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Impact of gonadotropin-releasing hormone agonist and hormone replacement therapy on pregnancy outcomes in single euploid frozen-thawed embryo transfer for patients with endometrial polyps

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生殖与发育医学(英文) 2024年第1期08卷 1-7页

作者： Zhao Qing Li Jie Wang Wei-Lin Liu Ying-Bo Li Jing Ni Tian-Xiang Zhou Wei Zhang Qian Yan Jun-Hao Center for Reproductive Medicine shandong University 3. Jinan 250012 4. China

Objective: Although consensus on the optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) is lacking, this is particularly true for patients with infertility and a history of endometrial polyps (EPs). In this study, we aimed to investigate whether a gonadotropin-releasing hormone agonist combined with hormone replacement therapy (GnRHa-HRT) could improve pregnancy outcomes in single euploid FET for patients with a history of ***: In this retrospective cohort study, 395 women who underwent their first single euploid FET cycle were divided into groups according to endometrial preparation protocols as follows: natural cycle (NC) (n = 220), hormone replacement therapy (HRT) (n = 122), and GnRHa-HRT groups (n = 53). Subsequently, the FET cycles in the three groups were subdivided according to maternal age. All patients underwent hysteroscopic polypectomy before FET, and their EPs were confirmed by ***: No statistically significant differences were observed in live birth rates among the three groups (58.64%vs. 58.20%vs. 56.60%,P = 0.964). Furthermore, the rates of miscarriage, ectopic pregnancy, premature live birth, and pregnancy complications were comparable among the three groups (P >0.05). After adjusting for potential confounding factors, no significant differences in pregnancy outcomes were reported between the groups (adjusted odds ratios [OR] and 95% credible intervals [CI] for live birth rate, HRTvs. NC: 1.119, 0.660–1.896,P = 0.677; GnRHa-HRTvs. NC: 1.165, 0.610–2.226,P = 0.643). Additionally, the pregnancy outcomes of the FET cycle were not influenced by the endometrial preparation protocols in the subgroups when stratified by maternal age (P >0.05).Conclusion: GnRHa-HRT did not improve the pregnancy outcomes of the single euploid FET in patients with a history of EPs.

关键词： Endometrial polyps Frozen-thawed embryo transfer GnRHa Hormone replacement therapy Preimplantation genetic testing

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UBE2T mediates the stemness properties of breast cancer cells through the mTOR signaling pathway

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BIOCELL 2024年第6期48卷 959-970页

作者： JIAWEI YIN YONGSHENG WANG GUANGWEI WEI MINGXIN WEN Department of Traumatology The Second Hospital of Shandong UniversityJinan250033China Department of Pathology Weifang People’s HospitalWeifang261000China Department of Human Anatomy Shandong University School of MedicineJinan250012China Department of Cell Biology and Key Laboratory of Experimental Teratology Shandong University School of MedicineJinan250012China

Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft ***:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent ***,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and *** UBE2T exhibited the opposite ***2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of *** target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in ***:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer.

关键词： UBE2T Breast cancer Breast cancer stem cell mTOR

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Inhalable nanoparticles with enhanced cuproptosis and cGAS-STING activation for synergistic lung metastasis immunotherapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3697-3710页

作者： Chongzheng Yan Huaiyou Lv Yafei Feng Yuhan Li Zhongxi Zhao Department of Pharmaceutics Key Laboratory of Chemical Biology of Ministry of EducationSchool of Pharmaceutical SciencesCheelloo College of MedicineShandong UniversityJinan 250012China Key University Laboratory of Pharmaceutics&Drug Delivery Systems of shandong Province School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Department of Pharmacy Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityYantai 264001China

