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CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis

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Science China(Life Sciences) 2024年第9期67卷 1881-1898页

作者： Jiaxin Chen Huijuan Wang Jianbin Xu Engeng Chen Qing Meng Jiawei Wang Haoyi Xiang Wei Zhou Ge Shan Zhenyu Ju Zhangfa Song department of Colorectal Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Key Laboratory of Biological Treatment of Zhejiang Province Hangzhou 310016China department of Pulmonary and Critical Care medicine Regional medical center for National Institute of Respiratory DiseaseSir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Key Laboratory of Regenerative medicine of Ministry of Education Institute of Aging and Regenerative MedicineJinan UniversityGuangzhou 510632China department of Breast Surgery the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China department of Orthopedic Surgery the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Aberrant expression of circular RNAs(circ RNAs)is frequently linked to colorectal cancer(CRC).Here,we identified circ ZFR as a promising biomarker for CRC diagnosis and *** ZFR was upregulated in CRC tissues and serum exosomes and its level was linked to cancer incidence,advanced-stages,and *** both in vitro and in vivo settings,circ ZFR promoted the growth and spread while suppressing apoptosis of *** with circ ZFR overexpression promoted the proliferation and migration of cocultured CRC ***,epithelial splicing regulatory protein 1(ESRP1)in CRC cells may enhance the production of circ ***2-associated transcription factor 1(BCLAF1)bound to circ ZFR,which prevented its ubiquitinated ***,circ ZFR sponged mi R-3127-5p to boost rhotekin 2(RTKN2)*** TCP1-CD-QDs nanocarrier was able to carry and deliver circ ZFR si RNA(si-circ ZFR)to the vasculature of CRC tissues and cells,which inhibited the growth of tumors in patient-derived xenograft(PDX)*** together,our results show that circ ZFR is an oncogenic circ RNA,which promotes the development and spread of CRC in a BCLAF1 and mi R-3127-5p-dependent *** ZFR is a possible serum biopsy marker for the diagnosis and a desirable target for further treatment of CRC.

关键词： circZFR exosome ESRP1 BCLAF1 miR-3127-5p nanoparticle(NP)

Neoadjuvant camrelizumab(an anti-PD-1 antibody)plus chemotherapy or apatinib(a VEGFR-2 inhibitor)for initially unresectable stage II–III non-small-cell lung cancer:a multicentre,two-arm,phase 2 exploratory study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3015-3023页

作者： Haoran Xia Han Zhang Zheng Ruan Huibiao Zhang Liangdong Sun Hezhong Chen Yongxin Zhou Lele Zhang Dongliang Bian Xinsheng Zhu Jing Zhang Fenghuan Sun Huansha Yu Nan Song Xiaogang Liu Yuming Zhu Haiping Zhang Wenxin He Jian Chen Jie Yang Guohan Chen Shiliang Xie Dongfang Tang Xiaomiao Zhang Liang Duan Deping Zhao Qinchuan Li Peng Zhang Gening Jiang department of Thoracic Surgery Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Thoracic Surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of Thoracic Surgery Huadong Hospital Affiliated to Fudan UniversityShanghaiChina department of Thoracic Surgery Changhai HospitalNaval Medical UniversityShanghaiChina department of Thoracic-Cardiovascular Surgery Tongji HospitalTongji University School of MedicineShanghaiChina Central Laboratory Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Experimental Animal Center Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Thoracic Surgery Shanghai East HospitalTongji University School of MedicineShanghaiChina

This multicentre,two-arm,phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II–III non-small-cell lung cancer(NSCLC).Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks(arm A)or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily(arm B),for 2–4 cycles,followed by *** primary endpoint was major pathological response(MPR)*** patients in arm A and 21 in arm B were *** rates were 50.0%(15/30)in arm A and 42.9%(9/21)in arm B,with all patients achieving R0 *** these patients,the MPR and pathological complete response rates were both 20.0%(95%CI 4.3–48.1)in arm A and were 55.6%(95%CI 21.2–86.3)and 11.1%(95%CI 0.3–48.2)in arm B,*** corresponding objective response rates were 33.3%(95%CI 11.8–61.6)and 55.6%(95%CI 21.2–86.3).With a median follow-up of 22.4 months(95%CI 19.0–26.0),the median event-free survival was not reached(NR;95%CI 13.6-NR)in arm A and 16.8 months(95%CI 8.6-NR)in arm *** 3 or above treatment-related adverse events occurred in eight(26.7%)patients in arm A and three(14.3%)in arm *** analysis showed baseline TYROBP expression was predictive of treatment response in arm *** camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II–III NSCLC.

