Western University of Health Sciences (WesternU) is a private medical school and health sciences university with its main campus in Pomona, California, with an additional osteopathic medical school in Lebanon, Oregon. With an enrollment of 3,814 students (2020–21), WesternU offers more than twenty academic programs in multiple colleges.Under the banner of WesternU Health, the university operates a variety of patient care facilities in California and Oregon. The Pomona and Portland (Oregon) campuses both include a medical center, dental center, eye care institute, pharmacy, and travel health center. WesternU-Pomona also is home to the Pet Health Center, which provides veterinary services. Dental services are offered at the Rancho Mirage campus, while a Los Angeles campus provides optometry services.Several nonprofit organizations are based at the WesternU Pomona campus, including the Harris Family Center for Disability and Health Policy. The Center for Oral Health, moved from the Bay area to the WesternU Pomona campus in 2012. In 2015, the Southern California Medical Museum moved to the Pomona campus.Founded in 1977, the first program at WesternU was its medical school, the College of Osteopathic Medicine of the Pacific (COMP). Since that time, the College of Veterinary Medicine opened in 2003, and colleges of dental medicine, optometry, and podiatric medicine opened in 2009. In 2011, the university opened an additional campus in Lebanon, Oregon, the College of Osteopathic Medicine of the Pacific - Northwest (COMP-Northwest). In 2015, the university's founding president, Philip Pumerantz, retired.All of the programs at WesternU have professional accreditation and the university is accredited by the Western Association of Schools and Colleges. The medical school (COMP) is also accredited by the American Osteopathic Association's Commission on Osteopathic College Accreditation.
Diabetic foot ulcers are a major cause of morbidity in patients with diabetes mellitus and remain challenging to treat despite advances in wound care. Growing evidence suggests that impaired axonal regeneration, along with chronic inflammation, impaired angiogenesis, and altered extracellular remodeling, is an important mechanism contributing to the chronic, nonhealing nature of cutaneous wounds. However, the mediators involved and the mechanisms by which they impair wound healing in the presence of hyperglycemia are poorly understood. Peripheral nerves coordinate inflammation, angiogenesis, and extracellular matrix remodeling during repair, and their dysfunction in diabetes disrupts these processes. This review examines how hyperglycemia and oxidative stress impair neuroregeneration ( mainly axonal and nerve regeneration), highlighting the downstream consequences for vascular and structural repair. Particular attention is given to the altered expression of activin A (associated with nerve growth and neural inflammation), TNFRSF10B (associated with neuronal damage and apoptosis, and synaptophysin (a marker of synaptic vesicles and involved in nerve regeneration, particularly in the early stages of axonal regrowth) as representative mediators linking neuronal injury to defective wound healing. By integrating findings across neural, vascular, and inflammatory pathways, this review supports impaired neuronal regeneration as an important contributor to nonhealing diabetic foot ulcer pathogenesis to identify potential molecular targets that may improve healing outcomes.
Mechanosensitive PIEZO channels are thought to open via tension-induced flattening of peripheral transmembrane arm domains, yet the structural basis of this activation remains unclear. Here, by leveraging hybrid-resolution molecular dynamics simulations, we uncover how large-scale PIEZO2 arm movements funnel into subtle gating motions in the central pore under physiological tension. Arm flattening correlates with anticlockwise rotation of the pore relative to the arms and with clockwise twisting of inner pore helices. These clockwork motions open the pore in a two-step fashion, yielding a fully conducting state and a stable subconducting state populated at a low tension, which was detected electrophysiologically. The fully open PIEZO2 pore is walled by both lipids and amino acids and recapitulates minimal pore size, conductance, ion selectivity and outward rectification of chloride currents measured electrophysiologically. These findings provide structural insights into PIEZO2 gating and demonstrate hybrid-resolution molecular dynamics as a powerful approach to study large-scale membrane protein dynamics and guide drug discovery.