Due to the insufficient Cu^(+)accumulation,Cu^(+)efflux mechanism,and highly immunosuppressive tumor microenvironment(TME)in lung metastasis,the cuproptosis efficacy is ***,an inhalable nanodevice(CLDCu)is constructed to successfully overcome the drawbacks of *** consists of a Cu^(2+)-chitosan shell and low molecular weight heparin-tocopherol succinate(LMWH-TOS,LT)core with disulfiram(DSF)*** prepared CLDCu can be inhaled and accumulate in large amounts in lung lesions(63.6%)with 56.5 times higher than intravenous *** tumor cells,the mild acidity triggers the co-release of DSF and Cu2+,thus generating bis(diethyldithiocarbamate)-copper(CuET)to block Cu^(+)efflux protein ATP7B and forming toxic Cu^(+),leading to enhanced ***,the released chitosan cooperates with CLDCu-induced cuproptosis to activate stimulator of interferon genes(STING)pathway,which significantly potentiates dendritic cells(DCs)maturation,as wells as evokes innate and adaptive *** lung metastatic mice model,CLDCu is found to induce cuproptosis and reverse the immunosuppressive TME by inhalation ***,CLDCu combined with anti-programmed cell death protein ligand-1 antibody(aPD-L1)provokes stronger antitumor ***,nanomedicine that combines cuproptosis with STING activation is a novel strategy for tumor immunotherapy.

关键词： Cuproptosis cGAS-STING activation Disulfiram Inhalation administration Tumor microenvironment PD-L1 checkpoint blockade Lung metastasis Immunotherapy

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Magmatic-hydrothermal Evolution and Mineralization Mechanisms of the Wangjiazhuang Cu(-Mo)Deposit in the Zouping Volcanic Basin,shandong Province,China:Constraints from Fluid Inclusions

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Acta Geologica Sinica(English Edition) 2024年第3期98卷 679-700页

作者： SHU Lei YANG Renchao SHEN Kun YANG Deping MAO Guangzhou LI Min LIU Pengrui MA Xiaodong shandong Provincial Key Laboratory of Depositional Mineralization and Sedimentary Minerals Shandong University of Science and TechnologyQingdaoShandong 266590China Key Laboratory of Gold Mineralization Processes and Resource Utilization MNR/Key Laboratory of Metallogenic Geological Processes and Resource UtilizationShandong Province/Shandong Institute of Geological SciencesJinan 250013China Laboratory for Marine Mineral Resources Qingdao Marine Science and Technology CenterQingdaoShandong 266237China

The Wangjiazhuang Cu(-Mo)deposit,located within the Zouping volcanic basin in western shandong Province,China,is unique in this area for having an economic *** order to expound the metallogenetic characteristics of this porphyry-like hydrothermal deposit,a detailed fluid inclusion study has been conducted,employing the techniques of representative sampling,fluid inclusion petrography,microthermometry,Raman spectroscopy,LA-ICP-MS analysis of single fluid inclusions,as well as cathode fluorescence spectrometer analysis of host mineral *** deposit contains mainly two types of orebodies,***-dissemination-stockwork orebodies in the K-Si alteration zone and pegmatiticquartz sulfide veins above *** addition,minor breccia ore occurs *** types of fluid inclusions in the deposit and altered quartz monzonite are identified:L-type one-or two-phase aqueous inclusions,V-type vapor-rich inclusions with V/L ratios greater than 50%-90%,D-type multiphase fluid inclusions containing daughter minerals or solids and S-type silicate-bearing fluid inclusions containing mainly muscovite and *** petrography and fluid inclusion study has revealed a three-stage mineralization process,driven by magmatic-hydrothermal fluid activity,as ***,a hydrothermal fluid,separated from the parent magma,infiltrated into the quartz monzonite,resulting in its extensive K-Si alteration,as indicated by silicate-bearing fluid inclusions trapped in altered quartz *** is followed by the early mineralization,the formation of quartz veinlets and dissemination-stockwork *** the main mineralization stage,due to the participation and mixing of meteoric groundwater with magmatic-sourced hydrothermal fluid,the cooling and phase separation caused deposition of metals from the hydrothermal *** a result,the pegmatitic-quartz sulfide-vein ores *** the late mineralization stage,decreasing fluid salinity led to the formation of L-type aqueous

关键词： fluid inclusions fluid immiscibility mineralization mechanisms Wangjiazhuang Cu(-Mo)deposit

