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Dietary Titanium Dioxide (E171) Alters the Colon Transcriptome-Evidence From a Human Dietary Intervention Study.

Food-grade titanium dioxide (E171) has been removed from the European food market due to concerns about its potential genotoxicity, yet human evidence remains limited. Given its continuous use outside the European Union, clarifying its potential hazard is essential for human risk assessment. In a randomized crossover study, 31 adults consumed 2&#xa0;mg/kg body weight/day of E171 for 2 weeks, with biospecimens collected after both control and exposure periods. Oral intake resulted in elevated titanium concentrations in feces (CTRL: 6.3&#xa0;mg/kg; E171: 377&#xa0;mg/kg). Particle characterization showed a median size of 228&#xa0;nm, with 9% <100&#xa0;nm. Systemic oxidative stress increased, evidenced by increased superoxide radical levels in whole blood (p = 0.057). Transcriptomic profiling of colon biopsies revealed activation of 73 pathways linked to oxidative stress, cellular metabolism, and colorectal cancer-associated processes. The observed transcriptional changes were consistent with findings of its proposed mode of action. This human intervention study characterizes the effects of dietary E171 following human gastrointestinal digestion and provides evidence that exposure to dietary E171 induces systemic oxidative stress and transcriptional changes in the colon. These findings strengthen regulatory concerns about E171 as a food additive and its potentially harmful effects on human gastrointestinal health.

Humans

Impact of polymorphisms on gene expression and splicing in response to exercise and diet-induced weight loss in human skeletal muscle tissues.

Weight loss through exercise and diet reduces the risk of type 2 diabetes, but the genetic regulation of gene expression and splicing in response to weight loss remains unclear in humans. We collected clinical data and skeletal muscle biopsies from 54 overweight/obese Asian individuals before and after a 16-week lifestyle intervention, which resulted in an average of &#x223c;10% weight loss, accompanied by an &#x223c;30% increase in insulin-stimulated glucose uptake. Improvements were observed in 118 of 252 clinical traits and six blood lipids. Transcriptomic analysis of paired skeletal muscle biopsies identified 505 differentially expressed genes enriched in mitochondrial function and insulin sensitivity. Thousands of muscle-specific expression/splicing quantitative trait loci (e/sQTLs) were detected pre- and post-intervention, including hundreds of lifestyle-responsive e/sQTLs. Notably, approximately 4.2% of eQTLs and 7.3% of sQTLs showed Asian specificity. Joint analysis with genome-wide association study (GWAS) identified 16 putative metabolic risk genes. Our study reveals gene-by-lifestyle interactions and how lifestyle modulates gene regulation in skeletal muscle.

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

Functional and Nutritional Potential of Chickpea Protein Hydrolysates: A Systematic Review and Plant-protein Network Analysis.

Chickpea is a protein-rich legume increasingly explored as a substrate for functional plant-based ingredients. Chickpea protein hydrolysates (CPHs) and chickpea-derived peptides (CPs), obtained through enzymatic hydrolysis or simulated gastrointestinal digestion, may provide technological and biological properties while supporting the valorization of chickpea fractions and by-products. This review integrates a network analysis of title-abstract terms from 5,728 unique Scopus and PubMed records on plant protein hydrolysates with a systematic review of 72 studies focused on CPH production, peptide characterization, bioactivity, and translational gaps. The evidence indicates that CPHs and CPs show promising antioxidant, antihypertensive, antidiabetic, anti-inflammatory, lipid-lowering, immunomodulatory, antimicrobial, and anticancer-related activities, mainly supported by biochemical assays, cell models, and animal studies. However, heterogeneous hydrolysis protocols, incomplete peptide characterization, inconsistent bioactivity methods, limited scale-up evidence, and the absence of human intervention trials restrict translation. Future studies should prioritize standardized protocols, mechanistic validation, bioavailability, sensory and regulatory assessment, food-matrix validation, and clinical trials.

Cicer

Intravenous Nicorandil in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI: The CLEAN Randomized Clinical Trial.

BACKGROUND: Nicorandil, an adenosine triphosphate-sensitive potassium-channel opener with nitrate-like properties, may reduce reperfusion injury and microvascular obstruction in ST-segment elevation myocardial infarction (STEMI), but large-scale randomized evidence on long-term clinical outcomes is inconclusive. OBJECTIVES: The CLEAN trial aimed to assess whether adjunctive intravenous nicorandil improves 12-month clinical outcomes in patients with STEMI undergoing primary percutaneous coronary intervention. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial conducted at 49 hospitals in China, patients aged 18 to 80 years with STEMI within 12 hours of symptom onset were randomly assigned (1:1) to receive intravenous nicorandil (6 mg bolus before reperfusion followed by 6 mg/h infusion for 48 h) or matching placebo. Oral nicorandil was prohibited during follow-up. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, or unplanned hospitalization for heart failure within 12 months. RESULTS: Between January 2021 and December 2023, 1,503 patients were enrolled and randomly assigned to nicorandil (n = 748) or placebo (n = 755). The primary composite outcome occurred in 98 patients (13.1%) in the nicorandil group (113 events over 717.2 person-years) and 99 (13.1%) in the placebo group (136 events over 710.3 person-years), with no significant difference between groups (rate ratio: 0.869; 95% CI: 0.650-1.162; P = 0.3429). Among secondary outcomes, nominal reductions were observed in cardiovascular death (1.9% vs 3.6%; HR: 0.515; 95% CI: 0.269-0.983) and target-vessel revascularization (1.1% vs 3.0%; HR: 0.322; 95% CI: 0.143-0.727), whereas rates of nonfatal myocardial infarction and unplanned hospitalization for heart failure were similar between groups. Adverse events did not differ between groups. CONCLUSIONS: In patients with STEMI undergoing primary percutaneous coronary intervention, adjunctive intravenous nicorandil did not significantly reduce the 12-month primary composite outcome. These findings do not support routine use of intravenous nicorandil in unselected patients with STEMI. (Clinical Efficacy and sAfety of Intravenous Nicorandil; NCT04665648).

Humans

Neuropsychiatric disease mechanisms and interventions from 22q11.2 deletion syndrome experimental studies.

A high genetic predisposition for neuropsychiatric disorders, such as schizophrenia and autism spectrum disorders (ASDs), is 22q11.2 deletion syndrome (22q11DS), caused by a hemizygous microdeletion in the q-arm of human chromosome 22. The deletion most often spans a 3&#x202f;Mb region, with variable breakpoints ranging from 1.5 to 3&#x202f;Mb. Experimental studies on 22q11DS have revealed several aspects of the pathophysiology of neuropsychiatric disorders and also identified various interventional and rescue strategies. Herein, we review these strategies by grouping the studies into three main mechanistic categories: (i) microRNA (miR)-mediated, (ii) mitochondrial, and (iii) neural circuit deficits in polygenic deletion, and also briefly describe a few other monogenic mechanisms implicated. Haploinsufficiency of Dgcr8, a 22q11DS gene involved in miR processing, forms the center of miR-mediated mechanisms and rescuing consequent pathophysiology rely on age-dependent, brain region-specific or global replenishment of miRs or their targets. Seven genes in the 22q11.2 genomic region encode mitochondrial proteins and approaches to mitigate these gene deficiencies concentrate on the respective mitochondrial functions affected. We briefly describe other potential monogenic mechanisms for intervention including transcriptional regulation, synaptic release, catecholamine metabolism, and cell-cell adhesion, represented by Tbx1, Sept5, Comt, Arvcf, and Cldn5. We also give examples of how the multifaceted pathophysiological mechanisms and rescue strategies can have convergent effects at the molecular, synaptic, cellular and circuit levels. Based on the experimental interventions identified in the 22q11DS studies, we inform on the supportive therapies possible now and the future potential of curative interventions.

Humans

BMT4me En Espa&#xf1;ol: Multisite Feasibility and Usability Testing of a Spanish-Language mHealth Adherence Support App for Spanish-Speaking Caregivers of Children After Hematopoietic Stem Cell Transplantation and Cancer Treatment.

BACKGROUND: Medication nonadherence during the first 100 days after pediatric hematopoietic stem cell transplantation (HSCT) and during oncology treatment increases risk for complications. BMT4me is a caregiver-facing mobile health (mHealth) application providing medication reminders, symptom tracking, and note-taking features to support medication management. Spanish-speaking caregivers are frequently excluded from digital adherence interventions due to the lack of language-accessible tools. PROCEDURE: We conducted a multisite, mixed-methods usability testing of a Spanish-language version of BMT4me ("BMT4me en Espa&#xf1;ol") with Spanish-speaking caregivers of children (ages 2-17 years) post-HSCT or with an oncology diagnosis on active treatment. Caregivers completed a facilitated, three-step usability session (unobtrusive observation, interactive observation, and debriefing), followed by a semi-structured interview, and then completed the system usability scale (SUS). Quantitative outcomes were summarized descriptively; qualitative data were analyzed using content analysis with constant comparison. RESULTS: Fifteen participants enrolled at each site for a total of 30 participants. Across both sites, the recruitment rate was 91%. All participants completed all parts of the study. The SUS score (M&#xa0;=&#xa0;80.09; SD&#xa0;=&#xa0;17.35) was above average (>68). Two key qualitative themes emerged: (1) the perceived positive impact of BMT4me on managing a serious illness and (2) the acceptance and sociocultural relevance of BMT4me for Spanish-speaking families. Caregivers also shared suggestions to add educational content and multiuser functionalities to BMT4me. CONCLUSIONS: The acceptance and perceived positive impact of the Spanish BMT4me app indicates that socioculturally relevant, Spanish mHealth interventions have strong potential to support Spanish-speaking caregivers in pediatric oncology and HSCT settings. CLINICAL TRIALS NCT: NCT06361173.

Adolescent

Antegrade dissection and re-entry vs retrograde strategy in chronic total occlusion percutaneous coronary intervention: Rationale and design of the ADRENALINE randomized study.

RATIONALE: While antegrade wiring (AW) is the most common initial strategy for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), difficult CTO lesions frequently require either antegrade dissection and re-entry (ADR) or a retrograde strategy. Comparative data between ADR and the retrograde approach remain limited. DESIGN: The Antegrade Dissection vs Retrograde re-ENtry And Load of Interventionalist Effort (ADRENALINE) is a prospective, multicenter randomized study with a superiority design. It is planned to enroll 121 patients with difficult coronary CTO (J-CTO score &#x2265;2) referred for CTO-PCI in accordance with the hybrid algorithm. Subjects undergoing successful AW will be included in the observational arm. Patients with failed or unattempted AW will be randomized 1:1 to ADR or retrograde CTO crossing strategy (n = 74). All patients will undergo pre- and postprocedural laboratory testing (including cardiac troponin T and creatine kinase-MB), cardiac magnetic resonance (CMR) for late gadolinium enhancement, and health status assessment by the Seattle Angina Questionnaire and the Rose Dyspnea Scale. The co-primary endpoints are total procedure time and successful guidewire crossing. Additionally, the relationship between different recanalization strategies and stress among interventional cardiologists will be explored. CONCLUSION: ADRENALINE is the first randomized study of ADR vs retrograde strategy for difficult CTO PCI, assessing procedural outcomes, CMR-detected myocardial infarction, and 3-month quality of life. ENROLMENT STATUS: The first patient was enrolled on July 29, 2025. As of June 14, 2026, 45 patients (26 randomized, 19 observational) of the planned 121 patients have been enrolled. TRIALS REGISTRATION: Clinicaltrials.gov: Identifier, NCT06878729.

Humans

A Multi-omics Exploration Revealing SLIT2 as a Prime Therapeutic Target for Peripheral Facial Paralysis: Integrating Single-Cell Transcriptomics and Plasma Proteome Data.

