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Treating incurable non-communicable diseases by targeting iron metabolism and ferroptosis

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Science China Life Sciences 2025年

作者： Ruoxuan Ni Jianwei Jiang Fudi Wang Junxia Min The First Affiliated Hospital Institute of Translational Medicine Zhejiang University School of Medicine The Second Affiliated Hospital School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine

Both iron metabolism and ferroptosis (an iron-dependent form of programmed cell death) have been connected to the development and progression of many currently incurable non-communicable diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis,Huntington’s disease, metabolic dysfunction-associated steatohepatitis, heart failure, and both treatment-relapsed and refractory cancers,such as pancreatic ductal adenocarcinoma and triple-negative breast cancer. Thus, understanding the relationship between iron and these diseases can pave the way for the development of novel therapeutic strategies. Here, we summarize the latest evidence supporting the pathological roles of dysregulated iron metabolism and ferroptosis in a wide range of preclinical animal models of these currently incurable non-communicable diseases. We also summarize the feasibility of targeting iron metabolism and ferroptosis for the prevention and treatment of iron-and ferroptosis-related diseases that currently have limited treatment options. In addition, we provide our perspectives on the challenges and promises regarding the translational potential of targeting dysregulated iron metabolism and ferroptosis to treat diseases,highlighting the future roadmap for developing iron-and ferroptosis-targeted therapeutics.

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Genetic variants and mRNA expression levels of KLF4 and KLF5 with hypertension:A combination of case-control study and cohort study

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Journal of Biomedical Research 2025年第1期39卷 103-113页

作者： Xu Han Wen Li Changying Chen Jiahui Liu Junxiang Sun Feifan Wang Chao Wang Jialing Mu Xincheng Gu Fangyuan Liu Hankun Xie Song Yang Chong Shen Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Cardiology the Affiliated Yixing People's Hospital of Jiangsu UniversityPeople's Hospital of Yixing CityWuxiJiangsu 214200China Department of Environmental Genomics School of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China

Hypertension(HT)is a major risk factor for cardiovascular ***üppel-like factors(KLFs)are important transcription factors in *** have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases,but population-based studies on associations between HT and KLF4 or KLF5 have rarely been ***,the current study investigated the associations of genetic variants and m RNA expression levels of KLF4 and KLF5 with HT,as well as the effects of antihypertensive drugs on the expression levels of these *** associations of one single-nucleotide polymorphism(SNP)in KLF4 and three SNPs in KLF5with HT were analyzed using a combination of case-control and cohort *** study populations were selected from a community-based cohort in four regions of Jiangsu *** risks of HT were estimated through logistic and Cox regression *** addition,m RNA expression levels of KLF4 and KLF5 were detected in 246 controls and 385 HT cases selected from the aforementioned *** the HT cases,263were not taking antihypertensive drugs[AHD(-)]and 122 were taking antihypertensive drugs[AHD(+)].In the case-control study,SNP rs9573096(C>T)in KLF5 was significantly associated with an increased risk of HT in the additive model(adjusted odds ratio[OR],1.106;95%confidence interval[CI],1.009 to 1.212).In the cohort study of the normotensive population,rs9573096 in KLF5 was also significantly associated with an increased risk of HT in the additive model(adjusted hazards ratio[HR],1.199;95%CI,1.070 to 1.344).KLF4 and KLF5m RNA expression levels were significantly higher in the AHD(-)group than in the control group(P<0.05),but lower in the AHD(+)group than in the AHD(-)group(P<0.05).The current study demonstrated the associations of KLF4 and KLF5 genetic variants with hypertension,as well as the association of the indicative variations in m RNA expression levels of KLF4 and KLF5 with the risk of hypertension and antihypertensive

关键词： hypertension KLF4 KLF5 single-nucleotide polymorphism mRNA expression antihypertensive drugs

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Susceptible Windows of Prenatal Ozone Exposure and Preterm Birth:A Hospital-Based Observational Study

