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.

Wound repair and infection have long posed significant challenges in clinical medicine.Am-phibians,adapting to complex environments through long-term natural selection,have evolved skin sys-tems with remarkable abilities to resist external damage and promote rapid wound healing,making them an important source for discovering candidate molecules for wound healing.In this study,a novel peptide composed of 22 amino acids,with the sequence"VGKAGLETAACKATNSCFNIDW"and a molecular weight of 2299.6 D,was screened from the cDNA library of Odorrana tormota and named PN-VW22.The peptide was synthesized by solid-phase synthesis,and its effects on cell proliferation were evaluated using the CCK-8 assay and scratch wound healing assay in human keratinocytes(HaCaT)and mouse em-bryonic fibroblasts(NIH3T3).Antibacterial activity was assessed by determining the minimum inhibitory concentration(MIC).Results showed that PN-VW22 at various concentrations had no significant effect on the cell viability in NIH3T3 cells(P＞0.05),but significantly enhanced HaCaT cell viability at 0.5μmol/L(P＜0.001).Meanwhile,PN-VW22 induced cell proliferation and promoted wound healing in HaCaT cells,with a healing rate of 64.44％after 24 h incubation at 0.5 μmol/L.Furthermore,PN-VW22 exhibited antibacterial activity against Staphylococcus aureus with an MIC value of 13.92 μmol/L.In sum,this study identified PN-VW22 as a novel bifunctional peptide with both wound repair and anti-infective properties,providing a new toxin peptide template for the development of wound healing drugs.

Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.

Objective:To investigate the risk factors for adverse outcomes in elderly patients with nonvalvular atrial fibrilla-tion(AF)after percutaneous left atrial appendage closure(LAAC)combined with radiofrequency ablation(RFA).Meth-ods:A total of 199 elderly AF patients who admitted in Department of Cardiology,Yuhuangding Hospital between Jan 1st,2019 and Aug 17th,2023 and underwent LAAC combined RFA were enrolled.The patients were divided into case group(n=78)and control group(n=121)according to presence of atrial arrhythmia and/or cerebral infarction(CI)within one year after operation.Baseline clinical data,laboratory indexes and color Doppler ultrasound indexes were compared be-tween the two groups,and multivariate Logistic regression was used to analyze the risk factors for postoperative atrial ar-rhythmia and/or CI.Receiver operating characteristic(ROC)curve was constructed to analyze the predictive efficacy of risk factors for atrial arrhythmia and/or CI after operation.Results:Univariate analysis indicated that compared with pa-tients in control group,those in case group had significant higher proportions of preoperative persistent atrial fibrillation(52.60％ vs.37.20％),old myocardial infarction(OMI)(11.50％vs.1.70％)and left atrial diameter(LAD)[(45.47±6.90)mm vs.(43.34±6.64)mm](P＜0.05 or＜0.01).Multivariate Logistic regression analysis indicated history of OMI(OR=8.736,95％CI 1.772～43.069,P=0.008)and LAD(OR=1.053,95％CI 1.006～1.102,P=0.027)were independent risk factors of adverse outcomes in elderly AF patients after LAAC+RFA.ROC analysis indicated that predic-tive efficacy of combined detection of OMI and LAD(AUC=0.663,95％CI 0.593～0.728)for adverse outcomes within 1 year in elderly AF patients after LAAC+RFA was significantly better than those of OMI(AUC=0.549,95％CI 0.477～0.620)and LAD(AUC=0.602,95％CI 0.531～0.671)alone(Z=3.045,2.312,P=0.002,0.021).Conclusion:His-tory of old myocardial infarction and left atrial diameter are independent risk factors for atrial arrhythmia and/or cerebral infarction within 1 year after percutaneous left atrial appendage closure combined with radiofrequency ablation in elderly patients with atrial fibrillation,and the combination has good predictive performance.

Objective:To investigate the risk factors for adverse outcomes in elderly patients with nonvalvular atrial fibrilla-tion(AF)after percutaneous left atrial appendage closure(LAAC)combined with radiofrequency ablation(RFA).Meth-ods:A total of 199 elderly AF patients who admitted in Department of Cardiology,Yuhuangding Hospital between Jan 1st,2019 and Aug 17th,2023 and underwent LAAC combined RFA were enrolled.The patients were divided into case group(n=78)and control group(n=121)according to presence of atrial arrhythmia and/or cerebral infarction(CI)within one year after operation.Baseline clinical data,laboratory indexes and color Doppler ultrasound indexes were compared be-tween the two groups,and multivariate Logistic regression was used to analyze the risk factors for postoperative atrial ar-rhythmia and/or CI.Receiver operating characteristic(ROC)curve was constructed to analyze the predictive efficacy of risk factors for atrial arrhythmia and/or CI after operation.Results:Univariate analysis indicated that compared with pa-tients in control group,those in case group had significant higher proportions of preoperative persistent atrial fibrillation(52.60％ vs.37.20％),old myocardial infarction(OMI)(11.50％vs.1.70％)and left atrial diameter(LAD)[(45.47±6.90)mm vs.(43.34±6.64)mm](P＜0.05 or＜0.01).Multivariate Logistic regression analysis indicated history of OMI(OR=8.736,95％CI 1.772～43.069,P=0.008)and LAD(OR=1.053,95％CI 1.006～1.102,P=0.027)were independent risk factors of adverse outcomes in elderly AF patients after LAAC+RFA.ROC analysis indicated that predic-tive efficacy of combined detection of OMI and LAD(AUC=0.663,95％CI 0.593～0.728)for adverse outcomes within 1 year in elderly AF patients after LAAC+RFA was significantly better than those of OMI(AUC=0.549,95％CI 0.477～0.620)and LAD(AUC=0.602,95％CI 0.531～0.671)alone(Z=3.045,2.312,P=0.002,0.021).Conclusion:His-tory of old myocardial infarction and left atrial diameter are independent risk factors for atrial arrhythmia and/or cerebral infarction within 1 year after percutaneous left atrial appendage closure combined with radiofrequency ablation in elderly patients with atrial fibrillation,and the combination has good predictive performance.

Objective:To investigate the clinical and pathological characteristics, treatment and prognosis of endometriosis (EM)-associated ovarian mesonephric-like adenocarcinoma (MLA).Methods:Clinical and pathological data were collected from nine patients diagnosed with EM-associated ovarian MLA at the Obstetrics and Gynecology Hospital of Fudan University between January 2022 and December 2024. Histological slides were re-reviewed, immunohistochemical examination and molecular testing were performed, and patient follow-up was conducted.Results:(1) Clinical characteristics: the median age of the nine patients was 54 years (range: 38-69 years). All patients presented with a pelvic mass; five cases also reported abdominal pain. Tumor location included five cases in the right ovary, two in the left ovary, and two involving both ovaries. International Federation of Gynecology and Obstetrics (FIGO) staging showed 3 cases at stage Ⅰ, 4 at stage Ⅱ, and 2 at stage Ⅲ. (2) Pathological features: gross examination revealed mixed solid-cystic masses with solid areas appearing gray-white or yellow-brown; the median maximum tumor diameter was 9.0 cm (range: 2.6-13.0 cm). Microscopically, tumors exhibited various architectural patterns, including tubular, glandular, papillary, slit-like, sex cord-like, glomeruloid, and solid structures, with tubular and glandular patterns being most common. Tumor cells demonstrated mild to moderate nuclear atypia. Of the 11 tumor foci in the 9 cases, 8 showed coexistence of MLA with other tumor components, such as endometrioid carcinoma, borderline endometrioid or borderline seromucinous tumors. In 1 case of MLA mixed with a borderline endometrioid tumor, both components exhibited squamous metaplasia. Immunohistochemistry showed variable expression of GATA-binding protein 3, thyroid transcription factor-1, CD 10, and calretinin, with positive rates of 9/11, 8/11, 5/11, and 3/6, respectively. Two tumor foci (2/11) exhibited focal expression of estrogen receptor and progesterone receptor. All cases displayed wild-type p53 expression. Molecular testing via next-generation sequencing in five patients revealed pathogenic mutations in the KRAS gene (5/5), with 3 cases (3/5) harboring additional pathogenic mutations in other genes. (3) Treatment and prognosis: all patients underwent surgery, supplemented by chemotherapy and (or) targeted therapy. Five patients underwent comprehensive staging surgery, four received cytoreductive surgery, and one patient received targeted therapy. The median follow-up duration was 7 months (range: 2-27 months). Three patients (3/9) experienced recurrence, and no deaths were reported during the follow-up period. Conclusions:EM-associated ovarian MLA demonstrates diverse morphological patterns and frequently coexists with other tumor types. Accurate diagnosis relies on an integrated evaluation of histomorphology, immunohistochemistry, and molecular testing. The primary treatment for EM-associated ovarian MLA is surgery, followed by adjuvant chemotherapy. Patients harboring pathogenic KRAS p.G12C mutations may benefit from targeted therapies. Ovarian MLA is an aggressive tumor, prone to recurrence in the short term, and has a poor prognosis.

