Design and development of pyrazol-5-ylbenzamide derivatives containing chiral oxazoline moiety as fungicides based on molecular docking.

Background: Development of novel chiral antifungal agents for effective control of plant pathogens is urgently needed. In this study, a series of pyrazol-5-yl-benzamide derivatives containing chiral oxazoline moiety were rationally designed and developed based on molecular docking.

Results: The in vitro antifungal assay results indicated that compounds (rac)-4h (R = Et), (S)-4 h (R = S-Et) and (R)-4 h (R = R-Et) exhibited remarkable antifungal activities against Valsa mali with median effective concentration (EC) values of 0.

Super-photostable organic dye for long-term live-cell single-protein imaging.

Organic dyes play a crucial role in live-cell imaging because of their advantageous properties, such as photostability and high brightness. Here we introduce a super-photostable and bright organic dye, Phoenix Fluor 555 (PF555), which exhibits an order-of-magnitude longer photobleaching lifetime than conventional organic dyes without the requirement of any anti-photobleaching additives. PF555 is an asymmetric cyanine structure in which, on one side, the indole in the conventional Cyanine-3 is substituted with 3-oxo-quinoline.

METTL3, m6A modification, and EGR1: interplay affecting myocardial I/R injury outcomes.

The occurrence of severe myocardial ischemia/reperfusion (I/R) injury is associated with the clinical application of reestablishment technique for heart disease, and understanding its underlying mechanisms is currently an urgent issue. Prior investigations have demonstrated the potential enhancement of MIRI through EGR1 suppression, although the precise underlying regulatory pathways require further elucidation. The core focus of this investigation is to examine the molecular pathways through EGR1 regulates mitophagy-mediated myocardial cell pyroptosis and its impact on MIRI.

A robust benchmark for detecting low-frequency variants in the HG002 Genome In A Bottle NIST reference material.

Somatic mosaicism is an important cause of disease, but mosaic and somatic variants are often challenging to detect because they exist in only a fraction of cells. To address the need for benchmarking subclonal variants in normal cell populations, we developed a benchmark containing mosaic variants in the Genome in a Bottle Consortium (GIAB) HG002 reference material DNA from a large batch of a normal lymphoblastoid cell line. First, we used a somatic variant caller with high coverage (300x) Illumina whole genome sequencing data from the Ashkenazi Jewish trio to detect variants in HG002 not detected in at least 5% of cells from the combined parental data.

hsa_circ_0088196 Predicts Adverse Pregnancy Outcomes in Preeclampsia Patients and Contributes to Endothelial Cell Injury Via Modulating the miR-145-5p/FLT1 Axis.

Preeclampsia (PE) is a specific hypertension-related disease in pregnancies, causing adverse pregnancy outcomes. Endothelial cell dysfunction is a major etiology of PE, of which the regulation could affect disease progression. This study focused on hsa_circ_0088196, evaluating its clinical significance in PE and its effect on endothelial cell injury, aiming to identify a novel biomarker for PE and complete its regulating mechanism in disease development.

Short-chain fatty acids regulate erastin-induced cardiomyocyte ferroptosis and ferroptosis-related genes.

Background: Ferroptosis has been proven to contribute to the progression of myocardial ischemia/reperfusion (I/R) injury and can be inhibited or promoted by ATF3. Short-chain fatty acids (SCFAs) have shown benefits in various cardiovascular diseases with anti-inflammatory and antioxidant effects. However, the impact of SCFAs on ferroptosis in ischemic-stimulated cardiomyocytes remains unknown.

Effect of tubastatin A on NLRP3 inflammasome activation in macrophages under hypoxia/reoxygenation conditions.

Background: There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock (HS). The aim of this study was to explore the potential of the histone deacetylase 6 (HDAC6)-specific inhibitor tubastatin A (TubA) to suppress nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation in macrophages under hypoxia/reoxygenation (H/R) conditions.

Methods: The viability of RAW264.

