The potential of medium-chain triglyceride(MCT)to enhance athletic performance remains controversial.This study aims to explore how long-term MCT supplementation may enhance endurance and predict individual responders compared to carbohydrates(CHO),while also validating the feasibility of applying the N-of-1 trial design in the field of personalized nutrition.It consists of a series of completed 6-week,single-center,randomized,double-blind,controlled N-of-1 trials,involving a total of 9 long-distance running enthusiasts from Wuhan University(Wuhan,China).The study was divided into 3 cycles,each lasting 2 weeks.During each cycle,participants randomly consumed 400 mL of MCT as the intervention or 400 mL of CHO as the control.The 5-kilometer time trial(5KTT)results were used to assess participants'endurance,and a Bayesian model was employed to assess individual and aggregated results.Results showed substantial variability in the intervention effect between participants,with improvements in the 5KTT on MCT relative to CHO ranging from-37.54 s(95％credible interval(CrI),-164.25 to 100.35)to 69.37 s(95％CrI,-81.14 to 215.45).The trial observed 1 CHO responder,with a posterior probability of 0.50;2 MCT responders,with posterior probabilities of 0.57 and 0.64;and 5 non-responders,respectively.The aggregate Bayesian analysis indicated that the posterior probability of achieving a clinically meaningful intervention effect for MCT compared to CHO was only 0.37.Based on these findings,MCT did not improve participants'running performance compared to CHO at the overall level.However,our study supports that using the N-of-1 trial design can provide more precise personalized recommendations for each participant.

Emotional intelligence is a crucial ability in adolescent development, with physical activity and social adaptation recognized as significant protective factors. Employing a network analysis approach, this study aimed to investigate the interrelationships among physical activity, social adaptation, and emotional intelligence in adolescents. A total of 616 adolescents completed the International Physical Activity Questionnaire-Short Form, the Emotional Intelligence Scale, and the Social Adaptation Scale. Network analysis was utilized to visualize and analyze the patterns of association among the variables. The network analysis revealed that the connections among variables within the same constructs were stronger than those across different constructs. The three strongest cross-construct associations identified in our study were “physical self-perception” and “high-intensity physical activity,” “physical self-perception” and “self-emotion regulation,” and “physical self-perception” and “emotion utilization.” Physical activity, social adaptation, and emotional intelligence formed a modular network. “Emotion utilization” emerged as the node with the highest strength and expected influence. “Physical self-perception” served as a key bridge between the physical activity and emotional intelligence modules, demonstrating the highest bridge expected influence. Physical activity, social adaptation, and emotional intelligence in adolescents form a dynamic network of associations, in which high-intensity physical activity and physical self-perception are core nodes. Furthermore, physical self-perception is identified as a pivotal bridging node between the physical activity and emotional intelligence systems. This study provides clear structural targets for mental health interventions in adolescents. In contexts where direct training of emotional intelligence is challenging, “enhancing physical self-perception” can be prioritized as an indirect intervention point. By leveraging its bridging position within the network, this approach can structurally link the physical activity and emotional intelligence subsystems, thereby facilitating the synergistic optimization of the entire protective network.

Multivitamins were widely used health supplements that replenished essential nutrients in the human body.Despite their popularity,the impact of multivitamins on the cognitive function of older adults remained unclear and contentious.This study offered a comprehensive review and meta-analysis of research published until June 2024,analyzing the effects of multivitamins on various cognitive functions in individuals aged 65 and older.We included ten randomized controlled trials encompassing 13 600 participants from multiple databases.These studies evaluated the impact of multivitamins on reasoning,memory,learning,visual perception,idea production,cognitive speed,psychomotor abilities,and higher cognitive functions.Our meta-analysis revealed that multivitamins significantly enhanced delayed free recall(standardized mean difference(SMD)=0.09,95％confidence interval(CI):[0.05,0.13],P＜0.000 1).However,they had no substantial effects on immediate free recall(SMD=0.85,95％CI:[-0.18,1.90],P=0.11),idea production(SMD=0.00,95％CI:[-0.04,0.03],P=0.86),or cognitive speed(SMD=0.34,95％CI:[-0.07,0.74],P=0.11).Thus,while multivitamins facilitated delayed free recall,they did not significantly improve other cognitive functions in older adults.