关键词： Surgery chemotherapy treatment

Compartmentalized regulation of organelle integrity in neurodegenerative diseases:lessons from the Drosophila motor neuron

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Neural Regeneration Research 2025年第1期20卷 195-196页

作者： Hyun Sung department of Neurology Johns Hopkins University School of MedicineBaltimoreMDUSA medical Research Institute and Department of PharmacologyPusan National University School of MedicineYangsanRepublic of Korea

Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell *** this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal *** some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal *** example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).

关键词： organelle regulation distribution

Trends in mortality among the geriatric population undergoing Surgical aortic valve replacement (SAVR) and potential racial disparities: a 20-year perspective via the national (Nationwide) Inpatient Sample

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Journal of Geriatric Cardiology 2024年第7期21卷 716-722页

作者： Nomesh Kumar Kamleshun Ramphul FNU Bawna Nitish Behary Paray Mansimran Si-ngh Dulay Jasninder Singh Dhaliwal Shruti Aggarwal Sebastian Mactaggart Suma Sri Chennapragada Shaheen Sombans Renuka Verma Hemamalini Sakthivel Raheel Ahmed department of internal medicine Detroit Medical Center Sinai Grace-Wayne State UniversityMichiganUSA In-dependent Researcher TrioletMauritius Independent researcher Farmington HillsMichiganUSA Royal Devon university Healthcare NHS Foundation Trust ExeterUnited Kingdom Royal Brompton Hospital part of Guy’s and St.Thomas’NHS Foundation TrustLondonUnited Kingdom department of internal medicine University of Cali-forniaRiversideUSA Independent Researcher New DelhiIndia Northumbria Hospitals NHS Foundation Trust NewcastleUnited Kingdom department of internal medicine Louisiana State UniversityShreveportUSA Sha-heen Sombans Independent ResearcherHyderabadIndia department of internal medicine Kirk Kerkorian School of Medicine at UNLVLas VegasUSA One Brooklyn Health System/Interfaith medical Ctr Program BrooklynNYUSA

Background Racial disparities in cardiovascular conditions are well *** similar race-based discrepancies in health outcomes also exist among elderly patients undergoing surgical aortic valve replacement(SAVR) for aortic stenosis remains *** We abstracted data from the national(Nationwide) Inpatient Sample over a 20-year period from 2001 to 2020 using specific ICD-9 and ICD-10 *** included patients aged ≥ 60 and ≤ 80 years with races recorded as White,African American,or Hispanic at the time of their hospitalization for *** analyzed and reported the baseline characteristics,risk-adjusted inhospital mortality,and complications stratified by *** Of 420,181 patients studied,90.0% identified as White,4.0% as African American and 6.0% as *** a decrease in overall in-hospital mortality rates from 3.8% between 2001-2005 to 1.8% between 2016-2020,African Americans had higher odds of all-cause in-hospital deaths compared to Whites(a OR = 1.390,P 241,P nd acute kidney injury(a OR = 1.314,P 2,P 2,P ndergoing SAVR for aortic stenosis,racial disparities in health outcomes remain pervasive with minorities more likely to report higher in-hospital morbidity and mortality.

关键词： mortality likely spite

AZGP1P2/UBA1/RBM15 Cascade Mediates the Fate Determinations of Prostate Cancer Stem Cells and Promotes Therapeutic Effect of Docetaxel in Castration-Resistant Prostate Cancer via TPM1 m6A Modification

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Research 2024年第3期6卷 151-167页

作者： Hong Wang Jj Liu Xiaojun Zhu Bin Yang Zuping He Xudong Yao department of Urology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina Urologic Cancer Institute School of MedicineTongji UniversityShanghaiChina. department of Urology Surgery The Affiliated Hospital of Inner Mongolia Medical UniversityHohhotChina. The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province School of MedicineHunan Normal UniversityThe Engineering Research Center of Reproduction and Translational Medicine of Hunan ProvinceChangshaChina Shanghai Key Laboratory of Reproductive medicine Shanghai Jiao Tong University School of MedicineShanghaiChina.

