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Trametinib boosts palbociclib’s efficacy in breast cancer via autophagy inhibition

Oncology Research 2024年第7期32卷 1197-1207页

作者： ANGUO WU jiao yan TING SU CHI FENG XIN LONG YIRU PAN RUPEI YE TIAN XIA HANAN LONG JIANMING WU XIULI XIAO Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou646000China The Department of Pathology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China The Department of Pathology Mianyang Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaMianyang621000China The Department of Pathology Yongchuan Hospital of Chongqing Medical UniversityChongqing402160China School of Basic Medical Sciences Southwest Medical UniversityLuzhou646000China School of Clinical Medical Sciences Southwest Medical UniversityLuzhou646000China

Breast cancer,a predominant global health issue,requires ongoing exploration of new therapeutic ***(PAL),a well-known cyclin-dependent kinase(CDK)inhibitor,plays a critical role in breast cancer *** its efﬁcacy is recognized,the interplay between PAL and cellular autophagy,particularly in the context of the RAF/MEK/ERK signaling pathway,remains insufﬁciently *** study investigates PAL’s inhibitory effects on breast cancer using both in vitro(MCF7 and MDA-MB-468 cells)and in vivo(tumor-bearing nude mice)*** at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib(TRA),an MEK inhibitor,our research seeks to address the challenge of PAL-induced drug ***ﬁndings reveal that PAL signiﬁcantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A ***,PAL also induces protective autophagy,potentially leading to drug resistance via the RAF/MEK/ERK pathway *** TRA effectively neutralized this autophagy,enhancing PAL’s anti-tumor efﬁcacy.A combination of PAL and TRA synergistically reduced cell viability and proliferation,and in vivo studies showed notable tumor size *** conclusion,the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance,offering a new horizon in breast cancer treatment.

关键词： Palbociclib Trametinib Protective autophagy RAF/MEK/ERK MCF7 MDA-MB-468

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E2F1-mediated Up-regulation of NCAPG Promotes Hepatocellular Carcinoma Development by Inhibiting Pyroptosis

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Journal of Clinical and Translational Hepatology 2024年第1期12卷 25-35页

作者： Cuicui Xiao jiao Gong Yusheng Jie Weicheng Liang yan Tai Wei Qin Tongyu Lu Yutian Chong Ziqing Hei Bo Hu Qi Zhang Biotherapy Center Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Anesthesiology Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Key Laboratory of Liver Disease of Guangdong Province Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Laboratory Medicine Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Infectious Diseases Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Cell-Gene Therapy Translational Medicine Research Center Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Hepatic Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Background and Aims:As a subunit of the condensin complex,NCAPG has an important role in maintaining chromosome condensation,but its biological function and regulatory mechanism in hepatocellular carcinoma(HCC)remains ***:The prognostic ability of NCAPG in HCC patients was examined by univariate and multivariate Cox regression *** curves were plotted to compare the predictive ability of NCAPG and *** luciferase reporter system,and ChIP were used to investigate transcriptional potential of E2F1 to *** was observed by scanning electron *** expression of NCAPG,E2F1,and major proteins constituting NLRP3 inflammasome was determined by western blotting and *** in vivo tumor formation assay was conducted to verify the in vitro ***:Up-regulated NCAPG was identified in HCC tissues compared with adjacent tissue and high NCAPG was positively correlated with poor *** NCAPG mRNA level was a prognostic factor in HCC patients and also a diagnostic factor with higher predictive ability compared with AFP[AUROC 0.766(95%CI:0.650–0.881)vs.0.649(95%CI 0.506–0.793)].HBx transfection resulted in concomitant up-regulation of E2F1 and NCAPG.E2F1 significantly increased the activity of luciferase reporter fused with NCAPG reporter,and the interaction of E2F1 and NCAPG gene was confirmed by *** of E2F1 resulted in significant down-regulation of *** of NCAPG promote pyroptosis mediated by NLRP3 inflammasome activation in multiple HCC cell lines and also suppressed tumorigenesis in ***:We identified a novel role of NCAPG in the regulation of NLRP3 inflammasome-mediated pyroptosis,which was regulated by its upstream transactivator,*** role of E2F1-NCAPG-NLRP3 regulation of pyroptosis network may be a potential target in HCC treatment.

关键词： NCAPG Hepatocellular carcinoma Pyroptosis NLRP3 inflammasome Serum marker circulating RNA.

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Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions

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World Journal of Gastroenterology 2024年第14期30卷 1968-1981页

作者： Hong-Ju Sun Bo jiao yan Wang Yue-Hua Zhang Ge Chen Zi-Xuan Wang Hong Zhao Qing Xie Xiao-Hua Song Department of General Medicine Qingdao Central HospitalUniversity of Health and Rehabilitation Sciences(Qingdao Central Medical Group)Qingdao 266042Shandong ProvinceChina Department of Gastroenterology Qingdao Central HospitalUniversity of Health and Rehabilitation Sciences(Qingdao Central Medical Group)Qingdao 266042Shandong ProvinceChina Department of Medical Administration Qingdao Central HospitalUniversity of Health and Rehabilitation Sciences(Qingdao Central Medical Group)Qingdao 266042Shandong ProvinceChina Qingdao Medical College Qingdao UniversityQingdao 266042Shandong ProvinceChina Department of Infectious Diseases Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver ***,the disease is underappreciated as a remarkable chronic disorder as there are rare managing *** studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic ***,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular *** the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the *** study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic ***,further studies are necessary.

关键词： Nonalcoholic fatty liver disease Apoptosis Necroptosis Cell death Diagnosis Treatment

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Construction and validation of a neovascular glaucoma nomogram in patients with diabetic retinopathy after pars plana vitrectomy

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World Journal of Diabetes 2024年第4期15卷 654-663页

作者： Yi Shi yan-Xin Zhang Ming-Fei jiao Xin-Jun Ren Bo-Jie Hu Ai-Hua Liu Xiao-Rong Li Surgical Retina Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China Glaucoma Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China Ocular Trauma Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China

BACKGROUND Neovascular glaucoma(NVG)is likely to occur after pars plana vitrectomy(PPV)for diabetic retinopathy(DR)in some patients,thus reducing the expected *** the risk factors for NVG occurrence and building effective risk prediction models are currently required for clinical *** To develop a visual risk profile model to explore factors influencing DR after *** We retrospectively selected 151 patients with DR undergoing *** patients were divided into the NVG(NVG occurrence)and No-NVG(No NVG occurrence)groups according to the occurrence of NVG within 6 months after *** risk factors for postoperative NVG were screened by logistic regression.A nomogram prediction model was established using R software,and the model’s prediction accuracy was verified internally and externally,involving the receiver operator characteristic curve and correction *** After importing the data into a logistic regression model,we concluded that a posterior capsular defect,preoperative vascular endothelial growth factor≥302.90 pg/mL,glycosylated hemoglobin≥9.05%,aqueous fluid interleukin 6(IL-6)≥53.27 pg/mL,and aqueous fluid IL-10≥9.11 pg/mL were independent risk factors for postoperative NVG in patients with DR(P<0.05).A nomogram model was established based on the aforementioned independent risk factors,and a computer simulation repeated sampling method was used to internally and externally verify the nomogram *** area under the curve(AUC),sensitivity,and specificity of the model were 0.962[95%confidence interval(95%CI):0.932-0.991],91.5%,and 82.3%,*** AUC,sensitivity,and specificity of the external validation were 0.878(95%CI:0.746-0.982),66.7%,and 95.7%,*** A nomogram constructed based on the risk factors for postoperative NVG in patients with DR has a high prediction *** study can help formulate relevant preventive and treatment measures.

关键词： Diabetic retinopathy Retinopathy Neovascular Glaucoma Risk factors Nomogram

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Comparison Between Threshold Method and Artificial Intelligence Approaches for Early Warning of Respiratory Infectious Diseases-Weifang City,Shandong Province,China,2020-2023

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China CDC weekly 2024年第26期6卷 635-641,I0010,I0011页

