Multiplexed single-cell imaging reveals diverging subpopulations with distinct senescence phenotypes during long-term senescence induction.

Cellular senescence is a phenotypic state that contributes to the progression of age-related disease through secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). Understanding the process by which healthy cells become senescent and develop SASP factors is critical for improving the identification of senescent cells and, ultimately, understanding tissue dysfunction. Here, we reveal how the duration of cellular stress modulates the SASP in distinct subpopulations of senescent cells.

Association of increased serum I-309 with phenotypes, disease activity, and cytokine pattern in primary Sjögren's syndrome.

The aim of this study was to determine serum I-309 levels in primary Sjögren's syndrome (pSS) patients, as well as the association with disease phenotype, systemic activity, and T helper cell-related cytokines. A total of 58 pSS patients and 30 healthy controls (HC) were enrolled in this study. The concentrations of serum I-309, interleukin-4 (IL-4), IL-6, IL-9, IL-13, IL-17, IL-22, IL-23, tumor-necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IFN-α, and IFN-β were measured with multiplex immunoassay.

Management of Systemic Anti-psoriatic Drugs in Psoriasis Patients with Concurrent Paraplegia or Tetraplegia: Insights From a 6-Year Multicenter, Retrospective Observational Study.

Introduction: Patients with psoriasis (PsO) and permanent spinal cord injuries (SCI) resulting in paraplegia and tetraplegia may experience a higher rate of infections compared to patients with PsO without SCI. It can result in further challenges for therapeutic management with immunosuppressants (biological and non-biological treatments). Thus,  we aimed to evaluate the rate of infections in patients with PsO and SCI treated with systemic immunosuppressants.

Hormone circuit explains why most HPA drugs fail for mood disorders and predicts the few that work.

Elevated cortisol in chronic stress and mood disorders causes morbidity including metabolic and cardiovascular diseases. There is therefore interest in developing drugs that lower cortisol by targeting its endocrine pathway, the hypothalamic-pituitary-adrenal (HPA) axis. However, several promising HPA-modulating drugs have failed to reduce long-term cortisol in mood disorders, despite effectiveness in other hypercortisolism conditions such as Cushing's syndrome.

Persimmon (Diospyros kaki L.) leaves accelerates skin tissue regeneration in excisional wound model: possible molecular mechanisms.

Persimmon (Diospyros kaki L.) leaves are a traditional medicinal herb used for treating many infectious and inflammatory-related conditions, including wound healing. To validate its traditional use, our study evaluates the acute toxicity and wound-healing effects of methanolic extracts of Persimmon (Diospyros kaki L.

Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.

Systemic IFN-I combined with topical TLR7/8 agonists promotes distant tumor suppression by c-Jun-dependent IL-12 expression in dendritic cells.

Dendritic cell (DC) activation by pattern recognition receptors like Toll-like-receptors (TLRs) is crucial for cancer immunotherapies. Here, we demonstrate the effectiveness of the TLR7/8 agonist imiquimod (IMQ) in treating both local tumors and distant metastases. Administered orally, IMQ activates plasmacytoid DCs (pDCs) to produce systemic type I interferons (IFN-I) required for TLR7/8 upregulation in DCs and macrophages, sensitizing them to topical IMQ treatment, which is essential for therapeutic efficacy.

Clinical spectrum of positional downbeat nystagmus: a diagnostic approach.

Positional downbeat nystagmus (pDBN) is a common finding in dizzy patients, with etiologies ranging from benign paroxysmal positional vertigo (BPPV) to central vestibular lesions. Although peripheral pDBN often presents with distinct clinical features that differentiate it from BPPV, diagnosing its etiology can be challenging. A thorough clinical evaluation, including the physical characteristics of the nystagmus, response to positional maneuvers, and neurological findings, is often sufficient to diagnose conditions that provoke pDBN such as anterior canal BPPV, atypical posterior canal BPPV, and central causes.

Clinical significance of PCT, CRP, IL-6, NLR, and TyG Index in early diagnosis and severity assessment of acute pancreatitis: A retrospective analysis.

To evaluate the clinical utility of PCT, CRP, IL-6, NLR, and TyG index in improving the early diagnosis and severity assessment of acute pancreatitis (AP). This retrospective study included 137 AP patients and 30 healthy controls from Hunan Provincial People's Hospital (January 2021-September 2023). Univariate and multivariate logistic regression analyses assessed the associations between biomarkers and severe acute pancreatitis (SAP).

CFD analysis of heat transfer enhancement in impinging jet array by varying number of jets and spacing.

Using the RANS approach with the standard k-ω turbulence model, this study offers a novel investigation into the dynamic and thermal properties of turbulent impinging jet arrays. Our study examines the combined effect of the number of jets (N) and the jet-jet spacing (S) on flow mechanisms and heat transfer performance, which is unique compared to previous research that frequently focuses on the individual effects of parameters. Through the investigation of the turbulent kinetic energy, friction coefficient, velocity contours, streamlines, pressure contours, and local and mean Nusselt numbers, we provide important information about how these parameters impact flow dynamics.

Individual-specific strategies inform category learning.

Categorization is an essential task for sensory perception. Individuals learn category labels using a variety of strategies to ensure that sensory signals, such as sounds or images, can be assigned to proper categories. Categories are often learned on the basis of extreme examples, and the boundary between categories can differ among individuals.