Peripheral facial paralysis (PFP) is a common neurological disorder characterized by facial-nerve dysfunction. Identifying therapeutic targets and understanding the molecular and cellular mechanisms underlying PFP are crucial for developing effective treatment strategies. This study combined Mendelian randomization (MR) analysis and single-cell RNA sequencing (scRNA-seq) to explore potential therapeutic candidates and their roles in PFP pathophysiology. The MR analysis included 1925 publicly available plasma protein cis-heritability instruments. Instrumental variables were selected for MR analysis to identify plasma proteins associated with PFP, followed by colocalization analysis to evaluate shared genetic variants between the identified proteins and PFP. After the initial identification of plasma proteins associated with Bell's palsy using MR analysis, a rat model of facial-nerve injury was established to further dissect underlying mechanisms at cellular and molecular levels. Using scRNA-seq technology, we delved deeply into cellular Heterogeneity and dynamic changes in gene expression in the facial-nerve nucleus tissues under both injured and control conditions, thereby achieving a systematic study ranging from macroscopic genetic associations to microscopic cellular functions. Finally, expression patterns were preliminarily validated by performing in vitro immunofluorescence analysis on the facial-nerve nucleus samples of SD rats. The MR analysis results identified 30 plasma proteins significantly associated with PFP, with nine target genes showing differential expression in the scRNA-seq data. Colocalization analysis demonstrated that slit guidance Ligand 2 (SLIT2), semaphorin 4D (SEMA4D), EGF containing fibulin extracellular matrix protein 1 (EFEMP1), and sprouty related EVH1 domain containing 2 (SPRED2) shared causal variants with PFP. SLIT2 was highly expressed in the microglia and inhibitory neurons in the experimental group, whereas SEMA4D showed elevated expression across multiple glial cell types in the same group. In contrast, EFEMP1 and SPRED2 showed distinct expression patterns in fibroblasts and oligodendrocytes. The role of SLIT2 has been previously well-documented in many central nervous system diseases. However, for the first time, this study detected SLIT2 alteration after facial-nerve injury. Altered intercellular signaling, particularly enhanced SLIT2-ROBO signaling between neurons and glial cells, was observed in the PFP group. Pseudotime analysis revealed dynamic SLIT2 expression during microglia and inhibitory neuron differentiation, mirroring changes in ROBO1 expression. Immunofluorescence analysis of rat facial-nerve nucleus samples verified that SLIT2 protein levels were significantly increased in the facial-nerve nuclei of injured samples. In conclusion, despite the fact that this study is primarily founded on animal models and despite notable differences existing between animals and humans in terms of the facial motor nucleus, this study successfully identified SLIT2 as potential therapeutic targets for PFP. The SLIT2-ROBO axis stands out as a particularly promising candidate. SLIT2 may play a role in modulating neuroimmune interactions and promoting nerve repair. These findings provide a foundation for future clinical studies and targeted interventions to enhance recovery from PFP. Future research should focus on human sample validation to enhance clinical translation.

Animals

Optimising Exercise Prescription: A Meta-Analysis Examining the Dose Response of Exercise Duration on Cardiorespiratory Fitness Following HIIT and MICT.

BACKGROUND: High-intensity interval training (HIIT) is often promoted as a time-efficient alternative to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness, yet the duration of HIIT sessions varies considerably across studies. OBJECTIVE: We aimed to characterise the dose-response relationship between exercise session duration and the improvement in cardiorespiratory fitness for HIIT and MICT. METHODS: A dose-response meta-analysis of randomised controlled trials comparing exercise duration in HIIT and MICT, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and registered in PROSPERO (CRD42022335590). Effect sizes were calculated using a random-effects meta-analysis. The primary outcome was maximal oxygen uptake (VO2max). Secondary outcomes included blood pressure, lipid profiles, glucose metabolism markers and body composition measures. A one-stage random-effects dose-response meta-analysis was performed to examine the relationship between exercise duration and adaptations. We searched PubMed and Google Scholar; eligibility criteria for selecting studies were randomised controlled trials in humans, published in English and exercise interventions lasting at least 4&#xa0;weeks. RESULTS: We identified 69 randomised controlled trials (2387 participants). High-intensity interval training elicited greater improvements in VO2max than MICT (d = 0.38, 95% confidence interval 0.27-0.49, p < 0.001). High-intensity interval training demonstrated a non-linear dose-response relationship between exercise session duration and VO2max, with 80% of maximal effect (changes in VO2max = 3.45&#xa0;mL/kg/min) achieved with only ~11&#xa0;min/session (95% confidence interval 9.5-40.2). Moderate-intensity interval training showed a linear dose-response relationship between exercise session duration and VO2max, requiring ~52&#xa0;min/session to achieve 80% of the&#xa0;maximal observed&#xa0;effect (95% confidence interval 30.4-55.8). The dose-response relationship was consistent across populations. High-intensity interval training and MICT had comparable effects in improving cardiometabolic risk factors. CONCLUSIONS: High-intensity interval training demonstrated a non-linear dose response, with 80% of maximal effect on VO2max in ~11&#xa0;min/session, whilst MICT required four to five times longer to reach similar responses. The different types of training had comparable effects on cardiometabolic risk factors.

