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Association Between Ticagrelor and Glucose Homeostasis Regulation: Insights from Genetic and Transcriptomic Analyses.

Emerging evidence has demonstrated the additional therapeutic benefits of ticagrelor in acute coronary syndrome (ACS) patients with diabetes. However, the underlying mechanisms of this association remain elusive. Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on ticagrelor, plasma proteomics and type 2 diabetes was employed to identify causal mediator proteins. RNA sequencing (RNA-seq) of ticagrelor-treated HepG2 cells revealed the molecular pathways regulating glucose metabolism. Genetically proxied ticagrelor was significantly associated with a reduced risk of diabetes (OR = 0.859, 95% CI: 0.783-0.934, P = 7.98E-05), and 24.41% of this effect was mediated by upregulation of BDH2 protein. In vitro experiments confirmed the enhanced effect of ticagrelor on glucose consumption. Transcriptome analysis revealed that mitochondrial respiratory chain transfer and oxidative phosphorylation (OXPHOS) were significantly enriched, and genes related to ATP biosynthesis were significantly upregulated. These findings highlight the non-platelet function of ticagrelor in maintaining glucose homeostasis, providing insights into potential drug repurposing in the future.

Humans

Functional role and regulatory network of miR-22-3p in chicken hepatic lipid metabolism.

Although microRNA-22-3p (miR-22-3p) is abundantly expressed in the avian liver, its epigenetic role in lipid homeostasis remains largely uncharacterized. To elucidate its in vivo function, 14-day-old female Qingyuan Partridge chickens were intravenously injected with lentiviral vectors to establish miR-22-3p overexpression and knockdown models. Phenotypic analysis demonstrated that miR-22-3p knockdown significantly elevated hepatic triglyceride (TG) levels (p&#xa0;<&#xa0;0.05) and drove marked steatosis, whereas its overexpression reduced TG content. Transcriptome sequencing (RNA-Seq) revealed profound metabolic remodeling, identifying 23 core lipid-associated genes (e.g., ELOVL6, FADS2, ACSBG2, and PTGIS) heavily enriched in steroid biosynthesis, fatty acid metabolism, and elongation pathways. In conclusion, miR-22-3p functions as a bidirectional epigenetic rheostat that negatively regulates hepatic lipid deposition by orchestrating a multilayered polygenic network, providing novel molecular targets for mitigating avian metabolic disorders and optimizing production traits in indigenous poultry breeds.

Animals

Genetic overlap between estimated glomerular filtration rate and cardiovascular disease identifies potential targets for cardiorenal syndrome.

Heart and kidney diseases frequently coexist, but the genetic basis of this relationship remains unclear. We analyzed genetic data from large-scale studies to investigate how kidney function (estimated glomerular filtration rate, eGFR) and six common cardiovascular diseases share genetic risk factors. Using MiXeR method, and conjunctional false discovery rate (conjFDR) to identify overlapping genetic regions, we found 478 shared genomic loci between eGFR and cardiovascular diseases. These shared genes are involved in tissue development and structure. We also identified 29 genes that could be targeted by existing medications approved by the US Food and Drug Administration, such as PRKAG2, PDE1A, and IGF1R. Among these, genetically predicted higher level of IGF1R expression is associated with a higher eGFR, which reflects good kidney function and is protective against cardiorenal diseases, such as atrial fibrillation, and myocardial infarction. These findings reveal genetic overlap between kidney function and cardiovascular diseases, highlighting potential targets for understanding and treating cardiorenal syndrome.

Humans

Voluntary Knowledge Brokering to Promote Evidence-Based Nursing Practice: A Qualitative Study.

