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| 1 | The structural and accessory proteins M,ORF 4a,ORF 4b,and ORF 5 of Middle East respiratory syndrome coronavirus(MERS-CoV)are potent interferon antagonists显示文摘The newly emerged Middle East respiratory syndrome coronavirus(MERS-CoV)is a highly pathogenic respira-tory virus with pathogenic mechanisms that may be driven by innate immune pathways.The goal of this study is to characterize the expression of the structural(S,E,M,N)and accessory(ORF 3,ORF 4a,ORF 4b,ORF 5)proteins of MERS-CoV and to determine whether any of these pro-teins acts as an interferon antagonist.Individual structural and accessory protein-coding plasmids with an N-terminal HA tag were constructed and transiently transfected into cells,and their native expression and subcellular localiza-tion were assessed using Wes tern blotting and indirect immunofl uorescence.While ORF 4b demonstrated majorly nuclear localization,all of the other proteins demonstrated cytoplasmic localization.In addition,for the fi rst time,our experiments revealed that the M,ORF 4a,ORF 4b,and ORF 5 proteins are potent interferon antagonists.Further exami-nation revealed that the ORF 4a protein of MERS-CoV has the most potential to counteract the antiviral effects of IFN via the inhibition of both the interferon production(IFN-βpromoter activity,IRF-3/7 and NF-κB activation)and ISRE promoter element signaling pathways.Together,our re-sults provide new insights into the function and pathogenic role of the structural and accessory proteins of MERS-CoV. | Yang Yang Ling Zhang Heyuan Geng Yao Deng Baoying Huang Yin Guo Zhengdong Zhao Wenjie Tan | 2013 | Protein & Cell2013，4，12： | 25 |
| 2 | Recurrent gain-of-function USP8 mutations in Cushing's disease显示文摘库欣的疾病,引起过量皮质醇生产的也已知的同样促肾上腺皮质的荷尔蒙(ACTH )-secreting 垂体腺瘤(舞步) ,占多达 85%corticotrophin 依赖的库欣的症候群盒子。然而,在这疾病的基因改变是不清楚的。这里,我们执行了从 12 秘密 ACTH 舞步导出并且匹配血样品的 DNA 定序的 whole-exome,它在候选人基因揭示了体的变化的三种类型, USP8 (编码 ubiquitin 特定的朊酶 8 ) ,专门在 exon 14 在 12 秘密 ACTH 舞步中的 8 个。我们进一步评估了体的 USP8 变化在另外由定序的 Sanger 的 258 舞步。进一步定序指向在 108 秘密 ACTH 舞步(62.04%) 中的 67 个识别了 USP8 变体的 17 种类型的一个总数。然而,任何一个都没在舞步的另外的类型这些变化被检测(n = 150 ) 。这些变化在 USP8 的 14-3-3 绑定主题以内聚集并且破坏在 USP8 和 14-3-3 蛋白质之间的相互作用,导致保护 EGFR 免受 lysosomal 降级的伤害的一个提高的能力。因此,有 EGFR 表示,提高的 EGFR 蛋白质丰富和 mRNA 表示的更高的发生 POMC 铺平的变异的 USP8 显示的舞步,它编码 ACTH 的先锋。有变异的 USP8 的舞步在尺寸是显著地更小的并且比野类型的舞步有更高的 ACTH 生产。在里面通过手术 resected 主要变异 USP8 的肿瘤房间, USP8 击倒或堵住的 EGFR 有效地稀释 ACTH 分泌物。一起拿,体的 gain-of-function USP8 变化是普通的并且在库欣的疾病贡献 ACTH 生产过剩。USP8 或 EGFR 的抑制为对待变异 USP8 的 corticotrophin 腺瘤是有希望的。我们的学习在库欣的疾病加亮潜在地功能的变异的基因并且提供卓见进这疾病的治疗学。 | Zeng-Yi Ma Zhi-Jian Song Jian-Hua Chen Yong-Fei Wang Shi-Qi Li Liang-Fu Zhou Ying Mao Yi-Ming Li Rong-Gui Hu Zhao-Yun Zhang Hong-Ying Ye Ming Shen Xue-Fei Shou Zhi-Qiang Li Hong Peng Qing-Zhong Wang Dai-Zhan Zhou Xiao-Lan Qin Jue Ji Jie Zheng Hong Chen Yin Wang Dao-Ying Geng Wei-Jun Tang Chao-Wei Fu Zhi-Feng Shi Yi-Chao Zhang Zhao Ye Wen-Qiang He Qi-Lin Zhang Qi-Sheng Tang Rong Xie Jia-Wei Shen Zu-Jia Wen Juan Zhou Tao Wang Shan Huang Hui-Jia Qiu Ni-Dan Qiao Yi Zhang Li Pan Wei-Min Bao Ying-Chao Liu Chuan-Xin Huang Yong-Yong Shi Yao Zhao | 2015 | Cell Research2015，25，3： | 16 |
| 3 | Chinese Tuina Downregulates the Elevated Levels of Tissue Plasminogen Activator in Sciatic Nerve Injured Sprague-Dawley Rats显示文摘Objective:To elucidate the mechanism of Chinese tuina in treating sciatic nerve crush injury,and to detect the levels of tissue plasminogen activator(t PA)and plasminogen activator inhibitor-1(PAI-1),which is thought to play an important role in nerve regeneration.Methods:Thirty-two adult male Sprague-Dawley rats were subjected to sciatic nerve crush injury and 16 rats(sham-operated group)went through a sham operation.Control group was given no treatment while tuina group