Author Report for: Liang JNo contact information in database for Liang J
Ang S, Liang J, Zheng W, Zhang Z, Li J, Yan Z, Wong WL, Zhang K, Chen M, Wu P Ref: Molecules, 28:, 2023 : PubMed ESTHER: Ang_2023_Molecules_28_ PubMedSearch: Ang 2023 Molecules 28 PubMedID: 37049799 Abstract A large number of studies have shown that matrine (MA) possesses various pharmacological activities and is one of the few natural, plant-derived pesticides with the highest prospects for promotion and application. Fifty-eight MA derivatives were prepared, including 10 intermediates and 48 target compounds in 3 series, to develop novel mosquitocidal agents. Compounds 4b, 4e, 4f, 4m, 4n, 6e, 6k, 6m, and 6o showed good larvicidal activity against Aedes albopictus, which is both a highly aggressive mosquito and an important viral vector that can transmit a wide range of pathogens. Dipping methods and a bottle bioassay were used for insecticidal activity evaluation. The LC(50) values of 4e, 4m, and 6m reached 147.65, 140.08, and 205.79 microg/mL, respectively, whereas the LC(50) value of MA was 659.34 microg/mL. Structure-activity relationship analysis demonstrated that larvicidal activity could be improved by the unsaturated heterocyclic groups introduced into the carboxyl group after opening the D ring. The MA derivatives with oxidized N-1 lost their mosquitocidal activities, indicating that the bareness of N-1 is crucial to maintain their anti-mosquito activity. However, the activity was not greatly influenced by introducing a cyan group at C-6 or a benzene sulfonyl group at N-16. Additionally, compounds 4e and 4m exhibited good inhibitory activities against acetylcholinesterase with inhibitory rates of 59.12% and 54.30%, respectively, at a concentration of 250 microg/mL, whereas the inhibitory rate of MA was 9.88%. Therefore, the structural modification and mosquitocidal activity of MA and its derivatives obtained here pave the way for those seeking strong mosquitocidal agents of plant origin. Title: A new benzaldehyde from the coral-derived fungus Aspergillus terreus C23-3 and its anti-inflammatory effects via suppression of MAPK signaling pathway in RAW264.7 cells Chen M, Liang J, Wang Y, Liu Y, Zhou C, Hong P, Zhang Y, Qian ZJ Ref: J Zhejiang Univ Sci B, 23:230, 2022 : PubMed ESTHER: Chen_2022_J.Zhejiang.Univ.Sci.B_23_230 PubMedSearch: Chen 2022 J.Zhejiang.Univ.Sci.B 23 230 PubMedID: 35261218 Abstract Marine fungi are important members of the marine microbiome, which have been paid growing attention by scientists in recent years. The secondary metabolites of marine fungi have been reported to contain rich and diverse compounds with novel structures (Chen et al., 2019). Aspergillus terreus, the higher level marine fungus of the Aspergillus genus (family of Trichocomaceae, order of Eurotiales, class of Eurotiomycetes, phylum of Ascomycota), is widely distributed in both sea and land. In our previous study, the coral-derived A. terreus strain C23-3 exhibited potential in producing other biologically active (with antioxidant, acetylcholinesterase inhibition, and anti-inflammatory activity) compounds like arylbutyrolactones, territrems, and isoflavones, and high sensitivity to the chemical regulation of secondary metabolism (Yang et al., 2019, 2020; Nie et al., 2020; Ma et al., 2021). Moreover, we have isolated two different benzaldehydes, including a benzaldehyde with a novel structure, from A. terreus C23-3 which was derived from Pectinia paeonia of Xuwen, Zhanjiang City, Guangdong Province, China. Title: Extraction and preparation of 5-lipoxygenase and acetylcholinesterase inhibitors from Astragalus membranaceus stems and leaves Liu R, Zhang Y, Li S, Liu C, Zhuang S, Zhou X, Li Y, Liang J Ref: J Sep Sci, :, 2022 : PubMed ESTHER: Liu_2022_J.Sep.Sci__ PubMedSearch: Liu 2022 J.Sep.Sci PubMedID: 36502278 Abstract In this study, an efficient method that employs 5-lipoxygenase and acetylcholinesterase as biological target molecules in receptor-ligand affinity ultrafiltration-liquid chromatography was developed for the screening of enzyme inhibitors derived from the Astragalus membranaceus stems and leaves. The effects of the extraction time, number of extraction cycles, ethanol concentration, and liquid-solid ratio on the total yield of the target compounds were investigated using response surface methodology, and the bioactive components were isolated using a combination of semi-preparative high-performance liquid chromatography and high-speed countercurrent chromatography via a two-phase solvent system consisting of n-hexane-ethyl acetate-methanol-water (1:6:2:6, v/v/v/v). Subsequently, ten naturally-occurring bioactive components in the Astragalus membranaceus stems and leaves, including wogonin, ononin, isoquercitrin, calycosin-7-glucoside, 3-hydroxy-9,10-dimethoxyptercarpan, hyperoside, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan, baicalein, calycosin, and soyasaponin, were screened using affinity ultrafiltration to determine their potential effects against Alzheimer's disease. Consequently, all target compounds had purities higher than 95.0%, and the potential anti-Alzheimer's disease effect of the obtained bioactive compounds was verified using molecular docking analysis. Based on the results, the back-to-back