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Cai Z, Li M, Zhu Z, Wang X, Huang Y, Li T, Gong H, Yan M Ref: Microorganisms, 11:, 2023 : PubMed ESTHER: Cai_2023_Microorganisms_11_ PubMedSearch: Cai 2023 Microorganisms 11 PubMedID: 37512834 Abstract Plastic and microplastic pollution has caused a great deal of ecological problems because of its persistence and potential adverse effects on human health. The degradation of plastics through biological processes is of great significance for ecological health, therefore, the feasibility of plastic degradation by microorganisms has attracted a lot of attention. This study comprises a preliminary discussion on the biodegradation mechanism and the advantages and roles of different bacterial enzymes, such as PET hydrolase and PCL-cutinase, in the degradation of different polymers, such as PET and PCL, respectively. With a particular focus on their modes of action and potential enzymatic mechanisms, this review sums up studies on the biological degradation of plastics and microplastics related to mechanisms and influencing factors, along with their enzymes in enhancing the degradation of synthetic plastics in the process. In addition, biodegradation of plastic is also affected by plastic additives and plasticizers. Plasticizers and additives in the composition of plastics can cause harmful impacts. To further improve the degradation efficiency of polymers, various pretreatments to improve the efficiency of biodegradation, which can cause a significant reduction in toxic plastic pollution, were also preliminarily discussed here. The existing research and data show a large number of microorganisms involved in plastic biodegradation, though their specific mechanisms have not been thoroughly explored yet. Therefore, there is a significant potential for employing various bacterial strains for efficient degradation of plastics to improve human health and safety. Title: Chemically programmed STING-activating nano-liposomal vesicles improve anticancer immunity Chen X, Meng F, Xu Y, Li T, Wang H Ref: Nat Commun, 14:4584, 2023 : PubMed ESTHER: Chen_2023_Nat.Commun_14_4584 PubMedSearch: Chen 2023 Nat.Commun 14 4584 PubMedID: 37524727 Abstract The often immune-suppressive tumor microenvironment (TME) may hinder immune evasion and response to checkpoint blockade therapies. Pharmacological activation of the STING pathway does create an immunologically hot TME, however, systemic delivery might lead to undesired off-target inflammatory responses. Here, we generate a small panel of esterase-activatable pro-drugs based on the structure of the non-nucleotide STING agonist MSA-2 that are subsequently stably incorporated into a liposomal vesicle for intravenous administration. The pharmacokinetic properties and immune stimulatory capacity of pro-drugs delivered via liposomes (SAProsomes) are enhanced compared to the free drug form. By performing efficacy screening among the SAProsomes incorporating different pro-drugs in syngeneic mouse tumor models, we find that superior therapeutic performance relies on improved delivery to the desired tumor and lymphoid compartments. The best candidate, SAProsome-3, highly stimulates secretion of inflammatory cytokines and creates a tumoricidal immune landscape. Notably, upon application to breast cancer or melanoma mouse models, SAProsome-3 elicits durable remission of established tumors and postsurgical tumor-free survival while decreasing metastatic burden without significant systemic toxicity. In summary, our work establishes the proof of principle for a better targeted and more efficient and safe STING agonist therapy. Title: Amelioration of walnut-derived novel peptides against D-galactose-induced cognitive impairment by modulating the gut microbiota composition Li T, Lin L, Li C, Zheng J, Chen B, Shen Y, Ren D Ref: Food Funct, :, 2023 : PubMed ESTHER: Li_2023_Food.Funct__ PubMedSearch: Li 2023 Food.Funct PubMedID: 37067262 Abstract In this work, RLWPF (Arg-Leu-Trp-Pro-Phe) and VLRLF (Val-Leu-Arg-Leu-Phe) were investigated for the effects against D-galactose (D-gal) induced cognitive impairment by modulating the gut microbiota composition. The effects on serum metabolite production were further investigated. The two novel peptides derived from walnut protein alkaline protease hydrolysates were predicted by docking to acetylcholinesterase (AChE) with the highest binding affinities, -10.3 and -9.9 kcal mol(-1), considered as the potential neuroprotective peptides. In behavioral experiments, RLWPF and VLRLF treatment significantly restored spatial learning and memory impairment induced by D-gal. The results showed that RLWPF and VLRLF could alleviate cholinergic dysfunction, oxidative stress, and inflammation to varying degrees caused by D-gal-induced aging. Furthermore, 16S rRNA analysis revealed that RLWPF and VLRLF treatment improved cognitive impairment by regulating the composition of the gut microbiota and the abundance of harmful bacteria, including the ratio of Firmicutes to Bacteroidetes, Helicobacter, Allobaculum, Alistipes, Mucispirillum, and Odoribacter. In addition to the same regulation, RLWPF and VLRLF had their marker and regulatory flora. Studies based on the gut microbiota would allow a better understanding of the neuroprotective effects of walnut-derived peptides, supporting that walnut-derived peptides could be potential functional ingredients in foods and nutraceuticals or drug candidates in the treatment of cognitive dysfunction. Title: A promising tool for clinical diagnostics: Dual-emissive carbonized polymer dots based cross-linking enhanced emission for sensitive detection of alkaline phosphatase and butyrylcholinesterase Li T, Wang D, Hu J, Fu X, Ji Y, Li R Ref: Biosensors & Bioelectronics, 238:115576, 2023 : PubMed ESTHER: Li_2023_Biosens.Bioelectron_238_115576 PubMedSearch: Li 2023 Biosens.Bioelectron 238 115576 PubMedID: 37557027 Abstract Compared with single signal readout, dual-signal readout commendably corrects the impact of systematic or background error, achieving more accurate results for the diagnosis of many diseases. This work aimed to design and prepare dual-emissive fluorescent probes for the construction of ratiometric fluorescence biosensors to detect liver disease biomarkers. Sodium alginate (SA) with numerous potential sub-fluorophores and active sites and 4,4',4'',4'''-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid) (TCPP) with macrocyclic conjugated structures were introduced to prepare the carbonized polymer dots (CPDs) with red/blue dual emission based on the cross-linking enhanced emission (CEE) effect and the luminescence of macrocyclic conjugated structures. The ratiometric fluorescence sensing systems were constructed by integrating the specific response of CPDs to Cu(2+) and the affinity difference of Cu(2+) to substrates or products of enzymes. The sensing systems, CPDs/Cu(2+)/PPi and CPDs/Cu(2+)/BTCh, were designed to detect liver disease biomarkers, alkaline phosphatase (ALP) and butyrylcholinesterase (BChE), respectively. The limit of detection for ALP and BChE was 0.35 U/L and 0.19 U/L, respectively. The proposed sensors were successfully applied to human serum samples from different health stages with satisfactory recoveries. These results demonstrate the successful design of a novel dual-emissive fluorescent probe and provide a feasible strategy for clinical detection. Title: Citrobacter sp. Y3 harbouring novel gene HBCD-hd-1 mineralizes hexabromocyclododecane via new metabolic pathways according to multi-omics characterization Peng X, Li T, Zheng Q, Lu Y, He Y, Tang Y, Qiu R Ref: J Hazard Mater, 442:130071, 2023 : PubMed ESTHER: Peng_2023_J.Hazard.Mater_442_130071 PubMedSearch: Peng 2023 J.Hazard.Mater 442 130071 PubMedID: 36183513 Abstract Hexabromocyclododecane (HBCD) is a typical persistent organic pollutant that is widely detected in the environment. Despite the significant efforts put into its mineralisation, there is still a lack of microorganism resources that can completely mineralise HBCD. Stable isotope analysis revealed that the Citrobacter sp. Y3 can use [(13)C]HBCD as its sole carbon source and degrade or even mineralise it into (13)CO(2), with a maximum conversion rate of 100% in approximately 14 days. Strain Y3 could completely mineralise HBCD, which it used as its only carbon source, and six debromination enzymes related to HBCD degradation were found in Y3, including haloalkane dehalogenase (DhaA), haloacid dehalogenase (HAD), etc. A functional gene named HBCD-hd-1, encoding a HAD, was found to be upregulated during HBCD degradation and heterologously expressed in Escherichia coli. Recombinant E. coli with the HBCD-hd-1 gene transformed the typical intermediate 4-bromobutyric acid to 4-hydroxybutanoic acid and showed excellent degradation performance on HBCD, accompanied by nearly 100% bromine (Br) ion generation. The expression of HBCD-hd-1 in Y3 rapidly accelerated the biodegradation of HBCD. With HBCD as its sole carbon source, strain Y3 could potentially degrade HBCD, especially in a low-nutrient environment. Title: Diacylglycerol lipase alpha promotes hepatocellular carcinoma progression and induces lenvatinib resistance by enhancing YAP activity Yan YC, Meng GX, Yang CC, Yang YF, Tan SY, Yan LJ, Ding ZN, Ma YL, Dong ZR, Li T Ref: Cell Death Dis, 14:404, 2023 : PubMed ESTHER: Yan_2023_Cell.Death.Dis_14_404 PubMedSearch: Yan 2023 Cell.Death.Dis 14 404 PubMedID: 37414748 Gene_locus related to this paper: human-DAGLA Abstract As an important hydrolytic enzyme that yields 2-AG and free fatty acids, diacylglycerol lipase alpha (DAGLA) is involved in exacerbating malignant phenotypes and cancer progression, but the role of the DAGLA/2-AG axis in HCC progression remains unclear. Here, we found that the upregulation of components of the DAGLA/2-AG axis in HCC samples is correlated with tumour stage and patient prognosis. In vitro and in vivo experiments demonstrated that the DAGLA/2-AG axis promoted HCC progression by regulating cell proliferation, invasion and metastasis. Mechanistically, the DAGLA/2AG axis significantly inhibited LATS1 and YAP phosphorylation, promoted YAP nuclear translocation and activity, and ultimately led to TEAD2 upregulation and increased PHLDA2 expression, which could be enhanced by DAGLA/2AG-induced activation of the PI3K/AKT pathway. More importantly, DAGLA induced resistance to lenvatinib therapy during HCC treatment. Our study demonstrates that inhibiting the DAGLA/2-AG axis could be a novel therapeutic strategy to inhibit HCC progression and enhance the therapeutic effects of TKIs, which warrant further clinical studies. Title: Spatial distribution differences of cholinesterase in healthy Chinese under the influence of geographical environmental factors Yang W, Ge M, Wang Z, Li T Ref: Environ Sci Pollut Res Int, :, 2023 : PubMed ESTHER: Yang_2023_Environ.Sci.Pollut.Res.Int__ PubMedSearch: Yang 2023 Environ.Sci.Pollut.Res.Int PubMedID: 36800095 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. Title: Interrelationship between 2019-nCov receptor DPP4 and diabetes mellitus targets based on protein interaction network Gao Q, Zhang W, Li T, Yang G, Zhu W, Chen N, Jin H Ref: Sci Rep, 12:188, 2022 : PubMed ESTHER: Gao_2022_Sci.Rep_12_188 PubMedSearch: Gao 2022 Sci.Rep 12 188 PubMedID: 34996987 Abstract Patients with diabetes are more likely to be infected with Coronavirus disease 2019 (COVID-19), and the risk of death is significantly higher than ordinary patients. Dipeptidyl peptidase-4 (DPP4) is one of the functional receptor of human coronavirus. Exploring the relationship between diabetes mellitus targets and DPP4 is particularly important for the management of patients with diabetes and COVID-19. We intend to study the protein interaction through the protein interaction network in order to find a new clue for the management of patients with diabetes with COVID-19. Diabetes mellitus targets were obtained from GeneCards database. Targets with a relevance score exceeding 20 were included, and DPP4 protein was added manually. The initial protein interaction network was obtained through String. The targets directly related to DPP4 were selected as the final analysis targets. Importing them into String again to obtain the protein interaction network. Module identification, gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were carried out respectively. The impact of DPP4 on the whole network was analyzed by scoring the module where it located. 