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Ancient DNA and Human Physiology.

Ancient DNA (aDNA) enables the reconstruction of chronologically sampled genomes from ancient humans, animals, plants, pathogens, and microorganisms, as well as environmental DNA, providing a record of biological changes through time. Improvements in short and degraded DNA extraction methods and low-cost sequencing now enable the generation of broad, cross-regional datasets that expand evolutionary analyses from past population demography to biological mechanisms. By tracking temporal shifts of allele frequencies, integrating functional genomics resources (e.g., gene expression, chromatin structure variation), modeling population demography to separate selection from genetic drift, and aligning genetic changes with archaeological, cultural, and climatic data, aDNA has the potential to link sequence variation to physiological function within their temporal and environmental contexts. In this review, we summarize illustrative case studies from aDNA research spanning complex traits, dietary adaptations, and responses to pathogens and other environmental changes, showing how human biology has evolved under multiple selective pressures through time. These dated signals help triage experimental work and expose mechanisms that are rare or absent in living cohorts. Although some challenges remain, such as geographic and temporal sampling disparities, limitations in data resolution and variant detection, and genotype-phenotype uncertainties, rapid methodological progress and stronger ethical frameworks are expanding what can be inferred, making aDNA a promising tool for refining physiological pathways, their timing, and their drivers.

Humans

Diet and sleep among college student populations: a systematic review.

College students are at-risk for both poor diet and poor sleep. We aimed to systematically review the evidence regarding associations between diet and sleep health within this population. A comprehensive electronic search was conducted in PubMed, Embase, Scopus, Web of Science, and PsycINFO from the earliest possible date through February 6, 2026. A total of 57 studies representing 44 countries were retained; most were cross-sectional. There were 22 studies that examined dietary patterns in relation to sleep, generally showing that healthier diet patterns, including the Mediterranean Diet, were related to better sleep quality. Among 20 studies that examined individual foods or nutrients, there was evidence that fruits, vegetables, dairy, protein, and lower intake of sugar-sweetened beverages were linked to better sleep health, although some findings were mixed. Finally, 15 studies related meal timing to sleep quality, showing that breakfast skipping and later last meals were associated with poor sleep health. Overall, these studies reveal robust cross-sectional associations between diet and sleep among college students, but more longitudinal studies and randomized controlled trials are needed to evaluate directionality. Moreover, a key direction for future study is consideration of sleep and nutrition situated within the unique contexts of college settings and academic schedules.

Humans

Maternal vitamin B12 deprivation exacerbates offspring obesity by reducing early-life colonization with Bifidobacterium pseudolongum.

Vitamin B12 deficiency during pregnancy and lactation is common, yet its mechanistic impact on reproductive outcomes and offspring health remains poorly understood. Here, we show that maternal dietary vitamin B12 deprivation not only impairs maternal glucose metabolism and reproductive outcomes but also exacerbates high-fat-diet-induced obesity in offspring. These effects are mediated by gut microbiota and associated with a marked reduction of Bifidobacterium pseudolongum (B. pseudolongum) in both dams and their offspring. Maternal vitamin B12 deprivation limits early-life acquisition of B. pseudolongum in offspring during lactation, subsequently intensifying obesity and metabolic dysregulation. Early-life restoration of B. pseudolongum or its key metabolite, acetate, effectively ameliorates this aggravated obesity. Mechanistically, acetate acts through the Ffar2 receptor to upregulate Ehhadh expression. Together, these data establish that perinatal nutrition imprints long-term metabolic phenotypes in offspring via early-life acquisition of the gut microbiota, with a critical window during lactation.

Animals

Ribosomal protein S3: a critical regulator of human disease mechanisms.

Ribosomal protein S3 (RPS3) is an essential structural component of the 40S ribosomal subunit, yet growing evidence highlights crucial extraribosomal roles in genome maintenance, cell-cycle control, and immune signaling. Dysregulation of RPS3 contributes to diverse human disorders, including cancer, inflammatory diseases, neurodegeneration, and resistance to antimicrobial and anticancer therapies. As a cofactor of NF-κB and a participant in DNA damage responses, RPS3 occupies a node that integrates stress signaling with transcriptional reprogramming, enabling both protective and pathological outcomes. The present review critically evaluates mechanistic insights into RPS3 biology, emphasizing recent findings that delineate its context-dependent effects, discrepancies across models, and remaining gaps that restrict translational applications. Understanding these complexities is essential to assess RPS3's potential as a biomarker and therapeutic target.

Humans

Characterisation of HIV-1 Gag Cytotoxic T-Lymphocyte Epitopes in the Southern African Region-A Systematic Review.

During early HIV-1 infection, robust Cytotoxic T-lymphocyte (CTL) responses are mostly targeted at immunodominant Gag p24 epitopes to reduce HIV-1 viraemia to a set-point. The aim of this study was to review the current body of knowledge on HIV-1 Gag CTL epitopes in the southern African region where subtype C is prevalent. Peer-reviewed records were obtained from three databases: PubMed Central, Web of Science Core Collection, and Scopus, using the following search terms: HIV subtype C Gag epitopes, and HIV clade C Gag epitopes. The search results were restricted to countries within the southern African region, and only data published in English and between the years 2000-2025 were considered for this review. The search from the three databases produced a total of 2103 peer-reviewed records, and 49 records were included in the review. The majority of studies (58.44%) were conducted in South Africa, followed by Botswana (15.58%), Zambia (10.39%), Malawi (7.79%), Zimbabwe (6.49%) and Angola (1.30%). There were no studies identified from other southern African countries. A total of 60 Gag CTL epitopes were identified, of which 17 (28.33%) were located within the matrix protein (p17), 33 (55.00%) within the capsid protein (p24), and 4 (6.67%) within the Gag polyprotein (p2p7p1p6). The commonly detected immunodominant epitopes were mostly located within the Gag p24 protein; and included TPQDLNTML (TL9, Gag p24 48-56) and TSTLQEQIGW (TW10, Gag p24 108-117) present at 16.00% and 13.3%, respectively. The proportion of HLA-A, B and C allotypes in this systematic review were 18%, 78%, and 4%, respectively. The more common HLA-B allotypes that restrict immunodominant Gag epitopes and facilitate better control of HIV-1 were HLA-B*57, -B*58:01, -B*42:01 and -B*81:01. This systematic review has provided important insights into the description of immunodominant Gag epitopes and HLA-I alleles that contribute to the control of HIV-1 viraemia in the southern African region. It has also exposed that some CTL epitopes identified in the southern African studies are not reported on the Los Alamos HIV database (LANL HIV database). This highlights a need to have this database updated with this information as it is used as a reference for epitopes. This review could provide insights into the design of an epitope-based HIV-1 vaccine that would also be effective in the southern African region.

Humans

Mechanistic Insights Into the Association Between Gut Microbiota Diversity and Atherosclerosis, Acute Coronary Syndrome, and Peripheral Arterial Disease Progression.

BACKGROUND: The gut microbiome has emerged as a potential contributor to cardiovascular diseases (CVDs), including atherosclerosis, acute coronary syndrome (ACS), and peripheral arterial disease (PAD). While observational studies link dysbiosis to CVD, causal relationships remain uncertain. METHODS: This narrative review synthesizes evidence from human observational studies, clinical interventions, and experimental models to distinguish association from mechanistic plausibility and clinical causality. Literature was searched through July 2026 in PubMed/MEDLINE, Web of Science, and Scopus. RESULTS: Microbial metabolites-including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, and lipopolysaccharide (LPS)-modulate endothelial function, immune cell programming, platelet activity, and plaque stability through receptor-mediated signaling and epigenetic regulation. SCFAs demonstrate potentially protective effects via GPCR and HDAC pathways, while TMAO is associated with atherothrombotic risk. However, much mechanistic evidence derives from preclinical studies. Heterogeneity from diet, geography, host characteristics, renal function, and medications substantially influences microbiota-CVD associations. CONCLUSION: The gut-vascular connection is biologically plausible, but definitive clinical causality remains unproven. Microbiome-directed therapies (dietary modulation, pre/pro/synbiotics, targeted metabolite inhibition) are investigational. Prospective, standardized, adequately powered human studies with clinically meaningful outcomes are essential before routine cardiovascular application.

