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Bacterial Infections in Acute-on-chronic Liver Failure:Epidemiology,Diagnosis,Pathogenesis,and Management

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Journal of Clinical and Translational Hepatology 2024年第7期12卷 667-676页

作者： Zhaoyu Xu Xiuding Zhang Jiyang Chen Yu Shi Shangwei Ji China-Japan Union Hospital of Jilin University ChangchunJilinChina State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangChina Department of infectious diseases China-Japan Union Hospital of Jilin UniversityChangchunJilinChina

Acute-on-chronic liver failure(ACLF)is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease,often leading to multi-organ failures and significant short-term *** infection is one of the most frequent triggers for ACLF and a common complication following its *** impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ *** addition,the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use,as well as accurate and prompt microbiological *** review provided an update on recent advances in the epidemiology,diagnosis,pathogenesis,and management of bacterial infections in ACLF.

关键词： Acute-on-chronic liver failure Bacterial infection Multidrug-resistant bacteria Spontaneoous bacterial peritonitis systemic inflammation Antibiotic Albumin

PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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Genes & diseases 2024年第4期11卷 340-352页

作者： Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang Key Laboratory of Molecular Biology for infectious diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Sichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteSichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduSichuan 610041China

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic *** carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor *** onco-genesis and progression of tumors are closely related to cancer stem *** is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular ***,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited ***,PCK1 increased the sensitivity of hepatocellular carci-noma cells to ***,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear *** reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of ***,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

关键词： Cancer stem cells Chemoresistance Gluconeogenesis Hepatocellular carcinoma YAP

Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling

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Genes & diseases 2024年第5期11卷 470-483页

作者： Zhirong Zhang Jiayao Yang Rui Liu Jing Ma Kai Wang Xiaojun Wang Ni Tang Key Laboratory of Molecular Biology for infectious diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China

Cancer stem cells(CSCs)play a crucial role in tumor initiation,recurrence,metastasis,and drug ***,the current understanding of CSCs in hepatocellular carcinoma(HCC)remains *** a comprehensive analysis of the database,it has been observed that 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR),a critical enzyme involved in cholesterol synthesis,is up-regulated in HCC tissues and liver ***,high expression of HMGCR is associated with a poor prognosis in patients with ***,HMGCR promotes the stemness and metastasis of HCC both in vitro and in *** screening various signaling pathway inhibitors,we have determined that HMGCR regulates stemness and metastasis by activating the Hedgehog signaling in ***,HMGCR positively correlates with the expression of the Smoothened receptor and facilitates the nuclear translocation of the transcriptional activator GLI family zinc finger *** of the Hedgehog pathway can reverse the stimulatory effects of HMGCR on stemness and metastasis in ***,simvastatin,an FDA-approved cholesterol-lowering drug,has been shown to inhibit stemness and metastasis of HCC by targeting *** together,our findings suggest that HMGCR promotes the regeneration and metastasis of HCC through the activation of Hedgehog signaling,and simvastatin holds the potential for clinical suppression of HCC metastasis.

关键词： Cancer stem cells Hedgehog Hepatocellular carcinoma Metastasis Statin

Endogenous retrovirus activation: potential for immunology and clinical applications

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National Science Review 2024年第4期11卷 21-23页

作者： Jundan Yu Peishan Qiu Jingwen Ai Bo Liu Guan-Zhu Han Fan Zhu Wenhong Zhang Jie Cui Department of infectious diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response National Medical Center for Infectious Diseases Huashan Hospital Shanghai Medical College Fudan University CAS Key Laboratory of Molecular Virology &Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai Huashen Institute of Microbes and Infections College of Life Sciences Nanjing Normal University State Key Laboratory of Virology and Department of Medical Microbiology School of Basic Medical SciencesWuhan University The Institute of Infection and Health research Fudan University Key Laboratory of Medical Molecular Virology(MOE/MOH) Shanghai Medical CollegeFudan University Laboratory for Marine Biology and Biotechnology Qingdao Marine Science and Technology Center

Endogenous retroviruses (ERVs), the remnants of ancient retrovirus infections, constitute approximately 8% of the human genome and play important roles in human evolution, development,and diseases. Multiple drugs, such as DNA methyltransferase inhibitors and lysine-specific histone demethylase 1inhibitors, reactivate ERVs, induce viral mimicry and trigger innate immune responses to enhance tumor immunogenicity.

