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The objective of this work is to study the effect of applying simultaneous ultrasonication and alkaline protease treatment to the wet‐milling of high‐amylose corn on improving the starch yield and reducing the starch protein content. After applying the optimal conditions of simultaneous ultrasonication and protease treatment to the wet milling, the starch yield is elevated to 61.3% and the starch protein content is decreased to 0.44% when compared to the conventional process (48.9% and 1.75%, respectively). High‐amylose corn starch extracted using simultaneous ultrasonication and protease treatment has crystalline structure, relative crystallinity, pasting properties, thermal properties, and enzymatic digestibility similar to the one extracted from the conventional process. The results suggest that simultaneous ultrasonication and protease treatment are a friendly approach in improving the yield of high‐amylose corn starch and reducing the starch protein content, causing no obvious change in starch physicochemical properties and enzymatic digestibility. This study provides useful information for scaling up simultaneous ultrasonication and protease treatment to industrial scale with minor modifications of the conventional wet‐milling process. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a prevalent malignancy with a pressing need for improved therapeutic response and prognosis prediction. This study delves into a novel predictive model related to ferroptosis, a regulated cell death mechanism disrupting metabolic processes. Results: Single-cell sequencing data analysis identified subpopulations of HCC cells exhibiting activated ferroptosis and distinct gene expression patterns compared to normal tissues. Utilizing the LASSO-Cox algorithm, we constructed a model with 10 single-cell biomarkers associated with ferroptosis, namely STMN1, S100A10, FABP5, CAPG, RGCC, ENO1, ANXA5, UTRN, CXCR3, and ITM2A. Comprehensive analyses using these biomarkers revealed variations in immune infiltration, tumor mutation burden, drug sensitivity, and biological functional profiles between risk groups. Specific associations were established between particular immune cell subtypes and certain gene expression patterns. Treatment response analyses indicated potential benefits from anti-tumor immune therapy for the low-risk group and chemotherapy advantages for the high-risk group. Conclusions: The integration of this single-cell level model with clinicopathological features enabled accurate overall survival prediction and effective risk stratification in HCC patients. Our findings illuminate the potential of ferroptosis-related genes in tailoring therapy and prognosis prediction for HCC, offering novel insights into the intricate interplay among ferroptosis, immune response, and HCC progression. [ABSTRACT FROM AUTHOR]

Background: MiRNAs are involved in the occurrence and development of many diseases. Extensive literature studies have demonstrated that miRNA-disease associations are stratified and encompass ~ 20% causal associations. Computational models that predict causal miRNA-disease associations provide effective guidance in identifying novel interpretations of disease mechanisms and potential therapeutic targets. Although several predictive models for miRNA-disease associations exist, it is still challenging to discriminate causal miRNA-disease associations from non-causal ones. Hence, there is a pressing need to develop an efficient prediction model for causal miRNA-disease association prediction. Results: We developed DNI-MDCAP, an improved computational model that incorporated additional miRNA similarity metrics, deep graph embedding learning-based network imputation and semi-supervised learning framework. Through extensive predictive performance evaluation, including tenfold cross-validation and independent test, DNI-MDCAP showed excellent performance in identifying causal miRNA-disease associations, achieving an area under the receiver operating characteristic curve (AUROC) of 0.896 and 0.889, respectively. Regarding the challenge of discriminating causal miRNA-disease associations from non-causal ones, DNI-MDCAP exhibited superior predictive performance compared to existing models MDCAP and LE-MDCAP, reaching an AUROC of 0.870. Wilcoxon test also indicated significantly higher prediction scores for causal associations than for non-causal ones. Finally, the potential causal miRNA-disease associations predicted by DNI-MDCAP, exemplified by diabetic nephropathies and hsa-miR-193a, have been validated by recently published literature, further supporting the reliability of the prediction model. Conclusions: DNI-MDCAP is a dedicated tool to specifically distinguish causal miRNA-disease associations with substantially improved accuracy. DNI-MDCAP is freely accessible at http://www.rnanut.net/DNIMDCAP/. [ABSTRACT FROM AUTHOR]

Background. Idiopathic hypogonadotropin hypogonadism (IHH) is caused by hypothalamic-pituitary-gonadal axis dysfunction. This is divided into Kallmann syndrome which has an impaired sense of smell and hypogonadotropin hypogonadism with normal olfactory (nIHH sense. Approximately 60% of patients are associated with Kallmann syndrome, whereas there are approximately 40% with hypogonadotropin hypogonadism (nIHH). This disease is associated with various variants in genes along with different phenotypic characteristics, and even those gene variations could also lead to the cancer formation in patients. So, current study has been designed to investigate and to better understand the characteristics of various IHH-associated genes and the correlation between IHH genes and phenotype. Methods. The cohort included 14 children with IHH (6 patients of KS and 8 patients of IHH), including 13 boys and 1 girl. Exclusion criteria are as follows: diagnosis of secondary hypogonadotropin hypogonadism due to tumor, trauma, drugs, or other systemic diseases. Clinical data and genetic results were analyzed. Results. Almost all male patients showed micropenis (12/13, 92.3%), and few of them had cryptorchidism (5/13, 41.7%). A total of 6 genes, CHD7, PROKR2, ANOS1, FGFR1, SEMA3A, and NDNF, were detected. CHD7 was the most common (11/17, 64.7%), and the main mutation type was missense mutation (14/16, 87.5%). Six reported variants and 10 new variants (5 genes, including entire ANSO1 duplicates) were found. Neonatal variation was detected in 3 patients with IHH. Eight patients inherited the variation from their father, while five patients inherited it from their mother. One patient had both FGFR1 and SEMA3A gene variants, while the other had two different CHD7 gene variants and entire ANSO1 repeats. According to ACMG criteria, 4 variants were pathogenic (P), 2 were possibly pathogenic (LP), and 8 had uncertain significance (US). In patients with P or LP (5/6, 83.3%), we found that extragonadal symptoms were more common. Conclusions. It was concluded that variations in the studied genes could lead to the IHH. Ten new variants have been reported which may lead to different symptoms of IHH. For CHD7 variants, the rare sequencing variants (RSVs) of P or LP showed commonly associated with CHARGE syndrome. Findings of the current study may help for the better diagnosis and treatment of IHH. [ABSTRACT FROM AUTHOR]