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The Relationship Between the Atmospheric Environment and Road Traffic Fatalities — shandong Province, China, 2012–2021

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China CDC weekly 2024年第13期6卷 267-271页

作者： Tao Wang Jie Chu Zhiying Yao Li Yang Zilong Lu Ge Tian Xiaolei Guo Cunxian Jia Department of Epidemiology School of Public HealthCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department for Chronic and Non-Communicable Disease Control and Prevention Shandong Center for Disease Control and PreventionJinanShandong ProvinceChina

Introduction:This study aims to analyze the potential impact of the meteorological environment and air pollutants on road traffic ***:Road traffic fatality data in shandong Province from 2012 to 2021 were obtained from the Population Death Information Registration Management *** and air pollutant data for the same period were collected from the *** Oceanic and Atmospheric Administration and the Ecological Environment Monitoring Center of shandong Province,***’s correlation and ridge regression were used to analyze the impact of the meteorological environment and air pollutants on road traffic ***:From 2012 to 2021,there were 163,863 road traffic fatality *** results of the ridge regression analysis showed that the daily average temperature was negatively correlated with total fatalities and passengers and positively correlated with pedestrians,nonmotorized drivers,and motorized *** daily minimum temperature was negatively correlated with total fatalities and positively correlated with motorized *** daily maximum temperature was positively correlated with both pedestrian and nonmotorized *** daily accumulated precipitation was negatively correlated with *** duration was positively correlated with both nonmotorized and motorized *** particulate matter(PM10)and nitrogen dioxide(NO2)were positively correlated with total fatalities,pedestrians,and nonmotorized *** dioxide(SO2)was positively correlated with total fatalities but negatively correlated with nonmotorized drivers,passengers,and motorized ***:Atmospheric factors associated with the occurrence of road traffic fatalities include air temperature,daily accumulated precipitation,sunshine duration,and air pollutants such as PM10,NO2,and SO2.

关键词： Ecological dioxide sunshine

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DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation

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Science China(Life Sciences) 2024年第8期67卷 1620-1634页

作者： Yunde Dou Rusong Zhao Han Wu Zhiheng Yu Changjian Yin Jie Yang Chaoyan Yang Xiaohua Luan Yixiao Cheng Tao Huang Yuehong Bian Shan Han Yuqing Zhang Xin Xu Zi-Jiang Chen Han Zhao Shigang Zhao Institute of Women Children and Reproductive HealthShandong UniversityJinan 250012China State Key Laboratory of Reproductive Medicine and Offspring Health Jinan 250012China Key laboratory of Reproductive Endocrinology of Ministry of Education Shandong UniversityJinan 250012China shandong Key Laboratory of Reproductive Medicine Shandong UniversityJinan 250012China shandong Provincial Clinical Research Center for Reproductive Health Jinan 250012China National Research Center for Assisted Reproductive Technology and Reproductive Genetics Shandong UniversityJinan 250012China The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal HospitalNanjing Medical UniversitySuzhou 215008China Gusu School Nanjing Medical UniversitySuzhou 215000China Guangdong Provincial People’s Hospital Guangdong Academy of Medical SciencesGuangzhou 510080China Guangdong-Hong Kong Metabolism&Reproduction Joint Laboratory Guangdong Second Provincial General HospitalGuangzhou 510317China Reproductive Medicine Center Guangdong Second Provincial General HospitalGuangzhou 510317China Research Unit of Gametogenesis and Health of ART-Offspring Chinese Academy of Medical Sciences(No.2021RU001)Jinan 250012China Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics Shanghai 200127China Center for Reproductive Medicine Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

Polycystic ovary syndrome(PCOS)is a complex ***-wide association studies(GWAS)have identified several genes associated with this condition,including ***1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular ***,the specific role of DENND1A in reproductive hormone abnormalities and follicle development disorders in PCOS remain poorly *** this study,we investigated DENND1A expression in ovarian granulosa cells(GCs)from PCOS patients and its correlation with *** results revealed an upregulation of DENND1A expression in GCs from PCOS cases,which was positively correlated with testosterone *** further explore the functional implications of DENND1A,we generated a transgenic mouse model overexpressing Dennd1a(TG mice).These TG mice exhibited subfertility,irregular estrous cycles,and increased testosterone production following PMSG ***,the TG mice displayed diminished responsiveness to FSH,characterized by smaller ovary size,less well-developed follicles,and abnormal expressions of FSH-priming ***,we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor(FSHR),promoting its internalization and inhibiting *** findings shed light on the reproductive role of DENND1A and uncover the underlying mechanisms,thereby contributing valuable insights into the pathogenesis of PCOS and providing potential avenues for drug design in PCOS treatment.

关键词： PCOS DENND1A FSHR ovarian granulosa cells

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Design and optimization of piperidinesubstituted thiophene[3,2-d]pyrimidine-based HIV-1 NNRTIs with improved drug resistance and pharmacokinetic profiles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3110-3124页

作者： Yanying Sun Zhenzhen Zhou Zhongling Shi Fabao Zhao Minghui Xie Zongji Zhuo Erik De Clercq Christophe Pannecouqueb Dongwei Kang Peng Zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJinan 250012China Rega Institute for Medical Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of shandong Province Jinan 250012China

HIV-1 reverse transcriptase(RT)has received great attention as an attractive therapeutic target for acquired immune deficiency syndrome(AIDS),but the inevitable drug resistance and side effects have always been major challenges faced by non-nucleoside reverse transcriptase inhibitors(NNRTIs).This work aimed to identify novel chemotypes of anti-HIV-1 agents with improved drugresistance profiles,reduced toxicity,and excellent druggability.A series of diarylpyrimidine(DAPY)derivatives were prepared via structural modifications of the leads K-5a2 and *** them,15a with dimethylphosphine oxide moiety showed the most prominent antiviral potency against all of the tested viral panel,being 1.6-fold(WT,EC_(50) Z 1.75 nmol/L),3.0-fold(L100I,EC_(50) Z 2.84 nmol/L),2.4-fold(K103N,EC_(50) Z 1.27 nmol/L),3.3-fold(Y181C,EC50 Z 5.38 nmol/L),2.9-fold(Y188L,EC_(50) Z 7.96 nmol/L),2.5-fold(E138K,EC_(50) Z 4.28 nmol/L),4.8-fold(F227L/V106A,EC_(50) Z 3.76 nmol/L)and 5.3-fold(RES056,EC_(50) Z 15.8 nmol/L)more effective than that of the marketed drug *** docking results illustrated the detailed interactions formed by compound 15a and WT,F227L/V106A,and RES056 ***,15a-HCl carried outstanding pharmacokinetic(t1/2 Z 1.32 h,F Z 40.8%)and safety profiles(LD_(50)>2000 mg/kg),which demonstrated that 15a HCl is a potential anti-HIV-1 drug candidate.

关键词： HIV-1 NNRTIs NNIBP Structural alert Anti-HIV-1 drug candidate

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A Wind Power Prediction Framework for Distributed Power Grids

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Energy Engineering 2024年第5期121卷 1291-1307页

作者： Bin Chen Ziyang Li Shipeng Li Qingzhou Zhao Xingdou Liu Power Grid Design Institute Shandong Electric Power Engineering Consulting Institute Co.Ltd.Jinan250013China School of Electrical Engineering Shandong UniversityJinan250012China

To reduce carbon emissions,clean energy is being integrated into the power *** power is connected to the grid in a distributed form,but its high variability poses a challenge to grid *** article combines wind turbine monitoring data with numerical weather prediction(NWP)data to create a suitable wind power prediction framework for distributed ***,high-precision NWP of the turbine range is achieved using weather research and forecasting models(WRF),and Kriging interpolation locates predicted meteorological data at the turbine ***,a preliminary predicted power series is obtained based on the fan’s wind speed-power conversion curve,and historical power is reconstructed using variational mode decomposition(VMD)filtering to form input variables in chronological ***,input variables of a single turbine enter the temporal convolutional network(TCN)to complete initial feature extraction,and then integrate the outputs of all TCN layers using Long Short Term Memory Networks(LSTM)to obtain power prediction sequences for all turbine *** proposed method was tested on a wind farm connected to a distributed power grid,and the results showed it to be superior to existing typical methods.