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for type 2 diabetes mellitus (T2DM), and its early identification and intervention offer opportunities for reversing diabetes mellitus.MethodsIn this study, we identified biomarkers for the MASLD dataset (GSE33814, GSE48452) and the T2DM dataset (GSE76895 and GSE89120) by bioinformatics analysis. Next, we constructed weighted gene co-expression network (WGCNA) for disease module analysis to screen out shared genes strongly associated with diseases. We also analyzed the enriched pathways of shared genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Next, hub gene validation was performed using the least absolute shrinkage and selection operator (LASSO) and receiver operating characteristic (ROC) curves. Finally, we used RT-qPCR, immunofluorescence, Western blotting and Elisa to validate hub gene expression in MASLD and T2DM mouse models.ResultsThis analysis identified 20 genes shared by MASLD and T2DM that were enriched in the bile secretion, phototransduction, cancer, carbohydrate digestion and absorption, cholesterol/glycerol metabolism, and retinol metabolism. The LASSO algorithm and ROC curve identified Retinol Dehydrogenase 10 (RDH10) as the best diagnostic gene for MASLD and T2DM. Immunofluorescence and Western blot showed that RDH10 expression was reduced in the liver and pancreatic islets of MASLD and T2DM model mice. Similarly, serum levels of RDH10 were significantly lower in MASLD and T2DM model mice and humans than in controls.ConclusionOur study suggests that RDH10 is a common diagnostic marker for MASLD and T2DM and provides new research directions for the prevention and treatment of MASLD and T2DM.

BackgroundAlthough there is an interaction between sex, body fat distribution, and cardiac structure and function, these relationships have not been fully elucidated yet. This study aims to reveal the causal relationship between genetic determinants of fat distribution pattern and function of the left ventricular structure in different sexes.MethodsGenetic variants for waist circumference, hip circumference, waist-to-hip ratio (WHR), and body mass index (BMI) were selected from genome-wide association studies conducted in European samples. The dataset for left ventricular (LV) parameters was obtained from over 35,000 European samples in the UK Biobank Cardiovascular Magnetic Resonance sub-study. Two-sample Mendelian randomization (MR) analysis was employed to explore causal relationships.ResultsAfter adjusting for BMI, WHR shows a positive causal relationship with LV hypertrophy and a significant negative causal relationship with LV volume and diastolic function. In further subgroup analysis, we only found similar results in WHR among the female population (FWHR), while in the male population, there was no significant causal relationship between MWHR and LV hypertrophy and diastolic function. Additionally, in our MR analysis, no causal relationship was found between WHR and LVEF.ConclusionsThis study indicates that the fat distribution pattern has unique effects on the structure and function of the LV, and these effects vary by sex. This study provides evidence for a causal relationship between fat distribution and LV structure and function across both sexes.

