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Objective. Genetic approaches are increasingly advantageous in characterizing treatmentresistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing bettertailored therapeutic targets. Methods. TRS-related proteome-wide association studies (PWAS) were conducted on genomewide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/- MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results. In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (PPWAS-ROS/MAP = 4.15 x 10-2 and PPWAS-Banner = 3.38 x 10-3 ) and APOL2 (PPWAS-ROS/MAP = 4.49 x 10-3 and PPWASBanner = 8.26 x 103 ). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions. Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role. [ABSTRACT FROM AUTHOR]

A typical vibration signal of fault bearing is composed of periodic repetitive transient impulses, multiple vibration disturbance and background noise. Variational mode decomposition (VMD) represents a potential tool for analyzing such signals. However, the reasonable selection of VMD algorithm parameters hinders its application in mechanical signal processing to a certain extent. According to the specific characteristics of rolling bearing fault signal, the composite dimensionless index is constructed as the objective function to ensure the optimal decomposition of VMD. To further enhance the fault characteristics, the tunable Q-factor wavelet transform (TQWT) along with sparse code shrinkage is proposed to denoise the modal components containing periodic impulses, which further highlights the impulses and improves the sparseness of fault signal. Simulation and experimental signal analysis verify the effectiveness and reliability of this method. The results show that the use of optimized VMD and TQWT based sparse code shrinkage dramatically sharpens the impulses from the mixed signal with noise interference and increases the sparseness to a level. [ABSTRACT FROM AUTHOR]

Cerebral venous sinus thrombosis (CVST) is a rare and devastating complication of inflammatory bowel disease (IBD). Early diagnosis and prompt treatment could improve prognosis. The aim of our study was to investigate the clinical data and predictive factors of inflammatory bowel disease in patients with a diagnosis of CVST. All IBD patient data were collected from July 2013 and September 2020. Clinical data, predictive factors and prognosis were compared between IBD patients with CVST and the IBD control group. The incidence of CVST in our study was 0.48%. The mean age of IBD patients with CVST was 34.9 years. The average duration of IBD was 4 years when cerebrovascular events occurred. The clinical presentation of CVST included headache (73.1%), vomiting (30.8%), limb dysmetria (26.9%), speech impairment (11.5%), blurred vision (7.7%), epileptic seizures (7.7%) and drowsiness (3.8%). The most common location for CVST was the transverse sinus (61.5%) followed by the superior sagittal sinus (30.8%). Anaemia, low albumin and elevated d-dimer were independent predictors of CVST in patients with IBD. Anticoagulation therapy was effective. The prognosis of IBD patients with CVST was worse than that of IBD patients without CVST. Early identification of the risk and clinical features of CVST in IBD patients is important. Prompt antithrombotic therapy is a safe and effective treatment. [ABSTRACT FROM AUTHOR]

Plant-derived polyphenols have been widely used to design new multifunctional materials for particle and surface modification. The lack of temporal and spatial control over the oxidation and deposition processes, however, limits possible applications of this diverse class of natural compounds. Autoxidation and deposition of phenolic compounds are uncontrollably triggered by basic pH and oxygen. In this project, inspired by the properties of natural antioxidants to scavenge free radicals and reactive oxygen species (ROS), we propose a method to effectively control the autoxidation and deposition of plant phenolic compounds under basic conditions. We demonstrate that natural antioxidants can inhibit autoxidation of plant polyphenols in basic pH in dark environment. However, UV irradiation of these solutions leads to on-demand temporal and spatial polymerization and deposition of polyphenols. This bioinspired method was used to demonstrate the controlled polymerization, and micropatterning on flat surfaces and inside microfluidic channels opening the way to well-defined 2D coatings based on natural polyphenols and introducing a new simple path to the fabrication of bioinspired functional materials, with potential applications in a wide range of fields. [ABSTRACT FROM AUTHOR]

Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of XBJ injection. At first, the stability of HSYA in solution and in a Xuebijing injection was investigated, then the mechanisms of the increased stability of HSYA in the XBJ injection were investigated to provide useful information on clinical safety. HSYA stability was investigated as a function of pH and temperature in aqueous solution and an XBJ injection, following the guidelines from the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Products were identified by UPLC-MS/MS. HSYA reaction followed first-order kinetics under all conditions. The half-life of HSYA in XBJ was almost 40 times longer than in aqueous solution. The activation energies of HSYA reaction in aqueous solution and XBJ were calculated to be 78.53 and 92.90 kJ∙mol-1 by using Arrhenius equation. The results indicated that HSYA was more stable in XBJ than in aqueous solution. Two products were identified and the mechanism was intra-molecular nucleophilic substitution. The excellent stability of HSYA in XBJ injection partly due to the micelles formed in the injection. The study may provide clues for compatibility in TCM prescription and also provide useful information for further preparation technology research of HSYA and assessment of clinical safety of XBJ. [ABSTRACT FROM AUTHOR]

