Wake Forest School of Medicine is the medical school of Wake Forest University, located in Winston-Salem, North Carolina, United States. It is affiliated with Wake Forest Baptist Medical Center, the academic medical center whose clinical arm is Wake Forest Baptist Health. In 2019, U.S. News & World Report ranked Wake Forest School of Medicine 50th best for research in the nation and 64th best for primary care. The School of Medicine also ranks in the top third of U.S. medical schools in funding from the National Institutes of Health (NIH).
Despite metabolic dysfunction–associated steatohepatitis (MASH) being a significant global health concern, there are few effective ways to prevent or treat MASH. Evidence from preclinical and clinical studies suggests that inflammatory polarization of Kupffer cells (KCs) and infiltration of monocyte-derived macrophages (MDMs) in liver macrophages play an essential role in the initiation and progression of MASH. Herein, we reported a liposomal nanoparticle (NP-OMg) that targets suppressive oligodeoxynucleotide (sODN) and magnesium ions (Mg2+) to KCs and MDMs. sODN acted as a potent inhibitor of multiple pattern recognition receptors (PRRs), while Mg2+ was chosen for its anti-oxidative and anti-pyroptotic effects, and its capability of coordinating with sODN in NP-OMg. Intravenously administrated NP-OMg was primarily engulfed by both KCs and MDMs in mouse liver. Therapeutically, NP-OMg mitigated hepatic steatosis, inflammation and fibrosis, and restored liver functions in mouse models of metabolic dysfunction–associated steatotic liver disease (MASLD)/MASH. Mechanistically, RNA-sequencing analysis revealed that NP-OMg largely reversed the aberrant gene expression and signaling pathways involved in the pathogenesis of MASLD/MASH. Through comprehensive targeting of inflammatory pathways in liver macrophages, NP-OMg treatment significantly reduced production of inflammatory cytokines/chemokines and decreased the liver recruitment of Ly6chigh inflammatory MDMs. These findings demonstrate the potential of a new liver macrophage-targeted nanomedicine strategy for the treatment of MASH.
Background & objective Consumption of diets insufficient in essential nutrients contributes to unhealthy aging. The objective of this study is to evaluate adequacy of key nutrients that reflect the food components of the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) dietary pattern, one deemed important for brain health. Setting/design Cross-sectional analyses of diets of participants in the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (US POINTER) trial Participants Adults, aged 60–79 years and at risk of cognitive impairment (sedentary, suboptimal diet, other risk factors) were enrolled in the US POINTER, a phase III two-year randomized controlled trial comparing the impact of two lifestyle interventions on brain health. Measurements Before randomization, participants completed a food frequency questionnaire (FFQ) assessing usual intake of foods and beverages, and vitamin and/or mineral supplements. Median daily nutrient intakes were expressed as a percentage of sex- and age-specific Estimated Average Requirement (EAR) or Adequate Intake (AI), and Tolerable Upper Limit (UL) criteria. Results Of the 2111 enrolled participants, 2041 completed the FFQs (69% women). Nearly half reported multivitamin multimineral supplement use (49%, men; 49%, women). Common individual supplements included vitamins D (36%), E (25%), C (23%), and B12 (19%) as well as calcium (16%). Based on food alone, the proportion of participants with inadequate intakes was high across several nutrients. Supplements improved nutrient adequacy for most (except for choline, fiber and potassium) but contributed to intakes for some that exceed the UL cutoffs (vitamins A (n=28), B9 (n=134), B3 (n=160) and zinc (n=196)). Conclusions Widespread nutrient inadequacy (especially those integral to the MIND dietary pattern) is evident among non-supplement users. Supplement use improves adequacy but raises concerns about excessive intakes that exceed ULs. Assessment of diet and supplement intake is essential to address nutrient inadequacies in at-risk older adults. Clinical Trial Registration Number : NCT03688126, submitted 9/26/2018.
The global wood adhesive market is dominated by formaldehyde-based resins that, despite good bonding performance, pose serious health and environmental risks. This study developed fully biobased hempseed protein adhesives modified with citric acid, glucose, and their combinations as sustainable alternatives. Hemp protein isolates were formulated and hot-pressed at 180 degrees C for two-layer plywood bonding. Structural (FTIR, XRD, SEM), thermal (DSC, TGA), rheological, and performance (shear strength, water resistance, hydrophobicity) analyses were performed to evaluate modification effects. Citric acid introduced ester and amide crosslinks that increased dry shear strength to 3.07 MPa and elevated denaturation temperatures above 144 degrees C. Glucose enhanced Schiffbase and Maillard-type crosslinking, yielding dry strengths up to 3.46 MPa, wet strength of 1.61 MPa, and surface hydrophobicity values exceeding 78 mu g bound SDS/mg sample. Dual-modifier systems exhibited pronounced synergy, producing dense covalent networks with dry, wet, and soaked strengths of 4.76, 2.49, and 4.14 MPa, respectively. Water resistance improved markedly, with residual mass retention reaching 82.9%, and DSC confirmed cooperative stabilization with enthalpies exceeding 11 J/g and endset temperatures above 160 degrees C. TGA revealed reduced moisture uptake and higher char yields, while rheological analysis indicated dual systems balanced elasticity and viscosity, forming stable suspensions prior to curing. These findings demonstrate that hemp protein-citric acid-glucose adhesives are high-performance, sustainable alternatives for engineered wood applications, advancing circular bioeconomy goals.
Introduction Aromatase inhibitors (AIs) reduce recurrence and mortality in hormone receptor-positive breast cancer; however, up to 70% of patients discontinue therapy early because of AI-associated arthralgia. Joint pain affects more than half of AI users and can be burdensome among breast cancer survivors. Exercise and education may reduce symptoms and improve adherence, but interventions tailored for older survivors remain limited. Materials and methods We evaluated REJOIN, a remotely delivered exercise and education intervention. In this pilot randomized controlled trial, 24 older breast cancer survivors receiving AI therapy were recruited from two cancer centers and randomized to REJOIN or enhanced standard care. The 16-week intervention included supervised resistance and aerobic exercise, education on AI-related side effects, and self-management strategies. Outcomes included joint pain measured by the Brief Pain Inventory and AI adherence measured by the Morisky-Levine-Green Medication Adherence Scale. Additional measures included accelerometer-assessed physical activity and a geriatric assessment. Results Participants (n = 24) had a mean age of 71.4 years (range 60–88), and more than one-third resided in rural communities. Retention was 80% over 12 months. Comparing REJOIN with standard care, changes from baseline to 4 months were evaluated using Wilcoxon tests and Cohen's d effect sizes. REJOIN showed a moderate reduction in joint pain interference (d = −0.47, p = 0.43). Self-reported AI medication adherence was high at baseline in both groups, limiting the ability to detect meaningful improvement; however, adherence patterns over follow-up favored the intervention group. Feasibility benchmarks were met, including accrual of the target sample, retention of 80% at 12 months, and achievement of the prespecified exercise-adherence benchmark, with 12 of 13 intervention participants (94%) completing the required supervised exercise and coaching sessions. Discussion REJOIN was feasible, safe, and acceptable among breast cancer survivors receiving AI therapy. Its remote delivery and engagement of rural participants suggest potential for dissemination and support progression to a larger efficacy trial.
