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Background/Aim: Self-defense products that use high-intensity light are being developed. The intense light generated by the high-power light-emitting diodes (LEDs) of such self-defense products causes temporary blindness. However, few studies have been conducted on the visual safety of their devices. We, therefore, evaluated the effects of strong light of a short duration on the eyes of rabbits in this study. Materials and Methods: The right eyes of 15 rabbits were irradiated for 5 s with a lighting device (25 W, 150 lm/W at 700 mA LED) and four eyes of two rabbits were non-irradiated as controls. Changes in the eye structure and function were evaluated before, and immediately, 30 min, 1 h, 24 h, 7 days and 14 days after light irradiation by full-field electroretinogram (ERG), slit-lamp biomicroscopy, and retinal camera. The thickness of the outer nuclear layer of the retina tissue was measured, and histopathological signs of retinal damage were analyzed. Results: The ERG results showed that night vision was not affected. In day vision, the ERG waveform was temporarily affected immediately after light irradiation; however, it recovered within 24 h. No histopathological signs of damage were observed. Conclusion: Application of high-power LED light with short duration as used for self-defense was found to cause temporary phototoxicity, but safety was confirmed as vision recovered within 24 h.

Here, we report the complete genome sequence of a novel polerovirus, "Plantago asiatica virus A" (PlaVA), detected in Plantago asiatica using high-throughput RNA sequencing and validated by Sanger sequencing. The complete PlaVA genome contains 5,881 nucleotides and has seven open reading frames (ORF0-5 and ORF3a) encoding putative proteins (P0-5 and P3a, respectively) in an arrangement that is similar to that of typical Polerovirus members. Pairwise sequence comparisons revealed that P0 to P5 encoded by PlaVA had the highest sequence identity (25.48%-79.21%) to the corresponding proteins of previously reported poleroviruses. A phylogenetic analysis using the PlaVA P1-2 and P3 amino acid sequences and those of members of the family Solemoviridae (formerly Luteoviridae) indicated that although PlaVA belongs to the genus Polerovirus, it does not represent a known species. Consequently, PlaVA should be considered a member of a new species within the genus Polerovirus.

We herein present the complete genome sequence of codonopsis torradovirus A (CoTVA), which was isolated from Codonopsis lanceolata (deodeok) in Gangwon-do, South Korea. The CoTVA genome contains two positive-sense RNA segments, namely RNA1 (6922 nucleotides), which encodes a predicted polyprotein, and RNA2 (4613 nucleotides), which encodes a movement protein and coat proteins (CPs). The proteinase-polymerase (Pro-Pol) and CP amino acid sequences were 75% and 54% identical, respectively, to those of motherwort yellow mosaic virus. Pairwise comparisons of the Pro-Pol and CP sequences revealed that the virus described in this study should be considered a member of a new torradovirus species. Phylogenetic analysis of the Pro-Pol sequence encoded by RNA1 and the CP region encoded by RNA2 indicated that CoTVA is a new member of the genus Torradovirus in the family Secoviridae. CoTVA is the first torradovirus detected in Codonopsis lanceolata.

OBJECTIVES To study the effects of adjuvant therapy in patients with sarcomatoid renal cell carcinoma (sRCC) enrolled in the randomised phase III clinical trial E2805. PATIENTS AND METHODS The original trial (E2805) was a randomised, double-blinded phase III clinical trial comparing outcomes in 1943 patients with RCC accrued between 2006 and 2010 and treated with up to 1 year of adjuvant placebo, sunitinib, or sorafenib. The present study analyses the cohort of patients with sRCC that participated in E2805. RESULTS A total of 171 patients (8.8%) had sarcomatoid features. Of these, 52 patients received sunitinib, 58 received sorafenib, and 61 received placebo. Most patients were pT3-4 (71.1%, 63.7%, and 70.5%, respectively); 17.3%, 19.0%, and 27.9% had pathologically positive lymph nodes; and 59.6%, 62.1%, and 62.3% of the patients were University of California Los Angeles (UCLA) Integrated Staging System (UISS) very-high risk. In 49% of patients with subsequent development of metastatic disease, recurrence occurred in the lung, followed by 30% in the lymph nodes, and 13% in the liver. There was a high local recurrence rate in the renal bed (16%, 29%, and 18%, respectively). The 5-year disease-free survival (DFS) rates were 33.6%, 36.0%, and 27.8%, for sunitinib, sorafenib and placebo, respectively (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.45-1.20 for sunitinib vs placebo, and HR 0.82, 95% CI 0.53-1.28 for sorafenib vs placebo). CONCLUSIONS Adjuvant therapy with sunitinib or sorafenib did not show an improvement in DFS or OS in patients with sRCC.

