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Background: Residual kidney function (RKF) impacts patients' survival rate and quality of life when undergoing peritoneal dialysis (PD). This meta-analysis was conducted to systematically identify risk and protective factors associated with RKF decline and loss. Methods: We searched three English and one Chinese databases from inception to January 31, 2023, for cohort and cross-sectional studies exploring factors associated with RKF decline or loss. The random effects model was employed to aggregate risk estimates and 95% confidence intervals (CIs) from multivariate analysis. Sensitivity and subgroup analyses were performed to explore the heterogeneity among the studies. Results: Twenty-seven studies comprising 13549 individuals and 14 factors were included in the meta-analysis. Based on the meta-analysis results, risk factors involving male gender (hazard ratio (HR) 1.689, 95%CI 1.385-2.061), greater body mass index (BMI) (odds ratio (OR) 1.081, 95% confidence interval (CI) 1.029-1.135), higher systolic blood pressure (SBP) (HR 1.014, 95%CI 1.005-1.024), diabetes mellitus (DM) (HRRKF loss 1.873, 95%CI 1.475-2.378), DM (ORRKF decline 1.906, 95%CI 1.262-2.879), peritonitis (relative ratio (RR) 2.291, 95%CI 1.633-3.213), proteinuria (OR 1.223, 95%CI 1.117-1.338), and elevated serum phosphorus (RR 2.655, 95%CI 1.679-4.201) significantly contributed to the risk of RKF decline and loss in PD patients. Conversely, older age (HR 0.968, 95%CI 0.956-0.981), higher serum albumin (OR 0.834, 95%CI 0.720-0.966), weekly Kt/V urea (HR 0.414, 95%CI 0.248-0.690), baseline urine volume (UV) (HR 0.791, 95%CI 0.639-0.979), baseline RKF (HR 0.795, 95%CI 0.739-0.857) exhibited protective effects. However, diuretics use, automatic peritoneal dialysis (APD) modality and baseline RKF did not significantly impact RKF decline. Conclusions: Patients with male gender, greater BMI, higher SBP, DM, peritonitis, proteinuria, and elevated serum phosphorus might have a higher risk of RKF decline and loss. In contrast, older age, higher serum albumin, weekly Kt/V urea, baseline UV, and baseline RKF might protect against RKF deterioration. [ABSTRACT FROM AUTHOR]

Excessive erythrocytosis (EE) is a major hallmark of patients suffering from chronic mountain sickness (CMS, also known as Monge's disease) and is responsible for major morbidity and even mortality in early adulthood. We took advantage of unique populations, one living at high altitude (Peru) showing EE, with another population, at the same altitude and region, showing no evidence of EE (non-CMS). Through RNA-Seq, we identified and validated the function of a group of long noncoding RNAs (lncRNAs) that regulate erythropoiesis in Monge's disease, but not in the non-CMS population. Among these lncRNAs is hypoxia induced kinase-mediated erythropoietic regulator (HIKER)/LINC02228, which we showed plays a critical role in erythropoiesis in CMS cells. Under hypoxia, HIKER modulated CSNK2B (the regulatory subunit of casein kinase 2). A downregulation of HIKER downregulated CSNK2B, remarkably reducing erythropoiesis; furthermore, an upregulation of CSNK2B on the background of HIKER downregulation rescued erythropoiesis defects. Pharmacologic inhibition of CSNK2B drastically reduced erythroid colonies, and knockdown of CSNK2B in zebrafish led to a defect in hemoglobinization. We conclude that HIKER regulates erythropoiesis in Monge's disease and acts through at least one specific target, CSNK2B, a casein kinase. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the elastic characteristics of the pulmonary trunk and distal branches in fetuses diagnosed with tetralogy of Fallot (TOF) using Doppler echocardiography. Methods: Data on 42 fetuses diagnosed with TOF and 84 gestational age-matched normal fetuses were prospectively collected from the Second Xiangya Hospital of Central South University between August 2022 and January 2023. The severity of TOF was classified into three categories based on the z-score of the pulmonary annulus diameter: mild (z-score =-2), moderate (-40.05). Conclusion: Fetuses diagnosed with TOF exhibited increased vascular stiffness in the MPA and reduced stiffness in the distal pulmonary artery (PA). Larger-scale follow-up studies are required to elucidate the relationships between these changes in vascular stiffness and PA development in patients with TOF. [ABSTRACT FROM AUTHOR]

Hypoxia is a critical pathological element in many human diseases, including ischemic stroke, myocardial infarction, and solid tumors. Of particular significance and interest of ours are the cellular and molecular mechanisms that underlie susceptibility or tolerance to low O2. Previous studies have demonstrated that Notch signaling pathway regulates hypoxia tolerance in both Drosophila melanogaster and humans. However, the mechanisms mediating Notch-conferred hypoxia tolerance are largely unknown. In this study, we delineate the evolutionarily conserved mechanisms underlying this hypoxia tolerant phenotype. We determined the role of a group of conserved genes that were obtained from a comparative genomic analysis of hypoxia-tolerant D.melanogaster populations and human highlanders living at the high-altitude regions of the world (Tibetans, Ethiopians, and Andeans). We developed a novel dual-UAS/Gal4 system that allows us to activate Notch signaling in the Eaat1-positive glial cells, which remarkably enhances hypoxia tolerance in D.melanogaster, and, simultaneously, knock down a candidate gene in the same set of glial cells. Using this system, we discovered that the interactions between Notch signaling and bnl (fibroblast growth factor), croc (forkhead transcription factor C), or Mkk4 (mitogen-activated protein kinase kinase 4) are important for hypoxia tolerance, at least in part, through regulating neuronal development and survival under hypoxic conditions. Becausethese genetic mechanisms are evolutionarily conserved, this group of genes may serve as novel targets for developing therapeutic strategies and have a strong potential to be translated to humans to treat/prevent hypoxia-related diseases. [ABSTRACT FROM AUTHOR]

Several decades ago, Mo2B was assumed to have an Al2Cu-type structure with I4/mcm space group. Using ab initio phonon calculations, we identify the earlier proposed Al2Cu-type structure is dynamically unstable at ambient pressure. An energetically more favorable phase with the tetragonal I4/m structure was then predicted by employing frozen-phonon technique. The currently predicted I4/m phase is mechanically and dynamically stable and energetically more favorable than that of the earlier proposed Al2Cu-type structure. The electronic structures calculations indicate that Mo2B is a metal with several bands crossing the Fermi level. Our analysis indicates that the three-dimensional network of the covalent Mo-B bond is responsible for the ultra-incompressible property of Mo2B. [ABSTRACT FROM AUTHOR]

