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Computer Modeling in Engineering & sciences 2024年第6期139卷 2289-2327页

作者： Saima Rashid Fahd Jarad department of Mathematics Government College UniversityFaisalabad38000Pakistan department of Natural sciences School of Arts and SciencesLebanese American UniversityBeirut11022801Lebanon department of Mathematics Faculty of Arts and ScienceÇnkaya UniversityAnkara06790Turkey department of medical Research China Medical UniversityTaichung40402TaiwanChina

Because of the features involved with their varied kernels,differential operators relying on convolution formulations have been acknowledged as effective mathematical resources for modeling real-world *** this paper,we constructed a stochastic fractional framework of measles spreading mechanisms with dual medication immunization considering the exponential decay and Mittag-Leffler *** this approach,the overall population was separated into five ***,the descriptive behavior of the system was investigated,including prerequisites for the positivity of solutions,invariant domain of the solution,presence and stability of equilibrium points,and sensitivity *** included a stochastic element in every cohort and employed linear growth and Lipschitz criteria to show the existence and uniqueness of *** numerical simulations for various fractional orders and randomization intensities are illustrated.

关键词： Measles epidemic model Atangana-Baleanu Caputo-Fabrizio differential operators existence and uniqueness qualitative analysis Newton interpolating polynomial

Epigenetic memory of drug exposure history controls neural stem cell quiescence in the adult brain

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Neural Regeneration Research 2024年第4期19卷 711-712页

作者： Masakazu Iwamoto Taito Matsuda department of Stem Cell Biology and Medicine Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

Neural stem cells(NSCs)are the source of all neurons and glial cells(astrocytes and oligodendrocytes)in the central nervous *** adult mammalian brain retains NSCs in the subgranular zone of the dentate gyrus in the hippocampus and ventricular subventricular zone lining the lateral ventricle(Olpe and Jessberger,2022).Adult NSCs in rodents are preserved throughout life and continuously produce new neurons that integrate into the pre-existing neuronal network.

关键词： neural integrate continuously

The next decade of SET:from an oncoprotein to beyond

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Journal of Molecular Cell Biology 2024年第1期16卷 1-14页

作者： Han Yao Meng Zhang Donglai Wang State Key laboratory of Common Mechanism Research for Major Diseases&department of medical Genetics Institute of Basic Medical Sciences&School of Basic MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeĳing 100005China

This year marks the fourth decade of research into the protein SET,which was discovered in *** was initially identified as an oncoprotein but later shown to be a multifaceted protein involved in regulating numerous biological processes under both physiological and pathophysiological *** dysfunction is closely associated with diseases,such as cancer and Alzheimer's *** the increasing understanding of how SET works and how it is regulated in cells,targeting aberrant SET has emerged as a potential strategy for disease *** this review,we present a comprehensive overview of the advancements in SET studies,encompassing its biological functions,regulatory networks,clinical implications,and pharmacological ***,we provide insights into the future prospects of SET research,with a particular emphasis on its promising potential in the realm of immune modulation.

关键词： SET biological process regulatory mechanism disease therapy

Metabolic plasticity of T cell fate decision

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Chinese medical Journal 2024年第7期137卷 762-775页

作者： Xiaoli Pan Jiajia Wang Lianjun Zhang Guideng Li Bo Huang National Key laboratory of Immunity and Inflammation Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhouJiangsu 215123China Key laboratory of Synthetic Biology Regulatory Element Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhouJiangsu 215123China department of Immunology&National Key laboratory of medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical CollegeBeijing 100005China department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanHubei 430030China

The efficacy of adaptive immune responses in cancer treatment relies heavily on the state of the T *** antigen exposure,T cells undergo metabolic reprogramming,leading to the development of functional effectors or memory ***,within the tumor microenvironment(TME),metabolic stress impairs CD8+T cell anti-tumor immunity,resulting in exhausted *** studies suggested that targeting T cell metabolism could offer promising therapeutic opportunities to enhance T cell *** this review,we provide a comprehensive summary of the intrinsic and extrinsic factors necessary for metabolic reprogramming during the development of effector and memory T cells in response to acute and chronic inflammatory ***,we delved into the different metabolic switches that occur during T cell exhaustion,exploring how prolonged metabolic stress within the TME triggers alterations in cellular metabolism and the epigenetic landscape that contribute to T cell exhaustion,ultimately leading to a persistently exhausted *** the intricate relationship between T cell metabolism and cancer immunotherapy can lead to the development of novel approaches to improve the efficacy of T cell-based treatments against cancer.