Microrobots that can be precisely guided to target lesions have been studied for in vivo medical applications. However, existing microrobots have challenges in vivo such as biocompatibility, biodegradability, actuation module, and intra- and postoperative imaging. This study reports microrobots visualized with real-time x-ray and magnetic resonance imaging (MRI) that can be magnetically guided to tumor feeding vessels for transcatheter liver chemoembolization in vivo. The microrobots, composed of a hydrogel-enveloped porous structure and magnetic nanoparticles, enable targeted delivery of therapeutic and imaging agents via magnetic guidance from the actuation module under real-time x-ray imaging. In addition, the microrobots can be tracked using MRI as postoperative imaging and then slowly degrade over time. The in vivo validation of microrobot system–mediated chemoembolization was demonstrated in a rat liver with a tumor model. The proposed microrobot provides an advanced medical robotic platform that can overcome the limitations of existing microrobots and current liver chemoembolization.

Background/Aim: N1S1 rat models are commonly used in human medicine to study hepatocellular carcinoma (HCC). However, their use in veterinary medicine has not been reported. Thus, the aim of this study was to investigate whether the N1S1 rat models could be used to study canine HCC. Materials and Methods: The animals were divided into four groups: normal rat, N1S1 rat, normal dog, and HCC dog. Liver tissues of all animals were evaluated for vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β, and c-kit by immunohistochemistry. Slides of each factor were scored according to the percentage of stained tumor cells and intensity of the staining. Results: Scores of VEGF and c-kit were high both in the tumor groups (the N1S1 rat and HCC dog groups) and the normal groups of dogs and rats. PDGFR-α was lower in the N1S1 rat group than that in the normal rat group (p=0.0042). It was also lower in the HCC dog group compared to the normal dog group (p=0.0008). PDGFR-β was higher in the HCC dog group than that in the normal dog group (p=0.0023) but was not detectable in the rat groups. EGFR was not detectable in any group. Conclusion: Based on immunochemistry results, PDGFR-α and PDGFR-β can be used as biomarkers of canine HCC. Because PDGFR-α showed consistency between rats and dogs, it can be used for studying canine HCC.

Tyrosine kinase inhibitors (TKIs) are essential for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and have allowed for effective, low intensity induction regimens including no or minimal chemotherapy. Whether the use of low intensity induction regimens impacts outcomes after allogeneic hematopoietic stem cell transplant (alloHCT) is less understood. We identified consecutive adult patients with Ph+ ALL undergoing alloHCT in first complete remission (CR1) at our center from 2010 to 2021 and examined the impact of pre-transplant induction intensity on outcomes. Among the 87 identified patients, 44 (51%) received low intensity induction and 43 (49%) received induction with high intensity chemotherapy. Patients receiving low intensity induction were older (median age 60 vs. 47 years, p 0.01). Following induction, measurable residual disease (MRD) negativity by BCR::ABL1 RT-PCR was similar in the low and high intensity induction cohorts (54% and 52% respectively). Receipt of reduced intensity transplant conditioning was not associated with intensity of induction regimen (39% vs. 19% in low vs. high, respectively, p = 0.06). At a median follow-up of 21 months from transplant, there was no difference between low and high intensity induction with respect to 2-year disease-free survival (58% vs. 56%), 2-year overall survival (62% vs. 63%), 2-year cumulative incidence of relapse (9% vs. 17%), and 2-year non-relapse mortality (33% vs. 29%). We also found no difference in outcomes when patients were segmented by both induction and conditioning regimen intensities. Our retrospective analysis suggests that induction intensity does not impact post-transplant outcomes among patients with Ph+ ALL transplanted in CR1.

BackgroundThis study aimed to investigate the prognostic value of left atrial (LA) strain in patients with significant mitral regurgitation (MR) after surgical mitral valve (MV) repair.MethodsA total of 169 patients (age 55 ± 15 years, 88 men) with moderate or severe MR on echocardiogram at least 6 months after surgical MV repair for primary MR were studied. Two-dimensional, Doppler, and speckle tracking echocardiography including MR quantitative measures, chamber size, and LA strain were comprehensively analyzed. The primary outcome was a composite of cardiovascular death, heart failure hospitalization, and MV reoperation.ResultsDuring a median of 44.4 months [interquartile range (IQR): 18.7–70.3 months] of follow-up, 44 patients (26%) experienced clinical events; these patients had greater MR volume, elevated mean diastolic pressure gradient and pulmonary artery systolic pressure, and enlarged chamber size compared with patients who did not experience events. Patients with events showed significantly lower LA strain [13.3% (IQR: 9.3–23.8%) vs. 24.0% (IQR: 13.1–31.4%), p = 0.003] and higher MR volume/LA strain [3.09 ml/% (IQR: 2.06–5.80 ml/%) vs. 1.57 ml/% (IQR: 1.04–2.72 ml/%), p < 0.001] than those without events. MR volume/LA strain was a good predictor of clinical outcomes (cut-off 1.57 ml/%, area under the curve 0.754, p < 0.001). On multivariable Cox proportional analysis, MR volume/LA strain was independently associated with clinical outcomes (hazard ratio: 1.269, 95% confidence interval: 1.109–1.452, p < 0.001) along with pulmonary artery systolic pressure.ConclusionA measure of LA mechanical function relative to MR volume is associated with clinical outcomes in patients with significant MR after surgical MV repair.