Mutations in the promoter of the human Telomerase Reverse Transcriptase (hTERT) gene are common and associated with its elevated expression in bladder cancer, melanoma, and glioblastoma. Though these mutations and TERT overexpression are associated with aggressive disease and poor outcome, an incomplete understanding of mutant TERT regulation limits treatment options directed at this gene. Herein, we unravel a signaling pathway that leads to upregulated hTERT expression resulting from the −124 bp promoter mutation, the most frequent variant across human cancer. We employed engineered bladder cancer cells that harbor a GFP insertion at the TSS region on −124 hTERT promoter for high-content screening drug discovery using a focused library of ~800 kinase inhibitors. Studies using in vitro and in vivo models prioritized AST-487, an inhibitor of the wild-type, and mutant RET (rearranged during transfection) proto-oncogene as a novel drug inhibitor of both wild-type and mutant promoter-driven hTERT expression. We also identified the RET kinase pathway, targeted by AST-487, as a novel regulator of mutant hTERT promoter-driven transcription in bladder cancer cells. Collectively, our work provides new potential precision medicine approaches for cancer patients with upregulated hTERT expression, perhaps, especially those harboring mutations in both the RET gene and the hTERT promoter, such as in thyroid cancer. [ABSTRACT FROM AUTHOR]

Molecular subtypes of muscle-invasive bladder cancer (MIBC) display differential survival and drug sensitivities in clinical trials. To date, they have not been used as a paradigm for phenotypic drug discovery. This study aimed to discover novel subtype-stratified therapy approaches based on high-content screening (HCS) drug discovery. Transcriptome expression data of CCLE and BLA-40 cell lines were used for molecular subtype assignment in basal, luminal, and mesenchymal-like cell lines. Two independent HCSs, using focused compound libraries, were conducted to identify subtype-specific drug leads. We correlated lead drug sensitivity data with functional genomics, regulon analysis, and in-vitro drug response-based enrichment analysis. The basal MIBC subtype displayed sensitivity to HDAC and CHK inhibitors, while the luminal subtype was sensitive to MDM2 inhibitors. The mesenchymal-like cell lines were exclusively sensitive to the ITGAV inhibitor SB273005. The role of integrins within this mesenchymal-like MIBC subtype was confirmed via its regulon activity and gene essentiality based on CRISPR–Cas9 knock-out data. Patients with high ITGAV expression showed a significant decrease in the median overall survival. Phenotypic high-content drug screens based on bladder cancer cell lines provide rationales for novel stratified therapeutic approaches as a framework for further prospective validation in clinical trials. [ABSTRACT FROM AUTHOR]

Neutrophil elastase (NE) plays a pivotal role in inflammation. However, the mechanism underlying NE-mediated inflammation in obesity remains unclear. Here, we report that NE activates protease-activated receptor-2 (PAR2), stimulates actin filament (F-actin) formation, decreases intercellular junction molecule VE-cadherin expression, and increases the permeability of human arterial endothelial cells (hECs). NE also prompts degradation of VE-cadherin and its binding proteins p120- and β-catenins via MG132-sensitive proteasomes. NE stimulates phosphorylation of myosin light-chain (MLC) and its regulator myosin phosphatase target subunit-1 (MYPT1), a target of Rho kinase (ROCK). Inhibitors of PAR2 and ROCK prohibit NE-induced F-actin formation, MLC phosphorylation, and VE-cadherin reduction in hECs, and impede monocyte transmigration through hEC monolayer pretreated with either neutrophils or NE. Further, administration of an NE inhibitor GW311616A significantly attenuates vascular leakage, leukocyte infiltration, and the expression of proinflammatory cytokines in the white adipose tissue from high-fat diet (HFD)-induced obese mice. Likewise, NE-deficient mice are resistant to HFD-induced vascular leakage in the heart. Together, NE regulates actomyosin cytoskeleton activity and VE-cadherin expression by activating PAR2 signaling in the endothelial cells, leading to increased vascular permeability and leukocyte extravasation. Hence, inhibition of NE is a potential approach to mitigate vascular injury and leukocyte infiltration in obesity-related systemic inflammation. [ABSTRACT FROM AUTHOR]

Simple Summary: The capture and transport of pheromone odorants to olfactory sensory neurons (OSNs) via the surfaces of thousands of antennal sensory hairs of male moths are the first and requisite steps that permit olfaction and upwind flight orientation to females to occur. Our investigations of the male pheromone-sensitive sensory hairs (trichoid sensilla) from five moth species using atomic force microscopy (AFM) revealed differences in the densities, heights and depths of pores and ridges involved in pheromone odorant capture and transport. Measurements of electrical surface potentials across sensilla in our study suggests that there is a heterogeneity in the distribution of surface lipids between ridges, pores and inter-ridge areas that likely facilitate the capture and transport of pheromone odorants to OSNs. Controlled heating of sensilla revealed that heating did not melt or change the shapes of small lipid exudates residing within the pores or of large exudates completely covering the pores. These results suggest that such exudates are crystalline wax blooms that comprise a different form of lipid than the free lipid monolayer that covers the rest of these olfactory hairs. The surfaces of trichoid sensilla on male moth antennae have been sculpted over evolutionary time to capture pheromone odorant molecules emitted by the females of their species and transport the molecules in milliseconds into the binding protein milieu of the sensillum lumen. The capture of pheromone molecules likely has been optimized by the topographies and spacings of the numerous ridges and pores on these sensilla. A monolayer of free lipids in the outer epicuticle covers the sensillar surfaces and must also be involved in optimal pheromone odorant capture and transport. Using electro-conductive atomic force microscopy probes, we found that electrical surface potentials of the pores, ridges and flat planar areas between ridges varied in consistent ways, suggesting that there is a heterogeneity in the distribution of surface lipid mixtures amongst these structures that could help facilitate the capture and transport of pheromone molecules down through the pores. We also performed experiments using peak force atomic force microscopy in which we heated the sensilla to determine whether there is a temperature-related change of state of some of the surface lipid exudates such as the prominent domes covering many of the pores. We found that these exudates were unaffected by heating and did not melt or change shape significantly under high heat. Additionally, we measured and compared the topographies of the trichoid sensilla of five species of moths, including the distributions, spacings, heights and diameters of ridges, pores and pore exudates. [ABSTRACT FROM AUTHOR]

Background. Diabetic retinopathy (DR) is a serious ophthalmopathy that causes blindness, especially in the proliferative stage. However, the pathogenesis of its effect on endothelial cells, especially its relationship with immune cell infiltration, remains unclear. Methods. The dataset GSE94019 was downloaded from the Gene Expression Omnibus (GEO) database to obtain DEGs. Through aggregate analyses such as Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis, a protein-protein interaction (PPI) network was constructed to analyze the potential function of DEGs. Weighted gene coexpression network analysis (WGCNA) and Cytoscape software including molecular complex detection (MCODE) and cytoHubba plug-ins were used to comprehensively analyze and determine the hub genes. ImmuCellAI analysis was performed to further study the relationship between samples, hub genes, and 24 types of immune cell infiltration. Finally, gene-set enrichment analysis (GSEA) was employed to identify the enrichment of immune cell infiltration and endothelial cell phenotype modifications in GO biological processes (BP) based on the expression level of hub genes. Results. 2393 DEGs were identified, of which 800 genes were downregulated, and 1593 genes were upregulated. The results of functional enrichment revealed that 1398 BP terms were significantly enriched in DEGs. Three hub genes, EEF1A1, RPL11, and RPS27A, which were identified by conjoint analysis using WGCNA and Cytoscape software, were positively correlated with the number of CD4 naive T cells and negatively correlated with the numbers of B cells. The number of CD4 naive T cells, T helper 2 (Th2) cells, and effector memory T (Tem) cells were significantly higher while CD8 naive T cells and B cells significantly were lower in the diabetic group than in the nondiabetic group. Conclusions. We unearthed the DEGs and Hub genes of endothelial cells related to the pathogenesis of PDR: EEF1A1, RPL11, and RPS27A, which are highly related to each other and participate in the specific biological process of inflammation-related immune cell infiltration and endothelial cell development, chemotaxis, and proliferation, thus providing new perspectives into the diagnosis of and potential "killing two birds with one stone" targeted therapy for PDR. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new molecular mechanism affecting neuron apoptosis is proposed in this study. • Neuron apoptosis along with astrocyte activation take place in Alzheimer's disease. • BAI1′s expression is downregulated and astrocyte activation upregulated in rat AD models. • In vitro results prove that BAI1 inhibits astrocyte activation and neuron apoptosis. • The STAT3/EZH2 axis regulates BAI1 expression in astrocytes. Alzheimer's disease (AD) is a common neurodegenerative disease. Previous studies have identified the critical role of astrocytes in the progression of AD. The focus of this study revolves around clarifying the regulatory mechanism of the STAT3/EZH2/BAI1 axis in astrocytes in AD. We successfully developed a rat model of AD, and measured the learning and cognitive ability of the rats by Morris water maze experiment. HE and Nissl's staining were used for histomorphological identification of the rat hippocampus. Meanwhile, immunofluorescence and immunohistochemistry were used to detect astrocyte activation and brain-specific angiogenesis inhibitor-1 (BAI1) expression in rat hippocampal tissue, respectively. The role of STAT3/EZH2/BAI1 regulating axis in astrocyte activation and neuronal cell apoptosis was verified by establishing the co-culture system of astrocytes and neuronal cells in vitro. Western Blot (WB) was used to detect the expression of associated proteins, and enzyme-linked immunosorbent assay (ELISA) was used to detect astrocyte neurotrophic factor secretion. Hochest/PI staining and flow cytometry were used to observe neuronal apoptosis. Compared with the sham group, AD rats showed significantly decreased cognitive and learning abilities, noticeable hippocampal tissue damage, and significantly low levels of BAI1 expression. In in vitro models, BAI1 was found to inhibit astrocyte activation and enhance the secretion of neurotrophins, resulting in decrease of neurone apoptosis. The regulation of BAI1 by the STAT3/EZH2 axis was shown to affect astrocyte activation and neuronal cell apoptosis. In conclusion, this study represents the pioneering discovery that regulated by the STAT3/EZH2 axis, BAI1 suppresses astrocyte activation, thus reducing neuronal apoptosis. [ABSTRACT FROM AUTHOR]