Journal Article

Six weeks of isometric resistance training led to evidence of corticospinal but not reticulospinal adaptation in previously untrained adult males.

The latest hypothesis regarding the source of enhanced neural activation from resistance training is the reticulospinal rather than the corticospinal tract, based on invasive animal and emerging human data. The present study employed a six-week isometric resistance training intervention in a randomized controlled design to address this knowledge gap. Thirty-nine healthy, untrained males (age ~23 y, sustained contraction group n = 13, explosive contraction group n = 9, control group n = 17) underwent neuromuscular and electrophysiological testing and completed all study requirements. Maximal isometric torque (MVC) and rate of torque development (RTD) were measured during a familiarization session as well as before and after the six-week period. Transcranial magnetic stimulation was used to assess motor-evoked potential (MEP) area and silent period duration while subjects contracted to 10% of MVC. Loud sound (120&#xa0;dB) was used to modulate MEP area and reaction time to visual stimuli during the StartReact test. Only the intervention groups demonstrated significant improvements in MVC (27%) and RTD (60%) (both P < 0.01), along with reduced MEP area (-&#xa0;21%) and silent period duration (-&#xa0;23%) (both P < 0.01). The sustained contraction group showed reduced modulation of reaction time and increased MEP suppression due to loud sound. Short-term resistance training seemed to reduce cortical inhibition and corticospinal excitability in both training groups. The study showed conflicting changes in measures purported to evaluate reticulospinal functioning. It is recommended to examine different forms of resistance training and longer training exposure in future.

Humans

Social work training of new health professionals.

The Child Health Associate program provides a model for using social workers in the training of new health professionals. Administratively, social workers have contributed to curriculum development in the behavioral sciences. They have influenced decisions regarding student selection and have developed and implemented a faculty adviser program. Because of their practical experience as primary care practitioners, social workers have been able to define effectively the skills needed by the new professionals to meet the social and emotional needs of their patients. Social workers have made use of their contacts in hospitals and communities to design and implement courses and clinics that combine in a meaningful manner theoretical material and practical experiences in patient contact. Evaluative research in the area of interviewing skills and crisis management demonstrates that the teaching methods applied by the social work profession are effective in increasing the level of students' interviewing skills in clinical practice and help prepare them to recognize familiy crises.

Colorado

The Interplay Between Sleep and Mental Health: A Genetic Perspective.

Although many facets of sleep, including subjective, behavioral, and neurophysiological features, are closely linked with psychiatric disorders, the natures of these relationships are generally unclear. A given alteration in sleep could reflect a cause (that may mediate genetic risk), consequence, symptom, trigger, epiphenomenon due to shared determinants, or some combination of these. In principle, genetic approaches can be informative: 1) by identifying specific genetic influences on disease mediated by or shared with sleep, which could help the search for biological mechanisms and therapeutic targets, and 2) by providing evidence for causality, which could suggest interventions for modifiable sleep traits. Here, we summarize recent human quantitative and molecular genetic studies on sleep and psychiatric disease, including twin and genome-wide association studies. Despite evidence for shared heritability across many domains, notably depression and insomnia, the field is in its early stages and faces significant challenges including the following: 1) putative causal effects are small, phenotypically nonspecific, not resolved to specific gene pathways, and often bidirectional; 2) most current discovery cohorts are demographically biased and do not capture profound age-related changes in sleep and its genetic architecture; 3) group-level analyses ignore patient-to-patient heterogeneity, including the presence or absence of specific sleep alterations; and 4) a paucity of objective, brain-based data in genetically informative samples hampers making connections with sleep neurophysiology. Nonetheless, as ever-growing genetic tools and resources still hold great potential for translational bridges between basic model systems, human epidemiology, and personalized clinical care, genetic approaches will still likely be needed to reveal sleep's roles in maintaining mental health.

Humans

Somatic mosaicism in the brain: linking development, ageing and neurodegeneration.

Somatic mosaicism is increasingly recognized as a pervasive feature of the human brain and a potential contributor to neurological disease across the lifespan. Unlike germline variants, somatic variants arise post-zygotically and are unevenly distributed across regions, cell types and even individual neurons, enabling focal biological effects that can scale to network-level dysfunction. In this Review, we synthesize current evidence that developmental timing, clonal architecture and cell-type-specific selective pressures shape how somatic variants influence brain structure and function. Early embryonic variants can produce broad regional clones and severe phenotypes, whereas later events are usually more restricted; with ageing, ongoing DNA damage and imperfect repair generate private variants that might cumulatively reduce cellular resilience. We also summarize advances in detection approaches, including bulk, error-corrected and single-cell sequencing, and discuss their strengths and current limitations for clinical translation. Emerging data link brain somatic variants to neurodevelopmental and neurodegenerative phenotypes, supporting a unified framework in which mosaic genetics bridges focal lesions and distributed neurological syndromes. Integrating genomic, cellular and physiological analyses in longitudinal human studies will be essential to define causality, identify biomarkers and guide future targeted interventions.

Journal Article

Proteomics-driven discovery of intervention windows and risk subtypes in osteoporosis: A prospective cohort study.

Given the limited feasibility of population-wide bone mineral density screening and the infrequency of long-term monitoring in healthy individuals, identifying the window for early intervention and the populations to be prioritized for screening is critical. This study aimed to identify intervention windows for osteoporosis and to determine potential high-risk subtypes within the healthy population. Based on proteomic data from 41,408 healthy adults, we conducted the DE-SWAN method to identify change peaks in plasma protein during the pre-diagnostic osteoporosis phase, and employed finite Gaussian mixture model-based clustering to delineate high-risk subtypes of osteoporosis. We identified 122 protein biomarkers significantly associated with osteoporosis risk throughout the follow-up period. Importantly, we identified two critical peaks occurring approximately 10 and 6&#xa0;years before diagnosis, with the former enriched in immune-related pathways and the latter prominently involving responses to retinoic acid and glucocorticoids. Furthermore, one high-risk subtype for osteoporosis was identified in both males and females, termed the Frailty and Obesity Subtype. This subtype is characterized by a high degree of frailty and obesity, accompanied by a significantly elevated risk of both osteoporosis and fractures. Finally, we developed a predictive model comprising 10 proteins for identifying high-risk subtypes of osteoporosis, which demonstrated better performance than the traditional risk factor model (AUC: 0.743 vs. 0.680). Our findings demonstrate that proteomic profiling can reveal early molecular changes and identify high-risk subtypes years before clinical onset, providing a foundation for screening and precision prevention of osteoporosis.

Proteomics

Short-term diet intervention comprising of olive oil, vitamin D, and omega-3 fatty acids alters the small non-coding RNA (sncRNA) landscape of human sperm.

Offspring health outcomes are often linked with epigenetic alterations triggered by maternal nutrition and intrauterine environment. Strong experimental data also link paternal preconception nutrition with pathophysiology in the offspring, but the mechanism(s) routing effects of paternal exposures remain elusive. Animal experimental models have highlighted small non-coding RNAs (sncRNAs) as potential regulators of paternal effects. Here, we characterised the baseline sncRNA landscape of human sperm and the effect of a 6-week dietary intervention on their expression profile. This study involves sncRNAseq profiling, that was performed on a subset (n&#x2009;=&#x2009;17) of the participants enrolled in the PREPARE trial: 9 from the control group and 8 from the intervention group. 5'tRFs, miRNAs and piRNAs were the most abundant sncRNA subtypes identified; their expression was associated with age, BMI, and sperm quality. Nutritional intervention with olive oil, vitamin D and omega-3 fatty acids altered expression of 3 tRFs, 15 miRNAs and 112 piRNAs, targeting genes involved in fatty acid metabolism and transposable elements in the sperm genome. PREPARE Trial registration number: ISRCTN50956936, Trial registration date: 10/02/2014.