Diabetes mellitus and inflammatory bowel disease are chronic inflammatory disorders characterized by immune dysregulation and rising global prevalence. Epidemiological studies increasingly suggest a bidirectional association between the two conditions, linked through shared mechanisms of intestinal barrier dysfunction, microbial dysbiosis, and sustained innate immune activation. Activated macrophages play a central role in driving mucosal inflammation through polarization toward a pro-inflammatory M1 phenotype, accompanied by increased production of inflammatory cytokines. These mediators disrupt tight junctions, induce epithelial apoptosis, and perpetuate cycles of immune activation and tissue injury. This macrophage–cytokine axis not only amplifies local inflammation but also sustains chronic barrier dysfunction, creating a pathogenic overlap between diabetes mellitus-associated intestinal injury and intestinal bowel disease. In this study, we used a low dose streptozotocin and high-fat diet-induced diabetic Sprague–Dawley rat model in both sexes to investigate the effects of chronic hyperglycemia on intestinal inflammation, with particular emphasis on macrophage activation and pro-inflammatory cytokine responses. We found inflammation in both small and large intestines with mucosal injury and barrier disruption, and immune activation involving macrophages and enhanced expression of CD68, iNOS, TNF-α, and IL-6. Female rats were more susceptible to gut-related inflammatory changes due to diabetes. These findings suggest a complex interplay between epithelial stress, immune signaling, and microbial factors supporting the role of intestinal inflammation in the immune–metabolic interaction in diabetes-associated intestinal changes, which may contribute to the pathogenesis of inflammatory bowel disease.
The design of reliable, valid, and diverse molecules is fundamental to modern drug discovery, as improved molecular generation supports efficient exploration of the chemical space for potential drug candidates and reduces the cost of early design efforts. Despite these needs, current chemical language models that generate molecules as SMILES strings are vulnerable to compounding token errors: many samples are unparseable or chemically implausible, and hard constraints meant to prevent failure can restrict exploration. To address this gap, we introduce TSSR, a Two-Stage, Swap-Reward-driven reinforcement learning (RL) framework for character-level SMILES generation. Stage one rewards local token swaps that repair syntax, promoting transitions from invalid to parseable strings. Stage two provides chemistry-aware feedback from RDKit diagnostics, rewarding reductions in valence, aromaticity, and connectivity issues. The reward decomposes into interpretable terms (swap efficiency, error reduction, distance to validity), is model agnostic, and requires no task-specific labels or hand-crafted grammars. We evaluated TSSR on the MOSES benchmark using a GRU policy trained with PPO in both pure RL (P-RL) from random initialization and fine-tuning RL (F-RL) starting from a pretrained chemical language model, assessing 10,000 generated SMILES per run. In P-RL, TSSR significantly improves syntactic validity, chemical validity, and novelty. In F-RL, TSSR preserves drug-likeness and synthesizability while increasing validity and novelty. Token-level analysis shows that syntax edits and chemistry fixes act jointly to reduce RDKit detected errors. TSSR converts a sparse terminal objective into a denser and more interpretable reward, improving both syntactic and chemical quality without reducing diversity. TSSR is dataset-agnostic and can be adapted to various reinforcement learning approaches.
Disease risk and severity are influenced by genetics, epigenetics, and environmental factors. However, immune responses vary even among genetically similar or related individuals, shaped by inherited and noninherited factors. Using Caenorhabditis elegans, we found that pathogen susceptibility can be predicted by preinfection biomarkers. Individuals with high-basal expression of irg-5, an infection response gene regulated by the p38 mitogen-activated protein kinase-1 (PMK-1) pathway, were more susceptible to Pseudomonas aeruginosa infection. A genome-wide screen identified the myeloid ecotropic viral integration site-1 (MEIS) homeobox protein UNC-62 as a regulator of irg-5 expression, acting through PMK-1 and GATA binding erythroid-like transcription factor (ELT-2). Further analysis revealed that maternal circadian timing shaped offspring immune heterogeneity and inhibition of clock genes eliminated the effects induced by maternal timing. These findings highlight circadian-driven immune variability as a potential adaptive strategy for resilience against infection.
