ObjectiveTo investigate the effects and potential mechanisms of morning and evening fasting on postprandial lipid responses, a post hoc analysis based on a crossover randomized controlled trial was conducted to assess the effects of different fasting strategies on postprandial lipid metabolism in community residents in Shanghai. MethodsA total of 23 participants took part in a randomized crossover trial involving two intervention days: morning fasting and evening fasting, with a washout period of 6 days between intervention days. Two-way analysis of variance was used to test the differences in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the relative expression of circadian clock genes before and after the next meal under fasting. Wilcoxon rank sum tests were used to analyze the different metabolites between the two groups. Principal component analysis and Orthogonal partial least squares-discriminant analysis were conducted to evaluate the ability of metabolites to differentiate between morning fasting and evening fasting and identify the important differential metabolites. After adjusting for age, sex, and BMI, a partial correlation analysis was performed to identify metabolites associated with plasma lipids. In addition, important metabolites associated with plasma lipids were computed by pathway enrichment analysis. ResultsAfter evening fasting intervention, fasting TG level [(0.37±0.29) vs (0.27±0.18)] mmol·L^-1, fasting and postprandial change values in TC [(2.74±0.47) vs (2.51±0.27)] mmol·L^-1 and LDL-C [(1.32±0.38) vs (0.99±0.27)] mmol·L^-1 were significantly lower than those after morning fasting (P<0.05). While, change values of fasting LDL-C [(0.89±0.37) vs (1.14±0.37)] mmol·L^-1 and TG [(1.14±0.19) vs (1.28±0.17)] mmol·L^-1 were significantly higher than those after morning fasting intervention (P<0.05). After fasting intervention, the relative expression of AMPK, CRY1, CLOCK, MTNR1B, AANAT, and ASMT was correlated with the amount of plasma lipid changes (P<0.05). Specifically, CLOCK and AANAT were upregulated following evening fasting and downregulated after morning fasting. Among the 217 important differential metabolites, 111 were correlated with plasma lipids, and which were primarily enriched in the cysteine and methionine metabolism pathways (P<0.05). ConclusionCompared to morning fasting, evening fasting was more effective in improving postprandial lipid responses, indicating that an evening fasting window during intermittent fasting could be conducive to cardiovascular disease prevention in adults. Meanwhile, it is suggested that morning and evening fasting may affect lipid responses through circadian rhythm oscillations and the cysteine and methionine metabolism pathways.

Objective: To study the efficacy of photosensitizer 8- methoxsalen (8-MOP) combined with ultraviolet radiation A (UVA) in inducing ferroptosis in mouse melanoma B16 cells, and to assess the resultant changes in immunogenicity, and their impact on subsequent immune activation after treatment. Methods: 1) Mouse melanoma B16 cells were cultured and treated with 8-MOP (100 ng/mL) and UVA (4 J/cm ), and then cultured in a constant temperature incubator (37℃, 5%CO ) for 24 hours after irradiation. 2) CCK8 (cell proliferation and toxicity) detection kit was used to detect the death rate of tumor cells. 3) LPO (lipid peroxide) and GSH (glutathione) detection kits were used to detect the degree of oxidative damage of tumor cells; Changes of Fe , mitochondrial membrane potential (JC-1) and BODIPY 581/591 C11 (lipid peroxidation detection kit) in tumor cells were detected by confocal microscope. Western blotting (WB) was performed to detect GPX4, SLC7A11 and NCOA4 to confirm ferroptosis. 4) The expression of HMGB1 (high mobility group protein 1), ATP and CRT (calreticulin) in the supernatant of tumor cell culture was detected by ELISA kit to evaluate the immunogenicity of tumor cells. 5) 1×10 B16 cells were injected subcutaneously into the skin of the back and neck of mice at a dose of 100 μL to construct a mouse melanoma model. Spleen mononuclear cells of tumor-bearing mice were extracted and immediately co-cultured with irradiated tumor cells for 48 h. Changes of dendritic cell (DC) maturity were detected by MHC-II, CD11c, CD80 and CD83 flow cytometry. Results: After UVAP, the survival rate of B16 cells decreased significantly (61.39±6.823 vs 84.81±7.026 vs 100.0±3.996, P<0.000 1, P<0.01). UVAP effectively induced ferroptosis in B16 cells, characterized by increased LPO and C11-bodipy lipid peroxidation, GSH depletion, Fe accumulation, mitochondrial membrane depolarization, decreased GPX4 and SLC7A11 protein expression, and increased NCOA4 expression, all in line with the trend of ferroptosis. UVAP also enhanced tumor cell immunogenicity, evidenced by elevated release of ATP, CRT, and HMGB1. The immunogenicity of B16 cells increased, the expressions of ATP, CRT and HMGB1 increased, and the DC maturity increased (CD80: 31.92±4.071 vs 19.77±3.177; CD83: 21.40±4.787 vs 12.19±1.487, P<0.001, P<0.01). Conclusion: The combined action of 8-MOP and UVA can induce ferroptosis in B16 tumor cells, enhance the immunogenicity of tumor cells, release more tumor antigens, promote the maturation of DC, present antigens better, thereby facilitating subsequent immune activation.