关键词： T cell immunotherapy T cell differentiation T cell exhaustion Metabolic reprogramming Tumor microenvironment

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

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Chinese medical Journal 2024年第2期137卷 181-189页

作者： Fangming Liu Yuting Wu Baohui Zhang Shuhui Yang Kezhuo Shang Jie Li Pengju Zhang Weiwei Deng Linlin Chen Liang Zheng Xiaochen Gai Hongbing Zhang department of Physiology State Key Laboratory of Common Mechanism Research for Major DiseasesHaihe Laboratory of Cell EcosystemInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China department of Physiology Institute of Basic Medical Sciences and School of Basic MedicineGraduate School of Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing100005China department of Physiology School of Life ScienceChina Medical UniversityShenyangLiaoning 110122China School of Life sciences Westlake UniversityHangzhouZhejiang 310024China Key laboratory of Pediatric Hematology and Oncology Ministry of HealthInstitute of Pediatric Translational MedicineShanghai Children’s Medical CenterShanghai Jiao Tong School of MedicineShanghai 200127China

Background:Liver cancer is largely resistant to *** study aimed to identify the effective chemotherapeutics forβ-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1(CTNNB1),the most frequently altered proto-oncogene in hepatic ***:Constitutiveβ-catenin-activated mouse embryonic fibroblasts(MEFs)were established by deleting exon 3(β-catenin^(Δ(ex3)/+)),the most common mutation site in CTNNB1 gene.A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibitedβ-catenin^(Δ(ex3)/+)but not for wild-type *** metabolomics was carried out to examine the alterations of metabolites in nucleotide *** efficacy and selectivity of methotrexate(MTX)onβ-catenin-activated human liver cancer cells were determined in ***-deficient nude mice subcutaneously inoculated withβ-catenin wild-type or mutant liver cancer cells and hepatitis B virus(HBV);β-catenin^(lox(ex3)/+)mice were used,respectively,to evaluate the efficacy of MTX in the treatment ofβ-catenin mutant liver ***:MTX was identified and validated as a preferential agent against the proliferation and tumor formation ofβ-catenin-activated *** nucleotide synthesis was the major metabolic aberration inβ-catenin-active cells,and this alteration was also the target of ***,MTX abrogated hepatocarcinogenesis of HBV;β-catenin^(lox(ex3)/+)mice,which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver ***:MTX is a promising chemotherapeutic agent forβ-catenin hyperactive liver *** repurposing MTX has the advantages of lower risk,shorter timelines,and less investment in drug discovery and development,a clinical trial is warranted to test its efficacy in the treatment ofβ-catenin mutant liver cancer.

关键词： Liver cancer β-catenin Methotrexate Nucleotide synthesis Chemotherapy

Reversal of tamoxifen resistance by artemisinin in ER+breast cancer:bioinformatics analysis and experimental validation

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Oncology Research 2024年第6期32卷 1093-1107页

作者： ZHILI ZHUO DONGNI ZHANG WENPING LU XIAOQING WU YONGJIA CUI WEIXUAN ZHANG MENGFAN ZHANG department of Oncology China Academy of Chinese Medical Sciences Guang’anmen HospitalBeijingChina

Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant ***(TAM)serves as the primary treatment for HR+breast ***,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence ***(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine *** study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental *** characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover *** functional enrichment analyses were *** findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized ***-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC *** target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance *** results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.

关键词： Artemisinin Tamoxifen resistance Breast cancer

CARD11 serves as a therapeutic biomarker for the drug therapies of ccRCC

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BIOCELL 2024年第5期48卷 817-834页

作者： KAIWEN TIAN HANZHONG CHEN QIANQIAN WANG FENGLIAN JIANG CHUNXIANG FENG TENG LI XIAOYONG PU YANLIN TANG JIUMIN LIU department of Urology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou510080China

Background:The incidence of clear cell renal cell carcinoma(ccRCC)is globally high;however,despite the introduction of innovative drug therapies,there remains a lack of effective biomarkers for evaluating treatment ***,Caspase recruiting domain-containing protein 11(CARD11)has garnered attention due to its significant association with tumor development and the immune ***:The expression of CARD11 mRNA and protein in ccRCC were analyzed by public database and *** focus of this study is on the epigenomic modifications of CARD11,its expression of ccRCC immunophenotype,and its correlation with response to immunotherapy and targeted ***,to investigate the mechanism of this molecule’s influence on different biological behaviors of cells,cell tests in vitro have been conducted to observe the impact of its expression ***:CARD11 expression was upregulated which may be mainly modified by body methylation and was correlated with poor prognosis in *** the tumor microenvironment of ccRCC,CARD11 expression was positively correlated with increased T lymphocyte infiltration and increased expression of inhibitory immune ***,ccRCC patients with high CARD11 expression had a better response to immunotherapy and targeted *** knockdown of CARD11 ultimately suppressed the proliferation,migration,and invasion capabilities of ccRCC cells while simultaneously enhancing tumor cell ***:We identified CARD11 as a novel therapeutic biomarker for immunotherapy and targeted therapy in ccRCC.

关键词： Clear cell renal cell carcinoma Tumor microenvironment CARD11 Immune checkpoint inhibitor Tyrosine kinase inhibitor

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

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Oncology Research 2024年第5期32卷 831-847页

作者： EFFAT ALEMZADEH LEILA ALLAHQOLI AFROOZ MAZIDIMORADI ESMAT ALEMZADEH FAHIMEH GHASEMI HAMID SALEHINIYA IBRAHIM ALKATOUT Infectious Diseases Research Center Birjand University of Medical SciencesBirjandIran department of Midwifery Ministry of Health and Medical EducationTehranIran Student Research Committee Shiraz University of Medical SciencesShirazIran department of Biotechnology Faculty of MedicineBirjand University of Medical SciencesBirjandIran Cellular and Molecular Research Center Birjand University of Medical SciencesBirjandIran Social Determinants of Health Research Center Birjand University of Medical SciencesBirjandIran Kiel School of Gynaecological Endoscopy Campus KielUniversity Hospitals Schleswig-HolsteinKielGermany

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to *** resistance(DR)poses the most significant challenge in treating patients with existing *** Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance ***,resistance to these new drugs has ***,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective *** this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

关键词： Chemotherapy Drug resistance mechanisms Ovarian cancer PARP inhibitors VEGF inhibitor

The spectrum of rare monogenic diseases in patients with premature coronary artery disease

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Chinese medical Journal 2024年第10期137卷 1246-1248页

作者： Yaqun Teng Tian Du Siqin Feng Ran Tian Yaping Liu Jian Guo Lei Wang Zhiyu Zhang Xiaodong Luan Shan He Shengsheng Zhuang Yifei Wang Shuyuan Zhang Shi Chen Zhenyu Liu Shuyang Zhang department of Cardiology State Key Laboratory of Complex Severe and Rare diseasePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China department of Internal Medicine Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China department of Basic medical sciences Tsinghua University School of MedicineBeijing 100084China department of Breast Oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Tsinghua University-Peking University Joint Center for Life sciences Beijing 100084China department of Cardiology Beijing Tsinghua Changgung HospitalTsinghua UniversityBeijing 102218China department of Endocrinology Key Laboratory of Endocrinology of National Health CommissionPeking Union Medical College HospitalChinese Research Center for Behavior Medicine in Growth and DevelopmentBeijing 100730China

To the Editor:The global burden of premature coronary artery disease(CAD)is increasing among the young *** CAD generally refers to the occurrence of obstructive coronary atherothrombotic lesions in men and women aged<55 years and<65 years,respectively,and particularly in those aged<45 years.[1]The incidence of CAD in the younger population has remained stable or has increased,despite the declining incidence in older *** with premature CAD have a poor long-term prognosis,experiencing a high rate of recurrent ischemic events,rapid progression to multivessel disease,and frequent premature death.[1]Thus,it is crucial to identify the underlying causes of premature CAD that are distinct from those of age-related CAD and improve patient outcomes through precise diagnosis and treatment.

关键词： premature younger precise

Emergency department management of acute agitation in the reproductive age female and pregnancy

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World Journal of Emergency Medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie department of Emergency Medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA department of Psychiatry and Behavioral sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA department of Emergency Medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and *** safety of psychotropic medications in the reproductive age female has not been well *** review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during ***:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant ***:While nonpharmacological management is preferred,ED visits for agitation often require medical *** should be selected based on the etiology of agitation and the clinical setting to avoid major adverse *** effects are common in pregnant *** mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse *** moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on *** has become the most frequently utilized psychotropic for agitation during *** generation psychotropics are often utilized as second-line therapy,including *** and ketamine have demonstrated adverse fetal ***:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in *** the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines