ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

ObjectiveCleft palate (CP) is a common congenital deformity often associated with velopharyngeal insufficiency (VPI), which disrupts the physiological coupling between respiration and speech. Conventional clinical assessments, such as nasometry and spirometry, provide limited static data and fail to visualize the dynamic spatiotemporal distribution of lung ventilation during phonation. This study introduces spatiotemporal electrical impedance tomography (ST-EIT) to evaluate speech-respiratory functional features in CP patients compared to normal controls (NC). The aim is to characterize multi-domain respiratory patterns and to validate an interpretable machine learning framework for providing objective, quantitative evidence for clinical assessment. MethodsSeventy-five participants were enrolled in this study, comprising 37 patients with surgically repaired CP and 38 healthy volunteers matched for age, gender, and body mass index (BMI). All subjects performed standardized sustained phonation tasks while undergoing synchronous monitoring with a 16-electrode EIT system and a pneumotachograph. A comprehensive feature engineering pipeline was developed to extract physiological parameters across 3 complementary domains. (1) Temporal domain: including inspiratory/expiratory phase duration (tPhase), time constants (Tau), and inspiratory-to-expiratory time ratios (TI/TE); (2) airflow domain: comprising mean flow, peak flow, and instantaneous flow at 25%, 50%, and 75% of tidal volume; and (3) spatial domain: quantifying global and regional tidal impedance variation (TIV), global inhomogeneity (GI), and center of ventilation (CoV). Extreme Gradient Boosting (XGBoost) classifiers were trained using 5 distinct data sources (Spirometry, Nasometry, Inspiratory-EIT, Expiratory-EIT, and fused ST-EIT). Model performance was rigorously evaluated via stratified 5-fold cross-validation, and Shapley additive explanations (SHAP) were employed to quantify global and local feature contributions. ResultsThe CP group exhibited a distinct respiratory phenotype compared to controls. In the temporal domain, CP patients showed significantly shorter inspiratory (1.60 s vs.1.85 s, P<0.001) and expiratory phase durations (2.45 s vs. 3.95 s, P<0.001), indicating a rapid, shallow breathing rhythm. In the airflow domain, while inspiratory flows were comparable, the CP group demonstrated significantly elevated mean and peak flows during the expiratory phase (P<0.001), reflecting compensatory respiratory effort. Spatially, CP patients presented significant ventilation redistribution, characterized by higher regional TIV in the right-anterior (ROI1) and left-posterior (ROI4) quadrants, but lower TIV in the left-anterior (ROI2) quadrant. In terms of diagnostic accuracy, the multi-modal ST-EIT model achieved the highest performance (AUC: 0.915±0.012, Accuracy: 0.843±0.019, F1-score: 0.872±0.017), substantially outperforming models based on spirometry (AUC: 0.721) or nasometry (AUC: 0.625) alone. Interpretability analysis revealed that spatial domain features were the most critical, contributing 53.4% to the model’s decision-making, followed by temporal (25.0%) and airflow (21.6%) features. ConclusionST-EIT successfully captures the temporal, airflow, and spatial deviations in CP speech respiration that are undetectable by conventional methods—specifically, rapid phase transitions, hyperdynamic expiratory airflow, and regional ventilation heterogeneity. This study validates ST-EIT as a robust, non-invasive, and radiation-free tool for characterizing speech-respiratory dysfunction, offering high clinical value for bedside screening, rehabilitation planning, and longitudinal monitoring of patients with cleft palate.

ObjectiveCleft palate (CP) is a common congenital deformity often associated with velopharyngeal insufficiency (VPI), which disrupts the physiological coupling between respiration and speech. Conventional clinical assessments, such as nasometry and spirometry, provide limited static data and fail to visualize the dynamic spatiotemporal distribution of lung ventilation during phonation. This study introduces spatiotemporal electrical impedance tomography (ST-EIT) to evaluate speech-respiratory functional features in CP patients compared to normal controls (NC). The aim is to characterize multi-domain respiratory patterns and to validate an interpretable machine learning framework for providing objective, quantitative evidence for clinical assessment. MethodsSeventy-five participants were enrolled in this study, comprising 37 patients with surgically repaired CP and 38 healthy volunteers matched for age, gender, and body mass index (BMI). All subjects performed standardized sustained phonation tasks while undergoing synchronous monitoring with a 16-electrode EIT system and a pneumotachograph. A comprehensive feature engineering pipeline was developed to extract physiological parameters across 3 complementary domains. (1) Temporal domain: including inspiratory/expiratory phase duration (tPhase), time constants (Tau), and inspiratory-to-expiratory time ratios (TI/TE); (2) airflow domain: comprising mean flow, peak flow, and instantaneous flow at 25%, 50%, and 75% of tidal volume; and (3) spatial domain: quantifying global and regional tidal impedance variation (TIV), global inhomogeneity (GI), and center of ventilation (CoV). Extreme Gradient Boosting (XGBoost) classifiers were trained using 5 distinct data sources (Spirometry, Nasometry, Inspiratory-EIT, Expiratory-EIT, and fused ST-EIT). Model performance was rigorously evaluated via stratified 5-fold cross-validation, and Shapley additive explanations (SHAP) were employed to quantify global and local feature contributions. ResultsThe CP group exhibited a distinct respiratory phenotype compared to controls. In the temporal domain, CP patients showed significantly shorter inspiratory (1.60 s vs.1.85 s, P<0.001) and expiratory phase durations (2.45 s vs. 3.95 s, P<0.001), indicating a rapid, shallow breathing rhythm. In the airflow domain, while inspiratory flows were comparable, the CP group demonstrated significantly elevated mean and peak flows during the expiratory phase (P<0.001), reflecting compensatory respiratory effort. Spatially, CP patients presented significant ventilation redistribution, characterized by higher regional TIV in the right-anterior (ROI1) and left-posterior (ROI4) quadrants, but lower TIV in the left-anterior (ROI2) quadrant. In terms of diagnostic accuracy, the multi-modal ST-EIT model achieved the highest performance (AUC: 0.915±0.012, Accuracy: 0.843±0.019, F1-score: 0.872±0.017), substantially outperforming models based on spirometry (AUC: 0.721) or nasometry (AUC: 0.625) alone. Interpretability analysis revealed that spatial domain features were the most critical, contributing 53.4% to the model’s decision-making, followed by temporal (25.0%) and airflow (21.6%) features. ConclusionST-EIT successfully captures the temporal, airflow, and spatial deviations in CP speech respiration that are undetectable by conventional methods—specifically, rapid phase transitions, hyperdynamic expiratory airflow, and regional ventilation heterogeneity. This study validates ST-EIT as a robust, non-invasive, and radiation-free tool for characterizing speech-respiratory dysfunction, offering high clinical value for bedside screening, rehabilitation planning, and longitudinal monitoring of patients with cleft palate.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Objective To identify risk factors for severe hand-foot-mouth disease(HFMD)cases in Fuzhou,providing scientific evidence for disease prevention and control.Methods Severe pediatric HFMD cases in Fuzhou between 2017 and 2024 were collected from the"China Disease Prevention and Control Information System".Non-severe cases were frequency-matched based on the same onset period,same affected region,same parents'educational level,and age(±1 year)to form a non-severe group.Demographic characteristics,clinical symptoms,medical history,and pathogen types of both groups were collected.Logistic regression was used to identify the risk factors for severe cases.Results From 2017 to 2024,Fuzhou reported 503 severe HFMD cases and 1053 matched non-severe cases.Demographically,severe group had a higher proportion of home-based childcare,rural residence,care-seeking delay>2 d,while EV71 vaccination rates,handwashing habits before meals and after defecation,and caregivers with HFMD prevention education were lower than those in non-severe group,with statistically significant difference(P<0.001).Clinically,severe group showed more frequent fever>3 d,altered consciousness/seizure,limb tremors/convulsions,the proportion of infectious disease and the proportion of EV71-positive cases than those in non-severe group(P<0.001).Multivariate logistic regression analysis showed that home-based childcare(OR=3.213,95%CI 1.913-5.398),rural residence(OR=2.121,95%CI 1.513-2.973),lack of EV7 vaccination(OR=3.141,95%CI 1.996-4.945),care-seeking delay>2 d(OR=2.004,95%CI 1.410-2.849),no handwashing habits before meals and after defecation(OR=3.927,95%CI 1.718-5.356),caregiver without HFMD education(OR=2.465,95%CI 1.807-3.362),fever>3 d(OR=2.585,95%CI 1.801-3.709),altered consciousness/seizures(OR=4.059,95%CI 2.731-6.031),limb tremors/convulsions(OR=2.087,95%CI 1.398-3.117),history of infectious disease(OR=3.369,95%CI 1.725-6.335)and EV71 positivity(OR=3.854,95%CI 2.678-5.545)were risk factors for severe HFMD cases.The recovery time in severe group was significantly longer than that in non-severe group[18(5,32)d vs.11(4,23)d,P<0.001].Conclusions Prevention and control efforts should target high-risk groups by strengthening health education,promoting EV71 vaccination and improving the treatment of severe HFMD cases to reduce the incidence of severe HFMD.

