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High Epidermal growth factor receptor (EGFR) in Cutaneous Squamous Cell Carcinoma (cSCC) is associated with poor prognosis and advanced metastatic stages, severely impeding the efficacy of EGFR-targeting immunotherapy. This is commonly attributed to the combinatory outcomes of hypoxic tumor microenvironment (TME) and immunosuppressive effector cells together. Herein, a novel paradigm of EGFR-targeting oxygen-saturated nanophotosensitizers, designated as CHPFN-O2, has been specifically tailored to mitigate tumor hypoxia in EGFR-positive cSCC and achieve Cetuximab (CTX)-mediated immunotherapy (CIT). The conjugated CTX in CHPFN-O2 serves to initiate immune responses by recruiting Fc receptor (FcR)-expressing immune effector cells towards tumor cells, thereby eliciting antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular trogocytosis (ADCT) and antibody-dependent cellular cytotoxicity (ADCC). Besides, CHPFN-O2 can engender a shift from a tumor-friendly to a tumor-hostile one through improved tumor oxygenation, contributing to oxygen-elevated photodynamic therapy (oxPDT). Notably, the combination of oxPDT and CIT eventually promotes T-cell-mediated antitumor activity and successfully inhibits the growth of EGFR-expressing cSCC with good safety profiles. This comprehensive oxPDT/CIT integration aims not only to enhance therapeutic efficacy against EGFRhigh cSCC but also to extend its applicability to other EGFRhigh malignancies, thus delineating a new avenue for the highly efficient synergistic treatment of EGFR-expressing malignancies.

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SCOPE: This research examines the effects of maternal high-fat (HF) diet and gestational diabetes mellitus (GDM) on offspring lipid metabolism and polyunsaturated fatty acids (PUFA) profile. METHODS AND RESULTS: GDM is induced using the insulin receptor antagonist S961. Weaning offspring are categorized into HF-GDM, HF-CON, NC-GDM, and NC-CON groups based on maternal diet or GDM. Adult offspring are then grouped into NC-CON-NC, NC-CON-HF, NC-GDM-NC, NC-GDM-HF, HF-CON-NC, HF-CON-HF, HF-GDM-NC, and HF-GDM-HF according to dietary patterns. Gas chromatography determines PUFA composition. Western blot assesses PI3K/Akt signaling pathway-related protein expression. Feeding a normal chow diet until adulthood improves the distribution of hepatic PUFA during weaning across the four groups. PI3K expression is upregulated during weaning in HF-CON and HF-GDM, particularly in HF-CON-NC and HF-GDM-NC, compared to NC-CON-NC during adulthood. Akt expression increases in NC-GDM-NC after weaning with a normal diet. The hepatic PUFA profile in HF-CON-HF significantly distinguishes among the maternal generation health groups. Maternal HF diet exacerbates the combined impact of maternal GDM and offspring HF diet on hepatic PUFA and PI3K/Akt signaling pathway-related proteins during adulthood. CONCLUSIONS: Early exposure to HF diets and GDM affects hepatic PUFA profiles and PI3K/Akt signaling pathway protein expression in male offspring during weaning and adulthood.

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Objective: Our study aimed to examine the association between delay discounting (DD) and body mass index (BMI) in individuals with hypertension. Additionally, we sought to explore and compare the potential mediating effects of self-efficacy, physical activity and sedentary behavior in this association. Methods: A cross-sectional survey was conducted in two cities in the Jiangsu province of China, specifically Nanjing and Yangzhou, from March to June 2023. A total of 972 hypertensive patients completed the questionnaire (M age = 64.7 years, SD age = 8.2 years, 54.2% female). Participants engaged in a money choice experiment on computers, provided their height and weight, and completed the International Physical Activity Questionnaire-Short Form (IPAQ-SF) and General Self-Efficacy Scale (GSES). The experimental program was generated using the programming software E-Prime version 2.0. Multiple hierarchical regression analysis was conducted to identify potential covariates. Two serial mediation models were conducted using PROCESS macro 4.1 in SPSS 27.0. Physical activity and sedentary behavior were designated as M2 to investigate and contrast their respective mediating effects in the association between delay discounting and body mass index. Results: Self-efficacy, physical activity, and sedentary behavior served as mediators in the relationship between delay discounting and BMI. Self-efficacy accounted for 14.9% and 14.3% of the total effect in Models 1 and 2, respectively, while physical activity and sedentary behavior each accounted for 14.9% and 9.5% of the total effect, respectively. The serial mediation effects of self-efficacy and physical activity, as well as self-efficacy and sedentary behavior, were significant (B = 0.01, 95% CI [0.01, 0.02]; B = 0.01, 95% CI [0.002, 0.01]), collectively contributing 2.1% and 2.4% of the total effect. Sedentary behavior played a smaller mediating role compared to physical activity in this association. Conclusion: The results indicated that self-efficacy, physical activity and sedentary behavior could act as mediators in the association between delay discounting and BMI, thus potentially mitigating the risk of obesity in hypertensive individuals.