Gastrointestinal Microbiome

Prevalence and risk factors of nutritional anaemia among adolescents in India: a systematic review with meta-analysis of prevalence.

BACKGROUND: Nutritional anaemia is a major public health concern among adolescents in India, threatening physical growth, cognitive development, and future maternal health. This systematic review with meta-analysis of prevalence aimed to estimate the pooled prevalence of nutritional anaemia among Indian adolescents aged 10-19 years and identify key associated risk factors. METHODS: A systematic search was conducted across PubMed, Embase, Web of Science, and Scopus up to February 2025. Data were extracted on study design, setting, diagnostic methods, prevalence, and risk factors. Quality was assessed with a modified Newcastle-Ottawa Scale. A random-effects meta-analysis estimated pooled prevalence, with subgroup analyses by state and gender, and pooled odds ratios for risk factors. RESULTS: Forty-five studies encompassing diverse Indian regions and 159,979 adolescents were included. The pooled prevalence of nutritional anaemia was 56% (95% CI: 49%-63%), with higher rates among girls (62%) than boys (39%). Iron deficiency (OR 2.38-4.68), other micronutrient deficiencies, low socioeconomic status, poor dietary diversity, female gender, and inadequate supplementation were consistently associated with higher anaemia risk. CONCLUSION: Nutritional anaemia impacts more than half of Indian adolescents, with notable regional and gender differences. Its complex nutritional, socioeconomic, and behavioural causes demand targeted, context-specific interventions to enhance adolescent health nationwide.

Humans

Single-cell RNA sequencing provides further insights into the immunostimulatory action of freeze-dried Lactiplantibacillus plantarum on Penaeus vannamei shrimp.

Immunostimulation through dietary interventions opened new avenues in developing disease control and prevention tools for shrimp aquaculture. We have previously shown that feeding with freeze-dried Lactiplantibacillus plantarum (LAB) increased disease resistance of Penaeus vannamei against both Vibrio parahaemolyticus and white spot syndrome virus (WSSV) based on bulk RNA sequencing of shrimp gills. This tissue participates in ion transport and serves as a first line of defense against environmental stressors and pathogenic infections. However, characterization of their cell composition and functions remains limited. Here, we implemented a single-cell RNA sequencing approach to further gather insights into how feeding with freeze-dried LAB modulates host immunity which may not be evident with bulk RNA sequencing approach. A total of five clusters with unique transcriptional signatures were identified, corresponding to pillar cells, septal cells, and sessile hemocytes. Pseudo-bulk analyses at global- and cluster-levels showed differential expression of genes related to host immunity and metabolism. We further revealed how overall transcriptomic changes are not exclusively caused by gene expression changes but may also be driven by cell population dynamics. This study highlighted how single-cell RNA sequencing approach may shed light on the mechanisms of action of immunostimulants which may be masked in bulk transcriptome analyses.

Animals

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n = 549) and a validation set (n = 236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60 mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60 mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans

Transcription regulation of cell fate plasticity - from embryonic development to tissue regeneration.

Cell fate plasticity refers to the capacity of cells sharing the same genome to alter, reverse, or reconfigure their identity under physiological, pathological, or experimental conditions. This property underlies embryonic development, cellular reprogramming, and tissue regeneration, but becomes progressively restricted as lineage identity is stabilized. Embryonic development represents an intrinsic process of fate transitions, whereas reprogramming and regeneration reveal how differentiated cells can dedifferentiate or transdifferentiate under specific conditions. Across these contexts, plasticity is governed by multilayered regulatory networks involving transcription factors, epigenetic regulators, cofactors, and the core transcription machinery. Robust regulatory programs stabilize cell identity, whereas stochastic fluctuations in gene expression and chromatin state can prime cells for fate transitions, adding a tunable dimension to plasticity control. In this review, we synthesize recent advances in the regulation of cell fate plasticity across development, reprogramming, and regeneration, highlighting how transcription factors, epigenetic modifications, transcriptional cofactors, and core transcription machinery cooperate to control cell fate decisions and plasticity.

Animals

Effects of different training modalities on lower-limb explosive power, acceleration, 20-m sprint performance, and change-of-direction ability in youth soccer players: a systematic review and network meta-analysis.

BACKGROUND: Youth soccer players repeatedly perform explosive actions, short accelerations, linear sprints, decelerations, and multidirectional movements. However, the comparative effects of different structured physical-conditioning programmes remain uncertain. METHODS: Seven databases were searched from inception to 3 July 2026 using a final expanded search strategy encompassing plyometric, strength or resistance, sprint, acceleration, speed, change-of-direction, neuromuscular, multicomponent, and combined training. Randomised controlled trials involving healthy youth soccer players were eligible. Intervention arms were classified using operational, content-based node definitions. Construct-restricted primary networks and expanded sensitivity networks were analysed using frequentist random-effects network meta-analysis. Hedges' adjusted g was preferentially calculated from post-intervention or final-follow-up means, standard deviations, and sample sizes. Estimates were presented so that positive values indicated better performance. P-scores were treated as descriptive ranking summaries. Risk of bias was assessed using an adapted study-level application of the five-domain RoB 2 framework, and confidence in the evidence was assessed using CINeMA. A post hoc strict-age sensitivity analysis excluded two age-boundary studies. RESULTS: Eighty-nine studies were included in the expanded quantitative analysis, of which 74 contributed to at least one construct-restricted primary network. The primary lower-limb explosive-power, acceleration, 20-m sprint, and planned change-of-direction networks included 55, 20, 25, and 38 studies, respectively. Compared with usual soccer training, plyometric training combined with sprint and/or change-of-direction training showed favourable estimates for lower-limb explosive power (SMD 0.79, 95% CI 0.55 to 1.03), acceleration (1.19, 0.90 to 1.49), 20-m sprint performance (0.80, 0.33 to 1.28), and planned change-of-direction ability (1.46, 1.13 to 1.80). Corresponding I² values were 34.6%, 21.8%, 65.0%, and 41.0%. Between-design inconsistency was detected in the 20-m sprint (P = 0.0036) and change-of-direction (P = 0.0007) networks. CINeMA confidence for these four comparisons was low, low, very low, and low, respectively. Expanded sensitivity networks showed substantially greater heterogeneity. The highest-ranked intervention differed across outcome domains but remained consistent within each outcome across the three analysis sets. Excluding the two age-boundary studies did not materially alter the principal estimates. CONCLUSIONS: Plyometric training combined with sprint and/or planned change-of-direction training produced favourable comparative estimates across the four performance outcomes. However, evidence for several nodes and active-versus-active comparisons was sparse, heterogeneity in programmes and outcomes was present, inconsistency was detected in some networks, and confidence in the evidence was low or very low. These limitations do not support a conclusion that any training category is universally superior. The findings should be interpreted as provisional category-level signals rather than definitive training prescriptions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420261347297, registered on 21 March 2026, https://www.crd.york.ac.uk/PROSPERO/view/CRD420261347297 .

Change-of-direction ability

Syndemics, violence and injury: exploring historical relationships between infectious disease epidemics and violent crime in South Africa.

This paper explores historical and contemporary intersections between mass-mortality epidemics and violent crime in South Africa, focusing on four major epidemics - Spanish Flu, tuberculosis, HIV, and Covid-19. The study integrates epidemiological data and contextual historical information such as crime statistics, archival records, and secondary scholarship to explore whether epidemic-driven mortality crises are associated with subsequent changes in violence and injury profiles. With the possible exception of gendered violence, the study finds little evidence that earlier epidemics directly contributed to rapid or sustained increases in violent crime, despite causing substantial adult mortality and long-term social and economic disruption. A comparison between epidemic and socio-economic profiles strongly suggests that the significant increases in violent crime recorded after the Covid-19 pandemic are highly localised, and may be more strongly related to lockdown responses, including alcohol restrictions, rather than the effects of disease itself.

Humans

The gut microbiota-obesity axis in the pathogenesis and prognosis of breast cancer.

BACKGROUND: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC. METHODS: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening. DISCUSSION: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived β-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies. CONCLUSION: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.

Humans

Causal Relationship of Polyunsaturated Fatty Acids With Mental Disorders: A Systematic Review and Meta-analysis.

CONTEXT: Mental disorders (MDs) pose a important global health challenge, with a complex pathogenesis complicating treatment development. Nutritional interventions, particularly polyunsaturated fatty acids (PUFAs), have gained attention as potential therapeutic options. OBJECTIVE: This Mendelian randomization (MR) meta-analysis aimed to evaluate the potential causal relationship between PUFAs and MDs. DATA SOURCES: Genome-wide association study data were utilized to analyze the association between PUFAs (including omega-3, omega-3 percentage [omega-3%], omega-6, omega-6 percentage [omega-6%], and omega-6 to omega-3 ratio) and 12 major MDs. DATA EXTRACTION: Two-sample MR technology was used to assess the role of PUFAs in MDs. DATA ANALYSIS: The MR analysis revealed that genetically predicted omega-3 was causally linked to MDs, such as obsessive-compulsive disorder, bipolar disorder, schizophrenia, and major depressive disorder. Omega-3% exhibited protective effects against emotional personality disorder. Conversely, omega-6 was inversely correlated with attention-deficit/hyperactivity disorder risk, while a high omega-6 to omega-3 ratio was associated with an increased risk of depression and other mood disorders. CONCLUSION: High omega-3 levels and omega-3% may reduce the risk of MDs, whereas a high omega-6:omega-3 ratio may elevate the risk. These findings highlight the potential of PUFAs, particularly omega-3, in MD prevention and treatment, while underscoring the need for further research into the complex interactions between omega-3 and omega-6. The study provides a scientific foundation for future clinical trials and dietary intervention strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42024598472.

Humans

Effects of Family-Based Intervention for Childhood Obesity on Parental and Offspring Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Childhood obesity is a global public health issue with strong familial and intergenerational transmission. However, existing syntheses often overlook the active role of parents and fail to assess outcomes beyond the child. This systematic review and meta-analysis specifically investigate the effects of family-based interventions, which position parents as active co-agents of change, on health outcomes for both children with obesity and their parents. METHODS: A systematic review and meta-analysis were conducted. Six databases were searched for randomized controlled trials (RCTs) targeting children with obesity and at least one family member. Primary outcomes were children's BMI z-score and parental BMI; secondary outcomes included other adiposity measures and dietary behaviors. Outcomes for both children and parents were synthesized. Subgroup analyses were conducted based on intervention characteristics. Risk of bias was assessed using RoB 2, and evidence certainty was evaluated using GRADE. RESULTS: Twenty RCTs with 1740 participants were included in the meta-analysis. The interventions demonstrated a significant reduction in children's BMI z-score. Additional benefits were observed for long-term BMI z-score and percentage of total body fat. The most effective interventions commonly integrate health education, behavioral strategies, and motivational support. Subgroup analyses indicated that interventions positioning parents as active co-participants, rather than mere supporters, yielded larger effects. However, no significant effects were found on parental BMI. CONCLUSION: This study demonstrates that family-based interventions can confer significant benefits for children with obesity. Their success hinges on strategically framing parents as active co-agents and integrating motivational strategies.

