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The pharmacogenomic landscape in the Chinese: An analytics of pharmacogenetic variants in 206,640 individuals

The Innovation 2025年第2期6卷 28-40,27页

作者： Lei-Yun Wang Bing Yu Ying Peng Kai Mou Yan Zhan Yi-Min Wang Wei Ji Chun Xu Le-Dong Xiao Yan Chen Hua Wang Zhi-Hua She Peng Dai Gan-Ye Zhao Yang Wang Lu-Lu Yu Miao Yu Ke Liu Jia-Jia Cui Rong Liu Xi Li Yuan-Fei Huang Zhao-Qian Liu Dong-Sheng Ouyang Wei Zhang Qing Li Xing-Liang Xiong Cheng-Xian Guo Jin-Gao Li Qiao-Li Lv Qing-He Xing Hai-Jian Wang Zhi-Ling Li Ji-Chu Wu Long-Jian Huang Jian He Li-Ming Tan Wen-Xu Hong Xue-Chang Wang Chao-Peng Li Qin Lu Long Zhang Xiang-Dong Kong Hong-Hao Zhou Ji-Ye Yin Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangsha 410078China Engineering Research Center of Applied Technology of Pharmacogenomics Ministry of EducationChangsha 410078China National Clinical Research Center for Geriatric Disorders Changsha 410008China Institute of Clinical Pharmacology Hunan Key Laboratory of PharmacogeneticsCentral South UniversityChangsha 410078China The Genetics and Prenatal Diagnosis Center The Department of Obstetrics and GynecologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Genetic Laboratory Zibo Maternal and Child Health HospitalZibo 255000China The Hunan Children’s Hospital Changsha 410000China National Health Commission Key Laboratory of Birth Defects Research Prevention and TreatmentHunan Provincial Maternal and Child Health Care HospitalChangsha 410000China Department of Pharmacy Hunan Provincial Maternal and Child Health Care HospitalChangsha 410008China Genetalks Co.Ltd. Changsha 410008China Xiangya Medical Laboratory Central South UniversityChangsha 410078China Salus Med Co.Ltd. Shenzhen 518107China Department of Pharmacy Traditional Chinese and Western Medicine Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Pharmacy Wuhan No.1 HospitalWuhan 430022China Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha 410078China Department of General Surgery Xiangya HospitalCentral South UniversityChangsha 410078China Department of Geriatric Surgery Xiangya HospitalCentral South UniversityChangsha 410078China Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha Duxact Biotech Co.Ltd.Changsha 410000China Center of Clinical Pharmacology The Third Xiangya HospitalCentral South UniversityChangsha 410013China Department of Radiation Oncology Jiangxi Cancer HospitalNanchang 330029China NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinom

Pharmacogenomic landscapes and related databases are important for identifying the biomarkers of drug response and ***,these data are still lacking for the Chinese *** this study,we constructed a pharmacogenomic landscape and an associated database using whole-genome sequencing data generated by non-invasive prenatal testing in 206,640 Chinese *** total,1,577,513 variants(including 331,610 novel variants)were identified among 3,538 pharmacogenes related to 2,086 *** found that the variant spectrum in the Chinese population differed among the seven major *** differences also exist among provinces in *** average numbers of drug enzyme,transporter,and receptor variants were 258,557,and 632,*** correlation analysis indicated that the pharmacogenes affecting multiple drugs had fewer *** the 16 categories of drugs,we found that nervous system,cardiovascular system,and genitourinary system/sex hormone drugs were more likely to be affected by variants of *** of the variants in the enzyme,transporter,and receptor subfamilies showed *** explore the clinical utility of these data,a genetic association study was conducted on 1,019 lung cancer *** novel variants,AKT2 chr19:40770621 C>G and SLC19A1 chr21:46934171 A>C,were identified as novel platinum response ***,a pharmacogenomic database,named the Chinese Pharmacogenomic Knowledge Base(CNPKB:http://***/),was constructed to collect all the *** summary,a pharmacogenomic landscape and database for the Chinese population were constructed in this study,which could support personalized Chinese medicine in the future.

关键词： pharmacogenomics Chinese population personalized medicine pharmacogenomic landscapes associated database whole genome sequencing identifying biomarkers pharmacogenetic variants

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Intestinal Microbiota in Early Life and Its Implications on Childhood Health

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Genomics, Proteomics & Bioinformatics 2019年第1期17卷 13-25页

作者： Lu Zhuang Haihua Chen Sheng Zhang Jiahui Zhuang Qiuping Li Zhichun Feng Affiliated Bayi Children's Hospital The Seventh Medical Center of PLA General Hospital National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology Beijing Key Laboratory of Pediatric Organ Failure The First Clinical Academy of Dalian Medical University College of the Environment Northeast Normal University

Trillions of microbes reside in the human body and participate in multiple physiological and pathophysiological processes that affect host health throughout the life cycle. The microbiome is hallmarked by distinctive compositional and functional features across different life *** evidence has shown that microbes residing in the human body may play fundamental roles in infant development and the maturation of the immune system. Gut microbes are thought to be essential for the facilitation of infantile and childhood development and immunity by assisting in breaking down food substances to liberate nutrients, protecting against pathogens, stimulating or modulating the immune system, and exerting control over the hypothalamic–pituitary–adrenal *** review aims to summarize the current understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the role of intestinal microbes in pediatric diseases. Furthermore, we also discuss the microbiota-mediated therapeutics that can reconfigure bacterial communities to treat dysbiosis.

关键词： Intestinal microbiota Immunity Gut-brain axis Early life Diseases Microbiota manipulation

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Corrigendum to "Raman-guided exploration of placental microplastic exposure: Unraveling the polymeric tapestry and assessing developmental implications" [J Hazard Mater 477 (2024) 135271]

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Journal of hazardous materials 2024年 479卷 135761页

作者： Xiang Yun Liyang Liang Jiaqi Tian Ning Li Zhen Chen Yongfei Zheng Shuyin Duan Lin Zhang Clinical Medical Research Center for Women and Children Diseases Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University Jinan 250001 China Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission Jinan 250001 China School of Public Health North China University of Science and Technology Tangshan 063000 China. Department of Surgery-oncology Tangshan Gongren Hospital Affiliated to Hebei Medical University Tangshan 063000 China. Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission Jinan 250001 China. School of Public Health Shandong Second Medical University Weifang 261053 China. School of Public Health Shandong First Medical University & Shandong Academy of Medical Sciences Jinan 250001 China. Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission Jinan 250001 China. Electronic address: zhanglin8901@***.

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Folic acid supplementation on congenital heart disease and its dual character

Current Research in Pharmacology and Drug Discovery

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Current Research in Pharmacology and Drug Discovery 2025年 8卷 100222页

作者： Wang, Yanli Cheng, Zhengpei He, Mingfang Gu, Rui Gu, Harvest F. National Health Commission Key Laboratory of Birth Defect Prevention Henan Institute of Reproductive Health Science and Technology Zhengzhou 450002 China School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University Nanjing 210009 China College of Biotechnology and Pharmaceutical Engineering Nanjing Tech University Nanjing 211816 China Institute of Biological Chinese Medicine Beijing Yichuang Institute of Biotechnology Industry Beijing 100023 China School of Pharmacy Qilu Medical University Zibo 255300 China

Pregnant women are vulnerable to folate deficiency as its requirement is substantially greater than folate requirements for non-pregnant women. Folic acid is a synthetic form of folate and has been used in the fortified foods and nutritional supplements. Since the 1990s, maternal folic acid supplementation has been adopted by the governments and health organizations around the world as the policy to prevent the birth defects, especially neural tube defects. Under the promotion of folic acid supplementation, however, the global prevalence of congenital heart disease continues to be increased. In the recent years, our research group has evaluated that the heterogeneity concerning the association between folic acid supplementation and congenital heart disease is high. Based on experiments with animal models such as zebrafish and mice, we have demonstrated that excessive folic acid supplementation led to cardiovascular development disorders and even early embryo death. In this review article, we first summarize the discovery of folic acid and the achievement of folic acid supplementation in the prevention of congenital diseases. We then discuss the transport and metabolism of folic acid particularly in the form of unmetabolized folic acid. Finally, we comment on the association of folic acid supplementation with congenital heart disease. Better understanding the dual character of folic acid supplementation on congenital heart disease may provide new insights into the potential role of folic acid and offer a fresh perspective on the prevention of congenital heart disease. © 2025

关键词： 6S-5-methyltetrahydrofolate-calcium Congenital heart disease Folic acid Metabolism Neural tube defects

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Corrigendum to "Molecular mechanism of regulating tat protein expression of pingganjiedu TCM in the treatment of AIDS based on network pharmacology" [Int. J. Biol. Macromol. 278(Pt 1) (Aug 8, 2024) 134599]

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International journal of biological macromolecules 2024年第PT 1期281卷 136228页

作者： Jiannan Lv Mingzhen Qin Xianwu Pang Lu Chen Yingqin Liao Yu Liu Song Li Zhe Wang Wuwei Wu National Immunological Laboratory of Traditional Chinese Medicines Department of Infection Affiliated Hospital of Youjiang Medical University for Nationalities Baise 533000 China. Electronic address: gxaidscc@***. National Engineering Research Center of Southwest Endangered Medicinal Resource Development Guangxi Botanical Garden of Medicinal Plants Nanning Guangxi 530023 China. Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention Nanning Guangxi 530021 China. National Immunological Laboratory of Traditional Chinese Medicines Department of Infection Affiliated Hospital of Youjiang Medical University for Nationalities Baise 533000 China. Key Laboratory of Rare Pediatric Diseases Ministry of Education University of South China Hengyang Hunan 421001 China National Health Commission Key Laboratory of Birth Defect Research and Prevention Hunan Provincial Maternal and Child Health Care Hospital Changsha Hunan 410008 China. Department of Pharmacology of Traditional Chinese Medicine The Second Clinical College of Guangzhou University of Chinese Medicine 111 Dade Road 510000 Guangzhou China.

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Dominant Follicle-Targeted Nanocarriers for GH Delivery to Alleviate Premature Ovarian Insufficiency

Materials Today Bio

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Materials Today Bio 2025年

作者： Shao Yang Yawei Sun Wei Luo Xiaofeng Zhou Xiao Gu Wenzhe Zhang Huashan Zhu Wenjia Wu Xueying Wu Mengru Yu Shan Wang Department of Reproductive Medicine Department of Obstetrics and Gynecology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong 250021 China Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention Shandong First Medical University Jinan Shandong 250021 China Jinan Engineering Laboratory of Reproductive Diagnosis and Treatment Technology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong 250021 China Shandong University Jinan Shandong 250000 China Department of Obstetrics and Gynecology Zibo Municipal Hospital Zibo Shandong 255400 China Shandong Second Medical University Weifang Shandong 252422 China

Premature ovarian insufficiency (POI) is characterized by ovarian functional damage, leading to infertility and severe complications. Current treatment is merely to relieve the clinical symptoms by hormone supplementation. Growth hormone (GH) shows efficacy in restoring ovarian function. However, GH has poor targeting specificity and stability, which limits its clinical application. Dominant follicles play a vital role in ovarian endocrine and reproductive function. Zona pellucida glycoprotein 3 (ZP3) is a specific component of the zona pellucida around the oocyte and is tightly associated with the dominant follicle. Therefore, we constructed a GH-loaded complex zeolitic imidazolate frameworks-8 (ZIF8)-GH@ZP3Ab, which uses ZIF8 to load GH and ZP3 antibody (ZP3Ab) to specifically bind ZP3. The results showed that ZIF8-GH@ZP3Ab had a good targeting ability to ovaries, especially the dominant follicles. This approach promoted the development of dominant follicles without increasing the depletion of primordial follicles. In vivo experiments demonstrated that ZIF8-GH@ZP3Ab promoted angiogenesis, reduced oxidative stress and apoptosis, and enhanced the secretion of IGF-1 in antral follicles. These effects restored ovarian function and fertility in cisplatin-induced POI in mice. In vitro experiments indicated that both ZIF8 and GH can protect granulosa cells from cisplatin-induced oxidative stress and apoptosis. In conclusion, ZIF8-GH@ZP3Ab is promising as an effective nanomedicine for the treatment of POI.

关键词： Premature ovarian insufficiency (POI) Growth hormone (GH) Zeolitic imidazolate framework-8 (ZIF8) Dominant follicles

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Correction: LncRNA sequencing reveals an essential role for the lncRNA-mediated ceRNA network in penile squamous cell carcinoma

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Genes and immunity 2024年第6期25卷 552页

作者： Jian Cao Lin Du Xueheng Zhao Zhizhong Liu Junbin Yuan Yanwei Luo Shanshan Zhang Zailong Qin Jie Guo Department of Urology The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University/Hunan Cancer Hospital Changsha China. Department of Blood Transfusion The Third Xiangya Hospital Central South University Changsha China. NHC Key Laboratory of Human Stem Cell and Reproductive Engineering Institute of Reproductive and Stem Cell Engineering School of Basic Medical Science Central South University Changsha China. Department of Urology Xiangya Hospital Central South University Changsha China. Department of Stomatology Xiangya Hospital Central South University Changsha China. Guangxi Key Laboratory of Reproductive Health and Birth Defect Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning China. qinzailong@***. Guangxi Key Laboratory of Precision Medicine for Genetic Diseases Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning China. qinzailong@***. Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning China. qinzailong@***. Genetic and Metabolic Central Laboratory Birth Defects Prevention and Control Institute of Guangxi Zhuang Autonomous Region Nanning China. qinzailong@***. Guangxi Clinical Research Center for Pediatric Diseases Nanning China. qinzailong@***. National Institution of Drug Clinical Trial Xiangya Hospital Central South University Changsha China. guojiexy@***. China National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University Changsha China. guojiexy@***.

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Biallelic MED16 variants disrupt neural development and lead to an intellectual disability syndrome

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Journal of genetics and genomics = Yi chuan xue bao 2025年

作者： Yan Huang Zhenglong Xiang Yaqin Xiang Hu Pan Mei He Zhenming Guo Oguz Kanca Chen Liu Zhao Zhang Huaizhe Zhan Yuan Wang Qing-Ran Bai Hugo J Bellen Hua Wang Shan Bian Xiao Mao Department of Medical Genetics & Pediatric Research Institute The Affiliated Children's Hospital of Xiangya School of Medicine Central South University (Hunan Children's Hospital) Changsha Hunan 410007 China. Institute for Regenerative Medicine State Key Laboratory of Cardiology and Medical Innovation Center Shanghai East Hospital Frontier Science Center for Stem Cell Research School of Life Sciences and Technology Tongji University Shanghai 200120 China. Department of Medical Genetics The Affiliated Children's Hospital of Xiangya School of Medicine Central South University (Hunan Children's Hospital) Changsha Hunan 410007 China. National Health Commission Key Laboratory of Birth Defect Research and Prevention Hunan Provincial Maternal and Child Health Care Hospital University of South China Changsha Hunan 410008 China. Department of Molecular and Human Genetics Baylor College of Medicine (BCM) Houston Texas 77030 USA Jan and Dan Duncan Neurological Research Institute Texas Children's Hospital Baylor College of Medicine Houston Texas 77030 USA. Neonatology Children's Hospital Affiliated to Shandong University Jinan Shandong 250022 China. Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji Hospital School of Medicine Tongji University 200065 Shanghai China. Institute for Regenerative Medicine State Key Laboratory of Cardiology and Medical Innovation Center Shanghai East Hospital Frontier Science Center for Stem Cell Research School of Life Sciences and Technology Tongji University Shanghai 200120 China National Health Commission Key Laboratory of Birth Defect Research and Prevention Hunan Provincial Maternal and Child Health Care Hospital University of South China Changsha Hunan 410008 China China Regional Research Center International Center for Genetic Engineering and Biotechnology Taizhou Jiangsu 225316China. Electronic address: shan_bian@tongji.edu.cn. Department of Medical G