Periodontitis is a chronic inflammatory disease that affects the tooth-supporting tissues, and it constitutes a major global public health concern. Methylation modifications, including DNA methylation, histone methylation, and RNA m6A modification, represent reversible processes coordinately regulated by methyltransferases, demethylases, and binding proteins. In periodontitis, aberrant methylation modifications suppress Toll-like receptor 2 expression, leading to oral microbial dysbiosis. These modifications further disrupt normal immune regulatory functions through C-C motif chemokine ligands, Fc-γ receptor-mediated phagocytosis, and NF-κB signaling pathways, resulting in localized immune-inflammatory imbalance in periodontal tissues. In addition, various methylation modifications regulate the expression of Runt-related transcription factor 2 (RUNX2), osteoblast-specific transcription factor Osterix (OSX), and receptor activator of nuclear factor-κB ligand (RANKL), thereby interfering with osteoclast and osteoblast differentiation, disrupting bone homeostasis, and ultimately driving alveolar bone resorption. Methylation-related biomarkers demonstrate promising potential for periodontitis screening and prognostic evaluation. While numerous abnormally methylated sites have been identified in periodontitis, the precise signaling pathways and comprehensive epigenetic regulatory networks remain to be fully elucidated. This review systematically summarizes the functional roles of DNA methylation modifications in the pathogenesis of periodontitis and explores their potential value in etiological studies, diagnostic biomarker discovery, and targeted therapeutic interventions, with the aim of providing novel perspectives for periodontitis prevention and treatment strategies.

ObjectiveTo explore the relationship between self-assessed health and age-adjusted Charlson comorbidity index （AICC） in older adults， and to further analyze the differences in this relationship across gender groups. MethodsBased on the China health and retirement longitudinal study （CHARLS） database， this study selected data on basic characteristics， chronic disease status， depressive symptoms， and self-assessed health of older adults aged ≥60 years. Chi-square tests were used to perform a preliminary analysis of the association between these factors and AICC scores. A multifactorial ordered logistic regression model was constructed to assess the effects of each influencing factor on AICC， while multiple linear regression analysis was used to explore the linear relationship between self-rated health and AICC scores. Additionally. Stratified analysis by gender was performed to evaluate gender differences. ResultsA total of 10 911 participants were included， with a mean age of 67.40±5.94 years； 6 249 （57.3%） were male and 4 662（42.7%） were female. The distribution of AICC scores was categorized into low-risk， moderate-risk， higher-risk， and high-risk groups， accounting for 23.5%， 50.2%， 20.6%， and 5.7%， respectively. Multifactorial logistic regression analysis revealed that self-rated health was negatively associated with AICC in the total population and in the male geriatric group （OR=0.843， 95% CI： 0.776， 0.917， P=0.001）， （OR=0.886， 95% CI： 0.796 ， 0.987， P=0.028）， but did not reach statistical significance in the female geriatric group . Linear regression analysis further indicated a significant negative linear relationship between self-rated health and AICC （b=-0.485， 95% CI： -0.516，-0.455， P＜0.001）.This relationship was consistent in both male （b=-0.356， 95% CI： -0.406，-0.305， P＜0.001） and female （b=-0.373， 95% CI： -0.435，-0.310， P＜0.001） subgroups， with a stronger negative association in females. ConclusionSelf-rated health is significantly negatively associated with AICC， and attention should be given to self-rated health in the female geriatric population. Self-rated health can serve as an important tool for identifying elderly group at high risk of comorbidities providing a valuable basis for precise intervention.

