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 in chemical constituents and pharmacological activities of Abelmoschi Corolla and prediction of its quality markers.
Shi-Han GUAN ; Chang LIU ; Xiao-Tong YAN ; Jin-Wei HAN ; Feng-Ting YIN ; Hui SUN ; Guang-Li YAN ; Ling KONG ; Ying HAN ; Xi-Jun WANG
China Journal of Chinese Materia Medica 2025;50(4):908-921
Abelmoschi Corolla, the dried corolla of Abelmoschus manihot, has anti-inflammatory, antioxidant, and anti-fibrosis activities. Its chemical constituents mainly include flavonoids, organic acids, steroids, and polysaccharides. This study reviewed the research progress in the chemical constituents and pharmacological activities of Abelmoschi Corolla in recent 20 years. According to the concept of quality marker(Q-marker), the Q-markers of Abelmoschi Corolla were predicted from plant phylogeny, chemical constituent specificity, traditional efficacy, chemical constituent measurability, and absorbed constituents. The primary Q-markers for Abelmoschi Corolla were anticipated to include quercetin-3'-O-β-D-glucopyranoside, gossypetin-8-O-β-D-glucuronide, isoquercetin, myricetin,quercetin, and hyperoside, with the aim of providing reference data for improving the quality evaluation system of Abelmoschi Corolla.
Abelmoschus/chemistry*
;
Drugs, Chinese Herbal/pharmacology*
;
Flowers/chemistry*
;
Humans
;
Animals
;
Quality Control
;
Flavonoids/chemistry*
4.Pharmaceutical process omics and its applications and prospects in drug quality control.
Yu-Ting LU ; Jia-Yu YANG ; Ying-Ting SHI ; Xin-Yuan XIE ; Jian-Yang PAN ; Hai-Bin QU
China Journal of Chinese Materia Medica 2025;50(13):3628-3634
The quality of drugs is a crucial premise for ensuring the safety and effectiveness of clinical medication, while quality control during the pharmaceutical process directly affects the quality and consistency of the final product formulation. However, there is a lack of a comprehensive and scientific system for assessing and optimizing the quality control level during the manufacturing process in the field of drug quality control. Therefore, this study proposed the concept of "pharmaceutical process omics", clarified its advantages in guiding drug production, and explored in depth the research approaches, diverse analytical techniques, and broad range of applications in drug quality control. In addition, this study anticipated the broad application prospects of pharmaceutical process omics in the field of drug quality control, aiming to provide a scientific basis for the development of pharmaceutical process quality control standards.
Quality Control
;
Humans
;
Drugs, Chinese Herbal/chemistry*
5.Research Progress in Copper Homeostasis and Diseases.
Shu-Ting QIU ; Xiao-Hua TAN ; Shi-Han SHAO ; Li YU ; Ying-Ying ZHANG ; Yue-Jia CAO ; Di CHUN-HONG
Acta Academiae Medicinae Sinicae 2025;47(1):102-109
As an indispensable trace element in the human body,copper plays an important role in various physiological and biochemical reactions.The dyshomeostasis of copper leads to the disorder of copper metabolism and the occurrence of related diseases.Cuproptosis,a newly proposed regulatory cell death mode,is different from the known apoptosis,pyroptosis,necroptosis,and ferroptosis.Recent studies have found that the dyshomeostasis of copper has been observed in a variety of cancers.Therefore,targeting copper for disease treatment may become a new strategy and a new idea.This article systematically summarizes the fundamental properties of copper,copper dyshomeostasis-related diseases (Menkes syndrome,Wilson's disease,and cancer) and their treatment,and reviews the research progress in cuproptosis.
Humans
;
Copper/metabolism*
;
Homeostasis
;
Neoplasms/metabolism*
;
Hepatolenticular Degeneration/metabolism*
;
Menkes Kinky Hair Syndrome/metabolism*
6.Advances in the Studies of MicroRNA-1976 in Aberrant Cell Cycle Diseases.
Hao-Yu JI ; Hao CHEN ; Liang SHI ; Meng ZHANG ; Ting CHEN ; Ying-Ming KONG ; Rong-Ke FENG
Acta Academiae Medicinae Sinicae 2025;47(4):644-650
Most tumor cells and healthy neurons are at rest during G0 phase.Once the cell cycle is abnormally re-entered under certain conditions,the proliferation of tumor cells and the degenerative necrosis of neurons can be initiated.From the perspective of the cell cycle,cancer and central nervous system diseases,two seemingly different disease types,have a common pathogenesis.This type of diseases is named aberrant cell cycle diseases.As a newly discovered microRNA(miR),miR-1976 is closely related to the regulation of the cell cycle.This review summarizes the progress in the research on miR-1976 in cancer and central nervous system diseases,aiming to provide a reference for the clinical application of miR-1976 in aberrant cell cycle diseases in the future.
MicroRNAs/genetics*
;
Humans
;
Cell Cycle/genetics*
;
Neoplasms/genetics*
;
Central Nervous System Diseases/genetics*
7.Clinical features and variant spectrum of FGFR3-related disorders.
Shi-Li GU ; Ling-Wen YING ; Guo-Ying CHANG ; Xin LI ; Juan LI ; Yu DING ; Ru-En YAO ; Ting-Ting YU ; Xiu-Min WANG
Chinese Journal of Contemporary Pediatrics 2025;27(10):1259-1265
OBJECTIVES:
To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders.
METHODS:
Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH).
RESULTS:
Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge.
