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Diabetic cardiomyopathy (DCM) is a prevalent complication of diabetes mellitus characterized by cardiac dysfunction and myocardial remodeling. Farrerol (FA), an active ingredient in Rhododendron with various pharmacological activities, has an unclear specific role in DCM. Therefore, this study aims to investigate the effects of FA on DCM rats and elucidate its mechanism. The type 2 diabetes mellitus (T2DM) model was induced in adult male Sprague-Dawley rats by administering a high-fat diet for 8 weeks along with STZ injection. Subsequent to successful modeling, FA and the positive drug Dapagliflozin (Dapa) were orally administered via gavage for an additional 8-week period. After administration, the rats' body weight, fasting blood glucose, fasting insulin, and blood lipid profiles were quantified. Cardiac function was assessed through evaluation of cardiac function parameters, histopathological examination and measurement of myocardial enzyme markers were conducted to assess myocardial injury and fibrosis, Oil red O staining was utilized to evaluate myocardial lipid accumulation, wheat germ agglutinin (WGA) staining was used for assessing cardiomyocyte hypertrophy, and Western blot analysis was used to detect the proteins expression level of AMP-activated protein kinase (AMPK) pathway. The rat cardiomyocyte H9c2 were induced with palmitic acid to establish an in vitro cell model of myocardial lipid toxicity. Subsequently, the cells were subjected to treatment with FA and AMPK inhibitor Compound C, followed by assessment of lipid formation and expression levels of proteins related to the AMPK signaling pathway. The findings demonstrated that both FA and Dapa exhibited efficacy in ameliorating diabetic symptoms, cardiac dysfunction, myocardial fibrosis, cardiomyocyte hypertrophy, and lipid accumulation in T2DM rats. Additionally, they were found to enhance AMPK phosphorylation and PPARα expression while down-regulating CD36. Similarly, FA was observed to inhibit lipid formation in H9c2 and activate the AMPK signaling pathway. However, the improved effect of FA on lipotoxic cardiomyocytes induced by palmitic acid was partially reversed by Compound C. Therefore, the activation of the AMPK signaling pathway by FA may enhance cardiac lipid metabolism, thereby improving cardiac dysfunction and myocardial fibrosis in DCM rats. [ABSTRACT FROM AUTHOR]

Current study aims to investigate the biological function of circular RNA (circRNA, circ_0000337) in cervical cancer (CC). Bioinformatic analyses were used to predict targets for circ_0000337 and miR-155-5p, and analyze the gene expression differences between cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tissues and normal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to assess mRNA and protein expressions of circ_0000337, microRNA-155-5p (miR-155-5p) and member RAS oncogene family (RAB3B), respectively. Following the establishment of gain/loss-of-function models, CCK-8 was performed to evaluate cell proliferation. Bioinformatics analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to identify the interaction in circ_0000337, miR-155-5p, and RAB3B. Circ_0000337 and RAB3B were upregulated, while miR-155-5p was downregulated in CC tissues and cell lines. circ_0000337 overexpression promoted cell proliferation, circ_0000337 knock down inhibited cell proliferation by sponging miR-155-5p. RAB3B was a target of miR-155-5p which was positively regulated by circ_0000337. In the collected CC tissues, there was a negative correlation between miR-155-5p and circ_0000337 or RAB3B, and a positive correlation between circ_0000337 and RAB3B. miR-155-5p was positively, while RAB3B was negatively correlated with OS in patients with CC, and they were negatively correlated. In conclusion, circ_0000337 upregulates RAB3B by sponging miR-155-5p to promote CC cell proliferation. [ABSTRACT FROM AUTHOR]

DNA is well-documented to stimulate immune response. However, the nature of the DNA to activate immune surveillance is less understood. Here, we show that the activation of cyclic GMP-AMP synthase (cGAS) depends on DNA mechanical flexibility, which is controlled by DNA-sequence, -damage and -length. Consistently, DNA-sequence was shown to control cGAS activation. Structural analyses revealed that a conserved cGAS residue (mouse R222 or human R236) contributed to the DNA-flexibility detection. And the residue substitution neutralised the flexibility-controlled DNA-potential to activate cGAS, and relaxed the DNA-length specificity of cGAS. Moreover, low dose radiation was shown to mount cGAS-mediated acute immune surveillance (AIS) via repairable (reusable) DNAs in hrs. Loss of cGAS-mediated AIS decreased the regression of local and abscopal tumours in the context of focal radiation and immune checkpoint blockade. Our results build a direct link between immunosurveillance and DNA mechanical feature. DNA is well-documented to stimulate immune response. Here the authors show that the activation of cyclic GMP-AMP synthase (cGAS) depends on DNA mechanical flexibility, itself determined by DNA-sequence, damage and length. [ABSTRACT FROM AUTHOR]

