1.The Role and Molecular Mechanism of N⁶-methyladenosine Modification in Spermatogenesis
Shi-Qi MENG ; Wen-Ting LU ; Xu CHENG ; Fan YANG ; Chang-Min NIU ; Ying ZHEGN
Progress in Biochemistry and Biophysics 2026;53(5):1297-1312
Spermatogenesis is a highly ordered and spatiotemporally regulated developmental process in the male reproductive system, during which spermatogonial stem cells (SSCs), supported by the seminiferous tubule microenvironment, sequentially undergo mitosis, meiosis, and spermiogenesis to ultimately generate structurally intact spermatozoa. This complex process is accompanied by extensive transcriptional reprogramming, chromatin remodeling, and finely tuned post-transcriptional regulation. Precise control of RNA fate is therefore essential for maintaining the continuity and fidelity of spermatogenesis, and its disruption represents a major molecular basis of male infertility. N6-methyladenosine (m6A), the most abundant internal RNA modification in eukaryotes, has emerged as a critical regulator of post-transcriptional gene expression. m6A methyltransferases (“writers”) catalyze the addition of a methyl group to the N6 position of adenosine, m6A demethylases (“erasers”) remove the modification, and m6A-binding proteins (“readers”) recognize m6A-modified transcripts. Through the coordinated actions of these factors, m6A regulates transcript fate at multiple levels, including RNA splicing, nuclear export, stability, translation, and decay. Emerging evidence indicates that m6A-mediated regulation is essential across multiple stages of spermatogenesis, including SSC self-renewal and differentiation, meiotic progression, maintenance of chromosomal stability, and sperm morphogenesis. Beyond its intrinsic functions in germ cells, m6A also contributes to the regulation of the testicular microenvironment. In sertoli cells, m6A is involved in maintaining blood-testis barrier integrity, RNA processing, and paracrine signaling, thereby providing structural and metabolic support for germ cell development. In Leydig cells, m6A regulates steroidogenesis, particularly testosterone synthesis, and participates in cellular stress responses and metabolic homeostasis. Through these mechanisms, m6A indirectly influences spermatogenesis by modulating the functional state of testicular somatic cells, highlighting an integrated regulatory mode that combines cell-intrinsic and microenvironment-mediated effects. Notably, distinct classes of m6A regulators exhibit pronounced stage-specific functions and coordinated division of labor, collectively forming a multilayered and dynamic regulatory network. Writers often display dosage- and temporal window-dependent effects; erasers contribute to stage-specific demethylation and functional compensation; while readers function through a “switch-buffer” dual-layer architecture, and RNA-binding proteins (RBPs) participate in substrate selection and post-transcriptional regulation. Importantly, emerging evidence suggests that some m6A-related proteins can function through noncanonical mechanisms independent of m6A recognition, such as intrinsic RNA-binding activity, helicase function, or ribonucleoprotein complex assembly, thereby expanding the functional landscape of the m6A regulatory system. Dysregulation of m6A machinery can lead to multiple spermatogenic defects, including impaired SSC self-renewal, meiotic arrest, abnormal chromatin remodeling, and defective sperm formation, ultimately resulting in male infertility. Despite substantial advances, several critical questions remain unresolved, including the distinction between m6A-dependent and -independent mechanisms, the spatiotemporal dynamics of m6A modifications at single-cell resolution, and the coordination and antagonism among different regulatory factors. In this review, we systematically summarize the dual regulation of spermatogenesis by germ cell-intrinsic mechanisms and the testicular microenvironment, and delineate the molecular mechanisms and stage-specific functions of the dynamic m6A regulatory network. We further discuss the current limitations in the field and propose feasible experimental strategies for future investigation. Collectively, this work aims to provide a comprehensive framework for understanding the epitranscriptomic regulation of spermatogenesis and to offer theoretical insights into the pathogenesis and clinical management of male infertility.
