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.

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.

Objective:To investigate the expression of long non-coding RNA plasmacytoma variant translocation 1(lncRNA-PVT1)in children with acute lymphoblastic leukemia(ALL)and its correlation with prognosis.Methods:Clinical data of 64 children with ALL were retrospectively analyzed.All children received standardized treatment according to CCLG-ALL-2015 protocol,and their overall survival(OS)was followed up.Bone marrow examination and lncRNA-PVT1 examination were performed before first diagnosis(T1),early intensive therapy(T2),consolidation therapy(T3),delayed intensive therapy(T4),and maintenance therapy(T5).Bone marrow samples of 25 children with thrombocytopenic purpura were collected during the same period as control group.LncRNA-PVT1 expression was compared between ALL group and control group.ALL children were divided into high-risk group and non-high-risk group according to the risk factors at T3,and the expression changes of lncRNA-PVT1 were analyzed.The correlation of lncRNA-PVT1 with clinical features and prognosis of ALL children was analyzed.Results:The expression of lncRNA-PVT1 in ALL children was significantly higher than that in control group(P＜0.001).ROC curve analysis showed that the area under curve(AUC)of lncRNA-PVT1 for ALL diagnosis was 0.919(95％CI:0.863-0.975),the optimal cut-off value was 1.465,sensitivity was 87.50％,and specificity was 98.80％.ALL children were divided into low lncRNA-PVT1 group(lncRNA-PVT1＜2.18)and high lncRNA-PVT1 group(lncRNA-PVT1 ≥2.18)according to the median lncRNA-PVT1 value(2.18).The high lncRNA-PVT1 group had higher Day 33 MRD compared with low lncRNA-PVT1 group(P＜0.01).At T3,T4 and T5,the expression of lncRNA-PVT1 in high-risk group was significantly higher than that in non-high-risk group(all P＜0.01).The expression of lncRNA-PVT1 were significantly increased in high-risk group at 5 time points(P＜0.001),while,there was no significant difference in non-high-risk group(P＞0.05).The median OS of low lncRNA-PVT1 group was 35(9-37)months,which was significantly higher than 25(5-33)months of high lncRNA-PVT1 group(P＜0.01).Univariate and multivariate Cox regression analysis showed that Day 33 MRD(＞10-2)and lncRNA-PVT1(≥2.18)were independent risk factors for OS in ALL children(both P＜0.05).Conclusion:LncRNA-PVT1 is involved in the pathogenesis of ALL in children and closely related to the prognosis.

Objective:To analyze the incidence of abnormal hemoglobin(Hb)in neonates in Guangzhou area,as well as the results of quantitative analysis of Hb in neonatal umbilical cord blood and genetic diagnosis of thalassemia in neonates with abnormal Hb;And to explore the hematological phenotypes and clinical characteristics of neonates with abnormal Hb and their parents,providing a reference for eugenics and childcare.Methods:650 neonates born at Guangdong Provincial People's Hospital who underwent Hb electrophoresis were included in this study.The results of routine blood test of umbilical cord blood,Hb electrophoresis and α-,β-thalassemia gene detection of the neonates were collected.The genotype distribution of thalassemia in the neonates was analyzed.Additionally,the abnormal Hb content of α and β variants was studied.Furthermore,the differences in hematological parameters between abnormal Hb neonates and normal neonates and α-thalassemia neonates,as well as between the parents of abnormal Hb neonates and normal adults were compared.Results:Among the 650 neonates,332(51.08％)were diagnosed with thalassemia,including 235 cases of α-thalassemia(36.15％),79 cases of β-thalassemia(12.15％),and 18 cases of compound α β-thalassemia(2.77％).Among all the α-thalassemia genotypes,the most prevalent one was--SEA/α α(48.94％),followed by-α3.7/α α(20.00％),-α42/α α(11.06％),and α α CS/α α(8.94％).The four most common genotypes of β-thalassemia were β CD41-42(32.91％),βIVS-Ⅱ-654(26.58％),β-28(21.52％),and β E(10.13％),respectively.275 cases of abnormal bands were found in Hb electrophoresis of umbilical cord blood,with a detection rate of 42.31％.The abnormal Hb content ofα-variant in the neonates was significantly higher than that of β-variant(P＜0.001).The levels of Hb,MCV,MCH,Hb A,and Hb F in neonates with abnormal Hb were lower than those in normal neonates,while the RDW-CV was higher than that in normal neonates,with statistical significantce(P＜0.05).The levels of RBC and Hb A in neonates with abnormal Hb were lower than those in neonates with α-thalassemia,while the level of MCH was higher than that in neonats withα-thalassemia,with statistical significance(P＜0.05).The levels of Hb,MCV,MCH,and Hb A in parents of neonates with abnormal Hb were lower than those in normal adults,while the RDW-CV was higher than that in normal adults,and the differences were statistically significant(P＜0.05).Conclusion:The abnormal Hb content of α-variant in the neonates is significantly higher than that of β-variant in the neonates in Guangzhou,which can help to presume whether it isα chain or β chain based on the abnormal Hb content,providing a reference for globin gene sequencing.Meanwhile,analysis of various hematological screening-related indicators in neonates in the early stage is beneficial for early warning of the occurrence of abnormal Hb combined with thalassemia,reducing missed diagnoses to a certain extent.