The effects of annealing temperature on the microstructure, mechanical properties, and tribological properties of TiAlSiCN coatings with C contents of 9.24 at.% and 19.45 at.% are systematically investigated. The results show that all coatings maintain cubic structures with strongly preferential orientation of (200) planes, and the microstructure transforms from amorphous embedded in (Ti, Al)(C, N) nanocrystalline to amorphous encapsulated nanocrystalline with increasing C content. Elevating annealing temperature to 800 °C leads to a continuous decline in hardness, whereas the elastic strain resistance H/E increases first and then decreases. Release of H 2 formed by the breaking of the C–H bonds at 400 °C induces a local stress transformation from compressive to tensile. The toughness and hardness decreases dramatically at 600 °C by conversion of sp3 to sp2. The wear mechanisms of the coating against Si 3 N 4 counterballs are adhesive and oxidative wear. The coefficient of friction (COF) and wear rate initially decrease followed by an increase. The coatings with a-C structure exhibit lower COF and the wear process is smoother, but showing higher wear rate. Thus, the annealed TiAlSiCN coatings with preferred C content could improve the mechanical and tribological properties. [ABSTRACT FROM AUTHOR]

Background: Prader-Willi syndrome (PWS) is a rare and complex genetic disorder caused by lacking expression of imprinted genes on the paternally derived chromosome 15q11-q13 region. This study aimed to characterize the perinatal features of 134 Chinese individuals with PWS.Methods: This study included the patients of a PWS registry in China. Anonymous data of 134 patients were abstracted. Perinatal and neonatal presentations were analyzed, and compared between the two PWS genetic subtypes. We also compared the perinatal features of PWS patients with the general population and other previous reported large cohorts from France, UK and USA.Results: This study included 134 patients with PWS (115 patients with 15q11-q13 deletion and 19 with maternal uniparental disomy). Higher mean maternal age was found in this cohort (30.5 vs. 26.7), particularly in the maternal uniparental disomy (UPD) group (36.0 vs. 26.7) comparing with the general population. 88.6% of mothers reported a decrease of fetal movements. 42.5 and 18.7% of mothers had polyhydramnios and oligohydramnios during pregnancy, respectively. 82.8% of the patients were born by caesarean section. 32.1% of neonates had birth asphyxia, 98.5% had hypotonia and 97.8% had weak cry or even no cry at neonatal period. Feeding difficulty existed in 99.3% of the infants, 94.8% of whom had failure to thrive. 69.4% of the infants ever used feeding tube during hospitalization, however, 97.8% of them discontinued tube feeding after discharge. Maternal age and pre-pregnancy weight were significantly higher in the UPD group (both P < 0.05).Conclusions: Differential diagnosis of PWS should be highlighted if infants having following perinatal factors including polyhydramnios, decreased intrauterine fetal movements, caesarean section, low birth weight, feeding difficulty, hypotonia and failure to thrive. Higher maternal age may be a risk factor of PWS, especially for UPD. Further studies are needed for elucidating the mechanism of PWS. [ABSTRACT FROM AUTHOR]

Background: Chronic spontaneous urticaria (CSU) is a skin disorder with an important immunologic profile. S100A8, S100A9, and S100A12 are the members of S100 family that have been reported to play important role in autoimmune diseases, but the characteristics of these three S100 members have not been defined in CSU. Aims: This study was performed to investigate the levels of these three S100s in patients with CSU and to study whether they were associated with the severity and clinical characteristics of CSU. Materials and Methods: The levels of plasma S100A8, S100A9, and S100A12 were measured in 51 CSU patients and 20 healthy controls using enzyme linked immunosorbent assay kits. The values in the patient group and that of the healthy controls were statistically compared. The relationships between the different markers were evaluated by correlation analysis. Results: The plasma levels of S100A8, S100A9, and S100A12 were significantly higher in CSU patients than those in controls. Interestingly, the level of S100A12 was significantly correlated with S100A8 and S100A9 in CSU patients (P < 0.05 and P < 0.001, respectively). In addition, S100A8, S100A9, and S100A12 were all significantly inversely correlated with blood basophil percentage. Conclusions: Plasma S100A8, S100A9, and S100A12 levels were elevated in CSU patients. They might be useful biomarkers of CSU, with the potential role in the pathogenesis of CSU. [ABSTRACT FROM AUTHOR]

Objective: To characterize the phenotype spectrum, diagnosis, and response to growth‐promoting therapy in patients with ACAN variants causing familial short stature. Methods: Three families with ACAN variants causing short stature were reported. Similar cases in the literature were summarized, and the genotype and phenotype were analyzed. Results: Three novel heterozygous variants, c.757+1G>A, (splicing), c.6229delG, p.(Asp2078Tfs*1), and c.6679C>T, p.(Gln2227*) in the ACAN gene were identified. A total of 314 individuals with heterozygous variants from 105 families and 8 individuals with homozygous variants from 4 families were confirmed to have ACAN variants from literature and our 3 cases. Including our 3 cases, the variants reported comprised 33 frameshift, 39 missense, 23 nonsense, 5 splicing, 4 deletion, and 1 translocation variants. Variation points are scattered throughout the gene, while exons 12, 15, and 10 were most common (25/105, 11/105, and 10/105, respectively). Some identical variants existing in different families could be hot variants, c.532A>T, p.(Asn178Tyr), c.1411C>T, p.(Gln471*), c.1608C>A, p.(Tyr536*), c.2026+1G>A, (splicing), and c.7276G>T, p.(Glu2426*). Short stature, early‐onset osteoarthritis, brachydactyly, midfacial hypoplasia, and early growth cessation were the common phenotypic features. The 48 children who received rhGH (and GnRHa) treatment had a significant height improvement compared with before (−2.18 ± 1.06 SD vs. −2.69 ± 0.95 SD, p < 0.001). The heights of children who received rhGH (and GnRHa) treatment were significantly improved compared with those of untreated adults (−2.20 ± 1.10 SD vs. −3.24 ± 1.14 SD, p < 0.001). Conclusion: Our study achieves a new understanding of the phenotypic spectrum, diagnosis, and management of individuals with ACAN variants. No clear genotype–phenotype relationship of patients with ACAN variants was found. Gene sequencing is necessary to diagnose ACAN variants that cause short stature. In general, appropriate rhGH and/or GnRHa therapy can improve the adult height of affected pediatric patients caused by ACAN variants. [ABSTRACT FROM AUTHOR]

