Discovery of novel arylpyridine derivatives for motile ciliogenesis.

Motile cilia are crucial for maintaining healthy bodily functions by facilitating fluid transport and removing foreign substances or debris from the body. The dysfunction of motile cilia leads to ciliopathy. In particular, damage to the motile cilia of the airways can cause or worsen respiratory disease, making it an attractive target for therapeutic interventions.

Ultra-Mild Fabrication of Highly Concentrated SWCNT Dispersion Using Spontaneous Charging in Solvated Electron System.

The efficient dispersion of single-walled carbon nanotubes (SWCNTs) has been the subject of extensive research over the past decade. Despite these efforts, achieving individually dispersed SWCNTs at high concentrations remains challenging. In this study, we address the limitations associated with conventional methods, such as defect formation, excessive surfactant use, and the use of corrosive solvents.

Innate Immune Training Initiates Efferocytosis to Protect against Lung Injury.

Innate immune training involves myelopoiesis, dynamic gene modulation, and functional reprogramming of myeloid cells in response to secondary heterologous challenges. The present study evaluates whether systemic innate immune training can protect tissues from local injury. Systemic pretreatment of mice with β-glucan, a trained immunity agonist, reduces the mortality rate of mice with bleomycin-induced lung injury and fibrosis, as well as decreasing collagen deposition in the lungs.

Epigenetic landscape analysis reveals the significance of early reduced chromatin accessibility in osteoclastogenesis.

Recently improved techniques could provide snapshots of chromatin structure generated based on chromatin accessibility. Since chromatin accessibility determines transcriptional potential, it has been attempted in a variety of cell systems. However, there has been no genome-wide analysis of chromatin accessibility for the entire murine osteoclast (OC) differentiation process.

Heparins are potent inhibitors of ectonucleotide pyrophosphatase/phospho-diesterase-1 (NPP1) - a promising target for the immunotherapy of cancer.

Introduction: Heparins, naturally occurring glycosaminoglycans, are widely used for thrombosis prevention. Upon application as anticoagulants in cancer patients, heparins were found to possess additional antitumor activities. Ectonucleotidases have recently been proposed as novel targets for cancer immunotherapy.

A Validation Study of a Deep Learning-Based Doping Drug Text Recognition System to Ensure Safe Drug Use among Athletes.

This study aimed to develop an English version of a doping drug-recognition system using deep learning-based optical character recognition (OCR) technology. A database of 336 banned substances was built based on the World Anti-Doping Agency's International Standard Prohibited List and the Korean Pharmaceutical Information Center's Drug Substance Information. For accuracy and validity analysis, 886 drug substance images, including 152 images of prescriptions and drug substance labels collected using data augmentation, were used.

Social informedness and investor sentiment in the GameStop short squeeze.

We examine investor behavior on social media platforms related to the GameStop (GME) short squeeze in early 2021. Individual investors stimulated the stock market via Reddit social posts in the presence of institutional investors who bet against GME's success as short sellers. We analyzed r/WallStreetBets subreddit posts related to GME's trading patterns.

Synthesis and structure-activity relationships of ticlopidine derivatives and analogs as inhibitors of ectonucleotidase CD39.

Ticlopidine is an antithrombotic prodrug of the thienotetrahydropyridine family. For platelet inhibition it has to undergo oxidative ring-opening by cytochrome P450 enzymes. The resulting thiol reacts with a cysteine residue of the purinergic P2Y receptor on thrombocytes resulting in covalent receptor blockade.

Machine learning-based obesity classification considering 3D body scanner measurements.

Obesity can cause various diseases and is a serious health concern. BMI, which is currently the popular measure for judging obesity, does not accurately classify obesity; it reflects the height and weight but ignores the characteristics of an individual's body type. In order to overcome the limitations of classifying obesity using BMI, we considered 3-dimensional (3D) measurements of the human body.

Experimental Assessment of Perhydro-Dibenzyltoluene Dehydrogenation Reaction Kinetics in a Continuous Flow System for Stable Hydrogen Supply.

The development of alternate clean energy resources is among the most pressing issues in the energy sector in order to preserve the global natural environment. One of the ideal candidates is the utilization of hydrogen as a primary fuel in lieu of fossil fuels. It can be safely stored in liquid organic hydrogen carrier (LOHC) materials and recovered on demand.

2-Substituted thienotetrahydropyridine derivatives: Allosteric ectonucleotidase inhibitors.

