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| 1 | Design and development of an oral remdesivir derivative W116 against SARS-CoV-2显示文摘Dear Editor,Since the declaration of COVID-19 as a global pandemic on March 11,2020,this pandemic has been circulating for 17 months throughout the world,leading to more than 200 million infections and nearly 4.4 million deaths as of August 15,2021.The pathogen of COVID-19 is a novel coronavirus named SARS-CoV-2,which shares-79%genome sequence identity with SARS-CoV.1 At the early stage of the COVID-19 outbreak,5ARS-CoV-2 caused great panic in the hardest-hit areas due to its high transmissibility and pathogenicity.To fight the COVID-19 crisis,drug repurposing was immediately pursued in order to find potential therapeutics. | Yuanchao Xie Wanchao Yin Yumin Zhang Weijuan Shang Zhen Wang Xiaodong Luan Guanghui Tian Haji A.Aisa Yechun Xu Gengfu Xiao Jia Li Hualiang Jiang Shuyang Zhanq Leike Zhang H.Eric Xu Jingshan Shen | 2021 | Cell Research2021，31，11： | 12 |
| 2 | Structure insights into mechanisms of ATP hydrolysis and the activation of human heat-shock protein 90显示文摘分子的女伴热吃惊蛋白质 90 的激活(Hsp90 ) 依赖于 ATP 绑定和水解作用,它发生在蛋白质的 N 终端域。这里,我们与 ATP 和 ATP 类似物在土著人并且在建筑群决定了人的 Hsp90 的 N 终端领域的三水晶结构,提供由 Hsp90 的 ATP 水解作用的催化机制的一个清楚的看法。另外, ATP 的绑定导致 N 终端领域是能被用来部分解释 Hsp90 的孤立的 N 终端领域为什么举办很弱的 ATP hydrolytic 活动的一个中间的状态。 | Jian Li Lihua Sun Chunyan Xu Feng Yu Huan Zhou Yanlong Zhao Jian Zhang Jianhua Cai Cheney Mao Lin Tang Yechun Xu Jianhua He | 2012 | Acta Biochimica et Biophysica Sinica2012，44，4： | 5 |
| 3 | Potential treatment of COVID-19 by inhibitors of human dihydroorotate dehydrogenase显示文摘The ongoing pandemic of severe acute respiratory syn・drome coronavirus 2(SARS・CoV・2),referred to as coronavirus disease 2019(COVID-19),has caused over 13 million infections and over 560,000 deaths worldwide(http://gffzz36b398b81f8a4a4csxv9fnvw6v5056uoo.ffgz.tsg.suse.edu.cn/emergencies/diseases/novel・coron avirus-2019/sit uation-reports),posing a significant threat to globally public health and economics.At present,no efficacious antiviral drugs and vaccines have been approved for the prophylaxis or treatment of COVID-19.Tremendous efforts have been made to develop drug and vaccine against SARS-CoV-2.The main protease(Mpro,also called 3CLpro)is an attractive drug target among coronaviruses,and several potent inhibitors of the SARS-CoV-23CLpro together with their crystal structures in complex with the protease have been reported(Dai et al.,2020;Jin et al.,2020;Zhang et al.,2020). | Yechun Xu Hualiang Jiang | 2020 | Protein & Cell2020，11，10： | 5 |
| 4 | Bispecific prodrug nanoparticles circumventing multiple immune resistance mechanisms for promoting cancer immunotherapy显示文摘Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance.Herein,a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms.A disulfide bond-linked bispecific prodrug of NLG919 and JQ1(namely NJ) was synthesized and self-assembled into a prodrug nanoparticle,which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ.Upon tumor accumulation via passive tumor targeting,the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug.NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond.JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1.In contrast,NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment,which thus restores robust antitumor immune responses.Photodynamic therapy(PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells.The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy. | Jiayi Ye Bo Hou Fangmin Chen Shunan Zhang Muya Xiong Tianliang Li Yechun Xu Zhiai Xu Haijun Yu | 2022 | Acta Pharmaceutica Sinica B2022，12，6： | 4 |
| 5 | Applying high-performance computing in drug discovery and molecular simulation显示文摘In recent decades, high-performance computing(HPC) technologies and supercomputers in China have significantly advanced, resulting in remarkable achievements. Computational drug discovery and design,which is based on HPC and combines pharmaceutical chemistry and computational biology, has become a critical approach in drug research and development and is financially supported by the Chinese government. This approach has yielded a series of new algorithms in drug design, as well as new software and databases. This review mainly focuses on the application of HPC to the fields of drug discovery and molecular simulation at the Chinese Academy of Sciences, including virtual drug screening, molecular dynamics simulation, and protein folding. In addition, the potential future application of HPC in precision medicine is briefly discussed. | Tingting Liu Dong Lu Hao Zhang Mingyue Zheng Huaiyu Yang Yechun Xu Cheng Luo Weiliang Zhu Kunqian Yu Hualiang Jiang | 2016 | National Science Review2016，3，1： | 2 |