Tyrosine kinase inhibitors are essential in treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) and have allowed for effective, low intensity induction regimens. Whether the use of low intensity induction regimens impacts outcomes after allogeneic stem cell transplant (alloHSCT) is less understood. We identified consecutive adult patients with Ph + ALL undergoing alloHSCT in first complete remission (CR1) at our center from 2010 to 2021 and examined the impact of induction intensity on outcomes. Among the 87 patients, 44 (51%) received low intensity induction and 43 (49%) received induction with high intensity chemotherapy. Patients receiving low intensity induction were older (median age 60 vs. 47, p BCR::ABL1 RT-PCR was similar in the low and high intensity cohorts (54% and 52% respectively). There was no difference between low and high intensity induction with respect to 2-year disease-free survival (58% vs. 56%), 2-year overall survival (62% vs. 63%), 2-year cumulative incidence of relapse (9% vs. 17%), and 2-year non-relapse mortality (33% vs. 29%). Outcomes were similar when patients were segmented by induction and conditioning regimen intensities. We demonstrate that induction intensity does not impact post-transplant outcomes among Ph + ALL patients Ph + ALL transplanted in CR1.

The complete genome sequence of Stellaria aquatica virus B (StAVB), a new member of the genus Polerovirus that infects Stellaria aquatica, was determined using high-throughput RNA sequencing with confirmation by Sanger sequencing. The complete StAVB genome (GenBank accession no. OP389993) is 5,900 nucleotide (nt) long with seven open reading frames (ORF0-5 and ORF3a) that encode putative proteins (P0-P5 and P3a) in a similar configuration to that of other typical poleroviruses. Pairwise sequence comparisons with other poleroviruses showed 38-50% nt sequence identity in the complete genome and 13-24%, 36-45%, 7-68%, and 6-50% amino acid sequence identity in (aa), for the P0, P1-2, P3, and P4 protein, respectively. These data, together with the results of phylogenetic analysis, indicate that StAVB should be classified as a new member of the genus Polerovirus, family Solemoviridae.

Objectives Falls are considered a significant public health issue and falls risk increases with age. There are many age-related physiologic changes that occur that increase postural instability and the risk for falls (i.e., age-related sensory declines in vision, vestibular, somatosensation, age-related orthopedic changes, and polypharmacy). Hearing loss has been shown to be an independent risk factor for falls. The primary objective of this study was to determine if hearing aid use modified (reduced) the association between self-reported hearing status and falls or falls-related injury. We hypothesized that hearing aid use would reduce the impact of hearing loss on the odds of falling and falls-related injury. If hearing aid users have reduced odds of falling compared with nonhearing aid users, then that would have an important implications for falls prevention healthcare. Design Data were drawn from the 2004-2016 surveys of the Health and Retirement Study (HRS). A generalized estimating equation approach was used to fit logistic regression models to determine whether or not hearing aid use modifies the odds of falling and falls injury associated with self-reported hearing status. Results A total of 17,923 individuals were grouped based on a self-reported history of falls. Self-reported hearing status was significantly associated with odds of falling and with falls-related injury when controlling for demographic factors and important health characteristics. Hearing aid use was included as an interaction in the fully-adjusted models and the results showed that there was no difference in the association between hearing aid users and nonusers for either falls or falls-related injury. Conclusions The results of the present study show that when examining self-reported hearing status in a longitudinal sample, hearing aid use does not impact the association between self-reported hearing status and the odds of falls or falls-related injury.

An 8-year-old, spayed female Maltese dog was presented with a one-month history of erythema, swelling and alopecia of periocular region with pruritus. The skin lesions were first detected at the age of three years, but this was the first time that symptoms had appeared in the eyes. Physical examination revealed markedly swollen and erythematous eyelids and conjunctiva including Meibomian glands. In addition, periocular alopecia and tears were identified. Slit lamp microscopy revealed erythema of conjunctiva and swelling of Meibomian glands. The Schirmer’s tear test was normal. Impression smear cytology of eyes revealed sterile neutrophils and corneal epithelial cells. There were no virus or bacterial infections in the eyes. On skin examination, generalized erythema was detected but there were no other skin lesions. A case of allergic blepharoconjunctivitis associated with canine atopic dermatitis was diagnosed based on history taking and skin examination. Treatment included cetirizine, cyclosporine, prednisolone and Forus eye drops®. The owner was instructed to wear an Elizabethan collar around his dog's neck at all times and restrict walking. And the diet was changed to hypoallergenic dog food. Medications and environmental restrictions significantly reduced erythema, edema and swelling of meibomian glands. Pruritus was also decreased. Six weeks later, the edema lesions of eyes disappeared.

