Search

Background/Aims Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF). Methods We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and an m-qSOFA ≥2 was considered high. Results Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than those with low m-qSOFA (Ps

Accurate, rapid and sensitive detection of specific immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in human samples is crucial for preventing and assessing pandemics, especially in the case of recent COVID-19 outbreaks. However, simultaneous and efficient detection of IgG and IgM in a single system remains challenging. Herein, we developed a multicolor nanosystem capable of quantitatively analyzing anti-SARS-CoV-2 IgG and IgM with high sensitivity within 20 ​min. The detection system consists of core-shell upconversion nanoparticles (csUCNPs), secondary antibodies labeled with fluorescent dyes (sab), and magnetic nanocrystals (PMF). By leveraging the Förster resonance energy transfer (FRET) effect, the photoluminescence (PL) intensity of blue and green regions is restored for IgG and IgM detection, respectively. Inspiringly, owing to the introducing of PMF, the limits of detection (LODs) of IgG and IgM tested are improved to 89 ​fmol ​L−1 and 19.4 ​fmol ​L−1, representing about 416-folds and 487-folds improvement over only-dye dependent system, respectively. Mechanistic investigations reveal that the high collective effect and surface energy transfer efficiency from csUCNPs to PMF contribute to the enhanced detection sensitivity. The assay enables us to quantify clinical vaccinated samples with high specificity and precision, suggesting our multicolor platform can be a promising alternative for clinical point-of-care serological assay.

Abstract Digital PCR (dPCR) is a technique for absolute quantification of nucleic acid molecules. To develop a dPCR technique that enables more accurate nucleic acid detection and quantification, we established a novel dPCR apparatus known as centrifugal force real-time dPCR (crdPCR). This system is efficient than other systems with only 2.14% liquid loss by dispensing samples using centrifugal force. Moreover, we applied a technique for analyzing the real-time graph of the each micro-wells and distinguishing true/false positives using artificial intelligence to mitigate the rain, a persistent issue with dPCR. The limits of detection and quantification were 1.38 and 4.19 copies/μL, respectively, showing a two-fold higher sensitivity than that of other comparable devices. With the integration of this new technology, crdPCR will significantly contribute to research on next-generation PCR targeting absolute micro-analysis.

Introduction: Low-density lipoprotein (LDL) cholesterol-lowering treatment is beneficial for the secondary or primary prevention of high-risk atherosclerotic cardiovascular disease (ASCVD). However, the prognostic implications of low LDL cholesterol levels in patients without previous ASCVD and without statin use remain elusive. Methods: From a nationwide cohort, 2,432,471 participants without previous ASCVD or statin use were included. For myocardial infarction (MI) and ischemic stroke (IS), participants were followed-up from 2009 to 2018. They were stratified according to 10-year ASCVD risk (

Abstract Hepatic ischemia‐reperfusion injury (HIRI) is a prevalent issue during liver resection and transplantation, with currently no cure or FDA‐approved therapy. A promising drug, Cyclosporin A (CsA), ameliorates HIRI by maintaining mitochondrial homeostasis but has systemic side effects due to its low bioavailability and high dosage requirements. This study introduces a biomimetic CsA delivery system that directly targets hepatic lesions using mesenchymal stem cell (MSC) membrane‐camouflaged liposomes. These hybrid nanovesicles (NVs), leveraging MSC‐derived proteins, demonstrate efficient inflammatory chemotaxis, transendothelial migration, and drug‐loading capacity. In a HIRI mouse model, the biomimetic NVs accumulated at liver injury sites entered hepatocytes, and significantly reduced liver damage and restore function using only one‐tenth of the CsA dose typically required. Proteomic analysis verifies the protection mechanism, which includes reactive oxygen species inhibition, preservation of mitochondrial integrity, and reduced cellular apoptosis, suggesting potential for this biomimetic strategy in HIRI intervention.

At present, energy storage in industrial and commercial scenarios has problems such as poor protection levels, flexible deployment, and poor battery performance. Aiming at the pain points and storage application scenarios of industrial and commercial energy, this paper proposes liquid cooling solutions. In this paper, the box structure was first studied to optimize the structure, and based on the liquid cooling technology route, the realization of an industrial and commercial energy storage thermal management scheme for the integrated cabinet was studied to ensure that the temperature between the cabinets was consistent and reduce the system capacity loss caused by the liquid-cooled battery module was inconsistent. The industrial and commercial energy storage integrated cabinet comprehensively considers the flexible deployment of the system, enhances the protection level of the cabinet, and the structural strength of the cabinet, and improves the temperature balance characteristics of the battery module in the cabinet.

