Yang PC , Zheng W , Zhou B , Abnet CC , Albanes D , Aldrich MC , Amos C , Amundadottir LT , Berndt SI , Blot WJ , Bock CH , Bracci PM , Burdett L , Buring JE , Butler MA , Carreon T , Chatterjee N , Chung CC , Cook MB , Cullen M , Davis FG , Ding T , Duell EJ , Epstein CG , Fan JH , Figueroa JD , Fraumeni JF, Jr. , Freedman ND , Fuchs CS , Gao YT , Gapstur SM , Patino-Garcia A , Garcia-Closas M , Gaziano JM , Giles GG , Gillanders EM , Giovannucci EL , Goldin L , Goldstein AM , Greene MH , Hallmans G , Harris CC , Henriksson R , Holly EA , Hoover RN , Hu N , Hutchinson A , Jenab M , Johansen C , Khaw KT , Koh WP , Kolonel LN , Kooperberg C , Krogh V , Kurtz RC , Lacroix A , Landgren A , Landi MT , Li D , Liao LM , Malats N , McGlynn KA , McNeill LH , McWilliams RR , Melin BS , Mirabello L , Peplonska B , Peters U , Petersen GM , Prokunina-Olsson L , Purdue M , Qiao YL , Rabe KG , Rajaraman P , Real FX , Riboli E , Rodriguez-Santiago B , Rothman N , Ruder AM , Savage SA , Schwartz AG , Schwartz KL , Sesso HD , Severi G , Silverman DT , Spitz MR , Stevens VL , Stolzenberg-Solomon R , Stram D , Tang ZZ , Taylor PR , Teras LR , Tobias GS , Viswanathan K , Wacholder S , Wang Z , Weinstein SJ , Wheeler W , White E , Wiencke JK , Wolpin BM , Wu X , Wunder JS , Yu K , Zanetti KA , Zeleniuch-Jacquotte A , Ziegler RG , de Andrade M , Barnes KC , Beaty TH , Bierut LJ , Desch KC , Doheny KF , Feenstra B , Ginsburg D , Heit JA , Kang JH , Laurie CA , Li JZ , Lowe WL , Marazita ML , Melbye M , Mirel DB , Murray JC , Nelson SC , Pasquale LR , Rice K , Wiggs JL , Wise A , Tucker M , Perez-Jurado LA , Laurie CC , Caporaso NE , Yeager M , Chanock SJ
Ref : American Journal of Human Genetics , 96 :487 , 2015
Abstract : Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
ESTHER : Machiela_2015_Am.J.Hum.Genet_96_487
PubMedSearch : Machiela_2015_Am.J.Hum.Genet_96_487
PubMedID: 25748358

Title : Butyrylcholinesterase K Variant and Alzheimer's Disease Risk: A Meta-Analysis - Wang_2015_Med.Sci.Monit_21_1408
Author(s) : Wang Z , Jiang Y , Wang X , Du Y , Xiao D , Deng Y , Wang J
Ref : Med Sci Monit , 21 :1408 , 2015
Abstract : Background Although many studies have estimated the association between the butyrylcholinesterase (BCHE) K variant and Alzheimer's disease (AD) risk, the results are still controversial. We thus conducted this meta-analysis. Material and Methods We searched NCBI, Medline, Web of Science, and Embase databases to find all eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Results We found a significant association between BCHE K variant and AD risk (OR=1.20; 95% CI 1.03-1.39; P=0.02). In the stratified analysis by ethnicity, we observed a significant association between BCHE K variant and AD risk in Asians (OR=1.32; 95% CI 1.02-1.72; P=0.04). However, no significant association between BCHE K variant and AD risk in Caucasians was found (OR=1.14; 95% CI 0.95-1.37; P=0.16). When stratified by the age of AD onset, we found that late-onset AD (LOAD) was significantly associated with BCHE K variant (OR=1.44; 95% CI 1.05-1.97; P=0.02). No significant association between BCHE K variant and early-onset AD (EOAD) risk was observed (OR=1.16; 95% CI 0.89-1.51; P=0.27). Compared with non-APOE epsilon4 and non-BCHE K carriers, no significant association between BCHE K variant and AD risk was found (OR=1.11; 95% CI 0.91-1.35; P=0.30). However, APOE epsilon4 carriers showed increased AD risk in both non-BCHE K carriers (OR=2.81; 95% CI 1.75-4.51; P=0.0001) and BCHE K carriers (OR=3.31; 95% CI 1.82-6.02; P=0.0001). Conclusions The results of this meta-analysis indicate that BCHE K variant might be associated with AD risk.
ESTHER : Wang_2015_Med.Sci.Monit_21_1408
PubMedSearch : Wang_2015_Med.Sci.Monit_21_1408
PubMedID: 25978873

