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Marein is a flavonoid compound that reduces blood glucose and lipids and has a protective effect in diabetes. However, the effect and mechanism(s) of marein on renal endothelial-mesenchymal transition in diabetic kidney disease (DKD) have not been elucidated. In this study, single-cell sequencing data on DKD were analyzed using a bioinformation method, and the data underwent reduced dimension clustering. It was found that endothelial cells could be divided into five subclusters. The developmental sequence of the subclusters was 0, 1, 4, 2, and 3, of which subcluster 3 had the most interstitial phenotype. The expression of mesenchymal marker protein:Vimentin(VIM), Fibronectin(FN1), and fibroblast growth factor receptor 1 (FGFR1) increased with the conversion of subclusters. In db/db mice aged 13-14 weeks, which develop DKD complications after 8-12 weeks of age, marein reduced blood levels of glucose, creatinine, and urea nitrogen, improved structural damage in kidney tissue, and reduced collagen deposition and the expression of FN1 and VIM. Marein also up-regulated autophagy marker:Light chain 3II/I(LC3II/I) and decreased FGFR1 expression in renal tissue. In an endothelial-mesenchymal transition model, a high glucose level induced a phenotypic change in human umbilical vein endothelial cells. Marein decreased endothelial cell migration, improved endothelial cell morphology, and decreased the expression of VIM and FN1. The use of the FGFR1 inhibitor, AZD4547, and autophagy inhibitor, 3-Methyladenine(3-MA), further demonstrated the inhibitory effect of marein on high glucose-induced endothelial-mesenchymal transition by reducing FGFR1 expression and up-regulating the autophagy marker protein, LC3II/I. In conclusion, this study suggests that marein has a protective effect on renal endothelial-mesenchymal transition in DKD, which may be mediated by inducing autophagy and down-regulating FGFR1 expression. [ABSTRACT FROM AUTHOR]

The optimal design of groundwater circulation wells (GCWs) is challenging. The key to purifying groundwater using this technique is its proficiency and productivity. However, traditional numerical simulation methods are limited by long modeling times, random optimization schemes, and optimization results that are not comprehensive. To address these issues, this study introduced an innovative approach for the optimal design of a GCW using machine learning methods. The FloPy package was used to create and implement the MODFLOW and MODPATH models. Subsequently, the formulated models were employed to calculate the characteristic indicators of the effectiveness of the GCW operation, including the radius of influence (R) and the ratio of particle recovery (Pr). A detailed collection of 3000 datasets, including measures of operational efficiency and key elements in machine learning, was meticulously compiled into documents through model execution. The optimization models were trained and evaluated using multiple linear regression (MLR), artificial neural networks (ANN), and support vector machines (SVM). The models produced by the three approaches exhibited notable correlations between anticipated outcomes and datasets. For the optimal design of circulating well parameters, machine learning methods not only improve the optimization speed, but also expand the scope of parameter optimization. Consequently, these models were applied to optimize the configuration of the GCW at a site in Xi’an. The optimal scheme for R (Q = 293.17 m3/d, a = 6.09 m, L = 7.28 m) and optimal scheme for Pr (Q = 300 m3/d, a = 3.64 m, L = 1 m) were obtained. The combination of numerical simulations and machine learning is an effective tool for optimizing and predicting the GCW remediation effect. [ABSTRACT FROM AUTHOR]

Background: Primary biliary cholangitis (PBC) is a chronic biliary autoimmune liver disease characterized by intrahepatic cholestasis. Swertia mussotii Franch. (SMF) is a Tibetan medicine with hepatoprotective and anti-inflammatory activities. In this study, the therapeutic effect and potential mechanisms of SMF on PBC were investigated by bioinformatics analysis and in vitro experimental validation, with the aim of promoting the progress of SMF and PBC research. Methods: We first explored the therapeutic effects and key targets of SMF on PBC using a network pharmacology approach, further screened the core targets using the GSE79850 dataset, and finally validated the results using molecular docking techniques and in vitro experiments. Results: By bioinformatics analysis, we identified core targets of SMF for PBC treatment (STAT3, JAK2, TNF-α, and IL-1β) and important signaling pathways: JAK-STAT, TNF, and PI3K-AKT. The molecular docking results showed that the significant components of SMF had good binding properties to the core targets. In vitro experiments showed that SMF extracts improved the extent of epithelial-mesenchymal transition in human intrahepatic biliary epithelial cells and had a significant reversal effect on epithelial-mesenchymal transition process markers and potential targets in PBC. Conclusion: SMF may exert its therapeutic effects on PBC by acting on important targets such as STAT3, JAK2, TNF-α, IL-1β, Vimentin, and E-cadherin and the pathways in which they are involved. [ABSTRACT FROM AUTHOR]

Background: Ambient fine particulate matter (PM2.5) is considered a plausible contributor to the onset of chronic obstructive pulmonary disease (COPD). Mechanistic studies are needed to augment the causality of epidemiologic findings. In this study, we aimed to test the hypothesis that repeated exposure to diesel exhaust particles (DEP), a model PM2.5, causes COPD-like pathophysiologic alterations, consequently leading to the development of specific disease phenotypes. Sprague Dawley rats, representing healthy lungs, were randomly assigned to inhale filtered clean air or DEP at a steady-state concentration of 1.03 mg/m3 (mass concentration), 4 h per day, consecutively for 2, 4, and 8 weeks, respectively. Pulmonary inflammation, morphologies and function were examined. Results: Black carbon (a component of DEP) loading in bronchoalveolar lavage macrophages demonstrated a dose-dependent increase in rats following DEP exposures of different durations, indicating that DEP deposited and accumulated in the peripheral lung. Total wall areas (WAt) of small airways, but not of large airways, were significantly increased following DEP exposures, compared to those following filtered air exposures. Consistently, the expression of α-smooth muscle actin (α-SMA) in peripheral lung was elevated following DEP exposures. Fibrosis areas surrounding the small airways and content of hydroxyproline in lung tissue increased significantly following 4-week and 8-week DEP exposure as compared to the filtered air controls. In addition, goblet cell hyperplasia and mucus hypersecretions were evident in small airways following 4-week and 8-week DEP exposures. Lung resistance and total lung capacity were significantly increased following DEP exposures. Serum levels of two oxidative stress biomarkers (MDA and 8-OHdG) were significantly increased. A dramatical recruitment of eosinophils (14.0-fold increase over the control) and macrophages (3.2-fold increase) to the submucosa area of small airways was observed following DEP exposures. Conclusions: DEP exposures over the courses of 2 to 8 weeks induced COPD-like pathophysiology in rats, with characteristic small airway remodeling, mucus hypersecretion, and eosinophilic inflammation. The results provide insights on the pathophysiologic mechanisms by which PM2.5 exposures cause COPD especially the eosinophilic phenotype. [ABSTRACT FROM AUTHOR]

The follicular helper T cells are derived from CD4+T cells, promoting the formation of germinal centers and assisting B cells to produce antibodies. This review describes the differentiation process of Tfh cells from the perspectives of the initiation, maturation, migration, efficacy, and subset classification of Tfh cells, and correlates it with autoimmune disease, to provide information for researchers to fully understand Tfh cells and provide further research ideas to manage immune-related diseases. [ABSTRACT FROM AUTHOR]

The seismic responses of functionally graded concrete piers with double plastic hinges were studied by finite element (FE) analysis, and especially the formation and effects of double plastic hinges were analyzed in details. The results showed that double plastic hinges in functionally graded concrete piers were made by the graded reinforcement with glass fiber reinforced plastic (GFRP) bars and steel bars. Because GFRP bars have large elastic deformability, double plastic hinges can be stably formed at the bottoms of two grades in turn under different seismic waves. Compared with the traditional reinforced concrete piers, the load bearing capacity, deformation capacity, energy consumption and resisted seismic acceleration of functionally graded concrete piers with double plastic hinges are significantly improved. [ABSTRACT FROM AUTHOR]

