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Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice

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Zoological Research 2024年第3期45卷 551-566页

作者： Chen Ling Su-Su Liu Yu-Ya Wang Gui-Tao Huo Yan-Wei Yang Nan Xu Hong Wang Yong Wu Yu-Fa Miao Rui Fu Yu-Wei Zhao Chang-Fa Fan College of Life Sciences Northwest UniversityProvincial Key Laboratory of Biotechnology of Shaanxi ProvinceXi’anShaanxi 710069China Division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China National Center for Safety Evaluation of Drugs National Institutes for Food and Drug Control(NIFDC)Beijing 100176China Division of HIV/aids and Sexually Transmitted Virus Vaccines Institute for Biological Products ControlNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China Division of Laboratory Animal Monitoring Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China

Hepatocellular carcinoma(HCC),a prevalent solid carcinoma of significant concern,is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic *** etiology and pathological progression of non-alcoholic steatohepatitis(NASH)-related HCC is multifactorial and ***,no single animal model can accurately mimic the full NASH-related HCC pathological progression,posing considerable challenges to transition and mechanistic ***,a novel conditional inducible wild-type human HRAS overexpressed mouse model(HRAS-HCC)was established,demonstrating 100%morbidity and mortality within approximately one month under normal dietary and lifestyle *** symptoms of HCC such as ascites,thrombus,internal hemorrhage,jaundice,and lung metastasis were successfully replicated in ***-depth pathological features of NASH-related HCC were demonstrated by pathological staining,biochemical analyses,and typical marker gene *** murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival,further confirming the accuracy and reliability of the *** on protein-protein interaction(PPI)network and RNA sequencing analyses,we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis,with subsequent progression to ***,our study successfully duplicated natural sequential progression in a single murine model over a very short period,providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.

关键词： HRAS THBS1 HCC driver factor NASH Fibrosis Cirrhosis HCC Treatment evaluation

DNA vaccine prime and replicating vaccinia vaccine boost induce robust humoral and cellular immune responses against MERS-CoV in mice

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Virologica Sinica 2024年第3期39卷 490-500页

作者： Xiuli Shen Shuhui Wang Yanling Hao Yuyu Fu Li Ren Dan Li Wenqi Tang Jing Li Ran Chen Meiling Zhu Shuo Wang Ying Liu Yiming Shao National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Center for AIDS/STD Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Changping Laboratory Yard 28Science Park RoadChangping DistrictBeijing 102206China state Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China

As of December 2022,2603 laboratory-identified Middle East respiratory syndrome coronavirus(MERS-CoV)infections and 935 associated deaths,with a mortality rate of 36%,had been reported to the World Health Organization(WHO).However,there are still no vaccines for MERS-CoV,which makes the prevention and control of MERS-CoV *** this study,we generated two DNA vaccine candidates by integrating MERS-CoV Spike(S)gene into a replicating Vaccinia Tian Tan(VTT)*** to homologous immunization with either vaccine,mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune *** immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012,England1 and KNIH strains of ***-Boost immunization also induced strong MERS-S specific T cells responses,with high memory and poly-functional(CD107a-IFN-γ-TNF-α)effector CD8t T *** conclusion,the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against *** study not only provides a promising set of MERS-CoV vaccine candidates,but also proposes a heterologous sequential immunization strategy worthy of further development.

关键词： MERS-CoV VTT vaccine DNA vaccine Humoral and cellular immune responses Prime/boost strategy

Advances in technology for the laboratory diagnosis of individuals with HIV/aids coinfected with Mycobacterium tuberculosis

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Biosafety and Health 2024年第3期6卷 133-142页

作者： Jin Sun Xiaoxu Han Hongxia Yan Xin Zhang Taiyi Jiang Tong Zhang Hao Wu Grigory Kaminskiy Yingmin Ma Eduard Karamov Bin Su Beijing Key Laboratory for HIV/aids Research Clinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China state Health Organization Tula Regional Center for control and Prevention of aids and Infectious Diseases Tula 300002Russia Department of Respiratory and Critical Care Medicine Beijing Youan HospitalCapital Medical UniversityBeijing 100069China Gamaleya National Research Centre for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation Moscow 123098Russia

The high morbidity and mortality rate of individuals with human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(aids)coinfected with Mycobacterium tuberculosis(MTB)is a tough challenge for current global tuberculosis prevention and control ***/MTB coinfection is more complex than a single infection,and the interaction between the two diseases aggravates the deterioration caused by the disease,resulting in increased hospitalizations and *** screening and early diagnosis facilitate the timely initiation of anti-tuberculosis treatment in HIV/MTB coinfected individuals,thereby reducing transmission and the incidence of adverse *** date,pathogenic detection has remained the gold standard for diagnosing tuberculosis,but its sensitivity and specificity are greatly affected by the body's immune status,which limits its application in the diagnosis of HIV/MTB ***,immunology and molecular detection technology has developed *** detection technologies,such as interferon-γ release assays,interferon-gamma inducible protein 10,and GeneXpert MTB/RIF assay have overcome the limitations of traditional detection methods,significantly improved the sensitivity and specificity of tuberculosis diagnosis,and brought new hope to the detection of HIV/MTB *** this article,the principle,scope of application,and latest research progress of relevant detection methods are reviewed to provide a reference for the early diagnosis of HIV/MTB coinfection.

关键词： Human immunodeficiency virus(HIV) Mycobacterium tuberculosis(MTB)coinfection Mycobacterium tuberculosis(MTB) Early diagnosis

Changing HIV Epidemic in North-Eastern India and Its Relationship with Development and Programmatic Indicators

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World Journal of aids 2015年第3期5卷 265-274页

作者： Chiranjeev Bhattacharjya Sangram Kishor Patel Samiran Panda Alok Kr. Deb assam state aids control society National AIDS Control Organization Guwahati India HIV and aids Program Population Council New Delhi India National Institute of Cholera and Enteric Diseases ICMR Kolkata India

Background: Although there has been significant reduction in HIV prevalence and new HIV infections in India, some of the low/moderate prevalence states have been showing long term increase in HIV prevalence and new HIV infections. assam, a state in northeast India is one such low HIV prevalence state where HIV prevalence and new HIV infections have almost doubled in the last few years. This study examined the trend of HIV prevalence across districts/regions of assam and its association with developmental and program indicators. Materials and Methods: A retrospective descriptive analysis of secondary data from the National aids control Program, Census of India-2011, and District Level Household and Facility Survey-3 was conducted. The time period covered under the secondary data analysis was 2007 to 2012. Correlation and Chi-square for trend tests were also used in this paper. Results: During 2007 and 2012, HIV positivity (%) increased relatively in North assam (46.9%) followed by South assam (11.5%) while there has been a relative decline in West assam (﹣51.5%). Correlation analysis showed statistically significant association between HIV prevalence and female literacy, population using mobile phone, population using internet, women (15 - 49 years) seeking treatment for any STI/RTI, proportion of brothel based FSWs, FSWs having state should be focus on the districts with increasing HIV prevalence. Emphasis should be given in planning strategies to address the program gaps among the high risk and vulnerable populations in the state.

关键词： HIV Epidemic Program and Development Indicator North-Eastern India

Causes of Death among HIV-Infected Adults Registered in Selected Anti-Retroviral Therapy Centers in North-Eastern India

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World Journal of aids 2015年第2期5卷 90-99页

作者： Chiranjeev Bhattacharjya Damodar Sahu Sangram Kishor Patel Niranjan Saggurti Arvind Pandey assam state aids control society National AIDS Control Organization Guwahati India National Institute of Medical Statistics ICMR New Delhi India HIV and aids Program Population Council New Delhi India

Background: Causes of death related studies in HIV infected population are necessary to devise disease specific preventive interventions at both state and national level HIV programs. This study examines the causes of death among HIV-infected individuals registered at selected Anti-Retroviral Therapy (ART) centers in the era of treatment in north-eastern India. Data and Methods: A retrospective chart review of causes of death was undertaken among HIV-infected patients who were treated between January 2006 and November 2012 at three selected ART centers in assam, a north-eastern state of India. Reported causes of death were coded as per the guidelines of the International Classification of Diseases (ICD-10) to determine the deaths to standard definitions. Results: Among 5612 HIV-infected patients registered over a period of 71 months, 370 deaths have occurred. Tuberculosis (28%) was the leading cause of death followed by death due to aids related complex (11%), wasting syndrome and multiple infections (9% each). Deaths due to selected causes were significantly associated with patient’s use of alcohol, WHO clinical stage, CD4 count at the time of diagnosis, presence of opportunistic infections during treatment and ART adherence. Median survival duration was shortest among patients who had CD4 count aids-related causes. Tuberculosis has remained the leading cause of death among the HIV patients on ART. Strengthening the linkages and referral between the HIV and TB program will be crucial to reduce the aids-related deaths attributed to tuberculosis.

关键词： Causes of Death HIV aids Tuberculosis ART assam Northeastern India

In situ probing of electron transfer at the dynamic MoS_(2)/graphene–water interface for modulating boundary slip

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Nano Research 2024年第8期17卷 7513-7521页

作者： Yishu Han Dameng Liu state Key Laboratory of Tribology in Advanced Equipment Tsinghua UniversityBeijing 100084China

The boundary slip condition is pivotal for nanoscale fluid *** research has primarily focused on simulating the interaction mechanism between the electronic structure of two-dimensional materials and slip of water at the nanoscale,raising the possibility for ultralow friction flow of water at the ***,experimentally elucidating electronic interactions at the dynamic solid–liquid interface to control boundary slip poses a significant *** this study,the crucial role of electron structures at the dynamic solid–liquid interface in regulating slip length was ***,the slip length of water on the molybdenum disulfide/graphene(MoS_(2)/G)heterostructure(100.9±3.6 nm)significantly exceeded that of either graphene(27.7±2.2 nm)or MoS_(2)(5.7±3.1 nm)*** was also analyzed how electron transfer significantly affected interface *** electrons played a crucial role in determining the type and proportion of excitons at both MoS_(2)–water and MoS_(2)/G–water ***,by applying voltage,distinct photoluminescence(PL)responses at static and dynamic interfaces were discovered,achieving a 5-fold modulation in PL intensity and a 2-fold modulation in the trion to exciton intensity *** electrons transfer from the top graphene to the bottom MoS_(2)at the MoS_(2)/G–water interface,reducing surface charge ***,the reduction of electrostatic interactions between the solid and water leads to an increased slip length of water on the MoS_(2)/G *** process aids in comprehending the origin of frictional resistance at the subatomic *** work establishes a foundation for actively controlling and designing of fluid transport at the nanoscale.

关键词： two-dimensional materials solid-liquid interface photoluminescence excitons electron transfer slip length

Impact of HIV Pretreatment Drug Resistance on Virological Failure After One-Year Antiretroviral Therapy--China,2018-2019

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China CDC weekly 2022年第25期4卷 535-540页

作者： Miaomiao Li Chang Song Aobo Dong Jing Hu Ruihua Kang Hui Xing Yuhua Ruan Yiming Shao Kunxue Hong Lingjie Liao state Key Laboratory of Infectious Disease Prevention and control National Center for AIDS/STD Control and PreventionChinese Center for Disease Control and PreventionBeijingChina

Summary What is already known about this topic?While antiretroviral therapy(ART)has been rapidly scaled-up among the population living with human immunodeficiency virus or acquired immune deficiency syndrome(HIV/aids)... 详细信息

关键词： Therapy Impact patients

Urban and Rural HIV Estimates among Adult Population (15 - 49 Years) in Selected states of India Using Spectrum Data

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World Journal of aids 2015年第3期5卷 226-237页

作者： Lincoln Priyadarshi Choudhury Jayaraman Prabakaran Guwahati India Tamil Nadu state aids control society (TANSACS) Chennai India

HIV estimation has become a standard tool for understanding the epidemic. Although the majority of India’s population lives in rural areas, to date, an exploration of the urban and rural HIV epidemic has not been undertaken. The objective of this study is to develop HIV estimation based on urban and rural adult populations in selected states of India to understand the difference in HIV related indices geographically. Ten states were selected based on HIV prevalence levels-Andhra Pradesh, Tamil Nadu, Karnataka, Maharashtra, Manipur, and Nagaland, Mizoram, Punjab, Odisha and Jharkhand. Spectrum, version 4.53 beta 19, was used. Data files of Indian national estimation, 2010-11 which included population, HIV Sentinel Surveillance, Integrated Bio Behavioral Assessment and program coverage data, were used and alterations made wherever necessary. The urban and rural sub epidemic structures and their subpopulations were separately configured in the Estimation projection package and curve fitting done. Outputs for each state were separately analyzed. Findings show that HIV prevalence is lower in urban than rural areas in Tamil Nadu and Maharashtra;in Karnataka there is no difference in HIV prevalence in the urban and rural populations;and in the remaining seven states urban HIV prevalence is higher as compared to rural HIV prevalence. In the states of Andhra Pradesh, Tamil Nadu, Maharashtra, Odisha and Punjab, the number of people living with HIV, new HIV infections and deaths among people living with HIV is higher in the rural than in the urban population. An early and lower peak in HIV prevalence and incidence in the urban population was seen in Andhra Pradesh, Tamil Nadu, Karnataka and Naga-land, while in Maharashtra the rural peak was earlier and higher. Mizoram shows an earlier and lower peak in the rural population while Manipur shows an earlier and higher urban peak. In Odisha, the epidemic peaked earlier and was lower in the rural than the urban population. HIV preva

关键词： HIV Sentinel Surveillance HIV Estimation HIV Prevalence HIV Incidence High Risk Group Biological Behavioral Assessment

Nef Mutations in Long-term Non-progressors from Former Plasma Donors Infected with HIV-1 Subtype B in China

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Biomedical and Environmental Sciences 2008年第6期21卷 485-491页

作者： SHU-HUA WANG HUI XING XIANG HE FENG-XIA ZHU ZHE-FENG MENG Yu-HUA RUAN YI-MING SHAO state Key Laboratory for Infection Diseases Prevention and control National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 100050 China The General Hospital of Civil Aviation Administration of China Beijing 100025 China

Objective To study the specific amino acid variation in Nef that may be related to disease progression after infection with HIV-1 subtype B, a predominant strain circulating in China, and to determine whether changes in Nef secondary structure may influence different stages of aids development based on the concept that the Nef gene of HIV infection dramatically alter the severity of viral infection and virus replication and disease progression, and that long-term non-progressors （LTNP） of HIV infection are commonly associated with either a deletion of the Nef gene or the defective Nef alleles. Methods The study subjects were divided into LTNPI（n=14）, LTNP2 （n=16） and slow progressor （SP, n=19） groups for mutational analysis of the Nef sequence. The data were obtained by using Bioedit, MEGA, Anthewin and SAS software. Results Residues in Nef TA48/49 and K151 occurred more frequently in the LTNP group while AA48/49 was more frequently observed in the SP group. Of the differences observed in the secondary structure comparison using Nef consensus sequences of these three groups, one was roughly corresponding to the Nef48/49 mutation site. Conclusion TA48/49, Kiss, and AA48/49 in the Nef gene might be associated with the different stages of HIV infection, and there may be a link between the Nef secondary structure and the progression of HIV- 1 infection.

关键词： HIV-1 Nef Long-term nonprogressors Sequence mutations Secondary structure prediction