| 6 | Steered molecular dynamics simulations of protein-ligand interactions显示文摘Studies of protein-ligand interactions are helpful to elucidating the mechanisms of ligands, providing clues for rational drug design. The currently developed steered molecular dy- namics (SMD) is a complementary approach to experimental techniques in investigating the biochemical processes occurring at microsecond or second time scale, thus SMD may provide dynamical and kinetic processes of ligand-receptor binding and unbinding, which cannot be ac- cessed by the experimental methods. In this article, the methodology of SMD is described, and the applications of SMD simulations for obtaining dynamic insights into protein-ligand interactions are illustrated through two of our own examples. One is associated with the simulations of bind- ing and unbinding processes between huperzine A and acetylcholinesterase, and the other is concerned with the unbinding process of α-APAfrom HIV-1 reverse transcriptase. | XU Yechun SHEN Jianhua LUO Xiaomin SHEN Xu CHEN Kaixian JIANG Hualiang | 2004 | Science China Chemistry2004，47，5： | 2 |
| 7 | Combination of magnesium ions and vitamin C alleviates synovitis and osteophyte formation in osteoarthritis of mice显示文摘Introduction:We previously demonstrated that magnesium ions(Mg^(2+))was a novel therapeutic alternative for osteoarthritis(OA)through promoting the hypoxia inducible factor-1α(HIF-1α)-mediated cartilage matrix synthesis.However,oxidative stress can inhibit the expression of HIF-1α,amplify the inflammation that potentially impairs the therapeutic efficacy of Mg^(2+) in OA.Vitamin(VC),a potent antioxidant,may enhance the efficacy of Mg^(2+) in OA treatment.This study aims to investigate the efficacy of combination of Mg^(2+)and VC on alleviating joint destruction and pain in OA.Material and methods:Anterior cruciate ligament transection with partial medial meniscectomy induced mice OA model were randomly received intra-articular injection of either saline,MgCl2(0.5 mol/L),VC(3 mg/ml)or MgCl2(0.5 mol/L)plus VC(3 mg/ml)at week 2 post-operation,twice weekly,for 2 weeks.Joint pain and pathological changes were assessed by gait analysis,histology,western blotting and micro-CT.Results:Mg^(2+) and VC showed additive effects to significantly alleviate the joint destruction and pain.The efficacy of this combined therapy could sustain for 3 months after the last injection.We demonstrated that VC enhanced the promotive effect of Mg^(2+) on HIF-1αexpression in cartilage.Additionally,combination of Mg^(2+) and VC markedly promoted the M2 polarization of macrophages in synovium.Furthermore,combination of Mg^(2+) and VC inhibited osteophyte formation and expressions of pain-related neuropeptides.Conclusions:Intra-articular administration of Mg^(2+)and VC additively alleviates joint destruction and pain in OA.Our current formulation may be a cost-effective alternative treatment for OA. | Hao Yao Jiankun Xu Jiali Wang Yifeng Zhang Nianye Zheng Jiang Yue Jie Mi Lizhen Zheng Bingyang Dai Wenhan Huang Shuhang Yung Peijie Hu Yechun Ruan Qingyun Xue Kiwai Ho Ling Qin | 2021 | Bioactive Materials2021，6，5： | 1 |
| 8 | Conformational transition of amyloid β-peptide显示文摘 | Yechun Xu Jianhua Shen Xiaoming Luo | 2005 | Proc Natl Acad Sci USA2005，102，： | 1 |