Skeletal abnormalities caused by a Connexin43 mutation in a mouse model for autosomal recessive craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD), a rare craniotubular disorder, occurs in an autosomal dominant (AD) or autosomal recessive (AR) form. CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones. Many patients with CMD suffer from neurological symptoms.

[Thoracoscopic minimally invasive surgery for the treatment of flail chest with multiple rib fractures].

Objective: To investigate the clinical efficacy of thoracoscopic minimally invasive surgery with nickel-titanium shape memory alloy wrap bone plate versus rib periosteal internal fixation in patients with multiple rib fractures (MRF) and flail chest.

Methods: A retrospective analysis was performed on 100 patients with MRF and flail chest treated with thoracoscopic minimally invasive surgery and internal fixation with rib fracture preservation between January 2019 and December 2022, including 54 males and 46 females, aged from 20 to 65 years old, with an average age of (38.0±18.

Remodeling the Proinflammatory Microenvironment in Osteoarthritis through Interleukin-1 Beta Tailored Exosome Cargo for Inflammatory Regulation and Cartilage Regeneration.

Osteoarthritis (OA) presents a significant therapeutic challenge, with few options for preserving joint cartilage and repairing associated tissue damage. Inflammation is a pivotal factor in OA-induced cartilage deterioration and synovial inflammation. Recently, exosomes derived from human umbilical cord mesenchymal stem cells (HucMSCs) have gained recognition as a promising noncellular therapeutic modality, but their use is hindered by the challenge of harvesting a sufficient number of exosomes with effective therapeutic efficacy.

Physical activity, cathepsin B, and cognitive health.

Regular physical activity (PA) is beneficial for cognitive health, and cathepsin B (CTSB) - a protease released by skeletal muscle during PA - acts as a potential molecular mediator of this association. PA-induced metabolic and mechanical stress appears to increase plasma/serum CTSB levels. CTSB facilitates neurogenesis and synaptic plasticity in brain regions (e.

Erector spinae plane block for management of acute opioid withdrawal in the emergency department: A case report.

Background: Gastrointestinal symptoms of acute opioid withdrawal are distressing for patients and are often difficult to manage with conventional therapies. Insufficiently managed opioid withdrawal symptoms may lead patients to leave against medical advice, which can increase their risk of relapse and result in poor outcomes from untreated conditions. We assessed the impact of an erector spinae plane block on the acute gastrointestinal symptoms of opioid withdrawal.

PD-1 cis-targeted IL-2v in combination with radiotherapy inhibits lung cancer growth and remodels the immune microenvironment.

Background: More efficient therapeutic options for non-small cell lung cancer (NSCLC) are needed as the survival at 5 years of metastatic disease is near zero. In this regard, we used a preclinical model of metastatic lung adenocarcinoma (SV2-OVA) to assess the safety and efficacy of novel radio-immunotherapy combining hypofractionated radiotherapy (HRT) with muPD1-IL2v immunocytokine and muFAP-CD40 bispecific antibody.

Methods: We evaluated the changes in the lung immune microenvironment at multiple timepoints following combination therapies and investigated their underlying antitumor mechanisms.

IMPACT OF PLANNED RESEARCH GAP YEAR ON UROLOGY RESIDENCY MATCH SUCCESS.

Objective: To assess the impact of a planned research gap year (RGY) on match outcomes and research productivity among urology residency applicants in the context of the highly competitive urology specialty and the new pass/fail format for the USMLE Step 1 exam.

Methods: We conducted an IRB-approved analysis of applicants to our program during the 2022-2023 and 2023-2024 application cycles. Data on demographics, medical school rank, having a home urology program, USMLE Step 1 scores, and ERAS research entries were collected.

Mastering the complexities of cancer nanomedicine with text mining, AI and automation.

In this contribution to the Orations - New Horizons of the Journal of Controlled Release, I present a personal perspective on the complexities of cancer nanomedicine and the approaches to master them. This oration draws mainly from my lab's journey to explore three transformative approaches to master complexities in the field: (1) leveraging text mining to construct dynamic knowledge bases for hypothesis generation in cell-specific drug delivery, (2) introducing the concept of meta-synergy to further optimize and classify multi-drug combinations across dimensions such as chemical loading, pharmacodynamics, and pharmacokinetics (3) utilizing automation to accelerate nanoparticle discovery with advanced screening methodologies such as aggregation-induced emission (AIE). I argue that by embracing complexity in nanomedicine, we can manifest new therapeutic possibilities, paving the way for more effective, precise, and adaptive treatment strategies.

An S100A8/A9 neutralizing antibody potently ameliorates contact hypersensitivity and atopic dermatitis symptoms.

Contact hypersensitivity (CHS) and atopic dermatitis (AD) are pervasive inflammatory skin diseases with similar symptoms, and the global prevalence of both conditions is steadily rising. Many compounds and biotics have been developed to target molecules critical to the etiology or pathogenesis of CHS and AD. However, such molecules are sometimes ineffective or lose potency over the therapeutic course.

Priming and release of cytokine IL-1β in microglial cells from the retina.

The P2X7 receptor (P2X7R) for extracellular ATP is implicated in several forms of retinal degeneration, including diabetic retinopathy, age-related macular degeneration, and glaucoma. P2X7R stimulation can trigger release of master cytokine IL-1β from microglia in the brain and from macrophages, but evidence of release from retinal microglia is indirect. Isolated mouse and rat retinal microglia, and wholemounts from CX3CR1 mice, were examined to determine if ATP induced IL-1β release directly from retinal microglial cells and if it also primed expression of IL-1β on an mRNA and protein level.