Mediator Complex Subunit 16 (MED16, MIM: 604062) is a member of the Mediator complex which controls many aspects of transcriptional activity in all eukaryotes. Here, we report two individuals from a non-consanguineous family with biallelic variants in MED16 identified by exome sequencing. The affected individuals present with global developmental delay, intellectual disability, and dysmorphisms. To assess the pathogenicity of the variants, functional studies were performed in Drosophila and patient-derived cells. The fly ortholog med16 is expressed in neurons and some glia of the developing central nervous system (CNS). Loss of med16 leads to a reduction in eclosion and lifespan, as well as impaired synaptic transmission. In neurons differentiated from the patient-derived induced pluripotent stem cells (iPSCs), the neurite outgrowth is impaired and rescued by expression of exogenous MED16. The patient-associated variants behave as loss-of-function (LoF) alleles in flies and iPSCs. Additionally, the transcription of genes related to neuronal maturation and function is preferentially altered in patient cells relative to differentiated H9 controls. In summary, our findings support that MED16 is important for appropriate development and function, and that biallelic MED16 variants cause a neurodevelopmental disease.

关键词： Drosophila Intellectual disability Loss-of-function variants MED16 Transcriptional regulation patient derived iPSCs

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Identification of tick-borne pathogen diversity by metagenomic analysis in Haemaphysalis longicornis from Xinyang,China

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Infectious Diseases of Poverty 2018年第1期7卷 440-447页

作者： Lu Zhuang Juan Du Xiao-Ming Cui Hao Li Fang Tang Pan-He Zhang Jian-Gong Hu Yi-Gang Tong Zhi-Chun Feng Wei Liu State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology20 Dong-Da StreetFengtai DistrictBeijing 100071People’s Republic of China Affiliated Bayi Children’s Hospital PLA Army General Hospital5 Nan-Men-CangDongcheng DistrictBeijing 100700People’s Republic of China National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology 5 Nan-Men-CangDongcheng DistrictBeijing 100700People’s Republic of China Center for Diseases Control and Prevention of Chinese Peoples’Armed Police Forces Beijing 102613China

Background:A wide variety of pathogens could be maintained and transmitted by Haemaphysalis *** aim of this study is to systematically examine the variety of pathogens carried by Haemaphysalis longicornis,an importnatn vector,in tick-borne diseases epidemic area,and to estimate the risk of human infection imposed by tick ***:Adult questing ticks were collected in Xinyang,central *** DNA and RNA were extracted from 144 *** ticks individually,and sequenced respectively as the templates for high-throughput *** reads were compared against the database of NCBI nucleotide collection and specific PCR was performed to confirm the presence of *** analysis was performed to explore the evolutionary status of ***:The assignment of reads to taxa based on BLASTN results revealed the existence of several potential pathogens,including Anaplasma spp.,Rickettsia spp.,Babesia sp.,as well as severe fever with thrombocytopenia syndrome bunyavirus(SFTSV).Comfirmantory PCR assays revealed the existence of Anaplasma bovis(13/144,9.03%),Anaplasma centrale(2/144,1.39%),Rickettsia heilongjiangensis(3/144,2.08%),Rickettsia ***-13(1/144,0.69%),Rickettsia raoultii(5/144,3.47%),Babesia sp.(1/144,0.69%).SFTSV accounted for the highest detected pathogen with a positive rate of 18.75%(27/144).Three of the ticks(2.08%)were co-infected with SFTSV and ***:Our study provided a broadened list of microorganism that harbored by *** previously unrecognized endemic regions,prokaryotic and eukaryotic infection including Anaplasma spp.,Rickettsiae spp.,and Babesia *** be considered,along with the well-known SFTSV for patients with tick bites history.A novel Babesia species was identified in local natural foci,which needs further investigation in the future.

关键词： Haemaphysalis longicornis Pathogens High-throughput sequencing

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CSDE1 enhances genotoxic drug resistance in cancer by modulating RPA2 through CSDE1-eIF3a regulatory complex

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Drug Resistance Updates 2025年 81卷 101249-101249页

作者： Cui, Jia-Jia Guo, Cheng-Xian Li, Jun Guo, Ao-Xiang Zhang, Zhao Li, Si-Yu Wang, Lei-Yun Jia, Xiang-Bin Guo, Hui Xia, Kun Hu, Zheng-Mao Ouyang, Qian-Ying Wang, Yang Xie, Yu-Ting Liu, Zhao-Qian Zhang, Jian-Ting Wu, Wei Chen, Yong-Heng Yin, Ji-Ye Department of Geratic Surgery Xiangya Hospital Central South University Xiangya Road 87 Hunan Changsha 410008 China Department of Clinical Pharmacology Xiangya Hospital Central South University Hunan Changsha 410008 China Institute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Hunan Changsha 410008 China Engineering Research Center of Applied Technology of Pharmacogenomics Ministry of Education 110 Xiangya Road Hunan Changsha 410000 China Department of Oncology NHC Key Laboratory of Cancer Proteomics & State Local Joint Engineering Laboratroy for Anticancer Drugs Xiangya Hospital Central South University Hunan Changsha 410008 China National Clinical Research Center for Geriatric Disorders 87 Xiangya Road Hunan Changsha 410008 China Department of General Surgery Xiangya Hospital Central South University Hunan Changsha 410008 China Key Laboratory of Biological Nanotechnology of National Health Commission Hunan Changsha 410008 China Center of Clinical Pharmacology the Third Xiangya Hospital Central South University Hunan Changsha 410000 China Institute of Clinical Medicine The First Affiliated Hospital of University of South China Hunan Hengyang 421001 China Department of Pharmacy The Seventh Affiliated Hospital Sun Yat-sen University Shenzhen 518107 China Xiangya School of Medicine Central South University Hunan Changsha 410013 China Department of Pharmacy Wuhan No.1 Hospital Hubei Wuhan 430022 China Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life Sciences Central South University Hunan Changsha 410000 China MOE Key Lab of Rare Pediatric Diseases Hengyang Medical School University of South China Hunan Hengyang 421000 China NHC Key Laboratory of Birth Defect for Research and Prevention Hunan Provincial Maternal and Child Health Care Hospital Hunan Changsha 410000 China Shenzhen Key Laboratory of Chinese Medicine Active substance screening and T

Aims: Genotoxic drug resistance is one of the major obstacles for cancer treatment. Our previous study demonstrates that cold shock domain containing E1 (CSDE1) is associated with drug resistance. In this study, we aim to demonstrate that CSDE1 regulates cellular response to genotoxic drugs and to investigate its mechanism of action in drug resistance. Methods: Tissues and blood samples from cancer patients were used to evaluate the relationship between CSDE1 and genotoxic drug response. Comet and immunofluorescence assays were conducted to investigate the role of CSDE1 in DNA damage repair. Systematic knockout mouse models were used to study the underlying mechanism involved. Biotin pull-down, EMSA and co-IP assays were used to probe the triplex structure of CSDE1-protein (eIF3a)-RNA (RPA2). Results: CSDE1 elevation correlates with poor response in patient and increased resistance in cell lines to genotoxic drugs. CSDE1 upregulated the nucleotide excision repair (NER) and homologous recombination (HR) pathways. In X-ray irradiation or bleomycin-induced DNA damage mouse model, systemic CSDE1 knockout resulted in increased DNA damage. In both a CSDE1 knockout mouse model and cancer cell lines, CSDE1 inhibited the cGAS-STING pathway through RPA2. Mechanistic studies indicated that CSDE1 serves as a hub for the binding of the CSDE1-protein (eIF3a)-RNA (RPA2) ternary complex. Conclusions: This study reveals the new role of CSDE1 in enhancing resistance to genotoxic drugs, and the detailed zipper-like cross ternary structural of CSDE1. It provides a new strategy for enhancing genotoxic drugs sensitivity. © 2025 The Authors

关键词： cGAS-STING CSDE1 DNA repair Genotoxic drugs RPA2

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