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CCDC181 is required for sperm flagellum biogenesis and male fertility in mice

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Zoological Research 2024年第5期45卷 1061-1072页

作者： Xiang-Jun Zhang Xiao-Ning Hou Jian-Teng Zhou Bao-Lu Shi Jing-Wei Ye Meng-Lei Yang Xiao-Hua Jiang Bo Xu Li-Min Wu Qing-Hua Shi division of Reproduction and Genetics First Affiliated Hospital of University of Science and Technology of China(USTC)Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Basic Medical SciencesDivision of Life Sciences and MedicineBiomedical Sciences and Health Laboratory of Anhui ProvinceInstitute of Health and MedicineHefei Comprehensive National Science CenterUniversity of Science and Technology of ChinaHefeiAnhui 230001China

The structural integrity of the sperm flagellum is essential for proper sperm *** defects can result in male infertility,yet the precise mechanisms underlying this relationship are not fully ***181,a coiled-coil domain-containing protein,is known to localize on sperm flagella and at the basal regions of motile *** this knowledge,the specific functions of CCDC181 in flagellum biogenesis remain *** this study,Ccdc181 knockout mice were *** absence of CCDC181 led to defective sperm head shaping and flagellum ***,the Ccdc181 knockout mice exhibited extremely low sperm counts,grossly aberrant sperm morphologies,markedly diminished sperm motility,and typical multiple morphological abnormalities of the flagella(MMAF).Additionally,an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified,with CCDC181 regulating the localization of LRRC46 within sperm *** findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.

关键词： Male infertility CCDC181 MMAF Spermiogenesis Flagellum biogenesis

RGS22 maintains the physiological function of ependymal cells to prevent hydrocephalus

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Science China Life sciences 2024年

作者： Xue Pang Lin Gu Qiu-Ying Han Jia-Qing Xing Ming Zhao Shao-Yi Huang Jun-Xi Yi Jie Pan Hao Hong Wen Xue Xue-Qing Zhou Zhi-Hui Su Xin-Ran Zhang Li-Ming Sun Shao-Zhen Jiang Dan Luo Ling Chen Zheng-Jie Wang Yu Yu Tian Xia Xue-Min Zhang Ai-Ling Li Tao Zhou Hong Cai Tao Li Nanhu Laboratory National Center of Biomedical Analysis School of basic Medical sciences Fudan University Department of basic Medical sciences School of Medicine Tsinghua University

Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid （CSF） flow by beating their motile cilia coordinately. The ependymal denudation or ciliary dysfunction causes hydrocephalus. Here, we report that the deficiency of regulator of Gprotein signaling 22 （RGS22） results in severe congenital hydrocephalus in both mice and rats. Interestingly, RGS22 is specifically expressed in ependymal cells within the brain. Using conditional knock-out mice, we further demonstrate that the deletion of Rgs22 exclusively in nervous system is sufficient to induce hydrocephalus. Mechanistically, we show that Rgs22 deficiency leads to the ependymal denudation and impaired ciliogenesis. This phenomenon can be attributed to the excessive activation of lysophosphatidic acid receptor （LPAR） signaling under Rgs22–/–condition, as the LPAR blockade effectively alleviates hydrocephalus in Rgs22–/–rats. Therefore, our findings unveil a previously unrecognized role of RGS22 in the central nervous system, and present RGS22 as a potential diagnostic and therapeutic target for hydrocephalus.

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Homozygous CCDC146 mutation causes oligoasthenoteratozoospermia in humans and mice

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Zoological Research 2024年第5期45卷 1073-1087页

作者： Jing-Wei Ye Tanveer Abbas Jian-Teng Zhou Jing Chen Meng-Lei Yang Xiong-Heng Huang Huan Zhang Hui Ma Ao Ma Bo Xu Ghulam Murtaza Qing-Hua Shi Bao-Lu Shi division of Reproduction and Genetics First Affiliated Hospital of University of Science and Technology of ChinaHefei National Laboratory for Physical Sciences at MicroscaleSchool of Basic Medical SciencesDivision of Life Sciences and MedicineBiomedical Sciences and Health Laboratory of Anhui ProvinceInstitute of Health and MedicineHefei Comprehensive National Science CenterUniversity of Science and Technology of ChinaHefeiAnhui 230026China Institute of Andrology Nanjing Drum Tower HospitalAffiliated Hospital of Nanjing University Medical SchoolNanjingJiangsu 210008China

