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Objectives　The average daily vegetable intake of adults in Japan remains below recommended levels. As foods are primarily purchased at supermarkets (SMs), this study examined whether nudge interventions implemented in SMs are associated with increased vegetable purchases, using a quasi-experimental design.Methods　Among SMs operated by the same company within a single city, three medium-sized stores with similar customer numbers and vegetable sales trends that were located at least 3-km apart were non-randomly assigned to the intervention (stores A and B) or control (store C) condition. In the intervention stores, shopping baskets were equipped with flyers recommending vegetable purchases (Easy-Attractive nudge). Furthermore, Store B displayed a poster that visually presented 70-g portions of popular seasonal vegetables in the produce section (Attractive-Social-Timely nudge). Store C served as the control and received no intervention. The 1-month observation and intervention periods were October and November 2024, respectively. By comparing point-of-sale (POS) data from October to November 2024 with data from the corresponding period in the previous year, we calculated the year-on-year increase rates for daily vegetable sales (primary outcome) as well as non-vegetable and total sales (secondary outcomes), adjusted for relative changes in customer volume. During the final 2 days of the intervention, 50 customers per store were surveyed to obtain their basic demographics, socioeconomic status, awareness of the intervention materials, and impressions. Average treatment effects (ATEs) were estimated using a difference-in-differences approach that modeled outcomes, intervention status, and store and time indicators for the first and second halves of October and November. Store-specific analyses (A versus B) were also performed.Results　No significant differences were observed between stores regarding basic customer characteristics or socioeconomic status. The ATE for vegetable sales was ＋4.0 percentage points (95% confidence interval: 0.6-7.5), indicating a statistically significant increase. In contrast, no significant ATE was observed for non-vegetable sales (－4.4 percentage points: －14.2 to 5.5) or total sales (－3.6 percentage points: －13.0 to 5.9). Store-specific analyses revealed no additional differences between stores B and A. Awareness of shopping basket flyers was 95%. Among those aware, 24% reported purchasing vegetables, 51% expressed positive opinions, and 8% expressed negative opinions. The corresponding figures for the produce-section poster were 36%, 28%, 61%, and 0%, respectively.Conclusions　Easy-Attractive nudge flyers in shopping baskets were associated with increased vegetable purchases. This intervention potentially represents an effective strategy for promoting vegetable selection without increasing the overall customer spending.

This study involves the evaluation of the Fei Jin Sheng formula (FJS), a well-established traditional Chinese medicine (TCM) treatment for non-small cell lung cancer (NSCLC), aiming to address the heightened mortality rates associated with this form of lung cancer. By examining its multi-targeted routes and activities in vivo, we hope to clarify its complex molecular mechanisms. Liquid chromatography-tandem mass spectrometry and network pharmacology were used to identify FJS components and targets. Using organ histology and bi-weekly weight assessments of tumors and bodies and Lewis tumor model tumors, FJS efficacy and safety were assessed, while immunohistochemistry of tumor tissues was used to elucidate anti-tumor mechanisms. Based on research that had been previously conducted, FJS controls over 30 pathways and targets 15 critical proteins, including the MAPK pathway, in treating NSCLC. In vivo studies demonstrate that FJS reduces tumor proliferation by decreasing expression of ERK1/2, p-ERK1/2, MEK1/2, and p-MEK1/2, without affecting the structure of the liver, spleen, or kidney in mice. FJS is non-toxic and has the potential to treat NSCLC in vivo by inhibiting the MAPK signaling pathway.

