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Abstract Two-dimensional (2D) materials and their heterostructures enable unconventional electronic properties and functionalities not accessible in their bulk counterparts. This approach is now being extended to magnetic materials to engineer their spin structures and magnetic fields produced by them. However, spin dynamics of 2D magnetic heterostructures remain largely unexplored. Here, we demonstrate that heterointerfacing Heisenberg square-lattice antiferromagnet (AF) Sr2IrO4 with its bilayer variant Ising AF Sr3Ir2O7 in a superlattice leads to liquid-like spin dynamics in the former, characterized by slow recovery of the AF order after its transient suppression by an optical pump, and complete absence of spin waves except in an immediate vicinity of the ordering wavevector. Instead, the spin excitation spectra are dominated by isotropic continua, which in previous works have been interpreted as fractional spin excitations, or spinons, that extends to unprecedentedly low energies. Thus, our results provide a pathway to frustrated magnetism in square lattices by heterointerfacing two distinct types of AFs.

Abstract Background Hepatocellular carcinoma (HCC) stands as the sixth most prevalent cancer globally, presenting a substantial health challenge, particularly due to late-stage diagnoses that limit treatment effectiveness. Sorafenib, a multi-kinase inhibitor, is the primary chemotherapeutic agent for advanced HCC, but it only extends survival by 2–3 months. However, drug resistance remains a major clinical challenge, necessitating the exploration of new molecular mechanisms, including the role of microRNAs (miRNAs) in sorafenib resistance. In this study, we aimed to identify miRNAs within exosomes derived from sorafenib-resistant HCC cells to elucidate the molecular mechanisms underlying resistance. Methods Sorafenib-resistant cells were generated by culturing the human HCC cell line Huh7 in a medium containing 20 µM sorafenib for six months. Exosomes were isolated from the conditioned medium 24 h before cell harvest using exosome-depleted serum medium. miRNA sequencing and western blotting were used to analyze the expression profiles of exosomal miRNAs and proteins, respectively. pH measurement was performed to assess pH changes in response to sorafenib treatment and miRNA modulation. Results A total of 180 exosomal miRNAs were found to be dysregulated between sorafenib-treated control Huh7 (Huh7S) and sorafenib-resistant Huh7 (Huh7RS) cells, as well as between untreated control Huh7 and Huh7RS cells. Among these, miR-6126 was significantly downregulated in Huh7RS cells compared to Huh7S cells. Functional studies using 2-dimensional (D) and 3D cell culture systems revealed that miR-6126 overexpression reduced sorafenib resistance in Huh7RS cells, while its inhibition increased resistance in Huh7 cells. miR-6126 downregulated key proteins involved in cancer stem cell maintenance, such as CD44 and HK2. Furthermore, the pH level was elevated in cells overexpressing miR-6126 following sorafenib treatment, whereas inhibiting miR-6126 resulted in a lower pH. Conclusions Exosomal miR-6126 plays a pivotal role in sorafenib resistance and tumorigenesis, highlighting its potential as a novel therapeutic target for overcoming drug resistance in HCC.

Abstract Sensations of the internal state of the body play crucial roles in regulating the physiological processes and maintaining homeostasis of an organism. However, our understanding of how internal signals are sensed, processed, and integrated to generate appropriate biological responses remains limited. Here, we show that the C. elegans PIEZO channel, encoded by pezo-1, regulates food movement in the intestine by detecting food accumulation in the anterior part of the intestinal lumen, thereby triggering rhythmical movement of the pharynx, referred to as the pharyngeal plunge. pezo-1 deletion mutants exhibit defects in the pharyngeal plunge, which is rescued by PEZO-1 or mouse PIEZO1 expression, but not by PIEZO2, in a single isolated non-neuronal tissue of the digestive tract, the pharyngeal-intestinal valve. Genetic ablation or optogenetic activation of this valve inhibits or induces the pharyngeal plunge, respectively. Moreover, pressure built in the anterior lumen of the intestine results in a pezo-1-dependent pharyngeal plunge, which is driven by head muscle contraction. These findings illustrate how interoceptive processes in a digestive organ regulate swallowing through the PIEZO channel, providing insights into how interoception coordinates ingestive processes in higher animals, including humans.

Abstract Background Previous research has shown that the use of renin-angiotensin system (RAS) blockers is linked to a lower prevalence of posttraumatic stress disorder (PTSD), but longitudinal studies are scarce. We aimed to estimate the association between the use of RAS blockers and the risk of PTSD among individuals taking antihypertensive medications. Methods This longitudinal study included participants aged 40–69 from the UK Biobank. Exposure data were obtained from the initial assessment (2006–10), while outcome data were obtained from the online mental health questionnaire administered 6–11 years later (2016–17). We included participants who were under antihypertensive treatment and did not have a prior diagnosis of PTSD before the initial assessment. Use of RAS blockers was defined as self-reported regular use, at the initial assessment, of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). Among participants who experienced adverse life experiences, cases of probable PTSD were defined with the six-item PTSD Checklist-Civilian version score ≥ 14. Logistic regression with inverse probability of treatment weighting was used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the association between RAS blocker use and the risk of probable PTSD. Results Of the 15,954 participants (mean age = 59.9 years; 42.6% women) under antihypertensive treatment with no prior history of PTSD at the initial assessment, 64.5% were taking RAS blockers. After a mean follow-up of 7.5 years, 1,249 (7.8%) were newly identified with probable PTSD. RAS blocker users had a lower risk of probable PTSD than RAS blocker non-users (OR = 0.84 [95% CI: 0.75–0.94]), whereas the use of other antihypertensive medications showed no such association (users vs. non-users; calcium channel blockers, OR = 0.99 [95% CI: 0.88–1.11]; beta-blockers, 1.20 [1.08–1.34]; and thiazide-related diuretics, 1.15 [1.03–1.29]). The association between probable PTSD risk and the use of ACEi vs. ARB showed no significant difference (p = 0.96). Conclusions Among individuals under antihypertensive treatment, the use of RAS blockers was associated with a decreased risk of probable PTSD. This added benefit of RAS blockers should be considered in the selection of antihypertensive medications.

Abstract Background Androgenetic alopecia (AGA) is a common form of hair loss. Androgens, such as testosterone and dihydrotestosterone, are the main causes of AGA. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) can reduce AGA. However, preparing therapeutic doses of MSCs for clinical use is challenging. Induced pluripotent stem cell-derived MSCs (iMSCs) are homogenous and easily expandable, enabling scalable production of EVs. Hyaluronic acid (HA) can exert various functions including free radical scavenging, immune regulation, and cell migration. Herein, we examined whether hyaluronic acid (HA) stimulation of iMSCs could produce EVs with enhanced therapeutic outcomes for AGA. Methods EVs were collected from iMSCs primed with HA (HA–iMSC–EVs) or without HA (iMSC–EVs). The characteristics of EVs were examined using dynamic light scattering, cryo-transmission electron microscopy, immunoblotting, flow cytometry, and proteomic analysis. In vitro, we compared the potential of EVs in stimulating the survival of hair follicle dermal papilla cells undergoing testosterone-mediated AGA. Additionally, the expression of androgen receptor (AR) and relevant growth factors as well as key proteins of Wnt/β-catenin signaling pathway (β-catenin and phosphorylated GSK3β) was analyzed. Subsequently, AGA was induced in male C57/BL6 mice by testosterone administration, followed by repeated injections of iMSC–EVs, HA–iMSC–EVs, finasteride, or vehicle. Several parameters including hair growth, anagen phase ratio, reactivation of Wnt/β-catenin pathway, and AR expression was examined using qPCR, immunoblotting, and immunofluorescence analysis. Results Both types of EVs showed typical characteristics for EVs, such as size distribution, markers, and surface protein expression. In hair follicle dermal papilla cells, the mRNA levels of AR, TGF-β, and IL-6 increased by testosterone was blocked by HA–iMSC–EVs, which also contributed to the augmented expression of trophic genes related to hair regrowth. However, no notable changes were observed in the iMSC–EVs. Re-activation of Wnt/β-catenin was observed in HA–iMSC–EVs but not in iMSC–EVs, as shown by β-catenin stabilization and an increase in phosphorylated GSK3β. Restoration of hair growth was more significant in HA–iMSC–EVs than in iMSC–EVs, and was comparable to that in mice treated with finasteride. Consistently, the decreased anagen ratio induced by testosterone was reversed by HA–iMSC–EVs, but not by iMSC–EVs. An increased expression of hair follicular β-catenin protein, as well as the reduction of AR was observed in the skin tissue of AGA mice receiving HA–iMSC–EVs, but not in those treated with iMSC–EVs. Conclusions Our results suggest that HA–iMSC–EVs have potential to improve AGA by regulating growth factors/cytokines and stimulating AR-related Wnt/β-catenin signaling.

El proceso de enseñanza y aprendizaje en la Educación Médica evoluciona con los avances tecnológicos. La Inteligencia Artificial (IA) se ha convertido en una herramienta cada vez más utilizada en el aprendizaje de estudiantes. Sin embargo, su implementación es cuestionada por docentes y alumnos de carreras relacionadas al ámbito sanitario. En este scoping review, se examinaron las percepciones, oportunidades y desafíos de estudiantes de pregrado de carreras de salud en relación a la implementación de la IA. Siguiendo las guías PRISMA, se realizaron búsquedas en MEDLINE/PubMed, Scopus y ISI/Web of Science por artículos pertinentes; se eliminaron artículos duplicados y se seleccionaron de acuerdo a nuestros criterios de elegibilidad. De los 121 estudios seleccionados, 14 se incluyeron en el estudio; se realizó un análisis temático basado en categorías de los estudios seleccionados. La mayoría de los hallazgos evidencian una buena percepción, interés y disposición de los estudiantes sobre la implementación de la IA en el currículum médico. No obstante, se destaca como desafío el desconocimiento de la utilidad de la IA, sumado a una resistencia al cambio por miedo a la sustitución de labores profesionales. Asimismo, se plantea como desafío ético la deshumanización de la medicina. La principal limitación es la temática de investigación aún en desarrollo, con una literatura disponible aún en etapas iniciales de investigación.

When used in organic solar cells, poly (3,4-ethylenedioxythiophene)-poly (styrenesulfonate) (PEDOT:PSS) aligns interfacial energy levels, promotes hole extraction, blocks electrons, and optimizes the active layer’s morphology. However, with an optimal thickness of approximately 30–40 ​nm, PEDOT:PSS has insufficient layer thickness tolerance, owing to its low conductivity and hole extraction property. Herein, a hole-selective-molecule doping strategy is proposed to enhance the properties of PEDOT:PSS by introducing MPA2FPh-BT-BA (abbreviated as 2F) into its layer. 2F assembles at the anode to form interfacial dipoles due to its unique donor–acceptor–anchor molecular configuration, altering the anode work function and hole-selective extraction. Additionally, 2F improves the aggregation properties of PEDOT:PSS by forming hydrogen bonds with the PSS group, enhancing the conductivity characteristics. These changes in the PEDOT:PSS layer further influence the overlaying morphology, leading to increased crystalline features of PM6 and the bulk heterojunction of PM6:Y6. When a 2F-PEDOT:PSS (2FPP) layer is used, power conversion efficiencies of 18.3%, 19.2%, and 19.1% are achieved in PM6:Y6, PM6:BTP-eC9, and PM6:L8-BO devices, respectively, outperforming counterparts with PEDOT:PSS. Specifically, the performance of PM6:Y6 devices with a 2FPP layer of 170 ​nm remains at > 15%, providing valuable guidance for designing a thickness-insensitive hole transport layer for high-efficiency organic solar cells.

Tracheobronchopathia osteoplastica is a rare condition involving large airways with multiple bone and cartilage nodules in the tracheobronchial submucosa. This can cause tracheal stenosis, leading to difficulty in endotracheal intubation. A 79-year-old female patient, who had a history of successful endotracheal intubation for general anesthesia 8 years prior, was scheduled for abdominal surgery. Preoperative chest computed tomography and bronchoscopy revealed slight progression of tracheobronchopathia osteoplastica. Attempts to intubate with a smaller endotracheal tube failed; even the smaller endotracheal tube could barely pass. Mechanical ventilation was successfully administered and the surgery was completed without complications. The use of a smaller endotracheal tube may be beneficial for managing difficult airways in patients with tracheobronchopathia osteoplastica. Chest CT and bronchoscopic examination may be beneficial for evaluating the airway and determining the most appropriate airway management strategy. However, relying solely on these measures may lead to unexpected challenges because there is no established method to evaluate airway in patient with tracheobronchopathia osteoplastica. It is crucial for anesthesiologists to be aware of the potential existence of rare conditions such as tracheobronchopathia osteoplastica and be prepared to handle anticipated or unanticipated difficult airway management.

ABSTRACT The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants presents challenges in global efforts to transition from the pandemic to an endemic stage. The spike protein of the SARS-CoV-2 virus, which is pivotal for cell entry, exhibits significant mutations in its variants, potentially affecting infectivity and therapeutic efficacy. Recent findings indicate upregulation of the epidermal growth factor receptor (EGFR) pathway, a key target in cancer therapy, by the spike protein of SARS-CoV-2. This study aimed to investigate the activity of the EGFR pathway against SARS-CoV-2 variants and to assess the inhibitory effects of EGFR inhibitors using SARS-CoV variant pseudoviral particles to guide future therapeutic strategies. Omicron variant SARS-CoV pseudoviral particles exhibited heightened infectivity in human angiotensin-converting enzyme 2 (hACE2)-expressing HEK293 and A549 lung cancer cells accompanied by increased EGFR pathway activation in infected cells. Using the EGFR tyrosine kinase inhibitor, osimertinib, we observed a reduction in viral infection rates in hACE2-HEK293 and A549 cells infected with the SARS-CoV-2 variant pseudoviral particles. We conducted further experiments to confirm that the reduction in infection efficacy with osimertinib treatment was not associated to a decrease in cell viability. Furthermore, this inhibitory effect of osimertinib in cell lines was corroborated in a spheroid cell culture model derived from hACE2-A549 cells. These findings suggest the potential application of EGFR-targeted antiviral therapy against highly infectious SARS-CoV-2 variants.IMPORTANCEThe emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is concerning as vaccines designed for one variant need not essentially protect against other novel variants. Therefore, there is an urgent need to identify therapies that can act against multiple novel variants that have heightened virulence compared with the wild type. It has been reported that the spike protein of the SARS-CoV-2 virus elicits an increased expression of the epidermal growth factor receptor (EGFR) pathway. We used this information and examined whether treatment with an EGFR inhibitor, osimertinib, which is already approved for clinical use in cancer therapy, can reduce the infection caused by SARS-CoV-2, wild type, and Omicron and Delta variants, in two cell lines and one spheroid model. The results showed that osimertinib treatment successfully reduced infection efficacy, particularly in variants, and that this effect was not related to a reduction in cell viability, making this a promising strategy for treating SARS-CoV-2 infections.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive solid tumor. Recently, the uptake of extracellular citrate by the sodium-dependent citrate transporter (NaCT), encoded by SLC13A5, has been demonstrated to exert profound effects on cancer cell metabolism. However, research on the function of extracellular citrate in PDAC pathogenesis and the relationship between NaCT expression and the tumor metabolic microenvironment is limited. Therefore, we aimed to evaluate the expression of citrate transporters across a spectrum of glucose concentrations in pancreatic cancer and systematically explore the effects of sodium citrate treatment on pancreatic cancer cells at different glucose concentrations. We observed a positive correlation between glucose concentration and NaCT expression in PDAC cell lines. Extracellular sodium citrate significantly reduced cell viability partially due to reduction in intracellular Ca2+ levels and decreased the migration of human PDAC cells. Furthermore, we observed a decrease in the levels of the stem cell marker prominin I (CD133) following sodium citrate treatment. Notably, the combination treatment of gemcitabine and extracellular sodium citrate exhibited a synergistic anticancer effect in both two-dimensional (2D) and three-dimensional (3D) culture systems. Additionally, we confirmed that pH slightly increased upon administration of sodium citrate, indicating that this could potentially augment the efficacy of gemcitabine. Altogether, these findings suggest that exogenous sodium citrate treatment, particularly in combination with gemcitabine, may represent a novel therapeutic strategy for treating PDAC. This approach holds promise for disrupting PDAC cell metabolism and inhibiting tumor progression.

Abstract Thermoelectric (TE) charge transport in organic TE nanocomposite systems is a critical consideration in designing high‐performance TE materials. Here, the relationship between the TE properties and energy structure of conducting polymer/quantum dot (QD) nanocomposites is systematically investigated by developing a potential wall or potential well in poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) with CdTe QDs. The added QDs are primarily distributed within the electrically insulating PSS shell and act as stepping stones for charge transport between PEDOT‐rich grains. The embedded QDs generate an energy‐filtering effect, which is induced by both potential wall and potential well states established by the QDs in the PEDOT:PSS films. The induced energy‐filtering effect increases the Seebeck coefficient S with limited loss of electrical conductivity σ, thereby overcoming the TE trade‐off relation S ∝ σ −1/4. The energy‐filtering effect is optimized by carefully controlling the QD size. The PEDOT:PSS/QD nanocomposite containing the smallest QDs exhibits a power factor of 173.8 µW m−1 K−2, which is 80% larger than the value for the pristine PEDOT:PSS film. This work suggests a strategy for designing TE nanocomposites with improved TE performance and emphasizes the importance of fine‐tuning the interfacial energy gap to achieve an effective energy‐filtering effect.

Abstract Background Myocardial infarction (MI), a representative form of ischemic heart disease, remains a huge burden worldwide. This study aimed to explore whether extracellular vesicles (EVs) secreted from hyaluronic acid (HA)-primed induced mesenchymal stem cells (HA-iMSC-EVs) could enhance the cardiac repair after MI. Results HA-iMSC-EVs showed typical characteristics for EVs such as morphology, size, and marker proteins expression. Compared with iMSC-EVs, HA-iMSC-EVs showed enhanced tube formation and survival against oxidative stress in endothelial cells, while reduced reactive oxygen species (ROS) generation in cardiomyocytes. In THP-1 macrophages, both types of EVs markedly reduced the expression of pro-inflammatory signaling players, whereas HA-iMSC-EVs were more potent in augmenting anti-inflammatory markers. A significant decrease of inflammasome proteins was observed in HA-iMSC-EV-treated THP-1. Further, phospho-SMAD2 as well as fibrosis markers in TGF-β1-stimulated cardiomyocytes were reduced in HA-iMSC-EVs treatment. Proteomic data showed that HA-iMSC-EVs were enriched with multiple pathways including immunity, extracellular matrix organization, angiogenesis, and cell cycle. The localization of HA-iMSC-EVs in myocardium was confirmed after delivery by either intravenous or intramyocardial route, with the latter increased intensity. Echocardiography revealed that intramyocardial HA-iMSC-EVs injections improved cardiac function and reduced adverse cardiac remodeling and necrotic size in MI heart. Histologically, MI hearts receiving HA-iMSC-EVs had increased capillary density and viable myocardium, while showed reduced fibrosis. Conclusions Our results suggest that HA-iMSC-EVs improve cardiac function by augmenting vessel growth, while reducing ROS generation, inflammation, and fibrosis in MI heart. Graphical Abstract

The primary drawback of concrete lies in its low tensile strength, prompting the development of various solutions to enhance this aspect. A notable approach is the utilization of Prestressed Reinforced Concrete (PRC) with tendons, aimed at bolstering its tensile strength. As the use of diverse tendon types in the PRC continues to surge, a review becomes imperative to delve into this evolution. Therefore, this study delved into the engineering characteristics, performance, and evolution of different tendon varieties, encompassing both steel and composite options. Despite certain drawbacks associated with employing composite materials such as Fiber Reinforced Polymer (FRP) tendons - such as heightened costs, limited availability of composite materials, and intricate manufacturing processes - there are distinct advantages and merits to incorporating FRP composite tendons in the realm of construction. In this respect, Carbon FRP tendons exhibited superior strength, comparable to their steel counterparts. Glass FRP tendons, lacking metallic components, possessed non-magnetic properties, rendering them resistant to corrosion. Additionally, Aramid FRP tendons boasted low flammability and exceptional resistance to elevated temperatures. Lastly, Basalt FRP tendons offered sustainability, rust resistance, and non-corrosiveness. The findings derived from this review study serve as a valuable resource for researchers seeking to advance the applications of steel tendons and FRP composite materials within the construction industry.

Abstract Background Acute kidney injury (AKI) has a complex pathophysiology and imposes serious health concerns worldwide. Extracellular vesicles (EVs) derived from induced mesenchymal stem cells (iMSCs) have been recognized as novel cell-free therapeutics for various inflammatory and degenerative disorders. In this study, we investigated whether iMSCs stimulated with a pan-peroxisome proliferator-activated receptor (PPAR) agonist could enhance the therapeutic efficacy of EVs against AKI. Methods Human iMSCs were primed with or without lanifibranor, a PPAR agonist for 24 h, and EVs were collected after an additional 24 h. The basic characteristics of EVs were evaluated using cryo-transmission electron microscopy imaging, immunoblot detection of EV markers, nanoparticle tracking analysis, and localization in AKI kidneys. In vitro, the potential of the EVs to promote the growth and survival of HK-2 cells undergoing cisplatin-induced apoptosis and anti-inflammatory effects in M1-polarized THP-1 was compared. Subsequently, AKI was induced in BALB/c mice using cisplatin. After 8 and 24 h of cisplatin treatment, iMSC-EVs or pan-PPAR-iMSC-EVs were injected intravascularly. At 96 h after cisplatin administration, the renoprotective effects of iMSC-EVs or pan-PPAR-iMSC-EVs in inhibiting inflammation and apoptosis were compared using serum biochemistry, histology, immunohistochemistry, and gene expression analysis by qPCR. Results Both EV types expressed EV markers and had typical EV morphology, and their localization in the renal tissue was confirmed. The proliferation and survival of HK-2 cells were higher in pan-PPAR-iMSC-EVs than those in iMSC-EVs. In M1-polarized THP-1 cells, the reduction in the mRNA expression of inflammatory cytokines was more significant in pan-PPAR-iMSC-EVs than that in iMSC-EVs. In the mouse model of cisplatin-induced AKI, pan-PPAR-iMSC-EVs markedly enhanced renoprotective effects compared to iMSC-EVs. Specifically, pan-PPAR-iMSC-EVs reduced tissue inflammation, immune cell infiltration, and apoptosis. Pan-PPAR-iMSC-EVs also increased renal capillary density. Conclusion Priming iMSCs with a PPAR agonist significantly improved the therapeutic potential of EVs by reducing inflammation and apoptosis. The reported strategy may contribute to the development of a novel cell-free option for AKI treatment. Trial registration: Not applicable.

Abstract Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide. Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that binds to programmed cell death-1 (PD-1), which is expressed in activated T cells and other immune cells and has been employed in cancer therapy, including HCC. Recently, PD-L1 overexpression has been documented in treatment-resistant cancer cells. Sorafenib is a multikinase inhibitor and the only FDA-approved treatment for advanced HCC. However, several patients exhibit resistance to sorafenib during treatment. This study aimed to assess the effect of glucose deprivation on PD-L1 expression in HCC cells. We used PD-L1-overexpressing HepG2 cells and IFN-γ-treated SK-Hep1 cells to explore the impact of glycolysis on PD-L1 expression. To validate the correlation between PD-L1 expression and glycolysis, we analyzed data from The Cancer Genome Atlas (TCGA) and used immunostaining for HCC tissue analysis. Furthermore, to modulate PD-L1 expression, we treated HepG2, SK-Hep1, and sorafenib-resistant SK-Hep1R cells with rapamycin. Here, we found that glucose deprivation reduced PD-L1 expression in HCC cells. Additionally, TCGA data and immunostaining analyses confirmed a positive correlation between the expression of hexokinase II (HK2), which plays a key role in glucose metabolism, and PD-L1. Notably, rapamycin treatment decreased the expression of PD-L1 and HK2 in both high PD-L1-expressing HCC cells and sorafenib-resistant cells. Our results suggest that the modulation of PD-L1 expression by glucose deprivation may represent a strategy to overcome PD-L1 upregulation in patients with sorafenib-resistant HCC.

Abstract Recently, kagome lattice materials have emerged as a new model material platform for discovering and engineering novel quantum phases of matter. In this work, we elucidate the driving mechanism of the $$\sqrt{{{3}}}$$ 3 × $$\sqrt{{{3}}}$$ 3 charge order in a newly discovered kagome metal ScV6Sn6. Through multimodal investigations combining angle-resolved photoemission spectroscopy, phonon dispersion calculations, and phase diagram study, we identify the central role of unstable planar Sn and Sc phonon modes, while the electronic instability and van Hove singularities originating from the V kagome lattice have a marginal influence. Our results highlight that the $$\sqrt{{{3}}}$$ 3 × $$\sqrt{{{3}}}$$ 3 charge order in ScV6Sn6 is fundamentally distinguished from the electronically driven 2 × 2 charge order in the canonical kagome system AV3Sb5, uncovering a new mechanism to induce symmetry-breaking phase transition in kagome lattice materials.

Abstract Background Magnetic resonance fingerprinting (MRF) enables fast myelin quantification via the myelin water fraction (MWF), offering a noninvasive method to assess brain development and disease. However, MRF-derived MWF lacks histological evaluation and remains unexamined in relation to leukodystrophy. This study aimed to access MRF-derived MWF through histology in mice and establish links between myelin, development, and leukodystrophy in mice and children, demonstrating its potential applicability in animal and human studies. Methods 3D MRF was performed on normal C57BL/6 mice with different ages, megalencephalic leukoencephalopathy with subcortical cyst 1 wild type (MLC1 WT, control) mice, and MLC 1 knock-out (MLC1 KO, leukodystrophy) mice using a 3 T MRI. MWF values were analyzed from 3D MRF data, and histological myelin quantification was carried out using immunohistochemistry to anti-proteolipid protein (PLP) in the corpus callosum and cortex. The associations between ‘MWF and PLP’ and ‘MWF and age’ were evaluated in C57BL/6 mice. MWF values were compared between MLC1 WT and MLC1 KO mice. MWF of normal developing children were retrospectively collected and the association between MWF and age was assessed. Results In 35 C57BL/6 mice (age range; 3 weeks–48 weeks), MWF showed positive relations with PLP immunoreactivity in the corpus callosum (β = 0.0006, P = 0.04) and cortex (β = 0.0005, P = 0.006). In 12-week-old C57BL/6 mice MWF showed positive relations with PLP immunoreactivity (β = 0.0009, P = 0.003, R2 = 0.54). MWF in the corpus callosum (β = 0.0022, P

Background: Although there is consensus to use immunoglobulins and corticosteroids as first-line treatments for multisystem inflammatory syndrome in children (MIS-C), the effectiveness of biological immunomodulators in patients refractory to standard therapy remains unclear. We aimed to outline real-world data on biological immunomodulators. Method: A literature search using Ovid-Medline, EMBASE, Cochrane CDSR, and KMBASE was conducted from September 2021 to August 2022; certainty of evidence was assessed via GRADE. Results: Among 258 studies, 10 were selected for analysis, of which 2 were observational studies (with control groups receiving standard therapy of either intravenous immunoglobulins and/or glucocorticoids) and 8 were single-arm studies. In all, 145 patients were treated with biological immunomodulators (anakinra (72; 49%) or infliximab (65; 44%)). In the first observational study, patients in the anakinra group initially exhibited a lower left ventricular ejection fraction than those in the control group. In the second study, patients in the infliximab group required less additional therapy and showed lower newly developed left ventricular dysfunction rate and reduced C-reactive protein levels. The clinical outcomes associated with each biological agent in single-arm studies were not reported individually. Conclusions: Biological immunomodulators are feasible therapeutic options for refractory MIS-C. Nevertheless, further research is warranted to demonstrate clinical efficacy.

This study presents a framework for determining the prioritization of vaccine introduction in the National Immunization Program (NIP) of the Republic of Korea, with a focus on case examples assessed in 2021 and 2023. We describe the predefined criteria for evaluating the prioritization of vaccines in the NIP and the established process in the Republic of Korea. These criteria included disease characteristics, vaccine characteristics, rationality and efficiency of resource allocation, and the acceptance of immunization. The process of prioritizing NIP introduction involved several sequential steps: a demand survey, evidence collection, preliminary evaluation, priority evaluation, and decision making. In 2021 and 2023, 14 and 25 committee members participated in evaluating the prioritization of vaccines in the NIP, respectively. Overall, 13 and 19 NIP vaccine candidates were included in the 2021 and 2023 evaluations, respectively. Through the Delphi survey and consensus processes, the priority order was determined: vaccination against Rotavirus infection was the top priority in 2021, while Influenza 4v (for chronic disease patients) took precedence in 2023. This study demonstrates an evidence-based decision-making process within the healthcare field. The outlined approach may provide valuable guidance for policymakers in other countries seeking to prioritize the inclusion of new vaccines in their NIP.

Around 8% of the global carbon dioxide emissions, are generated during cement manufacturing, which also involves significant use of raw materials, leading to adverse environmental effects. Consequently, extensive research is being conducted worldwide to explore the feasibility of utilizing different industrial waste by-products as alternatives to cement in concrete production. Fly ash (FA), Metakaolin (MK), Silica fume (SF), and ground granulated blast furnace slag (GGBS) are potential industrial materials that can serve as cement substitutes in pervious concrete. However, there exist conflicting findings in the literature regarding the impact of industrial supplementary cementitious materials (ISCMs) as partial cement replacements on the physical, mechanical, and durability properties of pervious concrete. The aim of this review is to investigate the feasibility and potential benefits of using ISCMs and compare them as partial cement replacements in the production of pervious concrete. The analysis primarily examines the effect of ISCMs as partial cement replacements on cementitious properties, including properties of ISMCs, mechanical properties, and durability of pervious concrete. The influence of ISCMs primarily stems from their pozzolanic reaction and filler characteristics. SF has the highest reactivity due to its high surface area and amorphous structure, resulting in a rapid pozzolanic reaction. GGBS and FA have moderate reactivity, while MK has relatively low reactivity due to its crystalline structure. Results from various studies indicate that the addition of FA, SF, and MK up to approximately 20% leads to a reduction in porosity and permeability while improving compressive strength and durability due to the filler effect of SF and MK. Incorporating GGBS increases permeability slightly while causing a slight decrease in compressive strength. The range of permeability and compressive strength for pervious concrete incorporating FA, SF, GGBS and MK were 0.17–1.46 cm/s and 4–35 MPa, 0.56–2.28 cm/s and 3.1–35 MPa, 0.19–0.64 cm/s and 8–42 MPa, 0.10–1.28 cm/s and 5.5–41 MPa, respectively, which are in the acceptable range for non-structural application of pervious concrete. In conclusion, it is possible to produce sustainable pervious concrete by substituting up to 20% of cement with FA, SF, GGBS, and MK, thereby reducing cement consumption, carbon footprint, energy usage, and air pollution associated with conventional cement production. However, further research is required to systematically assess the durability properties, long-term behavior, and, develop models for analyzing CO2 emissions and cost considerations of pervious concrete containing ISMCs.

Smart farms are integral to agriculture, evolving with technology while increasing energy consumption. Addressing issues like data scarcity is vital for smart farm-market growth. This study identified these issues and conducted an analysis of both correlation and causal relationship. Additionally, it created a growth strategy roadmap for the smart farm-market, tailored to stakeholders. To achieve carbon neutrality, government support, energy self-sufficiency tech, and energy reduction efforts are essential. These findings offer valuable guidance for policy formulation and operational planning, aiding the promotion of smart farm-market growth with sustainability in mind. In summary, smart farms are evolving alongside technology but face energy challenges, data issues, and the need for supportive policies and sustainable practices, all of which this study addresses to foster growth.

An endstation for resonant inelastic X-ray scattering (RIXS), dedicated to operations in the hard X-ray regime, has been constructed at the 1C beamline of Pohang Light Source II. At the Ir L3-edge, a total energy resolution of 34.2 meV was achieved, close to the theoretical estimation of 34.0 meV, which considers factors such as the incident energy bandpass, intrinsic analyzer resolution, geometrical broadening of the spectrometer, finite beam-size effect and Johann aberration. The performance of the RIXS instrument is demonstrated by measuring the RIXS spectra of Sr2IrO4. The endstation can be easily reconfigured to measure energy-integrated intensities with very low background for diffuse scattering and diffraction experiments.

Electromagnetic resonance in electric motors arises when the electromagnetic force frequency coincides with any of the motor's natural frequencies, causing excessive vibration and noise. To address this issue, it is crucial to design motors such that their natural frequencies do not closely align with the electromagnetic force frequency. However, vacuum cleaner motors operate across a broad range of speeds, generating a multitude of electromagnetic force frequencies, which makes it challenging to establish natural frequencies that can avoid all possible electromagnetic resonances. This article presents a novel approach for shifting natural frequencies by adjusting the stiffness of stator cores. By integrating an auxiliary component with various design factors into the motor, a range of natural frequencies can be achieved. An optimal natural frequency that mitigates electromagnetic resonance was identified among these modified frequencies, and the subsequent enhancement in acoustic characteristics was demonstrated.

Abstract Background Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation, pruritus, and abnormal epidermal barrier function. Compared with conventional mesenchymal stem cell (MSC), induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) is recognized as a unique source for producing extracellular vesicles (EVs) because it can be obtained in a scalable manner with an enhanced homogeneity. Stimulation of iMSCs with inflammatory cytokines can improve the immune-regulatory, anti-inflammatory, and tissue-repairing potential of iMSC-derived EVs. Results Proteome analysis showed that IFN-γ-iMSC-EVs are enriched with protein sets that are involved in regulating interferon responses and inflammatory pathways. In AD mice, expression of interleukin receptors for Th2 cytokines (IL-4Rα/13Rα1/31Rα) and activation of their corresponding intracellular signaling molecules was reduced. IFN-γ-iMSC-EVs decreased itching, which was supported by reduced inflammatory cell infiltration and mast cells in AD mouse skin; reduced IgE receptor expression and thymic stromal lymphopoietin and NF-kB activation; and recovered impaired skin barrier, as evidenced by upregulation of key genes of epidermal differentiation and lipid synthesis. Conclusions IFN-γ-iMSC-EVs inhibit Th2-induced immune responses, suppress inflammation, and facilitate skin barrier restoration, contributing to AD improvement.

The dataset currently available comprises data on the removal rates of heavy metals (Ba, Se, Cr, Fe, Cd, As, and Co) through the incorporation of seashells and palm oil kernel shells into pervious concrete for stormwater treatment. Stormwater runoff was collected from commercial areas in Taman University, Skudai, Johor, Malaysia. The stormwater samples underwent filtration and were preserved in high-density polyethylene (HDPE) bottles at a temperature of 4 °C for use as incoming water. The outgoing water, referred to as effluent, was obtained from tests performed on pervious concrete samples after a curing period of 28 days. The pervious concrete mixes were created with a water-to-binder ratio (w/b ratio) of 32% and a sand ratio of 10%. Three different levels of palm oil kernel shell and seashell content were used as coarse aggregate replacements: 0%, 25%, and 50%. Two single-size group were considered for both palm oil kernel shell and seashell: (6.3-9.5 mm) and (4.75-6.3 mm). Heavy metal analyses were conducted on the influent and effluent using a PerkinElmer ELAN 6100 Series Inductively Coupled Plasma– Mass Spectrometer (ICP-MS). The available datasets consist of both raw and analyzed data.

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder with a worldwide prevalence of 6–10 % of women of reproductive age. PCOS is a risk factor for cardiometabolic disorders such as type 2 diabetes, myocardial infarction, and stroke in addition to exhibiting signs of hyperandrogenism and anovulation. However, there is no known cure for PCOS, and medications have only ever been used symptomatically, with a variety of adverse effects. Drugs made from natural plant products may help treat PCOS because several plant extracts have been widely recognized to lessen the symptoms of PCOS. In light of this, 72 current studies on natural products with the potential to control PCOS were examined. By controlling the PI3K/AKT signaling pathway and decreasing NF-κB and cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6), certain plant-derived chemicals might reduce inflammation. Other substances altered the HPO axis, which normalized hormones. Additionally, other plant components increased glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels to reduce radiation-induced oxidative stress. The other substances prevented autophagy by impairing beclin 1, autophagy-related 5 (ATG5), and microtubule-associated protein 1A/1B-light chain 3 - II (LC3- II). The main focus of this comprehensive review is the possibility of plant extracts as natural bio-resources of PCOS treatment by regulating inflammation, hormones, reactive oxygen species (ROS), or autophagy.

The emergence of antimicrobial-resistant (AMR) bacteria has become a critical global One Health issue, mainly attributed to the extensive use of antimicrobial agents in human and agricultural settings. Regional and local AMR surveillance data is essential for implementing awareness and mitigation strategies. This article assesses AMR frequency in 1604 bacterial isolates consisting of Escherichia coli (E. coli) and Salmonella spp. isolated from diverse sources in Virginia, including farm animals, wildlife, environment, and food samples from 2007 to 2021. The results are based on the Kirby–Bauer disc diffusion assessment method of susceptibility to select antimicrobial agents, spanning nine distinct categories approved by the US Food and Drug Administration for clinical use. Streptomycin (STR) and tetracycline (TCY) exhibited the highest frequency of resistance in E. coli (39.1%) and Salmonella (25.2%), respectively. Multidrug resistance (MDR) was evident in 6.6% of E. coli and 10.9% of Salmonella isolates. Notably, 51% of E. coli and 36% of Salmonella isolates demonstrated resistance to more than one antimicrobial. None of the tested antimicrobials guaranteed effectiveness against the bacteria isolated from the surveyed sources and regions. The study found heightened MDR and distinct AMR patterns in bacteria isolated from food products compared to other sampled sources. These findings are vital for comprehending the current AMR landscape, prompting the development of strategies to mitigate the emergence of AMR bacteria, and advocating prudent antimicrobial use from a One Health perspective.

Abstract Background Aggregated amyloid-β (Aβ) is considered a pathogenic initiator of Alzheimer’s disease (AD), in strong association with tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. As the removal of amyloid burden from AD patient brains by antibodies has shown therapeutic potential, the development of small molecule drugs inducing chemical dissociation and clearance of Aβ is compelling as a therapeutic strategy. In this study, we synthesized and screened aryloxypropanolamine derivatives and identified 1-(3-(2,4-di-tert-pentylphenoxy)-2-hydroxypropyl)pyrrolidin-1-ium chloride, YIAD002, as a strong dissociator of Aβ aggregates. Methods The dissociative activity of aryloxypropanolamine derivatives against Aβ aggregates were evaluated through in vitro assays. Immunohistochemical staining, immunoblot assays, and the Morris water maze were used to assess the anti-Alzheimer potential in YIAD002-treated 5XFAD and transgenic APP/PS1 mice. Target-ligand interaction mechanism was characterized via a combination of peptide mapping, fluorescence dissociation assays, and constrained docking simulations. Results Among 11 aryloxypropanolamine derivatives, YIAD002 exerted strongest dissociative activity against β-sheet-rich Aβ aggregates. Upon oral administration, YIAD002 substantially reduced amyloid burden and accordingly, improved cognitive performance in the Morris water maze and attenuated major pathological hallmarks of AD including tauopathy, neuroinflammation, and synaptic protein loss. Mechanism studies suggest that YIAD002 interferes with intermolecular β-sheet fibrillation by directly interacting with KLVFFA and IGLMVG domains of Aβ. In addition, YIAD002 was found to possess dissociative activity against aggregates of pyroglutamate-modified Aβ and tau. Conclusions Collectively, our results evince the potential of chemical-driven dissociation of Aβ aggregates by aryloxypropanolamines as a therapeutic modality of the amyloid clearance approach.

Background: The purpose of this study was to investigate and compare the image quality of low-concentration-iodine (240 mgI/mL) contrast media (CM) and high-concentration-iodine (320 mgI/mL) CM according to the radiation dose. Methods: A total of 366 CT examinations were examined. Based on an assessment of quantitative and qualitative parameters by two radiologists, the quality was compared between Group A (low-concentration-iodine CM) and Group B (high-concentration-iodine CM) images of thyroid gland, sternocleidomastoid muscle (SCM), internal jugular vein (IJV), and common carotid artery (CCA). Another subgroup analysis compared Group a, (using ≤90 kVp in Group A), and Group b, (using ≥100 kVp in Group B) for finding the difference in image quality when the tube voltage is lowered. Results: Image quality did not differ between Groups A and B or between Groups a and b. The signal-to-noise ratio and contrast-to-noise ratio were significantly higher for Group B than Group A for the thyroid gland, IJV, and CCA. No statistical differences were found in the comparison of all structures between Groups a and b. Conclusion: There was no significant difference in image quality based on CM concentration with variable radiation doses. Therefore, if an appropriate CT protocol is applied, clinically feasible neck CT images can be obtained even using low-concentration-iodine CM.

Abstract Observations of comorbidity in heart diseases, including cardiac dysfunction (CD) are increasing, including and cognitive impairment, such as Alzheimer’s disease and dementia (AD/D). This comorbidity might be due to a pleiotropic effect of genetic variants shared between CD and AD/D. Here, we validated comorbidity of CD and AD/D based on diagnostic records from millions of patients in Korea and the University of California, San Francisco Medical Center (odds ratio 11.5 [8.5–15.5, 95% Confidence Interval (CI)]). By integrating a comprehensive human disease–SNP association database (VARIMED, VARiants Informing MEDicine) and whole-exome sequencing of 50 brains from individuals with and without Alzheimer's disease (AD), we identified missense variants in coding regions including APOB, a known risk factor for CD and AD/D, which potentially have a pleiotropic role in both diseases. Of the identified variants, site-directed mutation of ADIPOQ (268 G > A; Gly90Ser) in neurons produced abnormal aggregation of tau proteins (p = 0.02), suggesting a functional impact for AD/D. The association of CD and ADIPOQ variants was confirmed based on domain deletion in cardiac cells. Using the UK Biobank including data from over 500000 individuals, we examined a pleiotropic effect of the ADIPOQ variant by comparing CD- and AD/D-associated phenotypic evidence, including cardiac hypertrophy and cognitive degeneration. These results indicate that convergence of health care records and genetic evidences may help to dissect the molecular underpinnings of heart disease and associated cognitive impairment, and could potentially serve a prognostic function. Validation of disease–disease associations through health care records and genomic evidence can determine whether health conditions share risk factors based on pleiotropy.

We theoretically investigated the nitrogen substitution effect on the molecular structure and π-electron delocalization in linear nitrogen-substituted polycyclic aromatic hydrocarbons (N-PAHs). Based on the optimized molecular structures and magnetic field-induced parameters of fused bi- and tricyclic linear N-PAHs, we found that the local π-electron delocalization of subcycles (e.g., mono- and bicyclic constituent moieties) in linear N-PAHs is preserved, despite deviation from ideal structures of parent monocycles. The introduction of a fused five-membered ring with a pyrrolic N atom (N-5MR) in linear N-PAHs significantly perturbs the π-electronic condition of the neighboring fused six-membered ring (6MR). Monocyclic pyrrole exhibits substantial bond length alternations, strongly influencing the π-electronic systems of both the fused N-5MR and 6MR in linear N-PAHs, depending on the location of shared covalent bonds. A fused six-membered ring with a graphitic N atom in an indolizine moiety cannot generate monocyclic π-electron delocalization but instead contributes to the formation of polycyclic π-electron delocalization. This is evidenced by bifurcated diatropic ring currents induced by an external magnetic field. In conclusion, the satisfaction of Hückel’s 4n + 2 rule for both mono- and polycycles is crucial for understanding the overall π-electron delocalization. It is crucial to consider the unique characteristics of the three types of substituted N atoms and the spatial arrangement of 5MR and 6MR in N-PAHs.

Prolonged exposure to high temperatures is linked to a range of physiological responses in broiler chickens including reduced disease resistance, low growth rate, and high mortality rate. In this study, we investigated the effect of heat stress on gene expression levels in 4-week-old and 6-week-old chickens each exposed to environments conditioned at thermoneutral (21 °C) and high (32 °C) temperatures. The analysis of differentially expressed genes (DEGs) using microarray revealed that genes underlying reactive oxygen species (ROS) production, cell nutrient intake, glucose metabolism, and circadian rhythm were differentially regulated in association with heat stress. We also found that the deviation in expression levels across the transcriptome in response to heat stress was significantly stronger (P< 2.2×10−16) in 6-week-olds compared to younger chickens. We finally observed a significant trend (r = 0.78, P< 2.2×10−16) that genes with a higher estimate of expression in the microarray were more likely to have a higher expression level in RNA-sequencing. Together, our findings provide comprehensive insights into the physiology involved in stress responses at varying developmental stages, which may facilitate chicken breeding to maximize their productivity under adverse conditions.

Disposing fly ash in to landfill of coal fire power plant initiated environmental and health problems. A lot of researchers have conducted research to study the addition of fly ash (FA) as cement replacement in pervious concrete (PC). The aim of this paper was to review the impact of adding FA as partial substitution of cement in PC. The experimental outcomes from different previous studies have indicated that the void content and permeability of PC decreased with adding FA due to filler effect of FA. The optimum substitution level of cement with FA was obtained to be 10–30%. However, with increasing the level of replacement affects the hydration procedure resulting lower strength. PC containing FA showed higher abrasion resistance and lower drying shrinkage compared to normal PC. It can be concluded that using FA as partial substitution of cement would be environmentally friendly in association with more sustainable PC.

Abstract Background Extracellular vesicles (EVs) are recognized as novel cell-free therapeutics. Non-alcoholic steatohepatitis (NASH) remains a critical health problem. Herein, we show that EVs from pan peroxisome proliferator-activated receptor agonist-primed induced mesenchymal stem cell (pan PPAR-iMSC-EVs) has unique cargo protein signatures, and demonstrate its therapeutic function in NASH. Results A unique protein signatures were identified in pan PPAR-iMSC-EVs against those from non-stimulated iMSC-EVs. NASH mice receiving pan PPAR-iMSC-EVs showed reduced steatotic changes and ameliorated ER stress and mitochondiral oxidative stress induced by inflammation. Moreover, pan PPAR-iMSC-EVs promoted liver regeneration via inhibiting apoptosis and enhancing proliferation. Conclusions We conclude that our strategy for enriching unique cargo proteins in EVs may facilitate the development of novel therapeutic option for NASH. Graphical Abstract

The buildings’ indoor condition called “indoor environmental quality (IEQ)” has become a major goal, all IEQ elements must be maintained within a certain range for the comfort and health of the occupants. To achieve this goal, the previous studies focused on building occupants’ responses based on their activities and the changes in IEQ. Few studies, however, have comprehensively analyzed the above and reflected it in building design and operation. The study of this concept can be expressed as “human-building interaction management.” This approach is a paradigm for the healthy, sustainable, and simultaneous management of people, IEQ, and buildings. This study conducted an in-depth literature review on the above-mentioned studies. In addition, it ultimately proposed an intelligent planning unit (IPU), a new approach that can be used as a tool to apply the above human-building interaction concept to the practical design concept focusing on the planning phase. The IPU theory is designed to meet the customer expectations for the various objectives of a complex built environment. Eventually, it is expected that the proposed IPU concept will promote the spread of good health and environment-friendly buildings.

Objectives To mitigate greenhouse gas (GHG) emissions, our country is trying to replace fossil fuel to hydrogen (H2). H2 has higher energy yield (122 MJ/kg) than other energy sources (natural gas, coal, etc.), and is considered a clean fuel that produces only water upon combustion. The water electrolysis using renewable energy is one of the green-H2 producing methods, but its unstable characteristics depending on weather condition impede its practical application. Therefore, to establish green-H2 society, the use of waste and biomass is essential to fulfil the demand. Methods In this study, we estimated the biohydrogen potential of organic solid wastes: food waste, livestock manure, and sewage sludge, which are the main feedstock of domestic biogas plant. For the H2 generation process, dark fermentation (DF) and steam biogas reforming (SBR) were considered. Results and Discussion The potential amount of H2 through DF and SBR was 44,000 ton/y and 675,000 ton/y, respectively. The GHG reducing potential was estimated to be 5 million tons CO2-eq/year, but it can be lowered down to 2 million tons CO2-eq/year, considering the energy consumption during H2 generation process. Among the energy potential of produced H2, 7% and 60% is required for H2 production in DF and SBR, respectively. Conclusion The expected biohydrogen production was 718,000 ton/y which can account for about 14% of the domestic H2 production target in 2040 (526 million tons). The main source was livestock manure (86%), and minor fraction was from food waste (10%), and sewage sludge (4%). The GHG reducing potential was estimated to be 2 million tons CO2-eq/year, considering the energy consumption during H2 generation process.

The recent novel coronavirus disease (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is threatening global health. However, an understanding of the interaction of SARS-CoV-2 with human cells, including the physical docking property influenced by the host's genetic diversity, is still lacking. Here, based on germline variants in the UK Biobank covering 502,543 individuals, we revealed the molecular interactions between human angiotensin-converting enzyme 2 (hACE2), which is the representative receptor for SARS-CoV-2 entry, and COVID-19 infection. We identified six nonsense and missense variants of hACE2 from 2585 subjects in the UK Biobank covering 500000 individuals. Using our molecular dynamics simulations, three hACE2 variants from 2585 individuals we selected showed higher levels of binding free energy for docking in the range of 1.44-3.69 kcal/mol. Although there are diverse contributors to SARS-CoV-2 infections, including the mobility of individuals, we analyzed the diagnosis records of individuals with these three variants of hACE2. Our molecular dynamics simulations combined with population-based genomic data provided an atomistic understanding of the interaction between hACE2 and the spike protein of SARS-CoV-2.

BackgroundThis study aimed to investigate how social networks are associated with cognitive function in the middle-aged and elderly Korean population.MethodsA total of 7,704 individuals over the age of 50 were included from the baseline recruitment of the Cardiovascular and Metabolic Diseases Etiology Research Center cohort from the years 2013 to 2018. Egocentric social network characteristics including network size, intimacy, and frequency of face-to-face meetings were measured as exposures, and the Korean version of Mini-Mental State Examination (K-MMSE) score was measured to reflect general cognitive function as an outcome. We also stratified the analysis by income level into tertiles, with income caps of 42,000 thousand won and 72,000 thousand won. A general linear regression model was used, adjusting for age, gender, socioeconomic factors, lifestyle factors, depressive symptoms, and study settings.ResultsSocial network properties were positively associated with cognitive function in both men and women. However, the specific estimates varied according to gender and income level. In men, frequency was most significantly associated with cognitive function (standardized β = 0.093, p-value

BackgroundSepsis is diagnosed in millions of people every year, resulting in a high mortality rate. Although patients with sepsis present multimorbid conditions, including cancer, sepsis predictions have mainly focused on patients with severe injuries. ObjectiveIn this paper, we present a machine learning–based approach to identify the risk of sepsis in patients with cancer using electronic health records (EHRs). MethodsWe utilized deidentified anonymized EHRs of 8580 patients with cancer from the Samsung Medical Center in Korea in a longitudinal manner between 2014 and 2019. To build a prediction model based on physical status that would differ between sepsis and nonsepsis patients, we analyzed 2462 laboratory test results and 2266 medication prescriptions using graph network and statistical analyses. The medication relationships and lab test results from each analysis were used as additional learning features to train our predictive model. ResultsPatients with sepsis showed differential medication trajectories and physical status. For example, in the network-based analysis, narcotic analgesics were prescribed more often in the sepsis group, along with other drugs. Likewise, 35 types of lab tests, including albumin, globulin, and prothrombin time, showed significantly different distributions between sepsis and nonsepsis patients (P

To ensure the safety of structures, structural health monitoring (SHM) techniques that use cutting-edge sensing technologies have been developed. However, in the process of long-term structural health monitoring, sensor defects and data loss commonly occur, which pose limitations in the current SHM technique. To recover lost data and predict structural responses, convolutional neural networks (CNNs) have been used in SHM, but no obvious technique or rule for configuring CNN architecture with optimal performance has been presented yet. This study proposes a method for searching for the optimal CNN architecture capable of predicting the structural response of structures to evaluate their long-term safety. In this method, multi-objective optimization, considering both prediction performance and CNN training efficiency, is presented as a strategy. The optimization method using the two objective functions is applied to the structural response estimation, and the characteristics of the derived solutions are examined. Furthermore, the solutions derived using the two objective functions are classified into two solution groups that are biased to each objective function, and a strategy for minimizing the discrepancy between the two solution groups is additionally presented based on their trade-off relationship. The architecture characteristics, estimation performance, and training efficiency of the solutions derived by setting the discrepancy as the third objective function are investigated. The CNN derived by the proposed method with the third objective function reduced 40.35% of computational cost compared with that derived with two objective functions while they showed similar accuracies for the response estimation.

Prediction of construction cost and life-cycle cost through preliminary estimate is very important for the economic decision-making in the early phase of building projects. However, the conventional preliminary estimate has a high error range and low reliability because it relies only on the basic information of projects. In addition, the consideration of the life-cycle cost of the building is insufficient, causing problems such as budget shortage, inaccurate budgeting, and life-cycle cost increase. In this study, we propose a method of preliminary estimate based on BIM below the level of detail 2 and actual construction cost data to support the decision-making in the early design phase. To verify the proposed method, a web-based prototype was implemented and applied to three test cases. The range of error rate for three test cases was 1.93–7.16% (average error rate: 5.18%). It satisfies the criteria (−30% ~ +50%) of the “American Association of Cost Engineering”. As a result, the feasibility of the proposed model was validated. It is expected to be utilized as useful information in the decision-making occurring in the early design phase, and this allows for a rapid economic review of the design alternatives, a reduced LCC, and a shortened decision-making time.

Background: The Fazekas scale is one of the most commonly used visual grading systems for white matter hyperintensity (WMH) for brain disorders like dementia from T2-fluid attenuated inversion recovery magnetic resonance (MR) images (T2-FLAIRs). However, the visual grading of the Fazekas scale suffers from low-intra and inter-rater reliability and high labor-intensive work. Therefore, we developed a fully automated visual grading system using quantifiable measurements. Methods: Our approach involves four stages: (1) the deep learning-based segmentation of ventricles and WMH lesions, (2) the categorization into periventricular white matter hyperintensity (PWMH) and deep white matter hyperintensity (DWMH), (3) the WMH diameter measurement, and (4) automated scoring, following the quantifiable method modified for Fazekas grading. We compared the performances of our method and that of the modified Fazekas scale graded by three neuroradiologists for 404 subjects with T2-FLAIR utilized from a clinical site in Korea. Results: The Krippendorff’s alpha across our method and raters (A) versus those only between the radiologists (R) were comparable, showing substantial (0.694 vs. 0.732; 0.658 vs. 0.671) and moderate (0.579 vs. 0.586) level of agreements for the modified Fazekas, the DWMH, and the PWMH scales, respectively. Also, the average of areas under the receiver operating characteristic curve between the radiologists (0.80 ± 0.09) and the radiologists against our approach (0.80 ± 0.03) was comparable. Conclusions: Our fully automated visual grading system for WMH demonstrated comparable performance to the radiologists, which we believe has the potential to assist the radiologist in clinical findings with unbiased and consistent scoring.

We present a rare case of myoepithelioma in the subcutaneous layer of the shoulder with ultrasonography (US) and magnetic resonance imaging (MRI). US showed a lobulated hyperechoic mass, leading to an impression of lipoma. MRI showed the mass with low signal intensity on T1-weighted images (T1WI), high signal intensity on fat-suppressed T2-weighted images (T2WI), intermediate signal intensity on T2WI, and intense enhancement with adjacent fascial thickening. Imaging findings of soft tissue myoepithelioma have not been established. We report its US and MRI features mimicking features from a lipomatous tumor to infiltrative malignancy. Although soft tissue myoepithelioma has nonspecific image findings to confirm its diagnosis, some findings may help to make the differential diagnosis. Preoperative pathologic confirmation is recommended in a soft tissue neoplasm.

Ventilation air methane (VAM) is a potent greenhouse gas source originating from geological wells, current and extinct mineshafts and other terrestrial conduits venting methane to the atmosphere, contributing to global methane emissions and disproportionate warming potential. Herein, we introduce the concept of the methanotrophic material as an engineering solution. Such materials should be capable of converting methane at ambient temperatures and pressures to a binder product, capturing and permanently sequestering the methane while simultaneously restricting its further emission. While such materials are currently under research development, this goal is supported and facilities by the mathematical framework, introduced and used herein, to evaluate the ability to convert methane, using currently published activity data. We include a case study of the conversion of a characteristic stream of VAM (0.6% methane in air, 1.7 × 10 ^8 l hr ^−1 equivalent to 100 000 standard cubic feet per minute). We show that when appropriately designed, such systems require a surface coverage of less than 1000 m of mine tunnel length (equivalent to 20 000 m ^2 areal coverage) in order to reduce the methane emission from this stream by over 99%. Finally, we highlight formaldehyde as a reactive intermediate of methane oxidation which may itself be incorporated into these coating materials. As a component of binders and polymers already used ubiquitously in commercial products, this intermediate ultimately allows these systems to sequester the carbon from methane in a stable and solid form. The results presented here are easily extended to the treatment of other methane streams—either more concentrated or dilute—and the results herein will guide the design and development of a new class of carbon-negative materials.

Understanding Shiga toxin subtypes in E. coli from reservoir hosts may give insight into their significance as human pathogens. The data also serve as an epidemiological tool for source tracking. We characterized Shiga toxin subtypes in 491 goat E. coli isolates (STEC) from the mid-Atlantic US region (stx1 = 278, stx2 = 213, and stx1/stx2 = 95). Their serogroups, phylogroups, M13RAPD genotypes, eae (intimin), and hly (hemolysin) genes were also evaluated. STEC-positive for stx1 harbored Stx1c (79%), stx1a (21%), and stx a/c (4%). Those positive for Stx2 harbored stx2a (55%) and Stx2b (32%), while stx2a/stx2d and stx2a/stx2b were each 2%. Among the 343 STEC that were serogrouped, 46% (n = 158) belonged to O8, 20% (n = 67) to 076, 12% (n = 42) to O91, 5% (n = 17) to O5, and 5% (n = 18) to O26. Less than 5% belonged to O78, O87, O146, and O103. The hly and eae genes were detected in 48% and 14% of STEC, respectively. Most belonged to phylogroup B1 (73%), followed by D (10%), E (8%), A (4%), B2 (4%), and F (1%). M13RAPD genotyping revealed clonality of 091, O5, O87, O103, and O78 but higher diversity in the O8, O76, and O26 serogroups. These results indicate goat STEC belonged to important non-O157 STEC serogroups, were genomically diverse, and harbored Shiga toxin subtypes associated with severe human disease.

Rapid antigen tests (RATs) for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are widely used in the Coronavirus disease 2019 (COVID-19) pandemic caused by diverse variants. Information on the real-world performance of RATs for variants is urgently needed for decision makers. Systematic searches of the available literature and updates were conducted in PubMed, Ovid-MEDLINE, Ovid-EMBASE, CENTRAL, and KMBASE for articles evaluating the accuracy of instrument-free RATs for variants up until 14 March 2022. A bivariate random effects model was utilized to calculate pooled diagnostic values in comparison with real-time reverse transcription-polymerase chain reaction as the reference test. A total of 7562 samples from six studies were available for the meta-analysis. The overall pooled sensitivity and specificity of RATs for variants were 69.7% (95% confidence interval [CI] = 62.5% to 76.1%) and 100.0% (95% CI = 98.8% to 100.0%), respectively. When an additional 2179 samples from seven studies reporting sensitivities only were assessed, the pooled sensitivity dropped to 50.0% (95% CI = 44.0% to 55.0%). These findings suggest reassessment and monitoring of the diagnostic utility of RATs for variants, especially for the sensitivity aspect, to facilitate appropriate diagnosis and management of COVID-19 patients.

Olfactory receptors are ectopically expressed in extra-nasal tissues. The gut is constantly exposed to high levels of odorants where ectopic olfactory receptors may play critical roles. Activation of ectopic olfactory receptor 544 (Olfr544) by azelaic acid (AzA), an Olfr544 ligand, reduces adiposity in mice fed a high-fat diet (HFD) by regulating fuel preference to fats. Herein, we investigated the novel function of Olfr544 in the gut. In GLUTag cells, AzA induces the cAMP-PKA-CREB signaling axis and increases the secretion of GLP-1, an enteroendocrine hormone with anti-obesity effects. In wild-type (WT) mice injected AzA, GLP-1 plasma levels were elevated. The induction of GLP-1 secretion was negated in cells with Olfr544 gene knockdown and in Olfr544-deficient mice. Gut microbiome analysis revealed that AzA increased the levels of Bacteroides acidifaciens and microbiota associated with antioxidant pathways. In fecal metabolomics analysis, the levels of succinate and trehalose, metabolites correlated with a lean phenotype, were elevated by AzA. The function of Olfr544 in gut inflammation, a key feature in obesity, was further investigated. In RNA sequencing analysis, AzA suppressed LPS-induced activation of inflammatory pathways and reduced TNF-α and IL-6 expression, thereby improving intestinal permeability. The effects of AzA on the gut metabolome, microbiome, and colon inflammation were abrogated in Olfr544-KO mice. These results collectively demonstrated that activation of Olfr544 by AzA in the gut exerts multiple effects by regulating GLP-1 secretion, gut microbiome and metabolites, and colonic inflammation in anti-obesogenic phenotypes and, thus, may be applied for obesity therapeutics.

Understanding mortality, derived from debilitations consisting of multiple diseases, is crucial for patient stratification. Here, in systematic fashion, we report comprehensive mortality data that map the temporal correlation of diseases that tend toward deaths in hospitals. We used a mortality trajectory model that represents the temporal ordering of disease appearance, with strong correlations, that terminated in fatal outcomes from one initial diagnosis in a set of patients throughout multiple admissions. Based on longitudinal healthcare records of 10.4 million patients from over 350 hospitals, we profiled 300 mortality trajectories, starting from 118 diseases, in 311,309 patients. Three-quarters (75%) of 59,794 end-stage patients and their deaths accrued throughout 160,360 multiple disease appearances in a short-term period (

Perivascular epithelioid cell tumor (PEComa) is a very rare mesenchymal tumor with a distinctive morphology and immunophenotype. PEComas usually harbor TSC2 alterations, although TFE3 translocations, which occur in MiT family translocation renal cell carcinoma and alveolar soft part sarcoma, are also possible. We recently experienced a case of PEComa with TFE3 expression arising in the breast. An 18-year-old female patient presented with a right breast mass. Histologically, the tumor consisted of epithelioid cells with alveolar structure and showed a diffuse strong expression of HMB45 and TFE3. TSC2 was preserved. Melan A and smooth muscle actin were negative. To our knowledge, this is the first Korean case of PEComa of the breast that intriguingly presented with TFE3 expression.