Chemotherapy is the first choice for the treatment of cancer but it is still limited by insufficient kill efficiency and drug resistance. These problems urgently need to be overcome in a way that minimizes damage to the body. In this study, we designed the nanocomposite microparticles (NMPs) modified by cetuximab (Cet) and loaded anti-tumor agents-quercetin (QUE) and paclitaxel (PTX)-for eliciting specific drugs homing and enhancing the killing efficiency of chemotherapy drugs (P/Q@CNMPs). Physicochemical characteristics results presented that P/Q@CNMPs have a suitable aerodynamic diameter and uniform morphology that could meet the requirements of particles deposition in the lung. And it also had the characteristics of sustained-release and pH-responsive which could release the agents in the right place and has a continuous effect. In vitro and in vivo analysis results presented that P/Q@CNMPs have the accuracy targeting ability and killing effect on non-small cell lung cancer (NSCLC) which express positive epidermal growth factor receptor (EGFR) on the membrane. Furthermore, this system also has low toxicity and good biocompatibility. These results demonstrated that P/Q@CNMPs could be a potential intelligent targeting strategy used for chemo-resistant NSCLC therapies. [ABSTRACT FROM AUTHOR]

We present a 3D phononic crystal-based pH sensor made of a biocompatible hydrogel-SiO 2 composite, its classification via machine learning (ML), and theoretical and experimental evidence for the existence of a band gap (BG). Instead of spatial, spectral approach is considered to classify different pH levels. The transition in band diagram and transmission coefficient measured along [111] direction reveals that the composite is sensitive to pH variation. Dips showing the BG in transmission spectra shift towards lower frequencies as the pH value increases. In addition, we have demonstrated the potential of four ML algorithms: k -nearest neighbor (KNN), Naïve Bayes, Support vector machine (SVM) and Neural Networks (NNs) as a quick identifying tool for the expedited and accurate classification of pH values with sensitivity S=0.3508 MHz/pH up to resolution of R= 0.1 pH level change with only 53 observations. For boosting the predicting power of model, we apply data augmentation technique on dataset. Our work focuses on multiclass supervised ML techniques which have the ability to classify pH values between 4 and 7 in 31 labels. In this comparative study we have explored the capability of each algorithm based upon the performance metrics. In addition, we found that except Naïve Bayes all algorithms could predict with >99 % accuracy. Lastly, globally optimal hyperparameters for NNs are also presented. The proposed pH sensor and classification method has pronounced potential to be used for in-vivo powerless pH measurements. [Display omitted] • A 3D phononic crystal-based pH sensor made of biocompatible hydrogel-SiO 2 composite is developed. • The existence of a band gap (BG) is explored using theoretical and experimental study. • pH sensing is classified by machine learning in spectral data. • The proposed pH sensor and classification method has pronounced potential to be used for in-vivo powerless pH measurements. [ABSTRACT FROM AUTHOR]

A new approach to the synthesis of isoindolinones via direct coupling of N‐methoxybenzamides and bis(tosylamido)methane with rhodium(III) as catalyst has been developed. The reaction is performed under mild conditions without oxidant, and is compatible with various functional groups. Compared with the previously reported methods for constructing isoindolinone skeletons, this method involves a novel [3+2] cyclization, and affords a wide variety of isoindolinones in moderate to excellent yields. [ABSTRACT FROM AUTHOR]

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is becoming more common, of which the overall survival rate is still low, and less than 50%. The rise of immunotherapy and the combined immunotherapy have brought significant benefits to patients with HNSCC. The aim of this study was to identify key genes related to HNSCC in the tumor microenvironment. METHODS: The Cancer Genome Atlas (TCGA cbioportal) database and Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) website were used to pick out key genes in the microenvironment of HNSCC. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to construct protein-protein interaction network. RESULTS: One hundred thirty-six genes related to immune score and stromal score were picked out to be differently expressed in HNSCC. Finally, 50 hub genes were identified. The high expression of FOXP3, IL10RA, MPEG1 and SELL genes were associated with good overall survival of patients with HNSCC, and low expression of VSIG4 was related to good overall survival of patients with HNSCC. CONCLUSIONS: This study suggested that FOXP3, IL10RA, MPEG1, SELL and VSIG4 genes were significantly related to HNSCC. The role of the key genes in the immunotherapy and combined immunotherapy for patients with HNSCC needs further study. [ABSTRACT FROM AUTHOR]

Although inflammation is critical for the clearance of pathogens, uncontrolled inflammation also contributes to the development of multiple diseases such as cancer and sepsis. Since NF-κB-mediated transactivation in the nucleus is pivotal downstream of various stimuli to induce inflammation, searching the nuclear-localized targets specifically regulating NF-κB activation will provide important therapeutic application. Here, we have identified that homeodomaininteracting protein kinase 2 (HIPK2), a nuclear serine/threonine kinase, increases its expression in inflammatory macrophages. Importantly, HIPK2 deficiency or overexpression could enhance or inhibit inflammatory responses in LPS-stimulated macrophages, respectively. HIPK2-deficient mice were more susceptible to LPSinduced endotoxemia and CLP-induced sepsis. Adoptive transfer of Hipk2+/- bone marrow cells (BMs) also aggravated AOM/DSSinduced colorectal cancer. Mechanistically, HIPK2 bound and phosphorylated histone deacetylase 3 (HDAC3) at serine 374 to inhibit its enzymatic activity, thus reducing the deacetylation of p65 at lysine 218 to suppress NF-κB activation. Notably, the HDAC3 inhibitors protected wild-type or Hipk2-/- BMs-reconstituted mice from LPS-induced endotoxemia. Our findings suggest that the HIPK2- HDAC3-p65 module in macrophages restrains excessive inflammation, which may represent a new layer of therapeutic mechanism for colitis-associated colorectal cancer and sepsis. [ABSTRACT FROM AUTHOR]

We aimed to analyze the expression of caveolin-2 (CAV2) in patients with oral cancer and its correlations with clinicopathological parameters. The expression of CAV2 in oral cancer and its influence on the survival curves of oral cancer patients were inquired through the Human Protein Atlas Database. The cancer tissue specimens and normal paracancerous tissue specimens (=2 cm away from cancer tissues) were collected from 173 patients with oral cancer confirmed by pathology. Moreover, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were performed to detect the messenger ribonucleic acid (mRNA) and protein expressions of CAV2 in oral cancer tissues and corresponding paracancerous tissues, respectively, and their associations with the clinicopathological characteristics and survival conditions of oral cancer patients were analyzed. It was shown in the Human Protein Atlas Database that the expression of CAV2 was increased significantly in oral cancer tissues compared with that in normal tissues (P<0.05), and patients with a low expression of CAV2 had a longer survival time than those with a high expression of CAV2 (P<0.05). The results of qRT-PCR and immunohistochemistry manifested that the mRNA expression level of CAV2 and the percentage of CAV2-positive cells were significantly higher in oral cancer tissues than those in paracancerous tissues (P<0.05). The CAV2 expression was correlated with clinical stage and pathological differentiation degree (P<0.05). In comparison with those in patients with a low CAV2 expression, the overall survival (OS) curve, relapse-free survival (RFS) curve and survival rate declined significantly in patients with a high CAV2 expression (P=0.001). Besides, the CAV2 expression, clinical stage and pathological differentiation degree were independent influencing factors for the postoperative OS and RFS of patients. The expression of CAV2 had relatively high predictive value for the OS and RFS of patients with oral cancer within 5 years after operation, of which the area under curve was 0.827 and 0.874, and the optimal cut-off value was 27.97% and 32.84%, respectively. CAV2 is highly expressed in oral cancer. With rising CAV2 expression level, the survival time of patients is shortened and the relapse risk is elevated, suggesting a poor prognosis. [ABSTRACT FROM AUTHOR]

Despite the success of immune checkpoint inhibitors (ICIs) in treating solid tumors, lots of patients remain unresponsive to this therapy. Microwave ablation (MWA) stimulates systemic adaptive immunity against tumor cells by releasing tumor antigens. Additionally, IL-21 has demonstrated importance in stimulating T-cell effector function. The combination of these three therapies—MWA, IL-21, and anti-PD-1 monoclonal antibodies (mAbs)—has yet to be explored in the context of cancer treatment. In this study, we explored the impact of thermal ablation on IL-21R expression in tumor-infiltrating lymphocytes (TILs). Subsequently, we assessed alterations in the tumor microenvironment (TME) and peripheral lymphoid organs. Additionally, we conducted a thorough examination of tumor-infiltrating CD45+ immune cells across various treatment groups using single-cell RNA sequencing (scRNA-seq). Moreover, we determined the potential anti-tumor effects of the triple combination involving MWA, IL-21, and anti-PD-1 mAbs. Our findings revealed that MWA upregulated the expression of IL-21R on various immune cells in the untreated tumors. The combination of MWA with IL-21 exhibited a robust abscopal anti-tumor effect, enhancing the effector function of CD8+ T cells and facilitating dendritic cells' maturation and antigen presentation in the untreated tumor. Notably, the observed abscopal anti-tumor effect resulting from the combination is contingent upon T-cell recirculation, indicating the reliance of systemic adaptive immunity for this treatment regimen. Additionally, the combination of MWA, IL-21, and PD-1 mAbs demonstrated profound abscopal anti-tumor efficacy. Our findings provide support for further clinical investigation into a triple combination therapy involving MWA, IL-21, and ICIs for the treatment of metastatic cancer. [ABSTRACT FROM AUTHOR]

CD8+T cells secreting granzyme A (GZMA) can induce pyroptosis in tumor cells by effectively cleaving gasdermin B (GSDMB), which is stimulated by interferon-γ (IFN-γ). However, the interaction between GZMA-expressing CD8+T cells and GSDMB-expressing tumor cells in colon cancer remains poorly understood. Our research employed multi-color immunohistochemistry (mIHC) staining and integrated clinical data to explore the spatial distribution and clinical relevance of GZMA- and IFN-γ-expressing CD8+ tumor-infiltrating lymphocytes (TILs), as well as GSDMB-expressing CK+ cells, within the tumor microenvironment (TME) of human colon cancer samples. Additionally, we utilizing single-cell RNA sequencing (scRNA-seq) data to examine the functional dynamics and interactions among these cell populations. scRNA-seq analysis of colorectal cancer (CRC) tissues revealed that CD8+TILs co-expressed GZMA and IFN-γ, but not other cell types. Our mIHC staining results indicated that a significant reduction in the infiltration of GZMA+IFN-γ+CD8+TILs in colon cancer patients (P < 0.01). Functional analysis results indicated that GZMA+IFN-γ+CD8+TILs demonstrated enhanced activation and effector functions compared to other CD8+TIL subsets. Furthermore, GSDMB-expressing CK+ cells exhibited augmented immunogenicity. Correlation analysis highlighted a positive association between GSDMB+CK+ cells and GZMA+IFN-γ+CD8+TILs (r = 0.221, P = 0.033). Analysis of cell-cell interactions further showed that these interactions were mediated by IFN-γ and transforming growth factor-β (TGF-β), the co-stimulatory molecule ICOS, and immune checkpoint molecules TIGIT and TIM-3. These findings suggested that GZMA+IFN-γ+CD8+TILs modulating GSDMB-expressing tumor cells, significantly impacted the immune microenvironment and patients' prognosis in colon cancer. By elucidating these mechanisms, our present study aims to provide novel insights for the advancement of immunotherapeutic strategies in colon cancer. [ABSTRACT FROM AUTHOR]

The stability and reliability of hydraulic control system have a direct bearing on the overall dynamic performance of the press machine. Hydromechanical analysis on the hydraulic control system is of theoretical and practical significance to improving the transmission performance and structural design of the entire press machine. From a quantitative perspective, this paper firstly analyzes the fluid transmission features of the hydraulic control system for the press machine, and presents the fluid transmission route and design drawings of the hydraulic control system. The next step is the design of the hydraulic control system. The authors specified the steps of design and calculation for the hydraulic control cylinder, and the principles for determining the power of the diesel engine. After that, experiments were carried out to verify the dynamic and static features of the designed system, and prove that our system is scientific and rational. [ABSTRACT FROM AUTHOR]

3-Mercaptopyruvate sulfurtransferase (3-MST) is the major source of hydrogen sulfide (H2S) production in the brain and participates in many physiological and pathological processes. The present study was designed to investigate the role of 3-MST-derived H2S (3-MST/H2S) on oxygen-glucose deprivation/reoxygenation (OGD/R) injury in cerebrovascular endothelial cells (ECs). Using cerebrovascular specimens from patients with acute massive cerebral infarction (MCI), we found abnormal morphology of the endothelium and mitochondria, as well as decreases in H2S and 3-MST levels. In an OGD/R model of ECs, 3-mercaptopyruvate (3-MP) and l-aspartic acid (l-Asp) were used to stimulate or inhibit the production of 3-MST/H2S. The results showed that OGD/R induced significant decreases in H2S and 3-MST levels in both ECs and mitochondria, as well as increases in oxidative stress and mitochondrial energy imbalance. Cellular oxidative stress, destruction of mitochondrial ultrastructure, accumulation of mitochondrial reactive oxygen species (ROS), reduction of mitochondrial adenosine triphosphate (ATP) synthase activity and ATP production, and decreased mitochondrial membrane potential were all significantly ameliorated by 3-MP, whereas they were exacerbated by l-Asp pretreatment. Contrary to the effects of l-Asp, the increase in RhoA activity and expression of ROCK1 and ROCK2 induced by OGD/R were markedly inhibited by 3-MP pretreatment in subcellular fractions without mitochondria and mitochondrial fractions. In addition, 3-MST−/− rat ECs displayed greater oxidative stress than 3-MST+/+ rat ECs after OGD/R injury. These findings suggest that 3-MST/H2S protects ECs against OGD/R-induced injury, which may be related to preservation of mitochondrial function and inhibition of the RhoA/ROCK pathway. [ABSTRACT FROM AUTHOR]

The effect of 18-crown-6 ether (18C6) on the anionic polymerization of ε-caprolactone (ε -CL) using potassium tert-butoxide (t-BuOK) as the initiator was studied. The experimental results showed that 18C6 in combination with t-BuOK exhibited high selectivity for ring opening relative to trans-esterification and improved control toward the ROP of ε-CL, producing poly(ε- caprolactone) (PCL) with much higher molecular weight and relatively narrow distribution compared to those using t-BuOK alone as the initiator.The influences of reaction conditions, such as monomer concentration, monomer/initiator molar ratio, and [18C6]/[t-BuOK] molar ratio, as well as reaction temperature and time on the polymerization have been examined in detail. The resulting hopolymers were characterized by various analytical techniques, such as GPC, FTIR, 1H NMR, DSC, TGA, and MALDI-ToF MS, to monitor the structures and property changes of PCLs. [ABSTRACT FROM AUTHOR]

Although regional haze adversely affects human health and possibly counteracts global warming from increasing levels of greenhouse gases, the formation and radiative forcing of regional haze on climate remain uncertain. By combining field measurements, laboratory experiments, and model simulations, we show a remarkable role of black carbon (BC) particles in driving the formation and trend of regional haze. Our analysis of long-term measurements in China indicates declined frequency of heavy haze events along with significantly reduced SO2, but negligibly alleviated haze severity. Also, no improving trend exists for moderate haze events. Our complementary laboratory experiments demonstrate that SO2 oxidation is efficiently catalyzed on BC particles in the presence of NO2 and NH3, even at low SO2 and intermediate relative humidity levels. Inclusion of the BC reaction accounts for about 90-100% and 30-50% of the sulfate production during moderate and heavy haze events, respectively. Calculations using a radiative transfer model and accounting for the sulfate formation on BC yield an invariant radiative forcing of nearly zero W m-2 on the top of the atmosphere throughout haze development, indicating small net climatic cooling/warming but large surface cooling, atmospheric heating, and air stagnation. This BC catalytic chemistry facilitates haze development and explains the observed trends of regional haze in China. Our results imply that reduction of SO2 alone is insufficient in mitigating haze occurrence and highlight the necessity of accurate representation of the BC chemical and radiative properties in predicting the formation and assessing the impacts of regional haze. [ABSTRACT FROM AUTHOR]

Elevations in circulating levels of branched-chain amino acids (BCAAs) are associated with a variety of cardiometabolic diseases and conditions. Restriction of dietary BCAAs in rodent models of obesity lowers circulating BCAA levels and improves whole-animal and skeletal-muscle insulin sensitivity and lipid homeostasis, but the impact of BCAA supply on heart metabolism has not been studied. Here, we report that feeding a BCAA-restricted chow diet to Zucker fatty rats (ZFRs) causes a shift in cardiac fuel metabolism that favors fatty acid relative to glucose catabolism. This is illustrated by an increase in labeling of acetyl-CoA from [1-13C]palmitate and a decrease in labeling of acetyl-CoA and malonyl-CoA from [U-13C]glucose, accompanied by a decrease in cardiac hexokinase II and glucose transporter 4 protein levels. Metabolomic profiling of heart tissue supports these findings by demonstrating an increase in levels of a host of fatty-acid-derived metabolites in hearts from ZFRs and Zucker lean rats (ZLRs) fed the BCAA-restricted diet. In addition, the twofold increase in cardiac triglyceride stores in ZFRs compared with ZLRs fed on chow diet is eliminated in ZFRs fed on the BCAA-restricted diet. Finally, the enzymatic activity of branched-chain ketoacid dehydrogenase (BCKDH) is not influenced by BCAA restriction, and levels of BCAA in the heart instead reflect their levels in circulation. In summary, reducing BCAA supply in obesity improves cardiac metabolic health by a mechanism independent of alterations in BCKDH activity. [ABSTRACT FROM AUTHOR]

Background/aim: Acute aortic dissection (AAD) is a rare but fatal disease if left untreated. Symptoms are often similar to common conditions; therefore, the diagnostic strategy is important. We aimed to identify the atypical symptoms in a timely manner without putting patients at greater risk for undetected AAD. Materials and methods: We conducted a retrospective observational study of 59 AAD patients with both atypical and typical symptoms from January 2012 to December 2016. Patients with atypical symptoms continuing more than 30 min underwent a D-dimer test and computed tomography (CT) or computed tomographic angiography (CTA). Results: Of the 59 AAD patients, 22 were atypical. In the atypical group, the median delay time in our hospital was 3.1 h; average delay time after July 2015 was shorter than average delay time before June 2015 (16.59 ± 24.70 vs. 1.90 ± 0.57 h, P = 0.076). Conclusions: For patients in the emergency department who are suspected of having AAD, incorporating atypical symptoms with high levels of D-dimer into a triage strategy could improve the efficiency of clinical decision making. Furthermore, essential education directed towards the recognition of the atypical symptoms of AAD for front-line physicians may aid in a timely diagnosis, as compared with the usual assessments in the emergency department. [ABSTRACT FROM AUTHOR]

BCC-ESM1 is the first version of a fully-coupled Earth System Model with interactive atmospheric chemistry and aerosols developed by Beijing Climate Center, China Meteorological Administration. Major aerosol species (including sulfate, organic carbon, black carbon, dust and sea salt) and greenhouse gases are interactively simulated with a whole panoply of processes controlling emission, transport, gas-phase chemical reactions, secondary aerosol formation, gravitational settling, dry deposition, and wet scavenging by clouds and precipitation. Effects of aerosols on radiation, cloud, and precipitation are fully treated. The performance of BCC-ESM1 in simulating aerosols and their optical properties is comprehensively evaluated as required by the Aerosol Chemistry Model Intercomparison Project (AerChemMIP), covering the preindustrial mean state and time evolution from 1850 to 2014. The simulated aerosols from BCC-ESM1 are quite coherent with CMIP5-recommended data and in-situ measurements from surface networks (such as IMPROVE in the U.S. and EMEP in Europe). A comparison of the aerosol optical depth (AOD) at 550 nm for all aerosols with the satellite AOD observations retrieved from MODIS and MISR and surface AOD observations from AERONET shows reasonable agreement between simulated and observed AOD. However, BCC-ESM1 seems to show weaker upward transport of aerosols from the surface to the middle and upper troposphere, likely reflecting the deficiency of representing deep convective transport of chemical species in BCC-ESM1. With an overall good agreement between BCC-ESM1 simulated and observed aerosol properties, it demonstrates a success of the implementation of interactive aerosol chemistry in BCC-ESM1. [ABSTRACT FROM AUTHOR]

Context: The aim of this meta-analysis was to evaluate the efficacy and safety of glucocorticoid plus conventional therapy in hepatitis B-related liver failure. Evidence Acquisition: A systematic search was performed in PubMed, Embase, the Cochrane library, China National Knowledge Infrastructure, Wanfang database, and Google Scholar. The primary outcome was improvement in the mortality rate and the secondary outcome was the incidence of complications. Pooled data were based on the fixed-effect model. Results: Ten studies with 891 patients were included in the meta-analysis. Glucocorticoid plus conventional therapy (OR = 3.98, 95% CI: 2.80 - 5.66; P = 0.000) was superior to conventional treatment alone and reduced the mortality rate (OR = 0.38, 95% CI [0.20, 0.74], P = 0.004). Moreover, the incidence of complications, such as hepatic encephalopathy (OR = 0.34, 95% CI [0.19, 0.60], P = 0.000), hepatorenal syndrome (OR = 0.22, 95% CI [0.10, 0.47], P = 0.000), electrolyte imbalance (OR = 0.27, 95% CI [0.12, 0.62], P = 0.002), and ascites (OR = 0.50, 95% CI [0.28, 0.90], P = 0.021), were reduced. No statistically significant differences were found between the two groups in terms of lung infection (OR = 0.76, 95% CI [0.27, 2.10], P = 0.595), gastrointestinal bleeding (OR = 0.48, 95% CI [0.23, 1.00], P = 0.050), and bacterial peritonitis (OR = 0.70, 95% CI [0.31, 1.58], P = 0.396). Conclusions: Our meta-analysis suggests that glucocorticoid plus conventional treatment reduced the incidence of complications. Thus combination therapy could be an effective and safe approach in treating patients with hepatitis B-related liver failure. [ABSTRACT FROM AUTHOR]

This research pioneered the investigation of the role of doctoral students' thinking styles in then- program satisfaction and perceived intellectual competence. Participants were 285 STEM (science, technology, engineering, mathematics) students in Hong Kong. Results showed that students' thinking styles as measured by the Thinking Styles Inventory--Revised II (Sternberg, Wagner, & Zhang, 2007) statistically significantly predicted their program satisfaction and perceived intellectual competence as assessed by two of the scales in the newly constructed Graduate Student Survey (Shin et al., 2015)--beyond their gender, program year, and academic discipline. Findings have brought new insights into the assessment of doctoral students' program satisfaction and perceived intellectual competence. At the same time, findings have contributed to the literature on intellectual styles and that on doctoral education in STEM fields. Practical implications of the findings are proposed for STEM doctoral students in understanding their own ways of thinking and program experiences and outcomes, as well as for academics and senior managers in their efforts to enhance students' access to positive program experiences and outcomes. [ABSTRACT FROM AUTHOR]

Let Φ be an analytic self-map of unit disk D, H(D) the space of analytic functions on D, and g ξ H(D). For an analytic function... The boundedness and compactness of C[β] Φ,g from mixed-norm spaces H(p, q, µ) to Bloch-type spaces B! are discussed in this paper. [ABSTRACT FROM AUTHOR]

The effects of high-deductible health plans (HDHPs) on breast cancer diagnosis and treatment among vulnerable populations are unknown. We examined time to first breast cancer diagnostic testing, diagnosis, and chemotherapy among a group of women whose employers switched their insurance coverage from health plans with low deductibles ($500 or less) to plans with high deductibles ($1,000 or more) between 2004 and 2014. Primary subgroups of interest comprised 54,403 low-income and 76,776 high-income women continuously enrolled in low-deductible plans for a year and then up to four years in HDHPs. Matched controls had contemporaneous low-deductible enrollment. Low-income women in HDHPs experienced relative delays of 1.6 months to first breast imaging, 2.7 months to first biopsy, 6.6 months to incident early-stage breast cancer diagnosis, and 8.7 months to first chemotherapy. High-income HDHP members had shorter delays that did not differ significantly from those of their low-income counterparts. HDHP members living in metropolitan, nonmetropolitan, predominantly white, and predominantly nonwhite areas also experienced delayed breast cancer care. Policies may be needed to reduce out-of-pocket spending obligations for breast cancer care. [ABSTRACT FROM AUTHOR]

The application of droop control in the voltage-source converter-based multi-terminal direct current (VSC-MTDC) system has been previously proposed in the literature. However, how to determine the droop coefficients to stabilise the DC voltage is still the key issue to concern and research. This study presents a novel calculation methodology for droop coefficients in the case of outage or power step disturbance on any converter station. The overall design objective is to minimise the DC voltage deviation between pre- and post-disturbance, depicted with a quadratic programming model. In addition, the selection method of the optimal DC voltage signal for droop controllers is developed in both cases of communication failure and communication normal. Based on the calculated droop coefficients and selected DC voltage signal, the power coordinated control among the converter stations is implemented to stabilise the DC voltage of the post-disturbance system quickly. Case studies are conducted on the Nordic 32 and New England system, respectively. The simulation results show that the proposed methodology for droop coefficients can significantly reduce the steady-state DC voltage deviations without the limitation of preassigning the maximum allowable DC voltage deviation, compared to the methodologies existing in the literature. [ABSTRACT FROM AUTHOR]

Let φ be an analytic self-map of unit disk D, H(D) the space of analytic functions on D, and g ∈ H(D). For an analytic function f(z) = Σn=0∞ anzn on D, the generalized integral-type operator Cφ,g[β] is defined by (Cφ,g[β]f) (z) = ∫0z f[β](φ(w))g(w)dw, z ∈ D, where β ≥ 0, f[β](z) = ... and f[0](z) = f(z). The boundedness and compactness of Cφ,g[β] from mixed-norm spaces H(p, q, μ) to Bloch-type spaces Bω are discussed in this paper. [ABSTRACT FROM AUTHOR]

The local magnetic state induced by the composite defects, composed of an oxygen vacancy and a nitrogen substituting oxygen, in magnesium oxide has been studied by using ab initio calculation based on density functional theory. The calculated results show that local magnetic moment can be induced by the composite defects around the oxygen vacancy, when the exchange split of the oxygen vacancy is enhanced either by the hybridization between the N-p and nearest neighbor O-p orbitals or by applying on-site Coulomb repulsion (U) and exchange interaction (J). We show that the magnetic state induced by the composite defect is energetically more stable than the non-magnetic state. In addition, we show that the U and J applied on the p-orbitals of N and O atoms may significantly impact the calculated magnetic state of the composite defect, resulting in magnetic state for a configuration that is non-magnetic by generalized gradient approximation. [ABSTRACT FROM AUTHOR]

The interleukin-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine and a naturally occurring antagonist of the IL-1 receptor. It effectively counteracts the IL-1 signaling pathway mediated by IL-1α/β. Over the past few decades, accumulating evidence has suggested that IL-1 signaling plays an essential role in tumor formation, growth, and metastasis. Significantly, anakinra, the first United States Food and Drug Administration (FDA)-approved IL-1Ra drug, has demonstrated promising antitumor effects in animal studies. Numerous clinical trials have subsequently incorporated anakinra into their cancer treatment protocols. In this review, we comprehensively discuss the research progress on the role of IL-1 in tumors and summarize the significant contribution of IL-1Ra (anakinra) to tumor immunity. Additionally, we analyze the potential value of IL-1Ra as a biomarker from a clinical perspective. This review is aimed to highlight the important link between inflammation and cancer and provide potential drug targets for future cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Ramsay Hunt syndrome, associated with varicella zoster virus infection is characterized by herpes zoster oticus, facial nerve palsy, and cochleovestibular symptoms. Ramsay Hunt syndrome associated cranial polyneuropathy occasionally occurs with involvement beyond VII and VIII. We represent a patient of Ramsay Hunt syndrome who presented with only VI involvement at the first visit followed by cranial polyneuropathy. Varicella zoster virus infection was confirmed by the detection of varicella zoster virus-DNA in cerebrospinal fluid. [ABSTRACT FROM AUTHOR]

In recent years, a large number of time series microbial community data has been produced in molecular biological studies, especially in metagenomics. Among the statistical methods for time series, local similarity analysis is used in a wide range of environments to capture potential local and time-shifted associations that cannot be distinguished by traditional correlation analysis. Initially, the permutation test is popularly applied to obtain the statistical significance of local similarity analysis. More recently, a theoretical method has also been developed to achieve this aim. However, all these methods require the assumption that the time series are independent and identically distributed. In this paper, we propose a new approach based on moving block bootstrap to approximate the statistical significance of local similarity scores for dependent time series. Simulations show that our method can control the type I error rate reasonably, while theoretical approximation and the permutation test perform less well. Finally, our method is applied to human and marine microbial community datasets, indicating that it can identify potential relationship among operational taxonomic units (OTUs) and significantly decrease the rate of false positives. [ABSTRACT FROM AUTHOR]

A single-celled green alga Coccomyxa greatwallensis Shunan Cao & Qiming Zhou, sp. nov., isolated from a specimen of Antarctic lichen Psoroma hypnorum (Vahl) Gray, is described and illustrated based on a comprehensive investigation of morphology, ultrastructure, ecology and phylogeny. The cells of C. greatwallensis are ovoid to long ellipsoidal and measured 3-5 µm × 6-12 µm. The new species has distinct ITS rDNA and SSU rDNA sequences and differs from the phylogenetic closely related species C. antarctica, C. arvernensis and C. viridis in cell size, distribution and habitat. [ABSTRACT FROM AUTHOR]