This study focuses on exploring the co-morbid mechanisms by which Bisphenol A (BPA) induces non-alcoholic fatty liver disease (NAFLD) and osteoarthritis (OA). This study identified potential BPA targets utilizing the SwissTargetPrediction database. These targets were integrated with genes associated with NAFLD and OA, which were screened via Weighted Gene Co-expression Network Analysis and differential gene expression analysis. To elucidate the underlying biological mechanisms, functional enrichment and immune infiltration analyses were conducted. Core genes associated with comorbidity were pinpointed via machine learning. The interactions and cellular localization were further validated by molecular docking, molecular dynamics simulations, and single-cell transcriptomics. Finally, in vitro experiments were employed to verify the effects on chondrocyte function, and hepatic lipid metabolism. Functional enrichment analysis indicates that BPA-induced NAFLD and OA comorbidity pathways are enriched in muscle cell proliferation, DNA metabolism, and inflammation pathways. RHOB has been identified as a core gene, participating in disease progression by regulating signaling pathways such as Hippo and IL-17. Single-cell sequencing revealed that RHOB is primarily expressed in hepatocytes and cholangiocytes in NAFLD, while enriching in HomC and EC cell clusters in OA. In vitro experiments confirmed that BPA exposure suppresses RHOB expression, thereby promoting lipid accumulation in hepatocytes and impairing chondrocyte function. Concurrently, rescue experiments demonstrated that its overexpression significantly reversed these pathological states. BPA exposure drives the co-morbidity of OA and NAFLD by inhibiting RHOB. Consequently, limiting BPA exposure or modulating the RHOB pathway represents a viable approach for intervening in related diseases.

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Modern gerontology views aging as a plastic process, opening opportunities for its modulation through nutritional and pharmacological interventions. This review focuses on a comprehensive analysis of a unique marine biological source - holothurian (sea cucumber) tissues - considered as a promising multicomponent basis for the development of novel geroprotective agents. Key bioactive compounds, primarily isolated from the body wall, are examined in detail: low-molecular-weight matrikine peptides and a unique spectrum of triterpene glycosides. Their ability for synergistic, multitargeted action on key mechanisms of cellular and tissue aging is highlighted, such as the regulation of oxidative stress via activation of the Nrf2 pathway, suppression of chronic inflammation (inflammaging) through inhibition of the NF-κB signaling cascade, maintenance of extracellular matrix homeostasis, and modulation of cellular metabolism. The review systematizes current experimental data demonstrating the efficacy of holothurian hydrolysate in models of skin photoaging, accelerated wound repair, reduction of atherosclerotic manifestations, neuroprotection, and correction of metabolic disorders, among others. Particular attention is paid to a critical limitation for oral forms - the problem of age-associated bioavailability of active components. Promising pharmacotechnological solutions to overcome it are analyzed, particularly innovative delivery systems based on alginate matrices. This review aims to systematically summarize current experimental data on the molecular mechanisms underlying the geroprotective effects of bioactive compounds from sea cucumbers. The focus is on the synergistic, multitarget action of matrikine peptides and triterpene glycosides on key drivers of cellular and tissue aging. In addition, the review examines promising pharmacotechnological strategies designed to enhance the bioavailability of these compounds. The presented data substantiate the prospect of creating safe, standardized complexes based on holothurian hydrolysate, which aligns with current trends in preventive, multitargeted, and personalized gerontology. Современная геронтология рассматривает старение как пластичный процесс, открывающий возможности для его модуляции через нутритивные и фармакологические интервенции. В фокусе данного обзора находится комплексный анализ уникального морского биоисточника — тканей голотурий (морских огурцов), рассматриваемого в качестве многообещающей поликомпонентной основы для разработки новейших геропротекторных средств. Детальному рассмотрению подвергнуты ключевые биологически активные соединения, выделяемые преимущественно из стенки тела, — низкомолекулярные пептиды-матрикины и уникальный спектр тритерпеновых гликозидов. Освещена их способность к синергическому, мультитаргетному воздействию на ключевые механизмы клеточного и тканевого старения, такие как регуляция окислительного стресса через активацию пути Nrf2, подавление хронического воспаления (инфламэйджинга) посредством ингибирования сигнального каскада NF-κB, поддержание гомеостаза внеклеточного матрикса и модуляция клеточного метаболизма. В обзоре систематизированы актуальные экспериментальные данные, демонстрирующие эффективность гидролизата голотурии в моделях фотостарения кожи, ускорения репарации ран, снижения атеросклеротических проявлений, нейропротекции, коррекции метаболических нарушений и т. п. Отдельное внимание уделено критическому ограничению для пероральных форм — проблеме возраст-ассоциированной биодоступности активных компонентов. Проанализированы перспективные фармакотехнологические решения для её преодоления, в частности инновационные системы доставки на основе альгинатных матриц. Цель обзора — систематизация современных экспериментальных данных о молекулярных основах геропротекторного действия биоактивных компонентов голотурии с акцентом на синергическое мультитаргетное влияние пептидов-матрикинов и тритерпеновых гликозидов на ключевые механизмы клеточного и тканевого старения, а также анализ перспективных фармакотехнологических решений для повышения их биодоступности. Представленные данные обосновывают перспективу создания безопасных, стандартизированных комплексов на основе гидролизата голотурии, что соответствует современным трендам превентивной, мультитаргетной и персонализированной геронтологии.

