They warrant further investigation with stringent methods and criteria of evaluation for the ultimate treatment of neurological diseases.There is substantial evidence that cholinergic system function impairment plays a significant role in many central nervous system (CNS) disorders. During the past three decades, muscarinic receptors (mAChRs) have been implicated in various pathologies and have been prominent targets of drug-design efforts. However, due to the high sequence homology of the orthosteric binding site, many drug candidates resulted in limited clinical success. Although several advances in treating peripheral pathologies have been achieved, targeting CNS pathologies remains challenging for researchers. Nevertheless, significant progress has been made in recent years to develop functionally selective orthosteric and allosteric ligands targeting the mAChRs with limited side effect profiles. This review highlights past efforts and focuses on recent advances in drug design targeting these receptors for Alzheimer’s disease (AD), schizophrenia (SZ), and depression.Herein we report on the preparation of a bioactive glass (BAG)-based photocurable resin for the additive manufacturing of BAG scaffolds with high filler loadings. The preparation of glass/ceramics resins for stereolithography with high filler loading is always a challenge, especially for fillers with a high refractive index variance. Various photocurable resin compositions with and without bioactive glass fillers have been investigated to see the influence of bioactive glass on physical properties of the resin and resulting green body. The effect of concentration of monomers, reactive diluent, light absorber (Sudan orange G dye), photoinitiator (PI), non-reactive diluent, and fillers (BAG) on rheology and photocuring behavior of the resin and tomography of the resulting 3D structures have been investigated. The BAG contents affect the rheology of resin and influence the rate of the polymerization reaction. The resin compositions with 55-60% BAG, 10% PEG-200 (diluent), 1% of PI and 0.015% of the dye were found to be suitable compositions for the stereolithographic fabrication. A higher percentage of PI caused over-curing, while a higher amount of dye decreased the cure depth of the resin. The micro-computed tomography (µ-CT) and scanning electron microscopic (SEM) images of the resulting green bodies display a relatively dense glass scaffold without any visible cracks and good interlayer connection and surface finishing. These properties play an important role in the mechanical behavior of 3D scaffolds. This study will be helpful to prepare high density glass/ceramic slurries and optimize their printing properties.Facing an ongoing organ shortage in transplant medicine, strategies to increase the use of organs from marginal donors by objective organ assessment are being fostered. In this context, normothermic machine perfusion provides a platform for ex vivo organ evaluation during preservation. Consequently, analytical tools are emerging to determine organ quality. In this study, hyperspectral imaging (HSI) in the wavelength range of 550-995 nm was applied. Classification of 26 kidneys based on HSI was established using KidneyResNet, a convolutional neural network (CNN) based on the ResNet-18 architecture, to predict inulin clearance behavior. HSI preprocessing steps were implemented, including automated region of interest (ROI) selection, before executing the KidneyResNet algorithm. Training parameters and augmentation methods were investigated concerning their influence on the prediction. When classifying individual ROIs, the optimized KidneyResNet model achieved 84% and 62% accuracy in the validation and test set, respectively. With a majority decision on all ROIs of a kidney, the accuracy increased to 96% (validation set) and 100% (test set). These results demonstrate the feasibility of HSI in combination with KidneyResNet for non-invasive prediction of ex vivo kidney function. This knowledge of preoperative renal quality may support the organ acceptance decision.Low-energy shock wave (LESW) therapy is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW treatment has been demonstrated to be effective in treating chronic prostatitis and pelvic pain syndrome as well as overactive bladder, and it has a potential effect on interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. LESW reduces pain behavior, downregulates nerve growth factor expression, and suppresses bladder overactivity by decreasing the expression of inflammatory proteins. Previous rat IC models have shown that LESW can increase urothelial permeability, facilitate intravesical delivery of botulinum toxin A (BoNT-A), and block acetic acid-induced hyperactive bladder, suggesting that LESW might be a potential therapeutic module for relieving bladder inflammatory conditions, such as bladder oversensitivity, IC/BPS, and overactive bladder. A recent clinical trial showed that LESW monotherapy was associated with a significant reduction in pain scores and IC symptoms. BoNT-A detrusor injection or liposome-encapsulated BoNT-A instillation could also inhibit inflammation and improve IC symptoms. However, BoNT-A injection requires anesthesia and certain complications might occur. Our preliminary study using LESW plus intravesical BoNT-A instillation every week demonstrated an improvement in global response assessment without any adverse events. Moreover, an immunohistochemistry study revealed the presence of cleaved SNAP25 protein in the suburothelium of IC bladder tissue, indicating that BoNT-A could penetrate across the urothelial barrier after application of LESW. These results provide evidence for the efficacy and safety of this novel IC/BPS treatment by LESW plus BoNT-A instillation, without anesthesia, and no bladder injection. This article reviews the current evidence on LESW and LESW plus intravesical therapeutic agents on bladder disorders and the pathophysiology and pharmacological mechanism of this novel, minimally invasive treatment model for IC/BPS.