Knowledge brokering is a process of connecting knowledge producers with users to facilitate evidence-based practice through relationship building and information sharing. This descriptive qualitative study aimed to clarify knowledge brokering by nurses in Japanese hospitals. Twelve registered nurses in Japanese hospitals participated. They had over 5&#x2009;years' clinical experience, including experience in conducting research, particularly staff research, and education. Data were collected through semi-structured individual interviews and analyzed using qualitative content analysis. The analysis revealed a central theme: continuous efforts to foster empathy among colleagues and spontaneously promote evidence-based practice: multifaceted brokering activities by clinical nurses. Findings identified 10 categories categorized into four interconnected gears: establishing the foundational ground, assessing clinical needs and staff readiness, tailoring and diffusing evidence, and sustaining and evolving evidence-based practice. Even nurses without formal titles voluntarily bridged the research-practice gap, providing new insights into informal brokering. Brokers communicated considerately, balanced evidence with clinical context, negotiated practical compromises, and fostered staff research competency.

Humans

Food-derived extracellular vesicles as delivery platforms for medicine-food homology components in metabolic syndrome.

Diet-induced obesity and associated metabolic syndromes have become major global public health challenge, highlighting the urgent need for safe and effective strategies. Recently, food-derived extracellular vesicles (FDEVs) have garnered increasing attention as natural nanocarriers due to their excellent biocompatibility and specific targeted delivery capabilities. FDEVs can efficiently deliver medicine-food homology components (MFHCs) to precisely regulate lipid metabolism, inflammatory responses, and insulin sensitivity, thereby improving obesity and its metabolic abnormalities. This systematic review summarizes recent advances in the use of FDEVs as delivery vehicles for MFHCs to suppress diet-induced obesity and metabolic syndrome, with a particular focus on the underlying molecular mechanisms, including signaling pathway regulation and cellular metabolic remodeling. In addition, the clinical translational potential and industrial application prospects of FDEVs are evaluated, and key challenges related to preparation techniques, safety assessment, and large-scale production are discussed. By integrating current evidence, this review aims to provide theoretical framework and future perspectives for the development of FDEVs as a novel targeted delivery platform and treatment of metabolic diseases.

Extracellular Vesicles

Heat stress in cereal crops: reproductive development and grain filling.

Increasingly frequent extreme heat events threaten cereal production and food security under a changing climate. The reproductive-to-grain formation continuum of cereals is particularly vulnerable to elevated temperatures, as heat stress disrupts developmental processes from inflorescence formation and fertilization to grain filling and quality establishment. These disruptions reduce reproductive success, impair yield formation, and compromise grain quality. A comprehensive understanding of the developmental, physiological, molecular, and genetic basis of cereal heat tolerance is therefore essential for developing climate-adapted crops. This review summarizes recent advances in understanding heat stress during cereal reproduction and grain filling across major cereal crops. We first discuss how heat stress affects sequential developmental processes, including inflorescence development, gametophyte development, flowering and pollination, fertilization, and grain filling. We then integrate emerging evidence on cross-cutting mechanisms that connect stage-specific heat responses, focusing on hormonal and redox homeostasis, carbohydrate metabolism and source-sink coordination, proteostasis and endomembrane organization, and genome stability and multilayered gene regulation. Finally, we summarize the genetic basis of cereal heat tolerance by highlighting genetic determinants, favorable alleles, and their potential applications in breeding. We further discuss current bottlenecks and future opportunities for breeding heat-tolerant cereals.

Cereals

Adaptive Sports Exposure Across Physical Medicine and Rehabilitation Residency and Sports Medicine Fellowship Programs: A National Cross-Sectional Website Analysis.

Adaptive sports improve health and quality of life for people with disabilities, yet the extent of adaptive sports exposure in physical medicine and rehabilitation (PM&R) training is unclear. This cross-sectional study reviewed the public websites of 115 accredited physical medicine and rehabilitation residency programs and 26 sports medicine fellowship programs for any mention of adaptive sports, characterizing exposure type, target populations, and associated program characteristics. Adaptive sports were mentioned by 32 residency programs (27.8%) and 8 fellowship programs (30.8%). Mention varied significantly by geographic region in both cohorts (residency, West 64% vs. South 19%, P=.017; fellowship, Midwest 80% vs. South 0%, P=.035) and, among residencies, was associated with larger program size and a greater number of associated subspecialty fellowships. Residency exposure was predominantly volunteer-based, whereas fellowship exposure was exclusively clinical or undisclosed; target populations served were frequently unspecified. Programs have an opportunity to expand structured adaptive sports training and to clearly convey these opportunities to applicants and patients.

