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Colorectal cancer (CRC) is a common digestive system malignancy. Ferroptosis, a new form of regulated cell death, plays a vital role in the pathogenesis and therapy of cancers. We aimed to study the role of apatinib in ferroptosis of CRC cells and its potential mechanisms. Human CRC HCT116 cells were exposed to apatinib. Cell viability was examined using a CCK-8 kit. The concentrations of intracellular iron and reactive oxygen species (ROS) were detected using kits. Additionally, Western blot analysis was used to determine the expression of ferroptosis-related proteins. Elongation of very long-chain fatty acids family member 6 (ELOVL6) was one of the targets of apatinib predicted by SwissTargetPrediction. Therefore, ELOVL6 expression was evaluated after treatment with apatinib. Subsequently, the effects of ELOVL6 overexpression on ferroptosis of HCT116 cells were investigated. Finally, STRING database was applied to predict the potential proteins interacting with ELOVL6, and co-immunoprecipitation (co-IP) assay was applied for confirmation. Results indicated that apatinib decreased cell viability and increased the contents of intracellular iron ROS. Moreover, significantly upregulated ACSL4 expression was observed, accompanied by notable downregulation of GPx4 and FTH1 expression after apatinib exposure. Furthermore, ELOVL6 expression was remarkably enhanced in HCT116 cells, which was dramatically inhibited under apatinib intervention. ELOVL6 overexpression reversed the effects of apatinib on cell viability and ferroptosis of HCT116 cells. Moreover, ACSL4, a vital regulator of ferroptosis, could interact with ELOVL6 directly, which was confirmed by the result of co-IP. These findings demonstrated that apatinib promoted ferroptosis in CRC cells by targeting ELOVL6/ACSL4, providing a new mechanism support for apatinib application in the clinical treatment of CRC.

Immune checkpoint inhibitors (ICIs) are effective for non-small cell lung cancer (NSCLC) treatment, but the response rate remains low. Programmed cell death ligand 1 (PD-L1) in peripheral blood, including soluble form (sPD-L1), expression on circulating tumor cells (CTCs PD-L1) and exosomes (exoPD-L1), are minimally invasive and promising markers for patient selection and management, but their prognostic significance remains inconclusive. Here, we performed a meta-analysis for the prognostic value of PD-L1 blood markers in NSCLC patients treated with ICIs. Eligible studies were obtained by searching PubMed, EMBAS, Web of Science, and Cochrane Library prior to November 30, 2023. The associations between pre-treatment, post-treatment and dynamic changes of blood PD-L1 levels and progression-free survival (PFS)/over survival (OS) were analyzed by estimating hazard ratio (HR) and 95% confidence interval (CI). A total of 26 studies comprising 1606 patients were included. High pre- or post-treatment sPD-L1 levels were significantly associated with worse PFS (pre-treatment: HR=1.49, 95%CI 1.13-1.95; post-treatment: HR=2.09, 95%CI 1.40-3.12) and OS (pre-treatment: HR=1.83, 95%CI 1.25-2.67; post-treatment: HR=2.60, 95%CI 1.09-6.20, P=0.032). High pre-treatment exoPD-L1 levels predicted a worse PFS (HR=4.24, 95%CI 2.82-6.38, P<0.001). Pre-treatment PD-L1 CTCs tended to be correlated with prolonged PFS (HR=0.63, 95%CI 0.39-1.02) and OS (HR=0.58, 95%CI 0.36-0.93). Patients with up-regulated exoPD-L1 levels, but not sPD-L1, after ICIs treatment had significantly favorable PFS (HR=0.36, 95%CI 0.23-0.55) and OS (HR=0.24, 95%CI 0.08-0.68). PD-L1 blood markers, including sPD-L1, CTCs PD-L1 and exoPD-L1, can effectively predict prognosis, and may be potentially utilized for patient selection and treatment management for NSCLC patients receiving ICIs.