Assessment of the efficacy of a virtual reality-based program in improving cognition and affect in patients with mild cognitive impairment during inpatient treatment via randomized controlled trial. We compared the treatment outcomes between two groups of patients, aged 60 to 89, with mild cognitive impairment and varying comorbid conditions who underwent planned inpatient treatment at the Department of Geriatric Neurology at the Russian Gerontology Clinical Research Center. The experimental group (n = 31) received standard therapeutic treatment and took part in a virtual reality program for 2 weeks, while the control group (n = 31) received standard treatment only. All patients were assessed for cognitive function and symptoms of anxiety and depression before and after 2 weeks of treatment. Both groups exhibited statistically significant improvements in cognitive function, as measured by the Montreal Cognitive Assessment scale (MoCA), and a reduction in depression symptoms, as indicated by the Geriatric Depression Scale (GDS-15). The main group also showed statistically significant improvement of anxiety and depression subscales of the Hospital Anxiety and Depression Scale (HADS), p = 0.007. The virtual reality program combined with standard therapy resulted in more pronounced improvement of cognitive function indicators on the MoCA scale than standard therapy alone (2.6 ± 2.1 and 1.3 ± 1.5 points improvement in group 1 and group 2 respectively), as well as a more significant reduction of depressive symptoms according to the HADS depression subscale (-1.6 ± 3.2 and -0.3 ± 1.5 points improvement in group 1 and group 2 respectively), while anxiety subscale of HADS and GDS-15 showed statistically insignificant differences, which requires discussion. Despite the obvious limitations of the presented study, such as small sample power, lack of blinding and replacement intervention in the control group, results show the promise of further research and application of Virtual reality cognitive training for the stated purposes, demonstrating the probable effectiveness as an additional nonpharmacological treatment for certain cognitive and emotional symptoms in patients with mild cognitive impairment.

Longevity pharmacology has evolved from descriptive gerontology into a mechanistically driven field aiming to modulate fundamental processes of biological aging. Despite rapid scientific advances, whether this progress has translated into meaningful clinical outcomes remains uncertain. This critical perspective evaluates recent developments in longevity pharmacology and examines whether they represent genuine clinical progression or continued translational delay. A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science to identify English-language publications related to longevity pharmacology, gerotherapeutics, biomarkers of aging, and translational geroscience published between January 2000 and April 2026. We review evidence from senescence biology (including frailty), autophagy and mitophagy modulation, metabolic and nutrient-sensing pathways, stem cell and natural product - based rejuvenation strategies, microbiome-targeted interventions, and AI-enabled biomarker development. Particular emphasis is placed on systemic chronic inflammation as a central integrative driver of age-related disease. While selected interventions show early clinical signals, most remain preclinical or lack long-term validation. Key barriers include biomarker deficits, biological heterogeneity, safety concerns, regulatory misalignment, and limitations of animal models. Although mechanistic maturity is advancing rapidly, clinical translation remains incremental and fragmented. Near-term progress is most likely to arise from low-risk, system-level interventions supported by validated biomarkers and geroscience-informed clinical trial designs. People are living longer than ever, but many years of later life are affected by chronic diseases such as heart disease, diabetes, and dementia. Researchers are therefore exploring whether it is possible to develop medicines that target the biological processes of aging itself, rather than treating diseases one by one. This emerging field is known as longevity pharmacology. In this article, we review recent scientific advances to assess whether these discoveries are translating into real benefits for human health. Research has identified several promising biological targets involved in aging, including cellular senescence, mitochondrial dysfunction, chronic inflammation, and changes in the gut microbiome. Experimental treatments—such as senolytic drugs that remove damaged cells, compounds that improve mitochondrial function, and microbiome-based interventions—have shown encouraging results in laboratory and animal studies. However, most of these approaches have not yet been proven effective or safe in large human clinical trials. A major challenge is the lack of reliable biomarkers that can measure whether treatments truly slow biological aging. Regulatory frameworks and long-term clinical trial infrastructure are also still developing. Overall, the field has made significant scientific progress, but clear clinical breakthroughs remain limited. In the near future, safer and more modest interventions—such as metabolic, anti-inflammatory, or microbiome-targeted strategies—may provide incremental improvements in healthy aging while more ambitious rejuvenation therapies continue to be studied.