Prostate cancer(PCa)is a common malignant tumor with high morbidity and mortality *** prostate cancer stem cell(PCSC)model provides novel insights into the pathogenesis of PCa and its therapeutic ***,the roles and molecular mechanisms of specific genes in mediating fate decisions of PCSCs and carcinogenesis of PCa remain to be *** this study,we have explored the expression,function,and mechanism of AZGP1P2,a pseudogene of AZGP1,in regulating the stemness and apoptosis of PCSCs and treatment resistance of docetaxel in castration-resistant prostate cancer(CRPC).We revealed that AZGP1P2 was downregulated in CRPC cell lines and PCSCs,while it was positively associated with progression-free *** of the AZGP1P2 enhanced the sensitivity of docetaxel treatment in CRPCs via inhibiting their *** pull-down associated with mass spectrometry analysis,co-immunoprecipitation assay,and RNA immunoprecipitation assay demonstrated that AZGP1P2 could bind to UBA1 and RBM15 as a“writer”of methyltransferase to form a ***1,an E1 ubiquitin-activating enzyme,contributed to RBM15 protein degradation via ubiquitination *** RNA immunoprecipitation assay displayed that RBM15 controlled the mRNA decay of TPM1 in m6A ***,a xenograft mouse model and patient-derived organoids showed that the therapeutic effect of docetaxel in CRPC was increased by AZGP1P2 in ***,these results imply that AZGP1P2 mediates the stemness and apoptosis of PCSCs and promotes docetaxel therapeutic effect by suppressing tumor growth and metastasis via UBA1/RBM15-mediated TPM1 mRNA decay in CRPC.

关键词： Prostate TPM1 m6A

Heme oxygenase 1-mediated ferroptosis in Kupffer cells initiates liver injury during heat stroke

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3983-4000页

作者： Ru Li Riqing Wei Chenxin Liu Keying Zhang Sixiao He Zhifeng Liu Junhao Huang Youyong Tang Qiyuan An Ligen Lin Lishe Gan Liying Zhao Xiaoming Zou Fudi Wang Yuan Ping Qiang Ma The Seventh Affiliated Hospital Southern Medical UniversityFoshan 528244China department of Biopharmaceutics School of Laboratory Medicine and BiotechnologySouthern Medical UniversityGuangzhou 510000China medical Critical Care medicine General Hospital of Southern Theatre Command of PLAGuangzhou 510000China Guangdong Branch Center National Clinical Research Center for Geriatric Diseases(Chinese PLA General Hospital)Guangzhou 510000China State Key Laboratory of Quality Research in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoAvenida da UniversidadeTaip1Macao 999078China school of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 311402China department of General Surgery Nanfang Hospitalthe First School of Clinical MedicineSouthern Medical UniversityGuangzhou 510000China The Fourth Affiliated Hospital the First Affiliated HospitalSchool of Public HealthInstitute of Translational MedicineCancer CenterState Key Laboratory of Experimental HematologyZhejiang University School of MedicineHangzhou 310000China The First Affiliated Hospital the Second Affiliated HospitalBasic Medical SciencesSchool of Public HealthHengyang Medical SchoolUniversity of South ChinaHengyang 421200China College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310000China Liangzhu Laboratory Zhejiang University Medical CenterHangzhou 310000China Guangdong Provincial Key Laboratory of Immune Regulation and Immunotherapy School of Laboratory Medicine and BiotechnologySouthern Medical UniversityGuangzhou 510000China

With the escalating prevalence of global heat waves,heat stroke has become a prominent health concern,leading to substantial liver *** other forms of liver injury,heat strokeinduced damage is characterized by heat cytotoxicity and heightened inflammation,directly contributing to elevated mortality *** clinical assessments have identified elevated bilirubin levels as indicative of Kupffer cell dysfunction,their specific correlation with heat stroke liver injury remains *** hypothesis proposes the involvement of Kupffer cell ferroptosis during heat stroke,initiating IL-1bmediated *** single-cell RNA sequencing of murine macrophages,a distinct and highly susceptible Kupffer cell subtype,Clec4Ft/CD206t,emerged,with heme oxygenase 1(HMOX-1)playing a pivotal ***,heat-induced HMOX-1,regulated by early growth response factor 1,mediated ferroptosis in Kupffer cells,specifically in the Clec4F t/CD206 t subtype(KC2),activating phosphatidylinositol 4-kinase beta and promoting PI4P *** cascade triggered NLRP3 inflammasome activation and maturation of *** findings underscore the critical role of targeted therapy against HMOX-1 in ferroptosis within Kupffer cells,particularly in Clec4F t/CD206 t *** an approach has the potential to mitigate inflammation and alleviate acute liver injury in the context of heat stroke,offering a promising avenue for future therapeutic interventions.

关键词： Heat stroke Liver injury Kupffer cells Ferroptosis Heme oxygenase 1 Phosphatidylinositol 4-kinase beta NLRP3 Early growth response factor 1

DEAD-box helicase 17(DDX17)protects cardiac function by promoting mitochondrial homeostasis in heart failure