Objectives: Evidence on the link between long-term ambient particulate matter (PM) exposures and childhood sleep disorders were scarce. We examined the associations between long-term exposures to PM2.5 and PM1 (PM with an aerodynamic equivalent diameter

Abstract Recently, HfO2‐based ferroelectric thin films have attracted widespread interest in developing next‐generation nonvolatile memories. To form a metastable ferroelectric orthorhombic phase in HfO2, a post‐annealing process is typically necessary. However, the microscopic mechanism underlying the effect of annealing temperature on ferroelectric domain nucleation and growth is still obscure, despite its importance in optimizing the operation speed of HfO2‐based devices. In this study, the ferroelectric properties and polarization switching of Hf0.5Zr0.5O2 thin films annealed at different temperatures (550–700 °C) are systematically investigated. Evidently, the crystal structure, remnant polarization, and dielectric constant monotonically change with annealing temperature. However, microscopic piezoresponse force microscopy images as well as macroscopic switching current measurements reveal non‐monotonic changes in the polarization switching speed with annealing temperature. This intriguing behavior is ascribed to the difference in the ferroelectric‐domain nucleation process induced by the amount of oxygen vacancies in the Hf0.5Zr0.5O2 thin films annealed at different temperatures. This work demonstrates that controlling the defect concentration of ferroelectric HfO2 by tuning the post‐annealing process is critical for optimizing device performance, particularly polarization switching speed.

Based on the textual-analyzed data covering 2148 IPO firms in China’s stock market during the 2007–2018 period, the authors’ purpose is to examine the influence of anti-takeover provision (ATP) adoption on initial public offerings (IPO) underpricing and identify the reducing effect of the former. The authors examine the sample consisting of Chinese A-share listed IPO firms between 2007 and 2018 from China Stock Market Accounting Research and Chinese Research Data Services, with ATP data collected from the IPO firm chapters. Specifically, the authors use text analysis to identify whether there are ATPs in the IPO firm chapters, as well as the number of ATPs. H1: IPO underpricing is less severe for firms adopting ATPs. H2: The effect of ATP adoption on IPO underpricing is more salient for firms in worse information environments. The authors examine the influence of ATP adoption on IPO underpricing and identify the reducing effect of the former. This effect can be explained by the fact that adopting ATPs in IPO firm chapters can reduce information asymmetry to a large extent by helping external investors obtain more private information, which alleviates IPO underpricing. The authors also find that the reducing effect is more significant in the worsened information environment. Furthermore, the authors explore the influence of adopting ATPs on other IPO characteristics and find positive effects on IPO over-subscription, funds raised and trading activity and negative effects on listing fees. This study mainly contributes to the literature from the following two aspects. First, the study enriches the literature about the influencing factors of IPO underpricing. Second, the study also enriches the literature about the economic consequences of ATP adoption. This study also has important policy implications. With the coming of the era of decentralized ownership in China’s capital market, ATP adoption has become more important and attracted more attention. Also, investors focus more on pricing efficiency. The findings in this paper provide a more comprehensive understanding of the relationship between ATP adoption and IPO underpricing.

Abstract Aims Evidence for the effectiveness of left ventricular (LV) unloading in patients who received venoaterial extracorporeal membrane oxygenation (VA‐ECMO) for acute myocardial infarction (AMI) or non‐AMI induced cardiogenic shock (CS) is limited. The aim of the present study was to compare the effect of LV unloading in AMI‐induced and non‐AMI‐induced CS. Methods and results This is a single‐centre retrospective observational study of patients with CS undergoing VA‐ECMO from January 2011 to March 2019. Patients were classified as AMI‐induced and non‐AMI‐induced CS. The association of LV unloading with 90‐day mortality in both groups was analysed using Cox proportional hazard regression analysis. Results Of the 128 CS patients, 71 (55.5%) patients received VA‐ECMO due to AMI‐induced CS, and the remaining 57 (44.5%) received VA‐ECMO due to non‐AMI‐induced CS. The modality of LV unloading was predominantly with IABP (94.5%). In the AMI‐induced CS group, LV unloading did not reduce 90‐day mortality (adjusted hazard ratio 1.96, 95% confidence interval 0.90–4.27, P = 0.089). However, in the non‐AMI‐induced CS group, LV unloading combined with VA‐ECMO significantly reduced 90‐day mortality (adjusted hazard ratio 0.37, 95% confidence interval 0.14–0.96, P = 0.041; P for interaction = 0.029) as compared with those who received VA‐ECMO alone. Conclusions LV unloading with VA‐ECMO may reduce 90‐day mortality compared with VA‐ECMO alone in patients with non‐AMI‐induced CS, but not in AMI‐induced CS.

Xanthogranulomatous (XG) inflammatory disease is a rare benign disease involving various organs, including the gallbladder, bile duct, pancreas, spleen, stomach, small bowel, colon, appendix, kidney, adrenal gland, urachus, urinary bladder, retroperitoneum, and female genital organs. The imaging features of XG inflammatory disease are nonspecific, usually presenting as a heterogeneous solid or cystic mass. The disease may also extend to adjacent structures. Due to its aggressive nature, it is occasionally misdiagnosed as a malignant neoplasm. Herein, we review the radiological features and clinical manifestations of XG inflammatory diseases in various organs of the abdomen and pelvis.