Autobiographical memory is central to the construction and maintenance of identity and psychosocial functioning. In Alzheimer's disease (AD), autobiographical memory progressively deteriorates, disrupting personal narratives and self-perception. This article provides an integrative review of current knowledge on autobiographical memory and its impairment in AD. Neuroanatomical correlates are discussed, highlighting the key role of the hippocampus and its interactions with the frontal and parietal cortices and the amygdala. Preserved cognitive resources and current supportive strategies, including multisensory stimulation, narrative reconstruction, and immersive approaches, are also examined. The role of family caregivers is emphasized, as mediators of memories, supporters of identity continuity, and contributors to shared memory processes. Future perspectives include the development of digital tools and integrative methodologies aimed at bridging experimental rigor and the lived experience of patients. Such approaches are essential for advancing our understanding of autobiographical memory decline in AD and for developing tailored interventions that support identity, autonomy, and psychosocial well-being.

Epigenetic aging is a new dimensional advancement in geroscience that continually addresses factors beyond genetic determinants of longevity. It occurs through three conventional pathways, one of which is non-coding RNA production. miR-124 is a newly introduced miRNA that was found in aged skin and several tumorigenic cells and is associated with aging. Additionally, SIRT1, a protein from the NAD+-dependent family, is found to have a protective mechanism in the pathways of aging. On the other hand, vitamin D works as an epigenetic factor and often targets pathways related to the aging process. In this study, the aim is to identify the expression of miR-124 in circulating blood to address the epigenetic-related biomarker and link the facets with anti-aging SIRT1 and vitamin D cognate receptor (VDR) to understand vitamin D deficiency interception. A vitamin D deficiency middle-aged rat model was developed by assigning male Albino Wistar Rats. Paricalcitol was administered IP (intraperitoneal) to the experimental group (32 ng/day) to induce deficiency, along with a calcium-rich rescue diet. The study was conducted for 21 days following blood collection and storage. ELISA and RTqPCR were performed to estimate serum 25(OH)D and gene expression analysis, respectively. 25(OH)D comparison between the group p-value of 0.002. The log2 fold changes of SIRT1, VDR, and miR-124 were compared between the groups using boxplot visualisation. A linear regression model was developed to understand the explorative nature of aging index (R2 = 0.561; Adjusted R2 = 0.517; p = 0.005; n = 12). A putative epigenetic relation was found between miR-124 levels and their association with SIRT1. The investigated biomarkers of aging are associated with serum concentration of 25(OH) vitamin D in a middle-aged vitamin D-deficient rat model, which supports the need for mechanistic investigation in future studies.

