Broad-Spectrum Antiviral Agents against SARS-CoV-2 Variants Inhibit the Conserved Viral Protein Nsp1-RNA Interaction.

The ongoing global threats posed by COVID-19 pandemic, catalyzed by SARS-CoV-2, underscores the pressing need for effective antiviral strategies. The viral non-structural protein 1 (Nsp1) significantly influences pathogenicity by impeding host protein expression and enhancing viral RNA translation through its interaction with the stem-loop 1 (SL1) in the 5' untranslated region (UTR). We have developed a novel dual-luciferase reporter assay, designed to investigate the critical Nsp1-SL1 interaction, and identified P23E02 as a potential inhibitor.

Blume Alleviates Non-Alcoholic Fatty Liver Disease Promoted by N-(carboxymethyl)lysine.

Non-alcoholic fatty liver disease (NAFLD) is a major issue because it is closely associated with metabolic diseases. Advanced glycation end products (AGEs) are implicated as risk factors for steatosis during NAFLD progression. AGEs influence NAFLD progression through a receptor-independent pathway involving AGE cross-link formation and a receptor-dependent pathway that binds to receptors like receptors for advanced glycation end products (RAGE).

Discovery of (-)-epigallocatechin gallate, a novel olfactory receptor 2AT4 agonist that regulates proliferation and apoptosis in leukemia cells.

Olfactory receptors (ORs), the largest family of G protein-coupled receptors (GPCRs), are ectopically expressed in cancer cells and are involved in cellular physiological processes, but their function as anticancer targets is still potential. OR2AT4 is expressed in leukemia cells, influencing the proliferation and apoptosis, yet the limited number of known OR2AT4 agonists makes it challenging to fully generalize the receptor's function. In this study, we aimed to identify new ligands for OR2AT4 and to investigate their functions and mechanisms in K562 leukemia cells.

An ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation.

The immune escape of Omicron variants significantly subsides by the third dose of an mRNA vaccine. However, it is unclear how Omicron variant-neutralizing antibodies develop under repeated vaccination. We analyze blood samples from 41 BNT162b2 vaccinees following the course of three injections and analyze their B-cell receptor (BCR) repertoires at six time points in total.

Engineering of Cell Derived-Nanovesicle as an Alternative to Exosome Therapy.

Background: Exosomes, nano-sized vesicles ranging between 30 and 150 nm secreted by human cells, play a pivotal role in long-range intercellular communication and have attracted significant attention in the field of regenerative medicine. Nevertheless, their limited productivity and cost-effectiveness pose challenges for clinical applications. These issues have recently been addressed by cell-derived nanovesicles (CDNs), which are physically synthesized exosome-mimetic nanovesicles from parent cells, as a promising alternative to exosomes.

Deubiquitinase USP1 enhances CCAAT/enhancer-binding protein beta (C/EBPβ) stability and accelerates adipogenesis and lipid accumulation.

Dysregulation of the ubiquitin-proteasome system has been implicated in the pathogenesis of several metabolic disorders, including obesity, diabetes, and non-alcoholic fatty liver disease; however, the mechanisms controlling pathogenic metabolic disorders remain unclear. Transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) regulates adipogenic genes. The study showed that the expression level of C/EBPβ is post-translationally regulated by the deubiquitinase ubiquitin-specific protease 1 (USP1) and that USP1 expression is remarkably upregulated during adipocyte differentiation and in the adipose tissue of mice fed a high-fat diet (HFD).

Effect of surface matching mismatch of focal knee articular prosthetic on tibiofemoral contact stress using finite element analysis.

Aims: Focal knee arthroplasty is an attractive alternative to knee arthroplasty for young patients because it allows preservation of a large amount of bone for potential revisions. However, the mechanical behaviour of cartilage has not yet been investigated because it is challenging to evaluate in vivo contact areas, pressure, and deformations from metal implants. Therefore, this study aimed to determine the contact pressure in the tibiofemoral joint with a focal knee arthroplasty using a finite element model.

A herb mixture to ameliorate non-alcoholic fatty liver in rats fed a high-fat diet.

This study was performed to investigate the effects of an herb extract mixture (HM) in ameliorating non-alcoholic fatty liver disease (NAFLD). The HM contained equal amounts of 70% ethanol extracts from , , and . , the HM significantly inhibited lipid accumulation in oleic acid-stimulated HepG2 cells.

Serotonergic Modulation of the BNST-CeA Circuit Promotes Sex Differences in Fear Learning.

Post-traumatic stress disorder (PTSD) is characterized by intense fear memory formation and is diagnosed more often in women than men. Here, we show that serotonin differentially affects fear learning and communication in the extended amygdala of male and female mice. Females showed higher sensitivity to the effects of pharmacologically increasing serotonin during auditory fear conditioning, which enhanced fear memory recall in both sexes.

