Objective To explore the functional impact of A-to-I editing in the seed region of miR-411 during post-myocardial infarction (MI) fibrosis and elucidate its therapeutic potential. Methods Integrating GEO database with myocardial RNA-seq data from MI mouse models, we identified dynamic A-to-I RNA editing in small noncoding RNAs across MI progression (1 day to 8 weeks post-MI). Four miRNAs exhibited differential editing rates between MI and controls, with miR-411 showing progressive editing enhancement at seed region position 4 (P＜0.01). This editing event was validated in both murine MI models and human heart failure specimens. Results The A-to-I editing ratio change of the 4th nucleotide in the seed region of miR-411 mainly occurs in cardiac fibroblasts rather than cardiomyocytes, and the editing at this site depends on ADAR2 rather than ADAR1. Edited miR-411 (ED-miR-411) diverged from wild-type miR-411 (WT-miR-411) in suppressing collagen-related pathways (extracellular matrix [ECM]-receptor interaction, collagen-containing ECM, ECM organization; P＜0.01) in cardiac fibroblasts. Mechanistically, dual-luciferase assays confirmed ED-miR-411 directly targeted the 3′UTR and suppressed expression of type Ⅱ transforming growth factor (TGF)-beta receptor (TGFBR2) and CD44, which were key drivers of TGF-β-mediated fibroblast activation. ED-miR-411 overexpression blunted TGF-β-induced collagen synthesis and myofibroblast proliferation (P＜0.05). In vivo, intramyocardial delivery of ED-miR-411 mimics at 1 week post-MI reduced fibrosis by 40% and improved ejection fraction by 15% (P＜0.01 vs controls), whereas WT-miR-411 showed no therapeutic effect. Conclusions A-to-I editing of miR-411 emerges as an endogenous anti-fibrotic mechanism by repressing TGFBR2 and CD44, thereby disrupting TGF-β signaling and ECM dysregulation. Our findings highlight ED-miR-411 as a novel RNA-based therapeutic candidate to mitigate post-infarction cardiac remodeling.

Objective To explore the risk factors of the stone-free rate after flexible ureteroscopy for lower pole calculi,develop a predictive model based on these identified factors,with subsequent validation and evalua-tion of the established model.Methods A retrospective analysis was conducted on 154 patients with lower pole renal calculi who underwent flexible ureteroscopy(FURS)at Guangdong Provincial Hospital of Traditional Chinese Medicine from 2020 to 2024.Based on postoperative stone clearance status,patients were categorized into a stone-free group and a residual stone group.Univariate analysis was performed to screen potential risk factors,while Pear-son correlation coefficients and variance inflation factor(VIF)were employed to assess multicollinearity,retaining the indicator with the highest area under the curve(AUC).Independent predictors were identified through multi-variate logistic regression analysis,and a nomogram model was constructed.Internal validation was conducd using the bootstrap resampling method.The predictive performance and clinical utility of the model were evaluated using receiver operating characteristic(ROC)curves and decision curve analysis(DCA).Results Univariate analysis demonstrated that largest stone diameter(LSD),cumulative stone diameter(CSD),stone volume(SV),stone surface area(SA),mean stone density(MSDE),and infundibular pelvic angle(IPA)were significantly associated with stone-free rate(SFR)following flexible ureteroscopy(FURS)for lower pole calculi(all P<0.05).After collinearity diagnostics,LSD(area under the curve[AUC]=0.724)was retained as the optimal stone burden parameter.Multivariate logistic regression analysis confirmed LSD,MSDE,and IPA as independent predictors of postoperative SFR.The nomogram model exhibited robust predictive performance with an AUC of 0.786(sensitivity:79.6%,specificity:71.0%).Internal validation via 1000 bootstrap resamples yielded an AUC of 0.792,and deci-sion curve analysis(DCA)confirmed clinical utility with net benefit across threshold probabilities of 4%—75%.Conclusions The nomogram model developed in this study,which incorporates both stone characteristics and renal anatomical parameters,demonstrates effective prediction of stone-free rate(SFR)following flexible ureteros-copy for lower pole calyceal stones.With stable predictive performance and high clinical applicability,this model provides a reliable tool for preoperative personalized decision-making in endourological management.

Objective To explore the risk factors of the stone-free rate after flexible ureteroscopy for lower pole calculi,develop a predictive model based on these identified factors,with subsequent validation and evalua-tion of the established model.Methods A retrospective analysis was conducted on 154 patients with lower pole renal calculi who underwent flexible ureteroscopy(FURS)at Guangdong Provincial Hospital of Traditional Chinese Medicine from 2020 to 2024.Based on postoperative stone clearance status,patients were categorized into a stone-free group and a residual stone group.Univariate analysis was performed to screen potential risk factors,while Pear-son correlation coefficients and variance inflation factor(VIF)were employed to assess multicollinearity,retaining the indicator with the highest area under the curve(AUC).Independent predictors were identified through multi-variate logistic regression analysis,and a nomogram model was constructed.Internal validation was conducd using the bootstrap resampling method.The predictive performance and clinical utility of the model were evaluated using receiver operating characteristic(ROC)curves and decision curve analysis(DCA).Results Univariate analysis demonstrated that largest stone diameter(LSD),cumulative stone diameter(CSD),stone volume(SV),stone surface area(SA),mean stone density(MSDE),and infundibular pelvic angle(IPA)were significantly associated with stone-free rate(SFR)following flexible ureteroscopy(FURS)for lower pole calculi(all P<0.05).After collinearity diagnostics,LSD(area under the curve[AUC]=0.724)was retained as the optimal stone burden parameter.Multivariate logistic regression analysis confirmed LSD,MSDE,and IPA as independent predictors of postoperative SFR.The nomogram model exhibited robust predictive performance with an AUC of 0.786(sensitivity:79.6%,specificity:71.0%).Internal validation via 1000 bootstrap resamples yielded an AUC of 0.792,and deci-sion curve analysis(DCA)confirmed clinical utility with net benefit across threshold probabilities of 4%—75%.Conclusions The nomogram model developed in this study,which incorporates both stone characteristics and renal anatomical parameters,demonstrates effective prediction of stone-free rate(SFR)following flexible ureteros-copy for lower pole calyceal stones.With stable predictive performance and high clinical applicability,this model provides a reliable tool for preoperative personalized decision-making in endourological management.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Lung cancer is characterized by high incidence and mortality rates and invasiveness, and its occurrence and development are influenced by various factors. Mitochondria, as ubiquitous organelles in the human body, regulate cellular processes, such as metabolism, signal transduction, oxidative stress, and genomic instability, thereby affecting the initiation and progression of lung cancer. This article summarizes the recent research progress on mitochondrial-targeted drugs, mitochondrial transfer, and mitochondrial gene therapy for lung cancer treatment. This work also discusses the principles and prospects of mitochondrial therapy to provide new insights for lung cancer treatment.

Background and objective Both of lung cancer incidence and mortality rank first among all cancers in China.Previous lung cancer screening trials were mostly selective screening for high-risk groups such as smokers.Non-smoking women accounted for a considerable proportion of lung cancer cases in Asia.This study aimed to evaluate the outcome of community-based mass screening in Guangzhou and identify the high-risk factors for lung cancer.Methods Residents aged 40-74 years in Guangzhou were screened with low-dose computed tomography(LDCT)for lung cancer and the pulmonary nodules were classified and managed according to China National Lung Cancer Screening Guideline with Low-dose Computed Tomography(2018 version).The detection rate of positive nodules was calculated.Before the LDCT examination,residents were required to complete a"lung cancer risk factors questionnaire".The risk factors of the questionnaire were analyzed by least absolute shrinkage and selection operator(LASSO)penalized Logistic regression analysis.Results A total of 6256 residents were included in this study.1228 positive nodules(19.63％)and 117 lung cancers were confirmed,including 6 cases of Tis,103 cases of stage Ⅰ(accounting for 88.03％of lung cancer).The results of LASSO penalized Logistic regression analysis indicated that age ≥50 yr(OR=1.07,95％CI:1.06-1.07),history of cancer(OR=3.29,95％CI:3.22-3.37),textile industry(OR=1.10,95％CI:1.08-1.13),use coal for cooking in childhood(OR=1.14,95％CI:1.13-1.16)and food al-lergy(OR=1.10,95％CI:1.07-1.13)were risk factors of lung cancer for female in this district.Conclusion This study highlighted that numerous early stages of lung cancer cases were detected by LDCT,which could be applied to screen-ing of lung cancer in women.Besides,age ≥50 yr,personal history of cancer,textile industry and use coal for cooking in childhood are risk factors for women in this district,which suggested that it's high time to raise the awareness of early lung cancer screening in this group.

Objective:To analyze the syndrome differentiation medication law of TCM in treating overactive bladder (OAB) based on data mining techniques.Methods:The articles about the treatment of OAB with TCM were collected from China National Knowledge Infrastructure (CNKI), Wanfang database, Chongqing VIP database and SinoMed. A prescription database for OAB was established. Methods such as frequency statistics, association rule analysis, clustering analysis, and factor analysis were used to analyze the medication law of the prescriptions.Results:The results showed that a total of 91 prescriptions were included, involving 134 kinds of Chinese materia medica. Five drugs were with a usage frequency of >30%. The top 4 categories with medication frequency were herbs for tonifying deficiency, herbs for inducing diuresis and draining dampness, herbs for relieving exterior syndrome and herbs for regulating qi. The properties of the included herbs were characterized by mild and warm, and the tastes were mainly sweet, pungent and bitter. The majority of meridian tropism was kidney meridian, supplemented by spleen, liver and lung meridians. The association rule analysis showed eight high-relevance medicine pairs, and four new candidate prescriptions were summarized after the clustering analysis, and six common factors were extracted by factor analysis.Conclusions:The location of the lesion of overactive bladder is mainly about the kidney, related to the spleen, liver and lung. And the pathogenesis is based on the kidney deficiency, which also due to the adverse qi transformation in triple energizer. Clinical medication is mainly about the herbs for tonifying deficiency and the herbs for inducing diuresis and draining dampness; at the same time those herbs for regulating qi and relieving exterior syndrome should be paid attention to, which are able to smooth and regulate the qi of the whole body.

Self-assembly refers to the spontaneous process where basic units such as molecules and nanostructured materials form a stable and compact structure. Peptides can self-assemble by non-covalent driving forces to form various morphologies such as nanofibers, nano layered structures, and micelles. Peptide self-assembly technology has become a hot research topic in recent years due to the advantages of definite amino acid sequences, easy synthesis and design of peptides. It has been shown that the self-assembly design of certain peptide drugs or the use of self-assembled peptide materials as carriers for drug delivery can solve the problems such as short half-life, poor water solubility and poor penetration due to physiological barrier. This review summarizes the formation mechanism of self-assembled peptides, self-assembly morphology, influencing factors, self-assembly design methods and major applications in biomedical field, providing a reference for the efficient use of peptides.
Pharmaceutical Preparations ; Peptides/chemistry* ; Amino Acid Sequence ; Nanostructures/chemistry* ; Drug Delivery Systems

Objective To evaluate the analgesic effect of tetrodotoxin (TTX) in four types of acute pain models and provide experimental support for its rational application. Methods Mice or rats were intramuscularly pretreated with morphine (1 mg/kg) or TTX (0, 0.5, 1, 2, 4 and 8 μg/kg) 40 min before acetic acid writhing test, formalin stimulation test, hot plate test or tail flick test. Pain response or pain threshold were recorded, and inhibition rate was calculated during the tests. The arachidonic acid of serum was determined by Elisa. Results Significant analgesic effects were observed with morphine in all four acute pain models. TTX dose-dependently reduced the number of writhing induced by acetic acid and inhibited the pain response induced by formalin during phase I and phase II, with the highest inhibition rate of more than 80.00% in two pain models. TTX showed analgesic effect in tail flick test and hot plate test, with the highest inhibition rate of 25.00% and 19.79%, respectively. Both acetic acid and formalin increased arachidonic acid in animal serum, but TTX had no significant inhibitory effect on the releasing of arachidonic acid. Conclusion TTX showed significant analgesic effect in the chemical stimulation pain models induced by acetic acid and formalin, but limited analgesic effect was observed on the physical stimulation pain model induced by heat (hot plate and hot water). TTX may produce analgesic effect by blocking the inflammatory mediators mediating pain response.