Brain source localization technology enables precise characterization of the spatial distribution of neural activity, serving as a crucial tool for exploring the pathological mechanisms underlying dementia. However, effectively integrating complementary diagnostic information from source localization features across multiple frequency bands remains a major challenge to enhancing classification performance and model interpretability. An attention-based multi-frequency self-supervised fusion model (AM-SSF) is proposed to address this issue. Independent contrastive self-supervised encoders are trained for the θ (4-8 Hz), α (8-13 Hz), β (13-30 Hz), and γ (30-48 Hz) frequency bands to learn band-specific latent representations. Then, an attention-guided adaptive fusion module is introduced to dynamically allocate band weights through cross-entropy-based supervised optimization, thereby achieving effective cross-band information integration. Finally, a random forest classifier is employed to evaluate the model's performance in distinguishing Alzheimer's disease (AD) from frontotemporal dementia (FTD). Experimental results show that the proposed framework achieves a classification accuracy of 93.1% under five-fold cross-validation, significantly outperforming baseline methods such as single-band self-supervised learning (SSL) and average pooling fusion. Further analysis of the attention weight distributions revealed that the θ and β bands contributed most to model decision-making, providing interpretability regarding frequency-specific effects. In summary, the proposed AM-SSF model enhances AD and FTD classification performance while offering valuable insights into the discriminative roles of frequency band features.

Alzheimer's disease (AD) -a progressive neurodegenerative disorder that is characterized by insidious cognitive decline and distinct neuropathological features- significantly impacts daily life functioning and behavior and is disproportionally prevalent in women compared to men. The reasons and risk factors for sex-based disparities in AD prevalence are still largely unclear, however early life exposures (e.g., education and stress) may be important contributing factors. Therefore, it is increasingly important to disentangle the complex interactions between known early environmental protective and risk factors and genetic susceptibility and uncover how these factors might impact and shape neurobiological processes. Moreover, it is critical to assess how these processes, in turn, influence later cognitive and brain health outcomes that may confer sex-specific pathways of risk for developing AD. In this paper we describe the rationale and study protocol for The Reducing Inequities through Social and Educational Change Follow-Up in Early Adulthood Extension (RISE-Up EA+; R01AG089426) study, a follow-up study of 300 participants aged 24-26 years old that leverages a natural quasi-experimental cohort to investigate how health outcomes tied to socioeconomic mobility opportunity may contribute to sex-specific vulnerability for developing AD later in life. To examine how sex-specific vulnerabilities related to early educational experiences may set the stage for later AD risk, we will assess self-report, cognitive, biological (e.g., inflammation and microbiome), and brain health measures. Results from this work provide the opportunity to better understand how adolescent mobility opportunities might contribute to later life health outcomes and influence sex-specific developmental pathways important for later AD risk.

Extrachromosomal circular DNA (eccDNA) is an emerging tumor biomarker notable for its tumor-specific amplification and contribution to genomic heterogeneity. However, the substantial heterogeneity of eccDNAs poses a significant challenge for characterization. Current identification tools rely predominantly on single data types, overlooking the integrative potential of multi-omics layers and often discarding sparse but biologically meaningful signals. To address this, we developed eccDNAOmix, an AI-empowered framework that integrates a specialized eccDNA sequencing pipeline with multi-omics data to evaluate the relative contributions of different biological modalities. Basing matched tumor and adjacent normal tissues from colorectal cancer patients, eccDNAOmix employs a masking strategy to eliminate non-biological noise and features a multimodal deep learning model with an adaptive gated fusion mechanism. Our model achieved robust identification performance (AUC = 0.844), with the DNA sequence modality (AUC = 0.822) being the most identifiable feature for eccDNA identification. Leveraging this finding, we established a web server to facilitate practical eccDNA identification. Biological characterization showed that eccDNAs are preferentially derived from promoter regions and exhibit a significant enrichment of RNA modifications within 100 bp downstream of junction sites. Notably, eccDNAOmix rescued hidden eccDNA fragments from conventionally discarded unmapped sequencing reads and this was confirmed via experimental validation. By integrating multi-omics sequencing and eccDNA sequencing, this study provides the first comprehensive characterization of eccDNAs. Our multi-omics analysis demonstrates that the DNA sequence contributes the highest proportion to eccDNA identification. By leveraging this dominant identifiable role and providing an accessible single-modality identification tool, our work proposes a practical computational framework for advancing discovery in colorectal cancer.

