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.

ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

Objective:To analyze the risk factors associated with future exacerbations in patients with chronic obstructive pulmonary disease (COPD) who have no history of exacerbation in the past year.Methods:COPD patients with no exacerbation history in the past year, registered in the RealDTC study from January 2018 to December 2023, were enrolled. Demographic data, COPD Assessment Test (CAT) scores, modified Medical Research Council (mMRC) dyspnea questionnaire scores, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1) to forced vital capacity (FVC), Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, GOLD groups, and inhaled medication regimens were collected. All patients were followed up for one year, and the number of exacerbations was recorded. Patients were divided into an exacerbation group and a non-exacerbation group based on the occurrence of exacerbations during the follow-up period. Logistic regression analysis was used to screen the influencing factors for exacerbations in COPD patients. Results:A total of 2 901 COPD patients were included, among which 633 patients (21.8%) experienced exacerbations during the follow-up period. Compared with the non-exacerbation group, patients in the exacerbation group were older, with higher CAT and mMRC scores, lower body mass index (BMI), FEV 1%pred, and FEV 1/FVC. The proportions of patients with high school education or above and those using long-acting β 2-agonist (LABA) + long-acting muscarinic antagonist (LAMA) medications were also lower (all P<0.05). Logistic regression analysis showed that age ( OR=1.010, 95% CI: 1.000-1.021), CAT score ≥20 ( OR=1.415, 95% CI: 1.074-1.865), education level of junior high school or below ( OR=1.243, 95% CI: 1.003-1.540), LABA + LAMA inhalation ( OR=0.605, 95% CI: 0.432-0.848), and BMI ( OR=0.969, 95% CI: 0.943-0.995) were independent risk factors for future exacerbations in COPD patients with no exacerbation history in the past year (all P<0.05). Conclusions:The risk of future exacerbations remains high in COPD patients with no exacerbation history in the past year. High CAT scores, low education levels, and low BMI are associated with future exacerbations. Clinicians should pay close attention to the management of such patients and implement appropriate interventions.

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

Objective To explore the factors associated with complete resolution of sentinel lymph node metastasis(pCR)after neoadjuvant chemotherapy in breast cancer and to establish a predictive model.Methods The medical records of 136 female patients with breast cancer who received neoadjuvant chemotherapy in the First Hospital of Lanzhou University from January 2022 to February 2024 were retrospectively analyzed.According to the 80/20 rule,the patients were randomly divided into a training set(108 cases)and a validation set(28 cases).Based on the pathological examination results of axillary lymph node dissection(ALND)after neoadjuvant chemotherapy in breast cancer patients,they were classified into the sentinel lymph node pCR group and non-pCR group.Multivariate logistic regression analysis was used to screen the independent risk factors of sentinel lymph nodes failing to reach pCR.Build a nomogram prediction model based on the screened risk factors.By drawing the receiver operating characteristic(ROC)curve calculation curve,the area under ROC curve,sensitivity and specificity are used to evaluate the discrimination of the model.Results Among the 108 breast cancer patients,46 cases achieved pCR in the sentinel lymph nodes,accounting for 42.59％(46 cases/108 cases).In addition,33 cases(30.56％)achieved pCR in the primary tumor lesion.The non-pCR group showed a higher proportion of stage Ⅲ clinical staging,lymph node short-axis reduction of less than 50％before and after treatment,tumor maximum diameter reduction of less than 50％before and after treatment,lymph node type Ⅲ classification,and blood flow grade Ⅲ compared to the pCR group(P＜0.05).Multivariate logistic regression analysis showed that Clinical staging(OR=3.593,95％CI:1.276-10.121),lymph node short-axis reduction of less than 50％before and after treatment(OR=4.272,95％CI:1.517-12.032),tumor maximum diameter reduction of less than 50％before and after treatment(OR=3.710,95％CI:1.317-10.449),lymph node type(OR=3.827,95％CI:1.359-10.779),and blood flow grade(OR=4.764,95％CI:1.691-13.418)were identified as risk factors for not achieving pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients(P＜0.05).The sensitivity of the risk model for predicting non-achievement of pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in the training set of breast cancer patients was 0.826(95％CI:0.705-0.943),with a specificity of 0.826(95％CI:0.712-0.919)and an area under the ROC curve of 0.847(95％CI:0.738-0.952).In the validation set,the sensitivity for predicting non-achievement of pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients was 0.731(95％CI:0.608-0.904),with a specificity of 0.827(95％CI:0.713-0.941)and an area under the ROC curve of 0.834(95％CI:0.729-0.951).Conclusion Clinical staging,changes in lymph node short-axis before and after treatment,changes in tumor maximum diameter before and after treatment,lymph node type,and blood flow grade are associated with pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients.Constructing a predictive model can help evaluate the pCR status of sentinel lymph nodes after neoadjuvant chemotherapy.

