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Exosomes derived from BMSCs ameliorate cyclophosphamide-induced testosterone deficiency by enhancing the autophagy of Leydig cells via the AMPK-mTOR signaling pathway

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Asian Journal of Andrology 2023年第4期25卷 474-483页

作者： Hao-Yu Liang Fan Peng Min-Jia Pan Sen-Lin Liao cun Wei Guan-Yang Wei Xiao Xie Kang-Yi Xue Ming-Kun Chen Jian-Kun Yang Wen-Bin Guo cun-dong liu Qi-Zhao Zhou Department of Urology The Third Affiliated Hospital of Southern Medical UniversityGuangzhou 510630China The Third School of Clinical Medicine Southern Medical UniversityGuangzhou 510515China The First School of Clinical Medicine Southern Medical UniversityGuangzhou 510515China

Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severelyinfluences the quality of life of patients. Currently, several guidelines recommend patients suffering from CPTD receive testosteronereplacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxictreatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviatecyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment of male reproductive ***, we further investigated whether BMSCs-exos affect autophagy and testosterone synthesis in Leydig cells (LCs). Here,we examined the effects and probed the molecular mechanisms of BMSCs-exos on CPTD in vivo and in vitro by detecting theexpression levels of genes and proteins related to autophagy and testosterone synthesis. Furthermore, the testosterone concentrationin serum and cell-conditioned medium, and the photophosphorylation protein levels of adenosine monophosphate-activatedprotein kinase (AMPK) and mammalian target of rapamycin (mTOR) were measured. Our results suggest that BMSCs-exos couldbe absorbed by LCs through the blood–testis barrier in mice, promoting autophagy in LCs and improving the CP-induced low serumtestosterone levels. BMSCs-exos inhibited cell death in CP-exposed LCs, regulated the AMPK-mTOR signaling pathway to promoteautophagy in LCs, and then improved the low testosterone synthesis ability of CP-induced LCs. Moreover, the autophagy inhibitor,3-methyladenine (3-MA), significantly reversed the therapeutic effects of BMSCs-exos. These findings suggest that BMSCs-exospromote LC autophagy by regulating the AMPK-mTOR signaling pathway, thereby ameliorating CPTD. This study provides novelevidence for the clinical improvement of CPTD using BMSCs-exos.

关键词： autophagy bone marrow mesenchymal stem cells cyclophosphamide exosomes Leydig cells testosterone deficiency

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Protective effect of bone marrow mesenchymal stem cell-derived exosomes against the reproductive toxicity of cyclophosphamide is associated with the p38MAPK/ERK and AKT signaling pathways

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Asian Journal of Andrology 2021年第4期23卷 386-391页

作者： Xiao-Bin Guo Jia-Wen Zhai Hui Xia Jian-Kun Yang Jun-Hao Zhou Wen-Bin Guo Cheng Yang Ming Xia Kang-Yi Xue cun-dong liu Qi-Zhao Zhou Department of Urology The Third Affiliated Hospital of Southern Medical UniversityGuangzhou 510630China

Spermatogenic dysfunction caused by cyclophosphamide(CP)chemotherapy has seriously influenced the life quality of ***,treatments for CP-induced testicular spermatogenic dysfunction are limited,and the molecular mechanisms are not fully *** the first time,here,we explored the effects of bone marrow mesenchymal stem cell-derived exosomes(BMSC-exos)on CP-induced testicular spermatogenic dysfunction in vitro and in ***-exos could be taken up by spermatogonia(GC1-spg cells).CP-injured GC1-spg cells and BMSC-exos were cocultured at various doses,and then,cell proliferation was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)*** addition,photophosphorylation of extracellular-regulated kinase(ERK),p38 mitogen-activated protein kinase(p38MAPK),and protein kinase B(AKT)proteins was evaluated by western blotting as well as apoptosis in GC1-spg cells measured using flow *** with BMSC-exos enhanced cell proliferation and reduced apoptosis of CP-injured GCI-spg *** levels of ERK,AKT,and p38MAPK proteins were reduced in CP-injured spermatogonia when co-treated with BMSC-exos,indicating that BMSC-exos acted against the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling *** experiments in vivo,CP-treated rats received BMSC-exos by injection into the tail vein,and testis morphology was compared between treated and control *** showed that transfusion of BMSC-exos inhibited the pathological changes in CP-injured ***,BMSC-exos could counteract the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling *** findings provide a potential treatment for CP-induced male spermatogenic dysfunction using BMSC-exos.