screening of complex enzyme inhibitors and separation of the target bioactive compounds using complex chromatography could provide a new approach for the discovery and preparation of natural active ingredients. This article is protected by copyright. All rights reserved. Title: Marine fungal metabolite butyrolactone I prevents cognitive deficits by relieving inflammation and intestinal microbiota imbalance on aluminum trichloride-injured zebrafish Nie Y, Yang J, Zhou L, Yang Z, Liang J, Liu Y, Ma X, Qian Z, Hong P and Zhang Y <2 more author(s)> Nie Y, Yang J, Zhou L, Yang Z, Liang J, Liu Y, Ma X, Qian Z, Hong P, Kalueff AV, Song C, Zhang Y (- 2) Ref: J Neuroinflammation, 19:39, 2022 : PubMed ESTHER: Nie_2022_J.Neuroinflammation_19_39 PubMedSearch: Nie 2022 J.Neuroinflammation 19 39 PubMedID: 35130930 Abstract BACKGROUND: Mounting evidences indicate that oxidative stress, neuroinflammation, and dysregulation of gut microbiota are related to neurodegenerative disorders (NDs). Butyrolactone I (BTL-I), a marine fungal metabolite, was previously reported as an in vitro neuroprotectant and inflammation inhibitor. However, little is known regarding its in vivo effects, whereas zebrafish (Danio rerio) could be used as a convenient in vivo model of toxicology and central nervous system (CNS) diseases. METHODS: Here, we employed in vivo and in silico methods to investigate the anti-NDs potential of BTL-I. Specifically, we established a cognitive deficit model in zebrafish by intraperitoneal (i.p.) injection of aluminum trichloride (AlCl(3)) (21 microg) and assessed their behaviors in the T-maze test. The proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as well as acetylcholinesterase (AChE) activity or glutathione (GSH) levels were assayed 24 h after AlCl(3) injection. The intestinal flora variation of the zebrafish was investigated by 16S rDNA high-throughput analysis. The marine fungal metabolite, butyrolactone I (BTL-I), was used to modulate zebrafish cognitive deficits evoked by AlCl(3) and evaluated about its effects on the above inflammatory, cholinergic, oxidative stress, and gut floral indicators. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of BTL-I were studied by the in silico tool ADMETlab. RESULTS: BTL-I dose-dependently ameliorated AlCl(3)-induced cognitive deficits in zebrafish. While AlCl(3) treatment elevated the levels of central and peripheral proinflammatory cytokines, increased AChE activity, and lowered GSH in the brains of zebrafish, these effects, except GSH reduction, were reversed by 25-100 mg/kg BTL-I administration. Besides, 16S rDNA high-throughput sequencing of the intestinal flora of zebrafish showed that AlCl(3) decreased Gram-positive bacteria and increased proinflammatory Gram-negative bacteria, while BTL-I contributed to maintaining the predominance of beneficial Gram-positive bacteria. Moreover, the in silico analysis indicated that BTL-I exhibits acceptable drug-likeness and ADMET profiles. CONCLUSIONS: The present findings suggest that BTL-I is a potential therapeutic agent for preventing CNS deficits caused by inflammation, neurotoxicity, and gut flora imbalance. Title: Neuroligin Plays a Role in Ethanol-Induced Disruption of Memory and Corresponding Modulation of Glutamate Receptor Expression Rose JK, Butterfield M, Liang J, Parvand M, Lin CHS, Rankin CH Ref: Front Behavioral Neuroscience, 16:908630, 2022 : PubMed ESTHER: Rose_2022_Front.Behav.Neurosci_16_908630 PubMedSearch: Rose 2022 Front.Behav.Neurosci 16 908630 PubMedID: 35722190 Abstract Exposure to alcohol causes deficits in long-term memory formation across species. Using a long-term habituation memory assay in Caenorhabditis elegans, the effects of ethanol on long-term memory (> 24 h) for habituation were investigated. An impairment in long-term memory was observed when animals were trained in the presence of ethanol. Cues of internal state or training context during testing did not restore memory. Ethanol exposure during training also interfered with the downregulation of AMPA/KA-type glutamate receptor subunit (GLR-1) punctal expression previously associated with long-term memory for habituation in C. elegans. Interestingly, ethanol exposure alone had the opposite effect, increasing GLR-1::GFP punctal expression. Worms with a mutation in the C. elegans ortholog of vertebrate neuroligins (nlg-1) were resistant to the effects of ethanol on memory, as they displayed both GLR-1::GFP downregulation and long-term memory for habituation after training in the presence of ethanol. These findings provide insights into the molecular mechanisms through which alcohol consumption impacts memory. Title: Lactobacillus plantarum KSFY06 and geniposide counteract montmorillonite-induced constipation in Kunming mice Gan Y, Liang J, Diao W, Zhou X, Mu J, Pang L, Tan F, Zhao X Ref: Food Sci Nutr, 8:5128, 2020 : PubMed ESTHER: Gan_2020_Food.Sci.Nutr_8_5128 PubMedSearch: Gan 2020 Food.Sci.Nutr 8 5128 PubMedID: 32994973 Abstract Constipation is a common clinical manifestation of digestive system disorders and occurs worldwide. This study investigated the ability of Lactobacillus plantarum KSFY06 (LP-KSFY06) to promote the action of geniposide in preventing montmorillonite-induced constipation in Kunming