(1) Background The role of using artificial intelligence (AI) with electrocardiograms (ECGs) for the diagnosis of significant coronary artery disease (CAD) is unknown. We first tested the hypothesis that using AI to read ECG could identify significant CAD and determine which vessel was obstructed. (2) Methods We collected ECG data from a multi-center retrospective cohort with patients of significant CAD documented by invasive coronary angiography and control patients in Taiwan from 1 January 2018 to 31 December 2020. (3) Results We trained convolutional neural networks (CNN) models to identify patients with significant CAD (>70% stenosis), using the 12,954 ECG from 2303 patients with CAD and 2090 ECG from 1053 patients without CAD. The Marco-average area under the ROC curve (AUC) for detecting CAD was 0.869 for image input CNN model. For detecting individual coronary artery obstruction, the AUC was 0.885 for left anterior descending artery, 0.776 for right coronary artery, and 0.816 for left circumflex artery obstruction, and 1.0 for no coronary artery obstruction. Marco-average AUC increased up to 0.973 if ECG had features of myocardial ischemia. (4) Conclusions We for the first time show that using the AI-enhanced CNN model to read standard 12-lead ECG permits ECG to serve as a powerful screening tool to identify significant CAD and localize the coronary obstruction. It could be easily implemented in health check-ups with asymptomatic patients and identifying high-risk patients for future coronary events.It is now well known that oxidative stress promotes lipid peroxidation, protein oxidation, activation of proteases, fragmentation of DNA and alteration in gene expression for producing myocardial cell damage, whereas its actions for the induction of fibrosis, necrosis and apoptosis are considered to result in the loss of cardiomyocytes in different types of heart disease. The present article is focused on the discussion concerning the generation and implications of oxidative stress from various sources such as defective mitochondrial electron transport and enzymatic reactions mainly due to the activation of NADPH oxidase, nitric oxide synthase and monoamine oxidase in diseased myocardium. Oxidative stress has been reported to promote excessive entry of Ca2+ due to increased permeability of the sarcolemmal membrane as well as depressions of Na+-K+ ATPase and Na+-Ca2+ exchange systems, which are considered to increase the intracellular of Ca2+. In addition, marked changes in the ryanodine receptors and Ca2+-pump ATPase have been shown to cause Ca2+-release and depress Ca2+ accumulation in the sarcoplasmic reticulum as a consequence of oxidative stress. Such alterations in sarcolemma and sarcoplasmic reticulum are considered to cause Ca2+-handling abnormalities, which are associated with mitochondrial Ca2+-overload and loss of myofibrillar Ca2+-sensitivity due to oxidative stress. Information regarding the direct effects of different oxyradicals and oxidants on subcellular organelles has also been outlined to show the mechanisms by which oxidative stress may induce Ca2+-handling abnormalities. These observations support the view that oxidative stress plays an important role in the genesis of subcellular defects and cardiac dysfunction in heart disease.Ataxia-telangiectasia mutated (ATM) is a key DNA damage signaling kinase that is mutated in humans with ataxia-telangiectasia (A-T) syndrome. This syndrome is characterized by neurodegeneration, immune abnormality, cancer predisposition, and premature aging. To better understand the function of ATM in vivo, we engineered a viable zebrafish model with a mutated atm gene. Zebrafish atm loss-of-function mutants show characteristic features of A-T-like motor disturbance, including coordination disorders, immunodeficiency, and tumorigenesis. The immunological disorder of atm homozygote fish is linked to the developmental blockade of hematopoiesis, which occurs at the adulthood stage and results in a decrease in infection defense but, with little effect on wound healing. Malignant neoplasms found in atm mutant fish were mainly nerve sheath tumors and myeloid leukemia, which rarely occur in A-T patients or Atm-/- mice. These results underscore the importance of atm during immune cell development. This zebrafish A-T model opens up a pathway to an improved understanding of the molecular basis of tumorigenesis in A-T and the cellular role of atm.Cardiovascular disease is still the leading cause of morbidity and mortality worldwide. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become a valuable widespread in vitro model to study cardiac disease. Herein, we employ the hiPSC-CM model to identify novel miRNA-mRNA interaction partners during cardiac differentiation and β-adrenergic stress. Whole transcriptome and small RNA sequencing data were combined to identify novel miRNA-mRNA interactions. Briefly, mRNA and miRNA expression profiles were integrated with miRNA target predictions to identify significant statistical dependencies between a miRNA and its candidate target set. We show by experimental validation that our approach discriminates true from false miRNA target predictions. Thereby, we identified several differentially expressed miRNAs and focused on the two top candidates miR-99a-5p in the context of cardiac differentiation and miR-212-3p in the context of β-adrenergic stress. We validated some target mRNA candidates by 3’UTR luciferase assays as well as in transfection experiments in the hiPSC-CM model system.