Inhibiting the functional role of negative regulators in immune cells is an effective approach for developing immunotherapies. The serine/threonine kinase hematopoietic progenitor kinase 1 (HPK1) involved in the T-cell receptor signaling pathway attenuates T-cell activation by inducing the degradation of SLP-76 through its phosphorylation at Ser-376, reducing the immune response. Interestingly, several studies have shown that the genetic ablation or pharmacological inhibition of HPK1 kinase activity improves the immune response to cancers by enhancing T-cell activation and cytokine production; therefore, HPK1 could be a promising druggable target for T-cell-based cancer immunotherapy.
View Article and Find Full Text PDFIn the context of virus outbreaks, the need for early and accurate diagnosis has become increasingly urgent. In addition to being crucial for effective disease control, timely and precise detection of viral infections is also necessary for the implementation of essential public health measures, especially during pandemics. Among these measures, point-of-care testing (POCT) stands out as a powerful approach with the potential to revolutionize the landscape of viral diagnosis.
View Article and Find Full Text PDFAtherosclerosis, the leading cause of death, is a vascular disease of chronic inflammation. We recently showed that angiopoietin-like 4 (ANGPTL4) promotes cardiac repair by suppressing pathological inflammation. Given the fundamental contribution of inflammation to atherosclerosis, we assessed the role of ANGPTL4 in the development of atherosclerosis and determined whether ANGPTL4 regulates atherosclerotic plaque stability.
View Article and Find Full Text PDFThere are several reports that herpes zoster characterized by reactivation of varicella zoster virus (VZV) following coronavirus disease 2019 (COVID-19) vaccines can occur. Herein, we report VZV meningitis, herpes zoster ophthalmicus (HZO), and late neurotrophic keratitis after receiving a second dose of messenger RNA (mRNA) COVID-19 vaccine. A 74-year-old man developed a vesicular skin rash on the forehead, scalp, nose, and left upper eyelid with a severe headache.
View Article and Find Full Text PDFThe mechanism regulating proteasomal activity under proteotoxic stress conditions remains unclear. Here, we showed that arsenite-induced proteotoxic stress resulted in upregulation of Arabidopsis homologous PUB22 and PUB23 U-box E3 ubiquitin ligases and that pub22pub23 double mutants displayed arsenite-insensitive seed germination and root growth phenotypes. PUB22/PUB23 downregulated 26S proteasome activity by promoting the dissociation of the 19S regulatory particle from the holo-proteasome complex, resulting in intracellular accumulation of Ub -GFP, an artificial substrate of the proteasome complex, and insoluble poly-ubiquitinated proteins.
View Article and Find Full Text PDFThis work presents the first full disclosure of BALLU, Buoyancy Assisted Lightweight Legged Unit, and describes the advantages and challenges of its concept, the hardware design of a new implementation (BALLU2), a motion analysis, and a data-driven walking controller. BALLU is a robot that never falls down due to the buoyancy provided by a set of helium balloons attached to the lightweight body, which solves many issues that hinder current robots from operating close to humans. The advantages gained also lead to the platform's distinct difficulties caused by severe nonlinearities and external forces such as buoyancy and drag.
View Article and Find Full Text PDFCryogenic-electron microscopy (cryo-EM) is the preferred method to determine 3D structures of proteins and to study diverse material systems that intrinsically have radiation or air sensitivity. Current cryo-EM sample preparation methods provide limited control over the sample quality, which limits the efficiency and high throughput of 3D structure analysis. This is partly because it is difficult to control the thickness of the vitreous ice that embeds specimens, in the range of nanoscale, depending on the size and type of materials of interest.
View Article and Find Full Text PDFPurpose: This study aimed to evaluate the effects of head monted display based home-visits virtual reality simulation (HVRS) program developed for undergraduate nursing students.
Methods: A nonequivalent control group with a non-synchronized design was utilized and 84 participants (experimental group, 44; control group, 40) were recruited from August 31, 2020 to November 8, 2020 in Gwangju metropolitan city. The HVRS program consisted of scenarios of three nursing cases, hypertension, diabetes mellitus, and stroke.
Introduction: Identification of Baxter's nerve (BN) has proven challenging for less experienced practitioners using ultrasonography due to a lack of adequate landmarks. This study aimed to establish novel, user-friendly anatomical landmarks and to describe useful structures to localize BN.
Materials And Methods: We examined 10 fresh cadaveric feet and identified the interobserver agreement of measuring three surface landmarks: the most medially protruded point on the medial malleolus (P), the navicular tuberosity (Q), and the center of the calcaneus (B).
Light sheet fluorescence microscopy (LSFM) has become an indispensable tool in biomedical studies owing to its depth-sectioning capability and low photo-bleaching. The axial resolution in LSFM is determined mainly by the thickness of the illumination sheet, and a high numerical-aperture lens is thus preferred in the illumination to increase the axial resolution. However, a rapid divergence of the illumination beam limits the effective field-of-view (FoV), that provides high-resolution images.