The electrophysiological effects of Tongyang Huoxue granules on the ignition phase during hypoxia/reoxygenation injury in sinoatrial node cells.

Introduction: This study was undertaken to explore the potential therapeutic effects of Tongyang Huoxue Granules (TYHX) on sinoatrial node (SAN) dysfunction, a cardiac disorder characterized by impaired impulse generation or conduction. The research question addressed whether TYHX could positively influence SAN ion channel function, specifically targeting the sodium-calcium exchanger ( ) and L-type calcium channel ( ) of the SAN.

Methods: Sinoatrial node cells (SANCs) were isolated and cultured from neonatal Japanese big-eared white rabbits within 24 h of birth.

Artificial Intelligence Efficacy as a Function of Trainee Interpreter Proficiency: Lessons from a Randomized Controlled Trial.

Background And Purpose: Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees.

Use of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients With Type 2 Diabetes and the Incidence of Retinal Vein Occlusion in Taiwan.

Purpose: The purpose of this study was to evaluate the risk of newly diagnosed retinal vein occlusion (RVO) in patients with type 2 diabetes (T2D) using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared to dipeptidyl peptidase-4 inhibitors (DPP-4i).

Methods: Claims data from the National Health Insurance Research Database of Taiwan were used in this nationwide retrospective cohort study. A target trial emulation framework was applied.

IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial.

Inflammation mediated by interleukin-6 (IL-6) is strongly associated with cardiovascular risk. Here we evaluated clazakizumab, a monoclonal antibody targeting the IL-6 ligand, in a phase 2b dose-finding study. Adults with cardiovascular disease and/or diabetes receiving maintenance dialysis with high-sensitivity C-reactive protein (hs-CRP) ≥ 2 mg l at baseline were randomized to receive clazakizumab (2.

Effectiveness of Huddles in Improving the Patient Safety Attitudes Among Clinical Team Members.

Background And Objectives: Huddles among members of interdisciplinary medical teams involve short stand-up sessions and allow team members to focus on existing or emerging patient safety issues, thereby facilitating team communication. Hospital managers are able to recognize the current situation of the organization through patient safety attitudes, strengthen team members' awareness of patient safety, and improve the quality of health care. The purpose of this study was to determine the effects of huddles on improving team members' attitudes toward patient safety.

Uveitis Risk After the First Dose of COVID-19 Vaccination Based on Uveitis History: Matched Cohort and Crossover Case Series Study.

Purpose: To investigate the risk of noninfectious uveitis following the first dose of coronavirus disease 2019 (COVID-19) vaccination based on the uveitis history.

Design: Retrospective matched cohort and crossover case series study.

Methods: A random sample of 7 917 457 individuals who received COVID-19 vaccine between January 2021 and March 2022 in Korea, and had no recorded history of COVID-19 were categorized into the control and uveitis groups based on their uveitis history.

Abdominal Symptom Improvement During Clinical Trials of Tenapanor in Patients With Irritable Bowel Syndrome With Constipation: A Post Hoc Analysis.

Introduction: This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness.

Methods: The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]).

Aucubin protects against myocardial ischemia-reperfusion injury by regulating STAT3/NF-κB/HMGB-1 pathway.

The main characteristics of the myocardial ischemia/reperfusion injury (MI/RI) are oxidative stress, apoptosis, and an inflammatory response. Aucubin (AU) is an iridoid glycoside that possesses various biological properties and has been discovered to demonstrate antioxidant and anti-inflammatory impacts in pathological processes, such as ischemia-reperfusion. The objective of this research was to investigate if AU treatment could mitigate myocardial inflammation and apoptosis caused by ischemia/reperfusion (I/R) in both laboratory and animal models, and to elucidate its underlying mechanism.

Systematic discovery of neoepitope-HLA pairs for neoantigens shared among patients and tumor types.