| 9 | The genomic and bulked segregant analysis of Curcuma alismatifolia revealed its diverse bract pigmentation显示文摘Compared with most flowers where the showy part comprises specialized leaves(petals)directly subtending the reproductive structures,most Zingiberaceae species produce showy“flowers”through modifications of leaves(bracts)subtending the true flowers throughout an inflorescence.Curcuma alismatifolia,belonging to the Zingiberaceae family,a plant species originating from Southeast Asia,has become increasingly popular in the flower market worldwide because of its varied and esthetically pleasing bracts produced in different cultivars.Here,we present the chromosome-scale genome assembly of C.alismatifolia“Chiang Mai Pink”and explore the underlying mechanisms of bract pigmentation.Comparative genomic analysis revealed C.alismatifolia contains a residual signal of whole-genome duplication.Duplicated genes,including pigment-related genes,exhibit functional and structural differentiation resulting in diverse bract colors among C.alismatifolia cultivars.In addition,we identified the key genes that produce different colored bracts in C.alismatifolia,such as F3′5'H,DFR,ANS and several transcription factors for anthocyanin synthesis,as well as chlH and CAO in the chlorophyll synthesis pathway by conducting transcriptomic analysis,bulked segregant analysis using both DNA and RNA data,and population genomic analysis.This work provides data for understanding the mechanism of bract pigmentation and will accelerate breeding in developing novel cultivars with richly colored bracts in C.alismatifolia and related species.It is also important to understand the variation in the evolution of the Zingiberaceae family. | Xuezhu Liao Yuanjun Ye Xiaoni Zhang Dan Peng Mengmeng Hou Gaofei Fu Jianjun Tan Jianli Zhao Rihong Jiang Yechun Xu Jinmei Liu Jinliang Yang Wusheng Liu Luke RTembrock Genfa Zhu Zhiqiang Wu | 2022 | aBIOTECH2022，3，3： | 1 |
| 10 | Drug discovery and development targeting the life cycle of SARS-CoV-2显示文摘A newly emerged coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),belongs to the/β-coronavirus family and shows high similarities with SARS-CoV.O n March 11,2020,the World Health Organization(WHO)declared SARS-CoV-2 a global pandemic,and the disease was named the coronavirus disease 2019(COVID-19).The ongoing COVID-19 pandemic has caused over 46 million infections and over one million deaths worldwide,and the numbers are still increasing.Efficacious antiviral agents are urgently needed to combat this virus.The life cycle of SARS-CoV-2 mainly includes the viral attachment,membrane fusion,genomic replication,assembly and budding of virions.Accordingly,drug development against SARS-CoV-2 currently focuses on blocking spike protein binding to ACE2,inhibiting viral membrane fusion with host cells,and preventing the viral replication by targeting 3C-Iike protease,papain-like protease,RNA-dependent R N A polymerase as well as some host-cell proteins.In this review,the advances of drug development in these three major areas are elaborated. | Haixia Su Yechun Xu Hualiang Jiang | 2021 | Fundamental Research2021，1，2： | 1 |
| 11 | High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors显示文摘The global COVID-19 coronavirus pandemic has infected over 109 million people,leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment.Here,we screened about 1.8 million small molecules against the main protease(M^(pro))and papain like protease(PL^(pro)),two major proteases in severe acute respiratory syndrome-coronavirus 2 genome,and identified 1851M^(pro)inhibitors and 205 PL^(pro)inhibitors with low nmol/l activity of the best hits.Among these inhibitors,eight small molecules showed dual inhibition effects on both M^(pro)and PL^(pro),exhibiting potential as better candidates for COVID-19 treatment.The best inhibitors of each protease were tested in antiviral assay,with over 40%of M^(pro)inhibitors and over 20%of PL^(pro)inhibitors showing high potency in viral inhibition with low cytotoxicity.The X-ray crystal structure of SARS-CoV-2 M^(pro)in complex with its potent inhibitor 4a was determined at 1.8Åresolution.Together with docking assays,our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development. | Yi Zang Mingbo Su Qingxing Wang Xi Cheng Wenru Zhang Yao Zhao Tong Chen Yingyan Jiang Qiang Shen Juan Du Qiuxiang Tan Peipei Wang Lixin Gao Zhenming Jin Mengmeng Zhang Cong Li Ya Zhu Bo Feng Bixi Tang Han Xie Ming-Wei Wang Mingyue Zheng Xiaoyan Pan Haitao Yang Yechun Xu Beili Wu Leike Zhang Zihe Rao Xiuna Yang Hualiang Jiang Gengfu Xiao Qiang Zhao Jia Li | 2023 | Protein & Cell2023，14，1： | 0 |