Sweet osmanthus (Osmanthus fragrans) is a having general approval aromatic tree in China that is widely applied to landscaping and gardening. However, the evergreen tree adaptability is limited by many environmental stresses. Currently, limited information is available regarding the genetic analysis and functional identification of expansin genes in response to abiotic stress in sweet osmanthus. In this study, a total of 29 expansin genes were identified and divided into four groups by genome-wide analysis from the sweet osmanthus genome. Transcriptome and quantitative Real-time PCR analysis showed that the cell wall-localized protein expansin-like A (OfEXLA1) gene was significantly induced by salt and drought treatment. Histochemical GUS staining of transgenic Arabidopsis lines in which GUS activity was driven with the OfEXLA1 promoter, GUS activity was significantly induced by salt, drought, and exogenous abscisic acid (ABA). In yeast, we found OfEXLA1 overexpression significantly improved the population of cells compared with wild-type strains after NaCl and polyethylene glycol (PEG) treatment. Additionally, OfEXLA1 overexpression not only promoted plant growth, but also improved the salt and drought tolerance in Arabidopsis. To gain insight into the role of ABA signaling in the regulation of OfEXLA1 improving abiotic tolerance in sweet osmanthus, four differentially expressed ABA Insensitive 5 (ABI5)-like genes (OfABL4, OfABL5, OfABL7, and OfABL8) were identified from transcriptome, and dualluciferase (dual-LUC) and yeast one hybrid (Y1H) assay showed that OfABL4 and OfABL5 might bind to OfEXLA1 promoter to accumulate the OfEXLA1 expression by responding to ABA signaling to improve abiotic tolerance in sweet osmanthus. These results provide the information for understanding the molecular functions of expansin-like A gene and molecular breeding of sweet osmanthus in future. [ABSTRACT FROM AUTHOR]

Ferroelectric single crystal (1-x)Pb(Mg1/3Nb2/3)O3–xPbTiO3 (PMNT) has attracted considerable attention for its outstanding piezoelectric properties after poled along the <001> or <101> directions and it is being actively applied to various ultrasonic devices. However, almost all previous applications focus on the longitudinal extension, transverse extension, thickness extension and thickness shear vibration mode. Here, we investigated the radial vibration mode of the <001> poled 0.71Pb(Mg1/3Nb2/3)O3–0.29PbTiO3 single crystal. Both the finite element simulation and experimental results have shown that the performance of radial vibration mode is excellent. The coupling coefficient of radial vibration mode can reach 0.84 and the anisotropy of the circular plate is very weak after it was poled along the <001> direction. Based on this mode, we further designed and fabricated a disk-type piezoelectric transformer and the open circuit voltage step-up ratio reached about 50 with no spurious vibration mode around the resonance frequency. All these have shown that the radial vibration mode of PMNT single crystal is also promising and useful for other piezoelectric device applications. [ABSTRACT FROM AUTHOR]

Small-molecule electrolytes (SMEs) have attracted increasing interests owing to their intrinsic advantages, such as high repeatability, easy purification and well-defined structures. Interfacial engineering plays crucial roles in enhancing the power conversion efficiency (PCE) of polymer solar cells (PSCs). Through a green route one-step reaction with nonhalogen solvent, we reported the design and synthesis of one novel hyperbranched SME PNSO 3 Na as cathode interfacial layer (CIL). Owing to containing seven moles butyl sulfonate sodium, hyperbranched SMEs PNSO 3 Na CIL can form interfacial dipoles, tune the interfacial energy alignment, realize environment-friendly water/alcohol processing, induce the upper active layer to form order morphology and enhance the PCE of PSCs. Based on P3HT–PC61BM active layer, the PCE of the device based on PNSO 3 Na CIL was dramatically enhanced from 0.8 to 3.7% compared to the bare ITO device. [ABSTRACT FROM AUTHOR]

The solubility of the ionic liquid (IL) 1-butyl-3-methylimidazolium acetate ([Bmim]Ac) in supercritical carbon dioxide (scCO2) with cosolvents, including ethanol, acetone, dimethyl sulfoxide (DMSO), and acetonitrile, was determined at 40, 50, and 60 °C and with a pressure up to 15.0 MPa. The results showed that the addition of cosolvents has a significant effect on the solubility of [Bmim]Ac in scCO2. The ability of different cosolvents to enhance the solubility of [Bmim]Ac in scCO2 is in the following order: ethanol > DMSO > acetone > acetonitrile. The solubility of [Bmim]Ac in the scCO2/cosolvent mixture increased dramatically as the cosolvent concentration exceeded 20.0 mol %. The effect of the temperature on the solubility is more complicated. The solubility of [Bmim]Ac in scCO2/cosolvent increased slowly when using ethanol as the cosolvent, decreased slowly when using acetone or acetonitrile as the cosolvent, and increased first and then decreased when using DMSO as the cosolvent as the temperature increased from 40 to 60 °C. Moreover, the values of solubility increased as the pressure increased from 8 to 15 MPa. The increased tendency in the high pressure area is more obvious. The maximum solubility is 3.66 × 10-2 mol %, which can be obtained when using 26.0 mol % ethanol at 60 °C, 14.55 MPa, and the minimum solubility is 1.89 × 10-4 mol %, which can be obtained when using 10.5 mol % DMSO at 40 °C, 9.93 MPa. The modified Christal equation was used to correlate the solubility data, and the average absolute relative deviations are in the range of 4.36-14.35%. The maximum correlation accuracy is obtained when using ethanol as the cosolvent, and the minimum value for the system is obtained when using DMSO as the cosolvent. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed decarbonylative alkynylation of amides via C-N bond activation is developed. Compared with the reported Ni/Cu catalyzed reaction, which only proceeded well with silylacetylenes, this transformation was also applicable to both aromatic and aliphatic terminal alkynes, including those bearing functional groups, and thus provided a general and straightforward access to diverse internal alkynes. [ABSTRACT FROM AUTHOR]

A novel, transition-metal-free phosphorylation of cinnamic acids with P(O)H compounds has been developed via radical-promoted decarboxylation under mild conditions. This method provides simple, efficient, and versatile access to valuable (E)-alkenylphosphine oxides in satisfactory yields with a wide variety of substrates. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the use and effectiveness of a selective, partial, pedunculated (tongue-shaped) conjunctival flap (CF) for the treatment of refractory fungal keratitis (FK) with or without perforation. A total of 31 cases of corneal diseases treated by CF surgery between April 2014 and October 2015 were evaluated. Among the 31 cases, 16 cases (male:female, 11:5) with FK were selected. Logistic regression analysis was used to investigate factors associated with complications of CF surgery. A higher prevalence of FK was identified among male farmers compared with female farmers, in which plant trauma was the most prevalent cause of the disease. Only 4 patients had experienced corneal perforation prior to CF surgery. Patients aged 61-80 years had a higher prevalence of FK (50%) compared with other age groups; however, there was no statistically significant correlation between the prevalence of FK and sex or age. It was also demonstrated that age, sex, combined surgery and surgery duration were not significantly associated with post-surgical complications. All CF surgeries were performed following corneal ulcer scraping; however, 4 patients (12.5%) required additional surgery. The visual acuity of participants post-surgery decreased in 4 cases and remained unchanged in 12 cases. A total of 3 study patients experienced post-surgical complications of corneal perforation (1 patient) and purulent exudate spreading (2 patients). The post-surgical outcome was good for all study participants as the surgeries were able to control infection and preserve the eyeball, with the potential of future corneal transplant. These results suggest that CF surgery may be a useful alternative treatment for refractory FK in countries such as China where there is lack of cornea donors. [ABSTRACT FROM AUTHOR]

Objective(s): Chronic liver disease has become a major health problem that causes serious damage to human health. Since the existing treatment effect was not ideal, we need to seek new treatment methods. Materials and Methods: We utilized the gene recombination technology to obtain the human hair mesenchymal stem cells which overexpression of human hepatocyte growth factor (hHGF). Furthermore, we verified the property of transfected cells through detecting surface marker by flow cytometry. Results: We show here establishment of the hHGF-overexpressing lentivirus vector, and successfully transfection to human hair follicle mesenchymal stem cells. The verified experiments could demonstrate the human hair follicle mesenchymal stem cells which have been transfected still have the properties of stem cells. Conclusion: We successfully constructed human hair follicle mesenchymal stem cells which overexpression hHGF, and maintain the same properties compared with pro-transfected cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To systematically analyze the nature of measurement variability in lung cancer with multidetector computed tomography (CT) scans. METHODS: Multidetector CT scans of 67 lung cancer patients were analyzed. Unidimensional (Response Evaluation Criteria in Solid Tumor criteria), bidimensional (World Health Organization criteria), and volumetric measurements were performed independently by ten radiologists and were repeated after at least 5 months. Repeatability and reproducibility measurement variations were estimated by analyzing reliability, agreement, variation coefficient, and misclassification statistically. The relationship of measurement variability with various sources was also analyzed. RESULTS: Analyses of 69 lung tumors with an average size of 1.1–12.1 cm (mean 4.3 cm) indicated that volumetric technique had the minimum measurement variability compared to the unidimensional or bidimensional technique. Tumor characteristics (object effect) could be the primary factor to influence measurement variability while the effect of raters (subjective effect) was faint. Segmentation and size in tumor characteristics were associated with measurement variability, and some mathematical function was established between the volumetric variability and tumor size. CONCLUSION: Volumetric technique has the minimum variability in measuring lung cancer, and measurement variability is associated with tumor size by nonlinear mathematical function. [ABSTRACT FROM AUTHOR]

The problem of topology identification is valuable to understand and control complex networks. Furthermore, many complex networks are spatio-temporal in the real world. This study proposes a method to identify the topology of complex spatio-temporal networks with coupling time delay. Adaptive observer and novel updating laws are designed to provide the estimation of the topology. Finally, a numerical example is given to demonstrate the effectiveness of the proposed method. The result is general and can be applicable to contemporary network science and engineering. [ABSTRACT FROM AUTHOR]

Unsaturated column experiments were conducted with an undisturbed loamy sand soil to investigate the influence of flow interruption (FI) and ionic strength (IS) on the transport and retention of surfactant-stabilized silver nanoparticles (AgNP) and the results were compared to those obtained under continuous flow conditions. AgNP concentrations for breakthrough curves (BTCs) and retention profiles (RPs) were analyzed by ICP-MS. Experimental results were simulated by the numerical code HP1 (Hydrus-PhreeqC) with the DLVO theory, extended colloid filtration theory and colloid release model. BTCs of AgNP showed a dramatic drop after FI compared to continuous flow conditions. Evaporation increased due to FI, resulting in increased electrical conductivity of the soil solution, which led to a totally reduced mobility of AgNP. A reduction of IS after FI enhanced AgNP mobility slightly. Here the strongly increased Al and Fe concentration in the effluent suggested that soil colloids facilitated the release of AgNP (cotransport). The numerical model reproduced the measured AgNP BTCs and indicated that attachment to the air-water interface (AWI) occurring during FI was the key process for AgNP retention. [ABSTRACT FROM AUTHOR]

Aberrant regulation of glucose production makes a critical contribution to the impaired glycemic control that is observed in type 2 diabetes. Although isotopic tracer methods have proven to be informative in quantifying the magnitude of such alterations, it is presumed that one must rely on venous access to administer glucose tracers which therein presents obstacles for the routine application of tracer methods in rodent models. Since intraperitoneal injections are readily used to deliver glucose challenges and/or dose potential therapeutics, we hypothesized that this route could also be used to administer a glucose tracer. The ability to then reliably estimate glucose flux would require attention toward setting a schedule for collecting samples and choosing a distribution volume. For example, glucose production can be calculated by multiplying the fractional turnover rate by the pool size. We have taken a step-wise approach to examine the potential of using an intraperitoneal tracer administration in rat and mouse models. First, we compared the kinetics of [U-13C]glucose following either an intravenous or an intraperitoneal injection. Second, we tested whether the intraperitoneal method could detect a pharmacological manipulation of glucose production. Finally, we contrasted a potential application of the intraperitoneal method against the glucose-insulin clamp. We conclude that it is possible to 1) quantify glucose production using an intraperitoneal injection of tracer and 2) derive a "glucose production index" by coupling estimates of basal glucose production with measurements of fasting insulin concentration; this yields a proxy for clamp-derived assessments of insulin sensitivity of endogenous production. [ABSTRACT FROM AUTHOR]

Background: Genes in inflammatory pathways play a pivotal role in the development of colorectal cancer. We conducted a two-stage case-control study and aimed at screening the colorectal cancer-associated genetic variations in inflammatory genes. Methods: Twenty-three candidate variants were genotyped in 952 primary colorectal cancer cases and 875 cancerfree controls from eastern China. Promising single nucleotide polymorphisms were further genotyped in 518 cases and 554 controls from middle China. Expression quantitative trait loci and differential gene expression analyses were performed for the associated gene. Results: rs2282151 presented consistently significant associations with the risk of colorectal cancer in both stages (odds ratio (95 % confidence interval) = 1.30 (1.16-1.46), risk allele = C, Pcombined = 8.9E-6). Gene expression quantitative trait loci analyzes uncovered consistent cis-regulatory signals which showed that the C allele of rs2282151 was associated with increased expression level of heat shock protein 90 alpha family class B member 1 (HSP90AB1). Then we found that the mRNA expression levels of HSP90AB1 were significantly higher in tumor tissues than normal tissues (fold-change = 1.83) in 28 pairs of colorectal tissue samples. The expression difference was consistent with data from online datasets. Additionally, we observed notable peaks of H3K27ac and H3K4me3 near the first intron of HSP90AB1 using ChIP-seq data from multiple cell lines (including HCT116). Conclusions: Our findings indicate that the C allele of the novel colorectal cancer-associated variant rs2282151 is associated with increased expression levels of HSP90AB1, which is expressed higher in colorectal tumor tissues than in normal tissues. [ABSTRACT FROM AUTHOR]

Background: Double aortic arch (DAA) associated with other cardiac anomalies is uncommon. We review the outcomes of primary complete repair of DAA with concomitant cardiac anomalies in a single center.Methods: From September 2005 through March 2014, 15 patients underwent primary complete repair of DAA with concomitant cardiac anomalies. The mean age was 53 months (range, two months to 19 years).Results: All patients underwent primary complete correction through a median sternotomy. One patient died in hospital from severe pneumonia. The intubation time ranged from 20 to 68 h and the intensive care unit stay ranged from one day to five days. Postoperative complications were infrequent and included left vocal cord paralysis in one patient. A residual ventricular septal defect was found in one patient. During follow-up, all patients were in New York Heart Association Class I.Conclusions: Primary complete repair of DAA with concomitant cardiac anomalies is feasible and results in excellent long-term outcomes. [ABSTRACT FROM AUTHOR]

Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-ΚB activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-α, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-ΚB activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-ΚB activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis. [ABSTRACT FROM AUTHOR]

G protein-coupled receptor 120 (GPR120), an adipogenic receptor critical for the differentiation and maturation of adipocytes, plays an important role in controlling obesity in both humans and rodents and, thus, is an attractive target of obesity treatment studies. However, the mechanisms that regulate the expression of porcine GPR120 remain unclear. In this study, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) techniques were used to analyze and identify the binding of C/EBPβ (transcription factor CCAAT/enhancer binding protein beta) to the GPR120 promoter. C/EBPb overexpression and RNA interference studies showed that C/EBPβ regulated GPR120 promoter activity and endogenous GPR120 expression. The binding site of C/EBPb in the GPR120 promoter region from -101 to -87 was identified by promoter deletion analysis and site-directed mutagenesis. Overexpression of C/EBPb increased endogenous GPR120 expression in pig kidney cells (PK). Furthermore, when endogenous C/EBPβ was knocked down, GPR120 mRNA and protein levels were decreased. The stimulatory effect of C/EBPβ on GPR120 transcription and its ability to bind the transcription factor-binding site were confirmed by luciferase, ChIP, and EMSA. Moreover, the mRNA and protein expression levels of C/EBPβ were induced by high fat diet feeding. Taken together, it can be concluded that C/EBPβ plays a vital role in regulating GPR120 transcription and suggests HFD-feeding induces GPR120 transcription by influencing C/EBPβ expression. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) is a pivotal event in the progression of cancer towards metastasis. Given that pigment epithelium-derived factor (PEDF) inhibits angiogenesis, the present study analyzed whether PEDF expression is associated with EMT and prognosis in invasive ductal breast cancer (IDC). Immunohistochemical analysis was used to examine the expression levels of PEDF, E-cadherin, vimentin, Snail and nuclear factor-κB (NF-κB) in 119 cases of IDC. Correlations between PEDF expression and EMT-related genes, and clinicopathological features and clinical prognosis were analyzed. E-cadherin, vimentin, Snail and NF-κB expression was correlated with tumor size, lymph node metastasis and clinicopathological stage. PEDF expression was closely associated with tumor size. Spearman's rank correlation analysis revealed a positive correlation between PEDF and E-cadherin, vimentin, Snail and NF-κB expression (P<0.05). Additionally, Kaplan-Meier survival analysis demonstrated that the five-year survival rate was higher for patients with PEDF-.and E-cadherin-positive tumors, but was lower for those with vimentin-, Snail- and NF-κB-positive tumors. Vimentin, E-cadherin and NF-κB levels were dependent prognostic factors of favorable outcomes in IDC, as determined by Cox multivariate analysis. PEDF expression in breast cancer was significantly associated with EMT-related genes, suggesting that it may be an EMT suppressor. However, its potential as a prognostic indicator in breast cancer warrants further investigation. [ABSTRACT FROM AUTHOR]

Boron-rich tungsten borides are premier prototypes of a new class of ultrahard compounds. Here, we show by first-principles calculations that their stress-strain relations display surprisingly diverse and anomalous behavior under a variety of loading conditions. Most remarkable is the dramatically changing bonding configurations and deformation modes with rising boron concentration in WBn (n = 2, 3, 4), resulting in significantly different stress responses and unexpected indentation strength variations. This novel phenomenon stems from the peculiar structural arrangements in tungsten borides driven by boron's ability toform unusually versatile bonding states. Our results elucidate the intriguing deformation mechanisms that define a distinct type of ultrahard material. These new insights underscore the need to explore unconventional structure-property relations in a broad range of transition-metal light-element compounds. [ABSTRACT FROM AUTHOR]

To better understand human adaptation to stress, and in particular to hypoxia, we took advantage of one of nature's experiments at high altitude (HA) and studied Ethiopians, a population that is well-adapted to HA hypoxic stress. Using whole-genome sequencing, we discovered that EDNRB (Endothelin receptor type B) is a candidate gene involved in HA adaptation. To test whether EDNRB plays a critical role in hypoxia tolerance and adaptation, we generated EdnrB knockout mice and found that when EdnrB-/+ heterozygote mice are treated with lower levels of oxygen (O2), they tolerate various levels of hypoxia (even extreme hypoxia, e.g., 5% O2) very well. For example, they maintain ejection fraction, cardiac contractility, and cardiac output in severe hypoxia. Furthermore, O2 delivery to vital organs was significantly higher and blood lactate was lower in EdnrB-/+ compared with wild type in hypoxia. Tissue hypoxia in brain, heart, and kidney was lower in EdnrB-/+ mice as well. These data demonstrate that a lower level of EDNRB significantly improves cardiac performance and tissue perfusion under various levels of hypoxia. Transcriptomic profiling of left ventricles revealed three specific genes [natriuretic peptide type A (Nppa), sarcolipin (Sln), and myosin light polypeptide 4 (Myl4)] that were oppositely expressed (q < 0.05) between EdnrB-/+ and wild type. Functions related to these gene networks were consistent with a better cardiac contractility and performance. We conclude that EDNRB plays a key role in hypoxia tolerance and that a lower level of EDNRB contributes, at least in part, to HA adaptation in humans. [ABSTRACT FROM AUTHOR]

Chronic mountain sickness (CMS) is a disease that affects many high-altitude dwellers, particularly in the Andean Mountains in South America. The hallmark symptom of CMS is polycythemia, which causes increased risk of pulmonary hypertension and stroke (among other symptoms). A prevailing hypothesis in high-altitude medicine is that CMS results from a population-specific "maladaptation" to the hypoxic conditions at high altitude. In contrast, the prevalence of CMS is very low in other high-altitude populations (e.g., Tibetans and Ethiopians), which are seemingly well adapted to hypoxia. In recent years, concurrent with the advent of genomic technologies, several studies have investigated the genetic basis of adaptation to altitude. These studies have identified several candidate genes that may underlie the adaptation, or maladaptation. Interestingly, some of these genes are targeted by known drugs, raising the possibility of new treatments for CMS and other ischemic diseases. We review recent discoveries, alongside the methodologies used to obtain them, and outline some of the challenges remaining in the field. [ABSTRACT FROM AUTHOR]

A series of pleuromutilin derivatives containing alkylamine and nitrogen heterocycle groups were designed and synthesised under mild conditions. The in vitro antibacterial activity of these semisynthetic derivatives against four strains of Staphylococcus aureus (MRSA ATCC 43300, S.aureus ATCC 29213, S.aureus AD3, and S.aureus 144) were evaluated by the broth dilution method. Compound 13 was found to have excellent antibacterial activity against MRSA (MIC = 0.0625 µg/mL). Furthermore, compound 13 was further studied by the time-killing kinetics and the post-antibiotic effect approach. In the mouse thigh infection model, compound 13 exhibited superior antibacterial efficacy than that of tiamulin. Meanwhile, compound 13 showed a lower inhibitory effect than that of tiamulin on RAW264.7 and 16HBE cells at the concentration of 10 µg/mL. Molecular docking study revealed that compound 13 can effectively bind to the active site of the 50S ribosome (the binding free energy = - 9.66 kcal/mol). [ABSTRACT FROM AUTHOR]

Background Anopheles sinensis is an important mosquito vector of Plasmodium vivax, which is the most frequent and widely distributed cause of recurring malaria throughout Asia, and particularly in China, Korea, and Japan. Results We performed 454 next-generation sequencing and obtained a draft sequence of A. sinensis assembled into scaffolds spanning 220.8 million base pairs. Analysis of this genome sequence, we observed expansion and contraction of several immune-related gene families in anopheline relative to culicine mosquito species. These differences suggest that speciesspecific immune responses to Plasmodium invasion underpin the biological differences in susceptibility to Plasmodium infection that characterize these two mosquito subfamilies. Conclusions The A. sinensis genome produced in this study, provides an important resource for analyzing the genetic basis of susceptibility and resistance of mosquitoes to Plasmodium parasites research which will ultimately facilitate the design of urgently needed interventions against this debilitating mosquito-borne disease. [ABSTRACT FROM AUTHOR]

A widely distributed mayfly species Ametropus fragilis Albarda, recorded from Europe to North America and the Far East of Russia and Mongolia, was collected from Ili River (Xinjiang Uygur Autonomous Region, northwestern China). This updated distribution information shows it occupies a large geographic region and more water systems. The species, genus and family, all new for China, have unique and distinct identification characteristics: psammophilous nymphs having extensions on the anterior mesonotum, spinous pads at the base of forelegs and enlongated claws, male imagos with fused penes and two pair of long cubital intercalaries in forewings. However, the phylogenetic position of family Ametropodidae remains unclear although it is generally grouped in the superfamily Siphlonuroidea. [ABSTRACT FROM AUTHOR]

Tungsten borides are among a distinct class of transition-metal light-element compounds with superior mechanical properties that rival those of traditional superhard materials. An in-depth understanding of these compounds, however, has been impeded by uncertainties regarding their complex crystal structures. Here, we examine a wide range of chemical compositions of tungsten borides using a recently developed global structural optimization approach. We establish thermodynamically stable structures and identify a large number of metastable phases. These results clarify and correct previous structural assignments and predict new structures for possible synthesis. Our findings provide crucial insights for understanding the rich and complex crystal structures of tungsten borides, which have broad implications for further exploration of this class of promising materials. [ABSTRACT FROM AUTHOR]

Overnutrition, such as a highfat (HF) diet, is a feature followed by some in developed nations that leads to obesity and fatty liver disease. In rats, when fed a fat-high diet, some develop obesity (obesity prone, OP) while others display an obesity-resistant (OR) phenotype. The present study investigated the differences between OP and OR rats on their activation of hepatic cellular senescence pathways on a HF diet. Male OP and OR rats were fed a HF diet containing 45% kcal from fat for 13 wk, and livers were collected for analysis by quantitative real-time PCR, Western blot, and chromatin immunoprecipitation. OP rats were 41% heavier than OR rats, despite consuming the same amount of food. Triacylglycerol levels were increased significantly in both plasma and liver of OP rats. Gene analysis demonstrated a significant increase of both the amount and the transcription rates of p16INK4a and p21Cip1 mRNA in OP rats. The increased p16INK4a and p21Cip1 also caused a significant decrease in the level of phosphorylation of retinoblastoma protein. In OP rats, the increase of p16INK4a was associated with the higher acetylation levels of histone H4 at the p16INK4a promoter and coding region and lower methylation level of histone H3 lysine-27 in the p16INK4a coding region. The increase of pCip1 was associated with increased acetylation of both histone H3 and H4 and decreased trimethylation of histone H3 lysine-27 at the pCip1 promoter. In the p21Cip1 coding region, dimethylation of histone H3 lysine-4 was significantly higher (P <0.05) in livers of OP rats compared with OR rats. [ABSTRACT FROM AUTHOR]

It is well appreciated that reactive oxygen species (ROS) are deleterious to mammals, including humans, especially when generated in abnormally large quantities from cellular metabolism. Whereas the mechanisms leading to the production of ROS are rather well delineated, the mechanisms underlying tissue susceptibility or tolerance to oxidant stress remain elusive. Through an experimental selection over many generations, we have previously generated Drosophila melanogaster flies that tolerate tremendous oxidant stress and have shown that the family of antimicrobial peptides (AMPs) is over-represented in these tolerant flies. Furthermore, we have also demonstrated that overexpression of even one AMP at a time (e.g. Diptericin) allows wild-type flies to survive much better in hyperoxia. In this study, we used a number of experimental approaches to investigate the potential mechanisms underlying hyperoxia tolerance in flies with AMP overexpression. We demonstrate that flies with Diptericin overexpression resist oxidative stress by increasing antioxidant enzyme activities and preventing an increase in ROS levels after hyperoxia. Depleting the GSH pool using buthionine sulfoximine limits fly survival, thus confirming that enhanced survival observed in these flies is related to improved redox homeostasis. We conclude that 1) AMPs play an important role in tolerance to oxidant stress, 2) overexpression of Diptericin changes the cellular redox balance between oxidant and antioxidant, and 3) this change in redox balance plays an important role in survival in hyperoxia. [ABSTRACT FROM AUTHOR]

Through long-term laboratory selection (over 200 generations), we have generated Drosophila melanogaster populations that tolerate severe, normally lethal, levels of hypoxia. Because of initial experiments suspecting genetic mechanisms underlying this adaptation, we compared the genomes of the hypoxia-selected flies with those of controls using deep resequencing. By applying unique computing and analytical methods we identified a number of DNA regions under selection, mostly on the X chromosome. Several of the hypoxia-selected regions contained genes encoding or regulating the Notch pathway. In addition, previous expression profiling revealed an activation of the Notch pathway in the hypoxia-selected flies. We confirmed the contribution of Notch activation to hypoxia tolerance using a specific ?-secretase inhibitor, N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), which significantly reduced adult survival and life span in the hypoxia-selected flies. We also demonstrated that flies with loss-of-function Notch mutations or RNAi-mediated Notch knockdown had a significant reduction in hypoxia tolerance, but those with a gain-of-function had a dramatic opposite effect. Using the UAS-Gal4 system, we also showed that specific overexpression of the Notch intracellular domain in glial cells was critical for conferring hypoxia tolerance. Unique analytical tools and genetic and bioinformatic strategies allowed us to discover that Notch activation plays a major role in this hypoxia tolerance in Drosophila melanogaster. [ABSTRACT FROM AUTHOR]

Purpose: Angiogenesis, which plays an important role in tumor growth and metastasis, is regulated by a balance between angiogenic stimulators and inhibitors. Pigment epithelium-derived factor (PEDF), a secreted glycoprotein is an important inhibitor of angiogenesis. Although the precise mechanisms by which PEDF exerts its actions remain poorly understood, there is growing evidence supporting the role of PEDF as a candidate antitumor agent. In this study, we investigated the role of PEDF in breast cancer. Methods: We investigated the correlation of PEDF protein levels with cancer progression and prognosis in patients with invasive ductal breast cancer (IDC). We used immunohistochemistry in a cohort of 119 breast cancer patients to examine the expression of PEDF protein with an anti-PEDF antibody and to measure the microvessel density (MVD) with an anti-CD34 antibody. Results: PEDF was an endogenous inhibitor of angiogenesis in endothelial cells. Decreased intratumoral expression of PEDF was associated with a higher microvessel density (MVD), a more metastatic phenotype, and poorer clinical outcome. PEDF was positive in 43.7% patients. Patients with low PEDF expression had a significantly higher MVD count when compared with patients with high PEDF expression. In univariate and multivariate analysis, PEDF was an independent prognostic factor. Conclusion: The inverse correlation between PEDF expression and MVD in human breast cancer suggests that low PEDF expression is associated with angiogenesis in breast cancer. PEDF expression is therefore a potentially useful prognostic marker for breast cancer. [ABSTRACT FROM AUTHOR]

Although oxidative stress is deleterious to mammals, the mechanisms underlying oxidant susceptibility or tolerance remain to be elucidated. In this study, through a long-term laboratory selection over many generations, we generated a Drosophila melanogaster strain that can live and reproduce in very high O2 environments (90% O2), a lethal condition to naïve flies. We demonstrated that tolerance to hyperoxia was heritable in these flies and that these hyperoxia-selected flies exhibited phenotypic differences from naïve flies, such as a larger body size and increased weight by 20%. Gene expression profiling revealed that 227 genes were significantly altered in expression and two third of these genes were down-regulated. Using a mutant screen strategy, we studied the role of some altered genes (up- or down-regulated in the microarrays) by testing the survival of available corresponding P-element or UAS construct lines under hyperoxic conditions. We report that downregulation of several candidate genes including Tropomyosin 1, Glycerol 3 phosphate dehydrogenase, CG33129, and UGP as well as up-regulation of Diptericin and Attacin conferred tolerance to severe hyperoxia. In conclusion, we identified several genes that were not only altered in hyperoxia-selected flies but we also prove that these play an important role in hyperoxia survival. Thus our study provides a molecular basis for understanding the mechanisms of hyperoxia tolerance. [ABSTRACT FROM AUTHOR]

Abstract  Two deltamethrin resistance-associated serine protease genes (NYD-tr and NYD-ch) were isolated from Culex pipiens pallens in our previous study. To study the function of NYD-Tr and NYD-Ch in the metabolism of deltamethrin, we constructed the recombinant plasmid pET32a(+)/NYD-tr and pET32a(+)/NYD-ch with a 6× histidine tag. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analyses of the recombinant proteins revealed that the molecular weights of NYD-Tr and NYD-Ch are 42 and 50 kDa. Enzyme activity assay indicated that the recombinant NYD-Tr and NYD-Ch had the corresponding features of trypsin and chymotrypsin. Using BApNA as the substrate, NYD-Tr gave optimal activity between pH 9.0 and 10.5, while NYD-Ch was optimally active over the range of pH 8.0–11.0 using the S(Ala)2ProPhe-pNA as the substrate. Then, we investigated the metabolism of deltamethrin by NYD-Tr and NYD-Ch. Our results showed that NYD-Tr and NYD-Ch could hydrolyze deltamethrin. The acute oral toxicity of the metabolite to Wistar rats was much lower than deltamethrin. [ABSTRACT FROM AUTHOR]

A new method for parameter optimization of pharmacokinetics based on an artificial immune network named PKAIN is proposed. To improve local searching ability of the artificial immune network, a partition-based concurrent simplex mutation is developed. By means of evolution of network cells in the PKAIN artificial immune network, an optimal set of parameters of a given pharmacokinetic model is obtained. The Laplace transform is applied to the pharmacokinetic differential equations of remifentanil and its major metabolite, remifentanil acid. The PKAIN method is used to optimize parameters of the derived compartment models. Experimental results show that the two-compartment model is sufficient for the pharmacokinetic study of remifentanil acid for patients with mild degree of renal impairment. [ABSTRACT FROM AUTHOR]

A new spectrophotometric method using covalently attached capture antibody labeled with alkaline phosphatase is developed for the detection of fPSA. [ABSTRACT FROM AUTHOR]

The aims of the current study were to 1) examine the effects of hypoxia and acidosis on cultured cortical neurons and 2) explore the role of transporters and ion channels in hypoxic injury. Cell injury was measured in cultured neurons or hippocampal slices following hypoxia (1% O2) or acidosis (medium pH 6.8) treatment. Inhibitors of transporters and ion channels were employed to investigate their roles in hypoxic injury. Our results showed that 1) neuronal damage was apparent at 5-7 days of hypoxia exposure, i.e., 36-41% of total lactate dehydrogenase was released to medium and 2) acidosis alone did not lead to significant injury compared with nonacidic, normoxic controls. Pharmacological studies revealed 1) no significant difference in neuronal injury between controls (no inhibitor) and inhibition of Na+-K+-ATP pump, voltage-gated Na+ channel, ATP-sensitive K+ channel, or reverse mode of Na+/Ca2+ exchanger under hypoxia; however, 2) inhibition of NBCs with 500 μM DIDS did not cause hypoxic death in either cultured cortical neurons or hippocampal slices; 3) in contrast, inhibition of Na+/H+ exchanger isoform 1 (NHE1) with either 10 μM HOE-642 or 2 μM T-162559 resulted in dramatic hypoxic injury (+95% for HOE-642 and + 100% for T-162559 relative to normoxic control, P < 0.001) on treatment day 3, when no death occurred for hypoxic controls (no inhibitor). No further damage was observed by NHE1 inhibition on treatment day 5. We conclude that inhibition of NHE1 accelerates hypoxia-induced neuronal damage. In contrast, DIDS rescues neuronal death under hypoxia. Hence, DIDS-sensitive mechanism may be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Hypoxia is a hallmark of respiratory, neurological, or hematological diseases as well as life at high altitude. For example, chronic constant hypoxia (CCH) occurs in chronic lung diseases or at high altitude, whereas chronic intermittent hypoxia (CIH) occurs in diseases such as sleep apnea or sickle cell disease. Despite the fact that such conditions are frequent, the cellular and molecular mechanisms underlying the effect of hypoxia, whether constant or intermittent, are not well understood. In this study, we first determined the effect of CCH and CIH on global gene expression in different regions of mouse brain using microarrays and then investigated the biological role of genes of interest. We found that: 1) in the cortical region, the expression level of 80 genes was significantly altered by CIH (16 up- and 64 downregulated), and this number increased to 137 genes following CCH (34 up- and 103 downregulated); 2) a similar number of gene alterations was identified in the hippocampal area, and the majority of the changes in this region were upregulations; 3) two genes (Sspn and Ttc27) were downregulated in both brain regions and following both treatments; and 4) RNA interference-mediated knockdown of Sspn increased cell death in hypoxia in a cell culture system. We conclude that CIH or CCH induced significant and distinguishable alterations in gene expression in cortex and hippocampus and that Sspn seems to play a critical role in inducing cell death under hypoxic conditions. [ABSTRACT FROM AUTHOR]

A new two-dimensional-layered fluoroaluminophosphate (C4H11NOH)3.5[Al4(PO4)5F]·0.5H3O (denoted as AIPO-CJ20) with an Al/P ratio of 4:5 has been synthesized solvothermally by using 2-amino-2-methyl-1-propanol as the structure-directing agent. Its structure was determined by single-crystal X-ray diffraction analysis and further characterized by solid-state NMR techniques, including 27Al, 19F → 27Al cross-polarization, and 31P magic angle spinning NMR. The alternation of Al-centered tetrahedra (AlO4 and AIO3F) and PO3(O) tetrahedra gives rise to a new type of 4.6.16-net sheet. The inorganic sheets are stacked in an ABAB sequence along the [010] direction and further held together through strong H bonds between protonated template molecules and PO groups in the inorganic layers. Except for Mu-4, AIPO-CJ20 is the second layered aluminophosphate with an Al/P ratio of 4:5, and it contains the largest pore opening of 16-rings in the known layered aluminophosphates. Furthermore, the coordination of Al and P of fluoroaluminophosphates is summarized. Crystal data: (C4H11 NOH)3.5[Al4(PO4)5F]·-0.5H3O, monoclinic, C2/c (No. 15), a = 32.678(7) Å, b = 12.956(3) Å, c = 21.045(4) &#00C5;, &#03B2; = 115.17(3)°, V = 8064(3) &#00C5;&#00B3;, Z = 8, R1 = 0.0837 [I &#003E; 2&#03C3;(I)], and wR2 = 0.2428 (all data). [ABSTRACT FROM AUTHOR]

A series of anionic framework aluminophosphates, with different Al/P ratios, have been investigated by various solid-state NMR techniques, including 27Al, 31P magic angle spinning (MAS), 27Al → 31P cross polarization (CP), 27Al{31P} rotational echo double resonance (REDOR), and 31P{27Al} transfer of population double resonance (TRAPDOR). Different Al coordinations (AlO6 , AlO7 , and AlO6b) and P coordinations (PO6 , PO1 Ot, PO2bO06, and PObO16), where b represents bridging oxygens and t represents terminal oxygens, can be unambiguously determined based on the solid-state NMR spectroscopy. Furthermore, a new method to determine the Al/P ratio of open-framework aluminophosphates has been established, which is useful for the understanding of unknown aluminophosphate structures. [ABSTRACT FROM AUTHOR]

A new three-dimensional open-framework aluminophosphate(NH4)2Al4(PO4)4(HPO4)·H2O/denoted AIPO-CJ19) with an AI/P ratio of 4⁄5 has been synthesized, using pyridine as the solvent and 2-aminopyridine as the structure-directing agent, under solvothermal conditions. The structure was determined by single-crystal X-ray diffraction and further characterized by solid-state NMR techniques. The alternation of the Al-centered polyhedra (including AlO4, AlO5, and AlO6) and the P-centered tetrahedra (including PO4 and PO3OH) results in an interrupted open-framework structure with an eight-membered ring channel along the [100] direction. This is the first aluminophosphate containing three kinds of Al coordinations (AlO4, AlO5, and AlO6) with all oxygen vertexes connected to framework P atoms. ²⁷Al MAS NMR, ³¹P MAS NMR, and ¹H → ³¹p CPMAS NMR characterizations show that the solid-state NMR techniques are an effective complement to XRD analysis for structure elucidation. Furthermore, all of the possible coordinations of Al and P in the aluminophosphates with an Al/P ratio of 4⁄5 are summarized. Crystal data: (NH4)2Al4(PO4)4(HPO4)·H2O, monoclinic P21 (No. 4), a = 5.0568(3) Å, b = 21.6211 (18) Å, c = 8.1724(4) Å, β = 91.361(4) °, V = 893.27(10) ų Z = 2, R1 = 0.0456 (l > 2σ (l)), and wR2 = 0.1051 (all data). [ABSTRACT FROM AUTHOR]

In order to extend the potential applications of medical ultrasonic array transducers, two optimized directions with the maximal electromechanical coefficient k33′ and minimal k31 are determined for [001] and [110] poled 0.71Pb(Mg1/3Nb2/3)O3-0.29PbTiO3 single crystals using the experimental method. The maximum values of k33′ can reach 92.8% and 93.3%, respectively, corresponding to [001]W/[110]L and [110]W/[1–11]L cuts. Furthermore, we simulate the performances of three 3.5 MHz linear array transducers based on the determined directions by PIEZOCAD. Results indicate that under the [001]W/[110]L direction, 25% broader bandwidth, 40% shorter pulse length, and 3 dB higher sensitivity can be obtained compared to the traditional Pb(Zr1-xTix)O3 transducers. [ABSTRACT FROM AUTHOR]

Although the digital content industry (DCI) has been booming in recent years, there is no generally accepted definition of the industry. On the basis of reviewing prior studies on the subject, this paper traces the origin of the concept, explains the meaning of the industry, summarizes why some commonly-seen definitions were concluded, looks at their similarities and differences, and defines the relationship between DCI with other similar concepts like content industry, creative industry, copyright industry, information industry and information service industry. The paper then proposes the authors' understanding of DCI—an industrial cluster where cultural creation integrates with the information technology in various areas. [ABSTRACT FROM AUTHOR]

Background Educational inequalities in suicide have become increasingly prominent over the past decade. Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on suicide has the potential to reduce health disparities. Aims To examine the risk factors that mediate the relationship between educational attainment and suicide attempts and quantify their contributions to the mediation effect. Methods We conducted a two-sample Mendelian randomisation (MR) analysis to estimate the causal effect of educational attainment on suicide attempts, utilising genome-wide association study summary statistics from the Integrative Psychiatric Research (iPSYCH; 6024 cases and 44 240 controls) and FinnGen (8978 cases and 368 299 controls). We systematically evaluated 42 putative mediators within the causal pathway connecting reduced educational attainment to suicide attempts and employed two-step and multivariable MR to quantify the proportion of the mediated effect. Results In the combined analysis of iPSYCH and FinnGen, each standard deviation (SD) decrease in genetically predicted educational attainment (equating to 3.4 years of education) was associated with a 105% higher risk of suicide attempts (odds ratio (OR): 2.05; 95% confidence interval (CI): 1.81 to 2.31). Of the 42 risk factors analysed, the two-step MR identified five factors that mediated the association between educational attainment and suicide attempts. The respective proportions of mediation were 47% (95% CI: 29% to 66%) for smoking behaviour, 36% (95% CI: 0% to 84%) for chronic pain, 49% (95% CI: 36% to 61%) for depression, 35% (95% CI: 12% to 59%) for anxiety and 26% (95% CI: 18% to 34%) for insomnia. Multivariable MR implicated these five mediators collectively, accounting for 68% (95% CI: 40% to 96%) of the total effect. Conclusions This study identified smoking, chronic pain and mental disorders as primary intervention targets for attenuating suicide risk attributable to lower educational levels in the European population. [ABSTRACT FROM AUTHOR]

Exact solution of the nuclear mean-field plus separable pairing model is reexamined. New auxiliary constraints for solving the Bethe ansatz equations of the model are proposed. By using these auxiliary constraints, the Bethe ansatz form of eigenvectors of the mean-field plus separable pairing Hamiltonian with nondegenerate single-particle energies and nondegenerate separable pairing strengths purposed previously is verified. Since the solutions of the model with one- and two-orbit cases are known, verification of the solutions for these two special cases is made. To demonstrate structure and features of the solution, the model with three orbits in the ds shell is taken as a nontrivial example, of which two-pair results and the ground state of the three-pair case are provided explicitly. Since the number of equations involved increases with the number of orbits and pairs, to solve these equations for a large number of orbits and pairs seems still difficult. [ABSTRACT FROM AUTHOR]

Krüppel-like factor (KLF) 15 has emerged as a critical regulator of fibrosis in cardiovascular diseases. However, the precise role that KLF15 and its functional domain played in adventitial inflammation and fibrosis remains unclear. This study aims to investigate the role of the transactivation domain (TAD) of KLF15 in angiotensin II (Ang II)-induced adventitial pathologic changes. KLF15 expression was decreased in the vascular adventitia of Ang II-infused mice (1000 ng/kg/min, 14 d) and in adventitial fibroblasts (AFs) stimulated by Ang II (10-7 M). Adenovirus-mediated KLF15 overexpression normalized Ang II-induced vascular hypertrophy, increased collagen deposition, macrophage infiltration, and CCL2 and VCAM-1 expression. Interestingly, KLF15-ΔTAD (KLF15 with deletion of TAD at amino acids 132-152) overexpression showed no effect on the above pathologic changes. Similarly, perivascularly overexpression of KLF15 but not KLF15-ΔTAD in carotid arteries also attenuated Ang II-induced vascular inflammation and fibrosis. Furthermore, KLF15 overexpression after Ang II infusion rescued Ang II-induced vascular remodeling. CCL2 or VCAM-1-mediated monocyte and macrophage migration or adhesion to AFs in response to Ang II was negatively regulated by KLF15 through TAD. Ang II-enhanced Smad2/3 activation and adventitial migration, proliferation, and differentiation of AFs were suppressed by KLF15 but not KLF15-ΔTAD overexpression. Conversely, small interfering RNA knockdown of KLF15 aggravated Ang II-induced Smad2/3 activation and dysfunction of AFs. Luciferase, coimmunoprecipitation, and chromatin immunoprecipitation assay were used to demonstrate that interaction of KLF15 with Smad2/3 suppressed CCL2 expression through TAD. Mechanistically, activation of Ang II type 1 receptor/phospholipase Cγ 1/ERK1/2 signaling resulted in a decrease of KLF15 expression. In conclusion, these results demonstrate that KLF15 negatively regulates activation of AFs through TAD, which plays an important role in Ang II-induced adventitial inflammation and fibrosis. [ABSTRACT FROM AUTHOR]