Dad's Diet Shapes the Future: How Paternal Nutrition Impacts Placental Development and Childhood Metabolic Health.

Early-life programming is a major determinant of lifelong metabolic health, yet current preventive strategies focus almost exclusively on maternal factors. Emerging experimental and preclinical data reveal that a father's diet before conception, particularly high-fat intake, also shapes offspring physiology. Here, we synthesize the latest evidence on how such diets remodel the sperm epigenome during two discrete windows of vulnerability: (i) testicular spermatogenesis, via DNA methylation and histone modifications, and (ii) post-testicular epididymal maturation, where small non-coding RNAs are selectively gained.

Association of Inflammatory and Cardiovascular Proteomics Biomarkers With Indices of Heart Rate Variability in the General Population: KORA S4/FF4 Study.

Background: We sought to investigate the association between circulating inflammatory and cardiovascular proteomics biomarkers and cardiac autonomic nervous dysfunction-sensitive heart rate variability indices.

Methods: Using the population-based KORA (Cooperative Health Research in the Region of Augsburg) cohort, 233 proteomics biomarkers were quantified in baseline plasma samples of 1389 individuals using proximity extension assay technology. Five heart rate variability indices (Rényi entropy of the histogram with order [α] 4, total power of the density spectra, SD of word sequence, SD of the short-term normal-to-normal interval variability, compression entropy) were assessed at baseline in 982 individuals and in 407 individuals at baseline and at 14-year follow-up.

HIV-1 manipulates CD96 on CD4 T cells to subvert antiviral immunity.

HIV-1 evades immune responses by modulating plasma membrane receptors. Using a flow cytometry-based screening, we profiled 332 surface receptors on HIV-1-infected primary CD4 T cells and identified 23 down-regulated receptors, including known targets such as CD4, MHCI, CCR7, and CD62L. CD96, an inhibitory natural killer (NK) cell receptor poorly studied in human CD4 T cells, was markedly down-regulated.

A redundant system of thioredoxin and glutathione is essential for pancreatic acinar integrity.

Background & Aims: Oxidative stress and antioxidant defense mechanisms have long been implicated in the pathogenesis of acute pancreatitis (AP). However, there is a notable lack of in vivo experimental evidence clarifying their precise role.

Methods: We generated and analyzed mice with a pancreas-specific deletion of Txnrd1 (Txnrd1).

Urban pollution impact assessment in six lithuanian cities with a focus on road traffic emissions - integrated framework for environmental health studies.

An integrated framework is introduced and applied to assess the health impact of airborne pollution with greater physiological relevance, moving beyond conventional exposure metrics. Measured particle number size distribution data was integrated with a regional respiratory tract deposition fractions to estimate total and alveolar deposited particle surface area concentrations. Land use regression modeling, combined with randomized commuting patterns, enabled the evaluation of city-specific alveolar surface area deposition doses, providing new insight into localized average exposure and its implications for public health.

A Novel α-Synuclein K58N Missense Variant in a Patient with Parkinson's Disease.

Background: Parkinson's disease (PD) is a complex multifactorial disorder with a genetic component in about 15% of cases. Multiplications and point mutations in SNCA gene, encoding α-synuclein (aSyn), are linked to rare familial forms of PD.

Objective: Our goal was to assess the clinical presentation and the biological effects of a novel K58N aSyn mutation identified in a patient with PD.

APOE genotype influences on the brain metabolome of aging mice - role for mitochondrial energetics in mechanisms of resilience in APOE2 genotype.

Unlabelled: Alzheimer’s disease (AD) risk and progression are significantly influenced by APOE genotype with APOE4 increasing and APOE2 decreasing susceptibility compared to APOE3. While the effect of those genotypes was extensively studied on blood metabolome, less is known about their impact in the brain. Here we investigated the impacts of APOE genotypes and aging on brain metabolic profiles across the lifespan, using human APOE-targeted replacement mice.

Methanobactin rapidly facilitates biliary copper excretion in a Wilson disease rat model visualised by Cu PET/MRI.

Background And Purpose: Methanobactins are peptides with high copper affinity and potential to treat Wilson disease. We examined how two methanobactins (ARBM101 and MB-OB3b) affected copper handling in the LPP Atp7b Wilson disease rat model, compared to penicillamine or saline, by Cu positron emission tomography/magnetic resonance imaging. Heterozygotes served as controls.

Arterial stiffness and vascular aging: mechanisms, prevention, and therapy.

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. The central underlying mechanisms of cardiovascular diseases are vascular aging and associated arterial stiffness. Arterial stiffness is characterized by structural (e.

Adherence to digital pregnancy care - lessons learned from the SMART start feasibility study.

The World Health Organization increasingly highlights the role of digital health technologies in supporting prenatal care. Despite this potential, the real-world implementation of such technologies remains limited, even in high-income countries with established analog systems. We developed a comprehensive digital pregnancy care framework, SMART Start and evaluated it in a prospective study involving 528 pregnant individuals in Germany.

Assessing the effectiveness of the heat health warning system in preventing mortality in 15 German cities: A difference-in-differences approach.

Background: Heatwaves pose significant risks to human health. Implementing heat health warning systems (HHWS) has been widely adopted as a preventive measure. However, the effectiveness of the German HHWS in reducing mortality during heat episodes across different cities has scarcely been researched.

Short-term association between hot nights and mortality: a multicountry analysis in 178 locations considering hourly ambient temperature.

Background: The rise in hot nights over recent decades and projections of further increases due to climate change underscores the critical need to understand their impact. This knowledge is essential for shaping public health strategies and guiding adaptation efforts. Despite their significance, research on the implications of hot nights remains limited.

Skin Lipid-Microbe Interplay Links Staphylococcus hominis to Barrier Control in Adult Atopic Dermatitis.

Background: Skin surface lipids and commensal microbes are essential for the epidermal barrier, but their mutual interactions remain poorly understood.

Methods: We conducted high-resolution shotgun lipidomics of tape strips from lesional and non-lesional atopic dermatitis (AD) skin and healthy controls. Lipidomic data were integrated with 16S amplicon sequencing to construct lipid-microbe interaction networks.

DelSIEVE: cell phylogeny modeling of single nucleotide variants and deletions from single-cell DNA sequencing data.

With rapid advancements in single-cell DNA sequencing (scDNA-seq), various computational methods have been developed to study evolution and call variants on single-cell level. However, modeling deletions remains challenging because they affect total coverage in ways that are difficult to distinguish from technical artifacts. We present DelSIEVE, a statistical method that infers cell phylogeny and single-nucleotide variants, accounting for deletions, from scDNA-seq data.

YTHDF proteins and mA-RNA clients undergo autophagic turnover during contact inhibition.

The YTHDF protein family plays a critical role in cancer development by recognizing and regulating the stability of N6-methyladenosine (mA)-modified RNA. Here, we reveal an autophagy-dependent mechanism controlling YTHDF protein levels. Using contact inhibition as a cellular model system, we show YTHDF proteins to be rapidly degraded, coinciding with increased autophagy and decreased mTOR activity.

Glycaemic responses to metformin monotherapy by SNP clusters in patients with type 2 diabetes.

Aims: This study retrospectively investigates the association between polygenic risk scores (PRS) derived from SNP clusters and glycaemic response to metformin in patients with newly diagnosed T2D.

Materials And Methods: Utilizing a dataset from the Taiwan Precision Medicine Initiative, we evaluated alterations in fasting glucose (FBG) and glycated haemoglobin (HbA1c) in individuals newly diagnosed with T2D who underwent metformin monotherapy for a duration of 6 months. Glycaemic responses between those in the bottom 20% of PRS (Q1) and the top 20% of PRS (Q5) for each of the SNP clusters and for the combination of two clusters were analysed.

Magnesium Depletion, Metabolic Impairment, and Cardiac Alterations: The NAKO-MRI Study with Mendelian Randomization.

Context: Magnesium deficiency may contribute to subclinical cardiac changes, particularly metabolic diastolic cardiomyopathy.

Objective: To investigate the association between magnesium depletion, metabolic syndrome (MetS), and MRI-derived cardiac alterations in a population-based sample.

Methods: We cross-sectionally analyzed N = 9568 participants from the baseline examination of the German National Cohort (NAKO) who underwent whole-body MRI.

Mapping early human blood cell differentiation using single-cell proteomics and transcriptomics.

Single-cell transcriptomics (scRNA-seq) has facilitated the characterization of cell state heterogeneity and recapitulation of differentiation trajectories. However, the exclusive use of mRNA measurements comes at the risk of missing important biological information. Here we leveraged recent technological advances in single-cell proteomics by Mass Spectrometry (scp-MS) to generate an scp-MS dataset of an in vivo differentiation hierarchy encompassing over 2500 human CD34+ hematopoietic stem and progenitor cells.

First-in-human study of the benzothiazinone and DprE1 inhibitor BTZ-043, a novel drug candidate for the treatment of Tuberculosis.

Objectives: This first-in-human, single ascending dose study evaluated the safety, tolerability and pharmacokinetics (PK) of the decaprenylphosphoryl-β-D-ribose-2'-epimerase (DprE1) inhibitor BTZ-043.

Methods: BTZ-043 was administered as an oral suspension at doses of 125, 250 and 500 mg along with placebo to healthy participants. Safety assessments included evaluation of laboratory parameters, vital signs, physical and neurological examination, and 12-lead ECG.

Occurrence of coronary events in the absence of traditional risk factors: Understanding residual risk.

Background And Aims: The major predictors of future coronary heart disease (CHD) events in individuals without traditional modifiable cardiovascular risk factors (CVRFs) remain unknown. We investigated the association between circulating biomarkers, reflecting residual risk, with incident CHD in a general population, according to the presence of five CVRFs (hypertension, diabetes mellitus, hypercholesterolemia, smoking and obesity) at baseline.

Methods: Overall 212,598 CHD-free individuals from 21 European population-based cohorts were stratified by CVRF burden into three groups, having zero (n = 35,707), one (n = 68,548) or ≥2 (n = 108,343) risk factors at baseline.

Transient colonization by Priestia megaterium B1L5 alters the structure of the rhizosphere microbiome towards potential plant beneficial bacterial groups in apple plantlets.

Background: Plant growth-promoting bacteria (PGPB) can beneficially modulate rhizosphere microbial communities, potentially improving plant health and reducing disease incidence. Limited research exists on the influence of PGPB inoculation on the rhizosphere microbial communities of apple plants, particularly in soils affected by apple replant disease (ARD). Here, we evaluated the capacity of GFP-labelled B1 (designated as B1L5) to colonize the roots of apple plantlets grown in two soils: ARD-affected soil and ARD-unaffected grass soil.

A comprehensive review/expert statement on environmental risk factors of cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of mortality globally, with over 20 million deaths each year. While traditional risk factors-such as hypertension, diabetes, smoking, and poor diet-are well-established, emerging evidence underscores the profound impact of environmental exposures on cardiovascular health. Air pollution, particularly fine particulate matter (PM2.