mice, with the aim of providing a successful solution. The effects of LP-KSFY06 and geniposide on constipation were measured, and the results showed that the protective effect of geniposide on constipation was enhanced by LP-KSFY06 and that the combination resulted in increased weight, moisture content, and particle number of feces. The first black stool defecation time was decreased from 182 min to 87 min, which clearly indicates that defecating difficulty was alleviated in constipated mice. The synergic intervention of LP-KSFY06 and geniposide (LP + G) assisted in maintaining the body weight of constipated mice. The LP + G intervention significantly increased serum levels of motilin (MTL, 167.8 pg/ml), acetylcholinesterase (AChE, 45.3 pg/ml), substance P (SP, 61.0 pg/ml), vasoactive intestinal peptide (VIP, 70.5 pg/ml), endothelin-1 (ET-1, 16.1 pg/ml), and gastrin (73.0 pg/ml) and remarkably decreased somatostatin (SS, 35.2 pg/ml) when compared to those indexes in the LP-KSFY06 group and geniposide group. The LP + G treatment also significantly increased the mRNA expression of cluster of differentiation 117 (c-Kit), stem cell factor (SCF), glial cell-derived neurotrophic factor (GDNF), and remarkably downregulated the expression of inducible nitric oxide synthase (iNOS), transient receptor potential vanilloid-1 (TRPV1), and cyclooxygenase-2 (COX-2). The experimental results showed that the combination treatment has the strongest prevention effect against constipation, and LP-KSFY06 promotes the ability of geniposide to prevent constipation. Therefore, LP-KSFY06 is a potential probiotic strain with the capacity to prevent montmorillonite-induced constipation. Title: Systematic phenomics analysis of autism-associated genes reveals parallel networks underlying reversible impairments in habituation McDiarmid TA, Belmadani M, Liang J, Meili F, Mathews EA, Mullen GP, Hendi A, Wong WR, Rand JB and Rankin CH <3 more author(s)> McDiarmid TA, Belmadani M, Liang J, Meili F, Mathews EA, Mullen GP, Hendi A, Wong WR, Rand JB, Mizumoto K, Haas K, Pavlidis P, Rankin CH (- 3) Ref: Proc Natl Acad Sci U S A, 117:656, 2020 : PubMed ESTHER: McDiarmid_2020_Proc.Natl.Acad.Sci.U.S.A_117_656 PubMedSearch: McDiarmid 2020 Proc.Natl.Acad.Sci.U.S.A 117 656 PubMedID: 31754030 Abstract A major challenge facing the genetics of autism spectrum disorders (ASDs) is the large and growing number of candidate risk genes and gene variants of unknown functional significance. Here, we used Caenorhabditis elegans to systematically functionally characterize ASD-associated genes in vivo. Using our custom machine vision system, we quantified 26 phenotypes spanning morphology, locomotion, tactile sensitivity, and habituation learning in 135 strains each carrying a mutation in an ortholog of an ASD-associated gene. We identified hundreds of genotype-phenotype relationships ranging from severe developmental delays and uncoordinated movement to subtle deficits in sensory and learning behaviors. We clustered genes by similarity in phenomic profiles and used epistasis analysis to discover parallel networks centered on CHD8*chd-7 and NLGN3*nlg-1 that underlie mechanosensory hyperresponsivity and impaired habituation learning. We then leveraged our data for in vivo functional assays to gauge missense variant effect. Expression of wild-type NLG-1 in nlg-1 mutant C. elegans rescued their sensory and learning impairments. Testing the rescuing ability of conserved ASD-associated neuroligin variants revealed varied partial loss of function despite proper subcellular localization. Finally, we used CRISPR-Cas9 auxin-inducible degradation to determine that phenotypic abnormalities caused by developmental loss of NLG-1 can be reversed by adult expression. This work charts the phenotypic landscape of ASD-associated genes, offers in vivo variant functional assays, and potential therapeutic targets for ASD. 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: Soluble epoxide hydrolase inhibitor, TUPS, attenuates isoproterenol/angiotensin II-induced cardiac hypertrophy through mammalian target of rapamycin-mediated autophagy inhibition Zhang H, Zhang K, Liang J, Yan W, Wu F, Xu W, Wu Z, Chen Y, Pan R, Wu G Ref: J Pharm Pharmacol, 71:1291, 2019 : PubMed ESTHER: Zhang_2019_J.Pharm.Pharmacol_71_1291 PubMedSearch: Zhang 2019 J.Pharm.Pharmacol 71 1291 PubMedID: 31215026 Inhibitor(s) related to this paper: TUPS Abstract OBJECTIVES: To investigate the potential role and mechanism of TUPS, a soluble epoxide hydrolase inhibitor, in cardiac hypertrophy. METHODS: Rat and H9C2 cell models of cardiac hypertrophy were induced by isoproterenol and angiotensin II, respectively, followed by TUPS treatment. The expression of hypertrophic markers, ANP and BNP, was determined by quantitative real-time PCR. The abundance of Beclin-1, LC3, p-AMPK and phosphorylated-mammalian target of rapamycin (p-mTOR) proteins was analysed by Western blot and immunohistocytology. Cell morphology and viability were evaluated by F-actin staining and MTS. H9C2 cells were transfected with GFP-LC3 to evaluate autophagy flux. KEY FINDINGS: TUPS significantly inhibited rat heart size, heart weight-to-body weight ratio, heart wall thickness, hypertrophic H9C2 cell swelling and viability suppression as