Targeting the Receptor-Binding Motif of SARS-CoV-2 with D-Peptides Mimicking the ACE2 Binding Helix: Lessons for Inhibiting Omicron and Future Variants of Concern.

The COVID-19 pandemic continues to spread around the world, with several new variants emerging, particularly those of concern (VOCs). Omicron (B.1.

Computational analysis of tibial slope adjustment with fixed-bearing medial unicompartmental knee arthroplasty in ACL- and PCL-deficient models.

Aims: A functional anterior cruciate ligament (ACL) or posterior cruciate ligament (PCL) has been assumed to be required for patients undergoing unicompartmental knee arthroplasty (UKA). However, this assumption has not been thoroughly tested. Therefore, this study aimed to assess the biomechanical effects exerted by cruciate ligament-deficient knees with medial UKAs regarding different posterior tibial slopes.

Synthesis and structure-activity relationship study of saponin-based membrane fusion inhibitors against SARS-CoV-2.

We previously discovered that triterpenoid saponin platycodin D inhibits the SARS-CoV-2 entry to the host cell. Herein, we synthesized various saponin derivatives and established a structure-activity relationship of saponin-based antiviral agents against SARS-CoV-2. We discovered that the C3-glucose, the C28-oligosaccharide moiety that consist of (→3)-β-d-Xyl-(1 → 4)-α-l-Rham-(1 → 2)-β-d-Ara-(1 → ) as the last three sugar units, and the C16-hydroxyl group were critical components of saponin-based coronavirus cell entry inhibitors.

Finite element analysis of femoral component sagittal alignment in mobile-bearing total knee arthroplasty.

Background: Recently, there has been an increasing interest in mobile-bearing total knee arthroplasty (TKA). However, changes in biomechanics for femoral component alignment in mobile-bearing TKA have not been explored in depth.

Objective: This study aims to evaluate the biomechanical effect of sagittal alignment of the femoral component in mobile-bearing TKA.

What Are the Challenges of School Nurses in South Korea in Managing Obese Children From Low-Income Households?

Given that the obesity rate among school-age children is increasing, school nurses can play a vital role in managing obesity and encouraging healthy living in school settings. Obese children from low-income backgrounds are more vulnerable than other students and require more careful attention and intervention. This qualitative study aimed to explore and understand the barriers recognized by school nurses in managing obesity in low-income household children.

Computational Design of Potent D-Peptide Inhibitors of SARS-CoV-2.

Blocking the association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2) is an attractive therapeutic approach to prevent the virus from entering human cells. While antibodies and other modalities have been developed to this end, d-amino acid peptides offer unique advantages, including serum stability, low immunogenicity, and low cost of production. Here, we designed potent novel D-peptide inhibitors that mimic the ACE2 α1-binding helix by searching a mirror-image version of the PDB.

TMPRSS2 and RNA-Dependent RNA Polymerase Are Effective Targets of Therapeutic Intervention for Treatment of COVID-19 Caused by SARS-CoV-2 Variants (B.1.1.7 and B.1.351).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent of the coronavirus disease 2019 (COVID-19) pandemic, and the development of therapeutic interventions is urgently needed. So far, monoclonal antibodies and drug repositioning are the main methods for drug development, and this effort was partially successful. Since the beginning of the COVID-19 pandemic, the emergence of SARS-CoV-2 variants has been reported in many parts of the world, and the main concern is whether the current vaccines and therapeutics are still effective against these variant viruses.

Perceived barriers to implementing case management for medical-aid beneficiaries in South Korea.

Medical aid (MA) in South Korea, a national public assistance scheme, provides minimum medical security for low-income families. The Korean government has adopted a case management (CM) programme to control MA beneficiaries' inappropriate medical use and enhance beneficiaries' quality of life. This study aimed to explore case managers' experiences of implementing CM for MA beneficiaries' potential barriers.

Effect of post-cam design on the kinematics and contact stress of posterior-stabilized total knee arthroplasty.

Background: The post-cam mechanism in the posterior-stabilized (PS) implant plays an important role, such as durability and kinematic performances, in total knee arthroplasty (TKA).

Objective: The purpose of this study was to evaluate the difference in the kinematics and contact stress of five post-cam designs, which are flat-and-flat, curve-and-curve (concave), curve-and-curve (concave and convex), helical, and asymmetrical post-cam designs, using three-dimensional finite element models.

Methods: We designed the post-cam model with five different geometries.

The influence of the number of holes in the open wedge high tibial osteotomy on knee biomechanics using finite element analysis.

Background: The most significant differences of high tibial osteotomy (HTO) were found in terms of plate length, and this was related to number of holes distal region of the plate below wedge. The purpose of this study is to evaluate the biomechanical effects of three different designs medial opening wedge plates.

Hypothesis: The design of the HTO plate influenced the outcome of the biomechanics.