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Defects in phospholipase C zeta cause polyspermy and low fertilization after conventional IVF:not just ICSI failure

Asian Journal of Andrology 2024年第2期26卷 175-182页

作者： Jian-Fang Che Hui-Xia Wu Si-Cong Zeng Yue-Ren Wu Jing Dai De-Hua Cheng Fei Gong Guang-Xiu Lu Ge Lin Can Dai School of Medicine Hunan Normal UniversityChangsha 410013China Reproductive and Genetic Hospital of CITIC-Xiangya Changsha 410008China Clinical research center for Reproduction and Genetics in Hunan Province Changsha 410078China national engineering and research center of human stem cell Changsha 410205China

Phospholipase C zeta(PLC)is a key sperm-borne oocyte-activating factor that triggers Ca^(2+)oscillations and the subsequent block to polyspermy following gamete *** in PLCZ1,the gene encoding PLCζ,cause male infertility and intracytoplasmic sperm injection(ICSI)fertilization failure;and PLCζ expression and localization patterns are significantly correlated with ICSI fertilization rate(FR).However,in conventional in vitro fertilization(cIVF),whether and how sperm PLCζ affects fertilization remain ***,we identified one previously reported and two novel PLCZ1 mutations associated with polyspermy in vitro that are characterized by excessive sperm-zona binding and a delay in pronuclei(PN)*** staining and oocyte activation testing revealed that virtually all spermatozoa from patients lacked functional PLCζ and were thus unable to evoke Ca^(2+) *** with an artificial oocyte activation treatment successfully rescued the polyspermic phenotype and resulted in a live ***,we analyzed PLCζ in an additional 58 males after cIVF treatment in the Reproductive and Genetic Hospital of CiTiC-Xiangya(Changsha,China)between February 2019 and January *** found that the proportion of spermatozoa that expressed PLCζ was positively correlated with both 2PN rate and total *** optimal cutoff value below which males were likely to experience low FR(total FR≤30%)after clVF was 56.7%for the proportion of spermatozoa expressing *** study expands the mutation and the phenotypic spectrum of PLCZ1 and further suggests that PLCζ constitutes a promising biomarker for identifying low FRs cases in cIVF due to sperm-related oocyte activation deficiency and that sperm PLCζ analysis may benefit the widermale population and not onlymen with IcsI failure.

关键词： conventional IVF gene variants PLCζ polyspermy

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Ethical concerns in aging research: perspectives of global frontline researchers

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Science China Life Sciences 2024年第10期67卷 2149-2156页

作者： Yaojin Peng Lulu Ding Zhenyu Xiao Moshi Song Jianwei Lv Guang-Hui Liu Key Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive BiologyInstitute of ZoologyChinese Academy of Sciences University of Chinese Academy of Sciences Beijing Institute for stem cell and Regenerative Medicine Institute for stem cell and Regeneration Chinese Academy of Sciences Aging Biomarker Consortium (ABC) School of Life Science Beijing Institute of Technology School of Life Sciences Xiamen University Advanced Innovation center for human Brain Protection and national Clinical research center for Geriatric Disorders Xuanwu HospitalCapital Medical University Aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical University

This study investigated the ethical landscape of aging research amid the increasing global focus on extending the human lifespan and health span. Our global survey of 180 researchers across 38 jurisdictions revealed divergent perceptions of aging, a consensus regarding the feasibility of delaying aging, and multiple perspectives regarding lifespan extension. The present findings underscore a paradigm shift toward inclusive and ethically sound research, emphasizing the need for an approach that strikes a balance between basic and clinical research. In addition, this study highlighted key ethical concerns in aging research, including the effects of misleading advertising, potential inequality in access to aging interventions, and risks pertaining to the extrapolation of research findings from lower-model organisms to humans. The insights presented in this paper call for an integrated approach for overcoming the complex ethical and societal challenges in aging research to ensure responsible and equitable advancements in this burgeoning field.