In the primary visual cortex (V1) of many mammalian species, neurons are spatially organized according to their preferred orientation into a highly ordered map. However, whether and how the various presynaptic inputs to V1 neurons are organized relative to the neuronal orientation map remain unclear. To address this issue, we constructed genetically encoded calcium indicators targeting axon boutons in two colors and used them to map the organization of axon boutons of V1 intrinsic and V2– V1 feedback projections in tree shrews. Both connections are spatially organized into maps according to the preferred orientations of axon boutons. Dual-color calcium imaging showed that V1 intrinsic inputs are precisely aligned to the orientation map of V1 cell bodies, while the V2–V1 feedback projections are aligned to the V1 map with less accuracy. Nonselective integration of intrinsic presynaptic inputs around the dendritic tree is sufficient to reproduce cell body orientation preference. These results indicate that a precisely aligned map of intrinsic inputs could reinforce the neuronal map in V1, a principle that may be prevalent for brain areas with function maps. [ABSTRACT FROM AUTHOR]

Adipose tissue is a dynamic organ that makes critical contributions to whole-body metabolic homeostasis. Although recent studies have revealed that different fat depots have distinct molecular signatures, metabolic functions and adipogenic mechanisms, peroxisome proliferator-activated receptor γ (PPARγ) is still widely viewed as the master regulator of adipogenesis and critical for maintaining mature adipocyte function. Using an inducible, adipocyte-specific knockout system, we explored the role of PPARγ in mature adipocytes in vivo. Short-term PPARγ deficiency in adipocytes reduces whole-body insulin sensitivity, but adipocytes are viable both in vitro and in vivo. However, after exposure to a high-fat diet, even short-term PPARγ deficiency leads to rapid adipocyte death. When mature adipocytes are depleted of both PPARγ and CCAAT-enhancer-binding protein α (C/EBPα), they are rapidly depleted of lipids and undergo adipocyte death, both in vitro and in vivo. Surprisingly, although thiazolidinediones (TZDs; PPARγ agonists) are thought to act mainly on PPARγ, PPARγ in adipocytes is not required for the whole-body insulinsensitizing effect of TZDs. This offers new mechanistic aspects of PPARγ/TZD action and its effect on whole-body metabolic homeostasis. [ABSTRACT FROM AUTHOR]

The single celled green alga Coccomyxa antarctica Shunan Cao & Qiming Zhou, sp. nov. was isolated from the Antarctic torrential lichen Usnea aurantiacoatra (Jacq.) Bory. It is described and illustrated based on a comprehensive study of its morphology, ultrastructure, ecology and phylogeny. C. antarctica is a lichenicolous alga which has elongated cells and contains a parietal chloroplast as observed under the microscope. C. antarctica is clearly different from other species by phylogenetic analysis (ITS rDNA and SSU rDNA sequences), also it differs from its phylogenetic closely species C. viridis by its larger cell size. [ABSTRACT FROM AUTHOR]

Objective: High-deductible health plans (HDHPs) are now the predominant commercial health insurance benefit in the U.S. We sought to determine the effects of HDHPs on emergency department and hospital care, adverse outcomes, and total health care expenditures among patients with diabetes.Research Design and Methods: We applied a controlled interrupted time-series design to study 23,493 HDHP members with diabetes, aged 12-64, insured through a large national health insurer from 2003 to 2012. HDHP members were enrolled for 1 year in a low-deductible (≤$500) plan, followed by 1 year in an HDHP (≥$1,000 deductible) after an employer-mandated switch. Patients transitioning to HDHPs were matched to 192,842 contemporaneous patients whose employers offered only low-deductible coverage. HDHP members from low-income neighborhoods (n = 8,453) were a subgroup of interest. Utilization measures included emergency department visits, hospitalizations, and total (health plan plus member out-of-pocket) health care expenditures. Proxy health outcome measures comprised high-severity emergency department visit expenditures and high-severity hospitalization days.Results: After the HDHP transition, emergency department visits declined by 4.0% (95% CI -7.8, -0.1), hospitalizations fell by 5.6% (-10.8, -0.5), direct (nonemergency department-based) hospitalizations declined by 11.1% (-16.6, -5.6), and total health care expenditures dropped by 3.8% (-4.3, -3.4). Adverse outcomes did not change in the overall HDHP cohort, but members from low-income neighborhoods experienced 23.5% higher (18.3, 28.7) high-severity emergency department visit expenditures and 27.4% higher (15.5, 39.2) high-severity hospitalization days.Conclusions: After an HDHP switch, direct hospitalizations declined by 11.1% among patients with diabetes, likely driving 3.8% lower total health care expenditures. Proxy adverse outcomes were unchanged in the overall HDHP population with diabetes, but members from low-income neighborhoods experienced large, concerning increases in high-severity emergency department visit expenditures and hospitalization days. [ABSTRACT FROM AUTHOR]

The electrochemical-dependent and unstable intensity of electrochemiluminescence (ECL) makes it difficult to identify ECL in a waveband-resolved way on photomultiplier tube (PMT)-based traditional ECL analyzers. Herein, a dual-color ECL strategy is proposed by transferring ECL to two PMTs in a waveband-resolved way via dichroic mirror, simultaneously detecting wild-type p53 (WTp53) in near-infrared wavebands with CdTe (λmax = 782 nm) nanocrystals as tag and mutant p53 (MUp53) in eye-visible wavebands with CdSe (λmax = 554 nm) nanocrystals as tag. The two targets can be color-selectively determined from 10 fM to 100 pM with a limit of detection at 5 fM for MUp53 and from 50 fM to 100 pM with a limit of detection at 10 fM for WTp53, respectively. The dichroic mirror-involved ECL setup is easy to assemble for popularization, which would not only eventually enable PMT-based multiple-color ECL analysis but also make it is possible to directly determine the changed level of tumor suppressors for cancer diagnosis and therapeutic evaluation via one-pot ECL assay. [ABSTRACT FROM AUTHOR]

A site-selective rhodium-catalyzed asymmetric 1,4-/1,2-addition of arylboronic acids to challenging α,β-unsaturated cyclic ketimines was realized through a ligand-controlled strategy. By employing different chiral olefin ligands, a ligand-controlled switch in the reaction regioselectivity was attained for the first time. The reactions allow the synthesis of highly valuable α,α-disubstituted chiral allylic amines and enantioenriched 1,4-adducts. Further product transformation provided easy access to various quaternary carbon-containing chiral amines and amino acid derivatives bearing multifunctional groups. [ABSTRACT FROM AUTHOR]

Copper indium sulfide (CuInS2, CIS) nanocrystals (NCs) are a promising solution to the toxic issue of Cd- and Pb-based NCs. Herein, electrochemiluminescence (ECL) of CIS NCs in aqueous medium is investigated for the first time with L-glutathione and sodium citrate-stabilized water-soluble CIS/ZnS NCs as model. The CIS/ZnS NCs can be oxidized to hole-injected states via electrochemically injecting holes into valence band at 0.55 and 0.94 V (vs Ag/AgCl), respectively. The hole-injected state around 0.94 V can bring out efficient oxidative-reduction ECL with a similar color to Ru(bpy)3 2+ in the presence of tri-n-propylamine (TPrA) and enable CIS/ZnS NCs promising ECL tags with L-glutathione as linker for labeling. The ECL of CIS/ZnS NCs/TPrA can be utilized to determine vascular endothelial growth factor (VEGF) from 0.10 to 1000 pM with the limit of detection at 0.050 pM (S/N = 3). Although the holeinjected state around 0.55 V is generated ahead of oxidation of TPrA and fails to bring out coreactant ECL, annihilation ECL proves that both hole-injected states generated, at 0.55 and 0.94 V, can be involved in electrochemical redox-induced radiative charge transfer by directly stepping CIS/ZnS NCs from electron-injecting potential to hole-injecting potential. CIS/ZnS NCs are promising nontoxic electrochemiluminophores with lowered ECL triggering potential around 0.55 V for less electrochemical interference upon the development of coreactant. [ABSTRACT FROM AUTHOR]

Inflammation that complicates many autoimmune diseases, such as multiple sclerosis (MS), has been correlated to abnormal differentiation of Th17 cells. However, the reasons that promote Th17 cell-driven autoimmunity are yet to be discovered. In this study, we sought evidence that DNA-damage-inducible transcript 4 (DDIT4) and its associated long noncoding RNA DDIT4 (lncDDIT4) inhibit Th17 cell differentiation. We recruited 36 patients. Six MS patients and five healthy volunteers (controls) contributed PBMCs as material for microarray analysis. Microarray assays of lncDDIT4 and DDIT4 RNA expression identified outstanding differences between MS and control subjects, which were verified with real-time quantitative PCR. We then interrupted the expression of lncDDIT4 and DDIT4 mRNA in MS patient's naive CD4+ T cells and observed the resulting changes in Th17 cells. The expression of lncDDIT4 and DDIT4 mRNA were higher both in PBMCs and CD4+ T cells of MS patients than in healthy controls. DDIT4 (2.79-fold upregulation) was then recognized as a candidate for the cis-regulated target of lncDDIT4 (4.32-fold upregulation). Isolation of naive CD4+ T cells revealed enhanced levels of lncDDIT4 and DDIT4 after stimulated with Th17-inducing cytokines, but not after Th1, Th2, or T regulatory cell induction. Overexpression of lncDDIT4 in naive CD4+ T cells inhibited IL-17 transcription through increased DDIT4 expression and decreased activation of the DDIT4/mTOR pathway. Consistently, silencing lncDDIT4 in naive CD4+ T cells enhanced Th17 differentiation through increased activation of the DDIT4/mTOR pathway. However, these results vanished when DDIT4 was silenced. This outcome suggests that lncDDIT4 regulates Th17 cell differentiation by directly targeting DDIT4. [ABSTRACT FROM AUTHOR]

Host cells harbor various intrinsic mechanisms to restrict viral infections as a first line of antiviral defense. Viruses have evolved various countermeasures against these antiviral mechanisms. Here we show that N-Myc downstream-regulated gene 1 (NDRG1) limits productive hepatitis C virus (HCV) infection by inhibiting viral assembly. Interestingly, HCV infection downregulates NDRG1 protein and mRNA expression. The loss of NDRG1 increases the size and number of lipid droplets, which are the sites of HCV assembly. HCV suppresses NDRG1 expression by upregulating MYC, which directly inhibits the transcription of NDRG1. The upregulation of MYC also leads to the reduced expression of the NDRG1-specific kinase serum/glucocorticoid-regulated kinase 1 (SGK1), resulting in a markedly diminished phosphorylation of NDRG1. The knockdown of MYC during HCV infection rescues NDRG1 expression and phosphorylation, suggesting that MYC regulates NDRG1 at both the transcriptional and post-translational levels. Overall, our results suggest that NDRG1 restricts HCV assembly by limiting lipid droplet formation. HCV counteracts this intrinsic antiviral mechanism by downregulating NDRG1 via a MYC-dependent mechanism. IMPORTANCE Hepatitis C virus (HCV) is an enveloped single-stranded RNA virus that targets hepatocytes in the liver. HCV is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, and estimates suggest a global prevalence of 2.35%. Up to 80% of acutely infected individuals will develop chronic infection, and as many as 5% eventually progress to liver cancer. An understanding of the mechanisms behind virus-host interactions and viral carcinogenesis is still lacking. The significance of our research is that it identifies a previously unknown relationship between HCV and a known tumor-associated gene. Furthermore, our data point to a new role for this gene in the liver and in lipid metabolism. Thus, HCV infection serves as a great biological model to advance our knowledge of liver functions and the development of liver cancer. [ABSTRACT FROM AUTHOR]

Objective Benzene, ethylbenzene, meta/para-xylene, and ortho-xylene, collectively referred to as benzene, ethylbenzene, and xylene (BEX), constitute the main components of volatile organic aromatic compounds (VOACs) and can have adverse effects on human health. The relationship between exposure to BEX and hearing loss (HL) in the adult U.S. population was aimed to be assessed. Methods Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) for the years 2003–2004, 2011–2012, and 2015–2016 were analyzed. This dataset included complete demographic characteristics, pure-tone audiometry measurements, and volatile organic compound detection data from the NHANES database. A weighted multivariate logistic regression model was employed to investigate the associations between blood BEX concentrations HL, low-frequency hearing loss (SFHL), and high-frequency hearing loss (HFHL). Results 2174 participants were included, with weighted prevalence rates of HL, SFHL, and HFHL being 46.81%, 25.23%, and 45.86%, respectively. Exposure to benzene, ethylbenzene, meta/para-xylene, and ortho-xylene, and cumulative BEX concentrations increased the risk of hearing loss (odds ratios [ORs] were 1.36, 1.22, 1.42, 1.23, and 1.31, respectively; all P<0.05). In the analysis with SFHL as the outcome, ethylbenzene, m-/p-xylene, o-xylene, benzene, and overall BEX increased the risk (OR 1.26, 1.21, 1.28, 1.20, and 1.25, respectively; all P<0.05). For HFHL, exposure to ethylbenzene, m-/p-xylene, o-xylene, benzene, and overall BEX increased the risk (OR 1.36, 1.22, 1.42, 1.22, and 1.31, respectively; all P<0.05). Conclusion Our study indicated that a positive correlation between individual or cumulative exposure to benzene, ethylbenzene, meta/para-xylene, and ortho-xylene and the risk of HL, SFHL, and HFHL. Further research is imperative to acquire a more comprehensive understanding of the mechanisms by which organic compounds, notably BEX, in causing hearing loss and to validate these findings in longitudinal environmental studies. [ABSTRACT FROM AUTHOR]

The association between the quantitative and semi-quantitative parameters of myocardial blood flow obtained using cadmium-zinc-telluride single photon emission computed tomography (CZT-SPECT) and coronary stenosis remains unclear. Therefore, the objective of the present study was to evaluate the diagnostic value of two parameters obtained using CZT-SPECT in patients with suspected or known coronary artery disease. A total of 24 consecutive patients who underwent CZT-SPECT and coronary angiography within 3 months of each other were included in the study. To evaluate the predictive ability of the regional difference score (DS), coronary flow reserve (CFR), and the combination thereof for positive coronary stenosis at the vascular level, receiver operating characteristic (ROC) curves were plotted and the area under the curves (AUCs) were calculated. Comparisons of the reclassification ability for coronary stenosis between different parameters were assessed by calculating the net reclassification index (NRI) and the integrated discrimination improvement (IDI). The 24 participants (median age: 65 years; range: 46-79 years; 79.2% male) included in this study had a total of 72 major coronary arteries. When stenosis ≥50% was defined as the criteria for positive coronary stenosis, the AUCs and the 95% confidence interval (CI) for regional DS, CFR, and the combination of the two indices were 0.653 (CI, 0.541-0.766), 0.731 (CI, 0.610-0.852) and 0.757 (CI, 0.645-0.869), respectively. Compared with single DS, the combination of DS and CFR increased the predictive ability for positive stenosis, with an NRI of 0.197-1.060 (P<0.01) and an IDI of 0.0150-0.1391 (P<0.05). When stenosis ≥75% was considered as the criteria, the AUCs were 0.760 (CI, 0.614-0.906), 0.703 (CI, 0.550-0.855), and 0.811 (CI, 0.676-0.947), respectively. Compared with DS, CFR had an IDI of -0.3392 to -02860 (P<0.05) and the combination of DS and CFR also enhanced the predictive ability, with an NRI of 0.0313-1.0758 (P<0.01). In conclusion, both regional DS and CFR had diagnostic values for coronary stenosis, but the diagnostic abilities differed in distinguishing between different degrees of stenosis, and the efficiency was improved with a combination of DS and CFR. [ABSTRACT FROM AUTHOR]

The solid-liquid equilibria (SLE) in the ternary system of 2-methyl-1,4-naphthoquinone (2-MNQ) + phthalic anhydride (PA) + 1,4-dioxane were determined experimentally by using the isothermal dissolution equilibriam method within temperatures 283.15, 293.15, and 303.15 K, respectively. The ternary phase diagram could be helpful in the separation of 2-MNQ and PA. On the basis of the experimental data on solubilities the phase diagrams of the system were plotted. Two pure solid phases were formed at 283.15, 293.15 and 303.15 K, including pure PA and pure 2-MNQ, which were confirmed and determined by Schreinemakers' wet residue method. The phase diagram at 283.15 K is similar to those at 293.15 and 303.15 K and the crystalline regions of 2-MNQ and PA decrease with increasing temperature. NRTL and Wilson model were employed to correlate and calculate the solubility data for the ternary system. A comparison between the two models shows that the NRTL model agrees better with the experimental data than those with the Wilson model. In addition, the densities of equilibrium liquid phase were obtained at the corresponding temperatures versus composition in the system. [ABSTRACT FROM AUTHOR]

The effect of ulinastatin (UTI) on renal tubular epithelial apoptosis and interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) was investigated. A total of 18 male Wistar rats were randomly divided into the following 3 groups: The Sham group (n=6), the UUO group (n=6), and the UTI group (n=6). In the UUO and UTI groups, the left ureter was ligated to establish a UUO model. Starting from day 1 after surgery, an intervention treatment was performed using normal saline (1 ml/kg/d) and UTI (40,000 unit/kg/d). On day 7 after surgery, 6 rats from each group were sacrificed. In the Sham group, the left ureter was only freed, not ligated; after 7 days of abdominal closure, all of the rats were sacrificed. Blood samples were collected prior to sacrificing the animals to measure the blood urea nitrogen (BUN) and serum creatinine (Scr). The incidence of renal interstitial lesions on the obstruction side was observed by hematoxylin and eosin, and Masson staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical detection of apoptosis regulator Bax (Bax), apoptosis regulator Bcl-2 (Bcl-2) and caspase-3 were performed to observe the presence of renal tubular epithelial cell apoptosis. The UTI did not have a significant influence on the mouse BUN and Scr levels in any of the groups (P>0.05). Compared with that in the Sham group, renal tissue injury in the UUO group was significantly aggravated with renal tubular dilation, epithelial cell atrophy, renal interstitial inflammatory cell infiltration and fibrous tissue hyperplasia (P<0.01). Furthermore, the renal tubular epithelial TUNEL+ cell number and Bax and caspase-3 levels were increased, and the expression of Bcl-2 was decreased (P<0.01). Following the UTI treatment, the renal interstitial injury at the obstruction side was significantly attenuated (P<0.05), the renal tubular epithelial TUNEL+ cell number, and Bax and caspase-3 levels significantly decreased, and the expression of Bcl-2 was restored (P<0.05). UTI inhibited renal tubular epithelial apoptosis and interstitial fibrosis in UUO rats. [ABSTRACT FROM AUTHOR]

Angiogenesis, the formation of new blood vessels from preexisting endothelium, is a process that involves a series of interassociated and mutually interactive pathophysiological processes. It is accepted that microRNAs (miRNAs) regulate endothelial cell behavior, including their involvement in angiogenesis. However, it remains unclear whether miRNAs are involved in the regulation of angiogenesis following cerebral ischemia. Therefore, the present study aimed to investigate the role of miRNAs in angiogenesis and the underlying mechanism following cerebral ischemia. Expression profiles of miRNAs in rat brain samples following middle cerebral artery occlusion (MCAO) were investigated using a miRNA microarray. The expression of candidate miRNA, miR‑195 was further validated using reverse transcription‑quantitative polymerase chain reaction. Then, the effects of miR‑195 on cell migration and tube formation of human umbilical vein vascular endothelial cells (HUVECs) were investigated following miR‑195 silencing, and overexpression. The specific target genes of miR‑195 were predicted using microRNA prediction bioinformatics software (http://www.microrna.org/microrna/home.do), and then confirmed using a dual‑luciferase reporter assay and rescue experiment. It was demonstrated that miR‑195 was significantly downregulated in the brains of rats following MCAO and in hypoxia‑induced HUVECs. Furthermore, it was revealed that miR‑195 overexpression inhibited the invasion ability and tube formation of HUVECs in vitro, while miR‑195 silencing enhanced these functions. In addition, vascular endothelial growth factor A (VEGFA) was identified as a direct target of miR‑195 and was negatively correlated with miR‑195 expression. In addition, the rescue experiment revealed that overexpression of VEGFA reversed the inhibitory effects of miR‑195 overexpression on the invasion ability and tube formation of HUVECs. The present study has provided a novel insight into the promoting roles of miR‑195 downregulation on angiogenesis following cerebral infarction and suggests that the miR‑195/VEGFA signaling pathway is a putative therapeutic target in cerebral ischemia. [ABSTRACT FROM AUTHOR]

The amyloid precursor protein (APP) has long been appreciated for its role in Alzheimer's disease (AD) pathology. However, less is known about the physiologic function of APP outside of AD. Particularly, whether and how APP may regulate functions of cell surface receptors, including GPCRs, remains largely unclear. In this study, we identified a novel direct interaction between APP and the α2A-adrenergic receptor (α2AAR) that occurs at the intracellular domains of both proteins. The APP interaction with α2AAR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor. Consequently, the presence of APP attenuates α2AAR internalization and desensitization, which are arrestin-dependent processes. Furthermore, in neuroblastoma neuro-2A cells and primary superior cervical ganglion neurons, where APP is highly expressed, the lack of APP leads to a dramatic increase in plasma membrane recruitment of endogenous arrestin 3 following α2AAR activation. Concomitantly, agonist-induced internalization of α2AAR is significantly enhanced in these neuronal cells. Our study provided the first evidence that APP fine tunes GPCR signaling and trafficking. Given the important role of α2AAR in controlling norepinephrine release and response, this novel regulation of α2AAR by APP may have an impact on modulation of noradrenergic activity and sympathetic tone. [ABSTRACT FROM AUTHOR]

Urinary bladder cancer (UBC) is one of the most common urological cancer types. Muscle invasive bladder cancer possesses high propensity for metastasis with poor prognosis. Honokiol is a lignan isolated from Magnolia officinalis with high bioavailability and potent anticancer effects. The results of the present study demonstrated that honokiol significantly inhibited UBC cell migration and invasion in a dose-dependent manner compared with the vehicle-treated control group. In addition, honokiol treatment suppressed epithelial-mesenchymal transition by induction of E-cadherin and repression of N-cadherin. Honokiol was capable of significantly downregulating the expression of cell invasion-associated genes, steroid receptor coactivator-3 (SRC-3), matrix metalloproteinase (MMP)-2 and Twist1. Notably, the inhibition of UBC cell invasion by honokiol was reversed by reintroduction of oncoprotein SRC-3 expression, with the restoration of MMP-2 and Twist1, and reduction of E-cadherin expression. Furthermore, the results of the luciferase assay confirmed that SRC-3 could regulate Twist1 promoter activity. Taken together, the results of the present study suggest that honokiol is a promising agent against UBC cell invasion via downregulation of SRC-3 and its target genes. [ABSTRACT FROM AUTHOR]