Title : 'Obesity' is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism - Wang_2015_Sci.Rep_5_14187
Author(s) : Wang Z , Chen Z , Xu S , Ren W , Zhou K , Yang G
Ref : Sci Rep , 5 :14187 , 2015
Abstract : Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that 'obesity' might be an indicator of good health for cetaceans.
ESTHER : Wang_2015_Sci.Rep_5_14187
PubMedSearch : Wang_2015_Sci.Rep_5_14187
PubMedID: 26381091
Gene_locus related to this paper: delle-a0a2y9m8t8 , lipve-a0a0n6wyt2

Title : Inhibition of de novo Palmitate Synthesis by Fatty Acid Synthase Induces Apoptosis in Tumor Cells by Remodeling Cell Membranes, Inhibiting Signaling Pathways, and Reprogramming Gene Expression - Ventura_2015_EBioMedicine_2_808
Author(s) : Ventura R , Mordec K , Waszczuk J , Wang Z , Lai J , Fridlib M , Buckley D , Kemble G , Heuer TS
Ref : EBioMedicine , 2 :808 , 2015
Abstract : Inhibition of de novo palmitate synthesis via fatty acid synthase (FASN) inhibition provides an unproven approach to cancer therapy with a strong biological rationale. FASN expression increases with tumor progression and associates with chemoresistance, tumor metastasis, and diminished patient survival in numerous tumor types. TVB-3166, an orally-available, reversible, potent, and selective FASN inhibitor induces apoptosis, inhibits anchorage-independent cell growth under lipid-rich conditions, and inhibits in-vivo xenograft tumor growth. Dose-dependent effects are observed between 20-200snM TVB-3166, which agrees with the IC50 in biochemical FASN and cellular palmitate synthesis assays. Mechanistic studies show that FASN inhibition disrupts lipid raft architecture, inhibits biological pathways such as lipid biosynthesis, PI3K-AKT-mTOR and beta-catenin signal transduction, and inhibits expression of oncogenic effectors such as c-Myc; effects that are tumor-cell specific. Our results demonstrate that FASN inhibition has anti-tumor activities in biologically diverse preclinical tumor models and provide mechanistic and pharmacologic evidence that FASN inhibition presents a promising therapeutic strategy for treating a variety of cancers, including those expressing mutant K-Ras, ErbB2, c-Met, and PTEN. The reported findings inform ongoing studies to link mechanisms of action with defined tumor types and advance the discovery of biomarkers supporting development of FASN inhibitors as cancer therapeutics. RESEARCH IN CONTEXT: Fatty acid synthase (FASN) is a vital enzyme in tumor cell biology; the over-expression of FASN is associated with diminished patient prognosis and resistance to many cancer therapies. Our data demonstrate that selective and potent FASN inhibition with TVB-3166 leads to selective death of tumor cells, without significant effect on normal cells, and inhibits in vivo xenograft tumor growth at well-tolerated doses. Candidate biomarkers for selecting tumors highly sensitive to FASN inhibition are identified. These preclinical data provide mechanistic and pharmacologic evidence that FASN inhibition presents a promising therapeutic strategy for treating a variety of cancers.
ESTHER : Ventura_2015_EBioMedicine_2_808
PubMedSearch : Ventura_2015_EBioMedicine_2_808
PubMedID: 26425687

Title : Unraveling adaptation of Pontibacter korlensis to radiation and infertility in desert through complete genome and comparative transcriptomic analysis - Dai_2015_Sci.Rep_5_10929
Author(s) : Dai J , Dai W , Qiu C , Yang Z , Zhang Y , Zhou M , Zhang L , Fang C , Gao Q , Yang Q , Li X , Wang Z , Jia Z , Chen X
Ref : Sci Rep , 5 :10929 , 2015
Abstract : The desert is a harsh habitat for flora and microbial life due to its aridness and strong radiation. In this study, we constructed the first complete and deeply annotated genome of the genus Pontibacter (Pontibacter korlensis X14-1(T) = CCTCC AB 206081(T), X14-1). Reconstruction of the sugar metabolism process indicated that strain X14-1 can utilize diverse sugars, including cellulose, starch and sucrose; this result is consistent with previous experiments. Strain X14-1 is also able to resist desiccation and radiation in the desert through well-armed systems related to DNA repair, radical oxygen species (ROS) detoxification and the OstAB and TreYZ pathways for trehalose synthesis. A comparative transcriptomic analysis under gamma radiation revealed that strain X14-1 presents high-efficacy operating responses to radiation, including the robust expression of catalase and the manganese transport protein. Evaluation of 73 novel genes that are differentially expressed showed that some of these genes may contribute to the strain's adaptation to radiation and desiccation through ferric transport and preservation.
ESTHER : Dai_2015_Sci.Rep_5_10929
PubMedSearch : Dai_2015_Sci.Rep_5_10929
PubMedID: 26057562
Gene_locus related to this paper: 9bact-a0a0e3zf06 , 9bact-a0a0e3zhq7

Title : Comprehensive characterization of a time-course transcriptional response induced by autotoxins in Panax ginseng using RNA-Seq - Wu_2015_BMC.Genomics_16_1010
Author(s) : Wu B , Long Q , Gao Y , Wang Z , Shao T , Liu Y , Li Y , Ding W
Ref : BMC Genomics , 16 :1010 , 2015
Abstract : BACKGROUND: As a valuable medicinal plant, the yield of Panax ginseng is seriously affected by autotoxicity, which is a common phenomenon due to continuous cropping. However, the mechanism of autotoxicity in P. ginseng is still unknown.
RESULTS: In total, high throughput sequencing of 18 RNA-Seq libraries produced 996,000 000 100-nt reads that were assembled into 72,732 contigs. Compared with control, 3697 and 2828 genes were significantly up- and down-regulated across different tissues and time points, respectively. Gene Ontology enrichment analysis showed that 'enzyme inhibitor activity', 'carboxylesterase activity', 'pectinesterase activity', 'centrosome cycle and duplication' and 'mitotic spindle elongation' were enriched for the up-regulated genes. Transcription factors including AP2s/ERFs, MYBs, and WRKYs were up-regulated in roots after benzoic acid treatment. Moreover, reactive oxygen species, peroxidases and superoxide dismutase contigs were up-regulated in roots after benzoic acid treatment. Physiological and biochemical indexes showed that the proline and malondialdehyde content were restored to lower levels at a later stage after benzoic acid treatment. Benzoic acid inhibited the root hair development in a dose-dependent manner, and several differential expressed genes potentially involved in hair development were identified. Several key contigs in the flavonoid and ginsenoside biosynthesis pathways were repressed. Finally, 58,518 alternative splicing (AS) events from 12,950 genes were found after benzoic acid treatment. Interestingly, contigs in the ginsenoside biosynthetic pathway underwent AS, providing useful information about post-transcriptional regulation in P. ginseng.
CONCLUSIONS: This study revealed the stress-response molecular mechanisms in P. ginseng induced by benzoic acid.
ESTHER : Wu_2015_BMC.Genomics_16_1010
PubMedSearch : Wu_2015_BMC.Genomics_16_1010
PubMedID: 26608743

Title : Role of Neurexin-1beta and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats - Shen_2015_Stroke_46_2607
Author(s) : Shen H , Chen Z , Wang Y , Gao A , Li H , Cui Y , Zhang L , Xu X , Wang Z , Chen G
Ref : Stroke , 46 :2607 , 2015
Abstract : BACKGROUND AND PURPOSE: Neurexin-1beta and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1beta and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction.
METHODS: In vivo, 228 Sprague-Dawley rats were used. An experimental SAH model was induced by single blood injection to prechiasmatic cistern. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAH in vitro. Specific small interfering RNAs and expression plasmids for neurexin-1beta and neuroligin-1 were exploited both in vivo and in vitro. Western blot, immunofluorescence, immunoprecipitation, neurological scoring, and Morris water maze were performed to evaluate the mechanism of neurexin-1beta and neuroligin-1, as well as neurological outcome.
RESULTS: Both in vivo and in vitro experiments showed SAH-induced decrease in the expressions of neurexin-1beta and neuroligin-1 and the interaction between neurexin-1beta and neuroligin-1 in neurons. In addition, the interaction between neurexin-1beta and neuroligin-1 was reduced by their knockdown and increased by their overexpression. The formation of excitatory synapses was inhibited by oxyhemoglobin treatment, which was significantly ameliorated by overexpression of neurexin-1beta and neuroligin-1 and aggravated by the knockdown of neurexin-1beta and neuroligin-1. More importantly, neurexin-1beta and neuroligin-1 overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin-1beta and neuroligin-1 knockdown induced an opposite effect.
CONCLUSIONS: Enhancing the expressions of neurexin-1beta and neuroligin-1 could promote the interaction between them and the formation of excitatory synapses, which is helpful to improve cognitive dysfunction after SAH. Neurexin-1beta and neuroligin-1 might be good targets for improving cognitive function after SAH.
ESTHER : Shen_2015_Stroke_46_2607
PubMedSearch : Shen_2015_Stroke_46_2607
PubMedID: 26219651

