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The protective effects and underlying mechanisms of dapagliflozin on diabetes-induced testicular dysfunction

Asian Journal of Andrology 2023年第3期25卷 331-338页

作者： Zhi-Chao Luo zi-run jin Ya-Fei Jiang Tian-Jiao Wei Ya-Lei Cao Zhe Zhang Rui Wei Hui Jiang Department of Urology Peking University Third HospitalBeijing 100191China Department of Endocrinology and Metabolism Peking University Third HospitalBeijing 100191China Department of Reproductive Medicine Center Peking University Third HospitalBeijing 100191China

Male diabetic individuals present a marked impairment in fertility;however,knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory.The new hypoglycemic drug dapagliflozin has shown certain benefits,such as decreasing the risk of cardiovascular and renal events in patients with diabetes.Even so,until now,the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification.Here,we found that dapagliflozin lowered blood glucose levels,alleviated seminiferous tubule destruction,and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice.Moreover,the glucagon-like peptide-1 receptor(GLP-1R)antagonist exendin(9-39)had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice.We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2(BCL2)and X-linked inhibitor of apoptosis protein(XIAP)and inhibiting oxidative stress by enhancing the antioxidant status,including total antioxidant capacity,total superoxide dismutase(SOD)activity,and glutathione peroxidase(GPx)activity,as well as decreasing the level of 4-hydroxynonenal(4-HNE).Exendin(9-39)administration partially reversed these effects.Furthermore,dapagliflozin upregulated the glucagon-like peptide-1(GLP-1)level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog(Akt)phosphorylation in testicular tissue.Exendin(9-39)partially inhibited Akt phosphorylation.These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase(PI3K)/Akt signaling pathway.Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.

关键词： dapagliflozin diabetes glucagon-like peptide-1 receptor male infertility oxidative stress

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Turning point of organoid transplantation:first-in-human trial of iPSC-derived retinal organoid grafting in patients with retinitis pigmentosa

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Science China(Life Sciences) 2024年第5期67卷 1082-1084页

作者： Chang-Jun Zhang zi-Bing jin Beijing Institute of Ophthalmology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China

The discovery of induced pluripotent stem cells(iPSCs)has revolutionized the field of disease research,providing a promising platform for studying various conditions.Over the last decade,significant progress has been made in combining iPSCs with other cutting-edge technologies to investigate disease mechanisms and develop potential treatments.

关键词： conditions patients retinitis

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Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential

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World Journal of Stem Cells 2024年第5期16卷 512-524页

作者： Hang Zhang Ling-zi Wu Zhen-Yu Liu zi-Bing jin Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing 100730China

BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.AIM To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles(EVs)influence anomalous cell junction and differentiation potential.METHODS We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation.Chromo-somal karyotype analysis,flow cytometry,and immunofluorescent staining were utilized for hiPSC identification.Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential.Additionally,EVs were isolated from the supernatant,and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.RESULTS The generated hiPSCs,both with and without a MERTK mutation,exhibited normal karyotype and expressed pluripotency markers;however,hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential,as confirmed by transcriptomic and proteomic profiling.Furthermore,hiPSC-derived EVs were involved in various biological processes,including cell junction and differentiation.CONCLUSION HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential.Furthermore,hiPSC-derived EVs played a regulatory role in various biological processes,including cell junction and differentiation.

关键词： Cell junction Cellular differentiation Extracellular vesicle Human induced pluripotent stem cells Transcriptomics Proteomics

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Static recrystallization behaviors and mechanisms of 7Mo super-austenitic stainless steel with undissolved sigma precipitates during double-stage hot deformation

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Journal of Iron and Steel Research(International) 2024年第2期31卷 475-487页

作者： Shi-guang Xu jin-shan He run-ze Zhang Fu-cheng Zhang Xi-tao Wang Collaborative Innovation Center of Steel Technology University of Science and Technology BeijingBeijing100083China State Key Laboratory of Metastable Materials Science and Technology Yanshan UniversityQinhuangdao066004HebeiChina Shandong Provincial Key Laboratory for High Strength Lightweight Metallic Materials Advanced Materials InstituteQilu University of Technology(Shandong Academy of Science)Jinan250353ShandongChina

