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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

Genes & diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of Cellular&Molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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Combined hepatocellular cholangiocarcinoma: A clinicopathological update

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World Journal of Hepatology 2024年第5期16卷 766-775页

作者： Mukul Vij Fadl H Veerankutty Ashwin Rammohan Mohamed Rela Department of Pathology Institute of Liver Disease and TransplantationChennai 600044India comprehensive Liver Care Institute VPS LakeshoreCochin 682040India Institute of Liver Disease and Transplantation Dr.Rela Institute and Medical CentreChennai 600044India

Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling *** diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists *** diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored *** a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare *** this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.

关键词： Combined hepatocellular-cholangiocarcinoma Immunotherapy Nestin Hepatocellular carcinoma Cholangiocarcinoma Liver cancer Biomarker Immune checkpoint inhibitors Pathology Genomic landscape

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Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS): protocol of a prospective, multicentre, randomised, controlled trial

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Stroke & Vascular Neurology 2024年第1期9卷 66-74页

作者： Xuan Sun Ming Yang Dapeng Sun Guangge Peng Yiming Deng Xingquan Zhao Liping Liu Ning Ma Feng Gao Dapeng Mo Wengui Yu Yongjun Wang Yilong Wang Zhongrong Miao Department of Interventional Neuroradiology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Neurology Beijing Luhe HospitalCapital Medical UniversityBeijingChina Department of Neurology Comprehensive Stroke&Cerebrovascular CenterUniversity of California IrvineIrvineCaliforniaUSA Chinese Institute for Brain Research BeijingChina National Center for Neurological diseases BeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina China National Clinical Research Center for Neurological diseases BeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina

Background The superiority of balloon angioplasty plus aggressive medical management(AMM)to AMM alone for symptomatic intracranial artery stenosis(sICAS)on efficacy and safety profiles still lacks evidence from randomised controlled trials(RCTs).Aim To demonstrate the design of an RCT on balloon angioplasty plus AMM for *** Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis(BASIS)trial is a multicentre,prospective,randomised,open-label,blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with *** eligible in BASIS were 35–80 years old,with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis(70%–99%)of a major intracranial *** eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 *** groups will receive identical AMM,including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy,intensive risk factor management and life-style *** participants will be followed up for *** outcomes Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up,or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment,is the primary *** BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients,which may provide an alternative perspective for treating *** registration number NCT03703635;https://***.

关键词： balloon prospective centre

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Epidemiological Characteristics of Human Parainfluenza Viruses Infections-China,2019-2023

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China CDC weekly 2024年第12期6卷 235-241,I0003,I0004页

作者： Yixuan Gao Yingwei Ma Daxing Feng Feng Zhang Biao Wang Xiaoqing Liu Bing Zhu Hui Xie Linqing Zhao Xiaoru Long Ying Chen Bing Wang Jie Jiang Zhen Zhu Yan Zhang Aili Cui Baicheng Xia Naiying Mao National Key Laboratory of Intelligent Tracking and Forecasting for Infectious diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Precision Medicine Research Center Children’s Hospital of ChangchunChangchun CityJilin ProvinceChina Henan Provincial Center for Disease Control and Prevention Zhengzhou CityHenan ProvinceChina Laboratory of Viral diseases Qingdao Municipal Centre for Disease Control and PreventionQingdao CityShandong ProvinceChina Virus Laboratory Gansu Provincial Center for Disease Control and PreventionLanzhou CityGansu ProvinceChina Jiangxi Provincial Center for Disease Control and Prevention Nanchang CityGansu ProvinceChina Virus Laboratory Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina Institute for Immunization and Prevention Beijing Center for Disease Prevention and ControlAcademy for Preventive MedicineInstitute of Tuberculosis Control Research and PreventionBeijingChina Laboratory of Virology Beijing Key Laboratory of Etiology of Viral Diseases in ChildrenCapital Institute of PediatricsBeijingChina Department of Infection Children’s Hospital of Chongqing Medical UniversityChongqingChina Inner Mongolia Autonomous Region comprehensive Center for Disease Control and Prevention Hohhot CityInner Mongolia Autonomous RegionChina Shenyang Prefecture Center for Disease Control and Prevention Shenyang CityLiaoning ProvinceChina