The application of graphene oxide (GO) as a potential vaccine adjuvant has recently attracted considerable attention. However, appropriate surface functionalization of GO is crucial to improve its biocompatibility and enhance its adjuvant activity. In this study, we developed a simple method to prepare chitosan (CS)-functionalized GO (GO-CS) and further investigated its potential as a nanoadjuvant. Compared with GO, GO-CS possessed considerably smaller size, positive surface charge, and better thermal stability. The functionalization of GO with CS was effective in decreasing the non-specific protein adsorption and improving its biocompatibility. Furthermore, GO-CS significantly activated RAW264.7 cells and stimulated more cytokines for mediating cellular immune response, which was mainly due to the synergistic immunostimulatory effect of both GO and CS. GO-CS exhibits strong potential as a safe nanoadjuvant for vaccines and immunotherapy. [ABSTRACT FROM AUTHOR]

Five novel three-dimensional lanthanide metal-organic frameworks (Ln-MOFs) constructed by 4-(3′,5′-dicarboxylphenoxy) phthalic acid (H4dcppa), namely, {[Eu(Hdcppa)(H2O)2]·H2O}n (Eu-1), [Eu1.5(dcppa) (HCOO)0.5(H2O)2]n (Eu-2), {[Ln2K2(dcppa)2(H2O)6]·mH2O}n (Ln = Eu-3, Tb-4, Gd-5, m = 5 for Eu-3 and Tb-4; m = 4 for Gd-5) (HCOOH = formic acid) have been prepared by hydro(solvo)thermal method and fully characterized. Structural analyses indicated that H4dcppa ligand took four different coordination fashions in 1-5 and, thus, resulted in diversity of the targeted Ln-MOFs: Eu-1 displays the rare 3D (5,5)-connected vbk net, containing one-dimensional left- and right-handed helical chains; Eu-2 possesses a 3D (3,8)-connected tfz-d topology constructed by trinuclear paddlewheel [Eu3(CO2)6] SBUs; 3-5 are isostructural and show 3D (Ln-dcppa4-) + 2D (K-dcppa4-) → 3D (LnK-dcppa4-) structure. Eu-3, with regular 1D channels and open Lewis basic oxygen atoms on the pore surface was utilized for specific sensing and binding of metal ions through Lewis base interactions, shows high selectivity, fast response time (8 min), and high sensitivity (KSV = 4.3/5.2 × 104 L/mol) for Fe3+ and Cu2+ ions with luminescent quenching. Furthermore, the detection limit of the sensor is in the 10-6 M level. The triplet state (T1 = 23364 cm-1) of H4dcppa studied by the Gd(III)-MOF and Gd-5 demonstrates that the ligand ideally populates Eu(III)/Tb(III) emission with luminescent quantum yields (Φoverall) of 11.2% for Eu-1, 27.6% for Eu-2, 18.5% for Eu-3, and 62% for Tb-4, respectively. [ABSTRACT FROM AUTHOR]

The weld thinning phenomenon occurring in conventional friction stir welding (C-FSW) has negative effects on the formation quality and serviceable reliability of FSW joints. The existing methods for solving the weld thinning problem in FSW exhibit some universal deficiencies, such as low efficiency, low quality and narrow applicable range. Motivated by this challenge, a novel non-weld-thinning (NWT) FSW process, during which a zero shoulder plunge depth is applied to the welding tool, is proposed and investigated in the present paper. The results indicate that the high quality NWT-FSW joints can be efficiently produced by using this novel process. Microstructural analysis implies that the grains in weld nugget of NWT-FSW joints present smaller size and a more uniformly distributed feature than those of C-FSW joints. Compared with the C-FSW joints, the NWT-FSW joints are characterized by narrower softening regions and higher minimum hardness values, leading to an increase in tensile strength during tensile test. The temperature history analysis suggests that the thermal effect of tool shoulder is effectively controlled during NWT-FSW due to the application of zero shoulder plunge depth, which is the intrinsic reason for the grain refinement and strength improvement of NWT-FSW joints. [ABSTRACT FROM AUTHOR]

2A14-T6 aluminum alloy was bobbin tool friction stir welded (BT-FSW) at various welding speeds. The microstructural analysis indicates that in the weld nugget the grains of the upper layer are smaller than those of the lower layer, which should be attributed to the larger extent of heat dissipation through the top shoulder. An ellipse-shaped region and a triangle-shaped region characterized by large elongated grain structures are found in the middle layer of the weld nugget of BT-FSW joints. The insufficient material plastic deformation caused by the flat feature of tool pin is believed to be the reason for the formation of the both regions. The insufficiently stirred regions can significantly affect the fracture features of joints during tensile test. At low welding speeds, the joints are all fractured along the border of the ellipse-shaped region. While at high welding speeds, the fracture path is just through the triangle-shaped region. With increasing welding speed, the joint strength is firstly increased to a peak and then shows a sharp decrease due to the occurrence of void defects. A maximum strength efficiency of 75% is achieved in this study. [ABSTRACT FROM AUTHOR]

The article presents the discussion on benefits of time-restricted eating not being disregarded in persons with altered circadian rhythms.

