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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 | Cold-chain food contamination as the possible origin of COVID-19 resurgence in Beijing显示文摘COVID-19,caused by SARS-CoV-2[1,2],has been contained in China through stringent non-pharmaceutical interventions.Border control and quarantine have effectively prevented the virus from being spread by infected travellers,but the risk of resurgence caused by other routes of introduction and transmission remains unclear,and current strategies to prevent resurgence could be flawed.Since July,SARS-CoV-2 RNA contaminations in frozen food imported from countries with ongoing epidemics have been reported in nine provinces in China[3,4].However,there is no robust evidence of COVID-19 outbreaks initiated by environmentto-human transmission.Here we add to evidence of such transmission by investigating the recent COVID-19 resurgence in Beijing. | Xinghuo Pang Lili Ren Shuangsheng Wu Wentai Ma Jian Yang Lin Di Jie Li Yan Xiao Lu Kang Shichang Du Jing Du Jing Wang Gang Li Shuguang Zhai Lijuan Chen Wenxiong Zhou Shengjie Lai Lei Gao Yang Pan Quanyi Wang Mingkun Li Jianbin Wang Yanyi Huang Jianwei Wang COVID-19 Field Response Group COVID-19 Laboratory Testing Group | 2020 | National Science Review2020，7，12： | 51 |
| 3 | Characterization of the receptor-binding domain(RBD)of 2019 novel coronavirus:implication for development of RBD protein as a viral attachment inhibitor and vaccine显示文摘The outbreak of Coronavirus Disease 2019(COVID-19)has posed a serious threat to global public health,calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),also known as 2019 novel coronavirus(2019-nCoV).The CoV spike(S)protein plays the most important roles in viral attachment,fusion and entry,and serves as a target for development of antibodies,entry inhibitors and vaccines.Here,we identified the receptor-binding domain(RBD)in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2(ACE2)receptors.SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and,hence,attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells,thus inhibiting their infection to host cells.SARS-CoV RBD-specific antibodies could crossreact with SARS-CoV-2 RBD protein,and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2,suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection. | Wanbo Tai Lei He Xiujuan Zhang Jing Pu Denis Voronin Shibo Jiang Yusen Zhou Lanying Du | 2020 | Cellular & Molecular Immunology2020，17，6： | 35 |
| 4 | The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome显示文摘MicroRNAs(miRNAs)are a novel class of small,non-coding RNAs that play a significant role in both inflammatory and cardiovascular diseases.Immune cells,especially T helper(Th)cells,are critical in the development of atherosclerosis and the onset of acute coronary syndrome(ACS).To assess whether inflammation-related miRNAs(such as miR-155,146a,21,125a-5p,125b,31)are involved in the imbalance of Th cell subsets in patients with ACS,we measured the expression of related miRNAs in patients with acute myocardial infarction(AMI),unstable angina(UA),stable angina(SA)and chest pain syndrome(CPS);analyzed the relationship between miRNA expression and the frequency of Th cell subsets;and observed the co-expression of miR-155 and IL-17A in peripheral blood mononuclear cells(PBMCs)of patients with ACS.The results showed that the expression of miR-155 in the PBMCs of patients with ACS was decreased by approximately 60%,while the expression of both miR-21 and miR-146a was increased by approximately twofold.The expression patterns of miRNAs in plasma correlated with those in PBMCs,except for miR-21,which was increased by approximately sixfold in the AMI group and showed no significant difference between the UA group and the CPS group.We also found that the expression of miR-155 inversely correlated with the frequency of Th17 cells(r520.896,P,0.01)and that miR-155 was co-expressed with IL-17A in patients with ACS.In conclusion,our study revealed the expression patterns of inflammation-related miRNAs in patients with ACS and found that miR-155 may be associated with Th17 cell differentiation. | Rui Yao Yulan Ma Youyou Du Mengyang Liao Huanhuan Li Wei Liang Jing Yuan Zhijun Ma Xian Yu Hong Xiao Yuhua Liao | 2011 | Cellular & Molecular Immunology2011，8，6： | 32 |
