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Journal of Environmental Sciences 2024年第3期137卷 108-119页

作者： Jingming Wang Zhiquan Yu Yongfeng Wang Yuanyao Chen Lin Xiao Yanjun Zong Qiyuan Feng Lianqi Peng Huiping Zhang Chunyan Liu Institute of reproductive Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Ethylene thiourea(ETU)converted from ethylene bisdithiocarbamate(EBDC)fungicides has aroused great concern because of its prevalence and harmful *** ETU-induced neurotoxicity has been reported,the potential mechanisms remain *** study provided insights into its neurotoxic effects at environmentally relevant concentrations in *** findings showed that embryonic exposure to ETU decreased the hatch rate and delayed somite ***,ETU treatment significantly reduced the dark velocity in the locomotion *** upregulated tendency of the mitogen-activated protein kinases(MAPK)pathway(mknk1,atf4,mapkapk3)screened by transcriptome analysis implied motor neuron degeneration,which was validated by subsequent morphological observation,as axon length and branches were truncated in the 62.5μg/L ETU ***,although the rescue experiment with a p38 MAPK inhibitor(SB203580)successfully ameliorated axon degeneration,it failed to reverse the locomotion *** exploration of transcriptome data revealed the varied expression of presynaptic scaffold protein-related genes(pcloa,pclob,bsna),whose downregulation might impair the neuromuscular junction(NMJ).Therefore,we reasonably suspected that ETU-induced neurobehavioral deficits might result from the combined effects of the MAPK pathway and presynaptic *** this,we highlighted the necessity to take precautions and early interventions for susceptible ETU-exposed populations.

关键词： Ethylene thiourea(ETU) Behavior Neuromuscular junction MAPK signaling pathway Piccolo and bassoon Danio rerio

Toeless and reversible DNA strand displacement based on Hoogsteen-bond triplex

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Chinese Chemical Letters 2024年第5期35卷 330-337页

作者： Yang Qin Jiangtian Li Xuehao Zhang Kaixuan Wan Heao Zhang Feiyang Huang Limei Wang Hongxun Wang Longjie Li Xianjin Xiao Institute of reproductive Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pancreatic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Wuhan Polytechnic University Wuhan 430023China

Strand displacement reaction is a crucial component in the assembly of diverse DNA-based nanodevices,with the toehold-mediated strand displacement reaction representing the prevailing ***,the single-stranded Watson-Crick sticky region that serves as the trigger for strand displacement can also cause leakage reactions by introducing crosstalk in complex DNA ***,we proposed the toeless and reversible DNA strand displacement reaction based on the Hoogsteen-bond triplex,which is compatible with most of the existing DNA *** demonstrated that our proposed reaction can occur at pH 5 and can be reversed at pH *** also observed an approximately linear relationship between the degree of reaction and pH within the range of pH 5-6,providing the potential for precise regulation of the ***,by altering the sequence orientation,we have demonstrated that our proposed reaction can be initiated or regulated through the same toeless mechanism without the requirement for protonation in low pH *** on the proposed reaction principle,we further constructed a variety of DNA nanodevices,including two types of DNA logic gates that rely on pH 5/pH 9 changes for initiating and reversing:the AND gate and the OR *** also successfully constructed a DNA Walker based on our proposed reaction modes,which can move along a given track after the introduction of a programmable DNA sequence and complete a cycle after 4 *** findings suggest that this innovative approach will have broad utility in the development of DNA circuits,molecular sensors,and other complex biological systems.

关键词： DNA strand displacement Toeless Triplex DNA strands Reversible DNA circuit DNA walker

Regulable toehold lock for the effective control of strand displacement reaction sequence and circuit leakage

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Chinese Chemical Letters 2024年第7期35卷 372-376页

作者： Kuangdi Luo Yang Qin Xuehao Zhang Hanxu Ji Heao Zhang Jiangtian Li Xianjin Xiao Xinyu Wang Department of Breast Surgery Second Hospital of Jilin UniversityChangchun 130041China Institute of reproductive Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Laboratory medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pancreatic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China School of Life Science and Technology Wuhan Polytechnic UniversityWuhan 430023China

Strand displacement reaction enables the construction of enzyme-free DNA reaction networks,thus has been widely applied to DNA circuit and *** has the characteristics of high efficiency,universality and ***,the existing regulation tools cannot enable effective control of the reaction sequence,which undoubtedly limits the construction of complex nucleic acid ***,we developed a regulation tool,toehold lock,and achieved strict control of reaction sequence without loss of the main reaction signal ***,we applied the tool to scenarios such as seesaw circuits,AND/OR logic gates,and entropy-driven circuits,and respectively demonstrated its significant superiority compared to the original *** believe that the proposed toehold lock has greatly optimized the efficiency of DNA strand displacement-based networks,and we anticipate that the tool will be widely used in multiple fields.

