Discovery, synthesis, and biological mechanism evaluation of novel quinoline derivatives as potent NLRP3 inhibitors.

Targeting NLRP3 is a highly promising strategy for treating uncontrolled inflammation, which can cause a wide range of diseases or promote disease progression. More NLRP3-targeting inhibitors with different scaffolds are needed to increase the chances of developing safe and effective NLRP3 inhibitors and treating inflammation in different tissues. Here, we discovered the novel quinoline analogues that exhibit potent inhibitory activity against the NLRP3/IL-1β pathway in J774A.

T cell related osteoimmunology in fracture healing: Potential targets for augmenting bone regeneration.

Unlabelled: Last decade has witnessed increasing evidence which highlights the roles of immune cells in bone regeneration. Numerous immune cell types, including macrophages, T cells, and neutrophils are involved in fracture healing by orchestrating a series of events that modulate bone formation and remodeling. In this review, the role of T cell immunity in fracture healing has been summarized, and the modulatory effects of T cell immunity in inflammation, bone formation and remodeling have been highlighted.

Recent advances in immunotherapy targeting CETP proteins for atherosclerosis prevention.

Cholesteryl ester transfer protein (CETP) plays a key role in lipoprotein metabolism, and its activity has been linked to the risk of atherosclerosis (AS). CETP inhibitors, such as obicetrapib, represent a novel approach in immunotherapy to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) by targeting lipid metabolism. In addition, CETP vaccines are being explored as a novel strategy for the prevention and treatment of ASCVD by inducing the body to produce antibodies against CETP, which is expected to reduce CETP activity, thereby increasing high-density lipoproteins (HDL) levels.

TiO/CoO heterostructure decorated MIL-100(Fe) by atomic layer deposition for enhanced photocatalytic oxygen production.

Efficient separation of photogenerated charge carriers is essential for maximizing the photocatalytic efficiency of semiconductor materials in oxygen evolution reactions (OER). This study presents a novel trimetallic photocatalyst, MIL-100(Fe)/TiO/CoO, synthesized through a facile microwave-assisted hydrothermal method followed by atomic layer deposition (ALD). The porous MIL-100(Fe) serves as a support for the sequential deposition of TiO and CoO layers ALD, which enhances electron-hole pair separation and minimizes their recombination.

Multiscale Hierarchical Micro- and Nano-Surface Induced by High-Repetition-Rate Femtosecond Laser Promote Peri-Implant Osseointegration.

Micro- and nanomorphological modification and roughening of titanium implant surfaces can enhance osseointegration; however, the optimal morphology remains unclear. Laser processing of implant surfaces has demonstrated significant potential due to its precision, controllability, and environmental friendliness. Femtosecond lasers, through precise optimization of processing parameters, can modify the surface of any solid material to generate micro- and nanomorphologies of varying scales and roughness.

AAVone: A Cost-Effective, Single-Plasmid Solution for Efficient AAV Production with Reduced DNA Impurities.

Currently, the most common approach for manufacturing GMP-grade adeno-associated virus (AAV) vectors involves transiently transfecting mammalian cells with three plasmids that carry the essential components for production. The requirement for all three plasmids to be transfected into a single cell and the necessity for high quantities of input plasmid DNA, limits AAV production efficiency, introduces variability between production batches, and increases time and labor costs. Here, we developed an all-in-one, single-plasmid AAV production system, called AAVone.

Dynamic Self-Reconstruction Heterostructures: Boosting the High-Stability for Hydrogen Evolution of NiMo Alloys in Acidic Environments.

Electrocatalytic water splitting is considered one of the most promising approaches for large-scale hydrogen production. However, designing transition metal catalysts with high durability under acidic conditions remains a significant challenge. The durability of the catalyst is closely related to the changes of the catalyst during its operation, and constructing effective surface reconstruction strategies can help address the durability issues of transition metals in acidic hydrogen evolution reactions (HER).

Neutrophils exhibit flexible migration strategies and trail formation mechanisms on varying adhesive substrates.

Substrate anchorage is essential for cell migration, and actin polymerization at cell front and myosin contractility at cell rear are known to govern cell forward movement. Yet their differential driving strategies for neutrophil migration on distinct adhesiveness substrates and their contributions to the migration-induced trail formation remain unclear. Here we explore the morphological changes, migration dynamics, and trail formation of neutrophils on ICAM-1 and PLL substrates, with a focus on the relationships among adhesive forces, traction forces, and out-of-plane forces.

Probe into the treatment of tinnitus by acupuncture combined with medicine under the mechanism of pathophysiology: A review.

Tinnitus is a common medical disorder. The risk factors include hearing loss, ototoxic medications, head injuries, and depression. Therefore, ear disorders, anxiety, and depression should be considered in the treatment of tinnitus.

HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV.

Chronic HIV infection can dysregulate lipid/cholesterol metabolism in the peripheral system, contributing to the higher incidences of diabetes and atherosclerosis in HIV (+) individuals. Recently, accumulating evidence indicate that HIV proteins can also dysregulate lipid/cholesterol metabolism in the brain and such dysregulation could be linked with the pathogenesis of HIV-associated neurological disorders (HAND)/NeuroHIV. To further characterize the association between lipid/cholesterol metabolism and HAND, we employed HIV-inducible transactivator of transcription (iTAT) and control mice to compare their brain lipid profiles.

Polyprenylated xanthones with potential anti-inflammatory and anti-HIV effects from the stems and leaves of (Lour.) Blume.

A phytochemical study on the stems and leaves of (Lour.) Blume resulted in the isolation and characterisation of a new polyprenylated xanthone, cratocochinone (), as well as seven known analogues, fuscaxanthone K (), pruniflorone Q (), 1,3,5,8-tetrahy-droxy- 2-(3-methybut-2-enyl)-4-(3,7-dimethylocta-2,6-dienyl) xanthone (), cochinensoxanthone (), cratoxylum-xanthone B (), cochinchinone I () and cochinchinone K (). The chemical structure of was determined by comprehensive spectral analyses.

Genome-Wide Identification and Characterization of Ammonium Transporter (AMT) Genes in .

Ammonium transporters (AMTs) are vital plasma membrane proteins facilitating NH uptake and transport, crucial for plant growth. The identification of favorable AMT genes is the main goal of improving ammonium-tolerant algas. However, there have been no reports on the systematic identification and expression analysis of () AMT genes.

Advances on T cell immunity in bone remodeling and bone regeneration.

Bone remodeling and bone regeneration are essential for preserving skeletal integrity and maintaining mineral homeostasis. T cells, as key members of adaptive immunity, play a pivotal role in bone remodeling and bone regeneration by producing a range of cytokines and growth factors. In the physiological state, T cells are involved in the maintenance of bone homeostasis through interactions with mesenchymal stem cells, osteoblasts, and osteoclasts.

Oxidizing Role of Cu Cocatalysts in Unassisted Photocatalytic CO Reduction Using p-GaN/AlO/Au/Cu Heterostructures.

Photocatalytic CO reduction to CO under unassisted (unbiased) conditions was recently demonstrated using heterostructure catalysts that combine p-type GaN with plasmonic Au nanoparticles and Cu nanoparticles as cocatalysts (p-GaN/AlO/Au/Cu). Here, we investigate the mechanistic role of Cu in p-GaN/AlO/Au/Cu under unassisted photocatalytic operating conditions using Cu K-edge X-ray absorption spectroscopy and first-principles calculations. Upon exposure to gas-phase CO and HO vapor reaction conditions, the composition of the Cu nanoparticles is identified as a mixture of Cu and Cu oxide, hydroxide, and carbonate compounds without metallic Cu.

Two-year survival after scheduled extubation in patients with pneumonia or ARDS: a prospective observational study.

Purpose: To report two-year survival after scheduled extubation in patients with pneumonia or acute respiratory distress syndrome (ARDS).