Humans

Optimizing focal vibration therapy for balance and gait: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of focal (localized) vibration therapy (FVT) applied to muscles/tendons on balance, gait, and mobility, with a specific focus on defining optimal vibration protocols (frequency, amplitude, dosing) and muscle-targeting strategies to maximize sensorimotor recovery. METHODS: A systematic review was conducted across six databases (CINHAL, Embase, Medline, Web of Science, Scopus, CENTRAL) from January 2000 to May 2025. Studies were included if they involved human participants, applied FVT therapeutically, and reported balance, gait, or mobility outcomes. Data extraction included study characteristics, intervention protocols, and outcomes. Methodological quality was assessed using the PEDro scale. RESULTS: Sixty-two studies (n&#x202f;=&#x202f;2090 participants) were included. Methodological quality assessment (PEDro scale) indicated 44% of studies met high-quality standards. Biomechanical analysis identified the quadriceps, gastrocnemius/soleus, and plantar muscles as the most effective vibration sites, given their critical roles in gait propulsion and postural stability. The synthesis of protocol data indicated a promising therapeutic window characterized by a vibration frequency of 80-120&#x202f;Hz (primarily fixed sinusoidal waveforms at a single frequency) and an amplitude of 0.2-0.5&#x202f;mm (reported only in 12 studies; amplitude was not reported in 23 studies), applied bilaterally for a minimum of 3 sessions per week over 4-12 weeks, which could lead to improved balance and gait performance with benefits sustained for up to 5 months. CONCLUSION: FVT shows potential to improve gait and balance, particularly when targeting lower-extremity muscles with optimized vibration parameters. To advance the field, future research must prioritize the development of standardized protocols and investigate neurophysiological mechanisms to refine FVT as a precision bioengineering solution for mobility deficits.

Humans

Identifying potential therapeutic targets for high myopia via a case-control study and Mendelian randomisation analyses of the human blood metabolome.

BACKGROUND: High myopia increases the risk of pathological ocular changes that may lead to irreversible vision loss. Therefore, the identification of potential biomarkers and therapeutic targets for high myopia is essential for early intervention and prevention. METHODS: Summary statistics for 122 blood metabolites were obtained from three genome-wide association studies (GWASs), whereas data on high myopia were derived from a large GWAS conducted with 50,372 participants from the UK Biobank. Mendelian randomisation (MR) analyses were conducted to assess the causal relationships between blood metabolites and high myopia. A real-world case-control study was conducted to validate the causal associations identified in the MR analyses. RESULTS: The systematic MR analysis identified 5 blood metabolites as both biomarkers and potential drug targets for high myopia, including glutamine (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.97-1.00), tyrosine (OR: 0.98; 95% CI: 0.97-0.99), degree of unsaturation (OR: 0.98, 95% CI: 0.98-0.99), docosahexaenoic acid (DHA) (OR: 0.99; 95% CI: 0.98-1.00) and isobutyrylcarnitine (OR: 1.09, 95% CI: 1.05-1.13). The case-control study indicated that the levels of glutamine (OR&#x2009;=&#x2009;0.76, 95% CI: 0.58-0.98) and tyrosine (OR&#x2009;=&#x2009;0.72, 95% CI: 0.55-0.94) were significantly associated with a decreased risk of high myopia. CONCLUSIONS: Systematic MR analysis suggested that glutamine, tyrosine, the degree of unsaturation, DHA, and isobutyrylcarnitine may represent promising drug targets for high myopia prevention. Further investigations are needed to validate the therapeutic efficacy and elucidate the underlying mechanisms involved.

Humans