2.The Role and Molecular Mechanism of N⁶-methyladenosine Modification in Spermatogenesis
Shi-Qi MENG ; Wen-Ting LU ; Xu CHENG ; Fan YANG ; Chang-Min NIU ; Ying ZHEGN
Progress in Biochemistry and Biophysics 2026;53(5):1297-1312
Spermatogenesis is a highly ordered and spatiotemporally regulated developmental process in the male reproductive system, during which spermatogonial stem cells (SSCs), supported by the seminiferous tubule microenvironment, sequentially undergo mitosis, meiosis, and spermiogenesis to ultimately generate structurally intact spermatozoa. This complex process is accompanied by extensive transcriptional reprogramming, chromatin remodeling, and finely tuned post-transcriptional regulation. Precise control of RNA fate is therefore essential for maintaining the continuity and fidelity of spermatogenesis, and its disruption represents a major molecular basis of male infertility. N6-methyladenosine (m6A), the most abundant internal RNA modification in eukaryotes, has emerged as a critical regulator of post-transcriptional gene expression. m6A methyltransferases (“writers”) catalyze the addition of a methyl group to the N6 position of adenosine, m6A demethylases (“erasers”) remove the modification, and m6A-binding proteins (“readers”) recognize m6A-modified transcripts. Through the coordinated actions of these factors, m6A regulates transcript fate at multiple levels, including RNA splicing, nuclear export, stability, translation, and decay. Emerging evidence indicates that m6A-mediated regulation is essential across multiple stages of spermatogenesis, including SSC self-renewal and differentiation, meiotic progression, maintenance of chromosomal stability, and sperm morphogenesis. Beyond its intrinsic functions in germ cells, m6A also contributes to the regulation of the testicular microenvironment. In sertoli cells, m6A is involved in maintaining blood-testis barrier integrity, RNA processing, and paracrine signaling, thereby providing structural and metabolic support for germ cell development. In Leydig cells, m6A regulates steroidogenesis, particularly testosterone synthesis, and participates in cellular stress responses and metabolic homeostasis. Through these mechanisms, m6A indirectly influences spermatogenesis by modulating the functional state of testicular somatic cells, highlighting an integrated regulatory mode that combines cell-intrinsic and microenvironment-mediated effects. Notably, distinct classes of m6A regulators exhibit pronounced stage-specific functions and coordinated division of labor, collectively forming a multilayered and dynamic regulatory network. Writers often display dosage- and temporal window-dependent effects; erasers contribute to stage-specific demethylation and functional compensation; while readers function through a “switch-buffer” dual-layer architecture, and RNA-binding proteins (RBPs) participate in substrate selection and post-transcriptional regulation. Importantly, emerging evidence suggests that some m6A-related proteins can function through noncanonical mechanisms independent of m6A recognition, such as intrinsic RNA-binding activity, helicase function, or ribonucleoprotein complex assembly, thereby expanding the functional landscape of the m6A regulatory system. Dysregulation of m6A machinery can lead to multiple spermatogenic defects, including impaired SSC self-renewal, meiotic arrest, abnormal chromatin remodeling, and defective sperm formation, ultimately resulting in male infertility. Despite substantial advances, several critical questions remain unresolved, including the distinction between m6A-dependent and -independent mechanisms, the spatiotemporal dynamics of m6A modifications at single-cell resolution, and the coordination and antagonism among different regulatory factors. In this review, we systematically summarize the dual regulation of spermatogenesis by germ cell-intrinsic mechanisms and the testicular microenvironment, and delineate the molecular mechanisms and stage-specific functions of the dynamic m6A regulatory network. We further discuss the current limitations in the field and propose feasible experimental strategies for future investigation. Collectively, this work aims to provide a comprehensive framework for understanding the epitranscriptomic regulation of spermatogenesis and to offer theoretical insights into the pathogenesis and clinical management of male infertility.
3.Research progress on allergenic components in traditional Chinese medicine injections
YANG Wen ; WU Fang ; WANG Cheng ; YANG Xiaoli
Drug Standards of China 2026;27(1):0008-0014
Traditional Chinese medicine (TCM) injections, a hallmark achievement in the modernization of TCM, hold significant importance in advancing the development of TCM and enhancing clinical therapeutic effects. However, with the expanded clinical application of TCM injections, safety concerns have garnered widespread attention, particularly allergic reactions. Numerous researchers have delved into the safety issues of TCM injections. This paper summarized the research related to allergic reactions of TCM injections, including the types of allergic reactions, the allergenic components, their evaluation models and detection methods, as well as the challenges encountered in current research, aiming at providing references and basis for in-depth research and safe application of allergic reactions of TCM injections.
4.Mycobacterium tuberculosis Rv3641c inhibits macrophage type Ⅰ interferon responses and promotes intracellular survival in macrophages
Wen JIN ; Min GENG ; Su-jie HU ; Xin-yang ZHANG ; Wen-qin LI ; Cheng-kun ZHENG ; Xin-an JIAO ; Xiang CHEN ; Zheng-zhong XU
Chinese Journal of Zoonoses 2025;41(4):385-391
This study was aimed at investigating the immunoregulatory function of Mycobacterium tuberculosis Rv3641c gene in modulating host type Ⅰ interferon responses.The shuttle plasmid pMV261 was used to construct Rv3641c overexpression recombinant Mycobacterium smegmatis,and the biological characteristics of the recombinant bacteria were analyzed to explore the effect of Rv3641c on the growth curve,colony morphology and stress resistance of Mycobacterium.Subsequently,RAW264.7 cells were infected with Rv3641c overexpressing Mycobacterium smegmatis,and the transcriptional expression of genes related to the inhibition of type I inter-feron pathway was determined by RT-PCR.The expression level of IFN-βprotein was determined by ELISA,and the intracellular sur-vival level was determined.As a result,the recombinant rMS::pMV261-Rv3641c was successfully constructed.The results of biologi-cal characteristics analysis showed that Rv3641c did not affect the growth of mycobacteria,but significantly changed the colony mor-phology of mycobacteria and improved its resistance to H2O2.The results of recombinant bacteria infection experiments showed that Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1β in host cells,and Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1βin host cells.The results of intracellular colonization experiments showed that the intracellular mycobacte-ria in the overexpression recombinant bacteria infection group were significantly higher than those in the empty vector group,indicat-ing that Rv3641c could promote the intracellular surviv al of mycobacteria.In summary,the Rv3641c gene of M.tuberculosis can inhibit the host type I interferon response and promote the intracellular survival of M.tuberculosis,which provides a new idea for further explor-ing the immune escape function of M.tuberculosis and the discovery of new targets for anti-tuberculosis drugs.
