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Moon Jung Choi,1 Kang Chan Choi,1 Do Hyun Lee,1 Hwa Yeon Jeong,1 Seong Jae Kang,1 Min Woo Kim,1 In Ho Jeong,1 Young Myoung You,1 Jin Suk Lee,2 Yeon Kyung Lee,1 Chan Su Im,1 Yong Serk Park1 1Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea; 2Department of Anatomy, Yonsei University Wonju College of Medicine, Wonju, Republic of KoreaCorrespondence: Chan Su Im; Yong Serk Park, Department of Biomedical Laboratory Science, Yonsei University, Wonju, Gangwon, 220-710, Republic of Korea, Email chanzzhu@nate.com; parkys@yonsei.ac.krIntroduction: Avoiding phagocytic cells and reducing off-target toxicity are the primary hurdles in the clinical application of nanoparticles containing therapeutics. For overcoming these errors, in this study, nanoparticles expressing CD47 proteins inhibiting the phagocytic attack of immune cells were prepared and then evaluated as an anti-cancer drug delivery vehicle.Methods: The CD47+ cell-derived nanoparticles (CDNs) were prepared from the plasma membranes of human embryonic kidney cells transfected with a plasmid encoding CD47. And the doxorubicin (DOX) was loaded into the CDNs, and anti-EGF receptor (EGFR) antibodies were conjugated to the surface of the CDNs to target tumors overexpressing EGFR.Results: The CD47+iCDNs-DOX was successfully synthesized having a stable structure. The CD47+CDNs were taken up less by RAW264.7 macrophages compared to control CDNs. Anti-EGFR CD47+CDNs (iCDNs) selectively recognized EGFR-positive MDA-MB-231 cells in vitro and accumulated more effectively in the target tumor xenografts in mice. Moreover, iCDNs encapsulating doxorubicin (iCDNs-DOX) exhibited the highest suppression of tumor growth in mice, presumably due to the enhanced DOX delivery to tumor tissues, compared to non-targeting CDNs or CD47- iCDNs.Discussion: These results suggest that the clinical application of biocompatible cell membrane-derived nanocarriers could be facilitated by functionalization with macrophage-avoiding CD47 and tumor-targeting antibodies.Graphical Abstract: Keywords: cell-derived nanoparticles, immune surveillance, CD47, doxorubicin, tumor targeting, cancer therapy

ObjectiveGenome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis.MethodsWe built gene expression predictive models in blood B cells, CD4+and CD8+T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches.ResultsTWAS identified 171 genes for SLE (p–5); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association betweenCD83and SLE (p–8). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5×10–9) aroundCD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect onACAP1, and that presence of the SLE risk allele decreasedACAP1expression.ConclusionsCell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

Supplementary Figure 2 from Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival

Supplementary Figure 1 from Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival

Supplementary Figure 4 from Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival

Supplementary Methods from Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival

Triple-negative breast cancer (TNBC) cells do not contain various receptors for targeted treatment, a reason behind the poor prognosis of this disease. In this study, biocompatible theranostic erythrocyte-derived nanoparticles (EDNs) were developed and evaluated for effective early diagnosis and treatment of TNBC. The anti-cancer drug, doxorubicin (DOX), was encapsulated into the EDNs and diagnostic quantum dots (QDs) were incorporated into the lipid bilayers of EDNs for tumor bio-imaging. Then, anti-epidermal growth factor receptor (EGFR) antibody molecules were conjugated to the surface of EDNs for TNBC targeting (iEDNs). According to the confocal microscopic analyses and biodistribution assay, iEDNs showed a higher accumulation in EGFR-positive MDA-MB-231 cancers in vitro as well as in vivo, compared to untargeted EDNs. iEDNs containing doxorubicin (iEDNs-DOX) showed a stronger inhibition of target tumor growth than untargeted ones. The resulting anti-EGFR iEDNs exhibited strong biocompatibility, prolonged blood circulation, and efficient targeting of TNBC in mice. Therefore, iEDNs may be used as potential TNBC-targeted co-delivery systems for therapeutics and diagnostics.