Particulate matter with a diameter below 2.5 µm (PM2.5) is a major urban air pollutant. This is a well-acknowledged risk factor for diseases. PM2.5 positively correlates with the abundance and species of airborne bacteria. The sensitivity and fragility of neonates lead to this population being frequently admitted to the hospital and thus exposed to risk factors for nosocomial infection. However, the association between the outdoor PM2.5 concentration and nosocomial infection is under-researched. This study aimed to explore the association between the outdoor PM2.5 concentration and nosocomial bacterial infection in neonates. A total of 7482 neonates admitted to the neonatal ward at a hospital in Guangzhou, China, between 2017 and 2020 were recruited. Weather data and the average daily concentrations of PM2.5, PM10, SO2, and NO2 within the same period were collected. Multivariable Fine–Gray competing risk models were constructed to explore the association between PM2.5 and nosocomial bacterial infections in the form of a PM2.5 single-pollutant model and PM2.5 + SO2, PM2.5 + NO2, and PM2.5 + PM2.5~10 double-pollutant models. Sixty-two neonates experienced nosocomial infections within the follow-up period. In the PM2.5 single-pollutant model, we found a positive association between PM2.5 and bacterial infection. Every 10-µg increase in the average of daily PM2.5 concentration was associated with an average of 27% (95% CI, 1.02–1.55, P = 0.03) higher subdistribution hazard rate of nosocomial infection. No statistically significant association with infection was found in the PM2.5 + SO2, PM2.5 + NO2, and PM2.5 + PM2.5~10 models. The outdoor PM2.5 concentration is positively associated with nosocomial bacterial infection in neonates. [ABSTRACT FROM AUTHOR]

This study explored the effect of cellulose nanofibrils (CNFs) as a binder at different weight percentages, namely, 0%, 0.05%, 0.1%, and 0.15%, on the hydration, rheology, pore structure, and mechanical properties of ultra-high ductility cementitious composites (UHDCCs). The hydration kinetics with different CNF contents were studied using isothermal calorimetry (IC), showing a retardation effect on the early hydration of UHDCCs matrices at 70 h due to adsorption of CNFs on the surface of cement particles. Thermogravimetric analysis (TGA) demonstrated that CNFs improved the degree of hydration at 28 days by facilitating transport of water into unhydrated cement cores. The two rheological parameters, namely, the yield stress and plastic viscosity, of the fresh UHDCCs matrices increased with increasing CNF content. Low-field nuclear magnetic resonance (LF-NMR) analysis, as a nondestructive method, indicated that the addition of CNFs could reduce the porosity of the UHDCCs and refine their pore size distribution, and an 8.9–46.1% increase in the compressive strength of the corresponding specimens was found. Notably, CNFs increased the tensile initial cracking stress and tensile stress of UHDCCs by 91.2% and 30.8%, respectively, and maintained or increased their tensile strain-hardening capacity by over 8%. The flexural tests also found a 54.6% increase in the initial stress and a 14.8% increase in the peak stress. As a preliminary, CNFs show crucial promise as a greener nanomaterial to improve the strength and ductility of UHDCCs. [ABSTRACT FROM AUTHOR]

