Background High-speed train engineers' lower extremities are constrained by compulsive vigilance pedal tasks and limited space beneath the control console during driving. Shifts in alertness triggered by running route observation may share the same mental resource required by moderate-to-low physical exertion. Current research on improving cab design and maintaining optimal on-duty attention allocation remains limited. Objective To examine variations in lower extremity muscle load, gaze-tracking behavior, and driving performance under various combinations of vigilance pedal positions and route scenarios during simulated high-speed train tasks. To identify optimal working condition combinations that promote level and variety of physical activity and facilitate rational attention allocation. Methods A 4×2 within-subjects design were employed (4 vigilance pedal position profiles: knee front, side, and any; 2 route scenarios: monotonous and complex). Nine male college volunteers were recruited as simulated drivers to perform designated interval driving tasks. Surface electromyography and eye tracking were used to assess leg muscle load and gaze behavior respectively. Task performance and subjective fatigue were recorded. Results In all simulation driving tasks, skeletal muscle loads were low with the percentage of maximum voluntary contraction (%MVC) at approximately 4%. No fatigue tendencies were observed within single trial blocks (7 min), and the subjective fatigue ratings remained relatively low. While the activation of the dominant-side tibialis anterior was higher for the knee pedal than for the front (%MVC: 3.7% ± 3.13% vs. 1.08% ± 0.72%) or the side pedals (%MVC: 3.7% ± 3.13% vs. 1.4% ± 0.77%). The activation level of the dominant-side gastrocnemius was higher for the knee pedal than for the other three pedal profiles. For the any pedal condition, the intercept of the instantaneous median frequency curve for the dominant-side rectus femoris was lower in the monotonous route than in the complex route [(111.18 ± 35.78) Hz vs. (153.33 ± 39.12) Hz]. Among eye-tracking metrics, total fixations were higher during knee-level pedaling than side pedaling, while more saccades were recorded in monotonous routes than in complex ones. Regarding task performance, the any pedal yielded fewer missed signals than the front pedal, with 2/3 and 1/3 of participants preferring the front and knee pedals, respectively. The activation levels of the dominant tibialis anterior and dominant gastrocnemius muscles during the knee pedal × complex route combination were higher than any combination involving the front pedal. No statistically significant effect of pedal position or route scenario was found on other indicators. Conclusion The combination of knee pedal and complex route provides an optimal working setting for maximizing leg muscle mobility without compromising attention allocation or driving performance. It is recommended that train engineers modulate attention during monotonous routes to avoid emotional tension and increased muscle strain caused by over-monitoring. Given the ergonomic characteristics of high cognitive load, low physical exertion levels, and highly restricted lower limb mobility among high-speed train engineers, future cab designs should consider incorporating knee-level vigilance pedal and adjust safety alertness rules to allow reset via either front or knee pedal.

Background High-speed train engineers' lower extremities are constrained by compulsive vigilance pedal tasks and limited space beneath the control console during driving. Shifts in alertness triggered by running route observation may share the same mental resource required by moderate-to-low physical exertion. Current research on improving cab design and maintaining optimal on-duty attention allocation remains limited. Objective To examine variations in lower extremity muscle load, gaze-tracking behavior, and driving performance under various combinations of vigilance pedal positions and route scenarios during simulated high-speed train tasks. To identify optimal working condition combinations that promote level and variety of physical activity and facilitate rational attention allocation. Methods A 4×2 within-subjects design were employed (4 vigilance pedal position profiles: knee front, side, and any; 2 route scenarios: monotonous and complex). Nine male college volunteers were recruited as simulated drivers to perform designated interval driving tasks. Surface electromyography and eye tracking were used to assess leg muscle load and gaze behavior respectively. Task performance and subjective fatigue were recorded. Results In all simulation driving tasks, skeletal muscle loads were low with the percentage of maximum voluntary contraction (%MVC) at approximately 4%. No fatigue tendencies were observed within single trial blocks (7 min), and the subjective fatigue ratings remained relatively low. While the activation of the dominant-side tibialis anterior was higher for the knee pedal than for the front (%MVC: 3.7% ± 3.13% vs. 1.08% ± 0.72%) or the side pedals (%MVC: 3.7% ± 3.13% vs. 1.4% ± 0.77%). The activation level of the dominant-side gastrocnemius was higher for the knee pedal than for the other three pedal profiles. For the any pedal condition, the intercept of the instantaneous median frequency curve for the dominant-side rectus femoris was lower in the monotonous route than in the complex route [(111.18 ± 35.78) Hz vs. (153.33 ± 39.12) Hz]. Among eye-tracking metrics, total fixations were higher during knee-level pedaling than side pedaling, while more saccades were recorded in monotonous routes than in complex ones. Regarding task performance, the any pedal yielded fewer missed signals than the front pedal, with 2/3 and 1/3 of participants preferring the front and knee pedals, respectively. The activation levels of the dominant tibialis anterior and dominant gastrocnemius muscles during the knee pedal × complex route combination were higher than any combination involving the front pedal. No statistically significant effect of pedal position or route scenario was found on other indicators. Conclusion The combination of knee pedal and complex route provides an optimal working setting for maximizing leg muscle mobility without compromising attention allocation or driving performance. It is recommended that train engineers modulate attention during monotonous routes to avoid emotional tension and increased muscle strain caused by over-monitoring. Given the ergonomic characteristics of high cognitive load, low physical exertion levels, and highly restricted lower limb mobility among high-speed train engineers, future cab designs should consider incorporating knee-level vigilance pedal and adjust safety alertness rules to allow reset via either front or knee pedal.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Objective To investigate the clinical prognostic value of the prognostic nutritional index (PNI) in patients with renal cell carcinoma (RCC) undergoing partial nephrectomy.Methods A retrospective analysis was conducted on the clinical data of RCC patients who underwent partial nephrectomy at our hospital during 2020 and 2024.The optimal cutoff value of PNI was determined based on the maximum Youden index from the receiver operating characteristic (ROC) curve.The clinicopathological characteristics, overall survival (OS), and progression-free survival (PFS) between patients with different PNI levels were compared.Cox regression analysis was used to explore the independent prognostic factors for RCC patients. Results Based on the ROC curve, the optimal cutoff value corresponding to the maximum Youden index was calculated to be 46.675, at which point the sensitivity was 65.3% and the specificity was 62.2%.Of the 815 patients included in the study, 293 (36.0%) patients had a PNI＜46.675.Cox regression analysis confirmed that preoperative PNI, tumor diameter, ISUP classification, and ECOG score were independent risk factors for postoperative OS in patients with RCC who underwent PN (P＜0.05).In addition, preoperative PNI, tumor diameter, ISUP classification and ECOG score were independent risk factors for postoperative PFS (P＜0.05).After covariates in the multivariable Cox regression model were adjusted, patients in the low PNI group demonstrated significantly shorter overall survival (HR=2.392, P＜0.001) and significantly poorer progression-free survival (HR=2.076, P＜0.001) compared to those in the high PNI group.Conclusion Preoperative PNI has significant clinical value in evaluating the prognosis of RCC patients undergoing partial nephrectomy.An elevated preoperative PNI is associated with a better prognosis.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

Objective::To systematically study the mechanisms by which Yinzhihuang (YZH), a traditional Chinese medicine, ameliorates intrahepatic cholestasis of pregnancy (ICP), a liver disorder associated with significant maternal and fetal complications.Methods::This experimental study was conducted from January 2024 to August 2024, utilizing data from public databases (Traditional Chinese Medicine Systems Pharmacology, GeneCards, Online Mendelian Inheritance in Man, DisGeNET, Proteome Xchange) alongside in vitro cell culture experiments. Network pharmacology identified active components of YZH and potential therapeutic targets for ICP. Ultra-performance liquid chromatography–mass spectrometry characterized YZH oral liquid, and its effective doses were evaluated in taurocholic acid (TCA)-induced HTR-8/SVneo cells, an in vitro ICP model. ICP-related targets were gathered from multiple databases, and hub genes were selected through bioinformatics and previously identified differentially expressed proteins. Functional annotation and pathway enrichment analyses were conducted, with validation in TCA-induced cells treated with various YZH concentrations (0.1%–5.0%) compared to controls. Molecular docking confirmed predicted interactions.Results::Using network pharmacology, 104 active compounds and 241 potential targets of YZH were identified. Integration of multiple databases yielded 1897 YZH-related therapeutic targets and 3783 ICP-associated genes. Proteomic analysis identified 227 differentially expressed proteins, from which 10 hub genes were selected; among these, APOA2, COL1A1, and ADIPOQ were significantly upregulated in ICP samples. UPLC-ESI-MS/MS detected 2022 compounds, predominantly flavonoids (25.07%, 507/2022) and phenolic acids (14.44%, 292/2022). Molecular docking demonstrated strong binding affinities between several active compounds and the hub genes. In TCA-induced HTR-8/SVneo cells, 0.5% YZH treatment significantly enhanced cell viability and modulated hub gene expression, supporting a potential multi-target mechanism.Conclusion::This study systematically explored the active components and potential targets of YZH in ICP through network pharmacology, proteomics, and in vitro validation. The findings suggest that YZH may act via the PPAR signaling pathway by modulating genes such as PPARA, PPARG, ADIPOQ, and APOA2.

Objective:To explore the relationship between suicide attempts,school bullying,and psychological resilience in children and adolescents with major depressive disorder(MDD)and school bullying and psychological resilience.Methods:A total of 784 patients with MDD aged 10 to 18 years were included.The Chinese version of the Olweus Bullying Victimization Questionnaire,Adolescent Psychological Resilience Scale,and a suicide attempt assessment were utilized to evaluate school bullying,psychological resilience,and suicide attempt.Stepwise logistic regression was applied to identify the associated factors of suicide attempts.Results:The occurrence of suicide at-tempts in children and adolescents with MDD was positively associated with physical bullying(OR=1.85,95％CI:1.14-3.02)and indirect bullying(OR=1.48,95％CI:1.06-2.04),and negatively associated with higher levels of goal focus(OR=0.62,95％CI:0.45-0.85)and positive cognition(OR=0.62,95％CI:0.45-0.85)at higher levels.Conclusion:Bullying significantly increases the risk of suicide attempts in children and adolescents with MDD,while higher psychological resilience could mitigate this risk.

Objective To evaluate the application of carbapenem antibiotics in conjunction with hemofil-tration for patients with septic shock and to analyze the impact on serum levels of lncRNA XIST and miRNA-130a.Methods A prospective study was conducted on 80 patients with septic shock treated at our hospital from August 2022 to January 2024.These patients were randomly divided into a control group and an experimental group,each comprising 40 cases.The control group received carbapenem antibiotics,while the experimental group received carbapenem antibiotics in combination with hemofiltration.The clinical outcomes of both groups were evaluated,and comparisons were made regarding their hemodynamic indices[including cardiac output(CO),central venous pressure(CVP),and mean arterial pressure(MAP)],immune function indices[including interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-alpha(TNF-α)],oxygen metabolism indices[including blood oxygen saturation(SaO2),blood lactate(LAC),and oxygenation index(PaO2/FiO2)],as well as serum levels of lncRNA XIST and miRNA-130a expression.Results Following treatment,the levels of CO,CVP,MAP,SaO2,PaO2/FiO2,and miRNA-130a were significantly increased,whereas the levels of IL-6,CRP,TNF-α,LAC,and lncRNA XIST were significantly decreased compared to pre-treatment levels(all P<0.05).In comparison with the control group,the experimental group exhibited significantly higher levels of CO,CVP,MAP,and miRNA-130a,as well as significantly lower levels of IL-6,CRP,TNF-α,and lncRNA XIST(all P<0.05).The overall effective rate in the experimental group was significantly higher than that in the control group(χ2=4.501,P<0.05),while no significant difference was observed in the incidence of adverse reactions between the two groups(χ2=0.180,P>0.05).Conclusion Carbapenem antibiotics and hemofiltration therapy can alleviate the symptoms of septic shock patients by downregulating lncRNA XIST expression,upregulating miRNA-130a expression,modulating inflammatory factors,enhancing oxygen metabolism indices,and maintaining hemodynamic stability.

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.