Obesity exacerbates renal injury following lower limb ischaemia-reperfusion (LLIRI) through mechanisms involving calcium dysregulation and oxidative-inflammatory-apoptotic cascades. However, the underlying pathways remain to be identified. Thus, this study aimed to elucidate the underlying pathways by using transcriptomics, multi-omics, and pharmacological validation. Utilizing transcriptomics, multi-omics analysis, and targeted biochemical/molecular assays in a high-fat diet-induced obese mouse model of LLIRI, combined with pharmacological validation using nicardipine in human renal tubular cells exposed to oxidative stress, we elucidated the underlying pathways linking calcium dysregulation to renal injury. In high-fat diet-induced obese mice, LLIRI triggered profound renal transcriptomic reprogramming, with 1530 differentially expressed genes significantly enriched in calcium homeostasis disruption (GO:0055074), NF-κB signalling (KEGG:mmu04064), and apoptosis. Mechanistically, LLIRI-induced surge in reactive oxygen species promoted renal calcium influx by downregulating calcium efflux transporters Atp2b4 (PMCA4) and Kcnma1 (BK channel), which led to Ca2+ overload. This results in activation of the transcription hub JUN, which orchestrated a triad of injury: oxidative stress, as evidenced by Nox4 upregulation and ATP/NAD+ depletion, which elevated lipid (MDA↑), protein (carbonyls↑), and DNA (8-OHdG↑, γ-H2AX↑) damage; inflammation, as evidenced by tumour necrosis factor-α/interleukin (IL)-1β/IL-18 elevation and macrophage infiltration (F4/80+/HMGB1+); and apoptosis, as evidenced by PUMA (Bbc3) induction, caspase-3/8 activation, and Bax/Bcl-2 imbalance. In vitro, H2O2-induced oxidative stress in human renal tubules replicated Ca2+ overload and JUN-driven apoptosis/senescence. Treatment with the L-type calcium channel blocker nicardipine (2.5 μM) attenuated calcium influx, suppressed JUN/Nox4/PUMA expression, reduced caspase activation, and mitigated cellular damage. Our findings establish Ca2+ overload-JUN activation as a central axis integrating oxidative, inflammatory, and apoptotic networks in obesity-aggravated LLIRI renal injury. Integrating multi-omics and pharmacological evidence, we identify JUN as a master transcriptional regulator of the Nox4-inflammasome-PUMA apoptotic triad, thereby elucidating a previously unrecognized pathogenic pathway in obesity-exacerbated renal LLIRI. Targeting this axis with calcium channel blockers is a promising therapeutic strategy.

It remains unclear whether the history of switching antiretroviral therapy (ART) regimens is a standalone risk factor for lipid deterioration in people living with HIV (PLWH). This study aims to explore the relationship between ART regimen switching history and lipid profiles in PLWH. This is a retrospective analysis of data from HIV-positive individuals aged 16-82, enrolled at Jinyintan Hospital in Wuhan, China, between January 2018 and June 2022. We investigated the potential link between their history of switching ART regimens and their lipid profiles. Locally weighted scatter plot smoother (LOESS) curves were used to depict the dynamic changes in lipid profiles over time. Linear mixed-effects models were employed to assess the differences in lipid levels between individuals with and without a history of ART switches. Out of 708 patients with HIV who began ART between January 2018 and June 2022, 207 (29%) switched regimens at least once, while 501 (71%) remained on their initial regimen throughout the study. Individuals with a history of switching ART exhibited less favorable lipid profiles as identified by LOESS analysis. Linear mixed-effects models indicate that participants who had not previously altered their ART regimens displayed notably lower levels of total cholesterol to high-density lipoprotein (HDL) ratio, total cholesterol, and triglycerides compared to those with a history of ART regimen changes (total cholesterol to HDL ratio, difference -0.19, 95% CI: -0.34 to -0.04; total cholesterol, difference -0.13, 95% CI: -0.25 to 0.00; triglycerides, difference -0.27, 95% CI: -0.43 to -0.11). In contrast, individuals with a history of ART regimen switching had noticeably lower HDL cholesterol (HDL-C) levels [difference: 0.04; 95% confidence intervals (CI) 0.00 to 0.07]. This means that the history of switching ART regimens may be associated with lipid deterioration in PLWH.

