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).

Selective resection of the medial wall of the cavernous sinus in pituitary surgery: results of a prospective single center analysis.

Purpose: Pituitary adenomas, despite their histologically benign nature, can severely impact patients' quality of life due to hormone hypersecretion. Invasion of the medial wall of the cavernous sinus (MWCS) by these tumors complicates surgical outcomes, lowering biochemical remission rates and increasing recurrence. This study aims to share our institutional experience with the selective resection of the MWCS in endoscopic pituitary surgery.

Spatial Localization of Collagen Hydroxylated Proline Site Variation as an Ancestral Trait in the Breast Cancer Microenvironment.

Collagen stroma interactions within the extracellular microenvironment of breast tissue play a significant role in breast cancer, including risk, progression, and outcomes. Hydroxylation of proline (HYP) is a common post-translational modification directly linked to breast cancer survival and progression. Changes in HYP status lead to alterations in epithelial cell signaling, extracellular matrix remodeling, and immune cell recruitment.

The Definition and Diagnostic Criteria for Flexion Instability after Total Knee Arthroplasty is Highly Variable in the Published Literature.

Introduction: Flexion instability (FI) is increasingly being recognized as a common reason for failure after total knee arthroplasty (TKA). However, the diagnosis remains loosely defined and is often described by a constellation of symptoms and findings with the exclusion of other clinical entities. The purpose of this study was to examine the definition and diagnostic criteria of FI used in the current peer-reviewed literature.

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.

A 2D cell segmentation protocol for monitoring multiple STAT signaling pathways by fluorescence microscopy.

Microscopic cell segmentation typically requires complex imaging, staining, and computational steps to achieve acceptable consistency. Here, we describe a protocol for the high-fidelity segmentation of the nucleus and cytoplasm in cell culture and apply it to monitor interferon-induced signal transducer and activator of transcription (STAT) signaling. We provide guidelines for sample preparation, image acquisition, and segmentation.

Genomic highlights of the phylogenetically unique halophilic purple nonsulfur bacterium, Rhodothalassium salexigens.

Rhodothalassium (Rts.) salexigens is a halophilic purple nonsulfur bacterium and the sole species in the genus Rhodothalassium, which is itself the sole genus in the family Rhodothalassiaceae and sole family in the order Rhodothalassiales (class Alphaproteobacteria). The genome of this phylogenetically unique phototroph comprises 3.

COVID-19 health distress among autistic adults: Does psychological flexibility explain effects of health distress on mental health concerns?

In the United States, the COVID-19 Pandemic caused many autistic adults to be fearful and worried about their health. There is a lot of research that says that when autistic adults experience health distress it can worsen their mental health. We do not know, however, what might explain how experiencing health distress negatively affects mental health.

Evaluating sex and line differences in successive negative contrast and ethanol consumption using alcohol preferring and high alcohol drinking rats.

Background: The loss of a job or relationship are a couple of examples of unexpected reward loss. Life events, such as these can induce negative emotional reactions (e.g.

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.

The Use of Dansyl Chloride to Probe Protein Structure and Dynamics.

Dansyl labeling is a widely used approach for enhancing the detection of small molecules by UV spectroscopy and mass spectrometry. It has been successfully applied to identify and quantify a variety of biological and environmental specimens. Despite clear advantages, the dansylation reaction has found very few applications in the study of proteins.

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.

The Moderating Effect of Peer Attachment on Associations Between Children's and Adolescents' Cyberbullying Victimization, Bystanding, and Depressive Symptoms.

The primary objective of this short-term longitudinal study was to investigate how age groups affect the relationships between cyberbullying victimization, bystanding, and depression among a convenience sample of students across different educational levels; there was a total of 234 elementary school students (fourth and fifth graders), 363 middle school students (sixth to eighth graders), and 341 high school students (ninth to twelfth graders) from the United States who completed self-reported questionnaires on cyberbullying, depression, and peer attachment during 2020. Additionally, this study examined whether peer attachment acted as a moderator in these relationships. The results revealed that strong peer attachment significantly moderated the connections between cyberbullying involvement and depression, as measured six months later, with particularly pronounced effects among middle school students.

Antimicrobial Resistance in Curable Sexually Transmitted Infections.

Purpose Of Review: Antimicrobial resistance in sexually transmitted infections (STIs) has become an urgent global public health threat, raising the specter of untreatable infections. This review summarizes the determinants of resistance among the five most common curable STIs Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Treponema pallidum, and Trichomonas vaginalis, as well as strategies to mitigate the spread of resistance.

Recent Findings: Genetic mutations are key drivers of resistance for N.

Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria.

We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts.

Physiologic Pulmonary Phenotyping of Infants Born Preterm and Post-Discharge Respiratory Morbidity.

Objectives: To determine whether airway and parenchymal function identifies subgroups of infants born preterm according to the predominant pulmonary pathophysiology, and whether these subgroups have different risks for respiratory disease during infancy.

Study Design: We prospectively enrolled a cohort of 125 infants born preterm with planned clinical follow-up after NICU discharge. The study included monthly questionnaires for wheeze and visits to a physician or care provider for any respiratory illness.