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| 1 | Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression显示文摘Recently,increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease(AD)progression,yet the role of gut microbiota in AD pathogenesis remains obscure.Herein,we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression.Using AD mouse models,we discovered that,during AD progression,the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine,which stimulates the differentiation and proliferation of pro-inflammatory T helper 1(Thl)cells.The brain-infiltrated peripheral Th1 immune cells are associated with the Ml microglia aaivation,contributing to AD-associated neuroinflammation.Importantly,the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment(MCI)due to AD.Furthermore,GV-971,a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China,suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation,harnesses neuroinflammation and reverses the cognition impairment.Together,our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota. | Xinyi Wang Guangqiang Sun Teng Feng Jing Zhang Xun Huang Tao Wang Zuoquan Xie Xingkun Chu Jun Yang Huan Wang Shuaishuai Chang Yanxue Gong Lingfei Ruan Guanqun Zhang Siyuan Yan Wen Lian Chen Du Dabing Yang Qingli Zhang Feifei Lin Jia Liu Haiyan Zhang Changrong Ge Shifu Xiao Jian Ding Meiyu Geng | 2019 | Cell Research2019，29，10： | 192 |
| 2 | Inhibition of gasdermin D-dependent pyroptosis attenuates the progression of silica-induced pulmonary inflammation and fibrosis显示文摘Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide,but the molecular basis underlying its development remains unclear.An accumulating body of evidence supports gasdermin D(GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases.However,there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis.In this work,we investigated the role of GSDMD-mediated pyroptosis in silicosis.Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression.Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica.Measurement of interleukin-1βrelease,lactic dehydrogenase activity,and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages.Additionally,we verified that both canonical(caspase-1-mediated)and non-canonical(caspase-4/5/11-mediated)signaling pathways mediated silica-induced pyroptosis activation,in vivo and in vitro.Notably,Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes,which highlighted the pivotal role of pyroptosis in this disease.Taken together,our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis. | Meiyue Song Jiaxin Wang Youliang Sun Junling Pang Xiaona Li Yuan Liu Yitian Zhou Peiran Yang Tianhui Fan Ying Liu Zhaoguo Li Xianmei Qi Baicun Li Xinri Zhang Jing Wang Chen Wang | 2022 | Acta Pharmaceutica Sinica B2022，12，3： | 5 |
| 3 | Antidepressant-like effect of active fraction of Polyrhachisvicina Roger in a rat depression model显示文摘OBJECTIVE: To investigate the antidepressant-likeeffect of active fraction of Polyrhachis vicina Roger(AFPR) in a rat depression model, and to elucidate the underlying mechanism.METHODS: AFPR was extracted with ethanol followed by petroleum ether. Its antidepressant-like effect was investigated in mice by tail suspension test(TST), forced swimming test(FST) and open field test(OPT). A repeated dose of reserpine(0.5 mg/kg, daily for 14 d) was used to establish a rat depression model. Fluoxetine was used as positive control agent. The effect of AFPR on reserpine-induced ptosis, hypothermia and akinesia, the levels of monoamines and their metabolites, and the activity of monoamine oxidase(MAO) in hippocampus and prefrontal cortex were determined.RESULTS: Administration of AFPR by gavage at 160 and 320 mg/kg significantly reduced the duration of immobility in the FST and TST, and did not affect locomotor activity in the OPT. In the reserpine-induced depression model, AFPR attenuated anhedonia, demonstrated by reversing hypothermia, akinesia and sucrose consumption. AFPR significantly increased the concentration of monoamines, including dopamine, serotonin, noradrenaline and acetylcholine.CONCLUSION: AFPR normalized the metabolism rates of noradrenaline, serotonin and dopamine,and the activity of MAO, which were altered by chronic reserpine exposure. The findings suggest that modulation of the monoaminergic neurotransmitter system likely underlies the antidepressant-like effect of AFPR. | Wei Guining Chu Shifeng Su Qibiao Su Hua Lin Meiyu He Fei Lu Wenjie Lu Guoshou Huang Zhoufeng Tan Xiao Lin Xiao Zeng Xianbiao Wei Baowei Chen Naihong | 2018 | Journal of Traditional Chinese Medicine2018，38，1： | 4 |