Objective: To elucidate the chemical profile of Xanthocerais lignum’s extracts of different polarities and their impact on rheumatoid arthritis (RA), we identified anti-RA markers and predicted their action mechanisms. Methods: A collagen-induced arthritis rat model was established, and UPLC-Q-Exactive Orbitrap MS technology was employed to analyze and identify the chemical constituents within the alcohol extract of Xanthocerais lignum and its various extraction fractions, as well as their translocation into the bloodstream. Serum spectrum–effect correlation analysis was utilized to elucidate the pharmacodynamic material basis of Xanthocerais lignum against RA and to screen for Q-Markers. Finally, the potential anti-RA mechanisms of the Q-Markers were predicted through compound-target interaction data and validated using molecular docking techniques. Results: We identified 71 compounds, with flavan-3-ols and flavanones as key components. Of these, 36 were detected in the bloodstream, including 17 original and 19 metabolized forms. Proanthocyanidin A2, dihydroquercetin, catechin, and epicatechin (plus glucuronides) showed potential anti-RA activity. These compounds, acting as Q-Markers, may modulate ERK, NF-κB, HIF-1α, and VEGF in the HIF-1 pathway. Conclusions: This research clarifies Xanthocerais lignum’s pharmacodynamic material basis against RA, identifies 4 Q-Markers, and offers insights into their mechanisms, aiding quality assessment and lead compound development for RA treatment.

Background Overweight and obesity have become major public health concerns worldwide. Persistent stress can activate the human hypothalamic‒pituitary‒adrenal axis (HPA) and increase the intake of “self-rewarding food”, thereby raising the incidence of obesity. Health care workers (HCWs) experience higher workloads and mental stress than workers in many other industries, which may put them at increased risk for overweight/obesity. However, few studies have been carried out on overweight and obesity among HCWs in China, and the overall scenario and behind-the-scenes factors of their overweight and obesity are unknown. The aim of this study is to understand the epidemic of overweight and obesity and risk factors among Chinese HCWs. Methods Based on a cross-sectional web survey design, 23,234 HCWs from 100 health institutions in 5 provinces/autonomous regions/municipalities across China were sampled to answer a self-administered questionnaire that was purposely developed using a multi-staged clustered random-sampling method. Chi-square test and ANOVA were performed to compare variables between two or more groups. Univariate analyses were conducted to identify the influence of self-reported persistent stress and/or recurrent anxiety/depressed mood on lifestyle behaviors. A multivariate binary logistic regression model was used to analyse the risk factors of overweight/obesity. Results Among the respondents, 34.26% were overweight, and 11.22% were obese. Most of the respondents had regular exercise habits (68.17%), had habitually stayed-up late (65.06%) and had been affected by persistent stress and/or recurrent anxiety/depressed mood (62.04%). A higher proportion of those with persistent stress and/or recurrent anxiety/depressed mood than those without habitually staying-up late (76.18%); consumed take-out food (54.92%), fried food (49.93%), snacks or desserts (50.51%); drank sugary drinks (46.57%); smoked (14.27%); and drank alcohol (23.34%). Gender (Female) (OR: 0.314, 95%CI: 0.292–0.336), age (OR: 1.742–2.334, 95%CI: 1.544–2.858), education (OR: 0.620–0.728, 95%CI: 0.445–0.973), living and working area (OR: 1.271, 95%CI: 1.192–1.355), breakfast (OR: 0.898, 95%CI: 0.839–0.960), fried food (OR: 1.133, 95%CI: 1.048–1.224), and alcohol consumption (OR: 1.111, 95%CI: 1.017–1.214) were factors for overweight/obesity. All of the aforementioned results were significant ( P  < 0.05). Conclusions The overweight/obesity rate of Chinese HCWs is rather high, which might be directly associated with lifestyle behaviors. However, these behaviors fundamentally originated from persistent stress and/or recurrent anxiety/depression, mediated by lifestyle behaviors. Substantial measures should be taken for stress reduction and mental health promotion for overweight/obesity prevention and control among HCWs.

Intensive agricultural mechanization in Northeast China has exacerbated soil compaction and degraded water retention. Although biochar modifies soil hydraulics, its combined effect with matric suction on compressive behavior remains unclear. This study investigated the hydraulic and mechanical responses of repacked sandy clay brown soil to biochar (0, 0.5, 1 g kg−1) under varying matric suction (6–1000 kPa). We utilized water retention curves and uniaxial compression tests to assess mechanical properties, including pre-compression stress (σp), penetration resistance (PR), compression index (Cc) and swelling index (Cs). Additionally, an integrated model using the Entropy Weight Method (EWM), the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), and the Adversarial Interpretive Structure Model (AISM) was developed to evaluate soil resistance and resilience. Results indicated that 1 g kg−1 biochar significantly enhanced field capacity (θFC) and readily extractable water (θMRE) (p < 0.05). While individual factors influenced all mechanical properties, the biochar–suction interaction significantly affected pre-compression stress and the compression index (p < 0.05). The model identified 1 g kg−1 biochar at 1000 kPa suction as the optimal combination for maximizing soil structural stability. These findings highlight the critical role of biochar–matric suction interactions in accurately assessing and managing soil mechanical behavior.

Introduction Marathon, as a long-distance aerobic exercise, has become a fashionable or popular sport. However, little is known about the holistic metabolic changes occurring within the serum metabolome of athletes after the completion of a marathon. Objectives The goal of current study was to have an in-depth understanding of the impact of marathon on human metabolomics as well as the relationships among a variety of metabolites. Methods The 20 studied subjects were all adult males who participated in a marathon. The serum samples of these participants were collected before and after the marathon and the biochemical metabolites in the serum were identified by an untargeted two-dimensional gas chromatography time-of-flight mass spectrometry. Results All participants completed the marathon within 3 h. Compared to those before exercise, serum urea and creatine kinase, as well as cortisol, elevated significantly ( p  < 0.05), whereas testosterone decreased significantly ( p  < 0.01). Metabolomic analysis showed that, compared to those before the competition, metabolites pyruvic acid, glyceric acid, malic acid, cis-aconitic acid, galacturonic acid, methyl fumaric acid, maltotriose, and others increased significantly after the competition ( p  < 0.05), but glucosamine and O-succinyl-L-homoserine decreased significantly ( p  < 0.05). Amino acid indexes, such as alanine, L-tyrosine and phenylalanine, increased significantly after exercise compared with those before exercise ( p  < 0.05), whereas serine, valine and asparagine decreased significantly ( p  < 0.05). Lipid metabolism indexes, glycerol, glyceric acid, octanoic acid, and quinic acid increased significantly ( p  < 0.05). Theophylline, xanthine and other indicators of caffeine metabolism increased significantly ( p  < 0.05). Furthermore, marathon performance, fat percentage, VO 2 max, and hemoglobin were correlated with the serum metabonomic indicators, so were serum testosterone and cortisol. Conclusion These results illustrate that the metabolism of glucose and lipid of the athletes was enhanced following the marathon match. In addition, the metabolism of glucosamine was decreased and the metabolism of caffeine was increased. Our data provide new insights for marathon performance and nutritional status.

To enhance the precision, load capacity, disturbance rejection, and reliability of shipborne parallel stabilization platforms under complex sea conditions, this paper proposes a redundant, actuated, parasitic-motion-free 3-DOF 3RRS-RUS parallel stabilization platform. Based on the proposed 3RRS-RUS shipborne parallel stabilization platform, a Linear Active Disturbance Rejection Control (LADRC) approach, integrated with a Sliding Mode Disturbance Observer (SMDO), is developed. First, the mechanism is synthesized using screw theory, and its 2R1T 3-DOF characteristics are verified through parasitic motion analysis. Second, the inverse kinematics model is established. Third, the conventional LADRC is decoupled, and a new Linear Extended State Observer (LESO) together with its corresponding control law is designed. Moreover, an SMDO is incorporated into the motor’s three-loop control scheme to alleviate the estimation burden on the LESO and enhance the system’s disturbance rejection capability. Finally, experimental validations were carried out on both the CSPACE and SimMechanics platforms. The results demonstrate that the proposed SMDO–LADRC achieves superior tracking performance, high robustness, and strong disturbance rejection capability, The tracking errors along the RX, RY, and Z axes were reduced by 6.5%, 1.1%, and 16.6%, respectively, compared with the conventional LADRC, while also confirming the feasibility of the newly designed 3-DOF 3RRS-RUS shipborne parallel stabilization platform.

Sarcopenia, a geriatric syndrome characterized by the age-related loss of muscle mass and function, is increasingly recognized to be a dynamic process and exists bidirectional transitions with both possible worsening or improving transitions. With the rapid growth of aging population, developing effective interventions to delay or prevent the progression of sarcopenia is important and urgent. Recently, growing evidence demonstrated that whole body vibration training (WBVT) could significantly improve muscle mass and/or muscle strength in older adults, and may be a promising approach for elderly adults to treat sarcopenia, but there still exists inconsistent results. To clarify the moderating variables affecting the effectiveness of WBVT on muscle mass and strength, we conducted a comprehensively search of electronic database (PubMed, Web of Science and Embase) and performed subgroup analysis depending on the characteristics of subjects (sarcopenia vs. non-sarcopenia), frequency and amplitude (low frequency low amplitude, low frequency high amplitude, high frequency low frequency and high frequency high amplitude) and body position. We found that WBVT significantly enhanced muscle strength in older adults with or without sarcopenia, and the improvements on muscle strength were greatest after WBVT intervention with high frequency high amplitude, compared with WBVT with low frequency low amplitude, low frequency high amplitude, high frequency low frequency; WBVT only increased muscle mass in non-sarcopenic individuals, body position may be an important factor influencing the effectiveness of WBVT, compared with static body position, dynamic body position during WBVT has beneficial effects on muscle mass in older adults. Furthermore, skeletal muscle contraction is under the control of motor neuron and consumes a large amount of oxygen. The factors from intra-muscular including the protein synthesis and degradation and the proliferation and differentiation of satellite cells, to extra-muscular such as microcirculation and motor neuron control are all crucial for the maintenance of muscle mass and strength, therefore, we reviewed the regulatory effects of WBVT on these indicators, which would deepen our understandings about the mechanisms about the effects of WBVT on muscle mass and strength.

This study aimed to investigate the effects of aerobic exercise on skeletal muscle quality, gut microbiota composition, and estrogen levels in ovariectomized (OVX) mice, and to elucidate the potential underlying mechanisms, thereby providing experimental evidence for exercise intervention in postmenopausal women. Adult female C57BL/6J mice were randomly assigned to four groups (n = 6 per group): Sham, OVX, Sham+ET, and OVX+ET. After 6 weeks of recovery, the exercise groups received 8 weeks of treadmill training. Muscle morphology, function, and protein metabolism pathways were assessed using histology, grip tests, and Western blotting. Aromatase and estrogen levels were evaluated by immunofluorescence and ELISA. Gut microbiota composition was analyzed via 16S rRNA sequencing and correlated with muscle function. Eight weeks of aerobic exercise significantly improved skeletal muscle mass, fiber cross-sectional area, and grip strength in OVX mice, and reduced fatigue index compared to OVX controls. Immunofluorescence revealed increased aromatase expression and intramuscular E levels following exercise, with no significant difference in serum estradiol. Western blot analysis indicated activation of the Akt/mTOR/p-S6 pathway and inhibition of FOXO3-mediated protein degradation. 16S rRNA sequencing showed that exercise increased α-diversity (Shannon and Simpson indices) and altered microbial community structure, as shown by distinct clustering in PCoA plots. At the genus level, exercise modulated the relative abundance of several bacterial taxa. Spearman correlation analysis demonstrated that microbial diversity indices were positively associated with lean mass and fatigue resistance. Aerobic exercise significantly improves muscle mass and function in ovariectomized mice, potentially through a combined mechanism involving regulation of protein metabolism, enhancement of local estrogen synthesis, and modulation of gut microbiota composition.

We assess whether the sequential mediating effects of self-efficacy and depressive symptoms on the relationship between community efficacy for non-communicable disease management (COEN) and medication adherence and whether these relationships differed by sex and age. Overall, 662 individuals from 12 communities in China were interviewed twice 1 year apart. Serial mediation analysis examined whether the relationship between COEN and medication adherence was mediated by self-efficacy and depressive symptoms. Model invariance across sex and age groups was assessed using multi-group analysis. Serial mediation analysis indicated that self-efficacy and depressive symptoms sequentially mediated relationship between COEN and medication adherence. Multi-group analysis by sex showed that the path from self-efficacy to medication adherence was significant only for females and from depressive symptoms to medication adherence was significant only for males. Interventions that enhance individual self-efficacy may be beneficial in decreasing depressive symptoms and improving medication adherence.