| 5 | Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence worldwide.Multiple efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibitors,immune based therapies and combination of chemotherapy.However,limitations exist in current strategies including chemoresistance for instance.Tumor initiation and progression is driven by reprogramming of metabolism,in particular during HCC development.Recently,metabolic associated fatty liver disease(MAFLD),a reappraisal of new nomenclature for nonalcoholic fatty liver disease(NAFLD),indicates growing appreciation of metabolism in the pathogenesis of liver disease,including HCC,thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment.In this review,we introduce directions by highlighting the metabolic targets in glucose,fatty acid,amino acid and glutamine metabolism,which are suitable for HCC pharmaceutical intervention.We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment.Furthermore,opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed. | Danyu Du Chan Liu Mengyao Qin Xiao Zhang Tao Xi Shengtao Yuan Haiping Hao Jing Xiong | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 27 |
| 6 | Progresses on microwave remote sensing of land surface parameters显示文摘Highly accurate observations at various scales on the land surface are urgently needed for the studies of many areas,such as hydrology,meteorology,and agriculture.With the rapid development of remote sensing techniques,remote sensing has had the capacity of monitoring many factors of the Earth's land surface.Especially,the space-borne microwave remote sensing systems have been widely used in the quantitative monitoring of global snow,soil moisture,and vegetation parameters with their all-weather,all-time observation capabilities and their sensitivities to the characteristics of land surface factors.Based on the electromagnetic theories and microwave radiative transfer equations,researchers have achieved great successes in the microwave remote sensing studies for different sensors in recent years.This article has systematically reviewed the progresses on five research areas including microwave theoretical modeling,microwave inversion on soil moisture,snow,vegetation and land surface temperatures.Through the further enrichment of remote sensing datasets and the development of remote sensing theories and inversion techniques,remote sensing including microwave remote sensing will play a more important role in the studies and applications of the Earth systems. | SHI JianCheng DU Yang DU JinYang JIANG LingMei CHAI LinNa MAO KeBiao XU Peng NI WenJian XIONG Chuan LIU Qiang LIU ChenZhou GUO Peng CUI Qian LI YunQing CHEN Jing WANG AnQi LUO HeJia WANG YinHui | 2012 | Science China Earth Sciences2012，55，7： | 24 |
| 7 | Z-ligustilide attenuates lipopolysaccharide-induced proinflammatory response via inhibiting NF-KB pathway in primary rat microglia显示文摘 | Jing WANG Jun-rong DU Yu WANG Xi KUANG Cheng-yuan WANG | 2010 | Acta Pharmacologica Sinica2010，31，7： | 22 |
| 8 | Superhydrophobicity of Bionic Alumina Surfaces Fabricated by Hard Anodizing显示文摘 | Jing Li Feng Du Xianli Liu Zhonghao Jiang Luquan Ren | 2011 | Journal of Bionic Engineering2011，8，4： | 19 |
| 9 | Electroacupuncture induces acute changes in cerebral cortical mi RNA profile, improves cerebral blood flow and alleviates neurological deficits in a rat model of stroke显示文摘Electroacupuncture has been shown to improve cerebral blood flow in animal models of stroke. However, it is unclear whether electroacupuncture alters mi RNA expression in the cortex. In this study, we examined changes in the cerebral cortical mi RNA profile, cerebral blood flow and neurological function induced by electroacupuncture in a rat model of stroke. Electroacupuncture was performed at Renzhong(GV26) and Neiguan(PC6), with a frequency of 2 Hz, continuous wave, current intensity of 3.0 m A, and stimulation time of 1 minute. Electroacupuncture increased cerebral blood flow and alleviated neurological impairment in the rats. mi RNA microarray profiling revealed that the vascular endothelial growth factor signaling pathway, which links cell proliferation with stroke, was most significantly affected by electroacupuncture. Electroacupuncture induced changes in expression of rno-mi R-206-3p, rno-mi R-3473, rno-mi R-6216 and rno-mi R-494-3p, and these changes were confirmed by quantitative real-time polymerase chain reaction. Our findings suggest that changes in cell proliferation-associated mi RNA expression induced by electroacupuncture might be associated with the improved cerebral blood supply and functional recovery following stroke. | Hai-zhen Zheng Wei Jiang Xiao-feng Zhao Jing Du Pan-gong Liu Li-dan Chang Wen-bo Li Han-tong Hu Xue-min Shi | 2016 | Neural Regeneration Research2016，11，12： | 19 |
| 10 | Effect of electroacupuncture on expression of Ang/Tie-2 mRNA and protein in rats with acute cerebral infarction显示文摘OBJECTIVE: To identify the intervention mechanism of the effect of electroacupuncture on the expression of Ang/Tie-2 m RNA and protein in rats with acute cerebral infarction induced by middle cerebral artery occlusion(MCAO).METHODS: Altogether 120 Wistar rats were subjected to MCAO by inserting a nylon filament, andthen divided into 3 groups: control group, injured group and electroacupuncture group. The injured and electroacupuncture groups were further divided into the following 7 subgroups according to the time after MCAO: 3, 6, 12, 24 h, 3, 7 and 12 d, with 8 rats in each subgroup. The electroacupuncture group was given electroacupuncture treatment at Shuigou(GV 26) instantly after operation. The rats were killed at different time points according to their groups, and then the expression levels of Ang/Tie-2 m RNA and protein were detected using Real-Time polymerase chain reaction and immunohistochemical staining.RESULTS: The m RNA and protein expression levels of Ang/Tie-2 in the electroacupuncture group were significant higher than that in the injured group.CONCLUSION: The results suggested that electroacupuncture could significantly regulate the expression of Ang/Tie-2 m RNA and protein in the rats with acute cerebral infarction induced by MCAO, and enhance angiogenesis after ischemic penumbra. | Li Jing Bai Zonglu Du Yuanhao Li Yongfeng Zhang Xuezhu Pang Bo Zhang Jingjing | 2017 | Journal of Traditional Chinese Medicine2017，37，5： | 17 |
| 11 | 2D DEM simulation of particle mixing in rotating drum: A parametric study显示文摘Mixing behaviors of equal-sized glass beads in a rotating drum were investigated by both DEM simulations and experiments. The experiments indicated that higher rotation speed can significantly enhance mixing. The particle profiles predicted by 2D DEM simulation were compared with the experimental results from a quasi-2D drum, showing inconsistency due to reduction of contacts in the single-layer 2D simulation which makes the driving friction weaker than that in the quasi-2D test, better results could be reached by specifying a higher frictional coefficient between the particles and the cylinder wall. In order to explore the influences of physical properties (density, size or friction) on mixing behavior, numerical 2D simulations were carried out systematically, in which one examined specific property being examined was exaggerated while the others were kept the same as that in the control group. The DEM simulations reveal that particle density and size are the dominating factors affecting mixing behaviors, while the effect of frictional coefficient is less significant. However, segregation due to any of the factors can be diminished by specifying a proper particle size distribution (multi-size with lower size ratio). | Yong Xu Chunhui Xu Zhe Zhou Jing Du Daping Hu | 2010 | Particuology2010，8，2： | 16 |
