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| 1 | Improved Base Editor for Efficiently Inducing Genetic Variations in Rice with CRISPR/Cas9- Guided Hyperactive hAID Mutant显示文摘 | Bin Ren Fang Yan Yongjie Kuang Na Li Dawei Zhang Xueping Zhou Honghui Lin Huanbin Zhou | 2018 | Molecular Plant2018，11，4： | 46 |
| 2 | A CRISPR/Cas9 toolkit for efficient targeted base editing to induce genetic variations in rice显示文摘Dear Editor,Gene-targeting technologies using sequence specific nucleases have been widely adopted to induce genetic modifications in both plant molecular biology research and crop improvement,of which generating targeted point mutation for gain-of-function phenotype is of great value.Although tremendous efforts have been made in developing geneinsertion or replacement approaches by | Bin Ren Fang Yan Yongjie Kuang Na Li Dawei Zhang Honghui Lin Huanbin Zhou | 2017 | Science China(Life Sciences)2017，60，5： | 28 |
| 3 | Rationale and study design for one-stop assessment of renal artery stenosis and renal microvascular perfusion with contrast-enhanced ultrasound for patients with suspected renovascular hypertension显示文摘Background:Renal artery stenosis (RAS) is always associated with abnormalities in renal microvascular perfusion (RMP).However,few imaging methods can simultaneously evaluate the degree of luminal stenosis and RMP.Thus,this study will aim to evaluate the feasibility of using contrast-enhanced ultrasound (CEUS) for assessing both RAS and RMP to achieve a one-stop assessment of patients with suspected renovascular hypertension. Methods:This will be a single-center diagnostic study with a sample size of 440.Patients with chronic kidney disease (CKD) and suspected of having resistant hypertension will be eligible.Patients with Stages 1–3 CKD will undergo CEUS and computed tomography (CT) angiography (CTA).Values obtained by CEUS and CTA for diagnosing low-grade (lumen reduced by <60%) and high-grade (lumen reduced by ≥60%) RAS will be compared.Moreover,all patients will also undergo radionuclide imaging.The diagnostic value for RAS will be assessed by the receiver operating characteristic curve,including the accuracy,sensitivity,specificity,positive predictive values,negative predictive values,and area under the ROC.Pearson correlation analysis will be performed to assess the association between CEUS findings for RMP and glomerular filtration rate measured by a radionuclide imaging method. Conclusion:The data gathered from this study will be used to evaluate the feasibility of expanding clinical applications of CEUS for evaluation of patients with suspected renovascular hypertension. | Jun-Hong Ren Na Ma Si-Yu Wang You-Jing Sun Yue-Wei Zhang Fa-Jin Guo Yong-Jun Li Tian-Hui Li Hu Ai Wen-Duo Zhang Peng Li Wei-Hua Ma | 2019 | Chinese Medical Journal2019，，1： | 12 |
| 4 | Performance of the Prostate Health Index in predicting prostate biopsy outcomes among men with a negative digital rectal examination and transrectal ultrasonography显示文摘[-2]proPSA (p2PSA ) 和它的衍生物, p2PSA-to-free PSA 比率(% p2PSA ) ,和前列腺健康索引(PHI ) 极大地在前列腺活体检视有或没有前列腺癌症(PCa ) 改进了在人之间的辨别。然而,很少在数字直肠的考试(DRE ) 和 transrectal ultrasonography (TRUS ) 是否定的情况中对他们的表演被知道。在有否定 DRE 和 TRUS 的中国的 261 个连续病人的一个未来的队被招募并且经历前列腺活体检视。在活体检视被用来测量各种各样的 PSA 衍生物以前,一件浆液样品收集了,包括总数前列腺特定的抗原(tPSA ) ,免费 PSA,和 p2PSA。为每个病人, free-to-total PSA 比率(% fPSA ) , PSA 密度(PSAD ) , p2PSA-to-free PSA 比率(% p2PSA ) ,和 PHI 是计算的。歧视的性能在在 91% 敏感操作典型曲线(AUC ) 和活体检视率的接收装置下面用区域被估计。在关于年龄, tPSA, % fPSA, PSAD, p2PSA, % p2PSA,和 PHI 的全部队以内的 AUC 分数分别地是 0.598, 0.751, 0.646, 0.789, 0.814, 0.808,和 0.853。PHI 是前列腺活体检视结果的最好的预言者,特别在有 10.1-20 ng ml −1 的 tPSA 的病人。与另外的标记相比,在 91% 的敏感, PHI 为决定哪个人不需要经历活体检视是最有用的,从而避免不必要的过程。PHI 的使用能由在中国与否定 DRE 和 TRUS 在人之中预言前列腺活体检视结果改进 PCa 察觉的精确性。 | Guo-Peng Yu Rong Na Ding-Wei Ye Jun Qi Fang Liu Hai-Tao Chen Yi-Shuo Wu Gui-Ming Zhang Jie-Lin Sun Yao Zhu Li-Qun Huang Shan-Cheng Ren De-Ke Jiang S Lilly Zheng Hao-WenJiang Ying-Hao Sun Qiang Ding Jianfeng Xu | 2016 | Asian Journal of Andrology2016，18，4： | 10 |