received tuina therapy since day 7 post-surgery.Tuina treatment was performed once a day and lasted for 20 days.The sciatic functional index was examined every 5days during the treatment session.The rats'gastrocnemius muscles were evaluated for changes in mass and immunohistochemistry techniques were performed to detect the levels of tP A and PAI-1.Results:Tuina therapy improved the motor function of sciatic nerve injured rats(P<0.05),however,it did not increase muscle volume(P<0.05).Tuina downregulated the levels of t PA and PAI-1(P<0.05).Conclusions:The present study implies that tuina treatment could accelerate rehabilitation of peripheral nerve injury. | PAN Fan YU Tian-yuan Steven Wong XIAN Si-tong LU Meng-qian WU Jian-cong GAO Yu-feng LI Xiao-qin GENG Nan YAO Bin-bin | 2017 | Chinese Journal of Integrative Medicine2017，23，8： | 16 |
| 4 | MicroRNA-663 induces immune dysregulation by inhibiting TGF-β1 production in bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus显示文摘Mesenchymal stem cells(MSCs)are critical for immune regulation.Although several microRNAs(miRNAs)have been shown to participate in autoimmune pathogenesis by affecting lymphocyte development and function,the roles of miRNAs in MSC dysfunction in autoimmune diseases remain unclear.Here,we show that patients with systemic lupus erythematosus(SLE)display a unique miRNA signature in bone marrow-derived MSCs(BMSCs)compared with normal controls,among which miR-663 is closely associated with SLE disease activity.MiR-663 inhibits the proliferation and migration of BMSCs and impairs BMSC-mediated downregulation of follicular T helper(Tfh)cells and upregulation of regulatory T(Treg)cells by targeting transforming growth factorβ1(TGF-β1).MiR-663 overexpression weakens the therapeutic effect of BMSCs,while miR-663 inhibition improves the remission of lupus disease in MRL/lpr mice.Thus,miR-663 is a key mediator of SLE BMSC regulation and may serve as a new therapeutic target for the treatment of lupus. | Linyu Geng Xiaojun Tang Kangxing Zhou Dandan Wang Shiying Wang Genhong Yao Weiwei Chen Xiang Gao Wanjun Chen Songtao Shi Nan Shen Xuebing Feng Lingyun Sun | 2019 | Cellular & Molecular Immunology2019，16，3： | 16 |
| 5 | Increased expression of brain-derived neurotrophic factor is correlated with visceral hypersensitivity in patients with diarrheapredominant irritable bowel syndrome显示文摘BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome(IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor(BDNF) was found to mediate visceral hypersensitivity via facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS(IBS-D).AIM To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology.METHODS Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 ageand sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined.RESULTS The patients had a higher anxiety score [median(interquartile range), 6.0(2.0-10.0) vs 3.0(1.0-4.0), P = 0.003] and visceral sensitivity index score [54.0(44.0-61.0)vs 21.0(17.3-30.0), P < 0.001] than controls. The defecating sensation threshold[60.0(44.0-80.0) vs 80.0(61.0-100.0), P = 0.009], maximum tolerable threshold[103.0(90.0-128.0) vs 182.0(142.5-209.3), P < 0.001] and rectoanal inhibitory reflex threshold [30.0(20.0-30.0) vs 30.0(30.0-47.5), P = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46 E-2(3.06 E-2-4.44 E-2) vs3.07 E-2(2.91 E-2-3.48 E-2), P = 0.031] and mRNA [1.57(1.31-2.61) vs 1.09(0.74-1.42), P = 0.001] expression and nerve fiber density [4.12 E-2(3.07 E-2-7.46 E-2) vs1.98 E-2(1.21 E-2-4.25 E-2), P = 0.002] were significantly elevated in the patients.Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters.CONCLUSION Elevated mucosal BDNF may participate in the pathogenesis of IBS-D via facilitating mucosal nerve growth and increasing visceral sensitivity. | Yu Zhang Geng Qin De-Rong Liu Yan Wang Shu-Kun Yao | 2019 | World Journal of Gastroenterology2019，25，2： | 14 |
| 6 | High neutrophil-lymphocyte ratio indicates poor prognosis for acute-on-chronic liver failure after liver transplantation显示文摘AIM:To investigate the significance of pre-transplant neutrophil-lymphocyte ratio(NLR) in determining the prognosis of liver transplant(LT) recipients with acuteon-chronic liver failure(ACLF).METHODS:Data were collected from the liver transplantation data bank.The NLR values and other conventional inflammatory markers were evaluated for their ability to predict the prognosis of 153 patients with ACLF after LT.The NLR cut-off value was based on a receiver operating characteristic curve analysis.A Kaplan-Meier curve analysis and univariate and multivariate Cox regression models were used to define the independent risk factors for poor outcomes.RESULTS:The optimal NLR cut-off value was 4.6.Out of 153 patients,83(54.2%) had an NLR ≥ 4.6.The 1-,3-,and 5-year overall survival rates were 94.3%,92.5% and 92.5%,respectively,in the normal NLR group and 74.7%,71.8% and 69.8%,respectively,in patients with high NLRs(P < 0.001).Furthermore,there was a significant difference in infectious complications after LT between the high and normal NLR groups.There were no significant differences for other complications.In the multivariate Cox regression model,a high NLR was defined as a significant predictor of poor outcomes for LT.CONCLUSION:A high NLR is a convenient and available predictor for prognosis of LT patients and can potentially optimize the current criteria for LT in ACLF. | Bing-Yi Lin Lin Zhou Lei Geng Zhi-Yun Zheng Jun-Jun Jia Jing Zhang Jia Yao Shu-Sen Zheng | 2015 | World Journal of Gastroenterology2015，21，11： | 14 |
| 7 | Chemical screen identifies a geroprotective role of quercetin in premature aging显示文摘Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders. | Lingling Geng Zunpeng Liu Weiqi Zhang Wei Li Zeming Wu Wei Wang Ruotong Ren Yao Su Peichang Wang Liang Sun Zhenyu Ju Piu Chan Moshi Song Jing Qu Guang-Hui Liu | 2019 | Protein & Cell2019，10，6： | 13 |
| 8 | Serotonin transporter and cholecystokinin in diarrhea-predominant irritable bowel syndrome: Associations with abdominal pain, visceral hypersensitivity and psychological performance显示文摘BACKGROUND Visceral hypersensitivity and psychological performance are the main pathophysiological mechanisms of irritable bowel syndrome(IBS).Previous studies have found that cholecystokinin(CCK)can enhance colon movement and that serotonin transporter(SERT)is a transmembrane transport protein with high affinity for 5-hydroxytryptamine,which can rapidly reuptake 5-hydroxytryptamine and then regulate its action time and intensity.We speculate that SERT and CCK might play a role in the pathogenesis of diarrheapredominant IBS(IBS-D)by affecting visceral sensitivity and the brain-gut axis.AIM To determine SERT and CCK levels in IBS-D patients diagnosed using Rome IV criteria and to analyze their associations with abdominal pain,visceral hypersensitivity and psychological performance.METHODS This study collected data from 40 patients with IBS-D at the China-Japan Friendship Hospital from September 2017 to April 2018 and 18 healthy controls.The severity of abdominal pain,visceral sensitivity and psychological performance were evaluated in IBS-D patients and healthy controls,the levels of SERT and CCK in plasma and colonic mucosa were evaluated,and the correlations between them were analyzed.RESULTS There were significant differences in the initial sensation threshold(31.00±8.41 mL vs 52.22±8.09 mL,P<0.001),defecating sensation threshold(51.75±13.57 mL vs 89.44±8.73 mL,P<0.001)and maximum tolerable threshold(97.25±23.64 mL vs 171.11±20.83 mL,P<0.001)between the two groups.IBS-D patients had more severe anxiety(7.78±2.62 vs 2.89±1.02,P<0.001)and depressive(6.38±2.43 vs 2.06±0.73,P<0.001)symptoms than healthy controls.Significant differences were also found in mucosal CCK(2.29±0.30 vs 1.66±0.17,P<0.001)and SERT(1.90±0.51 vs 3.03±0.23,P<0.001)between the two groups.There was a significant positive correlation between pain scores and mucosal CCK(r=0.96,0.93,0.94,P<0.001).Significant negative correlations between anxiety(r=-0.98;P<0.001),depression(r=-0.99;P<0.001),pain evaluation(r=-0.96,-0.93,-0.95,P<0.001)and mucosal SERT were observed.CONCLUSION IBS-D patients had psychosomatic disorders and visceral hypersensitivity.SERT and CCK might be involved in the pathogenesis of IBS-D by regulating the braingut axis and affecting visceral sensitivity.This provides a new potential method for identifying a more specific and effective therapeutic target. | Geng Qin Yu Zhang Shu-Kun Yao | 2020 | World Journal of Clinical Cases2020，8，9： | 13 |
| 9 | Ultrasensitive skin‐like wearable optical sensors based on glass micro/nanofibers显示文摘Electronic skin,a class of wearable electronic sensors that mimic the functionalities of human skin,has made remarkable success in applications including health monitoring,human-machine interaction and electronic-biological interfaces.While electronic skin continues to achieve higher sensitivity and faster response,its ultimate performance is fundamentally limited by the nature of low-frequency AC currents.Herein,highly sensitive skin-like wearable optical sensors are demonstrated by embedding glass micro/nanofibers(MNFs)in thin layers of polydimethylsiloxane(PDMS).Enabled by the transition from guided modes into radiation modes of the waveguiding MNFs upon external stimuli,the skin-like optical sensors show ultrahigh sensitivity(1870 k·Pa^-1),low detection limit(7 mPa)and fast response(10μs)for pressure sensing,significantly exceeding the performance metrics of state-of-the-art electronic skins.Electromagnetic interference(EMI)-free detection of high-frequency vibrations,wrist pulse and human voice are realized.Moreover,a five-sensor optical data glove and a 2×2-MNF tactile sensor are demonstrated.These initial results pave the way toward a new category of optical devices ranging from ultrasensitive wearable sensors to optical skins. | Lei Zhang Jing Pan Zhang Zhang Hao Wu Ni Yao Dawei Cai Yingxin Xu Jin Zhang Guofei Sun Liqiang Wang Weidong Geng Wenguang Jin Wei Fang Dawei Di Limin Tong | 2020 | Opto-Electronic Advances2020，3，3： | 12 |
| 10 | Reoperation for benign biliary tract diseases in 149 cases: causes and prevention显示文摘BACKGROUND: Failure to diagnose and treat benign bi- liary tract disease relatively common surgical disease may cause serious consequences. Since the introduction of B- mode ultrasonography, CT, or MRI early and accurate diagnosis of the disease has been possible. In clinical prac- tice, however, these methods have not been adequately used. Inappropriate surgical procedures can also lead to bile duct injury or stenosis after injury, residual cholecystitis, stenosis after cholangiojejunostomy, or stenosis of the Od- di’ s sphincter. But improvement of the diagnosis and treat- ment of benign biliary tract disease remains a great chal- lenge to clinicians. METHODS: A total of 149 patients with benign biliary tract disease who had received reoperation from June 1988 to June 2001 were analyzed retrospectively. Among them 95 patients (63.76%) received operation twice and 38 (25.5%) underwent 3 operations. Sixteen patients (10.74%) needed 4 or more operations. The procedures for the first opera- tion included cholecystectomy (71 patients, 47.65%), cho- lecystectomy with exploration of the common bile duct (42, 28.19%), cholangiojejunostomy (21, 14.1%), and la- paroscopic cholecystectomy (15, 10.06%). RESULTS: The causes for reoperation included residual and recurrent bile duct stones in 53 patients (35.57%), bile duct injury or stenosis after injury in 41 (27.52%), residual cho- lecystitis with or without stones in 28 (18.8%), stenosis af- ter cholangiojejunostomy in 17 (11.41%), stenosis of the Oddi’s sphincter in 5 (5.35%), and others in 5 (5.35%). Four patients (2.68%) died after operation. CONCLUSIONS: To prevent reoperation for benign biliary tract diseases, the following measures should be taken to in- crease preoperative diagnostic rate, to understand condi- tions of the biliary tract by using imaging techniques and cholangiography, to examine comprehensively and careful- ly with choledochoscopy, cholangiography and B-mode ul-trasonography intraoperatively, to choose appropriate ope- rative procedures to decrease the rate of residual stones, and to decide the time for the first repair according to inju- ry type of the bile duct. Roux-en-Y hepaticojejunostomy with cholangioplasty is the best operation for the recon- struction of the biliary tract. | Qing-Guang Liu, Zhi-Min Geng, Sheng-Li Wu, Ying-Min Yao, Hao Sun and Cheng-En Pan Xi’an, China Department of Hepatobiliary Surgery, First Hospital of Xi’ an Jiaotong University, Xi’an 710061, China | 2004 | Hepatobiliary & Pancreatic Diseases International2004，3，2： | 9 |
| 11 | Aloin Protects Against Blood-Brain Barrier Damage After Traumatic Brain Injury in Mice显示文摘Aloin is a small-molecule drug well known for its protective actions in various models of damage.Traumatic brain injury(TBI)-induced cerebral edema from secondary damage caused by disruption of the blood-brain barrier(BBB) often leads to an adverse prognosis.Since the role of aloin in maintaining the integrity of the BBB after TBI remains unclear,we explored the protective effects of aloin on the BBB using in vivo and in vitro TBI models.Adult male C57 BL/6 mice underwent controlled cortical impact injury,and mouse brain capillary endothelial bEnd.3 cells underwent biaxial stretch injury,then both received aloin treatment.In the animal experiments,we found 20 mg/kg aloin to be the optimum concentration to decrease cerebral edema,decrease disruption of the BBB,and improve neurobehavioral performance after cortical impact injury.In the cellular studies,the optimum concentration of 40 μg/mL aloin reduced apoptosis and reversed the loss of tight junctions by reducing the reactive oxygen species levels and changes in mitochondrial membrane potential after stretch injury.The mechanisms may be that aloin downregulates the phosphorylation of p38 mitogen-activated protein kinase,the activation of p65 nuclear factor-kappa B,and the ratios of B cell lymphoma(Bcl)-2-associated X protein/Bcl-2 and cleaved caspase-3/caspase-3.We conclude that aloin exhibits these protective effects on the BBB after TBI through its anti-oxidative stress and anti-apoptotic properties in mouse brain capillary endothelial cells.Aloin may thus be a promising therapeutic drug for TBI. | Yao Jing Dian-Xu Yang Wei Wang Fang Yuan Hao Chen Jun Ding Zhi Geng Heng-Li Tian | 2020 | Neuroscience Bulletin2020，36，6： | 9 |
| 12 | Risk factors of CMV infection in patients after umbilical cord blood transplantation: a multicenter study in China显示文摘Objective:This retrospective study examined risk factors for cytomegalovirus(CMV)infection after umbilical cord blood transplantation(UCBT)and the impact of CMV infection on patient survival.Methods:In all 176 patients,plasma CMV DNA was negative prior to the transplantation,and examined twice a week for 100 d,and then once weekly for additional 300 d.Preemptive antiviral therapy(ganciclovir or foscarnet)was started in patients with>1,000/mL copies of CMV DNA but no full-blown CMV disease,and was discontinued upon two consecutive negative reports of blood CMV DNA test.The survival and risk factors for CMV infection or disease were examined using logistic regression.Results:CMV infection developed in 71%(125/176)of the patients,with a median onset of 32 d.Four patients(2.3%)developed CMV disease.Neither the 5-year overall survival(OS)nor event-free survival(EFS)differed significantly in infected patients vs.those with no infection(59.4%vs.64.8%,P=0.194;53.4%vs.59.1%,P=0.226).A stepwise multivariate analysis indicated an association of CMV infection with age,high-dose glucocorticoids,the number of transplanted CD34+cells,and the number of platelet transfusion,but not with gender,the conditioning regimen,and the day of neutrophil recovery and chronic graft-versushost disease(cGVHD).Conclusions:CMV infection is very common after UCBT,but does not seem to affect long-term survival with preemptive antiviral treatment. | Juan Tong Zimin Sun Huilan Liu Liangquan Geng Changcheng Zheng Baolin Tang Kaidi Song Wen Yao Xin Liu | 2013 | Chinese Journal of Cancer Research2013，25，6： | 8 |
| 13 | Two-fluid modeling of Geldart A particles in gas-solid micro-fluidized beds显示文摘The fluidizadon behavior of Geldart A particles in a gas-solid micro-fluidized bed was investigated by Eulerian-Eulerian numerical simulation.The commonly used Gidaspow drag model was tested first.The simulation showed that the predicted minimum bubbling velocities were significantly lower than the experimental data even when an extremely fine grid size(of approximately one particle diameter) was used.The modified Gibilaro drag model was therefore tested next.The predicted minimum bubbling velocity and bed voidage were in reasonable agreement with the experimental data available in literature.The experimentally observed regime transition phenomena from bubbling to slugging were also reproduced successfully in the simulations.Parametric studies indicated that the solid-wall boundary conditions had a significant impact on the predicted gas and solid flow behavior. | Xiaoxing Liu Chuanqiang Zhu Shujun Geng Meiqin Yao Jinhui Zhan Guangwen Xu | 2015 | Particuology2015，13，4： | 8 |
| 14 | Altered profiles of fecal metabolites correlate with visceral hypersensitivity and may contribute to symptom severity of diarrhea-predominant irritable bowel syndrome显示文摘BACKGROUND Fecal metabolites are associated with gut visceral sensitivity,mucosal immune function and intestinal barrier function,all of which have critical roles in the pathogenesis of irritable bowel syndrome(IBS).However,the metabolic profile and pathophysiology of IBS are still unclear.We hypothesized that altered profiles of fecal metabolites might be involved in the pathogenesis of IBS with predominant diarrhea(IBS-D).AIM To investigate the fecal metabolite composition and the role of metabolites in IBSD pathophysiology.METHODS Thirty IBS-D patients and 15 age-and sex-matched healthy controls(HCs)underwent clinical and psychological assessments,including the IBS Symptom Severity System(IBS-SSS),an Italian modified version of the Bowel Disease Questionnaire,the Bristol Stool Form Scale(BSFS),the Hospital Anxiety and Depression Scale,and the Visceral Sensitivity Index.Visceral sensitivity to rectal distension was tested using high-resolution manometry system by the same investigator.Fecal metabolites,including amino acids and organic acids,were measured by targeted metabolomics approaches.Correlation analyses between these parameters were performed.RESULTS The patients presented with increased stool water content,more psychological symptoms and increased visceral hypersensitivity compared with the controls.In fecal