1.Necroptosis in Exercise-induced Skeletal Muscle Damage: Roles and Regulatory Mechanisms
Zhi-Fei KE ; Wen-Jing SONG ; Yun-Feng DONG ; Hua-Yu SHANG
Progress in Biochemistry and Biophysics 2026;53(7):1884-1895
Exercise-induced muscle damage (EIMD) is a frequent form of skeletal muscle microdamage that occurs after high-intensity, prolonged, or unaccustomed exercise, especially exercise dominated by eccentric contractions. It is commonly characterized by delayed-onset muscle soreness, transient loss of muscle strength, local inflammation, structural disruption of myofibers, and delayed functional recovery. Although mild EIMD may serve as a stimulus for training adaptation, excessive or insufficiently recovered muscle damage can impair exercise performance, disturb training continuity, and reduce participation in physical activity. Therefore, clarifying the molecular mechanisms that underlie the initiation, amplification, and resolution of EIMD is important for optimizing athletic training, improving post-exercise recovery, and guiding evidence-based public fitness practice. Necroptosis is a regulated form of programmed cell death mediated primarily by the receptor-interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling axis. Recent studies have shown that necroptosis is closely involved in tissue injury, sterile inflammation, and repair remodeling. However, whether necroptosis acts as an initiating driver, a secondary damage amplifier, or an adaptive signal required for repair after EIMD remains unclear. This review aimed to summarize the potential role of necroptosis in EIMD and to establish a mechanistic framework linking regulated cell death, inflammatory amplification, immune regulation, and skeletal muscle repair. Relevant studies concerning EIMD, necroptosis, RIPK1/RIPK3/MLKL signaling, damage-associated molecular patterns (DAMPs), inflammatory responses, immune cell recruitment, extracellular matrix remodeling, and muscle regeneration were reviewed and integrated. On this basis, the possible temporal and functional involvement of necroptosis in different phases of EIMD was analyzed. The main evidence summarized in this review suggests that EIMD is not merely a consequence of primary mechanical disruption. Instead, it develops through a dynamic sequence that includes sarcolemmal instability, calcium overload, mitochondrial dysfunction, oxidative stress, inflammatory mediator production, immune cell infiltration, necrotic tissue clearance, and regeneration-associated remodeling. Necroptosis may participate in this process through at least two interconnected mechanisms. First, in the early or progressive phase of EIMD, activation of the RIPK1/RIPK3/MLKL signaling axis may promote MLKL phosphorylation and plasma membrane permeabilization, leading to the release of DAMPs such as high-mobility group box 1, ATP, mitochondrial DNA, and other intracellular components. These signals may activate innate immune pathways, amplify inflammatory cytokine production, and enhance the recruitment of neutrophils and macrophages, thereby aggravating secondary inflammation and extending muscle fiber injury. Second, during the resolution and repair phases, necroptosis-related signaling may also contribute indirectly to the formation of a regenerative microenvironment. By influencing the clearance of necrotic debris, the recruitment and phenotypic transition of immune cells, and the remodeling of extracellular matrix components, necroptosis may affect satellite cell activation, myogenic repair, and the eventual structural and functional recovery of injured skeletal muscle. Thus, the biological effect of necroptosis in EIMD may be context dependent rather than uniformly harmful. Its outcome may depend on exercise intensity, the extent of tissue damage, the timing of pathway activation, the involved cell types, inflammatory status, training background, age, and metabolic condition. In conclusion, necroptosis may represent an important molecular link between skeletal muscle injury, sterile inflammation, and tissue repair after damaging exercise. It may exert a dual role in EIMD by amplifying secondary damage while also contributing to repair coordination under appropriate temporal and microenvironmental conditions. Future studies should determine the activation pattern of RIPK1/RIPK3/MLKL signaling after different exercise protocols, identify the major cell populations undergoing necroptosis in injured skeletal muscle, and examine whether targeted modulation of necroptosis can reduce excessive inflammation without impairing necessary regenerative responses. This review provides a theoretical basis for understanding the pathogenesis of EIMD and for developing targeted strategies to improve skeletal muscle recovery after exercise-induced injury.
2.Exploring the evolution of nutritional support strategies for acute pancreatitis from ESPEN guidelines
Chan-Juan CHEN ; Zi-Qi LIN ; Guo-Qing ZHANG ; Ke FENG ; Wen HU ; Zhi-Yong RAO
Parenteral & Enteral Nutrition 2025;32(4):246-251
Acute pancreatitis(AP)is a common digestive disorder associated with moderate to high nutritional risks,necessitating timely nutritional support.Over the past five decades,medical nutrition therapy for AP has undergone a paradigm shift,transitioning from traditional fasting based on the"pancreatic rest theory"to the current emphasis on early enteral feeding to"awaken the gut."Currently,nutritional treatment has become a cornerstone of comprehensive AP management.The European Society for Clinical Nutrition and Metabolism(ESPEN),founded in 1980,is a leading professional organization dedicated to advancing research,clinical practice,and education in clinical nutrition and metabolism.To date,ESPEN has published five evidence-based guidelines on nutritional management in pancreatic diseases.This article reviews the evolution of AP nutritional therapy as outlined in these ESPEN guidelines,highlighting key recommendations and their clinical implications.