Infertility represents a significant health concern,with sperm quantity and quality being crucial determinants of male ***(OAT)is characterized by reduced sperm motility,lower sperm concentration,and morphological abnormalities in sperm heads and *** variants in several genes have been implicated in OAT,its genetic etiologies and pathogenetic mechanisms remain inadequately *** this study,we identified a homozygous nonsense mutation(c.916C>T,***306*)in the coiled-coil domain containing 146(CCDC146)gene in an infertile male patient with *** mutation resulted in the production of a truncated CCDC146 protein(amino acids 1-305),retaining only two out of five coiled-coil *** validate the pathogenicity of the CCDC146 mutation,we generated a mouse model(Ccdc146^(mut/mut))with a similar mutation to that of the ***,the Ccdc146mut/mut mice exhibited infertility,characterized by significantly reduced sperm counts,diminished motility,and multiple defects in sperm heads and ***,the levels of axonemal proteins,including DNAH17,DNAH1,and SPAG6,were significantly reduced in the sperm of Ccdc146^(mut/mut) ***,both human and mouse CCDC146 interacted with intraflagellar transport protein 20(IFT20),but this interaction was lost in the mutated versions,leading to the degradation of *** study identified a novel deleterious homozygous nonsense mutation in CCDC146 that causes male infertility,potentially by disrupting axonemal protein *** findings offer valuable insights for genetic counseling and understanding the mechanisms underlying CCDC146 mutant-associated infertility in human males.

关键词： Oligoasthenoteratozoospermia Human infertility Sperm flagellum CCDC146 Intraflagellar transport IFT20

Large-field objective lens for multi-wavelength microscopy at mesoscale and submicron resolution

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Opto-Electronic Advances 2024年第6期7卷 41-56页

作者： Xin Xu Qin Luo Jixiang Wang Yahui Song Hong Ye Xin Zhang Yi He Minxuan Sun Ruobing Zhang Guohua Shi School of biomedical Engineering(Suzhou) Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China Jiangsu Key Laboratory of Medical Optics Suzhou Institute of Biomedical Engineering and TechnologyChinese Academy of ScienceSuzhou 215163China

Conventional microscopes designed for submicron resolution in biological research are hindered by a limited field of view,typically around 1 *** restriction poses a challenge when attempting to simultaneously analyze various parts of a sample,such as different brain *** addition,conventional objective lenses struggle to perform consistently across the required range of wavelengths for brain imaging in *** we present a novel mesoscopic objective lens with an impressive field of view of 8 mm,a numerical aperture of 0.5,and a working wavelength range from 400 to 1000 *** achieved a resolution of 0.74μm in fluorescent beads *** versatility of this lens was further demonstrated through high-quality images of mouse brain and kidney sections in a wide-field imaging system,a confocal laser scanning system,and a two-photon imaging *** mesoscopic objective lens holds immense promise for advancing multi-wavelength imaging of large fields of view at high resolution.

关键词： mesoscopic objective lens large field-of-view high resolution multi-wavelength wide-field microscopy confocal laser scanning microscopy

维普期刊数据库

MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2024年第11期30卷 1497-1523页

作者： Qi-Ying Wei Feng Jin Zhong-Yu Wang Bing-Jie Li Wen-Bo Cao Zhi-Yan Sun Sai-Jun Mo Department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001Henan ProvinceChina Department of Perioperative Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina division of Special Service Department of Basic OncologySchool of Basic MedicineZhengzhou UniversityZhengzhou 450001Henan ProvinceChina Department of basic Science of Oncology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001Henan ProvinceChina

Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths *** increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality ***,there is currently no specific and effective marker to predict and treat metastasis in ***(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in *** are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of ***,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic *** review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.

关键词： MicroRNAs Esophageal squamous cell carcinoma Metastasis Signaling pathway Epigenetics mechanism

Microfluidic thermotaxic selection of highlymotile sperm and in vitro fertilization

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Bio-Design and Manufacturing 2024年第5期7卷 687-700页

作者： Sihan Chen Jiemin Chen Zihan Qin Jibo Wang Yuwen Wang Rong Liu Wen Zhao Ming Zhang Yuanzhen Zhang Mengcheng Luo Pu Chen Tissue Engineering and Organ Manufacturing(TEOM)Lab Department of Biomedical EngineeringTaiKang Medical School(School of Basic Medical Sciences)Wuhan UniversityWuhan 430071China Hubei Provincial Key Laboratory of Developmentally Originated Disease TaiKangMedical School(School of Basic Medical Sciences)Wuhan UniversityWuhan 430071China Reproductive Medicine Center Zhongnan Hospital of Wuhan UniversityWuhan 430071China TaiKang Center for Life and Medical sciences Wuhan UniversityWuhan 430071China

