Transparent Conductive Electrodes of ß-Ga2O3/Ag/ß-Ga2O3 Multilayer for Ultraviolet Emitters.

We investigated the optical and electrical properties of a ß-Ga2O3/Ag/ß-Ga2O3 multilayer transparent conductive electrode deposited on an α-Al2O3 (0001) substrate. For the deposition of a continuous Ag layer, we preliminarily performed anultraviolet-ozone pretreatment of the Ga2O3 bottom layer. To obtain a stable ß-phase of Ga2O3, the ß-Ga2O3/Ag/ß-Ga2O3 multilayer was annealed at 700 °C under N2 atmosphere. The transmittance and sheet resistance of the ß-Ga2O3/Ag/ß-Ga2O3 multilayer were critically affected by the surface morphology and thickness of the Ag interlayer. The multilayer with optimized thicknesses (ß-Ga2O3 top layer: 30 nm; Ag interlayer: 12 nm; ß-Ga2O3 bottom layer: 60 nm) exhibited a resistance of 8.48 Ωsq-1, an average optical transmittance of 87.16% in the ultraviolet wavelength range from 300 to 350 nm, and a figure of merit of 29.81 × 10-3 Ω-1.

qMAP enabled microanatomical mapping of human skin aging.

Aging is a major driver of diseases in humans. Identifying features associated with aging is essential for designing robust intervention strategies and discovering novel biomarkers of aging. Extensive studies at both the molecular and organ/whole-body physiological scales have helped determined features associated with aging. However, the lack of meso-scale studies, particularly at the tissue level, limits the ability to translate findings made at molecular scale to impaired tissue functions associated with aging. In this work, we established a tissue image analysis workflow - quantitative micro-anatomical phenotyping (qMAP) - that leverages deep learning and machine vision to fully label tissue and cellular compartments in tissue sections. The fully mapped tissue images address the challenges of finding an interpretable feature set to quantitatively profile age-related microanatomic changes. We optimized qMAP for skin tissues and applied it to a cohort of 99 donors aged 14 to 92. We extracted 914 microanatomic features and found that a broad spectrum of these features, represented by 10 cores processes, are strongly associated with aging. Our analysis shows that microanatomical features of the skin can predict aging with a mean absolute error (MAE) of 7.7 years, comparable to state-of-the-art epigenetic clocks. Our study demonstrates that tissue-level architectural changes are strongly associated with aging and represent a novel category of aging biomarkers that complement molecular markers. Our results highlight the complex and underexplored multi-scale relationship between molecular and tissue microanatomic scales.

A Comprehensive Overview of RNA Deconvolution Methods and Their Application.

Tumors are surrounded by a variety of tumor microenvironmental cells. Profiling individual cells within the tumor tissues is crucial to characterize the tumor microenvironment and its therapeutic implications. Since single-cell technologies are still not cost-effective, scientists have developed many statistical deconvolution methods to delineate cellular characteristics from bulk transcriptome data. Here, we present an overview of 20 deconvolution techniques, including cutting-edge techniques recently established. We categorized deconvolution techniques by three primary criteria: characteristics of methodology, use of prior knowledge of cell types and outcome of the methods. We highlighted the advantage of the recent deconvolution tools that are based on probabilistic models. Moreover, we illustrated two scenarios of the common application of deconvolution methods to study tumor microenvironments. This comprehensive review will serve as a guideline for the researchers to select the appropriate method for their application of deconvolution.

Nicotinamide (niacin) supplement increases lipid metabolism and ROS-induced energy disruption in triple-negative breast cancer: potential for drug repositioning as an anti-tumor agent.

Metabolic dysregulation is an important hallmark of cancer. Nicotinamide (NAM), a water-soluble amide form of niacin (vitamin B3), is currently available as a supplement for maintaining general physiologic functions. NAM is a crucial regulator of mitochondrial metabolism and redox reactions. In this study, we aimed to identify the mechanistic link between NAM-induced metabolic regulation and the therapeutic efficacy of NAM in triple-negative breast cancer (TNBC). The combined analysis using multiomics systems biology showed that NAM decreased mitochondrial membrane potential and ATP production, but increased the activities of reverse electron transport (RET), fatty acid ß-oxidation and glycerophospholipid/sphingolipid metabolic pathways in TNBC, collectively leading to an increase in the levels of reactive oxygen species (ROS). The increased ROS levels triggered apoptosis and suppressed tumour growth and metastasis of TNBC in both human organoids and xenograft mouse models. Our results showed that NAM treatment leads to cancer cell death in TNBC via mitochondrial dysfunction and activation of ROS by bifurcating metabolic pathways (RET and lipid metabolism); this provides insights into the repositioning of NAM supplement as a next-generation anti-metabolic agent for TNBC treatment.

Latrophilin-2 is a novel receptor of LRG1 that rescues vascular and neurological abnormalities and restores diabetic erectile function.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia, which causes endothelial dysfunction and peripheral neuropathy, ultimately leading to multiple complications. One prevalent complication is diabetic erectile dysfunction (ED), which is more severe and more resistant to treatment than nondiabetic ED. The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1) is a modulator of TGF-ß-mediated angiogenesis and has been proposed as a biomarker for a variety of diseases, including DM. Here, we found that the adhesion GPCR latrophilin-2 (LPHN2) is a TGF-ß-independent receptor of LRG1. By interacting with LPHN2, LRG1 promotes both angiogenic and neurotrophic processes in mouse tissue explants under hyperglycemic conditions. Preclinical studies in a diabetic ED mouse model showed that LRG1 administration into the penile tissue, which exhibits significantly increased LPHN2 expression, fully restores erectile function by rescuing vascular and neurological abnormalities. Further investigations revealed that PI3K, AKT, and NF-κB p65 constitute the key intracellular signaling pathway of the LRG1/LPHN2 axis, providing important mechanistic insights into LRG1-mediated angiogenesis and nerve regeneration in DM. Our findings suggest that LRG1 can be a potential new therapeutic option for treating aberrant peripheral blood vessels and neuropathy associated with diabetic complications, such as diabetic ED.