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Complementary and alternative medicine on cognitive defects and neuroinflammation after sepsis

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Journal of Traditional Chinese Medicine 2024年第2期44卷 408-416页

作者： LI Zhenxuan WANG Xuerui Luis Ulloa Ayman Youssef BAI Yunjing XU Xiaolong LIU Qingquan Department of infectious diseases Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing 100010China Beijing Key Laboratory of Basic research with Traditional Chinese Medicine on infectious diseases Beijing 100010China Infection immunity laboratory Beijing Institute of Traditional Chinese MedicineBeijing 100010China Clinical College of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Center for Perioperative Organ Protection Department of AnesthesiologyDuke University Medical CenterDurhamNorth Carolina 27710USA

Sepsis-associated encephalopathy(SAE)is a common manifestation of sepsis,ranging from mild confusion and delirium to severe cognitive impairment and deep *** is associated with higher mortality and long-term outcomes,particularly substantial declines in cognitive *** mechanisms of SAE probably include neuroinflammation that is mediated by systemic inflammation and ischemic lesions in the brain,a disrupted blood–brain barrier,oxidative stress,neurotransmitter dysfunction,and severe microglial *** evidence suggests that complementary and alternative medicine,especially Traditional Chinese Medicine(TCM),is favorable in alleviating cognitive decline after ***,we summarized the studies of traditional herbal remedies,TCM formulas and acupuncture therapy in animal models of neurological dysfunctions after sepsis in recent decades and reviewed their potential mechanisms.

关键词： sepsis-associated encephalopathy cognitive dysfunction complementary therapies neuroinflammatory diseases medicine Chinese traditional review

Reaction Mechanism of Actin ATP Hydrolysis Studied by QM/MM Calculations

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Chemical research in Chinese Universities 2024年第5期40卷 849-855页

作者： WANG Yiwen LIN Lirui XU Li-Yan LI En-Min DONG Geng Department of Biochemistry and Molecular Biology Shantou University Medical CollegeShantou515041P.R.China Department of Bioinformatics Shantou University Medical CollegeShantou515041P.R.China Medical Informatics research Center Shantou University Medical CollegeShantou515041P.R.China Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Area of Guangdong Higher Education Institutes Shantou University Medical CollegeShantou515041P.R.China Cancer research Center Shantou University Medical CollegeShantou515041P.R.China Guangdong Provincial Key Laboratory of infectious diseases and Molecular immunopathology Shantou University Medical CollegeShantou515041P.R.China

Actin fibers are an important part of the cytoskeleton,providing vital support for the plasma *** function is driven by its ATPase(ATP:adenosine triphosphate)activity,i.e.,ATP+H_(2)O→ADP+*** seemingly simple reaction has attracted much attention because the hydrolysis of ATP provides energy to support life ***,the reaction mechanism of ATP hydrolysis in actin is not *** order to gain deep insights into the functions of actin,it is essential to elucidate the reaction mechanism of the actin ATP *** this paper,we have studied the reaction mechanism of the ATP hydrolysis in actin by the combined quantum mechanical and molecular mechanics(QM/MM)*** results show that 1)bond cleavage of the Pγ—OS of ATP and bond formation between oxygen of the lytic water and Pγatoms take place simultaneously,and this is the rate-limiting step of the hydrolysis;2)the proton on the lytic water transfers to the phosphate to form H_(2)P_(γ)O_(4)−via one bridge *** energy barrier of the complete reaction is 17.6 kcal/mol(1 kcal=4.184 kJ),which is in high agreement with the experimental value.

