Fruit and vegetable intake has been associated with a reduced risk of noncommunicable diseases, however, few studies have assessed the necessary intake of fruits and vegetables to meet nutrient reference values for the dietary reference intake. This study aimed to estimate the amount of fruit and vegetable intake necessary to meet the reference values of the dietary reference intakes of Japanese people for selected nutrients using the current national dietary intake data for the Japanese adults. We used the data from 4927 Japanese adults aged 20 years and over who participated in the dietary survey in the 2019 National Health and Nutrition Survey. Nine scenarios (70-90% of Japanese adults consuming between 100 and 200 g of fruit) were used to predict the recommended average intake of fruits and vegetables that met the reference values of the dietary reference intakes of Japanese people for dietary fibre, vitamin A, and potassium as fruits and vegetables are the main sources of these nutrients. The scenario in which more than 90% of adults consumed 200 g of fruits per day would almost meet the values in the dietary reference intakes of Japanese people for dietary fibre and vitamin A excluding potassium. The estimated average intake of fruit and vegetables in this scenario was 200 g and 350 g, respectively. Our scenarios demonstrated that an intake of 200 g of fruits and 350 g of vegetables, which have previously been reported to reduce disease risk, would be sufficient to meet the values in the dietary reference intakes of Japanese people of most nutrients, mainly obtained from fruits and vegetables. Further research is needed to examine policies and interventions to increase fruit and vegetable consumption in the Japanese population.

Neurodegenerative diseases (ND) are a form of non-communicable disease that have placed immense social and financial burdens on society. The number of people affected by ND is an ongoing trend due to the global issue of an ageing population. Hence, more effort should be made to treat ND, so alternative options like natural components are considered. Tocotrienol (T3) is a form of vitamin E that possesses many beneficial properties, such as antioxidant, anti-cancer and anti-inflammatory properties. In recent years, many clinical studies revolving around diseases such as neurodegenerative diseases, cardiovascular diseases and osteoporosis appear to suggest that T3 supplementation can be effective in alleviating the symptoms of these diseases. Given that T3 has multiple health benefits and is a potential therapeutic agent for ND, it is important to understand the mechanism through which T3 exerts the beneficial works. One such pathway is the NF-κB signalling pathway, which is closely associated with neuroinflammation and neurodegenerative diseases. Understanding the mechanism of how T3 affects this pathway could be crucial to demonstrate the efficacy of T3 in the management of ND.

Lung adenocarcinoma (LUAD) sustains an immunosuppressive tumor microenvironment (TME) via stromal-immune interactions. Efferocytosis regulates immune suppression and tissue homeostasis, yet biomarkers stratifying its TME states are lacking in LUAD, hindering precision therapy. This study aimed to investigate efferocytosis-associated immune regulation with both causal and prognostic relevance in LUAD, and to identify key biomarkers with potential implications for tumor stratification and therapeutic guidance.

Gene expression profiles from The Cancer Genome Atlas (TCGA) LUAD cohort and Genotype-Tissue Expression (GTEx) underwent differential expression analysis. Efferocytosis-related genes (ERGs) from GeneCards were intersected to identify LUAD-associated candidates. Mendelian randomization (MR) and colocalization evaluated causal ERG-LUAD relationships. Risk-related ERGs were systematically analyzed for expression, biological functions, prognosis, and immune interactions. Single-cell RNA sequencing (scRNA-seq) mapped cellular expression specificity of core ERGs. Machine learning prognostic models (S1PR5-enriched NK cell-related prognostic signature, SENRPS) were developed and validated across independent cohorts.

S1PR5 expression was significantly lower in tumor tissues from LUAD patients compared to healthy lung tissue, at both the transcript and protein levels. We identified S1PR5 as a dual biomarker serving both as a protective factor against LUAD pathogenesis and a prognostic marker for survival outcomes, linked to favorable prognosis and enhanced therapy sensitivity. ScRNA-seq localized S1PR5 to natural killer (NK) cells, enhancing the anti-tumor activity of CD16⁺ NK cells and mediating interactions with antigen-presenting CEACAM8⁺ macrophages. The SENRPS model integrates molecular and cellular features for risk stratification and clinical decision-making.

S1PR5 serves as a causal protective gene and prognostic biomarker governing cytotoxic immunity. SENRPS bridges TME dynamics to clinical risk prediction and therapeutic optimization, advancing LUAD precision oncology.

