Author Report for: He JNo contact information in database for He J
Fang Y, Chao K, He J, Wang Z, Chen Z Ref: 3 Biotech, 13:138, 2023 : PubMed ESTHER: Fang_2023_3.Biotech_13_138 PubMedSearch: Fang 2023 3.Biotech 13 138 PubMedID: 37124986 Abstract Polyethylene terephthalate (PET) is the most abundantly produced plastic due to its excellent performance, but is also the primary source of poorly degradable plastic pollution. The development of environment-friendly PET biodegradation is attracting increasing interest. The leaf-branch compost cutinase mutant ICCG (F243I/D238C/S283C/Y127G) exhibits the best hydrolytic activity and thermostability of all known PET hydrolases. However, its superior PET degradation is highly dependent on its preparation as a purified enzyme, which critically reduces its industrial utility. Herein, we report the use of rational design and combinatorial mutagenesis to develop a novel ICCG mutant RITK (D53R/R143I/D193T/E208K) that demonstrated excellent whole-cell biocatalytic activity. Whole cells expressing RITK showed an 8.33-fold increase in biocatalytic activity compared to those expressing ICCG. Thermostability was also improved. After reacting at 85 degreesC for 3 h, purified RITK exhibited a 12.75-fold increase in depolymerization compared to ICCG. These results will greatly enhance the industrial utility of PET hydrolytic enzymes and further the progress of PET recycling. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-023-03557-4. Title: Crystal structures of herbicide-detoxifying esterase reveal a lid loop affecting substrate binding and activity Liu B, Wang W, Qiu J, Huang X, Qiu S, Bao Y, Xu S, Ruan L, Ran T, He J Ref: Nat Commun, 14:4343, 2023 : PubMed ESTHER: Liu_2023_Nat.Commun_14_4343 PubMedSearch: Liu 2023 Nat.Commun 14 4343 PubMedID: 37468532 Gene_locus related to this paper: 9rhiz-g9i933 Abstract SulE, an esterase, which detoxifies a variety of sulfonylurea herbicides through de-esterification, provides an attractive approach to remove environmental sulfonylurea herbicides and develop herbicide-tolerant crops. Here, we determined the crystal structures of SulE and an activity improved mutant P44R. Structural analysis revealed that SulE is a dimer with spacious binding pocket accommodating the large sulfonylureas substrate. Particularly, SulE contains a protruding beta hairpin with a lid loop covering the active site of the other subunit of the dimer. The lid loop participates in substrate recognition and binding. P44R mutation altered the lid loop flexibility, resulting in the sulfonylurea heterocyclic ring repositioning to a relative stable conformation thus leading to dramatically increased activity. Our work provides important insights into the molecular mechanism of SulE, and establish a solid foundation for further improving the enzyme activity to various sulfonylurea herbicides through rational design. Title: Serum alkaline phosphatase was independently associated with depression in patients with cerebrovascular disease Tao X, Yang C, He J, Liu Q, Wu S, Tang W, Wang J Ref: Front Psychiatry, 14:1184673, 2023 : PubMed ESTHER: Tao_2023_Front.Psychiatry_14_1184673 PubMedSearch: Tao 2023 Front.Psychiatry 14 1184673 PubMedID: 37469359 Abstract BACKGROUND AND PURPOSE: Blood markers have important value in the diagnosis of depressive disorders. Serum alkaline phosphatase (ALP) not only predicts stroke recurrence and poor functional prognosis in cerebrovascular disease (CVD) patients but also increases significantly in middle-aged women with depression. Thus, it has not been reported whether serum ALP is associated with the development of depression and/or vascular depression (VDe) in CVD patients. METHODS: This was a cross-sectional study of 353 CVD patients (stroke patients, n = 291; cerebral small vessel disease (CSVD) patients, n = 62). Baseline demographic information, fasting blood markers (such as blood counts, liver function, kidney function and lipids), and brain CT/MRI scans were collected. CVD patients were divided into non-depression, suspected vascular depression (SVD), and positive vascular depression (PVD) groups according to their Hamilton Rating Scale for Depression (HAMD) scores. Univariate analysis of baseline data, blood markers, and the prevalence of lesions (> 1.5 cm) was performed. Subsequently, the diagnostic performance of the univariate and combined variables for SVD and PVD was analyzed using binary logistic regression. The diagnostic value of the multivariate model for VDe was analyzed by ordinal logistic regression. RESULTS: (1) Serum ALP (p = 0.003) and hypersensitive C-reactive protein (hs-CRP, p = 0.001) concentrations increased as HAMD scores increased, and the prevalence of brain atrophy (p = 0.016) and lesions in the basal ganglia (p = 0.001) and parietal (p = 0.001), temporal (p = 0.002), and frontal lobes (p = 0.003) also increased, whereas the concentrations of hemoglobin (Hb, p = 0.003), cholinesterase (ChE, p = 0.001), and high-density lipoprotein cholesterol (HDL-C, p = 0.005) declined. Among these variables, hs-CRP (r = 0.218, p < 0.001) had a weak positively association with HAMD scores, and ChE (r = -0.226, p < 0.001) had a weak negative association. (2) The combination of Hb, hs-CRP, ChE, ALP, and HDL-C improved diagnostic performance for VDe [AUC = 0.775, 95% CI (0.706, 0.844), p < 0.001]. (3) Hb (OR = 0.986, p = 0.049), ChE (OR = 0.999, p = 0.020), ALP (OR = 1.017, p = 0.003), and basal ganglia lesions (OR = 2.197, p < 0.001) were important factors impacting VDe development. After adjusting for Hb, hs-CRP, ChE, HDL-C, lesions in the above mentioned four locations, sex, age and the prevalence of CSVD and brain atrophy, ALP [OR = 1.016, 95% CI (1.005, 1.027), p = 0.004] was independently associated with VDe. CONCLUSION: Hb, hs-CRP, ChE, ALP, and HDL-C concentrations are potential blood markers of depression in CVD patients and, when combined, may improve diagnostic performance for VDe. Serum ALP was independently associated with VDe in patients with CVD. Title: Discovering metabolic vulnerability using spatially resolved metabolomics for antitumor small molecule-drug conjugates development as a precise cancer therapy strategy Wang X, Zhang J, Zheng K, Du Q, Wang G, Huang J, Zhou Y, Li Y, Jin H, He J Ref: J Pharm Anal, 13:776, 2023 : PubMed ESTHER: Wang_2023_J.Pharm.Anal_13_776 PubMedSearch: Wang 2023 J.Pharm.Anal 13 776 PubMedID: 37577390 Abstract Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy. However, metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity. Herein, choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types, and a choline-modified strategy for small molecule-drug conjugates (SMDCs) design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy, instead of directly inhibiting choline metabolism. As a proof-of-concept, choline-modified SMDCs were designed, screened, and investigated for their druggability in vitro and in vivo. This strategy improved tumor targeting, preserved tumor inhibition and reduced toxicity of paclitaxel, through targeted drug delivery to tumor by highly expressed choline transporters, and site-specific release by carboxylesterase. This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy. Title: Efficient decolorization of melanoidin in raw molasses wastewater by thermophilic esterase in actual extreme conditions Zhang Z, Hu W, Xie Q, Shi Y, Zhao Y, Deng Y, He J, Wu X, Zhang Y and Wang W <3 more author(s)> Zhang Z, Hu W, Xie Q, Shi Y, Zhao Y, Deng Y, He J, Wu X, Zhang Y, Zhang W, Liu P, Yang H, Wang W (- 3) Ref: Bioresour Technol, 382:129191, 2023 : PubMed ESTHER: Zhang_2023_Bioresour.Technol_382_129191 PubMedSearch: Zhang 2023 Bioresour.Technol 382 129191 PubMedID: 37196742 Abstract This work was developed to explore the versatility of thermophilic esterase for decolorizing raw molasses wastewater at high temperature and acidic pH. Combining covalent crosslinking method with deep eutectic solvent, a thermophilic esterase from Pyrobaculum calidifontis was immobilized on chitosan/macroporous resin composite carrier. The application of this immobilized thermophilic esterase eliminated 92.35% of colorants in raw molasses wastewater, achieving maximal decolorization efficiency across all the enzymes tested. Strikingly, this immobilized thermophilic esterase was capable of engaging in continuous activity for a 5-day period while removing 76.23% of pigments from samples. It effectively and continuously eliminated BOD(5) and COD, effectively and directly facilitating raw molasses wastewater decolorization under extreme conditions more readily than control group. In addition, this thermophilic esterase was believed to achieve decolorization through an addition reaction that disrupted conjugated system of melanoidins. Together, these results highlight an efficient and practical means of achieving enzyme-based molasses wastewater decolorization. Title: Endoplasmic stress-inducing variants in carboxyl ester lipase and pancreatic cancer risk Kawamoto M, Yoshida T, Tamura K, Dbouk M, Canto MI, Burkhart R, He J, Roberts NJ, Klein AP, Goggins M Ref: Pancreatology, :, 2022 : PubMed ESTHER: Kawamoto_2022_Pancreatology__ PubMedSearch: Kawamoto 2022 Pancreatology PubMedID: 35995657 Abstract BACKGROUND: Endoplasmic reticulum (ER) stress-inducing variants in several pancreatic secretory enzymes have been associated with pancreatic disease. Multiple variants in CEL, encoding carboxyl ester lipase, are known to cause maturity-onset diabetes of the young (MODY8) but have not been implicated in pancreatic cancer risk. METHODS: The prevalence of ER stress-inducing variants in the CEL gene was compared among pancreatic cancer cases vs. controls. Variants were identified by next-generation sequencing and confirmed by Sanger sequencing. Variants of uncertain significance (VUS) were assessed for their effect on the secretion of CEL protein and variants with reduced protein secretion were evaluated to determine if they induced endoplasmic reticulum stress. RESULTS: ER stress-inducing CEL variants were found in 34 of 986 cases with sporadic pancreatic ductal adenocarcinoma, and 21 of 1045 controls (P = 0.055). Most of the variants were either the CEL-HYB1 variant, the I488T variant, or the combined CEL-HYB1/I488T variant; one case had a MODY8 variant. CONCLUSION: This case/control analysis finds ER stress-inducing CEL variants are not associated with an increased likelihood of having pancreatic cancer. Title: Phytochemical Properties and In Vitro Biological Activities of Phenolic Compounds from Flower of Clitoria ternatea L Li C, Tang W, Chen S, He J, Li X, Zhu X, Li H, Peng Y Ref: Molecules, 27:6336, 2022 : PubMed ESTHER: Li_2022_Molecules_27_6336 PubMedSearch: Li 2022 Molecules 27 6336 PubMedID: 36234873 Abstract Phenolic compounds from the flower of Clitoria ternatea L. (PCFCTL) were extracted using a high-speed shearing extraction technique and purified by AB-8 macroporous resins, and the phytochemical composition of the purified phenolic compounds from the flower of Clitoria ternatea L. (PPCFCTL) was then analyzed. Subsequently, its bioactivities including antioxidant properties, enzyme inhibitory activities, and antiproliferative activities against several tumor cell lines were evaluated. Results indicated that the contents of total phenolics, flavonoids, flavonols, flavanols, and phenolic acids in PPCFCTL were increased by 3.29, 4.11, 2.74, 2.43, and 2.96-fold, respectively, compared with those before being purified by AB-8 macroporous resins. The results showed PPCFCTL have significant antioxidant ability (measured by reducing power, RP, and ferric reducing antioxidant power method, FRAP) and good DPPH, ABTS(+), and superoxide anion radical scavenging activities. They can also significantly inhibit lipase, alpha-amylase, and alpha-glucosidase. In addition, morphological changes of HeLa, HepG2, and NCI-H460 tumor cells demonstrated the superior antitumor performance of PPCFCTL. However, the acetylcholinesterase inhibitory activity was relatively weak. These findings suggest that PPCFCTL have important potential as natural antioxidant, antilipidemic, anti-glycemic and antineoplastic agents in health-promoting foods. Title: Venom composition and pain-causing toxins of the Australian great carpenter bee Xylocopa aruana Shi N, Szanto TG, He J, Schroeder CI, Walker AA, Deuis JR, Vetter I, Panyi G, King GF, Robinson SD Ref: Sci Rep, 12:22168, 2022 : PubMed ESTHER: Shi_2022_Sci.Rep_12_22168 PubMedSearch: Shi 2022 Sci.Rep 12 22168 PubMedID: 36550366 Abstract Most species of bee are capable of delivering a defensive sting which is often painful. A solitary lifestyle is the ancestral state of bees and most extant species are solitary, but information on bee venoms comes predominantly from studies on eusocial species. In this study we investigated the venom composition of the Australian great carpenter bee, Xylocopa aruana Ritsema, 1876. We show that the venom is relatively simple, composed mainly of one small amphipathic peptide (XYTX(1)-Xa1a), with lesser amounts of an apamin homologue (XYTX(2)-Xa2a) and a venom phospholipase-A(2) (PLA(2)). XYTX(1)-Xa1a is homologous to, and shares a similar mode-of-action to melittin and the bombilitins, the major components of the venoms of the eusocial Apis mellifera (Western honeybee) and Bombus spp. (bumblebee), respectively. XYTX(1)-Xa1a and melittin directly activate mammalian sensory neurons and cause spontaneous pain behaviours in vivo, effects which are potentiated in the presence of venom PLA(2). The apamin-like peptide XYTX(2)-Xa2a was a relatively weak blocker of small conductance calcium-activated potassium (K(Ca)) channels and, like A. mellifera apamin and mast cell-degranulating peptide, did not contribute to pain behaviours in mice. While the composition and mode-of-action of the venom of X. aruana are similar to that of A. mellifera, the greater potency, on mammalian sensory neurons, of the major pain-causing component in A. mellifera venom may represent an adaptation to the distinct defensive pressures on eusocial Apidae. Title: Cornuside ameliorates cognitive impairments in scopolamine induced AD mice: Involvement of neurotransmitter and oxidative stress Wang ZX, Lian WW, He J, He XL, Wang YM, Pan CH, Li M, Zhang WK, Liu LQ, Xu JK Ref: J Ethnopharmacol, :115252, 2022 : PubMed ESTHER: Wang_2022_J.Ethnopharmacol__115252 PubMedSearch: Wang 2022 J.Ethnopharmacol 115252 PubMedID: 35405255 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis Sieb. et Zucc., traditional Chinese medicine, has been widely used in the treatment of dementia. Cornel iridoid glycosides of Cornus officinalis is therapeutic to Alzheimer's disease (AD), while its pharmacodynamic material basis is not clear. Cornuside, an iridoid glycoside extracted from of Cornus officinalis Sieb. et Zucc, might be a potential anti-AD candidate. AIM OF THE STUDY: Cornuside was evaluated for its effect on scopolamine induced AD mice, and its action mechanisms were explored. MATERIALS AND METHODS: ICR mice were administered with 1 mg/kg scopolamine intraperitoneally to induce amnesia. The therapeutic effect of cornuside of cognitive function was evaluated via series of behavioral tests, including Morris water maze test, step-through test and step-down test. In addition, specific enzyme reaction tests were used to detect the content of acetylcholine (ACh) and malondialdehyde (MDA), as well as the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), catalase (CAT), monoamine oxidase (MAO) in the brain. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). RESULTS: Cornuside ameliorated the spatial memory impairment in Morris water maze test and cognitive disruption in step-through and step-down test. Furthermore, cornuside improved the level of ACh by reducing the activities of AChE and BuChE, and increasing the activity of ChAT in hippocampus. Cornuside also increased the levels of monoamine neurotransmitters by inhibiting MAO activity in hippocampus and cortex. In addition, cornuside attenuated MDA by enhancing the activities of SOD and CAT in hippocampus and cortex. CONCLUSION: Cornuside improved cognitive dysfunction induced by scopolamine in behavioral tests. The mechanisms of cornuside were further investigated from the aspects of neurotransmitters and oxidative stress. Cornuside could inhibit oxidative stress and neurotransmitter hydrolases, increase ACh and monoamine neurotransmitters, which finally contributed to its therapeutic effect on scopolamine induced amnesia. Title: Tannic acid reduced apparent protein digestibility and induced oxidative stress and inflammatory response without altering growth performance and ruminal microbiota diversity of Xiangdong black goats Wang Z, Yin L, Liu L, Lan X, He J, Wan F, Shen W, Tang S, Tan Z, Yang Y Ref: Front Vet Sci, 9:1004841, 2022 : PubMed ESTHER: Wang_2022_Front.Vet.Sci_9_1004841 PubMedSearch: Wang 2022 Front.Vet.Sci 9 1004841 PubMedID: 36187804 Abstract The present study was performed to evaluate the impacts of tannic acid (TA) supplementation at different levels on the growth performance, physiological, oxidative and immunological metrics, and ruminal microflora of Xiangdong black goats. Twenty-four goats were randomly assigned to four dietary treatments: the control (CON, basal diet), the low-dose TA group [TAL, 0.3 % of dry matter (DM)], the mid-dose TA group (TAM, 0.6 % of DM), and the high-dose TA group (TAH, 0.9 % of DM). Results showed that the growth performance was unaffected (P > 0.05) by adding TA, whilst the 0.3 % and 0.6 % TA supplementation significantly decreased (P < 0.05) the apparent digestibility of crude protein (CP) and ruminal NH(3)-N concentration, and raised (P < 0.05) the level of total volatile fatty acid (TVFA) in rumen. The increments of alanine aminotransferase (ALT), triglyceride (TG), cortisol (CORT), total antioxidant capacity (T-AOC), interleukin (IL)-1beta, IL-6, and serumamyloid A (SAA), and decrements of globulin (GLB), immunoglobulin G (IgG), cholinesterase (CHE), glutathione reductase (GR), creatinine (CRE), growth hormone (GH), high-density lipoprotein cholesterol (HDLC), and insulin-like growth factor 1 (IGF-1) to different extents by TA addition were observed. Although the Alpha and Beta diversity of rumen bacterial community remained unchanged by supplementing TA, the relative abundance of the predominant genus Prevotella_1 was significantly enriched (P < 0.05) in TAL. It could hence be concluded that the TA supplementation in the present trial generally decreased CP digestion and caused oxidative stress and inflammatory response without influencing growth performance and ruminal microbiota diversity. More research is needed to explore the premium dosage and mechanisms of effects for TA addition in the diet of goats. Title: Plasma-Soluble Dipeptidyl Peptidase 4 and Risk of Major Cardiovascular Events After Ischemic Stroke: Secondary Analysis of China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) You S, Miao M, Lu Z, Bao A, Du J, Che B, Xu T, Zhong C, Cao Y and He J <2 more author(s)> You S, Miao M, Lu Z, Bao A, Du J, Che B, Xu T, Zhong C, Cao Y, Liu CF, Zhang Y, He J (- 2) Ref: Neurology, :, 2022 : PubMed ESTHER: You_2022_Neurology__ PubMedSearch: You 2022 Neurology PubMedID: 35654589 Abstract BACKGROUND AND OBJECTIVES: Recent studies have suggested that plasma soluble dipeptidyl peptidase-4 (sDPP4) have important physiological effects, which may influence the prognosis of ischemic stroke. Our study aimed to examine the relationship between plasma sDDP4 levels and long-term clinical outcomes among acute ischemic stroke patients. METHODS: Secondary analysis was conducted among 3,564 participants (2,270 men and 1,294 women) from the China Antihypertensive Trial in Acute Ischemic Stroke with baseline measurement of plasma sDPP4 levels. We evaluated the associations between plasma sDPP4 levels and 2-year clinical outcomes using logistic regression and Cox regression models. We further investigated the predictive utility of sDPP4 by calculating net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: The highest plasma sDPP4 quartile was associated with lower risk of cardiovascular events (HR 0.62, 95% CI 0.45-0.87), recurrent stroke (HR 0.70, 95% CI 0.49-0.99), all-cause mortality (HR 0.62, 95% CI 0.44-0.87), stroke-specific mortality (HR 0.65, 95% CI 0.44-0.94) and poor functional outcomes (OR 0.66, 95% CI 0.53-0.82) at 2 years compared with the lowest sDPP4 category in multivariable models. The addition of plasma sDPP4 to conventional risk factors model significantly improved risk prediction of all outcomes. DISCUSSION: In this study, we found that higher plasma sDPP4 levels in acute ischemic stroke patients were associated with decreased risks of cardiovascular events, recurrent stroke, all-cause mortality, and poor functional outcomes after ischemic stroke. These findings suggest that plasma sDPP4 may be a potential prognostic marker for initial risk stratification in patients with acute ischemic stroke. Title: Inhibition of Soluble Epoxide Hydrolase Attenuates Bosutinib-Induced Blood Pressure Elevation Cui Z, Li B, Zhang Y, He J, Shi X, Wang H, Zhao Y, Yao L, Ai D and Zhu Y <1 more author(s)> Cui Z, Li B, Zhang Y, He J, Shi X, Wang H, Zhao Y, Yao L, Ai D, Zhang X, Zhu Y (- 1) Ref: Hypertension, 78:1527, 2021 : PubMed Title: ANGPTL8 in metabolic homeostasis: more friend than foe? Guo C, Wang C, Deng X, He J, Yang L, Yuan G Ref: Open Biol, 11:210106, 2021 : PubMed ESTHER: Guo_2021_Open.Biol_11_210106 PubMedSearch: Guo 2021 Open.Biol 11 210106 PubMedID: 34582711 Abstract ANGPTL8 is an important cytokine, which is significantly increased in type 2 diabetes mellitus (T2DM), obesity and metabolic syndrome. Many studies have shown that ANGPTL8 can be used as a bio-marker of these metabolic disorders related diseases, and the baseline ANGPTL8 level has also been found to be positively correlated with retinopathy and all-cause mortality in patients with T2DM. This may be related to the inhibition of lipoprotein lipase activity and the reduction of circulating triglyceride (TG) clearance by ANGPTL8. Consistently, inhibition of ANGPTL8 seems to prevent or improve atherosclerosis. However, it is puzzling that ANGPTL8 seems to have a directing function for TG uptake in peripheral tissues; that is, ANGPTL8 specifically enhances the reserve and buffering function of white adipose tissue, which may alleviate the ectopic lipid accumulation to a certain extent. Furthermore, ANGPTL8 can improve insulin sensitivity and inhibit hepatic glucose production. These contradictory results lead to different opinions on the role of ANGPTL8 in metabolic disorders. In this paper, the correlation between ANGPTL8 and metabolic diseases, the regulation of ANGPTL8 and the physiological role of ANGPTL8 in the process of glucose and lipid metabolism were summarized, and the physiological/pathological significance of ANGPTL8 in the process of metabolic disorder was discussed. Title: PubChem in 2021: new data content and improved web interfaces Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q, Shoemaker BA, Thiessen PA and Bolton EE <3 more author(s)> Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q, Shoemaker BA, Thiessen PA, Yu B, Zaslavsky L, Zhang J, Bolton EE (- 3) Ref: Nucleic Acids Research, 49:D1388, 2021 : PubMed ESTHER: Kim_2021_Nucleic.Acids.Res_49_D1388 PubMedSearch: Kim 2021 Nucleic.Acids.Res 49 D1388 PubMedID: 33151290 Abstract PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves the scientific community as well as the general public, with millions of unique users per month. In the past two years, PubChem made substantial improvements. Data from more than 100 new data sources were added to PubChem, including chemical-literature links from Thieme Chemistry, chemical and physical property links from SpringerMaterials, and patent links from the World Intellectual Properties Organization (WIPO). PubChem's homepage and individual record pages were updated to help users find desired information faster. This update involved a data model change for the data objects used by these pages as well as by programmatic users. Several new services were introduced, including the PubChem Periodic Table and Element pages, Pathway pages, and Knowledge panels. Additionally, in response to the coronavirus disease 2019 (COVID-19) outbreak, PubChem created a special data collection that contains PubChem data related to COVID-19 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Title: Extraction and purification of total flavonoids from Eupatorium lindleyanum DC. and evaluation of their antioxidant and enzyme inhibitory activities Li C, Chen S, Sha J, Cui J, He J, Fu J, Shen Y Ref: Food Sci Nutr, 9:2349, 2021 : PubMed ESTHER: Li_2021_Food.Sci.Nutr_9_2349 PubMedSearch: Li 2021 Food.Sci.Nutr 9 2349 PubMedID: 34026054 Abstract The health benefits and promising medical treatment potential of total flavonoids from Eupatorium lindleyanum DC. (TFELDC) have been recognized. The process parameters of extracting total flavonoids from Eupatorium lindleyanum DC. by ultrasonic-microwave synergistic extraction (UMSE) were optimized, and they were purified by AB-8 macroporous resin in the current study. In addition, the antioxidant and enzyme inhibitory activities of the purified TFELDC (PTFELDC) were evaluated. The results showed that the optimal parameters of UMSE were as follows: ethanol volume fraction 71.5%, L/S ratio 12.2 ml/g, microwave power 318 W, and extraction time 143 s. After TFELDC were purified by AB-8 macroporous resin, the total flavonoid contents of PTFELDC increased from 208.18 +/- 1.60 to 511.19 +/- 3.21 mg RE/g FDS. Compared with TFELDC, the content of total flavonoids in PTFELDC was increased by 2.46 times. The antioxidant activities of PTFELDC were assessed using DPPH radical, superoxide anion radical, reducing power, and ferric reducing antioxidant power assays, and the IC(50) values were found to be 37.13, 19.62, 81.22, and 24.72 microg/ml, respectively. The enzyme inhibitory activities of PTFELDC were measured using lipase, alpha-amylase, alpha-glucosidase, and acetylcholinesterase assays with the IC(50) values 1.38, 2.08, 1.63, and 0.58 mg/ml, respectively. By comparing with their positive controls, it was found that PTFELDC had good antioxidant activities, and lipase, alpha-amylase, and alpha-glucosidase inhibitory activities, However, the acetylcholinesterase inhibitory activity was relatively weaker. These results suggested that PTFELDC have a promising potential as natural antioxidant, antilipidemic, and hypoglycemic drugs used in functional foods or pharmaceuticals. Title: Biodegradation and up-cycling of polyurethanes: Progress, challenges, and prospects Liu J, He J, Xue R, Xu B, Qian X, Xin F, Blank LM, Zhou J, Wei R and Jiang M <1 more author(s)> Liu J, He J, Xue R, Xu B, Qian X, Xin F, Blank LM, Zhou J, Wei R, Dong W, Jiang M (- 1) Ref: Biotechnol Adv, 48:107730, 2021 : PubMed ESTHER: Liu_2021_Biotechnol.Adv_48_107730 PubMedSearch: Liu 2021 Biotechnol.Adv 48 107730 PubMedID: 33713745 Abstract Polyurethanes (PUR) are ranked globally as the 6th most abundant synthetic polymer material. Most PUR materials are specifically designed to ensure long-term durability and high resistance to environmental factors. As the demand for diverse PUR materials is increasing annually in many industrial sectors, a large amount of PUR waste is also being generated, which requires proper disposal. In contrast to other mass-produced plastics such as PE, PP, and PET, PUR is a family of synthetic polymers, which differ considerably in their physical properties due to different building blocks (for example, polyester- or polyether-polyol) used in the synthesis. Despite its xenobiotic properties, PUR has been found to be susceptible to biodegradation by different microorganisms, albeit at very low rate under environmental and laboratory conditions. Discovery and characterization of highly efficient PUR-degrading microbes and enzymes capable of disassembling PUR polymer chains into oligo- and monomeric compounds is of fundamental importance for a circular plastic economy. In this review, the main methods used for screening PUR-degrading microbes and enzymes are summarized and compared in terms of their catalytic mechanisms. Furthermore, recycling and upcycling strategies of waste PUR polymers, including microbial conversion of PUR monomers into value added products, are presented. Title: Rivastigmine Regulates the HIF-1alpha/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats Liu Y, Li W, Ma X, He J, Lin Y, Lin D Ref: Front Pharmacol, 12:818907, 2021 : PubMed ESTHER: Liu_2021_Front.Pharmacol_12_818907 PubMedSearch: Liu 2021 Front.Pharmacol 12 818907 PubMedID: 35126151 Abstract Random skin flaps are frequently used to repair skin damage. However, the ischemic and hypoxic necrosis limits their wider application. Rivastigmine, a carbamate cholinesterase inhibitor (ChEI), has also been shown to reduce ischemia-reperfusion injury (IRI) and inflammation. This study was performed to examine the effect of rivastigmine on flap survival. Sixty male Sprague-Dawley rats with a modified McFarland flap were randomly divided into three groups: control group, 1 ml of solvent (10% DMSO + 90% corn oil); low-dose rivastigmine group (Riv-L), 1.0 mg/kg; and high-dose rivastigmine group (Riv-H), 2.0 mg/kg. All rats were treated once a day. On day 7, the skin flap survival area was measured. After staining with hematoxylin and eosin (H&E), the pathological changes and microvessel density (MVD) were examined. The expression of inflammatory factors IL-1beta and IL-18, CD34, hypoxia-inducible factor-1alpha (HIF-1alpha), and vascular endothelial growth factor (VEGF) was examined by immunohistochemical staining. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were examined to determine the degree of oxidative stress. Lead oxide/gelatin angiography showed neovascularization and laser Doppler blood flowmetry showed the blood filling volume. Rivastigmine significantly increased the flap survival area and improved neovascularization. CD34, VEGF, and HIF-1alpha expression were increased, These changes were more pronounced in the Riv-H group. Treatment with rivastigmine reduced the level of MDA, improved SOD activity, and reduced expression of IL-1beta and IL-18. Our results indicate that Rivastigmine can increase angiogenesis and significantly improve flap survival. Title: A survey of insecticide resistance-conferring mutations in multiple targets in Anopheles sinensis populations across Sichuan, China Qian W, Liu N, Yang Y, Liu J, He J, Chen Z, Li M, Qiu X Ref: Parasit Vectors, 14:169, 2021 : PubMed ESTHER: Qian_2021_Parasit.Vectors_14_169 PubMedSearch: Qian 2021 Parasit.Vectors 14 169 PubMedID: 33743789 Abstract BACKGROUND: Sichuan province is located in the southwest of China, and was previously a malaria-endemic region. Although no indigenous malaria case has been reported since 2011, the number of imported cases is on the rise. Insecticide-based vector control has played a central role in the prevention of malaria epidemics. However, the efficacy of this strategy is gravely challenged by the development of insecticide resistance. Regular monitoring of insecticide resistance is essential to inform evidence-based vector control. Unfortunately, almost no information is currently available on the status of insecticide resistance and associated mechanisms in Anopheles sinensis, the dominant malaria vector in Sichuan. In this study, efforts were invested in detecting the presence and frequency of insecticide resistance-associated mutations in three genes that encode target proteins of several classes of commonly used insecticides. METHODS: A total of 446 adults of An. sinensis, collected from 12 locations across Sichuan province of China, were inspected for resistance-conferring mutations in three genes that respectively encode acetylcholinesterase (AChE), voltage-gated sodium channel (VGSC), and GABA receptor (RDL) by DNA Sanger sequencing. RESULTS: The G119S mutation in AChE was detected at high frequencies (0.40-0.73). The predominant ace-1 genotype was GGC/AGC (119GS) heterozygotes. Diverse variations at codon 1014 were found in VGSC, leading to three different amino acid substitutions (L1014F/C/S). The 1014F was the predominant resistance allele and was distributed in all 12 populations at varying frequencies from 0.03 to 0.86. The A296S mutation in RDL was frequently present in Sichuan, with 296SS accounting for more than 80% of individuals in six of the 12 populations. Notably, in samples collected from Chengdu (DJY) and Deyang (DYMZ), almost 30% of individuals were found to be resistant homozygotes for all three targets. CONCLUSIONS: Resistance-related mutations in three target proteins of the four main classes of insecticides were prevalent in most populations. This survey reveals a worrisome situation of multiple resistance genotypes in Sichuan malaria vector. The data strengthen the need for regular monitoring of insecticide resistance and establishing a region-customized vector intervention strategy. Title: Brain-targeted delivery of obidoxime, using aptamer-modified liposomes, for detoxification of organophosphorus compounds Zhang Y, He J, Shen L, Wang T, Yang J, Li Y, Wang Y, Quan D Ref: J Control Release, 329:1117, 2021 : PubMed ESTHER: Zhang_2021_J.Control.Release_329_1117 PubMedSearch: Zhang 2021 J.Control.Release 329 1117 PubMedID: 33096123 Abstract Effective intracerebral delivery acetylcholinesterase (AChE) reactivator is key for the acute organophosphorus (OPs) poison treatment. However, the blood-brain barrier (BBB) restricts the transport of these drugs from blood into the brain. Herein, we developed transferrin receptor (TfR) aptamer-functionalized liposomes (Apt-LP) that could deliver AChE reactivator (obidoxime) across the BBB to act against paraoxon (POX) poisoning. The aptamer had strong affinity for TfR and was modified with 3'-inverted deoxythymidine (dT) to improve serum stability. The uptake of Apt-LP by bEnd.3 cells was significantly higher than that of non-targeting liposomes. The ability of Apt-LP to penetrate intact BBB was confirmed in in vitro BBB mice model and in vivo biodistribution studies. Treatment of POX-poisoned mice with Apt-LP-LuH-6 reactivated 18% of the brain AChE activity and prevented brain damage to some extent. Taken together, these results showed that Apt-LP may be