| 12 | Lipid levels in serum and cancerous tissues of colorectal cancer patients显示文摘AIM:To investigate the correlations between lipid metabolism disorder and the occurrence and development of colorectal cancer by monitoring the alterations in lipid levels in cancerous tissue and serum in patients with colorectal cancer.METHODS:The levels of total and free cholesterol(TCH and FCH),triglycerides(TG),low density lipoprotein-cholesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C),apolipoprotein A1(ApoA-1)and ApoB in serum of 206 patients with colorectal cancer,70patients with benign colorectal disease and 300 healthy participants,and in the cancerous tissue and paracancerous tissue of 152 patients with colorectal cancer were measured with an Olympus 600 auto-biochemical analyzer.The obtained data were statistically analyzed.RESULTS:Serum FCH level was significantly higher(1.9±0.4 mmol/L vs 1.3±0.3 mmol/L,1.9±0.4 mmol/L vs 1.2±0.4 mmol/L,P<0.05),whereas serum levels of TCH,LDL-C,ApoA-I and ApoB were significantly lower in patients with colorectal cancer than in patients with benign colorectal disease and healthy controls.The levels of FCH and TG in cancerous tissue were significantly lower(14.5±9.6μmol/g vs 19.3±13.9μmol/g,P<0.05;16.3±19.8μmol/g vs 44.1±38.1μmol/g,P<0.05),whereas HDL-C level was significantly higher(7.9±4.5μmol/g vs 5.7±3.9μmol/g,P<0.01)in cancerous tissue than in paracancerous tissue.The levels of TCH and TG in serum and the levels of TCH and HDL-C in cancerous tissue in patients with colorectal cancer were significantly correlated with TNM stage.The levels of TCH and LDL-C in serum were significantly lower,whereas HDL-C level in cancerous tissue was significantly higher in patients with lymph node metastasis than in patients without lymph node metastasis.The levels of TCH,FCH,TG,HDL-C and LDL-C in cancerous tissue were not significantly different from those in paracancerous tissue.The serum levels of FCH and TG were significantly higher,whereas serum HDL-C levels were significantly lower in patients with rectum cancer than in patients with colon cancer.CONCLUSION:The disordered and abnormally altered levels of lipids in cancerous tissue and serum of patients with colorectal cancer may be correlated with the occurrence and development of colorectal cancer. | Xin Zhang Xian-Wen Zhao Dong-Bo Liu Cun-Zhi Han Li-Li Du Jie-Xiang Jing Yan Wang | 2014 | World Journal of Gastroenterology2014，20，26： | 16 |
| 13 | Baseline Naive CD4+ T-cell Level Predicting Immune Reconstitution in Treated HIV-infected Late Presenters显示文摘 | Fu-Ping Guo Yi-Jia Li Zhi-Feng Qiu Wei Lv Yang Han Jing Xie Yan-Ling Li Xiao-Jing Song Shan-Shan Du Vikram Mehraj Tai-Sheng Li Jean-Pierre Routy | 2016 | Chinese Medical Journal2016，，22： | 16 |
| 14 | Optimum interval time of programmed intermittent epidural bolus of ropivacaine 0.08%with sufentanyl 0.3 mg/mL for labor analgesia:a biased-coin up-and-down sequential allocation trial显示文摘Background:The programmed intermittent epidural bolus(PIEB)technique is widely used in labor analgesia,but the parameter settings of PIEB have not yet been standardized.We designed a study to identify the optimal interval duration for PIEB using 10 mL of ropivacaine 0.08%and sufentanyl 0.3 mg/mL,a regimen commonly used to control labor pain in China,to provide effective analgesia in 90%of women during the first stage of labor without breakthrough pain.Methods:We conducted a double-blind sequential allocation trial to obtain the effective interval 90%(EI90%)during the first stage of labor between April 2019 and May 2019.This study included the American Society of Anesthesiologists physical status II–III nulliparous parturients at term,who requested epidural analgesia.The bolus volume was fixed at 10 mL of ropivacaine 0.08%with sufentanyl 0.3 mg/mL.Participants were divided into four groups(groups 60,50,40,and 30)according to the PIEB intervals(60,50,40,and 30 min,respectively).The interval duration of the first parturient was set at 60 min and that of subsequent parturients varied according to a biased-coin design.The truncated Dixon and Mood method and the isotonic regression analysis method were used to estimate the EI90%and its 95%confidence intervals(CIs).Results:Forty-four women were enrolled in this study.The estimated optimal interval was 44.1 min(95%CI 41.7–46.5 min)and 39.5 min(95%CI 32.5–50.0 min),using the truncated Dixon and Mood method and isotonic regression