3.Construction of CD8+T cell-associated Risk Model in Hepatocellular Carcinoma Based on Bulk and Single-cell RNA-seq Data
Xin-Tong ZHANG ; Jian-Jun ZHU ; Jin WU ; Hao WU ; Fan LU ; Wen-Tao ZHANG ; Jing-Jia CHANG ; Ting TANG ; Zhi-Gao OU ; Feng-Feng JIA ; Li LI ; Peng-Fei YU ; Ming LIU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(10):1511-1528
Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8+T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.
4.The cerebro protective effect of sivelestat sodium in cardiopulmonary bypass surgery
Zhi WEN ; Ou LIAO ; Jian WEN ; Feng REN ; Zheng WANG ; Changxue WU
China Modern Doctor 2025;63(3):53-56,72
Objective To investigate the cerebro protective effect of pre-filled sivelestat sodium during cardiopulmonary bypass(CPB)in patients with valve replacement surgery.Methods From January 2022 to December 2023,104 patients were included and randomly divided into experimental group(n=54)and control group(n=50).The sivelestat sodium 4.8mg/kg was mixed to the pre-filled solutions for CPB in experimental group,while an equal amount of physiological saline solution was mixed in control group.Internal jugular venous blood was collected 5 minutes after anesthesia induction and 10 minutes,4 hours,24 hours,and 72 hours after the aortic cross-clamp was released to detect plasma S-100 protein and interleukin(IL)-6 concentrations.Data on operation time,CPB time,mean arterial pressure,and hematocrit were also recorded.Results There were no statistical differences in operation time,CPB time,assisted circulation time,mean arterial pressure,and hematocrit between two groups(P>0.05).After anesthesia,there were no significant differences in S-100 protein and IL-6 between two groups(P>0.05).After,the plasma concentrations of S-100 protein and IL-6 increased in both groups,but the concentrations of S-100 protein and IL-6 in experimental group were significantly lower than those in control group at early stages(10 minutes,4 hours,24 hours)after the aortic cross-clamp was released(P<0.05).Conclusion Sivelestat sodium,as a cerebro protective drug in CPB heart surgery,can reduce the levels of S-100 protein and IL-6,demonstrating a protective effect on central nervous cells.
5.Effects of fangchinoline derivative LYY-32 on biological properties of BLM DNA helicase
Wang-ming ZHANG ; Qin-ying FENG ; Xiao-yu SONG ; Xin-zhong ZHOU ; Juan LU ; Wan-qing XIE ; Zhi-wen LAI ; Wei-dong PAN ; Jie-lin LIU
Chinese Pharmacological Bulletin 2025;41(9):1680-1686
Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17%.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49%.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3%at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100%.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.
6.The cerebro protective effect of sivelestat sodium in cardiopulmonary bypass surgery
Zhi WEN ; Ou LIAO ; Jian WEN ; Feng REN ; Zheng WANG ; Changxue WU
China Modern Doctor 2025;63(3):53-56,72
Objective To investigate the cerebro protective effect of pre-filled sivelestat sodium during cardiopulmonary bypass(CPB)in patients with valve replacement surgery.Methods From January 2022 to December 2023,104 patients were included and randomly divided into experimental group(n=54)and control group(n=50).The sivelestat sodium 4.8mg/kg was mixed to the pre-filled solutions for CPB in experimental group,while an equal amount of physiological saline solution was mixed in control group.Internal jugular venous blood was collected 5 minutes after anesthesia induction and 10 minutes,4 hours,24 hours,and 72 hours after the aortic cross-clamp was released to detect plasma S-100 protein and interleukin(IL)-6 concentrations.Data on operation time,CPB time,mean arterial pressure,and hematocrit were also recorded.Results There were no statistical differences in operation time,CPB time,assisted circulation time,mean arterial pressure,and hematocrit between two groups(P>0.05).After anesthesia,there were no significant differences in S-100 protein and IL-6 between two groups(P>0.05).After,the plasma concentrations of S-100 protein and IL-6 increased in both groups,but the concentrations of S-100 protein and IL-6 in experimental group were significantly lower than those in control group at early stages(10 minutes,4 hours,24 hours)after the aortic cross-clamp was released(P<0.05).Conclusion Sivelestat sodium,as a cerebro protective drug in CPB heart surgery,can reduce the levels of S-100 protein and IL-6,demonstrating a protective effect on central nervous cells.
7.A Pneumatic Micro-valve with Sandwich Structure Based on Micro-electro-mechanical System
Shao-Jie MA ; Wen-Bo LI ; Yu-Chen ZHU ; Zhi-Rui LI ; Bin ZHAO ; Fei FENG
Chinese Journal of Analytical Chemistry 2025;53(5):758-764
In this study,an ON/OFF type micro-valve with a sandwich(glass-silicon-glass)structure was designed and fabricated based on the micro-electro-mechanical system(MEMS)technique.The deformable membrane of this micro-valve was prepared on the silicon on insulator(SOI)substrate and sealed using Si-Si bonding and anodic bonding methods.The micro-valve had high-temperature stability and was suitable for integration with other gas chromatography components.The deformable membrane with a thickness of 10 μm was processed on the top silicon of the SOI substrate.The flow control of the micro-valve could be achieved by changing the driving pressure applied to the deformable membrane to deform it.Compared with polymer membranes,the deformable membrane prepared on the top layer silicon of SOI had better temperature stability and could be released using the deep reactive ion etching technique after silicon-silicon bonding,avoiding deformation during the preparation process.In addition,due to the small gap between the membrane and the inlet/outlet holes,the dead volume of the microvalve was very small.The test results indicated that the micro-valve achieved flow control and ON/OFF functions with good repeatability.
8.Research Progress on Electrochemical Sensing Techniques for Detection of Telomerase Activity
Hai-Tang YANG ; Peng-Hua SHU ; Wen-Lin LIU ; Wen-Bo MA ; Zi-Jun YANG ; Zhi-Feng DENG ; Xin-Yun ZHANG ; Wei WEI
Chinese Journal of Analytical Chemistry 2025;53(6):864-874
The telomere structure in the cell nucleus is crucial for maintaining the stability and functions of chromosomes.Telomerase is a ribonucleoprotein reverse transcriptase,which catalyzes the elongation of telomeres using its own RNA as a template,thereby counteracting the shortening of telomeres caused by chromosome replication and cell division.Due to its overexpression in over 85%of malignant tumor cells,telomerase has emerged as a highly promising biomarker and a novel target for cancer therapy.In recent years,given the importance of precise quantification of telomerase activity in guiding medical diagnosis and treatment strategies,researchers have developed various high-performance telomerase detection techniques.Among these,electrochemical biosensing technique has cause much attention due to its high sensitivity,operational convenience,rapid response,and ease of miniaturization.This paper focused on the latest advances in electrochemical sensing technique for detection of telomerase activity,aiming to provide inspiration for designing novel telomerase activity detection strategies by elucidating three unique properties of telomerase primer extension products.
9.A Monolithic Integrated Gas Chromatography Chip with Gas Chromatographic Column and Helium Discharge Ionization Detector
Yu-Chen ZHU ; Shao-Jie MA ; Wen-Bo LI ; Zhi-Rui LI ; Bin ZHAO ; Fei FENG
Chinese Journal of Analytical Chemistry 2025;53(7):1064-1071
A monolithic integrated gas chromatography chip,consisting of a micro gas chromatography column(μGCC)and a micro helium discharge ionization detector(μHDID)was proposed.The chip was fabricated using micro electromechanical system(MEMS)technique,and its sensitivity was improved from two aspects.On one hand,open tubular column was selected as the separation device,and the auxiliary helium channel width of μHDID was modulated based on the microchannel width of the μGCC to match the flow rates of μHDID and μGCC.On the other hand,the electrode structure inside the μHDID collection zone was optimized,a bias electrode group around the collection electrode was constructed,and the ion collection efficiency was improved.After coating HKUST-1 as the stationary phase,the monolithic integrated gas chromatography chip could achieve baseline separation and detection of light hydrocarbon gas mixture(methane,ethane,propane,andn-butane),with a detection limit for propane as low as 25 pg.The chip could carried out test under temperature-programmed conditions,with a resolution of 9.24 for ethane and propane.
10.A Micro Gas Chromatographic Column with Large Surface Area Based on Anodization
Shao-Jie MA ; Wen-Bo LI ; Yu-Chen ZHU ; Bo-Xin CHEN ; Zhi-Rui LI ; Bin ZHAO ; Fei FENG
Chinese Journal of Analytical Chemistry 2025;53(10):1607-1614
A micro gas chromatographic column with mesoporous surface micro column array prepared by anodization method was proposed.A porous support layer with a characteristic pore size of about 30 nm inside the chromatographic column was prepared in situ using anodization method,and a uniform alumina stationary phase was deposited on the mesoporous support layer using atom layer deposition(ALD)technique.The existence of a mesoporous support layer increased surface area of the chromatographic column,thereby increasing the total amount of stationary phase loading and enhancing column capacity,which facilitated chromatographic separation.The test results showed that the porous support layer significantly reduced the longitudinal molecular diffusion and mass transfer resistance of the micro gas chromatographic column,and significantly increased the number of theoretical plates(n-nonane increased by 290.2%).Furthermore,column efficiency of the chromatographic column was less affected by flow rate,which was conducive to rapid separation of heavy hydrocarbon mixtures.

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