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.Evaluation progress of the application of staplers in thoracoscopic lung surgery
Shenghui LI ; Yijiu REN ; Hang SU ; Minglei YANG ; Guofang ZHAO ; Yongxiang SONG ; Xuefei HU ; Deping ZHAO ; Qi XUE ; Chang CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):709-713
Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.
4.μQFR after target vessel pretreatment can predict the occurrence of VOCE events in patients with de novo coronary artery disease treated with drug-coated balloon
Yueming YAO ; Guoli ZHAO ; Qunxing LI ; Jie YANG ; Yuan CHANG ; Chunyuan JIANG ; Qi CHENG ; Jiayu LIU ; Xianzhen PENG ; Delu YIN
Chinese Journal of Arteriosclerosis 2025;33(6):523-530
Aim To investigate the predictive value of the Murray law-based quantitative flow ratio(μQFR)after target vessel pretreatment for vascular-related adverse events in patients with de novo coronary lesions treated with drug-coated balloon.Methods This retrospective study included 223 lesions from 223 patients who underwent drug-coated balloon-only strategy and completed 2-year clinical follow-up.Coronary angiographic images of target vessels pre-procedure,post-balloon and post-procedure were collected,and analyzed using a novel Murray's law-based algorithm.The μQFR analysis of each target vessel included not only the μQFR value of the target vessel,but also the length of the target vessel,the degree of vessel diameter stenosis,the reference lumen diameter,the minimum lumen diameter and blood flow velocity.The primary endpoint was defined as the postoperative vessel-oriented composite endpoint(VOCE).Results During the2-year clinical follow-up period,a total of 25 patients(11.2%)experienced VOCE events.Com-pared with the control group,patients with VOCE events after pretreatment showed a decrease in μQFR(P<0.001).Multivariate Logistic analysis showed that a lower target vessel μQFR after pretreatment(OR=0.931,95%CI:0.894~0.969,P<0.001)was an independent predictor of VOCE events.ROC curve analysis showed that the cut-off value for predicting 2-year VOCE events using preprocessed μQFR was 0.83(95%CI:0.727~0.840),with a sensitivity of 72.7%and a specificity of 84.0%(AUC=0.773,95%CI:0.676~0.870,P<0.001).Survival analysis showed that compared with patients with μQFR>0.83,patients with μQFR≤0.83 had a significantly higher incidence of VOCE events at 1 and 2 years,increasing to 3.909 times(16.9%vs.4.6%,HR=3.909,95%CI:1.539~9.930,P=0.004)and 2.867 times(19.7%vs.7.2%,HR=2.867,95%CI:1.301~6.316,P=0.009).After adjusting for potential con-founds,patients with pretreated μQFR≤0.83 had a 2.567 times in 2-year incidence of VOCE events(HR=2.567,95%CI:1.151~5.727,P=0.021)and a 3.712 times in 1-year incidence of VOCE events(HR=3.712,95%CI:1.478~9.810,P=0.006)compared to patients with good pretreatment.Conclusions For patients with in situ coronary artery disease,a lower μQFR after pretreatment increases the risk of postoperative adverse clinical events.μQFR≤0.83 may be used to evaluate the effectiveness of lesion pretreatment.
5.Study on performance evaluation method for lubricating coatings of intravascular catheters
Hong-jian CHEN ; Chong-chong AI ; Yuan-yu LI ; Li-ping HUANG ; Jia-qi NIE ; Chang-bin WANG ; Qian YANG ; Yu-xin BI ; Wen-bo LU
Chinese Medical Equipment Journal 2025;46(1):66-72
Three evaluation methods were recommended for the key properties of the intravascular catheter lubricating coating such as stability,lubricity and integrity,including insoluble particle test method,friction test procedure and appearance detection method.Fifteen batches of microcatheters produced by different manufacturers were selected for testing to clarify the three methods in test principle,step,result,characteristic.References were provided for the design,production,evaluation and regulation of intravascular catheters with lubricant coatings.[Chinese Medical Equipment Journal,2025,46(1):66-72]
6.Roles and mechanisms of TRIM family proteins in the regulation of bone metabolism.