43 DPP4-related proteins were finally selected from the diabetes mellitus targets and three functional modules were found by the cluster analysis. Module 1 was involved in insulin secretion and glucagon signaling pathway, module 2 and module 3 were involved in signaling receptor binding. The scoring results showed that LEP and apoB in module 1 were the highest, and the scores of INS, IL6 and ALB of cross module associated proteins of module 1 were the highest. DPP4 is widely associated with key proteins in diabetes mellitus. COVID-19 may affect DPP4 in patients with diabetes mellitus, leading to high mortality of diabetes mellitus combined with COVID-19. DPP4 inhibitors and IL-6 antagonists can be considered to reduce the effect of COVID-19 infection on patients with diabetes. Title: Experimental Study of the Adsorption and Decomposition of Sarin on Dry Copper(II) Oxide Leonard MB, Bruni E, Hall M, Li T, Rodriguez EE, Durke EM Ref: J Phys Chem Lett, :11663, 2022 : PubMed ESTHER: Leonard_2022_J.Phys.Chem.Lett__11663 PubMedSearch: Leonard 2022 J.Phys.Chem.Lett 11663 PubMedID: 36508258 Abstract Organophosphonates were originally developed as insecticides but were quickly identified as highly toxic acetylcholinesterase inhibitors, leading to their exploitation as chemical warfare agents (CWA). To develop next generation filtration technologies, there must be a fundamental understanding of the molecular interactions occurring with toxic chemicals, such as CWAs. In this paper, we investigate the interaction between dry CuO nanoparticles and sarin (GB), using infrared (IR) spectroscopy in an effort to build an atomic understanding. We show sarin strongly interacts with CuO and then quickly degrades, primarily through the cleavage of the P-F bond, creating a bridging species on the CuO surface with the assistance of lattice oxygen. Upon heating, the decomposition product isopropyl methyl phosphonic acid (IMPA) does not continue to decompose but desorbs from the surface. These observations are further elaborated through theoretical models of sarin on dry CuO (111). Title: Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease from Natural (+/-)-7,8-Dihydroxy-3-methyl-isochroman-4-one Li X, Jia Y, Li J, Zhang P, Li T, Lu L, Yao H, Liu J, Zhu Z, Xu J Ref: Molecules, 27:3090, 2022 : PubMed ESTHER: Li_2022_Molecules_27_3090 PubMedSearch: Li 2022 Molecules 27 3090 PubMedID: 35630563 Abstract Alzheimer's disease (AD) is a neurodegenerative disease that causes memory and cognitive decline as well as behavioral problems. It is a progressive and well recognized complex disease; therefore, it is very urgent to develop novel and effective anti-AD drugs. In this study, a series of novel isochroman-4-one derivatives from natural (+/-)-7,8-dihydroxy-3-methyl-isochroman-4-one [(+/-)-XJP] were designed and synthesized, and their anti-AD potential was evaluated. Among them, compound 10a [(Z)-3-acetyl-1-benzyl-4-((6,7-dimethoxy-4-oxoisochroman-3-ylidene)methyl)pyridin-1-ium bromide] possessed potent anti-acetylcholinesterase (AChE) activity as well as modest antioxidant activity. Further molecular modeling and kinetic investigations revealed that compound 10a was a dual-binding inhibitor that binds to both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the enzyme AChE. In addition, compound 10a exhibited low cytotoxicity and moderate anti-Abeta aggregation efficacy. Moreover, the in silico screening suggested that these compounds could pass across the blood-brain barrier with high penetration. These findings show that compound 10a was a promising lead from a natural product with potent AChE inhibitory activity and deserves to be further developed for the prevention and treatment of AD. Title: Ultrasensitive Acetylcholinesterase detection based on a surface-enhanced Raman scattering lever strategy for identifying nerve fibers Li T, Sui T, Wang B, Xu K, Zhang S, Cao X, Wang Y, Qian W, Dong J Ref: Talanta, 252:123867, 2022 : PubMed ESTHER: Li_2022_Talanta_252_123867 PubMedSearch: Li 2022 Talanta 252 123867 PubMedID: 36041317 Abstract Accurate discriminating nerve fibers is a prerequisite for right suturing nerves in nerve transfer operation. Various methods have been developed for identification of motor and sensory fibers, but no simple method meets the requirements in clinic. In this study, a surface-enhanced Raman scattering (SERS) lever strategy is designed and developed to detect Acetylcholinesterase (AchE) ultrasensitively, in which using produced thiocholine with weak intrinsic Raman activity (four ounces) to adjust absorbance of Rhodamine B with strong intrinsic Raman activity (thousand catties) on SERS-active substrates is to increase the sensitivity. Employing a miniaturized SERS substrate, SERS-active microneedles, is to decrease the volume of enzymolysis systems. Adopting an internal reference is to increase the repeatability of collected signal. The ultrasensitive AchE detection method discriminate samples with four times of difference in enzyme activity between 1-1 x 10(-4) U/mL in about 10 min of enzymolysis time. AchE amounts in 2-mm-long segments of ventral and dorsal roots were about 0.00025-0.001 U and 0.01-0.02 U, respectively. The developed method would be a reliable method met the requirements of identifying motor and sensory fibers in clinic. Title: Discovery of novel hybrids containing clioquinol-1-benzyl-1,2,3,6-tetrahydropyridine as multi-target-directed ligands (MTDLs) against Alzheimer's disease Li X, Li T, Zhang P, Lu L, Sun Y, Zhang B, Allen S, White L, Phillips J and Xu J <2 more author(s)> Li X, Li T, Zhang P, Lu L, Sun Y, Zhang B, Allen S, White L, Phillips J, Zhu Z, Yao H, Xu J (- 2) Ref: Eur Journal of Medicinal Chemistry, 244:114841, 2022 : PubMed ESTHER: Li_2022_Eur.J.Med.Chem_244_114841 PubMedSearch: Li 2022 Eur.J.Med.Chem 244 114841 PubMedID: 36257284 Inhibitor(s) related to this paper: Compound19n-quinolinol Abstract Based on the multitarget strategy, a series of novel clioquinol-1-benzyl-1,2,3,6-tetrahydropyridine hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation in vitro revealed that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE). The optimal compound, 19n, exhibited excellent AChE inhibitory potency (IC(50) = 0.11 microM), appropriate metal chelating functions, modulation of AChE- and metal-induced Abeta aggregation, neuroprotection against okadaic acid-induced mitochondrial dysfunction and ROS damage, and interesting properties that reduced p-Tau levels in addition to no toxicity on SH-SY5Y cells observed at a concentration up to 50 microM. Most importantly, compound 19n was more well tolerated (>1200 mg/kg) than donepezil (LD(50) = 28.124 mg/kg) in vivo. Moreover, compound 19n demonstrated marked improvements in cognitive and spatial memory in two AD mice models (scopolamine-induced and Abeta(1-42)-induced) and suppressed inflammation induced by Abeta(1-42) in the cortex. The multifunctional profiles of compound 19n demonstrate that it deserves further investigation as a promising lead in the development of innovatively multifunctional drugs for Alzheimer's disease. Title: Design, Synthesis, and Biological Evaluation of Novel Chromanone Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease Li X, Li T, Zhan F, Cheng F, Lu L, Zhang B, Li J, Hu Z, Zhou S and Yao H <6 more author(s)> Li X, Li T, Zhan F, Cheng F, Lu L, Zhang B, Li J, Hu Z, Zhou S, Jia Y, Allen S, White L, Phillips J, Zhu Z, Xu J, Yao H (- 6) Ref: ACS Chem Neurosci, :, 2022 : PubMed ESTHER: Li_2022_ACS.Chem.Neurosci__ PubMedSearch: Li 2022 ACS.Chem.Neurosci PubMedID: 36383455 Abstract Based on a multitarget strategy, a series of novel chromanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). The optimal compound C10 possessed excellent dual AChE/MAO-B inhibition both in terms of potency and equilibrium (AChE: IC(50) = 0.58 0.05 M; MAO-B: IC(50) = 0.41 0.04 M). Further molecular modeling and kinetic investigations revealed that compound C10 was a dual-binding inhibitor bound to both the catalytic anionic site and peripheral anionic site of AChE. In addition, compound C10 exhibited low neurotoxicity and potently inhibited AChE enzymatic activity. Furthermore, compound C10 more effectively protected against mitochondrial dysfunction and oxidation than donepezil, strongly inhibited AChE-induced amyloid aggregation, and moderately reduced glutaraldehyde-induced phosphorylation of tau protein in SH-SY5Y cells. Moreover, compound C10 displayed largely enhanced improvements in cognitive behaviors and spatial memory in a scopolamine-induced AD mice model with better efficacy than donepezil. Overall, the multifunctional profiles of compound C10 suggest that it deserves further investigation as a promising lead for the prospective treatment of AD. Title: An esterase-activatable prodrug formulated liposome strategy: potentiating the anticancer therapeutic efficacy and drug safety Shi L, Wu X, Li T, Wu Y, Song L, Zhang W, Yin L, Han W, Yang Y Ref: Nanoscale Adv, 4:952, 2022 : PubMed ESTHER: Shi_2022_Nanoscale.Adv_4_952 PubMedSearch: Shi 2022 Nanoscale.Adv 4 952 PubMedID: 36131817 Abstract Liposomal nanomedicine represents a common and versatile carrier for the delivery of both lipophilic and hydrophilic drugs. However, the direct formulation of many chemotherapeutics into a liposomal system remains an enormous challenge. Using the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38) as a model drug, we combined lipophilic prodrug construction with subsequent integration into an exogenous liposomal scaffold to assemble a prodrug-formulated liposome for systemic administration. Reconstructing SN38 with lipid cholesterol via the esterase-activatable bond endows the resulting prodrug with elevated miscibility with liposomal compositions and esterase-responsive drug release in cancerous cells. The systemic administration of the prodrug-based nanoassemblies (Chol-SN38@LP) exhibited preferential accumulation of therapeutic payloads in tumor lesions. Compared to the SN38 clinical counterpart irinotecan, our prodrug-based nanoassemblies with adaptive features showed elevated therapeutic efficacy (-1.5 times increase of tumor inhibition) in a preclinical A549 lung carcinoma cell-derived mouse model and improved drug tolerability (i.e., alleviated bloody diarrhea and liver damage) in multiple mice models. These results may be ascribed to extended systemic circulation and preferential tumor accumulation of our nanodrugs. Hence, our findings demonstrate that rational engineering of therapeutic nanomedicine is a promising approach for effective and safe delivery of antitumor chemotherapeutics, especially to rescue drug candidates that have failed in clinical trials owing to poor PK properties or severe toxicity in patients. Title: Acetylcholinesterase-capped mesoporous silica gated switches for selective detection of high-toxicity organophosphate compounds Zhang Y, Li T, Sun X, Liu H, Wang Y, Nie Z Ref: Anal Chim Acta, 1207:339708, 2022 : PubMed ESTHER: Zhang_2022_Anal.Chim.Acta_1207_339708 PubMedSearch: Zhang 2022 Anal.Chim.Acta 1207 339708 PubMedID: 35491047 Abstract Organophosphate (OP) compounds are widely used in agriculture, industry, and even terrorism. It is important to distinguish high-toxicity OP compounds from low-toxicity OP compounds in dealing with chemical accidents. However, there are very few portable and simple detection methods. Mesoporous silica gated switches may provide an effective solution. In this study, a gated switch based on mesoporous silica as an inorganic scaffold loaded with sulforhodamine B and capped with acetylcholinesterase (AChE) was prepared for specific detection of OP compounds. Carbamate derivatives (G1-G6) were designed and synthetized as grafting compounds in consideration of the binding ability with AChE. Through further modification and optimization, grafting compound G6 with phenylpyridine as the substituent showed the best capping capacity, and it achieved excellent blocking of mesoporous silica gated switches for loaded sulforhodamine B. In the presence of high-toxicity OP compounds, low-toxicity OP compounds, AChE substrates and reversible AChE inhibitors respectively, only high-toxicity OP compounds could make the gated switch release loaded sulforhodamine B. The limit of detection for paraoxon-ethyl was 10.6 micro. Furthermore, the preparation process of the gated switch is fast and simple, and the prepared gated switch has good stability and rapid distinguishing ability. The results of this paper provide a new idea for rapidly distinguishing high-toxicity OP compounds from low-toxicity OP compounds and other related compounds on the spot. Title: Molecular and functional characterization of three novel carboxylesterases in the detoxification of permethrin in the mosquito, Culex quinquefasciatus Gong Y, Li M, Li T, Liu N Ref: Insect Sci, :, 2021 : PubMed ESTHER: Gong_2021_Insect.Sci__ PubMedSearch: Gong 2021 Insect.Sci PubMedID: 34048147 Gene_locus related to this paper: culqu-b0xfi1, culqu-b0xfi2, culqu-b0xfi3 Abstract Carboxylesterases (CarEs) belong to a super family of multifunctional enzymes associated with the degradation of endogenous and exogenous compounds. Many insect CarEs are known to play important roles in catalyzing the hydrolysis of organophosphates (OPs), carbamates, and synthetic pyrethroids (SPs). The elevation of esterase activity through gene amplification and overexpression of estalpha2 and estbeta2 genes contributes to the development of resistance to OP insecticides in the mosquito Culex quinquefasciatus. Three additional CarE genes are upregulated in permethrin-resistant Cx. quinquefasciatus according to an RNA-seq analysis, but their function remains unknown. In this study, we, for the first time, characterized the function of these three novel genes using in vitro protein expression, an insecticide metabolism study and molecular docking analysis. All three CarE genes were significantly overexpressed in resistant mosquito larvae, but not adults, compared to susceptible strain. No gene copy differences in these three genes were found in the mosquitoes tested. In vitro high-performance liquid chromatography (HPLC) revealed that CPIJ018231, CPIJ018232, and CPIJ018233 metabolized 30.4% +/- 2.9%, 34.7% +/- 6.8%, and 23.2% +/- 2.2% of the permethrin, respectively. No mutations in resistant strains might significantly affect their CarE hydrolysis ability. A docking analysis further confirmed that these three CarEs from resistant strain all potentially metabolize permethrin. Taken together, these three carboxylesterase genes could play important roles in the development of permethrin resistance in Cx. quinquefasciatus larvae through transcriptional overexpression, metabolism, and detoxification. Title: Sugammadex enhances recovery after abdominal surgery in cancer patients: a real-world, observational study Gu X, Gao R, Li P, Jiao D, Song T, Li T, Gu L Ref: Ann Palliat Med, 10:12566, 2021 : PubMed ESTHER: Gu_2021_Ann.Palliat.Med_10_12566 PubMedSearch: Gu 2021 Ann.Palliat.Med 10 12566 PubMedID: 35016451 Abstract BACKGROUND: Sugammadex, a modified gamma-cyclodextrin that selectively binds to muscle relaxants, is increasingly being used to reverse neuromuscular blockade after surgery, but the potential benefits for cancer patients in the real-world setting are obscure. METHODS: This was a real-world, retrospective study. Adult cancer patients (<=18 years) undergoing abdominal surgery at Jiangsu Cancer Hospital, a tertiary care cancer hospital in China, between 2 March 2018 and 25 November 2019, were included in the analysis. Patients received 2 mg/kg (maximally 200 mg) sugammadex based on the discretion of the attending anesthetists. Patients were extubated as soon as they were awake and able to follow commands. The endpoint measures included extubation time, bowel function recovery and length of hospital stay. RESULTS: A total of 1,615 patients were included in the analysis: 795 participants received sugammadex at a dosage of 2 mg/kg (maximum 200 mg) upon completion of surgery; the remaining 820 participants did not receive sugammadex or neostigmine (another antidote for neuromuscular blockade). Despite several biases that clearly favored patients not receiving sugammadex [younger, better American Society of Anesthesiologists (ASA) status, and fewer comorbidities], the extubation time was significantly shorter in patients receiving sugammadex [median: 14 (range, 0-121) vs. 30.5 (range, 0-183) min; P<0.001]. In multivariate linear regression analysis, sugammadex use was associated with a significantly shorter extubation time (P<0.05). Patients who received sugammadex also had accelerated bowel function recovery and shorter postoperative hospital stay. CONCLUSIONS: Sugammadex shortens extubation time and accelerates postoperative recovery in cancer patients undergoing abdominal surgery. Title: Design, Synthesis, and Study of the Insecticidal Activity of Novel Steroidal 1,3,4-Oxadiazoles Ma S, Jiang W, Li Q, Li T, Wu W, Bai H, Shi B Ref: Journal of Agricultural and Food Chemistry, :, 2021 : PubMed ESTHER: Ma_2021_J.Agric.Food.Chem__ PubMedSearch: Ma 2021 J.Agric.Food.Chem PubMedID: 34554742 Abstract A series of novel steroidal derivatives with a substituted 1,3,4-oxadiazole structure was designed and synthesized, and the target compounds were evaluated for their insecticidal activity against five aphid species. Most of the tested compounds exhibited potent insecticidal activity against Eriosoma lanigerum (Hausmann), Myzus persicae, and Aphis citricola. Compounds 20g and 24g displayed the highest activity against E. lanigerum, showing LC(50) values of 27.6 and 30.4 microg/mL, respectively. Ultrastructural changes in the midgut cells of E. lanigerum were detected by transmission electron microscopy, indicating that these steroidal oxazole derivatives might exert their insecticidal activity by destroying the mitochondria and nuclear membranes in insect midgut cells. Furthermore, a field trial showed that compound 20g exhibited effects similar to those of the positive controls chlorpyrifos and thiamethoxam against E. lanigerum, reaching a control rate of 89.5% at a dose of 200 microg/mL after 21 days. We also investigated the hydrolysis and metabolism of the target compounds in E. lanigerum by assaying the activities of three insecticide-detoxifying enzymes. Compound 20g at 50 microg/mL exhibited inhibitory action on carboxylesterase similar to the known inhibitor triphenyl phosphate. The above results demonstrate the potential of these steroidal oxazole derivatives to be developed as novel pesticides. Title: MnO(2) switch-bridged DNA walker for ultrasensitive sensing of cholinesterase activity and organophosphorus pesticides Li W, Rong Y, Wang J, Li T, Wang Z Ref: Biosensors & Bioelectronics, 169:112605, 2020 : PubMed ESTHER: Li_2020_Biosens.Bioelectron_169_112605 PubMedSearch: Li 2020 Biosens.Bioelectron 169 112605 PubMedID: 32947079 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. Title: Ultrasensitive detection of butyrylcholinesterase activity based on the inner filter effect of MnO(2) nanosheets on sulfur nanodots 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 : PubMed ESTHER: Li_2020_Analyst_145_5206 PubMedSearch: Li 2020 Analyst 145 5206 PubMedID: 32578586 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. Title: Neuroprotective Effects of the Sonic Hedgehog Signaling Pathway in Ischemic Injury through Promotion of Synaptic and Neuronal Health 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 : PubMed ESTHER: Yin_2020_Neural.Plast_2020_8815195 PubMedSearch: Yin 2020 Neural.Plast 2020 8815195 PubMedID: 32802036 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. Title: A disposable acetylcholine esterase sensor for As(III) determination in groundwater matrix based on 4-acetoxyphenol hydrolysis Li T, Berberich J, Sahle-Demessie E, Varughese E Ref: Anal Methods, 11:5203, 2019 : PubMed ESTHER: Li_2019_Anal.Methods_11_5203 PubMedSearch: Li 2019 Anal.Methods 11 5203 PubMedID: 32021658 Abstract There is a lack of field compatible analytical method for the speciation of As(III) to characterize groundwater pollution at anthropogenic sites. To address this issue, an inhibition-based acetylcholine esterase (AchE) sensor was developed to determine As(III) in groundwater. 4-Acetoxyphenol was employed to develop an amperometric assay for AchE activity. This assay was used to guide the fabrication of an AchE sensor with screen-printed carbon electrode. An As(III) determination protocol was developed based on the pseudo-irreversible inhibition mechanism. The analysis has a dynamic range of 2-500 muM (150 - 37,500 mug L(-1)) for As(III). The sensor exhibited the same dynamic range and sensitivity in a synthetic groundwater matrix. The electrode was stable for at least 150 days at 22 +/- 2 degrees C. Title: A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review Li T, Feng Y, Liu Y, He C, Liu J, Chen H, Deng Y, Li M, Li W and Ling J <8 more author(s)> Li T, Feng Y, Liu Y, He C, Liu J, Chen H, Deng Y, Li M, Li W, Song J, Niu Z, Sang S, Wen J, Men M, Chen X, Li J, Liu X, Ling J (- 8) Ref: Gene, 704:113, 2019 : PubMed ESTHER: Li_2019_Gene_704_113 PubMedSearch: Li 2019 Gene 704 113 PubMedID: 30974196 Gene_locus related to this paper: human-ABHD12 Abstract Usher syndrome (USH) is a clinically common autosomal recessive disorder characterized by retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction. In this study, we identified a Hunan family of Chinese descent with two affected members clinically diagnosed with Usher syndrome type 3 (USH3) displaying hearing, visual acuity, and olfactory decline. Whole-exome sequencing (WES) identified a nonsense variant in ABHD12 gene that was confirmed to be segregated in this family by Sanger sequencing and exhibited a recessive inheritance pattern. In this family, two patients carried homozygous variant in the ABHD12 (NM_015600: c.249C>G). Mutation of ABHD12, an enzyme that hydrolyzes an endocannabinoid lipid transmitter, caused incomplete PHARC syndrome, as demonstrated in previous reports. Therefore, we also conducted a summary based on variants in ABHD12 in PHARC patients, and in PHARC patients showing that there was no obvious correlation between the genotype and phenotype. We believe that this should be considered during the differential diagnosis of USH. Our findings predicted the potential function of this gene in the development of hearing and vision loss, particularly with regard to impaired signal transmission, and identified a novel nonsense variant to expand the variant spectrum in ABHD12. Title: NDRG3 facilitates colorectal cancer metastasis through activating Src phosphorylation Li T, Sun R, Lu M, Chang J, Meng X, Wu H Ref: Onco Targets Ther, 11:2843, 2018 : PubMed ESTHER: Li_2018_Onco.Targets.Ther_11_2843 PubMedSearch: Li 2018 Onco.Targets.Ther 11 2843 PubMedID: 29844682 Abstract Background: NDRG3 is an N-myc downregulated gene (NDRG). The aim of this article was to identify the role of NDRG3 in colorectal cancer (CRC) and to determine the mechanism underlying its function. Methods: Using immunohistochemical staining, expression and clinicopathological variables of NDRG3 were analyzed in 170 CRC samples. Overexpression of NDRG3 was employed in SW1116 cells, downregulation of NDRG3 was achieved in RKO cells, then migration and invasion assays were performed in vitro, and a mouse model was constructed in vivo. Results: Increased expression of NDRG3 was observed in primary CRC tissues, and this expression was correlated with distant metastasis. Consistently, ectopic expression of NDRG3 in SW1116 cells enhanced cell migration and invasion, while knockdown of NDRG3 in RKO cells significantly suppressed CRC cell metastasis. The portal vein injection models suggested that NDRG3 overexpression facilitates liver metastasis. These events were associated with the phosphorylation of Src (c-Src) at Tyr 419 site. Conclusion: Our results showed that NDRG3 facilitates CRC migration and invasion by activating Src phosphorylation, suggesting the role of NDRG3 as a candidate oncogene. Title: Protein Crystallography and Site-Direct Mutagenesis Analysis of the Poly(ethylene terephthalate) Hydrolase PETase from Ideonella sakaiensis Liu B, He L, Wang L, Li T, Li C, Liu H, Luo Y, Bao R Ref: Chembiochem, 19:1471, 2018 : PubMed ESTHER: Liu_2018_Chembiochem_19_1471 PubMedSearch: Liu 2018 Chembiochem 19 1471 PubMedID: 29603535 Gene_locus related to this paper: idesa-peth Abstract Unlike traditional recycling strategies, biodegradation is a sustainable solution for disposing of poly(ethylene terephthalate) (PET) waste. PETase, a newly identified enzyme from Ideonella sakaiensis, has high efficiency and specificity towards PET and is, thus, a prominent candidate for PET degradation. On the basis of biochemical analysis, we propose that a wide substrate-binding pocket is critical for its excellent ability to hydrolyze crystallized PET. Structure-guided site-directed mutagenesis revealed an improvement in PETase catalytic efficiency, providing valuable insight into how the molecular engineering of PETase can optimize its application in biocatalysis. Title: Atlas of the Striatum and Globus Pallidus in the Tree Shrew: Comparison with Rat and Mouse Ni RJ, Huang ZH, Shu YM, Wang Y, Li T, Zhou JN Ref: Neurosci Bull, 34:405, 2018 : PubMed ESTHER: Ni_2018_Neurosci.Bull_34_405 PubMedSearch: Ni 2018 Neurosci.Bull 34 405 PubMedID: 29508249 Abstract The striatum and globus pallidus are principal nuclei of the basal ganglia. Nissl- and acetylcholinesterase-stained sections of the tree shrew brain showed the neuroanatomical features of the caudate nucleus (Cd), internal capsule (ic), putamen (Pu), accumbens, internal globus pallidus, and external globus pallidus. The ic separated the dorsal striatum into the Cd and Pu in the tree shrew, but not in rats and mice. In addition, computer-based 3D images allowed a better understanding of the position and orientation of these structures. These data provided a large-scale atlas of the striatum and globus pallidus in the coronal, sagittal, and horizontal planes, the first detailed distribution of parvalbumin-immunoreactive cells in the tree shrew, and the differences in morphological characteristics and density of parvalbumin-immunoreactive neurons between tree shrew and rat. Our findings support the tree shrew as a potential model for human striatal disorders. Title: The tree shrew cerebellum atlas: Systematic nomenclature, neurochemical characterization, and afferent projections Ni RJ, Huang ZH, Luo PH, Ma XH, Li T, Zhou JN Ref: Journal of Comparative Neurology, 526:2744, 2018 : PubMed ESTHER: Ni_2018_J.Comp.Neurol_526_2744 PubMedSearch: Ni 2018 J.Comp.Neurol 526 2744 PubMedID: 30155886 Abstract The cerebellum is involved in the control of movement, emotional responses, and reward processing. The tree shrew is the closest living relative of primates. However, little is known not only about the systematic nomenclature for the tree shrew cerebellum but also about the detailed neurochemical characterization and afferent projections. In this study, Nissl staining and acetylcholinesterase histochemistry were used to reveal anatomical features of the cerebellum of tree shrews (Tupaia belangeri chinensis). The cerebellar cortex presented a laminar structure. The morphological characteristics of the cerebellum were comprehensively described in the coronal, sagittal, and horizontal sections. Moreover, distributive maps of calbindin-immunoreactive (-ir) cells in the Purkinje cell layer of the cerebellum of tree shrews were depicted using coronal, sagittal, and horizontal schematics. In addition, 5th cerebellar lobule (5Cb)-projecting neurons were present in the pontine nuclei, reticular nucleus, spinal vestibular nucleus, ventral spinocerebellar tract, and inferior olive of the tree shrew brain. The anterior part of the paramedian lobule of the cerebellum (PMa) received mainly strong innervation from the lateral reticular nucleus, inferior olive, pontine reticular nucleus, spinal trigeminal nucleus, pontine nuclei, and reticulotegmental nucleus of the pons. The present results provide the first systematic nomenclature, detailed atlas of the whole cerebellum, and whole-brain mapping of afferent projections to the 5Cb and PMa in tree shrews. Our findings provide morphological support for tree shrews as an alternative model for studies of human cerebellar pathologies. Title: Lipase-mediated direct in situ ring-opening polymerization of E-caprolactone formed by a chemo-enzymatic method Zhang Y, Lu P, Sun Q, Li T, Zhao L, Gao X, Wang F, Liu J Ref: J Biotechnol, 281:74, 2018 : PubMed ESTHER: Zhang_2018_J.Biotechnol_281_74 PubMedSearch: Zhang 2018 J.Biotechnol 281 74 PubMedID: 29908204 Abstract A novel method to synthesize poly(sigma-caprolactone) (PCL) through a three-step, lipase-mediated chemo-enzymatic reaction from cyclohexanone using an immobilized lipase from Trichosporon laibacchii (T. laibacchii) CBS5791 was developed. The immobilized preparation with 1280 U. g(-1) used here was obtained by a method of purification and in situ immobilization where the crude intracellular lipase (cell homogenate) was subjected to partial purification by an aqueous two-phase system (ATPS) consisting of 12% (w/w) polyethylene glycol (PEG) 4000 and 13% (w/w) potassium phosphate (K(2)HPO(4)) and then in situ immobilization directly on diatomite from the top PEG-rich phase of ATPS. In this multi-step process, the sigma-caprolactone (sigma-CL) produced by lipase-mediated one-pot two-step chemo-enzymatic oxidation of cyclohexanone was directly subjected to in situ ring-opening polymerization (ROP) started by adding highly hydrophobic solvents. It is necessary to note that sigma-CL synthesis and its subsequent ROP were catalyzed by the same lipase. The impact of various reaction parameters, e.g., solvent, cyclohexanone: hydrogen peroxide molar ratio, hydrogen peroxide forms and reaction temperature were investigated. Toluene was selected as a preferred solvent due to supporting the highest molecular weight (M(n) = 2168) and moderate sigma-CL conversion (65.42%). Through the optimization of reaction conditions, PCL was produced with a M(n) of 2283 at 50 degreesC for 24 h. These results reveal that this lipase-mediated direct ring-opening polymerization of in situ formed sigma-CL is an alternative route to the conventional synthesis of PCL. Title: Sortilin 1 Modulates Hepatic Cholesterol Lipotoxicity in Mice via Functional Interaction with Liver Carboxylesterase 1 Li J, Wang Y, Matye DJ, Chavan H, Krishnamurthy P, Li F, Li T Ref: Journal of Biological Chemistry, 292:146, 2017 : PubMed ESTHER: Li_2017_J.Biol.Chem_292_146 PubMedSearch: Li 2017 J.Biol.Chem 292 146 PubMedID: 27881673 Abstract The liver plays a key role in cholesterol metabolism. Impaired hepatic cholesterol homeostasis causes intracellular free cholesterol accumulation and hepatocyte injury. Sortilin 1 (SORT1) is a lysosomal trafficking receptor that was identified by genome-wide association studies (GWAS) as a novel regulator of cholesterol metabolism in humans. Here we report that SORT1 deficiency protected against cholesterol accumulation-induced liver injury and inflammation in mice. Using an LC-MS/MS-based proteomics approach, we identified liver carboxylesterase 1 (CES1) as a novel SORT1-interacting protein. Mechanistic studies further showed that SORT1 may regulate CES1 lysosomal targeting and degradation and that SORT1 deficiency resulted in higher liver CES1 protein abundance. Previous studies have established an important role of hepatic CES1 in promoting intracellular cholesterol mobilization, cholesterol efflux, and bile acid synthesis. Consistently, high cholesterol atherogenic diet-challenged Sort1 knock-out mice showed less hepatic free cholesterol accumulation, increased bile acid synthesis, decreased biliary cholesterol secretion, and the absence of gallstone formation. SORT1 deficiency did not alter hepatic ceramide and fatty acid metabolism in high cholesterol atherogenic diet-fed mice. Finally, knockdown of liver CES1 in mice markedly increased the susceptibility to high cholesterol diet-induced liver injury and abolished the protective effect against cholesterol lipotoxicity in Sort1 knock-out mice. In summary, this study identified a novel SORT1-CES1 axis that regulates cholesterol-induced liver injury, which provides novel insights that improve our current understanding of the molecular links between SORT1 and cholesterol metabolism. This study further suggests that therapeutic inhibition of SORT1 may be beneficial in improving hepatic cholesterol homeostasis in metabolic and inflammatory liver diseases. Title: Neurexin Restricts Axonal Branching in Columns by Promoting Ephrin Clustering Liu L, Tian Y, Zhang XY, Zhang X, Li T, Xie W, Han J Ref: Dev Cell, 41:94, 2017 : PubMed ESTHER: Liu_2017_Dev.Cell_41_94 PubMedSearch: Liu 2017 Dev.Cell 41 94 PubMedID: 28366281 Abstract Columnar restriction of neurites is critical for forming nonoverlapping receptive fields and preserving spatial sensory information from the periphery in both vertebrate and invertebrate nervous systems, but the underlying molecular mechanisms remain largely unknown. Here, we demonstrate that Drosophila homolog of alpha-neurexin (DNrx) plays an essential role in columnar restriction during L4 axon branching. Depletion of DNrx from L4 neurons resulted in misprojection of L4 axonal branches into neighboring columns due to impaired ephrin clustering. The proper ephrin clustering requires its interaction with the intracellular region of DNrx. Furthermore, we find that Drosophila neuroligin 4 (DNlg4) in Tm2 neurons binds to DNrx and initiates DNrx clustering in L4 neurons, which subsequently induces ephrin clustering. Our study demonstrates that DNrx promotes ephrin clustering and reveals that ephrin/Eph signaling from adjacent L4 neurons restricts axonal branches of L4 neurons in columns. Title: Ameliorating effect of Alpinia oxyphylla-Schisandra chinensis herb pair on cognitive impairment in a mouse model of Alzheimer's disease Wang M, Bi W, Fan K, Li T, Yan T, Xiao F, He B, Bi K, Jia Y Ref: Biomed Pharmacother, 97:128, 2017 : PubMed ESTHER: Wang_2017_Biomed.Pharmacother_97_128 PubMedSearch: Wang 2017 Biomed.Pharmacother 97 128 PubMedID: 29080453 Abstract Alzheimer's disease (AD) is the most common cause of dementia. In our previous study, we found both Alpinia oxyphylla and Schisandra chinensis can improve the cognitive function of AD. To investigate whether the Alpinia oxyphylla - Schisandra chinensis herb pair (ASHP) has ameliorating effect on cognitive impairment, we used scopolamine to induce learning and memory impairments, as a mouse model of AD. Subsequently, we carried out Y-maze test and Morris water maze test to observe the behavior of mice. Finally, the level of Acetylcholine (Ach) and muscarinic receptor (M1) receptors, the activity of choline acetyltransferase (ChAT) and acetyl cholinesterase (AChE) were measured by commercial assay kits and ELISA kit. And we used hematoxylin-eosin (HE) staining to check the changes in cortex and the CA1 region of hippocampus. ASHP significantly protected against learning and memory impairments induced by scopolamine in Y-maze test and Morris water maze test. Besides, ASHP was able to increase the level of ACh and M1 receptors, and decrease the activity of AChE, but did not significantly affect the activity of ChAT. In addition, from the results of histopathological examination, we speculated ASHP may have neuroprotective effects. This study provided an experimental basis for further study of Alpinia oxyphylla - Schisandra chinensis herb pair in AD therapy. Title: Scallop genome provides insights into evolution of bilaterian karyotype and development Wang S, Zhang J, Jiao W, Li J, Xun X, Sun Y, Guo X, Huan P, Dong B and Bao Z <42 more author(s)> Wang S, Zhang J, Jiao W, Li J, Xun X, Sun Y, Guo X, Huan P, Dong B, Zhang L, Hu X, Sun X, Wang J, Zhao C, Wang Y, Wang D, Huang X, Wang R, Lv J, Li Y, Zhang Z, Liu B, Lu W, Hui Y, Liang