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Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

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Journal of Sport and Health Science 2024年第3期13卷 288-296,I0002页

作者： Tim Böttrich Pascal Bauer Vincent Gröβer Magdalena Huber Hartmann Raifer Torsten Frech Svenja Nolte Theresa Dombrowski Franz Cemic Natascha Sommer Robert Ringseis Klaus Eder Karsten Krüger Christopher Weyh department of Exercise Physiology and Sports Therapy Institute of Sports ScienceJustus-Liebig-UniversityGiessen 35394Germany department of Cardiology and Angiology Justus-Liebig-University GiessenGiessen 35392Germany Institute for Systems Immunology Center for Tumor und ImmunologyMarburg 35032Germany TH Mittelhessen Department of Computer ScienceUniversity of Applied Sciences GiessenGiessen 35390Germany department of Internal medicine Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Giessen 35394Germany Excellence Cluster Cardio-Pulmonary Institute(CPI) Justus-Liebig UniversityGiessen 35394Germany Institute of Animal Nutrition and Nutrition Physiology Justus-Liebig-University GiessenGiessen 35390Germany

Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent

关键词： Cardiorespiratory fitness Elderly Regulatory T cells Subclinical atherosclerosis

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Heyingwuzi formulation alleviates diabetic retinopathy by promoting mitophagy via the HIF-1α/BNIP3/NIX axis

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World Journal of Diabetes 2024年第6期15卷 1317-1339页

作者： Jia-Jun Wu Shu-Yan Zhang Lin Mu Zhi-Guo Dong Yin-Jian Zhang department of Ophthalmology Longhua Hospital Shanghai University of Traditional Chinese MedicineShanghai 200032China department of Ophthalmology Eye and ENT HospitalFudan UniversityShanghai 200031China

BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially those underlying mitophagy.METHODS Human retinal capillary endothelial cells(HRCECs)were treated with high glucose(hg),HYWZF serum,PX-478,or Mdivi-1 in vitro.Then,cell counting kit-8,transwell,and tube formation assays were used to evaluate HRCEC proliferation,invasion,and tube formation,respectively.Transmission electron microscopy was used to assess mitochondrial morphology,and Western blotting was used to determine the protein levels.Flow cytometry was used to assess cell apoptosis,reactive oxygen species(ROS)production,and mitochondrial membrane potential.Moreover,C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks.Blood glucose levels and body weight were monitored continuously.Changes in retinal characteristics were evaluated using hematoxylin and eosin,tar violet,and periodic acid-Schiff staining.Protein levels in retinal tissues were determined via Western blotting,immunohistochemistry,and immunostaining.RESULTS HYWZF inhibited excessive ROS production,apoptosis,tube formation,and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro.It increased the mRNA expression levels of BCL2-interacting protein 3(BNIP3),FUN14 domain-containing 1,BNIP3-like(BNIP3L,also known as NIX),PARKIN,PTEN-induced kinase 1,and hypoxia-inducible factor(HIF)-1α.Moreover,it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio.However,PX-478 and Mdivi-1 reversed these effects.Additionally,PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy.HYWZF intervention improved the symptoms of diabetes,tissue damage,number of acellular capillaries,and oxidative stress in vivo.Furthermore,in vivo experiments confirmed the results of in vitro ex

关键词： Diabetic retinopathy HIF-1α/BNIP3/NIX axis Mitophagy Heyingwuzi formulation Traditional Chinese medicine

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Mitophagy in intracerebral hemorrhage:a new target for therapeutic intervention

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Neural Regeneration Research 2024年第2期19卷 316-323页

作者： Yiyang Chen Wenxuan Tang Xinqi Huang Yumei An Jiawen Li Shengye Yuan Haiyan Shan Mingyang Zhang Institute of Forensic Sciences Suzhou Medical CollegeSoochow UniversitySuzhouJiangsu ProvinceChina Shanghai Key Lab of Forensic medicine Key Lab of Forensic ScienceMinistry of Justice(Academy of Forensic Science)ShanghaiChina department of Obstetrics and Gynecology The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhouJiangsu ProvinceChina

Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.

关键词： intracerebral hemorrhage mitochondrial dysfunction mitophagy neuroinflammation neuroprotection reactive oxygen species secondary brain injury therapeutic target

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Neuropathological characteristics of abnormal white matter functional signaling in adolescents with major depression

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World Journal of Psychiatry 2024年第2期14卷 276-286页

作者： Xin-Lin Huang Ju Gao Yong-Ming Wang Feng Zhu Jing Qin Qian-Nan Yao Xiao-Bin Zhang Hong-Yan Sun Imaging and Nuclear medicine Jiamusi UniversityJiamusi 154000Heilongjiang ProvinceChina department of Psychiatry The Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina School of Biology&Basic Medical Sciences Medical College of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina department of Radiology Shanghai Anting HospitalShanghai 20000China department of Radiology The Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina

BACKGROUND Major depression disorder(MDD)constitutes a significant mental health concern.Epidemiological surveys indicate that the lifetime prevalence of depression in adolescents is much higher than that in adults,with a corresponding increased risk of suicide.In studying brain dysfunction associated with MDD in adolescents,research on brain white matter(WM)is sparse.Some researchers even mistakenly regard the signals generated by the WM as noise points.In fact,studies have shown that WM exhibits similar blood oxygen level-dependent signal fluctuations.The alterations in WM signals and their relationship with disease severity in adolescents with MDD remain unclear.AIM To explore potential abnormalities in WM functional signals in adolescents with MDD.METHODS This study involved 48 adolescent patients with MDD and 31 healthy controls(HC).All participants were assessed using the Patient Health Questionnaire-9 Scale and the mini international neuropsychiatric interview(MINI)suicide inventory.In addition,a Siemens Skyra 3.0T magnetic resonance scanner was used to obtain the subjects'image data.The DPABI software was utilized to calculate the WM signal of the fractional amplitude of low frequency fluctuations(fALFF)and regional homogeneity,followed by a two-sample t-test between the MDD and HC groups.Independent component analysis(ICA)was also used to evaluate the WM functional signal.Pearson’s correlation was performed to assess the relationship between statistical test results and clinical scales.RESULTS Compared to HC,individuals with MDD demonstrated a decrease in the fALFF of WM in the corpus callosum body,left posterior limb of the internal capsule,right superior corona radiata,and bilateral posterior corona radiata[P<0.001,family-wise error(FWE)voxel correction].The regional homogeneity of WM increased in the right posterior limb of internal capsule and left superior corona radiata,and decreased in the left superior longitudinal fasciculus(P<0.001,FWE voxel correction).The ICA results of WM overlapped with tho

关键词： White matter Regional homogeneity The fractional amplitude of low-frequency fluctuations Independent component analysis Adolescents Major depression disorders

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Acute flaccid paralysis and neurogenic respiratory failure associated with enterovirus D68 infection in children: Report of two cases

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World Journal of Clinical Cases 2021年第14期9卷 3327-3333页

作者： Yv Zhang Sheng-Yuan Wang Da-Zhi Guo Shu-Yi Pan Yan Lv department of hyperbaric oxygen The Sixth Medical Center of PLA General HospitalBeijing 100048China

BACKGROUND Acute flaccid paralysis(AFP)and neurogenic respiratory failure rarely occur in children.At the end of 2018,some children with such symptoms were admitted to our hospital.In this study,we aimed to assess two children with AFP and neurogenic respiratory failure associated with enterovirus D68(EV-D68).CASE SUMMARY Two children admitted to our hospital presented with symptoms and imaging results different from those of acute disseminated encephalomyelitis and hand,foot,and mouth disease.Their main symptoms were AFP and neurogenic respiratory failure.Magnetic resonance imaging showed severe inflammatory injury mainly to the anterior horn cells of the spinal cord.Blood and cerebrospinal fluid samples were collected to assess for pathogens,including bacteria,tuberculosis,cryptococcus,herpes virus,and coxsackie virus,and the results were negative.At the beginning,the two cases were not assessed for EV-D68 in the nasopharyngeal,blood,and cerebrospinal fluid specimens.About 2 mo later,EVD68 was detected in the stool sample of one of the cases.The symptom of AFP was caused by injury to the anterior horn cells at levels C5-L5 of the spinal cord,while neurogenic respiratory failure was at levels C3-C5.CONCLUSION We should pay attention to the detection and diagnosis of EV-D68 and make efforts to develop antivirus drugs and vaccines.

关键词： Infection Enterovirus D68 Flaccid Paralysis Neurogenic Respiratory failure Case report

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Paradoxical systemic toxicity by inhaled paraquat poisoning: A case report

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Journal of Acute Disease 2024年第1期13卷 40-42,I0001-I0005页

作者： Tulika Garg Jaspreet Kaur Yuvraj Singh Cheema department of General medicine Government Medical College and HospitalChandigarhIndia

Rationale:Multi-organ failure is a symptom of paraquat poisoning,resulting in high mortality and morbidity rates.Though paraquat is widely available,poisoning through inhalation is rare.Patient’s Concern:A 37-year-old male reported to the emergency department with complaints of vomiting after an alleged history of inhalation of paraquat while at work.Diagnosis:Paraquat poisoning.Interventions:Supportive management along with multiple sessions of hemodialysis.Outcomes:Renal complications caused by paraquat were improved after multiple sessions of hemodialysis.However,the patient developed respiratory complications and later due to persistent hypoxemia and non-responsive to supportive therapy,he succumbed to his illness.Lessons:Acute kidney injury is a complication of paraquat poisoning.However,kidney involvement with the inhalational mode is rare.It is caused by reduction and oxidation cycles,as well as the formation of reactive oxygen species,necessitating hemodialysis as the treatment.Without a clear history,a specific clinical trait,or a diagnostic test,diagnosis can be difficult.Our case thus highlights the inhaled paraquat poisoning,presenting with acute kidney injury with late respiratory impairment as a consequence.

关键词： Paraquat poisoning Pesticide Acute kidney injury Respiratory insufficiency Hemodialysis

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COVID-19 and the Vascular Elderly Subject: Illustration of Therapeutic Management with Corticosteroids in an Elderly Diabetic Patient with COVID-19

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Open Journal of Clinical Diagnostics 2024年第1期14卷 1-6页

作者： Ibrahima Amadou Dembele Abrar-Ahmad Zulfiqar Romuald Nounga Nyanke Sékou Landoure Stéphane Loique Djeugoue Adama Sinayoko Nouhoum Kone Paul Antoni Amadou Nouroudine Rosunee Ahsveen Yacouba Koné Aoua Diarra Tania Mekuiko Ngeupi Mamadou Cissoko Mamadou Mallé Keïta Kaly Djibril Sy Djénébou Traoré Didier Mukéba Tshialala Assétou Soukho Kaya Emmanuel Andres Internal medicine department Medical Clinic B University Hospital Center of Strasbourg Strasbourg France Internal medicine department University Hospital Center Point G Bamako Mali Faculty of medicine and Odontostomatology University of Sciences Techniques and Technologies of Bamako Bamako Mali Faculty of medicine Pharmacy and Public Health University of Mbuji-Mayi Democratic Republic of Congo

Introduction: The severity of Sars-Cov-2 infection is associated with the development of acute respiratory distress syndrome (ARDS). The progression to ARDS appears to be driven by a major inflammatory mechanism potentially sensitive to corticosteroids. Observation: This article describes the case of an elderly patient was admitted to emergency departments for intense asthenia, accompanied by motor diarrhoea, dyspnoea with desaturation in ambient air, in a context of strong suspicion of infection linked to COVID-19. The article also reviews the existing literature on the diagnosis and treatment of this severe form of the disease. Conclusion: Corticosteroids, and in particular dexamethasone, have been shown to be effective in the management of patients with COVID-19, an oxygen-releasing disease.

关键词： COVID-19 Diabetes Mellitus Elderly person Corticosteroids Internal medicine

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Gene signatures to therapeutics:Assessing the potential of ivermectin against t(4;14)multiple myeloma

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World Journal of Clinical Oncology 2024年第1期15卷 115-129页

作者： Yang Song Hao-Jun Zhang Xia Song Jie Geng Hong-Yi Li Li-Zhong Zhang Bo Yang Xue-Chun Lu School of Basic medicine Medical School of Chinese PLABeijing 100853China School of Basic medicine Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina department of Hematology The Second Medical CentreChinese PLA General HospitalBeijing 100853China

BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermec

关键词： Multiple myeloma Functional enrichment analysis Molecular docking simulation Gene expression profiling Therapeutic target Ivermectin

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Mitochondrial dysfunction: A promising therapeutic target for liver diseases

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Genes & Diseases 2024年第3期11卷 324-337页

作者： Ping Chen Lichao Yao Mengqin Yuan Zheng Wang Qiuling Zhang Yingan Jiang Lanjuan Li department of Infectious Diseases Renmin Hospital of Wuhan UniversityWuhanHubei 430060China 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 HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiang 310003China

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the mitochondria.Liver tissues of pa-tients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mito-chondrial lesions,mitochondrial DNA damage,disturbed mitochondrial dynamics,and compromised ATP production.Overproduction of mitochondrial reactive oxygen species in-duces oxidative damage to mitochondrial proteins and mitochondrial DNA,decreases mito-chondrial membrane potential,triggers hepatocyte inflammation,and promotes programmed cell death,all of which impair liver function.Mitochondrial DNA may be a poten-tial novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B virus.We herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases,such as hepatocellular carcinoma,viral hepatitis,drug-induced liver injury,alcoholic liver disease,and non-alcoholic fatty liver disease.This review also discusses mito-chondrion-centric therapies for treating liver diseases.

关键词： Chronic diseases Liverdamage Mesenchymalstem cell Mitochondrial dysfunction Oxidativestress

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ZIF-8 coated gold nanospheres: A multi-responsive drug delivery system promoting the killing effect of photothermal therapy against osteosarcoma cells

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Nano Research 2024年第3期17卷 1772-1784页

作者： Miao Lei Weiye Cai Luetao Zou Bin Yu Lin Chen Yang Cao Shanlin Xiang Chao Song Jiandu Lei Wei Jiang Zhenming Hu department of Orthopedics Orthopedic Laboratory of Chongqing Medical UniversityThe First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China The Affiliated Traditional Chinese medicine Hospital of Southwest Medical University Luzhou 646699China department of Orthopedics The Third Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China department of Radiology The First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China department of Orthopedics Chongqing University Three Gorges HospitalChongqing 404000China department of Geriatrics The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550025China Beijing Key Laboratory of Lignocellulosic Chemistry College of Material Science and TechnologyBeijing Forestry UniversityBeijing 100083China

Photothermal therapy(PTT)has been widely used in the treatment of tumors,but its efficacy is greatly limited by the inability of precise drug delivery and the increase of heat shock proteins(HSPs)caused by high temperature.This article describes a therapeutic strategy to enhance PTT with starvation therapy in conjunction with ferroptosis mechanism.A nanoparticle platform ZIF-8@GA was constructed by wrapping together glucose oxidase(GOX)and gold nanospheres(AuNPs)loaded with dihydroartemisinin(DHA)with zeolitic imidazolate framework-8(ZIF-8).This platform can take advantage of the micro-environment of osteosarcoma(OS)cells,featuring low pH and high reactive oxygen species(ROS),for precision drug delivery.GOX can effectively catalyze glucose to produce gluconic acid and H_(2)O_(2),and DHA can also induce ROS production in OS cells.ROS produced by GOX and DHA can further generate lipid peroxidation(LPO)and lead to ferroptosis of OS cells.At the same time,ROS and LPO produced can inhibit the expression of HSPs,thereby increasing the therapeutic effect of PTT.In vitro experiments show that the nanoparticles are pH and ROS responsive.1μg/mL GOX combined with 0.2μg/mL DHA promotes ferroptosis of OS cells,and increases the killing effect of near-infrared(NIR)on OS cells.Further in vivo experiments showed that the nano drug-delivery platform combined with PTT can effectively inhibit the growth of OS cells.Meanwhile,this study provides a new idea for the treatment of OS with biomaterials combined with various treatment methods.

关键词： zeolitic imidazolate framework-8(ZIF-8) gold nanospheres(AuNPs) photothermal therapy(PTT) starvation therapy ferroptosis

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