Ferroptosis, an established form of programmed cell death discovered in 2012, is characterized by an imbalance in iron metabolism, lipid metabolism, and antioxidant metabolism. Activated CD8 + T cells can trigger ferroptosis in tumor cells by releasing interferon-γ, which initiates the ferroptosis program. Despite the remarkable progress made in treating various tumors with immunotherapy, such as anti-PD1/PDL1, there are still significant challenges to overcome, including limited treatment options and drug resistance. In this review, we exam the potential biological significance of the ferroptosis phenotype using bioinformatics and review the latest advancements in understanding the mechanism of ferroptosis-mediated anti-tumor immunotherapy. Furthermore, we revisit the host immune system, immune microenvironment, ferroptotic defense system, metabolic reprogramming, and key genes that regulate the occurrence and resistance of ferroptosis of tumor cell. Additionally, several immune-combined ferroptosis treatment strategies were put forward to improve immunotherapy efficacy and to provide new insights into reversing anti-tumor immune drug resistance. [Display omitted] • Unique approach: Exploring ferroptosis's crosstalk with the immune system in anti-tumor therapies. • Comprehensive analysis: Integrating bioinformatics and pan-cancer profiling to study ferroptosis in tumors and immune cells. • Specificity and implications: Specificity and implications: Context-dependent outcomes of ferroptosis, insights for combination treatments. [ABSTRACT FROM AUTHOR]

The microstructure, mechanical and tribological properties of TiAlSiN coatings with various annealing temperature were studied. Results showed that the oxygen content of the coating raised with the annealing temperature in the range of room temperature to 800 °C, while the hardness decreased monotonically. However, the elastic strain resistance H/E value increased firstly and then decreased. The maximum H/E value of 0.105 was obtained at 400 °C. The deposited coating composed of c-TiN, c-AlN and c-(Ti, Al)N, and Si element mainly existed in the form of SiN x amorphous structure. The adhesive and oxidation erosion were the main wear mechanism against GCr15 steel balls. The coefficient of friction (COF) decreased gradually, but the wear rate increased firstly and then decreased. The minimum wear rate of 1.2 × 10−5mm3/(N·m) was obtained at 400 °C. In addition, oxides including Ti–O, Al–O and Si–O generated on the adhesives play a role of lubricant, which could reduce the shearing resistance and COF of the coating. Therefore, TiAlSiN coatings with optimal annealing temperature has excellent mechanical properties and tribological performance. The research revealed that the annealing temperature has significant effect on the microstructure and properties of TiAlSiN coating. • The TiO 2 oxides, which exists above the detection limit of XRD, are formed at 600 °C. • In addition, the shear resistance and contact area were reduced due to the adhesive Ti–O, Al–O and Si–O composition with low coefficient of friction and high hardness. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The development of multifunctional nanocontainers for self-healing coatings is of great interest for environmental and healthcare applications. In this study, we developed a synthetic strategy for a hydrophobic and self-healing anticorrosion coating from carboxylic acid- and fluorine-containing nanocontainers. Initially, well-defined poly (acrylic acid- co -trifluoroethyl methacrylate) microspheres were synthesized with different crosslinking agents by precipitation polymerization. The carboxylic acid groups allow for pH-responsive function to control the release of the encapsulated healing inhibitor to the cracks of polymer coatings on metal surfaces. The fluorinated groups of the polymer nanocontainers can endow the coatings with hydrophobicity. The as-synthesized multifunctional nanocontainers were further doped into the polymer coatings to generate self-healing coatings. The self-healing polymer coatings exhibited good crack inhibition since the inhibitor benzotriazole in pH-responsive nanocontainers can autonomously form new nanobarriers on metal surfaces around cracks after corrosion occurs. Furthermore, due to the micro/nanostructures of hydrophobic microspheres in the polymer coatings, the self-healing coating also exhibited good water resistance. The hydrophobic self-healing polymer coatings from the as-synthesized carboxylic acid- and fluorine-containing nanocontainers for anticorrosion were analyzed by electrochemical impedance spectroscopy (EIS). [ABSTRACT FROM AUTHOR]

Highlights • Two bipolar coatings were prepared by exchanging inner/outer ion-selective coating sequence. • The coatings were immersed in H 2 S solution according to NACE standard. • The bipolar coating had good protection property due to existence of p-n junction. • The protection mechanism of the bipolar coating was proposed. Abstract SiO 2 nanoparticles were modified with the surfactants sodium dodecylbenzene sulfonate and hexadecyl trimethyl ammonium bromide. The modified SiO 2 nanoparticles were added to epoxy-resin coatings to obtain anion- and cation-selective coatings. Two kinds of bipolar epoxy-resin coatings were prepared by exchanging the sequence of anion- or cation-selective coating (i.e., cation/anion and anion/cation). The coatings were immersed in H 2 S solution, and electrochemical impedance spectroscopy was used to investigate their performance. Scanning electron microscopy and energy-dispersive X-ray spectroscopy were used to observe the morphology of the metals and metal/coating interface. Experimental results indicated that the coating sequence of inner and outer ion-selective coatings affected the protection performance of the bipolar coatings. The good protection property of the bipolar coatings was attributed to the existence of a space-charge region and an electric field between the inner and outer ion-selective coatings. [ABSTRACT FROM AUTHOR]