| 4 | Efficacy of Lidan Tang on high-fat-diet induced gallstone in mice and possible mechanism显示文摘OBJECTIVE:To investigate efficacy of Lidan Tang(LDT)on gallstone induced by high fat diet in mice,and to study its underlying mechanism.METHODS:Mice were fed with high fat diet every day and treated with LDT(9.01 times of human clinic dosage).Mice were randomly divided into 6 groups as control group,gallstone model group(high-fat diet),positive control ursodeoxycholic acid(UDCA)group(80 mg·kg^-1·d^-1,i.g.),LDT low dose group(6 kg/d,i.g.),LDT middle dose group(12 kg/d,i.g.),and LDT high dose group(24 kg/d,i.g.).The whole experiment was lasted for 4 weeks.The levels of ALT,AST,LDH,CHO,HDL-C and LDL-C in serum were measured,the pathological sections were observed by hematoxylin-eosin staining,the activities of antioxidant enzymes were measured by kits,and the proteins related to oxidative stress and lipid transport were detected by Western blot analysis.RESULTS:LDT could significantly reduce the contents of ALT and AST in serum and improve the pathological tissue of liver.LDT could significantly reduce the content of MDA and LPO,and increase the level of GSH and GSH-PX in liver tissue.The data of Western blot showed that LDT had antioxidant effect promoting Keap1/Nrf2 pathway and regulated the process of lipid transport,which was statistically significant.In addition,LDT treatment inhibited the expression of ATP-binding cassette transports ABCG5/8 in liver,and reduced cholesterol transport from the hepatocytes to the gallbladder.CONCLUSION:LDT has protective effect on gallstones induced by high fat diet in mice,which might be based on the protective effect on liver,including enhancing the antioxidant capacity of liver and reducing the production of lipid peroxides. | Gao Yan Liu Caipin Li Juntong Zhai Yingying Lin Meiyu Wu Qinglin Chu Shifeng Zhang Zhao Li Jianping Zhou Xin Li Yueting Chen Naihong | 2020 | Journal of Traditional Chinese Medicine2020，40，4： | 4 |
| 5 | Tetrahydroisoquinolines as novel histone deacetylase inhibitors for treatment of cancer显示文摘Histone acetylation is a critical process in the regulation of chromatin structure and gene expression.Histone deacetylases(HDACs)remove the acetyl group,leading to chromatin condensation and transcriptional repression.HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects.This paper describes our work on the structural determination and structure-activity relationship(SAR)optimization of tetrahydroisoquinoline compounds as HDAC inhibitors.These compounds were tested for their ability to inhibit HDAC 1,3,6 and for their ability to inhibit the proliferation of a panel of cancer cell lines.Among these,compound 82 showed the greatest inhibitory activity toward HDAC 1,3,6 and strongly inhibited growth of the cancer cell lines,with results clearly superior to those of the reference compound,vorinostat(SAHA).Compound 82 increased the acetylation of histones H3,H4 and tubulin in a concentration-dependent manner,suggesting that it is a broad inhibitor of HDACs. | Danqi Chen Aijun Shen Guanghua Fang Hongchun Liu Minmin Zhang Shuai Tang Bing Xiong Lanping Ma Meiyu Geng Jingkang Shen | 2016 | Acta Pharmaceutica Sinica B2016，6，1： | 4 |