OBJECTIVE: To review the research progress of pathological changes of glenohumeral capsule in patients with recurrent shoulder anterior dislocation (RSAD). METHODS: The literature on shoulder capsules, both domestic and international, was reviewed. The anatomy, histology, and molecular biology characteristics of the glenohumeral capsule in RSAD patients were summarized. RESULTS: Anatomically, the glenohumeral capsule is composed of four distinct parts: the upper, lower, anterior, and posterior sections. The thickness of these sections is uneven, and the stability of the capsule is further enhanced by the presence of the glenohumeral and coracohumeral ligaments. Histologically, the capsule tissue undergoes adaptive changes following RSAD, which improve its ability to withstand stretching and deformation. In the realm of molecular biology, genes associated with the regulation of structure formation, function, and extracellular matrix homeostasis of the shoulder capsule's collagen fibers exhibit varying degrees of expression changes. Specifically, the up-regulation of transforming growth factor β ₁ (TGF-β ₁), TGF-β receptor 1, lysyl oxidase, and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 facilitates the repair of the joint capsule, thereby contributing to the maintenance of shoulder joint stability. Conversely, the up-regulation of collagen type Ⅰ alpha 1 (COL1A1), COL3A1, and COL5A1 is linked to the recurrence of shoulder anterior dislocation, as these changes reflect the joint capsule's response to dislocation. Additionally, the expressions of tenascin C and fibronectin 1 may play a role in the pathological processes occurring during the early stages of RSAD. CONCLUSION Glenohumeral capsular laxity is both a consequence of RSAD and a significant factor contributing to its recurrence. While numerous studies have documented alterations in the shoulder capsule following RSAD, further research is necessary to confirm the specific pathological anatomy, histological, and molecular biological changes involved.
Humans ; Joint Capsule/metabolism* ; Shoulder Dislocation/metabolism* ; Recurrence ; Shoulder Joint/metabolism* ; Tenascin/metabolism* ; Transforming Growth Factor beta1/genetics* ; Collagen Type I/genetics* ; Extracellular Matrix/metabolism*

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS). Using this newly developed method, we screened the RNA-binding proteins that regulate PABPN1 phase separation and identified the tumor suppressor QKI as a promoter of PABPN1 phase separation. Furthermore, QKI exhibits decreased expression levels and diminished nuclear localization in colorectal cancer cells, resulting in reduced PABPN1 phase separation, which, in turn, promotes alternative polyadenylation (APA), cell proliferation, and migration in colorectal cancer.
Humans ; Colorectal Neoplasms/genetics* ; RNA-Binding Proteins/genetics* ; Poly(A)-Binding Protein I/genetics* ; CRISPR-Cas Systems ; Flow Cytometry ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement

Background Per- and polyfluoroalkyl substances (PFAS), a group of persistent organic pollutants associated with adverse health effects including hepatotoxicity, immunosuppression, and carcinogenicity, have undergone risk assessments by multiple international organizations, with dietary exposure being the primary pathway. Objective To characterize the exposure to PFAS from food and drinking water sources of elderly residents in Songjiang District of Shanghai and to evaluate associated health risk and health effects. Methods A cross-sectional study was conducted from May to July 2024 in Songjiang District based on the Shanghai Suburban Adult Cohort and Biobank (SSACB) cohort. Dietary surveys were administered via face-to-face interviews among older adults aged 65 years and above, yielding 4 583 valid questionnaires. The estimated daily intake (EDI) of PFAS was calculated by integrating data from the Sixth National Dietary Survey and recent literature on PFAS concentrations in food and drinking water in Shanghai. Health risk assessment was performed using health-based guideline values (HBGV) proposed by various institutions and studies. Additionally, correlation analysis and linear regression modeling of EDI and biochemical indicators in the elderly were conducted to evaluate potential adverse health effects. Results The elderly population in Songjiang District exhibited dietary characteristics consistent with the Eastern Healthy Diet Pattern. Among PFAS compounds, PFOA showed the highest level of oral exposure [mean: 1.495 ng·(kg·d⁻¹)], followed by PFOS [mean: 0.637 ng·(kg·d⁻¹)], PFHxS [mean: 0.636 ng·(kg·d⁻¹)], and PFBS [mean: 0.273 ng·(kg·d⁻¹)]. Specifically, drinking water was the primary source of PFOA [1.415 ng·(kg·d⁻¹), accounting for 94.60%], while aquatic products were the major source of PFOS [0.278 ng·(kg·d⁻¹), accounting for 43.66%]. Using the HBGV derived by China's epidemiological studies, the mean hazard index (HI) for PFAS exposure was 1.39, indicating 54.35% of the population had potential health risks (HI>1). Following the 2024 standard established by the Food Safety Commission of Japan (FSCJ), the HI value dropped to 0.11, suggesting negligible risk. PFAS exposure was negatively associated with triglyceride levels and the indicators of liver and kidney function, but positively associated with low-density lipoprotein cholesterol (LDL-C) and lung cancer markers in the elderly residents. Conclusion PFAS exposure among the elderly residents in Songjiang District is predominantly attributed to PFOA, PFOS, PFHxS, and PFBS, with drinking water and aquatic products identified as primary exposure sources. Current exposure levels demonstrate significant associations with biomarkers of lipid metabolism and lung cancer markers, suggesting potential population health risks. These findings underscore the urgent need to establish HBGV for PFAS compounds based on Chinese population-specific metabolic characteristics.

The biological nitrogen removal technology utilizing heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria has shown effectiveness in wastewater treatment. However, the nitrogen removal efficiency of HN-AD bacteria significantly decreases as the salinity increases. To tackle the challenge of treating high-salt and high-nitrogen wastewater, we isolated a moderately halophilic HN-AD strain 5505 from a salt lake in Xinjiang. The strain was identified based on morphological, physiological, and biochemical characteristics and the 16S rRNA gene sequence. Single-factor experiments were carried out with NH₄⁺-N, NO₃^--N, and NO₂^--N as sole or mixed nitrogen sources to study the nitrifying effect, denitrifying effect, and nitrogen metabolism pathway of the strain. The strain was identified as Halomonas sp.. It can grow in the presence of 1%-25% (W/V) NaCl and exhibited efficient nitrogen removal ability in the presence of 3%-8% NaCl. At the optimal NaCl concentration (8%), the strain showed the NH₄⁺-N, NO₃^--N and NO₂^--N removal rates of 100.0%, 94.11% and 74.43%, respectively. Strain 5505 removed inorganic nitrogen mainly by assimilation, which accounted for over 62.68% of total nitrogen removal. In the presence of mixed nitrogen sources, strain 5505 showed a preference for utilizing ammonia, with a potential HN-AD pathway of NH₄⁺→NH₂OH→NO₂^-→NO₃^-→NO₂^-→NO/N₂O/N₂. The findings provide efficient salt-tolerant bacterial resources, enhance our understanding of biological nitrogen removal, and contribute to the nitrogen removal efficiency improvement in the treatment of high-salt and high-nitrogen wastewater.
Halomonas/classification* ; Nitrogen/isolation & purification* ; Denitrification ; Nitrification ; Wastewater/microbiology* ; Aerobiosis ; Biodegradation, Environmental ; Salinity

Objective To analyze the effect of Hedysari Radix Chinese herbal pieces treatment in acute inferior myocardial infarction patients undergoing percutaneous coronary intervention(PCI).Methods A total of 200 patients with acute inferior myocardial infarction undergoing emergency PCI admitted to department of cardiology of Shijiazhuang People's Hospital from March 31,2020 to March 31,2023 were selected as the study objects.The patients were randomly divided into a control group and a treatment group according to a digital random table method.The control group received routine treatment after PCI,and the patients drank 500 mL of warm water in the morning and afternoon every day,continuing this regimen for up to 30 days post-surgery.The treatment group took 10 g of Hedysari Radix Chinese Herbal pieces in 500 mL of boiling water in the morning and afternoon,soaking it and drinking it coolly and temperately,continuing to take it until 30 days after surgery.Blood pressure,Dopamine dosage,and duration were observed in all patients on 1-5 days after surgery.Major adverse cardiovascular event(MACE),such as cardiac death,myocardial infarction,heart failure,and re-admission were tracked in all patients within 30 days,and adverse reactions and clinical symptom improvement were followed up,using the somatic self-rating scale(SSS).Results The total Dopamine dose in the treatment group was significantly lower than that in the control group(mg:960.4±287.9 vs.1 160.4±610.5,P<0.05),and the duration of use was significantly shorter than that in the control group(hours:60.7±16.9 vs.71.6±20.4,P<0.05).The systolic blood pressure in the treatment group was significantly higher than that in the control group at 1 day after PCI[mmHg(1 mmHg≈0.133 kPa):96.8±19.5 vs.90.2±11.1,P<0.05],until 5 days after PCI(mmHg:106.3±14.4 vs.99.7±13.9,P<0.05),while the changes in diastolic blood pressure were not significant in both groups.The incidence of MACE in the treatment group was significantly lower than that in the control group within 30 days after PCI[4.0%(4/100)vs.13.0%(13/100),P<0.05],and the SSS score was also significantly lower than that in the control group(31.56±11.58 vs.40.72±18.67,P<0.05).Conclusion The effect of Hedysari Radix Chinese herbal pieces treatment can significantly improve clinical efficacy without significant adverse reactions.