Adaptive sports

Interfacial engineering of cobalt tungstate-halloysite nanotube nanocomposite for electrochemical detection of synthetic vanillin in food matrices.

In processed foods and medicine, synthetic vanillin is widely used, although excessive intake poses toxicological risks. Due to the rising usage of synthetic vanillin in food products and associated health hazards, quick, sensitive, and reliable analytical methods are needed to precisely measure vanillin in complex food matrices. This work introduces a CoWO4@F-HNT/GCE nanocomposite as an efficient electrocatalytic modifier for glassy carbon electrodes aimed at trace-level synthetic vanillin detection. Structural and microscopic analyses confirmed phase-pure monoclinic CoWO4, preservation of the tubular aluminosilicate framework, and homogeneous nanoparticle anchoring on F-HNT. Differential pulse voltammetry provided a broad linear range from 0.01 to 372.14&#xa0;&#x3bc;M and a low detection limit of 4.3&#xa0;nM, together with excellent selectivity against common interferents, good cycling stability, and high inter-electrode reproducibility. These characteristics position the CoWO4@F-HNT-modified electrode as a cost-effective and reliable platform for on-site quality control of synthetic vanillin in complex food matrices.

Benzaldehydes

"Orphaned bereavement": Toward a public health model for bereavement.

Bereavement is increasingly recognized as a public health concern, yet support systems in many welfare states continue to allocate support according to the circumstances of death rather than the functional needs of bereaved families. Existing bereavement frameworks have substantially advanced understanding of social recognition and public legitimacy but provide more limited guidance for understanding how institutional responsibility for bereaved families is organized. using Israel as a bereavement-saturated case, this study introduces the concept of orphaned bereavement to describe bereavement in which no institution holds clearly defined and continuing responsibility for identifying needs, coordinating support, and ensuring continuity of care. Drawing on 25 semi-structured interviews with five bereaved family members and 20 professionals, analyzed using reflexive thematic analysis, the analysis generated three interrelated themes: institutionalized invisibility and unequal recognition; reorganizing life in the absence of institutional support; and pathways toward a needs-based model of bereavement support. The findings extend existing theories of disenfranchized grief and grievability by introducing institutional responsibility as a complementary lens for understanding bereavement inequality and support a needs-based public health approach in which support is organized according to families' evolving functional needs rather than the circumstances of death.

Journal Article

Morphology-engineered NiFe@C nanocages boosting electrochemical quantification of ractopamine in meat samples.

It is essential to acquire efficient electrocatalysts to develop ractopamine (RAC) electrochemical sensors. Herein, we report the synthesis of a series of carbon coated NiFe alloy nanostructures (e.g., NiFe@C nanoparticles, nanocubes and nanocages) using NiFe Prussian blue analogue (PBA) as the precursor. The NiFe@C nanocages exhibited the best electrocatalytic performance for RAC sensing. This is attributed to the embedded NiFe alloy nanoparticles that provide abundant active sites, and the unique nanocage structure facilitates electron transfer pathways while offering a high specific surface area. The resulting sensor achieves a low detection limit (LOD) of 54&#xa0;nM (S/N&#xa0;=&#xa0;3) within a linear range of 0.2-12&#xa0;&#x3bc;M. Moreover, the sensor demonstrates good reproducibility, stability, and excellent long-term stability. Practical applicability was confirmed in meat samples, yielding satisfactory recovery rates ranging from 98% to 108%. A feasible strategy was introduced herein for rational design of metal@carbon electrocatalysts.

Phenethylamines

Safe and Stable Germline Transmission of MSTN Mutations in Cattle.

With the global population expected to reach 10 billion by 2050, sustainable livestock production is critical. Gene editing of the myostatin (MSTN) gene represents a promising strategy to enhance muscle growth in cattle. In this study, MSTN-mutated founder (F0) cows were used to generate F1 offspring via ovum pick-up, in&#xa0;vitro fertilization, and embryo transfer. Four F1 calves were born, all confirmed to be heterozygous for the MSTN mutation. Long-term monitoring showed normal growth and no visible health abnormalities. Whole-genome sequencing identified SNPs, INDELs, and structural variants, most with minimal predicted functional effects. Proteomic profiling of Longissimus dorsi muscle quantified 2947 proteins, revealing only subtle expression differences between MSTN-mutated and wild-type cattle. These results demonstrate stable inheritance and confirm that MSTN editing does not disrupt genome integrity or protein expression. Overall, our findings support the safety and utility of MSTN gene editing to improve livestock productivity for future food security.

Animals

Circular RNAs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, with most cases lacking a clear genetic basis. Emerging evidence highlights the involvement of non-coding RNAs, particularly circular RNAs (circRNAs), in disease onset and progression. Here, we investigated circRNAs implicated in ALS and related motor neuron diseases (MNDs). Here, we provide a general overview of circular RNA metabolism and cellular functions. We then present our systematic literature review that identified ALS-associated circRNAs, followed by in silico analyses of 15 circular RNA candidates that were selected based on the most compelling data regarding ALS. Our results revealed that several circular RNAs regulate ALS-related genes, such as unfolded protein response, oxidative stress, cell cycle regulation, and apoptosis. Protein-RNA interaction analysis further showed that ALS-related circRNAs can sponge 20 RNA-binding proteins. Additionally, molecular docking analysis demonstrated that ALS-associated FUS variants significantly alter its binding affinity to circular RNAs. RNA-seq data from ALS patients confirmed significant alterations in the expression of host genes of ALS-related circRNAs and hub proteins in ALS-affected CNS tissues. Collectively, our findings identify circRNAs as potential key contributors to ALS pathogenesis.

Amyotrophic Lateral Sclerosis

Machine learning-assisted Mn-N-C nanozyme colorimetric sensor array for trace-level detection of biogenic amines in meat.

Accurate detection of biogenic amines (BAs) in meat remains challenging due to their high structural similarity and co-occurrence. Herein, an Mn-N-C nanozyme was synthesized via a metal-organic framework confined pyrolysis strategy, possessing excellent oxidase (OXD)- and peroxidase (POD)-like activities. The dual enzyme-like activity showed Km values of 0.1584&#xa0;mM (OXD) and 0.1498&#xa0;mM (POD), respectively, in detection system. Leveraging these properties, a colorimetric sensor array was constructed, enabling the detection of four representative BAs within a concentration range of 2-10&#xa0;ppm with 100% classification accuracy. In addition, a concentration independent recognition model based on an artificial neural network was developed to address signal nonlinearity interference in meat. The integrated system achieved accurate trace-level identification of BAs in perishable fish, pork, and chicken, demonstrating its applicability for early-stage BAs monitoring and quality deterioration warning during storage and transportation.

Biogenic Amines

Analysis of deep learning techniques in computer-aided diagnosis for meniscus injuries: a systematic literature review.

Meniscus informatics is a growing subject of study in the healthcare industry. One of the major hindrances to the healthcare system's transformation is obtaining knowledge and meaningful information from complicated, high-dimensional and diverse sources. Modern biomedical research, for instance, has seen an increase in the use of complex, dissimilar, poorly documented, and generally unstructured electronic health records, imaging, sensor data and text, even after many current techniques have been used to extract more robust and useful elements from the data for analysis. New efficient standards for building end-to-end learning models from complex data are therefore needed. Therefore, the current study aims to examine the most recent research on the use of deep learning techniques for diagnosing meniscus tears and recommend creating comprehensive and meaningful interpretable structures that might benefit the healthcare industry. We also draw attention to shortcomings and the need for better technique development, and we provide new perspectives about this exciting new development in the field.

Humans

Beyond risk factors: A capacity framework for cancer survivorship research.