well as the expression of ANP and BNP genes in hypertrophic models. In addition, autophagic markers Beclin-1 and LC3 were elevated in both cellular and animal models, which were suppressed by TUPS, with corresponding changes of autophagy flux. The abundance of p-AMPK was increased, while p-mTOR was decreased in hypertrophic cells, which were abolished by TUPS. Rapamycin decreased p-mTOR level, increased Beclin-1 and LC3 expression and induced cell size enlargement and cell viability inhibition in hypertrophic H9C2 cells treated with TUPS. CONCLUSIONS: TUPS inhibits cardiac hypertrophy by regulating mTOR/autophagy axis. Title: Psychosocial interventions for Alzheimer's disease cognitive symptoms: a Bayesian network meta-analysis Duan Y, Lu L, Chen J, Wu C, Liang J, Zheng Y, Wu J, Rong P, Tang C Ref: BMC Geriatr, 18:175, 2018 : PubMed ESTHER: Duan_2018_BMC.Geriatr_18_175 PubMedSearch: Duan 2018 BMC.Geriatr 18 175 PubMedID: 30086714 Abstract BACKGROUND: Alzheimer disease (AD) is the most common type of dementia with cognitive decline as one of the core symptoms in older adults. Numerous studies have suggested the value of psychosocial interventions to improve cognition in this population, but which one should be preferred are still matters of controversy. Consequently, we aim to compare and rank different psychosocial interventions in the management of mild to moderate AD with cognitive symptoms. METHODS: We did a network meta-analysis to identify both direct and indirect evidence in relevant studies. We searched MEDLINE, EMBASE, PsycINFO through the OVID database, CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating psychosocial interventions of cognitive symptoms in patients with Alzheimer disease, published up to August 31, 2017. We included trials of home-based exercise(HE), group exercise(GE), walking program(WP), reminiscence therapy(RT), art therapy(AT) or the combination of psychosocial interventions and acetylcholinesterase inhibitor (ChEIs). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. The outcomes investigated were Mini-Mental State Examination (MMSE) and compliance. We did a pair-wise meta-analysis using the fixed-effects model and then did a random-effects network meta-analysis within a Bayesian framework. RESULTS: We deemed 10 trials eligible, including 682 patients and 11 treatments. The quality of included study was rated as low in most comparison with Cochrane tools. Treatment effects from the network meta-analysis showed WP was better than control (SMD 4.89, 95% CI -0.07 to 10.00) while cognitive training and acetylcholinesterase inhibitor (CT + ChEIs) was significantly better than the other treatments, when compared with simple ChEIs treatment, assessed by MMSE. In terms of compliance, the pair-wise meta-analysis indicated that WP and HE are better than GE and AT, while CT + ChEIs, CST + ChEIs are better than other combined interventions. CONCLUSION: Our study confirmed the effectiveness of psychosocial interventions for improving cognition or slowing down the progression of cognitive impairment in AD patients and recommended several interventions for clinical practice. Title: Recovery of respiratory function and autonomic diaphragm movement following unilateral recurrent laryngeal nerve to phrenic nerve anastomosis in rabbits Wen J, Han Y, Guo S, Yang M, Li L, Sun G, Wang J, Hu F, Liang J and Tan J <3 more author(s)> Wen J, Han Y, Guo S, Yang M, Li L, Sun G, Wang J, Hu F, Liang J, Wei L, Zhou Q, Zhang W, Tan J (- 3) Ref: Journal of Neurosurgery Spine, :1, 2018 : PubMed ESTHER: Wen_2018_J.Neurosurg.Spine__1 PubMedSearch: Wen 2018 J.Neurosurg.Spine 1 PubMedID: 29979142 Abstract OBJECTIVE Respiratory dysfunction is the leading cause of mortality following upper cervical spinal cord injury (SCI). The authors' previous study suggested that vagus nerve (VN) and phrenic nerve (PN) anastomosis could partially improve respiratory function in rabbits that had been subjected to PN transection. As a branch of the VN and a motor fiber-dominated nerve, the recurrent laryngeal nerve (RLN) seems a better choice to anastomose with the PN for respiratory function restoration after upper cervical SCI. This study was designed to determine whether RLN-PN anastomosis could restore the respiratory function after upper cervical SCI in rabbits. METHODS Twelve male New Zealand rabbits were randomly divided into 3 groups: 1) sham group (no injury), 2) transection group (right RLN and PN were transected), and 3) bridge group (transected right RLN and PN were immediately anastomosed). Spontaneous discharges of the RLN and PN were compared using a bio-signal collection system. RLN and PN cross sections were stained for acetylcholinesterase (AChE), and the numbers of motor fibers were compared. Three months after the initial surgical procedures, the movement of the diaphragm was assessed using a digital subtraction angiography (DSA) system, and discharges from the right diaphragm muscle were recorded. Toluidine blue staining, electron microscopy, and staining for AChE were used to assess whether motor fibers from the RLN regenerated into the PN, and sections of diaphragm were examined after AChE staining to assess the motor endplates. RESULTS Both the RLN and PN exhibited highly rhythmic discharges, synchronized with respiration, and most fibers in the RLN and PN were found to be motor fibers. Numerous myelinated fibers were observed in anastomosed PN using toluidine blue staining and electron microscopy. Staining for AChE showed that those regenerated fibers had typical characteristics of motor fibers, and motor endplates with typical morphological characteristics were observed in the diaphragm. Reestablished rhythmic contraction of the hemidiaphragm was directly observed using the DSA system, and rhythmic spontaneous discharge was recorded from the reinnervated hemidiaphragm using the bio-signal collection system. CONCLUSIONS Motor fibers from the RLN could regenerate into the PN after end-to-end anastomosis and reinnervate the denervated hemidiaphragm in rabbits. Those regenerated motor fibers restored rhythmic and autonomic movement of the paralyzed diaphragm. These results suggest that the RLN is an optimal donor nerve to anastomose with the PN in order to reestablish the autonomic movement of paralyzed diaphragms after high-level SCI. Title: Scallop genome provides insights into evolution of bilaterian karyotype and development Wang S, Zhang J, Jiao W, Li J, Xun X, Sun Y, Guo X, Huan P, Dong B and Bao Z <42 more author(s)> Wang S, Zhang J, Jiao W, Li J, Xun X, Sun Y, Guo X, Huan P, Dong B, Zhang L, Hu X, Sun X, Wang J, Zhao C, Wang Y, Wang D, Huang X, Wang R, Lv J, Li Y, Zhang Z, Liu B, Lu W, Hui Y, Liang J, Zhou Z, Hou R, Li X, Liu Y, Li H, Ning X, Lin Y, Zhao L, Xing Q, Dou J, Mao J, Guo H, Dou H, Li T, Mu C, Jiang W, Fu Q, Fu X, Miao Y, Liu J, Yu Q, Li R, Liao H, Kong Y, Jiang Z, Chourrout D, Bao Z (- 42) Ref: Nat Ecol Evol, 1:120, 2017 : PubMed ESTHER: Wang_2017_Nat.Ecol.Evol_1_120 PubMedSearch: Wang 2017 Nat.Ecol.Evol 1 120 PubMedID: 28812685 Gene_locus related to this paper: mizye-a0a210qls6, mizye-a0a210qis3, mizye-a0a210qg00, mizye-a0a210ped6, mizye-a0a210q4h5, mizye-a0a210q4h9, mizye-a0a210q4j1, mizye-a0a210qf86, mizye-a0a210q332, mizye-a0a210pqn0, mizye-a0a210q7t5, mizye-a0a210pij5, mizye-a0a210qyk8, mizye-a0a210pwl7, mizye-a0a210q8u5, mizye-a0a210r5n9, mizye-a0a210qbv2, mizye-a0a210pu25, mizye-a0a210pek1, mizye-a0a210pul3, mizye-a0a210pum3, mizye-a0a210ptr6, mizye-a0a210ptq5, mizye-a0a210ptc4.1, mizye-a0a210ptc4.2, mizye-a0a210ptv1, mizye-a0a210ptv7, mizye-a0a210qgl6, mizye-a0a210qg90, mizye-a0a210ptq0, mizye-a0a210qg72, mizye-a0a210ptb1, mizye-a0a210pjd3, mizye-a0a210qg92, mizye-a0a210q8v2, mizye-a0a210qg93, mizye-a0a210q160.1, mizye-a0a210q160.2, mizye-a0a210qes4, mizye-a0a210pk25, mizye-a0a210q1b8, mizye-a0a210q110, mizye-a0a210r503, mizye-P021348901.1, mizye-P021348901.2 Abstract Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology. Title: Functional Characterization of a Novel Marine Microbial GDSL Lipase and Its Utilization in the Resolution of (+/-)-1-Phenylethanol Deng D, Zhang Y, Sun A, Liang J, Hu Y Ref: Appl Biochem Biotechnol, 179:75, 2016 : PubMed ESTHER: Deng_2016_Appl.Biochem.Biotechnol_179_75 PubMedSearch: Deng 2016 Appl.Biochem.Biotechnol 179 75 PubMedID: 26754423 Abstract A novel GDSL lipase (MT6) was cloned from the genome of Marinactinospora thermotolerans SCSIO 00652 identified from the South China Sea. MT6 showed its maximum identity of 59 % with a putative lipase from Nocardiopsis dassonville. MT6 was heterologously expressed in E. coli BL21(DE3) and further functionally characterized. MT6 could efficiently resolve racemic 1-phenylethanol and generate (R)-1-phenylethanol with high enantiomeric excess (99 %) and conversion rate (54 %) through transesterification reactions after process optimization. Our report was the first one report about the utilization of one GDSL lipase in the preparation of chiral chemicals by transesterification reactions, and the optical selectivity of MT6 was interestingly opposite to those of other common lipases. GDSL lipases represented by MT6 possess great potential for the generation of valuable chiral chemicals in industry. Title: Enantioselective Resolution of (+/-)-1-Phenylethanol and (+/-)-1-Phenylethyl Acetate by a Novel Esterase from Bacillus sp. SCSIO 15121 Liang J, Zhang Y, Sun A, Deng D, Hu Y Ref: Appl Biochem Biotechnol, 178:558, 2016 : PubMed ESTHER: Liang_2016_Appl.Biochem.Biotechnol_178_558 PubMedSearch: Liang 2016 Appl.Biochem.Biotechnol 178 558 PubMedID: 26467742 Abstract A novel microbial esterase BSE01281 identified from the Indian Ocean was cloned, expressed, and functionally characterized. Esterase BSE01281 could enanoselectively resolve (+/-)-1-phenylethanol and (+/-)-1-phenylethyl acetate through two types of enzymatic reactions. After the optimization of enzymatic reactions, BSE01281 could efficiently generate (R)-1-phenylethyl acetate with high enantiomeric excess (>99%) and high conversion (42%) after 96 h trans-esterification reactions. Additionally, BSE01281 could also produce (R)-1-phenylethanol (e.e. > 99%) and (S)-1-phenylethyl acetate (e.e. > 95%) at a conversion of 49% through direct hydrolysis of inexpensive racemic 1-phenylethyl acetate for 8 h. Optically pure (R)-1-phenylethanol generated from direct enzymatic hydrolysis of racemic 1-phenylethyl acetate by BSE01281 is not easily prepared by dehydrogenases, which generally follow the "Prelog's rule" and give (S)-1-phenylethanol