used as a promising brain-targeted drug delivery system against OPs toxicity. Title: Acupuncture of the Beishu acupoint participates in regulatory effects of ginsenoside Rg1 on T cell subsets of rats with chronic fatigue syndrome He J, Yu Q, Wu C, Sun Z, Wu X, Liu R, Zhang H Ref: Ann Palliat Med, 9:3436, 2020 : PubMed ESTHER: He_2020_Ann.Palliat.Med_9_3436 PubMedSearch: He 2020 Ann.Palliat.Med 9 3436 PubMedID: 33065794 Abstract BACKGROUND: There are close relationships between the spleen and limb muscles and thoughts. The study aims to test the effects of ginsenoside Rg1 in combination with acupuncture of the Beishu acupoint on T cell subsets of rats with chronic fatigue syndrome (CFS). METHODS: The model was set up by combining forced cold-water swimming with chronic restraint. The rats were randomly divided into blank control, model, ginsenoside, acupuncture, and ginsenoside plus acupuncture groups (n=10). For the acupuncture group, the Beishu acupoint was acupunctured on the 2nd day after modeling. For the ginsenoside group, the ginsenoside Rg1 solution was injected into the tail vein on the 2nd day after modeling. For the combination group, both processes were conducted. These groups were compared regarding exhausted swimming time, number of struggles, resting time, serum levels of IgA, IgG, IgM, IFN-alpha, IFN-beta, and IFN-gamma, lymphocyte transformation rate, T cell subsets, and skeletal muscle activities of malondialdehyde (MDA), total antioxidative capacity (T-AOC) and acetylcholinesterase (Ache). RESULTS: The exhausted swimming time, number of struggles, and resting time of combination group surpassed those in the ginsenoside and acupuncture groups significantly (P<0.05). The serum levels of IgA, IgG, IgM, IFN-beta, IFN-gamma, T-AOC, and Ache, together with CD3+ and CD8+ T cell percentages of combination groups, were significantly higher than those of ginsenoside and acupuncture groups. However, the IFN-alpha level, MDA activity, and CD4+ T cell percentage were significantly lower (P<0.05). Compared with the model group, the CD4+/CD8+ T cell ratios of acupuncture, ginsenoside, and combination groups decreased significantly (P<0.05). Compared with the combination group, the ratio of the ginsenoside group increased significantly (P<0.05). CONCLUSIONS: Both acupuncture of the Beishu acupoint and intravenous injection of ginsenoside Rg1 have anti-fatigue effects, and their combination works synergistically. This study supplies an experimental basis for joint therapy using acupuncture and drugs to combat fatigue synergistically. Title: Separation of saturated fatty acids from docosahexaenoic acid-rich algal oil by enzymatic ethanolysis in tandem with molecular distillation He J, Hong B, Lu R, Zhang R, Fang H, Huang W, Bai K, Sun J Ref: Food Sci Nutr, 8:2234, 2020 : PubMed ESTHER: He_2020_Food.Sci.Nutr_8_2234 PubMedSearch: He 2020 Food.Sci.Nutr 8 2234 PubMedID: 32405380 Abstract Algal oil, rich in docosahexaenoic acid (DHA) and an environmentally sustainable source of omega-3 fatty acids, is receiving increasing attention. In the present study, a novel approach combining ethanolysis with a 1,3-specific immobilized lipase (Lipozyme() TL IM) and molecular distillation was investigated to increase the DHA content of algal oil. Algal oil with a 45.94% DHA content was mixed with ethanol, pumped into a column filled with Lipozyme() TL IM, and then circulated for 4 hr at room temperature. The ethanol was then recycled by vacuum distillation. At an evaporator temperature of 150 degC, the residue was separated by molecular distillation into a heavy component enriched with DHA glycerides (in the form of triglyceride (TG), diglyceride (DG), and monoglyceride (MG)) and a light component enriched with palmitic acid (PA) and DHA ethyl ester (EE). As a result, 76.55% of the DHA from the algal oil was present in the heavy component, whose DHA content was 70.27%. DHA-MG was collected in the heavy component mostly in the form of 1-MG. Lipozyme() TL IM appeared to specifically target PA rather than DHA at the sn-1(3) position. The Lipozyme() TL IM allowed 90.03% of the initial DHA yield to be retained after seven reaction cycles. Therefore, an eco-friendly and simple method for increasing the DHA content in algal oil has been developed. Title: Structure and Catalytic Mechanism of a Pyrethroid Carboxylesterase PytH from Sphingobium faniae JZ-2 Xu D, Gao Y, Sun B, Ran T, Zeng L, He J, Wang W Ref: Applied Environmental Microbiology, :, 2020 : PubMed ESTHER: Xu_2020_Appl.Environ.Microbiol__ PubMedSearch: Xu 2020 Appl.Environ.Microbiol PubMedID: 32303545 Gene_locus related to this paper: sphwj-c0la90 Abstract Carboxylesterase PytH, isolated from a pyrethroid degrading bacterium Sphingobium faniae JZ-2, could rapidly hydrolyze the ester bond of a wide range of pyrethroid pesticides, including permethrin, fenpropathrin, cypermethrin, fenvalerate, deltamethrin, cyhalothrin and bifenthrin. To elucidate the catalytic mechanism of PytH, here we report the crystal structures of PytH with bifenthrin (BIF) and phenylmethylsulfonyl fluoride (PMSF) and two PytH mutants. Though PytH shares low sequence identity with reported alpha/beta-hydrolase fold proteins, the typical triad catalytic center with Ser-His-Asp triad (Ser78, His230 and Asp202) is present and vital for the hydrolase activity. However, no contact was found between Ser78 and His230 in the structures we solved, which may be due to the fact that the PytH structures we determined are in their inactive or low activity forms. The structure of PytH is composed of a core domain and a lid domain; some hydrophobic amino acid residues surrounding the substrate from both domains form a deeper and wider hydrophobic pocket than its homologous structures. This indicates that the larger hydrophobic pocket makes PytH fit for its larger substrates binding; both lid and core domains are involved in substrate binding and the lid domain induced core domain movement may make the active center correctly positioned with substrates.IMPORTANCE Pyrethroid pesticides are widely applied in agriculture and household, however, extensive use of these pesticides also causes serious environmental and health problems. The hydrolysis of pyrethroids by carboxylesterases is the major pathway of microbial degradation of pyrethroids, but the structure of carboxylesterases and its catalytic mechanism are still unknown. Carboxylesterase PytH from Sphingobium faniae JZ-2 could effectively hydrolyze a wide range of pyrethroid pesticides. The crystal structures of PytH are solved in this study. It showed that it belongs to the alpha/beta-hydrolase fold proteins with typical catalytic Ser-His-Asp triad though PytH has a low sequence identity (about 20%) with them. The special large hydrophobic binding pocket endowed PytH binding bigger pyrethroids family substrates. Our structures shed light on the substrate selectivity and the future application of PytH and deeper the understanding of alpha/beta-hydrolase members. Title: Traditional uses, phytochemistry, pharmacology and toxicological aspects of the genus Hosta (Liliaceae): A comprehensive review Yang L, He J Ref: J Ethnopharmacol, :113323, 2020 : PubMed ESTHER: Yang_2020_J.Ethnopharmacol__113323 PubMedSearch: Yang 2020 J.Ethnopharmacol 113323 PubMedID: 32871235 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hosta (Liliaceae family) represents an interesting source of natural bio-constituents, and the 50 species of this genus are widespread in the world. Five species have been used as traditional East Asian medicines for treating inflammation and pain-related diseases. However, the available data for this genus have not been comprehensively reviewed regarding their extracts and secondary metabolites. AIM OF THE STUDY: The present review aims to provide a deeper insight, better awareness and detailed knowledge of traditional uses, phytochemistry, pharmacology along with toxicological aspects of the genus Hosta in the past decades (February 1964 to August 2020). In addition, the relevance among traditional uses, pharmacology and phytochemistry in folk medicines were extensively discussed. MATERIALS AND METHODS: The relevant information of Hosta species was obtained from several databases. Moreover, the medical books, PhD and MSc dissertations in Chinese were also used to perform this work. RESULTS: Comprehensive analysis of the afore-mentioned databases, medical books and dissertations confirmed that ethnomedical uses of Hosta genus plants had been recorded in China, Japan, Korea and other countries. To date, only eight species have been studied for chemical constituents, and a total of 200 secondary metabolites (not include essential oil constituents), including steroids, flavonoids, alkaloids, furan derivatives, phenylpropanoids, phenethyl derivatives, terpenoids, aliphatics, and others. The crude extracts and isolated chemical constituents exhibited anti-inflammatory and analgesic, antioxidant, anti-tumor, anti-viral, acetylcholinesterase inhibitory, antimicrobial, anti-chronic prostatitis, and other effects. Moreover, only the n-butanol fraction of H. ventricosa (Salisb.) Stearn roots showed moderate acute toxicity in mice. In addition, the relevance among traditional uses, pharmacology and phytochemistry in folk medicines were extensively discussed. CONCLUSIONS: Hosta spp. are plants rich in steroids and flavonoids with valuable medicinal properties; though, there are several gaps in understanding the traditional uses in the current available data. More high scientific quality preclinical studies with new methodology are necessary to assess the safety, efficacy and mechanism of these plants. Title: Monoacylglycerol Lipase Knockdown Inhibits Cell Proliferation and Metastasis in Lung Adenocarcinoma Zhang H, Guo W, Zhang F, Li R, Zhou Y, Shao F, Feng X, Tan F, Wang J and He J <2 more author(s)> Zhang H, Guo W, Zhang F, Li R, Zhou Y, Shao F, Feng X, Tan F, Wang J, Gao S, Gao Y, He J (- 2) Ref: Front Oncol, 10:559568, 2020 : PubMed ESTHER: Zhang_2020_Front.Oncol_10_559568 PubMedSearch: Zhang 2020 Front.Oncol 10 559568 PubMedID: 33363004 Abstract Abnormal metabolism is one of the hallmarks of cancer cells. Monoacylglycerol lipase (MGLL), a key enzyme in lipid metabolism, has emerged as an important regulator of tumor progression. In this study, we aimed to characterize the role of MGLL in the development of lung adenocarcinoma (LUAD). To this end, we used tissue microarrays to evaluate the expression of MGLL in LUAD tissue and assessed whether the levels of this protein are correlated with clinicopathological characteristics of LUAD. We found that the expression of MGLL is higher in LUAD samples than that in adjacent non-tumor tissues. In addition, elevated MGLL expression was found to be associated with advanced tumor progression and poor prognosis in LUAD patients. Functional studies further demonstrated that stable short hairpin RNA (shRNA)-mediated knockdown of MGLL inhibits tumor proliferation and metastasis, both in vitro and in vivo, and mechanistically, our data indicate that MGLL regulates Cyclin D1 and Cyclin B1 in LUAD cells. Moreover, we found that knockdown of MGLL suppresses the expression of matrix metalloproteinase 14 (MMP14) in A549 and H322 cells, and in clinical samples, expression of MMP14 is significantly correlated with MGLL expression. Taken together, our results indicate that MGLL plays an oncogenic role in LUAD progression and metastasis and may serve as a potential biomarker for disease prognosis and as a target for the development of personalized therapies. Title: Directed Evolution of Sulfonylurea Esterase and Characterization of a Variant with Improved Activity Liu B, Peng Q, Sheng M, Hu S, Qian M, Fan B, He J Ref: Journal of Agricultural and Food Chemistry, 67:836, 2019 : PubMed ESTHER: Liu_2019_J.Agric.Food.Chem_67_836 PubMedSearch: Liu 2019 J.Agric.Food.Chem 67 836 PubMedID: 30585487 Gene_locus related to this paper: 9rhiz-g9i933 Abstract Esterase SulE detoxicates a variety of sulfonylurea herbicides through de-esterification. SulE exhibits high activity against thifensulfuron-methyl but low activity against other sulfonylureas. In this study, two variants, m2311 (P80R) and m0569 (P80R and G176A), with improved activity were screened from a mutation library constructed by error-prone PCR. Variant m2311 showed a higher activity against sulfonylureas in comparison variant m0569 and was further investigated. The kcat/ Km value of variant m2311 for metsulfuron-methyl, sulfometuron-methyl, chlorimuron-ethyl, tribenuron-methyl, and ethametsulfuron-methyl increased by 3.20-, 1.72-, 2.94-, 2.26- and 2.96-fold, respectively, in comparison with the wild type. Molecular modeling suggested that the activity improvement of variant m2311 is due to the substitution of Pro80 by arginine, leading to the formation of new hydrogen bonds between the enzyme and substrate. This study facilitates further elucidation of the structure and function of SulE and provides an improved gene resource for the detoxification of sulfonylurea residues and the genetic engineering of sulfonylurea-resistant crops. Title: Dietary mulberry leaf powder affects growth performance, carcass traits and meat quality in finishing pigs Liu Y, Li Y, Peng Y, He J, Xiao D, Chen C, Li F, Huang R, Yin Y Ref: J Anim Physiol Anim Nutr (Berl), 103:1934, 2019 : PubMed ESTHER: Liu_2019_J.Anim.Physiol.Anim.Nutr.(Berl)_103_1934 PubMedSearch: Liu 2019 J.Anim.Physiol.Anim.Nutr.(Berl) 103 1934 PubMedID: 31478262 Abstract This study was conducted to evaluate the effect of mulberry leaves as an alternative source of protein on growth performance, carcass traits and meat quality in finishing pigs. A total of 180 Xiangcun Black pigs were randomly assigned to five treatment groups with six pens of six pigs per pen. The pigs were provided with a basal diet or a diet contained 3%, 6%, 9% or 12% of mulberry leaf powder during a 50-day experiment period. The results showed that dietary mulberry leaf powder had no negative effect on growth performance in Xiangcun Black pigs, except in the 12% mulberry group, where final body weight and average daily gain decreased (p < .05) and feed to gain ratio of the pigs increased (p < .05). Dietary mulberry inclusion decreased (quadratic, p < .05) the back fat thickness, fibre mean cross-sectional area (CSA) in the longissimus dorsi (LD) muscle and mRNA expression levels of myosin heavy chain (MyHC) IIb in LD and biceps femoris (BF) muscles, while increased (linear or quadratic, p < .05) the plasma concentration of albumin, levels of crude protein (CP), inosine monophosphate (IMP) and several amino acids in muscle tissues. When compared with the other groups, the 9% mulberry diet increased (p < .05) loin-eye area and contents of CP and IMP in muscles, while decreased (p < .05) plasma activity of cholinesterase and concentrations of uric acid and urea. The 6% mulberry diet had the lowest fibre mean CSA and shear force and increased total fibre number of the LD muscle, when compared with the other groups. These results suggest that including mulberry in the diet at <12% is an effective feed crop to improve meat quality and the chemical composition of muscle without negatively affecting growth performance. Title: Circulating lncRNA ABHD11-AS1 serves as a biomarker for early pancreatic cancer diagnosis Liu Y, Feng W, Liu W, Kong X, Li L, He J, Wang D, Zhang M, Zhou G and Xu M <3 more author(s)> Liu Y, Feng W, Liu W, Kong X, Li L, He J, Wang D, Zhang M, Zhou G, Xu W, Chen W, Gong A, Xu M (- 3) Ref: J Cancer, 10:3746, 2019 : PubMed ESTHER: Liu_2019_J.Cancer_10_3746 PubMedSearch: Liu 2019 J.Cancer 10 3746 PubMedID: 31333792 Gene_locus related to this paper: human-ABHD11 Abstract Background: Recent studies have shown that circulating long noncoding RNAs (lncRNAs) could be stably detectable in the blood of cancer patients and play important roles in the diagnosis of many different cancers. However, the value of lncRNAs in the diagnosis of pancreatic cancer (PC) has not been fully explored. Methods: Eleven PC-related lncRNAs were selected by analyzing bioinformatics databases. The expression levels of the lncRNAs were further analyzed in a small set of plasma samples from a training group including 30 noncancer samples (15 healthy and 15 chronic pancreatitis (CP) subjects) and 15 PC samples. Then, the candidate lncRNAs were validated with data from 46 healthy controls, 97 CP patients and 114 PC patients. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the identified lncRNAs. Results: After selection and validation, three characteristic plasma candidate lncRNAs, ABHD11-AS1, LINC00176 and SNHG11, were identified, and their levels were significantly higher in PC patients than in normal controls. We found that among the three candidate lncRNAs, ABHD11-AS1 showed the best diagnostic performance for the detection of PC. Furthermore, ABHD11-AS1 had a higher area under the ROC curve (AUC) than CEA, CA199 and CA125 for early PC diagnosis, while the combination of ABHD11-AS1 and CA199 was more effective than ABHD11-AS1 alone. Conclusions: Plasma ABHD11-AS1 could serve as a potential biomarker for detecting PC, and the combination of ABHD11-AS1 and CA199 was more efficient for the diagnosis of PC than ABHD11-AS1 alone, particularly for early tumor screening. Title: Inhibition of soluble epoxide hydrolase ameliorates hyperhomocysteinemia-induced hepatic steatosis by enhancing beta-oxidation of fatty acid in mice Yao L, Cao B, Cheng Q, Cai W, Ye C, Liang J, Liu W, Tan L, Yan M and Zhu Y <7 more author(s)> Yao L, Cao B, Cheng Q, Cai W, Ye C, Liang J, Liu W, Tan L, Yan M, Li B, He J, Hwang SH, Zhang X, Wang C, Ai D, Hammock BD, Zhu Y (- 7) Ref: American Journal of Physiology Gastrointest Liver Physiol, 316:G527, 2019 : PubMed ESTHER: Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527 PubMedSearch: Yao 2019 Am.J.Physiol.Gastrointest.Liver.Physiol 316 G527 PubMedID: 30789748 Inhibitor(s) related to this paper: TPPU Abstract Hepatic steatosis is the beginning phase of nonalcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuating their cardiovascular protective effects. However, the involvement of sEH in HHcy-induced hepatic steatosis is unknown. The current study aimed to explore the role of sEH in HHcy-induced lipid disorder. We fed 6-wk-old male mice a chow diet or 2% (wt/wt) high-metnionine diet for 8 wk to establish the HHcy model. A high level of homocysteine induced lipid accumulation in vivo and in vitro, which was concomitant with the increased activity and expression of sEH. Treatment with a highly selective specific sEH inhibitor (0.8 mg.kg(-1).day(-1) for the animal model and 1 muM for cells) prevented HHcy-induced lipid accumulation in vivo and in vitro. Inhibition of sEH activated the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), as evidenced by elevated beta-oxidation of fatty acids and the expression of PPAR-alpha target genes in HHcy-induced hepatic steatosis. In primary cultured hepatocytes, the effect of sEH inhibition on PPAR-alpha activation was further confirmed by a marked increase in PPAR-response element luciferase activity, which was reversed by knock down of PPAR-alpha. Of note, 11,12-EET ligand dependently activated PPAR-alpha. Thus increased sEH activity is a key determinant in the pathogenesis of HHcy-induced hepatic steatosis, and sEH inhibition could be an effective treatment for HHcy-induced hepatic steatosis. NEW & NOTEWORTHY In the current study, we demonstrated that upregulation of soluble epoxide hydrolase (sEH) is involved in the hyperhomocysteinemia (HHcy)-caused hepatic steatosis in an HHcy mouse model and in murine primary hepatocytes. Improving hepatic steatosis in HHcy mice by pharmacological inhibition of sEH to activate peroxisome proliferator-activated receptor-alpha was ligand dependent, and sEH could be a potential therapeutic target for the treatment of nonalcoholic fatty liver disease. Title: Clinical spectrum and genetic landscape for hereditary spastic paraplegias in China Dong EL, Wang C, Wu S, Lu YQ, Lin XH, Su HZ, Zhao M, He J, Ma LX and Lin X <2 more author(s)> Dong EL, Wang C, Wu S, Lu YQ, Lin XH, Su HZ, Zhao M, He J, Ma LX, Wang N, Chen WJ, Lin X (- 2) Ref: Mol Neurodegener, 13:36, 2018 : PubMed ESTHER: Dong_2018_Mol.Neurodegener_13_36 PubMedSearch: Dong 2018 Mol.Neurodegener 13 36 PubMedID: 29980238 Abstract BACKGROUND: Hereditary spastic paraplegias (HSP) is a heterogeneous group of rare neurodegenerative disorders affecting the corticospinal tracts. To date, more than 78 HSP loci have been mapped to cause HSP. However, both the clinical and mutational spectrum of Chinese patients with HSP remained unclear. In this study, we aim to perform a comprehensive analysis of clinical phenotypes and genetic distributions in a large cohort of Chinese HSP patients, and to elucidate the primary pathogenesis in this population. METHODS: We firstly performed next-generation sequencing targeting 149 genes correlated with HSP in 99 index cases of our cohort. Multiplex ligation-dependent probe amplification testing was further carried out among those patients without known disease-causing gene mutations. We simultaneously performed a retrospective study on the reported patients exhibiting HSP in other Chinese cohorts. All clinical and molecular characterization from above two groups of Chinese HSP patients were analyzed and summarized. Eventually, we further validated the cellular changes in fibroblasts of two major spastic paraplegia (SPG) patients (SPG4 and SPG11) in vitro. RESULTS: Most patients of ADHSP (94%) are pure forms, whereas most patients of ARHSP (78%) tend to be complicated forms. In ADHSP, we found that SPG4 (79%) was the most prevalent, followed by SPG3A (11%), SPG6 (4%) and SPG33 (2%). Subtle mutations were the common genetic cause for SPG4 patients and most of them located in AAA cassette domain of spastin protein. In ARHSP, the most common subtype was SPG11 (53%), followed by SPG5 (32%), SPG35 (6%) and SPG46 (3%). Moreover, haplotype analysis showed a unique haplotype was shared in 14 families carrying c.334C > T (p.R112(*)) mutation in CYP7B1 gene, suggesting the founder effect. Functionally, we observed significantly different patterns of mitochondrial dynamics and network, decreased mitochondrial membrane potential (deltam), increased reactive oxygen species and reduced ATP content in SPG4 fibroblasts. Moreover, we also found the enlargement of LAMP1-positive organelles and abnormal accumulation of autolysosomes in SPG11 fibroblasts. CONCLUSIONS: Our study present a comprehensive clinical spectrum and genetic landscape for HSP in China. We have also provided additional evidences for mitochondrial and autolysosomal-mediated pathways in the pathogenesis of HSP. Title: Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer Tamura K, Yu J, Hata T, Suenaga M, Shindo K, Abe T, MacGregor-Das A, Borges M, Wolfgang CL and Goggins M <23 more author(s)> Tamura K, Yu J, Hata T, Suenaga M, Shindo K, Abe T, MacGregor-Das A, Borges M, Wolfgang CL, Weiss MJ, He J, Canto MI, Petersen GM, Gallinger S, Syngal S, Brand RE, Rustgi A, Olson SH, Stoffel E, Cote ML, Zogopoulos G, Potash JB, Goes FS, McCombie RW, Zandi PP, Pirooznia M, Kramer M, Parla J, Eshleman JR, Roberts NJ, Hruban RH, Klein AP, Goggins M (- 23) Ref: Proc Natl Acad Sci U S A, 115:4767, 2018 : PubMed ESTHER: Tamura_2018_Proc.Natl.Acad.Sci.U.S.A_115_4767 PubMedSearch: Tamura 2018 Proc.Natl.Acad.Sci.U.S.A 115 4767 PubMedID: 29669919 Abstract To evaluate whether germline variants in genes encoding pancreatic secretory enzymes contribute to pancreatic cancer susceptibility, we sequenced the coding regions of CPB1 and other genes encoding pancreatic secretory enzymes and known pancreatitis susceptibility genes (PRSS1, CPA1, CTRC, and SPINK1) in a hospital series of pancreatic cancer cases and controls. Variants in CPB1, CPA1 (encoding carboxypeptidase B1 and A1), and CTRC were evaluated in a second set of cases with familial pancreatic cancer and controls. More deleterious CPB1 variants, defined as having impaired protein secretion and induction of endoplasmic reticulum (ER) stress in transfected HEK 293T cells, were found in the hospital series of pancreatic cancer cases (5/986, 0.5%) than in controls (0/1,045, P = 0.027). Among familial pancreatic cancer cases, ER stress-inducing CPB1 variants were found in 4 of 593 (0.67%) vs. 0 of 967 additional controls (P = 0.020), with a combined prevalence in pancreatic cancer cases of 9/1,579 vs. 0/2,012 controls (P < 0.01). More ER stress-inducing CPA1 variants were also found in the combined set of hospital and familial cases with pancreatic cancer than in controls [7/1,546 vs. 1/2,012; P = 0.025; odds ratio, 9.36 (95% CI, 1.15-76.02)]. Overall, 16 (1%) of 1,579 pancreatic cancer cases had an ER stress-inducing CPA1 or CPB1 variant, compared with 1 of 2,068 controls (P < 0.00001). No other candidate genes had statistically significant differences in variant prevalence between cases and controls. Our study indicates ER stress-inducing variants in CPB1 and CPA1 are associated with pancreatic cancer susceptibility and implicate ER stress in pancreatic acinar cells in pancreatic cancer development. Title: Differential physiological effects of neonicotinoid insecticides on honey bees: A comparison between Apis mellifera and Apis cerana Li Z, Li M, He J, Zhao X, Chaimanee V, Huang WF, Nie H, Zhao Y, Su S Ref: Pestic Biochem Physiol, 140:1, 2017 : PubMed ESTHER: Li_2017_Pestic.Biochem.Physiol_140_1 PubMedSearch: Li 2017 Pestic.Biochem.Physiol 140 1 PubMedID: 28755688 Abstract Acute toxicities (LD50s) of imidacloprid and clothianidin to Apis mellifera and A. cerana were investigated. Changing patterns of immune-related gene expressions and the activities of four enzymes between the two bee species were compared and analyzed after exposure to sublethal doses of insecticides. Results indicated that A. cerana was more sensitive to imidacloprid and clothianidin than A. mellifera. The acute oral LD50 values of imidacloprid and clothianidin for A. mellifera were 8.6 and 2.0ng/bee, respectively, whereas the corresponding values for A. cerana were 2.7 and 0.5ng/bee. The two bee species possessed distinct abilities to mount innate immune response against neonicotinoids. After 48h of imidacloprid treatment, carboxylesterase (CCE), prophenol oxidase (PPO), and acetylcholinesterase (AChE) activities were significantly downregulated in A. mellifera but were upregulated in A. cerana. Glutathione-S-transferase (GST) activity was significantly elevated in A. mellifera at 48h after exposure to imidacloprid, but no significant change was observed in A. cerana. AChE was downregulated in both bee species at three different time points during clothianidin exposure, and GST activities were upregulated in both species exposed to clothianidin. Different patterns of immune-related gene expression and enzymatic activities implied distinct detoxification and immune responses of A. cerana and A. mellifera to imidacloprid and clothianidin. Title: Identification and characterization of a novel carboxylesterase (FpbH) that hydrolyzes aryloxyphenoxypropionate herbicides Wang C, Qiu J, Yang Y, Zheng J, He J, Li S Ref: Biotechnol Lett, 39:553, 2017 : PubMed ESTHER: Wang_2017_Biotechnol.Lett_39_553 PubMedSearch: Wang 2017 Biotechnol.Lett 39 553 PubMedID: 28058522 Gene_locus related to this paper: burvg-a4jl51 Abstract OBJECTIVE: To identify and characterize a novel aryloxyphenoxypropionate (AOPP) herbicide-hydrolyzing carboxylesterase from Aquamicrobium sp. FPB-1. Title: Efficacy and safety of a novel acetylcholinesterase inhibitor octohydroaminoacridine in mild-to-moderate Alzheimer's disease: a Phase II multicenter randomised controlled trial Xiao S, Wang T, Ma X, Qin Y, Li X, Zhao Z, Liu X, Wang X, Xie H and He J <11 more author(s)> Xiao S, Wang T, Ma X, Qin Y, Li X, Zhao Z, Liu X, Wang X, Xie H, Jiang Q, Sun L, Luo B, Shang L, Chen W, Bai Y, Tang M, He M, Wu L, Ma Q, Hou D, He J (- 11) Ref: Age Ageing, :1, 2017 : PubMed ESTHER: Xiao_2017_Age.Ageing__1 PubMedSearch: Xiao 2017 Age.Ageing 1 PubMedID: 28419192 Abstract Background: inhibition of acetylcholinesterase (AChE) has been a effective treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE inhibitor, is a potential treatment for AD. Method: we conducted a multicenter, randomised, double blind, placebo-controlled, parallel-group Phase II clinical trial to investigate the effects of octohydroaminoacridine in patients with mild-to-moderate AD. Patients were randomised to receive placebo thrice daily, octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle-dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose group were titrated over 2-4 weeks. Changes from baseline to Week 16 were assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's Interview-Based Impression of Change Plus (CIBIC+), activities of daily living (ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end point of the study. A two-way analysis of covariance and least squares mean t-test were used. Results: at Week 16, the changes from baseline in ADAS-cog were 1.4, -2.1, -2.2 and -4.2 for placebo, low-, middle- and high-dose groups, respectively. Patients in the high-dose group had better performance in CIBIC+ and ADL scores at the end of the study. There was no significant difference in the change in NPI score among the groups. The effects of octohydroaminoacridine were dose dependent, and were effective within 16 weeks of treatment. No evidence was found for more adverse events that occurred in different drug groups than placebo group. Conclusions: octohydroaminoacridine significantly improved cognitive function and behaviour in patients with mild-to-moderate AD and this effect was dose dependent. Title: Soluble epoxide hydrolase: A potential target for metabolic diseases He J, Wang C, Zhu Y, Ai D Ref: J Diabetes, 8:305, 2016 : PubMed ESTHER: He_2016_J.Diabetes_8_305 PubMedSearch: He 2016 J.Diabetes 8 305 PubMedID: 26621325 Abstract Epoxyeicosatrienoic acids (EETs), important lipid mediators derived from arachidonic acid, have many beneficial effects in metabolic diseases, including atherosclerosis, hypertension, cardiac hypertrophy, diabetes, non-alcoholic fatty liver disease, and kidney disease. Epoxyeicosatrienoic acids can be further hydrolyzed to less active diols by the enzyme soluble epoxide hydrolase (sEH). Increasing evidence suggests that inhibition of sEH increases levels of EETs, which have anti-inflammatory effects and can prevent the development of hypertension, atherosclerosis, heart failure, fatty liver, and multiple organ fibrosis. Arachidonic acid is the most abundant omega-6 polyunsaturated fatty acid (PUFA) and shares the same set of enzymes with omega-3 PUFAs, such as docosahexaenoic acid and eicosapentaenoic acid. The omega-3 PUFAs and metabolites, such as regioisomeric epoxyeicosatetraenoic acids and epoxydocosapentaenoic acids, have been reported to have strong vasodilatory and anti-inflammatory effects. Therefore, sEH may be a potential therapeutic target for metabolic disorders. In this review, we focus on our and other recent studies of the functions of sEH, including the effects of its eicosanoid products from both omega-3 and omega-6 PUFAs, in various metabolic diseases. We also discuss the possible cellular and molecular mechanisms underlying the regulation of sEH. Title: Five new Lycopodium alkaloids from the aerial parts of Phlegmariurus henryi Liu YC, Su J, Wu XD, Zhang ZJ, Fan M, Zhu QF, He J, Li XN, Peng LY and Zhao QS <1 more author(s)> Liu YC, Su J, Wu XD, Zhang ZJ, Fan M, Zhu QF, He J, Li XN, Peng LY, Cheng X, Zhao QS (- 1) Ref: Fitoterapia, 115:148, 2016 : PubMed ESTHER: Liu_2016_Fitoterapia_115_148 PubMedSearch: Liu 2016 Fitoterapia 115 148 PubMedID: 27769820 Abstract A series of new Lycopodium alkaloids, namely 1-epi-malycorin A (1), 1-epi-17S-hydroxymalycorin A (2), 6alpha-hydroxyphlegmariurine A (3), 2S,4R-dihydroxyfawcettimine (4), and 16-hydroxylycodine (5), together with 24 known ones, have been isolated from the club moss Phlegmariurus henryi. The structures of the new compounds were determined by extensive spectroscopic analysis, including 1D and 2D NMR, as well as X-ray crystallographic analysis. Among them, the absolute configurations of 1, 2, and 4 and the structure of 3 were confirmed on the basis of the single-crystal X-ray diffraction analysis. 1-Epi-17S-hydroxymalycorin A (2) was a unique C19N-type Lycopodium alkaloid consisting of a serratinine skeleton with 1,2-propanediol unit. 2S,4R-dihydroxyfawcettimine (4) was a 2,4-dihydroxy derivative of fawcettimine. 