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Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

Military Medical Research 2024年第2期11卷 180-205页

作者： hong weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence‑Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor Biological Behaviors Wuhan 430071China Department of Pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Pathology and Molecular Diagnostics Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain ***,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of ***:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan *** advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in *** expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting *** elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in *** Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical ***:ASPA was identified as a novel inhibitor of PCa *** expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,mig

关键词： Prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

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Unraveling Iterative Control Structures from Business Processes

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Journal of Computer Science & Technology 2021年第1期36卷 158-190页

作者： Yain-Whar Si weng-hong Yung Department of Computer and Information Science University of MacaoMacaoChina

Iterative control structures allow the repeated execution of tasks,activities or sub-processes according to the given conditions in a process *** control structures can significantly increase the risk of triggering temporal exceptions since activities within the scope of these control structures could be repeatedly executed until a predefined condition is *** this paper,we propose two approaches to unravel iterative control structures from process *** first approach unravels loops based on zero-one *** second approach unravels loops based on branching probabilities assigned at split *** proposed methods can be used to unfold structured loops,nested loops and crossing *** the unfolded model does not contain any iterative control structures,it can be used for further analysis by process designers during the modeling *** proposed methods are implemented based on workflow graphs,and therefore they are compatible with modeling languages such as Business Process Modelling Notation(BPMN).In the experiments,the execution behavior of unfolded process models is compared against the original models based on the concept of *** results reveal that runs generated from the original models can be correctly executed in the unfolded BPMN models that do not contain any loops.

关键词： business process management iterative control structure unravelling zero-one principle branching probability

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Seismic failure modes and seismic safety of Hardfill dam

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Water Science and Engineering 2013年第2期6卷 199-214页

作者： Kun XIONG Yong-hong weng Yun-long H Changjiang Institute of Survey Planning Design and Research National Dam Safety Research Center State Key Laboratory of Water Resources and Hydropower Engineering Science Wuhan University State Key Laboratory of Hydraulics and Mountain River Engineering Sichuan University

Based on microscopic damage theory and the finite element method, and using the Weibull distribution to characterize the random distribution of the mechanical properties of materials, the seismic response of a typical Hardfill dam was analyzed through numerical simulation during the earthquakes with intensities of 8 degrees and even greater. The seismic failure modes and failure mechanism of the dam were explored as well. Numerical results show that the Hardfill dam remains at a low stress level and undamaged or slightly damaged during an earthquake with an intensity of 8 degrees. During overload earthquakes, tensile cracks occur at the dam surfaces and extend to inside the dam body, and the upstream dam body experiences more serious damage than the downstream dam body. Therefore, under the seismic conditions, the failure pattern of the Hardfill dam is the tensile fracture of the upstream regions and the dam toe. Compared with traditional gravity dams, Hardfill dams have better seismic performance and ~reater seismic safety.

关键词： Hardfill dam, seismic failure mode, seismic safety microscopic damage model

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Notch3 regulates the activation of hepatic stellate cells

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World Journal of Gastroenterology 2012年第12期18卷 1397-1403页

作者： Yi-Xiong Chen Zhi-hong weng Shu-Ling Zhang Depart-ment of Hepatology and Infectious Disease Union HospitalTongji Medical College Huazhong University of Science andTechnology Wuhan 430022 Hubei Province China

AIM： To investigate whether Notch signaling is involved in liver fibrosis by regulating the activation of hepatic stellate cells （HSCs）.METHODS： Immunohistochemistry was used to detect the expression of Notch3 in fibrotic liver tissues of patients with chronic active hepatitis. The expression of Notch3 in HSC-T6 cells treated or not with transforming growth factor （TGF）-β1 was analyzed by iramunofluorescence staining, The expression of Notch3 and myofibroblastic marker （z-smooth muscle actin （（z-SMA） and collagen 1 in HSC-T6 cells transfected with pcDNA3. I-N3ICD or control vector were detected by Western blotting and immunofluorescence staining. Moreover, effects of Notch3 knockdown in HSC-T6 by Notch3 siRNA were investigated by Western blotting and immunofluorescence staining.RESULTS： The expression of Notch3 was significantly up-regulated in fibrotic liver tissues of patients withchronic active hepatitis, but not detected in normal liver tissues. Active Notch signaling was found in HSC-T6 cells. TGF-β1 treatment led to up-regulation of Notch3 expression in HSC-T6 cells, and over-expression of Notch3 increased the expression of α-SMA and collagen I in HSC-T6 without TGF-β1 treatment. Interestingly, transient knockdown of Notch3 decreased the expression of myofibroblastic marker and antagonized TGF-β1 induced expression of α-SMA and collagen I in HSC-T6.CONCLUSION： Notch3 may regulate the activation of HSCs, and the selective interruption of Notch3 may provide an anti -fibrotic strategy in hepatic fibrosis.

