Characteristics of secondary aerosol formation during shortened multiday reaction experiments in a smog chamber: Effects of relative humidity and ammonia.

Shortened multiday reaction experiments were conducted using the KIST chamber for atmospheric processes simulation (K-CAPS) to characterize the effects of ammonia (NH3) and relative humidity (RH) on the formation of secondary organic aerosols (SOA) due to photooxidation of a mixture of toluene and inorganic gases such as NOx, SO2, and NH3. UV lamps were repeatedly turned on for 3 h (daytime) and off for 6 h (nighttime), and precursors were injected to a reaction bag once (Multiday Initial injection, MI) or repeatedly (Multiday Cyclic injection, MC) to simulate high particulate matter episode due to foreign inflow episode and domestic stagnation episodes, respectively. As a result, the amount of SOA formed in the humid (RH 80 %) MI experiments with ammonia was approximately 1.1 times more than in the traditional single day experiment and approximately 1.6 times more than in the MC experiment, implying that aging processes including nighttime effects without additional emission of precursors during transport can produce more SOA as reactions progressed further under the experimental conditions of this study. The higher the initial RH, the more SOA was formed, with a slope increasing approximately 1.2 µg/m3 per unit RH, and the shorter run time required for SOA to increase to 30 µg/m3 (twice the WHO PM10 standard), with a slope decreasing approximately 0.3 h per unit RH, implying that more humid condition caused during long-range transport across the oceans is one of the possible reasons of high secondary aerosol formation. The SOA formation was reduced by approximately 60 % in the absence of ammonia, suggesting that ammonia reduction is needed to decrease not only secondary inorganic aerosols but also SOA. These results are useful to understand the major reason of high pollution of particulate matters by episode cases in urban areas.

Reduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection by blocking the epidermal growth factor receptor (EGFR) pathway.

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.

Anticancer effects of high-dose extracellular citrate treatment in pancreatic cancer cells under different glucose concentrations.

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.

Drug Discovery and Screening Tool Development for Tauopathies by Focusing on Pathogenic Tau Repeat 3 Oligomers.

Comprehending early amyloidogenesis is essential for the development of effective therapeutic strategies. In tauopathies like Alzheimer's disease (AD), the abnormal accumulation of tau protein is initiated by pathological tau seeds. Mounting evidence implies that the microtubule binding domain, consisting of three to four repeats, plays a pivotal role in this process, yet the exact region driving the formation of pathogenic species needs to be further scrutinized. Here, we chemically synthesized individual tau repeats to identify those exhibiting pathogenic prion-like characteristics. Notably, repeat 3 (R3) displayed a remarkable propensity to polymerize, form toxic filaments, and induce cognitive impairment, even in the absence of an aggregation-promoting inducer, highlighting its physiological relevance. Additionally, oligomeric R3 was identified as a particularly pathological form, prompting the establishment of a screening platform. Through screening, tolcapone was found to possess therapeutic efficacy against pathological tau aggregates in PS19 transgenic mice. This screening platform provides a valuable avenue for identifying compounds that selectively interact with peptides implicated in the progression of tauopathies.

Improvement of androgenic alopecia by extracellular vesicles secreted from hyaluronic acid-stimulated induced mesenchymal stem cells.

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/ß-catenin signaling pathway (ß-catenin and phosphorylated GSK3ß) 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/ß-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-ß, 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/ß-catenin was observed in HA-iMSC-EVs but not in iMSC-EVs, as shown by ß-catenin stabilization and an increase in phosphorylated GSK3ß. 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 ß-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/ß-catenin signaling.

Molecularly Engineered Alicyclic Organic Spacers for 2D/3D Hybrid Tin-based Perovskite Solar Cells.

The high defect density and inferior crystallinity remain great hurdles for developing highly efficient and stable Sn-based perovskite solar cells (PSCs). 2D/3D heterostructures show strong potential to overcome these bottlenecks; however, a limited diversity of organic spacers has hindered further improvement. Herein, a novel alicyclic organic spacer, morpholinium iodide (MPI), is reported for developing structurally stabilized 2D/3D perovskite. Introducing a secondary ammonium and ether group to alicyclic spacers in 2D perovskite enhances its rigidity, which leads to increased hydrogen bonding and intermolecular interaction within 2D perovskite. These strengthened interactions facilitate the formation of highly oriented 2D/3D perovskite with low structural disorder, which leads to effective passivation of Sn and I defects. Consequently, the MP-based PSCs achieved a power conversion efficiency (PCE) of 12.04% with superior operational and oxidative stability. This work presents new insight into the design of organic spacers for highly efficient and stable Sn-based PSCs.

Second-Line Uterotonics for Uterine Atony: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the comparative efficacy of two of the most commonly used second-line uterotonics-methylergonovine maleate and carboprost tromethamine. METHODS: We conducted a double-blind randomized trial at two large academic perinatal centers in patients undergoing nonemergency cesarean delivery with uterine atony refractory to oxytocin, as diagnosed by the operating obstetrician. The intervention included administration of a single dose of intramuscular methylergonovine or carboprost intraoperatively at diagnosis. The primary outcome, uterine tone on a 0-10 numeric rating scale 10 minutes after study drug administration, was rated by operating obstetricians blinded to the drug administered. Secondary outcomes included uterine tone score at 5 minutes, administration of additional uterotonic agents, other interventions for uterine atony or hemorrhage, quantitative blood loss, urine output, postpartum change in serum hematocrit, transfusion, length of hospital stay, adverse drug or transfusion reactions, and postpartum hemorrhage complications. A sample size of 50 participants per group was planned to detect a 1-point difference (with estimated within-group SD of 1.5) in the mean primary outcome with 80% power at a two-sided α level of 0.05 while accounting for potential protocol violations. RESULTS: A total of 1,040 participants were enrolled, with 100 randomized to receive one of the study interventions. Mean±SD 10-minute uterine tone scores were 7.3±1.7 after methylergonovine and 7.6±2.1 after carboprost, with an adjusted difference in means of -0.1 (95% CI, -0.8 to 0.6, P=.76). Additional second-line uterotonics were required in 30.0% of the methylergonovine arm and 34.0% in the carboprost arm (adjusted odds ratio 0.72, 95% CI, 0.27-1.89, P=.505), and geometric mean quantitative blood loss was 756 mL (95% CI, 636-898) and 708 mL (95% CI, 619-810) (adjusted ratio of geometric means 1.06, 95% CI, 0.86-1.31, P=.588), respectively. No differences were detected in the occurrence of other interventions for uterine atony or postpartum hemorrhage. CONCLUSION: No difference was detected in uterine tone scores 10 minutes after administration of either methylergonovine or carboprost for refractory uterine atony, indicating that either agent is acceptable. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03584854.

Comparison of Fracture Strength of Milled and 3D-Printed Crown Materials According to Occlusal Thickness.

This study aimed to measure the fracture strengths and hardness of final restorative milled and 3D-printed materials and evaluate the appropriate crown thickness for their clinical use for permanent prosthesis. One type of milled material (group M) and two types of 3D-printed materials (groups P1 and P2) were used. Their crown thickness was set to 0.5, 1.0, and 1.5 mm for each group, and the fracture strength was measured. Vickers hardness was measured and analyzed to confirm the hardness of each material. Scanning electron microscopy was taken to observe the surface changes of the 3D-printed materials under loads of 900 and 1500 N. With increased thickness, the fracture strength significantly increased for group M but significantly decreased for group P1. For group P2, the fracture strengths for the thicknesses of 0.5 mm and 1.5 mm significantly differed, but that for 1.0 mm did not differ from those for other thicknesses. The hardness of group M was significantly higher than that of groups P1 and P2. For all thicknesses, the fracture strength was higher than the average occlusal force for all materials; however, an appropriate crown thickness is required depending on the material and component.

Exploration and genetic analyses of canopy leaf pigmentation changes in soybean (Glycine max L.): unveiling a novel phenotype.

KEY MESSAGE: Pigmentation changes in canopy leaves were first reported, and subsequent genetic analyses identified a major QTL associated with levels of pigmentation changes, suggesting Glyma.06G202300 as a candidate gene. An unexpected reddish-purple pigmentation in upper canopy leaves was discovered during the late reproductive stages in soybean (Glycine max L.) genotypes. Two sensitive genotypes, 'Uram' and PI 96983, exhibited anomalous canopy leaf pigmentation changes (CLPC), while 'Daepung' did not. The objectives of this study were to: (i) characterize the physiological features of pigmented canopy leaves compared with non-pigmented leaves, (ii) evaluate phenotypic variation in a combined recombinant inbred line (RIL) population (N = 169 RILs) under field conditions, and (iii) genetically identify quantitative trait loci (QTL) for CLPC via joint population linkage analysis. Comparison between pigmented and normal leaves revealed different Fv/Fm of photosystem II, hyperspectral reflectance, and cellular properties, suggesting the pigmentation changes occur in response to an undefined abiotic stress. A highly significant QTL was identified on chromosome 6, explaining ~ 62.8% of phenotypic variance. Based on the QTL result, Glyma.06G202300 encoding flavonoid 3'-hydroxylase (F3'H) was identified as a candidate gene. In both Uram and PI 96983, a 1-bp deletion was confirmed in the third exon of Glyma.06G202300 that results in a premature stop codon in both Uram and PI 96983 and a truncated F3'H protein lacking important domains. Additionally, gene expression analyses uncovered significant differences between pigmented and non-pigmented leaves. This is the first report of a novel symptom and an associated major QTL. These results will provide soybean geneticists and breeders with valuable knowledge regarding physiological changes that may affect soybean production. Further studies are required to elucidate the causal environmental stress and the underlying molecular mechanisms.

Prioritization of Vaccines for Introduction in the National Immunization Program in the Republic of Korea.

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.

Quantum-Confined Lifshitz Transition on Weyl Semimetal Td-MoTe2.

Adsorption of alkali atoms onto material surfaces is widely utilized for controlling electronic properties and is particularly effective for two-dimensional materials. While tuning the chemical potential and band gap and creating quantum-confined states are well established for alkali adsorption on semiconductors, the effects on semimetallic systems remain largely elusive. Here, utilizing angle-resolved photoemission spectroscopy measurements and density functional theory calculations, we disclose the creation of two-dimensional electron gas and the quantum-confined Lifshitz transition at the surface of a Weyl semimetal Td-MoTe2 by potassium adsorption. Electrons from potassium adatoms are shown to be transferred mainly to the lowest unoccupied band within the gapped part of the Brillouin zone, which, in turn, induces strong surface band bending and quantum confinement in the topmost layer. The quantum-confined topmost layer evolves from a semimetal to a strong metal with a Lifshitz transition departing substantially from the bulk band. The present finding and its underlying mechanism can be exploited for the creation of electronic heterojunctions in van der Waals semimetals.

Nationwide Birth Prevalence of Crucial Congenital Heart Defects From 2014 to 2018 in Korea.

BACKGROUND AND OBJECTIVES: A comprehensive survey of congenital heart disease (CHD) prevalence has not yet been conducted in South Korea. This study aimed to investigate the prevalence of CHDs in Korean children and lay the foundation for national CHD epidemiology. METHODS: Target patients were infantile crucial CHDs, which include critical CHDs (requiring urgent procedures after birth with common hypoxemic defects) and diverse categorical defects excluding simple shunt defects. Data were obtained from the National Health Insurance Service over a 5-year period (2014-2018). Birth prevalence (new cases per 1,000 live births) of CHDs in Korea was analyzed and compared with that of other countries. RESULTS: The birth prevalences of right heart obstructive defects (pulmonary valve stenosis and pulmonary atresia), conus anomalies (tetralogy of Fallot and double outlet right ventricle), and total anomalous pulmonary venous return showed significant increases in the East Asian group (P < 0.001), whereas those of left heart obstructive defects (coarctation of aorta, aortic stenosis, and hypoplastic left heart syndrome), truncus anomalies (D-transposition of great artery and persistent truncus arteriosus), atrioventricular septal defect, and hypoplastic right heart syndrome were significantly decreased in the East Asian group (P < 0.001). CONCLUSIONS: The overall birth prevalence of crucial CHDs in Korea was similar to that of critical CHDs in previous studies from other countries. Some subtypes of right heart obstructive defects, left heart obstructive defects, and conotruncal anomalies showed significant differences between East Asian and Western populations. This study contributes to a foundation for national CHD epidemiology in Korean children.

Extracts of Phlomoides umbrosa Turczaninow alleviate allergic airway inflammation in lipopolysaccharide-stimulated RAW 264.7 cells and ovalbumin-induced hyper-responsiveness mouse model.

Phlomoides umbrosa Turczaninow (PU), a traditional Korean medicinal herb, exhibits osteogenic and anti-inflammatory effects. This research explored the effect of PU extracts on hyperimmune responses within the respiratory tract using lipopolysaccharide-stimulated RAW 264.7 cells and an ovalbumin-induced hyper-responsiveness model. The inflammatory cytokines, protein expression linked to airway inflammation, antioxidant enzyme activity, histopathological observation, and expectorant activity were measured. The results revealed that PU treatment led to a concentration-dependent reduction in Th2 cytokines and the expression of nuclear factor (NF)-κB, phosphatase-tensin homolog, mitogen-activated protein kinase (MAPK), and inducible nitric oxide synthase (iNOS). Simultaneously, antioxidant enzyme activity increased. Furthermore, PU exhibited substantial enhancements in lung tissue condition and expectorant activity relative to the allergic rhinitis-induced group. These findings indicate the potential of PU to mitigate airway inflammation and excessive mucus production by suppressing NF-κB, MAPK, and iNOS pathways. Consequently, PU emerges as a promising anti-inflammatory agent for respiratory tract applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01521-3.

Impact of vehicles at the roadside of expressway in urban area: Simultaneous measurement of particle size distribution and positive matrix factorization.

This study conducted real-time monitoring of size-resolved particle concentrations ranging from 9 nm to 10 µm simultaneously at four sites on the park ground and the roof of a five-story apartment buildings in the upwind and downwind areas of the Olympic Expressway next to apartment complex areas of Seoul, Korea. Using a positive matrix factorization model for source apportionment, eight factors were resolved at each monitoring site: four exhaust emissions of vehicles, one non-exhaust emission of vehicle, two regional sources, and one unknown source. After categorizing monitoring data into three cases by wind conditions, impact and contribution of each vehicle-related source on the local road to the roadside pollution was quantified and characterized by subtracting the urban background concentrations. Throughout the measurement period, the contribution of vehicle-related sources to the particle number concentration at each monitoring site ranged from 61 % to 69 %, while that to the particle mass concentration ranged from 39 % to 87 %. During periods of steady traffic flow and wind blowing from the road to three downwind sites at speeds exceeding >0.5 m/s during working hours, the particle number concentrations at the downwind sites were 2.2-2.5 times higher than the average levels. Among vehicle-related sources, gasoline vehicles with multiple injections or high-emitting diesel vehicles showed the highest contribution to particle number concentrations at all sites. As wind speed increased, the number concentrations of particles from vehicle exhaust and non-exhaust emissions decreased and increased, respectively, probably due to enhanced dilution and transport, respectively. In addition, particle number concentrations showed a parabolic curve-like trend with traffic volumes increasing to approximately 10,000 vehicles/h, and then decreasing for both vehicle exhaust and non-exhaust emissions. These results can be utilized in numerical modeling studies and in establishing traffic-related environmental policies to reduce seasonal and temporal particle exposure near the roadsides.

Eucalyptol Ameliorates Retinal Microvascular Defects through Modulating ER Stress and Angiopoietin-Tie Signaling in Diabetic Eyes.

Loss of the inner blood-retinal barrier (BRB) integrity is a main feature of ocular diseases such as diabetic macular edema. However, there is a lack of clarity on how inner BRB function is modulated within the diabetic retina. The current study examined whether eucalyptol inhibited inner BRB destruction and aberrant retinal angiogenesis in 33 mM glucose-exposed human retinal microvascular endothelial (RVE) cells and db/db mice. This study further examined the molecular mechanisms underlying endothelial dysfunction including retinal endoplasmic reticulum (ER) stress and angiopoietin (Ang)/Tie axis in conjunction with vascular endothelial growth factor (VEGF). Eucalyptol is a naturally occurring monoterpenoid and an achiral aromatic component of many plants including eucalyptus leaves. Nontoxic eucalyptol reduced the production of amyloid-ß (Aß) protein in glucose-loaded RVE cells and in diabetic mice. This natural compound blocked apoptosis of Aß-exposed RVE cells in diabetic mouse eyes by targeting ER stress via the inhibition of PERK-eIF2α-ATF4-CHOP signaling. Eucalyptol promoted activation of the Ang-1/Tie-2 pathway and dual inhibition of Ang-2/VEGF in Aß-exposed RVE cells and in diabetic eyes. Supply of eucalyptol reversed the induction of junction proteins in glucose/Aß-exposed RVE cells within the retina and reduced permeability. In addition, oral administration of eucalyptol reduced vascular leaks in diabetic retinal vessels. Taken together, these findings clearly show that eucalyptol inhibits glucose-induced Aß-mediated ER stress and manipulates Ang signaling in diabetic retinal vessels, which ultimately blocks abnormal angiogenesis and loss of inner BRB integrity. Therefore, eucalyptol provides new treatment strategies for diabetes-associated RVE defects through modulating diverse therapeutic targets including ER stress, Ang-1/Tie-2 signaling, and Ang-2/VEGF.

Clinical performance of the Roche Cobas Liat SARS-CoV-2 & influenza A/B assay: A systematic review and meta-analysis.

Respiratory tract infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses are persistent and critical. The Cobas Liat SARS-CoV-2 & influenza A/B assay (Multiplex Liat), the FDA-authorized point-of-care reverse transcriptase polymerase chain reaction (RT-PCR) assay, has a turnaround time of 20 min and high accuracy. This study evaluates the pooled performance of this assay to provide practical information. This meta-analysis was registered in PROSPERO (registration number: CRD42023467579). A systematic literature search was conducted within PubMed, Ovid-EMBASE, and the Cochrane Library for articles evaluating the accuracy of the Multiplex Liat assay through September 2023. A random-effects model was used to calculate the pooled diagnostic values with real-time RT-PCR (rRT-PCR) as a reference test. A total of 4,705 samples from eight studies were included in the primary meta-analysis. The overall pooled sensitivity and specificity of Multiplex Liat were 100.0 % (95 % confidence interval [CI] = 96.7 %-100.0 %) and 99.7 % (95 % CI = 98.7 %-99.9 %), respectively. The presence of variants of concern or in-house rRT-PCR assays as reference standards did not significantly affect the pooled diagnostic performance of the Multiplex Liat. When 5,333 samples from nine studies were assessed for sensitivity, the pooled sensitivity was 100.0 % (95 % CI = 85.8 %-100.0 %) without a significant difference. This meta-analysis demonstrates the usefulness of Multiplex Liat for the detection of SARS-CoV-2 based on pooled diagnostic values. These practical findings may facilitate appropriate settings for the diagnosis and management of patients with respiratory tract infections.

One Health Landscape of Antimicrobial Resistance in Bacteria Isolated from Virginia between 2007-2021.

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.

Chemically Driven Clearance of Amyloid Aggregates by Polyfunctionalized Furo[2,3-b:4,5-b']dipyridine-Chalcone Hybrids to Ameliorate Memory in an Alzheimer Mouse Model.

The aberrant assembly of amyloid-ß (Aß) is implicated in Alzheimer's disease (AD). Recent clinical outcomes of Aß-targeted immunotherapy reinforce the notion that clearing Aß burden is a potential therapeutic approach for AD. Herein, to develop drug candidates for chemically driven clearance of Aß aggregates, we synthesized 51 novel polyfunctionalized furo[2,3-b:4,5-b']dipyridine-chalcone hybrid compounds. After conducting two types of cell-free anti-Aß functional assays, Aß aggregation prevention and Aß aggregate clearance, we selected YIAD-0336, (E)-8-((1H-pyrrol-2-yl)methylene)-10-(4-chlorophenyl)-2,4-dimethyl-7,8-dihydropyrido[3',2':4,5]furo[3,2-b]quinolin-9(6H)-one, for further in vivo investigations. As YIAD-0336 exhibited a low blood-brain barrier penetration profile, it was injected along with aggregated Aß directly into the intracerebroventricular region of ICR mice and ameliorated spatial memory in Y-maze tests. Next, YIAD-0336 was orally administered to 5XFAD transgenic mice with intravenous injections of mannitol, and YIAD-0336 significantly removed Aß plaques from the brains of 5XFAD mice. Collectively, YIAD-0336 dissociated toxic aggregates in the mouse brain and hence alleviated cognitive deterioration. Our findings indicate that chemically driven clearance of Aß aggregates is a promising therapeutic approach for AD.

Assessment of Deep Learning-Based Triage Application for Acute Ischemic Stroke on Brain MRI in the ER.

RATIONALE AND OBJECTIVES: To assess a deep learning application (DLA) for acute ischemic stroke (AIS) detection on brain magnetic resonance imaging (MRI) in the emergency room (ER) and the effect of T2-weighted imaging (T2WI) on its performance. MATERIALS AND METHODS: We retrospectively analyzed brain MRIs taken through the ER from March to October 2021 that included diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences. MRIs were processed by the DLA, and sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were evaluated, with three neuroradiologists establishing the gold standard for detection performance. In addition, we examined the impact of axial T2WI, when available, on the accuracy and processing time of DLA. RESULTS: The study included 947 individuals (mean age ± standard deviation, 64 years ± 16; 461 men, 486 women), with 239 (25%) positive for AIS. The overall performance of DLA was as follows: sensitivity, 90%; specificity, 89%; accuracy, 89%; and AUROC, 0.95. The average processing time was 24 s. In the subgroup with T2WI, T2WI did not significantly impact MRI assessments but did result in longer processing times (35 s without T2WI compared to 48 s with T2WI, p < 0.001). CONCLUSION: The DLA successfully identified AIS in the ER setting with an average processing time of 24 s. The absence of performance acquire with axial T2WI suggests that the DLA can diagnose AIS with just axial DWI and FLAIR sequences, potentially shortening the exam duration in the ER.

Performances and properties of steel and composite prestressed tendons - A review.

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.