Development of efficient solvents to dissolve lignocellulose and its main components is of significant importance for the utilization/transformation of lignocellulose. Herein, several ionic liquid (IL)-based deep eutectic solvents (DESs) were prepared using four ILs as the hydrogen bond acceptors and four different hydrogen bond donors, including thiourea (TU), N-methylthiourea (NMTU), glycerol (Gly), and ethylene glycol (EG). Using the dissolution of xylan (a typical type of hemicellulose) as the example, it was observed that the synthesized IL-based DESs could efficiently dissolve xylan. Especially in the DES formed from 1-allyl-3-methylimidazolium chloride and EG, the xylan solubility could reach as high as 40.4 wt% at 343.15 K. More importantly, the solubility of xylan in IL-based DESs was much higher than that in the corresponding IL. The enhancement effect might be ascribed to that the formation of DESs could significantly decrease the viscosity and increase the hydrogen bond accepting ability. Additionally, the regeneration of the xylan from the DESs could be easily realized using ethanol as the anti-solvent, and the regenerated xylan kept a high consistency with the original xylan. Ionic liquid-based deep eutectic solvents were designed for highly efficient dissolution of xylan owing to the decreased viscosity and the increased hydrogen-bond accepting ability. [ABSTRACT FROM AUTHOR]

In order to maintain tissue homeostasis, cells communicate with the outside environment by receiving molecular signals, transmitting them, and responding accordingly with signaling pathways. Thus, one key challenge in engineering molecular signaling systems involves the design and construction of different modules into a rationally integrated system that mimics the cascade of molecular events. Herein, we rationally design a DNA-based artificial molecular signaling system that uses the confined microenvironment of a giant vesicle, derived from a living cell. This system consists of two main components. First, we build an adenosine triphosphate (ATP)-driven DNA nanogatekeeper. Second, we encapsulate a signaling network in the biomimetic vesicle, consisting of distinct modules, able to sequentially initiate a series of downstream reactions playing the roles of reception, transduction and response. Operationally, in the presence of ATP, nanogatekeeper switches from the closed to open state. The open state then triggers the sequential activation of confined downstream signaling modules. Cells communicate with the outside world to maintain homeostasis. Here the authors design a synthetic biology DNA-based signalling system AMSsys that responds to the presence of ATP. [ABSTRACT FROM AUTHOR]

In the recruitment domain, knowing the employer industry of jobs is important to get an insight about the demand in each industry. The existing system at CareerBuilder uses an employer name normalization system and an employer knowledge base (KB) to infer the employer industry of a job. However, errors may occur during the computation of the job employer and in the construction of the employer KB with the industry attributes. Since the KB is huge, it is not possible to manually detect the errors. Therefore, in this paper we use machine learning techniques to automatically detect the errors. With the observation that the main jobs posted by an employer often relate to the employer industry, e.g., truck driver jobs often correspond to employers in the transportation industry, we develop a system that classifies the industry of an employer using job posting data. We aggregate job postings from an employer and derive features from employer names, employer descriptions, job titles, and job descriptions to predict the industry of the employer. Two models are used for classification: (1) support vector machine and (2) random forest. Our experiments show that random forest is more effective than SVM in identifying the errors in the existing industry classification system, which achieves precision 0.69, recall 0.78, and f-score 0.73. It especially better handles mixed feature vectors when normalization errors occur. We also observe that generally our models perform better in detecting errors for industries that have higher error rates. [ABSTRACT FROM AUTHOR]

With the rapid development of nanotechnology, nanoparticles with various sizes and compositions have been synthesized and proposed for industrial applications. At the same time, the health effects and environmental impacts of nanoparticles become an emerging concern to be addressed. Both in vitro and in vivo studies are of importance to better understand the toxicity of nanoparticles. It is thus essential to have a nanoparticle disperser capable of dispersing individual nanoparticles for these studies. A twin-head electrospray (THES) nanoparticle disperser for animal inhalation exposure studies has recently become commercially available from TSE Systems Inc. Different from the cone-jet electrospray method used in the majority of literature, this particular disperser operates at the multi-jet mode. In this study, we reported our finding on the performance evaluation of the THES disperser with respect to its mass throughput and quality of size distribution of aerosol produced. Three different nanomaterials (TiO, ZnO, and NiO) were used in this study. It is found that the maximal mass throughput of the studied disperser was achieved by keeping the distance between two opposite spray capillary tips at 3.0 cm, operating the primary carrier-to-capillary sheath flow rates at the ratio of 4:3, and feeding spray suspensions at a flow rate of 20 µl/min. Under the above settings and operations, the highest mass concentration for nano-ZnO was measured at 14.56 mg/m. Nanoparticle streams with higher concentrations can be further produced by lowering the total carrier gas flow rate and spraying suspensions of higher nanomaterial concentrations. Our study also found that the particle mass throughput of the studied disperser had a good linear relationship with the mass concentration of spray suspension. In addition, the spatial uniformity of nano aerosol distribution in a TSE head-nose-only exposure chamber was investigated. An acceptable nano aerosol uniformity result was concluded based on the criteria of the coefficient of variation. Highlights: [ABSTRACT FROM AUTHOR]