The selection of the most motile and functionally competent sperm is an essential basis for in vitro fertilization(IVF)and normal embryonic *** adopted clinical approaches for sperm sample processing intensely rely on centrifugation and wash steps that may induce mechanical damage and oxidative stress to *** a few microfluidic sperm sorting devices may avoid these adverse effects by exploiting intrinsic guidance mechanisms of sperm swimming,none of these approaches have been fully validated by clinical-grade assessment *** this study,a microfluidic sperm sorting device that enables the selection of highly motile and functional sperm via their intrinsic thermotaxis is *** by the temperature microenvironment in the fallopian tube during natural sperm selection,a microfluidic device with controllable temperature gradients along the sperm separation channel was designed and *** study investigated the optimal temperature conditions for human sperm selection and fully characterized thermotaxis-selected sperm with 45 human sperm *** indicated that a temperature range of 35–36.5℃along the separation channel significantly improves human sperm motility rate((85.25±6.28)%vs.(60.72±1.37)%;P=0.0484),increases normal sperm morphology rate((16.42±1.43)%vs.(12.55±0.88)%;P<0.0001),and reduces DNA fragmentation((7.44±0.79)%vs.(10.36±0.72)%;P=0.0485)compared to the nonthermotaxis *** thermotaxis is species-specific,and selected mouse sperm displayed the highest motility in response to a temperature range of 36–37.5℃ along the separation ***,IVF experiments indicated that the selected sperm permitted an increased fertilization rate and improved embryonic development from zygote to *** microfluidic thermotaxic selection approach will be translated into clinical practice to improve the IVF success rate for patients with oligozoospermia and asthenozoospermia.

关键词： Microfluidic device Thermotaxis Sperm sorting Assisted reproductive technology In vitro fertilization

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Glaucoma surgery experiments using digital microscope-integrated optical coherence tomography and OCT-compatible instruments

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Journal of Innovative Optical Health sciences 2024年第5期17卷 105-113页

作者： Tianliang Jiang Jinyu Fan Ning Tang Yi He Guohua Shi School of biomedical Engineering(Suzhou)division of Life sciences and Medicine University of Science and Technology of China Hefei 230026 P.R.China Jiangsu Key Laboratory of Medical Optics Suzhou Institute of biomedical Engineering and Technology Chinese Academy of Science Suzhou 215163P.R.China

There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope *** this work,we present a digital microscope-integrated optical coherence tomography(MIOCT)system and several custom-made OCT-compatible instruments for glaucoma *** ophthalmologists were asked to perform trabeculectomy and canaloplasty on live porcine eyes using the system and *** surgery,a subjective feedback survey about the user experience was *** experiment results showed that our system can help surgeons easily locate important tissue structures during *** custom-made instruments also solved the shadowing problem in OCT *** preferred to use the system in their future practice.

关键词： Microscope-integrated optical coherence tomography OCT-compatible instruments glaucoma surgery trabeculectomy canaloplasty

Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

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World Journal of Clinical Cases 2024年第3期12卷 474-478页

作者： Yusuf Tutar Department of basic Pharmaceutical sciences Faculty of PharmacyDivision of BiochemistryUniversity of Health SciencesIstanbul 34668Turkey Health sciences Faculty Recep Tayyip Erdogan UniversityRize 53350Turkey Molecular Oncology division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey Molecular Medicine division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey

In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):*** all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural *** methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized *** is a popular technique for collecting direct mea-surements of metabolic activity from many biological ***,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme *** annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called *** network uses an approach that emphasizes metabolite-gene consensus via biochemical *** metabolomics and genomics data is ***,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical *** The genome and metabolites of biological organisms are not fully characterized with current ***,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug *** network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical ***,clinical data may be integrated to gene expression–metabolite expression by system genetics appr

关键词： Network pharmacology Metabologenomics Genome Pathways Cancer

Cytokine landscapes of pregnancy:mapping gestational immune phases

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Gynecology and Obstetrics Clinical Medicine 2024年第1期4卷 56-64页

作者： Sulagna Dutta Pallav Sengupta Fong Fong Liew basic Medical sciences Department College of MedicineAjman UniversityAjmanUAE Department of biomedical sciences Gulf Medical UniversityAjmanUAE Department of Preclinical sciences Faculty of DentistryMAHSA UniversityKuala LumpurMalaysia

Background Synchronised physiological adaptations occur during pregnancy to achieve systemic,immune and neuroendocrine equilibrium in the mother's body,allowing semiallogenic fetal *** text Depending on the cytokine profile alterations occurring through pregnancy,the latter can be divided into three distinct *** the first immunological phase of pregnancy,proinflammatory cytokines promote inflammatory reactions needed for *** the second phase,a possible change from proinflammatory to anti-inflammatory cytokines creates a symbiosis between maternal and fetal components,ensuring fetal *** the third phase,inflammatory and cytolytic cytokines operate again to reinforce an inflammatory environment for *** article offers a detailed account of immune adaptations during pregnancy and highlights the distinctive cytokine profiles that mark each *** By providing a simplified depiction of pregnancy phases based on cytokine profiles,the article aims to inspire more research in reproductive immunology and improve the management of pregnancy-related inflammation and infection.

关键词： pregnancy mother alterations