Substantial changes resulting from the interaction of environmental and dietary factors contribute to an increased risk of obesity, while their specific associations with obesity remain unclear. We identified inflammation-related dietary patterns (DP) and explored their associations with obesity among urbanised Tibetan adults under significant environmental and dietary changes. Totally, 1826 subjects from the suburbs of Golmud City were enrolled in an open cohort study, of which 514 were followed up. Height, weight and waist circumference were used to define overweight and obesity. DP were derived using reduced rank regression with forty-one food groups as predictors and high-sensitivity C-reactive protein and prognostic nutritional index as inflammatory response variables. Altitude was classified as high or ultra-high. Two DP were extracted. DP-1 was characterised by having high consumptions of sugar-sweetened beverages, savoury snacks, and poultry and a low intake of tsamba. DP-2 had high intakes of poultry, pork, animal offal, and fruits and a low intake of butter tea. Participants in the highest tertiles (T3) of DP had increased risks of overweight and obesity (DP-1: OR = 1·37, 95 % CI 1·07, 1·77; DP-2: OR = 1·48, 95 % CI 1·18, 1·85) than those in the lowest tertiles (T1). Participants in T3 of DP-2 had an increased risk of central obesity (OR = 2·25, 95 % CI 1·49, 3·39) than those in T1. The positive association of DP-1 with overweight and obesity was only significant at high altitudes, while no similar effect was observed for DP-2. Inflammation-related DP were associated with increased risks of overweight and/or obesity.

Older individuals are vulnerable to multiple non-communicable chronic diseases, leading to an increased risk of a decline in activities of daily living (ADLs) disability. Whether this association is affected by sociodemographic factors remains unclear. This study aimed to identify multimorbidity patterns and explore their association with ADLs. This study included 14,018 older adults (≥ 60 years) from five waves of the China Health and Retirement Longitudinal Study (2011–2020). Multimorbidity patterns were identified among 13 non-communicable chronic diseases using exploratory factor analysis. Associations between multimorbidity patterns and ADLs (basic ADL, BADL; instrumental ADL, IADL) were examined using mixed-effects models. Stratified and interaction analyses were used to explore the influence of sociodemographic factors on these associations. The prevalence of IADL disability among older individuals in China increased from 2011 to 2020.The prevalence of multimorbidity increased steadily from 2011 to 2018 but decreased in 2020. Four multimorbidity patterns were identified: visceral-skeletal, respiratory system, neurodegenerative, and cardiometabolic diseases. Higher factor scores of multimorbidity patterns were associated with increased risk of BADL and IADL disability, particularly for neurodegenerative diseases pattern (T3 vs. T1, BADL: OR 1.44, 95

Anaemia in obese patients who underwent major vascular surgery is closely associated with ischaemia-reperfusion injury (IRI)-driven erythrocyte damage and haemolysis. However, the obesity-specific mechanisms remain unknown. We investigated the interplay among oxidative stress, metabolic reprogramming, and cytoskeletal destabilisation in red blood cells (RBCs) during aortic IRI under obese conditions. Using a high-fat diet-induced obese mouse model subjected to abdominal aortic clamping-reperfusion, we systematically dissected the hierarchical mechanisms linking obesity to erythrocyte vulnerability during IRI. The key findings were-oxidative amplification-obese mice exhibited a pronounced intraerythrocytic reactive oxygen species surge post-IRI, accompanied by a compensatory upregulation of antioxidant enzymes (catalase and glutathione peroxidase). However, persistent accumulation of oxidative stress markers (malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and carbonylated proteins) indicated overwhelming oxidative stress. Metabolic iron dysregulation-elevated Fe3+ and methaemoglobin levels and NADPH/ATP depletion indicated concurrent iron homeostasis disruption and metabolic crisis, respectively. RBCs glycolytic reprogramming is characterized by imbalanced glycolytic flux with accumulation of intermediates (glucose-6-phosphate [G6P] and fructose-6-phosphate), despite compensatory activation of the pentose phosphate pathway (PPP) and Rapoport-Luebering shunt (RLS). Structural destabilisation: critical cytoskeletal protein expression including expression of Band 3, glycophorin C, α/β-spectrin, and adducin, was significantly downregulated, with tropomodulin 1 and tropomyosin displaying the most prominent reductions, resulting in membrane fragility and haemolysis (elevated levels of haemoglobin, bilirubin, and circulating methaemoglobin). Collectively, we identified an 'oxidative-metabolic-structural collapse' axis that mediates obesity-aggravated erythrocyte injury during IRI, providing a mechanistic foundation for developing perioperative erythrocyte-protective strategies in metabolic syndrome with potential to improve cardiovascular surgery outcomes.