Jing YANG ; Rui-Qi HUANG ; Ke XU ; Mian-Mian YANG ; Xue-Jie YI ; Bo CHANG ; Ting-Ting YAO
Acta Physiologica Sinica 2025;77(3):472-482
Tripartite motif-containing (TRIM) family proteins are crucial E3 ubiquitin ligases that have garnered significant attention for their regulatory roles in bone metabolism in recent years. This article reviews the function and regulatory mechanisms of TRIM family proteins in bone metabolism, focusing on their dual roles in bone formation and resorption. It also provides a detailed analysis of signaling pathways and molecular mechanisms by which TRIM family members regulate the activities of osteoblasts and osteoclasts. Research findings suggest that modulating the expression or activity of TRIM family proteins could be beneficial for treating bone diseases such as osteoporosis. This review highlights the molecular mechanisms of TRIM family members in bone physiology and pathology, aiming to provide theoretical basis and scientific guidance for developing novel therapeutic strategies for bone diseases.
Humans
;
Ubiquitin-Protein Ligases/physiology*
;
Bone and Bones/metabolism*
;
Animals
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Tripartite Motif Proteins/physiology*
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Osteoclasts/metabolism*
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Osteoblasts/metabolism*
;
Signal Transduction/physiology*
;
Osteogenesis/physiology*
7.Establishment of tissue culture and rapid propagation system of Artemisia stolonifera.
Chu WANG ; Ya XU ; Yang XU ; Ye WANG ; Na-Na CHANG ; Lu-Qi HUANG ; Hui LI
China Journal of Chinese Materia Medica 2025;50(11):2994-3000
As a high-quality moxibustion material, Artemisia stolonifera has high economic value and research prospects. However, due to difficulties in seed germination, its wild germplasm resources are sparsely distributed in China. This study used young stem segments grown in the current year to investigate the effects of explant sterilization, different combinations and concentrations of plant growth regulators on the proliferation and rooting of adventitious shoots, with the aim of constructing an in vitro rapid propagation technology system for A. stolonifera. The results showed that the lowest contamination rate of 25.83% was achieved when sterilizing the stem segments by rinsing with running water for 30 min, soaking in 75% ethanol for 30 s, followed by a 5 min treatment with 0.1% HgCl_2, 10 min with 8% NaClO, and 10 min with 0.6% phytosaniline. There was no browning of the stem segments, and surface sterilization of the A. stolonifera stem segments was successfully achieved. In the induction culture phase, when the concentration of kinetin(KT) was 0.05 mg·L~(-1) and 6-benzylaminopurine(6-BA) was 0.05 mg·L~(-1), the adventitious shoot proliferation coefficient was 2.02, effectively promoting the proliferation and growth of A. stolonifera. In the rooting culture phase, 0.1 mg·L~(-1) 1-naphthaleneacetic acid(NAA) effectively induced A. stolonifera test-tube seedlings to root within a short period, achieving a rooting rate of 100%. The addition of a small amount of activated charcoal also promoted rooting and strengthened seedling growth. The survival rate of A. stolonifera seedlings transplanted into a substrate consisting of 90% nutrient soil and 10% perlite was 100%. This study established an efficient in vitro rapid propagation system for A. stolonifera, overcoming difficulties with seed germination, shortening the breeding cycle, and reducing production and planting costs. It provides technical support for the introduction, domestication, seedling propagation, germplasm conservation, and industrial development of A. stolonifera.