| 6 | Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants显示文摘Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic antibodies.In this study,12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries.Of them,two RBD-binding antibodies(F61 and H121)showed high-affinity neutralization against SARS-Co V-2,whereas three S2-target antibodies failed to neutralize SARS-Co V-2.Following structure analysis,F61 identified a linear epitope located in residues G446–S494,which overlapped with angiotensinconverting enzyme 2(ACE2)binding sites,while H121 recognized a conformational epitope located on the side face of RBD,outside from ACE2 binding domain.Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-Co V-2.Importantly,these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351,and reacted with mutations of N501 Y,E484 K,and L452 R,indicated that it may also neutralize the recent India endemic strain B.1.617.The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants,which mitigated the risk of viral escape.Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-Co V-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-Co V-2 variants. | Yuanyuan Qu Xueyan Zhang Meiyu Wang Lina Sun Yongzhong Jiang Cheng Li Wei Wu Zhen Chen Qiangling Yin Xiaolin Jiang Yang Liu Chuan Li Jiandong Li Tianlei Ying Dexin Li Faxian Zhan Youchun Wang Wuxiang Guan Shiwen Wang Mifang Liang | 2021 | Virologica Sinica2021，36，5： | 3 |
| 7 | Discovery of a series of dimethoxybenzene FGFR inhibitors with 5H-pyrrolo[2,3-b]pyrazine scaffold: structure–activity relationship, crystal structural characterization and in vivo study显示文摘Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors(FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure–activity relationship was elaborated. Together with in vitro metabolic stability tests and in vivo pharmacokinetic profiling, a representative compound(35) was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor 35 was effective against tumors with FGFR genetic alterations, exhibiting potential for further development. | Peng Wei Bo Liu Ruifeng Wang Yinglei Gao Lanlan Li Yuchi Ma Zhiwei Qian Yuelei Chen Maosheng Cheng Meiyu Geng Jingkang Shen Dongmei Zhao Jing Ai Bing Xiong | 2019 | Acta Pharmaceutica Sinica B2019，9，2： | 2 |
| 8 | Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome (AIDS) drug candidate, targeting CD4 in lymphocytes显示文摘 | Benchun Miao Meiyu Geng Jing Li Fuchuan Li Haixia Chen Huashi Guan Jian Ding | 2004 | Biochemical Pharmacology2004，，4： | 1 |
| 9 | The preparation and characterization of Au@ TiO2 nanoparticles and their catalytic activity for CO oxidationCatalysis显示文摘 | Chen Yinglei Zhu Baolin Yao Meiyu | | 0，，12： | 1 |
| 10 | Detection of faviviruses by reverse transcriptase-polymerase chain reaction with the universal primer set 显示文摘 | Fang Meiyu Chen Huosheng Chen Cuihua | 1997 | Microbiol Immunol1997，41，： | 1 |
| 11 | GmPIN1-mediated auxin asymmetry regulates leaf petiole angle and plant architecture in soybean显示文摘Crop breeding during the Green Revolution resulted in high yields largely due to the creation of plants with semi-dwarf architectures that could tolerate high-density planting.Although semi-dwarf varieties have been developed in rice,wheat and maize,none was reported in soybean(Glycine max),and few genes controlling plant architecture have been characterized in soybean.Here,we demonstrate that the auxin efflux transporter PINFORMED1(GmPIN1),which determines polar auxin transport,regulates the leaf petiole angle in soybean.CRISPR-Cas9-induced Gmpin1abc and Gmpin1bc multiple mutants displayed a compact architecture with a smaller petiole angle than wildtype plants.GmPIN1 transcripts and auxin were distributed asymmetrically in the petiole base,with high levels of GmPIN1a/c transcript and auxin in the lower cells,which resulted in asymmetric cell expansion.By contrast,the(iso)flavonoid content was greater in the upper petiole cells than in the lower cells.Our results suggest that(iso)flavonoids inhibit GmPIN1a/c expression to regulate the petiole angle.Overall,our study demonstrates that a signal cascade that integrates(iso)flavonoid biosynthesis,GmPIN1a/c expression,auxin accumulation,and cell expansion in an asymmetric manner creates a desirable petiole curvature in soybean.This study provides a genetic resource for improving soybean plant architecture. | Zhongqin Zhang Le Gao Meiyu Ke Zhen Gao Tianli Tu Laimei Huang Jiaomei Chen Yuefeng Guan Xi Huang Xu Chen | 2022 | Journal of Integrative Plant Biology2022，64，7： | 1 |
| 12 | Determination of Multiple Pesticide Residues in Honey Using Gas Chromatography-Electron Impact Ionization-Mass Spectrometry显示文摘 | Zhen JIN Zhuguang LIN Meiyu CHEN Yu MA Jun TAN Yulan FAN Jiachen WEN Zhaobin CHEN Fengzhang TU | 2006 | Chinese Journal of Chromatography2006，，5： | 1 |