ABSTRACTPurpose Hypertensive disorder complicating pregnancy (HDCP) is a serious clinical disorder syndrome during pregnancy. This study aims at finding novel targets for HDCP therapy.Methods HDCP-related mRNAs were firstly screened out and subjected to gene enrichment analysis. We chose protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) as the research object. Thirty-nine HDCP patients at 32 to 40 weeks of gestation were selected as the HDCP group, and 39 normal controls who received cesarean section delivery at 37–42 weeks of pregnancy were enrolled in this study. Chorionic villi samples were collected within 30 min of delivery. The apoptosis of isolated placental trophoblasts was monitored to investigate the regulatory role of PRKAA2.Results PRKAA2 expression was further proven to be enhanced in the placental tissues of HDCP patients compared with that of normal puerpera. Subsequently, the results of flow cytometry analysis and western blot indicated that PRKAA2 overexpression accelerated primary placental cell apoptosis, while its knockdown attenuated cell apoptosis. Mechanistically, we determined that the level of PRKAA2 succinylation was elevated in the placental tissue of HDCP patients. Through in vitro succinylation assay and mutagenesis, we confirmed that sirtuin 5 (SIRT5) interacts with PRKAA2 at K69 and K260 to induce PRKAA2 desuccinylation. SIRT5 regulated primary HDCP cell apoptosis through PRKAA2. Finally, the animal study revealed that PRKAA2 elevates the systolic blood pressure of HDCP rat model.Conclusion Our findings indicated that SIRT5-mediated PRKAA2 succinylation modulates placental cell apoptosis in HDCP, suggesting that PRKAA2 is a potential therapeutic target for HDCP treatment.

Background Cardiovascular disease (CVD) is the most important comorbidity in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations not only contribute to COPD progression but may also elevate the risk of CVD. This study aimed to determine whether COPD exacerbations increase the risk of subsequent CVD events using up to 15 years of prospective longitudinal follow‐up data from the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study. Methods and Results The COPDGene study is a large, multicenter, longitudinal investigation of COPD, including subjects at enrollment aged 45 to 80 years with a minimum of 10 pack‐years of smoking history. Cox proportional hazards models and Kaplan‐Meier survival curves were used to assess the risk of a composite end point of CVD based on the COPD exacerbation rate. Frequent exacerbators exhibited a higher cumulative incidence of composite CVD end points than infrequent exacerbators, irrespective of the presence of CVD at baseline. After adjusting for covariates, frequent exacerbators still maintained higher hazard ratios (HRs) than the infrequent exacerbator group (without CVD: HR, 1.81 [95% CI, 1.47–2.22]; with CVD: HR, 1.92 [95% CI, 1.51–2.44]). This observation remained consistently significant in moderate to severe COPD subjects and the preserved ratio impaired spirometry population. In the mild COPD population, frequent exacerbators showed a trend toward more CVD events. Conclusions COPD exacerbations are associated with an increased risk of subsequent cardiovascular events in subjects with and without preexisting CVD. Patients with COPD experiencing frequent exacerbations may necessitate careful monitoring and additional management for subsequent potential CVD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00608764.

Objective: Low-density lipoprotein receptor-related protein-1 (LRP1) regulates energy homeostasis, blood–brain barrier integrity, and metabolic signaling in the brain. Deficiency of LRP1 in inhibitory gamma-aminobutyric acid (GABA)ergic neurons causes severe obesity in mice. However, the impact of LRP1 in inhibitory neurons on memory function and cognition in the context of obesity is poorly understood. Methods: Mice lacking LRP1 in GABAergic neurons (Vgat-Cre; LRP1loxP/loxP) underwent behavioral tests for locomotor activity and motor coordination, short/long-term and spatial memory, and fear learning/memory. This study evaluated the relationships between behavior and metabolic risk factors and followed the mice at 16 and 32 weeks of age. Results: Deletion of LRP1 in GABAergic neurons caused a significant impairment in memory function in 32-week-old mice. In the spatial Y-maze test, Vgat-Cre; LRP1loxP/loxP mice exhibited decreased travel distance and duration in the novel arm compared with controls (LRP1loxP/loxP mice). In addition, GABAergic neuron-specific LRP1-deficient mice showed a diminished capacity for performing learning and memory tasks during the water T-maze test. Moreover, reduced freezing time was observed in these mice during the contextual and cued fear conditioning tests. These effects were accompanied by increased neuronal necrosis and satellitosis in the hippocampus. Importantly, the distance and duration in the novel arm, as well as the performance of the reversal water T-maze test, negatively correlated with metabolic risk parameters, including body weight, serum leptin, insulin, and apolipoprotein J. However, in 16-week-old Vgat-Cre; LRP1loxP/loxP mice, there were no differences in the behavioral tests or correlations between metabolic parameters and cognition. Conclusions: Our findings demonstrate that LRP1 from GABAergic neurons is important in regulating normal learning and memory. Metabolically, obesity caused by GABAergic LRP1 deletion negatively regulates memory and cognitive function in an age-dependent manner. Thus, LRP1 in GABAergic neurons may play a crucial role in maintaining normal excitatory/inhibitory balance, impacting memory function, and reinforcing the potential importance of LRP1 in neural system integrity.

Abstract Outbreaks of infectious viruses offer a formidable challenge to public healthcare systems and early detection of viruses is essential for preventing virus propagation. In this work, an ultrasensitive plasmon‐enhanced fluorescence resonance energy transfer (FRET) biosensor based on core‐shell upconversion nanoparticle (csUCNP) and gold nanoparticle (AuNP) for accurate detection of SARS‐CoV‐2 viral RNA is presented. In this biodetection assay, the Tm3+/Er3+ co‐doped csUCNP NaGdF4:Yb/Tm@NaYF4:Yb/Er acts as an energy donor and AuNP serves as an energy acceptor. The upconversion emission of Tm3+ and the design of the core‐shell structure led to a simultaneous surface plasmon effect of AuNP. The localized surface plasmon resonance (LSPR) arising from collective oscillations of free electrons significantly enhanced FRET efficiency between Er3+ and AuNP. The as‐prepared biosensor obtained a limit of detection (LOD) as low as 750 am, indicating that the integration of FRET and surface plasmon into one biodetection assay significantly boosted the sensitivity of the biosensor. In addition, samples extracted from clinical samples are also utilized to validate the effectiveness of the biosensor. Therefore, this innovative plasmon‐enhanced FRET biosensor based on Tm3+/Er3+ co‐doped csUCNP may pave the way for rapid and accurate biodetection applications.

Abstract Introduction Characteristics of patients in clinical trials may differ from those of real‐world patients. Our objective was to describe biomarker testing and outcomes among patients with advanced non‐small cell lung cancer (aNSCLC) in a real‐world setting. Methods This retrospective cohort study included patients ≥18 years old, diagnosed with stage IIIB/C or IV NSCLC, and in the TEMPUS oncology dataset from January 1, 2012, to December 31, 2020. Patient characteristics associated with biomarker testing were evaluated in patients with positive biomarkers using univariate logistic regression models. Cox proportional hazard models were used to estimate median survival. Results Of 9540 patients included, 41.7% had biomarker testing, and 2158 had a positive biomarker result. Men (vs women; odds ratio [OR], 0.82; 95% CI: 0.74–0.91), Black patients (vs White; OR, 0.83; 95% CI: 0.72–0.97), patients with squamous (OR, 0.22; 95% CI: 0.19–0.25) or unknown histology (OR, 0.53; 95% CI: 0.45–0.61) (vs non‐squamous histology), and patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 2+ (OR, 0.69; 95% CI: 0.57–0.84) or missing (OR, 0.56; 95% CI: 0.48–0.66) (vs ECOG PS of 0) were less likely to undergo biomarker testing. Patients with positive biomarkers who received NCCN‐recommended treatment options (55.7%) had significantly longer median overall survival (OS) (hazard ratio [HR], 0.84; 95% CI: 0.75–0.95) and real‐world progression‐free survival (rwPFS) (HR, 0.68; 95% CI: 0.62–0.75). Conclusion More than 50% of patients were untested for biomarkers. Patients who were less likely to be tested included men, Black patients, current smokers, patients with squamous aNSCLC, and patients with an ECOG PS of 2+. Patients with positive biomarkers who received NCCN‐recommended treatment options had significantly longer OS and PFS.

Abstract In this study, numerical simulation was employed to predict the performance and internal flow characteristics of the inlet of an axial-flow pump by assigning an absolute flow angle to the inlet guide vane (IGV) trailing-edge flow. Further, the finite volume method based on the three-dimensional Reynolds-averaged Navier–Stokes equations was employed to discretize the governing equations. The shear stress transport model was used as the turbulence model, and an appropriate number of nodes were selected for the hexahedral grid system through a grid-dependency test. The performance curve and changes in the internal flow field were investigated based on the variation in the flow angle at the inlet of the axial-flow pump. These results can be used to establish an efficient operational plan by adjusting the IGV angle of IGV when installing a variable IGV for an axial-flow pump.

ABSTRACTBamboo root as by-product of bamboo shoot processing is rich in dietary fibre. The protective effects of bamboo root dietary fibre (BRDF) with different intake dose on the hyperlipidaemia mice were investigated. The mice weight in the high dose (HD) group was 31.18 g, lower than that of high fat diet (HFD) group (33.71 g, p

Abstract The vision Transformer structure performs better in salient object detection than the convolutional neural network (CNN)‐based approach. Vision Transformer predicts saliency by modelling long‐range dependencies from sequence to sequence with convolution‐free. It is challenging to distinguish the salient objects' location and obtain structural details for the influence of extracting irrelevant contextual information. A novel saliency sparse Transformer network is proposed to exploit sparse attention to guide saliency prediction. The convolution‐like with dilation in the token to token (T2T) module is replaced to achieve relationships in larger regions and to improve contextual information fusion. An adaptive position bias module is designed for the Vision Transformer to make position bias suitable for variable‐sized RGB images. A saliency sparse Transformer module is designed to improve the concentration of attention on the global context by selecting the Top‐k of the most relevant segments to improve the detection results further. Besides, cross‐modality to exploit the complementary RGB and depth modality fusion module (CMF) is used to take advantage of the complementary RGB image features and spatial depth information to enhance the feature fusion performance. Extensive experiments on multiple benchmark datasets demonstrate this method's effectiveness and superiority that it is suitable for saliency prediction comparable to state‐of‐the‐art RGB and RGB‐D saliency methods.

Astragalus membranaceus and Cinnamomum cassia are used as spices and flavorful ingredients, or medicinal herbs with pharmacological effects. In this study, the hair-growth-promoting effects of the YH complex, a newly developed formula consisting of membranaceus and C. cassia, are investigated with the prediction of its molecular mechanism. The target gene of the YH complex was about 74.8% overlapped with the gene set of ‘Hair growth’ on the GO Biological Process database. The oral administration of the YH complex promoted hair regrowth and increased hair-shaft thickness in depilated hair loss mice. In addition, the anagen/telogen hair follicle ratio was significantly increased by the YH complex. The growth factors affecting the growth of hair follicles were dose-dependently increased by treatment with the YH complex. The Wnt/β-catenin signaling pathway expressions in skin tissues were apparently increased by the administration of the YH complex. In conclusion, the YH complex consisting of A. membranaceus and C. cassia induced hair follicle differentiation and preserved the growing-anagen phase by increasing growth factors and the Wnt/β-catenin signaling pathway, leading to the restoration of hair loss. The YH complex can be a remedy for hair loss diseases, such as alopecia areata, androgenetic alopecia, telogen effluvium, and chemotherapy-induced alopecia.

Abstract Introduction Nephrotic syndrome (NS) is characterized by renal sodium and water retention. The mechanisms are not fully elucidated. Methods The NS rat model was established by single intraperitoneal injection of 100 mg/kg puromycin aminonucleoside (PAN). The plasma electrolyte level and urinary sodium excretion were monitored dynamically. The changes of some sodium transporters, including epithelial Na+ channel (ENaC), Na+/H+ exchanger 3 (NHE3), Na+-K+-2Cl− cotransporter 2 (NKCC2) and Na+-Cl− cotransporter (NCC) in renal cortex at different time points and the level of peripheral circulation factors were detected. Results The urinary sodium excretion of the model group increased significantly on the first day, then decreased compared with the control group, and there was no significant difference between the model group and the control group on the 12th day. The changes of peripheral circulation factors were not obvious. Some sodium transporters in renal cortex increased in varying degrees, while NKCC2 decreased significantly compared with the control group. Conclusions The occurrence of NS edema may not be related to the angiotensin system. The decrease of urinary sodium excretion is independent of the development of albuminuria. During the 18 days of observation, it can be divided into three stages: sodium retention, sodium compensation, and simple water retention. The mechanism is related to the increased expression of α-ENaC, γ-ENaC, NHE3 and NCC in a certain period of time, the compensatory decrease of NKCC2 expression and the continuous increase of aquaporin 2 (AQP2) expression.

The incidence of cardiovascular diseases, such as high blood pressure, is increasing worldwide, owing to population aging and irregular lifestyle habits. Previous studies have reported the vasorelaxant effects of Prunus yedoensis bark methanol extract. However, various solvent extracts of P. yedoensis bark and their vascular relaxation mechanisms have not been sufficiently studied. We prepared extracts of P. yedoensis bark using various solvents (water, 30% ethanol, and 70% ethanol). P. yedoensis bark 30% ethanol extract (PYB-30E) decreased the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in human umbilical vein endothelial cells (HUVECs) activated with 200 ng/mL TNF-α. Additionally, PYB-30E showed vasodilatory effects on isolated rat aortic rings. This was confirmed to be the result of the activation of the NO/cGMP pathway, regulation of non-selective calcium-activated K+ channels, and calcium channel blockade. Additionally, PYB-30E significantly reduced systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR). Taken together, our results indicated that PYB-30E is a candidate functional material with preventive and therapeutic effects against hypertension.

To solve the difficulties in applying the compressive creep test method for normal concrete to UHPC and to verify the validity of the recently proposed ASTM C 1856 standard test method, this study performed compressive creep tests on UHPC with the variables of specimen size, sustained load intensity, fiber length, and strain measuring method. The experimental results show that the strain meter method using the standard rod had limitations due to the error in the verification process using the standard rod and the observation error of the measurer, and a sustained load intensity of 15% to 40% of the actual compressive strength is preferable. It was found that it is possible to perform a compressive creep test for UHPC using a specimen with a size of ϕ75 mm or more, and the fiber length did not affect the creep behavior of the UHPC up to 19.5 mm. As a result of comparing the UHPC creep test results with the creep prediction model, the B3 model was found to most accurately predict the UHPC creep behavior. The creep coefficient pattern of the B3 model was very similar to the measured results and well reflects the effects of the mixing ratio and compressive strength of UHPC.

Fermentation is a process that improves health functionality by inducing the production and increase of bioactive compounds. In this study, to standardize the fermentation process for Benincasa hispida, marker compounds that are increased or produced during fermentation were identified based on UPLC-QTOF-MS/MS. Analysis method verification and content analysis were conducted using HPLC-PDA. The marker compounds produced or increased in content were identified as 2-furoic acid, 2,3-dihydroxybenzoic acid, and rubinaphthin A by comparing their retention times, UV and MS spectra, and molecular formulas with those reported in previous studies. In addition, the increase in the content of the marker compounds by fermentation was confirmed, and the analytical method was validated by measuring its specificity, linearity, limit of detection and quantitation, precision, and accuracy. These results suggest that the developed fermentation process, marker compound identification, and verified analysis method can be applied to develop potential functional food ingredients from fermented B. hispida.

IntroductionMesenchymal-epidermal transition factor gene amplification (METamp) is being investigated as a therapeutic target in advanced non-small cell lung cancer (NSCLC). We reviewed the epidemiology and disease characteristics associated with primary and secondary METamp, as well as the testing procedures used to identify METamp, in advanced NSCLC. Economic and humanistic burdens, and the practice patterns and treatments under investigation for METamp were also examined.MethodsEmbase and Medline (via ProQuest), ClinicalTrials.gov, and Cochrane Controlled Register of Trials (2015–2022) were systematically searched. Conference abstracts were searched via Embase and conference proceedings websites (2020–2022). The review focused on evidence from the United States; global evidence was included for identified evidence gaps.ResultsThe median rate of primary METamp in NSCLC across the references was 4.8% (n=4 studies) and of secondary METamp (epidermal growth factor receptor [EGFR]-mutant NSCLC) was 15% (n=10). Next-generation sequencing (NGS; n=12) and/or fluorescence in situ hybridization (FISH; n=11) were most frequently used in real-world studies and FISH testing most frequently used in clinical trials (n=9/10). METamp definitions varied among clinical trials using ISH/FISH testing (MET to chromosome 7 centromere ratio of ≥1.8 to ≥3.0; or gene copy number [GCN] ≥5 to ≥10) and among trials using NGS (tissue testing: GCN ≥6; liquid biopsy: MET copy number ≥2.1 to >5). Limited to no data were identified on the economic and humanistic burdens, and real-world treatment of METamp NSCLC. Promising preliminary results from trials enrolling patients with EGFR-mutated, METamp advanced NSCLC progressing on an EGFR-tyrosine kinase inhibitor (TKI) were observed with MET-TKIs (i.e., tepotinib, savolitinib, and capmatinib) in combination with EGFR-TKIs (i.e., gefitinib and osimertinib). For metastatic NSCLC and high-level METamp, monotherapy with capmatinib, crizotinib, and tepotinib are recommended in the 2022 published NSCLC NCCN Guidelines.ConclusionPrimary METamp occurs in approximately 5% of NSCLC cases, and secondary METamp in approximately 15% of cases previously treated with an EGFR inhibitor. Variability in testing methods (including ISH/FISH and NGS) and definitions were observed. Several treatments are promising in treating METamp NSCLC. Additional studies evaluating the clinical, economic, and humanistic burdens are needed.

Resistin plays an important role in the pathophysiology of obesity-mediated insulin resistance in mice. However, the biology of resistin in humans is quite different from that in rodents. Therefore, the association between resistin and insulin resistance remains unclear in humans. Here, we tested whether and how the endocannabinoid system (ECS) control circulating peripheral blood mononuclear cells (PBMCs) that produce resistin and infiltrate into the adipose tissue, heart, skeletal muscle, and liver, resulting in inflammation and insulin resistance. Using human PBMCs, we investigate whether the ECS is connected to human resistin. To test whether the ECS regulates inflammation and insulin resistance in vivo, we used 2 animal models such as “humanized” nonobese diabetic/Shi-severe combined immunodeficient interleukin-2Rγ (null) (NOG) mice and “humanized” resistin mouse models, which mimic human body. In human atheromatous plaques, cannabinoid 1 receptor (CB1R)-positive macrophage was colocalized with the resistin expression. In addition, resistin was exclusively expressed in the sorted CB1R-positive cells from human PBMCs. In CB1R-positive cells, endocannabinoid ligands induced resistin expression via the p38–Sp1 pathway. In both mouse models, a high-fat diet increased the accumulation of endocannabinoid ligands in adipose tissue, which recruited the CB1R-positive cells that secrete resistin, leading to adipose tissue inflammation and insulin resistance. This phenomenon was suppressed by CB1R blockade or in resistin knockout mice. Interestingly, this process was accompanied by mitochondrial change that was induced by resistin treatment. These results provide important insights into the ECS–resistin axis, leading to the development of metabolic diseases. Therefore, the regulation of resistin via the CB1R could be a potential therapeutic strategy for cardiometabolic diseases.

ABSTRACT: Background: Hypertension and dyslipidemia significantly contribute to cardiovascular disease development. Their coexistence poses challenges in managing multiple medications, influencing treatment adherence. Objective: This study aimed to assess the efficacy and safety of a combined treatment approach using a fixed-dose combination therapy. Methods: This multicenter, 8-week, randomized, double-blind, Phase IV trial was named Telmisartan/Amlodipine/Rosuvastatin from Samjin Pharmaceuticals and evaluated the efficacy and safety of fixed-dose combination treatment in patients with essential hypertension and dyslipidemia. They were randomly assigned to 2 fixed-dose combination therapy groups, telmisartan 40 mg/amlodipine 5 mg/rosuvastatin 10 mg (TEL/ALD/RSV) or amlodipine 5 mg/atorvastatin 10 mg (ALD/ATV) after washout/run-in period. The primary outcomes were the change in mean sitting systolic blood pressure and the percentage change of LDL-C after 8 weeks of medical treatment. Adverse drug reactions and events were assessed. Results: Of a total of 304 patients who underwent screening, 252 were randomized to the TEL/ALD/RSV group (125 patients) and the ALD/ATV group (127 patients). The mean (SD) ages of the TEL/ALD/RSV group and the ALD/ATV group were 67.4 (11.3) and 68.2 (10.6) years, respectively (P = 0.563). The least-squares mean (SE) in mean sitting systolic blood pressure changes between the 2 groups were –16.27 (0.93) mm Hg in the TEL/ALD/RSV group, –6.85 (0.92) mm Hg in the ALD/ATV group (LSM difference = –9.42 mm Hg; 95% CI, –11.99 to –6.84; P < .001). For LDL-C level changes, a significant difference was noted between the 2 groups: –50.03% (1.18%) in the TEL/ALD/RSV group, –39.60% (1.17%) in the ALD/ATV group (LSM difference = –10.43%; 95% CI, –13.70 to –7.16; P < .001). No severe adverse events were observed. Conclusions: TEL/ALD/RSV proved to be more efficient than ALD/ATV in lowering blood pressure and reducing LDL-C levels among patients with hypertension and dyslipidemia, with no notable safety concerns. (Curr Ther Res Clin Exp. 2024; XX:XXX–XXX). ClinicalTrials.gov identifier: NCT03860220.

Abstract Liquid biopsy, a noninvasive technique to obtain tumor information from body fluids, is an emerging technology for cancer diagnosis, prognosis, and monitoring, providing crucial support for the realization of precision medicine. The main biomarkers of liquid biopsy include circulating tumor cells, circulating tumor DNA, microRNA, and circulating tumor exosomes. Traditional liquid biopsy detection methods include flow cytometry, immunoassay, polymerase chain reaction (PCR)‐based methods, and next‐generation sequencing (NGS)‐based methods, which are time‐consuming, labor‐intensive, and cannot reflect cell heterogeneity. Droplet‐based microfluidics with high throughput, low contamination, high sensitivity, and single‐cell/single‐molecule/single‐exosome analysis capabilities have shown great potential in the field of liquid biopsy. This review aims to summarize the recent development in droplet‐based microfluidics in liquid biopsy for cancer diagnosis.

Recently, interest in functional foods that enhance immunity has increased owing to social and environmental changes. In this study, we investigated the immunomodulatory effects of fermented Benincasa hispida extract (FBE) in normal BALB/c mice. FBE enhanced nitric oxide (NO) production and natural killer (NK) cell activity. In addition, FBE increased perforin 1 and granzyme B production, demonstrating increased CD8+ cytotoxic T cell activity. CD4+ helper T cell activity was analyzed by measuring Th1 and Th2 cell-related cytokines. FBE enhanced the activity of Th1 and Th2 cells while maintaining their balance. Furthermore, FBE increased the mRNA expression of regulatory T cell-related genes (foxp3, IL-10, and TGF-β) that control excessive immune response, and upregulated the production of IgA and short-chain fatty acids (SCFA) that improve the immune environment in the intestine. Taken together, our results indicate that FBE represents a functional food ingredient with potential immunomodulatory activities.

Abstract Background This study aimed to examine the associations between osteoporosis and hand grip strength (HGS), a surrogate marker of muscular strength, among Korean adults stratified by body mass index (BMI), age, and renal function. Methods This study was conducted using the data obtained from the Korea National Health and Nutrition Examination Survey 2015–2019, a cross-sectional and nationally representative survey performed by the Korea Centers for Diseases Control and Prevention. Results Of the 26,855 subjects included in this study, those with low muscle strength (LMS) and normal muscle strength were showed in 4,135 (15.4%) and 22,720 (84.6%) subjects, respectively. The osteoporotic subjects had a higher prevalence rate for LMS than those without osteoporosis after adjusting for age [odds ratio (OR), 1.684; 95% confidence interval (CI), 1.500–1.890). The subjects with osteoporosis and BMI

Abstract Background Low-grade inflammation plays a role in the pathogenesis of metabolic syndrome (MetS), and measuring levels of inflammatory molecules, such as high-sensitivity C-reactive protein (hs-CRP), may indicate Mets progression. Serum uric acid (SUA) has also been identified as an independent risk factor for MetS. This study aimed to investigate the association between MetS components and levels of serum hs-CRP and SUA using representative and reliable data for the Korean population. Methods This study used the data of the Korea National Health and Nutrition Examination Survey 2016–2018, a cross-sectional and nationally representative survey performed by the Korean Centers for Disease Control and Prevention. Results We analysed the data of 13,454 individuals. High hs-CRP levels were observed in 1,164 (8.7%) subjects while 3,296 (24.5%) subjects had high SUA levels. Moreover, hs-CRP was negatively correlated with serum high-density lipoprotein (HDL) (OR, 1.703; 95% CI, 1.431–2.027). When stratified by sex, this trend remained, but the correlation was stronger in women than in men. Furthermore, high SUA levels were significantly associated with hypertension (HTN) (OR, 1.399; 95% CI, 1.210–1.616), hypertriglyceridemia (OR, 1.735; 95% CI, 1.486–2.026), and low HDL (OR, 1.257; 95% CI, 1.106–1.429), but not with diabetes mellitus (DM) (OR, 0.478; 95% CI, 0.382–0.597). When grouped by sex, this trend remained, however, all MetS components were found to be more prevalent in women with high SUA. Conclusions Our findings showed that low HDL was more prevalent in subjects with high hs-CRP, and high SUA levels were observed in subjects with HTN, hypertriglyceridemia, and low HDL. However, the prevalence of high SUA was lower in diabetic subjects.