analysis,respectively.The maximum sensory block level above T6 was in nearly 20%of parturients in group 30;however,5.3%,0%,and 0%of the parturients presented with sensory block level above T6 in groups 40,50,and 60,respectively.There were no cases of hypotension and only one parturient complained of motor block.Conclusion:With a fixed 10 mL dose of ropivacaine 0.08%with sufentanyl 0.3 mg/mL,the optimal PIEB interval is about 42 min.Further studies are warranted to define the efficacy of this regimen throughout all stages of labor. | Shuang-Qiong Zhou Jing Wang Wei-Jia Du Yu-Jie Song Zhen-Dong Xu Zhi-Qiang Liu | 2020 | Chinese Medical Journal2020，，5： | 16 |
| 15 | Physical and mechanical properties of sandstone containing a single fissure after exposure to high temperatures显示文摘In order to investigate the physical and mechanical properties of sandstone containing fissures after exposure to high temperatures,fissures with different angles α were prefabricated in the plate sandstone samples,and the processed samples were then heated at 5 different temperatures.Indoor uniaxial compression was conducted to analyze the change rules of physical properties of sandstone after exposure to high temperature,and the deformation,strength and failure characteristics of sandstone containing fissures.The results show that,with increasing temperature,the volume of sandstone increases gradually while the quality and density decrease gradually,and the color of sandstone remains basically unchanged while the brightness increases markedly when the temperature is higher than 585 ℃;the peak strength of sandstone containing fissures first decreases then increases when the temperature is between 25℃and 400℃.The peak strain of sandstone containing fissures increases gradually while the average modulus decreases gradually with increasing temperature,and the mechanical properties of sandstone show obvious deterioration after 400 ℃.The peak strain of sandstone containing fissures increases gradually while the average modulus decreases gradually with increasing temperature;with increasing angle αof the fissure,the evolution characteristics of the macro-mechanical parameters of sandstone are closely related to the their own mechanical properties.When the temperature is 800 ℃,the correlation between the peak strength and average modulus of sandstone and the angle α of the fissure is obviously weakened.The failure modes of sandstone containing fissures after high temperature exposure are of three different kinds including:tensile crack failure,tensile and shear cracks mixed failure,and shear crack failure.Tensile and shear crack mixed failure occur mainly at low temperatures and small angles;tensile crack failure occurs at high temperatures and large angles. | Zhu Tantan Jing Hongwen Su Haijian Yin Qian Du Mingrui Han Guansheng | 2016 | International Journal of Mining Science and Technology2016，26，2： | 15 |
| 16 | Variations of Laohugou Glacier No.12 in the western Qilian Mountains, China, from 1957 to 2015显示文摘Glaciers were solid reservoirs and important water resources in western China,but they were retreating significantly in context of global warming.Laohugou Glacier No.12 was the largest valley glacier in Qilian Mountains.In this study,realtime kinematic(RTK)data,topographic map and World View-2 satellite imagery were used to measure changes in terminus,extent and volume of Laohugou Glacier No.12.Results showed that Laohugou Glacier No.12 was shrinking significantly since 1957.From1960 to 2015,the terminus reduction of Laohugou Glacier No.12 was 402.96 m(3.99%)in total,and glacier length decreased to 9.7 km from 10.1 km.Reduction of glacier area and volume were the most obvious.From 1957 to 2015,glacier area and volume decreased by 1.54 km^2(7.03%)and 0.1816 km^3,respectively.Reduction trend of terminus and area was slowing in 1950-1980s,even stable for a period in the mid-1980s,and then accelerated.Ice core analysis result and nearly meteorological station data shown an increasing trend of temperature in 1957-2015,it was a main reason of continuous retreating of Laohugou Glacier No.12. | LIU Yu-shuo QIN Xiang CHEN Ji-zu LI Zhen-lin WANG Jing DU Wen-tao GUO Wan-qin | 2018 | Journal of Mountain Science2018，15，1： | 14 |
