LAPTM5 Confers the Resistance to Venetoclax via Promoting the Autophagosome-Lysosome Fusion in Multiple Myeloma.

Multiple myeloma (MM) is a haematological lymphoid malignancy marked by significant morbidity due to severe complications. Despite advances in targeted therapies, including proteasome inhibitors and the BCL-2 inhibitor venetoclax, drug resistance frequently occurs, with the underlying mechanisms poorly understood. This study investigates the role of lysosome-associated protein transmembrane 5 (LAPTM5) in conferring resistance to venetoclax in relapsed MM.

Restorative Effects of Short-Chain Fatty Acids on Corneal Homeostasis Disrupted by Antibiotic-Induced Gut Dysbiosis.

The gut microbiota plays a crucial regulatory role in various physiological processes, yet its impact on corneal homeostasis remains insufficiently understood. Here, we investigate the effects of antibiotic-induced gut dysbiosis (AIGD) and germ-free (GF) conditions on circadian gene expression, barrier integrity, nerve density, and immune cell activity in the corneas of mice. Through RNA sequencing, we found that both AIGD and GF conditions significantly disrupted the overall transcriptomic profile and circadian transcriptomic oscillations in the cornea.

Dual (oxy)hydroxide Cocatalyst Synergistically Boosts Solar Water Splitting of BiVO Photoanode.

Bismuth oxide (BiVO) is considered one of the most promising semiconductors for photoelectrochemical (PEC) water splitting due to its highly theoretical photocurrent of 7.5 mA cm. However, its sluggish kinetics and severe photocorrosion still hinder the real application of a large-area BiVO photoanode.

Conjugated hypercrosslinked polymers for in situ imprinting, selective sorption, and fluorescent turn-on sensing of oxalic acid.

Hypercrosslinked polymer (HCP) is a subclass of porous organic polymer possessing abundant microporosity, tailor-made functionality, and excellent stability. It features low-cost and easily direct knitting synthesis, facilitating the construction of π-conjugated frameworks with fluorescent properties by properly selecting building blocks (BBs) and linkers. Simultaneous imprinting of target molecules into the conjugated HCPs will create selective sorbents and sensors.

Physical-Matched Nanoplatelets Boost Heterogeneous Thrombi Targeting Through Self-Adaptive Deformation for Thrombolysis and Endothelial Repairing.

The heterogeneity of thrombi in terms of composition, structure, and blood rheology parameters presents a challenge for effective thrombus-targeting drug delivery. To address this, a self-adaptive nano-delivery system, termed D-PLT, is developed. It consists of platelet membrane-cloaked deformable mesoporous organic silicon dioxide nanocomposite, enabling it to respond to the challenge of the heterogeneity of thrombi in arteries and veins.

Effects of pedagogical intervention on Chinese EFL learners' use of motivational regulation strategies and oral English proficiency improvement.

This study investigated the role of motivational regulation strategies (MRSs) in English as a foreign language (EFL) pedagogy, with a focus on Chinese university students. While prior research has explored MRSs, their specific impact on the oral proficiency of Chinese EFL learners remains under-examined. This mixed-methods research offers empirical insights, advocating for the integration of MRSs into EFL instruction to bolster students' oral proficiency.

Mobile genetic elements contributing to horizontal gene transfer of blaNDM among Escherichia coli in the community setting.

Objective: To investigate the distribution of carbapenem-resistant Enterobacterales (CRE) in the community and to describe the genomic characteristics.

Methods: CRE screened from fecal samples in healthy people at the health examination center of a tertiary hospital in China underwent Whole genome sequencing (WGS) to analyze genotypic characteristics of CRE. The flanking DNA sequence of blaNDM-5 and mcr1.

Cyclodextrin-Based Nanogels for Stabilization and Sensing of Curcumin.

Curcumin (CUR), a polyphenolic substance from turmeric, displays diverse medicinal properties. However, its instability poses challenges in detection. Cyclodextrin-based nanogels (CyDngs) offer a transformative solution, enhancing CUR's stability in aqueous solutions.

Inhibition of Salmonella typhimurium and Listeria monocytogenes in coconut juice by graphene-doped photocatalyst rGO/TiO.

This research used the photocatalyst rGO/TiO prepared by hydrothermal method to inhibit the growth of these microorganisms in water and coconut juice. In coconut juice, the initial count of Salmonella typhimurium decreased from 3 × 10 CFU /mL to 6.3 × 10 CFU /mL, and the initial count of L.

Crosstalk between GBP2 and M2 macrophage promotes the ccRCC progression.

Clear cell renal cell carcinoma (ccRCC) represents a highly heterogeneous kidney malignancy associated with the poorest prognosis. The metastatic potential of advanced ccRCC tumors is notably high, posing significant clinical challenges. There is an urgent imperative to develop novel therapeutic approaches to address ccRCC metastasis.

Investigation of pyroptosis-related hub genes and the immune microenvironment in primary Sjögren's syndrome.

Objectives: Primary Sjögren's syndrome (pSS) is an inflammatory systemic autoimmune disease, while the role and mechanisms of pyroptosis in pSS remain largely undefined.

Methods: Pyroptosis-related genes and gene expression data were obtained from the Molecular Signatures Database and NCBI GEO databases. Differentially expressed genes (DEGs) and pyroptosis-related hub genes were identified by R software.

Discovery of a Highly Potent, Selective and Efficacious USP7 Degrader for the Treatment of Acute Lymphoblastic Leukemia.

USP7 is an attractive therapeutic target for cancers, especially for acute lymphoblastic leukemia (ALL) with wild-type p53. Herein, we report the discovery of as a highly potent, selective and efficacious USP7 proteolysis-targeting chimera degrader. achieves DC values of 0.

Boron Neutron Capture Therapy-Derived Extracellular Vesicles via DNA Accumulation Boost Antitumor Dendritic Cell Vaccine Efficacy.

Radiated tumor cell-derived extracellular vesicles (RT-EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT-EVs, thus the low abundance of DNA fragments limits immune responses of RT-EVs. Here, this study found that different radiations affected fates of DNA fragments in RT-EVs.

MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.

Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events.

Epidemiological and genomic characteristics of global blaNDM-carrying Escherichia coli.

Background: Escherichia. coli is the most frequent host for New Delhi metallo-β-lactamase (NDM) which hydrolyzes almost all β-lactams except aztreonam. The worldwide spread of blaNDM-carrying E.

LAPTM4B counteracts ferroptosis via suppressing the ubiquitin-proteasome degradation of SLC7A11 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide, necessitating the identification of novel therapeutic targets. Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is involved in biological processes critical to cancer progression, such as regulation of solute carrier transporter proteins and metabolic pathways, including mTORC1. However, the metabolic processes governed by LAPTM4B and its role in oncogenesis remain unknown.

Activation of the SST-SSTR5 signaling pathway enhances corneal wound healing in diabetic mice.

Corneal wound healing in diabetic patients is usually delayed and accompanied by excessive inflammation. However, the underlying cellular and molecular mechanisms remain poorly understood. Here, we found that somatostatin (SST), an immunosuppressive peptide produced by corneal nerve fibers, was significantly reduced in streptozotocin-induced diabetic mice.

Opioid Coprescription Through Risk Mitigation Guidance and Opioid Agonist Treatment Receipt.

Importance: At the onset of the COVID-19 pandemic, the government of British Columbia, Canada, released clinical guidance to support physicians and nurse practitioners in prescribing pharmaceutical alternatives to the toxic drug supply. These alternatives included opioids and other medications under the risk mitigation guidance (RMG), a limited form of prescribed safer supply, designed to reduce the risk of SARS-CoV-2 infection and harms associated with illicit drug use. Many clinicians chose to coprescribe opioid medications under RMG alongside opioid agonist treatment (OAT).

Boron-Containing Mesoporous Silica Nanoparticles with Effective Delivery and Targeting of Liver Cancer Cells for Boron Neutron Capture Therapy.

Nanocarriers have been researched comprehensively for the development of novel boron-containing agents in boron neutron capture therapy (BNCT). We designed and synthesized a multifunctional mesoporous silica nanoparticle (MSN)-based boron-containing agent. The latter was coated with a lipid bilayer (LB) and decorated with SP94 peptide (SFSIIHTPILPL) on the surface as SP94-LB@BA-MSN.

What is the ideal time to begin tapering opioid agonist treatment? A protocol for a retrospective population-based comparative effectiveness study in British Columbia, Canada.

Introduction: Opioid agonist treatment (OAT) tapering involves a gradual reduction in daily medication dose to ultimately reach a state of opioid abstinence. Due to the high risk of relapse and overdose after tapering, this practice is not recommended by clinical guidelines, however, clients may still request to taper off medication. The ideal time to initiate an OAT taper is not known.

Modular Microgel-Based Bioassembly Scaffold Induced Chondrogenic and Osteogenic Differentiation of BMSCs.

Bioactive scaffolds capable of simultaneously repairing osteochondral defects remain a big challenge due to the heterogeneity of bone and cartilage. Currently modular microgel-based bioassembly scaffolds are emerged as potential solution to this challenge. Here, microgels based on methacrylic anhydride (MA) and dopamine modified gelatin (GelMA-DA) are loaded with chondroitin sulfate (CS) (the obtained microgel named GC Ms) or bioactive glass (BG) (the obtained microgel named GB Ms), respectively.

A Dual Functional Bioinspired Lubricant for Osteoarthritis Treatment and Potential Prevention.

Osteoarthritis (OA), primarily characterized by the deterioration of articular cartilage, is a highly prevalent joint-disabling disease. The pathological onset and progression of OA are closely related to cartilage lubrication dysfunction and synovial inflammation. Synergistic options targeted at restorative lubrication and anti-inflammation are expected to be the most attractive candidates to treat OA and perhaps help prevent it.

Impact of physicochemical properties on biological effects of lipid nanoparticles: Are they completely safe.

Lipid nanoparticles (LNPs) are promising materials and human-use approved excipients, with manifold applications in biomedicine. Researchers have tended to focus on improving the pharmacological efficiency and organ targeting of LNPs, while paid relatively less attention to the negative aspects created by their specific physicochemical properties. Here, we discuss the impacts of LNPs' physicochemical properties (size, surface hydrophobicity, surface charge, surface modification and lipid composition) on the adsorption-transportation-distribution-clearance processes and bio-nano interactions.