AIM To investigate the effects of Wenfei Jiangzhuo Formula on mitochondrial function of Aβ25-35-induced BV-2 cells.METHODS In the establishment of cell model of Alzheimer's disease(AD)using Aβ25-35 on the BV-2 cells,the optimal concentration and time point of Aβ25-35 intervention were determined;and the groups for the intervention of LFHP-1c group(inhibitor)or the serum containing Wenfei Jiangzhuo Formula were set up.The detection of the optimal intervention concentration and time point by CCK-8 assay;the observation of cell migration and apoptosis by Transwell assay and Hoechst 33342 staining;the detection of the positive expressions of PGAM5 and Drp1 by immunofluorescence;and the detection of cellular PGAM5,Drp1,OPA1,and Mfn1/2 mRNA and protein expressions by RT-qPCR and Western blot were conducted.RESULTS The best AD cell model was established by 48 h exposure to 5 μmol/L of Aβ25-35,and most active cell viability was achieved with the 48 h use of serum containing 20％Wenfei Jiangzhuo Formula.Compared with the control group,the model group displayed decreased number of cell migration,more bright blue positive apoptotic cells,increased number of PGAM5 and Drp1 positive cells and their mRNA and protein expressions(P＜0.05);and decreased mRNA and protein expressions of OPA1 and Mfn1/2(P＜0.05).Compared with the model group,the groups intervened with the medicines shared increased number of cell migration,less bright blue positive apoptotic cells,decreased number of PGAM5 and Drp1 positive cells and their mRNA and protein expressions(P＜0.05);and elevated OPA1 and Mfn1/2 mRNA and protein expressions(P＜0.05).CONCLUSION Wenfei Jiangzhuo Formula exerts cerebroprotective effects to improve cognition by reducing cell damage and improving the balance of mitochondrial homeostasis through PGAM5-Drp1 axis in AD model.

Objective To explore the changes of durability properties of reusable surgical gowns when used in dry and wet conditions.Methods Reusable surgical gowns made of single-layer polyester fiber or 3-layer composite material were selected as test samples,and a Martindale abrasion and pilling tester was used as the basic test platform and modified to form fixtures suitable for the wet state environment.The reusable surgical gowns underwent abrasion experiments in wet and dry conditions to observe the changes in their fiber structure,and were subjected to water penetration resistance and swelling strength tests.Results Visually the reusable surgical gowns had few changes of the microscopic textile fiber structure in dry and wet conditions,and the gowns made of single-layer polyster fiber gained advantages over the outer layers of those of 3-layer composite material in abrasion resistance with the same friction cycles.In dry and wet conditions,the hydrostatic pressure values of the gowns of single-layer polyster fiber gradually decreased with the increase of the degree of abrasion,which were always lower than those of the gowns of 3-layer composite material;the swelling strength of the gowns of single-layer polyster fiber was always greater than that of the gowns of 3-layer composite material,which decreased with the deterioration of the wear more significantly than that of the gowns of 3-layer composite material.Conclusion The reusable surgical gowns made of single-layer polyester fiber or 3-layer composite material have few differences in durability and protective properties at the early stages of ablation in dry and wet conditions.The durability of the gowns decreases as the degree of wear increases,while the trend of the decrease is slowing down until the fabric breaks down and completely loses its barrier effect.[Chinese Medical Equipment Journal,2025,46(6):28-33]