Introduction:A retrospective study based on sentinel surveillance was conducted in 10 provinciallevel administrative divisions(PLADs)in China to enhance the understanding of the epidemiological characteristics of human parainfluenza viruses(HPIVs).Methods:From January 2019 to June 2023,respiratory specimens were collected from individuals with acute respiratory infections(ARIs)and screened for four HPIVs serotypes and other common respiratory viruses using multiplex real-time polymerase chain reaction(PCR).This study analyzed the association of HPIVs infections with seasonal patterns,geographical distribution,demographic profiles,clinical features,and co-infection ***:During the study period,a total of 12,866 ARIs were *** overall detection rate of HPIVs was 6.15%,varying from 5.04%in 2022 to 9.70%in *** median age of HPIVs-infected patients was 3 ***2 was more prevalent among individuals aged 5–17 years(42.57%),while HPIV4 was more common in those over 65 years(12.24%).HPIV3(54.16%)and HPIV1(27.18%)were the predominant serotypes,and their prevalence exhibited significant seasonal fluctuations postcoronavirus disease 2019(COVID-19)*** peak of HPIV3 shifted three months later in 2020 compared to 2019 and returned to a summer peak *** peaks of HPIV1 were observed in 2021 following the peak of ***,coinfections were frequent in HPIVs cases(overall rate:22.12%),with human rhinovirus being the most common co-infecting ***:The prevalence of HPIVs in China was predominantly due to HPIV3 and HPIV1,and their seasonal patterns were altered by pandemic ***,continuous surveillance of HPIVs is essential.

关键词： prevalence seasonal Human

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Biomass valorization via electrocatalytic carbon–carbon bond cleavage

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Journal of Energy Chemistry 2024年第4期91卷 542-578页

作者： Keping Wang Zhenyan Guo Min Zhou Ying Yang Lanyun Li Hu Li Rafael Luque Shunmugavel Saravanamurugan National Key Laboratory of Green Pesticide Key Laboratory of Green Pesticide&Agricultural BioengineeringMinistry of EducationState-Local Joint Laboratory for Comprehensive Utilization of BiomassCenter for R&D of Fine ChemicalsGuizhou UniversityGuiyang 550025GuizhouChina Departamento de Quimica Organica Universidad de CordobaCampus de RabanalesEdificio Marie Curie(C-3)Ctra Nnal IVKm.396E-14014 CordobaSpain Laboratory of Bioproduct Chemistry Centre of Innovative and Applied Bioprocessing(CIAB)Mohali 140306PunjabIndia

Renewable electrocatalytic upgrading of biomass feedstocks into valuable chemicals is one of the promising strategies to relieve the pressure of traditional energy-based *** electrocatalytic carbon–carbon bond cleavage of high selectivity,various functionalized molecules,such as organic acids,amides,esters,and nitriles,have great potential to be accessed from ***,it has merely received finite concerns and interests in the *** review first showcases the research progress on the electrocatalytic conversion of lipid/sugar-and lignin-derived molecules(e.g.,glycerol,mesoerythritol,xylose,glucose,1-phenylethanol,and cyclohexanol)into organic acids via specific carbon–carbon bond scission processes,with focus on disclosing reaction mechanisms,recognizing actual active species,and collecting feasible modification *** the guidance of further extensive studies on biomass valorization,organic transformations via a variety of reactions,including decarboxylation,ring-opening,rearrangement,reductive hydrogenation,and carboxylation,are also disclosed for the construction of similar carbon skeletons/*** remaining challenges,prospective applications,and future objectives in terms of biomass conversion are also *** review is expected to provide references to develop renewed electrocatalytic carbon–carbon bond cleavage transformation paths/strategies for biomass upgrading.

关键词： Electrocatalysis Biomass conversion Carbon-carbon bond cleavage Organic acids

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The sudden ocean warming and its potential influences on earlyfrozen landfast ice in the Prydz Bay, East Antarctica

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Acta Oceanologica Sinica 2024年第5期43卷 65-77页

作者： Haihan Hu Jiechen Zhao Jingkai Ma Igor Bashmachnikov Natalia Gnatiuk Bo Xu Fengming Hui School of Geospatial Engineering and Science Sun Yat-sen Universityand Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)Zhuhai 519082China Key Laboratory of comprehensive Observation of Polar Environment(Sun Yat-sen University) Ministry of EducationZhuhai 519082China Qingdao Innovation and Development Base(centre)of Harbin Engineering University Qingdao 266500China Key Laboratory for Polar Acoustics and Application of Ministry of Education(Harbin Engineering University) Harbin 150001China Key Laboratory of Research on Marine Hazards Forecasting National Marine Environmental Forecasting CentreBeijing 100081China Nansen International Environmental and Remote Sensing centre St.Petersburg 199034Russia Saint Petersburg State University St.Petersburg 199034Russia Antarctic Great Wall Ecology National Observation and Research Station Polar Research Institute of ChinaShanghai 201209China

The ocean conditions beneath the ice cover play a key role in understanding the sea ice mass balance in the polar *** integrated high-frequency ice-ocean observation system,including Acoustic Doppler Velocimeter,Conductivity-Temperature-Depth Sensor,and Sea Ice Mass Balance Array(SIMBA),was deployed in the landfast ice region close to the Chinese Zhongshan Station in Antarctica.A sudden ocean warming of 0.14℃(pcomprehensive investigation of the ocean’s influence on ice evolution at a daily scale.