Artemisia/drug effects*
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Tissue Culture Techniques/methods*
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Plant Growth Regulators/pharmacology*
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Plant Stems/drug effects*
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Plant Shoots/drug effects*
8.In Situ Analysis of Per-and Polyfluoroalkyl Substances Distribution Characteristics in Water-Sediment System Using Diffusive Gradients in Thin Films Probe
Qi-Si CAI ; Xing-Ying LI ; Fang ZHANG ; Jun-Wei YANG ; Si-Si LIU ; Chang-Er CHEN
Chinese Journal of Analytical Chemistry 2025;53(2):300-310,后插1-后插9
The water-sediment interface is an important zone for the migration and transformation of chemical substances,but traditional sampling methods make in situ sampling challenging,thus it is difficult to capture information on environmental processes at the micro-scale.In this study,diffusive gradients in thin films(DGT)probe technique was used as in situ tool to detect 18 kinds of typical per-and polyfluoroalkyl substances(PFAS)in the water-sediment system,elucidating their vertical distribution characteristics and patterns.The results showed that different PFAS exhibited distinct variation patterns with depth in water and sediment.Short-chain PFAS exhibited greater mobility,while the migration of long-chain PFAS was restricted in sediment and pore water due to their strong hydrophobicity and adsorption capacity,resulting in relatively small concentration changes in the sediment column.The PFAS concentrations measured by DGT ranged from 11.2 μg/L to 1305 μg/L.For long-chain PFAS,the concentrations measured by DGT were higher than those obtained from direct measurement of water and pore water,while the opposite results were obtained for short-chain PFAS.The DGT results indicated that although long-chain PFAS exhibited strong adsorption to sediment particles,the adsorbed PFAS were still bioavailable.DGT probe technique,with its advantages of in situ sampling and high spatial resolution,provides deep insights into the complex environmental processes occurring at the microscale in the water-sediment systems.DGT offers important technical support and scientific evidence for assessing the adsorption-desorption behavior,bioavailability,and ecological risks of these emerging pollutants in aquatic environment.
9.Predictive value of dose-surface histogram for acute radiation proctitis in prostate cancer patients following radiotherapy
Xin ZHAO ; Mei-Liu YANG ; Xiao-Hui HAO ; Tian-Xiong WEI ; Qi ZHANG ; Hao-Yu CHANG ; Xiu-Xia WU
Medical Journal of Chinese People's Liberation Army 2025;50(1):44-49
Objective To evaluate the predictive value of dose-surface histogram(DSH)for radiation proctitis(RP)in prostate cancer(PCa)patients undergoing radiotherapy.Methods This prospective randomized controlled clinical trial included 380 PCa patients who underwent image-guided radiotherapy in the First Affiliated Hospital of Hebei Northern University from January 2018 to January 2023.Patients were randomly divided into observation group(n=200)and control group(n=180).The rectal dose distribution of patients in the two groups was evaluated by using DSH and dose-volume histogram(DVH),respectively.The receiver operating characteristic(ROC)curve was utilized to evaluate the predictive value of DSH for acute RP,with DVH serving as a reference.Results The difference was not statistically significant in clinical information such as age,KPS score,and body mass index(BMI)between the observation and control groups(P>0.05),as well as in acute RP incidence(P>0.05).There were significant differences in S40 and V40,S50 and V50,S60 and V60,S70 and V70,and S78 and V78 between the two groups(P<0.05).S40,S50,V40,and V50 showed low efficacy(P<0.001)in predicting acute RP at each level,with AUC≤0.700.S60 and V60 showed moderate efficacy(P<0.001)in predicting acute RP at each level,with AUC 0.700-0.900.S70,S78,V70 and V78 showed high efficacy(P<0.001)in predicting acute RP at each level,with AUC>0.900.Conclusions The predictive value of DSH for rectal toxicity in patients with PCa is basically consistent with that of DVH.It is expected to become a novel and valuable tool for evaluating radiotherapy plans in the future.
10.Qingda Granule Attenuates Hypertension-Induced Cardiac Damage via Regulating Renin-Angiotensin System Pathway.
Lin-Zi LONG ; Ling TAN ; Feng-Qin XU ; Wen-Wen YANG ; Hong-Zheng LI ; Jian-Gang LIU ; Ke WANG ; Zhi-Ru ZHAO ; Yue-Qi WANG ; Chao-Ju WANG ; Yi-Chao WEN ; Ming-Yan HUANG ; Hua QU ; Chang-Geng FU ; Ke-Ji CHEN
Chinese journal of integrative medicine 2025;31(5):402-411
OBJECTIVE:
To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved.
METHODS:
Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively.
RESULTS:
The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01).
CONCLUSIONS
Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals
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Drugs, Chinese Herbal/therapeutic use*
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Hypertension/pathology*
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Renin-Angiotensin System/drug effects*
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Rats, Inbred SHR
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Oxidative Stress/drug effects*
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Male
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Rats, Inbred WKY
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Blood Pressure/drug effects*
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Myocardium/pathology*
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Rats
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Inflammation/pathology*

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