关键词： aging ethical landscape ethics surveys and questionnaires

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Current assessment and management of measurable residual disease in patients with acute lymphoblastic leukemia in the setting of CAR-T-cell therapy

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Chinese Medical Journal 2024年第2期137卷 140-151页

作者： Minghao Lin Xiaosu Zhao Yingjun Chang Xiangyu Zhao Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China

Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell *** MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and *** has been well documented that MRD positivity predicts a poor prognosis and even disease ***,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical *** review assesses the common and novel MRD assessment *** addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment ***,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

关键词： Measurable/minimal residual disease Acute lymphoblastic leukemia Chimeric antigen receptor-modified T-cell therapy Allogeneic hematopoietic stem cell transplantation Relapse

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One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

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Neural Regeneration research 2024年第2期19卷 458-464页

作者： Lin Feng Da Li Yao Tian Chengshun Zhao Yun Sun Xiaolong Kou Jun Wu Liu Wang Qi Gu Wei Li Jie Hao Baoyang Hu Yukai Wang State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Institute for stem cell and Regenerative Medicine Chinese Academy of SciencesBeijingChina national stem cell Resource center Chinese Academy of SciencesBeijingChina Savaid Medical School University of Chinese Academy of SciencesBeijingChina Beijing Institute for stem cell and Regenerative Medicine BeijingChina State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s *** of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s ***,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation ***,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor *** beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in ***,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell ***,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

关键词： axonal integrity cell cryopreservation cellular environment cellular niche cell replacement therapy dopaminergic progenitors human pluripotent stem cell mechanical damage neuronal cell delivery Parkinson’s disease small-aperture gelatin microcarriers

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Exploring the impact of pericentric inversion of chromosome 9 on fertility in sperm donors

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Asian Journal of Andrology 2024年第3期26卷 302-307页

作者： Qian Liu Wen-Jun Zhou Zeng-Hui Huang Xiu-Hai Huang Jian Wu Xi-Ren Ji Xue-Feng Luo Yu-Ling Tang Rui-Jun Wang Li-Qing Fan Chuan Huang Wen-Bing Zhu Institute of Reproductive and stem cell engineering Basic Medicine CollegeCentral South UniversityChangsha 410013China Clinical research center for Reproduction and Genetics in Hunan Province Reproductive and Genetic Hospital of CITIC-XiangyaChangsha 410005China

Pericentric inversion of chromosome 9(inv[9])is a common chromosomal structural variant,but its impact on clinical outcomesremains *** screening criteria of sperm banks are rarely mentioned to individuals with inv(9).In this study,we evaluatedthe fertility of sperm donors with inv(9)who met eligibility criteria for sperm banks(inv[9]-eligible donors).From March 2004 toMay 2022,chromosomal analysis of 16124 sperm donors at CITIC-Xiangya human Sperm Bank in Hunan Province(Changsha,China)found that 251(1.6%)had chromosome variations,with inv(9)being the most prevalent at 1.1%.All 169 inv(9)-eligibledonors were contacted to collect fertility outcome data,along with 206 eligible donors without inv(9)as *** addition,semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization(FISH),mitochondrial membrane potential,DNA fragmentation index,acrosome integrity,reactive oxygen species(ROS),andsperm *** showed that inv(9)did not significantly increase reproductive risks *** detecting ROSlevel differences,the clinical impact may be *** study provides new data on the inv(9)population that can serveas a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individualscarrying inv(9)variant.

关键词： male fertility pericentric inversion of chromosome 9 sperm bank sperm functional parameters

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OIP5 Interacts with NCK2 to Mediate human Spermatogonial stem cell Self-Renewal and Apoptosis through cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

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research 2024年第1期2023卷 455-469页

作者： Yinghong Cui Wei Chen Li Du Zuping He The Key Laboratory of Model Animals and stem cell Biology in Hunan Province The Research Center of Reproduction and Translational Medicine of Hunan ProvinceHunan Normal University School of MedicineChangsha 410013HunanChina