Objective. To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). Methods. We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. Results. In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. Conclusion. Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN. (J Rheum Dis 2021;28:150-158)

Objectives To investigate the causes and risk of death in a large cohort of Korean patients with rheumatoid arthritis (RA). Methods Patients in the Hanyang BAE (Bae registry of Autoimmune diseases for Epidemiology) RA cohort who fulfilled the American College of Rheumatology criteria were analyzed. A total of 2355 patients were enrolled from October 2001 to December 2015. Mortality data were derived by linking with data from the Korean National Statistical Office. Standardized mortality ratio was estimated by dividing observed deaths by expected number of deaths in the general population. Results Over the observation period, 225 deaths were reported. Total age- and sex-adjusted standardized mortality ratio was 1.65 (95% confidence interval 1.44-1.87). The most common cause of death was malignancy (40 cases; 17.8%), followed by respiratory disease (38 cases; 16.9%) and cardiovascular disease (32 cases; 14.2%). Mortality rate and causes of death differed according to year and age of RA onset. Compared with survivors, individuals who died were more likely to be male, smokers, diagnosed with RA at an older age, and to have long disease duration, higher erythrocyte sedimentation rate and C-reactive protein, higher rheumatoid factor positivity rate, more severe radiographic damage, and more comorbidities. Conclusion The mortality rate of patients with RA remains higher than that of the general population. Therefore, to improve the survival of patients with RA, attention should be paid to the management of comorbidities as well as to the RA itself.

Purpose To investigate the use of a retinal thickness deviation map generated from swept-source (SS) OCT images for hydroxychloroquine retinopathy screening. Design Retrospective cohort study. Participants This study included 1192 Korean patients with a history of hydroxychloroquine treatment: 881 patients (1723 eyes) in the discovery set and 311 patients (591 eyes) in the validation set. Patients were screened for retinal toxicity using SS OCT, fundus autofluorescence, and standard automated perimetry. Methods According to the 2016 American Academy of Ophthalmology guidelines, hydroxychloroquine retinopathy was diagnosed by the presence of abnormalities on ≥1 objective structural tests alongside corresponding visual field defects. The 12 × 9-mm2 macular volume SS OCT scan was performed, and the retinal thickness deviation map was generated automatically using the built-in software. On this map, yellow (retinal thickness, Main Outcome Measures The rate and patterns of abnormalities on the retinal thickness deviation map and sensitivity and specificity of the diagnostic criteria. Results The retinal thickness deviation map showed the following abnormal patterns in eyes with hydroxychloroquine retinopathy: pericentral (36.0%) or parafoveal (6.1%) ring, mixed-ring (34.2%), central island (13.2%), and whole macular thinning (10.5%). The criterion of ≥5 contiguous red pixels showing 1 of the 5 characteristic patterns in both eyes yielded the greatest diagnostic performance (sensitivity and specificity of 98.2% and 89.1% and of 100% and 87.5% in the discovery and validation set data, respectively). Moreover, the area of abnormal pixels on the map was correlated significantly with the mean deviation (P Conclusions The retinal thickness deviation map may facilitate the objective evaluation of hydroxychloroquine retinopathy because it does not require subjective, morphologic evaluation of the outer retinal layers. The map has the potential to enhance hydroxychloroquine retinopathy screening when used in conjunction with conventional screening methods.

ObjectiveSystemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.MethodsWe newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.ResultsWe identified 113 genetic regions including 46 novel loci at genome-wide significance (p−8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=−0.242) and non-albumin protein (rg=0.238).ConclusionThis study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

The nanoscale spatiotemporal resolution of single-particle tracking (SPT) renders it a powerful method for exploring single-molecule dynamics in living cells or tissues, despite the disadvantages of using traditional organic fluorescence probes, such as the weak fluorescent signal against the strong cellular autofluorescence background coupled with a fast-photobleaching rate. Quantum dots (QDs), which enable tracking targets in multiple colors, have been proposed as an alternative to traditional organic fluorescence dyes; however, they are not ideally suitable for applying SPT due to their hydrophobicity, cytotoxicity, and blinking problems. This study reports an improved SPT method using silica-coated QD-embedded silica nanoparticles (QD2), which represent brighter fluorescence and are less toxic than single QDs. After treatment of QD2 in 10 μg/mL, the label was retained for 96 h with 83.76% of labeling efficiency, without impaired cell function such as angiogenesis. The improved stability of QD2 facilitates the visualization of in situ endothelial vessel formation without real-time staining. Cells retain QD2 fluorescence signal for 15 days at 4 °C without significant photobleaching, indicating that QD2 has overcome the limitations of SPT enabling long-term intracellular tracking. These results proved that QD2 could be used for SPT as a substitute for traditional organic fluorophores or single quantum dots, with its photostability, biocompatibility, and superior brightness.

Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH-specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in silico analyses. The Japanese GWAS identified 4 significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 [odds ratio (OR) = 1.99, P-value = 1.1 × 10−9)], TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10−8) and MYO16 (OR = 3.91, P-value = 4.9 × 10−10), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. We identified three novel susceptibility loci for S-ONFH in SLE.

Sodium is a physiologically essential nutrient, but excessive intake is linked to the increased risk of various chronic diseases, particularly cardiovascular. It is, therefore, necessary to accomplish an evidence-based approach and establish the Korean Dietary Reference Intakes (KDRIs) index, to identify both the nutritional adequacy and health effects of sodium. This review presents the rationale for and the process of revising the KDRIs for sodium and, more importantly, establishing the sodium Chronic Disease Risk Reduction Intake (CDRR) level, which is a new specific set of values for chronic disease risk reduction. To establish the 2020 KDRIs for dietary sodium, the committee conducted a systematic literature review of the intake-response relationships between the selected indicators for sodium levels and human chronic diseases. In this review, 43 studies published from January 2014 to December 2018, using databases of PubMed and Web of Science, were finally included for evaluating the risk of bias and strength of evidence (SoE). We determined that SoE of the relationship between dietary sodium and cardiovascular diseases, cerebrovascular disease, and hypertension, was moderate to strong. However, due to insufficient scientific evidence, we were unable to establish the estimated average requirement and the recommended nutrient intake for dietary sodium. Therefore, the adequate intake of sodium for adults was established to be 1,500 mg/day, whereas the CDRR for dietary sodium was established at 2,300 mg/day for adults. Intake goal for dietary sodium established in the 2015 KDRIs instead of the tolerable upper intake level was not presented in the 2020 KDRIs. For the next revision of the KDRIs, there is a requirement to pursue further studies on nutritional adequacy and toxicity of dietary sodium, and their associations with chronic disease endpoint in the Korean population.

This study aimed to clarify the association between the frequency of dining out and the risk of obesity, diabetes mellitus, and dyslipidemia among Korean adults. This cross-sectional study surveyed 640 participants aged 20-69 years in Korea. Daily intake of energy, fat, protein, and cholesterol significantly increased as the frequency of dining out increased (

The purpose of this study was to develop a sodium index, which is a tool for estimating and assessing sodium intake easily and quickly, to assist in the prevention of various diseases induced by excess sodium intake in Korean adults.The 24-h urine collection and dietary behavior surveys were performed on 640 healthy people in 4 regions of South Korea, and an equation for the estimation of 24-h sodium intake was developed. The validity and reliability of the equation were verified with 200 adults. The sodium index was developed by converting the estimated sodium intake using the equation. Finally, the sodium intake status of 1,600 adults was assessed using the sodium index.The equation included sex, age, body mass index, eating habit and dietary behaviors related to sodium intake. In validity test of the equation, the mean bias between sodium intake using 24-h urine analysis and using the equation from the Bland-Altman plots was -1.5 mg/day. The sensitivity and specificity of the equation for estimation of sodium intake were 80.5% and 64.4%, respectively. In the reliability test of the equation, there was no significant difference between the first and second sodium intakes calculated using the equations, and Spearman's correlation coefficient between the 2 sodium intakes was 0.98. Sodium intake can be assessed as 'very moderate' for 75-100 on the sodium index, 'moderate' for 100-150, 'careful' for less than 75 or 150-200, and 'severe' for 250 or more. When sodium intake was assessed using the sodium index in 1,600 subjects, 54.3% and 24.3% of the subjects were assessed to be in the 'careful' and 'severe' categories, respectively.Using a simple questionnaire, the sodium index can be used to monitor and assess sodium intake status, assisting in nutrition education and counseling in a large population.

South Korea has been conducting the Sodium Reduction Restaurant Project since 2015 to reduce sodium contents in restaurant menus. The purpose of this study was to analyze changes in the sodium content of menus as determined by the Daegu Sodium Reduction Restaurant Project between 2015 and 2019.Intervention was aimed at reducing the sodium contents of over 10% of menu items in participating restaurants. On-site inspections and evaluations were conducted using a checklist, and reductions in sodium contents were determined by analyzing the salinities and sodium contents of menus after intervention.Post-intervention salinities and sodium contents were significantly lower than baseline values in 2016 (Positive correlations were found between duration of participation in the project and sodium reduction and designation rates. Sustainable long-term support at the national level is required to expand the project to other regions.

Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci1-8. Nevertheless, these loci only partially explain SLE heritability and provide limited biological insight. We report the largest study of SLE in East Asians (13,377 cases and 194,993 controls), identifying 233 association signals within 113 (46 novel) genetic loci. We detect six new lead missense variants and prioritize ten most likely putative causal variants, one of which we demonstrate exhibits allele-specific regulatory effect on ACAP1 in vitro. We suggest 677 effector genes with potential for drug repurposing, and provide evidence that two distinct association signals at a single locus act on different genes (NCF2 and SMG7). We demonstrate that SLE-risk variants overlap with cell-specific active regulatory elements, notably EBNA2-mediated super-enhancers in Epstein-Barr Virus-transformed B cells, and implicate the role for non-immune cells in SLE biology. These findings shed light on genetic and biological understandings of SLE.

Koreans tend to have high sodium intake in restaurants. This study assessed the effect of the sodium reduction project in restaurants in Daegu Metropolitan City.A total of 156 sodium reduction menu items offered by 90 restaurants were categorized into 11 food groups to compare sodium content and salinity before and after the project. In total, 162 owners and staff members of the restaurants, as well as 727 of their customers, were surveyed on their perceptions of and satisfaction with the sodium reduction project.Average salinity of the menu items was significantly reduced from 0.70% prior to the project to 0.49% after the project (p0.001), and average sodium content was also significantly reduced from 1,470 mg to 980 mg (p0.001). The food groups with the highest sodium reduction rate were soups (46.0%) and grilled dishes (39.5%), with an average sodium reduction rate of 36.1%. The restaurant owners' average satisfaction score with the project was 39.6 points (out of 50). Customers responded that the sodium reduction menus were moderate (62.4%) and bland (27.9%), and the taste was good (48.9%) and excellent (25.0%). Approximately 52.0% and 18.6% of customers were satisfied and very satisfied, respectively, with the sodium reduction menu.Overall, the sodium reduction project in restaurants in Daegu had a positive effect because it successfully reduced the sodium content of food while also boosting the satisfaction of the restaurant owners and staff and their customers with the project.

ObjectiveGenome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. As a continuous effort, we conducted GWAS in a large Korean RA case–control population.MethodsWe newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations.ResultsWe identified six new RA-risk loci (SLAMF6, CXCL13, SWAP70, NFKBIA, ZFP36L1 and LINC00158) with pmeta−8 and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases.ConclusionThis study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.

Purpose Child safety seats (CSS) are critical for the protection of children, in case of motor vehicle accidents. Although the national legislation mandates that all newborns must be placed in an appropriately installed CSS during transportation, people often do not perceive the importance of CSS and do not use it as recommended. The purpose of this survey was to understand the use of CSS for the safe transport of newborns from hospital to home. Methods We interviewed parents of newborn infants, using a structured questionnaire, at the time of their discharge from Cheil General Hospital a Women's Health Care Center, between May 2014 and July 2014. Results A total of 403 participants were interviewed. The rate of CSS use was only 14.9%. Overall, 76.4% of the families interviewed were not aware about the recommendations on CSS use for newborns when travelling in a car. The provision of education on using CSS significantly influenced their rate of use. Parents who were educated about mounting the CSS in a car used it more as compared with others (25.7% vs. 12.2%) (P=0.002). Furthermore, if parents had heard about the importance or necessity of CSS, they used it more than others did (19.5% vs. 10.6%, P=0.032). Conclusion Despite the legal regulation, most parents transport their newborn infants without a CSS while traveling from hospital to their home. The rate of CSS use was influenced by parental education and their knowledge about its necessity. Education programs for parents must be reinforced to increase the CSS use.

Jung Seok Kim,1,* Min Woo Kim,1,* Seong Jae Kang,1,* Hwa Yeon Jeong,1 Sang Il Park,1 Yeon Kyung Lee,1 Hong Sung Kim,2 Keun Sik Kim,3 Yong Serk Park1 1Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea; 2Department of Biomedical Laboratory Science, Korea Nazarene University, Cheonan, Republic of Korea; 3Department of Biomedical Laboratory Science, Konyang University, Daejeon, Republic of Korea *These authors contributed equally to this work Background: Efficient target-specific siRNA delivery has always been a primary concern in the field of siRNA clinical application. Purpose: In this study, four different types of anti-epidermal growth factor receptor (EGFR) antibody-conjugated immunonanoparticles were prepared and tested for cancer cell-targeted therapeutic siRNA delivery. Materials and methods: The prepared nanoparticles encapsulating siRNAs were characterized by gel retardation and particle analysis using a Zetasizer. In vitro transfection and reduction of target genes, vimentin and JAK3, were determined using quantitative reverse transcription polymerase chain reaction. In vivo tumor targeting and antitumoral efficacies of the nanoparticles were evaluated in mice carrying tumors. Results: Among these immunonanoparticles, anti-EGFR immunolipoplexes and immunoviroplexes exhibited remarkable cell binding and siRNA delivery to EGFR-expressing tumor cells compared to immunoliposomes and immunovirosomes. Especially, the anti-EGFR immunoviroplexes exhibited the most efficient siRNA transfection to target tumor cells. Therefore, antitumoral vimentin and Janus kinase-3 siRNAs were loaded in the anti-EGFR immunolipoplexes and immunoviroplexes, which were tested in mice carrying SK-OV-3 tumor xenografts. In fact, the therapeutic siRNAs were efficiently delivered to the tumor tissues by both delivery vehicles, resulting in significant inhibition of tumor growth. Moreover, administration of doxorubicin in combination with anti-EGFR immunoviroplexes resulted in remarkable and synergistic tumor growth inhibition. Conclusion: This study provides experimental proof that cancer cell-targeted immunoviroplexes are an efficient siRNA delivery system for cancer therapy. Moreover, this study also suggests that a combination of conventional chemotherapy and tumor-directed anticancer siRNA therapy would be a better modality for cancer treatment. Keywords: EGFR, siRNA delivery, anti-EGFR immunonanoparticles, anti-EGFR immunoviroplexes, combinatorial therapy

PURPOSE The purpose of this study was to investigate effects of activity tracker & application use on adherence, metabolic syndrome factor and body composition of middle and senior-aged. METHODS The subjects of this study were 1,196 middle and senior-aged man and women with health hazard factor. All of subjects divided to two groups, activity tracker & application use group 990(man=492, women=498) was participating in 24 weeks, and control group 206(man=71, women=135) was not in that program. They performed physical activity utilizing activity tracker & application for 24 weeks. The following items were measured before, middle and after the program : physical activity adherence, metabolic syndrome factor and body composition. RESULTS Results of this study showed that physical activity adherence appeared nothing in drop-rate of male(9.35%) and female(8.63%) : So adherence were male(90.65%) and female(91.37%). And changes of metabolic syndrome factor variables were significantly improved in total cholesterol, triglyceride, systolic blood pressure, and glucose in activity tracker & application use group and control group after 24 weeks. Also, body composition were showed significantly different in BMI, weight, waist. CONCLUSIONS Activity tracker & application use accompanied regular physical activity were effective in middle and senior-aged health promotion. This results can be utilized not only in new health promotion program of public health center but also in a local resident health management strategies.

The development of effective assay techniques for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently received research attention due to its rapid worldwide spread and considerable risk to human health. The receptor-binding domain (RBD) of the spike (S) protein in SARS-CoV-2, a key component for viral entry that has a unique sequence compared to other structural proteins, has been considered an important diagnostic target. In this respect, low-frequency vibrational modes have the advantage of providing information about compositional and structural dependencies at the peptide level. In this study, the sensitive and selective detection of peptides derived from the RBD in SARS-CoV-2 and SARS-CoV was investigated using metamaterial-based sensing chips with a terahertz time-domain spectroscopy (THz-TDS) system. Based on their RBD sequences, two pairs of peptides with 20 residues each were prepared. The sensitivity, specificity, and reproducibility of the proposed system were examined via quantitative analysis using THz metamaterials at three resonance frequencies, and it was found that the species could be discriminated based on their sequences. The THz signals were analyzed with regard to the major amino acid components of the peptides, and the molecular distributions were also investigated based on the hydropathy and net charge of the peptides.