关键词： DNA circuit Toehold lock DNA strand displacement Reaction sequence Seesaw circuit

Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

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Science China(Life Sciences) 2024年第7期67卷 1325-1337页

作者： Chengcheng Song Yingying Qin Yan Li Bingyi Yang Ting Guo Wenqing Ma Dian Xu Keyan Xu Fangfang Fu Li Jin Yanhua Wu Shuyan Tang Xiaojun Chen Feng Zhang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic EngineeringInstitute of Medical Genetics and GenomicsFudan UniversityShanghai 200011China Human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Center for reproductive medicine Cheeloo College of MedicineShandong UniversityJinan 250021China State Key Laboratory of reproductive medicine and Offspring Health Key Laboratory of Reproductive Endocrinology of Ministry of EducationNational Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthShandong UniversityJinan 250021China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China National Demonstration Center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China Department of Gynecology the Tenth People’s Hospital of Tongji UniversityShanghai 200072China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health Hospital of China Welfare InstituteShanghai 200030China

Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of *** represents a significant detriment to female ***,the known POI-causative genes currently account for only a fraction of *** elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in *** a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 *** variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 ***,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling *** analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and *** further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian ***,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse *** conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

关键词： POI RNF111 female fertility ovarian reserve

Antitumor Effect of Apcin on Endometrial Carcinoma via p21-Mediated Cell Cycle Arrest and Apoptosis

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Current medical Science 2024年第3期44卷 623-632页

作者： Ke NI Zi-li LI Zhi-yong HU Li HONG Department of Obstetrics and Gynecology Renmin Hospital of Wuhan UniversityWuhan430060China Institute of reproductive Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality *** underscores the critical need for novel therapeutic *** such potential target is cell division cycle 20(CDC20),which has been implicated in *** study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism *** The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow *** sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the *** studies were performed to evaluate the antitumor effects in *** analysis was also conducted to identify CDC20 as a potential therapeutic target in *** Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle *** associated with apoptosis and the cell cycle were activated following treatment with ***,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC *** vivo experiments confirmed that Apcin treatment significantly impeded tumor *** CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free *** CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.

关键词： endometrial carcinoma CDC20 apoptosis cell cycle arrest p21 BBC3

Downregulation of the circadian clock gene period 2 aggravates prognosis in breast cancer patients with obesity

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Oncology and Translational medicine 2024年第2期10卷 73-78页

作者： Ru-Xing Wu Dan Hu Han-Wang Zhang Xiao-Yuan Huang Liang Zhuang reproductive medicine Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Cancer Biology Research centre Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Cancer Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain *** study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with ***:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate ***,we validated the protein levels of these candidates using ***,we investigated the association between candidate genes and breast cancer prognosis at tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression ***:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight *** expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,*** 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.

关键词： Breast cancer Obesity PER2 Prognosis

MiR-450b-5p enhances the radiosensitivity of HR^(+) and HER2^(−) breast cancer by targeting CDK6

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Oncology and Translational medicine 2024年第4期10卷 198-203页

作者： Ruxing Wu Hanwang Zhang Xiaoyuan Huang Liang Zhuang reproductive medicine Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Cancer Biology Research centre Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Cancer Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Background:The sensitivity of breast cancer cells to radiation is a key cause of locoregional recurrence after postoperative *** studies have reported that microRNAs(miRNAs)are involved in the radiosensitivity of human breast cancer *** miRNA microarray study showed that miR-450b-5p was overexpressed 13.3-fold in patients with estrogen receptor–positive(ER^(+))and human epidermal growth factor receptor 2–negative(HER2−)breast cancer and no local relapse compared with local relapse ***,its underlying mechanism of action remains ***:The predicted target mRNAs of miR-450b-5p were screened using the TargetScan,miRDB,and miRWalk *** blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays explored the association between cyclindependent kinase 6(CDK6)and *** cell counting kit-8 assay and flow cytometry detected the proliferation of transfected MCF7 *** formation and xenograft tumors detected the radiosensitivity of the transfected MCF7 ***:Bioinformatics analysis,Western blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays demonstrated that CDK6 was the target gene of ***,in vitro and in vivo experiments showed that miR-450b-5p inhibited MCF7 cell proliferation and cell cycle progression,increased the sensitizer enhancement ratio,and decreased the volume of xenograft tumors after irradiation by regulating ***:This study demonstrates that miR-450b-5p enhances the radiosensitivity of hormone receptor–positive(HR^(+))and HER2−breast cancer cells and elucidates its ***-450b-5p may be considered a therapeutic target in HR^(+)and HER2−breast cancer treated with radiotherapy.