Abstract Molecular interplay between host epigenetic factors and viral proteins constitutes an intriguing mechanism for sustaining hepatitis B virus (HBV) life cycle and its chronic infection. HBV encodes a regulatory protein, HBx, which activates transcription and replication of HBV genome organized as covalently closed circular (ccc) DNA minichromosome. Here we illustrate how HBx accomplishes its task by hijacking Spindlin1, an epigenetic reader comprising three consecutive Tudor domains. Our biochemical and structural studies have revealed that the highly conserved N-terminal 2–21 segment of HBx (HBx2–21) associates intimately with Tudor 3 of Spindlin1, enhancing histone H3 “K4me3-K9me3” readout by Tudors 2 and 1. Functionally, Spindlin1-HBx engagement promotes gene expression from the chromatinized cccDNA, accompanied by an epigenetic switch from an H3K9me3-enriched repressive state to an H3K4me3-marked active state, as well as a conformational switch of HBx that may occur in coordination with other HBx-binding factors, such as DDB1. Despite a proposed transrepression activity of HBx2-21, our study reveals a key role of Spindlin1 in derepressing this conserved motif, thereby promoting HBV transcription from its chromatinized genome.

In this paper, we investigate the nonlinear characteristics of the flow in a two-dimensional and a three-dimensional counterflow model with symmetrical structures. Through numerical simulations, we obtain the velocity fields of the fluid flow in these models for different Re. The numerical results are analyzed to understand the nonlinear characteristics and differences between the two-dimensional and three-dimensional models. The findings indicate that, when Re varies, both the two-dimensional and three-dimensional models exhibit solution bifurcations and nonlinear phenomena such as symmetry breaking, self-sustained oscillations, and chaos. As Re increases, the two-dimensional counterflow model displays a unique solution, an asymmetric solution, and an oscillating solution. Specifically, when Re < 4320, both the laminar and turbulent models show a unique, symmetric, and steady-state velocity distribution. For 4652 < Re < 8639, the two-dimensional model solutions are not unique, presenting a pair of antisymmetric, asymmetric solutions that nevertheless remain steady-state. When Re > 8639, the solution becomes oscillatory and unsteady. The three-dimensional counterflow model exhibits a two-dimensional solution independent of the Z-axis. At Re = 4652, both the three-dimensional and two-dimensional models produce the same unique, symmetric, and steady-state velocity distribution with no three-dimensional flow (W = 0). At Re = 8639, the three-dimensional model solutions are not unique, showing a pair of antisymmetric, asymmetric solutions, while still being steady and time-independent. At Re = 87,627, the three-dimensional model solution becomes oscillatory and unsteady. By elucidating the flow characteristics and nonlinear features of both models, this study compares the differences between the two-dimensional and three-dimensional flows, thereby laying the groundwork for simplification of the problem and further theoretical research.

In recent years, cell migration assays (CMAs) have emerged as a tool to study the migration of cells along with their physiological responses under various stimuli, including both mechanical and bio-chemical properties. CMAs are a generic system in that they support various biological applications, such as wound healing assays. In this paper, we review the development of the CMA in the context of its application to wound healing assays. As such, the wound healing assay will be used to derive the requirements on CMAs. This paper will provide a comprehensive and critical review of the development of CMAs along with their application to wound healing assays. One salient feature of our methodology in this paper is the application of the so-called design thinking; namely we define the requirements of CMAs first and then take them as a benchmark for various developments of CMAs in the literature. The state-of-the-art CMAs are compared with this benchmark to derive the knowledge and technological gap with CMAs in the literature. We will also discuss future research directions for the CMA together with its application to wound healing assays.

Aquaculture farms cultivating Saccharina japonica are highly active in Wando, Korea, and Rongcheng, China. However, the yield of S. japonica significantly declined in the Rongcheng region in 2022 compared to previous records, whereas that in Wando remained at a normal level, presumably due to the presence of a pathogenic microbiome. We used environmental DNA (eDNA) metagenomic analysis to compare the microbial compositions of seawater from aquaculture farms in Wando and Rongcheng. Seawater samples were collected from one Korean site in Wando (WA) and two Chinese sites in Ailian Bay (AB) and Lidao Bay (LB). Metagenomic analysis focusing on the microbial 16S rRNA identified 38 phyla and 58 families of microbiomes in all regions. Potentially pathogenic bacterial groups associated with S. japonica in AB and LB were more abundant than in WA, suggesting their potential influence on mortality and the decline in the harvest yield of S. japonica. The microbial composition of WA was distinguished from those of the other two sites, which clustered together with higher similarity. Since the S. japonica aquaculture industry is important for both countries, this comparative eDNA monitoring is a valuable initiation towards the next step of problem-solving practices in coastal management in these two aquaculture systems.

The problems faced are uneven football field surface, uneven grass growth, many pebbles and boulders, stagnant and muddy during the rainy season and fractures in the soil during the dry season which make the field not of a good standard for use and have an impact on the incidence of injuries to field users. This study aims to improve the quality of grass for football field using quality local grass Cynodon dactylon in order to overcome the problem of bad fields and avoid field’s users injury. The method is through field rehabilitation technology by improving the surface design and soil media profile as well as the use of quality local grass. The rehabilitation technology includes improving the surface of the field to improve drainage by designing a “geger sapi” shape. The assessment of the rehabilitation results used a qualitative approach with a questionnaire survey to the local community of field users. The results of field grass rehabilitation make the quality of grass in the field after rehabilitation better growth by 45%, perception grass quality was very good by 43%, the surface of the field is flatter, no gravel and surface rocks are found so the flooded were not found by 83%. Field conditions with better grass quality also reduce the frequency of injuries incidents of player during competition about 61%. Hence, field grass rejuvenation benefits the environment and public health. This great benefit will increase the comfort and closeness between the local community.