| 12 | Flavonoids from the roots and rhizomes of Sophora tonkinensis and their in vitro anti-SARS-CoV-2 activity显示文摘Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)had caused a global pandemic since 2019,and posed a serious threat to global health security.Traditional Chinese medicine(TCM)has played an indispensable role in the battle against the epidemic.Many components originated from TCMs were found to inhibit the production of SARS-CoV-23C-like protease(3CLpro)and papain-like protease(PLpro),which are two promising therapeutic targets to inhibit SARS-CoV-2.This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis,which results in the characterization of 12 new flavonoids,including seven prenylated flavanones(1−7),one prenylated flavonol(8),two prenylated chalcones(9−10),one isoflavanone(11),and one isoflavan dimer(12),together with 43 known compounds(13−55).Their structures including the absolute configurations were elucidated by comprehensive analysis of MS,1D and 2D NMR data,and time-dependent density functional theory electronic circular dichroism(TDDFT ECD)calculations.Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-23CLpro with IC_(50) values of 34.89 and 19.88μmol·L^(−1),repectively while compounds 9,43 and 47 exhibited inhibitory effects against PLpro with IC_(50) values of 32.67,79.38,and 16.74μmol·L^(−1),respectively. | LI Zhuo XIE Hang TANG Chunping FENG Lu KE Changqiang XU Yechun SU Haixia YAO Sheng YE Yang | 2023 | Chinese Journal of Natural Medicines2023，21，1： | 0 |
| 13 | Structure-based development of potent and selective type-II kinase inhibitors of RIPK1显示文摘Receptor-interacting serine/threonine-protein kinase 1(RIPK1)functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases.A number of allosteric RIPK1 inhibitors(RIPK1i)have been developed,and some of them have already advanced into clinical evaluation.Recently,selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge.Here,we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i.We also describe the structure-guided lead optimization of a potent,selective,and orally bioavailable RIPK1i,62,which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases.Collectively,62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development. | Ying Qin Dekang Li Chunting Qi Huaijiang Xiang Huyan Meng Jingli Liu Shaoqing Zhou Xinyu Gong Ying Li Guifang Xu Rui Zu Hang Xie Yechun Xu Gang Xu Zheng Zhang Shi Chen Lifeng Pan Ying Li Li Tan | 2024 | Acta Pharmaceutica Sinica B2024，14，1： | 0 |
| 14 | Novel thieno[2,3-b]quinoline-procaine hybrid molecules:A new class of allosteric SHP-1 activators evolved from PTP1B inhibitors显示文摘Small molecule activators could equally provide powerful tools as inhibitors do for interrogating cellular signal transduction.However,targeted protein activation is chemically challenging.Developing activators against Src homology region 2 domain-containing phosphatase-1(SHP-1)to block STAT3 pathway represents a promising strategy for DLBCL therapy.Here we reported a new class of thieno[2,3-b]quinolineprocaine hybrid molecules as SHP-1 allosteric activators.The representative hybrid compound 3b displayed SHP-1 activating effect with EC50 of 5.48±0.28μmol/L.Further investigations confirmed that 3b allosterically interacted with SHP-1,switched it from close to open conformation,blocked SHP-1/p-STAT3 pathway,induced apoptosis and inhibited ABC-DLBCL cell proliferation in vitro,and delayed tumor growth in the xenograft model of SU-DHL-2.Overall,this work offered a novel paradigm to develop SHP-1 allosteric activators through chemical space evolution of PTPs inhibitors,and firstly validated the therapeutic strategy that directly activating SHP-1 alone could be a potential therapy against ABC-DLBCL via blocking STAT3 pathway. | Lei Xu Xuyang Mu Minmin Liu Zhijia Wang Chao Shen Qianwen Mu Bo Feng Yechun Xu Tingjun Hou Lixin Gao Haini Jiang Jia Li Yubo Zhou Wenlong Wang | 2023 | Chinese Chemical Letters2023，34，8： | 0 |
| 15 | Multi-omics for COVID-19:driving development of therapeutics and vaccines显示文摘The ongoing COVID-19 pandemic caused by SARS-CoV-2 has raised global concern for public health and economy.The development of therapeutics and vaccines to combat this virus is continuously progressing.Multi-omics approaches,including genomics,transcriptomics,proteomics,metabolomics,epigenomics and metallomics,have helped understand the structural and molecular features of the virus,thereby assisting in the design of potential therapeutics and accelerating vaccine development for COVID-19.Here,we provide an up-to-date overview of the latest applications of multi-omics technologies in strategies addressing COVID-19,in order to provide suggestions towards the development of highly effective knowledge-based therapeutics and vaccines. | Mengyu Guo Muya Xiong Jinying Peng Tong Guan Haixia Su Yanyi Huang Cai-Guang Yang Yang Li Diana Boraschi Thanigaimalai Pillaiyar Guanbo Wang Chengqi Yi Yechun Xu Chunying Chen | 2023 | National Science Review2023，10，9： | 0 |
| 16 | Natural variation in SlSOS2 promoter hinders salt resistance during tomato domestication显示文摘Increasing soil salinization seriously impairs plant growth and development,resulting in crop loss.The Salt-Overly-Sensitive(SOS)pathway is indispensable to the mitigation of Na+toxicity in plants under high salinity.However,whether natural variations of SOS2 contribute to salt tolerance has not been reported.Here a natural variation in the SlSOS2 promoter region was identified to be associated with root Na+/K+ratio and the loss of salt resistance during tomato domestication.This natural variation contains an ABI4-binding cis-element and plays an important role in the repression of SlSOS2 expression.Genetic evidence revealed that SlSOS2 mutations increase root Na+/K+ratio under salt stress conditions and thus attenuate salt resistance in tomato.Together,our findings uncovered a critical but previously unknown natural variation of SOS2 in salt resistance,which provides valuable natural resources for genetic breeding for salt resistance in cultivated tomatoes and other crops. | Yechun Hong Xijin Guan Xu Wang Dali Kong Shuojun Yu Zhiqiang Wang Yongdong Yu Zhen-Fei Chao Xue Liu Sanwen Huang Jian-Kang Zhu Guangtao Zhu Zhen Wang | 2023 | Horticulture Research2023，10，1： | 0 |
| 17 | Structural insights into dimerization and activation of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers显示文摘Nicotinamide adenine dinucleotide(NAD+)is a central metabolite in cellular processes.Depletion of NAD+has been demonstrated to be a prevalent theme in both prokaryotic and eukaryotic immune responses.Short prokaryotic Argonaute proteins(Agos)are associated with NADase domain-containing proteins(TIR-APAZ or SIR2-APAZ)encoded in the same operon.They confer immunity against mobile genetic elements,such as bacteriophages and plasmids,by inducing NAD+depletion upon recognition of target nucleic acids.However,the molecular mechanisms underlying the activation of such prokaryotic NADase/Ago immune systems remain unknown.Here,we report multiple cryo-EM structures of NADase/Ago complexes from two distinct systems(TIR-APAZ/Ago and SIR2-APAZ/Ago).Target DNA binding triggers tetramerization of the TIR-APAZ/Ago complex by a cooperative self-assembly mechanism,while the heterodimeric SIR2-APAZ/Ago complex does not assemble into higher-order oligomers upon target DNA binding.However,the NADase activities of these two systems are unleashed via a similar closed-to-open transition of the catalytic pocket,albeit by different mechanisms.Furthermore,a functionally conserved sensor loop is employed to inspect the guide RNA–target DNA base pairing and facilitate the conformational rearrangement of Ago proteins required for the activation of these two systems.Overall,our study reveals the mechanistic diversity and similarity of Ago protein-associated NADase systems in prokaryotic immune response. | Xinwei Wang Mu Wang Tuo Xu Ye Feng Qiang Shao Shuo Han Xiaojing Chu Yechun Xu Shuling Lin Qiang Zhao Beili Wu | 2023 | Cell Research2023，33，10： | 0 |
| 18 | Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2显示文摘Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is effective against SARS-CoV-2 and COVID-19.Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2(IC50=8.26μM),while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93μM(EC50).In comparison with vehicle-treated animals,rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals.At necropsy,nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude.A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center,which were randomized(1:1)to nelfinavir and control groups,showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days(9.0 vs.14.5 days,P=0.055)and the duration of fever time by 3.8 days(2.8 vs.6.6 days,P=0.014)in mild/moderate COVID-19 patients.The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients,together with its well-established good safety profile in almost all ages and during pregnancy,indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19. | Zhijian Xu Danrong Shi Jian-Bao Han Yun Ling Xiangrui Jiang Xiangyun Lu Chuan Li Likun Gong Guangbo Ge Yani Zhang Yi Zang Tian-Zhang Song Xiao-Li Feng Ren-Rong Tian Jia Ji Miaojin Zhu Nanping Wu Chunhui Wu Zhen Wang Yechun Xu Cheng Peng Min Zheng Junling Yang Feifei Du Junliang Wu Peipei Wang Jingshan Shen Jianliang Zhang Yong-Tang Zheng Hangping Yao Weiliang Zhu | 2023 | Signal Transduction and Targeted Therapy2023，8，5： | 0 |
| 19 | An alternative splicing variant of mineralocorticoid receptor discovered in preeclampsia tissues and its effect on endothelial dysfunction显示文摘The pathophysiology of preeclampsia(PE)remains unclear.PE spiral artery remodeling dysfunction and PE offspring cardiovascular future development has been a worldwide concern.We collected placental and umbilical artery samples from normotensive and PE pregnancies.Mineralocorticoid receptor(MR)and its alternative splicing variant(ASV)expression and their biological effects on PE were examined.An MR ASV was found to be highly expressed in all PE samples and slightly expressed in about half of the normotensive samples(umbilical artery,~57.58%;placenta,~36.84%).The MR ASV expression was positively associated with blood pressure in both groups.The MR ASV protein changed the aldosterone-induced expression pattern of MR target genes related to ion exchanges and cell signaling pathways.The MR ASV can also impair the proliferation,migration,and tube formation ability of endothelial cells.These findings indicate that MR ASV in PE placenta plays a pathogenic role in PE pathophysiology,especially in endothelial dysfunction,and the existence of the MR ASV in PE umbilical artery provides a new direction in the study of PE offspring with increased risk of cardiovascular diseases. | Mengxi Guo Chengliang Zhou Gufeng Xu Lin Tang Yechun Ruan Ying Yu Xianhua Lin Dandan Wu Hao Chen Priscilla Yu Luyang Jin Yinyu Wang Yimei Wu Kamran Ullah Tanzil Ur Rahman Xinmei Liu Jianzhong Sheng Hsiao-Chang Chan Hefeng Huang | 2020 | Science China(Life Sciences)2020，63，3： | 0 |
| 20 | Experimental investigation on separation characteristics of axial cyclone separator显示文摘Axial cyclone separator has been widely applied in chemical production as an efficient gas-liquid separation device.In this study,a new axial cyclone separator with integrated swirler and exhaust pipe is designed to achieve the development goal of compact structure for advanced engine,and the distribution characteristics of swirling flow patterns as well as the variation in separation characteristics are investigated under slug flow pattern.Based on flow visualizations and fluctuation characteristics of pressure signals,three typical flow patterns,namely,slug flow,swirling intermittent flow,and swirling annular flow,in the horizontal swirling separation flow are characterized.It is investigated how the inlet conditions affect the separation characteristic parameters.The separation purity and extreme points of the air separation efficiency are independent of the inlet liquid flow rate.The separation pressure drop is quadratically related to the inlet air flow rate.Based on the drift-flux model and other methods,the prediction methods for the air separation efficiency and pressure drop are proposed,and the prediction accuracy is within±20%,which may provide instructions for the practical application of axial cyclone separator. | WANG JinZhi WANG YeChun HAN JinZai XU Qiang XIE XiangDong PAN YingXiu GUO LieJin | 2023 | Science China(Technological Sciences)2023，66，11： | 0 |
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