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Signal Transduction and Targeted Therapy 2024年第4期9卷 1706-1720页

作者： Jian Zhang Kejia Zhao Wenjing Zhou Ran Kang Shiyou Wei Yueli Shu Cheng Yu Yin Ku Yonghong Mao Hao Luo Juqin Yang Jiandong Mei Qiang Pu Senyi Deng Zhengyu Zha Gang Yuan Shensi Shen Yaohui Chen Lunxu Liu Department of thoracic surgery and Institute of thoracic Oncology West China Hospital of Sichuan UniversityChengdu 610097China Western China Collaborative Innovation center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer Sichuan UniversityChengdu 610097China Biobank of West China Hospital Sichuan UniversityChengdu 610041China

Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical *** found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC *** perturbationof TET2 rendered parental cells more tolerant to TKI ***2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI *** or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in *** findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 ***,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

关键词： TET2 TKI resistance

Mechanism of PARP inhibitor resistance and potential overcoming strategies

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Genes & Diseases 2024年第1期11卷 306-320页

作者： Xiaoyu Fu Ping Li Qi Zhou Ruyuan He Guannan Wang Shiya Zhu Amir Bagheri Gary Kupfer Huadong Pei Juanjuan Li Department of Oncology Georgetown Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonDC 20057USA Department of Breast and Thyroid surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Cancer center Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of thoracic surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China

PARP inhibitors(PARPi)are a kind of cancer therapy that targets poly(ADP-ribose)*** is the first clinically approved drug to exert synthetic lethality by obstruct-ing the DNA single-strand break repair *** the significant therapeutic effect in pa-tients with homologous recombination(HR)repair deficiency,innate and acquired resistance to PARPi is a main challenge in the *** this review,we mainly discussed the underlying mechanisms of PARPi resistance and summarized the promising solutions to overcome PARPi resistance,aiming at extending PARPi application and improving patient outcomes.

关键词： Drug resistance Homologous recombination PARP PARP inhibitor Poly(ADP-ribose)polymerase

Mitochondrial diseases and mtDNA editing

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Genes & Diseases 2024年第3期11卷 303-310页

作者： Min Song Lingqun Ye Yongjin Yan Xuechun Li Xinglong Han Shijun Hu Miao Yu Department of cardiovascular surgery of the First Affiliated Hospital&Institute for cardiovascular Science Collaborative Innovation Center of HematologyState Key Laboratory of Radiation Medicine and ProtectionSuzhou Medical CollegeSoochow UniversitySuzhouJiangsu 215000China Hai'an People's Hospital NantongJiangsu 226600China

Mitochondrial diseases are a heterogeneous group of inherited disorders character-ized by mitochondrial dysfunction,and these diseases are often severe or even ***-chondrial diseases are often caused by mitochondrial DNA ***,there is no curative treatment for patients with pathogenic mitochondrial DNA *** the rapid development of traditional gene editing technologies,such as zinc finger nucleases and tran-scription activator-like effector nucleases methods,there has been a search for a mitochon-drial gene editing technology that can edit mutated mitochondrial DNA;however,there are still some problems hindering the application of these *** discovery of the DddA-derived cytosine base editor has provided hope for mitochondrial gene *** this paper,we will review the progress in the research on several mitochondrial gene editing technologies with the hope that this review will be useful for further research on mitochondrial gene editing technologies to optimize the treatment of mitochondrial diseases in the future.

关键词： Gene editing Mitochondrialdisease MitochondrialDNA mutation Transcription activator-like effectornucleases Zinc finger nucleases

Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2132-2142页

作者： Xinglong Han Lina Qu Miao Yu Lingqun Ye Liujia Shi Guangfu Ye Jingsi Yang Yaning Wang Hao Fan Yong Wang Yingjun Tan Chunyan Wang Qi Li Wei Lei Jianghai Chen Zhaoxia Liu Zhenya Shen Yinghui Li Shijun Hu Department of cardiovascular surgery of the First Affiliated Hospital&Institute for cardiovascular Science State Key Laboratory of Radiation Medicine and ProtectionSuzhou Medical CollegeSoochow UniversitySuzhouChina State Key Laboratory of Space Medicine China Astronaut Research and Training CenterBeijingChina Department of Hand surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

During spaceflight,the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac ***,the effects and mechanisms of microgravity on cardiac morphology,physiology,metabolism,and cellular biology need to be further *** China started constructing the China Space Station(CSS)in 2021,we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes(hPSC-CMs)to the Tianhe core module of the *** this study,hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium *** and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight,especially thiamine *** microgravity condition blocked the thiamine intake in *** decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid *** decreased ATP production,which led to cytoskeletal remodeling and calcium homeostasis imbalance in *** importantly,in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated *** study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical *** data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

关键词： programming battery modified

Impact of continuous care on cardiac function in patients with lung cancer complicated by coronary heart disease

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World Journal of Clinical Cases 2024年第2期12卷 314-321页

作者： Ting Gao Jin-Lan Luo Pan Guo Xi-Wen Hu Xiao-Yan Wei Yan Hu Division of cardiovascular First Ward Department of Internal MedicineLiyuan HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430077Hubei ProvinceChina Department of cardiovascular Medicine Wuhan Wuchang HospitalWuhan 430063Hubei ProvinceChina cardiovascular Clinical Medical center Liyuan HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430077Hubei ProvinceChina Department of Second thoracic surgery Hubei Cancer HospitalWuhan 430079Hubei ProvinceChina

BACKGROUND Despite sharing similar pathogenic factors,cancer and coronary heart disease(CHD)occur in comparable populations at similar ages and possess similar susceptibility ***,it is increasingly commonplace for patients to experience the simultaneous occurrence of cancer and CHD,a trend that is steadily *** To determine the impacts of continuing care on lung cancer patients with CHD following percutaneous coronary intervention(PCI).METHODS There were 94 lung cancer patients with CHD following PCI who were randomly assigned to the intervention group(n=38)and the control group(n=41).In the intervention group,continuing care was provided,while in the control group,routine care was *** evaluation of cardiac and pulmonary function,medication compliance,a 6-min walk test,and patient quality of life was *** Differences between the two groups were significant in left ventricular ejection fraction,6-min walk test,oxygen uptake,quality of life and medication compliance(P<0.05).In comparison with the control group,the enhancement in the intervention group was more *** intervention group had more patients with high medication compliance than the control group,with a statistically significant difference(P<0.05).CONCLUSION After undergoing PCI,lung patients with CHD could benefit from continued care in terms of cardiac and pulmonary function,medications compliance,and quality of life.

关键词： Lung cancer Continuing care Coronary heart disease Percutaneous coronary intervention

Coinfection of SARS-CoV-2 Omicron variant and other respiratory pathogens in children

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World Journal of Pediatrics 2024年第1期20卷 92-96页

作者： Wei Li Bing-Han Wang Bao-Hai Chen Yi Sun Lin Li Wen-Qing Xiang Ahmed Faisal Ali Lin-Xuan Su Hai-Yan Mao Hong-Qiang Shen Qiang Shu Department of Clinical Laboratory Children's HospitalNational Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhouChina School of Public Health Zhejiang University School of MedicineHangzhouChina Department of Information center Children's HospitalZhejiang University School of MedicineHangzhouChina Zhejiang Provincial center for Disease Control and Prevention HangzhouChina Department of thoracic&cardiovascular surgery Children's HospitalNational Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhouChina

Since the outbreak of coronavirus disease 2019(COVID-19),the entire world has been affected by the epidemic[1,2].On November 9,2021,a variant of the novel coronavirus B.1.1.529 was detected for the first time from case samples in South *** Omicron strain spread and mutated significantly *** variant has the characteristics of escape immunity,which can induce relatively extreme disease and reduce the neutralization of antibodies in vaccinators,and is more likely to be reinfected[3,4].The clinical presentation of severe acute respiratory syndrome coronavirus 2(SARSCoV-2)in children has mild symptoms and a lower risk of hospitalization and death.

关键词： respiratory immunity acute

Implications of T cell-mediated tumor killing genes for molecular heterogeneity and clinical stratification in lung adenocarcinoma

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Genes & Diseases 2024年第4期11卷 39-41页

作者： Tong Qiao Beining Yin Jun Liang Li Wei Department of thoracic surgery Henan Provincial People's HospitalZhengzhouHenan 450000China Reproductive Medicine center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Breast surgery Henan Provincial People's HospitalZhengzhouHenan 450000China

Due to the profound heterogeneity exhibited amongst patients with lung adenocarcinoma(LUAD),considerable variances in clinical efficacy emerge.1 For the aims of precision medicine,a clinical instrument to delineate distinct disease phenotypes and anticipate susceptibility to intervention is *** cytotoxicity mediated through T lymphocytes constitutes a pivotal mechanism of anti-tumoral immunity and the foundation for cancer immunotherapy.?Numerous genes regulating the sensitivity of tumor cells to killing mediated by T lymphocytes(GSTKKs)are conducive to satisfying the aforesaid medical necessity.

关键词： clinical mediated adenocarcinoma

Suppressor tRNA in gene therapy

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Science China(Life Sciences) 2024年第10期67卷 2120-2131页

作者： Jingjing Ruan Xiaoxiao Yu Huixia Xu Wenrui Cui Kaiye Zhang Chenyang Liu Wenlong Sun Xiaodan Huang Lei An Yue Zhang The Children's Hospital National Clinical Research Center for Child HealthZhejiang University School of MedicineLiangzhu LaboratoryHangzhou 310000China Liangzhu Laboratory Zhejiang University School of MedicineHangzhou 311121China Department of thoracic and cardiovascular surgery Huaihe Hospital of Henan UniversityHenan UniversityKaifeng 475000China Translational Medicine center Huaihe Hospital of Henan UniversityHenan UniversityKaifeng 475000China Eye center The Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China

Suppressor tRNAs are engineered or naturally occurring transfer RNA molecules that have shown promise in gene therapy for diseases caused by nonsense mutations,which result in premature termination codons(PTCs)in coding sequence,leading to truncated,often nonfunctional *** t RNAs can recognize and pair with these PTCs,allowing the ribosome to continue translation and produce a full-length *** review introduces the mechanism and development of suppressor t RNAs,compares suppressor tRNAs with other readthrough therapies,discusses their potential for clinical therapy,limitations,and *** also summarize the applications of suppressor tRNAs in both in vitro and in vivo,offering new insights into the research and treatment of nonsense mutation diseases.

关键词： suppressor tRNA PTC nonsense mutation readthrough gene therapy

Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

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Cancer Communications 2024年第2期44卷 287-293页

作者： Kouya Shiraishi Atsushi Takahashi Yukihide Momozawa Yataro Daigo Syuzo Kaneko Takahisa Kawaguchi Hideo Kunitoh Shingo Matsumoto Hidehito Horinouchi Akiteru Goto Takayuki Honda Kimihiro Shimizu Masahiro Torasawa Daisuke Takayanagi Motonobu Saito Akira Saito Yuichiro Ohe Shun-ichi Watanabe Koichi Goto Masahiro Tsuboi Katsuya Tsuchihara Sadaaki Takata Tomomi Aoi Atsushi Takano Masashi Kobayashi Yohei Miyagi Kazumi Tanaka Hiroyuki Suzuki Daichi Maeda Takumi Yamaura Maiko Matsuda Yoko Shimada Takaaki Mizuno Hiromi Sakamoto Teruhiko Yoshida Yasushi Goto Tatsuya Yoshida Taiki Yamaji Makoto Sonobe Shinichi Toyooka Kazue Yoneda Katsuhiro Masago Fumihiro Tanaka Megumi Hara Nobuo Fuse Satoshi S.Nishizuka Noriko Motoi Norie Sawada Yuichiro Nishida Kazuki Kumada Kenji Takeuchi Kozo Tanno Yasushi Yatabe Kuniko Sunami Tomoyuki Hishida Yasunari Miyazaki Hidemi Ito Mitsuhiro Amemiya Hirohiko Totsuka Haruhiko Nakayama Tomoyuki Yokose Kazuyoshi Ishigaki Toshiteru Nagashima Yoichi Ohtaki Kazuhiro Imai Ken Takasawa Yoshihiro Minamiya Kazuma Kobayashi Kenichi Okubo Kenji Wakai Atsushi Shimizu Masayuki Yamamoto Motoki Iwasaki Koichi Matsuda Johji Inazawa Yuichi Shiraishi Hiroyoshi Nishikawa Yoshinori Murakami Michiaki Kubo Fumihiko Matsuda Yoichiro Kamatani Ryuji Hamamoto Keitaro Matsuo Takashi Kohno Division of Genome Biology National Cancer Center Research InstituteTokyoJapan Department of Clinical Genomics National Cancer Center Research InstituteTokyoJapan Laboratory for Statistical Analysis Center for Integrative Medical SciencesRIKENYokohamaJapan Department of Genomic Medicine Research InstituteNational Cerebral and Cardiovascular CenterOsakaJapan Laboratory for Genotyping Development Center for Integrative Medical SciencesRIKENYokohamaJapan center for Antibody and Vaccine Therapy Research HospitalInstitute of Medical ScienceThe University of TokyoTokyoJapan Department of Medical Oncology and Cancer center and Center for Advanced Medicine against CancerShiga University of Medical ScienceOtsuJapan Division of Medical AI Research and Development National Cancer Center Research InstituteTokyoJapan center for Genomic Medicine Graduate School of MedicineKyoto UniversityKyotoJapan Department of Medical Oncology Japanese Red Cross Medical CenterTokyoJapan Department of thoracic Oncology National Cancer Center Hospital EastJapan Department of thoracic Oncology National Cancer Center HospitalTokyoJapan Department of Cellular and Organ Pathology Graduate School of MedicineAkita UniversityAkitaJapan Department of Respiratory Medicine Tokyo Medical and Dental UniversityBunkyo-kuTokyoJapan Division of General thoracic surgery Department of SurgeryShinshu University School of MedicineMatsumotoNaganoJapan Department of General Surgical Science Division of General Thoracic SurgeryGunma University Graduate School of MedicineIntegrative Center of General SurgeryGunma University HospitalGunmaJapan Department of Gastrointestinal Tract surgery Fukushima Medical University School of MedicineFukushimaJapan StaGen Co. LtdTokyoJapan Division of thoracic surgery National Cancer Center HospitalTokyoJapan Department of thoracic surgery National Cancer Center Hospital EastChibaJapan Division of Translational Informatics Exploratory Oncology Research and Clinical Trial Center(EPOC

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

关键词： adenocarcinoma lung Lung

Inducible RNA targeting and N^(6)-methyladenosine editing by a split-Cas13 architecture

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Journal of Molecular Cell Biology 2024年第1期16卷 66-69页

作者： Yang Li Qiang Sun Zhi Yang Gang Yuan International Institutes of Medicine the Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China Department of thoracic surgery and Institute of thoracic Oncology West China HospitalSichuan UniversityChengdu 610041China Future Health Laboratory Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314100China

Dear editor,Cas13,a class Ⅱ type Ⅵ CRISPR‒Cas endonuclease with two higher eukaryotes and prokaryotes nucleotide-binding(HEPN)domains,exclusively binds to and cleaves single-stranded RNA by a complementary guide RNA(gRNA)(Makarova et al.,2020).RfxCas13d(also known as CasRx)is an ortholog of CRISPR‒Cas13 with a relatively small size and robust RNA knockdown capability in mammalian cells(Konermann et al.,2018).Owing to its simplicity and high efficiency,CasRx has been applied for RNA targeting in various types of cells and ***,most of these studies failed to control the nuclease activity of CasRx *** re-engineered split-Cas9 system enables inducible genome editing and epigenetic modulation through chemical-induced reassembly of the Cas9 protein(Zetsche et al.,2015).However,tools that allow for efficient and controllable RNA knockdown by a split-Cas13 system remain to be established.

关键词： split system simplicity