Engineering Resilient CAR T Cells for Immunosuppressive Environment.

Chimeric Antigen Receptor (CAR) T cell therapy has revolutionized cancer treatment and is now being explored for other diseases, such as autoimmune disorders. While the tumor microenvironment (TME) in cancer is often immunosuppressive, in autoimmune diseases, the environment is typically inflammatory. Both environments can negatively impact CAR T cell survival: the former through direct suppression, hypoxia, and nutrient deprivation, and the latter through chronic T cell receptor (TCR) engagement, risking exhaustion.

Tissue nanotransfection-based endothelial PLCγ2-targeted epigenetic gene editing in vivo rescues perfusion and diabetic ischemic wound healing.

Diabetic wounds are complicated by underlying peripheral vasculopathy. Reliance on vascular endothelial growth factor (VEGF) therapy to improve perfusion makes logical sense, yet clinical study outcomes on rescuing diabetic wound vascularization have yielded disappointing results. Our previous work has identified that low endothelial phospholipase Cγ2 (PLCγ2) expression hinders the therapeutic effect of VEGF on the diabetic ischemic limb.

Mechanical Wear of Degraded Articular Cartilage.

Purpose: To evaluate the mechanical wear of cartilage with different types of degradation.

Methods: Bovine osteochondral explants were treated with interleukin-1β (IL-1β) to mimic inflammatory conditions, with chondroitinase ABC (ChABC) to specifically remove glycosaminoglycans (GAGs), or with collagenase to degrade the collagen network during 5 days of culture. Viscoelastic properties of cartilage were characterized via indentation.

Asymptomatic female softball pitchers have altered hip morphology and cartilage composition.

Few studies have explored hip morphology and cartilage composition in female athletes or the impact of asymmetric repetitive loading, such as occurs during softball pitching. The current cross-sectional study assessed bilateral bony hip morphology on computed tomography imaging in collegiate-level softball pitchers ('Pitch1', n = 25) and cross-country runners ('Run', n = 13). Magnetic resonance imaging was used to assess cartilage relaxation times in a second cohort of pitchers ('Pitch2', n = 10) and non-athletic controls ('Con', n = 4).

Systematic review and meta-analysis of pathogenic GJB2 variants in the Asian population.

Objectives: Define the extent to which pathogenic GJB2 (gap junction beta-2) variants are responsible for non-syndromic hearing loss (NSHL) in the Asian population.

Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. CINAHL, Embase, and PubMed's MEDLINE were accessed from 1997 to 2023 using permutations of the MeSH terms: "Asian," ''Southeast Asian,'' "South Asian," "East Asian," "Southeastern Asian," and "GJB2.

Dietary Interventions, Supplements, and Plant-Derived Compounds for Adjunct Vitiligo Management: A Review of the Literature.

Vitiligo is a chronic autoimmune pigmentation disorder shaped by a complex interplay of genetic predispositions and environmental triggers. While conventional therapies-phototherapy, corticosteroids, and immunosuppressants-can be effective, their benefits are often partial and temporary, with recurrence common once treatment stops. As such, there is increasing interest in exploring complementary approaches that may offer a more sustainable impact.

A Conserved Di-Lysine Motif in the E2 Transactivation Domain Regulates MmuPV1 Replication and Disease Progression.

The papillomavirus E2 protein regulates the transcription, replication, and segregation of viral episomes within the host cell. A multitude of post-translational modifications have been identified which control E2 functions. A highly conserved di-lysine motif within the transactivation domain (TAD) has been shown to regulate the normal functions of the E2 proteins of BPV-1, SfPV1, HPV-16, and HPV-31.

Utilization of Cannabidiol in Post-Organ-Transplant Care.

Cannabidiol (CBD) is one of the major phytochemical constituents of cannabis, , widely recognized for its therapeutic potential. While cannabis has been utilized for medicinal purposes since ancient times, its psychoactive and addictive properties led to its prohibition in 1937, with only the medical use being reauthorized in 1998. Unlike tetrahydrocannabinol (THC), CBD lacks psychoactive and addictive properties, yet the name that suggests its association with cannabis has significantly contributed to its public visibility.

Clinical and Genomic Features of Androgen Indifferent Prostate Cancer.

Androgen-indifferent prostate cancer (AIPC) is increasingly common and particularly lethal. Data describing these tumors are sparse, and AIPC remains a poorly understood malignancy. Utilizing the Oncology Research Information Exchange Network (ORIEN) database, we enriched for tumors with features of AIPC using previously described characteristics.

G Protein-Coupled Receptor 17 Inhibits Glucagon-like Peptide-1 Secretion via a Gi/o-Dependent Mechanism in Enteroendocrine Cells.

Gut peptides, including glucagon-like peptide-1 (GLP-1), regulate metabolic homeostasis and have emerged as the basis for multiple state-of-the-art diabetes and obesity therapies. We previously showed that G protein-coupled receptor 17 (GPR17) is expressed in intestinal enteroendocrine cells (EECs) and modulates nutrient-induced GLP-1 secretion. However, the GPR17-mediated molecular signaling pathways in EECs have yet to be fully deciphered.

Pediatric Non-Alcoholic Fatty Liver Disease (NAFLD): Trends, Mortality, and Socioeconomic Disparities in the U.S., 1998-2020.

Background/objectives: We aim to describe the changing inpatient epidemiology of NAFLD in the U.S. and identify major risk factors associated with mortality in the disease among hospitalized pediatric patients.

Detection of Toxoplasma gondii in Brain Tissues of Pet Birds with Neurological Symptoms Using Loop-Mediated Isothermal Amplification (LAMP) and PCR.

Background: This study seeks to close this divide by assessing the occurrence of Toxoplasma gondii (T. gondii) in the brain tissues of pet birds displaying neurological symptoms, utilizing Nested Polymerase Chain Reaction (PCR) and Loop-mediated Isothermal Amplification (LAMP) methods. Furthermore, it aims to evaluate and contrast the sensitivity and specificity of different diagnostic procedures.

Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients.

Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias.

Race to the Moon or the Bottom? Applications, Performance, and Ethical Considerations of Artificial Intelligence in Prosthodontics and Implant Dentistry.

This review aims to explore the applications of artificial intelligence (AI) in prosthodontics and implant dentistry, focusing on its performance outcomes and associated ethical concerns. Following the PRISMA guidelines, a search was conducted across databases such as PubMed, Medline, Web of Science, and Scopus. Studies published between January 2022 and May 2024, in English, were considered.

Comparative Foliar Atmospheric Mercury Accumulation across Functional Types in Temperate Trees.

Vegetation assimilation of atmospheric gaseous elemental mercury (GEM) represents the largest dry deposition pathway in global terrestrial ecosystems. This study investigated Hg accumulation mechanisms in deciduous broadleaves and evergreen needles, focusing on how ecophysiological strategies─reflected by δC, δO, leaf mass per area, and leaf dry matter content-mediated Hg accumulation. Results showed that deciduous leaves exhibited higher total Hg (THg) concentrations and accumulation rates (THg), which were 85.

Fast-Relaxing Hydrogels Promote Pancreatic Adenocarcinoma Cell Aggressiveness through Integrin β1 Signaling.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense extracellular matrix (ECM) exhibiting high stiffness and fast stress relaxation. In this work, gelatin-based viscoelastic hydrogels were developed to mimic the compositions, stiffness, and fast stress relaxation of PDAC tissues. The hydrogels were cross-linked by gelatin-norbornene-boronic acid (GelNB-BA), thiolated macromers, and a 1,2-diol-containing linear synthetic polymer PHD.

Large-bore aspiration thrombectomy for the treatment of pulmonary embolism in octogenarians.

Purpose: To evaluate outcomes in patients aged ≥ 80 years following large-bore aspiration thrombectomy (LBAT) for the treatment of pulmonary embolism (PE).

Materials And Methods: All patients ≥ 80 years of age with PE treated via LBAT at a single center were analyzed from September 2019 - August 2024. This included the octogenarian subgroup from a recently published retrospective analysis assessing all PE patients treated with LBAT at our center between September 2019 and January 2023.

How Polyproline Type II Conformation at P Residues Influences the Success of Proline-Based Peptidyl Inhibitors Against Coronavirus Main Protease.

In the wake of the pandemic, peptidyl protease inhibitors with Pro-based rigid Leu mimetics at the P position have emerged as potent drug candidates against the SARS-CoV-2 main protease. This success is intuitively attributed to the enhanced hydrophobic interactions and rigidity of Pro-based rigid Leu mimetics in the literature. However, the tertiary amide of proline P derivatives, which hinders the formation of a critical hydrogen bond with the enzyme active site, and the constrained PP conformation, which contradicts the protease preferred β-strand conformation, represent two overlooked disadvantages associated with these inhibitors over traditional inhibitors and, theoretically, should adversely affect their potency.

Experiences of sexual and reproductive health screening and counseling in the clinical setting among adolescents and young adults with rheumatic disease.

Background: Our objective was to describe differences among adolescents and young adults (AYAs) with rheumatic disease using teratogens compared to non-users in receipt of sexual and reproductive health (SRH) counseling, teratogenicity knowledge, perceived importance of SRH topics, and preferences around counseling.

Methods: AYAs ages 14-23 years and assigned female at birth were recruited from pediatric rheumatology clinics at a Midwest tertiary care program. Participants completed a one-time online survey assessing SRH.

Hypusinated and unhypusinated isoforms of the translation factor eIF5A exert distinct effects in models of pancreas development and function.

Hypusination of eukaryotic translation initiation factor 5A (eIF5A) is essential for its role in translation elongation and termination. Although the function of hypusinated eIF5A (eIF5A) in cellular proliferation is well-characterized, the role of its unhypusinated form (eIF5A) remains unclear. We hypothesized that eIF5A exerts independent, negative effects on cellular replication and metabolism, distinct from the loss of eIF5A.

Characterization of Tumor Antigens from Multi-omics Data: Computational Approaches and Resources.

Tumor-specific antigens, also known as neoantigens, have potential utility in anti-cancer immunotherapy, including immune checkpoint blockade (ICB), neoantigen-specific T cell receptor-engineered T (TCR-T), chimeric antigen receptor T (CAR-T), and therapeutic cancer vaccines (TCVs). After recognizing presented neoantigens, the immune system becomes activated and triggers the death of tumor cells. Neoantigens may be derived from multiple origins, including somatic mutations (single nucleotide variants, insertion/deletions, and gene fusions), circular RNAs, alternative splicing, RNA editing, and polymorphic microbiome.

Dynamic single cell transcriptomics defines kidney FGF23/KL bioactivity and novel segment-specific inflammatory targets.

Fibroblast growth factor 23 (FGF23) via its coreceptor αKlotho (KL) provides critical control of phosphate metabolism, which is altered in both rare and very common syndromes. However, the spatial-temporal mechanisms dictating kidney FGF23 functions remain poorly understood. Thus, developing approaches to modify specific FGF23-dictated pathways has proven problematic.