Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

ObjectiveBased on the regulation of macrophage M2 polarization， this study aims to explore the molecular mechanism and action targets of the Qijia Rougan prescription and its key effector ingredients in anti-fibrosis， thereby providing a basis and reference for the development of new drugs for hepatic fibrosis. MethodsA rat model of hepatic fibrosis was established by subcutaneous injection of 40%CCl₄， followed by oral administration of Qijia Rougan granules. The volume of collagen fibers was detected using Masson staining， the fibrosis markers Collagen Ⅰ and α-SMA were detected using immunohistochemistry， the proportion of M2 macrophages was detected by flow cytometry. The expression levels of M2 macrophage phenotype markers CD163 and CD206 were detected using immunofluorescence double staining. Western blot was used to detect the levels of the transforming growth factor-β （TGF-β）， platelet derived growth factor subunit B （PDGFB）， interleukin-10 （IL-10）， phosphorylated Janus kinase 1 （p-JAK1）， and phosphorylated signal transducer and activator of transcription 6 （p-STAT6）. Real-time fluorescent quantitative PCR was used to detect the relative expression levels of JAK1， STAT6， Arginase 1（Arg1）， and Fizz1. Based on the theory of serum pharmacology， liquid chromatography-mass spectrometry and WENN analysis were used to obtain the active ingredients of Qijia Rougan prescription. Molecular docking and molecular dynamics simulation were performed to analyze the effector ingredients and their targets. The identified effector ingredients were interfered with IL-4-induced M2 polarization of RAW264.7 macrophage in vitro to validate the targets. ResultsQijia Rougan prescription significantly reduced the content of fibrosis markers α-SMA and Collagen Ⅰ， as well as collagen fiber content （P<0.05）. It decreased the proportion of M2 macrophages and the levels of related cytokines IL-10， TGF-β and PDGFB， and up-regulated the levels of p-JAK1 and p-STAT6 （P<0.05）. A total of 1 214 compounds were identified from Qijia Rougan prescription， medicated serum and blank serum， and 29 ingredients were finalized by Venn analysis， including 15 blood-entry prototypes and 14 drug metabolites. Molecular docking showed that enoxolone and berberine bound more strongly to JAK1， with binding free energies of -9.6 kcal·mol^-1（1 cal≈4.184 J） and -9.1 kcal·mol^-1， respectively. Molecular dynamics simulations showed that JAK1-enoxolone and JAK1-berberine exhibited stable simulation trajectories within 100 ns， with essentially identical conformations and high protein overlap before and after simulation. Their binding free energies were -25.18 5.0.81 kcal·mol^-1 and -27.39 7.0.85 kcal·mol^-1， respectively. The number of hydrogen bonds formed between JAK1 and enoxolone ranges from 0 to 5， and most of the time can be maintained at 2-3. In vitro intervention with enoxolone or berberine significantly reduced p-JAK1 and p-STAT6 levels （P<0.05）. ConclusionQijia Rougan prescription inhibits M2 macrophage polarization in hepatic fibrosis. Enoxolone and berberine are the key effector ingredients of Qijia Rougan prescription to inhibit macrophage M2 polarization through targeting JAK1 and modulating the JAK1/STAT6 signaling pathway， thereby ameliorating hepatic fibrosis. This study provides a basis for prescription optimization， clinical application and new drug development， as well as a reference for monolithic anti-hepatic fibrosis research.

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.

Vitrification cryopreservation technology converts the liquid water in biological samples into glassy solids through ultra-rapid cooling. In this review, the core research of vitrification cryopreservation technology was mainly reviewed, such as the optimization of cryoprotectant formulations, the improvements to temperature control methods, the innovative carrier designs and the improvements to rewarming technology. The application status and issues in the fields of organ preservation, tumor research, reproductive medicine and rare cell preservation were also summarized. By combining the technical principles with glassy state detection methods, a theoretical basis was provided for optimizing the technical system and expanding application scenarios, thereby promoting its large-scale application in clinical and biological sample libraries.