Objective:To analyze the risk factors associated with future exacerbations in patients with chronic obstructive pulmonary disease (COPD) who have no history of exacerbation in the past year.Methods:COPD patients with no exacerbation history in the past year, registered in the RealDTC study from January 2018 to December 2023, were enrolled. Demographic data, COPD Assessment Test (CAT) scores, modified Medical Research Council (mMRC) dyspnea questionnaire scores, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1) to forced vital capacity (FVC), Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, GOLD groups, and inhaled medication regimens were collected. All patients were followed up for one year, and the number of exacerbations was recorded. Patients were divided into an exacerbation group and a non-exacerbation group based on the occurrence of exacerbations during the follow-up period. Logistic regression analysis was used to screen the influencing factors for exacerbations in COPD patients. Results:A total of 2 901 COPD patients were included, among which 633 patients (21.8%) experienced exacerbations during the follow-up period. Compared with the non-exacerbation group, patients in the exacerbation group were older, with higher CAT and mMRC scores, lower body mass index (BMI), FEV 1%pred, and FEV 1/FVC. The proportions of patients with high school education or above and those using long-acting β 2-agonist (LABA) + long-acting muscarinic antagonist (LAMA) medications were also lower (all P<0.05). Logistic regression analysis showed that age ( OR=1.010, 95% CI: 1.000-1.021), CAT score ≥20 ( OR=1.415, 95% CI: 1.074-1.865), education level of junior high school or below ( OR=1.243, 95% CI: 1.003-1.540), LABA + LAMA inhalation ( OR=0.605, 95% CI: 0.432-0.848), and BMI ( OR=0.969, 95% CI: 0.943-0.995) were independent risk factors for future exacerbations in COPD patients with no exacerbation history in the past year (all P<0.05). Conclusions:The risk of future exacerbations remains high in COPD patients with no exacerbation history in the past year. High CAT scores, low education levels, and low BMI are associated with future exacerbations. Clinicians should pay close attention to the management of such patients and implement appropriate interventions.

Objective To explore the factors associated with complete resolution of sentinel lymph node metastasis(pCR)after neoadjuvant chemotherapy in breast cancer and to establish a predictive model.Methods The medical records of 136 female patients with breast cancer who received neoadjuvant chemotherapy in the First Hospital of Lanzhou University from January 2022 to February 2024 were retrospectively analyzed.According to the 80/20 rule,the patients were randomly divided into a training set(108 cases)and a validation set(28 cases).Based on the pathological examination results of axillary lymph node dissection(ALND)after neoadjuvant chemotherapy in breast cancer patients,they were classified into the sentinel lymph node pCR group and non-pCR group.Multivariate logistic regression analysis was used to screen the independent risk factors of sentinel lymph nodes failing to reach pCR.Build a nomogram prediction model based on the screened risk factors.By drawing the receiver operating characteristic(ROC)curve calculation curve,the area under ROC curve,sensitivity and specificity are used to evaluate the discrimination of the model.Results Among the 108 breast cancer patients,46 cases achieved pCR in the sentinel lymph nodes,accounting for 42.59％(46 cases/108 cases).In addition,33 cases(30.56％)achieved pCR in the primary tumor lesion.The non-pCR group showed a higher proportion of stage Ⅲ clinical staging,lymph node short-axis reduction of less than 50％before and after treatment,tumor maximum diameter reduction of less than 50％before and after treatment,lymph node type Ⅲ classification,and blood flow grade Ⅲ compared to the pCR group(P＜0.05).Multivariate logistic regression analysis showed that Clinical staging(OR=3.593,95％CI:1.276-10.121),lymph node short-axis reduction of less than 50％before and after treatment(OR=4.272,95％CI:1.517-12.032),tumor maximum diameter reduction of less than 50％before and after treatment(OR=3.710,95％CI:1.317-10.449),lymph node type(OR=3.827,95％CI:1.359-10.779),and blood flow grade(OR=4.764,95％CI:1.691-13.418)were identified as risk factors for not achieving pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients(P＜0.05).The sensitivity of the risk model for predicting non-achievement of pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in the training set of breast cancer patients was 0.826(95％CI:0.705-0.943),with a specificity of 0.826(95％CI:0.712-0.919)and an area under the ROC curve of 0.847(95％CI:0.738-0.952).In the validation set,the sensitivity for predicting non-achievement of pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients was 0.731(95％CI:0.608-0.904),with a specificity of 0.827(95％CI:0.713-0.941)and an area under the ROC curve of 0.834(95％CI:0.729-0.951).Conclusion Clinical staging,changes in lymph node short-axis before and after treatment,changes in tumor maximum diameter before and after treatment,lymph node type,and blood flow grade are associated with pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients.Constructing a predictive model can help evaluate the pCR status of sentinel lymph nodes after neoadjuvant chemotherapy.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.