Diabetic nephropathy (DN) remains a major cause of end-stage kidney disease. Stem cell-derived exosomes have emerged as a promising therapeutic strategy due to their ability to deliver bioactive molecules to damaged tissues. This narrative review, conducted in accordance with PRISMA guidelines, aims to evaluate the therapeutic potential of exosomes derived from various stem cell sources, including mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), in the context of DN. A comprehensive literature search was performed using relevant databases (e.g., PubMed, Web of Science, Scopus) to identify preclinical and clinical studies investigating the effects of stem cell-derived exosomes on DN. The identified studies were assessed for quality and methodological rigor. Priority was given to high-impact studies and those with robust experimental evidence. The selected literature was synthesized thematically to provide a coherent overview of the current state of research on exosome-based therapies for DN, highlighting current findings, and future directions. Results from preclinical studies suggest that exosomes derived from different stem cell sources can exert reno-protective effects, including reducing inflammation, fibrosis, and oxidative stress. However, comparisons between different exosome types indicate that MSCs-derived exosomes (MSC-Exos) may offer superior therapeutic benefits. While clinical trials are ongoing to evaluate the safety and efficacy of stem cell-derived exosomes in DN patients, further research is needed to optimize exosome production, delivery, and therapeutic efficacy.

Hip fractures (HFs) are increasingly common in aging populations and often require surgical intervention, leading to significant blood loss from both the injury and the procedure, increasing the need for red blood cell (RBC) transfusions. Despite evidence from randomized controlled trials, indicating the risks associated with RBC transfusions, they remain a standard treatment for patients with HF. This systematic review and meta-analysis aimed to evaluate the impact of RBC transfusions on mortality and 30 d clinical outcomes. We conducted a systematic review of observational and experimental studies on RBC transfusions in adults undergoing HP surgery. Without language restrictions, we searched PubMed, Scopus, Web of Science, and EMBASE up to September 1, 2024. Effect sizes for continuous variables are reported as means with 95% confidence intervals (CIs), whereas dichotomous variables are reported as risk ratios with 95% CIs. A random-effects model was used for the analysis. We included 26 studies involving 59,627 patients with HF, 42% of whom received RBC transfusions. Transfusion rates varied widely by country. Women and older patients with HF received fewer RCB transfusions than men and those under 90 years old. RBC transfusions were associated with increased 30 d mortality, 30 d skin infections, and pneumonia, with a tendency toward higher 1 year mortality. RBC transfusions in patients with HF are associated with increased risks of 30 d mortality, 30 d skin infections, and pneumonia. Careful consideration is essential when administering transfusions to this vulnerable population.

ARHL (Age-related hearing loss) affects over one-third of people aged 65 and older worldwide. It is often viewed as an isolated sensory deficit, but whether it is associated with systemic biological aging remains unclear. We analyzed NHANES (n = 2530) and HRS (n = 2849) cohorts. GrimAgeAcc (GrimAge acceleration) was used to assess biological aging. GO/KEGG (Gene Ontology/Kyoto Encyclopedia of Genes and Genomes) and disease association analyses were performed on GrimAge-related proteins. Prospective associations between ARHL and dementia, CVD (Cardiovascular Disease), and diabetes were examined in HRS. Murine cochlear data (GEO: GDS5624, n = 5-6 per group) were analyzed as a preliminary exploratory dataset. Network pharmacology and molecular docking were used for in silico screening. An exploratory risk prediction model based on GrimAgeAcc and clinical covariates was developed for hypothesis generation. After adjustment for chronological age, GrimAgeAcc was independently associated with ARHL in both cohorts. GrimAge-related proteins showed enrichment in endoplasmic reticulum function, endocytosis, and inflammatory pathways. Prospective analysis in HRS indicated time-dependent associations between ARHL and dementia (HR = 2.94), CVD (HR = 1.43), and diabetes (HR = 1.14) after age adjustment. However, mediation analysis showed that chronological age explained 28-50% of these associations. In murine cochlear data, ADM expression was higher in adult vs. young mice (4-5% increase), but the effect size was small and no significant reversal was observed. In silico screening suggested that selumetinib (a MEK inhibitor) was associated with expression changes in several GrimAge-related genes. An exploratory risk prediction model showed preliminary calibration in HRS but requires external validation. Based on our data, GrimAgeAcc is associated with ARHL and systemic age-related diseases (dementia, CVD, diabetes), potentially through shared biological pathways (e.g., endocytosis, lysosomal, inflammatory). Chronological age explains 28-50% of these associations, yet ARHL remains independently associated with all three outcomes after age adjustment. The cochlea may be vulnerable, but causal evidence is lacking. All findings are hypothesis-generating and require experimental validation.

The "First 1000 Days" of life is a critical window for metabolic programming, while the long-term oncological consequences of nutritional exposures during this period remain understudied. We aimed to evaluate whether restricted sugar intake in utero and during early childhood reduces the risk of early-onset cancer diagnosis and mortality in adulthood, utilizing a natural experiment. We analyzed 63,819 UK Biobank participants born between October 1951 and March 1956, spanning the end of UK sugar rationing (September 1953). Leveraging a quasi-experimental birth cohort design, we compared participants exposed to sugar rationing in utero and during infancy versus those unexposed. Early-onset cancer incidence (&#x2264; 50 years) and mortality were ascertained via integrated national Cancer Registry and hospital inpatient records. Multivariable Cox proportional hazards models (including Gompertz distribution) were used to estimate hazard ratios (HRs), with exploratory site-specific analyses. Among 63,819 participants (56.3% female), 40,397 were exposed to rationing and 23,422 were unexposed. Early-life sugar restriction significantly reduced early-onset cancer risk [HR, 0.66 (0.53, 0.81); P < 0.001]. A dose-response relationship was observed, with peak protection in individuals exposed for up to 24 months postnatally. This protection was observed systemically across solid tumors, independent of specific cancer sites. Specificity was corroborated by null associations with negative controls (herpes zoster and cataract). No significant difference was found for cancer-specific mortality. Restricting sugar intake during the first 1000 days is associated with a reduced risk of early-onset cancer, extending the disease-free lifespan. The divergence between reduced incidence and unchanged mortality suggests early-life metabolic environments primarily influence tumor latency rather than biological aggressiveness. These findings highlight the potential long-term public health implications of early-life dietary guidelines against the rising burden of early-onset cancer.

Elevated uric acid (UA) has been linked to impaired nervous system and skeletal muscle function. This study aimed to investigate the relationship between UA and digital gait characteristics in older adults. We enrolled 651 older adults (&#x2265;&#x2009;60&#xa0;years) who completed a wearable device-based walking test and blood sample detection. Multidimensional sensors were used to measure 15 gait parameters. Asymmetry index (AI) and coefficient of variation (CV) were calculated for each parameter. Multiple linear regression analyses were employed to examine the associations between UA and gait characteristics. The mean age of all participants was 70.45&#x2009;&#xb1;&#x2009;6.12&#xa0;years, with a mean UA concentration of 298.60&#x2009;&#xb1;&#x2009;92.39&#xa0;&#x3bc;mol/L. After full adjustment for demographic characteristics and multiple health indicators, per 1-SD increase in UA was positively associated with swing time (&#x3b2;&#x2009;=&#x2009;6.953, P&#x2009;=&#x2009;0.007). Conversely, UA was negatively associated with thigh swing work (&#x3b2;&#x2009;= -&#x2009;0.023, P&#x2009;=&#x2009;0.003), foot landing control force (&#x3b2;&#x2009;= -&#x2009;0.134, P&#x2009;<&#x2009;0.001), stride frequency (&#x3b2;&#x2009;= -&#x2009;1.074, P&#x2009;=&#x2009;0.049) and stride length (&#x3b2;&#x2009;= -&#x2009;0.014, P&#x2009;=&#x2009;0.012). After false discovery rate (FDR) correction for multiple comparisons, all these associations remained statistically significant except for stride frequency. Higher UA levels were associated with higher AIs of thigh acceleration (&#x3b2;&#x2009;=&#x2009;0.034, P&#x2009;=&#x2009;0.013), ground reaction force (&#x3b2;&#x2009;=&#x2009;0.033, P&#x2009;=&#x2009;0.002), foot landing control force (&#x3b2;&#x2009;=&#x2009;0.048, P&#x2009;<&#x2009;0.001) and toe-off angle (&#x3b2;&#x2009;=&#x2009;0.061, P&#x2009;=&#x2009;0.001). UA was positively associated with CVs of swing time (&#x3b2;&#x2009;=&#x2009;0.032, P&#x2009;<&#x2009;0.001), ground reaction force (&#x3b2;&#x2009;=&#x2009;0.015, P&#x2009;=&#x2009;0.001), foot landing control force (&#x3b2;&#x2009;=&#x2009;0.018, P&#x2009;=&#x2009;0.001) and toe-off angle (&#x3b2;&#x2009;=&#x2009;0.035, P&#x2009;=&#x2009;0.002). All these associations with gait symmetry and stability indices remained statistically significant after FDR correction. Exploratory analyses identified high-sensitivity C-reactive protein, interleukin-6, superoxide dismutase, and glutathione reductase as potential biomarkers linking the association between UA and gait performance. Higher UA levels are associated with poorer gait performance in terms of vigor, symmetry, and stability. The underlying inflammatory and oxidative stress mechanisms need to be elucidated in future experimental studies. Not applicable.