instead. Title: Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect Guo Y, Menezes MJ, Menezes MP, Liang J, Li D, Riley LG, Clarke NF, Andrews PI, Tian L and Xu X <9 more author(s)> Guo Y, Menezes MJ, Menezes MP, Liang J, Li D, Riley LG, Clarke NF, Andrews PI, Tian L, Webster R, Wang F, Liu X, Shen Y, Thorburn DR, Keating BJ, Engel A, Hakonarson H, Christodoulou J, Xu X (- 9) Ref: Neuromuscular Disorders, 25:257, 2015 : PubMed ESTHER: Guo_2015_Neuromuscul.Disord_25_257 PubMedSearch: Guo 2015 Neuromuscul.Disord 25 257 PubMedID: 25557462 Abstract Clinical phenotypes of congenital myasthenic syndromes and primary mitochondrial disorders share significant overlap in their clinical presentations, leading to challenges in making the correct diagnosis. Next generation sequencing is transforming molecular diagnosis of inherited neuromuscular disorders by identifying novel disease genes and by identifying previously known genes in undiagnosed patients. This is evident in two patients who were initially suspected to have a mitochondrial myopathy, but in whom a clear diagnosis of congenital myasthenic syndromes was made through whole exome sequencing. In patient 1, whole exome sequencing revealed compound heterozygous mutations c.1228C > T (p.Arg410Trp) and c.679C > T (p.Arg227*) in collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). In patient 2, in whom a deletion of exon 52 in Dystrophin gene was previously detected by multiplex ligation-dependent probe amplification, Sanger sequencing revealed an additional homozygous mutation c.1511_1513delCTT (p.Pro504Argfs*183) in docking protein7 (DOK7). These case reports highlight the need for careful diagnosis of clinically heterogeneous syndromes like congenital myasthenic syndromes, which are treatable, and for which delayed diagnosis is likely to have implications for patient health. The report also demonstrates that whole exome sequencing is an effective diagnostic tool in providing molecular diagnosis in patients with complex phenotypes. Title: Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1) provides insights into genome evolution Li F, Fan G, Lu C, Xiao G, Zou C, Kohel RJ, Ma Z, Shang H, Ma X and Yu S <30 more author(s)> Li F, Fan G, Lu C, Xiao G, Zou C, Kohel RJ, Ma Z, Shang H, Ma X, Wu J, Liang X, Huang G, Percy RG, Liu K, Yang W, Chen W, Du X, Shi C, Yuan Y, Ye W, Liu X, Zhang X, Liu W, Wei H, Wei S, Zhu S, Zhang H, Sun F, Wang X, Liang J, Wang J, He Q, Huang L, Cui J, Song G, Wang K, Xu X, Yu JZ, Zhu Y, Yu S (- 30) Ref: Nat Biotechnol, 33:524, 2015 : PubMed ESTHER: Li_2015_Nat.Biotechnol_33_524 PubMedSearch: Li 2015 Nat.Biotechnol 33 524 PubMedID: 25893780 Gene_locus related to this paper: gosra-a0a0d2rxs2, gosra-a0a0d2tng2, gosra-a0a0d2twz7, goshi-a0a1u8hr03, gosra-a0a0d2vdc5, goshi-a0a1u8ljh5, gosra-a0a0d2vj24, goshi-a0a1u8pxd3, gosra-a0a0d2sr31, goshi-a0a1u8knd1, goshi-a0a1u8nhw9, goshi-a0a1u8mt09, goshi-a0a1u8kis4, goshi-a0a1u8ibk3, goshi-a0a1u8ieg2, goshi-a0a1u8iki6, goshi-a0a1u8jvp4, goshi-a0a1u8jw35, gosra-a0a0d2pzd7 Abstract Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6% approximately 96.7% of the AtDt genome, are anchored and oriented to 26 pseudochromosomes. Comparison of this G. hirsutum AtDt genome with the already sequenced diploid Gossypium arboreum (AA) and Gossypium raimondii (DD) genomes revealed conserved gene order. Repeated sequences account for 67.2% of the AtDt genome, and transposable elements (TEs) originating from Dt seem more active than from At. Reduction in the AtDt genome size occurred after allopolyploidization. The A or At genome may have undergone positive selection for fiber traits. Concerted evolution of different regulatory mechanisms for Cellulose synthase (CesA) and 1-Aminocyclopropane-1-carboxylic acid oxidase1 and 3 (ACO1,3) may be important for enhanced fiber production in G. hirsutum. Title: Conditional neuroligin-2 knockout in adult medial prefrontal cortex links chronic changes in synaptic inhibition to cognitive impairments Liang J, Xu W, Hsu YT, Yee AX, Chen L, Sudhof TC Ref: Mol Psychiatry, 20:850, 2015 : PubMed ESTHER: Liang_2015_Mol.Psychiatry_20_850 PubMedSearch: Liang 2015 Mol.Psychiatry 20 850 PubMedID: 25824299 Abstract Abnormal activity in the medial prefrontal cortex (mPFC) is consistently observed in neuropsychiatric disorders, but the mechanisms involved remain unclear. Chronic aberrant excitation and/or inhibition of mPFC neurons were proposed to cause cognitive impairments. However, direct evidence for this hypothesis is lacking because it is technically challenging to control synaptic properties in a chronic and locally restricted, yet specific, manner. Here, we generated conditional knockout (cKO) mice of neuroligin-2 (Nlgn2), a postsynaptic cell-adhesion molecule of inhibitory synapses linked to neuropsychiatric disorders. cKO of Nlgn2 in adult mPFC rendered Nlgn2 protein undetectable after already 2-3 weeks, but induced major reductions in synaptic inhibition after only 6-7 weeks, and caused parallel impairments in anxiety, fear memory and social interaction behaviors. Moreover, cKO of Nlgn2 severely impaired behavioral stimulation of immediate-early gene expression in the mPFC, suggesting that chronic reduction in synaptic inhibition uncoupled the mPFC from