Refractive Index-Corrected Light-Sheet Microscopy for Macro-View Cardiovascular Imaging.

Light-sheet fluorescence microscopy (LSFM) enables rapid data acquisition with minimal phototoxicity, while optical clearing reduces light scattering by matching sample and imaging medium refractive indices (RIs). Emerging clearing methods extend from cells and organoids to entire organs and organisms, prompting macro-view LSFM microscopes with macro-objectives for low-magnification imaging of larger specimens at adequate resolution. In cardiovascular studies, multiple organs often require imaging, yet clearing protocols optimized for different organs alter the sample RIs inconsistently.

Extracellular vesicles derived from salivary gland stem cells cultured on microwell scaffolds loaded with WNT3A promote the recovery of salivary gland function damaged by radiation via the YWHAZ-PI3K-AKT pathway.

Salivary gland (SG) stem cell-derived extracellular vesicles (EVs) are promising agents for regenerative therapy, but efficient production and targeted delivery remain key challenges. We developed a WNT3A-releasing double-layered microwell scaffold by integrating WNT3A-loaded poly(D,L-lactide-co-glycolide) (PLGA) nanofibers with a polycaprolactone (PCL)-based microwell array. This 3D platform promotes salivary gland epithelial stem cell (sgEpSC) spheroid formation and sustained biochemical stimulation.

Habitual Exercise Modulates Neuroimmune Interaction to Mitigate Aortic Stiffness.

Background: Exercise augments hemodynamic shear to activate mechano-sensitive molecular transducers in the vascular endothelium. Recently, the central nervous system has been reported to mediate neuroimmune interactions in the aortic adventitia (AA). Whether exercise modulates sympathetic nerve interactions with the immune cells to mitigate aortic stiffness remains unknown.

Bryostatin-1 improves function in arteries with suppressed endothelial cell autophagy.

We have previously reported that when autophagy is suppressed in endothelial cells (ECs), a glycolytic defect limits shear-stress -induced ATP production to an extent that purinergic 2Y1 receptor (P2Y1R)-mediated activation of EC nitric oxide (NO) synthase (eNOS) is compromised. Subsequently we demonstrated the functional relevance of this finding in arteries from mice with genetic, pharmacological, and age-associated EC autophagy impairment. Using gain and loss of function approaches in vitro, we further revealed that p-PKCδ serves as a signaling link between P2Y1R activation and NO generation.

CD9-enriched extracellular vesicles from chemically reprogrammed basal progenitors of salivary glands mitigate salivary gland fibrosis.

Extracellular vesicles (EVs) derived from stem cells offer promising potential for cell-free therapy. However, refining their cargo for precise disease targeting and delivery remains challenging. This study employed chemical reprogramming via dual inhibition of transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) to expand salivary gland basal progenitor cells (sgBPCs).

Neoadjuvant chemoradiotherapy up-regulates PD-L1 in radioresistant colorectal cancer.

Background: Combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) is a promising strategy that can enhance the therapeutic efficacy of ICIs. However, little is known about RT-induced changes in the expression of immune checkpoints, such as PD-L1, and their clinical implications in colorectal cancer (CRC). This study aimed to investigate the association between responsiveness to RT and changes in PD-L1 expression in human CRC tissue and cell lines.

An Analysis of Components and Enhancement Strategies for Advancing Memristive Neural Networks.

Advancements in artificial intelligence (AI) and big data have highlighted the limitations of traditional von Neumann architectures, such as excessive power consumption and limited performance improvement with increasing parameter numbers. These challenges are significant for edge devices requiring higher energy and area efficiency. Recently, many reports on memristor-based neural networks (Mem-NN) using resistive switching memory have shown efficient computing performance with a low power requirement.

Rapid prediction of acute thrombosis via nanoengineered immunosensors with unsupervised clustering for multiple circulating biomarkers.

The recent SARS-CoV-2 pandemic underscores the need for rapid and accurate prediction of clinical thrombotic events. Here, we developed nanoengineered multichannel immunosensors for rapid detection of circulating biomarkers associated with thrombosis, including C-reactive protein (CRP), calprotectin, soluble platelet selectin (sP-selectin), and D-dimer. We fabricated the immunosensors using fiber laser engraving of carbon nanotubes and CO laser cutting of microfluidic channels, along with the electrochemical deposition of gold nanoparticles to conjugate with biomarker-specific aptamers and antibody.

Retroductal dexamethasone administration promotes the recovery from obstructive and inflammatory salivary gland dysfunction.

Introduction: Salivary gland dysfunction, often resulting from salivary gland obstruction-induced inflammation, is a prevalent condition. Corticosteroid, known for its anti-inflammatory and immunomodulatory properties, is commonly prescribed in clinics. This study investigates the therapeutic implications and potential side effects of dexamethasone on obstructive sialadenitis recovery using duct ligation mice and salivary gland organoid models.

Non-Invasive Detection of Early-Stage Fatty Liver Disease via an On-Skin Impedance Sensor and Attention-Based Deep Learning.

Early-stage nonalcoholic fatty liver disease (NAFLD) is a silent condition, with most cases going undiagnosed, potentially progressing to liver cirrhosis and cancer. A non-invasive and cost-effective detection method for early-stage NAFLD detection is a public health priority but challenging. In this study, an adhesive, soft on-skin sensor with low electrode-skin contact impedance for early-stage NAFLD detection is fabricated.

The effect of renal function on the pharmacokinetics and pharmacodynamics of enavogliflozin, a potent and selective sodium-glucose cotransporter-2 inhibitor, in type 2 diabetes.

Aims: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM).

Methods: An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.

Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy.

The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there is a growing demand for off-the-shelf universal cell therapies. In this study, we have generated universal CAR-engineered NKT (CAR-NKT) cells by integrating iNKT TCR engineering and HLA gene editing on hematopoietic stem cells (HSCs), along with an ex vivo, feeder-free HSC differentiation culture.

A 52-week efficacy and safety study of enavogliflozin versus dapagliflozin as an add-on to metformin in patients with type 2 diabetes mellitus: ENHANCE-M extension study.

Aim: To evaluate the long-term safety and efficacy of enavogliflozin 0.3 mg/day added to metformin in patients with type 2 diabetes mellitus.

Materials And Methods: After 24 weeks of a randomized, double-blind treatment period with enavogliflozin 0.

Exercise mitigates flow recirculation and activates metabolic transducer SCD1 to catalyze vascular protective metabolites.

Exercise promotes pulsatile shear stress in the arterial circulation and ameliorates cardiometabolic diseases. However, exercise-mediated metabolic transducers for vascular protection remain under-investigated. Untargeted metabolomic analysis demonstrated that wild-type mice undergoing voluntary wheel running exercise expressed increased endothelial stearoyl-CoA desaturase 1 (SCD1) that catalyzes anti-inflammatory lipid metabolites, namely, oleic (OA) and palmitoleic acids (PA), to mitigate NF-κB-mediated inflammatory responses.

Subchronic inhalation exposure to ultrafine particulate matter alters the intestinal microbiome in various mouse models.

Exposure to ultrafine particles (UFPs) has been associated with multiple adverse health effects. Inhaled UFPs could reach the gastrointestinal tract and influence the composition of the gut microbiome. We have previously shown that oral ingestion of UFPs alters the gut microbiome and promotes intestinal inflammation in hyperlipidemic Ldlr mice.

Integrating 4-D light-sheet fluorescence microscopy and genetic zebrafish system to investigate ambient pollutants-mediated toxicity.

Ambient air pollutants, including PM (aerodynamic diameter d ~2.5 μm), PM (d ~10 μm), and ultrafine particles (UFP: d < 0.1 μm) impart both short- and long-term toxicity to various organs, including cardiopulmonary, central nervous, and gastrointestinal systems.

Gemcitabine and rapamycin-loaded mixed polymeric thermogel for metastatic pancreatic cancer therapy.

Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death and has a poor 5-year overall survival. The superior therapeutic benefits of combination or co-administration of drugs as intraperitoneal chemotherapy have increased interest in developing strategies to deliver chemotherapeutic agents to patients safely. In this study, we prepared a gel comprising the thermosensitive poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) polymer and gemcitabine (GEM), which is currently used as the primary chemotherapy for PDAC and rapamycin (RAPA), a mammalian TOR (mTOR) inhibitor, to deliver the drug through intraperitoneal injection.

Quantitative 4D imaging of biomechanical regulation of ventricular growth and maturation.

Abnormal cardiac development is intimately associated with congenital heart disease. During development, a sponge-like network of muscle fibers in the endocardium, known as trabeculation, becomes compacted. Biomechanical forces regulate myocardial differentiation and proliferation to form trabeculation, while the molecular mechanism is still enigmatic.

Umbelliferone Ameliorates Memory Impairment and Enhances Hippocampal Synaptic Plasticity in Scopolamine-Induced Rat Model.

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by memory loss and cognitive decline. Among the suggested pathogenic mechanisms of AD, the cholinergic hypothesis proposes that AD symptoms are a result of reduced synthesis of acetylcholine (ACh). A non-selective antagonist of the muscarinic ACh receptor, scopolamine (SCOP) induced cognitive impairment in rodents.

Exercise Mitigates Flow Recirculation and Activates Mechanosensitive Transcriptome to Uncover Endothelial SCD1-Catalyzed Anti-Inflammatory Metabolites.

Exercise modulates vascular plasticity in multiple organ systems; however, the metabolomic transducers underlying exercise and vascular protection in the disturbed flow-prone vasculature remain under-investigated. We simulated exercise-augmented pulsatile shear stress (PSS) to mitigate flow recirculation in the lesser curvature of the aortic arch. When human aortic endothelial cells (HAECs) were subjected to PSS ( = 50 dyne·cm , ∂τ/∂t = 71 dyne·cm ·s , 1 Hz), untargeted metabolomic analysis revealed that Stearoyl-CoA Desaturase (SCD1) in the endoplasmic reticulum (ER) catalyzed the fatty acid metabolite, oleic acid (OA), to mitigate inflammatory mediators.

FSP-1 expression in cancer cells is relevant to long-term oncological outcomes in nonmetastatic colorectal cancer.

Purpose: Recent studies have revealed that the expression of cancer-associated fibroblast (CAF) activation biomarkers in cancer cells is associated with clinical outcomes in patients with certain types of malignant tumors. However, whether the expression of CAF activation biomarkers affects the prognosis of colorectal cancer (CRC) has not been fully elucidated. This study aimed to evaluate the association between the expression of CAF activation biomarkers in cancer cells with cancer invasion and long-term oncological outcomes in patients with CRC.

Naringin enhances long-term potentiation and recovers learning and memory deficits of amyloid-beta induced Alzheimer's disease-like behavioral rat model.

Alzheimer's disease (AD), as the most typical type of dementia, is a chronic neurodegenerative disorder characterized by progressive learning and memory impairment. It is known that the main causes of AD are the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Naringin is a flavonoid from citrus fruits, especially in grapefruit, which has anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective activities.