Little is known about how long-term ambient air pollution exposure modifies the potential benefits of physical activity against chronic obstructive pulmonary disease (COPD). We aimed to examine the interaction between ambient air pollution and physical activity in relation to risk of COPD hospitalization.

In a prospective cohort study of 467,944 adults recruited from 10 areas of China and without spirometry-defined airflow obstruction at baseline in 2004-2008, we examined the exposure-response relationships of total physical activity levels (metabolic-equivalent of task-hour/day; MET-h/d) with COPD hospitalization, stratified by long-term exposure to ambient PM_2.5 (median: 58.7 μg/m³), NO₂ (33.3 μg/m³), and O₃ (87.8 μg/m³), respectively, using multivariable Cox regression.

In 467,944 adults (mean [SD] age = 51.8 [10.6] years; 280,590 females, 187,354 males), 14,688 incidents of COPD were recorded during 5.9 million person-years of follow-up. Physical activity was inversely associated with COPD in participants exposed to low air pollution but showed weak or no association in those exposed to high air pollution (all p-interaction < 0.001). Comparing participants at the highest (≥29.8 MET-h/d) versus lowest quartile (<10.7 MET-h/d) of physical activity, there were 18-23% statistically significant lower risks among those with low air pollution exposure, but marginally significant elevated risks among those with high air pollution exposure (for PM_2.5 and NO₂). The effect modification strengthened when stratifying participants by higher cut-offs of air pollution exposure.

Long-term exposure to ambient air pollution is associated with attenuation of the potential benefits of physical activity against COPD in Chinese adults.

Sino-British Fellowship Trust, National Key Research and Development Program of China, Kadoorie Charitable Foundation, Wellcome, Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, UK Medical Research Council, Cancer Research UK, British Heart Foundation.

Colorectal cancer (CRC) remains a leading cause of cancer-related death worldwide, with limited treatment options for patients with metastatic disease. Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells represent a novel immunotherapeutic approach with potential advantages in safety and allogeneic applicability.

This is a multi-arm phase I clinical trial (NCT05213195) evaluating the safety and feasibility of NKG2D-based CAR-NK cells expressing membrane-bound IL-15 (mbIL-15) in advanced CRC. Here, we report the results from the cohort expansion stage of this trial. Totally, six heavily pretreated patients were enrolled and received lymphodepletion chemotherapy followed by four infusions of CAR-NK cells in 2 weeks. Two cohorts were designed to assess extended infusion routes and combination with anti-PD-1 antibodies.

CAR-NK therapy was well tolerated, with no treatment-related death or serious non-hematologic toxicities. Common adverse events included reversible cytokine-release syndrome (CRS) and mild gastrointestinal symptoms. Notably, potential clinical benefits were observed in patients who received CAR-NK cells in combination with anti-PD-1 therapy, including one patient who achieved stable disease (SD) and two others who experienced prolonged overall survival exceeding 700 days, suggesting a potential synergistic effect. Meanwhile, CAR-NK cells were detectable in peripheral blood within two weeks after infusion. And the combination with PD-1 blockade was associated with substantially increased peak CAR transgene levels compared to monotherapy (median CAR copies, 45,593 versus 1001).

NKG2D CAR-NK cell therapy, alone or combined with PD-1 blockade, demonstrated a favorable safety profile and potential clinical benefit in advanced CRC, warranting further investigation in larger cohorts.

Edentulism(partial/complete) is a significant public health concern, impacting masticatory function, nutritional intake, and overall quality of life. Emerging evidence underscores the bidirectional relationship between oral and systemic health, where chronic oral inflammation like dental caries, periodontal diseases, trauma, and tooth loss may contribute to or exacerbation of systemic conditions such as cardiovascular diseases, hypertension, diabetes mellitus and osteoporosis.

To determine prevalence of systemic diseases among edentulous patients attending dental department of a tertiary hospital in Nepal.

A descriptive, cross-sectional study was conducted among 384 edentulous patients consented to participate visiting dental department of Patan Academy of Health Sciences (PAHS) from September 2019 to September 2022. Ethical clearance was obtained from Institutional Review Committee, PAHS (Ref: drs1805291179). Sociodemographic data, medical history, current history of medications for self-reported conditions and dental history were collected through face-to-face interviews. A comprehensive intraoral examination was then conducted to record in Performa sheet and verify missing permanent dentition. Data obtained were entered in Epi data version 5 followed by bivariate and multivariable analysis in Statistical Package for Social Sciences (SPSS) version 21.