关键词： Notch signaling Myofibroblast Liver fibrosis Hepatic stellate cells siRNA

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Transcription networks in liver development and acute liver failure

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Liver Research 2023年第1期7卷 47-55页

作者： Rilu Feng Roman Liebe hong-Lei weng Department of Medicine II Section Molecular HepatologyUniversity Medical Center MannheimMedical Faculty MannheimHeidelberg UniversityMannheimGermany Clinic of Gastroenterology Hepatology and Infectious DiseasesHeinrich Heine UniversityDüsseldorfGermany Department of Medicine II Saarland University Medical CentreSaarland UniversityHomburgGermany

Acute liver failure(ALF)is a medical emergency due to massive hepatocyte *** such a harsh condition,maintaining transcriptional regulation in the remaining hepatocytes while activating similar transcription factor networks in liver progenitor cells(LPCs)to ensure essential liver functions are two critical processes to rescue patients from liver failure and *** this review,we discuss the formation and functions of transcription networks in ALF and liver *** focus on a hierarchical network of transcription factors that responds to different pathophysiological circumstances:(1)Under normal circumstances,pioneer factor forkhead box protein A2(FOXA2)coordinates several constitutive hepatic transcription factors,such as hepatic nuclear factor 4 alpha(HNF4a)and CCAAT-enhancer binding protein a(C/EBPa),which ensure normal liver function;(2)When the expression of both HNF4a and C/EBPa in hepatocytes are disrupted by severe inflammation,retinoic acid receptor(RAR)is the alternative transcription factor that compensates for their absence;(3)When massive hepatic necrosis occurs,a similar transcription network including FOXA2 and HNF4a,is activated as a“rescue network”in LPCs to maintain vital liver functions when hepatocytes fail,and thus ensures *** of these master transcription factors in hepatocytes and LPCs is tightly regulated by hormone signals and *** performance of this hierarchical transcription network,in particularly the“rescue network”described above,significantly affects the clinical outcome of ALF.

关键词： Pioneer transcription factor Lineage-determining transcription factor Signal-driven transcription factor Hepatocyte Massive hepatic necrosis Liver progenitor cell

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Innovation in neglected tropical disease drug discovery and development

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Infectious Diseases of Poverty 2018年第1期7卷 654-662页

作者： hong-Bo weng Hai-Xia Chen Ming-Wei Wang School of Pharmacy Fudan University826 Zhangheng RoadPudong New DistrictShanghai 201203China The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences(CAS)189 Guoshoujing RoadPudong New DistrictShanghai 201203China School of Life Science and Technology ShanghaiTech University393 Middle Huaxia RoadPudong New DistrictShanghai 201210China

Background:Neglected tropical diseases(NTDs)are closely related to poverty and affect over a billion people in developing *** unmet treatment needs cause high mortality and disability thereby imposing a huge burden with severe social and economic *** coordinated by the World Health Organization,various philanthropic organizations,national governments and the pharmaceutical industry have been making efforts in improving the situation,the control of NTDs is still inadequate and extremely difficult *** lack of safe,effective and affordable medicines is a key contributing *** paper reviews the recent advances and some of the challenges that we are facing in the fight against *** body:In recent years,a number of innovations have demonstrated propensity to promote drug discovery and development for *** of multilateral collaborations leads to continued efforts and plays a crucial role in drug *** approaches and advanced technologies are urgently needed in drug innovation for ***,the control and elimination of NTDs remain a formidable task as it requires persistent international cooperation to make sustainable progresses for a long period of *** currently employed strategies were proposed and verified to be successful,which involve both mechanisms of‘Push’which aims at cutting the cost of research and development for industry and‘Pull’which aims at increasing market *** to this effort should be the exercise of shared responsibility globally to reduce risks,overcome obstacles and maximize *** NTDs are closely associated with poverty,it is absolutely essential that the stakeholders take concerted and long-term measures to meet multifaceted challenges by alleviating extreme poverty,strengthening social intervention,adapting climate changes,providing effective monitoring and ensuring timely ***:The ongoing endeavor at the global scale wil