Static recrystallization(SRX)behaviors and corresponding recrystallization mechanisms of 7Mo super-austenitic stainless steel were studied under different deformation conditions.The order of influence of deformation parameters on static recrystallization behaviors,from high to low,is followed by temperature,first-stage strain and strain rate.Meanwhile,the effect of holding time on static recrystallization behaviors is significantly controlled by temperature.In addition,with the increase in temperature from 1000 to 1200°C,the static recrystallization mechanism evolves from discontinuous static recrystallization and continuous static recrystallization(cSRX)to metadynamic recrystallization and cSRX,and finally to cSRX.The cSRX exists at all temperatures.This is because high stacking fault energy(56 mJ m−2)promotes the movement of dislocations,making the deformation mechanism of this steel is dominated by planar slip of dislocation.Large undissolved sigma precipitates promote static recrystallization through particle-stimulated nucleation.However,small strain-induced precipitates at grain boundaries hinder the nucleation of conventional SRX and the growth of recrystallized grains,while the hindering effect decreases with the increase in temperature.

关键词： 7Mo super-austenitic stainless steel Double-stage hot deformation Conventional static recrystallization Metadynamic recrystallization Strain-induced precipitation

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Effects and the underlying mechanisms for the treatment of electroacupuncture on asthenozoospermia in a rat model

Effects and the underlying mechanisms for the treatment of e...

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中国神经科学学会第十二届全国学术会议

作者： zi-run jin Bo-Heng Liu Jie Cai Wen-Hao Tang Hui Jiang Guo-Gang Xing Neuroscience Research Institute Peking University Department of Urology the Third Hospital Peking University

Objective: Asthenozoospermia is one of the most common causes of male infertility on clinic. However, the mechanisms underlying the pathogenesis of asthenozoospermia remain largely unknown. Up to now, there is still not effective method for the treatment of asthenozoospermia in clinic. Electroacupuncture（EA） has been widely used for the treatment of multiple disorders in clinic including chronic pain, drug abuse as well as female infertility. In this study, we investigated effects of EA on asthenozoospermia in a rat model. Methods: A rat model of asthenozoospermia was induced by intragastric administration of ornidazole（ORN）, which was confirmed by evaluating the sperm motility using computer-assisted sperm analysis（CASA） and by detecting the calcium influx using calcium fluorescence imaging. When the rat model of asthenozoospermia was successfully induced, parts of the rats were treated with electroacupuncture（EA） from day 15. All the rats were intragastric administration of ORN continually during the treatment of EA or mock EA. Results:（1） 2 Hz EAtreatment once per day had no significantly effect on all of the sperm motility indexes to the asthenozoospermic rats.（2） 2 Hz EA-treatment once every other day for 5 days could increase the sperm viability, the sperm motility and the grade A+B sperm in asthenozoospermic rats.（3） 2 Hz EA-treatment once every other day for 9 days could markedly improve all the other parameters of sperm motility except for the linearity and the straightness in the asthenozoospermic rats. Similarly, the decreased calcium influx signal in the sperm of ORN-induced asthenozoospermic rats also was dramatically restored after EA-treatment.（4） 100 Hz EA-treatment once every other day for 9 days: the sperm indexes in asthenozoospermic rats including the sperm viability, the sperm motility, and the grade A+B sperm also could be improved after the EA-treatment. Conclusion: The down-regulation of calcium in epididymal spermatozoa contributes to the pathogenesis of asthenozoospermia, while the up-re

关键词： Asthenozoospermia electroacupuncture（EA） computer-assisted sperm analysis（CASA） calcium sperm motility

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Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

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World Journal of Stem Cells 2024年第4期16卷 444-458页