Among 384 edentulous patients, 35.70% self- reported at least one systemic disease, with hypertension (21.60%) and diabetes (10.70%) were most prevalent. While 87.60% of those with systemic disease were under medication, 12.04% remained untreated and only 8.7% acknowledged a link between systemic disease and tooth loss. Bivariate analysis showed significant associations between systemic disease and age, edentulousness duration, occupation, and cause of tooth loss. However, in multivariable analysis age and edentulousness duration demonstrated inverse association, suggesting possible reverse causality. Periodontitis and trauma were significantly more common cause of tooth loss in individuals with systemic diseases.

Edentulous patients exhibit a high burden of systemic disease, often without full treatment or awareness of systemic links. Regression analysis suggests a complex, potentially bidirectional relationship between edentulism and systemic disease, challenging assumption of linear causality. Surprisingly, people with higher education or professional jobs were not protected from these conditions. These results highlight the need for better awareness, integrated care between dental and medical services.

Despite the growing burden of youth-onset type 2 diabetes (Y-T2D), the long-term risk for fatal/non-fatal cardiovascular disease (CVD) in Y-T2D compared to peers is unknown. The International Childhood Cardiovascular Cohort (i3C) combined-risk z-score is a novel tool for predicting 35-year risk of adult CVD events. In Y-T2D compared to peers (Lean and overweight/obesity [OW/OB]), we estimated predicted CVD events and evaluated the relationship of the i3C z-score with risk-enhancing factors.

In a pooled cohort cross-sectional analysis of 1547 adolescents and young adults (AYA) aged 10-25 years [627 Lean, 803 OW/OB, 117 Y-T2D], i3C combined-risk z-scores and estimated hazard ratios (HR) were obtained from the published i3C equation using risk z-scores of systolic blood pressure, body mass index (BMI), smoking history, total cholesterol, and triglycerides. ANCOVA regression models were used: 1) to compare i3C z-scores and HR in AYA with Y-T2D, OW/OB and Lean peers, and 2) to measure associations between i3C estimated HR and risk-enhancing factors including apolipoprotein B (ApoB), total low density lipoprotein particle number (LDL-P), and high sensitivity C reactive protein (hsCRP). Models were adjusted for diagnosis group, race, study center and multiple comparisons with Bonferroni.

Y-T2D had the highest i3C z-score (Y-T2D: 1.23 [1.10, 1.36] vs. OW/OB: 0.84 [0.80, 0.88] vs. Lean: -0.11 [-0.15, -0.06], mean[95%CI]) and estimated HR for predicted CVD events (Y-T2D: 4.25 [3.65-4.86] vs. OW/OB: 3.04 [2.85-3.22] vs. Lean: 0.95 [0.74-1.17], HR [95% CI]). Risk-enhancing factors increased the HR for predicted CVD risk by 0.3 for each 10 mg/dL increase in ApoB, 0.1 for each 100 nmol/L increase in LDL-P, and 0.16 for each 2 mg/L increase in hsCRP, all P < 0.001.

Y-T2D had an estimated 4.5- and 1.4-times higher risk for predicted CVD events compared to Lean and OW/OB peers, respectively. Lipoprotein and inflammatory risk-enhancing factors may help stratify and guide primary prevention strategies in high-risk AYA.

This study aimed to determine the optimal cut-off values of various cardio-metabolic indices for predicting MetS in Iranian adults with T2DM.

This cross-sectional analytical study included 400 Iranian adults with T2DM. Anthropometric and biochemical parameters were assessed, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), lipid profile, fasting blood glucose (FBG), and blood pressure. Several cardio-metabolic indices-including the cardio-metabolic index (CMI), lipid accumulation product (LAP), and atherogenic index of plasma (AIP)-were calculated. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off points, sensitivity, and specificity of these indices for MetS diagnosis.

All cardio-metabolic indices, including LCI, CMI, AI, AC, CHOL index, CRI, LAP, and AIP, were significantly associated with an increased risk of MetS across all three models (p < 0.05). Among them, LAP and CMI demonstrated the highest predictive accuracy, with area under the ROC curve (AUC) values of 0.90 and 0.88, respectively. The optimal cut-off point for LAP was 66.84 (sensitivity = 0.76, specificity = 0.93), while for CMI, it was 2.19 (sensitivity = 0.74, specificity = 0.88). Multivariable logistic regression analysis confirmed the strong association of these indices with MetS risk, with LAP showing the highest odds ratio (OR = 56.28, 95% CI: 26.10-121.34, p < 0.001). These associations remained significant across all three models: Model 1 (unadjusted), Model 2 (adjusted for age and gender), and Model 3 (adjusted for age, gender, race, education, occupation, disease duration, physical activity, and medications).

All cardio-metabolic indices significantly predicted MetS risk, but LAP and CMI emerged as the most effective predictors of MetS in Iranian adults with T2DM, demonstrating high diagnostic performance. These indices can serve as valuable, cost-effective screening tools in clinical practice, enabling early intervention and risk reduction in high-risk populations. Future studies should validate these findings across diverse ethnic groups and assess their long-term predictive value for MetS-related complications.

Diabetes mellitus increases the risk of developing tuberculosis (TB) and negatively affects TB treatment outcomes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are used in glycemic control but can also modulate immune pathways involved in immune-mediated diseases. Considering the immunoregulatory effects of DPP-4 inhibitors, this emulated target trial compared the risk of pulmonary TB in users and non-users of DPP-4 inhibitors with type 2 diabetes mellitus (T2DM).

We identified 328,842 pairs of DPP-4 inhibitor users and non-users from Taiwan's National Health Insurance Research Database from January 1, 2007, and December 31, 2019. Cox proportional hazard models were used to determine the risk of new-onset pulmonary TB between the study and control groups.

The follow-up duration was 5.06 years for DPP-4 inhibitor users and 4.05 years for non-users. The incidence rates of new-onset pulmonary TB were 1.93 and 2.18 cases per 1,000 person-years in DPP-4 inhibitor users and non-users, respectively. Compared with non-users, DPP-4 inhibitor users had a significantly lower risk of developing pulmonary TB, with an adjusted hazard ratio (aHR) of 0.85 (95% CI: 0.81-0.90). Kaplan-Meier analysis showed a significantly lower cumulative incidence of new-onset pulmonary TB among DPP-4 inhibitor users than non-users (log-rank test, p < 0.001). Furthermore, a longer cumulative duration of DPP-4 inhibitor use was associated with a lower risk of pulmonary TB.

In patients with T2DM, the use of DPP-4 inhibitors was associated with a significantly lower risk of developing pulmonary TB compared to non-use. Additionally, a longer cumulative duration of DPP-4 inhibitor may further reduce the TB risk.

Gestational Diabetes Mellitus (GDM) is a prevalent metabolic condition during pregnancy that can affect up to 24.9% of pregnancies in the United Arab Emirates (UAE). GDM can impair the mother's Quality of life (QOL) due to physical, psychological, and social challenges. Understanding how GDM affects the QOL is essential for effective treatment and intervention. This study aims to assess the QOL among women with GDM in the UAE, with a focus on how the condition impacts their overall well-being.

A cross-sectional descriptive study was conducted at Thumbay University Hospital in Ajman, UAE. The study assessed the quality of life of 90 pregnant women with dietary or insulin-treated GDM who visited the antenatal/postnatal OPD and labor unit. A structured questionnaire was used to collect data on "socio-demographic" and obstetrical parameters and the standardized GDMQ-36 for QOL assessment on a five-point Likert scale (strongly agree to strongly disagree) with a score range from 1 to 5.

The study found that 77.8% of the mothers experienced moderate QOL, while 22.2% had high QOL. Furthermore, concerns about high-risk pregnancy had the highest mean score (Mean = 29.59, SD = 10.902), while Medication and treatment had the lowest mean score (Mean = 15.71, SD = 3.036), suggesting lower perceived burden. Support was perceived as moderate (Mean = 23.24, SD = 3.718) and Perceived constraints (Mean = 20.7, SD = 6.173) and complications of GDM (Mean = 16.17, SD = 4.465) also contributed to overall QOL. This study also found that Education level (χ² = 12.936, p = 0.044) and Previous history of GDM (χ² = 5.625, p = 0.018) were significantly associated with QOL, with woman with higher education and no history of GDM reporting a higher QOL.

The study highlights that concerns about high-risk pregnancy and complications of GDM negatively impact QOL. Higher education and no previous GDM history were associated with better QOL, emphasizing the role of education and early intervention, and supportive care in shaping the mother's well-being.