关键词： Breast cancer Cyclin-dependent kinase 6 miR-450b-5p Radiosensitivity

Effect of Acupuncture on Endometrial Blood Flow in Women Undergoing in vitro Fertilization Embryo Transfer: A Single Blind, Randomized Controlled Trial

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Chinese Journal of Integrative medicine 2024年第1期30卷 10-17页

作者： DONG Hao-xu Wu Xiao ZHOU Qin HUANG Dong-mei ZHANG Ming-min HUANG Guang-ying YANG Wei Department of Integrated Traditional Chinese and Western medicine Tongji HospitalHuazhong University of Science and TechnologyWuhan(430030)China Department of Obstetrics and Gynecoiogy Tongji HospitalHuazhong University of Science and TechnologyWuhan(430030)China Institute of Integrated Traditional Chinese and Western medicine Tongji HospitalHuazhong University of Science and TechnologyWuhan(430030)China Department of reproductive medicine Tongji HospitalHuazhong University of Science and TechnologyWuhan(430030)China

Objective: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional(3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer(IVF-ET). Methods: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days(from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the reproductive medicine Center and Outpatient Department of Integrated Traditional Chinese and Western medicine, tongji Hospital, tongji medicine college, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji(CV3), Qihai(CV 6), Sanyinjiao(SP6), Taichong(LR 3), Tianshu(ST 25), Guilai(ST 29) and Zusanli(ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index(VI), flow index(FI) and vascularization flow index(VFI), endometrial thickness and volume, subendometrial VI(sVI), subendometrial FI(sFI), subendometrial VFI(sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. Results: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group(P0.05). Conclusions: Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometr

关键词： acupuncture endometrial blood flow endometrial receptivity in vitro fertilization randomized controlled trial

Arginine methylation of ALKBH5 by PRMT6 promotes breast tumorigenesis via LDHA-mediated glycolysis

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Frontiers of medicine 2024年第2期18卷 344-356页

作者： Xue Han Chune Ren Aifang Jiang Yonghong Sun Jiayi Lu Xi Ling Chao Lu Zhenhai Yu Department of reproductive medicine Affiliated Hospital of Weifang Medical UniversityWeifang261053China Department of Pathology Affiliated Hospital of Weifang Medical UniversityWeifang261053China

ALKBH5 is a master regulator of N6-methyladenosine(m6A)modification,which plays a crucial role in many biological ***,we show that ALKBH5 is required for breast tumor ***,PRMT6 directly methylates ALKBH5 at R283,which subsequently promotes breast tumor ***,arginine methylation of ALKBH5 by PRMT6 increases LDHA RNA stability via m6A demethylation,leading to increased aerobic ***,PRMT6-mediated ALKBH5 arginine methylation is confirmed in PRMT6-knockout ***,these findings identify a PRMT6-ALKBH5-LDHA signaling axis as a novel target for the treatment of breast cancer.

关键词： PRMT6 ALKBH5 N6-methyladenosine glycolysis tumor growth

Aluminum exposure impairs oocyte quality via subcellular structure disruption and DNA damage-related apoptosis in mice

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Journal of Environmental Sciences 2024年第5期139卷 308-319页

作者： Hongge Li Jingcai Liu Weihua Nong Mengying Shen Sheng Dou Shaochen Sun Junli Wang The Affiliated Hospital of Youjiang medical University for Nationalities Guangxi 533000China college of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210095China School of medical Laboratory Youjiang Medical University for NationalitiesGuangxi 533000China Industrial college of Biomedicine and Health Industry Youjiang Medical University for NationalitiesGuangxi 533000China reproductive medicine Guangxi Medical and Health Key Discipline Construction ProjectThe Affiliated Hospital of Youjiang Medical University for NationalitiesGuangxi 533000China

Aluminum(Al)can lead to an exposure of creature in varieties ways for its universality,and it could disturb normal physiological metabolism,with the damage to multisystem including *** the oocyte quality is critical for female reproduction,we inspected the toxicity of Al on mouse oocyte *** constructed in vitro exposure mouse model,and we found that 5 mmol/L Al had adverse effects on oocyte maturation by impairing organelle and *** spindle and misaligned chromosomes which might be considered to be caused by elevated levels of acetylation,as well as abnormal distribution of actin dynamics could hinder normal meiosis of *** dysfunction indicated that Al affected proteins synthesis,transport and digestion,which would further damage oocyte *** order to explore the mechanism of Al toxicity,our further investigation demonstrated that Al caused mitochondrial dysfunction and imbalance calcium homeostasis,resulting in limited energy ***,high level of reactive oxygen species,DNA damage and apoptosis caused by oxidative stress were also the manifestation of Al toxicity on *** conclusion,our study provided the evidence that Al exposure affected oocyte quality through its effects on spindle organization,actin dynamics,organelle function and the induction of DNA damage-related apoptosis with mouse model.

关键词： Aluminum Oocyte Cytoskeleton Organelle DNA damage