It is always difficul to reserve rings andmain truck lines in the real engineering of feature extraction for terrain model. In this paper, a new skeleton feature extraction method is proposed to solve these problems, which put forward a simplification algorithm based on morphological theory to eliminate the noise points of the target points produced by classical profile recognition. As well all know, noise point is the key factor to influence the accuracy and efficiency of feature extraction. Our method connected the optimized feature points subset after morphological simplification; therefore, the efficiency of ring process and pruning has been improved markedly, and the accuracy has been enhanced without the negative effect of noisy points. An outbranching concept is defined, and the related algorithms are proposed to extract sufficient long trucks, which is capable of being consistent with real terrain skeleton. All of algorithms are conducted on many real experimental data, including GTOPO30 and benchmark data provided by PPA to verify the performance and accuracy of our method. The results showed that our method precedes PPA as a whole. [ABSTRACT FROM AUTHOR]

Multiresolution hierarchy based on features (FMRH) has been applied in the field of terrain modeling and obtained significant results in real engineering. However, it is difficult to schedule multiresolution data in FMRH from external memory. This paper proposed new multiscale feature model and related strategies to cluster spatial data blocks and solve the scheduling problems of FMRH using spatial neighborhood. In the model, the nodes with similar error in the different layers should be in one cluster. On this basis, a space index algorithm for each cluster guided by Hilbert curve is proposed. It ensures thatmulti-resolution terrain data can be loaded without traversing the whole FMRH; therefore, the efficiency of data scheduling is improved. Moreover, a spatial closeness theorem of cluster is put forward and is also proved. It guarantees that the union of data blocks composites a whole terrain without any data loss. Finally, experiments have been carried out on many different large scale data sets, and the results demonstrate that the schedule time is shortened and the efficiency of I/O operation is apparently improved, which is important in real engineering. [ABSTRACT FROM AUTHOR]

Characteristic symptoms of hyperthyroidism include weight loss, heart palpitation, and sweating. Thyroid hormones (TH) can stimulate thermogenesis through central and peripheral mechanisms. Previous studies have shown an association between dysfunction of cardiotrophin-like cytokine factor 1 (CLCF1) and cold-induced sweating syndrome, with recent research also indicating a link between CLCF1 and brown adipose tissue thermogenesis. However, it remains unclear whether CLCF1 and TH have synergistic or antagonistic effects on thermogenesis. This study aims to investigate the influence of thyroid hormone on circulating CLCF1 levels in humans and explore the potential possibilities of thyroid hormone in regulating energy metabolism by modulating Clcf1 in mice. By recruiting hyperthyroid patients and healthy subjects, we observed significantly lower serum CLCF1 levels in hyperthyroid patients compared to healthy subjects, with serum CLCF1 levels independently associated with hyperthyroidism after adjusting for potential confounders. Tissue analysis from mice treated with T3 revealed a decrease in CLCF1 expression in BAT and iWAT of C57BL/6 mice. These findings suggest that TH may play a role in regulating CLCF1 expression in adipose tissue. [ABSTRACT FROM AUTHOR]

an important role in thermogenesis and energy metabolism. However, the regulatory factors that inhibit BAT activity remain largely unknown. Here, cardiotrophin-like cytokine factor 1 (CLCF1) is identified as a negative regulator of thermogenesis in BAT. Adenovirus-mediated overexpression of CLCF1 in BAT greatly impairs the thermogenic capacity of BAT and reduces the metabolic rate. Consistently, BAT-specific ablation of CLCF1 enhances the BAT function and energy expenditure under both thermoneutral and cold conditions. Mechanistically, adenylate cyclase 3 (ADCY3) is identified as a downstream target of CLCF1 to mediate its role in regulating thermogenesis. Furthermore, CLCF1 is identified to negatively regulate the PERK-ATF4 signaling axis to modulate the transcriptional activity of ADCY3, which activates the PKA substrate phosphorylation. Moreover, CLCF1 deletion in BAT protects the mice against diet-induced obesity by promoting BAT activation and further attenuating impaired glucose and lipid metabolism. Therefore, our results reveal the essential role of CLCF1 in regulating BAT thermogenesis and suggest that inhibiting CLCF1 signaling might be a potential therapeutic strategy for improving obesity-related metabolic disorders. [ABSTRACT FROM AUTHOR]

Platelets (PLTs) are classically used in the clinical setting to maintain hemostasis. Recent evidence supports important roles for PLTs in host inflammatory and immune responses, and PLT-rich plasma has been demonstrated to inhibit the growth of bacteria in vitro and in vivo; however, few studies have examined whether PLTs can inhibit bacterial growth directly, and related mechanisms have not been elucidated further. Accordingly, in this study, we evaluated the effects of PLTs on bacterial growth. We washed and purified PLTs from peripheral blood, then confirmed that PLTs significantly inhibited the growth of Staphylococcus aureus when cocultured in vitro. Moreover, PLTs damaged DNA and blocked cell division in S. aureus. During coculture, PLT-derived TGF-ß1 was dramatically down-regulated compared with that in PLT culture alone, and the addition of TGF-ß1 to the coculture system promoted the inhibition of PLTs on S. aureus. Analysis of a murine S. aureus infection model demonstrated that the depletion of PLTs exacerbated the severity of infection, whereas the transfusion of PLTs alleviated this infection. Our observations demonstrate that PLTs could directly inhibit the growth of S. aureus by damaging DNA and blockage cell division, and that PLT-derived TGF-ß1 may play an important role in this machinery.--Xu, J., Yi, J., Zhang, H., Feng, F., Gu, S., Weng, L., Zhang, J., Chen, Y., An, N., Liu, Z., An, Q., Yin, W., Hu, X. Platelets directly regulate DNA damage and division of Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN) are the most common contaminants in cereals worldwide, causing a wide range of adverse health effects on animals and humans. Many environmental factors can affect the production of these mycotoxins. Here, we have used response surface methodology (RSM) to optimize the Fusarium graminearum strain 29 culture conditions for maximal toxin production. Three factors, medium pH, incubation temperature and time, were optimized using a Box-Behnken design (BBD). The optimized conditions for DON production were pH 4.91 and an incubation temperature of 23.75 °C for 28 days, while maximal ZEN production required pH 9.00 and an incubation temperature of 15.05 °C for 28 days. The maximum levels of DON and ZEN production were 2811.17 ng/mL and 23789.70 ng/mL, respectively. Considering the total level of DON and ZEN, desirable yields of the mycotoxins were still obtained with medium pH of 6.86, an incubation temperature of 17.76 °C and a time of 28 days. The corresponding experimental values, from the validation experiments, fitted well with these predictions. This suggests that RSM could be used to optimize Fusarium mycotoxin levels, which are further purified for use as potential mycotoxin standards. Furthermore, it shows that acidic pH is a determinant for DON production, while an alkaline environment and lower temperature (approximately 15 °C) are favorable for ZEN accumulation. After extraction, separation and purification processes, the isolated mycotoxins were obtained through a simple purification process, with desirable yields, and acceptable purity. The mycotoxins could be used as potential analytical standards or chemical reagents for routine analysis. [ABSTRACT FROM AUTHOR]

Background: To humanize yeast N-glycosylation pathways, genes involved in yeast specific hyper-mannosylation must be disrupted followed by the introduction of genes catalyzing the synthesis, transport, and addition of human sugars. However, deletion of these genes, for instance, OCH1, which initiates hyper-mannosylation, could cause severe defects in cell growth, morphogenesis and response to environmental challenges. Results: In this study, overexpression of RHO1, which encodes the Rho1p small GTPase, is confirmed to partially recover the growth defect of Saccharomyces cerevisiae Δalg3Δoch1 double mutant strain. In addition, transmission electron micrographs indicated that the cell wall structure of RHO1-expressed cells have an enhanced glucan layer and also a recovered mannoprotein layer, revealing the effect of Rho1p GTPase on cell wall biosynthesis. Similar complementation phenotypes have been confirmed by overexpression of the gene that encodes Fks2 protein, a catalytic subunit of a 1,3-β-glucan synthase. Besides the recovery of cell wall structure, the RHO1-overexpressed Δalg3Δoch1 strain also showed improved abilities in temperature tolerance, osmotic potential and drug sensitivity, which were not observed in the Δalg3Δoch1-FKS2 cells. Moreover, RHO1 overexpression could also increase N-glycan site occupancy and the amount of secreted glycoproteins. Conclusions: Overexpression of RHO1 in 'humanized' glycoprotein producing yeasts could significantly facilitate its future industrial applications for the production of therapeutic glycoproteins. [ABSTRACT FROM AUTHOR]

Single source multipath fault propagation analysis has contributed much on system fault modeling, fault location, and fault diagnosis. Studies have shown that the electronic system has small world network features. In this study, a new model of small world was established to observe the rapidly fault propagation of the electronic systems. In order to meet the higher requirements of testability and reliability for complex electronic systems, an improved fault propagation analysis method based on small world algorithm was proposed. First, inspired by the idea of small-world networks, a small world algorithm was proposed to greatly improve the speed of getting the fault path compared with other evolutionary algorithm. In addition, calculating entropy was firstly introduced to distinguish the importance of different nodes in systems. Finally, the proposed method was applied to a radar transmitter system for fault propagation analysis. The result shows that the performance is improved a lot by introducing the small world characteristic and simplified entropy. Simulation results demonstrate the computation method. Also, fault propagation could be applied to large-scale systems, which is meaningful for test points selection and fault diagnosis. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. However, the molecular mechanisms that promote dysregulation of hepatic triglyceride metabolism and lead to NAFLD are poorly understood, and effective treatments are limited. Leukemia inhibitory factor (LIF) is a member of the interleukin-6 cytokine family and has been shown to regulate a variety of physiological processes, although its role in hepatic triglyceride metabolism remains unknown. In the present study, we measured circulating LIF levels by ELISA in 214 patients with biopsy-diagnosed NAFLD as well as 314 normal control patients. We further investigated the potential role and mechanism of LIF on hepatic lipid metabolism in obese mice. We found that circulating LIF levels correlated with the severity of liver steatosis. Patients with ballooning, fibrosis, lobular inflammation, and abnormally elevated liver injury markers alanine transaminase and aspartate aminotransferase also had higher levels of serum LIF than control patients. Furthermore, animal studies showed that white adipose tissue– derived LIF could ameliorate liver steatosis through activation of hepatic LIF receptor signaling pathways. Together, our results suggested that targeting LIF-LIF receptor signaling might be a promising strategy for treating NAFLD. [ABSTRACT FROM AUTHOR]

Background: The long-term efficacy and safety of time-restricted eating for weight loss are not clear.Methods: We randomly assigned 139 patients with obesity to time-restricted eating (eating only between 8:00 a.m. and 4:00 p.m.) with calorie restriction or daily calorie restriction alone. For 12 months, all the participants were instructed to follow a calorie-restricted diet that consisted of 1500 to 1800 kcal per day for men and 1200 to 1500 kcal per day for women. The primary outcome was the difference between the two groups in the change from baseline in body weight; secondary outcomes included changes in waist circumference, body-mass index (BMI), amount of body fat, and measures of metabolic risk factors.Results: Of the total 139 participants who underwent randomization, 118 (84.9%) completed the 12-month follow-up visit. The mean weight loss from baseline at 12 months was -8.0 kg (95% confidence interval [CI], -9.6 to -6.4) in the time-restriction group and -6.3 kg (95% CI, -7.8 to -4.7) in the daily-calorie-restriction group. Changes in weight were not significantly different in the two groups at the 12-month assessment (net difference, -1.8 kg; 95% CI, -4.0 to 0.4; P = 0.11). Results of analyses of waist circumferences, BMI, body fat, body lean mass, blood pressure, and metabolic risk factors were consistent with the results of the primary outcome. In addition, there were no substantial differences between the groups in the numbers of adverse events.Conclusions: Among patients with obesity, a regimen of time-restricted eating was not more beneficial with regard to reduction in body weight, body fat, or metabolic risk factors than daily calorie restriction. (Funded by the National Key Research and Development Project [No. 2018YFA0800404] and others; ClinicalTrials.gov number, NCT03745612.). [ABSTRACT FROM AUTHOR]

Proteins achieve efficient energy storage and conversion through electron transfer along a series of redox cofactors. Multiheme cytochromes are notable examples. These proteins transfer electrons over distance scales of several nanometers to >10 μm and in so doing they couple cellular metabolism with extracellular redox partners including electrodes. Here, we report pump-probe spectroscopy that provides a direct measure of the intrinsic rates of heme-heme electron transfer in this fascinating class of proteins. Our study took advantage of a spectrally unique His/Met-ligated heme introduced at a defined site within the decaheme extracellular MtrC protein of Shewanella oneidensis. We observed rates of heme-to-heme electron transfer on the order of 109 s-1 (3.7 to 4.3 Å edge-to-edge distance), in good agreement with predictions based on density functional and molecular dynamics calculations. These rates are among the highest reported for ground-state electron transfer in biology. Yet, some fall 2 to 3 orders of magnitude below the Moser-Dutton ruler because electron transfer at these short distances is through space and therefore associated with a higher tunneling barrier than the through-protein tunneling scenario that is usual at longer distances. Moreover, we show that the His/Met-ligated heme creates an electron sink that stabilizes the charge separated state on the 100-μs time scale. This feature could be exploited in future designs of multiheme cytochromes as components of versatile photosynthetic biohybrid assemblies. [ABSTRACT FROM AUTHOR]

When machine tool spindles are running at a high rotation speed, thermal deformation will be introduced due to the generation of large amounts of heat, and machining accuracy will be influenced as a result, which is a generalized issue in numerous industries. In this paper, a new approach based on machine vision is presented for measurements of spindle thermal error. The measuring system is composed of a Complementary Metal-Oxide-Semiconductor (CMOS) camera, a backlight source and a PC. Images are captured at different rotation angles during end milling process. Meanwhile, the Canny edge detection and Gaussian sub-pixel fitting methods are applied to obtain the bottom edge of the end mill which is then used to calculate the lowest point coordinate of the tool. Finally, thermal extension of the spindle is obtained according to the change of the lowest point at different time steps of the machining process. This method is validated through comparison with experimental results from capacitive displacement sensors. Moreover, spindle thermal extension during the processing can be precisely measured and used for compensation in order to improve machining accuracy through the proposed method. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of Kawasaki disease (KD) suggests that an infectious agentmaybe a potential disease trigger in susceptible children. Several studies have shown that the cause of KD may be associated with Mycoplasma pneumoniae (M. pneumoniae) infection. Objectives:We aimed to investigate the relationship between M. pneumoniae infection and coronary artery aneurysm (CAA) in children with KD in China. Methods: From January 2015 to December 2018, a total of 330 children with KD met the inclusion criteria. Relevant data were extracted and analysed. Results: The children were stratified into two groups according to M. pneumoniae infection status. Significant differences were identified in the proportion of patients with fever > 10 days, the occurrence of small CAA, and the average serum sodium, prealbumin (PA), and albumin levels but not in the occurrence of medium and giant CAA between the two groups. According to binary logistic regression, M. pneumoniae infection (OR: 0.515; 95% CI: 0.309 - 0.860; P = 0.011), serum sodium levels (OR: 0.910; 95% CI: 0.851 - 0.972; P =0.005), and PA (OR: 0.900; 95% CI: 0.854 - 0.949; P≤ 0.001) levels were independently associated with occurrence of small CAA. Conclusions: We demonstrated that M. pneumoniae infection, serum sodium and PA levels are inversely related to the occurrence of small CAA. These results suggest that M. pneumoniae infection may be associated with a decreased incidence of small CAA. Further large-sample studies are needed. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) has become an expanding global public health problem. Although the glucocorticoid receptor (GR) is an important regulator of glucose metabolism, the relationship between circulating glucocorticoids (GCs) and the features of T2DM remains controversial. Here, we show that 17-hydroxyprogesterone (17-OHP), an intermediate steroid in the biosynthetic pathway that converts cholesterol to cortisol, binds to and stimulates the transcriptional activity of GR. Hepatic 17-OHP concentrations are increased in diabetic mice and patients due to aberrantly increased expression of Cyp17A1. Systemic administration of 17-OHP or overexpression of Cyp17A1 in the livers of lean mice promoted the pathogenesis of hyperglycemia and insulin resistance, whereas knockdown of Cyp17A1 abrogated metabolic disorders in obese mice. Therefore, our results identify a Cyp17A1/17-OHP/GR-dependent pathway in the liver that mediates obesity-induced hyperglycemia, suggesting that selectively targeting hepatic Cyp17A1 may provide a therapeutic avenue for treating T2DM. [ABSTRACT FROM AUTHOR]

Heparosan is a natural precursor of heparin biosynthesis in mammals. It is stable in blood circulation but can be degraded in lysosomes, showing good biocompatibility and long circulation features. So heparosan can be designed as anticancer drug carriers to increase tumor selectivity and improve the therapeutic effect. A novel redox-sensitive heparosancystamine- vitamin E succinate (KSV) micelle system was constructed for intracellular delivery of doxorubicin (DOX). Simultaneously, the redox-insensitive heparosan-adipic acid dihydrazide-vitamin E succinate copolymer (KV) was synthesized as control. DOX-loaded micelles (DOX/KSV) with an average particle size of 90-120 nm had good serum stability and redox-triggered depolymerization. In vitro drug release test showed that DOX/KSV micelles presented obvious redox-triggered release behavior compared with DOX/KV. Cytotoxicity and cell uptake were investigated using MGC80-3 tumor cells and COS7 fibroblast-like cells. The cell survival rate of blank micelles was more than 90%, and the cytotoxicity of DOX/KSV in MGC80-3 cells was higher than in COS7 cells, indicating that the carrier has better biocompatibility and less toxicity side effect. The cytotoxicity of DOX/KSV against MGC80-3 cells was significantly greater than that of free DOX and DOX/KV. Furthermore, compared with DOX/KV in MGC80-3 cells, DOX/KSV micelles uptook more anticancer drugs and then released DOX faster into the cell nucleus. The micelles were endocytosed by multiple pathways, but clathrin-mediated endocytosis was the main pathway. Therefore, heparosan polysaccharide could be a potential option as anticancer carrier for enhancing efficacy and mitigating toxicity. [ABSTRACT FROM AUTHOR]

Five-axis machine with rotary-tilting spindle head (RTSH) is always used for sculptured surface machining, and the tool-tip dynamics in various machining postures along the tool path directly affect the machining accuracy and stability. To rapidly evaluate the tool-tip dynamics at different postures during the structural design of tool-spindle-spindle head (TSSH) assembly, this paper proposes a coupled dynamic model of tool-spindle-bearing system (TSBS) and RTSH. The model is a rigid-flexible multibody dynamic model with 36 degrees-of-freedom (DOFs), where in the rotary shaft, swivel shaft and housing are treated as rigid bodies; the tool, tool holder, and spindle shaft are modeled by reduced beams; the bearings and flexible joints are modeled as spring-damping elements. The fully Cartesian coordinates and Lagrangian method are employed to deduce a general parametric dynamic equation. The analytical method for calculating the contact stiffness of bearings and flexible joints is systematically presented, including tool-holder joint, holder-spindle joint, spindle bearings, hirth coupling, and the bearings and locking joints of rotary and swivel shafts. The model is verified by the frequency response functions (FRFs) testing and modal testing at different postures. The experimental results show that the proposed model can be used for accurate and efficient evaluation of the tool-tip FRFs, natural frequencies and mode shapes of TSSH at an arbitrary posture. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) has become one of the most serious and long-term threats to human health. However, the molecular mechanism that links obesity to insulin resistance remains largely unknown. Here, we show that F-box and WD repeat domain-containing 7 (FBXW7), an E3 ubiquitin protein ligase, is markedly downregulated in the liver of two obese mouse models and obese human subjects. We further identify a functional low-frequency human FBXW7 coding variant (p.Ala204Thr) in the Chinese population, which is associated with elevated blood glucose and T2DM risk. Notably, mice with liver-specific knockout of FBXW7 develop hyperglycemia, glucose intolerance, and insulin resistance even on a normal chow diet. Conversely, overexpression of FBXW7 in the liver not only prevents the development of high-fat diet-induced insulin resistance but also attenuates the disease signature of obese mice. Mechanistically, FBXW7 directly binds to hepatokine fetuin-A to induce its ubiquitination and subsequent proteasomal degradation, comprising an important mechanism maintaining glucose homeostasis. Thus, we provide evidence showing a beneficial role of FBXW7 in glucose homeostasis. [ABSTRACT FROM AUTHOR]

Background: Neuregulin 4 (Nrg4) is a secreted adipokine recently identified as playing an important role in modulating systemic energy metabolism and the development of obesity-associated disorders. However, information is not available regarding the association between circulating Nrg4 and risk of metabolic syndrome (MetS) in humans. Methods: We measured serum Nrg4 in 1212 obese adult subjects (aged 40 years or older), with a waist circumference greater than 90 cm for men or 80 cm for women, recruited from the community. Results: MetS subjects had lower levels of circulating Nrg4 than healthy controls (P < 0.01). The prevalence of MetS was higher in subjects with lower levels of circulating Nrg4 compared to those with higher values (67.3 % vs. 57.4 %, P < 0.05). Likewise, subjects with low levels of circulating Nrg4 had high prevalence of raised fasting glucose and blood pressure, but there was no association with raised triglycerides and reduced HDL-c. In multivariable logistic regression analyses, increased serum Nrg4 was significantly associated with reduced risk of MetS (OR: 0.603; 95 % CI, 0.439-0.828; P = 0.002), adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic blood pressure, fasting glucose, triglyceride, HDL-c, HOMA-IR, and body fat mass; however, such associations with serum Nrg4 were not noted for each component of MetS. Conclusions: These findings indicate that circulating Nrg4 concentrations are inversely associated with risk of MetS in obese Chinese adults, suggesting that circulating Nrg4 concentrations may be a protective factor in the development of MetS. [ABSTRACT FROM AUTHOR]

Six novel luminescent materials In(III)-2,3-H2qldc/phen metal-organic assemblies (MOAs), namely, [In2(phen)3Cl6]·CH3CN (In1), [In2(phen)3Cl6]·CH3CN·2H2O (In2), [In2(phen)2Cl6] (In3), [In(3-qlc)2(phen)Cl] (In4), [In(3-qlc)2(2,2'-bipy)Cl]·2H2O (In5) and [In(3-qlc)3(phen)]·H2O (In6) (2,3-H2qldc = quinoline-2,3-dicarboxylic acid; 3-Hqlc = quinoline-3-carboxylic acid, which is formed from the decarboxylation reaction of 2,3-H2qldc; phen = 1,10-phenanthrolin; 2,2'-bipy = 2,2'-bipyridine) have been hydro(solvo)thermally synthesized and characterized by single-crystal X-ray diffraction, infrared (IR), elemental analysis, ¹H NMR spectra, and thermogravimetric analysis (TGA). The crystal structures of In1-In6 indicate that the hydrogen bonding and p···p stacking interactions play critical roles in the formation of the extended supramolecular array. In1 displays the rare hexatomic ring 3D (4,5)-connected supramolecular architecture through twofold interpenetrating of 2D cell membrane-like structures. In2 exhibits a 3D 4-connected sra supramolecular architecture. In3 is built from binuclear [In2Cl2] clusters and possesses an interesting 2D (4,4)-connected sql supramolecular network. Due to existing hydrogen bonds forming coplanar dimers, In4 and In5 show more extended p-conjugated system and appear as 3D diamond-like supramolecular architectures with point symbol 66. In6 is coordinated with four almost vertical ligands and further form a 3D diamond-like supramolecular architecture via hydrogen bonding and p···p stacking interactions. Complexes In1-In6 exhibit tunable luminescence with emission maxima containing deep blue, blue, light blue, green, and yellow green at 298 and 77 K both in DMSO solvent and in the solid state. It is worth noting that In4 and In5 exhibit good aggregation-induced emission (AIE) properties in the solid state. Both of them show very weak luminescence in dimethyl sulfoxide (DMSO, good solvent) while their intensity increased enormously by the addition of water (H2O, poor solvent) due to aggregation. [ABSTRACT FROM AUTHOR]

The pure nano-sized copper tungstate (CuWO4) powders were prepared by hydrothermal method and consequent annealing at 500°C for 120min. The thermogravimetric analysis was used to study dehydration processes, and the scanning electron microscopy (SEM) indicated that CuWO4 particles were mostly spherical in the size range from 60 to 90nm. Hydrogen reduction at 800°C for 60min converted the CuWO4 to W-Cu composite powders. The hydrogen reduction results showed that nano-sized CuWO4 particles calcining at 500°C for 120min indicated finer microstructure than the other calcination temperatures of 0°C, 400°C, 620°C, 650°C and 700°C. W-Cu particles were observed finest and homogeneous in the size range from 90 to 150nm by SEM images. Homogeneous distribution of W and Cu particles was clearly demonstrated by elemental mapping. Encapsulation of Cu phase by the W phase was observed by EDS and TEM. From FFT and HRTEM images, the orientation relationship of (01-1)Cu(01-1)W and a semicoherent interface between W and Cu phases could be observed. A good correlation between the HRTEM image and the calculated lattice misfit (&#948) was obtained. [ABSTRACT FROM AUTHOR]