Objective:To analyze clinical characteristics and prognosis of B-cell acute lymphoblastic leukemia(B-ALL)patients with IKZF1 deletion.Methods:72 patients with B-ALL admitted to our hospital from April 2020 to January 2023 were selected,IKZF1 deletion were detected,and clinical characteristics and prognosis were analyzed.Results:Among the 72 patients,a total of 32 patients(44.4％)were identified with IKZF1 deletions(IKZF1+).There was no statistically significant difference in basic clinical data between patients with normal IKZF1(IKZF1-)and those with IKZF1+(P＞0.05).The proportion of patients with IKZF1+in Ph+group was significantly higher than that in Ph-group(P＜0.05).The main types of IKZF1+were exon 1-8 deletion(34.4％)and exon 4-7 deletion(31.2％).The median OS and PFS of IKZF1-patients were significantly longer than those of IKZF1+patients(OS:26.0 months vs 16.0 months,x2=23.094,P＜0.05;PFS:26.0 months vs 16.0 months,x2=11.150,P＜0.05).Among IKZF1+patients,the median OS of patients who received allogeneic hematopoietic stem cell transplantation(allo-HSCT)was significantly longer than that of patients who did not receive allo-HSCT(no reached vs 15.0 months,x2=5.685,P＜0.05).Conclusion:IKZF1 deletion is a risk factor affecting the prognosis of B-ALL patients.

Ureaplasma urealyticum (UU) is one of the most commonly occurring pathogens associated with genital tract infections in infertile males, but the impact of seminal UU infection in semen on intrauterine insemination (IUI) outcomes is poorly understood. We collected data from 245 infertile couples who underwent IUI at The First Affiliated Hospital of USTC (Hefei, China) between January 2021 and January 2023. The subjects were classified into two groups according to their UU infection status: the UU-positive group and the UU-negative group. We compared semen parameters, pregnancy outcomes, and neonatal birth outcomes to investigate the impact of UU infection on IUI outcomes. There were no significantly statistical differences in various semen parameters, including semen volume, sperm concentration, total and progressive motility, sperm morphology, leukocyte count, the presence of anti-sperm antibody, and sperm DNA fragmentation index (DFI), between the UU-positive and UU-negative groups of male infertile patients (all P > 0.05). However, the high DNA stainability (HDS) status of sperm differed between the UU-positive and UU-negative groups, suggesting that seminal UU infection may affect sperm nuclear maturation ( P = 0.04). Additionally, there were no significant differences in pregnancy or neonatal birth outcomes between the two groups (all P > 0.05). These results suggest that IUI remains a viable and cost-effective option for infertile couples with UU infection who are facing infertility issues.
Humans ; Male ; Ureaplasma Infections/complications* ; Female ; Infertility, Male/therapy* ; Ureaplasma urealyticum/isolation & purification* ; Pregnancy ; Adult ; Pregnancy Outcome ; Semen Analysis ; Insemination, Artificial ; Semen/microbiology* ; China

The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis,pri-marily transmitted through respiratory droplets,and poses a significant global public health challenge.Despite the availability of vaccines and chemotherapy regimens,the emergence of drug resistance and high incidence rates continue to render the prevention and control situation severe.The intestinal mi-crobiota modulates host immunity through metabolites such as short-chain fatty acids,influencing macrophage function,T-cell differentiation,and inflammatory responses,thereby regulating tubercu-losis susceptibility,disease progression,and treatment responses.This review systematically summa-rized the role of intestinal microecology in immune regulation of tuberculosis and its potential applica-tion strategies,delved into the possible immune regulatory mechanisms,proposed that the interaction between intestinal microbiota and immune checkpoint inhibitors may serve as a warning for the clinical risk of tuberculosis reactivation,and analyzed the potential of intestinal microecology as a therapeutic target for tuberculosis.

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats