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In this study, the photoelectric properties of a complete series of GaS 1- x Se x (0 ≤ x ≤ 1) layered crystals are investigated. The photoconductivity spectra indicate a decreasing bandgap of GaS 1- x Se x as the Se composition x increases. Time-resolved photocurrent measurements reveal a significant improvement in the response of GaS 1- x Se x to light with increasing x . Frequency-dependent photocurrent measurements demonstrate that both pure GaS crystals and GaS 1- x Se x ternary alloy crystals exhibit a rapid decrease in photocurrents with increasing illumination frequency. Crystals with lower x exhibit a faster decrease in photocurrent. However, pure GaSe crystal maintains its photocurrent significantly even at high frequencies. Measurements for laser-power-dependent photoresponsivity and bias-voltage-dependent photoresponsivity also indicate an increase in the photoresponsivity of GaS 1- x Se x as x increases. Overall, the photoresponsive performance of GaS 1- x Se x is enhanced with increasing x , and pure GaSe exhibits the best performance. This result contradicts the findings of previous reports. Additionally, the inverse trends between bandgap and photoresponsivity with increasing x suggest that GaS 1- x Se x -based photodetectors could potentially offer a high response and wavelength-selectivity for UV and visible light detection. Thus, this work provides novel insights into the photoelectric characteristics of GaS 1- x Se x layered crystals and highlights their potential for optoelectronic applications.

This study aims to evaluate the safety of MK-7 produced by fermentation process using a Bacillus subtilis var. natto strain for human ingestion via acute oral toxicity, repeated dose 90-day oral toxicity, 28-day recovery test, and genotoxicity tests. The acute oral toxicity test results indicated that all subjects survived at the dose of 5000 mg/kg with no toxic effects. For the repeated dose 90-day oral toxicity test, MK-7 was administered to rats at 500, 1500, and 4500 mg/kg for 90 d. No abnormal findings were detected in clinical observations or in clinical pathological and histopathological examinations. The no-observed-adverse-effect level(NOAEL) was determined to be 4500 mg/kg/d, the maximum dose tested. For the evaluation of genotoxicity, reverse mutation, chromosomal aberration, and micronucleus tests were performed. In the reversion mutation test, vitamin K2 did not induce reversion in bacterial strains, and no chromosomal abnormality was observed in the chromosomal abnormality test using Chinese hamster lung cells. In the micronucleus test, micronuclei were not induced using ICR mouse bone marrow cells. All the toxicity test results suggest that vitamin K2 produced by fermentation processes using Bacillus subtilis var. natto induced no toxicological changes under the experimental conditions., (© 2024. The Author(s).)

Purpose: Vessel wall imaging (VWI) for carotid plaque is better for detecting unstable carotid plaque such as intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and thin/ruptured fibrous cap. However, the role of VWI before carotid artery stenting (CAS) is unclear. Thus, this study aimed to determine the findings of symptomatic carotid stenosis before CAS on angiography and carotid VWI and to evaluate the imaging findings associated with post-procedural clinical events after CAS., Materials and Methods: This retrospective study included 173 consecutive patients who underwent carotid VWI, CAS, and post-procedural diffusion-weighted imaging (DWI) after CAS. Findings of unstable plaque on carotid VWI and unstable findings on angiography were analyzed. We also analyzed the incidence of post-procedural clinical events, any stroke, myocardial infarction (MI), and death within 30 days of CAS., Results: Of 173 patients, 101 (58.4%) had initial ischemic symptoms and positive findings on DWI. Symptomatic patients were significantly higher in patients with IPH than in patients without IPH (62.4% vs. 45.8%, P=0.031). Degree of stenosis, thrombus of the stenotic lesion, flow delay of internal carotid artery, and flow arrest by filter thrombus had significantly higher prevalence in the symptomatic group. Twenty patients (11.6%) had post-procedural clinical events such as any stroke, clinical symptoms, and/or MI. Hyperlipidemia and intraluminal thrombus on angiography were identified as significant factors influencing post-procedural events after CAS., Conclusion: An intraluminal thrombus on angiography was identified as a significant factor influencing post-procedural clinical events after CAS.

Background and Purpose: This study aimed to investigate the clinical outcomes of emboli to distal territories (EDT) after aspiration thrombectomy in patients with acute anterior circulation occlusion., Materials and Methods: From January 2016 to December 2022, all eligible patients who underwent endovascular treatment (EVT) due to acute anterior circulation occlusion were retrospectively reviewed. During this period, patients with EDT after EVT underwent magnetic resonance (MR) perfusion with angiography and diffusion-weighted imaging within 12 hours from recanalization. Hypoperfusion was defined as a Tmax value > 6-second volume., Results: Of the 104 eligible patients (65 males, median age 74 years), 79 (76.0 %; 2a: 19, 2b: 55, 2c: 5) had hypoperfusion on perfusion MR (PWI). Complete mismatch on diffusion-weighted imaging (DWI) of the hypoperfusion area was significantly higher in patients with successful recanalization than in patients with incomplete recanalization (58.3 % vs. 31.6 %, p = 0.0437). Of the 79 patients with hypoperfusion, 24 had EDT in the M2, 39 in the M3, and 16 in the M4. Complete mismatch on DWI and PWI was significantly higher in patients with a distal EDT (M3 or M4) than in patients with an M2 EDT (65.8 % vs. 20.8 %, p < 0.001)., Conclusions: EDT to the M3 or more distal branches after EVT had a higher rate of complete DWI-PWI mismatch on early follow-up MRI than EDT to M2., Competing Interests: Declaration of competing interest None of the authors have potential conflict of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence this work., (Copyright © 2023. Published by Elsevier Inc.)

Background/objectives: This study aimed to assess the current mean daily intake of 10 food groups, analyze the sociodemographic factors associated with food consumption, and determine the associations between food consumption/dietary intake and the prevalence rates of obesity, type 2 diabetes (T2D), and hypertension (HTN) in Jakarta, Indonesia., Subjects/methods: A total of 600 participants aged 20-85 yrs were included in this cross-sectional study. Food consumption and dietary habits were assessed using a food frequency questionnaire. To determine the association between food consumption/dietary habits and the abovementioned diseases, logistic regression analysis was performed., Results: The average vegetable and fruit intake was lower, while sugar and salt consumption were higher than that recommended by Indonesia's national dietary guidelines. A high intake of ultra-processed foods (UPFs) was associated with young age, men, "single" status, a high education level, and employment with a high monthly income. Obesity and T2D were positively correlated with high intakes of cereals and tubers, UPFs, sugars, fats, and oils. Conversely, an inverse association was found between legume, vegetable, and fruit consumption and obesity risk. An inverse correlation was also observed between vegetable consumption and T2D risk. Moreover, a high salt intake was inversely correlated with fruit consumption in terms of HTN risk. Non-indulgence in habitual late-night snacking and refrainment from consuming more than one dish at each meal were also negatively related to the prevalence of obesity, T2D, and HTN. Inverse correlations were also observed between the prevalence rates of T2D and HTN and abstaining from adding sugar to beverages., Conclusion: Foods high in fat, sugar, and sodium were strongly associated with the risks of obesity, T2D, and HTN. Additionally, poor eating habits were also associated with disease development., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Importance: Viruses are constantly evolving to promote propagation in the host. Here, we show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes host RAD51 for replication. Silencing of RAD51 impaired SARS-CoV-2 propagation. Viral RNA colocalized with RAD51 in the cytoplasm of SARS-CoV-2-infected cells, suggesting that both viral RNA and RAD51 may form a replication complex. We, therefore, evaluated RAD51 inhibitors as possible therapeutic agents against SARS-CoV-2. Indeed, RAD51 inhibitors exerted antiviral activities against not only Wuhan but also variants of SARS-CoV-2. Molecular docking model shows that RAD51 inhibitors impede SARS-CoV-2 propagation by interfering with dimerization of RAD51. These data suggest that RAD51 may represent a novel host-based drug target for coronavirus disease 2019 treatment., Competing Interests: The authors declare no conflict of interest.