| 5 | Study of endorectal ultrasonography in the staging of rectal cancer显示文摘 | REN Jun-hong GUO Fa-jin DAI Wei-de HAN Xiu-jie MA Na | 2012 | Chinese Medical Journal2012，，20： | 10 |
| 6 | Risk factors and pain status due to diabetic neuropathy in chronic long-term diabetic patients in a Chinese urban population显示文摘 | JI Na ZHANG Nan REN Zhan-jie JIA Ke-bao WANG Li NI Jia-xiang MA Jun | 2012 | Chinese Medical Journal2012，，23： | 10 |
| 7 | Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction显示文摘From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12 th day of pregnancy, 300 mg/kg taurine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neo-natal rats with intrauterine growth restriction undergoing taurine supplement were obtained for fur-ther experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. Immu-nohistochemical staining revealed that taurine supplement increased glial cell line-derived neuro-trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain. | Jing Liu Xiaofeng Wang Ying Liu Na Yang Jing Xu Xiaotun Ren | 2013 | Neural Regeneration Research2013，8，23： | 9 |
| 8 | Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China显示文摘Objective Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.Methods A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients’ medical records. Multivariable logistic regression models were used to estimate the odds ratio(OR) and 95% confidence interval(95% CI) of the associations between comorbidities(cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19.Results Overall, 158(13.6%) patients were diagnosed with severe illness and 32(2.7%) had unfavorable outcomes. Hypertension(2.87, 1.30–6.32), type 2 diabetes(T2 DM)(3.57, 2.32–5.49),cardiovascular disease(CVD)(3.78, 1.81–7.89), fatty liver disease(7.53, 1.96–28.96), hyperlipidemia(2.15, 1.26–3.67), other lung diseases(6.00, 3.01–11.96), and electrolyte imbalance(10.40, 3.00–26.10)were independently linked to increased odds of being severely ill. T2 DM(6.07, 2.89–12.75), CVD(8.47,6.03–11.89), and electrolyte imbalance(19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission(5.46,3.25–9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes(6.58, 1.46–29.64) within two weeks.Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes. | MA Yan ZHU Dong Shan CHEN Ren Bo SHI Nan Nan LIU Si Hong FAN Yi Pin WU Gui Hui YANG Pu Ye BAI Jiang Feng CHEN Hong CHEN Li Ying FENG Qiao GUO Tuan Mao HOU Yong HU Gui Fen HU Xiao Mei HU Yun Hong HUANG Jin HUANG Qiu Hua HUANG Shao Zhen JI Liang JIN Hai Hao LEI Xiao LI Chun Yan LI Min Qing LI Qun Tang LI Xian Yong LIU Hong De LIU Jin Ping LIU Zhang MA Yu Ting MAO Ya MO Liu Fen NA Hui WANG Jing Wei SONG Fang Li SUN Sheng WANG Dong Ting WANG Ming Xuan WANG Xiao Yan WANG Yin Zhen WANG Yu Dong WU Wei WU Lan Ping XIAO Yan Hua XIE Hai Jun XU Hong Ming XU Shou Fang XUE Rui Xia YANG Chun YANG Kai Jun YUAN Sheng Li ZHANG Gong Qi ZHANG Jin Bo ZHANG Lin Song ZHAO Shu Sen ZHAO Wan Ying ZHENG Kai ZHOU Ying Chun ZHU Jun Teng ZHU Tian Qing ZHANG Hua Min WANG Yan Ping WANG Yong Yan 无 | 2020 | Biomedical and Environmental Sciences2020，33，12： | 8 |
| 9 | Development and characterization of a cell line from the embryos of half smooth tongue sole (Cynoglossus semilaevis)显示文摘A new cell line,CSEC,has been successfully established from embryos at gastrula stage of a cultured marine fish,half smooth tongue sole(Cynoglossus semilaevis).CSEC cells grow actively and stably more than 50 passages for over 200 d in DMEM medium supplemented with 15% FBS(fetal bovine serum),2.5 ng/cm 3 bFGF(basic fibroblast growth factor),1 ng/cm 3 LIF(leukemia inhibitory factor) and 50 mmol/dm 3 2-ME(2-mecaptoethanol).The cells grew well in the temperature range of 24-30 ℃ and the optimal growth temperature was 24℃.FBS and bFGF concentrations are the two key components for CSEC cells proliferation.Chromosome analysis reveals that CSEC cells have a normal diploid karyotype with 2n=42t.The significant fluorescent signals were observed in CSEC after transfection with the GFP reporter gene,suggesting that the CSEC cell line can be used as a useful tool for transgenic and genetic manipulation studies.CSEC cells showed the cytopathic effect(CPE) after infection with lymphosystis disease virus(LCDV) in 2 d.Moreover,the LCDV particles can be observed in the cytoplasm of virus-infected cells by electron microscopy.It suggests that CSEC could be potentially used for the study of aquatic virus. | SHA Zhenxia REN Guocheng WANG Xianli WANG Na CHEN Songlin | 2010 | Acta Oceanologica Sinica2010，29，2： | 7 |
| 10 | A novel ASBT inhibitor, IMB17-15, repressed nonalcoholic fatty liver disease development in high-fat diet-fed Syrian golden hamsters显示文摘The manipulation of bile acid (BA) homeostasis by blocking the ileal apical Na+-dependent bile salt transporter (ASBT/SLC10A2) may have therapeutic effects in nonalcoholic fatty liver disease. We developed a novel ASBT inhibitor, an N-(3,4-o-dichlorophenyl)?2-(3-trifluoromethoxy) benzamide derivative referred to as IMB17–15, and investigated its therapeutic effects and the molecular mechanisms underlying the effects. Syrian golden hamsters were challenged with high-fat diet (HFD) to induce NAFLD and were subsequently administered 400 mg/kg IMB17–15 by gavage daily for 21 days. Serum, liver, and fecal samples were collected for further analysis. Plasma concentration-time profiles of IMB17–15 were also constructed. The human hepatocyte cell line HL-7702 was treated with Oleic acid (OA) with or without IMB17–15. Western blotting and real-time PCR were used to study the molecular mechanisms of IMB17–15. We found that IMB17–15 inhibited ASBT and subsequently suppressed ileal farnesoid X receptor (FXR) and FXR-activated fibroblast growth factor15/19 (FGF15/19) expression, which reduced the hepatic phosphorylated extracellular regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) levels and upregulated the cholesterol 7α-hydroxylase (CYP7A1) activity. Additionally, IMB17–15 stimulated adenosine monophosphate (AMP)-activated protein kinase (AMPKα) phosphorylation and enhanced peroxisome proliferator activated receptor α(PPARα) expression and thus promoted triglyceride (TG) oxidation and high-density lipoprotein cholesterol (HDL-c) metabolism through an ASBT-independent mechanism. In conclusion, a novel ASBT inhibitor known as IMB17–15 protected hamsters against HFD-induced NFALD by manipulating BA and lipid homeostasis. IMB17–15 also reduced lipid deposition in human hepatic cell lines, indicating that it may be useful as a therapy for NAFLD patients. | Mao-xu Ge Wei-xiao Niu Jin-feng Ren Shi-ying Cai Dong-ke Yu Hong-tao Liu Na Zhang Yi-xuan Zhang Yu-cheng Wang Rong-guang Shao Ju-xian Wang Hong-wei He | 2019 | Acta Pharmacologica Sinica2019，40，7： | 7 |
| 11 | In situ grown Fe_(3)O_(4)particle on stainless steel:A highly efficient electrocatalyst for nitrate reduction to ammonia显示文摘NH_(3)is an essential feedstock for fertilizer synthesis.Industry-scale NH_(3)synthesis mostly relies on the Haber-Bosch method,however,which suffers from massive CO_(2) emission and high energy consumption.Electrocatalytic NO_(3)-reduction is an attractive substitute to the Haber-Bosch method for synthesizing NH_(3)under mild conditions.As this reaction will produce a variety of products,it highly desires efficient and selective electrocatalyst for NH_(3)generation.Here,we report in situ grown Fe_(3)O_(4)particle on stainless steel(Fe_(3)O_(4)/SS)as a high-efficiency electrocatalyst for NO_(3)^(-)reduction to NH_(3).In 0.1 M NaOH with 0.1 M NaNO_(3),such Fe_(3)O_(4)/SS reaches a remarkable Faradaic efficiency of 91.5%and a high NH_(3)yield of 10,145μg·h^(-1)·cm^(-2)at-0.5 V vs.reversible hydrogen electrode(RHE).Furthermore,it owns robust structural and electrochemical stability.This work provides useful guidelines to expand the scope of metallic oxide electrocatalysts for NH_(3)synthesis.The catalytic mechanism is uncovered and discussed further by theoretical calculations. | Xiaoya Fan Lisi Xie Jie Liang Yuchun Ren Longcheng Zhang Luchao Yue Tingshuai Li Yonglan Luo Na Li Bo Tang Yang Liu Shuyan Gao Abdulmohsen Ali Alshehri Qian Liu Qingquan Kong Xuping Sun | 2022 | Nano Research2022，15，4： | 7 |
| 12 | Effects of Brassinosteroid Associated with Auxin and Gibberellin on Apple Tree Growth and Gene Expression Patterns显示文摘Brassinosteroid is an important hormone that interacts with auxin and gibberellin to regulate plant growth and development. However,there is currently a relative lack of information regarding brassinosteroid in apple. Previous study confirmed that exogenous brassinosteroid treatments increased growth and endogenous brassinosteroid, auxin, as well as gibberellin levels of apple nursery trees. Here we succeeded to find that exogenous brassinosteroid treatments upregulated the transcript expression of auxin biosynthesis, transport, and positive signal transduction genes as well as gibberellin biosynthesis genes. In contrast, the application of exogenous brassinosteroid downregulated the expression of genes encoding negative regulators of auxin and gibberellin signal transductions. Rapid responses of several brassinosteroid-,auxin-, and gibberellin-related genes to the brassinosteroid and brassinazole treatments inferred the crosstalk of BR and IAA or GA. Furthermore,the expression levels of cell growth-related genes were also enhanced by exogenous brassinosteroid. Auxin and gibberellin treatments also influenced growth of apple tree and enhanced the expression of brassinosteroid-and cell growth-related genes. These results indicate that the growth of apple tree is regulated by the interaction between brassinosteroid, auxin, and gibberellin. Our work opened new avenues for deep portfolio of apple tree growth and laid the foundation for future studies aimed at elucidating the mechanisms regulating hormone interactionsmediated growth in apple trees. | Liwei Zheng Cai Gao Caide Zhao Lizhi Zhang Mingyu Han Na An Xiaolin Ren | 2019 | Horticultural Plant Journal2019，5，3： | 7 |
| 13 | Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline(updated version)显示文摘The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnosis and treatment guidelines for clinicians caring for patients are needed.In the early stage,we have issued'A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)';now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline.We formed a working group of clinical experts and methodologists.The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas:chemoprophylaxis,diagnosis,treatments,and discharge management.We searched the literature for direct evidence on the management of COVID-19,and assessed its certainty generated recommendations using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach.Recommendations were either strong or weak,or in the form of ungraded consensus-based statement.Finally,we issued 34 statements.Among them,6 were strong recommendations for,14 were weak recommendations for,3 were weak recommendations against and 11 were ungraded consensus-based statement.They covered topics of chemoprophylaxis(including agents and Traditional Chinese Medicine(TCM)agents),diagnosis(including clinical manifestations,reverse transcription-polymerase chain reaction(RT-PCR),respiratory tract specimens,IgM and IgG antibody tests,chest computed tomography,chest X-ray,and CT features of asymptomatic infections),treatments(including lopinavirritonavir,umifenovir,favipiravir,interferon,remdesivir,combination of antiviral drugs,hydroxychloroquine/chloroquine,interleukin-6 inhibitors,interleukin-1 inhibitors,glucocorticoid,qingfei paidu decoction,lianhua qingwen granules/capsules,convalescent plasma,lung transplantation,invasive or noninvasive ventilation,and extracorporeal membrane oxygenation(ECMO)),and discharge management(including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge).We also created two figures of these recommendations for the implementation purpose.We hope these recommendations can help support healthcare workers caring for COVID-19 patients. | Ying-Hui Jin Qing-Yuan Zhan Zhi-Yong Peng Xue-Qun Ren Xun-Tao Yin Lin Cai Yu-Feng Yuan Ji-Rong Yue Xiao-Chun Zhang Qi-Wen Yang Jianguang Ji Jian Xia Yi-Rong Li Fu-Xiang Zhou Ya-Dong Gao Zhui Yu Feng Xu Ming-Li Tu Li-Ming Tan Min Yang Fang Chen Xiao-Ju Zhang Mei Zeng Yu Zhu Xin-Can Liu Jian Yang Dong-Chi Zhao Yu-Feng Ding Ning Hou Fu-Bing Wang Hao Chen Yong-Gang Zhang Wei Li Wen Chen Yue-Xian Shi Xiu-Zhi Yang Xue-Jun Wang Yan-Jun Zhong Ming-Juan Zhao Bing-Hui Li Lin-Lu Ma Hao Zi Na Wang Yun-Yun Wang Shao-Fu Yu Lu-Yao Li Qiao Huang Hong Weng Xiang-Ying Ren Li-Sha Luo Man-Ru Fan Di Huang Hong-Yang Xue Lin-Xin Yu Jin-Ping Gao Tong Deng Xian-Tao Zeng Hong-Jun Li Zhen-Shun Cheng Xiao-Mei Yao Xing-Huan Wang | 2020 | Military Medical Research2020，7，3： | 6 |
| 14 | Synthesis and biological evaluation of novel triazole derivatives as antifungal agents显示文摘A series of 1-(benzylamino)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-l-yl)propan-2-ols compounds were synthesized and evaluated for their antifungal activities in vitro.The results showed that compounds 6A and 6B exhibited good antifungal activity.Compound 6A8 showed the strongest antifungal activity,which was significantly higher than that of the lead compounds and positive-control drugs Fluconazole and Itraconazole.In particular,the antifungal activity of compound 6A8 against Candida albicans and Candida krusei(MIC80 both at 0.00097μg/mL) was 515 and 64 times that of Fluconazole,respectively.The structure-activity relationships of the synthesized compounds were discussed,and the docking model of the target compounds with fungal lanosterol 14α-demethylase (CYP51) was analyzed. | Hui Tang Can-Hui Zheng Xiao-Hui Ren Jia Liu Na Liu Jia-Guo Lv Ju Zhu You-Jun Zhou | 2013 | Chinese Chemical Letters2013，24，3： | 6 |
| 15 | Study of asphaltene deposition from Tahe crude oil显示文摘Borehole blockage caused by asphaltene deposition is a problem in crude oil production in the Tahe Oilfield, Xinjiang, China. This study has investigated the influences of crude oil compositions, temperature and pressure on asphaltene deposition. The asphaltene deposition trend of crude oil was studied by saturates, aromatics, resins and asphaltenes (SARA) method, and the turbidity method was applied for the first time to determine the onset of asphaltene flocculation. The results showed that the asphaltene deposition trend of crude oil by the turbidity method was in accordance with that by the SARA method. The asphaltene solubility in crude oil decreased with decreasing temperature and the amount of asphaltene deposits of T739 crude oil (from well T739, Tahe Oilfield) had a maximum value at 60 o C. From the PVT results, the bubble point pressure of TH10403CX crude oil (from well TH10403CX, Tahe Oilfield) at different temperatures can be obtained and the depth at which the maximum asphaltene flocculation would occur in boreholes can be calculated. The crude oil PVT results showed that at 50 , 90 and 130 o C, the bubble point pressure of TH10403CX crude oil was 25.2, 26.4 and 27.0 MPa, respectively. The depth of injecting asphaltene deposition inhibitors for TH10403CX was determined to be 2,700 m. | CHEN Chaogang GUO Jixiang AN Na REN Bo LI Yaguang JIANG Qingzhe | 2013 | Petroleum Science2013，10，1： | 5 |