The antithrombotic prodrugs ticlopidine and clopidogrel are thienotetrahydro-pyridine derivatives that are metabolized in the liver to produce thiols that irreversibly block adenosine diphosphate (ADP)-activated P2Y receptors on thrombocytes. In their native, nonmetabolized form, both drugs were reported to act as inhibitors of ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1, CD39). CD39 catalyzes the extracellular hydrolysis of nucleoside tri- and diphosphates, mainly adenosine 5'-triphosphate (ATP) and ADP, yielding adenosine monophosphate, which is further hydrolyzed by ecto-5'-nucleotidase (CD73) to produce adenosine.

Hexosamine Biosynthetic Pathway-Derived O-GlcNAcylation Is Critical for RANKL-Mediated Osteoclast Differentiation.

O-linked-N-acetylglucosaminylation (O-GlcNAcylation) performed by O-GlcNAc transferase (OGT) is a nutrient-responsive post-translational modification (PTM) via the hexosamine biosynthetic pathway (HBP). Various transcription factors (TFs) are O-GlcNAcylated, affecting their activities and significantly contributing to cellular processes ranging from survival to cellular differentiation. Given the pleiotropic functions of O-GlcNAc modification, it has been studied in various fields; however, the role of O-GlcNAcylation during osteoclast differentiation remains to be explored.

Discovery of potent nucleotide pyrophosphatase/phosphodiesterase3 (NPP3) inhibitors with ancillary carbonic anhydrase inhibition for cancer (immuno)therapy.

Nucleotide pyrophosphatase/phosphodiesterase3 (NPP3) catalyzes the hydrolysis of extracellular nucleotides. It is expressed by immune cells and some carcinomas, of kidney and colon. Together with ecto-5'-nucleotidase (CD73), NPP3 produces immunosuppressive, cancer-promoting adenosine, and has therefore been proposed as a target for cancer therapy.

Circular Radio-Frequency Electrode With MEMS Temperature Sensors for Laparoscopic Renal Sympathetic Denervation.

Objective: Laparoscopic renal denervation (LRDN) ablates sympathetic nerves on the outer wall of a renal artery to treat autonomic nervous system disorders such as hypertension and arrhythmia. Here, we developed a new circular radio frequency (RF) electrode for LRDN using micro-electro-mechanical systems (MEMS) technology.

Methods: The electrode consists of a parallel bipolar MEMS electrode, two MEMS thermocouples, and a shape-memory alloy (SMA) substrate.

Laparoscopic Ablation System for Complete Circumferential Renal Sympathetic Denervation.

Goal: The catheter-based renal denervation (RDN) showed promising results for patients in lowering BP, but there were also many non-responders. One of the possible reasons was the incomplete neural ablation due to the ablation of renal nerves at random sites resulting in asymmetric innervation patterns along the renal artery.

Methods: We developed a laparoscopic ablation system that is optimized for complete RDN regardless of renal arterial innervation and size.

Sulfated Polysaccharides from Macroalgae Are Potent Dual Inhibitors of Human ATP-Hydrolyzing Ectonucleotidases NPP1 and CD39.

Extracellular ATP mediates proinflammatory and antiproliferative effects via activation of P2 nucleotide receptors. In contrast, its metabolite, the nucleoside adenosine, is strongly immunosuppressive and enhances tumor proliferation and metastasis. The conversion of ATP to adenosine is catalyzed by ectonucleotidases, which are expressed on immune cells and typically upregulated on tumor cells.

Glutamine metabolite α-ketoglutarate acts as an epigenetic co-factor to interfere with osteoclast differentiation.

Osteoclasts (OCs) have been well-known involved in the exacerbation of bone-related diseases. However, the role of metabolites on osteoclastogenesis has not been well characterized. Herein, we found osteoclastogenesis was negatively regulated by α-ketoglutarate (αKG) in vitro and in vivo (C57BL/6 mouse).

Particulate Matter Exposure During Oocyte Maturation: Cell Cycle Arrest, ROS Generation, and Early Apoptosis in Mice.

Particulate matter (PM) is a general atmospheric pollutant released into the air by an anthropogenic and naturally derived mixture of substances. Current studies indicate that fine dust can result in different health defects, including endothelial dysfunction, asthma, lung cancer, cardiovascular diseases, uterine leiomyoma, deterioration in sperm quality, and overall birth impairment. However, the most prominent effects of PM (diameter < 10 μM) exposure on the female reproductive system, especially with respect to oocyte maturation, remain unclear.

Nucleotide Analog ARL67156 as a Lead Structure for the Development of CD39 and Dual CD39/CD73 Ectonucleotidase Inhibitors.

Nucleoside triphosphate diphosphohydrolase1 (NTPDase1, CD39) inhibitors have potential as novel drugs for the (immuno)therapy of cancer. They increase the extracellular concentration of immunostimulatory ATP and reduce the formation of AMP, which can be further hydrolyzed by ecto-5'-nucleotidase (CD73) to immunosuppressive, cancer-promoting adenosine. In the present study, we synthesized analogs and derivatives of the standard CD39 inhibitor ARL67156, a nucleotide analog which displays a competitive mechanism of inhibition.

The effects of visual feedback balance training on the pain and physical function of patients with chronic degenerative knee arthritis.

[Purpose] This study aimed to investigate the effects of visual feedback balance training on the pain and dysfunction of patients with chronic degenerative knee arthritis. [Participants and Methods] Twenty-six patients with chronic degenerative knee arthritis participated in this study; the control group (n=13) performed muscle strength training and the experimental group (n=13) performed visual feedback balance training. General physical therapy was applied to both groups three times a week for eight weeks.

The effects of manual manipulation therapy on pain and dysfunction in patients with lumbar spinal stenosis.

[Purpose] This study investigated the effects of manual manipulation therapy on the pain and dysfunction of patients with lumbar spinal stenosis. [Participants and Methods] In this study, 30 patients with chronic back pain were evenly divided into an experimental group, who received manual traction therapy, and a control group, who received intermittent traction therapy. Both groups received therapy three times a week for eight weeks.

Development of a nitinol-actuated surgical instrument for laparoscopic renal denervation: feasibility test in a swine survival model.

In this study, we developed a novel nitinol-actuated surgical instrument to conduct laparoscopic renal denervation for the treatment of resistant hypertension. We investigated whether shape and temperature settings of nitinol specimens fit well into the design goals. Furthermore, we conducted a pilot study to validate the mechanical and physiological performance of nerve ablation without damaging the renal artery.

Recombinant expression of ecto-nucleotide pyrophosphatase/phosphodiesterase 4 (NPP4) and development of a luminescence-based assay to identify inhibitors.

Nucleotide pyrophosphatase/phosphodiesterase 4 (NPP4) is a membrane-bound enzyme that hydrolyzes extracellular diadenosine polyphosphates such as diadenosine triphosphate (ApA) and diadenosine tetraphosphate (ApA) yielding mononucleotides. NPP4 on the surface of endothelial cells was reported to promote platelet aggregation by hydrolyzing ApA to ADP, which activates pro-thrombotic G protein-coupled P2Y and P2Y receptors. Thus, NPP4 inhibitors have potential as novel antithrombotic drugs.

Lower limb muscle activities and gain in balancing ability following two types of stair gait intervention in adult post-chronic stroke patients: A preliminary, randomized-controlled study.

Objectives: This study aims to compare the changes in lower limb muscle activities after stair ascending and descending training at two different heights of stairs in patients with chronic stroke and to suggest a stair height which is more effective in improving the strength and balancing ability of these patients.

Patients And Methods: Between November 2016 and February 2017, a total of 20 patients (14 males, 6 females; mean age 56 years; range, 52 to 61 years) with hemiparesis were included in this randomized-controlled study. The patients were randomly assigned to the 10- or 15-cm stair height group (10- and 15-cm groups, respectively; n=10 in each).

Laparoscopic Renal Denervation System for Treating Resistant Hypertension: Overcoming Limitations of Catheter-Based Approaches.

Goal: In a pivotal clinical trial, the percutaneous catheter-based renal denervation system developed to treat resistant hypertension did not show effectiveness in reducing blood pressure because of its fundamental limitation to ablate deeper nerves present around the renal artery.

Methods: We propose a new renal denervation strategy called laparoscopicdenervation system (LDS) based-on laparoscopy procedure to ablate the renal nerves completely but inhibit the thermal arterial damage.The system has flexible electrodes to bend around the arterial wall to ablate nervesThe simulation study using validated in-silico models evaluated the heat distributionon the outer arterial wall,and an acute animal study (swine model) was conducted to demonstrate the feasibility of LDS in vivo.