关键词： bone marrow mesenchymal stem cells cyclophosphamide exosomes reproductive toxicity

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MicroRNA-27a-mediated repression of cysteine-rich secretory protein 2 translation in asthenoteratozoospermic patients

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Asian Journal of Andrology 2017年第5期19卷 591-595页

作者： Jun-Hao Zhou Qi-Zhao Zhou Jian-Kun Yang Xiao-Ming Lyu Jun Bian Wen-Bin Guo Zi-Jian Chen Ming Xia Hui Xia Tao Qi Xin Li cun-dong liu Department of Urology The Third Affiliated Hospital of Southern Medical University Guangzhou China Laboratory Medical Center The Third Affiliated Hospital of Southern Medical University Guangzhou China Laboratory Medicine Center Nanfang Hospital Southern Medical University Guangzhou China Cancer Research Institute Southern Medical University Guangzhou China

Cysteine-rich secretory protein 2 （CRISP2） is an important protein in spermatozoa that plays roles in modulating sperm flagellar motility, the acrosome reaction, and gamete fusion. Spermatozoa lacking CRISP2 exhibit low sperm motility and abnormal morphology. However, the molecular mechanisms underlying the reduction of CRISP2 in asthenoteratozoospermia （ATZ） remain unknown. In this study, low expression of CRISP2 protein rather than its mRNA was observed in the ejaculated spermatozoa from ATZ patients as compared with normozoospermic males. Subsequently, bioinformatic prediction, luciferase reporter assays, and microRNA-27a （miR-27a） transfection experiments revealed that miR-27a specifically targets CRISP2 by binding to its 3＇ untranslated region （3＇-UTR）, suppressing CRISP2 expression posttranscriptionally. Further evidence was provided by the clinical observation of high miR-27a expression in ejaculated spermatozoa from ATZ patients and a negative correlation between miR-27a expression and CRISP2 protein expression. Finally, a retrospective follow-up study supported that both high miR-27a expression and low CRISP2 protein expression were associated with low progressive sperm motility, abnormal morphology, and infertility. This study demonstrates a novel mechanism responsible for reduced CRISP2 expression in ATZ, which may offer a potential therapeutic target for treating male infertility, or for male contraception.

关键词： asthenoteratozoospermia cysteine-rich secretory protein 2 male infertility microRNA-27a

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A novel robust nomogram based on peripheral monocyte counts for predicting lymph node metastasis of prostate cancer

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Asian Journal of Andrology 2021年第4期23卷 409-414页

作者： Jia-Wei Zhou Yun-Hua Mao Yang liu Hai-Tao Liang Chandni Chandur Samtani Yue-Wu Fu Yun-Lin Ye Gang Xiao Zi-Ke Qin cun-dong liu Jian-Kun Yang Qi-Zhao Zhou Wen-Bin Guo Kang-Yi Xue Shan-Chao Zhao Ming-Kun Chen Department of Urology The Third Affiliated Hospital of Southern Medical UniversityGuangzhou 510630China Department of Urology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Urology Cancer Center of Sun Yat-sen UniversityGuangzhou 510060China Department of International Medical Education The Southern Medical UniversityGuangzhou 510515China Department of Surgery The First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Department of Laboratory Medicine The Third Affiliated Hospital of Southern Medical UniversityGuangzhou 510630China Department of Urology Nanfang Hospital of Southern Medical UniversityGuangzhou 510515China

Accurate methods for identifying pelvic lymph node metastasis(LNM)of prostate cancer(PCa)prior to surgery are still *** aimed to investigate the predictive value of peripheral monocyte count(PMC)for LNM of PCa in this *** hundred and ninety-eight patients from three centers were divided into a training set(n=125)and a validation set(n=173).In the training set,the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses,and the optimal cutoff value was calculated by the receiver operating characteristic(ROC)*** sensitivity and specificity of the optimal cutoff were authenticated in the validation ***,a nomogram based on the PMC was constructed for predicting *** analyses of the training cohort demonstrated that clinical T stage,preoperative Gleason score,and PMC were independent risk factors for *** subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405×10^(9)l^(−1)with a sensitivity of 60.0%and a specificity of 67.8%.In the validation set,the optimal cutoff value showed significantly higher sensitivity than that of conventional magnetic resonance imaging(MRI)(0.619 vs 0.238,P<0.001).The nomogram involving PMC,free prostate-specific antigen(fPSA),clinical T stage,preoperative Gleason score,and monocyte-to-lymphocyte ratio(MLR)was generated,which showed a robust predictive capacity for predicting LNM before the *** results indicated that PMC as a single agent,or combined with other clinical parameters,showed a robust predictive capacity for LNM in *** can be employed as a complementary factor for the decision of whether to conduct pelvic lymph node dissection.