Spermatogonial stem cells(SSCs)have important applications in both reproduction and regenerative ***,specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain ***,we have demonstrated for the first time that OIP5(Opa interacting protein 5)controlled the self-renewal and apoptosis of human *** sequencing identified that NCK2 was a target for OIP5 in human SSCs,and interestingly,OIP5 could interact with NCK2 as shown by Co-IP(co-immunoprecipitation),IP-MS(mass spectrometry),and GST pulldown ***2 silencing decreased human SSC proliferation and DNA synthesis but enhanced their ***,NCK2 knockdown reversed the influence of OIP5 overexpression on human ***,OIP5 inhibition decreased the numbers of human SSCs at S and G2/M phases,while the levels of numerous cell cycle proteins,including cyclins A2,B1,D1,E1 and H,especially cyclin D1,were remarkably ***,whole-exome sequencing of 777 patients with nonobstructive azoospermia(NOA)revealed 54 singlenucleotide polymorphism mutations of the OIP5 gene(6.95%),while the level of OIP5 protein was obviously lower in testes of NOA patients compared to fertile ***,these results implicate that OIP5 interacts with NCK2 to modulate human SSC self-renewal and apoptosis via cell cyclins and cell cycle progression and that its mutation and/or lower expression is correlated with *** such,this study offers novel insights into molecular mechanisms underlying the fate determinations of human SSCs and the pathogenesis of NOA,and it provides new targets for treating male infertility.

关键词： OIP5 Apoptosis reversed

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Dynamic transcriptional programs define distinct mammalian cortical lineages

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Neural Regeneration research 2024年第2期19卷 387-389页

作者： Tanzila Mukhtar Verdon Taylor Department of Biomedicine University of BaselBaselSwitzerland Eli and Edythe Broad center of Regeneration Medicine and stem cell research University of CaliforniaSan FranciscoCAUSA

The cerebral cortex is composed of billions of neurons and glia that are generated sequentially during *** cells are generated in an organized fashion during *** early stages of brain development,neural stem cells(NSC... 详细信息

关键词： cortex cerebral development

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Identification and characterization of human hematopoietic mesoderm

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Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China CAMS center for stem cell Medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China Division of cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage *** is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental *** this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic *** discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM ***,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its *** of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell *** conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

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A food-grade and senescent cell-targeted fisetin delivery system based on whey protein isolate-galactooligosaccharides Maillard conjugate

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Food Science and human Wellness 2024年第2期13卷 688-697页

作者： Shuai Hou Chutong Lai Yukun Song Haitao Wang Jialu Ni Mingqian Tan Academy of Food Interdisciplinary Science School of Food Science and TechnologyDalian Polytechnic UniversityDalian 116034China Institute of Cancer stem cell Cancer CenterDalian Medical UniversityDalian 116044China national engineering research center of Seafood Dalian Polytechnic UniversityDalian 116034China Collaborative Innovation center of Seafood Deep Processing Dalian Polytechnic UniversityDalian 116034China

cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend *** natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited *** this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent *** fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well ***,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in ***,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.

关键词： Fisetin Nanoparticle cellular senescence Targeted delivery

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Comparison of clinical features of nephrotic syndrome after haploidentical and matched donor hematopoietic stem cell transplantation

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Chinese Medical Journal 2024年第4期137卷 478-480页

作者： Wei Sun Yuanyuan Zhang Yuhong Chen Yuqian Sun Yifei Cheng Fengrong Wang Huan Chen Yao Chen Chenhua Yan Xiaodong Mo Wei Han Lanping Xu Yu Wang Xiaohui Zhang Kaiyan Liu Xiaojun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationPeking UniversityBeijing 10004China

To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is one of the most effective options for hematological ***,allo-HSCT treatment can cause serious ***-transplant kidney damage is an important *** this study,we retrospectively analyzed the frequency of nephrotic syndrome(NS)after allo-HSCT and compared the frequency and clinical characteristics of NS between haploidentical donor(HID)and matched donor(MD)HSCT(including matched sibling donors[MSD]and unrelated donors[URD]).

关键词： hematopoietic clinical matched

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