The damage to retinal pigment epithelium (RPE) cells can lead to vision loss and permanent blindness. Therefore, an effective therapeutic strategy has emerged to replace damaged cells through RPE cell delivery. In this study, we fabricated injectable gellan gum (GG)/silk sericin (SS) hydrogels as a cell carrier by blending GG and SS. To determine the appropriate concentration of SS for human RPE ARPE-19, 0, 0.05, 0.1, and 0.5% (w/v) of SS solution were blended in 1% (w/v) GG solution (GG/SS 0%, GG/SS 0.05%, GG/SS 0.1%, and GG/SS 0.5%, respectively). The physical and chemical properties were measured through Fourier-transform infrared spectroscopy, scanning electron microscopy, mass swelling, and weight loss. Also, viscosity, injection force, and compressive tests were used to evaluate mechanical characteristics. Cell proliferation and differentiation of ARPE-19 were evaluated using quantitative dsDNA analysis and real-time polymerase chain reaction, respectively. The addition of SS gave GG/SS hydrogels a compressive strength similar to that of natural RPE tissue, which may well support the growth of RPE and enhance cell proliferation and differentiation. In particular, the GG/SS 0.5% hydrogel showed the most similar compressive strength (about 10 kPa) and exhibited the highest gene expression related to ARPE-19 cell proliferation. These results indicate that GG/SS 0.5% hydrogels can be a promising biomaterial for cell delivery in retina tissue engineering.

The genome of a new potyvirus from a Lamprocapnos spectabilis plant in South Korea was sequenced by high-throughput sequencing and confirmed by Sanger sequencing. The new potyvirus was tentatively named "lamprocapnos virus A" (LaVA); its complete genome contains 9,745 nucleotides, excluding the 3'-terminal poly(A) tail. The LaVA genome structure is similar to that of members of the genus Potyvirus and contains an open reading frame encoding a large putative polyprotein of 3,120 amino acids (aa) with conserved motifs. The complete genome shared 48%-56% nucleotide sequence identity and the polyprotein shared 41%-52% aa sequence identity with those of other potyviruses. These values are below the standard thresholds for potyvirus species demarcation. Phylogenetic analysis based on polyprotein sequences showed that LaVA belongs to the genus Potyvirus. To our knowledge, this is the first report of the complete genome sequence and genome characterization of a potyvirus infecting Lamprocapnos spectabilis.

This study shows tunable stress relaxing gellan gum (GG) hydrogel for enhanced cell growth and regenerative medicine. The molecular weight and physical crosslinking density of GG were tuned and characterized with physicochemical analysis and mechanical tests. The result showed that a decrease in the molecular weight of the GG correlated with a decline in the mechanical properties but faster stress relaxing character. We also discovered that human-derived bone marrow stem cells (hBMSC) showed active viability, proliferation, and remodeling in the fast stress relaxing GG hydrogel. In particular, hBMSC showed an enhanced release profile of growth factors and exosomes (Exo) in the fast stress relaxing GG hydrogel. The secretome obtained from hBMSC embedded in hydrogel exhibited similar cytotoxicity and wound healing properties to that of secretome extracted from hBMSC cultured in a tissue culture plate (TCP) a standard culture condition. Thus, this work demonstrates the potential of fast stress relaxing GG hydrogels for medical application.

Diabetes is one of the important risk factors in cardiovascular disease associated with atherosclerosis, and cardiovascular disease is the leading cause of death in patients with diabetes mellitus. Recent randomized placebo-controlled cardiovascular outcome trials of all new antidiabetic drugs have linked SGLT-2 inhibitors and GLP1-agonists to not only increased cardiovascular stability but significant reduction of cardiovascular disease. These results have led to preferential selection of the most effective and beneficial antidiabetic drugs with the evidence of cardiovascular safety and efficacy. Herein, we address cardiovascular stability and the effectiveness of antidiabetic drugs, focusing on recently developed ones. (Korean J Med 2021;96:85-91)

Aims To investigate sex differences in the association of metabolic syndrome (MetS) and/or low-density lipoprotein cholesterol (LDL-C) with the incidence of cardiovascular and cerebrovascular disease (CCVD). Methods and results A total of 4 702 458 individuals, aged between 40 and 70, without a previous diagnosis of CCVD, underwent at least two health screenings between 2009 and 2011. Of them, 4 193 878 individuals (48.6% women) fulfilled the study requirements. The main outcome measured was the incidence of CCVD. By the end of 2017, 68 921 CCVD events occurred. Men in high LDL-C only, MetS only, and both MetS and high LDL-C groups had higher risks of CCVD. Women in MetS only and both MetS and high LDL-C groups, but not those in high LDL-C only group, had higher risks of CCVD than those in the reference group. The effect of the interaction between the presence of MetS and high LDL-C levels on the primary outcome was found among women (P for interaction 0.016) but not among men (P for interaction 0.897). A combination of MetS and LDL-C > 3.4 mmol/L increased the risk of CCVD as compared to MetS or LDL-C > 3.4 mmol/L alone in both men and women. Conclusions Metabolic syndrome confers an increased risk of CCVD irrespective of sexes; LDL-C > 3.4 mmol/L alone has a greater influence on CCVD occurrence in men than in women. Metabolic syndrome and high LDL-C beget a synergistically detrimental impact on the incidence of CCVD in both men and women. Treatment of dyslipidaemia and metabolic syndrome should be tailored according to patient characteristics.