16-Hydroxylycodine (5) was the oxidative product of lycodine with an unusual hydroxymethyl group at C-15. All new compounds were evaluated for in vitro acetylcholinesterase (AChE) inhibitory activity and cytotoxicity against four human cancer cell lines. Title: Display of fungal hydrophobin on the Pichia pastoris cell surface and its influence on Candida antarctica lipase B Wang P, He J, Sun Y, Reynolds M, Zhang L, Han S, Liang S, Sui H, Lin Y Ref: Applied Microbiology & Biotechnology, 100:5883, 2016 : PubMed ESTHER: Wang_2016_Appl.Microbiol.Biotechnol_100_5883 PubMedSearch: Wang 2016 Appl.Microbiol.Biotechnol 100 5883 PubMedID: 26969039 Abstract To modify the Pichia pastoris cell surface, two classes of hydrophobins, SC3 from Schizophyllum commune and HFBI from Trichoderma reesei, were separately displayed on the cell wall. There was an observable increase in the hydrophobicity of recombinant strains. Candida antarctica lipase B (CALB) was then co-displayed on the modified cells, generating strains GS115/SC3-61/CALB-51 and GS115/HFBI-61/CALB-51. Interestingly, the hydrolytic and synthetic activities of strain GS115/HFBI-61/CALB-51 increased by 37 and 109 %, respectively, but decreased by 26 and 43 %, respectively, in strain GS115/SC3-61/CALB-51 compared with the hydrophobin-minus recombinant strain GS115/CALB-GCW51. The amount of glycerol by-product from the transesterification reaction adsorbed on the cell surface was significantly decreased following hydrophobin modification, removing the glycerol barrier and allowing substrates to access the active sites of lipases. Electron micrographs indicated that the cell wall structures of both recombinant strains appeared altered, including changes to the inner glucan layer and outer mannan layer. These results suggest that the display of hydrophobins can change the surface structure and hydrophobic properties of P. pastoris and affect the catalytic activities of CALB displayed on the surface of P. pastoris cells. Title: Strategies for production of butanol and butyl-butyrate through lipase-catalyzed esterification Xin F, Basu A, Yang KL, He J Ref: Bioresour Technol, 202:214, 2016 : PubMed ESTHER: Xin_2016_Bioresour.Technol_202_214 PubMedSearch: Xin 2016 Bioresour.Technol 202 214 PubMedID: 26710347 Abstract In this study, a fermentation process for production of butanol and butyl-butyrate by using Clostridium sp. strain BOH3 is developed. This strain is able to produce butyric acid and butanol when it ferments 60 g/L xylose. Meanwhile, it also excreted indigenous lipases (induced by olive oil) which naturally convert butyric acid and butanol into 1.2 g/L of butyl-butyrate. When Bio-OSR was used as both an inducer for lipase and extractant for butyl-butyrate, the butyl-butyrate concentration can reach 6.3 g/L. To further increase the yield, additional lipases and butyric acid are added to the fermentation system. Moreover, kerosene was used as an extractant to remove butyl-butyrate in situ. When all strategies are combined, 22.4 g/L butyl-butyrate can be produced in a fed-batch reactor spiked with 70 g/L xylose and 7.9 g/L butyric acid, which is 4.5-fold of that in a similar system (5 g/L) with hexadecane as the extractant. Title: Geissoschizine methyl ether N-oxide, a new alkaloid with antiacetylcholinesterase activity from Uncaria rhynchophylla Jiang WW, Su J, Wu XD, He J, Peng LY, Cheng X, Zhao QS Ref: Nat Prod Res, 29:842, 2015 : PubMed ESTHER: Jiang_2015_Nat.Prod.Res_29_842 PubMedSearch: Jiang 2015 Nat.Prod.Res 29 842 PubMedID: 25496282 Abstract Geissoschizine methyl ether N-oxide, a new oxindole alkaloid, along with 14 known alkaloids, was isolated from the aerial part of Uncaria rhynchophylla. Their structures were identified by comprehensive spectral methods, including 2D NMR experiments, and confirmed by comparing with the literature data. In vitro acetylcholinesterase (AChE) inhibitory activity assay showed that the new compound exhibited anti-AChE activity with IC(5)(0) value of 23.4 muM. Title: Obscurumines H-P, new Lycopodium alkaloids from the club moss Lycopodium obscurum Jiang WW, Liu YC, Zhang ZJ, He J, Su J, Cheng X, Peng LY, Shao LD, Wu XD and Zhao QS <1 more author(s)> Jiang WW, Liu YC, Zhang ZJ, He J, Su J, Cheng X, Peng LY, Shao LD, Wu XD, Yang JH, Zhao QS (- 1) Ref: Fitoterapia, 109:155, 2015 : PubMed ESTHER: Jiang_2015_Fitoterapia_109_155 PubMedSearch: Jiang 2015 Fitoterapia 109 155 PubMedID: 26739385 Abstract Seven new fawcettimine-type (1-7) and two new lycopodine-type (8 and 9) Lycopodium alkaloids, as well as 10 known compounds, were isolated from the club moss, Lycopodium obscurum L. The structures of obscurumines H-P (1-9) were determined based on high-resolution MS and 1D and 2D NMR data. Compounds 1 and 2 include a new skeleton that is formed via the linkage of C-9-N-2', which is rarely present in Lycopodium alkaloids. The in vitro acetylcholinesterase (AChE) inhibitory activity assay showed that 5 exhibited weak anti-AChE activity with an IC50 value of 81.0muM. Compound 8 exhibited inhibition of the secretion of IL-2 in phytohemagglutinin (PHA) and phorbol myristate acetate (PMA) stimulated Jurkat cells, and the IC50 value was 17.2muM. Title: Four new fawcettimine-related alkaloids from Phlegmariurus squarrosus Liu YC, Fan M, Jiang WW, Liu F, Wu XD, He J, Cheng X, Peng LY, Su J and Zhao QS <1 more author(s)> Liu YC, Fan M, Jiang WW, Liu F, Wu XD, He J, Cheng X, Peng LY, Su J, Zhang ZJ, Zhao QS (- 1) Ref: J Asian Nat Prod Res, 17:967, 2015 : PubMed ESTHER: Liu_2015_J.Asian.Nat.Prod.Res_17_967 PubMedSearch: Liu 2015 J.Asian.Nat.Prod.Res 17 967 PubMedID: 26287979 Abstract Four new fawcettimine-related alkaloids (1-4), together with 17 known ones, were isolated from club moss Phlegmariurus squarrosus. Notably, compound 1 was the derivative of lycoflexine with an unprecedented additional methyl group at C-17. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR, and HR-MS, as well as by comparison with the literature data. All new compounds were tested for their beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AChE) inhibitory activities. Title: Soluble epoxide hydrolase is involved in the development of atherosclerosis and arterial neointima formation by regulating smooth muscle cell migration Wang Q, Huo L, He J, Ding W, Su H, Tian D, Welch C, Hammock B, Ai D, Zhu Y Ref: American Journal of Physiology Heart Circ Physiol, :ajpheart 00289 2015, 2015 : PubMed ESTHER: Wang_2015_Am.J.Physiol.Heart.Circ.Physiol__ajpheart 00289 2015 PubMedSearch: Wang 2015 Am.J.Physiol.Heart.Circ.Physiol ajpheart 00289 2015 PubMedID: 26453326 Abstract Epoxyeicosatrienoic acids (EETs) have beneficial effects on cardiovascular disease. Soluble epoxide hydrolase (sEH) metabolizes EETs to less active diols, thus diminishing biological activity. sEH inhibitors can suppress the progression of atherosclerotic lesions in animal models. However, the regulation of sEH in vascular smooth muscle cells (VSMCs) and role of sEH in patients with atherosclerosis have not been evaluated. We hypothesize that sEH in VSMC plays a pivotal role in atherosclerosis and injury-induced neointima formation. In this study, sEH expression in human autopsy atherosclerotic plaque was determined by immunohistochemistry. In cultured rat and human VSMCs, the phenotypic switching marker and sEH expression induced by platelet-derived growth factor-BB (PDGF-BB) were examined by western blot analysis. Carotid-artery balloon injury was performed after adenovirus-mediated overexpression of sEH or oral administration of a potent sEH inhibitor in Sprague-Dawley rats. sEH was highly expressed in VSMCs of the intima and media within human atherosclerotic plaque. In vitro, PDGF-BB upregulated the expression in VSMCs post-transcriptionally and promoted cell proliferation and migration, the latter effect could be largely attenuated by sEH inhibitor. Adenovirus-mediated overexpression of sEH could mimic the effect of PDGF-BB, induced VSMC proliferation and migration. In vivo, sEH inhibitor significantly decreased the injury-induced neointima formation in a rat carotid-artery injury model. These data establish the impact of sEH expression on atherosclerotic progression and vascular remodeling after injury, thus identifying a novel integrative role of sEH in VSMC phenotypic modulation and migration. Blocking sEH activity may be a potential therapeutic approach for ameliorating vascular occlusive disease. Title: Differential expression of lipid metabolism-related genes and myosin heavy chain isoform genes in pig muscle tissue leading to different meat quality Zhang C, Luo JQ, Zheng P, Yu B, Huang ZQ, Mao XB, He J, Yu J, Chen JL, Chen DW Ref: Animal, 9:1073, 2015 : PubMed ESTHER: Zhang_2015_Animal_9_1073 PubMedSearch: Zhang 2015 Animal 9 1073 PubMedID: 25716066 Abstract The aim of this study was to investigate the variations in meat quality, lipid metabolism-related genes, myosin heavy chain (MyHC) isoform genes and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) gene mRNA expressions in longissimus dorsi muscle (LM) of two different pig breeds. Six Rongchang and six Landrace barrows were slaughtered at 161 days of age. Subsequently, meat quality traits and gene expression levels in LM were observed. Results showed that Rongchang pigs not only exhibited greater pH, CIE a*24 h and intramuscular fat content but also exhibited lower body weight, carcass weight, dressing percentage, LM area and CIE b*24 h compared with Landrace pigs (P<0.05). Meanwhile, the mRNA expression levels of the lipogenesis (peroxisome proliferator-activated receptor gamma, acetyl-CoA carboxylase and fatty acid synthase) and fatty acid uptake (lipoprotein lipase)-related genes were greater in the Rongchang (P<0.05), whereas the lipolysis (adipose triglyceride lipase and hormone sensitive lipase) and fatty acid oxidation (carnitine palmitoyltransferase-1B)-related genes were better expressed in the Landrace. Moreover, compared with the Landrace, the mRNA expression levels of MyHCI, MyHCIIa and MyHCIIx were greater, whereas the mRNA expression levels of MyHCIIb were lower in the Rongchang pigs (P<0.05). In addition, the mRNA expression levels of PGC-1alpha were greater in Rongchang pigs than in the Landrace (P<0.05), which can partly explain the differences in MyHC isoform gene expressions between Rongchang and Landrace pigs. Although the small number of samples does not allow to obtain a definitive conclusion, we can suggest that Rongchang pigs possess better meat quality, and the underlying molecular mechanisms responsible for the better meat quality in fatty pigs may be partly due to the higher mRNA expression levels of lipogenesis and fatty acid uptake-related genes, as well as the oxidative and intermediate muscle fibers, and due to the lower mRNA expression levels of lipolysis and fatty acid oxidation-related genes, as well as the glycolytic muscle fibers. Title: Complete genome sequences of one human respiratory syncytial antigenic group a virus from china and its four mouse-adapted isolates Zhang K, He J, Li C, Bose ME, Henrickson KJ, Zhou J, Zheng BJ Ref: Genome Announc, 3:, 2015 : PubMed ESTHER: Zhang_2015_Genome.Announc_3_0 PubMedSearch: Zhang 2015 Genome.Announc 3 0 PubMedID: 25744999 Gene_locus related to this paper: 9noca-a0a0d5aa12, 9noca-a0a0d5abi2 Abstract In this study, one human respiratory syncytial antigenic group A virus (HRSV-A-GZ08-0) and its four BALB/c mouse-adapted isolates were sequenced and elucidated. Nineteen nucleotides were mutated between HRSV-A-GZ08-0 and the four mouse-adapted isolates. Title: Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes Biftu T, Sinha-Roy R, Chen P, Qian X, Feng D, Kuethe JT, Scapin G, Gao YD, Yan Y and Weber AE <19 more author(s)> Biftu T, Sinha-Roy R, Chen P, Qian X, Feng D, Kuethe JT, Scapin G, Gao YD, Yan Y, Krueger D, Bak A, Eiermann G, He J, Cox J, Hicks J, Lyons K, He H, Salituro G, Tong S, Patel S, Doss G, Petrov A, Wu J, Xu SS, Sewall C, Zhang X, Zhang B, Thornberry NA, Weber AE (- 19) Ref: Journal of Medicinal Chemistry, 57:3205, 2014 : PubMed ESTHER: Biftu_2014_J.Med.Chem_57_3205 PubMedSearch: Biftu 2014 J.Med.Chem 57 3205 PubMedID: 24660890 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: Omarigliptin Abstract In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development. Title: (-)-phenserine attenuates soman-induced neuropathology Chen J, Pan H, Chen C, Wu W, Iskandar K, He J, Piermartiri T, Jacobowitz DM, Yu QS and Marini AM <2 more author(s)> Chen J, Pan H, Chen C, Wu W, Iskandar K, He J, Piermartiri T, Jacobowitz DM, Yu QS, McDonough JH, Greig NH, Marini AM (- 2) Ref: PLoS ONE, 9:e99818, 2014 : PubMed ESTHER: Chen_2014_PLoS.One_9_e99818 PubMedSearch: Chen 2014 PLoS.One 9 e99818 PubMedID: 24955574 Abstract Organophosphorus (OP) nerve agents are deadly chemical weapons that pose an alarming threat to military and civilian populations. The irreversible inhibition of the critical cholinergic degradative enzyme acetylcholinesterase (AChE) by OP nerve agents leads to cholinergic crisis. Resulting excessive synaptic acetylcholine levels leads to status epilepticus that, in turn, results in brain damage. Current countermeasures are only modestly effective in protecting against OP-induced brain damage, supporting interest for evaluation of new ones. (-)-Phenserine is a reversible AChE inhibitor possessing neuroprotective and amyloid precursor protein lowering actions that reached Phase III clinical trials for Alzheimer's Disease where it exhibited a wide safety margin. This compound preferentially enters the CNS and has potential to impede soman binding to the active site of AChE to, thereby, serve in a protective capacity. Herein, we demonstrate that (-)-phenserine protects neurons against soman-induced neuronal cell death in rats when administered either as a pretreatment or post-treatment paradigm, improves motoric movement in soman-exposed animals and reduces mortality when given as a pretreatment. Gene expression analysis, undertaken to elucidate mechanism, showed that (-)-phenserine pretreatment increased select neuroprotective genes and reversed a Homer1expression elevation induced by soman exposure. These studies suggest that (-)-phenserine warrants further evaluation as an OP nerve agent protective strategy. Title: Huperserines A-E, Lycopodium alkaloids from Huperzia serrata Jiang WW, Liu F, Gao X, He J, Cheng X, Peng LY, Wu XD, Zhao QS Ref: Fitoterapia, 99C:72, 2014 : PubMed ESTHER: Jiang_2014_Fitoterapia_99C_72 PubMedSearch: Jiang 2014 Fitoterapia 99C 72 PubMedID: 25218968 Abstract A phytochemical study on Huperzia serrata led to the isolation of four new 5-deoxyfawcettimine-related Lycopodium alkaloids, huperserines A-D (1-4), and one new lycodine-type alkaloid, huperserine E (5). Their structures were elucidated based on spectroscopic data, including 1D and 2D NMR techniques. 5-Carbonyl or 5-hydroxyl group is a typical characteristic of lycopodine- and fawcettimine-type alkaloids. This is the first report of the 5-deoxyfawcettimine type Lycopodium alkaloids. In vitro acetylcholinesterase (AChE) inhibitory activity assay showed that huperserine E exhibited moderate anti-AChE activity with an IC50 value of 6.71muM. Title: Carinatines A and B, Alkaloids from Liu F, Liu YC, Jiang WW, He J, Wu XD, Peng LY, Su J, Cheng X, Zhao QS Ref: Nat Prod Bioprospect, 4:221, 2014 : PubMed ESTHER: Liu_2014_Nat.Prod.Bioprospect_4_221 PubMedSearch: Liu 2014 Nat.Prod.Bioprospect 4 221 PubMedID: 25089240 Abstract Carinatine A (1), a C16N2-type Lycopodium alkaloid possessing a 5/6/6/6 ring system formed by a new C-4/C-12 bond, and carinatine B (2), the first derivative of lycojaponicumin C, along 16 known compounds, were isolated from the whole plant of Phlegmariurus carinatus. Their structures were elucidated based on the spectroscopic data. The two new isolates were no inhibitory activity for the acetylcholinesterase (AChE). Title: Design, Synthesis, and Evaluation of 7H-thiazolo-[3,2-b]-1,2,4-triazin-7-one Derivatives as Dual Binding Site Acetylcholinesterase Inhibitors Liu S, Shang R, Shi L, Zhou R, He J, Wan DC Ref: Chemical Biology Drug Des, 84:169, 2014 : PubMed ESTHER: Liu_2014_Chem.Biol.Drug.Des_84_169 PubMedSearch: Liu 2014 Chem.Biol.Drug.Des 84 169 PubMedID: 24890706 Abstract New dual binding site acetylcholinesterase (AChE) inhibitors have been designed and synthesized as a new drug candidate for the treatment of Alzheimer's disease (AD) through the binding to both catalytic and peripheral sites of the enzyme. Therefore, a series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives 6a-j were synthesized and investigated for their ability to inhibit the activity of human AChE (hAChE) in comparison with huperzine-A. All the compounds were found to inhibit AChE activity, especially compounds 6c and 6i with the inhibition value of 76.10% and 77.82%, respectively. The molecular docking study indicated that they were nicely accommodated by AChE. The molecular docking study revealed that 6c and 6i possessed a more optimal binding conformation than 6a and can perfectly fit into the active and peripheral site of hAChE, and consequently exhibited highly improved inhibitor potency to hAChE. Title: Elucidating how the saprophytic fungus Aspergillus nidulans uses the plant polyester suberin as carbon source Martins I, Hartmann DO, Alves PC, Martins C, Garcia H, Leclercq CC, Ferreira R, He J, Renaut J and Silva Pereira C <1 more author(s)> Martins I, Hartmann DO, Alves PC, Martins C, Garcia H, Leclercq CC, Ferreira R, He J, Renaut J, Becker JD, Silva Pereira C (- 1) Ref: BMC Genomics, 15:613, 2014 : PubMed ESTHER: Martins_2014_BMC.Genomics_15_613 PubMedSearch: Martins 2014 BMC.Genomics 15 613 PubMedID: 25043916 Abstract BACKGROUND: Lipid polymers in plant cell walls, such as cutin and suberin, build recalcitrant hydrophobic protective barriers. Their degradation is of foremost importance for both plant pathogenic and saprophytic fungi. Regardless of numerous reports on fungal degradation of emulsified fatty acids or cutin, and on fungi-plant interactions, the pathways involved in the degradation and utilisation of suberin remain largely overlooked. As a structural component of the plant cell wall, suberin isolation, in general, uses harsh depolymerisation methods that destroy its macromolecular structure. We recently overcame this limitation isolating suberin macromolecules in a near-native state. Title: A novel angular dioxygenase gene cluster encoding 3-phenoxybenzoate 1',2'-dioxygenase in Sphingobium wenxiniae JZ-1 Wang C, Chen Q, Wang R, Shi C, Yan X, He J, Hong Q, Li S Ref: Applied Environmental Microbiology, 80:3811, 2014 : PubMed ESTHER: Wang_2014_Appl.Environ.Microbiol_80_3811 PubMedSearch: Wang 2014 Appl.Environ.Microbiol 80 3811 PubMedID: 24747891 Gene_locus related to this paper: 9sphn-q0kjt3, sphwj-a0a059u2z8 Abstract Sphingobium wenxiniae JZ-1 utilizes a wide range of pyrethroids and their metabolic product, 3-phenoxybenzoate, as sources of carbon and energy. A mutant JZ-1 strain, MJZ-1, defective in the degradation