Hepatosteatosis is characterized by an aberrant accumulation of triglycerides in the liver; however, the factors that drive obesity-induced fatty liver remain largely unknown. Here, we demonstrated that the secreted cell adhesion protein periostin is markedly upregulated in livers of obese rodents and humans. Notably, overexpression of periostin in the livers of WT mice promoted hepatic steatosis and hypertriglyceridemia. Conversely, both genetic ablation of periostin and administration of a periostin-neutralizing antibody dramatically improved hepatosteatosis and hypertriglyceridemia in obese mice. Overexpression of periostin resulted in reduced expression of peroxisome proliferator-activated receptor α (PPARα), a master regulator of fatty acid oxidation, and activation of the JNK signaling pathway. In mouse primary hepatocytes, inhibition of α6β4 integrin prevented activation of JNK and suppression of PPARα in response to periostin. Periostin-dependent activation of JNK resulted in activation of c-Jun, which prevented RORα binding and transactional activation at the Ppara promoter. Together, these results identify a periostin-dependent pathway that mediates obesity-induced hepatosteatosis. [ABSTRACT FROM AUTHOR]

The role of resveratrol (Res) in inflammation induced by ischemia/reperfusion is not well understood. The aim of the present study was to investigate whether Res modulates neutrophil accumulation and tumor necrosis factor-α (TNF-α) induction in an ischemia/reperfusion-injured rat heart model. The rats were randomly exposed to sham surgery, myocardial ischemia/reperfusion (MI/R) alone, MI/R + Res, MI/R + Res + L-NG-nitroarginine methyl ester (L-NAME) and MI/R + Res + methylene blue (MB). The results demonstrated that compared with MI/R, Res reduced the myocardial infarct area, myocardial myeloperoxidase levels, serum creatinine kinase and lactate dehydrogenase levels, and serum and myocardial TNF-α production. All the effects of Res demonstrated were inhibited by L-NAME (a nitric oxide (NO) synthase inhibitor) and MB [a cyclic guano-sine monophosphate (cGMP) inhibitor]. Thus, Res produces cardioprotective and anti-inflammatory effects. These effects may be associated with an increase in NO production, the inhibition of neutrophil accumulation, TNF-α induction and cGMP signaling pathways in myocardium subjected to MI/R. [ABSTRACT FROM AUTHOR]

Background Non-alcoholic fatty liver disease (NAFLD) is characterised by accumulation of excessive triglycerides in the liver. Obesity is usually associated with NAFLD through an unknown mechanism. Objective To investigate the roles of Yin Yang 1 (YY1) in the progression of obesity-associated hepatosteatosis. Methods Expression levels of hepatic YY1 were identified by microarray analysis in high-fat-diet (HFD)- induced obese mice. Liver triglyceride metabolism was analysed in mice with YY1 overexpression and suppression. Results YY1 expression was markedly upregulated in HFD-induced obese mice and NAFLD patients. Overexpression of YY1 in healthy mice promoted hepatosteatosis under high-fat dietary conditions, whereas liver-specific ablation of YY1 using adenoviral shRNA ameliorated triglyceride accumulation in obese mice. At the molecular level, YY1 suppressed farnesoid X receptor (FXR) expression through binding to the YY1 responsive element at intron 1 of the FXR gene. Conclusions These findings indicate that YY1 plays a crucial role in obesity-associated hepatosteatosis, through repression of FXR expression. [ABSTRACT FROM AUTHOR]

Gluconeogenesis is critical in maintaining blood glucose levels in a normal range during fasting. In this study, we investigated the role of Yin Yang 1 (YY1), a key transcription factor involved in cell proliferation and differentiation, in the regulation of hepatic gluconeogenesis. Our data showed that hepatic YY1 expression levels were induced in mice during fasting conditions and in a state of insulin resistance. Overexpression of YY1 in livers augmented gluconeogenesis, raising fasting blood glucose levels in C57BL/6 mice, whereas liver-specific ablation of YY1 using adenoviral shRNA ameliorated hyperglycemia in wild-type and diabetic db/db mice. At the molecular level, we further demonstrated that the major mechanism of YY1 in the regulation of hepatic glucose production is to modulate the expression of glucocorticoid receptor. Therefore, our study uncovered for the first time that YY1 participates in the regulation of hepatic gluconeogenesis, which implies that YY1 might serve as a potential therapeutic target for hyperglycemia in diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Globally, only 13.8% of adults with hypertension have controlled blood pressure (BP). Effective strategies are needed to overcome barriers to BP control. The overall objective is to determine the comparative-effectiveness of implementation strategies to reduce BP in adults with hypertension. Methods: We searched Medline and Embase (through November 2015) for randomized controlled trials of implementation strategies targeting barriers to hypertension control compared to usual care. One hundred trials with 48,070 hypertensive participants met our eligibility criteria and were included in this analysis. These trials were grouped by intervention strategy, and the effects of the intervention on BP change were combined using random effects models. Results: Multi-component team-based care with and without non-physician providers titrating medications had the greatest reduction in systolic and diastolic BP. Health coaching, home BP monitoring, and a combination of the two also resulted in significant reductions in BP. Few studies of BP audit and feedback and clinical decision support systems were available, and they did not result in significant reductions in systolic BP. Provider training did not significantly reduce BP. Conclusions: Team-based collaborative care is the most effective strategy for BP control among patients with hypertension. In addition, health coaching and home BP monitoring are useful patient-level strategies for hypertension control. These strategies should be prioritized in future BP control efforts. [ABSTRACT FROM AUTHOR]