关键词： Wind power prediction distributed power grid WRF mode deep learning variational mode decomposition

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Computed tomography-based radiomics combined with machine learning allows differentiation between primary intestinal lymphoma and Crohn's disease

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World Journal of Gastroenterology 2024年第25期30卷 3155-3165页

作者： Meng-Jun Xiao Yu-Teng Pan Jia-He Tan Hai-Ou Li Hai-Yan Wang Department of Radiology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina Medical Science and Technology Innovation Center Shandong First Medical University&Shandong Academy of Medical SciencesJinan 250000Shandong ProvinceChina University of California DavisCA 95616United States Qilu Hospital Cheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Due to similar clinical manifestations and imaging signs,differential diagnosis of primary intestinal lymphoma(PIL)and Crohn's disease(CD)is a challenge in clinical *** To investigate the ability of radiomics combined with machine learning methods to differentiate PIL from *** We collected contrast-enhanced computed tomography(CECT)and clinical data from 120 patients form center 1.A total of 944 features were extracted singlephase images of CECT *** the last absolute shrinkage and selection operator model,the best predictive radiographic features and clinical indications were *** from 54 patients were collected at center 2 as an external validation set to verify the robustness of the *** area under the receiver operating characteristic curve,accuracy,sensitivity and specificity were used for *** A total of five machine learning models were built to distinguish PIL from *** on the results from the test group,most models performed well with a large area under the curve(AUC)(>0.850)and high accuracy(>0.900).The combined clinical and radiomics model(AUC=1.000,accuracy=1.000)was the best model among all *** Based on machine learning,a model combining clinical data with radiologic features was constructed that can effectively differentiate PIL from CD.

关键词： Primary intestinal lymphoma Crohn's disease Radiomics Machine learning Diagnosis

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MYB2 and MYB108 regulate lateral root development by interacting with LBD29 in Arabidopsis thaliana

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Journal of Integrative Plant Biology 2024年第8期66卷 1675-1687页

作者： Feng Zhang Junxia Wang Tingting Ding Xuefeng Lin Haiying Hu Zhaojun Ding Huiyu Tian The Key Laboratory of Plant Development and Environmental Adaptation Biology Ministry of EducationSchool of Life SciencesShandong UniversityQingdao 266237China Advanced Medical Research Institute Cheeloo College of MedicineShandong UniversityJinan 250012China

AUXIN RESPONSE FACTOR 7(ARF7)-mediated auxin signaling plays a key role in lateral root(LR)development by regulating downstream LATERAL ORGAN BOUNDARIES DOMAIN(LBD)transcription factor genes,including LBD16,LBD18,and *** proteins are believed to regulate the transcription of downstream genes as homodimers or ***,whether LBD29 forms dimers with other proteins to regulate LR development remains ***,we determined that the Arabidopsis thaliana(L.)*** transcription factors MYB2 and MYB108 interact with LBD29 and regulate auxin-induced LR *** MYB2 and MYB108 were induced by auxin in an ARF7-dependent *** of MYB2 by fusion with an SRDX domain severely affected auxin-induced LR formation and the ability of LBD29 to induce LR *** contrast,overexpression of MYB2 or MYB108 resulted in greater LR numbers,except in the lbd29 mutant *** findings underscore the interdependence and importance of MYB2,MYB108,and LBD29 in regulating LR *** addition,MYB2–LBD29 and MYB108–LBD29 complexes promoted the expression of CUTICLE DESTRUCTING FACTOR 1(CDEF1),a member of the GDSL(Gly-Asp-Ser-Leu)lipase/esterase family involved in LR *** summary,this study identified MYB2–LBD29 and MYB108–LBD29 regulatory modules that act downstream of ARF7 and intricately control auxin-mediated LR development.

关键词： ARF7 auxin lateral roots LBD29 MYB108 MYB2

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