关键词： Actin Adenosine triphosphate(ATP)hydrolysis Quantum mechanical and molecular mechanics(QM/MM) Reaction mechanism

Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis

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Science China Life Sciences 2024年

作者： Xizi Luo Nan Zhang Yuntao Liu Beibei Du Xuan Wang Tianxu Zhao Bingqiang Liu Shishun Zhao Jiazhang Qiu Guoqing Wang State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic infectious diseases Key Laboratory for Zoonosis Research of the Ministry of Education College of Basic Medicine Jilin University State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic infectious diseases Key Laboratory for Zoonosis Research of the Ministry of Education College of Veterinary Medicine Jilin University College of Mathematics Jilin University Bioinformatic Lab School of Mathematics Shandong University Department of Cardiology China-Japan Union Hospital Jilin University

The coronavirus disease 2019(COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) developed into a global health emergency. systemic microthrombus caused by SARS-CoV-2 infection is a common complication in patients with COVID-19. Cardiac microthrombosis as a complication of SARS-CoV-2 infection is the primary cause of cardiac injury and death in patietns with severe COVID-19. In this study, we performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors,patients who died during the hypercoagulable period of characteristic coagulation abnormality(CAC), and patients who died during the fibrinolytic period of CAC. We collected 61,187 cells enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. We found that in the course of SARS-CoV-2 infected heart microthrombus, MYO1EhighRASGEF1Bhighmonocyte-derived macrophages promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating chemokines CCL3, CCL5. This series of events is the main cause of cardiac microthrombi following SARS-CoV-2 infection. In a SARS-CoV-2 infected heart microthrombus, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in increased sugar uptake via the glycosaminoglycan synthesis pathway. In addition, high levels of reactive oxygen species generated by elevated iron levels promote increased endogenous malondialdehyde synthesis in a subpopulation of cardiac endothelial cells. This exacerbates endothelial cell dysfunction and exacerbates the coagulopathy process.

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Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： Ying-Yan Wang Yun-Qing Zhou Li-Juan Luo Cui-Jin Wang Nan Shen Hao Li Ji-Wen Wang Department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of infectious diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Clinical research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency *** Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome *** analyzed the patients’convulsions and treatment with antiepileptic *** patients were followed up at different time periods after ketogenic diet *** Six patients with SLC2A1 mutations were included in this *** patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their *** were then treated with a ketogenic diet for at least four *** analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet *** patients were seizure-free within a month of receiving the diet *** patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this *** antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment *** severe adverse events occurred during the *** Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 ***,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 Ketogenic diet SLC2A1

research progress toward the influence of mosquito salivary proteins on the transmission of mosquito-borne viruses

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Insect Science 2024年第3期31卷 663-673页

作者： Zhao-Yang Wang Kai-Xiao Nie Ji-Chen Niu Gong Cheng Tsinghua University-Peking University Joint Center for Life Sciences School of MedicineTsinghua UniversityBejingChina Institute of infectious diseases Shenzhen Bay LaboratoryShenzhenGuangdongChina Department of Pathogen Biology School of Basic MedicineShandong First Medical University&Shandong Academy of Medical SciencesJinanChina

Mosquito-borne viruses(MBVs)are a large class of viruses transmitted mainly through mosquito bites,including dengue virus,Zika virus,Japanese encephalitis virus,West Nile virus,and chikungunya virus,which pose a major threat to the health of people around the *** global warming and extended human activities,the incidence of many MBVs has increased *** saliva contains a variety of bioactive protein *** not only enable blood feeding but also play a crucial role in regulating local infection at the bite site and the remote dissemination of MBVs as well as in remodeling the innate and adaptive immune responses of host ***,we review the physiological functions of mosquito salivary proteins(MSPs)in detail,the influence and the underlying mechanism of MSPs on the transmission of MBVs,and the current progress and issues that urgently need to be addressed in the research and development of MSP-based MBV transmission blocking vaccines.

关键词： immune response mosquito-borne virus mosquito salivary protein saliva vaccine transmission