作者： Ting Zhang Liuyang yang Ziliang Fan Xuancheng Hu jiao yang yan Luo Dazhu Huo Xuya Yu Ling Xin Xuan Han Jie Shan Zhongjie Li Weizhong yang School of Population Medicine and Public Health Chinese Academy of Medical Sciences(CAMS)&Peking Union Medical College(PUMC)BeijingChina State Key Laboratory of Respiratory Health and Multimorbidity BeijingChina Key Laboratory of Pathogen Infection Prevention and Control(Peking Union Medical College) Ministry of EducationBeijingChina The Third Affiliated Hospital of Kunming Medical University Yunnan Cancer HospitalKunming CityYunnan ProvinceChina School of Data Science Fudan UniversityShanghaiChina Weifang Center for Disease Control and Prevention Weifang CityShandong ProvinceChina School of Health Policy and Management Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Introduction:Respiratory infectious diseases,such as influenza and coronavirus disease 2019(COVID-19),present significant global public health *** emergence of artificial intelligence(AI)and big data offers opportunities to improve traditional disease surveillance and early warning ***:The study analyzed data from January 2020 to May 2023,comprising influenza-like illness(ILI)statistics,Baidu index,and clinical data from *** methodologies were evaluated:the adaptive dynamic threshold method(ADTM)for dynamic threshold adjustments,the machine learning supervised method(MLSM),and the machine learning unsupervised method(MLUM)utilizing anomaly *** comparison focused on sensitivity,specificity,timeliness,and warning ***:ADTM issued 37 warnings with a sensitivity of 71%and a specificity of 85%.MLSM generated 35 warnings,with a sensitivity of 82%and a specificity of 87%.MLUM produced 63 warnings with a sensitivity of 100%and specificity of 80%.The initial warnings from ADTM and MLUM preceded those from MLSM by five *** Kappa coefficient indicated moderate agreement between the methods,with values ranging from 0.52 to 0.62(P<0.05).Discussion:The study explores the comparison between traditional methods and two machine learning approaches for early warning *** emphasizes the validation of machine learning’s reliability and underscores the unique advantages of each ***,it stresses the significance of integrating machine learning models with various data sources to enhance public health preparedness and response,alongside acknowledging limitations and the need for broader validation.

关键词： specificity integrating utilizing

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Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids

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Zoological Research 2024年第2期45卷 233-241页

作者： Peng Li Ting Zhang Ruo Wu Jun-Yu Zhang yan Zhuo Shan-Gang Li jiao-Jian Wang Wen-Ting Guo Zheng-Bo Wang Yong-Chang Chen State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan 650500China Yunnan Key Laboratory of Primate Biomedical Research KunmingYunnan 650500China

Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube *** folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain *** SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains *** tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural *** determine the role of SHROOM3 in early developmental morphogenesis,we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate *** of SHROOM3 resulted in shorter neuroepithelial cells and smaller *** morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins,namely fibrous actin(F-actin),myosin II,and phospho-myosin light chain(PMLC),to the apical side of the neuroepithelial ***,these defects were not rescued by folate *** sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ *** summary,we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.

关键词： Neural tube defects SHROOM3 Neuroepithelial Organoids Cynomolgus monkey

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Prediction of pathological complete response and prognosis in locally advanced rectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2520-2530页

作者： Yi-Jun Xu Dan Tao Song-Bing Qin Xiao-yan Xu Kai-Wen yang Zhong-Xu Xing Ju-Ying Zhou yang jiao Li-Li Wang Department of Radiation Oncology The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Department of Radiation Oncology The Fourth Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina School of Radiation Medicine and Protection Medical College of Soochow UniversitySuzhou 215123Jiangsu ProvinceChina

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death *** chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before *** date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient *** To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with *** Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively *** were categorized into pCR and non-pCR *** analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting *** 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank *** Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with *** results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for *** analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR *** deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC *** pCR demonstrates longer DFS and *** correlate with poor pr

关键词： Locally advanced rectal cancer Neoadjuvant chemoradiotherapy Pathological complete response Carcinoembryonic antigen Inflammation-related markers Tumor deposit Prognosis

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Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles

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Bone Research 2024年第1期12卷 137-152页

作者： Weicheng Lu Jianfei yan Chenyu Wang Wenpin Qin Xiaoxiao Han Zixuan Qin Yu Wei Haoqing Xu Jialu Gao Changhe Gao Tao Ye Franklin R.Tay Lina Niu Kai jiao Department of Stomatology Tangdu Hospital&State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Stomatology School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina The Dental College of Georgia Augusta UniversityAugustaGAUSA

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary ***-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal *** proteins initiate inflammatory dysfunction,such as neurogenic heterotopic *** recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention ***,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two *** examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast *** relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in *** injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in *** present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.

关键词： neurogenic ossification pathogenesis

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Expression analysis of the R2R3-MYB gene family in upland cotton and functional study of GhMYB3D5 in regulating Verticillium wilt resistance

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Journal of Integrative Agriculture 2024年第10期23卷 3294-3310页

作者： Jie Liu Zhicheng Wang Bin Chen Guoning Wang Huifeng Ke Jin Zhang Mengjia jiao yan Wang Meixia Xie yanbin Li Dongmei Zhang Xingyi Wang Qishen Gu Zhengwen Sun Liqiang Wu Xingfen Wang Zhiying Ma yan Zhang State Key Laboratory of North China Crop Improvement and Regulation/North China Key Laboratory for Germplasm Resources Ministry of Education/College of AgronomyHebei Agricultural UniversityBaoding 071001China

Improving plant resistance to Verticillium wilt(VW),which causes massive losses in Gossypium hirsutum,is a global *** plants need to efficiently allocate their limited energy resources to maintain a balance between growth and ***,few transcriptional regulators specifically respond to Verticillium dahliae and the underlying mechanism has not been identified in *** this study,we found that the that expression of most R2R3-MYB members in cotton is significantly changed by *** infection relative to the other MYB *** novel R2R3-MYB transcription factor(TF)that specifically responds to ***,GhMYB3D5,was ***3D5 was not expressed in 15 cotton tissues under normal conditions,but it was dramatically induced by *** *** functionally characterized its positive role and underlying mechanism in VW *** *** infection,the up-regulated GhMYB3D5 bound to the GhADH1 promoter and activated *** addition,GhMYB3D5 physically interacted with GhADH1 and further enhanced the transcriptional activation of ***,the transcriptional regulatory module GhMYB3D5-GhADH1 then promoted lignin accumulation by improving the transcriptional levels of genes related to lignin biosynthesis(GhPAL,GhC4H,Gh4CL,and GhPOD/GhLAC)in cotton,thereby enhancing cotton VW *** results demonstrated that the GhMYB3D5 promotes defense-induced lignin accumulation,which can be regarded as an effective way to orchestrate plant immunity and growth.

关键词： cotton Verticillium wilt resistance GhMYB3D5 GhADH1 transcriptional regulatory module

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Spontaneous mutations and mutational responses to penicillin treatment in the bacterial pathogen Streptococcus pneumoniae D39

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Marine Life Science & Technology 2024年第3期6卷 198-211页

作者： Wanyue Jiang Tongtong Lin jiao Pan Caitlyn ERivera Clayton Tincher Yaohai Wang Yu Zhang Xiang Gao yan Wang Ho‑Ching T.Tsui Malcolm E.Winkler Michael Lynch Hongan Long Institute of Evolution and Marine Biodiversity KLMMEOcean University of ChinaQingdao 266003China Laboratory for Marine Biology and Biotechnology Laoshan LaboratoryQingdao 266237China Department of Biology Indiana UniversityBloomingtonIN 47405USA School of Mathematics Science Ocean University of ChinaQingdao 266000China State Key Laboratory of Microbial Technology Microbial Technology InstituteSchool of Life ScienceShandong UniversityQingdao 266237China Biodesign Center for Mechanisms of Evolution Arizona State UniversityTempeAZ 85281USA

Bacteria with functional DNA repair systems are expected to have low mutation rates due to strong natural selection for genomic ***,our study of the wild-type Streptococcus pneumoniae D39,a pathogen responsible for many common diseases,revealed a high spontaneous mutation rate of 0.02 per genome per cell division in mutation-accumulation(MA)*** rate is orders of magnitude higher than that of other non-mutator bacteria and is characterized by a high mutation bias in the A/T *** high mutation rate may have resulted from a reduction in the overall efficiency of selection,conferred by the tiny effective population size in *** line with this,*** D39 also exhibited the lowest DNA mismatch-repair(MMR)efficiency among *** with the antibiotic penicillin did not elevate the mutation rate,as penicillin did not induce DNA damage and *** lacks a stress response *** findings suggested that the MA results are applicable to within-host scenarios and provide insights into pathogen evolution.

关键词： Neutral evolution Mutation spectrum Antibiotics DNA mismatch repair Oxidative damage repair

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