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Aryl 2-pyridyl esters could efficiently undergo cross-electrophile couplings with aryl bromides with the aid of magnesium as a reducing metal in the absence of a transition-metal catalyst, leading to the unsymmetrical diaryl ketones in modest to good yields with wide functionality compatibility. In addition, the reaction could be easily scaled up and applied in the late-stage modification of biologically active molecules. Preliminary mechanistic study showed that the coupling reaction presumably proceeds through the in situ formation of arylmagnesium reagents as key intermediates.

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Many amines with high toxicity always cause a serious threat to the ecological environment and human health; thus, their detection is important. Herein, a dual-mode colorimetric and ratiometric fluorescent sensor based on cellulose for detecting amines has been constructed by a new strategy. This sensor is made of a "negative response" indicator (Lum-MDI-CA) and a "positive response" indicator (perylene tetracarboxylic acid, PTCA). Lum-MDI-CA was obtained by attaching luminol onto cellulose chains, which emitted blue fluorescence and was quenched upon contact with amines. A possible mechanism of fluorescence quenching phenomenon is proposed by the intramolecular charge transfer (ICT) of Lum-MDI-CA. Subsequently, by simply mixing Lum-MDI-CA with PTCA, a dual-mode fluorescence sensor was designed for visual detection and classification of amines. When adding ammonia (NH3), morpholine (MOR), benzylamine (BNZ), diethylamine (DEA), and triethylamine (TEA), respectively, the dual-mode sensor showed visible different color changes under both UV light and daylight. In addition, owing to the excellent processibility and formability of cellulose acetate backbone, the prepared sensor can be easily processed into different material forms, including inks, coatings, films, and fibers, which still exhibit excellent fluorescence emission. Such sensors based on cellulose fluorescent materials are of great value in anti-counterfeiting and information encryption.

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Background: Understanding the genetic causes for variability in chromatin accessibility can shed light on the molecular mechanisms through which genetic variants may affect complex traits. Thousands of ATAC-seq samples have been collected that hold information about chromatin accessibility across diverse cell types and contexts, but most of these are not paired with genetic information and come from diverse distinct projects and laboratories. Results: We report here joint genotyping, chromatin accessibility peak calling, and discovery of quantitative trait loci which influence chromatin accessibility (caQTLs), demonstrating the capability of performing caQTL analysis on a large scale in a diverse sample set without pre-existing genotype information. Using 10,293 profiling samples representing 1,454 unique donor individuals across 653 studies from public databases, we catalog 23,381 caQTLs in total. After joint discovery analysis, we cluster samples based on accessible chromatin profiles to identify context-specific caQTLs. We find that caQTLs are strongly enriched for annotations of gene regulatory elements across diverse cell types and tissues and are often strongly linked with genetic variation associated with changes in expression (eQTLs), indicating that caQTLs can mediate genetic effects on gene expression. We demonstrate sharing of causal variants for chromatin accessibility and diverse complex human traits, enabling a more complete picture of the genetic mechanisms underlying complex human phenotypes. Conclusions: Our work provides a proof of principle for caQTL calling from previously ungenotyped samples, and represents one of the largest, most diverse caQTL resources currently available, informing mechanisms of genetic regulation of gene expression and contribution to disease.