The perovskite nanocrystals (PeNCs) are emerging as a promising emitter for light-emitting diodes (LEDs) due to their excellent optical and electrical properties. However, the ultrafast growth of PeNCs often results in large sizes exceeding the Bohr diameter, leading to low exciton binding energy and susceptibility to nonradiative recombination, while small-sized PeNCs exhibit a large specific surface area, contributing to an increased defect density. Herein, Zn2+ ions as a negative catalyst to realize quantum-confined FAPbBr3 PeNCs with high photoluminescence quantum yields (PL QY) over 90%. Zn2+ ions exhibit robust coordination with Br- ions is introduced, effectively retarding the participation of Br- ions in the perovskite crystallization process and thus facilitating PeNCs size control. Notably, Zn2+ ions neither incorporate into the perovskite lattice nor are absorbed on the surface of PeNCs. And the reduced growth rate also promotes sufficient octahedral coordination of PeNC that reduces defect density. The LEDs based on these optimized PeNCs exhibits an external quantum efficiency (EQE) of 21.7%, significantly surpassing that of the pristine PeNCs (15.2%). Furthermore, the device lifetime is also extended by twofold. This research presents a novel approach to achieving high-performance optoelectronic devices. The ultrafast crystallization process of perovskite nanocrystals is effectively suppressed through using Zn2+ ions as negative catalysts to coordinate with Br- ions. The Zn2+ ions neither incorporate into the perovskite lattice nor are absorbed on the surface of PeNCs. This strategy not only reduces defect density but also realizes the color tunability of PeNCs, yielding efficient LEDs with the highest EQE of 21.7%. image

Objectives: This study aimed to investigate knowledge, attitudes, and practices related to pre-prepared foods among college students in Central China. Methods: From the end of May 2024 to June 2024, we completed a cross-sectional study using an online questionnaire. A total of 1676 questionnaires were distributed online, and 1566 valid questionnaires were collected. Data were analyzed using Kruskal–Wallis tests or Wilcoxon rank-sum tests for univariate analysis. A multiple linear regression model was employed with knowledge, attitudes, and practices scores as dependent variables to identify factors associated with the scores on pre-prepared food knowledge, attitudes, and practices. Results: The survey results showed that 56.7% of the participants had high knowledge scores, 4% of the participants had high attitudes scores, and only 0.4% of the participants had high practices scores. Multiple linear regression analysis showed that ethnicity, the number of children in the family, academic qualifications, and monthly living expenses were associated with college students’ knowledge of pre-prepared foods (p < 0.05). Gender and the satisfaction with school catering services were associated with college students’ attitudes of pre-prepared foods (p < 0.05). Gender, knowledge and attitudes were associated with practices of pre-prepared foods (p < 0.05). Conclusions: College students have a relatively high level of knowledge of pre-prepared foods. However, they have more negative attitudes and practices towards pre-prepared foods, and the overall KAP levels are low.

This study investigated the association of hypertension with cognitive impairment and determined whether better adherence to plant-based diet (PBD) patterns may modify the association. We analyzed 4485 elderly individuals with normal cognition at baseline from the Chinese Longitudinal Healthy Longevity Survey (2011−2018). Cognitive function was assessed by the Mini-mental State Examination (MMSE), and cognitive impairment was defined as an MMSE score below 18 points. Diet patterns were assessed using the overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) derived from a simplified food frequency questionnaire (FFQ). Blood pressure was measured through physical examination. Cox proportional hazard regression and restricted cubic spline were performed. Participants with hypertension had an increased risk of cognitive impairment compared with normal group. The associations between hypertension and cognitive impairment were more pronounced among participants with lower PDI than those with higher PDI, among participants with lower hPDI than those with higher hPDI, and among participants with higher uPDI than those with lower uPDI. A healthful PBD pattern may attenuate hypertension-induced cognitive impairment, while an unhealthful PBD pattern may exacerbate hypertension-induced cognitive impairment in elderly. Adherence to healthful PBD pattern could be used to prevent or mitigate adverse neurological effects in the hypertensive population.