of 3-phenoxybenzoate was obtained by successive streaking on LB agar. Comparison of the draft genomes of strains JZ-1 and MJZ-1 revealed that a 29,366-bp DNA fragment containing a putative angular dioxygenase gene cluster (pbaA1A2B) is missing in strain MJZ-1. PbaA1, PbaA2, and PbaB share 65%, 52%, and 10% identity with the corresponding alpha and beta subunits and the ferredoxin component of dioxin dioxygenase from Sphingomonas wittichii RW1, respectively. Complementation of pbaA1A2B in strain MJZ-1 resulted in the active 3-phenoxybenzoate 1',2'-dioxygenase, but the enzyme activity in Escherichia coli was achieved only through the coexpression of pbaA1A2B and a glutathione reductase (GR)-type reductase gene, pbaC, indicating that the 3-phenoxybenzoate 1',2'-dioxygenase belongs to a type IV Rieske non-heme iron aromatic ring-hydroxylating oxygenase system consisting of a hetero-oligomeric oxygenase, a [2Fe-2S]-type ferredoxin, and a GR-type reductase. The pbaC gene is not located in the immediate vicinity of pbaA1A2B. 3-Phenoxybenzoate 1',2'-dioxygenase catalyzes the hydroxylation in the 1' and 2' positions of the benzene moiety of 3-phenoxybenzoate, yielding 3-hydroxybenzoate and catechol. Transcription of pbaA1A2B and pbaC was induced by 3-phenoxybenzoate, but the transcriptional level of pbaC was far less than that of pbaA1A2B, implying the possibility that PbaC may not be the only reductase that can physiologically transfer electrons to PbaA1A2B in strain JZ-1. Some GR-type reductases from other sphingomonad strains could also transfer electrons to PbaA1A2B, suggesting that PbaA1A2B has a low specificity for reductase. Title: Genomic characterization of three unique Dehalococcoides that respire on persistent polychlorinated biphenyls Wang S, Chng KR, Wilm A, Zhao S, Yang KL, Nagarajan N, He J Ref: Proc Natl Acad Sci U S A, 111:12103, 2014 : PubMed ESTHER: Wang_2014_Proc.Natl.Acad.Sci.U.S.A_111_12103 PubMedSearch: Wang 2014 Proc.Natl.Acad.Sci.U.S.A 111 12103 PubMedID: 25028492 Gene_locus related to this paper: dehm1-q3z6q3, dehmv-d2bg80 Abstract Fastidious anaerobic bacteria play critical roles in environmental bioremediation of halogenated compounds. However, their characterization and application have been largely impeded by difficulties in growing them in pure culture. Thus far, no pure culture has been reported to respire on the notorious polychlorinated biphenyls (PCBs), and functional genes responsible for PCB detoxification remain unknown due to the extremely slow growth of PCB-respiring bacteria. Here we report the successful isolation and characterization of three Dehalococcoides mccartyi strains that respire on commercial PCBs. Using high-throughput metagenomic analysis, combined with traditional culture techniques, tetrachloroethene (PCE) was identified as a feasible alternative to PCBs to isolate PCB-respiring Dehalococcoides from PCB-enriched cultures. With PCE as an alternative electron acceptor, the PCB-respiring Dehalococcoides were boosted to a higher cell density (1.2 x 10(8) to 1.3 x 10(8) cells per mL on PCE vs. 5.9 x 10(6) to 10.4 x 10(6) cells per mL on PCBs) with a shorter culturing time (30 d on PCE vs. 150 d on PCBs). The transcriptomic profiles illustrated that the distinct PCB dechlorination profile of each strain was predominantly mediated by a single, novel reductive dehalogenase (RDase) catalyzing chlorine removal from both PCBs and PCE. The transcription levels of PCB-RDase genes are 5-60 times higher than the genome-wide average. The cultivation of PCB-respiring Dehalococcoides in pure culture and the identification of PCB-RDase genes deepen our understanding of organohalide respiration of PCBs and shed light on in situ PCB bioremediation. Title: Genome of the Chinese tree shrew Fan Y, Huang ZY, Cao CC, Chen CS, Chen YX, Fan DD, He J, Hou HL, Hu L and Yao YG <23 more author(s)> Fan Y, Huang ZY, Cao CC, Chen CS, Chen YX, Fan DD, He J, Hou HL, Hu L, Hu XT, Jiang XT, Lai R, Lang YS, Liang B, Liao SG, Mu D, Ma YY, Niu YY, Sun XQ, Xia JQ, Xiao J, Xiong ZQ, Xu L, Yang L, Zhang Y, Zhao W, Zhao XD, Zheng YT, Zhou JM, Zhu YB, Zhang GJ, Wang J, Yao YG (- 23) Ref: Nat Commun, 4:1426, 2013 : PubMed ESTHER: Fan_2013_Nat.Commun_4_1426 PubMedSearch: Fan 2013 Nat.Commun 4 1426 PubMedID: 23385571 Gene_locus related to this paper: tupch-l9l8p0, tupch-l9l7d8.1, tupch-l9l7d8.2, tupch-l9l7d8.3, tupch-l8y4e3, tupch-l9jqg5, tupch-l9l3m0, tupch-l9kxg8, tupch-l9knn8, tupch-l9kf47, tupch-l9ja32, tupch-l9l5b1, tupch-l9khv5 Abstract Chinese tree shrews (Tupaia belangeri chinensis) possess many features valuable in animals used as experimental models in biomedical research. Currently, there are numerous attempts to employ tree shrews as models for a variety of human disorders: depression, myopia, hepatitis B and C virus infections, and hepatocellular carcinoma, to name a few. Here we present a publicly available annotated genome sequence for the Chinese tree shrew. Phylogenomic analysis of the tree shrew and other mammalians highly support its close affinity to primates. By characterizing key factors and signalling pathways in nervous and immune systems, we demonstrate that tree shrews possess both shared common and unique features, and provide a genetic basis for the use of this animal as a potential model for biomedical research. Title: Nearly finished genomes produced using gel microdroplet culturing reveal substantial intraspecies genomic diversity within the human microbiome Fitzsimons MS, Novotny M, Lo CC, Dichosa AE, Yee-Greenbaum JL, Snook JP, Gu W, Chertkov O, Davenport KW and Han CS <11 more author(s)> Fitzsimons MS, Novotny M, Lo CC, Dichosa AE, Yee-Greenbaum JL, Snook JP, Gu W, Chertkov O, Davenport KW, McMurry K, Reitenga KG, Daughton AR, He J, Johnson SL, Gleasner CD, Wills PL, Parson-Quintana B, Chain PS, Detter JC, Lasken RS, Han CS (- 11) Ref: Genome Res, 23:878, 2013 : PubMed ESTHER: Fitzsimons_2013_Genome.Res_23_878 PubMedSearch: Fitzsimons 2013 Genome.Res 23 878 PubMedID: 23493677 Gene_locus related to this paper: 9stre-k0zi65 Abstract The majority of microbial genomic diversity remains unexplored. This is largely due to our inability to culture most microorganisms in isolation, which is a prerequisite for traditional genome sequencing. Single-cell sequencing has allowed researchers to circumvent this limitation. DNA is amplified directly from a single cell using the whole-genome amplification technique of multiple displacement amplification (MDA). However, MDA from a single chromosome copy suffers from amplification bias and a large loss of specificity from even very small amounts of DNA contamination, which makes assembling a genome difficult and completely finishing a genome impossible except in extraordinary circumstances. Gel microdrop cultivation allows culturing of a diverse microbial community and provides hundreds to thousands of genetically identical cells as input for an MDA reaction. We demonstrate the utility of this approach by comparing sequencing results of gel microdroplets and single cells following MDA. Bias is reduced in the MDA reaction and genome sequencing, and assembly is greatly improved when using gel microdroplets. We acquired multiple near-complete genomes for two bacterial species from human oral and stool microbiome samples. A significant amount of genome diversity, including single nucleotide polymorphisms and genome recombination, is discovered. Gel microdroplets offer a powerful and high-throughput technology for assembling whole genomes from complex samples and for probing the pan-genome of naturally occurring populations. Title: Effects of magnolol on impairment of learning and memory abilities induced by scopolamine in mice Li YS, Hong YF, He J, Lin JX, Shan YL, Fu DY, Chen ZP, Ren XR, Song ZH, Tao L Ref: Biol Pharm Bull, 36:764, 2013 : PubMed ESTHER: Li_2013_Biol.Pharm.Bull_36_764 PubMedSearch: Li 2013 Biol.Pharm.Bull 36 764 PubMedID: 23445942 Abstract Alzheimer's disease (AD), one of the most common forms of dementia, is primarily ascribed to the cholinergic deficits and neuronal dysfunction. Magnolol (Mag), a bioactivator extracted from Magnolia officinalis, has protective effects on cholinergic neurons, but the specific mechanism remains unknown. To further evaluate the therapeutic effects of Mag on the learning and memory impairment in a scopolamine (Scop)-induced mouse model, the passive avoidance and the Morris water maze tests, the measurement of the ratio of brain/hippocampus to body weight, activities of acetyl cholinesterase (AChE), superoxide dismutase (SOD), total nitric oxide synthase (total NOS) and the content of methane dicarboxylic aldehyde (MDA) in hippocampus homogenate as well as the immunefluorescence staining of the AChE positive nerve fibers were performed. Therapeutically treated with Mag, the impaired abilities of learning and memory of the Scop-induced mice were almost restored to the native levels. The restored AChE, total NOS and SOD activities and the MDA level were observed, with a relatively normal density of AChE positive nerve fibers in hippocampus CA3 molecular layer. The improving efficacy of Mag on learning and memory impairment induced by Scop is dose-dependent, indicating that Mag has potential neuroprotective effects against neuronal impairment and memory dysfunction induced by Scop in mice. The underlying mechanisms may be associated with the anti-oxidative effects of Mag and its protective effects on hippocampus cholinergic neurons. Title: Preparation and in vitro and in vivo evaluation of HupA PLGA Microsphere Ye L, Fu F, Liu W, Sun K, Li Y, He J, Yu X, Yu P, Tian J Ref: Pak J Pharm Sci, 26:315, 2013 : PubMed ESTHER: Ye_2013_Pak.J.Pharm.Sci_26_315 PubMedSearch: Ye 2013 Pak.J.Pharm.Sci 26 315 PubMedID: 23455202 Abstract Acetylcholinesterase inhibitors (AChEIs), including Huperzine A (HupA), have been the mainstay of treatment for Alzheimer's disease (AD). However, AChEIs can cause gastrointestinal side effects, which has been related to the high C and short tmax after oral administration. Clinical trials have verified that extended-release formulation with lower C and prolonged tmax, such as rivastigmine patch, could perform a similar efficacy with significantly improved tolerability compared with the oral formulations. In this study, we developed an extended-release microspheres formulation of HupA (called as HAM) with poly(lactide-co-glycolide) (PLGA) as drug carrier. HAM has showed the loading rate as 1.35% (w/w) and yielded 42% with mean particle size at 72.6 mum. In vitro and in vivo pharmacokinetics studies have showed that HAM produced a relatively smooth and continuous drug concentration in 14 days. Furthermore, in vivo pharmacokinetics data have demonstrated that the C was lower and the tmax was considerably later in single intramuscular administration of HAM (1,000 mug/kg) than the counterparts in single intragastric administration of HAT (75 mug/kg/d). Meanwhile, HAM has performed a continuous inhibition to brain AChE activity in normal rats and improvement of memory deficit in Abeta i.c.v. infused AD rat model for 14 days. The results have suggested that HAM has performed good extended-release properties and good prolonged pharmacological efficacy in vivo in the 2-week period, and could exert a similar efficacy with significantly lowered gastrointestinal side effects as compared with oral formulation. Title: SulE, a sulfonylurea herbicide de-esterification esterase from Hansschlegelia zhihuaiae S113 Hang BJ, Hong Q, Xie XT, Huang X, Wang CH, He J, Li SP Ref: Applied Environmental Microbiology, 78:1962, 2012 : PubMed ESTHER: Hang_2012_Appl.Environ.Microbiol_78_1962 PubMedSearch: Hang 2012 Appl.Environ.Microbiol 78 1962 PubMedID: 22247165 Gene_locus related to this paper: 9rhiz-g9i933 Abstract De-esterification is an important degradation or detoxification mechanism of sulfonylurea herbicide in microbes and plants. However, the biochemical and molecular mechanisms of sulfonylurea herbicide de-esterification are still unknown. In this study, a novel esterase gene, sulE, responsible for sulfonylurea herbicide de-esterification, was cloned from Hansschlegelia zhihuaiae S113. The gene contained an open reading frame of 1,194 bp, and a putative signal peptide at the N terminal was identified with a predicted cleavage site between Ala37 and Glu38, resulting in a 361-residue mature protein. SulE minus the signal peptide was synthesized in Escherichia coli BL21 and purified to homogeneity. SulE catalyzed the de-esterification of a variety of sulfonylurea herbicides that gave rise to the corresponding herbicidally inactive parent acid and exhibited the highest catalytic efficiency toward thifensulfuron-methyl. SulE was a dimer without the requirement of a cofactor. The activity of the enzyme was completely inhibited by Ag(+), Cd(2+), Zn(2+), methamidophos, and sodium dodecyl sulfate. A sulE-disrupted mutant strain, DeltasulE, was constructed by insertion mutation. DeltasulE lost the de-esterification ability and was more sensitive to the herbicides than the wild type of strain S113, suggesting that sulE played a vital role in the sulfonylurea herbicide resistance of the strain. The transfer of sulE into Saccharomyces cerevisiae BY4741 conferred on it the ability to de-esterify sulfonylurea herbicides and increased its resistance to the herbicides. This study has provided an excellent candidate for the mechanistic study of sulfonylurea herbicide metabolism and detoxification through de-esterification, construction of sulfonylurea herbicide-resistant transgenic crops, and bioremediation of sulfonylurea herbicide-contaminated environments. Title: Cloning of a novel arylamidase gene from Paracoccus sp. strain FLN-7 that hydrolyzes amide pesticides Zhang J, Yin JG, Hang BJ, Cai S, He J, Zhou SG, Li SP Ref: Applied Environmental Microbiology, 78:4848, 2012 : PubMed ESTHER: Zhang_2012_Appl.Environ.Microbiol_78_4848 PubMedSearch: Zhang 2012 Appl.Environ.Microbiol 78 4848 PubMedID: 22544249 Abstract The bacterial isolate Paracoccus sp. strain FLN-7 hydrolyzes amide pesticides such as diflubenzuron, propanil, chlorpropham, and dimethoate through amide bond cleavage. A gene, ampA, encoding a novel arylamidase that catalyzes the amide bond cleavage in the amide pesticides was cloned from the strain. ampA contains a 1,395-bp open reading frame that encodes a 465-amino-acid protein. AmpA was expressed in Escherichia coli BL21 and homogenously purified using Ni-nitrilotriacetic acid affinity chromatography. AmpA is a homodimer with an isoelectric point of 5.4. AmpA displays maximum enzymatic activity at 40 degrees C and a pH of between 7.5 and 8.0, and it is very stable at pHs ranging from 5.5 to 10.0 and at temperatures up to 50 degrees C. AmpA efficiently hydrolyzes a variety of secondary amine compounds such as propanil, 4-acetaminophenol, propham, chlorpropham, dimethoate, and omethoate. The most suitable substrate is propanil, with K(m) and k(cat) values of 29.5 muM and 49.2 s(-1), respectively. The benzoylurea insecticides (diflubenzuron and hexaflumuron) are also hydrolyzed but at low efficiencies. No cofactor is needed for the hydrolysis activity. AmpA shares low identities with reported arylamidases (less than 23%), forms a distinct lineage from closely related arylamidases in the phylogenetic tree, and has different biochemical characteristics and catalytic kinetics with related arylamidases. The results in the present study suggest that AmpA is a good candidate for the study of the mechanism for amide pesticide hydrolysis, genetic engineering of amide herbicide-resistant crops, and bioremediation of amide pesticide-contaminated environments. Title: Adolescent binge drinking alters adult brain neurotransmitter gene expression, behavior, brain regional volumes, and neurochemistry in mice Coleman LG, Jr., He J, Lee J, Styner M, Crews FT Ref: Alcohol Clin Exp Res, 35:671, 2011 : PubMed ESTHER: Coleman_2011_Alcohol.Clin.Exp.Res_35_671 PubMedSearch: Coleman 2011 Alcohol.Clin.Exp.Res 35 671 PubMedID: 21223304 Abstract BACKGROUND: Binge drinking is common in human adolescents. The adolescent brain is undergoing structural maturation and has a unique sensitivity to alcohol neurotoxicity. Therefore, adolescent binge ethanol may have long-term effects on the adult brain that alter brain structure and behaviors that are relevant to alcohol-use disorders. Title: Dense genotyping of candidate gene loci identifies variants associated with high-density lipoprotein cholesterol Edmondson AC, Braund PS, Stylianou IM, Khera AV, Nelson CP, Wolfe ML, Derohannessian SL, Keating BJ, Qu L and Rader DJ <11 more author(s)> Edmondson AC, Braund PS, Stylianou IM, Khera AV, Nelson CP, Wolfe ML, Derohannessian SL, Keating BJ, Qu L, He J, Tobin MD, Tomaszewski M, Baumert J, Klopp N, Doring A, Thorand B, Li M, Reilly MP, Koenig W, Samani NJ, Rader DJ (- 11) Ref: Circ Cardiovasc Genet, 4:145, 2011 : PubMed ESTHER: Edmondson_2011_Circ.Cardiovasc.Genet_4_145 PubMedSearch: Edmondson 2011 Circ.Cardiovasc.Genet 4 145 PubMedID: 21303902 Gene_locus related to this paper: human-LIPG Abstract BACKGROUND: Plasma levels of high-density lipoprotein cholesterol (HDL-C) are known to be heritable, but only a fraction of the heritability is explained. We used a high-density genotyping array containing single-nucleotide polymorphisms (SNPs) from HDL-C candidate genes selected on known biology of HDL-C metabolism, mouse genetic studies, and human genetic association studies. SNP selection was based on tagging SNPs and included low-frequency nonsynonymous SNPs. METHODS AND Title: Complete genome sequence of Bacillus thuringiensis subsp. chinensis strain CT-43 He J, Wang J, Yin W, Shao X, Zheng H, Li M, Zhao Y, Sun M, Wang S, Yu Z Ref: Journal of Bacteriology, 193:3407, 2011 : PubMed ESTHER: He_2011_J.Bacteriol_193_3407 PubMedSearch: He 2011 J.Bacteriol 193 3407 PubMedID: 21551307 Gene_locus related to this paper: bacan-BA3703, bacan-BA5009, bacan-DHBF, bacce-BC0192, bacce-BC0968, bacce-BC1788, bacce-BC2141, bacce-BC4854, bacce-BC4862, bacce-PHAC, baccr-pepx Abstract Bacillus thuringiensis has been widely used as an agricultural biopesticide for a long time. As a producing strain, B. thuringiensis subsp. chinensis strain CT-43 is highly toxic to lepidopterous and dipterous insects. It can form various parasporal crystals consisting of Cry1Aa3, Cry1Ba1, Cry1Ia14, Cry2Aa9, and Cry2Ab1. During fermentation, it simultaneously generates vegetative insecticidal protein Vip3Aa10 and the insecticidal nucleotide analogue thuringiensin. Here, we report the finished, annotated genome sequence of B. thuringiensis strain CT-43. Title: In vitro stability and metabolism of O2', O3', O5'-tri-acetyl-N6-(3-hydroxylaniline) adenosine in rat, dog and human plasma: chemical hydrolysis and role of plasma esterases Liu Y, He J, Abliz Z, Zhu H Ref: Xenobiotica, 41:549, 2011 : PubMed ESTHER: Liu_2011_Xenobiotica_41_549 PubMedSearch: Liu 2011 Xenobiotica 41 549 PubMedID: 21486191 Abstract O2', O3', O5'-tri-acetyl-N(6)-(3-hydroxylaniline)adenosine (WS070117), a new structure-type lipid regulator, is being developed in pre-clinical study. In order to monitor drug kinetics it is essential to understand pre-analytical factors that may affect drug assay. In vitro stability and metabolism were investigated using high-performance liquid chromatography (HPLC) method in this study. The hydrolysis products were identified by HPLC-mass spectrometry (MS)/MS method. The esterases involved in WS070117 hydrolysis was assigned via inhibition rate assay. It was found that WS070117 was chemically unstable in alkaline solutions compared to acidic and near neutral solutions. Enzymatic hydrolysis was even more rapid. Hydrolytic rate constants differ between species, being 4.24, 5.96 x 10(-3) and 6.85 x 10(-2) min(-1) in rat, dog and human plasma at 37 degrees C, respectively. The hydrolysis was catalyzed by plasma esterase because NaF (sodium fluoride: a general esterase inhibitor) inhibited WS070117 hydrolysis and metabolite production. Hydrolysis was fast in rat plasma and was catalysed by carboxylesterase and butyrylcholinesterase. In dog plasma, carboxylesterase, butyrylcholinesterase and paraoxonase were mainly responsible. Butyrylcholinesterase was the major esterase involved in WS070117 hydrolysis in human plasma. The WS070117 hydrolysis in plasma proceeded by gradual loss of acetyl groups. The knowledge of in vitro drug stability and metabolic pathways identified in this study will be essential for future pre-clinical and clinical pharmacokinetics studies. Title: Degradation of cyhalofop-butyl (CyB) by Pseudomonas azotoformans strain QDZ-1 and cloning of a novel gene encoding CyB-hydrolyzing esterase Nie ZJ, Hang BJ, Cai S, Xie XT, He J, Li SP Ref: Journal of Agricultural and Food Chemistry, 59:6040, 2011 : PubMed ESTHER: Nie_2011_J.Agric.Food.Chem_59_6040 PubMedSearch: Nie 2011 J.Agric.Food.Chem 59 6040 PubMedID: 21534595 Gene_locus related to this paper: pseaz-e9nwd3 Abstract Cyhalofop-butyl (CyB) is a widely used aryloxyphenoxy propanoate (AOPP) herbicide for control of grasses in rice fields. Five CyB-degrading strains were isolated from rice field soil and identified as Agromyces sp., Stenotrophomonas sp., Aquamicrobium sp., Microbacterium sp., and Pseudomonas azotoformans; the results revealed high biodiversity of CyB-degrading bacteria in rice soil. One strain, P. azotoformans QDZ-1, degraded 84.5% of 100 mg L(-1) CyB in 5 days of incubation in a flask and utilized CyB as carbon source for growth. Strain QDZ-1 could also degrade a wide range of other AOPP herbicides. An esterase gene, chbH, which hydrolyzes CyB to cyhalofop acid (CyA), was cloned from strain QDZ-1 and functionally expressed. A chbH-disrupted mutant dchbH was constructed by insertion mutation. Mutant dchbH could not degrade and utilize CyB, suggesting that chbH was the only esterase gene responsible for CyB degradation in strain QDZ-1. ChbH hydrolyzed all AOPP herbicides tested as well as permethrin. The catalytic efficiency of ChbH toward different AOPP herbicides followed the order quizalofop-P-ethyl = fenoxaprop-P-ethyl > CyB = fluazifop-P-butyl > diclofop-methyl = haloxyfop-P-methyl; the results indicated that the chain length of the alcohol moiety strongly affected the biodegradability of the AOPP herbicides, whereas the substitutions in the aromatic ring had only a slight influence. Title: Effects of subchronic exposure to benzo[a]pyrene (B[a]P) on learning and memory, and neurotransmitters in male Sprague-Dawley rat Xia Y, Cheng S, He J, Liu X, Tang Y, Yuan H, He L, Lu T, Tu B, Wang Y Ref: Neurotoxicology, 32:188, 2011 : PubMed ESTHER: Xia_2011_Neurotoxicol_32_188 PubMedSearch: Xia 2011 Neurotoxicol 32 188 PubMedID: 21216261 Abstract The harmful effects of the environmental carcinogen, benzo[a]pyrene (B[a]P), on mammalian neurodevelopment and behavior as yet remain unclear. Several studies have suggested that B[a]P impairs learning and memory. In the present investigation, we investigated the effects of subchronic exposure to B[a]P on rats. Male rats received daily injection of B[a]P (0, 1.0, 2.5, and 6.25 mg/kg, i.p.) or vehicle for 13 weeks. Employing the Morris water maze (MWM) test, we observed that rats exposed to either 2.5 mg/kg or 6.25 mg/kg B[a]P had modified behavior compared to controls as indicated by the increased mean latencies, the decreased number of crossing platform and the decreased swimming time in the target area. B[a]P treatment decreased the levels of malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), acetylcholine (ACh), choline acetyltransferase (ChAT), and increased the activity of acetylcholinesterase (AChE). Endogenous monoamine levels, norepinephrine (NE), adrenaline (A), dopamine (DA) and 5-hydroxytryptamine (5-HT) and their selected metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus were measured using high performance liquid chromatography (HPLC). B[a]P at both doses, 2.5 and 6.25 mg/kg, increased NE, DA, DOPAC and 5-HT content in the hippocampus. Our results suggested a close link between the modified levels of neurotransmitters in the hippocampus and the impaired behavioral performance, indicating that B[a]P is a potential neurotoxic pollutant. Title: Genome sequence and analysis of the tuber crop potato Xu X, Pan S, Cheng S, Zhang B, Mu D, Ni P, Zhang G, Yang S, Li R and Visser RG <87 more author(s)> Xu X, Pan S, Cheng S, Zhang B, Mu D, Ni P, Zhang G, Yang S, Li R, Wang J, Orjeda G, Guzman F, Torres M, Lozano R, Ponce O, Martinez D, De la Cruz G, Chakrabarti SK, Patil VU, Skryabin KG, Kuznetsov BB, Ravin NV, Kolganova TV, Beletsky AV, Mardanov AV, Di Genova A, Bolser DM, Martin DM, Li G, Yang Y, Kuang H, Hu Q, Xiong X, Bishop GJ, Sagredo B, Mejia N, Zagorski W, Gromadka R, Gawor J, Szczesny P, Huang S, Zhang Z, Liang C, He J, Li Y, He Y, Xu J, Zhang Y, Xie B, Du Y, Qu D, Bonierbale M, Ghislain M, Herrera Mdel R, Giuliano G, Pietrella M, Perrotta G, Facella P, O'Brien K, Feingold SE, Barreiro LE, Massa GA, Diambra L, Whitty BR, Vaillancourt B, Lin H, Massa AN, Geoffroy M, Lundback S, DellaPenna D, Buell CR, Sharma SK, Marshall DF, Waugh R, Bryan GJ, Destefanis M, Nagy I, Milbourne D, Thomson SJ, Fiers M, Jacobs JM, Nielsen KL, Sonderkaer M, Iovene M, Torres GA, Jiang J, Veilleux RE, Bachem CW, De Boer J, Borm T, Kloosterman B, van Eck H, Datema E, Hekkert B, Goverse A, van Ham RC, Visser RG (- 87) Ref: Nature, 475:189, 2011 : PubMed ESTHER: Xu_2011_Nature_475_189 PubMedSearch: Xu 2011 Nature 475 189 PubMedID: 21743474 Gene_locus related to this paper: soltu-q2tqv0, soltu-q4h433, soltu-m0zl00, soltu-m1aw23, soltu-m0zxh5, soltu-m1d3q4, soltu-m1bz14, soltu-m1d3q6, sollc-k4b1g3, soltu-m0zzn8, soltu-m1ba60, sollc-k4bf33, soltu-m1c8d8, soltu-m1ced9, soltu-m1a385, soltu-m1bz15, soltu-m1a7s9, soltu-m1bc84, soltu-m1bpd1, sollc-k4bm34, soltu-m1a487, soltu-m1a5u0, soltu-m1cjx7, soltu-m1bvq8, soltu-m1baq1, soltu-m1cfh4, soltu-m1azl4, soltu-m0ztj0, soltu-m1d6d0 Abstract Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop. Title: Complete genome sequence of Bacillus thuringiensis mutant strain BMB171 He J, Shao X, Zheng H, Li M, Wang J, Zhang Q, Li L, Liu Z, Sun M and Yu Z <1 more author(s)> He J, Shao X, Zheng H, Li M, Wang J, Zhang Q, Li L, Liu Z, Sun M, Wang S, Yu Z (- 1) Ref: Journal of Bacteriology, 192:4074, 2010 : PubMed ESTHER: He_2010_J.Bacteriol_192_4074 PubMedSearch: He 2010 J.Bacteriol 192 4074 PubMedID: 20525827 Gene_locus related to this paper: bacan-BA3703, bacan-DHBF, bacce-BC0192, bacce-BC0968, bacce-BC1677, bacce-BC1788, bacce-BC2141, bacce-BC2171, bacce-BC2456, bacce-BC2458, bacce-BC3133, bacce-BC4102, bacce-BC4854, bacce-BC4862, bacce-BC5130, bacce-PHAC, baccr-pepx Abstract Bacillus thuringiensis has been widely used as a biopesticide for a long time. Here we report the finished and annotated genome sequence of B. thuringiensis mutant strain BMB171, an acrystalliferous mutant strain with a high transformation frequency obtained and stocked in our laboratory. Title: Regulated expression of pancreatic triglyceride lipase after rat traumatic brain injury Jia J, Yan M, Lu Z, Sun M, He J, Xia C Ref: Molecular & Cellular Biochemistry, 335:127, 2010 : PubMed ESTHER: Jia_2010_Mol.Cell.Biochem_335_127 PubMedSearch: Jia 2010 Mol.Cell.Biochem 335 127 PubMedID: 19760487 Abstract Pancreatic triglyceride lipase (PTL), an enzyme of digestive system, plays very important roles in the digestion and absorption of lipids. However, its distribution and function in the central nervous system (CNS) remains unclear. In the present study, we mainly investigated the expression and cellular localization of PTL during traumatic brain injury (TBI). Western blot and RT-PCR analysis revealed that PTL was present in normal rat brain cortex. It gradually increased, reached a peak at the 3rd day after TBI, and then decreased. Double immunofluorescence staining showed that PTL was co-expressed with neuron, but had a few colocalizations in astrocytes. When TBI occurred in the rat cortex, the expression of PTL gradually increased, reached the peak at the 3rd day after TBI, and then decreased. Importantly, more PTL was colocalized with astrocytes, which is positive for proliferating cell nuclear antigen (PCNA). In addition, Western blot detection showed that the 3rd day post injury was not only the proliferation peak indicated by the elevated expression of PCNA, glial fibrillary acidic protein (GFAP) and cyclin D1, but also the apoptotic peak implied by the alteration of caspase-3 and bcl-2. These data suggested that PTL may be involved in the pathophysiology of TBI and PTL may be complicated after injury, more PTL was colocalized with astrocytes. Importantly, injury-induced expression of PTL was colabelled by proliferating cell nuclear antigen (proliferating cells marker), and the western blot for GFAP, PCNA and cyclin D1, showed that 3 days post injury was the proliferation peak, in coincidence to it, the protein level change of caspase-3 and bcl-2 revealed that the stage was peak of apoptotic too. These data suggested that PTL may be involved in the pathophysiology of TBI and that PTL may be implicated in the proliferation of astrocytes and the recovery of neurological outcomes. But the inherent mechanisms remained unknown. Further studies are needed to confirm the exact role of PTL after brain injury. Title: The genome of the cucumber, Cucumis sativus L Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B and Du Y <77 more author(s)> Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B, Ni P, Ren Y, Zhu H, Li J, Lin K, Jin W, Fei Z, Li G, Staub J, Kilian A, van der Vossen EA, Wu Y, Guo J, He J, Jia Z, Tian G, Lu Y, Ruan J, Qian W, Wang M, Huang Q, Li B, Xuan Z, Cao J, Asan, Wu Z, Zhang J, Cai Q, Bai Y, Zhao B, Han Y, Li Y, Li X, Wang S, Shi Q, Liu S, Cho WK, Kim JY, Xu Y, Heller-Uszynska K, Miao H, Cheng Z, Zhang S, Wu J, Yang Y, Kang H, Li M, Liang H, Ren X, Shi Z, Wen M, Jian M, Yang H, Zhang G, Yang Z, Chen R, Ma L, Liu H, Zhou Y, Zhao J, Fang X, Fang L, Liu D, Zheng H, Zhang Y, Qin N, Li Z, Yang G, Yang S, Bolund L, Kristiansen K, Li S, Zhang X, Wang J, Sun R, Zhang B, Jiang S, Du Y (- 77) Ref: Nat Genet, 41:1275, 2009 : PubMed ESTHER: Huang_2009_Nat.Genet_41_1275 PubMedSearch: Huang 2009 Nat.Genet 41 1275 PubMedID: 19881527 Gene_locus related to this paper: cucsa-a0a0a0ktw5, cucsa-a0a0a0lnt6, cucsa-a0a0a0kpn7, cucsa-a0a0a0lvt9, cucsa-a0a0a0kdx8, cucsa-a0a0a0m228, cucsa-a0a0a0kz31, cucsa-a0a0a0k5t5, cucsa-a0a0a0kfs7, cucsa-a0a0a0kjj7, cucsa-a0a0a0kzs7, cucsa-a0a0a0l0a6, cucsa-a0a0a0l4w4, cucsa-a0a0a0lpz0, cucsa-a0a0a0ls66 Abstract Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system. Title: Cloning of a novel pyrethroid-hydrolyzing carboxylesterase gene from Sphingobium sp. strain JZ-1 and characterization of the gene product Wang BZ, Guo P, Hang BJ, Li L, He J, Li SP Ref: Applied Environmental Microbiology, 75:5496, 2009 : PubMed ESTHER: Wang_2009_Appl.Environ.Microbiol_75_5496 PubMedSearch: Wang 2009 Appl.Environ.Microbiol 75 5496 PubMedID: 19581484 Gene_locus related to this paper: sphwj-c0la90 Abstract A novel esterase gene, pytH, encoding a pyrethroid-hydrolyzing carboxylesterase was cloned from Sphingobium sp. strain JZ-1. The gene contained an open reading frame of 840 bp. Sequence identity searches revealed that the deduced enzyme shared the highest similarity with many alpha/beta-hydrolase fold proteins (20 to 24% identities). PytH was expressed in Escherichia coli BL21 and purified using Ni-nitrilotriacetic acid affinity chromatography. It was a monomeric structure with a molecular mass of approximately 31 kDa and a pI of 4.85. PytH was able to transform p-nitrophenyl esters of short-chain fatty acids and a wide range of pyrethroid pesticides, and isomer selectivity was not observed. No cofactors were required for enzyme activity. Title: Isolation and Characterization of a Methomyl-Degrading Paracoccus sp. mdw-1 Xu JL, Wu J, Wang ZC, Wang K, Li MY, Jiang JD, He J, Li SP Ref: Pedosphere, 19:238, 2009 : PubMed ESTHER: Xu_2009_Pedosphere_19_238 PubMedSearch: Xu 2009 Pedosphere 19 238 Abstract Methomyl, an extremely toxic pesticide, is widely used in agriculture. A strain named mdw-1 capable of degrading methomyl rapidly was successfully isolated from activated sludge in this study. It could utilize methomyl as the sole carbon or nitrogen source. The optimal temperature and medium pH for its growth and methomyl biodegradation were 30 C and 7.0, respectively. It was identified as a Paracoccus sp. according to its morphological features, physiological and biochemical characteristics, and phylogenetic analysis based on the sequence of 16S rDNA. Gas chromatography-mass spectrometry (GC-MS) analysis showed that methomyl could be completely transformed to S-methyl-N-hydroxythioacetamidate in 10 h of incubation with the isolate mdw-1. Title: Phthalates biodegradation in the environment Liang DW, Zhang T, Fang HH, He J Ref: Applied Microbiology & Biotechnology, 80:183, 2008 : PubMed ESTHER: Liang_2008_Appl.Microbiol.Biotechnol_80_183 PubMedSearch: Liang 2008 Appl.Microbiol.Biotechnol 80 183 PubMedID: 18592233 Abstract Phthalates are synthesized in massive amounts to produce various plastics and have become widespread in environments following their release as a result of extensive usage and production. This has been of an environmental concern because phthalates are hepatotoxic, teratogenic, and carcinogenic by nature. Numerous studies indicated that phthalates can be degraded by bacteria and fungi under aerobic, anoxic, and anaerobic conditions. This paper gives a review on the biodegradation of phthalates and includes the following aspects: (1) the relationship between the chemical structure of phthalates and their biodegradability, (2) the biodegradation of phthalates by pure/mixed cultures, (3) the biodegradation of phthalates under various environments, and (4) the biodegradation pathways of phthalates. Title: A gene linB2 responsible for the conversion of beta-HCH and 2,3,4,5,6-pentachlorocyclohexanol in Sphingomonas sp. BHC-A Wu J, Hong Q, Han P, He J, Li S Ref: Applied Microbiology & Biotechnology, 73:1097, 2007 : PubMed ESTHER: Wu_2007_Appl.Microbiol.Biotechnol_73_1097 PubMedSearch: Wu 2007 Appl.Microbiol.Biotechnol 73 1097 PubMedID: 16977465 Gene_locus related to this paper: sphpi-linb Abstract Commercial formulations of hexachlorocyclohexane (HCH) consist of a mixture of four isomers: alpha, beta, gamma, and delta. All four isomers are toxic and recalcitrant pollutants. beta-HCH is more problematic due to its longer persistence in the environment. Sphingomonas sp. BHC-A was able to degrade not only alpha-, gamma-, and delta-HCH but also beta-HCH. To clone a gene responsible for the degradation of beta-HCH, a Tn5 mutation was introduced into BHC-A, and one mutant BHC-A45 defective in beta-HCH degradation was selected. Sequencing analysis showed this mutant had a Tn5 insertion at the site of one haloalkane dehalogenase gene, designated linB2. linB2 was overexpressed in Escherichia coli and the 32-kDa product LinB2 showed the conversion activity of not only beta-HCH to beta-2,3,4,5,6-pentachlorocyclohexanol (beta-PCHL) but also beta-PCHL to beta-2,3,5,6-tetrachloro-1,4-cyclohexanediol. Title: (2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]tr iazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes Edmondson SD, Mastracchio A, Mathvink RJ, He J, Harper B, Park YJ, Beconi M, Di Salvo J, Eiermann GJ and Weber AE <16 more author(s)> Edmondson SD, Mastracchio A, Mathvink RJ, He J, Harper B, Park YJ, Beconi M, Di Salvo J, Eiermann GJ, He H, Leiting B, Leone JF, Levorse DA, Lyons K, Patel RA, Patel SB, Petrov A, Scapin G, Shang J, Roy RS, Smith A, Wu JK, Xu S, Zhu B, Thornberry NA, Weber AE (- 16) Ref: Journal of Medicinal Chemistry, 49:3614, 2006 : PubMed ESTHER: Edmondson_2006_J.Med.Chem_49_3614 PubMedSearch: Edmondson 2006 J.Med.Chem 49 3614 PubMedID: 16759103 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: MK0626 Abstract A series of beta-substituted biarylphenylalanine amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the metabolic profile of early analogues led to the discovery of (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]tr iazolo[1,5-a]pyridin-6-ylphenyl)butanamide (6), a potent, orally active DPP-4 inhibitor (IC(50) = 6.3 nM) with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models. Compound 6 was selected for further characterization as a potential new treatment for type 2 diabetes. Title: Effect of surface hydrophobicity/hydrophilicity of mesoporous supports on the activity of immobilized lipase He J, Xu Y, Ma H, Zhang Q, Evans DG, Duan X Ref: J Colloid Interface Sci, 298:780, 2006 : PubMed ESTHER: He_2006_J.Colloid.Interface.Sci_298_780 PubMedSearch: He 2006 J.Colloid.Interface.Sci 298 780 PubMedID: 16430912 Abstract Taking advantage of the virtue of hydrophilic surface, lipase was firstly immobilized on SBA-15 as a support. Then the surface of the SBA-15 with enzyme entrapped inside the channels was modified by grafting with organic moieties. It has been found that the silylation with n-decyltrimethoxysilane (DE) and 3-(trimethoxysilyl)propyl methacrylate (MA) following the lipase immobilization increases the surface hydrophobicity. But the surface modified by MA shows more hydrophilicity than that modified by DE. The activity assay indicates that the hydrolytic activity for the hydrolysis of insoluble or partly soluble substrates increases with enhanced surface hydrophobicity. Title: Isolation and characterization of a denitrifying monocrotophos-degrading Paracoccus sp. M-1 Jia KZ, Cui ZL, He J, Guo P, Li SP Ref: FEMS Microbiology Letters, 263:155, 2006 : PubMed ESTHER: Jia_2006_FEMS.Microbiol.Lett_263_155 PubMedSearch: Jia 2006 FEMS.Microbiol.Lett 263 155 PubMedID: 16978350 Abstract A bacterium strain, which is capable of degrading monocrotophos, was isolated from sludge collected from the bottom of a wastewater treatment system of a chemical factory, and named M-1. On the basis of the results of the cellular morphology, physiological and chemotaxonomic characteristics and phylogenetic similarity of 16S rDNA gene sequences, the strain was identified as a Paracoccus sp. The ability of the strain to mineralize monocrotophos was investigated under different culture conditions. Other organophosphorus insecticides and amide herbicides were also degraded by M-1. The key enzyme (s) involved in the initial biodegradation of monocrotophos in M-1 was shown to be a constitutively expressed cytosolic protein. The addition of M-1 (10(6) CFU g(-1)) to fluvo-aquic soil and a high-sand soil containing monocrotophos (50 mg kg(-1)) resulted in a higher degradation rate than that obtained from noninoculated soil. This microbial culture has great potential utility for the bioremediation of wastewater or soil contaminated with organophosphorus pesticides and amide herbicides. Title: Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial Lee DG, Urbach JM, Wu G, Liberati NT, Feinbaum RL, Miyata S, Diggins LT, He J, Saucier M and Ausubel FM <7 more author(s)> Lee DG, Urbach JM, Wu G, Liberati NT, Feinbaum RL, Miyata S, Diggins LT, He J, Saucier M, Deziel E, Friedman L, Li L, Grills G, Montgomery K, Kucherlapati R, Rahme LG, Ausubel FM (- 7) Ref: Genome Biol, 7:R90, 2006 : PubMed ESTHER: Lee_2006_Genome.Biol_7_R90 PubMedSearch: Lee 2006 Genome.Biol 7 R90 PubMedID: 17038190 Gene_locus related to this paper: pseae-a3kt39, pseae-CPO, pseae-metx, pseae-PA0231, pseae-PA0308, pseae-PA0368, pseae-PA0480, pseae-PA0502, pseae-PA0599, pseae-PA1239, pseae-PA1291, pseae-PA1558, pseae-PA1621, pseae-PA1622, pseae-PA2086, pseae-PA2451, pseae-PA2689, pseae-PA2745, pseae-PA2764, pseae-PA2927, pseae-PA2934, pseae-PA2949, pseae-PA3053, pseae-PA3132, pseae-PA3226, pseae-PA3301, pseae-PA3324, pseae-PA3429, pseae-PA3586, pseae-PA3628, pseae-PA3695, pseae-PA3994, pseae-PA4152, pseae-PA5080, pseae-PCHF, pseae-phag, pseae-rhla, pseae-q9i252 Abstract BACKGROUND: Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important opportunistic human pathogen. Generally, the acquisition of genes in the form of pathogenicity islands distinguishes pathogenic isolates from nonpathogens. We therefore sequenced a highly virulent strain of P. aeruginosa, PA14, and compared it with a previously sequenced (and less pathogenic) strain, PAO1, to identify novel virulence genes. RESULTS: The PA14 and PAO1 genomes are remarkably similar, although PA14 has a slightly larger genome (6.5 megabses [Mb]) than does PAO1 (6.3 Mb). We identified 58 PA14 gene clusters that are absent in PAO1 to determine which of these genes, if any, contribute to its enhanced virulence in a Caenorhabditis elegans pathogenicity model. First, we tested 18 additional diverse strains in the C. elegans model and observed a wide range of pathogenic potential; however, genotyping these strains using a custom microarray showed that the presence of PA14 genes that are absent in PAO1 did not correlate with the virulence of these strains. Second, we utilized a full-genome nonredundant mutant library of PA14 to identify five genes (absent in PAO1) required for C. elegans killing. Surprisingly, although these five genes are present in many other P. aeruginosa strains, they do not correlate with virulence in C. elegans. CONCLUSION: Genes required for pathogenicity in one strain of P. aeruginosa are neither required for nor predictive of virulence in other strains. We therefore propose that virulence in this organism is both multifactorial and combinatorial, the result of a pool of pathogenicity-related genes that interact in various combinations in different genetic backgrounds. Title: Discovery of potent and selective phenylalanine based dipeptidyl peptidase IV inhibitors Xu J, Wei L, Mathvink R, He J, Park YJ, He H, Leiting B, Lyons KA, Marsilio F and Weber AE <3 more author(s)> Xu J, Wei L, Mathvink R, He J, Park YJ, He H, Leiting B, Lyons KA, Marsilio F, Patel RA, Wu JK, Thornberry NA, Weber AE (- 3) Ref: Bioorganic & Medicinal Chemistry Lett, 15:2533, 2005 : PubMed ESTHER: Xu_2005_Bioorg.Med.Chem.Lett_15_2533 PubMedSearch: Xu 2005 Bioorg.Med.Chem.Lett 15 2533 PubMedID: 15863311 Abstract anti-Substituted beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and DPP9. These are among the most potent compounds reported to date lacking an electrophilic trap. The most potent compound among these is 5-oxo-1,2,4-oxadiazole 44, which is a 3 nM DPP-IV inhibitor. Title: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution Hillier LW, Miller W, Birney E, Warren W, Hardison RC, Ponting CP, Bork P, Burt DW, Groenen MA and Wilson RK <164 more author(s)> Hillier LW, Miller W, Birney E, Warren W, Hardison RC, Ponting CP, Bork P, Burt DW, Groenen MA, Delany ME, Dodgson JB, Chinwalla AT, Cliften PF, Clifton SW, Delehaunty KD, Fronick C, Fulton RS, Graves TA, Kremitzki C, Layman D, Magrini V, McPherson JD, Miner TL, Minx P, Nash WE, Nhan MN, Nelson JO, Oddy LG, Pohl CS, Randall-Maher J, Smith SM, Wallis JW, Yang SP, Romanov MN, Rondelli CM, Paton B, Smith J, Morrice D, Daniels L, Tempest HG, Robertson L, Masabanda JS, Griffin DK, Vignal A, Fillon V, Jacobbson L, Kerje S, Andersson L, Crooijmans RP, Aerts J, van der Poel JJ, Ellegren H, Caldwell RB, Hubbard SJ, Grafham DV, Kierzek AM, McLaren SR, Overton IM, Arakawa H, Beattie KJ, Bezzubov Y, Boardman PE, Bonfield JK, Croning MD, Davies RM, Francis MD, Humphray SJ, Scott CE, Taylor RG, Tickle C, Brown WR, Rogers J, Buerstedde JM, Wilson SA, Stubbs L, Ovcharenko I, Gordon L, Lucas S, Miller MM, Inoko H, Shiina T, Kaufman J, Salomonsen J, Skjoedt K, Ka-Shu Wong G, Wang J, Liu B, Yu J, Yang H, Nefedov M, Koriabine M, deJong PJ, Goodstadt L, Webber C, Dickens NJ, Letunic I, Suyama M, Torrents D, von Mering C, Zdobnov EM, Makova K, Nekrutenko A, Elnitski L, Eswara P, King DC, Yang S, Tyekucheva S, Radakrishnan A, Harris RS, Chiaromonte F, Taylor J, He J, Rijnkels M, Griffiths-Jones S, Ureta-Vidal A, Hoffman MM, Severin J, Searle SM, Law AS, Speed D, Waddington D, Cheng Z, Tuzun E, Eichler E, Bao Z, Flicek P, Shteynberg DD, Brent MR, Bye JM, Huckle EJ, Chatterji S, Dewey C, Pachter L, Kouranov A, Mourelatos Z, Hatzigeorgiou AG, Paterson AH, Ivarie R, Brandstrom M, Axelsson E, Backstrom N, Berlin S, Webster MT, Pourquie O, Reymond A, Ucla C, Antonarakis SE, Long M, Emerson JJ, Betran E, Dupanloup I, Kaessmann H, Hinrichs AS, Bejerano G, Furey TS, Harte RA, Raney B, Siepel A, Kent WJ, Haussler D, Eyras E, Castelo R, Abril JF, Castellano S, Camara F, Parra G, Guigo R, Bourque G, Tesler G, Pevzner PA, Smit A, Fulton LA, Mardis ER, Wilson RK (- 164) Ref: Nature, 432:695, 2004 : PubMed ESTHER: Hillier_2004_Nature_432_695 PubMedSearch: Hillier 2004 Nature 432 695 PubMedID: 15592404 Gene_locus related to this paper: chick-a0a1d5pmd9, chick-b3tzb3, chick-BCHE, chick-cb043, chick-d3wgl5, chick-e1bsm0, chick-e1bvq6, chick-e1bwz0, chick-e1bwz1, chick-e1byn1, chick-e1bz81, chick-e1c0z8, chick-e1c7p7, chick-f1nby4, chick-f1ncz8, chick-f1ndp3, chick-f1nep4, chick-f1nj68, chick-f1njg6, chick-f1njk4, chick-f1njs4, chick-f1njs5, chick-f1nk87, chick-f1nmx9, chick-f1ntp8, chick-f1nvg7, chick-f1nwf2, chick-f1p1l1, chick-f1p3j5, chick-f1p4c6, chick-f1p508, chick-fas, chick-h9l0k6, chick-nlgn1, chick-NLGN3, chick-q5f3h8, chick-q5zhm0, chick-q5zi81, chick-q5zij5, chick-q5zin0, chick-thyro, chick-f1nrq2, chick-e1byd4, chick-e1c2h6, chick-a0a1d5pk92, chick-a0a1d5pzg7, chick-f1nbc2, chick-f1nf25, chick-f1nly5, chick-f1p4h5, chick-f1nzi7, chick-f1p5k3, chick-f1nm35, chick-a0a1d5pl11, chick-a0a1d5pj73, chick-f1nxu6, chick-a0a1d5nwc0, chick-e1bxs8, chick-f1p2g7, chick-f1nd96 Abstract We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture. Title: 4-Amino cyclohexylglycine analogues as potent dipeptidyl peptidase IV inhibitors Parmee ER, He J, Mastracchio A, Edmondson SD, Colwell L, Eiermann G, Feeney WP, Habulihaz B, He H and Weber AE <9 more author(s)> Parmee ER, He J, Mastracchio A, Edmondson SD, Colwell L, Eiermann G, Feeney WP, Habulihaz B, He H, Kilburn R, Leiting B, Lyons K, Marsilio F, Patel RA, Petrov A, Di Salvo J, Wu JK, Thornberry NA, Weber AE (- 9) Ref: Bioorganic & Medicinal Chemistry Lett, 14:43, 2004 : PubMed ESTHER: Parmee_2004_Bioorg.Med.Chem.Lett_14_43 PubMedSearch: Parmee 2004 Bioorg.Med.Chem.Lett 14 43 PubMedID: 14684294 Abstract Substituted 4-amino cyclohexylglycine analogues were evaluated for DP-IV inhibitory properties. Bis-sulfonamide 15e was an extremely potent 2.6 nM inhibitor of the enzyme with excellent selectivity over all counterscreens. 2,4-difluorobenzenesulfonamide 15b and 1-naphthyl amide 16b, however, combined an acceptable in vitro profile with good pharmacokinetic properties in the rat, and 15b was orally efficacious at 3 mpk in an OGTT in lean mice. Title: Enzymatic enantioselective transcyanation of silicon-containing aliphatic ketone with (S)-hydroxynitrile lyase from Manihot esculenta Xu R, Zong MH, Liu YY, He J, Zhang YY, Lou WY Ref: Applied Microbiology & Biotechnology, 66:27, 2004 : PubMed ESTHER: Xu_2004_Appl.Microbiol.Biotechnol_66_27 PubMedSearch: Xu 2004 Appl.Microbiol.Biotechnol 66 27 PubMedID: 15309340 Abstract (S)-Hydroxynitrile lyase from Manihot esculenta (MeHNL) was shown for the first time to be able to catalyze the enantioselective transcyanation of acetyltrimethylsilane (ATMS) with acetone cyanohydrin to form (S)-2-trimethylsilyl-2-hydroxyl-propionitrile in an aqueous/organic biphasic system. To better understand the reaction, various influential variables were examined. The most suitable organic phase, optimal buffer pH, aqueous phase content, shaking rate, temperature, concentration of ATMS, acetone cyanohydrin and crude enzyme were diisopropyl ether (DIPE), 5.4, 13% (v/v), 190 rpm, 40 degrees C, 10 mM, 20 mM, and 35 U/ml, respectively, under which the initial reaction rate, substrate conversion and product enantiomeric excess (e.e.) were 19.5 mM/h, 99.0% and 93.5%, respectively. A comparative study demonstrated that silicon atoms in the substrate had a great effect on the reaction, and that ATMS was a much better substrate for MeHNL than its carbon analogue 3,3-dimethyl-2-butanone (DMBO) with respect to the initial reaction rate, substrate conversion and product e.e. MeHNL has greater affinity towards ATMS than its carbon analogue as indicated by the much lower K(m). The activation energy of MeHNL-catalyzed transcyanation of ATMS was also markedly lower than that of DMBO. The silicon effect on the reaction was rationalized on the basis of the special characteristics of silicon atoms and the catalytic mechanism of MeHNL. Title: Organizational and mutational analysis of a complete FR-008/candicidin gene cluster encoding a structurally related polyene complex Chen S, Huang X, Zhou X, Bai L, He J, Jeong KJ, Lee SY, Deng Z Ref: Chemical Biology, 10:1065, 2003 : PubMed ESTHER: Chen_2003_Chem.Biol_10_1065 PubMedSearch: Chen 2003 Chem.Biol 10 1065 PubMedID: 14652074 Gene_locus related to this paper: 9acto-q6w5p8, strgr-pabt Abstract The complete gene cluster for biosynthesis of a polyene complex, FR-008, spans 137.2 kb of the genome of Streptomyces sp. FR-008 consisting of six genes for a modular PKS and 15 additional genes. The extensive similarity to the partially characterized candicidin gene cluster in Streptomyces griseus IMRU3570, especially for genes involved in mycosamine biosynthesis, prompted us to compare the compounds produced by Streptomyces sp. FR-008 and Streptomyces griseus IMRU3570, and we found that FR-008 and candicidin complex are identical. A model for biosynthesis of a set of four structurally related FR-008/candicidin compounds was proposed. Deletion of the putative regulatory genes abolished antibiotic production, while disruption of putative glycosyltransferase and GDP-ketosugar aminotransferase functionalities led to the productions of a set of nonmycosaminated aglycones and a novel polyene complex with attachment of altered sugar moiety, respectively. Title: Iteration as programmed event during polyketide assembly; molecular analysis of the aureothin biosynthesis gene cluster He J, Hertweck C Ref: Chemical Biology, 10:1225, 2003 : PubMed ESTHER: He_2003_Chem.Biol_10_1225 PubMedSearch: He 2003 Chem.Biol 10 1225 PubMedID: 14700630 Gene_locus related to this paper: 9acto-q70kh4 Abstract Analysis of the type I modular polyketide synthase (PKS) involved in the biosynthesis of the rare nitroaryl polyketide metabolite aureothin (aur) from Streptomyces thioluteus HKI-227 has revealed only four modules to catalyze the five polyketide chain extensions required. By heterologous expression of the aur PKS cluster, direct evidence was obtained that these modules were sufficient to support aureothin biosynthesis. It appears that one module catalyzes two successive cycles of chain extension, one of the first examples of a PKS in which such iteration or "stuttering" is required to produce the normal polyketide product. In addition, lack of a specified loading domain implicates a novel PKS priming mechanism involving the unique p-nitrobenzoate starter unit. The 27 kb aur gene cluster also encodes a novel N-oxidase, which may represent the first member of a new family of such enzymes. Title: [Correlation of NDRG1 gene with liver tissue differentiation and hepatocarcinogenesis] He J, Zhou R Ref: Beijing Da Xue Xue Bao, 35:471, 2003 : PubMed ESTHER: He_2003_Beijing.Da.Xue.Xue.Bao_35_471 PubMedSearch: He 2003 Beijing.Da.Xue.Xue.Bao 35 471 PubMedID: 14601301 Abstract OBJECTIVE: To detect the expression profile of NDRG1 gene in different tissues and cell lines and explore the relationship of NDRG1 with liver tissue differentiation and hepatocarcinogenesis. | |||||||
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