5.Isolation,identification,and analysis of drug resistance and virulence genes in Escherichia coli isolated from artificially bred sika deer
Cheng-yang ZHANG ; Xue JI ; Bo-wen JIANG ; Bing LIANG ; Rong-lei HUANG ; Chong-tao DU ; Yang SUN
Chinese Journal of Zoonoses 2025;41(5):522-528
To understand the background of Escherichia coli(E.coli)carried by artificially bred sika deer and the biological characteristics of the isolated strains,such as drug resistance and pathogenicity,in April 2024,we collected 184 fresh deer fecal samples from four deer farms in Luxiang Township,Shuangyang District,Changchun City,Jilin Province,for isolation and cultivation of E.coli.The isolates were tested for drug resistance and biochemical identification with a BD PhoenixTM-100 Automated Microbiology System.The virulence genes were detected with PCR,and the strains were molecularly typed with ERIC-PCR.A total of 165 E.coli strains were isolated from 184 samples of deer feces,with an isolation rate of 89.67%.Twenty strains had a drug resistance phenotype,and the drug resistance rate was 12.12%;these strains included 15 strains of multi-drug resistant bacteria and 11 strains of ESBL-producing bacteria.Virulence gene detection indicated that the sika deer isolates carried multiple diarrhea-associated virulence genes,such as EAST-1(12.12%),eae(1.21%),stx1(7.88%),stx2(7.27%),and STa(1.82%).ERIC-PCR demonstrated that the isolates showed high polymorphism.The ESBL-producing E.coli carried by sika deer are likely to spread drug resistance in the community and livestock population.Some isolates carried multiple diarrhea-associated virulence genes,thus posing a human transmission risk.Therefore,monitoring of drug resistance and virulence genes must be strengthened,and antibiotics must be used reasonably during the breeding process to avoid excessive use and misuse.
6.Radial artery hemostatic device applied in trans-brachial coronary intervention
Ning WANG ; Guan-liang CHENG ; Liang WANG ; Quan YANG ; Wen-chao ZHANG
Chinese Journal of Interventional Cardiology 2025;33(4):195-200
Objective To investigate the safety and efficacy of the radial artery hemostatic device in trans-brachial coronary intervention,and assess its effectiveness.Methods A retrospective analysis was conducted on patients who underwent trans-brachial coronary intervention at Peking University International Hospital from January 1,2018 to December 31,2023.The patients were divided into the radial artery hemostatic device group(170 cases)and the conventional compression group(100 cases)based on the postoperative hemostasis method,and the incidence of complications and clinical characteristics were compared between the two groups.Results A total of 270 patients underwent trans-brachial coronary intervention,with 18 complications occurring.Among them,17 cases were hemorrhage around the puncture site(16 cases were mild and 1 case was severe)and 1 was transient median nerve injury.The overall complication rate was 6.7%,and the incidence of hemorrhage around the puncture site was 6.3%.The hemorrhage rate in the radial artery hemostatic device group was 5.9%,while that in the conventional compression group was 7.0%,with no statistically significant difference between the two groups(P=0.715).Multivariate regression analysis indicated that female was an independent risk factor for hemorrhage around the puncture site(OR 4.57,95%CI 1.40-14.96,P=0.012).With the accumulation of technology,the application of trans-brachial access and radial artery hemostatic devices increased year by year(both P<0.010).Conclusions The radial artery hemostatic device effectively controls bleeding in trans-brachial coronary interventions and demonstrates satisfactory safety.Its simplicity and efficacy provide a new strategy for hemostatic management in percutaneous trans-brachial access,which may gradually become the new standard in the future.
7.Isolation,identification,and analysis of drug resistance and virulence genes in Escherichia coli isolated from artificially bred sika deer
Cheng-yang ZHANG ; Xue JI ; Bo-wen JIANG ; Bing LIANG ; Rong-lei HUANG ; Chong-tao DU ; Yang SUN
Chinese Journal of Zoonoses 2025;41(5):522-528
To understand the background of Escherichia coli(E.coli)carried by artificially bred sika deer and the biological characteristics of the isolated strains,such as drug resistance and pathogenicity,in April 2024,we collected 184 fresh deer fecal samples from four deer farms in Luxiang Township,Shuangyang District,Changchun City,Jilin Province,for isolation and cultivation of E.coli.The isolates were tested for drug resistance and biochemical identification with a BD PhoenixTM-100 Automated Microbiology System.The virulence genes were detected with PCR,and the strains were molecularly typed with ERIC-PCR.A total of 165 E.coli strains were isolated from 184 samples of deer feces,with an isolation rate of 89.67%.Twenty strains had a drug resistance phenotype,and the drug resistance rate was 12.12%;these strains included 15 strains of multi-drug resistant bacteria and 11 strains of ESBL-producing bacteria.Virulence gene detection indicated that the sika deer isolates carried multiple diarrhea-associated virulence genes,such as EAST-1(12.12%),eae(1.21%),stx1(7.88%),stx2(7.27%),and STa(1.82%).ERIC-PCR demonstrated that the isolates showed high polymorphism.The ESBL-producing E.coli carried by sika deer are likely to spread drug resistance in the community and livestock population.Some isolates carried multiple diarrhea-associated virulence genes,thus posing a human transmission risk.Therefore,monitoring of drug resistance and virulence genes must be strengthened,and antibiotics must be used reasonably during the breeding process to avoid excessive use and misuse.
8.Mechanisms and intervention strategies of aging based on epigenetics
Li-yuan ZHANG ; Hao-nan SHI ; Wen-feng ZHANG ; Ming-qian ZHANG ; Zi-yang ZHAO ; Zhen-zhen CHENG ; Ti ZHANG ; Zhen-teng YAN ; Jian-ning SUN ; Shi-fen DONG
Chinese Pharmacological Bulletin 2025;41(12):2230-2235
Aging is comprehensively influenced by multiple fac-tors such as internal genes,cellular metabolism,external envi-ronment,and lifestyle habits.Among them,epigenetic regula-tion plays a core role.Epigenetic modifications,including DNA methylation,histone modification,heterochromatin remodeling,and non-coding RNA regulation,act in concert with the three-di-mensional genome architecture to precisely regulate gene expres-sion.This review elaborates on the factors influencing epigenetic regulation,as well as the mechanisms of how epigenetics affects the occurrence of organismal aging and the corresponding inter-vention strategies,providing relevant insights for uncovering the mechanisms of aging and preventing/treating aging-related disea-ses.
9.Research on the anti-hepatocellular carcinoma activity and mechanisms of glycyrrhetinic acid derivatives
Xu-xin CUI ; Wen-ping CUI ; Yan-xing BI ; Fan CHENG ; Yu-ning LI ; Bao-lai ZHANG ; Quan-yi ZHAO ; Xiao-lai YANG
Chinese Pharmacological Bulletin 2025;41(11):2150-2157
Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.
10.Radial artery hemostatic device applied in trans-brachial coronary intervention
Ning WANG ; Guan-liang CHENG ; Liang WANG ; Quan YANG ; Wen-chao ZHANG
Chinese Journal of Interventional Cardiology 2025;33(4):195-200
Objective To investigate the safety and efficacy of the radial artery hemostatic device in trans-brachial coronary intervention,and assess its effectiveness.Methods A retrospective analysis was conducted on patients who underwent trans-brachial coronary intervention at Peking University International Hospital from January 1,2018 to December 31,2023.The patients were divided into the radial artery hemostatic device group(170 cases)and the conventional compression group(100 cases)based on the postoperative hemostasis method,and the incidence of complications and clinical characteristics were compared between the two groups.Results A total of 270 patients underwent trans-brachial coronary intervention,with 18 complications occurring.Among them,17 cases were hemorrhage around the puncture site(16 cases were mild and 1 case was severe)and 1 was transient median nerve injury.The overall complication rate was 6.7%,and the incidence of hemorrhage around the puncture site was 6.3%.The hemorrhage rate in the radial artery hemostatic device group was 5.9%,while that in the conventional compression group was 7.0%,with no statistically significant difference between the two groups(P=0.715).Multivariate regression analysis indicated that female was an independent risk factor for hemorrhage around the puncture site(OR 4.57,95%CI 1.40-14.96,P=0.012).With the accumulation of technology,the application of trans-brachial access and radial artery hemostatic devices increased year by year(both P<0.010).Conclusions The radial artery hemostatic device effectively controls bleeding in trans-brachial coronary interventions and demonstrates satisfactory safety.Its simplicity and efficacy provide a new strategy for hemostatic management in percutaneous trans-brachial access,which may gradually become the new standard in the future.

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