Natural products and herbal medicine have been widely used in drug discovery for treating infectious diseases. Recent outbreak of COVID-19 requires various therapeutic strategies. Here, we used YSK-A, a mixture of three herbal components Boswellia serrata, Commiphora myrrha, and propolis, to evaluate potential antiviral activity against SARS-CoV-2. We showed that YSK-A inhibited SARS-CoV-2 propagation with an IC 50 values of 12.5 µg/ml and 15.42 µg/ml in Vero E6 and Calu-3 cells, respectively. Using transcriptome analysis, we further demonstrated that YSK-A modulated various host gene expressions in Calu-3 cells. Among these, we selected 9 antiviral- or immune-related host genes for further study. By siRNA-mediated knockdown experiment, we verified that MUC5AC, LIF, CEACAM1, and GDF15 host genes were involved in antiviral activity of YSK-A. Therefore, silencing of these genes nullified YSK-A-mediated inhibition of SARS-CoV-2 propagation. These data indicate that YSK-A displays an anti-SARS-CoV-2 activity by targeting multiple antiviral genes. Although the exact antiviral mechanism of each constituent has not been verified yet, our data indicate that YSK-A has an immunomodulatory effect on SARS-CoV-2 and thus it may represent a novel natural product-derived therapeutic agent for treating COVID-19., (© 2023. The Author(s).)

Background: High-resolution vessel wall imaging (HR-VWI) can identify vertebrobasilar artery dissections (VBADs) due to its good intramural hematoma and intimal flap visualization. Although the clinical course of VBADs is known to be benign, changes in VBADs visible using HR-VWI at follow-up are unknown. Thus, this study aimed to assess serial changes in VBADs using HR-VWI at follow-up., Materials and Methods: Patients with neurological symptoms from VBADs who had undergone both initial and follow-up HR-VWI examinations were retrospectively enrolled. Enrolled patients with VBADs at the initial HR-VWI after acute symptom onset underwent serial follow-up with HR-VWI at 3, 6, 12, and 24 months. Patients were classified into three groups based on the results of follow-up HR-VWI examinations: type 1 = wall thickness of the dissected artery; type 2 = no interval change; and type 3 = occlusion., Results: Fifteen patients (median age: 50 years, nine males) were enrolled in this study. All patients initially showed an intimal flap and a double lumen. Twelve (80%) patients showed strong wall enhancement. Nine (60%) patients had an intramural hematoma. During serial follow-up, nine (60.0%) patients showed type 1 lesions due to attachment of the intimal flap to the vessel wall, five (33.3%) showed type 2, and one showed type 3. Four patients with BA dissection showed type 2 lesions without change in the intimal flap or the double lumen., Conclusions: Changes in VBADs in HR-VWI were observed during the follow-up period. Most patients with VBADs showed the healing process, such as the disappearance of the intimal flap and the double lumen.

Scope: Ultra-processing food (UPF) has been a nutrition and health interest. This study is aimed to investigate the association between UPF consumption and the risk of obesity or dyslipidemia., Methods and Results: This study is performed using an ongoing cohort study including 17 310 individuals aged ≥40 years in South Korea. UPF is categorized by the NOVA system and FCS, respectively. After an average 5-year follow-up, there is a positive association between NOVA-defined UPF and dyslipidemia. The risk of the Q4 group is almost 20% higher than that of the Q1 group (men, adjusted HR = 1.209 [95% CI 1.039-1.407], women, adjusted HR = 1.195 [95% CI 1.096-1.303]). Consuming high-FCS foods (less processed and healthier foods) show a lower risk for dyslipidemia in both sexes and lower obesity risk in women compared to low-FCS consumption (men, dyslipidemia, adjusted HR = 0.857 [95% CI 0.744-0.988]; women, dyslipidemia, adjusted HR = 0.919 [95% CI 0.850-0.993], obesity, adjusted HR = 0.759 [95% CI 0.628-0.916])., Conclusion: Higher UPF intakes assessed by the NOVA system and FCS are associated with increased incidences of dyslipidemia and obesity. Furthermore, NOVA-defined UPF shows a statistically significant negative association with AMED score, indicating poor diet quality., (© 2023 Wiley-VCH GmbH.)

Adinazolam (ADZ) is a benzodiazepine-type new psychoactive substance (NPS) with anxiolytic, anticonvulsant, and antidepressant effects. High ADZ doses have been reported to impair psychomotor performance and memory; however, the abuse potential and drug dependence of ADZ have not yet been fully investigated. In this study, we evaluated whether ADZ has abuse potential and leads to drug dependence and withdrawal symptoms. The intravenous self-administration (IVSA) test revealed that ADZ (0.01, 0.03, and 0.1 mg/kg/infusion) was self-administered significantly above vehicle levels, suggesting the reinforcing effect of ADZ. Furthermore, we revealed that treatment discontinuation following chronic ADZ administration (3 and 6 mg/kg) caused several somatic withdrawal symptoms in mice, including body tremor. Moreover, it induced motivational withdrawal signs, such as anxiety-related behavior in the elevated plus maze (EPM) test and memory deficits in the Y-maze test. After the IVSA test, an enzyme-linked immunosorbent assay (ELISA) showed that ADZ administration significantly increased the dopamine contents in the thalamus, nucleus accumbens (NAc), and ventral tegmental area (VTA). This finding was also supported by the results of the Western blot. Taken together, our results suggest that ADZ has abuse potential and can lead to drug dependence and withdrawal syndrome.

African swine fever virus (ASFV), an extremely contagious virus with high mortality rates, causes severe hemorrhagic viral disease in both domestic and wild pigs. Fortunately, ASFV cannot be transmitted from pigs to humans. However, ongoing ASFV outbreaks could have severe economic consequences for global food security. Although ASFV was discovered several years ago, no vaccines or treatments are commercially available yet; therefore, the identification of new anti-ASFV drugs is urgently warranted. Using molecular docking and machine learning, we have previously identified pentagastrin, cangrelor, and fostamatinib as potential antiviral drugs against ASFV. Here, using machine learning combined with docking simulations, we identified natural products with a high affinity for AsfvPolX proteins. We selected five natural products (NPs) that are located close in chemical space to the six known natural flavonoids that possess anti-ASFV activity. Polygalic acid markedly reduced AsfvPolX polymerase activity in a dose-dependent manner. We propose an efficient protocol for identifying NPs as potential antiviral drugs by identifying chemical spaces containing high-affinity binders against ASFV in NP databases., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Fish-derived collagen hydrolysate (CH) has shown promise in improving hair and skin health. Therefore, this study sought to comprehensively assess the effects of CH extracted from Mozambique tilapia ( Oreochromis mossambicus ) scales on hair and skin using in vitro and in vivo models. Human dermal papilla cells (hDPCs) were used for antioxidant and gene expression analyses, while C57BL/6 mice were orally administered CH for six weeks to assess hair growth patterns. The mice were divided into four groups: negative control (NC; distilled water), positive control (PC; 1 mg/kg finasteride), CH500 (500 mg/kg BW CH), and CH1000 (1000 mg/kg BW CH). CH mitigated catalase activity reduction in hDPCs, increased IGF-1 and VEGF levels, and decreased TGF-β1, TNF-α, and IL-1β expression. In vivo, CH treatment improved hair growth index, length, diameter, weight, and density. Scanning electron microscopy revealed reduced hair damage. Moreover, CH up-regulated IGF-1, VEGF, Elastin, and HAS2 mRNA expression while down-regulating TNF-α and IL-1β. CH enhanced hair shine, growth, and skin health while alleviating inflammation. These findings demonstrate the potential of CH in alleviating oxidative stress, promoting hair growth, and enhancing skin health, both in vitro and in vivo. Fish-derived CH offers a cost-effective and bioavailable option for improving hair and skin health.

2-(2,5-Dimethoxy-4-methylphenyl)- N -(2-methoxybenzyl)&#95;ethanamine (25D-NBOMe), an analogue of the 2C family, is a newly synthesized psychoactive substance. It acts as an agonist at the 5-HT 2A receptor and has a similar mechanism to that of NBOMe compounds. However, the pharmacological mechanism for its rewarding and reinforcing effects has not been revealed. In the present study, intravenous self-administration (IVSA) test and conditioned place preference (CPP) test were performed to investigate whether 25D-NBOMe has abuse potential. We also evaluated the effects of 25D-NBOMe on neurochemical changes using western blot analysis and microdialysis. The IVSA test revealed increased self-administration in 25D-NBOMe (0.03 mg/kg)-treated rats. In addition, the CPP test revealed rewarding effects in 25D-NBOMe (1 mg/kg)-treated mice. In the neurochemical studies, 25D-NBOMe treatment affected the expression of dopamine (DA) receptor D1 (DRD1), DA receptor D2 (DRD2), tyrosine hydroxylase, DA transporter (DAT), and phospho-DAT ( p -DAT) in the nucleus accumbens (NAc). In addition, microdialysis revealed that treatment with progressively increasing doses (1, 3, and 10 mg/kg) of 25D-NBOMe increased the extracellular levels of DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the rat NAc. Taken together, our results show the abuse potential and neurochemical changes related to addictive behavior after administration of 25D-NBOMe.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2 propagation is mediated by the protein interaction between viral proteins and host cells. Tyrosine kinase has been implicated in viral replication, and hence, it has become a target for developing antiviral drugs. We have previously reported that receptor tyrosine kinase inhibitor blocks the replication of hepatitis C virus (HCV). In the present study, we investigated two receptor tyrosine kinase-specific inhibitors, amuvatinib and imatinib, for their potential antiviral efficacies against SARS-CoV-2. Treatment with either amuvatinib or imatinib displays an effective inhibitory activity against SARS-CoV-2 propagation without an obvious cytopathic effect in Vero E6 cells. Notably, amuvatinib exerts a stronger antiviral activity than imatinib against SARS-CoV-2 infection. Amuvatinib blocks SARS-CoV-2 infection with a 50% effective concentration (EC 50 ) value ranging from ~0.36 to 0.45 μM in Vero E6 cells. We further demonstrate that amuvatinib inhibits SARS-CoV-2 propagation in human lung Calu-3 cells. Using pseudoparticle infection assay, we verify that amuvatinib blocks SARS-CoV-2 at the entry step of the viral life cycle. More specifically, amuvatinib inhibits SARS-CoV-2 infection at the binding-attachment step. Moreover, amuvatinib exhibits highly efficient antiviral activity against emerging SARS-CoV-2 variants. Importantly, we demonstrate that amuvatinib inhibits SARS-CoV-2 infection by blocking ACE2 cleavage. Taken together, our data suggest that amuvatinib may provide a potential therapeutic agent for the treatment of COVID-19. IMPORTANCE Tyrosine kinase has been implicated in viral replication and has become an antiviral drug target. Here, we chose two well-known receptor tyrosine kinase inhibitors, amuvatinib and imatinib, and evaluated their drug potencies against SARS-CoV-2. Surprisingly, amuvatinib displays a stronger antiviral activity than imatinib against SARS-CoV-2. Amuvatinib blocks SARS-CoV-2 infection by inhibiting ACE2 cleavage and the subsequent soluble ACE2 receptor. All these data suggest that amuvatinib may be a potential therapeutic agent in SARS-CoV-2 prevention for those experiencing vaccine breakthroughs., Competing Interests: The authors declare no conflict of interest.

Purpose: The purpose of this study was to investigate the utilization of gadolinium enhancement on vessel wall imaging (VWI) in treatment decision-making for patients with two intracranial aneurysms presenting as a subarachnoid hemorrhage (SAH)., Materials and Methods: We prospectively performed VWI using 3.0-Tesla (3T) magnetic resonance imaging (MRI) before treatment with endovascular coiling or surgical clipping in patients with one or two intracranial aneurysms. The VWI protocol includes three different scans: black blood (BB) T1-weighted, BB T2-weighted, TOF axial, and BB contrast-enhanced T1-weighted imaging. We analyzed all aneurysm ruptures both with and without gadolinium enhancement of the aneurysm wall., Results: Thirty-eight patients with 48 aneurysms were enrolled in this study. Of these patients, 28 had a single aneurysm (15 ruptured and 13 unruptured), and 10 had two aneurysms and SAH (9 patients with two aneurysms and 1 patient with three aneurysms). Of the 15 single ruptured aneurysms, 12 (80.0%) showed positive wall enhancement, whereas 2 of the 13 single unruptured aneurysms (15.4%) demonstrated positive wall enhancement. Ten patients with SAH and two aneurysms showed wall enhancement of a single aneurysm, and these aneurysms were treated first., Conclusion: Gadolinium enhancement of an aneurysm wall on MRI was associated with aneurysm rupture. In patients with two aneurysms and SAH, this type of imaging can play an important role in determining the order of aneurysm treatment., (© 2022. The Author(s) under exclusive licence to Belgian Neurological Society.)

Purpose: This study aimed to evaluate angiographic and contrast enhancement (CE) patterns on three-dimensional (3D) black blood (BB) contrast-enhanced MRI in patients with acute medulla infarction., Materials and Methods: From January 2020 to August 2021, we retrospectively analyzed stroke 3D BB contrast-enhanced magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) findings of patients visiting the emergency room for symptom evaluation of acute medulla infarction. In total, 28 patients with acute medulla infarction were enrolled in this study. Four types of 3D BB contrast-enhanced MRI and MRA were classified as follows: 1=unilateral contrast-enhanced vertebral artery (VA)+no visualization of VA on MRA; 2=unilateral enhanced VA+hypoplastic VA; 3=no enhanced VA+unilateral complete occlusion of VA; 4=no enhanced VA+normal VA (including hypoplasia) on MRA., Results: Of the 28 patients with acute medulla infarction, 7 (25.0%) showed delayed positive findings after 24 hours on diffusion-weighted imaging (DWI). Of these patients, 19 (67.9%) showed CE of the unilateral VA on 3D BB contrast-enhanced MRI (type 1 and 2). Of the 19 patients with CE of VA on 3D BB contrast-enhanced MRI, 18 showed no visualization of enhanced VA on MRA (type 1), and 1 showed hypoplastic VA. Of the 7 patients with delayed positive findings on DWI, 5 showed CE of the unilateral VA and no visualization of the enhanced VA on MRA (type 1). Symptom onset to door time or initial MR check time was significantly shorter in the groups with delayed positive findings on DWI (P<0.05)., Conclusion: Unilateral CE on 3D BB contrast-enhanced MRI and no visualization of the VA on MRA are related to the recent occlusion of the distal VA. These findings suggest that the recent occlusion of the distal VA is related to acute medulla infarction, including delayed visualization on DWI.

Introduction: Tumor necrosis factor (TNF)-α released after follicular injury such as that caused by plucking plays a role in the activation of hair regeneration. Microneedle (MN) treatment is applied to the scalp to increase permeability and facilitate the delivery of any number of compounds. Because the MN treatment causes injury to the epidermis, albeit minor, we reasoned that this treatment would lead to a temporary TNF-α surge and thereby promote hair regeneration., Methods: To investigate the effects of MN-treatment-induced microinjury and TNF-α on hair growth, we used C57BL/6N mice which were divided into six experimental groups: three groups of 1) negative control (NC), 2) plucking positive control (PK), and 3) MN therapy system (MTS) mice; and three groups identical to above were treated with a TNF-α blocker for 3 weeks: 4) NCB, 5) PKB, and 6) MTSB group., Results: After injury, TNF-α surge occurred on day 3 in the PK group and on day 6 in the MTS group. Wnt proteins and VEGF expression were markedly increased in the PK group on day 3 and on day 6 in the MTS group compared to the NC group. Following wound healing, only MTS and PK groups displayed thickened epidermis and longer HF length. Within the 2 weeks following treatment, the rate of hair growth was much slower in the injured mice treated with the TNF-α blocker., Conclusion: Our findings indicate that microinjury stimulates the wound-healing mechanism via TNF-α/Wnt/VEGF surge to induce hair growth, and that blocking TNF-α inhibits this growth process., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Purpose: The purpose of this study was to compare the imaging findings on three-dimensional (3D) black-blood (BB) contrast-enhanced MR imaging between intracranial atherosclerotic occlusion (IAO) and thrombotic occlusion (TO) of the middle cerebral artery (MCA) territory., Materials and Methods: From August 2020 to September 2021, we retrospectively reviewed the BB contrast-enhanced MR imaging of patients visiting the emergency room for evaluation of acute ischemic stroke. In total, 77 patients with complete occlusion of the MCA territory on 3D BB contrast-enhanced MR imaging and cerebral angiography were enrolled in this study. We divided the IAO and TO groups according to occlusion causes based on angiography findings., Results: Of 77 patients, 44 (57.1%) had an IAO in the M1 and M2 and 33 had a TO. Lesion length contrast enhancement (CE) in patients with a TO was significantly longer than that in patients with an IAO (18.95 mm [IQR: 20.91] vs. 7.1 mm [8.92], p <0.001). Overall, 38 (39.4%) patients showed a disconnection of CE on 3D BB contrast-enhanced MR imaging, and 35 showed CE before and after the stenotic or thrombotic lesion. Symptomatic lesions on diffusion-weighted imaging in the TO group were significantly higher than that of the IAO group (97.0% vs, 70.5%, p = 0.003)., Conclusion: The long segment CE on 3D BB contrast-enhanced MR imaging was related to TO of MCA. CE before and after a stenotic or thrombotic lesion is a common finding on 3D BB contrast-enhanced MR imaging., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Expansion of intracranial hemorrhage (ICH) is an important predictor of poor clinical outcomes. Various imaging markers on non-contrast computed tomography (NCCT) or computed tomographic angiography (CTA) have been reported as predictors of ICH expansion. We aimed to compare the associations between various CT imaging markers and ICH expansion. Patients with spontaneous ICH who underwent initial NCCT, CTA, and subsequent NCCT between January 2016 and December 2019 were retrospectively identified. ICH expansion was defined as a volume increase of > 33% or > 6 mL. We analyzed the presence of imaging markers such as the black hole sign, blend sign, island sign, or swirl sign on initial NCCT or spot sign on CTA. An alternative free-response receiver operating characteristic curve analysis was performed using a 4-point scoring system based on the consensus of the reviewers. The predictive value of each marker was assessed using univariate and multivariate logistic regression analyses. A total of 250 patients, including 60 (24.0%) with ICH expansion, qualified for the analysis. Among the patients with spontaneous ICH, 118 (47.2%) presented with a black hole sign, 52 (20.8%) with a blend sign, 93 (37.2%) with an island sign, 79 (31.6%) with a swirl sign, and 56 (22.4%) with a spot sign. In univariate logistic regression, the initial ICH volume (P = .038), initial intraventricular hemorrhage (IVH) presence (P < .001), swirl sign (P < .001), and spot sign (P < .001) were associated with ICH expansion. Multivariate analysis confirmed that the presence of initial IVH (odds ratio, 4.111; P = .002) and spot sign (odds ratio, 109.5; P < .001) were independent predictors of ICH expansion. Initial ICH volume, IVH, swirl sign, and spot sign are associated with ICH expansion. The presence of spot signs and IVH were independent predictors of ICH expansion., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

RUL (remaining useful life) shapelets were recently developed to overcome the shortcomings of similarity-based RUL prediction methods, such as high sensitivity to parameters. RUL shapelets are informative subsequences whose distances to a run-to-failure time series sample are very useful for predicting the RUL of the sample. However, the prediction performance and interpretability highly depend on the set of RUL shapelets, and it is very difficult to compose an optimized set. In this paper, we mathematically formalize the RUL shapelet composition problem with multiple objective functions. In addition, we analyze the characteristics of good RUL shapelet sets and develop a solution methodology based on a genetic algorithm. From the various experiments, we validate that the proposed method outperforms previous ones and suggest how to use the proposed method. The solution methodology developed in this paper can be applied to solve various RUL prediction problems. In addition, the findings on the RUL shapelets can help researchers develop their RUL shapelet-based solution., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Hepatitis C virus (HCV) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV employs diverse strategies to evade host antiviral innate immune responses to mediate a persistent infection. In the present study, we show that nonstructural protein 5A (NS5A) interacts with an NF-κB inhibitor immunomodulatory kinase, IKKε, and subsequently downregulats beta interferon (IFN-β) promoter activity. We further demonstrate that NS5A inhibits DDX3-mediated IKKε and interferon regulatory factor 3 (IRF3) phosphorylation. We also note that hyperphosphorylation of NS5A mediats protein interplay between NS5A and IKKε, thereby contributing to NS5A-mediated modulation of IFN-β signaling. Lastly, NS5A inhibits IKKε-dependent p65 phosphorylation and NF-κB activation. Based on these findings, we propose NS5A as a novel regulator of IFN signaling events, specifically by inhibiting IKKε downstream signaling cascades through its interaction with IKKε. Taken together, these data suggest an additional mechanistic means by which HCV modulates host antiviral innate immune responses to promote persistent viral infection.

Fish-derived collagen has recently emerged as an alternative collagen source with bioactive properties, including the enhancement of hair and skin health. It is also cost-effective and has high bioavailability, in addition to having fewer side-effects compared to collagen from porcine skin or bovine skin. Collagen peptides (CPs) extracted from the scales of Mozambique tilapia ( Oreochromis mossambicus ) reportedly promote hair and skin health. This study sought to evaluate the effects of CPs on hair growth using in vitro and in vivo models. CP significantly enhanced hair regrowth and the proliferation of human dermal papilla cells (hDPCs) in vitro. CP was orally administered to C57BL/6 mice for 6 weeks to confirm the hair-growth-promoting effects. The mice were divided into four groups: negative control (distilled water), positive control (1 mg/kg of finasteride), CP500 (500 mg/kg of CP), and CP1000 (1000 mg/kg of CP). CP treatment significantly enhanced the proliferation of hDPCs compared to 0.2 μM finasteride, in addition to enhancing hair regrowth. Particularly, CP1000 treatment achieved a hair-growth index similar to that of the PC. In H&E staining, the CP groups exhibited a high A/T ratio. Furthermore, CP increased the expression of hair growth factors (IGF-1, VEGF, krt27, Gprc5d, and Ki67) and decreased the growth inhibitory factor (TGF-β1). Furthermore, CP significantly upregulated the Wnt/β-catenin pathways and downregulated the BMP pathways. Therefore, these results indicate that CP could be used as food supplements and nutraceuticals for hair loss prevention as well as hair regrowth during alopecia.

Background: The purpose of this study was to evaluate the diagnostic value of contrast enhancement in a unilateral distal vertebral artery (VA) using black blood (BB)-enhanced magnetic resonance (MR) imaging in patients with acute neurological symptoms and asymmetrical VA geometry. Methods: From January 2020 to August 2021, we retrospectively analyzed BB-contrast-enhanced MR imaging and MR angiography (MRA) findings in stroke patients visiting the emergency room for an evaluation of acute neurological symptoms. We classified four patterns according to asymmetrical VA geometry using MRA and contrast enhancement using BB-enhanced MR imaging: type 1 = enhanced VA + no visualization of VA, type 2 = enhanced VA + hypoplastic VA, type 3 = non-enhanced VA + hypoplastic VA, or type 4 = non-enhanced VA + no visualization of VA. Results: In total, 288 patients (type 1 = 65, type 2 = 17, type 3 = 130, type 4 = 76) were enrolled in this study. Of these patients, 82 (28.5%) showed contrast enhancement of a unilateral distal VA on BB-enhanced MR imaging, and 51 (17.8%) had positive findings on diffusion-weighted imaging (DWI) in the ipsilateral medulla, pons, or posterior inferior cerebellar artery (PICA) territory. The contrast enhancement of a unilateral distal VA using BB-enhanced MR imaging demonstrated a significantly higher prevalence in patients with acute infarction on DWI (50.0% vs. 4.9%, p < 0.001). Conclusions: The contrast enhancement of a unilateral distal VA on BB-enhanced MR imaging is associated with acute infarction of the medulla, pons, or PICA territory and suggests acute occlusion of a distal VA.

Background: To determine the prevalence of symptomatic nonstenotic carotid disease (SyNC) using simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) imaging for patients with acute stroke as an MR screen protocol and to assess imaging findings of carotid plaques. Patients and Methods: From May 2020 to October 2021, 2459 patients with suspected acute neurological symptoms were evaluated with brain diffusion-weighted imaging (DWI) and carotid SNAP imaging. We analyzed the degree of stenosis and intraplaque hemorrhage (IPH) using SNAP imaging. Prevalence of SyNC and risk factors for stroke in patients with SyNC were determined. We performed subgroup multivariate analysis between SyNC and other etiologies of stroke (non-SyNC). Results: Of 4608 carotid arteries in 2304 patients enrolled in this study, 454 (9.9%) plaques (both lesions in 128 patients) were found on SNAP imaging. Of these plaques, 353 (77.8%) showed stenosis of <50%. Of plaques with <50% stenosis, 47 (13.3%) patients had a territorial acute focal infarction. Seventeen (36.2%) were classified with embolic stroke of undetermined source (ESUS) and SyNC. High maximal wall thickness and carotid IPH were identified as influencing factors for SyNC. Conclusion: For patients with <50% stenosis and territorial infarction, SyNC is a relatively important source of stroke. Especially, high maximal wall thickness and carotid IPH are important risk factors for SyNC.

In this study, we present the investigation of optical properties on a series of HfS 2-x Se x crystals with different Se compositions x changing from 0 to 2. We used the chemical-vapor transport method to grow these layered ternary compound semiconductors in bulk form. Their lattice constants and crystal properties were characterized by X-ray diffraction, high-resolution transmission electron microscopy, and Raman spectroscopy. We have performed absorption spectroscopies to determine their optical band-gap energies, which started from 2.012 eV with x = 0, and gradually shifts to 1.219 eV for x = 2. Furthermore, we measured the absorption spectroscopies at different temperatures in the range of 20-300 K to identify the temperature dependence of band-gap energies. The band-gap energies of HfS 2-x Se x were determined from the linear extrapolation method. We have noticed that the band-gap energy may be continuously tuned to the required energy by manipulating the ratio of S and Se. The parameters that describe the temperature influence on the band-gap energy are evaluated and discussed.

Objectives: Antioxidants are common dietary compounds with multiple health benefits. This study aimed to identify the association between dietary antioxidant consumption and the incidence of type 2 diabetes (T2D) mellitus (defined using the Korean Diabetes Association criteria) in South Korean adults., Design: Baseline and follow-up data from the Health Examinees (HEXA) study, a large-scale community-based genomic cohort study conducted in South Korea SETTING: A South Korean community., Participants: A total of 20 594 participants, aged 40-79 years, who participated in the baseline and follow-up surveys of the HEXA study were included. After an average of 5 years of follow-up, there were 332 men and 360 women with T2D., Results: Participants with the highest total flavonoid consumption (Q5) had a lower risk of T2D (men: HR 0.63; 95% CI 0.42 to 0.93; p value for trend=0.0169; and women: HR 0.54; 95% CI 0.438 to 0.78; p value for trend=0.0001) than those with the lowest consumption (Q1). Dietary total antioxidant capacity was significantly inversely associated with the development of T2D mellitus in women participants alone (HR 0.58; 95% CI 0.40 to 0.83; p value for trend=0.0004). Stratified analyses according to age and body mass index (BMI) showed that dietary total flavonoid consumption and total antioxidant capacity had a negative association with the development of T2D in women aged >52 years and women with BMI >25 kg/m 2 ., Conclusions: Dietary flavonoid consumption and total antioxidant capacity were associated with a lower risk of T2D in South Korean adults, especially in women aged >52 years and overweight. The findings of this study may provide reference data for the modification of dietary guidelines for South Koreans., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Adeno-associated virus (AAV)-mediated gene delivery holds great promise for gene therapy. However, the non-invasive delivery of AAV for lung tissues has not been adequately established. Here, we revealed that the intratracheal administration of an appropriate amount of AAV2/8 predominantly targets lung tissue. AAV-mediated gene delivery that we used in this study induced the expression of the desired protein in lung parenchymal cells, including alveolar type II cells. We harnessed the technique to develop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-susceptible mice. Three kinds of immune function-relevant gene knockout (KO) mice were transduced with AAV encoding human angiotensin-converting enzyme 2 (hACE2) and then injected with SARS-CoV-2. Among these mice, type I interferon receptor (IFNAR) KO mice showed increased viral titer in the lungs compared to that in the other KO mice. Moreover, nucleocapsid protein of SARS-CoV-2 and multiple lesions in the trachea and lung were observed in AAV-hACE2-transduced, SARS-CoV-2-infected IFNAR KO mice, indicating the involvement of type I interferon signaling in the protection of SARS-CoV-2. In this study, we demonstrate the ease and rapidness of the intratracheal administration of AAV for targeting lung tissue in mice, and this can be used to study diverse pulmonary diseases., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Tin disulfide (SnS 2 ) is a promising semiconductor for use in nanoelectronics and optoelectronics. Doping plays an essential role in SnS 2 applications, because it can increase the functionality of SnS 2 by tuning its original properties. In this study, the effect of zinc (Zn) doping on the photoelectric characteristics of SnS 2 crystals was explored. The chemical vapor transport method was adopted to grow pristine and Zn-doped SnS 2 crystals. Scanning electron microscopy images indicated that the grown SnS 2 crystals were layered materials. The ratio of the normalized photocurrent of the Zn-doped specimen to that of the pristine specimen increased with an increasing illumination frequency, reaching approximately five at 10 4 Hz. Time-resolved photocurrent measurements revealed that the Zn-doped specimen had shorter rise and fall times and a higher current amplitude than the pristine specimen. The photoresponsivity of the specimens increased with an increasing bias voltage or decreasing laser power. The Zn-doped SnS 2 crystals had 7.18 and 3.44 times higher photoresponsivity, respectively, than the pristine crystals at a bias voltage of 20 V and a laser power of 4 × 10 -8 W. The experimental results of this study indicate that Zn doping markedly enhances the optical response of SnS 2 layered crystals.

Hepatitis C virus (HCV) is a major cause of chronic liver disease and is highly dependent on cellular proteins for viral propagation. Using protein microarray analysis, we identified 90 cellular proteins as HCV nonstructural 5A (NS5A) interacting partners, and selected telomere length regulation protein (TEN1) for further study. TEN1 forms a heterotrimeric complex with CTC and STN1, which is essential for telomere protection and maintenance. Telomere length decreases in patients with active HCV, chronic liver disease, and hepatocellular carcinoma. However, the molecular mechanism of telomere length shortening in HCV-associated disease is largely unknown. In the present study, protein interactions between NS5A and TEN1 were confirmed by immunoprecipitation assays. Silencing of TEN1 reduced both viral RNA and protein expression levels of HCV, while ectopic expression of the siRNA-resistant TEN1 recovered the viral protein level, suggesting that TEN1 was specifically required for HCV propagation. Importantly, we found that TEN1 is re-localized from the nucleus to the cytoplasm in HCV-infected cells. These data suggest that HCV exploits TEN1 to promote viral propagation and that telomere protection is compromised in HCV-infected cells. Overall, our findings provide mechanistic insight into the telomere shortening in HCV-infected cells.

Aim: To characterize the anti-inflammatory and anti-apoptotic effects of N-acetylcysteine (NAC) in streptozotocin (STZ)-induced diabetic rat corneal epithelium and human corneal epithelial cells (HCECs) exposed to a high-glucose environment., Methods: HCECs were incubated in 0, 5, 50 mmol/L glucose medium, or 50 mmol/L glucose medium with NAC for 24h. Diabetes was induced in rats by intraperitoneal injection of 65 mg/kg STZ and some of these rats were topically administered NAC to corneas with 3 mice per group. We characterized receptor for advanced glycation end-products (RAGE) expression using immunofluorescence, and interleukin (IL)-1β and cleaved caspase-3 (CCAP-3) expression using immunohistochemistry. Circulating tumor necrosis factor (TNF)-α concentration was measured by ELISA and cleaved poly-ADP ribose polymerase (PARP) concentration was quantified by Western blotting. Apoptotic cells were detected using TUNEL assay and annexin V and propidium iodide staining., Results: Diabetic rats had higher expression of RAGE (2.46±0.13 fold), IL-1β, and CCAP-3 in apoptotic cells of their corneas than control rats. The expression of RAGE (1.83±0.11 fold), IL-1β, and CCAP-3, and the number of apoptotic cells, were reduced by topical NAC treatment. HCECs incubated in 50 mmol/L glucose medium showed high concentrations of TNF-α (310±2.00 pg/mL) and cleaved PARP (7.43±0.56 fold), and more extensive apoptosis than cells in 50 mmol/L glucose medium. However, the addition of NAC reduced the concentrations of TNF-α (153.67±2.31 pg/mL) and cleaved PARP (5.55±0.31 fold) and the number of apoptotic cells., Conclusion: NAC inhibits inflammation and apoptosis in the corneas of diabetic rats and HCECs maintained in a high-glucose environment., (International Journal of Ophthalmology Press.)

African swine fever virus (ASFV) is a highly contagious virus that causes severe hemorrhagic viral disease resulting in high mortality in domestic and wild pigs, until few antiviral agents can inhibit ASFV infections. Thus, new anti-ASFV drugs need to be urgently identified. Recently, we identified pentagastrin as a potential antiviral drug against ASFVs using molecular docking and machine learning models. However, the scoring functions are easily influenced by properties of protein pockets, resulting in a scoring bias. Here, we employed the 5'-P binding pocket of Asfv PolX as a potential binding site to identify antiviral drugs and classified 13 Asfv PolX structures into three classes based on pocket parameters calculated by the SiteMap module. We then applied principal component analysis to eliminate this scoring bias, which was effective in making the SP Glide score more balanced between 13 Asfv PolX structures in the dataset. As a result, we identified cangrelor and fostamatinib as potential antiviral drugs against ASFVs. Furthermore, the classification of the pocket properties of Asfv PolX protein can provide an alternative approach to identify novel antiviral drugs by optimizing the scoring function of the docking programs. Here, we report a machine learning-based novel approach to generate high binding affinity compounds that are individually matched to the available classification of the pocket properties of Asfv PolX protein.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a global health concern. Various SARS-CoV-2 vaccines have been developed and are being used for vaccination worldwide. However, no therapeutic agents against coronavirus disease 2019 (COVID-19) have been developed so far; therefore, new therapeutic agents are urgently needed. In the present study, we evaluated several hepatitis C virus direct-acting antivirals as potential candidates for drug repurposing against COVID-19. Theses include asunaprevir (a protease inhibitor), daclatasvir (an NS5A inhibitor), and sofosbuvir (an RNA polymerase inhibitor). We found that asunaprevir, but not sofosbuvir and daclatasvir, markedly inhibited SARS-CoV-2-induced cytopathic effects in Vero E6 cells. Both RNA and protein levels of SARS-CoV-2 were significantly decreased by treatment with asunaprevir. Moreover, asunaprevir profoundly decreased virion release from SARS-CoV-2-infected cells. A pseudoparticle entry assay revealed that asunaprevir blocked SARS-CoV-2 infection at the binding step of the viral life cycle. Furthermore, asunaprevir inhibited SARS-CoV-2 propagation in human lung Calu-3 cells. Collectively, we found that asunaprevir displays broad-spectrum antiviral activity and therefore might be worth developing as a new drug repurposing candidate for COVID-19.

Automatic three-dimensional (3-D) reconstruction of the coronary arteries (CA) from medical imaging modalities is still a challenging task. In this study, we present a deep learning-based method of automatic identification of the two ends of the vessel from X-ray coronary angiography (XCA). We also present a method of using template models of CA in matching the two-dimensional segmented vessels from two different angles of XCA. For the deep learning network, we used a U-net consisting of an encoder (Resnet) and a decoder. The two ends of the vessel were manually labeled to generate training images. The network was trained with 2,342, 1,907, and 1,523 labeled images for the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA), respectively. For template models of CA, ten reconstructed 3-D models were averaged for each artery. The accuracy of correspondence using template models was compared with that of manual matching. The deep learning network pointed the proximal region (20% of the total length) in 97.7, 97.5, and 96.4% of 315, 201, and 167 test images for LAD, LCX, and RCA, respectively. The success rates in pointing the distal region were 94.9, 89.8, and 94.6%, respectively. The average distances between the projected points from the reconstructed 3-D model to the detector and the points on the segmented vessels were not statistically different between the template and manual matchings. The computed FFR was not significantly different between the two matchings either. Deep learning methodology is feasible in identifying the two ends of the vessel in XCA, and the accuracy of using template models is comparable to that of manual correspondence in matching the segmented vessels from two angles., Competing Interests: MH, S-BH, HY, JK, DK, WH, A-JR, HC, and ES were employed by the company AI Medic, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hwang, Hwang, Yu, Kim, Kim, Hong, Ryu, Cho, Zhang, Koo and Shim.)

Purpose: To investigate the one-step detection of intraplaque hemorrhage (IPH) in the carotid artery (CA) and vertebrobasilar artery (VBA) using simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP)., Methods: From January 2019 to March 2020, 1820 consecutive patients who visited our emergency room for evaluation of neurologic symptoms underwent brain MR imaging, including the SNAP sequence. SNAP imaging examined the coronal section from the CA to the VBA. IPH was defined as plaque in the CA and VBA with 200 % higher signal intensity on SNAP than in adjacent muscle in at least two consecutive slices., Results: Of these patients, 360 (19.8 %) had carotid plaque (both sides = 141, 39.2 %; single side = 219, 61.8 %). Of patients with carotid plaque, 185 (51.4 %) had IPH. Of 141 patients with plaques on both sides, 35 (24.8 %) had bilateral IPH. In total, 73 (4.0 %) patients had VBA IPH (30 with carotid plaque, 43 without carotid plaque). In addition, 18 (1.0 %) patients had carotid IPH and VBA IPH. Maximal wall thickness was significantly higher in the carotid IPH groups (4.5 ± 0.1 vs. 4.1 ± 0.1, p = 0.009). Prevalence of high grade stenosis (>70 %) was significantly higher in the carotid IPH group (17.5 % vs. 6.2 %, p < 0.001)., Conclusions: SNAP imaging can be evaluated with a one-step examination of CA and VBA IPH., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Shiga toxin-producing Escherichia coli (STEC) is a global foodborne bacterial pathogen that is often accountable for colon disorder or distress. STEC commonly induces severe diarrhea in hosts but can cause critical illnesses due to the Shiga toxin virulence factors. To date, there have been a significant number of STEC serotypes have been evolved. STECs vary from nausea and hemorrhoid (HC) to possible lethal hemolytic-based uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP). Inflammation-based STEC is usually a foodborne illness with Shiga toxins ( Stx 1 and 2 ) thought to be pathogenesis. The STEC's pathogenicity depends significantly on developing one or more Shiga toxins, which can constrain host cell protein synthesis leading to cytotoxicity. In managing STEC infections, antimicrobial agents are generally avoided, as bacterial damage and discharge of accumulated toxins are thought the body. It has also been documented that certain antibiotics improve toxin production and the development of these species. Many different groups have attempted various therapies, including toxin-focused antibodies, toxin-based polymers, synbiotic agents, and secondary metabolites remedies. Besides, in recent years, antibiotics' efficacy in treating STEC infections has been reassessed with some encouraging methods. Nevertheless, the primary role of synbiotic effectiveness (probiotic and prebiotic) against pathogenic STEC and other enteropathogens is less recognized. Additional studies are required to understand the mechanisms of action of probiotic bacteria and yeast against STEC infection. Because of the consensus contraindication of antimicrobials for these bacterial pathogens, the examination was focused on alternative remedy strategies for STEC infections. The rise of novel STEC serotypes and approaches employed in its treatment are highlighted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hwang, Chelliah, Kang, Rubab, Banan-MwineDaliri, Elahi and Oh.)

This study investigated the hypothesis that Portulaca oleracea L. exerts antiobesity and antidiabetic effects by evaluating blood lipid profiles, blood glucose control factors, protein expression of lipid metabolism, and insulin sensitivity improvement. Three groups of high-fat diet (HFD) induced obese C57BL/6 mice ( n  = 8) received treatment with low (5%; HFD + PO5%) or high (10%; HFD + PO10%) concentrations of P. oleracea powder for 12 weeks or no treatment (HFD) and were compared with each other and a fourth control group. Weight gain was reduced by 34% in the HFD + PO10% group compared to the HFD group. Moreover, the perirenal and epididymal fat contents in the HFD + PO10% group were 6.3-fold and 1.5-fold, respectively, lower than those in the HFD group. The atherogenic index (AI) and cardiac risk factor (CRF) results in the P. oleracea -treated groups were significantly lower than those in the HFD group. The homeostasis model assessment of insulin resistance (HOMA-IR) levels was lower in the HFD + PO10% group than in the HFD group. The protein expression levels of the proliferator-activated receptor (PPAR)- α , glucose transporter (GLUT) 4 and PPAR- γ were upregulated in the HFD + PO10% group compared to the HFD group. However, the protein expression levels of tumor necrosis factor (TNF)- α were lower in the P. oleracea -treated groups than in the HFD group. Our results demonstrate that P. oleracea powder could be effectively used to treat and prevent obesity and diabetes-associated diseases through suppression of weight gain and reduction in body fat and blood glucose levels., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Jae Hyun Jung et al.)

African swine fever virus (ASFV) causes a highly contagious and severe hemorrhagic viral disease with high mortality in domestic pigs of all ages. Although the virus is harmless to humans, the ongoing ASFV epidemic could have severe economic consequences for global food security. Recent studies have found a few antiviral agents that can inhibit ASFV infections. However, currently, there are no vaccines or antiviral drugs. Hence, there is an urgent need to identify new drugs to treat ASFV. Based on the structural information data on the targets of ASFV, we used molecular docking and machine learning models to identify novel antiviral agents. We confirmed that compounds with high affinity present in the region of interest belonged to subsets in the chemical space using principal component analysis and k -means clustering in molecular docking studies of FDA-approved drugs. These methods predicted pentagastrin as a potential antiviral drug against ASFVs. Finally, it was also observed that the compound had an inhibitory effect on Asfv PolX activity. Results from the present study suggest that molecular docking and machine learning models can play an important role in identifying potential antiviral drugs against ASFVs.

Purpose: Intraplaque hemorrhage (IPH) and dissection in the vertebrobasilar artery (VBA) on time of flight (TOF) source imaging are seen as focal eccentric high-signal intensity. The purpose of this study is to identify IPH and dissection in the VBA using high-resolution magnetic resonance imaging (HR-MRI)., Methods: A total of 78 patients (VBA IPH: 55; dissection: 23) with focal high-signal intensity in the VBA on simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) of HR-MRI were included in this study. The focal high-signal intensity in the VBA on SNAP was defined as >200% than that of the adjacent muscle. We analyzed the signal intensity ratio (area of focal high signal intensity area/lumen) on TOF imaging and black blood (BB) T2-weighted imaging., Results: The VBA IPH group was older than the dissection group and had more hypertension. Signal intensity of a false lumen in patients with dissection on TOF imaging was significantly higher than that of VBA IPH ( p < 0.001). The signal intensity ratio between lumen and lesion on TOF imaging was significantly higher in the dissection group ( p < 0.001). The signal intensity of a false lumen in patients with dissection on BB T2-weighted imaging was significantly lower than that of VBA IPH ( p < 0.001). The signal intensity ratio between lumen and lesion on BB T2-weighted imaging was significantly higher in the VBA IPH group ( p < 0.001)., Conclusions: TOF imaging and BB T2-weighted imaging on HR-MRI in patients with focal eccentric high-signal intensity on TOF imaging can distinguish between VBA IPH and dissection.

Purpose: The purpose of this study was to evaluate contrast enhancement patterns on three-dimensional (3D) black blood (BB) contrast-enhanced magnetic resonance (MR) imaging in patients with occlusion or stenosis of the anterior intracranial artery., Materials and Methods: From January 2018 to January 2020 we retrospectively reviewed stroke 3D BB contrast-enhanced MR imaging and MR angiography findings of patients visiting the emergency room for evaluation of non-traumatic brain lesions. In total, 92 patients with positive findings on 3D BB contrast-enhanced MR imaging were enrolled in this study. We divided the enrolled group according to whether MR angiography findings suggested complete occlusion, high-grade stenosis (51-99 %), or low-grade stenosis (10-50 %)., Results: Of 92 patients, 33 had complete occlusion in the anterior intracranial artery, 36 had high-grade stenosis, and 23 had low-grade stenosis. The complete occlusion group showed concentric and segmental enhancement on 3D BB enhanced MR imaging. The high-grade stenosis group frequently showed concentric and focal enhancement. The high signal vessel sign in the complete occlusion group was significantly higher compared to the stenosis group (p < 0.001). The contrast ratio between the lesion and pituitary gland in the occlusion group was significantly lower than that of the stenosis group (p < 0.05)., Conclusion: Bright contrast enhancement and high signal vessel sign on 3D BB contrast enhanced MR imaging are related to contrast stagnation of the occlusion site and slow flow of a distal portion of the occlusion site., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study investigated the hair regeneration promotion and hair loss prevention properties of Nelumbinis Semen (NS) extract in vitro and in vivo . The effect of NS on the proliferation and migration of human dermal papilla cells (hDPCs) was measured in vitro via CCK-8 and scratch migration assays, after which the antioxidant activity of NS was also quantified. NS extracts were then applied to the back of 7-week-old C57BL/6 mice for 3 weeks to monitor hair growth patterns and hair follicle (HF) histology. The mice were divided into three groups: negative control group (NC; DMSO), positive control group (PC; 3% minoxidil), and experimental group (NS extract 1,000 ppm). Moreover, to study the molecular mechanisms by which NS extract regenerates hair growth, real-time PCR was used to analyze factors related to the hair growth cycle. The NS extracts were found to possess high antioxidant properties due to their high flavonoid contents and electron-donating ability. Moreover, NS extracts enhanced hDPC proliferation and migration in a concentration-dependent manner (15.63-125 ppm). The hair growth index and growth area of the NS group (2.81 score, 81%) on day 14 were higher than those of the PC group (2.65 score, 68%) ( p < 0.05). Additionally, the HFs of the NS group were located deep in the subcutis, similar to the PC group with developed hair roots. Moreover, the mRNA expression of VEGF and IGF-1 was higher in the NS group compared to the PC group, whereas TGF- β 1 expression was lower ( p < 0.05). Our findings indicate that NS modulates hair growth by increasing IGF-1 and VEGF expression while inhibiting that of TGF- β 1. Therefore, our findings suggest that NS extract is a promising new hair loss treatment derived from a natural substance that helps promote hair growth and prevent hair loss., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Hyeon Ju Park et al.)

Objective: Intravenous contrast agent enhanced, high-resolution magnetic resonance imaging of the inner ear (iMRI) confirmed that patients with Menière's disease (MD) and vestibular migraine (VM) could present with endolymphatic hydrops (EH). The present study aimed to investigate EH characteristics and their interrelation to neurotologic testing in patients with VM, MD, or VM with concurrent MD (VM-MD). Methods: Sixty-two patients (45 females, aged 23-81 years) with definite or probable VM ( n = 25, 19 definite), MD ( n = 29, 17 definite), or showing characteristics of both diseases ( n = 8) were included in this study. Diagnostic workup included neurotologic assessments including video-oculography (VOG) during caloric stimulation and head-impulse test (HIT), ocular and cervical vestibular evoked myogenic potentials (o/cVEMP), pure tone audiometry (PTA), as well as iMRI. EH's degree was assessed visually and via volumetric quantification using a probabilistic atlas-based segmentation of the bony labyrinth and volumetric local thresholding (VOLT). Results: Although a relevant number of VM patients reported varying auditory symptoms (13 of 25, 52.0%), EH in VM was only observed twice. In contrast, EH in VM-MD was prevalent (2/8, 25%) and in MD frequent [23/29, 79.3%; χ 2 (2) = 29.1, p < 0.001, φ = 0.7]. Location and laterality of EH and neurophysiological testing classifications were highly associated (Fisher exact test, p < 0.005). In MD, visual semi-quantitative grading and volumetric quantification correlated highly to each other ( r S = 0.8, p < 0.005, two-sided) and to side differences in VOG during caloric irrigation (vestibular EH ipsilateral: r S = 0.6, p < 0.05, two-sided). In VM, correlations were less pronounced. VM-MD assumed an intermediate position between VM and MD. Conclusion: Cochlear and vestibular hydrops can occur in MD and VM patients with auditory symptoms; this suggests inner ear damage irrespective of the diagnosis of MD or VM. The EH grades often correlated with auditory symptoms such as hearing impairment and tinnitus. Further research is required to uncover whether migraine is one causative factor of EH or whether EH in VM patients with auditory symptoms suggests an additional pathology due to MD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Oh, Dieterich, Lee, Boegle, Kang, Lee, Gerb, Hwang and Kirsch.)

Campylobacter spp. are the leading global cause of bacterial colon infections in humans. Enteropathogens are subjected to several stress conditions in the host colon, food complexes, and the environment. Species of the genus Campylobacter , in collective interactions with certain enteropathogens, can manage and survive such stress conditions. The stress-adaptation mechanisms of Campylobacter spp. diverge from other enteropathogenic bacteria, such as Escherichia coli , Salmonella enterica serovar Typhi, S. enterica ser. Paratyphi, S. enterica ser. Typhimurium, and species of the genera Klebsiella and Shigella . This review summarizes the different mechanisms of various stress-adaptive factors on the basis of species diversity in Campylobacter , including their response to various stress conditions that enhance their ability to survive on different types of food and in adverse environmental conditions. Understanding how these stress adaptation mechanisms in Campylobacter , and other enteric bacteria, are used to overcome various challenging environments facilitates the fight against resistance mechanisms in Campylobacter spp., and aids the development of novel therapeutics to control Campylobacter in both veterinary and human populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kim, Chelliah, Ramakrishnan, Perumal, Bang, Rubab, Daliri, Barathikannan, Elahi, Park, Jo, Hwang and Oh.)

Hepatitis C virus (HCV) life cycle is highly dependent on cellular proteins for viral propagation. In order to identify the cellular factors involved in HCV propagation, we previously performed a protein microarray assay using the HCV nonstructural 5A (NS5A) protein as a probe. Of ∼9,000 human cellular proteins immobilized in a microarray, adenosylhomocysteinase like 1 (AHCYL1) was among 90 proteins identified as NS5A interactors. Of these candidates, AHCYL1 was selected for further study. In the present study, we verified the physical interaction between NS5A and AHCYL1 by both in vitro pulldown and coimmunoprecipitation assays. Furthermore, HCV NS5A interacted with endogenous AHCYL1 in Jc1-infected cells. Both NS5A and AHCYL1 were colocalized in the cytoplasmic region in HCV-replicating cells. siRNAmediated knockdown of AHCYL1 abrogated HCV propagation. Exogenous expression of the siRNA-resistant AHCYL1 mutant, but not of the wild-type AHCYL1, restored HCV protein expression levels, indicating that AHCYL1 was required specifically for HCV propagation. Importantly, AHCYL1 was involved in the HCV internal ribosome entry site-mediated translation step of the HCV life cycle. Finally, we demonstrated that the proteasomal degradation pathway of AHCYL1 was modulated by persistent HCV infection. Collectively, these data suggest that HCV may modulate the AHCYL1 protein to promote viral propagation.

In the Visible Korean, serially sectioned images with real color and high resolution have been prepared from four cadaveric subjects: male whole body, female whole body, male head, and female pelvis. Recently, segmented images of the female whole body were manufactured, permitting the distribution of the complete four data sets. The purpose of this report was to promote the applications of sectioned and segmented images from the Visible Korean by announcing them. Reduced image data were loaded to self-developed browsing software; using the browsing software, the contents could be quickly grasped and evaluated by other investigators. The four data sets were compared to disclose the individual merits and demerits. The sectioned and segmented images showed the possibility to be used to reconstruct the stereoscopic volume and surface models of body structures. The Visible Korean is expected to contribute to the interactive simulation of medical learning and clinical practice.

The purpose of this study was to investigate whether and how topical nerve growth factor (NGF) attenuates streptozotocin (STZ)-induced diabetic cataracts in vivo. Rats were randomly divided into three groups, including the normal control rat group, STZ-induced diabetic cataract rat group (DM group), and STZ-induced diabetic cataract rat group treated with 200 μg/mL recombinant rat β-NGF (DM + NGF group). Cataract formation was evaluated by portable slit lamp biomicroscopy following pupil dilation at 8 weeks. The expression levels of NGF, aldose reductase (AR), and Na + /K + -ATPase in the lens epithelial cells (LECs) of the three groups were measured in the presence or absence of topical NGF. TUNEL-positive LECs were quantified to determine if hyperglycemia caused LEC apoptosis. At 8 weeks, the mean cataract score in the control group was significantly lower than that in DM and DM + NGF groups, and the score in the DM + NGF group was significantly lower than that in the DM group. At the equatorial zone and anterior central zone of lens, NGF and Na + /K + -ATPase expression levels were significantly decreased in the DM group; however, they were partially restored in the DM + NGF group. At the equatorial zone and anterior central zone of lens, AR expression and TUNEL-positive apoptotic LECs were significantly increased in the DM group compared with the control group, however, they were significantly decreased in the DM + NGF group. In conclusion, topical NGF could delay the progression of diabetic cataracts by attenuating polyol pathway activation and increasing Na + /K + -ATPase protein levels., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Nelumbinis Semen (NS, the seeds of Nelumbo nucifera ) extract is a traditional Korean medicine with anti-oxidant activity. The present study examined the anti-obesity and antidiabetic effects of NS powder in high-fat diet (HFD)-induced obese C57BL/6 mice. Mice ( n = 8/group) were fed a normal diet (CON), HFD, HFD containing 5% NS powder (HFD-NS5%), or HFD containing 10% NS powder (HFD-NS10%) for 12 weeks. Food intake was relatively higher in groups HFD-NS5% and HFD-NS10%, while the food efficiency ratio was highest in group HFD ( p < 0.05). HFD-NS5% reduced the body weight (-39.1%) and fat weight (-26.6%), including epididymal fat and perirenal fat, and lowered the serum triglyceride levels (-20.6%) compared with HFD. Groups HFD-NS5% and HFD-NS10% showed hepatoprotective properties, reducing the serum ALT levels ( p < 0.05) and fat globules (size and number) in the liver compared with group HFD. HFD-NS5% and HFD-NS10% regulated the blood glucose, improved the glucose intolerance, and showed a 12.5% and 15.0% reduction in the area under the curve (AUC) of intraperitoneal glucose tolerance test (IPGTT), and a 26.8% and 47.3% improvement in homeostatic model assessment insulin resistance (HOMA-IR), respectively, compared with HFD ( p < 0.05). Regarding the expressions of genes related to anti-obesity and antidiabetes, there was a 1.7- and 1.3-fold increase in PPAR-α protein expression, 1.4- and 1.6-fold increase in PPAR-γ protein expression, and 0.7- and 0.6-fold decrease in TNF-α protein expression, respectively, following HFD-NS5% and HFD-NS10% treatments, compared with HFD, and GLUT4 protein expression increased relative to CON ( p < 0.05). These results comprehensively provide the fundamental data for NS powder's functional and health-promoting benefits associated with anti-obesity and antidiabetes.

Hepatitis C virus (HCV) exploits cellular proteins to facilitate viral propagation. To identify the cellular factors involved in the HCV life cycle, we previously performed protein microarray assays using either HCV nonstructural 5A (NS5A) protein or core protein as a probe. Interestingly, cellular cortactin strongly interacted with both NS5A and core. Cortactin is an actin-binding protein critically involved in tumor progression by regulating the migration and invasion of cancerous cells. Protein interaction between cortactin and NS5A or core was confirmed by coimmunoprecipitation and immunofluorescence assays. We showed that cortactin interacted with NS5A and core via the N-terminal acidic domain of cortactin. Cortactin expression levels were not altered by HCV infection. Small interfering RNA (siRNA)-mediated knockdown of cortactin dramatically decreased HCV protein expression and infectivity levels, whereas overexpression of cortactin increased viral propagation. Ectopic expression of the siRNA-resistant cortactin recovered the viral infectivity, suggesting that cortactin was specifically required for HCV propagation. We further showed that cortactin was involved in the assembly step without affecting viral entry, HCV internal ribosome entry site (IRES)-mediated translation, and the replication steps of the HCV life cycle. Of note, silencing of cortactin markedly reduced both NS5A and core protein levels on the lipid droplets (LDs), and this effect was reversed by the overexpression of cortactin. Importantly, NS5A and core promoted cell migration by activating the phosphorylation of cortactin at tyrosine residues 421 and 466. Taken together, these data suggest that cortactin is not only involved in HCV assembly but also plays an important role in the cell migration. IMPORTANCE Cortactin is a cytoskeletal protein that regulates cell migration in response to a number of extracellular stimuli. The functional involvement of cortactin in the virus life cycle is not yet fully understood. The most significant finding is that cortactin strongly interacted with both hepatitis C virus (HCV) core and NS5A. Cortactin is involved in HCV assembly by tethering core and NS5A on the lipid droplets (LDs) with no effect on LD biogenesis. It was noteworthy that HCV NS5A and core activated cortactin by phosphorylation at tyrosines 421 and 466 to regulate cell migration. Collectively, our study shows that cortactin is a novel host factor involved in viral production and HCV-associated pathogenesis., (Copyright © 2020 American Society for Microbiology.)

It is well known that reducing consumption of sugar is a global public health priority. Beverages were the primary source of total sugar intake from processed foods. However, there are few studies investigating the trend of beverage consumption among children and adolescents in Korea. We examined the overall trend in beverage consumption among 11,996 participants aged 10-18 years who were enrolled in the Korea National Health and Nutrition Examination Survey (KNHANES) (1998-2018). Further, we examined the effect of beverage types on beverage consumption-related demographic factors and obesity among 6121 participants using the recent 24 h dietary recall data (2010-2018) that captured the consumption of fruit and vegetable juices, soft drinks, milk and milk-based products and alcoholic beverages. Demographic characteristics, including sex, age, body mass index, household income level and residential area, were considered. Consumers' overall beverage intake and the percentage of energy derived from fruit and vegetable juices and soft drinks steadily increased from 1998 to 2016-2018 ( p -trend < 0.0001); in contrast, dairy product consumption declined since 2010-2012. The main sources of beverage-based calories were fruit and vegetable juices (107.5 kcal/day), soft drinks (145.2 kcal/day), dairy products (181.8 kcal/day) and alcoholic beverages (103.5 kcal/day). Also, Korean adolescents aged 16-18 years consumed more soft drinks, fewer dairy products and higher alcoholic drinks than other age groups; particularly, boys consumed more energy from beverages ( p < 0.0001). The odds ratios of obesity prevalence tended to be higher for soft drink consumption than for other beverages but this was not significant. The consumption of fruit and vegetable juices and milk and milk products showed a marginal association with a reduced risk of obesity prevalence. Since beverage consumption has increased steadily among Korean children and adolescents, appropriate interventions are needed. In the future, data from a larger sample of Korean children and adolescents are necessary to identify significant differences and longitudinal studies are necessary to examine the causalities.