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.

Wound repair and infection have long posed significant challenges in clinical medicine.Am-phibians,adapting to complex environments through long-term natural selection,have evolved skin sys-tems with remarkable abilities to resist external damage and promote rapid wound healing,making them an important source for discovering candidate molecules for wound healing.In this study,a novel peptide composed of 22 amino acids,with the sequence"VGKAGLETAACKATNSCFNIDW"and a molecular weight of 2299.6 D,was screened from the cDNA library of Odorrana tormota and named PN-VW22.The peptide was synthesized by solid-phase synthesis,and its effects on cell proliferation were evaluated using the CCK-8 assay and scratch wound healing assay in human keratinocytes(HaCaT)and mouse em-bryonic fibroblasts(NIH3T3).Antibacterial activity was assessed by determining the minimum inhibitory concentration(MIC).Results showed that PN-VW22 at various concentrations had no significant effect on the cell viability in NIH3T3 cells(P＞0.05),but significantly enhanced HaCaT cell viability at 0.5μmol/L(P＜0.001).Meanwhile,PN-VW22 induced cell proliferation and promoted wound healing in HaCaT cells,with a healing rate of 64.44％after 24 h incubation at 0.5 μmol/L.Furthermore,PN-VW22 exhibited antibacterial activity against Staphylococcus aureus with an MIC value of 13.92 μmol/L.In sum,this study identified PN-VW22 as a novel bifunctional peptide with both wound repair and anti-infective properties,providing a new toxin peptide template for the development of wound healing drugs.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

AIM To explore the differential metabolites of different aged Citrus reticulate'Chachi'and their processed cakes.METHODS Non-targeted metabolomics technology of GC-TOF-MS was used to analyze the chemical constituents.The data was processed by principal component analysis and orthogonal partial least squares discriminant analysis,and the differential metabolites were identified.RESULTS A total of 74 differential metabolites were identified,including 16 glycosides,14 organic acids and their derivatives,11 amino acids and their derivatives,and 4 flavonoids.Comparative analysis revealed 40 and 30 differential metabolites between fresh C.reticulate'℃hachi'and 3-year or 5-year aged samples,respectively.Furthermore,27 and 34 differential metabolites were identified between the 3-year or 5-year aged samples and their corresponding processed cakes,respectively.Differential metabolites among fresh,aged C.reticulate'Chachi',and processed cakes were predominantly enriched in 6 metabolic pathways,including the biosynthesis of secondary metabolites.Specifically,differential metabolites between 3-year aged C.reticulate'Chachi'and its processed cake were significantly enriched in 4 pathways,such as ABC transporters.Differential metabolites between 5-year aged C.reticulate'Chachi'and its processed cake were mainly enriched in 5 pathways,including carbon metabolism.CONCLUSION Non-targeted metabolomics technology can elucidate the chemical compositional differences among fresh/aged and processed cakes of C.reticulate'Chachi',laying a foundation for the research into C.reticulate'Chachi'aging processing techniques and the development of processed products.