Cancer survivorship research has identified numerous biological, behavioral, psychosocial, health care, and structural factors that influence recovery. However, these factors are typically studied as separate determinants rather than interacting influences. This commentary proposes available survivorship capacity as a unifying framework that explains how these diverse determinants collectively shape recovery and survivorship outcomes. Concepts from geroscience, health care delivery, rehabilitation, occupational therapy, and human factors science were synthesized to develop a conceptual framework of available survivorship capacity. The framework conceptualizes recovery as a function of the capacity remaining after competing health care and life demands draw upon survivors' finite physical, cognitive, emotional, social, financial, temporal, and health care resources. It generates testable propositions for measurement, intervention research, health care delivery, and implementation science while positioning available survivorship capacity as a common mechanism linking diverse determinants of recovery and identifying actionable targets for intervention. Available capacity offers a unifying conceptual framework for understanding heterogeneity in survivorship outcomes and intervention effectiveness while generating a research agenda for future survivorship science. Measuring and strengthening survivors' available capacity, while reducing unnecessary demands, may improve engagement in care, health behaviors, and long-term recovery.

Humans

Proteomics in environmental pollution research: Advances, challenges, and future directions.

Environmental proteomics has emerged as a powerful approach for elucidating the molecular mechanisms underlying pollutant-induced biological effects. Although this field has developed rapidly, the systematic review of recent proteomics applications in environmental pollution research remains limited. This review explored the emerging roles of toxicoproteomics in biomarker discovery and mechanistic elucidation, as well as ecotoxicoproteomics in ecological risk assessment and bioremediation strategies. Here, we review the field, highlighting recent trends such as the integration of proteomics with genomics, transcriptomics, and metabolomics to provide a comprehensive view of biological responses to environmental stressors. We further discuss the growing application of artificial intelligence in improving proteomics data interpretation and accelerating biomarker discovery. In addition, recent technological advances in environmental proteomics are highlighted, including next-generation tissue microarray proteomics, nanoscale proteomics, single-cell proteomics, and spatial proteomics. Despite its potential, proteomics faces challenges, such as high operational costs, computational complexity in analysis, and technical limitations in low-abundance protein detection. We propose that the convergence of proteomics with artificial intelligence and multi-omics approaches offers promising solutions to these challenges, enhancing the practical application of proteomics in environmental monitoring and risk assessment.

Proteomics

Facilitating Thought Progression via a Gamified Mobile Application for Depression: Possible Mediators of Outcomes.

Mobile health interventions represent a scalable and accessible alternative to traditional therapy, which often is out of reach due to high costs and societal stigma. Rumination is considered a key mechanism of emotional disorders and represents a potential treatment target for digital health interventions. The current study investigated the role of rumination as a mediator of the reduction in depression and anxiety reported after the use of a gamified mobile app based on the Facilitating Thought Progression (FTP) framework. One hundred-one adults with mild to moderate depression were randomized to the FTP intervention or a waitlist control group and completed weekly assessments of depression, anxiety, and rumination over 8 weeks. Multilevel structural equation modeling revealed that reduction in rumination significantly mediated decreases in depression and anxiety in the intervention group but not in the waitlist condition. These findings suggest that the FTP app targeted rumination and further highlights its role as a critical target for interventions for depression and anxiety.

Adult

Walking Together: A Cross-Cultural Study of the Relationship Between Religiosity and Substance Use Disorder.

The literature suggests that religiosity is a protective factor for substance use. However, individuals with substance use disorder (SUD) may actively cultivate their religiosity during substance use. This qualitative study analyzed the perceptions and meanings homeless people attribute to their substance use trajectories and religiosity, as well as the potential connections between these two themes. The analysis was conducted based on the content analysis technique proposed by Bardin. A total of 40 semi-structured interviews were conducted with 20 Brazilian and 20 Portuguese participants. The present study found that religiosity can play a role in the substance use trajectory and the development of SUD by offering a subjective sense of protection, serving as a marker for the need for change, or providing relief from the suffering associated with SUD. We discuss how homeless people with SUD experience religiosity and how religious aspects traditionally seen as protective in the literature, such as church attendance, may paradoxically become risk factors for these socially vulnerable populations.

Humans