Discovery of RNA-Protein Molecular Clamps Using Proteome-Wide Stability Assays.

Uncompetitive inhibition is an effective strategy for suppressing dysregulated enzymes and their substrates, but discovery of suitable ligands depends on often-unavailable structural knowledge and serendipity. Hence, despite surging interest in mass spectrometry-based target identification, proteomic studies of substrate-dependent target engagement remain sparse. Herein, we describe a strategy for the discovery of substrate-dependent ligand binding.

Discovery of a Pyrazolopyridinone-Based MYC Inhibitor That Selectively Engages Intracellular c-MYC and Disrupts MYC-MAX Heterodimerization.

c-MYC is an oncogenic transcription factor that plays a crucial role in the regulation of downstream targets involved in proliferation, apoptosis, differentiation, metabolism, signaling, and immune response processes whose deregulation leads to the progression of different pathologies. The development of selective and potent small-molecule inhibitors of c-MYC remains a grand challenge in chemical biology and medicine due to its undruggability, derived from extensive intrinsic disorder. In this study, we identified a novel dihydro pyrazolo pyridinone scaffold, , that selectively targets c-MYC in cells and disrupts MYC-MAX interaction.

Understanding the Stress Process Among Mexican American Adults aged 50 and older in the United States.

Objectives: Compared to non-Latino White adults, Mexican Americans in the U.S. are disproportionally exposed to more social, environmental, and economic stress that increase risk for poor physical and mental health outcomes.

Precision Medicine in Cardiovascular Disease Prevention: Clinical Validation of Multi-Ancestry Polygenic Risk Scores in a U.S. Cohort.

Background: Polygenic risk score (PRS) quantifies the cumulative effects of common genetic variants across the genome, including both coding and non-coding regions, to predict the risk of developing common diseases. In cardiovascular medicine, PRS enhances risk stratification beyond traditional clinical risk factors, offering a precision medicine approach to coronary artery disease (CAD) prevention. This study evaluates the predictive performance of a multi-ancestry PRS framework for cardiovascular risk assessment using the All of Us (AoU) short-read whole-genome sequencing dataset comprising over 225,000 participants.

Host Transcriptome and Microbial Variation in Relation to Visceral Hyperalgesia.

Background: Chronic visceral hypersensitivity is associated with an overstressed pain response to noxious stimuli (hyperalgesia). Microbiota are active modulators of host biology and are implicated in the etiology of visceral hypersensitivity.

Objectives: we studied the association between the circulating mRNA transcriptome, the intensity of induced visceral pain (IVP), and variation in the oral microbiome among participants with and without baseline visceral hypersensitivity.

Developing and Testing a User-Focused, Web GIS-Based Food Asset Map for an Under-Resourced Community in Northeastern Connecticut.

Access to healthy and affordable food remains a challenge for under-resourced communities due to uneven food distribution and the need for reliable transportation. This study developed and evaluated an interactive Geographic Information System (GIS)-based food asset map for a low-income community in Windham, Connecticut to improve awareness of food resources and expand opportunities for fresh food access. Using the human-centered design (HCD) framework and the Asset-Based Community Development (ABCD) model, the map integrates food locations, transportation routes, and assistance eligibility.

Phytochemical-Mediated Ah Receptor Activity Is Dependent on Dietary Context.

The aryl hydrocarbon receptor (AHR) is an important mediator of intestinal homeostasis. The AHR senses certain classes of phytochemicals, including many flavonoids and tryptophan metabolites generated in the intestinal tract. Several in vitro studies demonstrate the presence of AHR ligands in numerous plants commonly consumed by humans.

Consumption of the Food Groups with the Revised Benefits in the New WIC Food Package: A Scoping Review.

Background: On 18 April 2024, the United States Department of Agriculture (USDA) published the first food package changes to the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in over a decade, which reduced some food benefits (juice, milk, canned fish, and infant fruits and vegetables) and offered substitutes (cash-value vouchers (CVVs) or cash-value benefits (CVBs) to redeem for fruits and vegetables, cheese, soymilk, or other dairy products).

Methods: To assess the impact of the changes on the consumption and redemption of these food groups, a systematic search was conducted, identifying 23 peer-reviewed publications between 2010 and 2024.

Results: They revealed significant shifts in consumption after the 2009 food package changes; e.

Sleep Duration is Associated with Fruit and Vegetable Intake in Lower Income Adults from the San Francisco Bay Area: A Cross-Sectional Analysis.

Few studies have examined whether sleep is related to dietary intake in aging adults. To address this gap, this study investigated (1) the associations between sleep duration and sleep quality with fruits and vegetables (FV), fiber, and fat intake in lower-income midlife and older adults and (2) sex differences in these relationships. Baseline data from 163 ethnically diverse, lower-income midlife and older adults in the NIH-funded trial were analyzed.

"Salt and Eat It or No Salt and Trash It?" Shifts in Support for School Meal Program Flexibilities in Public Comments.

The Healthy, Hunger-Free Kids Act was passed in 2010 to update nutrition standards in the National School Lunch and Breakfast Programs to be in accordance with evidence-based guidelines. In 2017 and 2020, the United States Department of Agriculture proposed flexibilities to the nutrition standards for milk, whole grains, and sodium. This study examines the positions used by stakeholders in support for or opposition to the proposed rules.

A Multi-Level Approach to Childhood Obesity Prevention and Management: Lessons from Japan and the United States.

Background: Childhood obesity is a pressing global public health challenge, marked by significant disparities in prevalence and management across countries. Japan and the United States offer contrasting approaches to addressing this issue, presenting a valuable opportunity for comparative analysis.

Objective: This review examines the effectiveness of public health policies, cultural dietary habits, and lifestyle factors in combating childhood obesity in Japan and the United States.

Impact of Prenatal Dietary Soy on Cerebellar Neurodevelopment and Function in Experimental Fetal Alcohol Spectrum Disorder.

Prenatal alcohol exposure (PAE) models can cause neurodevelopmental abnormalities like those observed in fetal alcohol spectrum disorder (FASD). Previous studies link experimental PAE effects in the brain to impaired signaling through insulin/IGF and Notch pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Importantly, concurrent administration of peroxisome proliferator-activated receptor agonists or dietary soy prevented many aspects of FASD due to their insulin-sensitizing, anti-inflammatory, and antioxidant properties.

Endothelial Homeostasis Under the Influence of Alcohol-Relevance to Atherosclerotic Cardiovascular Disease.

Alcohol, in the form of ethyl alcohol or ethanol, is a widely consumed substance with significant implications for human health. Research studies indicate multifaceted effects of alcohol on the cardiovascular system with both protective and harmful effects on atherosclerotic cardiovascular disease (ASCVD), depending on the amount involved and the pattern of consumption. Among the critical components of the cardiovascular system are endothelial cells which line blood vessels.

Factors Associated with High Sugary Beverage Intake Among Children in Louisiana: A Survey of Caregivers in New Orleans and Baton Rouge.

: Sugar-sweetened beverage (SSB) consumption is associated with child obesity, an understudied issue in the southern United States, where obesity rates are the highest in the country. We examined the factors associated with high SSB intakes among children aged 2-12 years in two major cities in Louisiana, New Orleans and Baton Rouge. : We conducted a cross-sectional study using an online survey.

Impact of Consultation with Registered Dietitians on Reducing Inappropriate Weight Gain in Pregnant Patients with Food Insecurity.

: Screening for food insecurity, while common practice in pediatric populations, remains novel in pregnancy. Food insecurity during pregnancy is associated with medical comorbidities that in turn confer additional obstetric risks to the maternal-fetal dyad. Few studies have evaluated the impact of interventions for patients with food insecurity in the prenatal period.

The Relationship Between Fiber Intake and Gut Bacterial Diversity and Composition During the Third Trimester of Pregnancy.

Background/objectives: High fiber (34-36 g/day) diets are recommended during pregnancy due to inverse associations with constipation and adverse pregnancy health outcomes, including pre-eclampsia and gestational diabetes. However, the mechanism for this protective effect is poorly defined. Fiber may be protective due to its impact on the composition and function of specific bacteria within the pregnancy gut microbiome.

Tissue-Specific Ablation of Liver Fatty Acid-Binding Protein Induces a Metabolically Healthy Obese Phenotype in Female Mice.

Obesity is associated with numerous metabolic complications including insulin resistance, dyslipidemia, and a reduced capacity for physical activity. Whole-body ablation of liver fatty acid-binding protein (LFABP) in mice was shown to alleviate several of these metabolic complications; high-fat (HF)-fed LFABP knockout (LFABP) mice developed higher fat mass than their wild-type (WT) counterparts but displayed a metabolically healthy obese (MHO) phenotype with normoglycemia, normoinsulinemia, and reduced hepatic steatosis compared with WT. Since LFABP is expressed in both liver and intestine, in the present study, we generated LFABP conditional knockout (cKO) mice to determine the contributions of LFABP specifically within the liver or within the intestine, to the whole-body phenotype of the global knockout.

Cognitive Performance in Relation to Systemic and Brain Iron at Perimenopause.

Background: The literature on the relationships among blood iron levels, cognitive performance, and brain iron levels specific to women at the menopausal transition is ambiguous at best. The need to better understand these potential relationships in women for whom monthly blood loss (and thus iron loss) is ceasing is highlighted by iron's accumulation in brain tissue over time, thought to be a factor in the development of neurodegenerative disease.

Methods: Non-anemic women who were either low in iron or had normal iron levels for their age and race/ethnicity provided blood samples, underwent MRI scans to estimate brain iron levels, and performed a set of cognitive tasks with concurrent EEG.

Complementary Feeding and Infant Gut Microbiota: A Narrative Review.

: The complementary feeding period, spanning from 6 to 24 months of age, marks the transition from an exclusive liquid diet in infants to a dietary pattern requiring the introduction of solid foods to meet nutritional demands. Complementary feeding coincides with other critical development windows, including the maturation of the gut microbiome. However, the effects of specific solid foods on gut microbiota and the subsequent influence on health outcomes require further investigation.

Advances in Mechanisms of Anaphylaxis in Wheat Allergy: Utility of Rodent Models.

Wheat is a staple and nutritious food that is consumed globally. However, it is identified as a major allergenic food because of its capacity to trigger life-threatening systemic anaphylaxis. The specific mechanisms that underlie this systemic anaphylaxis in wheat allergy are incompletely understood.

Sensory Properties and Acceptability of Fermented Pearl Millet, a Climate-Resistant and Nutritious Grain, Among Consumers in the United States-A Pilot Study.

Millets are climate-resistant, potential alternatives to wheat that could provide environmental, food security, and health benefits (e.g., lower glycemic index).

Characterization of Extruded Sorghum-Soy Blends to Develop Pre-Cooked and Nutritionally Dense Fortified Blended Foods.

Food aid commodities are essential food items in global food aid programming. Some are primarily made from an extrusion of corn and soybeans. However, there are concerns about the genetically modified organisms (GMOs) of some of these grains.

Bayesian Updating of Fatigue Crack Growth Parameters for Failure Prognosis of Miter Gates.

Navigable waterways play a vital role in the efficient transportation of millions of tons of cargo annually. Inland traffic must pass through a lock, which consists of miter gates. Failures and closures of these gates can significantly disrupt waterborne commerce.

Improving Simulation Model Accuracy for Friction Stir Welding of AA 2219.

Modeling of friction stir welding (FSW) is challenging, as there are large gradients in both strain rate and temperature (typically between 450 and 500 °C in aluminum alloys) that must be accounted for in the constitutive law of the material being joined. Constitutive laws are most often calibrated using flow stresses from hot compression or hot torsion testing, where strain rates are much lower than those seen in the stir zone of the FSW process. As such, the current work employed a recently developed method to measure flow stresses at high strain rates and temperatures in AA 2219-T67, and these data were used in the development of a finite element (FE) simulation of FSW.

The Effect of Leisure-Time Exercise on Mental Health Among Adults: A Bibliometric Analysis of Randomized Controlled Trials.

Adequate levels of leisure-time exercise (LTE) are associated with mental health benefits. Despite increased research in recent years through randomized controlled trials (RCTs), a systematic literature review summarizing these findings is lacking. Here, we examined publication trends, impact, and research gaps regarding LTE's effects on mental health in the form of a bibliometric analysis.