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2774-2790页

作者： Mingjing Yan Junpeng Gao Ming Lan Que Wang Yuan Cao Yuxuan Zheng Yao Yang Wenlin Li Xiaoxue Yu Xiuqing Huang Lin Dou Bing Liu Junmeng Liu Hongqiang Cheng Kunfu Ouyang Kun Xu Shenghui Sun Jin Liu Weiqing Tang Xiyue Zhang Yong Man Liang Sun Jianping Cai Qing He Fuchou Tang Jian Li Tao Shen The Key Laboratory of Geriatrics Beijing Institute of GeriatricsInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing Hospital/National Center of Gerontology of National Health CommissionBeijing 100730China Peking university Fifth school of Clinical medicine Beijing 100730China department of Laboratory medicine Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China Biomedical Pioneering Innovation Center School of Life SciencesPeking UniversityBeijing 100871China Emergency Center Zhongnan Hospital of Wuhan UniversityWuhan 430071China department of Cardiology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Graduate school of Peking Union medical College Beijing 100730China department of Health Care Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China department of Pathology and Pathophysiology and department of Cardiology at Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou 310058China department of Cardiovascular Surgery Peking University Shenzhen HospitalShenzhen 518036China Experimental Technology Center for Life Sciences at Beijing Normal university Beijing 100875China

DEAD-box helicase 17(DDX17)is a typical member of the DEAD-box family with transcriptional cofactor *** DDX17 is abundantly expressed in the myocardium,its role in heart is not fully *** generated cardiomyocyte-specific Ddx17-knockout mice(Ddx17-cKO),cardiomyocyte-specific Ddx17 transgenic mice(Ddx17-Tg),and various models of cardiomyocyte injury and heart failure(HF).DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte ***-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis,leading to progressive cardiac dysfunction,maladaptive remodeling and progression to heart *** of DDX17 expression in cardiomyocytes protects cardiac function under pathological *** studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6(BCL6)and inhibit the expression of dynamin-related protein 1(DRP1).When DDX17 expression is reduced,transcriptional repression of BCL6 is attenuated,leading to increased DRP1 expression and mitochondrial fission,which in turn leads to impaired mitochondrial homeostasis and heart *** also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart *** findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

关键词： DDX17 homeostasis cardiac

Disparate outcomes in Hispanic patients with metabolic dysfunctionassociated steatotic liver disease/steatohepatitis and type 2 diabetes: Large cohort study

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World Journal of Diabetes 2024年第5期15卷 886-897页

作者： Joseph Matthew Gosnell George Golovko Esteban Arroyave Akshata Moghe Michael L Kueht Omar AbdulSaldarriaga Kevin H McKinney Heather L Stevenson Monique R Ferguson department of Pathology University of Texas Medical BranchGalvestonTX 77555United States department of Pharmacology&Toxicology University of Texas Medical BranchGalvestonTX 77555United States department of medicine University of Texas Health Science Center at HoustonHoustonTX 77030United States department of Surgery University of Texas Medical BranchGalvestonTX 77555United States Center for Tropical Diseases Department of Internal MedicineUniversity of Texas Medical BranchGalvestonTX 77555United States department of internal medicine University of Texas Medical BranchGalvestonTX 77555United States

BACKGROUnd Metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH)are a growing health burden across a significant portion of the global patient ***,these conditions seem to have disparate rates and outcomes between different ethnic *** combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma(HCC),and Hispanic patients experience the greatest burden,particularly those in South *** To compare outcomes between Hispanic and non-Hispanic patients in the United States,while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic *** This cohort analysis was conducted with data obtained from TriNetX,LLC(“TriNetX”),a global federated health research network that provides access to deidentified medical records from healthcare organizations *** cohort networks were used:university of Texas medical Branch(UTMB)hospital and the United States national database collective to determine whether disparities were related to geographic regions,like Southeast *** This study findings revealed Hispanics/Latinos have a statistically significant higher occurrence of HCC,type 2 diabetes mellitus,and liver fibrosis/cirrhosis in both the United States and the UTMB Hispanic/Latino *** mortality in Hispanics/Latinos was lower within the United States group and not statistically elevated in the UTMB *** This would appear to support that Hispanic patients in Southeast Texas are not uniquely affected compared to the national Hispanic population.

关键词： Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis Hispanic Diabetes mellitus TriNetX Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Steatotic liver disease Hepatocellular carcinoma

Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

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World Journal of Pediatrics 2024年第4期20卷 413-421页

作者： Zhe-Wen Qin Qian-Nan Ren Hong-Xi Zhang Ya-Ru Liu Ke Huang Wei Wu Guan-Ping Dong Yan Ni Jun-Fen Fu Division of Endocrinology National Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalDepartment of EndocrinologyNational Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalZhejiang University School of MedicineHangzhou310052China

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver *** anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with *** A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology department as the derivation *** external validation cohort comprised 77 *** assessment of liver fat content was performed using proton magnetic resonance *** and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation *** Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive *** The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner *** adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in ***,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

关键词： Biochemical markers Children Magnetic resonance spectroscopy Nonalcoholic fatty liver disease Pediatric obesity