| 13 | Pharmacokinetics,distribution,and excretion of sodium oligomannate,a recently approved anti-Alzheimer's disease drug in China显示文摘The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer’s disease.In this study,an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices.The plasma pharmacokinetics,tissue distribution,and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were systematically investigated.Despite its complicated structural composition,the absorption,distribution,metabolism,and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate.Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration,with very low oral bioavailability in rats(0.6%-1.6%)and dogs(4.5%-9.3%).Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues.Sodium oligomannate could penetrate the blood-cerebrospinal fluid(CSF)barrier of rats,showing a constant area under the concentration-time curve ratio(CSF/plasma)of approximately 5%.The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability,supporting that excretion was predominantly renal,whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats.Moreover,only 33.7%(male)and 26.3%(female)of the oral dose were recovered in the rat excreta within 96 h following a single oral administration,suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient. | Jiaojiao Lu Qiongqun Pan Jieqiang Zhou Yan Weng Kaili Chen Lv Shi Guanxiu Zhu Chunlin Chen Liang Li Meiyu Geng Zhenqing Zhang | 2022 | Journal of Pharmaceutical Analysis2022，12，1： | 1 |
| 14 | Cloning, characterization, and expression analysis of hepcidin gene from red sea bream (Chrysophrys major) 显示文摘 | CHEN Songlin XU Meiyu JI Xiangshan | 2005 | Antimi- crobial agents and chemotherapy2005，49，4： | 1 |
| 15 | Evaluation of the Rural Human Settlement in Shandong Province显示文摘Taking Shandong Province as the research object,this paper uses the principal component analysis method to evaluate the status of the rural human settlement in Shandong Province.It establishes the evaluation index system of the rural residential environment in Shandong Province,including living environment,economy,infrastructure,public service facilities,and ecological environment,in total five comprehensive index,and 20 secondary indexes.Through measurement and sorting of rural human environment development level of Shandong Province in 2010,the 17 cities are divided into-excellent,good,ordinary,poor-four development areas and are analyzed based on the restriction factor in the development of the region. | Xu Hong Shen Meiyu Chen Xiangxiang | 2012 | Chinese Journal of Population,Resources and Environment2012，10，4： | 1 |
| 16 | The structure of compact yarn显示文摘 | WU Hui CHEN Meiyu WANG Wei | 2009 | Textile Research Journal2009，79，9： | 1 |
| 17 | Molecular polymorphism and expression analysis of MHC class Ⅱ B gene from red sea bream(Chrysophrys major)显示文摘 | Chen Songlin Zhang Yuxi Xu Meiyu | 2006 | Developmental and Comparative Immunology2006，30，： | 1 |
| 18 | Gefitinib and fostamatinib target EGFR and SYK to attenuate silicosis:a multi-omics study with drug exploration显示文摘Silicosis is the most prevalent and fatal occupational disease with no effective therapeutics,and currently used drugs cannot reverse the disease progress.Worse still,there are still challenges to be addressed to fully decipher the intricated pathogenesis.Thus,specifying the essential mechanisms and targets in silicosis progression then exploring anti-silicosis pharmacuticals are desperately needed.In this work,multi-omics atlas was constructed to depict the pivotal abnormalities of silicosis and develop targeted agents.By utilizing an unbiased and time-resolved analysis of the transcriptome,proteome and phosphoproteome of a silicosis mouse model,we have verified the significant differences in transcript,protein,kinase activity and signaling pathway level during silicosis progression,in which the importance of essential biological processes such as macrophage activation,chemotaxis,immune cell recruitment and chronic inflammation were emphasized.Notably,the phosphorylation of EGFR(p-EGFR)and SYK(pSYK)were identified as potential therapeutic targets in the progression of silicosis.To inhibit and validate these targets,we tested fostamatinib(targeting SYK)and Gefitinib(targeting EGFR),and both drugs effectively ameliorated pulmonary dysfunction and inhibited the progression of inflammation and fibrosis.Overall,our drug discovery with multi-omics approach provides novel and viable therapeutic strategies for the treatment of silicosis. | Mingyao Wang Zhe Zhang Jiangfeng Liu Meiyue Song Tiantian Zhang Yiling Chen Huiyuan Hu Peiran Yang Bolun Li Xiaomin Song Junling Pang Yanjiang Xing Zhujie Cao Wenjun Guo Hao Yang Jing Wang Juntao Yang Chen Wang | 2022 | Signal Transduction and Targeted Therapy2022，7，6： | 1 |
| 19 | Eupalinolide B inhibits hepatic carcinoma by inducing ferroptosis and ROS-ER-JNK pathway显示文摘Primary hepatic carcinoma is a common malignant tumor.The classic molecular targeted drug sorafenib is costly and is only effective for some patients.Therefore,it is of great clinical significance to search for new molecular targeted drugs.Eupalinolide B(EB)from Eupatorium lindleyanum DC.is used to treat chronic tracheitis in clinical practice.However,the role of EB in hepatic carcinoma is unknown.In this study,we first measure the effect of EB on tumor growth in a xenograft model and PDX model.The cell proliferation and migration are also detected in human hepatocarcinoma cell lines(SMMC-7721 and HCCLM3).Then,we investigate cell cycle,cell apoptosis,cell necrosis,cell autophagy,and ferroptosis by flow cytometry,western blot analysis and electron microscopy.The results demonstrate that EB exerts anti-proliferative activity in hepatic carcinoma by blocking cell cycle arrest at S phase and inducing ferroptosis mediated by endoplasmic reticulum(ER)stress,as well as HO-1 activation.When HO-1 is inhibited,EB-induced cell death and ER protein expression are rescued.The migration-related mechanism consists of activation of the ROS-ER-JNK signaling pathway and is not connected to ferroptosis.In summary,we first discover that EB inhibits cell proliferation and migration in hepatic carcinoma,and thus EB is a promising anti-tumor compound that can be used for hepatic carcinoma. | Yonghui Zhang Haoyang Zhang Jinage Mu Meiyue Han Zhihao Cao Feng Dong Tingting Wang Lian Pan Wujing Luo Jiaxin Li Huan Liu Lishan Jin Wenxuan Ding Yong Wei Xuesong Deng Dan Liu Xiuzhen He Yi Pang Xiao Mu Zhongjun Wu Dilong Chen | 2022 | Acta Biochimica et Biophysica Sinica2022，54，7： | 1 |
| 20 | Light-modulated vertical heterojunction phototransistors with distinct logical photocurrents显示文摘The intriguing carrier dynamics in graphene heterojunctions have stimulated great interest in modulating the optoelectronic features to realize high-performance photodetectors.However,for most phototransistors,the photoresponse characteristics are modulated with an electrical gate or a static field.In this paper,we demonstrate a graphene/C_(60)/pentacene vertical phototransistor to tune both the photoresponse time and photocurrent based on light modulation.By exploiting the power-dependent multiple states of the photocurrent,remarkable logical photocurrent switching under infrared light modulation occurs in a thick C_(60) layer(11 nm)device,which implies competition of the photogenerated carriers between graphene/C_(60) and C_(60)/pentacene.Meanwhile,we observe a complete positive-negative alternating process under continuous 405 nm irradiation.Furthermore,infrared light modulation of a thin C_(60)(5 nm)device results in a photoresponsivity improvement from 3425 A/W up to 7673 A/W,and we clearly probe the primary reason for the distinct modulation results between the 5 and 11 nm C_(60) devices.In addition,the tuneable bandwidth of the infrared response from 10 to 3×10^(3) Hz under visible light modulation is explored.Such distinct types of optical modulation phenomena and logical photocurrent inversion characteristics pave the way for future tuneable logical photocurrent switching devices and high-performance phototransistors with vertical graphene heterojunction structures. | Jiayue Han Meiyu He Ming Yang Qi Han Fang Wang Fang Zhong Mengjian Xu Qing Li He Zhu Chongxin Shan Weida Hu Xiaoqing Chen Xinran Wang Jun Gou Zhiming Wu Jun Wang | 2020 | Light(Science & Applications)2020，9，1： | 1 |
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