experience-dependent inputs. Our results indicate that Nlgn2 is required for continuous maintenance of inhibitory synapses in the adult mPFC, and that chronic impairment of local inhibition disengages the mPFC from its cognitive functions by partially uncoupling the mPFC from experience-induced inputs. Title: Fast identification of lipase inhibitors in oolong tea by using lipase functionalised Fe3O4 magnetic nanoparticles coupled with UPLC-MS/MS Zhu YT, Ren XY, Yuan L, Liu YM, Liang J, Liao X Ref: Food Chem, 173:521, 2015 : PubMed ESTHER: Zhu_2015_Food.Chem_173_521 PubMedSearch: Zhu 2015 Food.Chem 173 521 PubMedID: 25466054 Inhibitor(s) related to this paper: Epicatechin-gallate, Epigallocatechin-gallate Abstract Oolong tea is an important member in tea family, which claims for various health benefits such as preventing obesity and improving lipid metabolism. In this work, using pancreatic lipase (PL) functionalised magnetic nanoparticles (PL-MNPs) as solid phase extraction absorbent in combination with ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS), we developed a method for rapid screening and identification of lipase inhibitors from oolong tea. Three PL ligands were selectively extracted and identified as (-)-epigallocatechin-3-O-gallate (EGCG), (-)-gallocatechin-3-O-gallate (GCG) and (-)-epicatechin-3-O-gallate (ECG). Their lipase inhibitory activities were significantly higher than those non-ligands. Structure-activity analysis revealed that the presence of a galloyl moiety in the structure was required for binding to PL-MNPs, and therefore, exhibiting a strong inhibition on the enzyme. Taking advantages of the specificity in enzyme binding and the convenience of magnetic separation, this method has great potential for fast screening of lipase inhibitors from natural resources. Title: Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes Udpa N, Ronen R, Zhou D, Liang J, Stobdan T, Appenzeller O, Yin Y, Du Y, Guo L and Haddad GG <17 more author(s)> Udpa N, Ronen R, Zhou D, Liang J, Stobdan T, Appenzeller O, Yin Y, Du Y, Guo L, Cao R, Wang Y, Jin X, Huang C, Jia W, Cao D, Guo G, Claydon VE, Hainsworth R, Gamboa JL, Zibenigus M, Zenebe G, Xue J, Liu S, Frazer KA, Li Y, Bafna V, Haddad GG (- 17) Ref: Genome Biol, 15:R36, 2014 : PubMed ESTHER: Udpa_2014_Genome.Biol_15_R36 PubMedSearch: Udpa 2014 Genome.Biol 15 R36 PubMedID: 24555826 Gene_locus related to this paper: human-LIPE Abstract BACKGROUND: Although it has long been proposed that genetic factors contribute to adaptation to high altitude, such factors remain largely unverified. Recent advances in high-throughput sequencing have made it feasible to analyze genome-wide patterns of genetic variation in human populations. Since traditionally such studies surveyed only a small fraction of the genome, interpretation of the results was limited. Title: Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W and Shi Q <31 more author(s)> You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W, Zhang X, Sun Y, Chen S, Hong W, Li Y, Cheng S, Fan G, Shi C, Liang J, Tom Tang Y, Yang C, Ruan Z, Bai J, Peng C, Mu Q, Lu J, Fan M, Yang S, Huang Z, Jiang X, Fang X, Zhang G, Zhang Y, Polgar G, Yu H, Li J, Liu Z, Ravi V, Coon SL, Yang H, Venkatesh B, Shi Q (- 31) Ref: Nat Commun, 5:5594, 2014 : PubMed ESTHER: You_2014_Nat.Commun_5_5594 PubMedSearch: You 2014 Nat.Commun 5 5594 PubMedID: 25463417 Gene_locus related to this paper: 9gobi-a0a3b4bh68, 9gobi-a0a3b4bmj6, 9gobi-a0a3b4alj9, 9gobi-a0a3b4biy6, 9gobi-a0a3b4ah01, 9gobi-a0a3b3z8m7, 9gobi-a0a3b4aaj5, 9gobi-a0a3b4b6y7 Abstract Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates. Title: Sodium selenite induces apoptosis in cultured cortical neurons with special concomitant changes in expression of the apoptosis-related genes Xiao R, Qiao JT, Zhao HF, Liang J, Yu HL, Liu J, Guo AM, Wang W Ref: Neurotoxicology, 27:478, 2006 : PubMed ESTHER: Xiao_2006_Neurotoxicol_27_478 PubMedSearch: Xiao 2006 Neurotoxicol 27 478 PubMedID: 16542727 Abstract Sodium selenite was used to examine whether selenium compound is able to trigger apoptotic degeneration in cultured cortical neurons in vitro and to explore the detailed changes in expression of the related genes during the apoptotic processes using molecular biological and flow cytometric examinations. The results indicated that: (1) cortical neurons treated with sodium selenite with different dosages (0.0008, 0.004, 0.0200, 0.1000, and 0.5000 microM) and different exposure times (2, 4, 24, and 48 h) exhibited dose- and time-dependent apoptotic processes as revealed by typical DNA ladder formation detected by agarose gel electrophoresis; (2) the internucleosomal DNA fragmentation detected by flow cytometric examination showed a prominent peak of hypodiploid DNA contents as early as 4h after exposure of 0.1 microM sodium selenite; (3) the DNA fragmentation induced by sodium selenite as revealed by the above two examinations could be blocked by aurintricarboxylic acid; (4) the transcriptions of mRNAs related to bcl-2, bax, c-fos, p53, and acetylcholinesterase (AChE) genes, as detected by RT-PCR assays, showed down-regulation for bcl-2 and up-regulation for bax, c-fos, p53, and AChE genes after exposure of sodium selenite. This study suggests that the sodium