关键词： sudden ocean warming oceanic heat flux landfast ice Zhongshan Station in-situ observation

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Multi‑omics integration identifies regulatory factors underlying bovine subclinical mastitis

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Journal of Animal Science and Biotechnology 2024年第3期15卷 987-1007页

作者： Mengqi Wang Naisu Yang Mario Laterriere David Gagne Faith Omonijo Eveline M.Ibeagha‑Awemu Agriculture and Agri‑Food Canada Sherbrooke Research and Development CentreSherbrookeQCCanada Department of Animal Science Universite LavalQuebec CityQCCanada Quebec Research and Development centre Agriculture and Agri-Food CanadaQuebec CityQCCanada

Background Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy ***-omics approaches enable the comprehensive investigation of the complex interactions between mul-tiple layers of information to provide a more holistic view of disease ***,this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data(mRNA and lncRNA),small RNA sequencing data(miRNA)and DNA methylation sequencing data of milk somatic cells from 10 healthy cows and 20 cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus *** Functional investigation of the data sets through gene set analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis,provided further insights into subclin-ical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical *** abundant genomic and epigenomic signatures with sig-nificant alterations related to subclinical mastitis were observed,including 30,846,2552,1276 and 57 differential methylation haplotype blocks(dMHBs),differentially expressed genes(DEGs),lncRNAs(DELs)and miRNAs(DEMs),***,5 factors presenting the principal variation of differential multi-omics signatures were *** important roles of Factor 1(DEG,DEM and DEL)and Factor 2(dMHB and DEM),in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were *** of the omics within Factors 1 and 2 explained about 20%of the source of variation in subclinical ***,networks of impor-tant functional gene sets with the involvement of multi-omics signatures were demonstrated,which contributed to a comprehensive view of the possible regu

关键词： Candidate discriminant multi-omics signature Gene Long non-coding RNA Methylation haplotype block MicroRNA Multi-omics integration Natural killer cell mediated cytotoxicity pathway Staphylococcus aureus infection pathway

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Long-term follow-up of intravesical abobotulinumtoxinA (Dysport®) injections in women with idiopathic detrusor overactivity

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Asian Journal of Urology 2024年第1期11卷 93-98页

作者： Mohammad Sajjad Rahnama'i Amin Bagheri Elham Jahantabi Hanieh Salehi-Pourmehr Hadi Mostafaei Brigitte Schurch Aida Javan Balegh Marand Sakineh Hajebrahimi Department of Urology St.Elisabeth-Tweesteden Hospital Tilburgthe Netherlands Research Center for Evidence-based Medicine Iranian EBM Centre:A Joanna Briggs Institute(JBI)Center of ExcellenceTabriz University of Medical SciencesTabrizIran Urology Department Faculty of MedicineTabriz University of Medical SciencesTabrizIran Department of Urology Comprehensive Cancer CenterMedical University of ViennaViennaAustria Service de Neuroréhabilitation CHUVLausanneSwitzerland Society of Urological Research and Education(SURE) Heerlenthe Netherlands

Objective:Only a few numbers of studies have been published on the use of abobotulinumtoxinA(Dysport®)in idiopathic detrusor overactivity(IDO).This study reported the long-term follow-up of women with IDO who were treated with intravesical Dysport®***:Two hundred and thirty-six patients with IDO who had failed first-line conservative and antimuscarinic therapy received 500-900 units of Dysport®between April 2014 and July *** patients were followed up for 5 years after their initial injection and interviewed on the ***:A total of 236 women with IDO aged from 18 years to 84 years(mean±standard deviation:49.6±15.9 years)were included in our *** median follow-up time for patients was 36.5(range:10-70)months,and the median recovery time after injection was 18.5(range:0-70)months.A total of 83(35.2%)patients stated that they had subjective improvement of their symptoms whereas 84(35.6%)patients did not report any improvement in *** initial International Consultation on Incontinence Questionnaire Overactive Bladder mean score was 6.9(standard deviation 3.4).There was a positive association between the median recovery time and the components of the International Consultation on Incontinence Questionnaire Overactive Bladder ***:In a sub-population of overactive bladder patients with IDO who have failed first-line therapy,a single intravesical Dysport®injection can resolve patient symptoms completely or reduce the symptoms to an acceptable level that can be controlled with antimuscarinics or re-injection on demands.

