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Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1359-1388页

作者： Qian Zhou Yu Meng Daishi Li Lei Yao Jiayuan Le Yihuang Liu Yuming Sun Furong Zeng Xiang Chen Guangtong Deng Department of Dermatology Xiangya HospitalCentral South University87 Xiangya RoadChangsha 410008 Hunan ProvinceChina National engineering research center of Personalized Diagnostic and Therapeutic Technology 87 Xiangya RoadChangsha 410008 Hunan ProvinceChina Furong Laboratory 87 Xiangya RoadChangsha 410008 Hunan ProvinceChina hunan Key Laboratory of skin Cancer and Psoriasis Hunan Engineering Research Center of Skin Health and DiseaseXiangya HospitalCentral South University87 Xiangya RoadChangsha 410008 Hunan ProvinceChina National Clinical research center for Geriatric Disorders Xiangya Hospital87 Xiangya RoadChangsha 410008 Hunan ProvinceChina Department of General Surgery Xiangya HospitalCentral South University87 Xiangya RoadChangsha 410008 Hunan ProvinceChina Department of Plastic and Cosmetic Surgery Xiangya HospitalCentral South University87 Xiangya RoadChangsha 410008 Hunan ProvinceChina Department of Oncology Xiangya HospitalCentral South University87Xiangya RoadChangsha 410008Hunan ProvinceChina

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation of iron-dependent membranelocalized lipid peroxides.It acts as an innate tumor suppressor mechanism and participates in the biological processes of tumors.Intriguingly,mesenchymal and dedifferentiated cancer cells,which are usually resistant to apoptosis and traditional therapies,are exquisitely vulnerable to ferroptosis,further underscoring its potential as a treatment approach for cancers,especially for refractory cancers.However,the impact of ferroptosis on cancer extends beyond its direct cytotoxic effect on tumor cells.Ferroptosis induction not only inhibits cancer but also promotes cancer development due to its potential negative impact on anticancer immunity.Thus,a comprehensive understanding of the role of ferroptosis in cancer is crucial for the successful translation of ferroptosis therapy from the laboratory to clinical applications.In this review,we provide an overview of the recent advancements in understanding ferroptosis in cancer,covering molecular mechanisms,biological functions,regulatory pathways,and interactions with the tumor microenvironment.We also summarize the potential applications of ferroptosis induction in immunotherapy,radiotherapy,and systemic therapy,as well as ferroptosis inhibition for cancer treatment in various conditions.We finally discuss ferroptosis markers,the current challenges and future directions of ferroptosis in the treatment of cancer.

关键词： cancer mechanisms treatment

A piezoelectric-driven microneedle platform for skin disease therapy

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The Innovation 2024年第3期5卷 110-121页

作者： Ziyan Chen Xin Liu Zixi Jiang Huayi Wu Tao Yang Lanyuan Peng Lisha Wu Zhongling Luo Mi Zhang Juan Su Yan Tang Jinmao Li Yang Xie Han Shan Qibo Lin Xiuli Wang Xiang Chen Hanmin Peng Shuang Zhao Zeyu Chen Department of Dermatology Xiangya HospitalCentral South UniversityChangsha 410008China Furong Laboratory(Precision Medicine) Changsha 410008China National engineering research center of Personalized Diagnostic and Therapeutic Technology Xiangya HospitalCentral South UniversityChangsha 410008China hunan engineering research center of skin health and disease Xiangya HospitalCentral South UniversityChangsha 410008China hunan Key Laboratory of skin Cancer and Psoriasis Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical research center of Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China School of Mechanical and Electrical engineering Central South UniversityChangsha 410083China Department of Dermatology Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi 710000China State Key Laboratory of Mechanics and Control for Aerospace Structures Nanjing University of Aeronautics&AstronauticsNanjing 210016China Institute of Photomedicine Shanghai Skin Disease HospitalSchool of MedicineTongji UniversityShanghai 200443China

With over a million cases detected each year,skin disease is a global public health problem that diminishes the quality of life due to its difficulty to eradicate,propensity for recurrence,and potential for post-treatment scarring.Photodynamic therapy(PDT)is a treatment with minimal invasiveness or scarring and few side effects,making it well tolerated by patients.However,this treatment requires further research and development to improve its effective clinical use.Here,a piezoelectric-driven microneedle(PDMN)platform that achieves high efficiency,safety,and non-invasiveness for enhanced PDT is proposed.This platform induces deep tissue cavitation,increasing the level of protoporphyrin IX and significantly enhancing drug penetration.A clinical trial involving 25 patients with skin disease was conducted to investigate the timeliness and efficacy of PDMN-assisted PDT(PDMN-PDT).Our findings suggested that PDMN-PDT boosted treatment effectiveness and reduced the required incubation time and drug concentration by 25%and 50%,respectively,without any anesthesia compared to traditional PDT.These findings suggest that PDMN-PDT is a safe and minimally invasive approach for skin disease treatment,which may improve the therapeutic efficacy of topical medications and enable translation for future clinical applications.

关键词： needle anesthesia clinical

Allergic Phenotypes and Sarcopenia:Evidence from Observational Studies and Mendelian Randomization Analysis

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Phenomics

Phenomics 2024年第1期4卷 46-50页

作者： Zhenwei Tang Guowei Zhou Yi Xiao Hong Liu Xiang Chen Minxue Shen Department of Dermatology Xiangya HospitalCentralSouth University110 Xiangya RoadChangsha 410008HunanChina hunan Key Laboratory of skin Cancer and Psoriasis HunanEngineering Research Center of Skin Health and DiseaseCentral South UniversityChangsha 410008HunanChina Department of Dermatology Second AfliatedHospitalZhejiang University School of MedicineHangzhou 310009ZhejiangChina Furong Laboratory Changsha 410008HunanChina Department of Social Medicine and health Management Xiangya School of Public HealthCentral South UniversityChangsha 410008HunanChina

Commonly afected in early-life population,the impact of allergic phenotypes on mid-or late-life health is less discussed.This study is to explore the association of allergic phenotypes including atopic dermatitis(AD),asthma,eosinophils count(EC),and sarcopenia.We conducted observational studies and mendelian randomization(MR)analysis based on UK Biobank(UKB),the China health and Retirement Longitudinal Study(CHARLS)and data from genome-wide association study(GWAS).Based on the UKB data,AD,asthma and EC were positively correlated with pre-sarcopenia and decreased skeletal muscle mass index and hand grip in fully adjusted model.Asthma and EC were signifcantly associated with sarcopenia while AD was marginally associated(p=0.095).Based on the CHARLS cohort,asthma signifcantly added 109.4%risk for pre-sarcopenia in adjusted model(relative risk=2.094;p=0.002),respectively.Both asthma(β=0.100,p=0.006)and EC(β=0.023,p=0.017)exerted signifcantly casual efects on pre-sarcopenia.However,as for sarcopenia,merely EC exhibited a signifcantly casual efect(β=0.005,p=0.048).Signifcant casual efects of AD(β=–0.027,p=0.003),asthma(β=–0.029,p=0.027)and EC(β=–0.041,p<0.001)on decreased appendicular lean mass(ALM)were observed using the inverse-variance weighted method and the Mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)method.Our results revealed a contributory role of AD,asthma and EC on sarcopenia,especially in terms of decreased ALM,an indicator for sarcopenia diagnosis.The fndings of our study will raise the awareness of preventing aging-related disorders or geriatric syndromes among allergic populations.

关键词： Sarcopenia Atopic dermatitis Asthma Aging Eosinophils

Identification and effective regulation of scarb1 gene involved in pigmentation change in autotetraploid Carassius auratus

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Zoological research 2024年第2期45卷 381-397页

作者： Xi-Dan Xu Yue Zhou Chong-Qing Wang Xu Huang Kun Zhang Xiao-Wei Xu Li-Wen He Xin-Yue Zhang Xin-Zhu Fu Ming Ma Qin-Bo Qin Shao-Jun Liu State Key Laboratory of Developmental Biology of Freshwater Fish Engineering Research Center of Polyploid Fish Reproduction and Breeding of the State Education MinistryCollege of Life SciencesHunan Normal UniversityChangshaHunan 410081China Nansha-South China Agricultural University Fishery research Institute GuangzhouGuangdong 511458China hunan Yuelu Mountain Science and Technology Co.Ltd.for Aquatic Breeding ChangshaHunan 410081China College of Chemistry and Chemical engineering Hunan Normal UniversityChangshaHunan 410081China

The autotetraploid Carassius auratus(4nRR,4n=200,RRRR)is derived from whole-genome duplication of Carassius auratus red var.(RCC,2n=100,RR).In the current study,we demonstrated that chromatophores and pigment changes directly caused the coloration and variation of 4nRR skin(red in RCC,brownish-yellow in4nRR).To further explore the molecular mechanisms underlying coloration formation and variation in 4nRR,we performed transcriptome profiling and molecular functional verification in RCC and 4nRR.Results revealed that scarb1,associated with carotenoid metabolism,underwent significant down-regulation in 4nRR.Efficient editing of this candidate pigment gene provided clear evidence of its significant role in RCC coloration.Subsequently,we identified four divergent scarb1 homeologs in 4nRR:two original scarb1 homeologs from RCC and two duplicated ones.Notably,three of these homeologs possessed two highly conserved alleles,exhibiting biased and allelespecific expression in the skin.Remarkably,after precise editing of both the original and duplicated scarb1homeologs and/or alleles,4nRR individuals,whether singly or multiply mutated,displayed a transition from brownishyellow skin to a cyan-gray phenotype.Concurrently,the proportional areas of the cyan-gray regions displayed a gene-dose correlation.These findings illustrate the subfunctionalization of duplicated scarb1,with all scarb1genes synergistically and equally contributing to the pigmentation of 4nRR.This is the first report concerning the functional differentiation of duplicated homeologs in an autopolyploidfish,substantiallyenrichingour understanding of coloration formation and change within this group of organisms.

关键词： Autopolyploidization Coloration change scarb1 Functional differentiation Genetic changes

Magnitude and direction of temperature variability affect hospitalization for myocardial infarction and stroke:population-based evidence from Guangzhou,China

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Frontiers of Environmental Science & engineering 2024年第3期18卷 1-11页

作者： Zhou Yang Murui Zheng Ze-Lin Yan Hui Liu Xiangyi Liu Jie-Qi Jin Jiagang Wu Chun-Quan Ou State Key Laboratory of Organ Failure research Department of BiostatisticsGuangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public HealthSouthern Medical UniversityGuangzhou 510515China Guangzhou center for disease Control and Prevention Guangzhou 510440China

Relationships between nonoptimal temperatures and cardiovascular disease(CVD)mortality have been well documented.However,evidence of the association between temperature variability(TV)and CVD morbidity is limited.This study aimed to quantify the risk and burden of CVD-related hospitalization associated with the magnitude and direction of TV.Data on meteorology and population-based hospitalizations for myocardial infarction(MI)and stroke were collected in Guangzhou,China,from 2013 to 2017.Hourly temperature variability(HTV)was measured as the standard deviation of hourly temperature records over specific exposure days.The direction(upward or downward)of HTV was defined as the average daily mean temperature change relative to that of the previous day during the exposure period.Quasi-Poisson regression was applied to assess the impact of HTV after adjusting for the daily mean temperature,and the hospitalization fractions attributable to HTV were calculated.A 1℃-increase in HTV was significantly associated with a 2.24%and 1.72%increase in hospitalizations for MI and hemorrhagic stroke(HS)at lag 0–1 d,respectively,and a 1.55%increase in hospitalizations for ischemic stroke(IS)at lag 0–3 d.During the study period,5.99%,4.64%,and 4.53%of MI,HS,and IS hospitalizations,respectively,were attributable to HTV.The upward TV exerts acute effects on CVD hospital admissions,whereas the impact of downward TV generally lags.These findings highlight the importance of the magnitude and direction of temperature fluctuations,in addition to the mean level,in assessing the adverse health impacts of temperature variations.

关键词： Hourly temperature variability Cardiovascular Hospitalization Direction China

The Impact of Regular Diet Recovery on Postoperative Rehabilitation After Elective Cesarean Section

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Maternal-Fetal Medicine 2024年第2期6卷 78-83页

作者： Caihong Hu KuilinFei Yuelan Liu Xiaoe Jiang WenjingYong Weishe Zhang Ping Li Department of Obstetrics Xiangya HospitalCentral South UniversityChangsha 410008China hunan engineering research center of Early Life Development and disease Prevention Xiangya HospitalCentral South UniversityChangsha 410008China.

Objective To determine the role of regular diet recovery after restoration of normal muscle strength of both lower extremities in promoting postoperative recovery in women undergoing elective cesarean section.Methods This was a prospective observational cohort study.Patients who underwent elective cesarean section at Xiangya Hospital,Central South University,from October 2022 to December 2022,were categorized into two groups based on the duration of postoperative fasting:the observation group resumed eating after regaining lower extremity muscle strength,while the control group adhered to traditional postoperative fasting guidelines,waiting 6 hours before eating.Primary outcomes included postoperative pain levels assessed by visual analog scale(VAS)pain scores and time to first flatus.Demographic characteristics,time to first lactation,hospital stay length,and patient satisfaction were also assessed.Statistical analysis was conducted using Student’s t test and Chi-squared test,with significance set at P0.05).Conclusion Food intake after restoration of lower extremity muscle strength improves first flatus,relieves postope

关键词： Obstetrics Cesarean section Early food intake

FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2260-2274页

作者： Hao Meng Zhiying Liao Yanting Ji Dong Wang Yang Han Chaolin Huang Xujuan Hu Jingyi Chen Hengrui Zhang Zonghong Li Changliang Wang Hui Sun Jiaqi Sun Lihua Chen Jiaxiang Yin Jincun Zhao Tao Xu Huisheng Liu School of Biomedical engineering Guangzhou Medical UniversityGuangzhou 511495 GuangdongChina Guangzhou National Laboratory Guangzhou 510320 GuangdongChina State Key Laboratory of Respiratory disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China center for Translational Medicine Wuhan Jinyintan HospitalWuhan 430023 HubeiChina School of Biomedical Sciences and engineering South China University of TechnologyGuangzhou 510006 GuangdongChina

The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19.In the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2 expression within the islets,facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion.Using hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2(FGFR2)and FGFR1 to upregulate ACE2 expression predominantly inβcells.This upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2 infection.Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation,subsequently reducing viral infection and replication in the islets.Furthermore,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms.Finally,animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in situ.Taken together,our research offers a potential regulatory strategy for ACE2 by controlling FGF7,thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

关键词： ACE2 FGF7 islet

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

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Acta Pharmaceutica Sinica B 2024年第2期14卷 437-454页

作者： Jiamei Le Yilong Chen Wei Yang Ligong Chen Jianping Ye Shanghai Key Laboratory of Molecular Imaging Zhoupu HospitalShanghai University of Medicine and Health SciencesShanghai 201318China School of health Science and engineering University of Shanghai for Science and TechnologyShanghai 200093China Metabolic disease research center Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhou 450007China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China research center for Basic Medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

Solute carriers(SLCs) constitute the largest superfamily of membrane transporter proteins.These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions.They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake(e.g., SLC2A4/GLUT4), glucose reabsorption(e.g., SLC5A2/SGLT2), thermogenesis(e.g., SLC25A7/UCP-1), and ATP production(e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone(SLCO1B1/OATP1B1) and metformin(SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

关键词： Solute carriers(SLCs) Energ ymetabolism ATP production Type 2 diabetes mellitus(T2DM) Glucose homeostasis Polymorphisms

Recent progress in functional modification and crosslinking of bioprosthetic heart valves

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Regenerative Biomaterials 2024年第1期3卷 1-16页

作者： Cheng Zheng Li Yang Yunbing Wang National engineering research center for Biomaterials Sichuan UniversityChengdu 610064China

Valvular heart disease(VHD),clinically manifested as stenosis and regurgitation of native heart valve,is one of the most prevalent cardiovascular diseases with high mortality.Heart valve replacement surgery has been recognized as golden standard for the treatment of VHD.Owing to the clinical application of transcatheter heart valve replacement technic and the excellent hemodynamic performance of bioprosthetic heart valves(BHVs),implantation of BHVs has been increasing over recent years and gradually became the preferred choice for the treatment of VHD.However,BHVs might fail within 10-15 years due to structural valvular degeneration(SVD),which was greatly associated with drawbacks of glutaraldehyde crosslinked BHVs,including cytotoxicity,calcification,component degradation,mechanical failure,thrombosis and immune response.To prolong the service life of BHVs,much effort has been devoted to overcoming the drawbacks of BHVs and reducing the risk of SVD.In this review,we summarized and analyzed the research and progress on:(i)modification strategies based on glutaraldehyde crosslinked BHVs and(ii)nonglutaraldehyde crosslinking strategies for BHVs.

关键词： bioprosthetic heart valves modification crosslinking anticalcification antithrombosis