关键词： Innovation Collaboration Open-source Neglected tropical diseases

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A large basal cell adenoma extending to the ipsilateral skull base and mastoid in the right parotid gland: A case report

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World Journal of Clinical Cases 2019年第11期7卷 1351-1357页

作者： Lu-Yang Du Xiu-hong weng Zhen-Yu Shen Bo Cheng Department of Stomatology Union Hospital Tongji Medical College HuaZhong University of Science and Technology Wuhan 430022 Hubei Province China Department of Stomatology Zhongnan Hospital of Wuhan University Wuhan 430071 Hubei Province China

BACKGROUND Basal cell adenoma (BCA) is a rare benign tumour that has unique histological characteristics and primarily arises in the parotid glands. According to published reports, nearby tissue destruction by BCA seems impossible. CASE SUMMARY We presented a case of a 54-year-old woman with a mass in the deep lobe of the right parotid gland involving the ipsilateral skull base and mastoid. The patient exhibited gradual right facial swelling but no other obvious symptoms. Combined resection of the total right parotid gland and partial skull base excision were performed. The biopsy conducted before the surgery and sections cut from intraoperatively obtained tissues were not definitive for identifying the character of the neoplasm. A final diagnosis of tubular BCA without malignant elements was established based on postoperative pathology results and immunohistochemical analysis. The tumour did not recur during the 12-mo follow-up period. CONCLUSION A diagnosis of BCA can only be established based on a histopathological examination after an excisional biopsy, and tubular BCA should carefully be considered as a destructive type.

关键词： Basal cell adenoma Mastoid Parotid gland Skull base Total parotidectomy Case report

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Synthesis and Structure of Mixed Distannoxane Dimers [ClR_2SnOSnR'_2Cl]_2

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Chinese Chemical Letters 2002年第2期13卷 185-188页

作者： Yan Lu Lin hong weng Zhi Li LAN Jing LI Qing Lan XIE National Key Laboratory of Elemento-Organic Chemistry Nankai UniversityTianjin 300071

Mixed distannoxane dimers [ClR2SnOSnR'2Cl]2 were synthesized by the reaction of R2SnO (R = Bu, Pr) and R2SnCl2 (R = Me, Ph, Cy, Oct). The crystal structures of compound 1 and 5 show they are ladder-type dimers that c... 详细信息

关键词： Asymmetric tetraorganodistannoxane synthesis crystal structure.

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Inhibition of hepatitis B virus replication by pokeweed antiviral protein in vitro

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World Journal of Gastroenterology 2008年第10期14卷 1592-1597页

作者： Yong-Wen He Chun-Xia Guo Yan-Feng Pan Cheng Peng Zhi-hong weng Department of Infectious Disease Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 Hubei Province China Department of Infectious Disease the First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 Henan Province China

AIM: To explore the inhibitory effects of pokeweed antiviral protein seed (PAP-S) and PAP encoded by a eukaryotic expression plasmid on hepatitis B virus (HBV) replication in vitro. METHODS: HepG2 2.2.15 cells in cultured medium were treated with different concentrations of PAP-S. HBsAg, HBeAg and HBV DNA in supernatants were determined by ELISA and fluorescent quantitative PCR respectively. MTT method was used to assay for cytotoxicity. HepG2 were cotransfected with various amounts of PAP encoded by a eukaryotic expression plasmid and replication competent wild-type HBV 1.3 fold over- length plasmid. On d 3 after transfection, HBsAg and HBeAg were determined by using ELISA. Levels of HBV core-associated DNA and RNA were detected by using Southern and Northern blot, respectively. RESULTS: The inhibitory effects of PAP-S on HBsAg, HBeAg and HBV DNA were gradually enhanced with the increase of PAP concentration. When the concentration of PAP-S was 10 μg/mL, the inhibition rates of HBsAg, HBeAg and HBV DNA were 20.9%, 30.2% and 50%, respectively. After transfection of 1.0 μg and 2.0 μg plasmid pXF3H-PAP, the levels of HBV nucleocapside- associated DNA were reduced by 38.0% and 74.0% respectively, the levels of HBsAg in the media by 76.8% and 99.7% respectively, and the levels of HBeAg by 72.7% and 99.3% respectively as compared with controls. Transfection with 2 μg plasmid pXF3H-PAP reduced the levels of HBV nucleocapside-associated RNA by 69.0%.CONCLUSION: Both PAP-S and PAP encoded by a eukaryotic expression plasmid could effectively inhibit HBV replication and antigen expression in vitro, and the inhibitory effects were dose-dependent.

关键词： Pokeweed antiviral protein Hepatitis B virus Antiviral agent

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Computed tomography vs liver stiffness measurement and magnetic resonance imaging in evaluating esophageal varices in cirrhotic patients:A systematic review and meta-analysis

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World Journal of Gastroenterology 2020年第18期26卷 2247-2267页

作者： Yue Li Lei Li hong-Lei weng Roman Liebe Hui-Guo Ding Department of Gastroenterology and Hepatology Beijing You’an Hospital Affiliated with Capital Medical UniversityBeijing 100069China Department of Medicine Ⅱ Section Molecular HepatologyMedical Faculty MannheimHeidelberg UniversityMannheim 68167Germany Department of Medicine Ⅱ Saarland University Medical CenterHomburg 66424Germany

BACKGROUND Computed tomography(CT),liver stiffness measurement(LSM),and magnetic resonance imaging(MRI)are non-invasive diagnostic methods for esophageal varices(EV)and for the prediction of high-bleeding-risk EV(HREV)in cirrhotic ***,the clinical use of these methods is *** To evaluate the accuracy of LSM,CT,and MRI in diagnosing EV and predicting HREV in cirrhotic *** We performed literature searches in multiple databases,including Pub Med,Embase,Cochrane,CNKI,and Wanfang databases,for articles that evaluated the accuracy of LSM,CT,and MRI as candidates for the diagnosis of EV and prediction of HREV in cirrhotic *** sensitivity and specificity,positive likelihood ratio and negative likelihood ratio,diagnostic odds ratio,and the areas under the summary receiver operating characteristic curves were *** quality of the articles was assessed using the quality assessment of diagnostic accuracy studies-2 *** was examined by Q-statistic test and I2 index,and sources of heterogeneity were explored using metaregression and subgroup *** bias was evaluated using Deek’s funnel *** statistical analyses were conducted using Stata12.0,Meta Disc1.4,and Rev *** Overall,18,17,and 7 relevant articles on the accuracy of LSM,CT,and MRI in evaluating EV and HREV were retrieved.A significant heterogeneity was observed in all analyses(P<0.05).The areas under the summary receiver operating characteristic curves of LSM,CT,and MRI in diagnosing EV and predicting HREV were 0.86(95%confidence interval[CI]:0.83-0.89),0.91(95%CI:0.88-0.93),and 0.86(95%CI:0.83-0.89),and 0.85(95%CI:0.81-0.88),0.94(95%CI:0.91-0.96),and 0.83(95%CI:0.79-0.86),respectively,with sensitivities of 0.84(95%CI:0.78-0.89),0.91(95%CI:0.87-0.94),and 0.81(95%CI:0.76-0.86),and 0.81(95%CI:0.75-0.86),0.88(95%CI:0.82-0.92),and 0.80(95%CI:0.72-0.86),and specificities of 0.71(95%CI:0.60-0.80),0.75(95%CI:0.68-0.82),and 0.82(9

关键词： Multidetector computed tomography imaging Magnetic resonance imaging Liver stiffness measurement Liver cirrhosis Esophageal varices Meta-analysis

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