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Biomedical and Environmental Sciences 2025年第2期38卷 255-260,I0001-I0004页

作者： Rongrong Qu Dongqin Zhang Hanying Li Jiayin Zhi Yanxi Chen Ling Chao Zhenzhen Liang Chenguang Zhang Weidong Wu Jie Song Henan International Collaborative Laboratory for health Effects and Intervention of Air Pollution School of Public HealthXinxiang Medical UniversityXinxiang 453003HenanChina school of Medical Technology Xinxiang Medical UniversityXinxiang 453003HenanChina

Preterm birth(PTB)is defined as delivery before 37 weeks of *** is associated with increased cardiovascular risk,neurodevelopmental disorders,and other diseases in infancy,childhood,and adulthood[1].Globally,approximately 15 million PTB cases are reported annually,posing a huge burden on individual families and the community economy[2].In the context of climate warming,O_(3) pollution has continuously increased in many countries in recent years,including China;therefore,scientific communities and government agencies must strive to mitigate ozone pollution.

关键词： Windows individual annually

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Clinicopathological features and treatment of gastrointestinal schwannomas

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World Journal of Gastroenterology 2025年第5期31卷 32-42页

作者： Peng-Cheng Zhang Shu-Hui Wang Jun Li Jing-Jie Wang Hong-Tan Chen Ai-Qing Li Department of Gastroenterology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Department of Epidemiology&health Statistics School of Public HealthSchool of MedicineZhejiang UniversityHangzhou 310058Zhejiang ProvinceChina Department of Pathology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Gastrointestinal schwannomas(GIS)are rare neurogenic tumors arising from Schwann cells in the gastrointestinal *** on GIS are limited to small case reports or focus on specific tumor sites,underscoring the diagnostic and thera-peutic challenges they *** To comprehensively examine the clinical features,pathological characteristics,treatment outcomes,associated comorbidities,and prognosis of *** The study population included patients diagnosed with GIS at the First Affiliated Hospital,Zhejiang university school of Medicine,between June 2007 and April *** were retrospectively collected and analyzed from medical records,including demographic characteristics,endoscopic and imaging findings,treatment modalities,pathological evaluations,and follow-up *** In total,229 patients with GIS were included,with a mean age of 56.00 years and a male-to-female ratio of 1:*** mean tumor size was 2.75 cm,and most(76.9%)were located in the ***,6.6%of the patients had other malig-nant *** imaging and endoscopy frequently misdiagnosed GIS as gastrointestinal stromal ***,accurate preoperative diagnosis was achieved using endoscopic ultrasound-guided fine-needle aspiration combined with immunohistochemical analysis,in which S100 and SOX-10 markers were mostly *** tumors were typically managed with endoscopic resection,while larger lesions were treated with surgical ***-up results showed that most patients experienced favorable *** Preoperative diagnosis of GIS via clinical characteristics,endoscopy,and imaging examinations remains challenging but *** therapy provides a minimally invasive and effective option for patients.

关键词： Gastrointestinal schwannoma Diagnosis Treatment Endoscopictherapy Complications

Genome of tropical bed bug Cimex hemipterus(Cimicidae,Hemiptera)reveals tetraspanin expanded in bed bug ancestor

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Insect Science 2025年第1期32卷 42-54页

作者： Sean Tsz Sum Law Wenyan Nong Chade Li Tze Kiu Chong Ho Yin Yip Thomas Swale Siu Wai Chiu Roger Yat-Nork Chung Hon-Ming Lam Samuel Y.S.Wong Hung Wong Jerome H.L.Hui school of Life Sciences Simon F.S.Li Marine Science LaboratoryState Key Laboratory of AgrobiotechnologyInstitute of EnvironmentEnergy and SustainabilityThe Chinese University of Hong KongHong KongChina Dovetail Genomics The United States of America school of Life Sciences The Chinese University of Hong KongHong KongChina school of public health and Primary Care CUHK Institute of Health EquityThe Chinese University of Hong KongHong KongChina school of Life Sciences State Key Laboratory of AgrobiotechnologyInstitute of EnvironmentEnergy and SustainabilityThe Chinese University of Hong KongHong KongChina Department of Social Work CUHK Institute of Health EquityInstitute of EnvironmentEnergy and SustainabilityThe Chinese University of Hong KongHong KongChina

Cimex species are ectoparasites that exclusively feed on warm-blooded animals such as birds and *** cimicid species are known to be persistent pests for humans,including the tropical bed bug Cimex hemipterus,common bed bug Cimex lectularius,and Eastern bat bug Leptocimex *** date,genomic information is restricted to the common bed bug ***,which limits understanding their biology and to provide controls of bed bug ***,a chromosomal-level genome assembly of ***(495 Mb[megabase pairs])contained on 16 pseudochromosomes(scaffold N50=34 Mb),together with 9 messenger RNA and small RNA transcriptomes were *** comparison between hemipteran genomes,we found that the tetraspanin superfamily was expanded in the Cimex *** study provides the first genome assembly for the tropical bed bug ***,and offers an unprecedented opportunity to address questions relating to bed bug infestations,as well as genomic evolution to hemipterans more widely.

关键词： bedbug genome microRNA sesquiterpenoid tetraspanin

Development and validation of a nomogram prediction model for overall survival in patients with rectal cancer

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 93-104页

作者： Ling Liang Xiao-Sheng Li Ze-Jun Huang Zu-Hai Hu Qian-Jie Xu Yu-Liang Yuan Wei Zhang Hai-Ke Lei Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment Chongqing University Cancer HospitalChongqing 400030China Chongqing Cancer Multiomics Big Data Application Engineering Research Center Chongqing University Cancer HospitalChongqing 400030China Department of health Statistics School of Public HealthChongqing Medical UniversityChongqing 400016China

BACKGROUND Rectal cancer is prevalent and associated with substantial morbidity and *** To develop a nomogram prediction model for overall survival(OS)in patients with rectal cancer by leveraging a comprehensive analysis of demographic,clinicopathological,haematological,and follow-up data to identify independent prognostic *** We conducted a prospective cohort study in China involving rectal cancer patients and applied Cox regression and least absolute shrinkage and selection operator regression to assess the significance of various variables as independent prognostic factors for *** identified factors were integrated into a nomogram model,which was evaluated for predictive accuracy via the C-index,area under the curve(AUC),calibration curve,and decision curve analysis(DCA).RESULTS Multivariate analysis revealed independent predictors of OS,including the Karnofsky performance status,age,sex,TNM stage,chemotherapy,surgery,targeted therapy,β2-microglobulin,lactate dehydrogenase,and the neutrophil-to-lymphocyte *** nomogram demonstrated a C-index of 0.80 for the training and validation cohorts,with AUC values indicating high predictive accuracy for 1-year,3-year,and 5-year *** calibration curves confirmed the model's excellent agreement with the observed survival rates,and DCA revealed the superior clinical utility of the nomogram over the TNM staging *** In this study,a novel prognostic model that accurately predicts the OS of rectal cancer patients was *** model exhibited excellent discriminatory and calibration capabilities,thus offering a reliable tool for health care professionals to estimate patient survival.

关键词： Rectal cancer Overall survival Nomogram Prognosis

Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

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Neural Regeneration Research 2025年第1期20卷 159-173页

作者： Man Han Deyang Zeng Wei Tan Xingxing Chen Shuyuan Bai Qiong Wu Yushan Chen Zhen Wei Yufei Mei Yan Zeng Brain Science and Advanced Technology Institute Wuhan University of Science and TechnologyWuhanHubei ProvinceChina Geriatric Hospital Affiliated to Wuhan university of Science and Technology WuhanHubei ProvinceChina school of public health Wuhan University of Science and TechnologyWuhanHubei ProvinceChina

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral *** studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and *** how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress *** this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of *** focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine *** determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic ***,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

关键词： amygdala chronic mild stress chronic social defeat stress corticolimbic system depression hippocampus medial prefrontal cortex nucleus accumbens social stress models ventral tegmental area

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Supply Chain Disruption and Import Strategy:Evidence from the Great East Japan Earthquake

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China & World Economy 2025年第1期33卷 132-161页

作者： Fan Lu Zhicong Li Xinrong Cai school of public Finance and Taxation Central University of Finance and EconomicsChina school of Finance and Taxation Zhongnan University of Economics and LawChina

Global supply chain networks foster collaboration but accelerate cross-border risk *** study investigates the effect of the 2011 East Japan earthquake on Chinese firms'import *** findings reveal that the disruption led to a shift toward supply chain concentration,with firms reducing the diversification of import *** was a slight increase in the number of countries from which firms sourced imports but import shares became more concentrated,reflecting a reliance on fewer,centralized *** affected by the earthquake prioritized long-term partnerships and sought suppliers in regions with lower natural disaster risks,aiming to mitigate supply chain vulnerabilities and reduce switching *** findings also show that state-owned enterprises,private firms,and research and development-intensive firms were more inclined to centralize their import *** suggests that these firms,leveraging their larger scale,substantial resources,and robust risk management strategies,favored a more concentrated sourcing approach in order to better control their supply chains and ensure stability in the face of global disruptions.

关键词： firm behavior import strategy natural disaster supply chain

Relationship between gastric mucosal atrophy by endoscopy and non-ampullary duodenal epithelial tumors

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 84-92页

作者： Kazuya Ohno Eiji Nakatani Takafumi Kurokami Asami Kawai Ryosuke Itai Masanori Matsuda Yuichi Masui Tatsunori Satoh Shinya Ikeda Taiyo Hirata Shodai Takeda Makoto Suzuki Ken Haruma Department of Gastroenterology Shizuoka General HospitalShizuoka 420-8527Japan Research Support Center Graduate School of Public HealthShizuoka Graduate University of Public HealthShizuoka 420-0881Japan Department of Pathology Shizuoka General HospitalShizuoka 420-8527Japan Department of General Internal Medicine 2 Kawasaki Medical SchoolOkayama 700-8505Japan

BACKGROUND The pathogenesis of non-ampullary duodenal epithelial tumors(NADETs)is not fully *** that express gastric-type mucin phenotypes(GNADETs)are noteworthy because of their high *** foveolar metaplasia,from which G-NADETs originate,protects the duodenal mucosa from gastric *** gastric acid secretion is affected by endoscopic gastric mucosal atrophy(EGMA),we hypothesized that EGMA would be associated with *** To evaluate the association between EGMA and the occurrence of *** This cross-sectional retrospective study investigated the relationship between EGMA and NADETs in 134 *** duodenum was divided into parts 1(bulb),2(superior duodenal angle to the papilla),and 3(anal side of the papilla to the horizontal part).The effects of gastric acidity and presence of Brunner’s glands were *** was divided into types C(no or mild atrophy)and O(severe atrophy).Mucin phenotype expressions in NADETs were divided into gastric,intestinal,gastrointestinal,and *** When NADETs were classified according to EGMA,105 were classified as type C and 29 as type O.G-NADETs were present in 11.9%(16 cases)of all cases,and all 16 cases were of type *** G-NADETs,93.8%(15 cases)were present in part 1 or *** was an association between G-NADETs and type C in part 1,and 50.0%(eight of 16 cases)of G-NADETs were associated with a current or previous Helicobacter pylori infection ***,all eight cases occurred in part *** G-NADETs were significantly associated with type *** acidity and Brunner's gland growth may be associated with G-NADETs.

关键词： Gastric acidity Gastric foveolar metaplasia Gastric mucosal atrophy Helicobacter pylori Mucin phenotype Nonampullary duodenal epithelial tumor