J, Zhou Z, Hou R, Li X, Liu Y, Li H, Ning X, Lin Y, Zhao L, Xing Q, Dou J, Mao J, Guo H, Dou H, Li T, Mu C, Jiang W, Fu Q, Fu X, Miao Y, Liu J, Yu Q, Li R, Liao H, Kong Y, Jiang Z, Chourrout D, Bao Z (- 42) Ref: Nat Ecol Evol, 1:120, 2017 : PubMed ESTHER: Wang_2017_Nat.Ecol.Evol_1_120 PubMedSearch: Wang 2017 Nat.Ecol.Evol 1 120 PubMedID: 28812685 Gene_locus related to this paper: mizye-a0a210qls6, mizye-a0a210qis3, mizye-a0a210qg00, mizye-a0a210ped6, mizye-a0a210q4h5, mizye-a0a210q4h9, mizye-a0a210q4j1, mizye-a0a210qf86, mizye-a0a210q332, mizye-a0a210pqn0, mizye-a0a210q7t5, mizye-a0a210pij5, mizye-a0a210qyk8, mizye-a0a210pwl7, mizye-a0a210q8u5, mizye-a0a210r5n9, mizye-a0a210qbv2, mizye-a0a210pu25, mizye-a0a210pek1, mizye-a0a210pul3, mizye-a0a210pum3, mizye-a0a210ptr6, mizye-a0a210ptq5, mizye-a0a210ptc4.1, mizye-a0a210ptc4.2, mizye-a0a210ptv1, mizye-a0a210ptv7, mizye-a0a210qgl6, mizye-a0a210qg90, mizye-a0a210ptq0, mizye-a0a210qg72, mizye-a0a210ptb1, mizye-a0a210pjd3, mizye-a0a210qg92, mizye-a0a210q8v2, mizye-a0a210qg93, mizye-a0a210q160.1, mizye-a0a210q160.2, mizye-a0a210qes4, mizye-a0a210pk25, mizye-a0a210q1b8, mizye-a0a210q110, mizye-a0a210r503, mizye-P021348901.1, mizye-P021348901.2 Abstract Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology. Title: The Aegilops tauschii genome reveals multiple impacts of transposons Zhao G, Zou C, Li K, Wang K, Li T, Gao L, Zhang X, Wang H, Yang Z and Jia J <5 more author(s)> Zhao G, Zou C, Li K, Wang K, Li T, Gao L, Zhang X, Wang H, Yang Z, Liu X, Jiang W, Mao L, Kong X, Jiao Y, Jia J (- 5) Ref: Nat Plants, 3:946, 2017 : PubMed ESTHER: Zhao_2017_Nat.Plants_3_946 PubMedSearch: Zhao 2017 Nat.Plants 3 946 PubMedID: 29158546 Gene_locus related to this paper: horvv-m0utz9, wheat-a0a3b6c2m6, wheat-a0a3b5zwb6, wheat-a0a3b6bzs8, wheat-a0a1d5zte7 Abstract Wheat is an important global crop with an extremely large and complex genome that contains more transposable elements (TEs) than any other known crop species. Here, we generated a chromosome-scale, high-quality reference genome of Aegilops tauschii, the donor of the wheat D genome, in which 92.5% sequences have been anchored to chromosomes. Using this assembly, we accurately characterized genic loci, gene expression, pseudogenes, methylation, recombination ratios, microRNAs and especially TEs on chromosomes. In addition to the discovery of a wave of very recent gene duplications, we detected that TEs occurred in about half of the genes, and found that such genes are expressed at lower levels than those without TEs, presumably because of their elevated methylation levels. We mapped all wheat molecular markers and constructed a high-resolution integrated genetic map corresponding to genome sequences, thereby placing previously detected agronomically important genes/quantitative trait loci (QTLs) on the Ae. tauschii genome for the first time. Title: Enrichment of omega-3 fatty acids in cod liver oil via alternate solvent winterization and enzymatic interesterification Lei Q, Ba S, Zhang H, Wei Y, Lee JY, Li T Ref: Food Chem, 199:364, 2016 : PubMed ESTHER: Lei_2016_Food.Chem_199_364 PubMedSearch: Lei 2016 Food.Chem 199 364 PubMedID: 26775983 Abstract Enrichment of omega-3 fatty acids in cod liver oil via alternate operation of solvent winterization and enzymatic interesterification was attempted. Variables including separation method, solvent, oil concentration, time and temperature were optimized for the winterization. Meanwhile, Novozyme 435, Lipozyme RM IM and Lipozyme TL IM were screened for interesterification efficiency under different system air condition, time and temperature. In optimized method, alternate winterization (0.1g/mL oil/acetone, 24h, -80 degC, precooled Buchner filtration) and interesterification (Lipozyme TL IM, N2 flow, 2.5h, 40 degC) successfully doubled the omega-3 fatty acid content to 43.20 mol%. (1)H NMR was used to determine omega-3 fatty acid content, and GC-MS to characterize oil product, which mainly contained DHA (15.81 mol%) and EPA (20.23 mol%). The proposed method offers considerable efficiency and reduce production cost drastically. Oil produced thereof is with high quality and of particular importance for the development of omega-3 based active pharmaceutical ingredients. Title: A novel fluorogenic probe for the investigation of free thiols: Application to kinetic measurements of acetylcholinesterase activity Mertens MD, Bierwisch A, Li T, Gutschow M, Thiermann H, Wille T, Elsinghorst PW Ref: Toxicol Lett, 244:161, 2016 : PubMed ESTHER: Mertens_2016_Toxicol.Lett_244_161 PubMedSearch: Mertens 2016 Toxicol.Lett 244 161 PubMedID: 26494253 Abstract A novel coumarin-derived thiol probe, based on the thiol-promoted cleavage of a quenching 2,4-dinitrobenzenesulfonyl group is described. The probe shows a sensitive fluorescence turn-on and sufficient solubility in aqueous environments. As a proof of concept, a new assay for AChE activity was developed as a useful addition to the established Ellman method. The observed reaction kinetics followed an asymmetric sigmoidal pattern and were successfully evaluated applying a three parameter Gompertz equation. Providing a linear relationship between the detected fluorescence formation curves and corresponding enzyme activities, this probe appears as a valuable tool for AChE activity measurements. Title: Design, synthesis and evaluation of novel ferulic acid-memoquin hybrids as potential multifunctional agents for the treatment of Alzheimer's disease Pan W, Hu K, Bai P, Yu L, Ma Q, Li T, Zhang X, Chen C, Peng K and Sang Z <1 more author(s)> Pan W, Hu K, Bai P, Yu L, Ma Q, Li T, Zhang X, Chen C, Peng K, Liu W, Sang Z (- 1) Ref: Bioorganic & Medicinal Chemistry Lett, 26:2539, 2016 : PubMed ESTHER: Pan_2016_Bioorg.Med.Chem.Lett_26_2539 PubMedSearch: Pan 2016 Bioorg.Med.Chem.Lett 26 2539 PubMedID: 27072909 Inhibitor(s) related to this paper: Memoquin Abstract A novel series of ferulic acid-memoquin hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro studies showed that most of the compounds exhibited a significant ability to inhibit acetylcholinesterase (AChE) (IC50 of 3.2-34.7muM) and self-induced beta-amyloid (Abeta1-42) aggregation (30.8-39.1%, 25muM), to act as potential antioxidants (ORAC-FL value of 0.9-1.3). In particular, compound 17d had the greatest ability to inhibit AChE (IC50=3.2muM), and Abeta1-42 aggregation (30.8%) was also an excellent antioxidant and neuroprotectant. Moreover, it is capable of disaggregating self-induced Abeta aggregation. Furthermore, 17d could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 17d is a potential multifunctional agent for the treatment of AD. Title: Genome sequencing of the perciform fish Larimichthys crocea provides insights into molecular and genetic mechanisms of stress adaptation Ao J, Mu Y, Xiang LX, Fan D, Feng M, Zhang S, Shi Q, Zhu LY, Li T and Chen X <19 more 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 (- 19) Ref: PLoS Genet, 11:e1005118, 2015 : PubMed 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 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. Title: Identification and Characterization of Lipase Activity and Immunogenicity of LipL from Mycobacterium tuberculosis Cao J, Dang G, Li H, Li T, Yue Z, Li N, Liu Y, Liu S, Chen L Ref: PLoS ONE, 10:e0138151, 2015 : PubMed ESTHER: Cao_2015_PLoS.One_10_e0138151 PubMedSearch: Cao 2015 PLoS.One 10 e0138151 PubMedID: 26398213 Abstract Lipids and lipid-metabolizing esterases/lipases are highly important for the mycobacterial life cycle and, possibly, for mycobacterial virulence. In this study, we expressed 10 members of the Lip family of Mycobacterium tuberculosis. Among the 10 proteins, LipL displayed a significantly high enzymatic activity for the hydrolysis of long-chain lipids. The optimal temperature for the lipase activity of LipL was demonstrated to be 37 degrees C, and the optimal pH was 8.0. The lipase active center was not the conserved motif G-x-S-x-G, but rather the S-x-x-K and GGG motifs, and the key catalytic amino acid residues were identified as G50, S88, and K91, as demonstrated through site-directed mutagenesis experiments. A three-dimensional modeling structure of LipL was constructed, which showed that the GGG motif was located in the surface of a pocket structure. Furthermore, the subcellular localization of LipL was demonstrated to be on the mycobacterial surface by Western blot analysis. Our results revealed that the LipL protein could induce a strong humoral immune response in humans and activate a CD8+ T cell-mediated response in mice. Overall, our study identified and characterized a novel lipase denoted LipL from M. tuberculosis, and demonstrated that LipL functions as an immunogen that activates both humoral and cell-mediated responses. Title: Effects of brain-derived neurotrophic factor-pretreated neuron stem cell transplantation on Alzheimer's disease model mice Li T, Yu Y, Cai H Ref: Int J Clin Exp Med, 8:21947, 2015 : PubMed ESTHER: Li_2015_Int.J.Clin.Exp.Med_8_21947 PubMedSearch: Li 2015 Int.J.Clin.Exp.Med 8 21947 PubMedID: 26885166 Abstract Alzheimer's disease (AD) is a common case of dementia and its possible therapies, such as neuron stem cell (NSC) transplantation therapy, have been studied for years. In order to improve NSC transplantation effects, we were inspired to pretreat NSC using brain-derived neurotrophic factor (BDNF) before transplantation. The AD mouse model was constructed and effects of BDNF+NSC transplant group and traditional NSC transplant group were compared using the four indicators: conditions of learning and memory ability recovery tested by Morris Water Maze (MWM), number of basal forebrain cholinergic neurons, expression of synaptophysin, and number of acetylcholinesterase (ACHE)-positive fibers detected by chemical staining. Results showed all the four indicators were significantly lower in the AD model group than the control group (P < 0.05). Traditional NSC transplantation could improve these indicators to some extent but still possessed significant differences from the control group (P < 0.05). Especially, the BDNF+NSC transplant group showed significant improvements in the four indicators when compared with the AD model group (P < 0.05). Taken these data together, BDNF pretreatment improved the NSC transplantation effects, showing advantages over the traditional NSC transplantation. Our study could facilitate the application of stem cell transplantation therapy to AD treatment. Title: Complete Genome Sequence of Elizabethkingia meningoseptica, Isolated from a T-Cell Non-Hodgkin's Lymphoma Patient Sun G, Wang L, Bao C, Li T, Ma L, Chen L Ref: Genome Announc, 3:, 2015 : PubMed ESTHER: Sun_2015_Genome.Announc_3_e00673 PubMedSearch: Sun 2015 Genome.Announc 3 e00673 PubMedID: 26112786 Gene_locus related to this paper: elimr-a0a0a2h0j3 Abstract An Elizabethkingia meningoseptica infection was detected at the end stage of a patient with T-cell non-Hodgkin's lymphoma. The complete genome of this isolated strain, FMS-007, was generated in one contig with a total size of 3,938,967 bp. A preliminary screening indicated that the genome contains drug resistance genes to aminoglycosides and beta-lactams. A clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (CRISPR/Cas) system with 16 direct repeats and 15 spacers was identified. Title: [Effects of methomyl on acetylcholinesterase in erythrocyte membrane and various brain areas] Zhao F, Li T, Zhang C, Xu Y, Xu H, Shi N Ref: Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 33:417, 2015 : PubMed ESTHER: Zhao_2015_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_33_417 PubMedSearch: Zhao 2015 Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi 33 417 PubMedID: 26653373 Abstract OBJECTIVE: To study the toxicity of methomyl to acetylcholinesterase (AChE) in different regions. Title: Synthesis and evaluation of odour-active methionyl esters of fatty acids via esterification and transesterification of butter oil Li C, Sun J, Fu C, Yu B, Liu SQ, Li T, Huang D Ref: Food Chem, 145:796, 2014 : PubMed ESTHER: Li_2014_Food.Chem_145_796 PubMedSearch: Li 2014 Food.Chem 145 796 PubMedID: 24128547 Abstract Methionol-derived fatty acid esters were synthesised by both chemical and lipase catalysed esterification between fatty acids and methionol. Beneficial effects of both methods were compared qualitatively and quantitatively by GC-MS/GC-FID results. And the high acid and heat stability of our designed methionyl esters meet the requirement of the food industry. Most importantly, the sensory test showed that fatty acid carbon-chain length had an important effect on the flavour attributes of methionyl esters. Moreover, through Lipozyme TL IM-mediated transesterification, valuable methionol-derived esters were synthesised from the readily available natural material butter oil as the fatty acid source. The conversion of methionol and yield of each methionyl ester were also elucidated by GC-MS-FID. Title: Chemical and enzymatic synthesis of a library of 2-phenethyl esters and their sensory attributes Li C, Sun J, Li T, Liu SQ, Huang D Ref: Food Chem, 154:205, 2014 : PubMed ESTHER: Li_2014_Food.Chem_154_205 PubMedSearch: Li 2014 Food.Chem 154 205 PubMedID: 24518334 Abstract We report a simple enzymatic approach to synthesise phenethyl esters as natural flavouring materials. Chemical and lipase-catalysed esterification reactions between fatty acids of C4-C18 and 2-phenethyl alcohol were studied. Both methods were compared qualitatively and quantitatively by GC-MS/FID. The acid and thermal stabilities of 2-phenethyl esters were excellent and can meet the requirements of food matrices under most processing conditions. Sensory evaluation showed that each 2-phenethyl ester with a different carbon-chain-length fatty acid had unique sensory notes. Moreover, through Lipozyme TL IM-mediated transesterification, valuable 2-phenethyl alcohol-derived esters were synthesised from butter oil and 2-phenethyl alcohol. The influence of several physicochemical parameters (temperature, substrate molar ratio, enzyme loading, shaking speed and time) on the transesterification reaction was investigated to give optimal reaction conditions, leading to a high yield of 80.0%. Title: The genome of Eucalyptus grandis Myburg AA, Grattapaglia D, Tuskan GA, Hellsten U, Hayes RD, Grimwood J, Jenkins J, Lindquist E, Tice H and Schmutz J <70 more author(s)> Myburg AA, Grattapaglia D, Tuskan GA, Hellsten U, Hayes RD, Grimwood J, Jenkins J, Lindquist E, Tice H, Bauer D, Goodstein DM, Dubchak I, Poliakov A, Mizrachi E, Kullan AR, Hussey SG, Pinard D, van der Merwe K, Singh P, van Jaarsveld I, Silva-Junior OB, Togawa RC, Pappas MR, Faria DA, Sansaloni CP, Petroli CD, Yang X, Ranjan P, Tschaplinski TJ, Ye CY, Li T, Sterck L, Vanneste K, Murat F, Soler M, Clemente HS, Saidi N, Cassan-Wang H, Dunand C, Hefer CA, Bornberg-Bauer E, Kersting AR, Vining K, Amarasinghe V, Ranik M, Naithani S, Elser J, Boyd AE, Liston A, Spatafora JW, Dharmwardhana P, Raja R, Sullivan C, Romanel E, Alves-Ferreira M, Kulheim C, Foley W, Carocha V, Paiva J, Kudrna D, Brommonschenkel SH, Pasquali G, Byrne M, Rigault P, Tibbits J, Spokevicius A, Jones RC, Steane DA, Vaillancourt RE, Potts BM, Joubert F, Barry K, Pappas GJ, Strauss SH, Jaiswal P, Grima-Pettenati J, Salse J, Van de Peer Y, Rokhsar DS, Schmutz J (- 70) Ref: Nature, 510:356, 2014 : PubMed ESTHER: Myburg_2014_Nature_510_356 PubMedSearch: Myburg 2014 Nature 510 356 PubMedID: 24919147 Gene_locus related to this paper: eucgr-a0a059d0n8, eucgr-a0a059cm68, eucgr-a0a059d783, eucgr-a0a059af93, eucgr-a0a059awi0, eucgr-a0a059awt4, eucgr-a0a059ar83, eucgr-a0a059ayw5, eucgr-a0a059az75, eucgr-a0a059azj1, eucgr-a0a059azq5, eucgr-a0a059bkm2, eucgr-a0a059bl38, eucgr-a0a059a7m2, eucgr-a0a059a6p6, eucgr-a0a059a6p1, eucgr-a0a059a5e9 Abstract Eucalypts are the world's most widely planted hardwood trees. Their outstanding diversity, adaptability and growth have made them a global renewable resource of fibre and energy. We sequenced and assembled >94% of the 640-megabase genome of Eucalyptus grandis. Of 36,376 predicted protein-coding genes, 34% occur in tandem duplications, the largest proportion thus far in plant genomes. Eucalyptus also shows the highest diversity of genes for specialized metabolites such as terpenes that act as chemical defence and provide unique pharmaceutical oils. Genome sequencing of the E. grandis sister species E. globulus and a set of inbred E. grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression. The E. grandis genome is the first reference for the eudicot order Myrtales and is placed here sister to the eurosids. This resource expands our understanding of the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology. Title: Genome Sequence of Mycoplasma columbinum Strain SF7 Guo Z, Xu X, Zheng Q, Li T, Kuang S, Zhang Z, Chen Y, Lu X, Zhou R and Jin H <1 more author(s)> Guo Z, Xu X, Zheng Q, Li T, Kuang S, Zhang Z, Chen Y, Lu X, Zhou R, Bi D, Jin H (- 1) Ref: Genome Announc, 1:e0015713, 2013 : PubMed ESTHER: Guo_2013_Genome.Announc_1_e0015713 PubMedSearch: Guo 2013 Genome.Announc 1 e0015713 PubMedID: 23599295 Abstract Mycoplasma columbinum is a member of nonglycolytic Mycoplasma species which can hydrolyze arginine. Increasingly research has revealed that M. columbinum is associated with respiratory disease of pigeons and that the respiratory disease symptoms could be eliminated via the use of mycoplasma treatment medicine. Here we report the genome sequence of M. columbinum strain SF7, which is the first genome report for M. columbinum. Title: [Impacts that dimethoate inhibited the benchmark dose of acetylcholinesterase based on experimental designs] He X, Li T, Yi N, Wu H, Zhao M, Yao X, Wang C Ref: Wei Sheng Yan Jiu, 42:999, 2013 : PubMed ESTHER: He_2013_Wei.Sheng.Yan.Jiu_42_999 PubMedSearch: He 2013 Wei.Sheng.Yan.Jiu 42 999 PubMedID: 24459918 Abstract OBJECTIVE: To obtain the impacts of experimental design on benchmark dose (BMD), and the result was applied to test the computer simulation by software Slob (optimal method to calculate the BMD: for a certain sample capacity, to add the experimental groups by reducing the amount of animals in each group) , consequently, this method can be widely used in the future. Title: Whole-Genome Sequence of Microcystis aeruginosa TAIHU98, a Nontoxic Bloom-Forming Strain Isolated from Taihu Lake, China Yang C, Zhang W, Ren M, Song L, Li T, Zhao J Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Yang_2013_Genome.Announc_1_e00333 PubMedSearch: Yang 2013 Genome.Announc 1 e00333 PubMedID: 23766403 Abstract Microcystis aeruginosa is a dominant bloom-forming cyanobacterium in many freshwater lakes. This report describes the first whole-genome sequence of the nontoxic strain of M. aeruginosa TAIHU98, which was isolated from Taihu Lake in eastern China. Title: Alzheimer's therapeutics: translation of preclinical science to clinical drug development Savonenko AV, Melnikova T, Hiatt A, Li T, Worley PF, Troncoso JC, Wong PC, Price DL Ref: Neuropsychopharmacology, 37:261, 2012 : PubMed ESTHER: Savonenko_2012_Neuropsychopharmacology_37_261 PubMedSearch: Savonenko 2012 Neuropsychopharmacology 37 261 PubMedID: 21937983 Abstract Over the past three decades, significant progress has been made in understanding the neurobiology of Alzheimer's disease. In recent years, the first attempts to implement novel mechanism-based treatments brought rather disappointing results, with low, if any, drug efficacy and significant side effects. A discrepancy between our expectations based on preclinical models and the results of clinical trials calls for a revision of our theoretical views and questions every stage of translation-from how we model the disease to how we run clinical trials. In the following sections, we will use some specific examples of the therapeutics from acetylcholinesterase inhibitors to recent anti-Abeta immunization and gamma-secretase inhibition to discuss whether preclinical studies could predict the limitations in efficacy and side effects that we were so disappointed to observe in recent clinical trials. We discuss ways to improve both the predictive validity of mouse models and the translation of knowledge between preclinical and clinical stages of drug development. Title: SAR of alpha7 nicotinic receptor agonists derived from tilorone: exploration of a novel nicotinic pharmacophore Schrimpf MR, Sippy KB, Briggs CA, Anderson DJ, Li T, Ji J, Frost JM, Surowy CS, Bunnelle WH and Meyer MD <1 more author(s)> Schrimpf MR, Sippy KB, Briggs CA, Anderson DJ, Li T, Ji J, Frost JM, Surowy CS, Bunnelle WH, Gopalakrishnan M, Meyer MD (- 1) Ref: Bioorganic & Medicinal Chemistry Lett, 22:1633, 2012 : PubMed ESTHER: Schrimpf_2012_Bioorg.Med.Chem.Lett_22_1633 PubMedSearch: Schrimpf 2012 Bioorg.Med.Chem.Lett 22 1633 PubMedID: 22281189 Inhibitor(s) related to this paper: Tilorone Abstract The well-known interferon-inducer tilorone was found to possess potent affinity for the agonist site of the alpha7 neuronal nicotinic receptor (K(i)=56 nM). SAR investigations determined that both basic sidechains are essential for potent activity, however active monosubstituted derivatives can also be prepared if the flexible sidechains are replaced with conformationally rigidified cyclic amines. Analogs in which the fluorenone core is replaced with either dibenzothiophene-5,5-dioxide or xanthenone also retain potent activity. Title: Genome sequence of Mycoplasma iowae strain 695, an unusual pathogen causing deaths in turkeys Wei S, Guo Z, Li T, Zhang T, Li X, Zhou Z, Li Z, Liu M, Luo R and Jin H <3 more author(s)> Wei S, Guo Z, Li T, Zhang T, Li X, Zhou Z, Li Z, Liu M, Luo R, Bi D, Chen H, Zhou R, Jin H (- 3) Ref: Journal of Bacteriology, 194:547, 2012 : PubMed ESTHER: Wei_2012_J.Bacteriol_194_547 PubMedSearch: Wei 2012 J.Bacteriol 194 547 PubMedID: 22207750 Abstract Mycoplasma iowae is associated mainly with reduced hatchability in turkeys and is well known for the unusual ability of phenotypic variation in the Mycoplasma surface components as well as a relative resistance to heat, bile salts, and many antimicrobials. A subset of unique genes and a gene cluster responsible for these characteristics could be identified from the genome. Here, we report the first genome sequence of this species. Title: The MDGA1 gene confers risk to schizophrenia and bipolar disorder Li J, Liu J, Feng G, Li T, Zhao Q, Li Y, Hu Z, Zheng L, Zeng Z and Shi Y <2 more author(s)> Li J, Liu J, Feng G, Li T, Zhao Q, Li Y, Hu Z, Zheng L, Zeng Z, He L, Wang T, Shi Y (- 2) Ref: Schizophr Res, 125:194, 2011 : PubMed ESTHER: Li_2011_Schizophr.Res_125_194 PubMedSearch: Li 2011 Schizophr.Res 125 194 PubMedID: 21146959 Abstract OBJECTIVE: The structural, cytoarchitectural and functional brain abnormalities reported in patients with mental disorders may be due to aberrant neuronal migration influenced by cell adhesion molecules. MDGA1, like Ig-containing cell adhesion molecules, has several cell adhesion molecule-like domains. Moreover, Kahler et al. (2008) reported that the MDGA1 gene was a schizophrenia susceptibility gene in Scandinavian population. To further investigate whether the MDGA1 gene is a shared risk factor of schizophrenia, bipolar disorder and major depressive disorder in Chinese Han population, we conducted this study. Title: Synthesis and in vitro activity of N-benzyl-1-(2,3-dichlorophenyl)-1H-tetrazol-5-amine P2X(7) antagonists Perez-Medrano A, Donnelly-Roberts D, Florjancic AS, Nelson DW, Li T, Namovic MT, Peddi S, Faltynek CR, Jarvis MF, Carroll WA Ref: Bioorganic & Medicinal Chemistry Lett, 21:3297, 2011 : PubMed ESTHER: Perez-Medrano_2011_Bioorg.Med.Chem.Lett_21_3297 PubMedSearch: Perez-Medrano 2011 Bioorg.Med.Chem.Lett 21 3297 PubMedID: 21536435 Abstract Synthesis and biological evaluation of a novel class of substituted N-benzyl-1-(2,3-dichlorophenyl)-1H-tetrazol-5-amine derivatives resulted in the identification of potent P2X(7) antagonists. These compounds were assayed for activity at both the human and rat P2X(7) receptors. On the benzyl moiety, a variety of functional groups were tolerated, including both electron-withdrawing and electron-donating substituents. Ortho-substitution on the benzyl group provided the greatest potency. The ortho-substituted analogs showed approximately 2.5-fold greater potency at human compared to rat P2X(7) receptors. Compounds 12 and 38 displayed hP2X(7)pIC(50)s>7.8 with less than 2-fold difference in potency at the rP2X(7). Title: Production of extremely pure diacylglycerol from soybean oil by lipase-catalyzed glycerolysis Wang W, Li T, Ning Z, Wang Y, Yang B, Yang X Ref: Enzyme Microb Technol, 49:192, 2011 : PubMed ESTHER: Wang_2011_Enzyme.Microb.Technol_49_192 PubMedSearch: Wang 2011 Enzyme.Microb.Technol 49 192 PubMedID: 22112408 Abstract Research work was objectively targeted to synthesize highly pure diacylglycerol (DAG) with glycerolysis of soybean oil in a solvent medium of t-butanol. Three commercial immobilized lipases (Lipozyme RM IM, Lipozyme TL IM and Novozym 435) were screened, and Novozym 435 was the best out of three candidates. Batch reaction conditions of the enzymatic glycerolysis, the substrate mass ratio, the reaction temperature and the substrate concentration, were studied. The optimal reaction conditions were achieved as 6.23:1 mass ratio of soybean oil to glycerol, 40% (w/v) of substrate concentration in t-butanol and reaction temperature of 50 degreeC. A two-stage molecular distillation was employed for purification of DAG from reaction products. Scale-up was attempted based on the optimized reaction conditions, 98.7% (24 h) for the conversion rate of soybean oil, 48.5% of DAG in the glycerolysis products and 96.1% for the content of DAG in the final products were taken in account as the results. Title: Syntheses and structure-activity relationship (SAR) studies of 2,5-diazabicyclo[2.2.1]heptanes as novel alpha7 neuronal nicotinic receptor (NNR) ligands Li T, Bunnelle WH, Ryther KB, Anderson DJ, Malysz J, Helfrich R, Gronlien JH, Hakerud M, Peters D and Ji J <2 more author(s)> Li T, Bunnelle WH, Ryther KB, Anderson DJ, Malysz J, Helfrich R, Gronlien JH, Hakerud M, Peters D, Schrimpf MR, Gopalakrishnan M, Ji J (- 2) Ref: Bioorganic & Medicinal Chemistry Lett, 20:3636, 2010 : PubMed ESTHER: Li_2010_Bioorg.Med.Chem.Lett_20_3636 PubMedSearch: Li 2010 Bioorg.Med.Chem.Lett 20 3636 PubMedID: 20472430 Abstract Biaryl substituted 2,5-diazabicyclo[2.2.1]heptanes have been synthesized and tested for their affinity toward alpha7 neuronal nicotinic receptors (NNRs). SAR studies established that 5-N-methyl substituent, heteroaryl linker and the nature of terminal aryl group are critical for the ligand to achieve potent alpha7 NNR agonist activity. Title: Comparative genomic characterization of Actinobacillus pleuropneumoniae Xu Z, Chen X, Li L, Li T, Wang S, Chen H, Zhou R Ref: Journal of Bacteriology, 192:5625, 2010 : PubMed ESTHER: Xu_2010_J.Bacteriol_192_5625 PubMedSearch: Xu 2010 J.Bacteriol 192 5625 PubMedID: 20802045 Gene_locus related to this paper: actp2-a3mzf9, actp2-a3n347, actp7-b3h2v1, actp7-b3h2x2 Abstract The Gram-negative bacterium Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumoniae, a lethal respiratory infectious disease causing great economic losses in the swine industry worldwide. In order to better interpret the genetic background of serotypic diversity, nine genomes of A. pleuropneumoniae reference strains of serovars 1, 2, 4, 6, 9, 10, 11, 12, and 13 were sequenced by using rapid high-throughput approach. Based on 12 genomes of corresponding serovar reference strains including three publicly available complete genomes (serovars 3, 5b, and 7) of this bacterium, we performed a comprehensive analysis of comparative genomics and first reported a global genomic characterization for this pathogen. Clustering of 26,012 predicted protein-coding genes showed that the pan genome of A. pleuropneumoniae consists of 3,303 gene clusters, which contain 1,709 core genome genes, 822 distributed genes, and 772 strain-specific genes. The genome components involved in the biogenesis of capsular polysaccharide and lipopolysaccharide O antigen relative to serovar diversity were compared, and their genetic diversity was depicted. Our findings shed more light on genomic features associated with serovar diversity of A. pleuropneumoniae and provide broader insight into both pathogenesis research and clinical/epidemiological application against the severe disease caused by this swine pathogen. Title: S-palmitoylation of gamma-secretase subunits nicastrin and APH-1 Cheng H, Vetrivel KS, Drisdel RC, Meckler X, Gong P, Leem JY, Li T, Carter M, Chen Y and Thinakaran G <6 more author(s)> Cheng H, Vetrivel KS, Drisdel RC, Meckler X, Gong P, Leem JY, Li T, Carter M, Chen Y, Nguyen P, Iwatsubo T, Tomita T, Wong PC, Green WN, Kounnas MZ, Thinakaran G (- 6) Ref: Journal of Biological Chemistry, 284:1373, 2009 : PubMed ESTHER: Cheng_2009_J.Biol.Chem_284_1373 PubMedSearch: Cheng 2009 J.Biol.Chem 284 1373 PubMedID: 19028695 Abstract Proteolytic processing of amyloid precursor protein (APP) by beta- and gamma-secretases generates beta-amyloid (Abeta) peptides, which accumulate in the brains of individuals affected by Alzheimer disease. Detergent-resistant membrane microdomains (DRM) rich in cholesterol and sphingolipid, termed lipid rafts, have been implicated in Abeta production. Previously, we and others reported that the four integral subunits of the gamma-secretase associate with DRM. In this study we investigated the mechanisms underlying DRM association of gamma-secretase subunits. We report that in cultured cells and in brain the gamma-secretase subunits nicastrin and APH-1 undergo S-palmitoylation, the post-translational covalent attachment of the long chain fatty acid palmitate common in lipid raft-associated proteins. By mutagenesis we show that nicastrin is S-palmitoylated at Cys(689), and APH-1 is S-palmitoylated at Cys(182) and Cys(245). S-Palmitoylation-defective nicastrin and APH-1 form stable gamma-secretase complexes when expressed in knock-out fibroblasts lacking wild type subunits, suggesting that S-palmitoylation is not essential for gamma-secretase assembly. Nevertheless, fractionation studies show that S-palmitoylation contributes to DRM association of nicastrin and APH-1. Moreover, pulse-chase analyses reveal that S-palmitoylation is important for nascent polypeptide stability of both proteins. Co-expression of S-palmitoylation-deficient nicastrin and APH-1 in cultured cells neither affects Abeta40, Abeta42, and AICD production, nor intramembrane processing of Notch and N-cadherin. Our findings suggest that S-palmitoylation plays a role in stability and raft localization of nicastrin and APH-1, but does not directly modulate gamma-secretase processing of APP and other substrates. Title: Genetic and epigenetic inactivation of LPL gene in human prostate cancer Kim JW, Cheng Y, Liu W, Li T, Yegnasubramanian S, Zheng SL, Xu J, Isaacs WB, Chang BL Ref: International Journal of Cancer, 124:734, 2009 : PubMed ESTHER: Kim_2009_Int.J.Cancer_124_734 PubMedSearch: Kim 2009 Int.J.Cancer 124 734 PubMedID: 19004026 Abstract Lipoprotein lipase (LPL) is in chromosome 8p22, site of one of the most common somatic deletions in prostate tumors. Additionally, a CpG island (CGI) was identified in the LPL promoter region. To test the hypothesis that LPL is a tumor suppressor gene, which is inactivated by somatic deletion and hypermethylation in prostate cancer, we evaluated somatic DNA deletion and methylation status at LPL in 56 pairs of DNA samples isolated from prostate cancer tissues and matching normal controls and 11 prostate cell lines. We found that the DNA in 21 of 56 primary cancers (38%) was methylated in the LPL promoter CGI, whereas no methylation was detected in any normal samples. In addition, we found a hemizygous deletion at LPL in 38 of the 56 tumors (68%). When the results of deletion and methylation were considered together, we found LPL promoter CGI methylation occurred in 45% of LPL deleted tumors and in 22% of LPL retained tumors. Within several clinical characteristics tested, the preoperative PSA levels were found to be significantly higher in subjects with LPL promoter CGI methylation compared with subjects without LPL promoter methylation (p=0.0012). Additionally, demethylation of the LPL promoter CGI was accompanied by transcriptional reactivation of LPL in the prostate cancer cell lines DU145 and PC3. In summary, we report a novel finding that the LPL gene is commonly methylated in prostate tumors, and our results suggest that biallelic inactivation of LPL by chromosomal deletion and promoter hypermethylation may play a role in human prostate cancer. Title: Structure-based substrate screening for an enzyme Xu T, Zhang L, Wang X, Wei D, Li T Ref: BMC Bioinformatics, 10:257, 2009 : PubMed ESTHER: Xu_2009_BMC.Bioinformatics_10_257 PubMedSearch: Xu 2009 BMC.Bioinformatics 10 257 PubMedID: 19695105 Abstract BACKGROUND: Nowadays, more and more novel enzymes can be easily found in the whole enzyme pool with the rapid development of genetic operation. However, experimental work for substrate screening of a new enzyme is laborious, time consuming and costly. On the other hand, many computational methods have been widely used in lead screening of drug design. Seeing that the ligand-target protein system in drug design and the substrate-enzyme system in enzyme applications share the similar molecular recognition mechanism, we aim to fulfill the goal of substrate screening by in silico means in the present study. RESULTS: A computer-aided substrate screening (CASS) system which was based on the enzyme structure was designed and employed successfully to help screen substrates of Candida antarctica lipase B (CALB). In this system, restricted molecular docking which was derived from the mechanism of the enzyme was applied to predict the energetically favorable poses of substrate-enzyme complexes. Thereafter, substrate conformation, distance between the oxygen atom of the alcohol part of the ester (in some compounds, this oxygen atom was replaced by nitrogen atom of the amine part of acid amine or sulfur atom of the thioester) and the hydrogen atom of imidazole of His224, distance between the carbon atom of the carbonyl group of the compound and the oxygen atom of hydroxyl group of Ser105 were used sequentially as the criteria to screen the binding poses. 223 out of 233 compounds were identified correctly for the enzyme by this screening system. Such high accuracy guaranteed the feasibility and reliability of the CASS system. CONCLUSION: The idea of computer-aided substrate screening is a creative combination of computational skills and enzymology. Although the case studied in this paper is tentative, high accuracy of the CASS system sheds light on the field of computer-aided substrate screening. Title: Toxic effects of chlorpromazine on Carassius auratus and its oxidative stress Li T, Zhou Q, Zhang N, Luo Y Ref: J Environ Sci Health B, 43:638, 2008 : PubMed ESTHER: Li_2008_J.Environ.Sci.Health.B_43_638 PubMedSearch: Li 2008 J.Environ.Sci.Health.B 43 638 PubMedID: 18941986 Inhibitor(s) related to this paper: Chlorproethazine Abstract Under laboratory conditions, ecotoxicological effects of chlorpromazine (CPZ) on freshwater goldfish (Carassius auratus) were examined using the toxic culture experiment. The results showed that the median lethal concentration (LC(50)) of CPZ toxic to Carassius auratus in 24, 48 and 96 h was 1.11, 0.43 and 0.32 mg/L, respectively. Thus, CPZ is an extreme toxicant to goldfish. Furthermore, there were significantly positive correlations between the ecotoxicological effects of CPZ and its concentrations, and the toxicity became higher as the exposure time increased. The activity of superoxide dismutase (SOD) and catalase (CAT) in goldfish livers was significantly influenced by CPZ. At the same exposure time, the activity of SOD reduced first, and increased then, whereas the activity of CAT enhanced first and decreased then. At the same exposure levels of CPZ, the activity of SOD and CAT changed similarly, decreased first, then increased and decreased at last. Within the range of exposure concentrations, the changes in the activity of CAT can more easily reflect the oxidation stress in Carassius auratus by CPZ than those of SOD. Title: Genome biology of Actinobacillus pleuropneumoniae JL03, an isolate of serotype 3 prevalent in China Xu Z, Zhou Y, Li L, Zhou R, Xiao S, Wan Y, Zhang S, Wang K, Li W and Chen H <16 more author(s)> Xu Z, Zhou Y, Li L, Zhou R, Xiao S, Wan Y, Zhang S, Wang K, Li W, Jin H, Kang M, Dalai B, Li T, Liu L, Cheng Y, Zhang L, Xu T, Zheng H, Pu S, Wang B, Gu W, Zhang XL, Zhu GF, Wang S, Zhao GP, Chen H (- 16) Ref: PLoS ONE, 3:e1450, 2008 : PubMed ESTHER: Xu_2008_PLoS.ONE_3_E1450 PubMedSearch: Xu 2008 PLoS.ONE 3 E1450 PubMedID: 18197260 Gene_locus related to this paper: actp2-a3n347, actp7-b3h2v1, actp7-b3h2x2, actpj-b0bpm3, actpj-b0bqd8 Abstract Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, a cause of considerable world wide economic losses in the swine industry. We sequenced the complete genome of A. pleuropneumoniae, JL03, an isolate of serotype 3 prevalent in China. Its genome is a single chromosome of 2,242,062 base pairs containing 2,097 predicted protein-coding sequences, six ribosomal rRNA operons, and 63 tRNA genes. Preliminary analysis of the genomic sequence and the functions of the encoded proteins not only confirmed the present physiological and pathological knowledge but also offered new insights into the metabolic and virulence characteristics of this important pathogen. We identified a full spectrum of genes related to its characteristic chemoheterotrophic catabolism of fermentation and respiration with an incomplete TCA system for anabolism. In addition to confirming the lack of ApxI toxin, identification of a nonsense mutation in apxIVA and a 5'-proximal truncation of the flp operon deleting both its promoter and the flp1flp2tadV genes have provided convincing scenarios for the low virulence property of JL03. Comparative genomic analysis using the available sequences of other serotypes, probable strain (serotype)-specific genomic islands related to capsular polysaccharides and lipopolysaccharide O-antigen biosyntheses were identified in JL03, which provides a foundation for future research into the mechanisms of serotypic diversity of A. pleuropneumoniae. Title: A thermodynamic ligand binding study of the third PDZ domain (PDZ3) from the mammalian neuronal protein PSD-95 Saro D, Li T, Rupasinghe C, Paredes A, Caspers N, Spaller MR Ref: Biochemistry, 46:6340, 2007 : PubMed ESTHER: Saro_2007_Biochemistry_46_6340 PubMedSearch: Saro 2007 Biochemistry 46 6340 PubMedID: 17474715 Abstract The thermodynamic parameters associated with the binding of several series of linear peptides to the third PDZ domain (PDZ3) of the postsynaptic density 95 protein (PSD-95) have been measured using isothermal titration calorimetry (ITC). Two strategies were pursued in developing these binding ligands: (1) systematic N-terminal truncation of sequences derived from the C-terminal regions of identified PDZ3-binding proteins (CRIPT, neuroligin-1, and citron) and (2) selective mutation of specific positions within a consensus hexapeptide (KKETEV) known to bind PDZ3. Each synthetically prepared peptide was used to titrate PDZ3, which yielded the changes in Gibbs free energy (DeltaG), enthalpy (DeltaH), and entropy (TDeltaS) for the binding event. Selected peptides were subjected to additional analysis, which entailed (1) measuring the change in heat capacity (DeltaCp) upon association, to assess the character of the binding interface, and (2) constructing thermodynamic double mutant cycles, to determine the presence of cooperative effects. From the first series, the CRIPT protein proved to be the better source for higher affinity sequences. From the second series, enhanced binding was associated with peptides that closely adhered to the established motif for class I PDZ domain C-termini, X-(T/S)-X-(V/I/L), and more specifically to a narrower motif of X-T-X-V. Further, in both series a length of six residues was necessary and sufficient to capture maximal affinity. In addition, there were significant influences upon binding by modifying the abutting "X" positions. The cumulative results provide greater detail into the specific nature of ligand binding to PDZ3 and will assist in the development of selective molecular probes for the study of this and structurally homologous PDZ domains. Title: Neutral lipids and peroxisome proliferator-activated receptor-{gamma} control pulmonary gene expression and inflammation-triggered pathogenesis in lysosomal acid lipase knockout mice Lian X, Yan C, Qin Y, Knox L, Li T, Du H Ref: American Journal of Pathology, 167:813, 2005 : PubMed ESTHER: Lian_2005_Am.J.Pathol_167_813 PubMedSearch: Lian 2005 Am.J.Pathol 167 813 PubMedID: 16127159 Gene_locus related to this paper: mouse-1llip Abstract The functional roles of neutral lipids in the lung are poorly understood. However, blocking cholesteryl ester and triglyceride metabolism in lysosomal acid lipase gene knockout mice (lal-/-) results in severe pathogenic phenotypes in the lung, including massive neutrophil infiltration, foamy macrophage accumulation, unwanted cell growth, and emphysema. To elucidate the mechanism underlining these pathologies, we performed Affymetrix GeneChip microarray analysis of 1-, 3-, and 6-month-old mice and identified aberrant gene expression that progressed with age. Among changed genes, matrix metalloproteinase (MMP)-12, apoptosis inhibitor 6 (Api-6), erythroblast transformation-specific domain (Ets) transcription factor family member Spi-C, and oncogene MafB were increased 100-, 70-, 40-, and 10-fold, respectively, in lal-/- lungs versus the wild-type lungs. The pathogenic increases of these molecules occurred primarily in alveolar type II epithelial cells. Transcriptional activities of the MMP-12 and Api-6 promoters were stimulated by Spi-C or MafB in respiratory epithelial cells. Treatment with 9-hydroxyoctadecanoic acids and ciglitazone significantly rescued lal-/- pulmonary inflammation and aberrant gene expression. In addition, both compounds as well as peroxisome proliferator-activated receptor gamma inhibited MMP-12 and Api-6 promoter activities. These data suggest that inflammation-triggered cell growth and emphysema during lysosomal acid lipase deficiency are partially caused by peroxisome proliferator-activated receptor-gamma inactivation. Title: [Effect of genetic polymorphisms of microsomal epoxide hydrolase on urinary 1-hydroxypyrene levels in coke oven workers] Leng SG, Zheng YX, Huang CF, Dai YF, Li XH, Niu Y, Pan ZF, Li T, He FS Ref: Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 22:245, 2004 : PubMed ESTHER: Leng_2004_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_22_245 PubMedSearch: Leng 2004 Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi 22 245 PubMedID: 15355699 Abstract OBJECTIVE: To investigate the associations of polymorphisms of metabolic enzyme genes with urinary 1-hydroxypyrene levels in coke oven workers. Title: [A study on the inherited susceptibility of chromosomal damage in peripheral blood lymphocytes among coke oven workers] Leng SG, Zheng YX, Pan ZF, Niu Y, Dai YF, Wang YW, Zhang WZ, Xiao J, Wang ZX and He FS <1 more author(s)> Leng SG, Zheng YX, Pan ZF, Niu Y, Dai YF, Wang YW, Zhang WZ, Xiao J, Wang ZX, Li T, He FS (- 1) Ref: Zhonghua Yu Fang Yi Xue Za Zhi, 38:94, 2004 : PubMed ESTHER: Leng_2004_Zhonghua.Yu.Fang.Yi.Xue.Za.Zhi_38_94 PubMedSearch: Leng 2004 Zhonghua.Yu.Fang.Yi.Xue.Za.Zhi 38 94 PubMedID: 15061915 Abstract OBJECTIVE: To investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers. Title: Sequence and analysis of rice chromosome 4 Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y and Han B <61 more author(s)> Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y, Hu X, Jia P, Zhao Q, Ying K, Yu S, Tang Y, Weng Q, Zhang L, Lu Y, Mu J, Zhang LS, Yu Z, Fan D, Liu X, Lu T, Li C, Wu Y, Sun T, Lei H, Li T, Hu H, Guan J, Wu M, Zhang R, Zhou B, Chen Z, Chen L, Jin Z, Wang R, Yin H, Cai Z, Ren S, Lv G, Gu W, Zhu G, Tu Y, Jia J, Chen J, Kang H, Chen X, Shao C, Sun Y, Hu Q, Zhang X, Zhang W, Wang L, Ding C, Sheng H, Gu J, Chen S, Ni L, Zhu F, Chen W, Lan L, Lai Y, Cheng Z, Gu M, Jiang J, Li J, Hong G, Xue Y, Han B (- 61) Ref: Nature, 420:316, 2002 : PubMed ESTHER: Feng_2002_Nature_420_316 PubMedSearch: Feng 2002 Nature 420 316 PubMedID: 12447439 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q7F959, orysa-q7f9i3, orysa-q7x7y5, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-Q7XTM8, orysa-q7xts6, orysa-q7xue7, orysa-q7xv53, orysa-Q7XVB5, orysa-Q7XVG5, orysj-q0jaf0, orysj-q7f8x1 Abstract Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis. Title: An imprinted PEG1/MEST antisense expressed predominantly in human testis and in mature spermatozoa Li T, Vu TH, Lee KO, Yang Y, Nguyen CV, Bui HQ, Zeng ZL, Nguyen BT, Hu JF and Hoffman AR <2 more author(s)> Li T, Vu TH, Lee KO, Yang Y, Nguyen CV, Bui HQ, Zeng ZL, Nguyen BT, Hu JF, Murphy SK, Jirtle RL, Hoffman AR (- 2) Ref: Journal of Biological Chemistry, 277:13518, 2002 : PubMed ESTHER: Li_2002_J.Biol.Chem_277_13518 PubMedSearch: Li 2002 J.Biol.Chem 277 13518 PubMedID: 11821432 Abstract PEG1 (or MEST) is an imprinted gene located on human chromosome 7q32 that is expressed predominantly from the paternal allele. In the mouse, Peg1/Mest is associated with embryonic growth and maternal behavior. Human PEG1 is transcribed from two promoters; the transcript from promoter P1 is derived from both parental alleles, and the transcript from P2 is exclusively from the paternal allele. We characterized the P1 and P2 transcripts in various normal and neoplastic tissues. In the normal tissues, PEG1 was transcribed from both promoters P1 and P2, whereas in six of eight neoplastic tissues, PEG1 was transcribed exclusively from promoter P1. Bisulfite sequencing demonstrated high levels of CpG methylation in the P2 region of DNA from a lung tumor. In the region between P1 and P2, we identified a novel transcript, PEG1-AS, in an antisense orientation to PEG1. PEG1-AS is a spliced transcript and was detected as a strong 2.4-kilobase band on a Northern blot. PEG1-AS and PEG1 P2-sense transcript were expressed exclusively from the paternal allele. Fragments of DNA from within the 1.5-kilobase region between PEG1-AS and the P2 exon were ligated to a pGL3 luciferase reporter vector and transfected into NCI H23 cells. This DNA exhibited strong promoter activity in both the sense and antisense directions, indicating that PEG1-AS and P2 exon share a common promoter region. Treatment of the transfected DNA fragments with CpG methylase abolished the promoter activity. Of interest, PEG1-AS was expressed predominantly in testis and in mature motile spermatozoa, indicating a possible role for this transcript in human sperm physiology and fertilization. Title: Repetitive nerve stimulation and stimulation single fiber electromyography studies in rats intoxicated with single or mixed insecticides Yang D, He F, Li T Ref: Toxicology, 161:111, 2001 : PubMed ESTHER: Yang_2001_Toxicology_161_111 PubMedSearch: Yang 2001 Toxicology 161 111 PubMedID: 11295260 Abstract The function of the neuromuscular transmission in rats dosed with phoxim (P), methomyl (M), fenvalerate (F), and mixtures of P+M and P+F was studied by using both the stimulation single fiber electromyography (SSFEMG) and repetitive nerve stimulations (RNS) to determine the single muscle fiber action potential and compound muscle action potential (CMAP) respectively. The results showed that the mean consecutive difference (MCD) in SSFEMG was significantly prolonged in P, P+M and P+F intoxicated rats during the presence of myasthenia, but not in rats dosed with F and M when stimuli were given at 10 Hz or 20 Hz, thus indicating a transmission blocking at the neuromuscular junction (NMJ) induced by P. The frequency of neuromuscular transmission abnormalities detected by SSFEMG was significantly higher than those detected by RNS. This study demonstrated that the neuromuscular junction (NMJ) blocking is more frequently seen in P, P+M and P+F poisoning than in M and F poisoning, and that SSFEMG is a more sensitive electrophysiological method than RNS for detecting neuromuscular transmission blockage in myasthenia rats with acute insecticides poisoning. | |||||||
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