selenite is effective for inducing apoptosis in cultured cortical neurons and that relevant changes in expression of several apoptosis-related genes might further our understanding of the mechanism(s) that initiates and maintains the apoptotic processes. Title: Macrophage-derived lipoprotein lipase increases aortic atherosclerosis in cholesterol-fed Tg rabbits Ichikawa T, Liang J, Kitajima S, Koike T, Wang X, Sun H, Morimoto M, Shikama H, Watanabe T and Fan J <1 more author(s)> Ichikawa T, Liang J, Kitajima S, Koike T, Wang X, Sun H, Morimoto M, Shikama H, Watanabe T, Yamada N, Fan J (- 1) Ref: Atherosclerosis, 179:87, 2005 : PubMed ESTHER: Ichikawa_2005_Atherosclerosis_179_87 PubMedSearch: Ichikawa 2005 Atherosclerosis 179 87 PubMedID: 15721013 Abstract Lipoprotein lipase (LPL) produced by macrophages is upregulated in the atherosclerotic lesions; however, it is not fully understood whether increased macrophage-derived LPL is pro-atherogenic. To examine the hypothesis that macrophage-derived LPL in the arterial wall enhances atherosclerotic lesion formation, we generated transgenic (Tg) rabbits that express the human LPL transgene under the control of the human scavenger receptor enhancer/promoter, which drives macrophage-specific expression of the human LPL gene. We fed Tg and non-Tg littermate rabbits a diet containing 0.3% cholesterol for 16 weeks and compared their lipoproteins and aortic atherosclerosis. We found that there was no difference in plasma lipid or lipoprotein profiles between Tg and non-Tg rabbits; however, atherosclerotic lesions were significantly increased in Tg compared to non-Tg rabbits. There was a 1.4-fold increase in total aortic en face lesions and a 2-fold increase in intimal lesions evaluated by image analysis system. Furthermore, immunohistochemical staining revealed that the increased atherosclerotic lesions present in Tg rabbits were characterized by marked accumulation of macrophage-derived foam cells and frequently associated with the deposition of oxidized LDL. These results support the notion that macrophage-derived LPL in the arterial wall is pro-atherogenic, possibly via the enhancement of foam cell formation during atherogenesis. Title: Enhanced aortic atherosclerosis in transgenic Watanabe heritable hyperlipidemic rabbits expressing lipoprotein lipase Koike T, Liang J, Wang X, Ichikawa T, Shiomi M, Sun H, Watanabe T, Liu G, Fan J Ref: Cardiovascular Research, 65:524, 2005 : PubMed ESTHER: Koike_2005_Cardiovasc.Res_65_524 PubMedSearch: Koike 2005 Cardiovasc.Res 65 524 PubMedID: 15639492 Abstract OBJECTIVE: This study was designed to address the effects of increased lipoprotein lipase (LPL) activity on atherosclerosis in the setting of LDL receptor deficiency. Title: Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis Ichikawa T, Kitajima S, Liang J, Koike T, Wang X, Sun H, Okazaki M, Morimoto M, Shikama H and Fan J <2 more author(s)> Ichikawa T, Kitajima S, Liang J, Koike T, Wang X, Sun H, Okazaki M, Morimoto M, Shikama H, Watanabe T, Yamada N, Fan J (- 2) Ref: Lab Invest, 84:715, 2004 : PubMed ESTHER: Ichikawa_2004_Lab.Invest_84_715 PubMedSearch: Ichikawa 2004 Lab.Invest 84 715 PubMedID: 15122303 Abstract Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. Previous studies using transgenic mice and rabbits have demonstrated that high level of LPL activity in adipose and skeletal muscle protects against diet-induced hypercholesterolemia and subsequently prevents aortic atherosclerosis. However, it is unknown, per se, whether increased LPL activity itself is antiatherogenic, or whether the antiatherogenic effect of LPL is dependent upon the LPL lipid-lowering effect. To address this issue, we fed LPL transgenic and littermate rabbits diets containing different amounts of cholesterol (0.3-0.6%) adjusted to maintain their plasma cholesterol concentrations at similarly high levels for 16 weeks. We analyzed their lipoprotein profiles and compared their susceptibility to atherosclerosis. The results showed that the overexpression of LPL in transgenic rabbits reduced remnant lipoproteins (beta-VLDL, d<1.006 g/ml) but concomitantly led to a significant increase of the large (d=1.02-1.04 g/ml) and small LDLs (d=1.04-1.06 g/ml) compared to the amounts in control rabbits. Furthermore, we found that with equally high hypercholesterolemia, transgenic rabbits developed 1.8-fold more extensive aortic atherosclerosis than control rabbits. To examine the hypothesis that altered lipoprotein profiles may be responsible for the enhanced atherosclerosis in transgenic rabbits, we studied the atherogenic properties of apoB-containing lipoproteins in vitro. These studies revealed that small-sized LDLs of transgenic rabbits were more susceptible to copper-induced oxidation and had higher affinity to biglycan than large remnant lipoproteins. We conclude, therefore, that LPL exerts a dual function in terms of its atherogenicity, namely antiatherogenicity, through enhancing receptor-mediated remnant lipoprotein catabolism and proatherogenicity via the generation of a large amount of small-sized LDLs. At an equal atherogenic-cholesterol level, small and dense LDLs are more atherogenic than large remnant lipoproteins. | |||||||
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