作者： Cheng-jin Ai Ling-Juan Chen Li-Xuan Guo Ya-Ping Wang zi-Yi Zhao Department of Laboratory Medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Department of Ophthalmology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Central Laboratory Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Traditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan Province Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

关键词： Leukemia stem cells Gossypol acetic acid Reactive oxygen species Mitochondrial dysfunction Interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling

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Botulinum toxin type A in treating early-stage patients with small-angle acute acquired comitant esotropia

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1094-1101页

作者： run-Ting Ma Die-Wen-Jie Hu Lian-Hong Zhou Wen-Ping Li Yuan-jin Li Bei-Xi Yi Department of Ophthalmology Renmin Hospital of Wuhan UniversityWuhan 430060Hubei ProvinceChina

AIM:To investigate botulinum toxin A(BTXA)efficacy on small-angle(≤25Δ)acute acquired concomitant esotropia(AACE)in early-stage patients.METHODS:The electronic medical record data of AACE patients during March 2019 and June 2023 were collected in this retrospective and hospital-based cohort study.A total of 72 small-angle AACE patients received BTXA extraocular muscle injection.Patients were grouped by onset-to-treatment time(Group A:≤6mo,Group B:>6mo).Deviation of esotropia,eye alignment and stereopsis were analyzed at the period of pre/post-injection(1wk,1,3,and 6mo).Orthophoria rate at 6mo(horizontal deviation0.05)between two groups except onset-to-treatment time(2mo vs 11mo,P0.05);while in 3 and 6mo Group A was significantly smaller than group B(all P6mo)may reduce BTXA efficacy.Early BTXA intervention benefits long-term eye alignment and stereopsis recovery.

关键词： acute acquired comitant esotropia botulinum toxin type A stereopsis

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Design strategies of high-performance lead-free electroceramics for energy storage applications

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Rare Metals 2024年第3期43卷 853-878页

作者： Biao Guo Fei jin Li Li zi-Zhao Pan Xin-Wei Xu Hong Wang Department of Materials Science and Engineering College of EngineeringSouthern University of Science and TechnologyShenzhen518055China School of Microelectronics and State Key Laboratory for Mechanical Behavior of Materials Xi’an Jiaotong UniversityXi’an710049China

A greater number of compact and reliable electrostatic capacitors are in demand due to the Internet of Things boom and rapidly growing complex and integrated electronic systems,continuously promoting the development of high-energy-density ceramic-based capacitors.Although significant successes have been achieved in obtaining high energy densities in lead-based ferroelectric ceramics,the utilization of lead-containing ceramies has been restricted due to environmental and health hazards of lead.Lead-free ferroelectric ceramics have garnered tremendous attention and are expected to replace lead-based ceramics in the near future.However,the energy density of lead-free ceramics is still lagging behind that of lead-containing cou.nterparts,severely limiting their applications.Significant efforts have been made to enhance the energy storage performance of lead-free ceramics using multi-scale design strategies,and exciting progress has been achieved in the past decade.This review briefly discusses the energy storage mechanism and fundamental characteristics of a dielectric capacitor,summarizes and compares the state-of-the-art design strategies for high-energy-density lead-free ceramics,and highlights several critical issues and requirements for industrial production.The prospects and challenges of lead-free ceramics for energy storage applications are also discussed.

关键词： Dielectric materials Lead-free ceramic Environment friendly Energy storage Design strategy

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RsaL is a self-regulatory switch that controls alternative biosynthesis of two AHL-type quorum sensing signals in Pseudomonas aeruginosa PA1201

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mLife 2024年第1期3卷 74-86页

作者： Ya-Wen He zi-jing jin Ying Cui Kai Song Bo Chen Lian Zhou State Key Laboratory of Microbial Metabolism Joint International Research Laboratory of Metabolic and Developmental SciencesSJTU-NLBP Joint R&D Centre for Biopesticides and BiofertilizersSchool of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghaiChina Zhiyuan Innovative Research Centre Student Innovation CentreZhiyuan CollegeShanghai Jiao Tong UniversityShanghaiChina

Pseudomonas aeruginosa is a ubiquitous and metabolically versatile microorganism naturally found in soil and water.It is also an opportunistic pathogen in plants,insects,animals,and humans.In response to increasing cell density,P.aeruginosa uses two acylhomoserine lactone(AHL)quorum-sensing(QS)signals(i.e.,N-3-oxo-dodecanoyl homoserine lactone[3-oxo-C12-HSL]and Nbutanoyl-homoserine lactone[C4-HsL]),which regulate the expression of hundreds of genes.However,how the biosynthesis of these two QS signals is coordinated remains unknown.We studied the regulation of these two QS signals in the rhizosphere strain PA1201.PA1201 sequentially produced 3-oxo-C12-HSL and C4-HSL at the early and late growth stages,respectively.The highest 3-oxo-C12-HSL-dependent elastase activity was observed at the early stage,while the highest C4-HSL-dependent rhamnolipid production was observed at the late stage.The atypical regulator RsaL played a pivotal role in coordinating 3-oxo-C12-HSL and C4-HSL biosynthesis and QS-associated virulence.RsaL repressed las/transcription by binding the-10 and-35 boxes of the lasl promoter.In contrast,RsaL activated rhll transcription by binding the region encoding the 5'-untranslated region of the rhll mRNA.Further,RsaL repressed its own expression by binding a nucleotide motif located in the-35 box of the rsaL promoter.Thus,RsaL acts as a molecular switch that coordinates the sequential biosynthesis of AHL QS signals and differential virulence in PA1201.Finally,C4-HSL activation by RsaL was independent of the Las and Pseudomonas quinolone signal(PQS)QS signaling systems.Therefore,we propose a new model of the QS regulatory network in PA1201,in which RsaL represents a superior player acting at the top of the hierarchy.

关键词： N-3-oxo-dodecanoyl homoserine lactone N-butanoyl-homoserine lactone Pseudomonas aeruginosa quorum sensing RsaL

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Laser powder bed fusion of NiTiFe shape memory alloy via premixed powder: microstructural evolution, mechanical and functional properties

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Rare Metals 2024年第5期43卷 2300-2316页

作者： Bo Yuan jin-Guo Ge Liang Zhang Hong-Jun Chen Long-Sha Wei Yu-Duo Zhou run-Hua Song Institute of Intelligent Manufacturing Technology Shenzhen Polytechnic School of Mechanical and Electrical Engineering Guilin University of Electronic Technology Guangdong Advanced Polymer Composite EngineeringTechnology Research Center Shenzhen Academy of Aerospace Technology Jihua Laboratory Testing Center Jihua Laboratory

High-cost pre-alloyed powder is the bottleneck problem that limits the widespread application of additivemanufactured shape memory alloys. In this work, the lowcost ternary NiTiFe shape memory alloy is fabricated by laser powder bed fusion (LPBF) technique via mechanically mixed pre-alloy NiTi powder and varying contents pure Fe powder (1, 2, 3 wt%). All NiTiFe alloys show a relative density of up to 99.8%by optimizing the LPBF processing parameters. Owing to the heterogeneous nucleation effect of micron-sized Fe particles, both grain refinement and texture weakening are generated in the NiTiFe alloys, accompanied by the reduction of dislocation density. For the room-temperature mechanical properties,the NiTi-3Fe alloy shows the highest microhardness of HV370, but the fracture strength and elongation reduce to1701 MPa and 23%simultaneously. The evolution of mechanical properties is attributed to the high internal defects, low dislocation density and the incoherent oxide.Moreover, the NiTi-3Fe alloy shows the quasi-linear superelasticity behavior; the superelastic recoverable strain of NiTi-1Fe and NiTi-2Fe decreased with the increase in Fe content. This study provided a new-fangled insight for the development of multi-component NiTi-based shape memory alloys by additive manufacturing.

关键词： Additive manufacturing Shape memory alloy Metal matrix composite Microstructure Mechanical properties

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