Objective:To analyze the clinical features of patients with traumatic optic neuropathy (TON) and to explore its clinical patterns and treatment outcomes.Methods:A retrospective analysis was conducted on data from 323 patients (334 eyes) with TON, who were treated in the Department of Otorhinolaryngology Head and Neck Surgery, the Affiliated Hospital of Qingdao University from April 1999 to October 2024. Among these patients, 288 were male and 35 were female, with ages ranging from 4 to 70 years. All patients were followed up for a period of 6 to 24 months, with the final follow-up visual acuity recorded as the ultimate visual outcome. The visual acuity evaluation criteria were classified into five levels: no light perception, light perception, hand movement in front of the eye, counting fingers at 1 meter, and "chart-visible acuity". A treatment outcome was deemed effective if the post-treatment visual acuity improved by one level or more compared to pre-treatment, or if the chart-visible acuity improved by two lines or more on the logMAR chart. The clinical characteristics of patients, causes of injury, complications, treatment methods, and changes in visual acuity before and after treatment were summarized. Logistic regression analyses were performed to identify the influencing factors affecting treatment efficacy.Results:TON occurred mostly in young (215/323, 66.56%) males (288/323, 89.16%), the majority of patients came from villages and towns (236/323, 73.07%). Traffic accidents (232/323, 71.83%) remained the main etiology. Most patients had craniofacial injuries and other bodily injuries. The effective rate of vision improvement was 50.30% (168/334). Multiple logistic regression analyses identified that residual vision (light perception or better) at presentation ( OR=3.26, P<0.001) and receiving treatment within 7 days after injury ( OR=2.04, P=0.008) were protective factors on visual acuity recovery, while the presence of orbital wall fracture was a risk factor for visual acuity recovery ( OR=0.26, P<0.001). Additionally, undergoing surgical treatment was a protective factor for visual improvement in patients with no light perception ( OR=2.94, P=0.007). For patients with residual vision at presentation, orbital wall fracture was a significant risk factor ( OR=0.28, P=0.009). Conclusions:TON is more prevalent in young males and is primarily caused by traffic accidents, leading to a poor prognosis. Timely medical intervention following injury significantly influences prognostic outcomes. Early surgical intervention (within 7 days) is recommended, particularly for patients with no light perception at presentation.

Subunit 5B of constitutively photomorphogenic 9 signalosome(CSN5B)is an inhibitory factor for the biosynthesis of vitamin C in the L-galactose synthesis pathway in plants.To create mutants with richer vitamin C in tomato fruits,a dual-target vector of pKSE402-SlCSN5Bwas constructed and trans-formed into the breeding parent of 1912.Based on the molecular biological assay and DNA sequencing,17 transgenic positive lines were determined,and 6 lines of them were genetically mutated at the target site of SlCSN5B,with an editing efficiency of 35.3％.Among the mutants,2 lines were homozygous mu-tants,csn5b-6 with 180 bp deletion and csn5b-8 with 3 bp deletion.The biological traits of two types of deficiency homozygotes without exogenous T-DNA insertion derived from the T1 generation were observed,and there were no significant differences in phenotypes of the plant and fruit.Through physiological tes-ting of red-ripe fruits from T,generation lines of csn5b-6,the GMPase activity and the vitamin C content significantly increased by 43％and 37.8％,respectively,the content of hydrogen peroxide significantly decreased by 25.9％,and the content of soluble solids did not obviously change,compared with the wild type.There were no significant differences in plant traits and physiological characteristics between T1 gen-eration lines of csn5b-8 and the wild type.Based on gene expression analysis and protein structure predic-tion,the results showed that the gene of SlCSN5B normally transcribed,and the loss of large peptide seg-ments of CSN5B encoded by SlCSN5B caused changes in its structure to affect functioning,which led to an increase of vitamin C content in the line of csn5b-6-1 1.The findings suggest that the vitamin C content of tomato fruit can be improved by CRISPR/Cas9-mediated SlCSN5B gene editing,which provides the valuable resources for high-quality breeding in tomato.

