Discovery of 1,4-Disubstituted Cyclohexene Analogues as Selective GPR119 Agonists for the Treatment of Type 2 Diabetes.

GPR119 has emerged as a promising target for treating type 2 diabetes and associated obesity, as its stimulation induces the secretion of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide in the intestinal tract as well as the glucose-dependent release of insulin in pancreatic β-cells. We describe the design and synthesis of novel GPR119 agonists containing a 1,4-disubstituted cyclohexene scaffold. Compound displayed nanomolar potency (EC = 3.

Age at Menopause and Development of Type 2 Diabetes in Korea.

Importance: There is limited evidence regarding the association between age at menopause and incident type 2 diabetes (T2D).

Objective: To investigate whether age at menopause and premature menopause are associated with T2D incidence in postmenopausal Korean women.

Design, Setting, And Participants: This population-based cohort study was conducted among a nationally representative sample from the Korean National Health Insurance Service database of 1 125 378 postmenopausal women without T2D who enrolled in 2009.

Tear film lipid layer thickness and blink dynamics in patients with blepharospasm.

Background: This study investigates the effect of botulinum toxin A on lipid layer thickness (LLT) and blink dynamics in patients with benign essential blepharospasm (BEB) compared to dry eye disease (DED) patients.

Methods: We reviewed the medical records of patients with dry eye disease (DED) and BEB treated with botulinum toxin A (BoT A) injections. Data on demographics, lipid layer thickness (LLT), meiboscore, and blink dynamics measured using a LipiView II interferometer before and 2 months after BoT A were collected.

Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.

Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance.

Targeted dual-receptor phage cocktail against : insights into phage-host interactions and resistance mechanisms.

Introduction: is a notorious foodborne pathogen, frequently contaminating powdered infant formula and causing life-threatening diseases in infants. The escalating emergence of antibiotics-resistant mutants has led to increased interest in using bacteriophage as an alternative antimicrobial agent.

Methods: Two phages, CR8 and S13, were isolated from feces and soil samples and their morphology, physiology, and genomics were characterized.

Efficacy of combining aspirin with hydroxychloroquine in pregnancies at high risk for pre-eclampsia: a prospective, multicentre, open-label, single-arm clinical trial, investigator-initiated study (HUGS study).

Introduction: The use of hydroxychloroquine (HCQ) during pregnancies complicated by systemic lupus erythematosus or refractory antiphospholipid antibody syndrome has demonstrated a significant ability to prevent pre-eclampsia (PE). As such, the potential for the administration of HCQ to prevent PE in other high-risk pregnancies is an important clinical research agenda among maternal and fetal medicine specialists. Mechanistically, the anti-inflammatory and immunomodulatory effects of HCQ can offer vascular protection and inhibit the placental dysfunction-associated thrombotic changes underlying the pathophysiology of PE, fetal growth restriction (FGR) and fetal death in utero (FDIU).

Increased adsorption of diflubenzuron onto polylactic acid microplastics after ultraviolet weathering can increase acute toxicity in the water flea (Daphnia magna).

The ultraviolet (UV) weathering of microplastics (MPs) can lead to higher adsorption of harmful contaminants, thus increasing the potential risks of their combined effects. Because biodegradable MPs are more susceptible to UV weathering than conventional MPs, concerns have arisen about their ecological toxicity and environmental impact. Therefore, this study investigated the mechanisms associated with the adsorption of the pesticide diflubenzuron (DFB) onto polylactic acid (PLA) MP particles after UV weathering and the acute effects (48 h) of their combination on the water flea Daphnia magna.

Immunogenic clearance combined with PD-1 blockade elicits antitumor effect by promoting the recruitment and expansion of the effector memory-like CD8T cell.

Immune checkpoint inhibition shows promise for cancer treatment, but only a minority of patients respond. Combination strategies have been explored to overcome this resistance. Combining immunogenic clearance using immunogenic cell death inducers with a rho kinase inhibitor enhances phagocytosis of immunogenically dying cancer cells by antigen-presenting cells, stimulating tumor-specific immune responses by activating CD8T cells via dendritic cell-mediated priming.

Elucidation and engineering of Sphingolipid biosynthesis pathway in Yarrowia lipolytica for enhanced production of human-type sphingoid bases and glucosylceramides.

Sphingolipids are vital membrane components in in mammalian cells, plants, and various microbes. We aimed to explore and exploit the sphingolipid biosynthesis pathways in an oleaginous and dimorphic yeast Yarrowia lipolytica by constructing and characterizing mutant strains with specific gene deletions and integrating exogenous genes to enhance the production of long-chain bases (LCBs) and glucosylceramides (GlcCers). To block the fungal/plant-specific phytosphingosine (PHS) pathway, we deleted the SUR2 gene encoding a sphinganine C4-hydroxylase, resulting in a remarkably elevated secretory production of dihydrosphingosine (DHS) and sphingosine (So) without acetylation.

Increasing Very Low-Dose Edoxaban Prescription: Effectiveness and Safety Data of Korean AF Patients.

Background And Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily).

Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included.

HiMolformer: Integrating graph and sequence representations for predicting liver microsome stability with SMILES.

In the initial stages of drug discovery or pre-clinical studies, understanding the metabolic stability of new molecules is crucial. Recently, research on pre-trained deep learning for molecular property prediction has been actively progressing, with various models being made open-source. However, most of these models rely on either 2D graph or 1D sequence for training, and the representation varies depending on the data format used.

Pd-WO Nanowire MEMS Gas Sensor for Ultraselective Dual Detection of Hydrogen and Ammonia.

Demand for real-time detection of hydrogen and ammonia, clean energy carriers, in a sensitive and selective manner, is growing rapidly for energy, industrial, and medical applications. Nevertheless, their selective detection still remains a challenge and requires the utilization of diverse sensors, hampering the miniaturization of sensor modules. Herein, a practical approach via material design and facile temperature modulation for dual selectivity is proposed.

Novel coumarin benzamides as potent and reversible monoamine oxidase-B inhibitors: Design, synthesis, and neuroprotective effects.

A series of new 6-amidocoumarin derivatives, 3a-j, was synthesized and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase. All compounds, except 3 g, showed higher inhibitory activity towards MAO-B than MAO-A. Compound 3i most potently inhibited MAO-B with an IC value of 0.

Inhibitory Effects of Decursin Derivative against Lipopolysaccharide-Induced Inflammation.

Background: This study aims to explore the protective role of JB-V-60-a novel synthetic derivative of decur-sin-against lipopolysaccharide (LPS)-induced inflammation.

Methods: We examined the effects of JB-V-60 on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human pulmonary artery endothelial cells (HPAECs). Additionally, we assessed its effects on iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in LPS-exposed mice.

Electric Field Mediated Unclogging of Angstrom-Scale Channels.

Angstrom-scale fluidic channels offer immense potential for applications in areas such as desalination, molecular sieving, biomolecular sequencing, and dialysis. Inspired by biological ion channels, nano- and angstrom (Å)-scale channels are fabricated that mimic these molecular or atomic-scale dimensions. At the Å-scale, these channels exhibit unique phenomena, including selective ion transport, osmotic energy generation, fast water and gas flows, and neuromorphic ion memory.

Comparison of pediatric injury patterns before and during the COVID-19 pandemic in Korea: a retrospective study.

Purpose: The COVID-19 pandemic led to significant changes in the lifestyle patterns of children and affected the patterns of pediatric injuries. This study analyzed the changing patterns of pediatric injury overall and by age groups, based on the datasets before and during the COVID-19 pandemic.

Methods: This study is based on the data of patients who presented with injuries at 23 hospital emergency departments participating in the Emergency Department-based Injury In-depth Surveillance (EDIIS) conducted by the Korea Disease Control and Prevention Agency.

The biodegradation of polylactic acid microplastic and their toxic effect after biofouling in activate sludge.

Biodegradable microplastics (MPs) can form biofilms through interactions with various microorganisms in aquatic system and can be exposed to organisms. This study first investigated biodegradability of polylactic acid (PLA) MPs and the characterization of PLA MPs before/after biofouling (4 weeks) and their toxic effects on the freshwater invertebrate Daphnia magna. The biodegradability rate of PLA MPs was up to 50% over 28 days, suggesting that even biodegradable MPs do not easily decompose under environmental conditions.

Association Between Body Mass Index Changes and All-Cause Mortality in Parkinson's Disease.

Background: Whether body weight changes are associated with Parkinson's disease (PD) mortality remains uncertain.

Objective: To investigate the association between changes in body mass index (BMI) and all-cause mortality in patients with PD.

Methods: This nationwide cohort study enrolled 20,703 individuals with new-onset PD (ICD-10 code: G20 and a rare intractable disease registration code: V124) who underwent health screening program by the Korean National Health Insurance Service within two years from pre- and post-PD diagnosis.