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BACKGROUND: Child maltreatment and child protective service (CPS) involvement negatively impacts families, and disproportionately impact families of color. Urban neighborhood greenspace is associated with improved mental health and decreased community violence, however correlations between greenspace and CPS involvement have not been evaluated. OBJECTIVE: To examine the association between greenspace and CPS involvement. METHODS: This is a secondary analysis of City of Philadelphia CPS report data from 2008 to 2018. Logistic regression was used to determine associations between greenspace and 3 CPS outcomes (substantiated reports, cases accepted for CPS services, and foster care placements) at the census block level, adjusting for sociodemographic information and area deprivation index, a composite measure combining education, employment, housing, and poverty characteristics at the census block group level. 13,336 census blocks were included, which had key exposure, covariate, and outcome data, and had a child population of at least 1. RESULTS: 66,043 CPS reports were included. In the adjusted model, compared to blocks with >30 % greenspace, blocks with <10 % greenspace had 1.52 times the odds of a substantiated report (95 % CI 1.30-1.76, p < 0.001) and 1.52 times the odds of a case accepted for CPS services (95 % CI 1.30-1.77, p < 0.001). Blocks with less greenspace had increased odds of foster care placement than blocks with >30 % greenspace, however the correlation was less strong. CONCLUSION: Increased density of neighborhood greenspace is associated with decreased risk of substantiated child maltreatment and cases accepted for CPS services, suggesting that greenspace may confer protection against CPS involvement.

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Lipid nanobubbles with different gas cores may integrate the biocompatibility of lipids, powerful physicochemical properties of nanobubbles, and therapeutic effects of gas molecules, which thus promote enormous biomedical applications such as ultrasound molecular imaging, gene/drug delivery, and gas therapy. In order for further more precise applications, the exact molecular mechanisms for the interactions between lipid nanobubbles and biological systems should be studied. Molecular dynamics (MD) simulation provides a powerful computational tool for this purpose. However, previous state-of-the-art MD simulations of free gas nanobubble/lipid nanobubble employed the vacuum as their gas cores, which is not suitable for studying the interactions between functional lipid nanobubbles and biological systems and revealing the biological roles of gas molecules. Hence, in this work, we developed and optimized the CHARMM36 all-atom gas parameters for six gases including N2, O2, H2, CO, CO2, and SO2, which accurately reproduced the gas density at different pressures as well as the spontaneous formation of gas nanobubbles. Subsequent applications of these gas parameters for lipid nanobubble simulations also reproduced the self-assembly process of the lipid nanobubble. We further developed a Python script to generate all-atom lipid nanobubble simulation systems, which was proven to be efficient for all-atom MD simulations of lipid nanobubbles and to be able to capture the exact dynamics of gas molecules at the gas-lipid and lipid-water interfaces of the lipid nanobubble. In summary, the all-atom gas models proposed in this work are suitable for simulating free gas nanobubbles and lipid nanobubbles, which are supposed to overcome the shortcomings of previous state-of-the-art MD simulations with the vacuum replacing the gas core and play key roles in revealing the molecular-level interactions between lipid nanobubbles and biological systems.

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Objective: Schizonepeta tenuifolia -Saposhnikovia divaricata (Jingjie-Fangfeng, JF) has been used for years to treat allergic inflammatory skin diseases like atopic dermatitis, but the specific effects and mechanisms of JF are still unclear. Purpose: We aim to investigate the therapeutic effect and mechanism of JF in MC903-induced atopic dermatitis-like model. Methods: JF decoction was subjected to rigorous HPLC and GC analysis. The JF decoction was then freshly prepared and administered to MC903-induced atopic dermatitis -like mice models to investigate its therapeutic effects. Our evaluation focused on several markers of inflammation including the TEWL index, ear thickness, swelling, and specific inflammation indicators such as TSLP, IL33, IgE, and immune cell presence at the lesion sites. We measured Transient Receptor Potential Vanilloid 1 (TRPV1) expression levels through immunofluorescent staining in skin tissue from both atopic dermatitis patients and the MC903-treated mice. Furthermore, TRPV1 expression and macrophage activation markers were measured in LPS/IFN-γ-stimulated Raw264.7 and THP-1 cell models in vitro. Additionally, we developed cell lines that overexpress TRPV1 and investigated how JF treatment affects NF-κB p65 phosphorylation in these cells to understand better the role of TRPV1 in atopic dermatitis. Results: The JF decoction met the standards outlined in the Chinese pharmacopeia. The JF decoction significantly alleviated inflammatory skin symptoms and helped restore skin barrier function. Additionally, it reduced the levels of IgE and pro-inflammatory cytokines TSLP, IL-33, and IL-4. There was also a noticeable decrease in mast cell infiltration and degranulation. Notably, JF decoction reduced infiltrated macrophages with limited affection on T cell infiltration. It also decreased F4/80+/TRPV1+ cells in atopic dermatitis mice and TRPV1 expression in LPS/IFNγ-stimulated microphages. Additionally, we observed that CD68+/TRPV1+ cells increased in human atopic dermatitis tissue. Further studies showed that JF water extract (JF-WE) suppressed TRPV1 expression in macrophages, potentially by affecting NF-κB p65 phosphorylation rather than the JAK-STAT6 pathway. Conclusion: This study offers initial evidence of the effectiveness of JF-WE in suppressing inflammation in atopic dermatitis. The therapeutic effect might stems from its ability to downregulate TRPV1 expression and subsequent NF-κB p65 phosphorylation in macrophages.

