Biomarkers.

Background: C-reactive protein (CRP) is widely used in clinical practice as a marker for inflammatory condition. Previous studies have examined the association between CRP levels in peripheral blood and Alzheimer's disease (AD) dementia, but have yielded mixed results. In this study, we investigated the association between serum CRP levels and in vivo cerebral beta-amyloid (Aβ) deposition in nondemented older adults.

Developing Topics.

Background: We investigated heterogeneities in clinical progression trajectories among cognitively impaired (CI) older adults who were positive for both beta-amyloid (Aβ) and neurodegeneration biomarkers of Alzheimer's disease (AD) using trajectory clustering analysis. We then compared clinical and neuroimaging variables across clusters with different clinical trajectories.

Method: CI older adults, consisting of individuals with mild cognitive impairment (MCI) or mild AD dementia were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE).

Discovery of TCP-(MP)-caffeic acid analogs as a new class of agents for treatment of osteoclastic bone loss.

Inhibition of LSD1 was proposed as promising and attractive therapies for treating osteoporosis. Here, we synthesized a series of novel TCP-(MP)-Caffeic acid analogs as potential LSD1 inhibitors to assess their inhibitory effects on osteoclastogenesis by using TRAP-staining assay and try to explore the preliminary SAR. Among them, TCP-MP-CA (11a) demonstrated osteoclastic bone loss both in vitro and in vivo, showing a significant improvement in the in vivo effects compared to the LSD1 inhibitor GSK-LSD1.

Long-term prediction of algal chlorophyll based on empirical models and the machine learning approach in relation to trophic variation in Juam Reservoir, Korea.

This study analyzed spatiotemporal variation and long-term trends in water quality indicators and trophic state conditions in an Asian temperate reservoir, Juam Reservoir (JR), and developed models that forecast algal chlorophyll (CHL-a) over a period of 30 years, 1993-2022. The analysis revealed that there were longitudinal gradients in water quality indicators along the reservoir, with notable influences from tributaries and seasonal variations in nutrient regimes and suspended solids. The empirical model showed phosphorus was found to be the key determinant of algal biomass, while suspended solids played a significant role in regulating water transparency.

Promising properties of cytochrome P450 BM3 reconstituted from separate domains by split intein.

Recombinant cytochrome P450 monooxygenases possess significant potential as biocatalysts, and efforts to improve heme content, electron coupling efficiency, and catalytic activity and stability are ongoing. Domain swapping between heme and reductase domains, whether natural or engineered, has thus received increasing attention. Here, we successfully achieved split intein-mediated reconstitution (IMR) of the heme and reductase domains of P450 BM3 both in vitro and in vivo.

Construction and characterization of a functional variant hFGF7 with enhanced properties by circular permutation.

Human fibroblast growth factor 7 (hFGF7) is a member of the paracrine-acting FGF family and mediates various reactions such as wound healing, tissue homeostasis, and liver regeneration. These activities make it a plausible candidate for pharmaceutical applications as a drug. However, the low expression level and stability of the recombinant hFGF7 were known to be major hurdles for further applications.

Association between brain amyloid deposition and longitudinal changes of white matter hyperintensities.

Background: Growing evidence suggests that not only cerebrovascular disease but also Alzheimer's disease (AD) pathological process itself cause cerebral white matter degeneration, resulting in white matter hyperintensities (WMHs). Some preclinical evidence also indicates that white matter degeneration may precede or affect the development of AD pathology. This study aimed to clarify the direction of influence between in vivo AD pathologies, particularly beta-amyloid (Aβ) and tau deposition, and WMHs through longitudinal approach.

Development of a Cognitive Composite for Preclinical Alzheimer's Disease in Korean Older Adults.

Background: As tracking subtle cognitive declines in the preclinical stage of Alzheimer's disease (AD) is difficult with traditional individual outcome measures, need for cognitive composite for preclinical AD is widely recognized.

Objective: We aimed to develop culturally appropriate cognitive composite that sensitively identifies subtle cognitive decline of preclinical AD in Korean older adults.

Methods: A total 225 cognitively normal elderly individuals from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, were included.

One-step metal affinity purification of recombinant hFGF19 without using tags.

Human fibroblast growth factor 19 (hFGF19) belongs to the endocrine FGF19 superfamily and is considered a potential agent to treat severe or relapsing nonalcoholic fatty liver disease. Numerous studies have confirmed the beneficial effects of this hormone on the related symptoms of the disease and attempts at producing recombinant proteins in various hosts are steadily proliferating. Recently, we reported that authentic hFGF19 can be solubly expressed through combining synonymous codon substitutions and co-expression with disulfide-bond isomerase (DsbC) in Escherichia coli.

Enhanced Light Absorption and Efficient Carrier Collection in MoS Monolayers on Au Nanopillars.

We fabricated hybrid nanostructures consisting of MoS monolayers and Au nanopillar (Au-NP) arrays. The surface morphology and Raman spectra showed that the MoS flakes transferred onto the Au-NPs were very flat and nonstrained. The Raman and photoluminescence intensities of MoS/Au-NP were 3- and 20-fold larger than those of MoS flakes on a flat Au thin film, respectively.

Mental Health and Quality of Life for Healthcare Workers in a University Hospital Under COVID-19.

Objective: The aim of this study was to assess the psychosocial characteristics of the employees working at a university hospital and investigated the factors affecting their quality of life (QOL) under COVID-19.

Methods: This study enrolled 1,191 healthcare workers from a university hospital, including doctors, nurses, administrative officer and technicians. Besides demographic information, depression, anxiety, somatization, insomnia, resilience, and QOL were assessed.

A designed fusion tag for soluble expression and selective separation of extracellular domains of fibroblast growth factor receptors.

Fibroblast growth factor receptors (FGFRs) generate various transduction signals by interaction with fibroblast growth factors (FGFs) and are involved in various biological functions such as cell proliferation, migration, and differentiation. Malfunction of these proteins may lead to the development of various diseases, including cancer. Accordingly, FGFRs are considered an alternative therapeutic target for protein and/or gene therapy.

The Korean Version of Fear of COVID-19 Scale: Psychometric Validation in the Korean Population.

Objective: Coronavirus disease 2019 (COVID-19) has psychological effects such as anxiety and depression as well as direct infection in people. The Fear of COVID-19 scale is a scale that can measure anxiety related to COVID-19 in a short time. The purpose of this study was to verify the reliability and validity the Korean version of Fear of COVID-19 scale (KF-COVID-19S).

Enhanced optical absorption in conformally grown MoS layers on SiO/Si substrates with SiO nanopillars with a height of 50 nm.

The integration of transition metal dichalcogenide (TMDC) layers on nanostructures has attracted growing attention as a means to improve the physical properties of the ultrathin TMDC materials. In this work, the influence of SiO nanopillars (NPs) with a height of 50 nm on the optical characteristics of MoS layers is investigated. Using a metal organic chemical vapor deposition technique, a few layers of MoS were conformally grown on the NP-patterned SiO/Si substrates without notable strain.

Soluble Expression of hFGF19 without Fusion Protein through Synonymous Codon Substitutions and DsbC Co-Expression in .

Human fibroblast growth factor 19 (hFGF19) is a difficult-to-express protein that is frequently fused with another protein for soluble expression. However, residual amino acids after cleavage with protease represent one of the major problems in therapeutic protein development. Here, we introduced synonymous codon substitutions in the N-terminal region encoding sequence of and co-expressed disulfide bond isomerase (ΔssDsbC) to functionally express hFGF19 without any fusion protein.

Soluble overexpression of a flagellin derivative from Salmonella enterica using synonymous codon substitutions of 5'-coding region in Escherichia coli.

Objective: To obtain a recombinant flagellin derivative CBLB502, expressed in functionally soluble form, the technology of library construction and screening of synonymous codon variants was employed, and its expression, solubility, and activity were assessed.

Results: We screened several synonymous codon variants scvCBLB502s with the enhanced solubility from the constructed library, harboring the random substitutions of the first ten amino acid residues of the parental CBLB502 with synonymous codons. Among them, scvCBLB502-5 was purified (> 8.

Engineering of Immunoglobulin Fc Heterodimers Using Yeast Surface-Displayed Combinatorial Fc Library Screening.

Immunoglobulin Fc heterodimers, which are useful scaffolds for the generation of bispecific antibodies, have been mostly generated through structure-based rational design methods that introduce asymmetric mutations into the CH3 homodimeric interface to favor heterodimeric Fc formation. Here, we report an approach to generate heterodimeric Fc variants through directed evolution combined with yeast surface display. We developed a combinatorial heterodimeric Fc library display system by mating two haploid yeast cell lines, one haploid cell line displayed an Fc chain library (displayed FcCH3A) with mutations in one CH3 domain (CH3A) on the yeast cell surface, and the other cell line secreted an Fc chain library (secreted FcCH3B) with mutations in the other CH3 domain (CH3B).

Crystal structures of immunoglobulin Fc heterodimers reveal the molecular basis for heterodimer formation.

We determined the X-ray crystal structure of an immunoglobulin fragment crystallizable (Fc) heterodimer, EW-RVT, at a resolution of 2.5Å and found that the designed asymmetric interaction residues located in the heterodimeric CH3 interface favor Fc heterodimer formation. We further generated an inter-CH3 disulfide-bonded heterodimeric Fc variant, EW-RVT(S-S), which exhibited improved heterodimer formation and thermodynamic stability compared with the parent EW-RVT variant.

The benefit of microsatellite instability is attenuated by chemotherapy in stage II and stage III gastric cancer: Results from a large cohort with subgroup analyses.

We previously reported that the prognosis of microsatellite instability high (MSI-H) gastric cancer is similar to that of MSI-low/microsatellite stable (MSI-L/MSS) gastric cancer. The reason for this seemed to be related to the effects of chemotherapy. To verify this hypothesis, we expanded the study population and reanalyzed the prognosis of MSI-H gastric cancer.

A heterodimeric Fc-based bispecific antibody simultaneously targeting VEGFR-2 and Met exhibits potent antitumor activity.

Heterodimeric Fc designed by engineering the CH3 homodimeric interface of immunoglobulin G1 serves as an attractive scaffold for the generation of bispecific antibodies (bsAb) due to the favorable properties of the Fc region. In this study, we describe a heterodimeric Fc generated by substituting the conserved electrostatic interactions at the CH3 core interface with asymmetric hydrophobic interactions and introducing asymmetric, long-range electrostatic interactions at the rim of the CH3 interface. Coexpression of Fc proteins carrying the combined CH3 variant pairs in HEK293F cells produced the heterodimer, which was purified with more than 90% yield, and retained wild-type Fc biophysical properties.

The proteasome inhibitor MG132 potentiates TRAIL receptor agonist-induced apoptosis by stabilizing tBid and Bik in human head and neck squamous cell carcinoma cells.

Head and neck squamous cell carcinoma (HNSCC) is often resistant to conventional chemotherapy and thus requires novel treatment regimens. Here, we investigated the effects of the proteasome inhibitor MG132 in combination with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or agonistic TRAIL receptor 1 (DR4)-specific monoclonal antibody, AY4, on sensitization of TRAIL- and AY4-resistant human HNSCC cell lines. Combination treatment of HNSCC cells synergistically induced apoptotic cell death accompanied by caspase-8, caspase-9, and caspase-3 activation and Bid cleavage into truncated Bid (tBid).

Expression of soluble and functional human neonatal Fc receptor in Pichia pastoris.

The neonatal Fc receptor (FcRn) is a non-covalently associated heterodimeric protein composed of a transmembrane anchored heavy chain (alphaFcRn) and a soluble light chain beta2-microglobulin (beta2m). In addition to its role in the transfer of maternal immunoglobulin Gs (IgGs) to the fetus, FcRn plays a key role in prolonging the serum half-life of IgGs in vivo. Herein, we report a strategy for functional expression of soluble human FcRn (shFcRn) in Pichia pastoris using a two-promoter vector system, where alphaFcRn and beta2m are co-expressed under their respective promoters in a single vector.