关键词： AbobotulinumtoxinA Dysport Intravesical ldiopathic Detrusor overactivity

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Comprehending drivers of land use land cover change from 1999 to 2021 in the Pithoragarh District,Kumaon Himalaya,Uttarakhand,India

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Journal of Mountain Science 2024年第7期21卷 2394-2407页

作者： Mahika PHARTIYAL Sanjeev SHARMA centre for the Study of Regional Development Jawaharlal Nehru UniversityNew Delhi 110067India

The Himalayan region has been experiencing stark impacts of climate change,demographic and livelihood pattern *** analysis of land use and land cover(LULC)change provides insights into the shifts in spatial and temporal patterns of *** changes are the combined effects of anthropogenic and natural/climatic *** present study attempts to monitor and comprehend the main drivers behind LULC changes(1999-2021)in the Himalayan region of Pithoragarh district,*** district is a border district,remotely located in the north-east region of Uttarakhand,*** study draws upon primary and secondary data sources.A total of 400 household surveys and five group discussions from 38 villages were conducted randomly to understand the climate perception of the local community and the drivers of *** imagery,CRU(Climatic Research Unit)climate data and climate perception data from the field have been used to comprehensively comprehend,analyze,and discuss the trends and reasons for LULC *** and remote sensing techniques were used to construct LULC *** multifaceted approach ensures comprehensive and corroborated *** classes were identified and formed viz-cultivation,barren,settlement,snow,and *** show that vegetation and builtup have increased whereas cultivation,barren land,and snow cover have *** study further aims to elucidate the causes behind LULC changes in the spatially heterogeneous region,distinguishing between those attributed to human activities,climate shifts,and the interconnected impacts of *** study provides a comprehensive picture of the study area and delivers a targeted understanding of local drivers and their potential remedies by offering a foundation for formulating sustainable adaptation policies in the region.

关键词： Himalayan region Land use/land cover change Anthropogenic factors Climate change Socioecological system

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First-line penpulimab(an anti-PD1 antibody)and anlotinib(an angiogenesis inhibitor)with nab-paclitaxel/gemcitabine(PAAG)in metastatic pancreatic cancer:a prospective,multicentre,biomolecular exploratory,phase II trial

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2960-2969页

作者： Huizi Sha Fan Tong Jiayao Ni Yi Sun Yahui Zhu Liang Qi Xiaoqin Li Wei Li Yan Yang Qing Gu Xing Zhang Xiaoxuan Wang Chan Zhu Dongsheng Chen Baorui Liu Juan Du The comprehensive Cancer Center Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University&Clinical Cancer Institute of Nanjing UniversityNanjingChina The comprehensive Cancer Center Nanjing Drum Tower HospitalClinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingChina Department of Oncology The Affiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology The First Affiliated Hospital of Soochow UniversitySuzhouChina Department of Oncology The Affiliated Jiangning Hospital of Nanjing Medical UniversityNanjingChina National Institute of Healthcare Data Science at Nanjing University NanjingChina State Key Laboratory of Neurology and Oncology Drug Development Jiangsu Simcere Diagnostics Co.Ltd.Nanjing Simcere Medical Laboratory Science Co.Ltd.NanjingChina

Metastatic pancreatic cancer(mPC)has a dismal ***,we conducted a prospective,multicentre,single-arm,phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine(PAAG)in patients with first-line mPC(NCT05493995).The primary endpoints included the objective response rate(ORR)and disease control rate(DCR),while secondary endpoints encompassed progression-free survival(PFS),overall survival(OS),and *** 66 patients analysed for efficacy,the best response,indicated by the ORR,was recorded at 50.0%(33/66)(95%CI,37.4–62.6%),with 33 patients achieving partial response(PR).Notably,the DCR was 95.5%(63/66,95%CI,87.3–99.1%).The median PFS(mPFS)and OS(mOS)were 8.8(95%CI,8.1–11.6),and 13.7(95%CI,12.4 to not reached)months,*** 3/4 treatment-related adverse events(TRAEs)were reported in 39.4%of patients(26/66).In prespecified exploratory analysis,patients with altered SWI/SNF complex had a poorer ***,low serum CA724 level,high T-cell recruitment,low Th17 cell recruitment,and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable *** conclusion,PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for *** biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

关键词： CA724 prospective centre

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