Accelerometer data collected from wearable devices have recently been used to monitor physical activities (PAs) in daily life. While the intensity of PAs can be distinguished with a cut-off approach, it is important to discriminate different behaviors with similar accelerometry patterns to estimate energy expenditure. We aim to overcome the data imbalance problem that negatively affects machine learning-based PA classification by extracting well-defined features and applying undersampling and oversampling methods. We extracted various temporal, spectral, and nonlinear features from wrist-, hip-, and ankle-worn accelerometer data. Then, the influences of undersampilng and oversampling were compared using various ML and DL approaches. Among various ML and DL models, ensemble methods including random forest (RF) and adaptive boosting (AdaBoost) exhibited great performance in differentiating sedentary behavior (driving) and three walking types (walking on level ground, ascending stairs, and descending stairs) even in a cross-subject paradigm. The undersampling approach, which has a low computational cost, exhibited classification results unbiased to the majority class. In addition, we found that RF could automatically select relevant features for PA classification depending on the sensor location by examining the importance of each node in multiple decision trees (DTs). This study proposes that ensemble learning using well-defined feature sets combined with the undersampling approach is robust for imbalanced datasets in PA classification. This approach will be useful for PA classification in the free-living situation, where data imbalance problems between classes are common.

The complete genomic nucleotide sequence of hemisteptia virus A (HemVA) from a Hemisteptia lyrata Bunge plant in South Korea was identified by high-throughput sequencing. The HemVA genome consists of 6,122 nucleotides and contains seven putative open reading frames, ORF0-5 and ORF3a, encoding the putative proteins P0-P5 and P3a, respectively. Pairwise amino acid sequence analysis shows that the HemVA P1-P5 proteins have the highest sequence identity (23.68%-54.15%) to the corresponding proteins of members of the families Solemoviridae and Tombusviridae. Phylogenetic analysis of the P1-P2 and P3 amino acid sequences indicated that HemVA should be classified as a member of a distinct species in the genus Polerovirus.

Coronavirus disease 2019 caused by the novel human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a major threat to public health worldwide. To deal with the needs of vaccine, we developed four DNA vaccine candidates against SARS-CoV-2, based on the full-length spike (S) or truncated S protein. Following mice vaccination, we measured T-cell response and antigen-specific neutralizing antibody (NAb) titer. All four candidates induced humoral immune responses, including elevated levels of total IgG and NAbs, and cell-mediated immune responses, including multiple cytokine expression. However, the full-length S DNA vaccine enhanced the immune responses most significantly. We then evaluated its appropriate antigen dose and vaccination schedule. Although all immunized groups showed higher immune response than the control group, inoculation with 50 μg antigen led to the highest NAb titer. Immunity was significantly increased after the third inoculation. Thus, the full-length S DNA vaccine can potentially prevent SARS-CoV-2 infection.

The effectiveness of small-diameter vascular grafts depends on their antithrombogenic properties and ability to undergo accelerated endothelialization. The extreme hydrophobic nature of poly(ε-caprolactone) (PCL) hinders vascular tissue integration, limiting its use in medical implants. To enhance the antithrombogenicity of PCL as a biomaterial, we grafted 2-aminoethyl methacrylate (AEMA) hydrochloride onto the PCL surface using gamma irradiation; developed a biodegradable heparin-immobilized PCL nanofibrous scaffold using gamma irradiation and N-(3-dimethylaminopropyl)-N′-ethyl carbodiimide hydrochloride/N-hydroxysuccinimide reaction chemistry; and incorporated vascular endothelial growth factor (VEGF) into the scaffold to promote vascular endothelial cell proliferation and prevent thrombosis on the vascular grafts. We assessed the physicochemical properties of PCL, heparin-AEMA-PCL (H-PCL), and VEGF-loaded heparin-AEMA-PCL (VH-PCL) vascular grafts using scanning electron microscopy, attenuated total reflection–Fourier transform infrared spectroscopy, toluidine blue O staining, and fibrinogen adsorption and surface wettability measurement. In addition, we implanted the vascular grafts into 24-month-old Sprague Dawley rats and evaluated them for 3 months. The H-PCL and VH-PCL vascular grafts improved the recovery of blood vessel function by promoting the proliferation of endothelial cells and preventing thrombosis in clinical and histological evaluation, indicating their potential to serve as functional vascular grafts in vascular tissue engineering.

Objective: The efficiency of the knock-in process is very important to successful gene editing in domestic animals. Recently, it was reported that transient loosening of the nucleosomal folding of transcriptionally inactive chromatin might have the potential to enhance homologous recombination efficiency. The objective of this study was to determine whether histone deacetylases (HDAC) inhibitor and RAD51 recombinase (RAD51) expression were associated with increased knock-in efficiency on the β-casein (bCSN2) gene locus in mammary alveolar-large T antigen (MAC-T) cells using the transcription activator-like effector nucleases (TALEN) system.Methods: MAC-T cells were treated with HDAC inhibitors, valproic acid, trichostatin A, or sodium butyrate for 24 h, then transfected with a knock-in vector, RAD51 expression vector and TALEN to target the bCSN2 gene. After 3 days of transfection, the knock-in efficiency was confirmed by polymerase chain reaction and DNA sequencing of the target site.Results: The level of HDAC 2 protein in MAC-T cells was decreased by treatment with HDAC inhibitors. The knock-in efficiency in MAC-T cells treated with HDAC inhibitors was higher than in cells not treated with inhibitors. However, the length of the homologous arm of the knock-in vector made no difference in the knock-in efficiency. Furthermore, DNA sequencing confirmed that the precision of the knock-in was more efficient in MAC-T cells treated with sodium butyrate.Conclusion: These results indicate that chromatin modification by HDAC inhibition and RAD51 expression enhanced the homologous recombination efficiency on the bCSN2 gene locus in MAC-T cells.

Single image dehazing has been a challenging problem because of its ill-posed nature. For this reason, numerous efforts have been made in the field of haze removal. This paper proposes a simple, fast, and powerful algorithm for haze removal. The medium transmission is derived as a function of the saturation of the scene radiance only, and the saturation of scene radiance is estimated using a simple stretching method. A different medium transmission can be estimated for each pixel because this method does not assume that transmission is constant in a small patch. Furthermore, this paper presents a color veil removing algorithm, which is useful for an image with fine or yellow dust, using the white balance technique. The proposed algorithm requires no training, prior, and refinement process. The simulation results show that the proposed dehazing scheme outperforms state-of-the-art dehazing approaches in terms of both computational complexity and dehazing efficiency.

NT-pro B-type natriuretic peptide (NT-proBNP) is a powerful prognostic factor for acute heart failure. We investigated whether NT-proBNP levels differ based on the type of heart failure present.Using the Korean Acute Heart Failure Registry, a prospective, multicenter cohort, we categorized patients into two groups: de novo heart failure (DNHF, n = 1617) and acute decompensated chronic heart failure (ADHF, n = 1212). NT-proBNP levels were measured on admission. The primary outcome was all-cause mortality, and the secondary outcomes were re-hospitalization for heart failure and a composite of all-cause mortality or re-hospitalization for heart failure at 90 days and 1 year.NT-proBNP levels were significantly lower in patients with DNHF than in those with ADHF (median 4213 vs. 5523 ng/L, p 0.001). Compared to patients with DNHF, patients with ADHF had a significantly worse prognosis for 1-year all-cause mortality (adjusted hazard ratio (HR) = 1.46 [95% confidence interval (CI) = 1.07-1.98], p = 0.017). A higher NT-proBNP level was associated with higher 1-year all-cause mortality for both heart failure types (adjusted HR = 2.00, p = 0.002 in ADHF; adjusted HR = 2.41, p = 0.003 in DNHF). However, all-cause mortality risk was always higher in patients with ADHF than in those with DNHF for any given NT-proBNP level.NT-proBNP levels are an important prognostic factor for both DNHF and ADHF. Notably, patients with ADHF had consistently higher risks than those with DNHF with the same NT-proBNP level for 1-year all-cause mortality.

Three cotton leafroll dwarf virus (CLRDV; genus Polerovirus, family Solemoviridae) genotypes have recently been identified (Tabassum et al., 2021; Ramos-Sobrinho et al., 2021). This virus is widespread in the United States (Thiessen et al., 2020; Aboughanem-Sabanadzovic et al., 2019; Tabassum et al., 2020) and has also been reported to infect chickpea (Cicer arietinum) in Uzbekistan (Kumari et al., 2020). As well, CLRDV was detected from 23 weed species (16 families), including Hibiscus sabdariffa (Sedhain et al., 2021, Hagan et al., 2019). From June to September 2019, virus-like symptoms, including mild leaf stunting, crinkling, and deformation, were observed in multiple plants (n=14) in several provinces of South Korea (e-Xtra Table. 1). To characterize the associated viruses, pooled leaf tissues from all 14 samples were used for total RNA isolation, followed by paired-end high-throughput sequencing (HTS) on the Illumina NovaSeq 6000 platform (Macrogen, South Korea). A total of 614,424,952 trimmed and high-quality reads were assembled into 506,024 contigs using Trinity de novo transcriptome assembly. The resulting contigs were compared with viral sequences in the GenBank database using BLASTx analysis. Several viral contigs were identified, including cucumber mosaic virus, apple stem pitting virus, apple stem grooving virus, cherry virus A, and CLRDV. The CLRDV contig of 5,800 nucleotides (nt) with an average coverage of 307x shared 92.1% identity (query coverage: 99%) with the CLRDV isolate CN-S5 (KX588248). To confirm CLRDV infection and to obtain its complete genome sequence, total RNA was extracted from each of the 14 samples and used for reverse transcription (RT)-PCR with six overlapping sets of primers designed from the HTS contig (e-Xtra Table. 2). The expected product sizes were obtained only for the Hibiscus syriacus L. (family: Malvaceae) sample showing foliar mild vein clearing symptoms on the leaves (e-Xtra Fig.1). All RT-PCR products were cloned using the RBC TA Cloning vector (Taipei, Taiwan) and at least five positive clones per cloned DNA fragment were sequenced. The 5 and 3 termini sequences were determined as described previously (Zhao et al. 2016). The complete genome of CLRDV isolate SK (OK073299) was determined to be 5,862 nt and it shared 89-91% complete genome identity with 12 other CLRDV isolates based on pairwise comparisons (e-Xtra Table. 3). Maximum likelihood phylogenetic analysis based on the complete genome and P3-CP aa sequences showed that CLRDV-SK is more closely related CN-S5 (e-Xtra Fig. 2). In the fall of 2021, additional H. syriacus samples (n=18) with mild chlorosis, blistering and crinkling symptoms were collected from 2 provinces of South Korea and tested by RT-PCR using the primers: CLRDV-SK-101-120 ForCLRDV-SK-1021-1040 Rev targeting a region of the ORF0. Two of 18 samples (11.1%) tested positive for CLRDV. The 16 negative samples only showed symptoms of mild yellowing. The RT-PCR products were cloned and sequenced. In pairwise comparisons, the obtained sequences (OM339522-23) were 95.85% and 96.06% identical to the corresponding sequences of CLRDV isolate SK. This is the first report of CLRDV occurrence in H. syriacus in South Korea to the best of our knowledge. Our findings will assist further studies on the epidemiology and sustainable management of diseases caused by CLRDV. Acknowledgments This work was supported by IPET (Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries; Project No. AGC1762111), Ministry of Agriculture, Food and Rural Affairs, Republic of Korea. References Tabassum, A., et al., 2021. PloS One. 16: e0252523 Ramos-Sobrinho, R., et al., 2021. Viruses. 13:2230 Thiessen, L.D., et al. 2020. Plant Dis. 104:3275 Aboughanem-Sabanadzovic, N., et al. 2019. Plant Dis. 103:1798 Tabassum, A., et al. 2020. Microbiol. Res. Announce. 9:e00812-20 Kumari, S.G., et al. 2021. Plant Dis. 104:2532 Sedhain, N.P., et al. 2021. Crop protection 144:105604 Hagan, A., er al. 2019. Alabama Cooperative Extension System. ANR:2539 Zhao, F., et al. 2016. Arch. Virol. 161:2047 Conflict of interest The authors declare that they have no conflict of interest.

Herein, a facile macro- and microporous polycaprolactone/duck's feet collagen scaffold (PCL/DC) was fabricated and characterized to confirm its applicability in bone tissue engineering. A biomimetic scaffold for bone tissue engineering and regeneration for bone defects is an important element. PCL is a widely applied biomaterial for bone tissue engineering due to its biocompatibility and biodegradability. However, the high hydrophobicity and low cell attachment site properties of PCL lead to an insufficient microenvironment in designing a scaffold. Collagen is a nature-derived biomaterial that is widely used in tissue engineering and has excellent biocompatibility, mechanical properties, and cell attachment moieties. Among the resources from which collagen can be obtained, DC contains a high amount of collagen type I (COL1), is biocompatible, and is cost-effective. In this study, the scaffolds were fabricated by blending DC with PCL in various ratios and applied non-solvent-induced phase separation (NIPS) and thermal-induced phase separation (TIPS) (N-TIPS), solvent casting and particulate leaching (SCPL), and gas foaming method to fabricate macro- and microporous structure. The characterization of the fabricated scaffolds was carried out by morphological analysis, bioactivity test, physicochemical analysis, and mechanical test.

A new virus, tentatively named "kudzu virus D" (KuVD) was discovered in kudzu (Pueraria montana var. lobata) in South Korea. Its complete genome comprises 7,922 nucleotides, excluding the poly(A) tail, and contains five open reading frames (ORFs) encoding, from 5' to 3', a replicase (ORF1), three triple gene block proteins TGB1-3 (ORF2-ORF4), and a coat protein (ORF5). This genome organization is typical of members of the subfamily Quinvirinae of the family Betaflexiviridae. Pairwise alignment analysis revealed that the nucleotide sequences of the replicase and coat protein of KuVD were 12.13-54.46% and 24.03-50.67% identical, respectively, to those of other members of the family Betaflexiviridae. These values are far below the current species ICTV demarcation threshold. Consequently, KuVD should be considered a member of a new species in the subfamily Quinvirinae.

The genome of a novel virus identified in Cnidium officinale is composed of a monopartite ssRNA of 16,755 nucleotides that shares 68.73% (query coverage, 20%) sequence identity with carrot yellow leaf virus (CYLV, accession no. FJ869862.1). It contains 11 putative open reading frames and has an organization typical of closteroviruses. It shares 30-50% nucleotide sequence identity with other closteroviruses. The heat shock protein 70-like protein (HSP70), putative RNA-dependent RNA polymerase (RdRp), and coat protein (CP) show 39-66%, 16-60%, and 24-41% amino acid sequence identity, respectively, to the homologous proteins of previously identified closteroviruses. Molecular and HSP70-based phylogenetic analysis of the genome and encoded protein sequences suggested that this virus is a novel member of the genus Closterovirus in the family Closteroviridae, which we have tentatively named "cnidium closterovirus 1" (CnClV1).

The complete genome sequence of a new caulimovirus in Pueraria montana was determined using high-throughput sequencing. The 7,572 nucleotide genome of pueraria virus A (PVA) contains genes that encode a movement protein, an aphid transmission factor, a virion-associated protein, a coat protein, a protease + reverse transcriptase + ribonuclease H, and a transactivator/viroplasmin protein, as well as two intergenic regions, which are all common features of members of the genus Caulimovirus. A sequence alignment revealed that the complete genome of PVA shares 66.82% nucleotide sequence identity with strawberry vein banding virus (GenBank accession no. KX249738.1). The results of phylogenetic analysis and the observation that the nucleotide sequence of the polymerase coding region differed by more than 20% indicated that PVA is a member of a new species the genus Caulimovirus, family Caulimoviridae.

The complete genomic sequence of a plant rhabdovirus that was identified in Cnidium officinale in Yeongyang-dun, South Korea, is reported here. The virus, tentatively named "cnidium virus 1" (CnV1), has a negative-sense RNA genome of ~ 14 kb, and its organization most closely resembles that of unsegmented plant rhabdoviruses, containing six antisense open reading frames (ORFs) in the order 3'-N-P-P3-M-G-L-5'. Intergenic regions containing conserved sequences separate the genes. The genome of CnV1 is 37.8-56% identical in its complete nucleotide sequence to betanucleorhabdoviruses and other related rhabdoviruses. Therefore, based on the sequence similarity criteria for species demarcation, its genome organization, and its phylogenetic position, CnV1 should be classified as a new member of the genus Betanucleorhabdovirus in the family Rhabdoviridae. CnV1 is the first rhabdovirus found in C. officinale.

The skin protects the body from external barriers. Certain limitations exist in the development of technologies to rapidly prepare skin substitutes that are therapeutically effective in surgeries involving extensive burns and skin transplantation. Herein, we fabricated a structure similar to the skin layer by using skin-derived decellularized extracellular matrix (dECM) with bioink, keratinocytes, and fibroblasts using 3D-printing technology. The therapeutic effects of the produced skin were analyzed using a chimney model that mimicked the human wound-healing process. The 3D-printed skin substitutes exhibited rapid re-epithelialization and superior tissue regeneration effects compared to the control group. These results are expected to aid the development of technologies that can provide customized skin-replacement tissues produced easily and quickly via 3D-printing technology to patients.

Due to high demand but limited supply, there has been an increase in the need to replace autologous bone grafts with alternatives that fulfill osteogenic requirements. In this study, two different types of bone grafts were tested for their drug carrying abilities along with their osteogenic properties. Two different types of alendronate-loaded bone grafts, Bio-Oss (bovine bone graft) and InRoad (biphasic synthetic bone graft) were observed to see how different concentrations of alendronate would affect the sustained release to enhance osteogenesis. In this study, defected ovariectomize-induced osteoporotic rat calvarias were observed for 28 days with three different concentrations of alendronate (0 mg, 1 mg, 5 mg) for both Bio-Oss and InRoad. A higher concentration (5 mg) allowed for a more controlled and sustained release throughout the 28-day comparison to those of lower concentrations (0 mg, 1 mg). When comparing Bio-Oss and InRoad through histology and Micro-CT, InRoad showed higher enhancement in osteogenesis. Through this study, it was observed that alendronate not only brings out robust osteogenesis with InRoad bone grafts, but also enhances bone regeneration in an alendronate-concentration-dependent manner. The combination of higher concentration of alendronate and multiple porous bone graft containing internal micro-channel structure of InRoad resulted in higher osteogenesis with a sustained release of alendronate.

In this Letter, we report a demonstration of p-channel tin monoxide (SnO) thin-film transistors (TFTs) with high field-effect mobility ( μFE) exceeding 10 cm2/Vs and hysteresis-free like behavior. We demonstrate that maintaining metallic states before encapsulation is a key process to enhance μFE in p-type SnO thin-films. Sustaining this meta-stability involves the following two processes during fabrication: (1) postdeposition annealing (PDA) in two steps and (2) encapsulation in the middle of each PDA. This simple process not only suppresses creation of oxidized states such as adverse Sn4+ but also facilitates the lateral growth of crystals with improved crystallinity by interfacial energy stabilization. The resultant SnO TFT reveals a record-high μFE up to 15.8 cm2/Vs with a negligible hysteresis of 0.1 V. This study suggests a practical route to grant high μFE to p-channel SnO TFTs without any dopant or complex postdeposition treatment.

The complete genome sequence of a putative new virus isolate, provisionally named "Fagopyrum esculentum endornavirus 2" (FeEV2), is 15,706 nucleotides long with a single, large open reading frame and a typical endornavirus genome organization. FeEV2 shares 19.4%-22.1% nucleotide sequence identity with other known endornavirus genome sequences. The putative polyprotein, RNA-dependent RNA polymerase (RdRp), helicase, and glycosyltransferase (GT) share 10.6%-24.3%, 30.4%-66.1%, 16.3%-45.7%, and 10.1%-21.6% amino acid sequence identity, respectively, with the homologous sequenced proteins from known endornaviruses. This suggests that it is a member of a new, distinct species. Phylogenetic analysis of RdRp sequences places FeEV2 with other Alphaendornavirus genus members (family Endornaviridae). This is the first report of the complete genome sequence of FeEV2, which was isolated from Fagopyrum esculentum in South Korea.