Purpose: To determine the rate and extent of the maternal-fetal transplacental passage of bromocriptine (BCT) in the dually perfused human placental model. Methods: Twenty term placentas were included in an ex vivo human placental perfusion experiment with a closed-circuit model. At the start of the perfusion, BCT at the concentration of 10 or 100 ng/ml along with 100 µg/ml antipyrine which used as a positive marker were added to the maternal reservoir. Samples were collected for the measurements of BCT and markers of placental viability both from the maternal reservoir and fetal reservoir throughout the perfusion which lasted for 3 h. Determination of BCT was carried out with liquid chromatography-tandem mass spectrometry. Results: At the end of the study, the concentration in the fetal compartment was 0.82 ± 0.32 ng/ml in the low concentration group and 5.02 ± 0.97 ng/ml in the high concentration group with a fetal transfer rate of 6.13 ± 1.94% and 5.46 ± 0.87%, respectively. Conclusion: These data showed that only trace amount of BCT could transport across the human placenta in vitro which suggested that fetal exposure to maternally administered BCT may be insignificant. More additional studies are required to explore the safety of BCT administrated in pregnancy. [ABSTRACT FROM AUTHOR]

Abstract Nervous necrosis virus (NNV) causes viral nervous necrosis (VNN), a disease that leads to almost 100% mortality among larvae and juvenile fish, severely affecting the aquaculture industry. VNN vaccines based on inactivated viruses or virus-like particles (VLPs) are unsuitable for fish fry with immature adaptive immune systems. Here, we applied an anti-NNV strategy based on affinity peptides (AFPs). Three phage display peptide libraries were screened against RBS, the VLP of orange-spotted grouper nervous necrosis virus (OGNNV). From the positive clones, a dodecapeptide with the highest binding capacity (BC) to RBS was selected. This AFP agglutinated or disrupted virion particles, inhibiting RBS entry into sea bass (SB) cells. To enhance BC and solubility, we amended the AFP sequence as "LHWDFQSWVPLL" and named as 12C. One to three copies of 12C in tandem were prokaryotically expressed with a maltose binding protein (MBP) linked by a flexible peptide. Of the recombinant proteins expressed, MBP-triple-12C (MBP-T12C) exhibited the highest BC, efficiently blocked RBS entry, and strongly inhibited OGNNV infection at viral entry. Moreover, MBP-T12C bound the VLPs of all NNV serotypes, displaying broad-spectrum anti-NNV ability, and recognized only OGNNV and mud crab virus, demonstrating binding specificity. Therefore, these anti-NNV AFPs specifically bound NNV, aggregating or disrupting the viral particles, to reduce the contact probability between the virus and cell surface, subsequently inhibiting viral infection. Our results not only provided a candidate of anti-NNV AFP, but a framework for the development of antiviral AFP. Highlights • Three affinity peptides (AFP) against OGNNV VLP (RBS) were obtained by screening. • A soluble 12-mer AFP agglutinated or disrupted virion particles to inhibit RBS entry. • A prokaryotic fusion protein of triple tandem AFP (MBP-T12C) was generated. • MBP-T12C bound all serotypes of NNV and a highly homogenous crab virus. • MBP-T12C hindered RBS entry and inhibited OGNNV infection by blocking viral entry. [ABSTRACT FROM AUTHOR]

Attributing to its advantages including no residue, low friction and complete gel breaking, viscoelastic surfactant (VES) fracturing fluids are attracting more and more attention. However, high price and high consumption restrict the wide applications of VES. SiO 2 nanoparticle-assisted VES fracturing fluid (NAVES) with low concentration is proposed in this study. The NAVES system consisting of 1% EDAA and 0.01% SiO 2 maintains a shear viscosity of above 33 mPa·s at 70 °C for 2 h; in contrast, the viscosity of a 1% EDAA (VES) solution is 24 mPa·s at 70 °C for 2 h. This could be attributing to the formation of a strong dynamic network structure, in which the surfactant micelles attach to the surface of SiO 2 nano-particles that are negatively charged through electrostatic interactions. The pseudo-crosslinking between the SiO 2 and micelles also improves the shear resistance and relaxation time of the VES, without affecting the gel breaking performance. The NAVES system could break completely within 100 min, as reflected by the fact that its viscosity decreased to less than 3 mPa·s. The settling rate of quartz sand in an EDAA/SiO 2 system at 25 °C was 0.0021 cm/s, which was lower than that of traditional VES fracturing fluid. Therefore, NAVES could serve as a low-concentration hydraulic fracturing fluid. In addition, the current study provides a cost-effective approach for hydraulic fracturing. [ABSTRACT FROM AUTHOR]

Background/Aims: Fish is a protein-rich food and is increasingly favored by consumers. It has been well recognized that the flesh composition of fish is closely related to its maturation and growth stage, but few studies have explored these differences. Additionally, hormone residues in fish after artificial induction of reproduction also attract consumer concern. In this study, we attempt to address these concerns by using a combination of transcriptomics and metabolomics analyses to identify key regulated pathways, genes, and metabolites that may affect the flesh nutrition of one typical aquaculture species in China, blunt snout bream (Megalobrama amblycephala). Methods: The four groups of fish were used for transcriptomics and metabolomics analyses, including one-year-old immature (group I), two-year-old immature (group II), two-year-old mature (group III) and successfully spawned (group IV) female M. amblycephala after artificial induction of reproduction. Results: We identified a total of 1460 differential compounds and 1107 differentially expressed unigenes in muscle among the different groups. Differential metabolites related to fish age (group II vs group I, group III vs group I) were largely enriched in “Glycerophospholipid metabolism”, “Linoleic acid metabolism”, “α-Linolenic acid metabolism”, and “Biosynthesis of unsaturated fatty acids”. Between these two pairwise comparisons, metabolites that are beneficial to human health, such as docosapentaenoic acid, α-Linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid were found to be significantly decreased in two-year-old (group II, group III) compared with one-year-old (group I) M. amblycephala. Only one differential metabolite related to fish maturation, a triglyceride, was detected between groups III and II. Transcriptomics data showed that differently expressed genes (between group III vs group II, group III vs group I) related to maturation were highly enriched in “Cell adhesion molecules (CAMs)”, “Sphingolipid metabolism” and “Phagosome”. DEGs (between group II vs group I, group III vs group I) relating to fish age were enriched in the “cGMP-PKG signaling pathway”, “FoxO signaling pathway”, and “AMPK signaling pathway”. The gene-metabolite interaction network showed pivotal genes, including fumarate hydratase and GNPAT, which played a major role in the regulation of glycerphospholipid metabolism. The nutritional components were also measured, which verified the metabolomics results. Moreover, the metabolomics results showed that after 24 hours of artificial hormone injection, the drug was completely metabolized. Conclusion: Integrated analysis demonstrated that the nutrition value of fish fillet was much more related to fish age compared with maturation status in M. amblycephala females. [ABSTRACT FROM AUTHOR]

Family Nodaviridae consists of two genera: Alphanodavirus and Betanodavirus , and the latter is classified into four genotypes, including red-spotted grouper nervous necrosis virus, tiger puffer nervous necrosis virus, striped jack nervous necrosis virus, and barfin flounder nervous necrosis virus. Type I interferons (IFNs) play a central role in the innate immune system and antiviral responses, and the interactions between IFN and NNV have been investigated in this study. We have found that the RNA-dependent RNA polymerase (RdRp) from orange-spotted nervous necrosis virus (OGNNV), named protein A, was capable of activating IFN promoter in fathead minnow (FHM) cells. Transient expression of protein A was found to induce IFN expression and secretion, endowing FHM cells with anti-tiger frog virus ability. Protein A from SJNNV can also induce IFN expression in FHM cells but that from Flock House virus (FHV), a well-studied representative species of genus Alphanodavirus , cannot. RdRp activity and mitochondrial localization were shown to be required for protein A to induce IFN expression by means of activating IRF3 but not NFκB. Furthermore, DsRNA synthesized in vitro transcription and poly I:C activated IFN promoter activity when transfected into FHM cells, and dsRNA were also detected in NNV-infected cells. We postulated that dsRNA, a PAMP, was produced by protein A, leading to activation of innate immune response. These results suggest that protein As from NNV are the agonists of innate immune response. This is the first work to demonstrate the interaction between NNV protein A and innate immune system, and may help to understand pathogenesis of NNV. [ABSTRACT FROM AUTHOR]

We performed single-sensillum recordings from male and female antennae of the Asian longhorned beetle, Anoplophora glabripennis, that included as stimuli the two components of this species’ aggregation-sex pheromone in addition to various general odorants. We compared the aggregation-sex-pheromone-component responses of olfactory sensory neurons (OSNs) to those of OSNs that responded to a variety of plant-related odorants. In the smooth-tipped, tapered, trichoid sensilla on the most distal antennal flagellomeres nos. 10 or 11 of both males and females, we found OSNs with high-amplitude action potentials that were tuned to the aldehyde and alcohol pheromone components and that did not respond to various plant-related volatiles. Because this OSN type responded to both the alcohol and aldehyde components it cannot be considered to be specifically tuned to either component. These large-spiking OSNs were co-compartmentalized in these sensilla with a second, smaller-spiking OSN responding to plant-related volatiles such as geraniol, citronellal, limonene, 1-octanol, nerol and citral. The large-spiking OSNs thus appear to be a type that will be involved in aggregation-sex pheromone pathways targeting a specific glomerulus in the antennal lobe and in generating pheromone-related behavioral responses in A. glabripennis. In other sensilla located in these distal antennal flagellomeres as well as those located more proximally, i.e., mid-length along the antenna on flagellomere nos. 4-7, we found OSNs in blunt-tipped basiconic sensilla that were responsive to other plant-related volatiles, especially the terpenoids, (E,E)-alpha farnesene, (E)-β-farnesene, β-caryophyllene, and eugenol. Some of these terpenoids have been implicated in improving attraction to pheromone-baited traps. Some of these same OSNs responded additionally to either of the two sex pheromone components, but because these OSNs also responded to some of the above plant volatiles as shown by cross-adaptation experiments, these OSNs will not be the types that convey sex-pheromone-specific information to the antennal lobe. [ABSTRACT FROM AUTHOR]