View Article and Find Full Text PDFBackground: β-blockers (BBs) are considered primary therapy in stable heart failure (HF) with reduced ejection fraction (HFrEF) without atrial fibrillation (AF); evidence-based benefits of BB on outcome have been documented. However, BBs have not been shown to improve mortality or reduce hospital admissions in HF patients with AF. This study assessed the relationship between BBs at discharge and relevant clinical outcomes in acute heart failure (AHF) patients with AF.
View Article and Find Full Text PDFAim: To evaluate the correlation between intraocular pressure (IOP) and various obesity-related health factors in patients with ocular hypertension in Korea.
Methods: A total of 40 850 subjects underwent age, sex, body weight, and height assessments and automated multiphasic tests, including non-contact tonometry, automated perimetry, fundus photography, systolic/diastolic blood pressure measurement, and evaluation of obesity-related health parameters such as obesity index, body mass index (BMI), a body shape index (ABSI), and waist-to-height ratio (WtHR). Subjects were divided into ocular hypertension group and normal IOP group according to IOP after matching of age and sex.
Eur J Clin Pharmacol
August 2020
Purpose: Cytochrome P450 (CYP) is involved in the metabolism of valproic acid (VPA). Specifically, CYP2C9 and CYP2A6 are the main enzymes responsible for VPA metabolism. However, the correlation between plasma VPA concentrations and CYP2C9 and CYP2A6 gene variations is uncertain.
View Article and Find Full Text PDFAlthough some methods to improve phase-change memory efficiency have been proposed, an effective experimental approach to induce a phase-change like process without external heat energy has not yet been reported. Herein we have shown that GeTe is a prototype phase-change material, which can exhibit a non-thermal phase-change-like process under uniaxial stress. Due to its structural characteristics like directional structural instability and resonance bonding under 1% uniaxial stress, we observed that bond switching in the GeTe film between short and long bonds is possible.
View Article and Find Full Text PDFAdvances in the field of nanomedicine have led to the development of various gene carriers with desirable cellular responses. However, unfavorable stability and physicochemical properties have hindered their applications in vivo. Therefore, multifunctional, smart nanocarriers with unique properties to overcome such drawbacks are needed.
View Article and Find Full Text PDFBackground: There have been few studies to evaluate the prognostic implications of guideline-directed therapy according to the temporal course of heart failure. This study assessed the relationship between adherence to guideline-directed therapy at discharge and 60-day clinical outcomes in acute heart failure (AHF) and acute decompensated chronic heart failure (ADCHF) separately.
Methods: Among 5,625 AHF patients who were recruited from a multicenter cohort registry of Korean Acute Heart Failure, 2,769 patients with reduced ejection fraction were analyzed.
Acute myocardial infarction (AMI) is a fatal cardiovascular disease, and mortality is relatively high; therefore, integrated assessment is necessary for its management. There are several risk predictive models, but treatment trends have changed due to newly introduced medications and the universal use of percutaneous coronary intervention (PCI). The author aimed to find out predictive factors of in-hospital mortality in Korean patients with AMI.
View Article and Find Full Text PDFRecently, the modification of the epigenetic status of somatic cell nuclear transfer (SCNT) embryos by treatment with histone deacetylase inhibitors (HDACis) has made it possible to alter epigenetic traits and improve the developmental competence of these embryos. In the current study, we examined the effects of an HDACi, quisinostat (JNJ), on the in vitro development of porcine cloned embryos and their epigenetic nuclear reprogramming status. SCNT embryos were cultured under various conditions, and we found that treatment with 100 nM JNJ for 24 h post activation could improve blastocyst formation rates compared to the control (P < 0.
View Article and Find Full Text PDFVarious commercial vaccines are used for immunization against hepatitis B. However, these immunotherapeutic vaccines require invasive administration, which can induce side effects, and require multiple shots to elicit an immune response, limiting their efficacy. Compared to traditional hepatitis B vaccines, polymer nanoparticles have more advantageous inherent properties as vaccine delivery carriers, providing increased stability of encapsulated antigen, the possibility of single-shot immunotherapy, and the capability of mucosal administration, which allows various routes of vaccination.
View Article and Find Full Text PDFAtUBC32, AtUBC33, and AtUBC34 comprise Arabidopsis group XIV E2 ubiquitin-conjugating enzymes. Yeast two-hybrid, in vitro pull-down, and bimolecular fluorescence complementation assays revealed that group XIV E2s are interacting partners of the U-box-type E3 ligase PUB19, a negative regulator of drought stress response. These three AtUBCs are co-localized with PUB19 to the punctae-like structures, most of which reside on the endoplasmic reticulum membrane of tobacco leaf cells.
View Article and Find Full Text PDFJ Ocul Pharmacol Ther
October 2018
Purpose: To compare the efficacy of 0.1%, 0.18%, and 0.
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