To study the influence of multi-wall carbon nanotubes (MWCNTs) on the mechanical and microstructural properties of cementitious composites, 0.00, 0.02, 0.08, 0.10, and 0.20 wt% of multi-wall carbon nanotubes were added into cement mortar, in which the cement-sand ratio was 1:1.5. The flexural and compressive strengths of cement mortar at the age of 3, 7, 28 and 90 d and the fracture performance at the age of 28 d were determined, its 2D micrograph was tested by means of SEM, and the 3D defects distribution was firstly determined with or without CNTs by means of XCT (X-ray computerized tomography). The results showed that 0.08 wt% of CNTs improved the compressive strength and flexural strength by 18% and 19%, respectively, and a significant improvement of its fracture property was observed. Moreover lower addition of carbon nanotubes to cement mortars can improve its microstructure and decrease the defects significantly compared to the cement mortar without CNTs. With the increase of the content of CNTs, the mechanical properties of cement mortars presented to be declined largely due to the agglomeration of CNTs. [ABSTRACT FROM AUTHOR]

Currently, relatively large errors are found in numerical results in some low-specific-speed centrifugal pumps with unshrouded impeller because the effect of clearances and holes are not accurately modeled. Establishing an accurate analytical model to improve performance prediction accuracy is therefore necessary. In this paper, a three-dimensional numerical simulation is conducted to predict the performance of a low-specific-speed centrifugal pump, and the modeling, numerical scheme, and turbulent selection methods are discussed. The pump performance is tested in a model pump test bench, and flow rate, head, power and efficiency of the pump are obtained. The effect of taking into consideration the back-out vane passage, clearance, and balance holes is analyzed by comparing it with experimental results, and the performance prediction methods are validated by experiments. The analysis results show that the pump performance can be accurately predicted by the improved method. Ignoring the back-out vane passage in the calculation model of unshrouded impeller is found to generate better numerical results. Further, the calculation model with the clearances and balance holes can obviously enhance the numerical accuracy. The application of disconnect interface can reduce meshing difficulty but increase the calculation error at the off-design operating point at the same time. Compared with the standard k-ɛ, renormalization group k-ɛ, and Spalart-Allmars models, the Realizable k-ɛ model demonstrates the fastest convergent speed and the highest precision for the unshrouded impeller flow simulation. The proposed modeling and numerical simulation methods can improve the performance prediction accuracy of the low-specific-speed centrifugal pumps, and the modeling method is especially suitable for the centrifugal pump with unshrouded impeller. [ABSTRACT FROM AUTHOR]

Although legumain has been found to be a prognostic factor in both breast cancer and colorectal cancer, its effects on gastric cancer are unknown. In this study, we investigated effects of legumain on gastric cancer and the correlation between legumain expression and prognosis of gastric cancer patients. SGC7901 cells were transduced with legumain cDNA (SGC7901-hLeg) for overexpression of legumain or with legumain shRNA to knock down legumain. In vitro tumor migration was examined by wound healing assay. Furthermore, a tumorigenicity and metastasis mouse model was used to examine legumain function in vivo; asparaginyl endopeptidase inhibitor (AEPI, an inhibitor of legumain) was injected to the mice (i.p.) to evaluate its therapeutic effect. Tissue microarray analysis from 112 gastric cancer patients was performed to evaluate the association between legumain expression and the cumulative survival time. Legumain was highly expressed in gastric cancer patients and some gastric cancer cell lines. Legumain promoted gastric cell migration in vitro and promoted gastric tumor growth and metastasis in vivo, and these effects were reversed by knockdown of legumain with shRNA or treated with AEPI. In gastric cancer clinical samples, legumain expression in tumor was significantly higher than in non-tumor and was negatively associated with the cumulative survival rate. In conclusion, legumain was highly expressed in gastric adenocarcinoma; legumain promoted gastric cancer tumorigenesis and metastasis in vitro and in vivo. Legumain expression in tumor was a poor prognostic factor for gastric cancer patients, and legumain could be a potential target molecule for gastric cancer therapy in clinic. [ABSTRACT FROM AUTHOR]