CONCLUSIONS
ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans
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Receptor, Fibroblast Growth Factor, Type 3/genetics*
;
Child
;
Male
;
Child, Preschool
;
Female
;
Infant
;
Adolescent
;
Dwarfism/genetics*
;
Achondroplasia/genetics*
;
Lordosis/genetics*
;
Infant, Newborn
;
Retrospective Studies
;
Genetic Association Studies
;
Bone and Bones/abnormalities*
;
Phenotype
;
Limb Deformities, Congenital
8.Autonomous drug delivery and scar microenvironment remodeling using micromotor-driven microneedles for hypertrophic scars therapy.
Ting WEN ; Yanping FU ; Xiangting YI ; Ying SUN ; Wanchen ZHAO ; Chaonan SHI ; Ziyao CHANG ; Beibei YANG ; Shuling LI ; Chao LU ; Tingting PENG ; Chuanbin WU ; Xin PAN ; Guilan QUAN
Acta Pharmaceutica Sinica B 2025;15(7):3738-3755
Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO2 bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.
9.Bufotaline Enhances the Sensitivity of Pancreatic Cancer Cells to Adriamycin Treatment by Inhibiting DNA Damage Repair
Ming-Wen YIN ; Shu-Ting HAN ; Jiao XUE ; Jun-Jie MIAO ; Shi-Ying ZHAO ; Ze YU ; Jing JIN
Chinese Journal of Biochemistry and Molecular Biology 2025;41(10):1410-1420
Pancreatic cancer has emerged as one of the most challenging malignancies worldwide,with its high resistance to chemotherapy being the primary cause of treatment failure.Therefore,enhancing the chemosensitivity of pancreatic cancer has become a major focus of current research.In this study,we in-vestigated how Bufotaline,a bufadienolide extracted from the traditional Chinese medicine toad venom,exhibits its antitumor activity.Specifically,we explored the potential of Bufotaline to enhance the chemo-sensitivity of pancreatic cancer cells to Adriamycin and elucidated its underlying molecular mechanisms.Using CCK-8 and colony formation assays,we demonstrated that Bufotaline enhances the inhibitory effect of Adriamycin on the survival of pancreatic cancer cell lines Patu-8988T,Aspc-1,and Patu-8988S.No-tably,Bufotaline treatment reduced the IC50 of Adriamycin in drug-resistant pancreatic cancer cells to lev-els comparable to those in non-resistant cells.Results from Western blot,immunofluorescence,comet as-say,and TUNEL assays revealed that Bufotaline promotes Adriamycin-induced DNA damage in pancreatic cancer cells.RNA-seq analysis of Patu-8988T cells treated with Adriamycin alone or in combination with Bufotaline showed significant changes in gene expression,and qRT-PCR analysis further confirmed that Bu-fotaline downregulates the expression of DNA damage repair proteins NBS1 and RAD50.Moreover,Western blot analysis revealed that Bufotaline reduces the levels of DNA damage response repair proteins,and Im-munofluorescence experiments indicated that Bufotaline inhibits the activation of the ATM/CHK2 signaling pathway.Finally,in a subcutaneous xenograft mouse model,the combination of Adriamycin and Bufotaline treatment significantly suppressed pancreatic cancer cell growth.In conclusion,Bufotaline enhances Adria-mycin-induced chemosensitivity in pancreatic cancer cells;the combination of Adriamycin and Bufotaline downregulates the expression of DNA damage response repair proteins NBS1 and RAD50,and inhibits the ATM/CHK2-mediated DDR signaling pathway,thereby delaying DNA damage repair.
10.Effect of Guanxinning injection on myocardial infarction by regulating cardiac immunity through CCL21
Yu-xin BAI ; Ying-xue ZHANG ; Ting-ting SHI ; Si-nan ZHU ; Zhen-kun XU ; Hong WANG ; Lu CHEN
Chinese Pharmacological Bulletin 2025;41(5):960-969
Aim To investigate the mechanism of Guanxinning injection regulating cardiac immune mi-croenvironment to improve myocardial infarction in mice.Methods In this study,MI model was estab-lished by permanent ligation of left anterior descending coronary artery in mice.The mice were divided into five groups:sham operation group,model group,Guanxinning injection low dose group,Guanxinning in-jection high dose group and positive drug captopril group.Hearts were weighed,heart tissues were collect-ed,and Masson staining was used for pathological anal-ysis of heart tissues;immunofluorescence staining was used to detect apoptosis and CCL21 expression in the infarct border zone;flow cytometry was used to detect the proportion of immune cells in myocardial ischemia tissues and lymph nodes;PCR was used to detect CCL21 expression in heart and in vitro human lymphat-ic endothelial cells(HLEC).Results Compared with the model group,the low and high dose groups of Guanxinning injection significantly improved cardiac hypertrophy.Apoptosis in the border zone of myocardi-al infarction was reduced in the low and high dose groups of Guanxinning injection and captopril group.Compared with the model group,the proportion of leu-kocytes in the infarct border zone was dreduced and the proportion of CD4+T cells,Treg cells,and CD8+T cells in the mediastinal lymph nodes and infarct border zone of the heart was regulated in the low and high dose groups of Guanxinning injection;CCL21 secretion by the heart and lymphatic vessels increased.Conclu-sions Guanxinning injection can significantly improve cardiac hypertrophy and fibrosis in MI mice,reduce ap-optosis in the infarct border zone,and play a role in an-ti-myocardial ischemia injury by promoting CCL21 ex-pression in lymphatic vessels to regulate the proportion of mediastinal lymph nodes and cardiac T cells after myocardial infarction.

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