| 17 | Relationship between Prognosis and Time Interval from Cholecystectomy to Reoperation in Postoperative Incidental Gallbladder Carcinoma显示文摘 | Jing Du Xin-Wei Yang Zhi-Jian Wen Chen Xue Yao-Min Wu Meng-Chao Wu Lu-Lu Zhang | 2018 | Chinese Medical Journal2018，，20： | 14 |
| 18 | Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats显示文摘Hyperlipidemia(HPL)characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases.Proprotein convertase subtilsin/kexin type 9(PCSK9)is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor(LDLR)in the lysosome of hepatocytes.Aloe-emodin(AE)is one of potentially bioactive components of Chinese traditionalmedicine Daming capsule.In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models.High-fat diet-induced rats were treated with AE(100 mg/kg per day,ig)for 6 weeks.We found that AE administration significantly decreased the levels of total cholesterol(TC)and LDL in the serum and liver tissues.Moreover,AE administration ameliorated HPL-induced hepaticlipid aggregation.But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats.A cellular model of HPL was established in human hepatoma(HepG2)cells treated with cholesterol(20 μg/mL)and 25-hydroxycholesterol(2 μg/mL),which exhibited markedly elevated cholesterol levels.The increased cholesterol levels could be reversed by subsequent treatment with AE(30 μM).In both the in vivo and in vitro HPL models,we revealed that AE selectively suppressed the stero-regulatory element-binding protein-2(SREBP-2)and hepatocyte nuclear factor(HNF)1α-mediated PCSK9 signaling,which in turn upregulated LDL receptor(LDLR)and promoted LDL uptake.This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway. | Zhen-li Su Peng-zhou Hang Juan Hu Yu-yang Zheng Han-qi Sun Jing Guo Ke-yu Liu Zhi-min Du | 2020 | Acta Pharmacologica Sinica2020，41，8： | 14 |
| 19 | Lack of Efficacy of Ulinastatin Therapy During Cardiopulmonary Bypass Surgery显示文摘 | Yan Qiu Jing Lin Yang Yang Jing Zhou Li-Na Gong Zhen Qin Lei Du | 2015 | Chinese Medical Journal2015，，23： | 13 |
| 20 | PARylation regulates stress granule dynamics, phase separation, and neurotoxicity of disease-related RNA-binding proteins显示文摘Mutations in RNA-binding proteins (RBPs) localized in ribonucleoprotein (RNP) granules, such as hnRNP A1 and TDP-43, promote aberrant protein aggregation, which is a pathological hallmark of various neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Protein posttranslational modifications (PTMs) are known to 佗gulate RNP granules. In this study, we investigate the function of poly(ADP-ribosyl)ation (PARylation), an important PTM involved in DNA damage repair and cell death, in RNP granule-related neurodegeneration. We reveal that PARylation levels are a major regulator of the assembly-disassembly dynamics of RNP granules containing disease-related RBPs, hnRNP A1 and TDP-43. We find that hnRNP A1 can both be PARylated and bind to PARylated proteins or poly(ADP-ribose)(PAR). We further uncover that PARylation of hnRNP A1 at K298 controls its nucleocytoplasmic transport, whereas PAR-binding via the PAR-binding motif (PBM) of hnRNP Al regulates its association with stress granules. Moreover, we reveal that PAR not only dramatically enhances the liquid-liquid phase separation of hnRNP A1, but also promotes the co-phase separation of hnRNP A1 and TDP-43 in vitro and their interaction in vivo. Finally, both genetic and pharmacological inhibition of PARP mitigates hnRNP Al- and TDP-43-mediated neurotoxicity in cell and Drosophila models of ALS. Together, our findings suggest a novel and crucial role for PARylation in regulating the dynamics of RNP granules, and that dysregulation in PARylation and PAR levels may con tribute to ALS disease pathoge nesis by promoting protei n aggregation. | Yongjia Duan Aiying Du Jinge Gu Gang Duan Chen Wang Xinrui Gui Zhiwei Ma Beituo Qian Xue Deng Kai Zhang Le Sun Kuili Tian Yaoyang Zhang Hong Jiang Cong Liu Yanshan Fang | 2019 | Cell Research2019，29，3： | 13 |
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