Objective To investigate the effect of gender on prognosis after transcatheter patent foramen ovale(PFO)closure in patients with cerebral infarction or transient ischemic attack.Methods A retrospective cohort study was conducted involving patients with cerebral infarction or transient ischemic attack(TIA)who underwent PFO closure at our hospital between January 2013 and December 2023.The patients were grouped by gender,and related data were collected,including age,comorbidities,Risk of Paradoxical Embolism(RoPE)score,laboratory results,findings of transthoracic/transesophageal echocardiography(TTE/TEE),and post-procedural complications,such as device-related thrombosis(DRT),recurrent stroke,bleeding,and atrial fibrillation(AF).Results A total of 112 patients were enrolled,including 59 males and 53 females,at a mean age of 42.47±12.35 years.The females had significantly higher preoperative RoPE score than the males(6.6±1.4 vs 6.0±1.5,P=0.046),and a statistical difference was observed in the distribution of infarction sites between them(Chi-square=10.25,P=0.006),indicating that the males were prone to posterior circulation infarction.Intraoperative transthoracic echocardiography revealed a greater distance from the PFO to the aortic root in the females(9.3±2.4 mm vs 7.6±2.0 mm,P<0.001).During a median follow-up of 4 years,the male group had 1 case of myocardial infarction,1 cerebral hemorrhage,1 paroxysmal AF,2 gingival bleeding episodes,and 1 skin ecchymosis.In the female group,1 case experienced pulmonary embolism,1 paroxysmal atrial fibrillation,3 gingival bleeding episodes,2 skin ecchymoses,2 recurrent cerebral infarctions,and 2 recurrent TIAs.There was no statistical difference in overall adverse events between gender(P=0.291).Although the females had higher rates of recurrent cerebral infarction and TIA,this difference lacked statistical significance(P=0.222).Multivariate Cox regression analysis indicated that after adjusting for various potential confounding factors,such as RoPE score,age,hypertension,coronary heart disease,and other factors,gender was not an independent predictor of composite endpoint events after surgery.Conclusion Gender does not significantly affect overall prognosis after PFO closure in patients with cerebral infarction or TIA.However,females showed a trend toward higher rates of recurrent cerebral infarction and TIA.

Plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in the environment are important"fingerprint"nuclides in the study of nuclear activity traceability.The content of plutonium isotopes in the environmental metrics is usually very low,and the measurement of these isotopes,especially 238Pu,using mass spectrometry is seriously interfered with by the coexisting 238U.The analysis of several plutonium isotopes in soil usually requires combination of multiple measurement techniques,which leads to a long analysis time and large uncertainty in the isotope ratio.In this work,the hydrous titanium oxide(HTiO)precipitated by the hydrolysis of titanium oxydichloride(TiOCl2)under near-neutral condition was used to preconcentrate plutonium from the soil digestion solution,and the highly efficient decontamination of 238U in the sample was achieved by TK200 resin column chromatography with a decontamination factor of 108.Simulation resuts of density functional theory(DFT)showed that NH3 was considered as a promising reaction gas to eliminate the interference of 238U from 238Pu measurement using mass spectrometry due to the significant discrepancy of the chemical reactivity of U+and Pu+with the reactive gas NH3.Experiments confirmed that by optimizing the flow rates of collision gas(He)and reaction gas(NH3),the interference of 238U could be effectively suppressed,and the decontamination factor of 238U was 104.Combined with chemical separation,the overall decontamination factor of 238U could reach 1012 by using the developed method.By combining chemical separation and tandem quadrupole inductively coupled plasmon-mass spectrometry(ICP-MS/MS)measurement,the simultaneous determination of four ultra-trace plutonium isotopes in soil was realized,and the detection limit of plutonium isotopes was at the femtogram level.Analysis of the international standard reference materials(NIST-SRM-4357 and IAEA-384)showed that the established method could be successfully used for the accurate analysis of ultra-trace four plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in soil samples.

Foodborne illnesses caused by Salmonella pose significant threats to worldwide public health safety.In this study,a rapid method for screening viable Salmonella in oyster sauce and milk was developed by utilizing an electronic microbial growth analyzer(EMGA).Target food samples were diluted 10-fold with RVS broth and loaded into test tubes.Test tubes were positioned in the EMGA to determine the bacterial growth curves and the time required to reach the maximum growth rate(Tmgr).Using Salmonella typhimurium(S.typhimurium)asan model species,there was linear relationship between the logarithmic value of viable bacterial concentration(lgC)and Tmgr over the range of 5×101-5×106 CFU/mL,with a detection limit of 10 CFU/mL.For oyster sauce,the regression equation was Tmgr(min)=-80.775lg[C/(CFU/mL)]+754.96(R2=0.9907),and the recovery rates of S.typhimurium ranged from 95.2%to 119.8%,with relative standard deviations(RSD)ranging from 3.5%to 16.3%.For milk,the regression equation was Tmgr(min)=-71.922 lg[C/(CFU/mL)]+618.65(R2=0.9985),with recovery rates ranging from 98.4%to 110.6%and RSD ranging from 6.4%to 12.8%.The EMGA method required only one portable instrument,and involving only three manual steps,i.e.,dilution,transfer,and insertion.When S.typhimurium contamination reached 106 CFU/mL,the total time consumption,from the unwrapping of samples to the readout of bacterial concentration,was no more than 7 h.When applied to detection of actual oyster sauce and milk samples,the new method demonstrated strong consistency with plate counting results in positive detection rates.This method was superior to the plate counting method,which was generally considered as a gold standard,in terms of accuracy,precision,simplicity and efficiency,representing a promising alternative for the on-site screening and quantification of viable Salmonella in oyster sauce and milk products.

Objective To explore whether ferroptosis is involved in α-amanitin-induced hepatocyte in-jury by detecting iron deposition in mice liver tissues,oxidative stress indicators in hepatocytes and L-02 cells,and expressions of ferroptosis-related proteins after α-amanitin exposure.Methods The poi-soning models of α-amanitin C57BL/6J mice and L-02 cell were established.The Lillie ferrous iron staining and Prussian blue staining were used to detect iron deposition;the kits were applied to detect the levels of superoxide dismutase(SOD),catalase(CAT),malondialdehyde(MDA),and glutathione(GSH).Western blotting was performed to analyze expressions of p53,solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4).Results Compared with the control group,after α-amanitin exposure,positive cell rates of Fe2+and Fe3+in mice liver tissues increased significantly.In the liver tissues of medium(0.35 mg/kg)and high(0.45 mg/kg)dose groups and L-02 cells treated with 1 μmol/L α-amanitin,the level of GSH decreased,the level of MDA increased,and the activities of SOD and CAT decreased significantly.In addition,α-amanitin upregulated the expression of p53 in a concentration-and time-dependent manner and inhibited the expressions of SLC7A11 and GPX4.Con-clusion Ferroptosis plays an important role in α-amanitin-induced hepatocyte injury.Abnormalities of ferroptosis-related indicators can provide references for the forensic identification of α-amanitin poisoning.