Title : Resurfaced fluorescent protein as a sensing platform for label-free detection of copper(II) ion and acetylcholinesterase activity - Lei_2015_Anal.Chem_87_1974
Author(s) : Lei C , Wang Z , Nie Z , Deng H , Hu H , Huang Y , Yao S
Ref : Analytical Chemistry , 87 :1974 , 2015
Abstract : Protein engineering by resurfacing is an efficient approach to provide new molecular toolkits for biotechnology and bioanalytical chemistry. H39GFP is a new variant of green fluorescent protein (GFP) containing 39 histidine residues in the primary sequence that was developed by protein resurfacing. Herein, taking H39GFP as the signal reporter, a label-free fluorometric sensor for Cu(2+) sensing was developed based on the unique multivalent metal ion-binding property of H39GFP and fluorescence quenching effect of Cu(2+) by electron transfer. The high affinity of H39GFP with Cu(2+) (Kd, 16.2 nM) leads to rapid detection of Cu(2+) in 5 min with a low detection limit (50 nM). Using acetylthiocholine (ATCh) as the substrate, this H39GFP/Cu(2+) complex-based sensor was further applied for the turn-on fluorescence detection of acetylcholinesterase (AChE) activity. The assay was based on the reaction between Cu(2+) and thiocholine, the hydrolysis product of ATCh by AChE. The proposed sensor is highly sensitive (limit of detection (LOD) = 0.015 mU mL(-1)) and is feasible for screening inhibitors of AChE. Furthermore, the practicability of this method was demonstrated by the detection of pesticide residue (carbaryl) in real food samples. Hence, the successful applications of H39GFP in the detection of metal ion and enzyme activity present the prospect of resurfaced proteins as versatile biosensing platforms.
ESTHER : Lei_2015_Anal.Chem_87_1974
PubMedSearch : Lei_2015_Anal.Chem_87_1974
PubMedID: 25560517

Title : Genome sequencing of adzuki bean (Vigna angularis) provides insight into high starch and low fat accumulation and domestication - Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
Author(s) : Yang K , Tian Z , Chen C , Luo L , Zhao B , Wang Z , Yu L , Li Y , Sun Y , Li W , Chen Y , Zhang Y , Ai D , Zhao J , Shang C , Ma Y , Wu B , Wang M , Gao L , Sun D , Zhang P , Guo F , Wang W , Wang J , Varshney RK , Ling HQ , Wan P
Ref : Proc Natl Acad Sci U S A , 112 :13213 , 2015
Abstract : Adzuki bean (Vigna angularis), an important legume crop, is grown in more than 30 countries of the world. The seed of adzuki bean, as an important source of starch, digestible protein, mineral elements, and vitamins, is widely used foods for at least a billion people. Here, we generated a high-quality draft genome sequence of adzuki bean by whole-genome shotgun sequencing. The assembled contig sequences reached to 450 Mb (83% of the genome) with an N50 of 38 kb, and the total scaffold sequences were 466.7 Mb with an N50 of 1.29 Mb. Of them, 372.9 Mb of scaffold sequences were assigned to the 11 chromosomes of adzuki bean by using a single nucleotide polymorphism genetic map. A total of 34,183 protein-coding genes were predicted. Functional analysis revealed that significant differences in starch and fat content between adzuki bean and soybean were likely due to transcriptional abundance, rather than copy number variations, of the genes related to starch and oil synthesis. We detected strong selection signals in domestication by the population analysis of 50 accessions including 11 wild, 11 semiwild, 17 landraces, and 11 improved varieties. In addition, the semiwild accessions were illuminated to have a closer relationship to the cultigen accessions than the wild type, suggesting that the semiwild adzuki bean might be a preliminary landrace and play some roles in the adzuki bean domestication. The genome sequence of adzuki bean will facilitate the identification of agronomically important genes and accelerate the improvement of adzuki bean.
ESTHER : Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
PubMedSearch : Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
PubMedID: 26460024
Gene_locus related to this paper: phaan-a0a0l9ttq5 , phaan-a0a0l9vh69 , phaan-a0a0l9vh89 , phaan-a0a0s3tc53 , vigrr-a0a1s3v914 , phaan-a0a0s3s998 , phaan-a0a0s3siv8 , phaan-a0a0l9uys5 , phaan-a0a0s3rp07 , phaan-a0a0s3rbq0 , vigrr-a0a1s3tul4 , phaan-a0a0s3smk7 , phaan-a0a0s3slm9 , phaan-a0a0l9ujf5 , phaan-a0a0l9til9 , phaan-a0a0l9uqr2 , phaan-a0a0l9v1m8 , phaan-a0a0l9uc60 , phaan-a0a0l9ucr8

Title : Genome sequencing of the perciform fish Larimichthys crocea provides insights into molecular and genetic mechanisms of stress adaptation - Ao_2015_PLoS.Genet_11_e1005118
Author(s) : Ao J , Mu Y , Xiang LX , Fan D , Feng M , Zhang S , Shi Q , Zhu LY , Li T , Ding Y , Nie L , Li Q , Dong WR , Jiang L , Sun B , Zhang X , Li M , Zhang HQ , Xie S , Zhu Y , Jiang X , Wang X , Mu P , Chen W , Yue Z , Wang Z , Wang J , Shao JZ , Chen X
Ref : PLoS Genet , 11 :e1005118 , 2015
Abstract : The large yellow croaker Larimichthys crocea (L. crocea) is one of the most economically important marine fish in China and East Asian countries. It also exhibits peculiar behavioral and physiological characteristics, especially sensitive to various environmental stresses, such as hypoxia and air exposure. These traits may render L. crocea a good model for investigating the response mechanisms to environmental stress. To understand the molecular and genetic mechanisms underlying the adaptation and response of L. crocea to environmental stress, we sequenced and assembled the genome of L. crocea using a bacterial artificial chromosome and whole-genome shotgun hierarchical strategy. The final genome assembly was 679 Mb, with a contig N50 of 63.11 kb and a scaffold N50 of 1.03 Mb, containing 25,401 protein-coding genes. Gene families underlying adaptive behaviours, such as vision-related crystallins, olfactory receptors, and auditory sense-related genes, were significantly expanded in the genome of L. crocea relative to those of other vertebrates. Transcriptome analyses of the hypoxia-exposed L. crocea brain revealed new aspects of neuro-endocrine-immune/metabolism regulatory networks that may help the fish to avoid cerebral inflammatory injury and maintain energy balance under hypoxia. Proteomics data demonstrate that skin mucus of the air-exposed L. crocea had a complex composition, with an unexpectedly high number of proteins (3,209), suggesting its multiple protective mechanisms involved in antioxidant functions, oxygen transport, immune defence, and osmotic and ionic regulation. Our results reveal the molecular and genetic basis of fish adaptation and response to hypoxia and air exposure. The data generated by this study will provide valuable resources for the genetic improvement of stress resistance and yield potential in L. crocea.
ESTHER : Ao_2015_PLoS.Genet_11_e1005118
PubMedSearch : Ao_2015_PLoS.Genet_11_e1005118
PubMedID: 25835551
Gene_locus related to this paper: larcr-a0a0f8ay25 , larcr-a0a0f8cf53 , larcr-a0a0f8cir1 , larcr-a0a0f8d1j2 , larcr-a0a0f8alq6 , larcr-a0a0f8bdu4 , larcr-a0a0f8abw1 , larcr-a0a0f8ahh1 , larcr-a0a0f8avc6 , larcr-a0a0f8al93 , larcr-a0a0f8aed8 , larcr-a0a0f7ir14 , larcr-a0a0f8aje8 , larcr-k9lsm3 , larcr-a0a0f8but5 , larcr-a0a0f8af44

Title : FgRIC8 is involved in regulating vegetative growth, conidiation, deoxynivalenol production and virulence in Fusarium graminearum - Wu_2015_Fungal.Genet.Biol_83_92
Author(s) : Wu J , Liu Y , Lv W , Yue X , Que Y , Yang N , Zhang Z , Ma Z , Talbot NJ , Wang Z
Ref : Fungal Genet Biol , 83 :92 , 2015
Abstract : Proteins of the resistance to inhibitors of cholinesterase 8 (Ric8) group act as guanine nucleotide exchange factors (GEFs) and play important roles in regulating G-protein signaling in animals. In filamentous fungi, putative Ric8 orthologs have so far been identified in Magnaporthe oryzae, Neurospora crassa, Aspergillus nidulans and Aspergillus fumigatus. Here, we report the functional investigation of a potential RIC8 ortholog (FgRIC8) in the wheat head blight pathogen Fusarium graminearum. Targeted gene deletion mutants of FgRIC8 exhibited a significant reduction in vegetative growth, conidiation, pigment production as well as deoxynivalenol (DON) biosynthesis. Pathogenicity assays using a point-inoculated spikelet approach showed that the mutants were severely impaired in virulence on flowering wheat heads. Quantitative RT-PCR analysis revealed that genes encoding F. graminearum Galpha (FgGpa1 and FgGpa3), Gbeta (FgGpb1) and Ggamma (FgGpg1) subunits were significantly down-regulated in Fgric8 mutants. Moreover, we showed that FgRic8 physically interacts with both FgGpa1 and FgGpa3, but not FgGpa2, in yeast two-hybrid assays. The intracellular cAMP levels in Fgric8 mutants were significantly decreased compared to the isogenic wild-type strain. Taken together, our results indicate that FgRic8 plays critical roles in fungal development, secondary metabolism and virulence in F. graminearum and may act as a regulator of G protein alpha subunits.
ESTHER : Wu_2015_Fungal.Genet.Biol_83_92
PubMedSearch : Wu_2015_Fungal.Genet.Biol_83_92
PubMedID: 26341536

Title : [Effects of lingonberry extraction on the mice cognitive function damaged by chronic stress] - Zuo_2015_Wei.Sheng.Yan.Jiu_44_943
Author(s) : Zuo C , Li W , Wang L , Zhu J , Wang Z
Ref : Wei Sheng Yan Jiu , 44 :943 , 2015
Abstract : OBJECTIVE: To study the effects of lingonberry extraction on mice cognitive impairment caused by chronic stress.
METHODS: Kunming mice were randomly divided into six groups, which were control group, stress model group, the fluoxetine group (dose of 4.4 mg . kg(-1) . d(-1)), lingonberry extraction low, medium and high dose group (respectively 50, 100 and 200 mg . kg(-1) . d(-1)). All groups were given chronic uncertainty stress but the control group, and were intragastric administration for 18 days. Then the cognition of the mice was tested by using water maze, the contents of the SOD, GSH-Px, MDA and the activity of the neurotransmitters such as noradreline (NE), serotonin (5-HT), glucocorticoids (GC), acetylcholinesterase (AchE) were measured by using kit.
RESULTS: Lingonberry extraction improved the cognition and memory of the mice induced by chronic uncertainty stress, increased the content of the SOD and GSH-Px in mice brain, and decreased the content of oxidative damage markers MDA. Lingonberry extraction could also inhibit the increase of GC, inhibit the activity of AchE in blood serum, elevated the content of 5-HT and NE in mice blood serum and brain. CONCLUSION: Lingonberry extraction improved the cognition and memory of the mice induced by chronic uncertainty stress. The possible mechanism was that lingonberry enhanced the antioxidative ability of tissue and improved the disorder of neurotransmitter levels caused by chronic stress.
ESTHER : Zuo_2015_Wei.Sheng.Yan.Jiu_44_943
PubMedSearch : Zuo_2015_Wei.Sheng.Yan.Jiu_44_943
PubMedID: 26738388

Title : Lignin binding to pancreatic lipase and its influence on enzymatic activity - Zhang_2014_Food.Chem_149_99
Author(s) : Zhang J , Xiao L , Yang Y , Wang Z , Li G
Ref : Food Chem , 149 :99 , 2014
Abstract : In this paper, we find that the effect of lignin on pancreatic lipase (PL) is dependent on reaction medium and substrate used. Experimental results reveal that lignin can gradually bind to PL to form a PL-lignin complex, resulting in an increased activity of the enzyme. The binding process is spontaneous and the PL-lignin complex formation is an endothermic reaction induced by hydrophobic and electrostatic interaction. There is a non-radiation energy transfer from PL to lignin during the binding process, and the binding of lignin to PL conforms to a secondary exponential decay function. Moreover, the alpha-helix content of the enzyme will be changed and the rigidity of its side chain will be enhanced due to the formation of lignin-PL complex. This study has not only provided the activation effect of lignin on PL, but also given an insight into the interaction between lignin and the enzyme, which would benefit the application of lignin in the pharmacy and food industry, as well as other fields.
ESTHER : Zhang_2014_Food.Chem_149_99
PubMedSearch : Zhang_2014_Food.Chem_149_99
PubMedID: 24295682

Title : Purification, Characterization, and Sensitivity to Pesticides of Carboxylesterase From Dendrolimus superans (Lepidoptera: Lasiocampidae) - Zou_2014_J.Insect.Sci_14_
Author(s) : Zou C , Cao C , Zhang G , Wang Z
Ref : J Insect Sci , 14 : , 2014
Abstract : Through a combination of steps including centrifugation, ammonium sulfate gradient precipitation, sephadex G-25 gel chromatography, diethylaminoethyl cellulose 52 ion-exchange chromatography and hydroxyapatite affinity chromatography, carboxylesterase (CarE, EC3.1.1.1) from sixth instar larch caterpillar moth, Dendrolimus superans (Lepidoptera: Lasiocampidae) larvae was purified and its biochemical properties were compared between crude homogenate and purified CarE. The final purified CarE after hydroxyapatite chromatography had a specific activity of 52.019 mumol/(min.mg protein), 138.348-fold of crude homogenate, and the yield of 2.782%. The molecular weight of the purified CarE was approximately 84.78 kDa by SDS-PAGE. Three pesticides (dichlorvos, lambda-cyhalothrin, and avermectins) showed different inhibition to crude CarE and purified CarE, respectively. In vitro median inhibitory concentration indicated that the sensitivity of CarE (both crude homogenate and final purified CarE) to pesticides was in decreasing order of dichlorvos > avermectins > lambda-cyhalothrin. By the kinetic analysis, the substrates alpha-naphthyl acetate (alpha-NA) and beta-naphthyl acetate (beta-NA) showed lesser affinity to crude extract than purified CarE. The results also indicated that both crude homogenate and purified CarE had more affinity to alpha-NA than to beta-NA, and the Kcat and Vmax values of crude extract were lower than purified CarE using alpha-NA or beta-NA as substrate.
ESTHER : Zou_2014_J.Insect.Sci_14_
PubMedSearch : Zou_2014_J.Insect.Sci_14_
PubMedID: 25525114

Title : Structural and functional characterization of a novel alpha\/beta hydrolase from cariogenic pathogen Streptococcus mutans - Wang_2014_Proteins_82_695
Author(s) : Wang Z , Li L , Su XD
Ref : Proteins , 82 :695 , 2014
Abstract : The protein Smu.1393c from Streptococcus mutans is annotated as a putative alpha/beta hydrolase, but it has low sequence identity to the structure-known alpha/beta hydrolases. Here we present the crystal structure of Smu.1393c at 2.0 A resolution. Smu.1393c has a fully open alkaline substrate pocket, whose conformation is unique among other similar hydrolase structures. Three residues, Ser101, His251, and Glu125, were identified as the active center of Smu.1393c. By screening a series of artificial hydrolase substrates, we demonstrated Smu.1393c had low carboxylesterase activity towards short-chain carboxyl esters, which provided a clue for exploring the in vivo function of Smu.1393c. Proteins 2014; 82:695-700. (c) 2013 Wiley Periodicals, Inc.
ESTHER : Wang_2014_Proteins_82_695
PubMedSearch : Wang_2014_Proteins_82_695
PubMedID: 24115105
Gene_locus related to this paper: strmu-SMU.1393C

Title : Rapid and sensitive detection of the inhibitive activities of acetyl- and butyryl-cholinesterases inhibitors by UPLC-ESI-MS\/MS - Liu_2014_J.Pharm.Biomed.Anal_94_215
Author(s) : Liu W , Yang Y , Cheng X , Gong C , Li S , He D , Yang L , Wang Z , Wang C
Ref : J Pharm Biomed Anal , 94 :215 , 2014
Abstract : Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are legitimate therapeutic targets for Alzheimer's disease. The classical approach for screening potential AChE/BChE inhibitors was developed by Ellman. However, the background color of compounds or plant extracts remained uncertain and frequently interfered with the detection of the secondary reaction, thereby easily yielding false positive or false negative results. Rapid, selective, and sensitive ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry method was developed and used for the detection of AChE and BChE inhibition by directly determining the common product, choline (Ch). Proper separation was achieved for choline and chlormequat (internal standard) within 1.2min via isocratic elution (0.1% fromic acid:methanol=98:2) on an HSS T3 column following a simple precipitation of proteins for sample treatment. The relative standard deviations of the intra- and inter-day precisions were below 7.34 and 9.09%, respectively, whereas the mean accuracy for the quality control samples was 100.31+/-10.93%. The method exhibited the advantages of small total reaction volume (100muL), short analysis time (1.2min), high sensitivity (LOQ of 0.036muM for Ch), and low cost (little consumption enzymes of 0.0035 and 0.008unitmL(-1) for AChE and BChE, and substrates of 5.505 and 7.152muM for ACh and BCh in individual inhibition, respectively), and without matrix effect (90.00-105.03%). The developed method was successfully applied for detecting the AChE and BChE inhibitive activities for model drugs, including galanthamine, tacrine, neostigmine methylsulfate, eserine, as well as beta-carboline and quinazoline alkaloids from Peganum harmala.
ESTHER : Liu_2014_J.Pharm.Biomed.Anal_94_215
PubMedSearch : Liu_2014_J.Pharm.Biomed.Anal_94_215
PubMedID: 24631841

Title : Comparative genomic and transcriptomic analysis of wangiella dermatitidis, a major cause of phaeohyphomycosis and a model black yeast human pathogen - Chen_2014_G3.(Bethesda)_4_561
Author(s) : Chen Z , Martinez DA , Gujja S , Sykes SM , Zeng Q , Szaniszlo PJ , Wang Z , Cuomo CA
Ref : G3 (Bethesda) , 4 :561 , 2014
Abstract : Black or dark brown (phaeoid) fungi cause cutaneous, subcutaneous, and systemic infections in humans. Black fungi thrive in stressful conditions such as intense light, high radiation, and very low pH. Wangiella (Exophiala) dermatitidis is arguably the most studied phaeoid fungal pathogen of humans. Here, we report our comparative analysis of the genome of W. dermatitidis and the transcriptional response to low pH stress. This revealed that W. dermatitidis has lost the ability to synthesize alpha-glucan, a cell wall compound many pathogenic fungi use to evade the host immune system. In contrast, W. dermatitidis contains a similar profile of chitin synthase genes as related fungi and strongly induces genes involved in cell wall synthesis in response to pH stress. The large portfolio of transporters may provide W. dermatitidis with an enhanced ability to remove harmful products as well as to survive on diverse nutrient sources. The genome encodes three independent pathways for producing melanin, an ability linked to pathogenesis; these are active during pH stress, potentially to produce a barrier to accumulated oxidative damage that might occur under stress conditions. In addition, a full set of fungal light-sensing genes is present, including as part of a carotenoid biosynthesis gene cluster. Finally, we identify a two-gene cluster involved in nucleotide sugar metabolism conserved with a subset of fungi and characterize a horizontal transfer event of this cluster between fungi and algal viruses. This work reveals how W. dermatitidis has adapted to stress and survives in diverse environments, including during human infections.
ESTHER : Chen_2014_G3.(Bethesda)_4_561
PubMedSearch : Chen_2014_G3.(Bethesda)_4_561
PubMedID: 24496724
Gene_locus related to this paper: exodn-h6bmp3 , exodn-h6btr2 , exodn-h6c4y3

Title : Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears - Liu_2014_Cell_157_785
Author(s) : Liu S , Lorenzen ED , Fumagalli M , Li B , Harris K , Xiong Z , Zhou L , Korneliussen TS , Somel M , Babbitt C , Wray G , Li J , He W , Wang Z , Fu W , Xiang X , Morgan CC , Doherty A , O'Connell MJ , McInerney JO , Born EW , Dalen L , Dietz R , Orlando L , Sonne C , Zhang G , Nielsen R , Willerslev E , Wang J
Ref : Cell , 157 :785 , 2014
Abstract : Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans.
ESTHER : Liu_2014_Cell_157_785
PubMedSearch : Liu_2014_Cell_157_785
PubMedID: 24813606
Gene_locus related to this paper: ursma-a0a384cw87 , ursma-a0a384cqm7 , ursma-a0a452vbh6 , ursma-a0a384cyu0

Title : Enzymatic resolution of ibuprofen in an organic solvent under ultrasound irradiation - Zhao_2014_Biotechnol.Appl.Biochem_61_655
Author(s) : Zhao D , Yue H , Chen G , Jiang L , Zhang H , Wang Z , Liu G
Ref : Biotechnol Appl Biochem , 61 :655 , 2014
Abstract : Ultrasound has been successfully adopted to improve the biocatalytic properties of APE1547 (a novel esterase from the archaeon Aeropyrum pernix K1) in the resolution of ibuprofen. After optimizing the conditions (ultrasound power, 200 W; temperature, 35 degrees C), the best biocatalytic performance of APE1547 (enzyme activity, 5.39 micromol/H/mg; E value, 130.8) was obtained. Compared with the conventional reaction in an orbital shaker, the enzyme activity was significantly enhanced about 90-fold, and the enantioselectivity was enhanced about fourfold after an ultrasound. The results of