The broad application of precision cancer immunotherapies is limited by the number of validated neoepitopes that are common among patients or tumor types. To expand the known repertoire of shared neoantigen-human leukocyte antigen (HLA) complexes, we developed a high-throughput platform that coupled an in vitro peptide-HLA binding assay with engineered cellular models expressing individual HLA alleles in combination with a concatenated transgene harboring 47 common cancer neoantigens. From more than 24,000 possible neoepitope-HLA combinations, biochemical and computational assessment yielded 844 unique candidates, of which 86 were verified after immunoprecipitation mass spectrometry analyses of engineered, monoallelic cell lines.

Noninfectious Uveitis Risk After COVID-19 Vaccination: A Nationwide Retrospective Cohort Study.

Purpose: To investigate the incidence and risk of noninfectious uveitis (NIU) following COVID-19 vaccination compared with an unvaccinated, uninfected control group.

Design: Retrospective population-based cohort study.

Methods: We included 5,185,153 individuals who received the first vaccine dose in the exposed group and 2,680,164 individuals in the unexposed, uninfected control group.

Surgical management and outcome of newly diagnosed glioblastoma without contrast enhancement (low-grade appearance): a report of the RANO resect group.

Background: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement.

Tongyang Huoxue decoction (TYHX) ameliorating hypoxia/reoxygenation-induced disequilibrium of calcium homeostasis via regulating β-tubulin in rabbit sinoatrial node cells.

Ethnopharmacological Relevance: β-tubulin is a skeletal protein of sinoatrial node cells (SANCs) that maintains the physiological structure of SANCs and inhibits calcium overload. Tongyang Huoxue decoction (TYHX) is widely used to treat sick sinus syndrome (SSS) owing to its effects on calcium channels regulation and SANCs protection.

Aim Of The Study: This study focuses on the mechanism of TYHX in improving the hypoxia/reoxygenation (H/R)-induced disequilibrium of calcium homeostasis in SANCs via regulating β-tubulin.

Salivary Biomarkers to Differentiate between and Influenza A Virus-Related Pneumonia in Children.

Community-acquired pneumonia (CAP) is common among children and can be fatal in certain conditions. In children, CAP can be caused by viral or bacterial infections. Identification of pathogens can help select appropriate therapeutic strategies.

A chimeric antigen receptor uniquely recognizing MICA/B stress proteins provides an effective approach to target solid tumors.

Background: The advent of chimeric antigen receptor (CAR) T cell therapies has transformed the treatment of hematological malignancies; however, broader therapeutic success of CAR T cells has been limited in solid tumors because of their frequently heterogeneous composition. Stress proteins in the MICA and MICB (MICA/B) family are broadly expressed by tumor cells following DNA damage but are rapidly shed to evade immune detection.

Methods: We have developed a novel CAR targeting the conserved α3 domain of MICA/B (3MICA/B CAR) and incorporated it into a multiplexed-engineered induced pluripotent stem cell (iPSC)-derived natural killer (NK) cell (3MICA/B CAR iNK) that expressed a shedding-resistant form of the CD16 Fc receptor to enable tumor recognition through two major targeting receptors.

HDAC1 disrupts the tricarboxylic acid (TCA) cycle through the deacetylation of Nur77 and promotes inflammation in ischemia-reperfusion mice.

Histone deacetylase enzymes (HDACs) regulate protein acetylation. HDAC1 is known to enhance ischemia/reperfusion (I/R) injury, but its underlying mechanism(s) of action have not been defined. Here, in vivo mouse models of myocardial I/R were used to investigate the role of HDAC1 during I/R myocardial injury.

Association Between Oral Metformin Use and the Development of Age-Related Macular Degeneration in Diabetic Patients: A Systematic Review and Meta-Analysis.

Purpose: Metformin is a biguanide derivative that is commonly used for the treatment of diabetes mellitus (DM). It demonstrates antioxidative, anti-inflammatory, and antiangiogenic activity within the ocular tissue and thus may be implicated in the treatment of age-related macular degeneration (AMD). However, epidemiological studies have shown conflicting results.

Survival After Invasive or Conservative Management of Stable Coronary Disease.

Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing.