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Background/Objectives: Patients with chronic rhinosinusitis (CRS) accompanied by asthma often show poor prognoses and require continuous management. This study aimed to assess the prognostic value of eosinophil counts in nasal polyp tissue for selecting individuals who would benefit from ongoing management in CRS patients with asthma. Methods: Patients with asthma who underwent endoscopic sinus surgery for CRS with nasal polyps were included in the study. Eosinophil counts in nasal polyp tissues were quantified, and retrospective data were collected from laboratory and clinical findings, including endoscopic examinations, CT scans, and Japan Endoscopic Sinus Surgery Rating and Evaluation Committee (JESREC) scores. Disease control status was evaluated through endoscopic examination 6 months post-surgery. Results: A total of 42 patients were divided into two groups based on their disease management status 6 months post-operation: the well-control group (24 patients, 57.14%) and the poor-control group (18 patients, 42.86%). Demographics and laboratory findings did not show significant differences between the groups. However, the JESREC score ( p = 0.04) and tissue eosinophil count ( p = 0.02) were significantly different. Multivariate analysis identified tissue eosinophil count as the only risk factor associated with prognosis, with a cut-off value of 90/HPF. Conclusions: In CRS patients with asthma, high tissue eosinophil counts in nasal polyps were associated with poor disease control, which is the most potent predictor of prognosis. The assessment of eosinophil counts in nasal polyp tissue could aid in identifying patients who would benefit from continuous management and tailored interventions for improved outcomes.

Background/Objectives : Relatively little has been established about the association of rapid ventricular response (RVR) with further recurrence of atrial fibrillation (AF). This study investigated the impact of RVR on the recurrence of AF. Methods : Data were obtained from a multicenter, prospective registry of non-valvular AF patients. RVR was defined as AF with a ventricular rate > 110 bpm. The primary endpoint was the recurrence of AF, defined as the first AF detected on 12-lead electrocardiography during follow-up. Secondary endpoints included manifestation of AF during follow-up and major adverse cardiovascular events (MACEs), a composite of thromboembolic events, major bleeding, myocardial infarction, and death. Results : Among 5533 patients, 493 (8.9%) presented RVR. Patients with RVR were younger, had smaller left atrial diameters, and more frequently had paroxysmal AF. During the mean follow-up duration of 28.6 months, the RVR group exhibited significantly lower recurrence of AF (hazard ratio: 0.58, 95% confidence interval: 0.53-0.65, p < 0.001). There was no significant difference in the occurrence of MACEs between patients with RVR and those without RVR (0.96, 0.70-1.31, p = 0.800). AF with RVR was identified as an independent negative predictor of AF recurrence (0.61, 0.53-0.71, p < 0.001). Conclusions : In patients with AF, those with RVR had a significantly lower recurrence of AF without an increase in MACEs. RVR is a favorable marker that may benefit from early rhythm control.

Owing to their physical and chemical properties and stimuli-responsive nature, gels and hydrogels play vital roles in diverse application fields. The three-dimensional polymeric network structure of hydrogels is considered an alternative to many materials, such as conductors, ordinary films, constituent components of machines and robots, etc. The most recent applications of gels are in different devices like sensors, actuators, flexible screens, touch panels, flexible storage, solar cells, batteries, and electronic skin. This review article addresses the devices where gels are used, the progress of research, the working mechanisms of hydrogels in those devices, and future prospects. Preparation methods are also important for obtaining a suitable hydrogel. This review discusses different methods of hydrogel preparation from the respective raw materials. Moreover, the mechanism by which gels act as a part of electronic devices is described.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged as a global outbreak in 2019, profoundly affecting both human health and the global economy. Various vaccine modalities were developed and commercialized to overcome this challenge, including inactivated vaccines, mRNA vaccines, adenovirus vector-based vaccines, and subunit vaccines. While intramuscular vaccines induce high IgG levels, they often fail to stimulate significant mucosal immunity in the respiratory system. We employed the Newcastle disease virus (NDV) vector expressing the spike protein of the SARS-CoV-2 Beta variant (rK148/beta-S), and evaluated the efficacy of intranasal vaccination with rK148/beta-S in K18-hACE2 transgenic mice. Intranasal vaccination with a low dose (10 6.0 EID 50 ) resulted in an 86% survival rate after challenge with the SARS-CoV-2 Beta variant. Administration at a high dose (10 7.0 EID 50 ) led to a reduction in lung viral load and 100% survival against the SARS-CoV-2 Beta and Delta variants. A high level of the SARS-CoV-2 spike-specific IgA was also induced in vaccinated mice lungs following the SARS-CoV-2 challenge. Our findings suggest that rK148/beta-S holds promise as an intranasal vaccine candidate that effectively induces mucosal immunity against SARS-CoV-2.

In energy applications, the use of materials with hierarchical porous structures and large surface areas is essential for efficient charge storage. These structures facilitate rapid electron and ion transport, resulting in high power density and quick charge/discharge capabilities. Carbon-based materials are extensively utilized due to their tunable properties, including pore sizes ranging from ultra- to macropores and surface polarity. Incorporating heteroatoms such as nitrogen, oxygen, sulfur, phosphorus, and boron modifies the carbon structure, enhancing electrocatalytic properties and overall performance. A hierarchical pore structure is necessary for optimal performance, as it ensures efficient access to the material's core. The microstructure of carbon materials significantly impacts energy storage, with factors like polyaromatic condensation, crystallite structure, and interlayer distance playing crucial roles. Carbon aerogels, derived from the carbonization of organic gels, feature a sponge-like structure with large surface area and high porosity, making them suitable for energy storage. Their open pore structure supports fast ion transfer, leading to high energy and power densities. Challenges include maintaining mechanical or structural integrity, multifunctional features, and scalability. This review provides an overview of the current progress in carbon-based aerogels for energy applications, discussing their properties, development strategies, and limitations, and offering significant guidance for future research requirements.

Along with serving as drug delivery sensors and flexible devices, hydrogels are playing pioneering roles in water purification. Both chemical and radiation methods can produce hydrogels, with the latter method gaining preference for its pure adducts. The water treatment process entails the removal of heavy and toxic metals (above the threshold amount), dyes, and solid wastes from industrial effluents, seawater, and groundwater, as well as sterilization for microorganism destruction. This review analyzed the different types of hydrogels produced by applying various radiations for water treatment. Particularly, we examined the hydrogels created through the application of varying levels of gamma and electron beam radiation from the electron gun and Co-60 sources. Moreover, we discuss the optimized radiation doses, the compositions (monomers and polymers) of raw materials required for hydrogel preparation, and their performance in water purification. We present and predict the current state and future possibilities of radiation-induced hydrogels. We explain and compare the superiority of one radiation method over other radiation methods (UV-visible, X-ray, microwave, etc.) based on water treatment.

Hydrogen is one of the most promising green energy alternatives due to its high gravimetric energy density, zero-carbon emissions, and other advantages. In this work, a CoFeBP micro-flower (MF) electrocatalyst is fabricated as an advanced water-splitting electrocatalyst by a hydrothermal approach for hydrogen production with the highly efficient hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). The fabrication process of the CoFeBP MF electrocatalyst is systematically optimized by thorough investigations on various hydrothermal synthesis and post-annealing parameters. The best optimized CoFeBP MF electrode demonstrates HER/OER overpotentials of 20 mV and 219 mV at 20 mA/cm 2 . The CoFeBP MFs also exhibit a low 2-electrode (2-E) cell voltage of 1.60 V at 50 mA/cm 2 , which is comparable to the benchmark electrodes of Pt/C and RuO 2 . The CoFeBP MFs demonstrate excellent 2-E stability of over 100 h operation under harsh industrial operational conditions at 60 °C in 6 M KOH at a high current density of 1000 mA/cm 2 . The flower-like morphology can offer a largely increased electrochemical active surface area (ECSA), and systematic post-annealing can lead to improved crystallinity in CoFeBP MFs.

(1) Background: This study investigated changes in the gut microbial composition of individuals with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and their relationship with positron emission tomography (PET) amyloid accumulation. (2) Methods: In total, 17 cognitively normal individuals without amyloid-beta (Aβ) accumulation (Aβ - NC) and 24 with Aβ-positive mild cognitive impairment (Aβ + MCI) who underwent 18 F-florbetaben PET and fecal bacterial 16S ribosomal RNA gene sequencing were enrolled. The taxonomic compositions of the Aβ - NC and Aβ + MCI groups were compared. The abundance of taxa was correlated with the standardized uptake value ratio (SUVR), using generalized linear models. (3) Results: There were significant differences in microbiome richness (ACE, p = 0.034 and Chao1, p = 0.024), alpha diversity (Shannon, p = 0.039), and beta diversity (Bray-Curtis, p = 0.018 and Generalized UniFrac, p = 0.034) between the Aβ - NC and Aβ + MCI groups. The global SUVR was positively correlated with the genus Intestinibacter ( q = 0.006) and negatively correlated with the genera Roseburia ( q = 0.008) and Agathobaculum ( q = 0.029). (4) Conclusions: In this study, we identified significant changes in the gut microbiota composition that occur in individuals with MCI due to AD. In particular, the correlation analysis results between PET amyloid burden and gut microbial abundance showed that amyloid deposition is associated with a reduction in specific taxa involved in butyrate production.

Background : The objective of this study is to establish a potential correlation between postoperative improvement in upper eyelid ptosis, measured by the marginal reflex distance 1 (MRD1), and the immediate postoperative degrees of lagophthalmos (IPDL). The established correlation is then used to assess whether IPDL can be used as a reliable indicator of successful treatment of eyelid ptosis. Methods : This retrospective study involved 19 patients, aged 1 to 11, with a total of 28 eyes affected by ptosis, who underwent surgery under general anesthesia at Seoul National University Bundang Hospital from January 2018 to December 2022. We monitored the MRD1 of the patients for over six months postoperatively and measured the IPDL. Results : After ptosis correction surgery, no statistically significant correlation was observed between the improvement in MRD1 and IPDL. Furthermore, the degree of postoperative eyelid ptosis improvement was found to vary and was not consistently sustained, attributable to a range of factors. Conclusions : Our study did not establish a statistically significant correlation between IPDL and ptosis improvement as measured by MRD1. Further research is needed to draw definitive conclusions about their correlation.

Continuous worldwide demands for more clean energy urge researchers and engineers to seek various energy applications, including electrocatalytic processes. Traditional energy-active materials, when combined with conducting materials and non-active polymeric materials, inadvertently leading to reduced interaction between their active and conducting components. This results in a drop in active catalytic sites, sluggish kinetics, and compromised mass and electronic transport properties. Furthermore, interaction between these materials could increase degradation products, impeding the efficiency of the catalytic process. Gels appears to be promising candidates to solve these challenges due to their larger specific surface area, three-dimensional hierarchical accommodative porous frameworks for active particles, self-catalytic properties, tunable electronic and electrochemical properties, as well as their inherent stability and cost-effectiveness. This review delves into the strategic design of catalytic gel materials, focusing on their potential in advanced energy conversion and storage technologies. Specific attention is given to catalytic gel material design strategies, exploring fundamental catalytic approaches for energy conversion processes such as the CO 2 reduction reaction (CO 2 RR), oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and more. This comprehensive review not only addresses current developments but also outlines future research strategies and challenges in the field. Moreover, it provides guidance on overcoming these challenges, ensuring a holistic understanding of catalytic gel materials and their role in advancing energy conversion and storage technologies.

Multi-layered hydrogels consisting of bi- or tri-layers with different swelling ratios are designed to soft hydrogel actuators by self-folding. The successful use of multi-layered hydrogels in this application greatly relies on the precise design and fabrication of the curvature of self-folding. In general, however, the self-folding often results in an undesired mismatch with the expecting value. To address this issue, this study introduces an interfacial layer formed between each layered hydrogel, and this layer is evaluated to enhance the design and fabrication precision. By considering the interfacial layer, which forms through diffusion, as an additional layer in the multi-layered hydrogel, the degree of mismatch in the self-folding is significantly reduced. Experimental results show that as the thickness of the interfacial layer increases, the multi-layered hydrogel exhibits a 3.5-fold increase in its radius of curvature during the self-folding. In addition, the diffusion layer is crucial for creating robust systems by preventing the separation of layers in the muti-layered hydrogel during actuation, thereby ensuring the integrity of the system in operation. This new strategy for designing multi-layered hydrogels including an interfacial layer would greatly serve to fabricate precise and robust soft hydrogel actuators.

A higher risk of pseudophakic cystoid macular edema (PCME) has been reported in patients with preoperative idiopathic epiretinal membrane (ERM); however, whether the formation of PCME depends on the grade of ERM has not been well established. We conducted a retrospective case-control study of 87 eyes of 78 patients who were preoperatively diagnosed with idiopathic ERM and had undergone cataract surgery. Patients were divided into two groups: PCME and non-PCME groups. After cataract surgery, the ERM status was graded using the Gass and Govetto classifications. Both the central macular thickness (CMT) and ERM grade increased after surgery, and higher preoperative CMT and ERM grades were found in the PCME group. The association between higher-grade ERM and the development of PCME was significant in the Govetto classification (grade 2, odds ratio (OR): 3.13; grade 3, OR: 3.93; and grade 4, OR: 16.07). The study results indicate that close attention should be given to patients with ERM with the presence of an ectopic inner foveal layer before cataract surgery.

A few drugs need non-aqueous gels for release in the specific region of the intestine. The present work focuses on preparing N , N -Dimethyl acrylamide-Diallyl Maleate (DMAA-DAM) gel in Dimethyl sulfoxide (DMSO) solvent by applying different doses of gamma radiation and then characterization. The blend solution of 10%: 10%-DMAA: DAM was prepared in DMSO and irradiated at 2, 5, 10, 20, and 30 kGy doses from the Co-60 gamma source. After extraction, it was observed that all of the radiation doses yielded more than 95% gel content. The best gel content was found for 10 kGy dose, which was 97%. The equilibrium swelling was optimized 1800% of the dried gel for 5 kGy dose. Gel formation was confirmed by analyzing characteristic functional groups and the environment of protons in the gel structure by using FTIR and NMR spectroscopy. The thermal stability was tested using DSC and TGA which showed the glass transition temperature at 86.55 °C and the degradation started at 320 °C. The XRD pattern analysis revealed the semi-crystalline nature of the gel. Therefore, DMAA-DAM gels can be a good candidate for use in different fields of study, especially in drug delivery.

Despite the importance of speaking up for patient safety, hesitancy to do so remains a major contributing factor to communication failure. This study aimed to investigate the experiences of South Korean nurses in speaking up to prevent patient safety incidents. Twelve nurses responsible for patient safety tasks or with experience in patient safety education were recruited from five hospitals (three university hospitals, two general hospitals) in city "B". Data were collected through open-ended questions and in-depth interviews, transcribed, and analyzed using the inductive content analysis method. The study resulted in the identification of four main categories and nine subcategories that captured commonalities among the experience of the 12 nurses. The four main categories were as follows: the current scenario of speaking up, barriers to speaking up, strategies for speaking, and confidence training. There is a scarcity of research on speaking-up experiences for patient safety among nurses in South Korean. Overall, it is necessary to overcome cultural barriers and establish an environment that encourages speaking up. In addition, developing speaking-up training programs for nursing students and novice nurses is imperative to prevent patient safety incidents.

Gamma radiation technique for the preparation of pure hydrogels is gaining popularity worldwide. Superabsorbent hydrogels play vital roles in different fields of application. The present work mainly focuses on the preparation and characterization of 2,3-Dimethylacrylic acid-(2-Acrylamido-2-methyl-1-propane sulfonic acid) (DMAA-AMPSA) superabsorbent hydrogel by applying gamma radiation and optimization of the proper dose. To prepare DMAA-AMPSA hydrogel, different doses ranging from 2 kGy to 30 kGy were imparted on the blend aqueous solution of the monomers. The equilibrium swelling increases with increasing radiation dose, followed by decreasing after reaching a certain level, and the highest result is found to be 26,324.9% at 10 kGy. Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy confirmed the formation of co-polymer by showing the characteristic functional groups and proton environment of the gel. X-ray Diffraction (XRD) pattern indicates the crystalline/amorphous nature of the gel. The Differential Scanning Calorimetry (DSC) and Thermogravimetry Analysis (TGA) revealed the thermal stability of the gel. The surface morphology and constitutional elements were analyzed and confirmed by Scanning Electron Microscopy (SEM) equipped with Energy Dispersive Spectroscopy (EDS). Finally, it can be stated that hydrogels can be usable in metal adsorption, drug delivery, and other relevant fields.

Although obesity is a well-established risk factor of cardiovascular event, the linkage between obesity and sudden cardiac arrest (SCA) is not fully understood. Based on a nationwide health insurance database, this study investigated the impact of body weight status, measured by body-mass index (BMI) and waist circumference, on the SCA risk. A total of 4,234,341 participants who underwent medical check-ups in 2009 were included, and the influence of risk factors (age, sex, social habits, and metabolic disorders) was analyzed. For 33,345,378 person-years follow-up, SCA occurred in 16,352 cases. The BMI resulted in a J-shaped association with SCA risk, in which the obese group (BMI ≥ 30) had a 20.8% increased risk of SCA compared with the normal body weight group (18.5 ≤ BMI < 23.0) ( p < 0.001). Waist circumference showed a linear association with the risk of SCA, with a 2.69-fold increased risk of SCA in the highest waist circumference group compared with the lowest waist circumference group ( p < 0.001). However, after adjustment of risk factors, neither BMI nor waist circumference was associated with the SCA risk. In conclusion, obesity is not independently associated with SCA risk based on the consideration of various confounders. Rather than confining the findings to obesity itself, comprehensive consideration of metabolic disorders as well as demographics and social habits might provide better understanding and prevention of SCA.

The gamma radiation technique is simple and time-saving for the synthesis of pure hydrogels. The present work focuses on synthesizing and characterizing Diallyldimethylammonium Chloride-Acrylic acid-(3-Acrylamidopropyl) trimethylammonium Chloride (DADMAC-AAc-APTAC) superabsorbent hydrogels. The hydrogels were synthesized by applying gamma radiation of different doses (2 kGy to 30 kGy) to two different compositions of monomers. The equilibrium swelling was found to be 33483.48% of dried gel for a 1:0.5:1 composition ratio of monomers at a 2 kGy radiation dose. Therefore, on the basis of equilibrium swelling, 2 kGy is the optimum radiation dose for synthesizing the hydrogel. Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR) spectroscopy, and X-ray diffraction (XRD) characterization techniques were used to analyze and confirm the structure of the hydrogel. Thermogravimetric analysis (TGA) and Scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS) clearly showed the thermal stability and surface morphology of the gel. Therefore, it can be concluded that hydrogels can be used in metal adsorption, drug delivery, and other fields of study.

Background: The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) is an expert consensus guideline for depressive disorder created in 2002, and since then, four revisions (2006, 2012, 2017, 2021) have been published. In this study, changes in the content of the KMAP-DD survey and recommendations for each period were examined., Methods: The development process of the KMAP-DD was composed of two stages. First, opinions from experts with abundant clinical experience were gathered through surveys. Next, a final guideline was prepared through discussion within the working committee regarding the suitability of the results with reference to recent clinical studies or other guidelines., Results: In mild depressive symptoms, antidepressant (AD) monotherapy was preferred, but when severe depression or when psychotic features were present, a combination of AD and atypical antipsychotics (AD + AAP) was preferred. AD monotherapy was preferred in most clinical subtypes. AD monotherapy was preferred for mild depressive symptoms, and AD + AAP was preferred for severe depression and depression with psychotic features in children, adolescents, and the elderly., Conclusions: This study identified the changes in the KMAP-DD treatment strategies and drug preferences in each period over the past 20 years. This work is expected to aid clinicians in establishing effective treatment strategies.

Background: Diabetes mellitus (DM) can cause various atherosclerotic cardiovascular disease including sudden cardiac death (SCD). The impact of being underweight on the risk of SCD in people with DM remains to be revealed. We aimed to evaluate the risk of SCD according to body-mass index (BMI; kg/m 2 ) level in DM population., Methods: We used a nationwide healthcare insurance database to conduct this study. We identified people with DM among those who underwent nationwide health screening during 2009 to 2012. Medical follow-up data was available until December 2018., Results: A total of 2,602,577 people with DM with a 17,851,797 person*year follow-up were analyzed. The underweight group (BMI < 18.5) showed 2.4-fold increased risk of SCD during follow-up (adjusted-hazard ratio [HR] = 2.40; 95% confidence interval [CI] = 2.26-2.56; p < 0.001). When normal-BMI group (18.5 ≤ BMI < 23) was set as a reference, underweight group (adjusted-HR = 2.01; 95% CI = 1.88-2.14) showed even higher risk of SCD compared with the obesity group (BMI ≥ 30; adjusted-HR = 0.89; 95% CI = 0.84-0.94). When BMI was stratified by one unit, BMI and SCD risk showed a U-curve association with the highest risk observed at low BMI levels. The lowest risk was observed in 27 ≤ BMI < 28 group. The association between being underweight and increased SCD risk in DM people was maintained throughout various subgroups., Conclusions: Being underweight is significantly associated with an increased risk of SCD in the DM population. A steep rise in the risk of SCD was observed as the BMI level decreased below 23. The lowest risk of SCD was observed in 27 ≤ BMI < 28 group.

A prospective observational cohort study investigated the prevalence of post-intensive care syndrome (PICS) among non-COVID-19 ICU survivors during the COVID-19 pandemic. Adults who had been admitted to the ICU for more than 24 h were enrolled, and followed-up at 3, 6, and 12 months post-discharge. PICS (mental health, cognitive, and physical domains) was measured using the Hospital Anxiety and Depression Scale, Posttraumatic Diagnosis Scale, Montreal Cognitive Assessment, and Korean Activities of Daily Living (ADL) scale. Data were analyzed from 237 participants who completed all three follow-up surveys. The prevalence of PICS was 44.7%, 38.4%, and 47.3%, at 3, 6, and 12 months of discharge, respectively. The prevalence of PICS in the mental health and cognitive domains decreased at 6 and increased at 12 months. The prevalence of PICS in the physical domain declined over time. Changes in PICS scores other than ADL differed significantly according to whether participants completed follow-up before or after December 2020, when COVID-19 rapidly spread in South Korea. In the recent group, anxiety, depression, post-traumatic stress disorder, and cognition scores were significantly worse at 12 months than at 6 months post-discharge. The COVID-19 pandemic may have adversely affected the recovery of non-COVID-19 ICU survivors.

Olfactory receptors (ORs) are the largest protein superfamily in mammals. Certain ORs are ectopically expressed in extranasal tissues and regulate cell type-specific signal transduction pathways. OR2AT4 is ectopically expressed in skin cells and promotes wound healing and hair growth. As the capacities of wound healing and hair growth decline with aging, we investigated the role of OR2AT4 in the aging and senescence of human keratinocytes. OR2AT4 was functionally expressed in human keratinocytes (HaCaT) and exhibited co-expression with G-protein-coupled receptor signaling components, G olfα and adenylate cyclase 3. The OR2AT4 ligand sandalore modulates the intracellular calcium, inositol phosphate, and cyclic adenosine monophosphate (cAMP) levels. The increased calcium level induced by sandalore was attenuated in cells with OR2AT4 knockdown. OR2AT4 activation by sandalore inhibited the senescent cell phenotypes and restored cell proliferation and Ki-67 expression. Sandalore also inhibited the expression of senescence-associated β-galactosidase and increased p21 expression in senescent HaCaT cells in response to hydrogen peroxide. Additionally, sandalore activated the CaMKKβ/AMPK/mTORC1/autophagy signaling axis and promoted autophagy. OR2AT4 knockdown attenuated the increased in the intracellular calcium level, cell proliferation, and AMPK phosphorylation induced by sandalore. These findings demonstrate that the effects of sandalore are mediated by OR2AT4 activation. Our findings suggest that OR2AT4 may be a novel therapeutic target for anti-aging and anti-senescence in human keratinocytes.

Ultra-fine hydrogen produced by electrochemical water splitting without carbon emission is a high-density energy carrier, which could gradually substitute the usage of traditional fossil fuels. The development of high-performance electrocatalysts at affordable costs is one of the major research priorities in order to achieve the large-scale implementation of a green hydrogen supply chain. In this work, the development of a vanadium-doped FeBP (V-FeBP) microsphere croissant (MSC) electrocatalyst is demonstrated to exhibit efficient bi-functional water splitting for the first time. The FeBP MSC electrode is synthesized by a hydrothermal approach along with the systematic control of growth parameters such as precursor concentration, reaction duration, reaction temperature and post-annealing, etc. Then, the heteroatom doping of vanadium is performed on the best FeBP MSC by a simple soaking approach. The best optimized V-FeBP MSC demonstrates the low HER and OER overpotentials of 52 and 180 mV at 50 mA/cm 2 in 1 M KOH in a three-electrode system. In addition, the two-electrode system, i.e., V-FeBP || V-FeBP, demonstrates a comparable water-splitting performance to the benchmark electrodes of Pt/C || RuO 2 in 1 M KOH. Similarly, exceptional performance is also observed in natural sea water. The 3D MSC flower-like structure provides a very high surface area that favors rapid mass/electron-transport pathways, which improves the electrocatalytic activity. Further, the V-FeBP electrode is examined in different pH solutions and in terms of its stability under industrial operational conditions at 60 °C in 6 M KOH, and it shows excellent stability.

Extensive research has been performed on the in-field nondestructive evaluation (NDE) of the physicochemical properties of 'Madoka' peaches, such as chromaticity (a*), soluble solids content (SSC), firmness, and titratable acidity (TA) content. To accomplish this, a snapshot-based hyperspectral imaging (HSI) approach for filed application was conducted in the visible and near-infrared (Vis/NIR) region. The hyperspectral images of 'Madoka' samples were captured and combined with commercial HSI analysis software, and then the physicochemical properties of the 'Madoka' samples were predicted. To verify the performance of the field-based HSI application, a lab-based HSI application was also conducted, and their coefficient of determination values (R 2 ) were compared. Finally, pixel-based chemical images were produced to interpret the dynamic changes of the physicochemical properties in 'Madoka' peach. Consequently, the a* values and SSC content shows statistically significant R 2 values (0.84). On the other hand, the firmness and TA content shows relatively lower accuracy (R 2 = 0.6 to 0.7). Then, the resultant chemical images of the a* values and SSC content were created and could represent their different levels using grey scale gradation. This indicates that the HSI system with integrated HSI software used in this work has promising potential as an in-field NDE for analyzing the physicochemical properties in 'Madoka' peaches.

Background : Serum biomarkers associated with severe non-cystic fibrosis (CF) bronchiectasis are currently lacking. We assessed the association of serum fibrinogen, adiponectin, and angiopoietin-2 levels with the severity and exacerbation of bronchiectasis. Methods : Serum levels of fibrinogen, adiponectin, and angiopoietin-2 were measured and compared in patients with stable non-CF bronchiectasis ( n = 61) and healthy controls ( n = 16). The correlations between the three biomarkers and the bronchiectasis severity index (BSI) or FACED scores were assessed. Univariate and multivariate linear regression analyses were performed to identify variables independently associated with BSI and FACED scores in patients with bronchiectasis. Additionally, the exacerbation-free survival was compared between groups of patients with high and low fibrinogen levels, while the predictors of exacerbation were analyzed using Cox proportional hazards regression. Results : Patients with non-CF bronchiectasis carried higher fibrinogen (3.00 ± 2.31 vs. 1.52 ± 0.74 µg/mL; p = 0.016) and adiponectin (12.3 ± 5.07 vs. 9.17 ± 5.30 µg/mL; p = 0.031) levels compared with healthy controls. The serum level of angiopoietin-2 was comparable between the two groups (1.49 ± 0.96 vs. 1.21 ± 0.79 ng/mL, p = 0.277). Correlations of adiponectin and angiopoietin-2 with BSI and FACED scores were not significant. However, there were significant correlations between fibrinogen and both BSI (r = 0.428) and FACED scores (r = 0.484). Multivariate linear regression analysis revealed that fibrinogen level was an independent variable associated with both BSI and FACED scores. A total of 31 (50.8%) out of 61 patients experienced exacerbation during the follow-up period of 25.4 months. Exacerbation-free survival was significantly longer in patients with low fibrinogen levels than in those with high fibrinogen (log-rank test, p = 0.034). High fibrinogen levels and Pseudomonas colonization were independent risk factors for future exacerbation (HR 2.308; p = 0.03 and HR 2.555; p = 0.02, respectively). Conclusions : Serum fibrinogen, but not adiponectin or angiopoietin-2, is a potential biomarker closely associated with the severity and exacerbation of non-CF bronchiectasis.

The presence of amyloid-β (Aβ) deposition is considered important in patients with amnestic mild cognitive impairment (aMCI), since they can progress to Alzheimer's disease dementia. Amyloid positron emission tomography (PET) has been used for detecting Aβ deposition, but its high cost is a significant barrier for clinical usage. Therefore, we aimed to develop a new predictive scale for amyloid PET positivity using easily accessible tools. Overall, 161 aMCI patients were recruited from six memory clinics and underwent neuropsychological tests, brain magnetic resonance imaging (MRI), apolipoprotein E ( APOE ) genotype testing, and amyloid PET. Among the potential predictors, verbal and visual memory tests, medial temporal lobe atrophy, APOE genotype, and age showed significant differences between the Aβ-positive and Aβ-negative groups and were combined to make a model for predicting amyloid PET positivity with the area under the curve (AUC) of 0.856. Based on the best model, we developed the new predictive scale comprising integers, which had an optimal cutoff score ≥ 3. The new predictive scale was validated in another cohort of 98 participants and showed a good performance with AUC of 0.835. This new predictive scale with accessible variables may be useful for predicting Aβ positivity in aMCI patients in clinical practice.

Chronic rhinosinusitis with nasal polyps (CRSwNP) in asthmatic patients has a high recurrence rate even after surgery. For this reason, oral steroids are frequently used, but their long-term use may cause side effects. The purpose of this study is to investigate the long-term effects of budesonide nasal irrigation (BNI) in CRSwNP and asthma. An analysis of 33 patients with CRSwNP and well-controlled asthma, who performed BNI for more than 12 months, was performed. We compared oral steroid and antibiotic dosages as well as nasal endoscopy scores before, and every six months after, BNI. The six-month dosages of oral steroids and antibiotics prescribed were significantly decreased at all time points after BNI compared to before BNI. When the dosages were compared at the time point immediately preceding six months, oral steroid intake decreased significantly until 12 months, and antibiotic intake decreased until 6 months. Furthermore, the endoscopic score decreased significantly until 12 months. The nasal symptom questionnaire score also significantly improved after BNI. Therefore, BNI is considered an effective treatment method that can improve subjective symptoms and objective intranasal findings while reducing oral steroid and antibiotic doses after long-term use in patients with CRSwNP accompanied by asthma.

We investigated the survival time of each clinical syndrome of frontotemporal dementia (FTD) and the impacts of behavioral and motor features on survival of FTD. A total of 216 patients with FTD [82 behavioral variant FTD (bvFTD), 78 semantic variant primary progressive aphasia (svPPA), 43 non-fluent/agrammatic variant PPA (nfvPPA), 13 FTD-motor neuron disease (MND)] were enrolled from 16 centers across Korea. Behaviors and parkinsonism were assessed using the Frontal Behavioral Inventory and Unified Parkinson's Disease Rating Scale Part III, respectively. The Kaplan-Meier method was used for the survival analysis and the Cox proportional hazards model was applied for analysis of the effect of behavioral and motor symptoms on survival, after controlling vascular risk factors and cancer. An overall median survival of FTD was 12.1 years. The survival time from onset was shortest for FTD-MND and longest for svPPA. The median survival time of patients with bvFTD was unavailable but likely comparable to that of patients with nfvPPA. In the bvFTD group, negative behavioral symptoms and akinetic rigidity were significantly associated with survival. In the nfvPPA group, the presence of dysarthria had a negative impact on survival. These findings provide useful information to clinicians planning for care.

Although a few studies comparing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and non-SARS-CoV-2 respiratory viruses have been reported, clinical features and outcomes comparing SARS-CoV-2 and non-SARS-CoV-2 respiratory viruses associated acute respiratory distress syndrome (ARDS) are still lacking. We retrospectively identified patients with SARS-CoV-2 (November 2020 to January 2022) and non-SARS-CoV-2 respiratory viruses associated ARDS (February 2015 to November 2020) at a single tertiary hospital. Their clinical data were obtained by medical record review. All viral infections were confirmed by RT-PCR. Thirty-one SARS-CoV-2 and seventy-one patients with non-SARS-CoV-2 respiratory viruses associated ARDS patients were identified. Influenza (62%) was the most common in non-SARS-CoV-2 respiratory viruses associated ARDS patients. Patients with SARS-CoV-2 were more likely to be female and had higher body mass index, lower clinical frailty, APACHE II, and SOFA score than those with non-SARS-CoV-2 respiratory viruses. All patients with SARS-CoV-2 were treated with corticosteroids and used more high-flow nasal oxygen than those with non-SARS-CoV-2 respiratory viruses. The concomitant respiratory bacterial infection was significantly higher in non-SARS-CoV-2 respiratory viruses than SARS-CoV-2. Although there were no significant differences in the 28-, 60-day, and in-hospital mortality rates between SARS-CoV-2 and non-SARS-CoV-2 respiratory viruses associated ARDS, the duration of mechanical ventilation and length of hospital stay were significantly longer in patients with SARS-CoV-2 than those with non-SARS-CoV-2 respiratory viruses. Although the severity of illness and the concomitant bacterial infection rate were lower in patients with SARS-CoV-2 associated ARDS, mortality rates did not differ from non-SARS-CoV-2 respiratory viruses associated ARDS.

Background: Metabolic syndrome is associated with a significantly increased risk of sudden cardiac death (SCD). However, whether temporal changes in the metabolic syndrome status are associated with SCD is unknown. We aimed to determine whether metabolic syndrome and gamma-glutamyl transferase (ɣ-GTP), including their temporal changes, are associated with the risk of SCD. Methods: We performed a nationwide population-based analysis using the Korean National Health Insurance Service. People who underwent a national health check-up in 2009 and 2011 were enrolled. The influence of metabolic syndrome and ɣ-GTP on SCD risk was evaluated. Results: In 2009, 4,056,423 (848,498 with metabolic syndrome) people underwent health screenings, 2,706,788 of whom underwent follow-up health screenings in 2011. Metabolic syndrome was associated with a 50.7% increased SCD risk (adjusted hazard ratio (aHR) = 1.507; p < 0.001). The SCD risk increased linearly as the metabolic syndrome diagnostic criteria increased. The ɣ-GTP significantly impacted the SCD risk; the highest quartile had a 51.9% increased risk versus the lowest quartile (aHR = 1.519; p < 0.001). A temporal change in the metabolic syndrome status and ɣ-GTP between 2009 and 2011 was significantly correlated with the SCD risk. Having metabolic syndrome in 2009 or 2011 indicated a lower SCD risk than having metabolic syndrome in 2009 and 2011 but a higher risk than having no metabolic syndrome. People with a ≥20-unit increase in ɣ-GTP between 2009 and 2011 had an 81.0% increased SCD risk versus those with a change ≤5 units (aHR = 1.810; p < 0.001). Conclusions: Metabolic syndrome and ɣ-GTP significantly correlated with an increased SCD risk. SCD was also influenced by temporal changes in the metabolic syndrome status and ɣ-GTP, suggesting that appropriate medical treatment and lifestyle modifications may reduce future SCD risk.

Patients with vascular dementia, caused by cerebral ischemia, experience long-term cognitive impairment due to the lack of effective treatment. The mechanisms of and treatments for vascular dementia have been investigated in various animal models; however, the insufficient information on gene expression changes that define pathological conditions hampers progress. To investigate the underlying mechanism of and facilitate treatment development for vascular dementia, we established a mouse model of chronic cerebral hypoperfusion, including bilateral carotid artery stenosis, by using microcoils, and elucidated the molecular pathway underlying vascular dementia development. Rho-associated protein kinase (ROCK) 1/2, which regulates cellular structure, and inflammatory cytokines (IL-1 and IL-6) were upregulated in the vascular dementia model. However, expression of claudin-5, which maintains the blood-brain barrier, and MAP2 as a nerve cell-specific factor, was decreased in the hippocampal region of the vascular dementia model. Thus, we revealed that ROCK pathway activation loosens the tight junction of the blood-brain barrier and increases the influx of inflammatory cytokines into the hippocampal region, leading to neuronal death and causing cognitive and emotional dysfunction. Our vascular dementia model allows effective study of the vascular dementia mechanism. Moreover, the ROCK pathway may be a target for vascular dementia treatment development in the future.

The value of the red cell distribution width (RDW) is associated with prognosis in critically ill patients. A simplex combined index-the RDW/albumin ratio-has been proposed for the prediction of mortality, as has the lactate/albumin ratio. The aim of this study was to evaluate the clinical utility of the RDW/albumin ratio regarding 28-day mortality in critically ill patients with pneumonia. Clinical data of critically ill patients with pneumonia who were hospitalized in the medical intensive care unit from May 2018 to December 2020, and received invasive mechanical ventilation (IMV), were reviewed retrospectively. The values of RDW, lactate, and albumin measured at the time of IMV, were used for the index calculations. Of the 234 patients, the median age was 76 years, and 74.2% were male. The 28-day mortality rate was 47.3%. The median RDW/albumin ratio was significantly higher in non-survivors than survivors at 28 days (5.8 vs. 4.9, p < 0.001). A higher RDW/albumin ratio was significantly associated with increased 28-day mortality (odds ratio [OR] 1.338, 95% confidence interval [CI] 1.094-1.637, p = 0.005). The area under the receiver operating curve (AUROC) was 0.694 (95% CI: 0.630-758, p < 0.005) to discern 28-day mortality without significant difference, compared with that of the lactate/albumin ratio. Our data suggest that high RDW/albumin ratio has a similar predictability to the lactate/albumin ratio in critically ill patients with pneumonia receiving IMV.

Due to recent abnormal weather caused by global warming, peach flowering has gradually accelerated, and spring frost damage caused by premature de-acclimation has increased. In this study, under a simulated spring frost environment using a Soil-Fruit-Daylit-System (SFDS) chamber, we investigated whether treatment with 2% cellulose nanocrystals (CNCs) could enhance the freezing tolerance of the flower buds from 2-year-old whole peach trees. Visual changes in the ice propagation were observed using an infrared camera at the same time. After the peach flower buds in the calyx red stage were placed in the SFDS chamber with a minimum temperature of -4 °C for ~20 h, the percentage of browning in the pistils and stamens was 57.0% in the control group and 14.1% in the group treated with 2% CNCs. During the first pink stage, the percentages of browning in the pistils and stamens in the control group and the group treated with 2% CNCs were 98.2% and 70.3%, respectively. However, when peach flower buds in the group treated with 2% CNCs were exposed to a -6 °C-targeted chamber, they could not mitigate frost injury. Almost all flower buds were damaged. Infrared thermal images showed that the first exotherm in the control group began at 2:33:03 am, whereas that of the group treated with 2% CNCs began at 3:01:33 am. The control started to express exothermic behavior at -4.2 °C, while the group treated with 2% CNCs started expressing exothermic behavior at -5.1 °C. Thus, treatment with 2% CNCs enhanced the freezing tolerance by -0.9 °C and delayed the first instance of exothermic behavior by ~28 min. These results indicate that treatment with 2% CNCs could mitigate the frost damage of peach flower buds in a frost environment of -5 °C.

The development of COVID-19 vaccines is critical in controlling global health issues under the COVID-19 pandemic. The subunit vaccines are the safest and most widely used vaccine platform and highly effective against a multitude of infectious diseases. An adjuvant is essential for subunit vaccines to enhance the magnitude and durability of immune responses. In this study, we determined whether a combination of toll-like receptor (TLR)1/2 and TLR3 agonists (L-pampo) can be a potent adjuvant for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine. We measured a neutralizing antibody (nAb) and an angiotensin-converting enzyme 2 (ACE2) receptor-blocking antibody against SARS-CoV-2 receptor-binding domain (RBD). We also detected interferon-gamma (IFN-γ) production by using ELISPOT and ELISA assays. By employing a ferret model, we detected nAbs and IFN-γ producing cells and measured viral load in nasal wash after the challenge of SARS-CoV-2. We found that SARS-CoV-2 antigens with L-pampo stimulated robust humoral and cellular immune responses. The efficacy of L-pampo was higher than the other adjuvants. Furthermore, in the ferret model, SARS-CoV-2 antigens with L-pampo elicited nAb response and antigen-specific cellular immune response against SARS-CoV-2, resulting in substantially decreased viral load in their nasal wash. Our study suggests that SARS-CoV-2 antigens formulated with TLR agonists, L-pampo, can be a potent subunit vaccine to promote sufficient protective immunity against SARS-CoV-2.

Clonorchis sinensis , a high-risk pathogenic human liver fluke, provokes various hepatobiliary complications, including epithelial hyperplasia, inflammation, periductal fibrosis, and even cholangiocarcinogenesis via direct contact with worms and their excretory-secretory products (ESPs). These pathological changes are strongly associated with persistent increases in free radical accumulation, leading to oxidative stress-mediated lesions. The present study investigated C. sinensis infection- and/or carcinogen N -nitrosodimethylamine (NDMA)-associated fibrosis in cell culture and animal models. The treatment of human cholangiocytes (H69 cells) with ESPs or/and NDMA increased reactive oxidative species (ROS) generation via the activation of NADPH oxidase (NOX), resulting in augmented expression of fibrosis-related proteins. These increased expressions were markedly attenuated by preincubation with a NOX inhibitor (diphenyleneiodonium chloride) or an antioxidant ( N -acetylcysteine), indicating the involvement of excessive NOX-dependent ROS formation in periductal fibrosis. The immunoreactive NOX subunits, p47 phox and p67 phox , were observed in the livers of mice infected with C. sinensis and both infection plus NDMA, concomitant with collagen deposition and immunoreactive fibronectin elevation. Staining intensities are proportional to lesion severity and infection duration or/and NDMA administration. Thus, excessive ROS formation via NOX overactivation is a detrimental factor for fibrogenesis during liver fluke infection and exposure to N-nitroso compounds.

Obesity and insulin resistance accelerate aging-related sarcopenia, which is associated with iron load and oxidative stress. Lipocalin-2 (LCN2) is an iron-binding protein that has been associated with skeletal muscle regeneration, but details regarding its role in obese sarcopenia remain unclear. Here, we report that elevated LCN2 levels in skeletal muscle are linked to muscle atrophy-related inflammation and oxidative stress in leptin-deficient ob/ob mice. RNA sequencing analyses indicated the LCN2 gene expression is enhanced in skeletal muscle of ob/ob mice with sarcopenia. In addition to muscular iron accumulation in ob/ob mice, expressions of iron homeostasis-related divalent metal transporter 1, ferritin, and hepcidin proteins were increased in ob/ob mice compared to lean littermates, whereas expressions of transferrin receptor and ferroportin were reduced. Collectively, these findings demonstrate that LCN2 functions as a potent proinflammatory factor in skeletal muscle in response to obesity-related sarcopenia and is thus a therapeutic candidate target for sarcopenia treatment.

Aster yomena ( A. yomena ) extract has anti-inflammatory, antioxidant, anti-asthma, and anti-atopic effects. However, the commercial use of A. yomena extract requires a long processing time with specific processing steps (including heat treatment and ethanol precipitation), and there are various environmental problems. We aimed to build a system to produce A. yomena extract by culturing the callus in a bioreactor that can allow rapid process scale-up to test the effect of extract (AYC-CS-E) isolated from culture supernatant of A. yomena callus on photoaging of human keratinocytes (HaCaT) caused by ultraviolet B (UVB) exposure. Through screening analysis based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), 17 major metabolites were tentatively identified from AYC-CS-E for the first time. The suppression of cell proliferation caused by UVB was effectively alleviated in UVB-irradiated HaCaT cells treated with AYC-CS-E. Treatment with AYC-CS-E strongly induced the formation of type I procollagen and the inhibition of elastase in UVB-irradiated HaCaT cells and significantly reduced the expression of matrix metalloproteinase (MMP)-1. In addition, treatment of UVB-irradiated HaCaT cells with AYC-CS-E effectively improved various factors associated with an inflammatory reaction, skin damage recovery, skin moisture retention, and hyper-keratinization caused by photoaging, such as reactive oxygen species (ROS), pro-inflammatory cytokines, transforming growth factor beta (TGF-β), MMP-3, MMP-9, filaggrin, hyaluronic acid synthase 2 (HAS-2), keratin 1 (KRT-1), nuclear factor-kappa B (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2) at the gene and protein levels. These results suggest that AYC-CS-E can be used as a cosmetic ingredient for various skin diseases caused by photoaging, and the current callus culture system can be used commercially to supply cosmetic ingredients.

Auto-detection of cerebral aneurysms via convolutional neural network (CNN) is being increasingly reported. However, few studies to date have accurately predicted the risk, but not the diagnosis itself. We developed a multi-view CNN for the prediction of rupture risk involving small unruptured intracranial aneurysms (UIAs) based on three-dimensional (3D) digital subtraction angiography (DSA). The performance of a multi-view CNN-ResNet50 in accurately predicting the rupture risk (high vs. non-high) of UIAs in the anterior circulation measuring less than 7 mm in size was compared with various CNN architectures (AlexNet and VGG16), with similar type but different layers (ResNet101 and ResNet152), and single image-based CNN (single-view ResNet50). The sensitivity, specificity, and overall accuracy of risk prediction were estimated and compared according to CNN architecture. The study included 364 UIAs in training and 93 in test datasets. A multi-view CNN-ResNet50 exhibited a sensitivity of 81.82 (66.76-91.29)%, a specificity of 81.63 (67.50-90.76)%, and an overall accuracy of 81.72 (66.98-90.92)% for risk prediction. AlexNet, VGG16, ResNet101, ResNet152, and single-view CNN-ResNet50 showed similar specificity. However, the sensitivity and overall accuracy were decreased (AlexNet, 63.64% and 76.34%; VGG16, 68.18% and 74.19%; ResNet101, 68.18% and 73.12%; ResNet152, 54.55% and 72.04%; and single-view CNN-ResNet50, 50.00% and 64.52%) compared with multi-view CNN-ResNet50. Regarding F1 score, it was the highest in multi-view CNN-ResNet50 (80.90 (67.29-91.81)%). Our study suggests that multi-view CNN-ResNet50 may be feasible to assess the rupture risk in small-sized UIAs.

Among the various types of breast cancer, the luminal B subtype is the most common in young women, and ESR1-CCDC170 (E:C) fusion is the most frequent oncogenic fusion driver of the luminal B subtype. Nevertheless, treatments targeting E:C fusion has not been well established yet. Hence, the aim of this study is to investigate potential therapies targeting E:C fusion based on systematic bioinformatical analysis of the Cancer Genome Atlas (TCGA) data. One thousand related genes were extracted using transcriptome analysis, and major signaling pathways associated with breast cancer were identified with over-representation analysis. Then, we conducted drug-target network analysis based on the OncoKB and CIViC databases, and finally selected potentially applicable drug candidates. Six major cancer-related signaling pathways (p53, ATR/ATM, FOXM1, hedgehog, cell cycle, and Aurora B) were significantly altered in E:C fusion-positive cases of breast cancer. Further investigation revealed that nine genes ( AURKB , HDAC2 , PLK1 , CENPA , CHEK1 , CHEK2 , RB1 , CCNA2 , and MDM2 ) in coordination with E:C fusion were found to be common denominators in three or more of these pathways, thereby making them promising gene biomarkers for target therapy. Among the 21 putative actionable drugs inferred by drug-target network analysis, palbociclib, alpelisib, ribociclib, dexamethasone, checkpoint kinase inhibitor AXD 7762, irinotecan, milademetan tosylate, R05045337, cisplatin, prexasertib, and olaparib were considered promising drug candidates targeting genes involved in at least two E:C fusion-related pathways.

Clade 2.3.4.4c H5N6 avian influenza A viruses (AIVs) may have originally adapted to infect chickens and have caused highly pathogenic avian influenza (HPAI) in poultry and human fatalities. Although A/Puerto Rico/8/1934 (H1N1) (PR8)-derived recombinant clade 2.3.4.4c H5N6 vaccine strains have been effective in embryonated chicken eggs-based vaccine production system, they need to be improved in terms of immunogenicity and potential mammalian pathogenicity. We replaced the PB2 gene alone or the PB2 (polymerase basic protein 2), NP (nucleoprotein), M (matrix protein) and NS (non-structural protein) genes together in the PR8 strain with corresponding genes from AIVs with low pathogenicity to remove mammalian pathogenicity and to match CD8+ T cell epitopes with contemporary HPAI viruses, respectively, without loss of viral fitness. Additionally, we tested the effect of the H103Y mutation of hemagglutinin (HA) on antigen productivity, mammalian pathogenicity and heat/acid stability. The replacement of PB2 genes and the H103Y mutation reduced the mammalian pathogenicity but increased the antigen productivity of the recombinant vaccine strains. The H103Y mutation increased heat stability but unexpectedly decreased acid stability, probably resulting in increased activation pH for HA. Interestingly, vaccination with inactivated recombinant virus with replaced NP, M and NS genes halted challenge virus shedding earlier than the recombinant vaccine without internal genes replacement. In conclusion, we successfully generated recombinant clade 2.3.4.4c H5N6 vaccine strains that were less pathogenic to mammals and more productive and heat stable than conventional PR8-derived recombinant strains by optimization of internal genes and the H103Y mutation of HA.

A super-porous hybrid platform can offer significantly increased number of reaction sites for the analytes and thus can offer advantages in the biosensor applications. In this work, a significantly improved sensitivity and selectivity of hydrogen peroxide (H 2 O 2 ) detection is demonstrated by a super-porous hybrid CuO/Pt nanoparticle (NP) platform on Si substrate as the first demonstration. The super-porous hybrid platform is fabricated by a physiochemical approach combining the physical vapor deposition of Pt NPs and electrochemical deposition of super-porous CuO structures by adopting a dynamic hydrogen bubble technique. Under an optimized condition, the hybrid CuO/Pt biosensor demonstrates a very high sensitivity of 2205 µA/mM·cm 2 and a low limit of detection (LOD) of 140 nM with a wide detection range of H 2 O 2 . This is meaningfully improved performance as compared to the previously reported CuO-based H 2 O 2 sensors as well as to the other metal oxide-based H 2 O 2 sensors. The hybrid CuO/Pt platform exhibits an excellent selectivity against other interfering molecules such as glucose, fructose, dopamine, sodium chloride and ascorbic acid. Due to the synergetic effect of highly porous CuO structures and underlying Pt NPs, the CuO/Pt architecture offers extremely abundant active sites for the H 2 O 2 reduction and electron transfer pathways.

The threat posed by coronaviruses to human health has necessitated the development of a highly specific and sensitive viral detection method that could differentiate between the currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-related coronaviruses (SARSr-CoVs). In this study, we developed a peptide nucleic acid (PNA)-based real-time quantitative polymerase chain reaction (RT-qPCR) assay targeting the N gene to efficiently discriminate SARS-CoV-2 from other SARSr-CoVs in human clinical samples. Without compromising the sensitivity, this method significantly enhanced the specificity of SARS-CoV-2 detection by 100-fold as compared to conventional RT-qPCR. In addition, we designed an RT-qPCR method for the sensitive and universal detection of ORF3ab-E genes of SARSr-CoV with a limit of detection (LOD) of 3.3 RNA copies per microliter. Thus, the developed assay serves as a confirmative dual-target detection method. Our PNA-mediated dual-target RT-qPCR assay can detect clinical SARS-CoV-2 samples in the range of 18.10-35.19 Ct values with an 82.6-100% detection rate. Furthermore, our assay showed no cross-reactions with other coronaviruses such as human coronaviruses (229E, NL63, and OC43) and Middle East respiratory syndrome coronavirus, influenza viruses (Type B, H1N1, H3N2, HPAI H5Nx, and H7N9), and other respiratory disease-causing viruses (MPV, RSV A, RSV B, PIV, AdV, and HRV). We, thus, developed a PNA-based RT-qPCR assay that differentiates emerging pathogens such as SARS-CoV-2 from closely related viruses such as SARSr-CoV and allows diagnosis of infections related to already identified or new coronavirus strains.

There is a need for measures that can prevent the onset of dementia in the rapidly aging population. Reportedly, sustained physical exercise can prevent cognitive decline and disability. This study aimed to assess the feasibility of a 12-week physical exercise intervention (PEI) for delay of cognitive decline and disability in the at-risk elderly population in Korea. Twenty-six participants (aged 67.9 ± 3.6 years, 84.6% female) at risk of dementia were assigned to facility-based PEI ( n = 15) or home-based PEI ( n = 11). The PEI program consisted of muscle strength training, aerobic exercise, balance, and stretching using portable aids. Feasibility was assessed by retention and adherence rates. Physical fitness/cognitive function were compared before and after the PEI. Retention and adherence rates were 86.7% and 88.3%, respectively, for facility-based PEI and 81.8% and 62.3% for home-based PEI. No intervention-related adverse events were reported. Leg strength/endurance and cardiopulmonary endurance were improved in both groups: 30 s sit-to-stand test (facility-based, p = 0.002; home-based, p = 0.002) and 2 -min stationary march (facility-based, p = 0.001; home-based, p = 0.022). Cognitive function was improved only after facility-based PEI (Alzheimer's Disease Assessment Scale-cognitive total score, p = 0.009; story memory test on Literacy Independent Cognitive Assessment, p = 0.026). We found that, whereas our PEI is feasible, the home-based program needs supplementation to improve adherence.

Marian Cove is experiencing some of the most rapid environmental changes in the Antarctic region; however, little is known about the response of bacterial communities to these changes. The main purpose of this study was to investigate the spatial variation of physical‒biogeochemical‒bacterial community features in the Marian Cove surface waters and the environmental parameters governing the spatial variation in the bacterial community composition during the summer of 2018. The Marian Cove surface waters are largely composed of two different characteristics of water masses: relatively low-temperature, -salinity, and -nutrient surface glacier water (named SGW) and relatively high-temperature, -salinity, and -nutrient surface Maxwell Bay water (named SMBW). The SGW bacterial communities were dominated by unclassified Cryomorphaceae, Sedimenticola, and Salibacter genera, while the SMBW bacterial communities were dominated by Sulfitobacter, Arcobacter, and Odoribacter genera. Spatial variations in bacterial community composition were mainly attributed to physical and biogeochemical characteristics, suggesting that the bacterial community composition of the Marian Cove surface waters is mainly determined by environmental characteristics. These findings provide a foundation to improve the understanding of bacterial community variations in response to a rapidly changing Marian Cove in the Antarctic.

Background: The present study aims to evaluate the diagnostic roles of various immunohistochemical (IHC) markers in thymic tumors, including thymic carcinoma (TC) and thymoma (TM). Methods: Eligible studies were obtained by searching the PubMed databases and screening the searched articles. Thirty-eight articles were used in the present meta-analysis and included 636 TCs and 1861 TMs. Besides, for IHC markers with statistical significance, a diagnostic test accuracy review was performed. Results: The comparison of various IHC expressions between TC and TM was performed for 32 IHC markers. Among these IHC markers, there were significant differences between TC and TM for beta-5t, B-cell lymphoma 2 (Bcl-2), calretinin, CD1a, CD5, carcinoembryonic antigen (CEA), cytokeratin19 (CK19), CD117, glucose transporter 1 (Glut-1), insulin-like growth factor 1 receptor (IGF-1R), mesothelin, MOC31, mucin1 (MUC1), p21, and terminal deoxynucleotidyl transferase (TdT). Markers with higher expressions in TCs were Bcl-2, calretinin, CD5, CEA, CD117, Glut-1, IGF-1R, mesothelin, MOC31, MUC1, and p21. Among these markers, there were no significant differences between TC and TM type B3 in immunohistochemistries for Bcl-2 and CK19. On the other hand, β -catenin and CD205 showed a considerable difference in IHC expressions between TC and TM type B3, but not between TC and overall TM. In diagnostic test accuracy review, MUC1 and beta-5t were the most useful markers for TC and TM, respectively. Conclusions : Taken together, our results showed that the expression rates for various IHC markers significantly differed between TC and TM. The IHC panel can be useful for differentiation from limited biopsied specimens in daily practice.

Lindera obtusiloba is widespread in northeast Asia and used for treatment of improvement of blood circulation and anti-inflammation. In this study, we investigated anti-inflammatory and anti-oxidant effects of the methanolic extract of L. obtusiloba leaves (LOL) in an ovalbumin (OVA)-challenged allergic asthma model and tumor necrosis factor (TNF)-α-stimulated NCI-H292 cell. Female BALB/c mice were sensitized with OVA by intraperitoneal injection on days 0 and 14, and airway-challenged with OVA from days 21 to 23. Mice were administered 50 and 100 mg/kg of LOL by oral gavage 1 h before the challenge. LOL treatment effectively decreased airway hyper-responsiveness and inhibited inflammatory cell recruitment, Th2 cytokines, mucin 5AC (MUC5AC) in bronchoalveolar lavage fluid in OVA-challenged mice, which were accompanied by marked suppression of airway inflammation and mucus production in the lung tissue. LOL pretreatment inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) with suppression of activator protein (AP)-1 and MUC5AC in the lung tissue. LOL also down-regulated expression of inflammatory cytokines, and inhibited the activation of NF-κB in TNF-α-stimulated NCI-H292 cells. LOL elevated the translocation of nuclear factor-erythroid 2-related factor (Nrf-2) into nucleus concurrent with increase of heme oxyngenase-1 (HO-1) and NAD(P)H quinine oxidoreductase 1 (NQO1). Moreover, LOL treatment exhibited a marked increase in the anti-oxidant enzymes activities, whereas effectively suppressed the production of reactive oxygen species and nitric oxide, as well as lipid peroxidation in lung tissue of OVA-challenged mice and TNF-α-stimulated NCI-H292 cells. These findings suggest that LOL might serve as a therapeutic agent for the treatment of allergic asthma., Competing Interests: The authors declare no conflict of interest.

Hepatic peptide hormone hepcidin, a key regulator of iron metabolism, is induced by inflammatory cytokine interleukin-6 (IL-6) in the pathogenesis of anemia of inflammation or microbial infections. Small heterodimer partner-interacting leucine zipper protein (SMILE)/CREBZF is a transcriptional corepressor of nuclear receptors that control hepatic glucose and lipid metabolism. Here, we examined the role of SMILE in regulating iron metabolism by inflammatory signals. Overexpression of SMILE significantly decreased activation of the Janus kinase 2-signal transducer and activator of transcription 3 (STAT3)-mediated hepcidin production and secretion that is triggered by the IL-6 signal in human and mouse hepatocytes. Moreover, SMILE co-localized and physically interacted with STAT3 in the nucleus in the presence of IL-6, which significantly suppressed binding of STAT3 to the hepcidin gene promoter. Interestingly, epigallocatechin-3-gallate (EGCG), a major component of green tea, induced SMILE expression through forkhead box protein O1 (FoxO1), as demonstrated in FoxO1 knockout primary hepatocytes. In addition, EGCG inhibited IL-6-induced hepcidin expression, which was reversed by SMILE knockdown. Finally, EGCG significantly suppressed lipopolysaccharide-induced hepcidin secretion and hypoferremia through induction of SMILE expression in mice. These results reveal a previously unrecognized role of EGCG-inducible SMILE in the IL-6-dependent transcriptional regulation of iron metabolism.

Background: The association between optimal carbohydrate antigen (CA) 19-9 concentration after neoadjuvant chemotherapy (NACT) and prognosis has not been confirmed in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC)., Methods: This retrospective study included 122 patients with BRPC and 103 with LAPC who underwent surgery after NACT between 2012 and 2019 in a tertiary referral center. Prognostic models were established based on relative difference of the CA 19-9 (RDC), with their prognostic performance compared using C-index and Akaike information criterion (AIC)., Results: CA 19-9 concentrations of 37-1000 U/mL before NACT showed prognostic significance in patients with BRPC and LAPC (hazard ratio [HR]: 0.262; 95% confidence interval [CI]: 0.092-0.748; p = 0.012). Prognostic models in this subgroup showed that RDC was independently prognostic of better overall survival (HR: 0.262; 95% CI: 0.093-0.739; p = 0.011) and recurrence free survival (HR: 0.299; 95% CI: 0.140-0.642; p = 0.002). The prognostic performances of RDC (C-index: 0.653; AIC: 227.243), normalization of CA 19-9 after NACT (C-index: 0.625; AIC: 230.897) and surgery (C-index: 0.613; AIC: 233.114) showed no significant differences., Conclusion: RDC was independently associated with better prognosis after NACT in patients with BRPC or LAPC. Decreased CA19-9 after NACT was a prognostic indicator of better survival and recurrence, as was normalization of CA 19-9 after both NACT and surgery.

Neutropenic sepsis is a fatal consequence of chemotherapy, and septic complications are the principal cause of mortality. Chemotherapy-induced neutropenia leads to the formation of microscopic ulcers in the gastrointestinal epithelium that function as a portal of entry for intraluminal bacteria, which translocate across the intestinal mucosal barrier and gain access to systemic sites, causing septicemia. A cyclophosphamide-induced mouse model was developed to mimic the pathophysiologic sequence of events that occurs in patients with neutropenic sepsis. The TLR5 agonist bacterial flagellin derived from Vibrio vulnificus extended the survival of cyclophosphamide-treated mice by reducing the bacterial load in internal organs. The protective effect of flagellin was mediated by the antimicrobial protein lipocalin 2 (Lcn2), which is induced by TLR5-NF-κB activation in hepatocytes. Lcn2 sequestered iron from infecting bacteria, particularly siderophore enterobactin-dependent members of the Enterobacteriaceae family, thereby limiting their proliferation. Lcn2 should be considered for the treatment of neutropenic sepsis and gastrointestinal damage during chemotherapy to prevent or minimize the adverse effects of cancer chemotherapy.

Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT : OR (odds ratio) = 27.02, p = 8.80 × 10 -94 ; GT : OR = 15.87, p = 2.62 × 10 -9 ) and EuroAs ( TT : OR = 18.13, p = 2.69 × 10 -108 ; GT : OR = 12.63, p = 3.44 × 10 -64 ), and rs405509- T homozygotes had a younger onset and more severe cortical atrophy than those with G -allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.