| 16 | Prevalence of Metabolic Syndrome in Chinese Nickel-exposed Workers显示文摘The prevalence of metabolic syndrome(MS was investigated in Chinese nickel-exposed workers A total of 35 104 subjects were enrolled in this study.The age-adjusted prevalence of MS,BMI≥25diabetes,hypertension,and abnormal lipid was13.9%,29.5%,12.8%,27.5%,and 47.1%respectively.The prevalence of BMI≥25hyperglycemia,and hypertension increased | YANG Ai Min BAI Ya Na PU Hong Quan ZHENG Tong Zhang CHENG Ning LI Juan Sheng LI Hai Yan ZHANG Ya Wei DING Jiao SU Hui REN Xiao Wei HU Xiao Bin | 2014 | Biomedical and Environmental Sciences2014，27，6： | 5 |
| 17 | Pantoprazole ameliorates liver fibrosis and suppresses hepatic stellate cell activation in bile duct ligation rats by promoting YAP degradation显示文摘Liver fibrosis is one of the most severe pathologic consequences of chronic liver diseases,and effective therapeutic strategies are urgently needed.Proton pump inhibitors(PPIs)are H+/K+-ATPase inhibitors and currently used to treat acid-related diseases such as gastric ulcers,which have shown other therapeutic effects in addition to inhibiting acid secretion.However,few studies have focused on PPIs from the perspective of inhibiting hepatic fibrosis.In the present study,we investigated the effects of pantoprazole(PPZ),a PPI,against liver fibrosis in a bile duct ligation(BDL)rat model,human hepatic stellate cell(HSC)line LX-2 and mouse primary HSCs(pHSCs),and explored the potential mechanisms underlying the effects of PPZ in vitro and in vivo.In BDL rats,administration of PPZ(150 mg·kg^(−1)·d^(−1),i.p.for 14 d)significantly attenuated liver histopathological injury,collagen accumulation,and inflammatory responses,and suppressed fibrogenesis-associated gene expression including Col1a1,Acta2,Tgfβ1,and Mmp-2.In LX-2 cells and mouse pHSCs,PPZ(100–300μM)dose-dependently suppressed the levels of fibrogenic markers.We conducted transcriptome analysis and subsequent validation in PPZ-treated LX-2 cells,and revealed that PPZ inhibited the expression of Yes-associated protein(YAP)and its downstream targets such as CTGF,ID1,survivin,CYR61,and GLI2.Using YAP overexpression and silencing,we demonstrated that PPZ downregulated hepatic fibrogenic gene expression via YAP.Furthermore,we showed that PPZ promoted the proteasome-dependent degradation and ubiquitination of YAP,thus inhibiting HSC activation.Additionally,we showed that PPZ destabilized YAP by disrupting the interaction between a deubiquitinating enzyme OTUB2 and YAP,and subsequently blocked the progression of hepatic fibrosis. | Zhen-ning Lu Wei-xiao Niu Na Zhang Mao-xu Ge Yun-yang Bao Yu Ren Xiu-li Guo Hong-wei He | 2021 | Acta Pharmacologica Sinica2021，42，11： | 5 |
| 18 | Osteoclasts are not a source of SLIT3显示文摘The axon guidance cue SLIT3 was identified as an osteoanabolic agent in two recent reports. However, these reports conflict in their nomination of osteoblasts versus osteoclasts as the key producers of skeletal SLIT3 and additionally offer conflicting data on the effects of SLIT3 on osteoclastogenesis. Here, aiming to address this discrepancy, we found no observable SLIT3 expression during human or mouse osteoclastogenesis and the only modest SLIT3-mediated effects on osteoclast differentiation. Conditional deletion of SLIT3 in cathepsin K(CTSK)-positive cells, including osteoclasts, had no effect on the number of osteoclast progenitors, in vitro osteoclast differentiation, overall bone mass, or bone resorption/formation parameters. Similar results were observed with the deletion of SLIT3 in Lys M-positive cells, including osteoclast lineage cells. Consistent with this finding, bone marrow chimeras made from Slit3-/-donors that lacked SLIT3 expression at all stages of osteoclast development displayed normal bone mass relative to controls. Taken in context, multiple lines of evidence were unable to identify the physiologic function of osteoclast-derived SLIT3,indicating that osteoblasts are the major source of skeletal SLIT3. | Na Li Kazuki Inoue Jun Sun Yingzhen Niu Sarfaraz Lalani Alisha Yallowitz Xu Yang Chao Zhang Rong Shen Baohong Zhao Ren Xu Matthew B.Greenblatt | 2020 | Bone Research2020，8，2： | 4 |
