Hexamethylene amiloride induces lysosome-mediated cell death in multiple myeloma through transcription factor E3.

Multiple myeloma (MM) is the second common hematological malignancy characterized by the abnormal proliferation of plasma cells. Although advances in the past decades have led to improved outcomes and longer survival, MM remains largely incurable. New targets and targeted therapy may help to achieve better outcomes.

Insights into the transcriptomic heterogeneity of brain endothelial cells in normal aging and Alzheimer's disease.

Drug development for Alzheimer's disease Is extremely challenging, as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-β cascade hypothesis. More recently, advances in the development of Lecanemab, an anti-amyloid-β monoclonal antibody, have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early- stage Alzheimer's disease in the Phase III clinical trial (Clarity Alzheimer's disease). Despite these promising results, side effects such as amyloid-related imaging abnormalities (ARIA) may limit its usage.

Idarubicin-loaded degradable hydrogel for TACE therapy enhances anti-tumor immunity in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common and deadly cancer, often diagnosed at advanced stages, limiting surgical options. Transcatheter arterial chemoembolization (TACE) is a primary treatment for inoperable and involves the use of drug-eluting microspheres to slowly release chemotherapy drugs. However, patient responses to TACE vary, with some experiencing tumor progression and recurrence.

Myeloid response evaluated by noninvasive CT imaging predicts post-surgical survival and immune checkpoint therapy benefits in patients with hepatocellular carcinoma.

Background: The potential of preoperative CT in the assessment of myeloid immune response and its application in predicting prognosis and immune-checkpoint therapy outcomes in hepatocellular carcinoma (HCC) has not been explored.

Methods: A total of 165 patients with pathological slides and multi-phase CT images were included to develop a radiomics signature for predicting the imaging-based myeloid response score (iMRS). Overall survival (OS) and recurrence-free survival (RFS) were assessed according to the iMRS risk group and validated in a surgical resection cohort ( = 98).

Wearable Systems of Reconfigurable Microneedle Electrode Array for Subcutaneous Multiplexed Recording of Myoelectric and Electrochemical Signals.

The real-time monitoring of in vivo electrophysiological and biochemical signals provides critical insights into the activities of tissues and organs. As the activity and metabolic state of different sites in the muscle vary, multichannel detection is necessary to capture the functional state of the whole muscle, yet the access to the bio-information in subcutaneous space remained challenging. This work reports the development of a reconfigurable microneedle electrode array integrated system designed to achieve painless and minimally invasive monitoring of subcutaneous electromyogram (EMG), oxygen species, and pH through an array of thumbtack-shaped microneedle (TSMN) electrode.

Causal association of inflammation with ischemic stroke and its subtypes: a bidirectional Mendelian randomization study.

Background: Emerging evidence underscores a bidirectional relationship between ischemic stroke (IS) and inflammation, yet the causality of this association remains uncertain. We conducted a two-sample bidirectional Mendelian randomization (MR) study aimed at investigating the causal links between inflammation and IS.

Methods: Single nucleotide polymorphism from genome-wide association studies of 112 inflammatory cytokines and IS were chosen as instrumental variables.

C3G improves lipid droplet accumulation in the proximal tubules of high-fat diet-induced ORG mice.

Obesity-related glomerulopathy (ORG) represents an escalating public health with no effective treatments currently available. Abnormal lipid metabolism and lipid droplet deposition in the kidneys are key contributors to ORG. Cyanidin-3-glucoside (C3G) has shown potential in regulating lipid metabolism and may offer reno-protective effects; however, its therapeutic efficacy and underlying mechanisms in ORG remain unclear.

Dual-Enhanced SERS Satellite Immuno-Nanocomplex for Multiple PSA-Mediated PHI Assay Toward Clinical Prostate Cancer Screening.

Prostate specific antigen (PSA) is widely used in liquid biopsy of prostate cancer (PCa) but still faces challenges due to the poor specificity. Herein, this study reports a double-SERS satellite immunoassay, made of an Au-Ag dealloyed intra-nanogap nanoflower (Au-Ag DINF) with strong SERS signals and Au magnetic nanoparticles (AuMNPs) with magnetic capture and SERS amplification, for sensing multiple PSA (free PSA (fPSA), complexed PSA (cPSA) and [-2]proPSA (p2PSA)) toward potential PCa screening. Unlike the previous studies focus on the tPSA and fPSA/tPSA ratio (f/t PSA%), this work introduces a multiple PSA-mediated Prostate Health Index (PHI) assay with significantly increased the predictive accuracy and specificity of PCa, especially the patients with a tPSA level in the "diagnostic gray zone".

An international Delphi consensus on patient preparation for metabolic and bariatric surgery.

Global obesity rates have risen dramatically, now exceeding deaths from starvation. Metabolic and bariatric surgery (MBS), initially for severe obesity (BMI ≥35 kg/m), is performed globally over 500 000 times annually, offering significant metabolic benefits beyond weight loss. However, varying eligibility criteria globally impact patient care and healthcare resources.

A multimodal model in the prediction of the delivery mode using data from a digital twin-empowered labor monitoring system.

Objective: This study aims to address the limitations of current clinical methods in predicting delivery mode by constructing a multimodal neural network-based model. The model utilizes data from a digital twin-empowered labor monitoring system, including computerized cardiotocography (cCTG), ultrasound (US) examination data, and electronic health records (EHRs) of pregnant women.

Methods: The model integrates three modalities of data from 105 pregnant women (76 vaginal deliveries and 29 cesarean deliveries) at the Department of Obstetrics and Gynecology of The First Affiliated Hospital of Jinan University, Guangzhou, China.

Extracellular vesicles-based vaccines: Emerging immunotherapies against cancer.

Cancer vaccines are promising therapeutic approaches to enhance specific T-cell immunity against most solid tumors. By stimulating anti-tumor immunity, clearing minimal residual disease, and minimizing adverse effects, these vaccines target tumor cells and are effective when combined with immune checkpoint blockade or other immunotherapies. However, the development of tumor cell-based vaccines faces quality issues due to poor immunogenicity, tumor heterogeneity, a suppressive tumor immune microenvironment, and ineffective delivery methods.

Conversion of human glial cells into neurons in ex vivo culture of human brain tissue: essential roles of the transcription factors NeuroD1 and Ascl1.

Transcription factor-mediated cell conversion has been reported in the central nervous system of both rodents and nonhuman primates. In particular, glia-to-neuron conversion has been achieved in the brain and spinal cord of animal models for neural regeneration and repair. However, whether glia-to-neuron conversion can be used for brain repair in humans needs to be explored.

Novel benzothiazole derivatives target the Gac/Rsm two-component system as antibacterial synergists against infections.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, (IC = 43.

Hypoimmunogenic CD19 CAR-NK cells derived from embryonic stem cells suppress the progression of human B-cell malignancies in xenograft animals.

Background: Chimeric antigen receptor (CAR) engineered natural killer (NK) cells exhibit advantages such as MHC-independent recognition and strong anti-tumor functions. However, allogeneic CAR-NK cells derived from human tissues are heterogeneous and susceptible to clearance by hosts.

Methods: We generated a B2M knockout, HLA-E and CD19 CAR ectopic expressing embryonic stem cell (ESC) line, which differentiated normally and gave rise to homogeneous CD19 CAR-NK (CD19 CAR-UiNK) cells using an organoid aggregate induction method.

Linking Gut Microbiota, Oral Microbiota, and Serum Metabolites in Insomnia Disorder: A Preliminary Study.

Purpose: Despite recent findings suggesting an altered gut microbiota in those suffering from insomnia disorder (ID), research into the gut microbiota, oral microbiota, serum metabolites, and their interactions in patients with ID is sparse.

Patients And Methods: We collected a total of 114 fecal samples, 133 oral cavity samples and 20 serum samples to characterize the gut microbiota, oral microbiota and serum metabolites in a cohort of 76 ID patients (IDs) and 59 well-matched healthy controls (HCs). We assessed the microbiota as potentially biomarkers for ID for ID by 16S rDNA sequencing and elucidated the interactions involving gut microbiota, oral microbiota and serum metabolites in ID in conjunction with untargeted metabolomics.

Impact of the Coronavirus disease pandemic on early breast cancer.

Objective: To assess the impact of the COVID-19 pandemic on the presentation, treatment, and survival of patients with early breast cancer (Stage I-III).

Methods: This study utilized data from the Surveillance, Epidemiology, and End Results database from January 1, 2018, to December 31, 2020. Patients diagnosed with primary breast cancer in 2020 were compared to those diagnosed in 2018 or 2019.

Curcumin-release antibacterial dressings with antioxidation and anti-inflammatory function for diabetic wound healing and glucose monitoring.

Diabetic wound healing remains a challenge due to high levels of oxidative stress, excessive inflammation, and bacterial infection. Smart dressings loaded with natural active monomers are proving to be effective strategies for enhancing diabetic wound healing. Herein, the bio-composites (PTIGA-Cur and PTIGA-Cur-Ag) with curcumin (Cur) responsive release were reported for promoting angiogenesis and diabetic wound repair, showing excellent anti-inflammatory, antioxidant, and antibacterial properties.

Angiogenic and neurogenic potential of dental-derived stem cells for functional pulp regeneration: A narrative review.

Background: Dental pulp tissue engineering is expected to become an ideal treatment for irreversible pulpitis and apical periodontitis. However, angiogenesis and neurogenesis for functional pulp regeneration have not yet met the standard for large-scale clinical application, and need further research.

Objective: This review focused on the potential mechanisms of angiogenesis and neurogenesis in pulp regeneration, including stem cell types, upstream and downstream regulatory molecules and cascade signalling pathways, thereby providing a theoretical basis and inspiring new ideas to improve the effectiveness of dental pulp tissue engineering.

Fibroblast Growth Factor Receptor 4 Promotes Triple-Negative Breast Cancer Progression via Regulating Fatty Acid Metabolism Through the AKT/RYR2 Signaling.

Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Previous studies have found that fibroblast growth factor receptor 4 (FGFR4) plays a crucial role in tumor development and metastasis. However, the potential role and underlying mechanisms of FGFR4 in the progression of TNBC remain unclear.

Green tea polyphenols alleviate di (2-ethylhexyl) phthalate-induced testicular injury in mice via lncRNA-miRNA-mRNA axis.

Background: Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer known for its toxic effects on the male reproductive system. Green tea polyphenols (GTPs), recognized for their antioxidant and anti-inflammatory properties, have demonstrated protective effects on various organs, but the mechanisms by which GTPs mitigate DEHP-induced testicular damage remain unclear.

Methods: Healthy male C57BL/6 J mice were divided into five groups: Control, DEHP, DEHP + GTP treatment, GTP, and Oil groups.