The aim of this study was to assess the association of long-term air pollution exposure and its changes with body weight and blood pressure in children and adolescents.Physical health data of children and adolescents in Wuhan from 2013 to 2015 were used in the analyses. A land use regression model was developed to assess the air pollution exposure levels of the study participants. Body mass index, systolic and diastolic blood pressure were quantitatively analyzed by mixed-effects modeling in relation to air pollutant exposure concentrations. Mixed-effects models found that elevated concentrations of all four air pollutants led to increased BMI-z scores, but only PM2.5, NO2, and CO were relevant for the risk ratio of overweight/obesity. For blood pressure, only NO2 was not statistically significantly associated with diastolic blood pressure, while changes in the concentration of the remaining three air pollutants were positively associated with diastolic blood pressure, and after adjustment for covariates PM2.5 and CO were associated with an increased risk of developing hypertension. For example, the risk ratios for overweight/obesity and hypertension were 1.14 (1.10, 1.18) and 1.06 (1.01, 1.12) per unit increase in PM2.5(10μg/m3). In stratified analyses, it was found that participants with overweight or obesity at baseline displayed higher systolic and diastolic blood pressure increase effect values when exposed to air pollutants than normal weight participants. Increased air pollutant exposure concentrations are associated with increases BMI-z scores and blood pressure levels in children and adolescents, with implications for overweight/obesity and hypertension. Obesity amplified the association of chronic air pollution exposure with blood pressure and hypertension in Chinese children.

Background: It is unclear how changes in plant-based dietary quality are linked to the subsequent risk of cognitive impairment.Objectives: This study aims to evaluate this relationship using data from the Chinese Longitudinal Healthy Longevity Survey.Methods: A total of 6662 participants free of cognitive impairment in 2008 were included and followed <2018. Plant-based dietary quality was assessed by 3 indices: overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). Changes in plant-based diet quality from 2008 to 2011 were classified into quintiles. In addition, we assessed incident cognitive impairment (from 2011 to 2018) by using the Mini-Mental State Ex-amination. Cox proportional-hazards models were performed.Results: We recorded 1571 incident cases of cognitive impairment during a median of 10 y of follow-up. Compared with participants whose plant-based diet had no change or was relatively stable over 3 y, the full-adjusted hazard ratios (HRs) with 95% confidence intervals (CI) for cognitive impairment were 0.77 (0.64, 0.93), 0.72 (0.60, 0.86), and 1.50 (1.27, 1.77) among participants with a large increase in PDI, hPDI, and uPDI, respectively. The HRs with 95% CI were 1.22 (1.02, 1.44), 1.30 (1.11, 1.54), and 0.80 (0.67, 0.96) among participants with a large decrease in PDI, hPDI, and uPDI, respectively. Every 10-point increase in PDI and hPDI was associated with a 26% and 30% lower risk of cognitive impairment, whereas every 10-point increase in uPDI was associated with a 36% higher risk.Conclusions: Older adults with increased adherence to an overall plant-based diet and a healthful plant-based diet over 3 y have a lower risk of cognitive impairment, whereas those with increased adherence to an unhealthy plant-based diet had a higher risk of cognitive impairment.