metabolites,His[IBS-D:0.0642(0.0388,0.1484),HC:0.2636(0.0780,0.3966),P=0.012],Ala[IBS-D:0.5095(0.2826,0.9183),HC:1.0118(0.6135,1.4335),P=0.041],Tyr[IBS-D:0.1024(0.0173,0.4527),HC:0.5665(0.2436,1.3447),P=0.018],Phe[IBS-D:0.1511(0.0775,0.3248),HC:0.3967(0.1388,0.7550),P=0.028],and Trp[IBS-D:0.0323(0.0001,0.0826),HC:0.0834(0.0170,0.1759),P=0.046]were decreased in IBS-D patients,but isohexanoate[IBS-D:0.0127(0.0060,0.0246),HC:0.0070(0.0023,0.0106),P=0.028]was significantly increased.Only Tyr was mildly correlated with BSFS scores in all subjects(r=-0.347,P=0.019).A possible potential biomarker panel was identified to correlate with IBS-SSS score(R2 Adjusted=0.693,P<0.001).In this regression model,the levels of Tyr,Val,hexanoate,fumarate,and pyruvate were significantly associated with the symptom severity of IBS-D.Furthermore,visceral sensation,including abdominal pain and visceral hypersensitivity,was correlated with isovalerate,valerate and isohexanoate.CONCLUSION Altered profiles of fecal metabolites may be one of the origins or exacerbating factors of symptoms in IBS-D via increasing visceral sensitivity. | Wen-Xue Zhang Yu Zhang Geng Qin Kai-Min Li Wei Wei Su-Yun Li Shu-Kun Yao | 2019 | World Journal of Gastroenterology2019，25，43： | 8 |
| 15 | A natural variation in Ribonuclease H-like gene underlies Rht8 to confer“Green Revolution”trait in wheat显示文摘Dear Editor,Introduction of gibberellin(GA)-insensitive Reduced height(Rht)genes,Rht-B1b and Rht-D1b,has resulted in the“Green Revolution”in modern wheat cultivars(Triticum aestivum)that has skyrocketed wheat grain yields worldwide since the 1960s(Peng et al.,1999;Velde et al.,2021).However,Rht-B1b/D1b also reduce coleoptiles,which is undesired in dryland regions where deep planting is essential for seedling establishment(Rebetzke et al.,1999,Rebetzke et al.,2001;Ellis et al.,2004). | Lingling Chai Mingming Xin Chaoqun Dong Zhaoyan Chen Huijie Zhai Junhong Zhuang Xuejiao Cheng Naijiao Wang Jia Geng Xiaobo Wang Ruolin Bian Yingyin Yao Weilong Guo Zhaorong Hu Huiru Peng Guihua Bai Qixin Sun Zhenqi Su Jie Liu Zhongfu Ni | 2022 | Molecular Plant2022，15，3： | 8 |
| 16 | Free-standing porous carbon electrodes derived from wood for high-performance Li-O2 battery applications显示文摘 | Jingru Luo Xiahui Yao Lei Yang Yang Han Liao Chen Xiumei Geng Vivek Vattipalli Qi Dong Wei Fan Dunwei Wang Hongli Zhu | 2017 | Nano Research2017，10，12： | 7 |
| 17 | Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction显示文摘Cockayne syndrome(CS)is a rare autosomal recessive inherited disorder characterized by a variety of clinical features,including increased sensitivity to sunlight,progressive neurological abnormalities,and the appearance of premature aging.However,the pathogenesis of CS remains unclear due to the limitations of current disease models.Here,we generate integration-free induced pluripotent stem cells(iPSCs)from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic genecorrected CS-iPSCs(GC-iPSCs)using the CRISPR/Cas9 system.CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells(MSCs)and neural stem cells(NSCs),both of which display increased susceptibility to DNA damage stress.Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6.We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives(MSCs and NSCs)in the absence or presence of ultraviolet(UV)and replicative stresses,revealing that defects in DNA repair account for CS pathologies.Moreover,we generate autologous GC-MSCs free of pathogenic mutation under a cGMP(Current Good Manufacturing Practice)-compliant condition,which hold potential for use as improved biomaterials for future stem cell replacement therapy for CS.Collectively,our models demonstrate novel disease features and molecular mechanisms and lay a foundation for the development of novel therapeutic strategies to treat CS. | Si Wang Zheying Min Qianzhao Ji Lingling Geng Yao Su Zunpeng Liu Huifang Hu Lixia Wang Weiqi Zhang Keiichiro Suzuiki Yu Huang Puyao Zhang Tie-Shan Tang Jing Qu Yang Yu Guang-Hui Liu Jie Qiao | 2020 | Protein & Cell2020，11，1： | 7 |
| 18 | Hypertensive stretch regulates endothelial exocytosis of WeibeI-Palade bodies through VEGF receptor 2 signaling pathways显示文摘Weibel-Palade 身体(WPB ) 的调整 endothelial exocytosis,在白血球 trafficking 的第一个阶段,在发炎和损害起一个枢轴的作用。尖锐的机械段仔细与脉管的发炎被联系了,尽管精确机制是未知的。这里,我们证明那高血压的段通过 VEGF 受体 2 调整 endothelial 房间(EC ) 的 WPB 的 exocytosis (VEGFR2 ) 表明小径。段触发一个快速的版本(在分钟以内) 从在有教养的人的 EC 的 WPB 的 von Willebrand 因素和 interleukin-8,通过 P-selectin 的 translocation 把在白血球和 EC 之间的相互作用提升到房间膜。我们进一步证明那高血压的段显著地导致未经触动的 EC 的 P-selectin translocation 并且两个都提高白血球粘附前 vivo 并且在 vivo。导致段的 endothelial exocytosis 经由 VEGFR2/PLCγ 被调停; 1/calcium 小径。有趣地,段也经由一条 VEGFR2/Akt/nitric 氧化物小径导致否定反馈。如此的双效果在颈动脉动脉片断,以及在尖锐高血压的老鼠模型用药理学和基因途径被证实。这些研究为 endothelial exocytosis 作为有势力收缩筋揭示机械段,它被 VEGFR2 发信号调制。因此, VEGFR2 发信号小径可以在限制高血压的段相关的发炎代表新奇治疗学的目标。 | Yan Xiong Zhenqian Hu Xiaofan Han Beibei Jiang Rongli Zhan Xiaoyu Zhang Yao Lu Chenyang Geng Wei Li Yulong He Yingqing Huo Masabuml Shlbuya Jincai Luo | 2013 | Cell Research2013，23，6： | 7 |
| 19 | Monte Carlo simulation based on Geant4 of single event upset induced by heavy ions显示文摘The present work is a computational simulation of single event upset(SEU) induced by heavy ions passing through the device with Geant4-tool based on Monte Carlo transport code.Key parameters affecting SEU occurrence are examined,and related geometrical construction and critical charge are quantified.The MUlti-Functional Package for SEU Analysis(MUFPSA) has been successfully programmed and applied for SEU occurrence after the completion of device geometrical construction,critical charge,and SEU cross section calculation.The proposed MUFPSA has yielded a good agreement with MRED.Specifically,the results show that higher LET incident ions lead to increased SEU vulnerability due to more diffusion and higher energy deposition.In addition,the analytical method of radial ionization profile provides a good complementary interpretation. | GENG Chao LIU Jie ZHANG ZhanGang HOU MingDong SUN YouMei XI Kai GU Song DUAN JingLai YAO HuiJun MO Dan LUO Jie | 2013 | Science China(Physics,Mechanics & Astronomy)2013，56，6： | 6 |
| 20 | MicroRNA-135a in ABCA1-labeled Exosome is a Serum Biomarker Candidate for Alzheimer’s Disease显示文摘Objective In the present study,the ABCA1 was used as a label to capture specific exosomes,the level of ABCA1-labeled exosomal microRNA-135 a(miR-135 a)was evaluated for the diagnosis of Alzheimer’s disease(AD),especially in patients with early stages of AD.Methods This is a preliminary research focused on the levels of ABCA1 in WBCs,RBCs,HT-22 cells,and neuron cells.The diagnostic value of ABCA1-labeled exosomal miR-135 a was examined using the CSF and serum of APP/PS1 double transgenic mice,and 152 patients with SCD,131 patients with MCI,198 patients with DAT,and 30 control subjects.Results The level of ABCA1 exosomes harvested from HT-22 cells and neuron culture medium was significantly higher compared to that of RBCs and WBCs(P<0.05).The levels of ABCA1-labeled exosomal miR-135 a increased in the CSF of MCI and DAT group compared to those of control group(P<0.05),slightly increased(P>0.05)in the serum of SCD patient group,and significantly increased in MCI and DAT patient groups compared to those of the control group(P<0.05).Conclusion This study outlines a method to capture specific exosomes and detect them using immunological methods,which is more efficient for early diagnosis of AD. | LIU Chen Geng MENG Shuang LI Ying LU Yao ZHAO Yue WANG Pei Chang | 2021 | Biomedical and Environmental Sciences2021，34，1： | 5 |
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