PD-L1 expression and immune profiling cannot predict osimertinib efficacy in lung cancer with EGFR T790 M mutation: A translational study.

Background: PD-L1 is associated with poor efficacy of first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in untreated EGFR-mutant non-small-cell lung cancer (NSCLC). Whether PD-L1 is also predictive of osimertinib efficacy in pre-treated patients with an acquired EGFR T790 M mutation is unclear.

Patients And Methods: PD-L1 expression and tumor microenvironments were evaluated in tumors from EGFR-mutant T790 M + NSCLC patients treated with osimertinib.

Interleukin-37 exacerbates liver inflammation and promotes IFN-γ production in NK cells.

Interleukin (IL)-37, a unique member of the IL-1 family, is known for its anti-inflammatory properties. However, its effects on immune-mediated liver diseases, such as primary biliary cholangitis (PBC) and acute immune-mediated hepatitis, remain unclear. Using mouse models of autoimmune cholangitis and hepatitis induced by 2-OA-OVA and concanavalin A (Con A) respectively, we introduced the human IL-37 gene via a liver-preferred adeno-associated virus vector (AAV-IL-37) to mice, as mice lack endogenous IL-37.

Novel Isoalantolactone-Based Derivatives as Potent NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization.

The NLRP3 inflammasome has been recognized as a promising therapeutic target in drug discovery for inflammatory diseases. Our initial research identified a natural sesquiterpene isoalantolactone (IAL) as the active scaffold targeting NLRP3 inflammasome. To improve its activity and metabolic stability, a total of 64 IAL derivatives were designed and synthesized.

Recommendations for physical activity and exercise in persons living with Systemic Lupus Erythematosus (SLE): consensus by an international task force.

Objective: This international task force aimed to provide healthcare professionals and persons living with systemic lupus erythematosus (SLE) with consensus-based recommendations for physical activity and exercise in SLE.

Methods: Based on evidence from a systematic literature review and expert opinion, 3 overarching principles and 15 recommendations were agreed on by Delphi consensus.

Results: The overarching principles highlight the importance of shared decision-making and the need to explain the benefits of physical activity to persons living with SLE and other healthcare providers.

A Lung Cancer Mouse Model Database.

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. Here we established the Lung Cancer Mouse Model Database (LCMMDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model.

Morphologies and magnetic properties of α-FeO nanoparticles calcined at different temperatures.

Different morphologies and sizes of α-FeO were prepared by a coprecipitation method using polyvinylpyrrolidone as a dispersant. In the preparation process, homogeneous and dispersed nanoscale FeOOH particles were first obtained by the coprecipitation method, and then the FeOOH particles were calcined at high temperature to form α-FeO. The growth and aggregation of the α-FeO particles at different calcination temperatures resulted in α-FeO powders with diversiform morphologies (nanoscale microsphere, pinecone ellipsoidal, polyhedral, and quasi-spherical structures).

Correlation of Hematological Indices and Acute-Phase Reactants in Rheumatoid Arthritis Patients on Disease-Modifying Antirheumatic Drugs: A Retrospective Cohort Analysis.

Acute-phase markers are often used to evaluate the disease activity of rheumatoid arthritis (RA). Occasionally, the serum levels of acute-phase reactants remain normal in patients with obvious inflamed joints. Hematological indices derived from complete blood counts have been shown to correlate with disease activity.

High-fat diet induces C-reactive protein secretion, promoting lung adenocarcinoma via immune microenvironment modulation.

To understand the effects of a high-fat diet (HFD) on lung cancer progression and biomarkers, we here used an inducible mutant epidermal growth factor receptor (EGFR)-driven lung cancer transgenic mouse model fed a regular diet (RD) or HFD. The HFD lung cancer (LC-HFD) group exhibited significant tumor formation and deterioration, such as higher EGFR activity and proliferation marker expression, compared with the RD lung cancer (LC-RD) group. Transcriptomic analysis of the lung tissues revealed that the significantly changed genes in the LC-HFD group were highly enriched in immune-related signaling pathways, suggesting that an HFD alters the immune microenvironment to promote tumor growth.

Behavioral Health Care Delivery Through Street Medicine Programs in California.

Mental health and substance use disorders are prevalent among people experiencing homelessness. Street Medicine can reach unhoused people who face barriers to accessing healthcare in more traditional medical settings including shelter-based clinics. However, there is little guidance on best practices for mental health and substance use treatment through Street Medicine.

Proteomic analysis identifies subgroups of patients with active systemic lupus erythematosus.

Objective: Systemic lupus erythematosus (SLE) is a clinically and biologically heterogenous autoimmune disease. We aimed to investigate the plasma proteome of patients with active SLE to identify novel subgroups, or endotypes, of patients.

Method: Plasma was collected from patients with active SLE who were enrolled in the British Isles Lupus Assessment Group Biologics Registry (BILAG-BR).

MiR-503 pleiotropically regulates epithelial-mesenchymal transition and targets PTK7 to control lung cancer metastasis.

Objective: In lung cancer patients, most deaths are caused by the distant dissemination of cancer cells. Epithelial-mesenchymal transition (EMT) and collective cell migration are distinct and important mechanisms involved in cancer invasion and metastasis. Additionally, microRNA dysregulation contributes significantly to cancer progression.

Senomorphic effect of diphenyleneiodonium through AMPK/MFF/DRP1 mediated mitochondrial fission.

With an aging population and the numerous health impacts associated with old age, the identification of anti-aging drugs has become an important new research direction. Although mitochondria have been recognized to affect aging, anti-aging drugs specifically targeting the mitochondria are less well characterized. In this study, diphenyleneiodonium (DPI) was identified as a potential senomorphic drug that functions by promoting mitochondrial fission.

Apolipoprotein A1 suppresses the hypoxia-induced angiogenesis of human retinal endothelial cells by targeting PlGF.

Aim: To investigate the anti-angiogenic effect of apolipoprotein A1 (apoA1) on primary human retinal vascular endothelial cells (HRECs) and explore the possible mechanism.

Methods: The primary HRECs were transfected with apoA1-GFP recombinant lentiviral and were compared with cells undergoing transfection with empty lentiviral vectors. Hypoxia chambers were used to simulate the anoxic environment of cells under pathological condition.

Acute Orbital Apex Syndrome Caused by Idiopathic Sclerosing Orbital Inflammation.

Idiopathic sclerosing orbital inflammation (ISOI) is a distinct entity among other orbital diseases. It is characterized by marked fibrosis and inflammatory cell infiltration that can damage orbital structures. Clinical manifestations were variable, including ocular and periocular redness, proptosis, and pain.

Tissue Proteogenomic Landscape Reveals the Role of Uncharacterized SEL1L3 in Progression and Immunotherapy Response in Lung Adenocarcinoma.

The fundamental pursuit to complete the human proteome atlas and the unmet clinical needs in lung adenocarcinoma have prompted us to study the functional role of uncharacterized proteins and explore their implications in cancer biology. In this study, we characterized SEL1L3, a previously uncharacterized protein encoded from chromosome 4 as a dysregulated protein in lung adenocarcinoma from the large-scale tissue proteogenomics data set established using the cohort of Taiwan Cancer Moonshot. SEL1L3 was expressed in abundance in the tumor parts compared with paired adjacent normal tissues in 90% of the lung adenocarcinoma patients in our cohorts.

Idiopathic Multicentric Castleman Disease with Strikingly Elevated IgG4 Concentration in the Serum and Abundant IgG4-Positive Cells in the Tissue: A Case Report.

Idiopathic multicentric Castleman disease (iMCD) can be challenging to distinguish clinically and histopathologically from Immunoglobulin G4-related disease (IgG4RD). A 73-year-old man was referred to a rheumatologist for suspected autoimmune-related polyclonal hypergammaglobulinemia. The patient had a history of multiple lymphadenopathies in the neck for over 20 years.

Assessment of the Impact on 20 Pelagic Fish Species by the Taiwanese Small-Scale Longline Fishery in the Western North Pacific Using Ecological Risk Assessment.

Ecological risk assessment (ERA) has been applied on assessing the relative risk of bycatch species in recent years. ERA index is calculated by productivity of species and susceptibility of fisheries on fish species. In this study, a semi-quantitative method was used to evaluate the risks of exploitation for 20 pelagic fish species by the small-scale longline fisheries in the western North Pacific Ocean.

HLJ1 amplifies endotoxin-induced sepsis severity by promoting IL-12 heterodimerization in macrophages.

Heat shock protein (HSP) 40 has emerged as a key factor in both innate and adaptive immunity, whereas the role of HLJ1, a molecular chaperone in HSP40 family, in modulating endotoxin-induced sepsis severity is still unclear. During lipopolysaccharide (LPS)-induced endotoxic shock, HLJ1 knockout mice shows reduced organ injury and IFN-γ (interferon-γ)-dependent mortality. Using single-cell RNA sequencing, we characterize mouse liver nonparenchymal cell populations under LPS stimulation, and show that HLJ1 deletion affected IFN-γ-related gene signatures in distinct immune cell clusters.