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Recombinant adenovirus containing hyper-interleukin-6 and hepatocyte growth factor ameliorates acute-on-chronic liver failure in rats

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World Journal of Gastroenterology 2016年第16期22卷 4136-4148页

作者： Dan-Dan Gao Jia Fu Bo Qin wen-xiang huang Chun Yang Bei Jia Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases Department of Infectious Diseases The First Affiliated Hospital of Chongqing Medical University

AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6 (Hyper-IL-6, HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF (Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure (ACLF).METHODS: The recombinant adenoviruses containing HIL-6 and/or HGF were constructed. We established an ACLF model, and rats were randomly assigned to control, model, Ad-GFP, Ad-HIL-6, Ad-HGF or Ad-HGF-HIL-6 group. We collected serum and liver tissue samples to test pathological changes, biochemical indexes and molecular biological ***: Attenuated alanine aminotransferase, prothrombin time, high-mobility group box 1 (HMGB1), endotoxin, tumour necrosis factor (TNF)-α and interferon-γ were observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. Likewise, reduced hepatic damage and apoptotic activity, as well as reduced HMGB1 and Bax proteins, but raised expression of Ki67 and Bcl-2 proteins and Bcl-2/Bax ratio were also observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. More significant changes were observed in the Ad-HGF-HIL-6 treatment group without obvious side effects. Furthermore, caspase-3 at the protein level decreased in the Ad-HIL-6 and Ad-HGF-HIL-6 treatment groups, more predominantly in the latter ***: This study identifies that the protective efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 in ACLF rats, with no significant side effects.

关键词： Acute-on-chronic liver failure Recombinant adenovirus Hyper-interleukin-6 Hepatocyte growth factor Inflammatory cytokines

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Efficacy of Nonsteroidal Anti-inflammatory Drugs for Treatment of Uncomplicated Lower Urinary Tract Infections in Women:A Meta-analysis

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Infectious Microbes & Diseases 2020年第2期2卷 77-82页

作者： Yu Zhang Jian-Guo Wu Hong-Ji Zhou wen-xiang huang Bei Jia Department of Infectious Diseases The Affiliated Hospital of Medical School of Ningbo UniversityNingboZhejiangChina Key Laboratory of Infectious and Parasitic Diseases in Chongqing Infectious Disease DepartmentThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Infectious Diseases Chongqing Fengjie County People’s HospitalChongqing 404600China

Urinary tract infections(UTIs)are among the most frequent causes for antibiotic prescription and;therefore,alternative treatment options for UTIs can potentially reduce antibiotic usage and development of *** evaluate the efficacy of nonsteroidal antiinflammatory drugs(NSAIDS)for the treatment of uncomplicated lower UTIs in women,this study implemented a meta-analytic approach to evaluate the results of available randomized clinical studies from online databases.A total of four trials involving 1144 patients with uncomplicated lower UTIs were included in the final *** showed that symptom resolution at Day 3-4 in the NSAIDs group was significantly lower than that in the antibiotics group[pooled odds ratio(OR)=0.41,95%confidence interval(CI):0.23-0.74,P<0.05].However,there was no significant difference between the NSAIDs and antibiotics groups in symptom resolution at Day 7(pooled OR=0.43,95%CI:0.17-1.06,P=0.07),secondary antibiotic treatment rate at Day 28-30(pooled OR=1.15,95%CI:0.16-7.98,P=0.89)and adverse events rate(pooled OR=1.09,95%CI:0.61-1.96,P=0.77).Therefore,this metaanalysis suggests that,although inferior to antibiotics in fast symptom resolution,symptomatic treatment with NSAIDs can be considered as an alternative treatment option for uncomplicated lower UTIs in ***,given the low number of randomized controlled trials that met inclusion criteria in this meta-analysis,efficacy of NSAIDs for treatment of uncomplicated lower UTIs should be further evaluated in more comprehensive clinical studies.

关键词： nonsteroidal anti-inflammatory drugs NSAID uncomplicated lower urinary tract infections UTI meta-analysis

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Dynamical complexity of Anosov systems driven by a quasi-periodic force

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Science China Mathematics 2025年第1期 89-136页

作者： wen huang Zeng Lian Kening Lu Department of Mathematics University of Science and Technology of China School of Mathematics Sichuan University

Consider C2Anosov systems on a compact manifold driven by a quasi-periodic *** study their dynamical complexity on various levels from the perspectives of both path-wise dynamics and stochastic *** that these systems are non-wandering（i.e.,every point in the phase space is nonwandering）,we prove a set of results:（1） the existence of abundance of random periodic points;（2） a random Liv?ic theorem;（3） a random Ma?é-Bousch-Conze-Guivarc'h lemma;（4） the existence of strong random ***,a concrete example constructed on a 2-dimensional torus is also given to uncover some interesting phenomena of the systems.

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The relationship between SARS-COV-2 RNA positive duration and the risk of recurrent positive

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Infectious Diseases of Poverty 2021年第2期10卷 97-97页

作者： Hong Zhao Chi Zhang Xian-xiang Chen Qi Zhu wen-xiang huang Yi-Lan Zeng Ying-Xia Liu Guo-Jun Li Wei-Jun Du Jing Yao Jia-wen Li Peng Peng Gui-Qiang Wang Department of Infectious Disease Center for Liver DiseasePeking University First HospitalBeijingChina 不详 Administrative Office Wuhan Pulmonary HospitalWuhanChina

Background:The management of discharge COVID-19 patients with recurrent positive SARS-CoV-2 RNA is ***,there are fewer scientific dissertations about the risk of recurrent *** aim of this study was to explore the rela... 详细信息

关键词： SARS-CoV-2 COVID-19 SARS-CoV-2 RNA positive duration Recurrent positive Prevention

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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-wen Alvin huang John Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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表面源激发的瑞利波传播特性分析

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岩土力学 2017年第2期38卷 325-332,340页

作者：柴华友柯文汇黄祥国李忠超李天祥武汉工程大学资源与土木工程学院湖北武汉430073 武汉市市政建设集团有限公司湖北武汉430023 清华大学土木工程系北京100084

自由状态下层状介质中平面瑞利波相速度与频率及层状介质特性参数有关,表面源激发的瑞利波以柱面波阵面传播,传播速度不仅与频率有关,而且还与传播距离有关,这样,自由状态下层状介质中平面瑞利波传播特性理论不能有效地用于激发瑞利波... 详细信息

自由状态下层状介质中平面瑞利波相速度与频率及层状介质特性参数有关,表面源激发的瑞利波以柱面波阵面传播,传播速度不仅与频率有关,而且还与传播距离有关,这样,自由状态下层状介质中平面瑞利波传播特性理论不能有效地用于激发瑞利波相速度分析。以薄层法得到的圆盘状表面垂直源激发瑞利波位移响应为基础,导出激发瑞利波相速度,比较激发模态与简正模态相速度差异,分析激发模态空间特性,揭示这种空间特性形成机制。结果表明:源对激发模态传播影响距离不超过一个波长,波场距源越近,激发模态竖直振动传播速度越低;在多模波场,激发模态间相长相干或相消相干导致表观相速度具有较明显的空间特性。该研究可为发展考虑瑞利波频率及空间特性反演数学模型及算法提供指导。

关键词：薄层法主动源瑞利波频散特性空间特性

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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期 204-218页

作者： Chen Xiong Hong Ling Yingdan huang Hanzhi Dong Bangxiang Xie Qian Hao xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期 308-316页

作者： Sili Wang Jiancheng huang Yanan Du Wei huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University National Health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

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The potential mechanism and clinical application value of remote ischemic conditioning in stroke

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Neural Regeneration Research 2025年第6期20卷 1613-1627页

作者： Yajun Zhu Xiaoguo Li Xingwei Lei Liuyang Tang Daochen wen Bo Zeng Xiaofeng Zhang Zichao huang Zongduo Guo The First Affiliated Hospital of Chongqing Medical University ChongqingChina

Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.

关键词： Akt apoptosis autophagy cerebral perfusion cerebral vascular stenosis clinical transformation hemorrhagic stroke ischemic stroke neuroinflammation neuroprotection Notch1 PI3K remote ischemic conditioning stroke

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Visualization of the protective role of estrogen against female liver fibrosis via an ER viscosity NIR fluorescent probe

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Science China Chemistry 2025年第1期 360-368页

作者： Zheng Liu Changyu Zhang Zipeng Li Wanying Ma Jia Liu xiang Xia Ning Xu wen Sun Jianjun Du Jiangli Fan Xiaojun Peng State Key Laboratory of Fine Chemicals Dalian University of Technology Ningbo Institute of Dalian University of Technology

Endoplasmic reticulum(ER) viscosity has emerged as a new potential biomarker for hepatic fibrosis(HF). Herein, we report the first ER-targeting viscosity-responsive near-infrared(NIR) fluorescent probe HBT-PP for investigations of HF *** twisted intramolecular charge transfer(TICT) and the excited state intramolecular proton transfer(ESIPT) are combined to endow HBT-PP with the selective response towards viscosity(～62-fold) and a super large stokes shift(～320 nm). HBT-PP mainly targets organelle ER and is able to image the drug-or alcohol-induced viscosity elevation in living cells. Significantly,HBT-PP was successfully applied to visualize the gender difference in HF and the protective role of estrogen in restraining HF progression. Of note, after 10 min of stain with HBT-PP, HF lesions showed a stage-based response, indicating the potential of this probe in fast and early diagnosis of HF. These results clearly demonstrated the promising application of HBT-PP as a new tool for exploring ER viscosity-involved physiological and pathological processes.

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