Methods: This was a prospective observational study performed in a respiratory ICU of a teaching hospital. Pneumonia or ARDS patients who successfully completed a spontaneous breathing trial were enrolled.

Precision in Action: The Role of Clustered Regularly Interspaced Short Palindromic Repeats/Cas in Gene Therapies.

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated enzyme-CAS holds great promise for treating many uncured human diseases and illnesses by precisely correcting harmful point mutations and disrupting disease-causing genes. The recent Food and Drug Association (FDA) approval of the first CRISPR-based gene therapy for sickle cell anemia marks the beginning of a new era in gene editing. However, delivering CRISPR specifically into diseased cells in vivo is a significant challenge and an area of intense research.

S309-CAR-NK cells bind the Omicron variants and reduce SARS-CoV-2 viral loads in humanized ACE2-NSG mice.

Unlabelled: Recent progress on chimeric antigen receptor (CAR)-NK cells has shown promising results in treating CD19-positive lymphoid tumors with minimal toxicities [including graft versus host disease (GvHD) and cytokine release syndrome (CRS) in clinical trials. Nevertheless, the use of CAR-NK cells in combating viral infections has not yet been fully explored. Previous studies have shown that CAR-NK cells expressing S309 single-chain fragment variable (scFv), hereinafter S309-CAR-NK cells, can bind to SARS-CoV-2 wildtype pseudotyped virus (PV) and effectively kill cells expressing wild-type spike protein .

PaCO is nonlinearly associated with NIV failure in patients with hypoxemic respiratory failure.

Objective: To explore the association between PaCO and noninvasive ventilation (NIV) failure in patients with hypoxemic respiratory failure.

Methods: A retrospective study was performed in a respiratory ICU of a teaching hospital. Patients admitted to ICU between 2011 and 2019 were screened.

SAH is a major metabolic sensor mediating worsening metabolic crosstalk in metabolic syndrome.

In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia and in human coronary artery disease by analyzing metabolic profiles. We found that HHcy worsening is most sensitive to other metabolic disorders. To identify metabolic genes and metabolites responsible for the worsening metabolic crosstalk, we examined mRNA levels of 324 metabolic genes in Hcy, glucose-related and lipid metabolic systems.

Interplay between lipid dysregulation and ferroptosis in chondrocytes and the targeted therapy effect of metformin on osteoarthritis.

Introduction: Osteoarthritis (OA) is a devastating whole-joint disease affecting a large population worldwide; the role of lipid dysregulation in OA and mechanisms underlying targeted therapy effect of lipid-lowering metformin on OA remains poorly defined.

Objectives: To investigate the effects of lipid dysregulation on OA progression and to explore lipid dysregulation-targeting OA treatment of metformin.

Methods: RNA-Seq data, biochemical, and histochemical assays in human and murine OA cartilage as well as primary chondrocytes were utilized to determine lipid dysregulation.

Modulating the Primary and Secondary Coordination Spheres of Single Ni(II) Sites in Metal-Organic Frameworks for Boosting Photocatalysis.

Though the coordination environment of single metal sites has been recognized to be of great importance in promoting catalysis, the influence of simultaneous precise modulation of primary and secondary coordination spheres on catalysis remains largely unknown. Herein, a series of single Ni(II) sites with altered primary and secondary coordination spheres have been installed onto metal-organic frameworks (MOFs) with UiO-67 skeleton, affording UiO-Ni-X-Y (X = S, O; Y = H, Cl, CF) with X and Y on the primary and secondary coordination spheres, respectively. Upon deposition with CdS nanoparticles, the resulting composites present high photocatalytic H production rates, in which the optimized CdS/UiO-Ni-S-CF exhibits an excellent activity of 13.

Design, synthesis and biological evaluation of tanshinone IIA derivatives as NLRP3 inflammasome inhibitors.

Natural product structures have long provided valuable pharmacophores and even candidates for drug discovery. Tanshinone scaffold showed moderately inhibitory activity in NLRP3 inflammasome/IL-1β pathway. Herein, we designed a series of derivatives on different regions of Tanshinone IIA (TNA) scaffold.