Humans

Stroke risk following BNT162b2 vaccination: a systematic review and meta-analysis of self-controlled case series studies.

INTRODUCTION: Whether BNT162b2 (Pfizer-BioNTech) vaccination increases stroke risk remains a public health concern. This is the first meta-analysis to synthesize self-controlled case series (SCCS)-derived stroke risk estimates specifically for BNT162b2 vaccination. METHODS: PubMed and Embase were searched from inception through 9 May 2026, following PRISMA 2020 guidelines. Eight eligible SCCS studies were pooled using a random-effects model with restricted maximum likelihood (REML) estimation and the Knapp-Hartung adjustment. RESULTS: Eight studies across six countries encompassing several million vaccinated individuals were included. The pooled incidence rate ratio (IRR) was 0.967 (95% CI 0.892-1.049; I2 = 69.2%), indicating no statistically significant increase in stroke risk. Subgroup analyses showed no evidence of effect modification across continent, risk-window length, dose category, SCCS variant, or age group. CONCLUSIONS: These findings provide no evidence of increased short-term stroke risk following BNT162b2 vaccination at the population level. The observed heterogeneity appeared to be partly driven by methodological differences rather than true biological variation in vaccine effect.

Humans

The interplay between circadian misalignment or sleep disturbances and cognition and brain function in individuals with different degrees of insulin resistance - a systematic review.

Disruption of sleep increases the risk of type 2 diabetes and worsens cognitive outcomes, yet few studies have evaluated the interaction between insulin resistance and sleep parameters in relation to cognitive outcomes or the risk of dementia. This systematic review examines how circadian misalignment and sleep disturbances affect cognition and neuroimaging findings in individuals with varying degrees of insulin resistance. Across 27 studies, disrupted circadian rhythmicity and sleep disturbances were negatively associated with brain health, possibly through its effects on insulin sensitivity, whereas the impact of sleep duration and quality were inconclusive. Methodological heterogeneity, reliance on cross-sectional designs, and limited control for confounders restricted definitive conclusions and highlighted the need for longitudinal and interventional studies with objective measurements. Nonetheless, the findings support circadian rhythmicity as a potentially modifiable risk factor for preserving cognition in insulin-resistant populations. Future research should prioritise prospective and interventional studies and focus on biological markers rather than self-reported outcomes.

Humans

Engineered MXene-based nanozyme platform: NIR-II photothermal and dual enzyme-mimetic potentiated chemodynamic synergy for precision tumor eradication.

The antioxidant defense barrier in the tumor microenvironment, particularly glutathione (GSH), considerably restricts the therapeutic efficacy of chemodynamic therapy (CDT). Moreover, CDT generally exhibits relatively mild therapeutic efficacy owing to its intrinsic reaction kinetics, making it difficult to achieve complete tumor eradication within a short time. To address these issues, we construct a functionalized nanotherapeutic platform, Nb2CTx@Ru-PEG2000-FA (NCRPF), for tumor photothermal ablation and enhanced CDT resulting from GSH depletion. NCRPF possesses three key advantages: 1. Efficient near-infrared II photothermal conversion (η = 42.08%), raising the tumor temperature above 45 °C within 90 s for rapid ablation; 2. Dual peroxidase-like and glutathione peroxidase-like activities, simultaneously depleting GSH and generating a burst of ·OH to eliminate residual tumors; 3. Targeted tumor accumulation with 2.9-fold higher efficiency than passive diffusion. Both in vitro and in vivo results confirm that this combined strategy achieves complete tumor eradication with favorable biosafety. Collectively, the NCRPF nanotherapeutic system provides a powerful new paradigm with high translational potential for the complete eradication of breast cancer.

Animals