This study aimed to evaluate the associations of baseline high-sensitivity C-reactive protein (Hs-CRP) and its change with subsequent cognitive decline and cognitive impairment. Data for this study were obtained from the China Health and Retirement Longitudinal Study, a national community-based prospective cohort study. Hs-CRP level and cognitive function were measured repeatedly over a 7-year follow-up. Linear mixed models and cox proportional hazard models were used to evaluate the associations. The study comprised 7385 participants (50.67% women, mean age 59.08 ± 8.86 years) with baseline Hs-CRP ranging from 0.03 to 178.10 mg/L (median: 1.01 mg/L, IQR: 0.55–2.11 mg/L). During a median of 5.79 years follow-up, the highest quartile of the Hs-CRP group showed a faster rate of cognitive decline (−0.0053 SD/year, p = 0.006) and a higher risk of cognitive impairment (HR 1.0814, p = 0.044) than those in the lowest quartile. Individuals in the elevated group of Hs-CRP change had a significantly faster cognitive decline (−0.0070 SD/year, p = 0.016) compared with those in the stable group. In this study, significant longitudinal associations between baseline Hs-CRP, elevated Hs-CRP, and long-term cognitive deterioration were observed. Hs-CRP level could perhaps serve as a predictor for cognitive deterioration in middle-aged and older adults.

Nicotinamide N-methyltransferase (NNMT) has been reported to be linked to methylation reprogramming in cancer cells. However, the role of NNMT in the tumour microenvironment (TME) remains elusive. Here, we found that the expression of NNMT was elevated in the stroma of oral squamous cell carcinoma (OSCC). Using a fibroblast-attached organoids (FAOs) model, we confirmed that stromal NNMT expression contributed to the generation of assembled tumour organoids. In a tumour regeneration assay with co-implanted OSCC cells and cancer-associated fibroblasts (CAFs), the tumour-initiating activity was reduced when NNMT was silenced in CAFs. In contrast, overexpression of NNMT in paracancerous fibroblasts (PFs) accelerated tumour growth in co-inoculation experiments. Notably, fibroblast-specific NNMT can regulate type I collagen deposition in both FAOs and xenografts. Further investigations confirmed that the stromal NNMT-aggravated oncogenic activities were attenuated by treatment with inhibitors of either collagen synthesis (e.g. losartan, tranilast, and halofuginone) in fibroblasts, or the focal adhesion kinase (FAK) signal (i.e. defactinib) in cancer cells. Mechanistically, overexpression of NNMT reduced the enrichment of H3K27me3 at the promoter of the gene encoding lysyl oxidase (LOX), a key enzyme that regulates the cross-linking of collagen I. Overall, we propose that the NNMT-LOX-FAK cascade contributes to the crosstalk between cancer cells and fibroblasts during OSCC development, and that NNMT-centric extracellular matrix remodelling is a novel therapeutic target for patients with OSCC.

Background The reported associations between body mass index (BMI), waist circumference (WC), and cognitive decline are not consistent, especially in older adults. Objective This study aims to investigate the longitudinal associations of BMI, WC, and their change values with cognitive decline among Chinese adults aged 60 years and older and to examine the potential moderating effect of sex on these relationships. Methods The participants in this study were from waves one to four (2011–2018) of the China Health and Retirement Longitudinal Study (CHARLS). Cognition function, BMI, and WC were measured at four examinations over 7 years. The interview-based cognitive assessments of memory, orientation and attention, and visuospatial ability were recorded. Standardized global cognitive scores were generated. BMI and WC were objectively measured. Mixed-effects models were performed to evaluate the associations. Results A final sample of 3,035 Chinese older adults [mean (SD) age, 66.94 (5.43) years; 40.16% (n = 1,219) women] were included. Higher BMI (estimate = 0.0107; SE = 0.0024; p < 0.0001) and WC (estimate = 0.0019; SE = 0.0006; p = 0.0037) were associated with slower cognition score decline over a 7-year follow-up, while greater BMI variability (estimate = −0.0365; SE = 0.0116; p = 0.0017) was related to faster cognition score decline. The results were not modified by sex. BMI-defined overweight (estimate = 0.0094; SE = 0.0043; p = 0.0298) was associated with a slower cognition score decline, and both large weight gain (estimate = −0.0266; SE = 0.0074; p = 0.0003) and large WC loss (estimate = −0.0668; SE = 0.0329; p = 0.0426) were associated with faster cognition score decline. Conclusion Among Chinese older adults, higher BMI, higher WC, and overweight are related to slower cognitive decline, while greater BMI variability, large weight gain, and large WC loss are associated with faster cognitive decline.