| 19 | Translation and validation of the Tibetan confusion assessment method for the intensive care unit显示文摘Background: At present, there is no available delirium translated assessment method for 3.3 million Tibetans. This study ai provide a method for delirium assessment for Tibetan patients speaking this language by validating a translation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Methods: The study was conducted between July 2018 and November 2018. Patients were screened for delirium by a neurologist using the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). Patients were subsequently screened by two nurses using Tibetan translations of the CAM-ICU. With DSM-IV criterion as the reference standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the validity of the CAM-ICU criterion. Interrater reliability was determined by comparing the CAM-ICU ratings of nurse 1 vs. nurse 2 using the k coefficient. Results: Ninety-six patients were assessed independently by two nurses and one neurologist. According to DSM-IV standard, 42 out of 96 (43.8%) patients developed delirium. The sensitivities of Tibetan CAM-ICU were 90.5% for nurse 1 and 92.9% for nurse 2, respectively. Their specificities were 85.2% and 90.7%, respectively. The PPV were 82.6% for nurse 1 and 88.6% for nurse 2. Their NPV were 92.0% and 94.2%, respectively. The Tibetan CAM-ICU was done with good interrater reliability between nurse 1 and nurse 2 (k=0.91, P<0.001). Conclusion: The Tibetan CAM-ICU shows good validity and might be incorporated into clinical practice in Tibetan Intensive Care Units. | Qu-Zhen Danzeng Na Cui Hao Wang Wen-Jun Pan Yun Long Yang-Zong Deji Cheng Ze Zeng Ren | 2019 | Chinese Medical Journal2019，，10： | 4 |
| 20 | The jasmonate-induced bHLH gene SlJIG functions in terpene biosynthesis and resistance to insects and fungus显示文摘Jasmonic acid(JA)is a key regulator of plant defense responses.Although the transcription factor MYC2,the master regulator of the JA signaling pathway,orchestrates a hierarchical transcriptional cascade that regulates the JA responses,only a few transcriptional regulators involved in this cascade have been described.Here,we identified the basic helix-loop-helix(bHLH)transcription factor gene in tomato(Solanum lycopersicum),METHYL JASMONATE(MeJA)-INDUCED GENE(SlJIG),the expression of which was strongly induced by MeJA treatment.Genetic and molecular biology experiments revealed that SlJIG is a direct target of MYC2.SlJIG knockout plants generated by gene editing had lower terpene contents than the wild type from the lower expression of TERPENE SYNTHASE(TPS)genes,rendering them more appealing to cotton bollworm(Helicoverpa armigera).Moreover,SlJIG knockouts exhibited weaker JA-mediated induction of TPSs,suggesting that SlJIG may participate in JA-induced terpene biosynthesis.Knocking out SlJIG also resulted in attenuated expression of JA-responsive defense genes,which may contribute to the observed lower resistance to cotton bollworm and to the fungus Botrytis cinerea.We conclude that SlJIG is a direct target of MYC2,forms a MYC2-SlJIG module,and functions in terpene biosynthesis and resistance against cotton bollworm and B.cinerea. | Yunyun Cao Lun Liu Kangsheng Ma Wenjing Wang Hongmei Lv Ming Gao Xinman Wang Xichun Zhang Shuxin Ren Na Zhang Yang-Dong Guo | 2022 | Journal of Integrative Plant Biology2022，64，5： | 4 |
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