关键词： Iymph node metastasis magnetic resonance imaging monocyte nomogram prostate cancer

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Low-cost and fluoride-free synthesis of MFI zeolite nanosheets with enhanced stability for benzene alkylation with ethanol

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Journal of Energy Chemistry 2025年第1期100卷 458-468页

作者： Peng Zhu cun liu Yiren Yu Guoshu Gao Yumeng Zhao Xiongfu Zhang Guodong liu Guohui Yang State Key Laboratory of Fine Chemicals School of Chemical Engineering Dalian University of Technology State Key Laboratory of Catalysis Dalian Institute of Chemical Physics Chinese Academy of Sciences

Zeolite nanosheets with a short b-axis thickness are highly desirable in lots of catalytic reactions due to their reduced diffusion resistance. Nevertheless, conventional synthesis methods usually require expensive structure-directing agents(SDAs), pricey raw materials, and eco-unfriendly fluorine-containing additives. Here, we contributed a cost-effective and fluoride-free synthesis method for synthesizing high-quality MFI zeolite nanosheets through a Silicalite-1(Sil-1) seed suspension and urea cooperative strategy, only with inexpensive colloidal silica as the Si source. Our approach was effective for synthesizing both Sil-1 and aluminum-containing ZSM-5 nanosheets. By optimizing key synthesis parameters,including seed aging time, seed quantity, and urea concentration, we achieved precise control over the crystal face aspect ratio and b-axis thickness. We also revealed a non-classical oriented nanosheet growth mechanism, where Sil-1 seeds induced the formation of quasi-ordered precursor particles, and the(010)crystal planes of these particles facilitated urea adsorption, thereby promoting c-axis-oriented *** obtained ZSM-5 nanosheets exhibited exceptional catalytic performance in the benzene alkylation with ethanol, maintaining stability for over 500 h, which is 5 times longer than traditional ZSM-5 catalysts. Furthermore, large-scale production of ZSM-5 nanosheets was successfully carried out in a 3 L highpressure autoclave, yielding samples consistent with those from laboratory-scale synthesis. This work marks a significant step forward in the sustainable and efficient production of MFI nanosheets using inexpensive and environmentally friendly raw materials, offering the broad applicability in catalysis.

关键词： MFI zeolite ZSM-5 Nanosheets Scale-up synthesis Aromatic alkylation

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Corrigendum to“MicroRNA-27a-mediated repression of cysteine-rich secretory protein 2 translation in asthenoteratozoospermic patients”

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Asian Journal of Andrology 2023年第6期25卷 758-758页

作者： Jun-Hao Zhou Qi-Zhao Zhou Jian-Kun Yang Xiao-Ming Lyu Jun Bian Wen-Bin Guo Zi-Jian Chen Ming Xia Hui Xia Tao Qi Xin Li cun-dong liu Department of Urology The Third Affiliated Hospital of Southern Medical UniversityGuangzhouChina Laboratory Medical Center The Third Affiliated Hospital of Southern Medical UniversityGuangzhouChina Laboratory Medicine Center Nanfang HospitalSouthern Medical UniversityGuangzhouChina Cancer Research Institute Southern Medical UniversityGuangzhouChina

In the published article by Zhou et al.,1 two errors were found in Figure 2c and Figure *** Figure 2c,two labels of abscissa“Norm”and“ATZ”were *** Figure 3a,the scale values of abscissa were not consistent with those in Figure 3b,Figure 4a,and Figure *** error occurred due to mislabeling of the computer file folders,in which images collected from similar categories of experiments were *** authors replotted Figure 3c according to original *** correct Figure 2 and 3 are as follows.

关键词： Figure reversed error

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High-resolution imaging through dynamic scattering media: Iterative optimization based on polarimetric characteristics

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Science China Technological Sciences 2025年第1期 82-84页

作者： Meng XIANG Kai DENG Tianyu WANG Jinpeng liu Xue dong Teli XI Fei liu Xiaopeng SHAO School of Optoelectronic Engineering Xidian University Xi'an Key Laboratory of Computational Imaging National Key Laboratory of Infrared Detection Technologies

High-resolution imaging through randomly dynamic scattered fields and highly scattered walls is an extensively sought-after capability with potential applications in various fields such as underwater imaging, biomedical imaging, and seeing through fog. Numerous methods have been proposed to unscramble object information from degraded scattered images, resulting in considerable improvements in image contrast in degraded scenarios [1].

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Single-cell omics: experimental workflow, data analyses and applications

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Science China Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-dong J.Han Qi liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for Stem Cells School of Life Sciences and TechnologyTongji University Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

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Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway

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Neural Regeneration Research 2025年第11期20卷 3245-3258页

作者： Jiayi Wang Mengke Zhao dong Fu Meina Wang Chao Han Zhongyue Lv Liang Wang Jing liu Stem Cell Clinical Research Center The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation Institute of Stem Cell and Precision Medicine DalianLiaoning ProvinceChina Institute(College)of Integrative Medicine Dalian Medical UniversityDalianLiaoning ProvinceChina

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived *** lays a foundation for the development of potentially potent new treatment modalities for ischemic ***,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical *** promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic *** found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal *** human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase *** findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling ***,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety ***,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

关键词： behavior exosome extracellular vesicles ischemic stroke mammalian target of rapamycin(mTOR) middle cerebral artery occlusion neural stem cells neuronal apoptosis phosphoinositide 3-kinase(PI3K) protein kinase B(AKT)

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Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin Long Chuanhua Ge Yueyang Zhao Yuanjie liu Qinghua Zeng Qing Tang Zhifang dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina Department of Anatomy Chongqing Medical UniversityChongqingChina Department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of Child Development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research Center for Child Health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

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