This paper presents a reliability-based sensitivity method for mechanical components with arbitrary distribution parameters. Techniques from the perturbation method, the Edgeworth series, the reliability-based design theory, and the sensitivity analysis approach were employed directly to calculate the reliability-based sensitivity of mechanical components on the condition that the first four moments of the original random variables are known. The reliability-based sensitivity information of the mechanical components can be accurately and quickly obtained using a practical computer program. The effects of the design parameters on the reliability of mechanical components were studied. The method presented in this paper provides the theoretic basis for the reliability-based design of mechanical components. [ABSTRACT FROM AUTHOR]

The reliability sensitivity analysis of uncertain multi-degree-of-freedom nonlinear vibration systems with independent failure modes subjected to random excitation is examined. An earlier version of the statistical fourthmoment method is extended to deal with vector-valued and matrix-valued functions and is developed to determine the first four moments of the system response and state function. Random variables and system derivatives are conveniently arranged into 2D matrices by means of Kronecker algebra. The distribution function of the system state function is approximately determined by the standard normal distribution functions using Edgeworth series technique, and its reliability and reliability sensitivity are presented and discussed. [ABSTRACT FROM AUTHOR]

Anion starch nanoparticles (StNP) were prepared in water-in-oil microemulsion. Folate modified with PEG was conjugated to the surface of StNP to obtain the folate-conjugated starch nanoparticles (FA-PEG/StNP). The average diameter of FA-PEG/StNP determined by AFM and Zeta-Sizer apparatus was about 130 nm. Doxorubicin (DOX)-loaded FA-PEG/StNP was obtained via infiltrating combination. The result of UV spectrophotometer showed that the saturation concentration of DOX-loaded FA-PEG/StNP was 28 µg/mg, which was effective for the controlled release of anticancer drug DOX. The cell experiments showed that the Lc50 of DOX-loaded FA-PEG/StNP and DOX-loaded StNP was higher than that of DOX, which indicates that FA-PEG/StNP and StNP can decrease the toxicity of DOX; while the lethal rate of DOX-loaded FA-PEG/StNP was 3 times that of DOX-loaded StNP with the same quantity of DOX, which indicates that FA in FA-PEG/StNP is effective for improving the targeting function of nanoparticles, thus enhancing the inhibition effect of anticancer drug to cancer cell. This work demonstrates that the FA-PEG/StNP system is a potentially useful system for the targeted delivery of anticancer drug DOX. [ABSTRACT FROM AUTHOR]

Based on the generalized probabilistic finite element method, this paper presents an approximate solution technique for general multi-degree-of-freedom nonlinear random vibration systems with random parameters. The fourth-moment technique, maximum entropy theory and incomplete probability information theory are employed to systematically develop a reliability analysis method for dynamic random structural systems with correlation failure modes under unavailable joint probability density functions of basic random variables. The first passage problem of multi-degree-of-freedom nonlinear random vibration systems is solved. [ABSTRACT FROM AUTHOR]

Abundant studies of cyclic wetting-drying of concrete have suggested a “maximum phenomenon” by which chloride concentrations first increase with depth to a local maximum and then decrease at greater depths. This phenomenon may arise primarily because of carbonation, but may also be exacerbated by cyclic capillary suction and moisture evaporation during wetting-drying cycles. This paper investigates the mechanism responsible for the maximum phenomenon under conditions that exclude cyclic capillary suction. The results show that different chloride maxima form near the surface of all specimens under conditions of either accelerated carbonation or carbonation in normal air environment. A large amount of bound chloride is released when carbonation causes decomposition of Friedel’s salt and C-S-H gel, and the decrease in water content significantly increases the chloride concentration in the pore solution near the specimen surface. The resulting chloride concentration gradient drives free chloride diffusion from the surface to the interior, thereby reducing the actual chloride content near the exposed surface. More severe carbonation conditions increase the severity of the maximum phenomenon. [ABSTRACT FROM AUTHOR]