Folate, along with the metabolically-related B vitamins (B12, B6 and riboflavin), play essential roles in human health throughout life. Notably, recent UK Biobank evidence implicates folate deficiency in hypertension, the major risk factor contributing to mortality worldwide. An estimated 15% of pregnancies are affected by hypertension, which contributes to serious adverse maternal and offspring outcomes, a greater risk of stroke later in life in the mother and long-term disease risk in the child. Clinical and genome-wide association studies link the C677T polymorphism in the gene encoding the folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) with an increased risk of hypertension. Riboflavin (as flavin adenine dinucleotide; FAD) is required as a cofactor for MTHFR, and randomized trials show that intervention with riboflavin lowers blood pressure, specifically in individuals with the MTHFR 677TT genotype, independently of antihypertensive medications. The health implications of this gene-nutrient interaction are important, especially for populations worldwide with the highest frequencies of the variant TT genotype in MTHFR, including Guatemala (up to 66%), Mexico (32-44%), and Northern China (24%). Further investigation is required to elucidate the mechanisms linking folate-mediated one-carbon metabolism with blood pressure and how riboflavin alleviates the excess genetic risk of hypertension in affected individuals. Riboflavin deficiency is highly prevalent worldwide, particularly in women, but is typically overlooked in health and research settings. This review highlights the roles of folate and riboflavin in blood pressure and the opportunity for a precision nutrition approach to reduce hypertension in at-risk individuals by addressing riboflavin deficiency and thus optimizing folate metabolism.

Acute physiological responses to walking in natural versus urban environments remain uncertain. We reviewed studies of healthy adults completing single walks in actual outdoor settings. Six databases were searched through January 12, 2026, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. We included 21 studies; 20 contributed 57 effect estimates to a three-level meta-analysis. Pooled Hedges' g estimates with 95% confidence intervals were -0.01 [-0.26, 0.23] for heart rate (p = 0.90), 0.11 [-0.40, 0.62] for systolic blood pressure (p = 0.63), and -0.14 [-0.36, 0.08] for diastolic blood pressure (p = 0.18). Evidence was inconclusive for high frequency heart rate variability (g = -0.14 [-0.94, 0.66], p = 0.66) and the root mean square of successive differences between normal interbeat intervals (g = -0.01 [-0.89, 0.87], p = 0.98), with few estimates and wide intervals. Exploratory analyses found no clear moderating associations with walking duration or study sample sex composition, although small subgroups limited precision. Overall, current evidence does not show a consistent additional acute physiological response to natural walking. This does not establish equivalence or rule out true differences. Estimates reflect heterogeneous routes and protocols and cannot isolate a uniform causal effect of nature exposure. Psychological restoration, sustained physical activity, disease prevention, and clinical outcomes require separate evidence. Future studies should better characterize environmental exposures and standardize walking and measurement procedures.

Seasonal environmental variation is a widespread stressor for wildlife and can induce plastic changes in DNA methylation. Blood DNA methylation is an integrative molecular indicator of overall physiological status, yet its seasonal dynamics in the giant panda remain unclear. This study aimed to profile genome-wide blood methylation patterns in giant pandas under natural field conditions and to reveal the epigenetic strategies underlying their seasonal adaptation. Twelve blood samples were collected from three wild-trained giant pandas in the Daxiangling Nature Reserve during winter (n = 6) and summer (n = 6) between 2023 and 2025 and were subjected to whole-genome bisulfite sequencing. The genome-wide mC/C ratio (4.18-4.98%) was dominated by the CG context. Winter-summer comparison identified 7113 differentially methylated regions and 3063 differentially methylated genes. These genes were enriched in transcriptional regulation, cell surface receptor signaling, miRNA metabolism, and MAPK, Ras, and T/B cell receptor signaling pathways. Winter-hypermethylated genes were enriched in both immune defense and energy-consuming processes, whereas winter-hypomethylated genes showed limited enrichment, indicating that hypermethylation-mediated suppression dominates seasonal adaptation. This study reveals, for the first time, a seasonal methylation fingerprint in giant panda blood characterized by a "summer immune enhancement, winter energy conservation" pattern. As sampling occurred in natural habitats, these differences reflect integrated epigenetic responses to temperature, photoperiod, food availability, and pathogen pressure rather than single-factor effects. These findings provide molecular evidence for seasonal adaptation in endangered mammals and candidate markers for captive panda management and wild-release assessment.

Medication use is common in large-scale population cohorts, and can modify phenotypic traits of interest. This can potentially bias effect estimates in genome-wide association studies (GWAS) and impact downstream analyses such as Mendelian randomisation (MR). The best approach to account for medication use in GWAS is unclear. In this study, we compared seven different methods of adjusting for antihypertensive use in a systolic blood pressure (SBP) GWAS of 407,960 White British individuals in the UK Biobank. We found that direct adjustments to measured SBP (adding constants, class-specific constants, censored normal regression) in general yielded a greater number of genome-wide significant variant associations and unmasked stronger GWAS effect estimates than unadjusted measures of SBP. Adjustment for class-specific constants showed the greatest difference relative to unadjusted GWAS. Restriction methods which limit the sample to either untreated individuals or age ranges with low levels of antihypertensive use had less power, due to reduced sample sizes. Effect estimates of treated individuals were deflated relative to untreated individuals, demonstrating the importance of medication adjustment. In MR analyses, we found no substantial differences in inverse-variance weighted (IVW) estimates when using differing exposure GWAS methods in estimation of the effect of SBP on coronary artery disease. Larger variations in IVW estimates were observed for the causal effect of body mass index on SBP across adjustment approaches. This suggests that bias may arise in MR analyses when the exposure included in the estimation affects the probability of treatment. Finally, we demonstrate that medication adjustment can reveal potentially novel genetic loci, offering additional insight into the biology of a trait.

Guidelines suggest at least 30 mL/kg of crystalloid within three hours in septic shock but do not specify when vasopressors should begin in relation to that bolus. Hence, we systematically reviewed contemporary evidence on initiating vasopressors before fluid resuscitation is complete. For this review, early initiation was defined as commencement of a first-line vasopressor before the treating team or study protocol judged initial volume expansion complete, and every included study's own time-zero anchor, threshold, and definition of completeness were extracted. PubMed, Scopus, Web of Science, and ClinicalTrials.gov were searched from 1 January 2021 to 18 August 2026, supplemented by citation searching. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, and synthesis followed Synthesis Without Meta-analysis. Eligible studies were randomised controlled trials (RCTs) and comparative observational studies in adults with septic shock or sepsis-induced hypotension, contrasting earlier with later vasopressor initiation relative to fluid loading. Risk of bias was assessed with Risk of Bias 2 and Risk of Bias in Non-randomized Studies - of Interventions, and certainty of evidence with the Grading of Recommendations Assessment, Development, and Evaluation. Heterogeneity in exposure definition precluded meta-analysis. In total, 11 studies (two multicentre RCTs and nine comparative observational studies; 18,362 adults; eight countries) were included. Thresholds for "early" spanned 25 minutes to three hours and were anchored variably to triage, shock recognition, or the first fluid bolus; completeness of fluid resuscitation was protocolised in only the two RCTs and left to clinician judgement in seven cohorts, with the pre-vasopressor fluid volume unmeasured in two. Both RCTs were neutral for their primary patient-centred endpoints (moderate certainty) despite achieving 1.1 to 2.1 L separation in 24-hour fluid volume (high certainty). Observational findings were discordant (very low certainty): four cohorts reported lower mortality with earlier initiation, one propensity-matched registry analysis reported higher 28-day mortality, and three found no association. Benefit was concentrated in patients meeting Sepsis-3 criteria, with high predicted vasopressor requirement, and with marked diastolic hypotension and a wide pulse pressure. No safety penalty was identified (moderate certainty). Initiating vasopressors before fluid resuscitation is complete is safe and reduces early fluid exposure and time to haemodynamic target, but does not improve survival when applied indiscriminately. The evidence supports the 2026 Surviving Sepsis Campaign position that concurrent vasopressor administration be reserved for case-by-case use in unstable shock, and future trials should enrol by vasoplegic phenotype rather than by time alone.

In this paper, we propose a photoplethysmogram (PPG) signal quality-aware pulse rate (PR) classification and rhythm (regular/irregular) recognition framework. The proposed method comprises preprocessing, PPG signal quality assessment (PPG-SQA), systolic peak detection and decision rules. In this study, we collected a wide variety of normal and abnormal PPG signals from standard PPG databases. Further, the PPG signals are recorded with various sensors and subjects to validate the accuracy and robustness of the method under intra-subject, inter-subject and sensor variability. Evaluation results demonstrate that the average peak-to-peak interval ( PPI avg )-based PR classification method had a higher accuracy (bradycardia [BC]: 100%, normal: 99.31%, tachycardia [TC]: 95.68% for normotension [NT] blood pressure [BP] class PPG segments) as compared to the counting approach-based PR classification method. Results further showed that the rhythm recognition method with a 4 bpm threshold outperformed, achieving a sensitivity (SE) of 99.89%, specificity (SP) of 99.33% and accuracy (ACC) of 99.80%. To reduce false alarms, we present four PPG-SQA approaches to explore a lightweight and best PPG-SQA with higher SE for detecting noise-free PPG signals. Results demonstrated that the quality-aware PR classification and rhythm recognition methods can improve the trustworthiness of cardiac arrhythmia recognition and BP analysis while reducing false alarms and computational power by discarding noisy PPG signals, which are unavoidable in continuous and long-term health monitoring.

Flexible piezoresistive sensors are pivotal in personalized healthcare. However, simultaneously achieving high sensitivity and a broad linear range remains a formidable challenge owing to rapid structural densification of porous materials. Inspired by the multiscale composite structure of bamboo, this study addresses the existing challenge by proposing a novel MXene aerogel sensor, reinforced by compounding cellulose nanofiber (CNF) Several instances of CNFs (which were introduced during copyediting) have been reverted back to CNF, consistent with our original submission where the abbreviation was defined as cellulose nanofiber (CNF). Corresponding grammatical adjustments are made to match this usage. This change only standardizes the abbreviation and does not alter any scientific content. and bamboo cellulose. By leveraging a uniform conductive network constructed on CNF (simulating bamboo parenchyma cells to disperse the vascular bundles) and the supporting effect of the bamboo cellulose skeleton (mimicking vascular bundles to provide support), premature collapse is effectively resisted. Moreover, inspired by the hollow cell cavity structure of bamboo, a stable porous architecture is constructed via gas foaming and freeze-drying, enabling it to effectively reconcile the inherent trade-off between sensitivity and the detection range. The sensor exhibits a high sensitivity of 148.29 kPa-1 (0-15 kPa) and a wide effective working range extending up to 100 kPa. This superior electromechanical performance enables the precise detection of full-spectrum physiological signals ranging from subtle pulse waveforms to large-scale joint movements and facilitates assistive rehabilitation for post-stroke finger therapy via human-computer interaction. Augmented by a support vector machine algorithm, the sensor has a wireless sleep monitoring capability and achieves a high classification accuracy of 96.5% in identifying distinct breathing states. The proposed sensor demonstrates significant application potential in next-generation intelligent home health management systems.

There is growing evidence on the positive effects of the arts and arts therapies for mental health (MH) outcomes. This review aims to fill a research gap by establishing the evidence on the effects of arts-based interventions on selected MH outcomes for children and young people (CYP).