Older patients often suffer from multiple disorders and are hence frequently burdened by polypharmacy. Prevention of cardiovascular events using antiplatelet drugs might be indicated among older populations, but there are no studies assessing platelet function in these patients. Using impedance aggregometry, we compared platelet reactivity to 7 aggregation inducers between a group of 44 polymorbid older patients aged 78&#x2009;+&#x2009;years (PP), and 50 generally healthy younger controls (median age, 44&#xa0;years). None of the subjects were treated with antiplatelet therapy. We also examined their response to antiplatelet drugs (acetylsalicylic acid, ticagrelor, vorapaxar) and an experimental compound, 4-methylcatechol, a small polyphenol metabolite of many natural polyphenolic compounds. Data analysis was performed in the whole group as well as after removing or splitting the groups based on concomitantly administered drugs. Linear mixed-effects modelling was used to investigate the impact of both drugs and comorbidities on the obtained results. A clinically achievable concentration of ASA (30&#xa0;&#xb5;M) failed to block platelet aggregation when arachidonic acid was used as an inducer, but the response to ticagrelor, vorapaxar, and 4-methylcatechol with relevant inducers was significant. However, the sensitivity to ticagrelor and vorapaxar was lower in PP when compared to healthy controls. The analysis also confirmed similar activity for 4-methylcatechol, but lower activity for acetylsalicylic acid in our PP. Further analyses excluding specific drugs did not significantly alter these outcomes. Inflammatory markers and the presence of type 2 diabetes mellitus were significant predictors of platelet reactivity while basic blood parameter data had no clear impact. The ex vivo response of platelets from PP to the standard antiplatelet drugs was lower. In contrast, they responded well to 4-methylcatechol.

Fracture-related disability is a major public health concern among older adults, with osteoporosis as a key contributor. However, opportunities for early identification of declining bone strength are often missed until after a first fragility fracture, highlighting the need for accessible, low-cost, field-based screening tools. This cross-sectional study compared the associations or lower-limb power measured during a single sit-to-stand repetition (STSp) and combined bilateral grip strength (CGS) with radial bone parameters in 58 community-dwelling older adults aged 60-95&#xa0;years (57.1% female). Radial bone strength parameters were assessed at the 66% cortical and 4% trabecular sites using peripheral quantitative computed tomography (pQCT). Both STSp and CGS were moderately to strongly correlated with radial parameters (r&#xa0;=&#xa0;0.42-0.83; p&#xa0;<&#xa0;0.001). In hierarchical multiple regression (HMR) analyses, STSp was significantly and positively associated with geometric, architectural, and strength parameters at the 66% site after adjusting for sex. At the 4% radial site, neither STSp nor CGS was significantly associated with any bone outcomes, whereas sex remained significantly associated only with bone strength and quantity parameters. Overall, STSp was more strongly associated with radial bone strength parameters than CGS. These findings support further investigation of the STSp test as a practical tool for community-based bone assessment and musculoskeletal health monitoring in older adults.