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OBJECTIVE: To analyze primary angle closure suspect (PACS) patients' anatomical characteristics of anterior chamber configuration, and to establish artificial intelligence (AI)-aided diagnostic system for PACS screening. METHODS: A total of 1668 scans of 839 patients were included in this cross-sectional study. The subjects were divided into two groups: PACS group and normal group. With anterior segment optical coherence tomography scans, the anatomical diversity between two groups was compared, and anterior segment structure features of PACS were extracted. Then, AI-aided diagnostic system was constructed, which based different algorithms such as classification and regression tree (CART), random forest (RF), logistic regression (LR), VGG-16 and Alexnet. Then the diagnostic efficiencies of different algorithms were evaluated, and compared with junior physicians and experienced ophthalmologists. RESULTS: RF [sensitivity (Se) = 0.84; specificity (Sp) = 0.92; positive predict value (PPV) = 0.82; negative predict value (NPV) = 0.95; area under the curve (AUC) = 0.90] and CART (Se = 0.76, Sp = 0.93, PPV = 0.85, NPV = 0.92, AUC = 0.90) showed better performance than LR (Se = 0.68, Sp = 0.91, PPV = 0.79, NPV = 0.90, AUC = 0.86). In convolutional neural networks (CNN), Alexnet (Se = 0.83, Sp = 0.95, PPV = 0.92, NPV = 0.87, AUC = 0.85) was better than VGG-16 (Se = 0.84, Sp = 0.90, PPV = 0.85, NPV = 0.90, AUC = 0.79). The performance of 2 CNN algorithms was better than 5 junior physicians, and the mean value of diagnostic indicators of 2 CNN algorithm was similar to experienced ophthalmologists. CONCLUSION: PACS patients have distinct anatomical characteristics compared with health controls. AI models for PACS screening are reliable and powerful, equivalent to experienced ophthalmologists.

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Metabolic syndrome has become a significant public health concern. This study aims to investigate the impact of dietary patterns on metabolic syndrome in young adults and how physical activity modulates this effect. A cross-sectional study was conducted at a health management center in Tianjin, China, from September 2022 to March 2023. Participants aged 18-35 years were recruited using convenience sampling. Dietary intake was assessed using a validated food frequency questionnaire. Logistic regression models evaluated associations between these patterns and metabolic syndrome, adjusting for potential confounders. Among 442 participants, four dietary patterns were identified: Legume-Nut, Alcohol-Meat, Sugar-Processed, and Egg-Vegetable. The Legume-Nut dietary pattern was associated with a higher risk of metabolic syndrome (OR = 2.63, 95% CI: 1.08-6.37), while the Egg-Vegetable dietary pattern was associated with a lower risk (OR = 0.26, 95% CI: 0.10-0.70). No significant associations were found for the Sugar-Processed and Alcohol-Meat patterns. Subgroup analysis revealed that the Legume-Nut pattern increased the risk of metabolic syndrome among those with irregular physical activity, whereas the Egg-Vegetable pattern decreased the risk. These findings highlight the significant influence of dietary patterns on the risk of metabolic syndrome in young adults and the modifying effect of regular physical activity, underscoring the need for targeted dietary and lifestyle interventions to prevent metabolic syndrome in this population.

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Background: Improving health-related quality of life (HRQoL) among hypertensive individuals has emerged as a significant public health issue. However, current research has ignored the individual heterogeneity of perceived social support (PSS) among hypertensive patients. The potential mechanism of delay discounting (DD), living alone, and PSS on HRQoL remains unclear, and further exploration is required. Aim: This study aimed to ascertain PSS profiles among hypertensive patients and examine the hypotheses that DD mediates the relationship between PSS and HRQoL and that this mediating process is moderated by living alone in hypertensive patients. Methods: A cross-sectional study was carried out in Jiangsu, China. In total, 1815 hypertensive patients completed socio-demographic and HRQoL questionnaires, a PSS scale, and a DD task. Data analyses included a latent profile analysis, χ2-test, Spearman correlation analysis, and PROCESS macro for regression analysis. Results: Four potential PSS profiles were identified: lowest (3.2%), moderate-low (26.6%), moderate-high (42.4%), and highest (27.8%). DD mediated the association between PSS and HRQoL. The first half of this mediating process was moderated by living alone. Conclusion: Our findings indicated that PSS, DD, and living alone significantly influence the HRQoL of individuals with hypertension. Healthcare professionals should consider variations in PSS among hypertensive patients and implement interventions to reduce DD by enhancing PSS, in order to improve the HRQoL of this population.

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Background: Catheter-related thrombosis (CRT) is a common complication for patients who receive central venous catheter (CVC) placement. This study investigated the risk factors for CRT and developed a nomogram for CRT prediction among cancer patients. Methods: This nested case-control study was conducted in the Third Affiliated Hospital of Kunming Medical University between January 2019 and February 2021. Univariable and multivariable logistic regression analyses were used to identify the risk factors for CRT. A nomogram was developed to predict CRT. Receiver operating curves (ROC), calibration curves, and decision curves were used to evaluate the performance of the nomogram in the training and validation sets. Results: A total of 4,691 cancer patients were included in this study. Among them, 355 (7.57%) had CRT, and 70% of CRTs occurred in the first week of insertion. Among the 3,284 patients in the training set, the multivariable analysis showed that nine characteristics were independently associated with CRT, and a nomogram was constructed based on the multivariable analysis. The ROC analysis indicated good discrimination in the training set (area under the curve [AUC] = 0.832, 95% CI: 0.802-0.862) and the testing set (AUC = 0.827, 95% CI: 0.783-0.871) for the CRT nomogram. The calibration curves showed good calibration abilities, and the decision curves indicated the clinical usefulness of the prediction nomograms. Conclusion: The validated nomogram accurately predicts CRT occurrence in cancer patients. This model may assist clinicians in developing treatment plans for each patient.

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Fibronectin type III domain containing 4 (FNDC4) is highly homologous with FNDC5, which possesses various cardiometabolic protective functions. Emerging evidence suggests a noteworthy involvement of FNDC4 in fat metabolism and inflammatory processes. This study aimed to characterize the role of FNDC4 in myocardial ischemia/reperfusion (MI/R) injury and decrypt its underlying mechanisms. MI/R models of mice were established to investigate the alteration of FNDC4 in plasma and myocardium. We observed that plasma FNDC4 in MI/R-injury mice and patients experiencing acute myocardial infarction were both significantly reduced as opposed to their respective controls. Likewise, FNDC4 expression of myocardium decreased markedly in MI/R mice compared to the sham-operated group. Mice of FNDC4 knockout and myocardial overexpression were further introduced to elucidate the role of FNDC4 in MI/R injury by detecting cardiomyocyte apoptosis, myocardial infarct size, and cardiac function. Ablation of FNDC4 exacerbated cardiac dysfunction, increased myocardial infarction area and cardiomyocyte apoptosis when matched with wild-type mice post-MI/R. In contrast, FNDC4 overexpression through intramyocardial injection of rAAV9-Fndc4 significantly ameliorated cardiac function, reduced myocardial infarction area and cardiomyocyte apoptosis compared to sham group. Additionally, hypoxia-reoxygenation (H/R) was used to induce cardiomyocyte apoptosis, and to further elucidate the direct effects of FNDC4 on cardiomyocytes in vitro, and the results demonstrated that neonatal rat ventricular cardiomyocytes overexpressing FNDC4 showed less H/R-induced apoptosis, as evidenced by cleaved caspase 3 expression, TUNEL staining and flow cytometry. By performing RNA-seq analysis followed by cause-effect analysis, ERK1/2-Nrf2 pathway-mediated antioxidative effects were responsible for the protective roles of FNDC4 on cardiomyocytes. In summary, FNDC4 exerts cardioprotection against MI/R injury predominantly through mitigating oxidative stress responses and reducing cardiomyocyte apoptosis. These insights solidify the proposition of FNDC4 as a potential therapeutic aim for tackling MI/R damage.

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Heterochromatin, a key component of the eukaryotic nucleus, is fundamental to the regulation of genome stability, gene expression and cellular functions. However, the factors and mechanisms involved in heterochromatin formation and maintenance still remain largely unknown. Here, we show that insulin receptor tyrosine kinase substrate (IRTKS), an I-BAR domain protein, is indispensable for constitutive heterochromatin formation via liquid‒liquid phase separation (LLPS). In particular, IRTKS droplets can infiltrate heterochromatin condensates composed of HP1α and diverse DNA-bound nucleosomes. IRTKS can stabilize HP1α by recruiting the E2 ligase Ubc9 to SUMOylate HP1α, which enables it to form larger phase-separated droplets than unmodified HP1α. Furthermore, IRTKS deficiency leads to loss of heterochromatin, resulting in genome-wide changes in chromatin accessibility and aberrant transcription of repetitive DNA elements. This leads to activation of cGAS-STING pathway and type-I interferon (IFN-I) signaling, as well as to the induction of cellular senescence and senescence-associated secretory phenotype (SASP) responses. Collectively, our findings establish a mechanism by which IRTKS condensates consolidate constitutive heterochromatin, revealing an unexpected role of IRTKS as an epigenetic mediator of cellular senescence.

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DSS1, essential for BRCA2-RAD51 dependent homologous recombination (HR), associates with the helical domain (HD) and OB fold 1 (OB1) of the BRCA2 DSS1/DNA-binding domain (DBD) which is frequently targeted by cancer-associated pathogenic variants. Herein, we reveal robust ss/dsDNA binding abilities in HD-OB1 subdomains and find that DSS1 shuts down HD-OB1's DNA binding to enable ssDNA targeting of the BRCA2-RAD51 complex. We show that C-terminal helix mutations of DSS1, including the cancer-associated R57Q mutation, disrupt this DSS1 regulation and permit dsDNA binding of HD-OB1/BRCA2-DBD. Importantly, these DSS1 mutations impair BRCA2/RAD51 ssDNA loading and focus formation and cause decreased HR efficiency, destabilization of stalled forks and R-loop accumulation, and hypersensitize cells to DNA-damaging agents. We propose that DSS1 restrains the intrinsic dsDNA binding of BRCA2-DBD to ensure BRCA2/RAD51 targeting to ssDNA, thereby promoting optimal execution of HR, and potentially replication fork protection and R-loop suppression.

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BACKGROUND: Due to the essential role of calcium in vital biological functions, diet low in calcium (DLC) is associated with various diseases. However, there is a lack of study about the current prevalence and health burden due to DLC using reliable data sources. METHODS: We used data from the Global Burden of Disease study 2019 (GBD 2019) to estimate the prevalence and health burden of DLC in 204 countries from 1990 to 2019, by age, sex, and sociodemographic index (SDI). The estimates were produced in DisMod-MR 2.1, a Bayesian meta-regression tool. Summary exposure value (SEV) was used to show the prevalence of DLC, while diseases adjusted life year (DALY) was used to represent the disease burden. The disease burden was estimated for DLC-induced colorectal cancer. Spearman Rank Order correlation was used for correlation analysis, and estimated annual percentage (EAPC) was used to reflect the temporal trends. RESULTS: From 1990 to 2019, the global prevalence of DLC decreased (EAPC of SEV, -0.47; 95% CI, -0.5 to -0.43), but have increased in Oceania region and in many countries, such as United Arab Emirates, New Zealand, Japan, and France. The global DALYs associated with low in calcium were estimated to be 3.14 million (95% uncertainty interval (UI), 2.25-4.26 million) in 2019, with an age standardized rate of 38.2 (95% UI, 27.2-51.8) per 100,000. Unlike the prevalence, the global age standardized DALY rates has remained unchanged (EAPC, -0.03; 95% CI, -0.12 to 0.07), but has increased in over 80 of the 204 countries, located mainly in Asia, Africa, and South America. In all years and regions, the age standardized SEV and DALY rates were higher in male people than that in female people. The prevalence (rho = -0.823; P < 0.001) and disease burden (rho = -0.433; P < 0.001) associated with diet in low calcium were strongly correlated to SDI. The prevalence decreased with age, but the DALY rates increased with age and peaked at about 90 years. The prevalence of DLC has decreased worldwide and in most countries, but the disease burden of DLC induced colorectal cancer has increased in over 40% of countries worldwide. CONCLUSION: Countries with low sociodemographic level and male people are more likely to experience the risk of DLC and related disease burden. Related measures in improve dietary calcium intake are in need to address diet in low calcium related health problems.

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Approximately two-thirds of patients with asthma, a common inflammatory airway disease, are thought to present with allergies. Probiotics and tryptophan metabolites are becoming increasingly important in treating allergic asthma. This study aimed to identify potential probiotic strains and tryptophan metabolites that could alleviate asthma symptoms. Based on in vitro fermentation experiments, we evaluated variations in probiotic capacity to metabolize tryptophan. Of the eight tested strains, Bifidobacterium animalis subsp. lactis CCFM1274 produced relatively high levels of indole-3-carboxaldehyde (I3C). A mouse model of allergic asthma was established by oral administration of ovalbumin (OVA) and was subjected to oral administration of probiotics. The results demonstrated that treatment with CCFM1274 reduced the tendency for body weight loss and mortality in OVA-induced asthmatic mice. Ingestion of CCFM1274 improved the infiltration of perivascular and peribronchial inflammatory cells in the lung sections stained with hematoxylin and eosin (H&E). This outcome was accompanied by a reduction in the serum levels of OVA-specific immunoglobulin E (OVA-sIgE) and in the levels of IL-10 and IL-17 in the bronchoalveolar lavage fluid (BALF). The linear discriminant analysis effect size (LEfSe) of the gut microbiota showed that CCFM1274 increased the relative abundance of Bifidobacterium. In conclusion, CCFM1274 remodeled intestinal tryptophan metabolism in mice and contributed to the improvement of allergic asthma.

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BACKGROUND: Sarcopenia, a hallmark of age-related muscle function decline, significantly impacts elderly physical health. This systematic review aimed to investigate the impact of gut microbiota on sarcopenia. METHODS: Publications up to September 24, 2023 were scrutinized on four databases - PubMed, Web of Science, Cochrane Library, and Embase - using relevant keywords. Non-English papers were disregarded. Data regarding gut microbiota alterations in sarcopenic patients/animal models were collected and examined. RESULTS: Thirteen human and eight animal studies were included. The human studies involved 732 sarcopenic or potentially sarcopenic participants (aged 57-98) and 2559 healthy subjects (aged 54-84). Animal studies encompassed five mouse and three rat experiments. Results indicated an increase in opportunistic pathogens like Enterobacteriaceae, accompanied by changes in several metabolite-related organisms. For example, Bacteroides fluxus related to horse uric acid metabolism exhibited increased abundance. However, Roseburia, Faecalibacterium, Faecalibacterium prausnitzii, Eubacterium retale, Akkermansiaa, Coprococcus, Clostridium_XIVa, Ruminococcaceae, Bacteroides, Clostridium, Eubacterium involved in urolithin A production, and Lactobacillus, Bacteroides, and Clostridium associated with bile acid metabolism displayed decreased abundance. CONCLUSIONS: Age-related sarcopenia and gut microbiota alterations are intricately linked. Short-chain fatty acid metabolism, urolithin A, and bile acid production may be pivotal factors in the gut-muscle axis pathway. Supplementation with beneficial metabolite-associated microorganisms could enhance muscle function, mitigate muscle atrophy, and decelerate sarcopenia progression.

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OBJECTIVES: As populations age, the issue of social participation among older adults has gained prominence. Studies indicate variability in social participation trajectories among this demographic, yet the transition patterns and their effects on depression remain unclear. This longitudinal study aims to explore the latent classes and transition patterns in social participation among older adults and to evaluate their effects on depression. METHODS: Data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2014 (T1) and 2018 (T2) were analyzed, including 2293 older adults. Latent class analysis (LCA) and latent transition analysis (LTA) were employed to identify latent classes of social participation at T1 and T2, as well as the transition probabilities between these classes. Multinomial logistic regression was used to examine predictors of transitions, and depression levels at T2 were compared across transition patterns. RESULTS: The LCA results supported a 3-class model labeled as low, moderate, and high social participation. The probabilities of remaining stable and transitioning to other classes were similar across the three classes (ranging from 0.50 to 0.54). Age, gender, and other baseline characteristics emerged as significant predictors of transition patterns. Older adults experiencing positive transitions exhibited reduced depression compared to those in their original class over time, while those with negative transitions showed increased depression. CONCLUSIONS: This research prompts a deep understanding of social participation dynamics in older adults and their effects on depression. Identifying social participation classes and transition patterns could inform interventions to enhance social participation and reduce depression among older adults.

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