Objective To determine the median effective concentration(EC50)of ropivacaine at the volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block in children aged 6 to 10 years.Methods A prospective dose-finding trial was conducted based a sequential Dixon up-and-down allocation.We recruited children aged 6 to 10 years who were scheduled for unilateral surgery on upper extremity regions in our hospital from April to December 2022.All of them were subjected to general intravenous anaesthesia combined with ultrasound-guided interscalene brachial plexus block.The ropivacaine volume for each patient was 0.5 mL/kg.The concentration of 0.2%for the first patient,subsequent concentrations were adjusted based on the block effect of previous patient,increase or decrease by 0.02%.The trial was stopped when there were 7 turning points.Isotonic regression and Bootstrap were used to calculate the values of EC50 and 95%effective concentration(EC95),along with their 95%confidence intervals(CI).General data,incidence of adverse events,and score of postoperative pain were recorded.Results A total of 26 children aged 6 to 10 years were included.The EC50 of ultrasound-guided interscalene brachial plexus block was determined to be 0.091%(95%CI:0.077%～0.105%),and the EC95 was estimated to be 0.117%(95%CI:0.110%～0.118%).Successful blockade was achieved in 16 cases(61.5%),while 10 cases(38.5%)failed.No statistical differences existed between successful and failed cases regarding sex,age,body weight,surgical site,surgical laterality,operative time,or anesthesia duration.None of the patients experienced adverse events such as pneumothorax,vascular injury,or Horner's syndrome,and the score of postoperative pain were all<6 by modified Children's Hospital of Eastern Ontario Pain Scale.Conclusion In children aged 6 to 10 years,the EC50 of ropivacaine is 0.091%at a volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block,and this low dose of regional anesthetic can reduce the risks such as systemic toxicity and direct neurotoxicity.

Metal-organic frameworks(MOFs)are porous materials composed of metal ions or metal clusters and organic ligands by coordination,which have the advantages of large specific surface area,good thermal stability and adjustable pore size,and have a promising application in gas chromatographic separation.In recent years,MOFs materials have been used as stationary phases for gas chromatography mainly including ZIF,MIL,UiO-66,HKUST-1,IRMOFs,etc.Based on the molecular sieve effect,van der Waals forces,hydrogen bonding and π-π interactions,the pore size,pore microenvironment,unsaturated metal site and special functional group of the MOFs stationary phase materials can be specifically designed and regulated.MOFs materials as stationary phases have unique separation performance for n-alkanes and their isomers,aromatic compounds and their isomers,alcohols/ketones/aldehydes and their isomers,and chiral compounds.The combination of organic polymers and novel nanomaterials with MOFs materials can improve the separation performance and stability of MOFs.Therefore,MOFs materials are expected to be the promising stationary phase that can be applied to gas separation in complex environments.In this article,the research advances of various stationary phases based on MOFs for gas chromatography in recent years were reviewed.The separation performance and separation mechanism of MOFs stationary phases for mixed gas samples were discussed,and the development trends in the future were prospected.

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.

A pyrene-phenol-based fluorescent probe PyP which showed typical intramolecular charge transfer(ICT)and monomer-excimer activities was synthesized by using pyrene carboxaldehyde hydrazone and 4-tert-butyl-2,6-diformylphenol as the raw materials.The effects of solvents on PyP were studied,and the results showed that the color of protic polar solvents(Ethanol,N,N-dimethylformamide,methanol and H2O)were successfully identified.Based on the solvent polarity-regulated PyP monomer-excimer switching,the rapid and highly sensitive ratiometric probe,"Turn-off"and"Turn-on"multimodal probes were established for detection of trace water content in organic solvents(Dimethyl sulfoxide,N,N-dimethylformamide,ethanol and methanol),with detection limits(3σ/k)of 0.0021％,0.046％,0.062％and 0.024％.The method was successfully used to detect water content in dimethyl sulfoxide,N,N-dimethy lformamide,ethanol and methanol commercial organic solvents,with recoveries ranging from 97.2％to 108.0％.The developed method showed good accuracy and stability,and had good application prospect.