[Display omitted] • Aimed to create a non-invasive method to monitor aquatic animals' health. • Proposed a microHI (microbiota health index) based on three microbial phenotypes. • Tested the viability of using gut microHI to predict host health in 11 fishes. • Verified the positive correlation between environmental microHI & fish gut microHI. • Showed the possibility of using environmental microHI to predict animals' health. In aquatic animals, the gut microbiota has a significant function in host health and is impacted by the environmental microbiota. To conveniently monitor, assess and predict aquatic animals' health, a general and effective microbiota health index (microHI) would be helpful, and the correlation between the aquatic environmental microHI and wildlife gut microHI could be expected. Here, we proposed a general microHI based on the microbial phenotypes of mobile element content, potential pathogenicity and oxidative stress tolerance, and then tested the reliability of the fish gut microHI and its correlation with the environmental microHI in the middle Yangtze River. The results showed that there were positive correlations among the abundance ratios of microbes with the microbial phenotypes of mobile element content, potential pathogenicity and oxidative stress tolerance, suggesting that defining the microHI using the average abundance ratios of microbes without these microbial phenotypes is suitable. Fish gut samples with a lower microHI were more likely to have been obtained from specimens with a disordered microbiota (always means unhealthy host), indicating that the gut microHI has the potential to be used to evaluate the health status of aquatic animals. In the middle Yangtze River, the aquatic environmental microHI had hundred-kilometers-scale high spatial heterogeneity but month-scale low temporal heterogeneity from June to September 2020, and in the section with a low aquatic environmental microHI, the fish gut samples were more likely to have relatively low gut microHIs, indicating that the environmental microHI has the potential to be used to predict the health status of aquatic animals at the community level. The current work initially showed the possibility of using environmental microHI to predict aquatic animals' health although it was not very exact and precise. We encourage more researches to assess the quantitative relationship between the aquatic environmental microHI and aquatic animal gut microHI. [ABSTRACT FROM AUTHOR]

CDP138 is a calcium- and lipid-binding protein that is involved in membrane trafficking. Here, we report that mice without CDP138 develop obesity under normal chow diet (NCD) or high-fat diet (HFD) conditions. CDP138-1- mice have lower energy expenditure, oxygen consumption, and body temperature than wild-type (WT) mice. CDP138 is exclusively expressed in adrenal medulla and is colocalized with tyrosine hydroxylase (TH), a marker of sympathetic nervous terminals, in the inguinal fat. Compared with WT controls, CDP138-1- mice had altered catecholamine levels in circulation, adrenal gland, and inguinal fat. Adrenergic signaling on cyclic AMP (cAMP) formation and hormone-sensitive lipase (HSL) phosphorylation induced by cold challenge but not by an exogenous β3 adrenoceptor against CL316243 were decreased in adipose tissues of CDP138-1- mice. Cold-induced beige fat browning, fatty acid oxidation, thermogenesis, and related gene expression were reduced in CDP138-1- mice. CDP138-1- mice are also prone to HFD-induced insulin resistance, as assessed by Akt phosphorylation and glucose transport in skeletal muscles. Our data indicate that CDP138 is a regulator of stress response and plays a significant role in adipose tissue browning, energy balance, and insulin sensitivity through regulating catecholamine secretion from the sympathetic nervous terminals and adrenal gland. [ABSTRACT FROM AUTHOR]

Purpose: To determine the rate and extent of the maternal-fetal transplacental passage of bromocriptine (BCT) in the dually perfused human placental model. Methods: Twenty term placentas were included in an ex vivo human placental perfusion experiment with a closed-circuit model. At the start of the perfusion, BCT at the concentration of 10 or 100 ng/ml along with 100 µg/ml antipyrine which used as a positive marker were added to the maternal reservoir. Samples were collected for the measurements of BCT and markers of placental viability both from the maternal reservoir and fetal reservoir throughout the perfusion which lasted for 3 h. Determination of BCT was carried out with liquid chromatography-tandem mass spectrometry. Results: At the end of the study, the concentration in the fetal compartment was 0.82 ± 0.32 ng/ml in the low concentration group and 5.02 ± 0.97 ng/ml in the high concentration group with a fetal transfer rate of 6.13 ± 1.94% and 5.46 ± 0.87%, respectively. Conclusion: These data showed that only trace amount of BCT could transport across the human placenta in vitro which suggested that fetal exposure to maternally administered BCT may be insignificant. More additional studies are required to explore the safety of BCT administrated in pregnancy. [ABSTRACT FROM AUTHOR]

Some reports have shown that nicotinamide N-methyltransferase (NNMT) is associated with the body mass index (BMI) and energy metabolism. Here we explored the association between NNMT gene polymorphisms and obesity. The subjects were recruited from male Chinese Han college student. 289 of them (19 ≤ body fat percentage (BF%)) were selected as the high body fat group (HBFG), 494 of them (3 ≤ BF% < 13.5) were selected as the low body fat group (LBFG), and then a case-control study (fat versus thin) was carried out to explore the association between the NNMT gene polymorphism and the body composition using tagSNPs method. A tagSNP (rs10891644) in NNMT gene was found significantly associated with the body composition (P<0.0026). At this locus, the BF% for the genotype GT, TT, and GG were 14.56±8.35, 13.47±8.11, and 12.42±7.50, respectively, and the differences between the GT and the GG + TT were highly significant (P<0.01); the ORadjusted value of the GT versus (GG + TT) was 1.716 (Padjusted=0.002, 95% CI = 1.240–2.235). Therefore, the variation of the tagSNP, rs10891644, is significantly associated with obesity and the GT carriers are the susceptible population. [ABSTRACT FROM AUTHOR]

The literature on bullying among students with disabilities is burgeoning. The purpose of this study was to examine risk factors for adolescents’ involvement in bullying across the bullying continuum. Drawing from the National Longitudinal Transition Study–2 (NLTS2), 2,870 adolescents with disabilities were sampled. Results from multinomial regression analyses indicated that internalizing symptoms and interpersonal skills were significant predictors of victimization and bully-victimization risk, respectively. Disability status emerged as a significant predictor only for bullying behavior. Ethnic differences were found for victimization roles, but not for bullying, suggesting that Caucasian students were most vulnerable to being the target of bullying or serving dual roles as bully-victims relative to students from other ethnic backgrounds. Implications for these findings are discussed. [ABSTRACT FROM AUTHOR]

3D organotypic culture models such as organoids and multicellular tumor spheroids (MCTS) are becoming more widely used for drug discovery and toxicology screening. As a result, 3D culture technologies adapted for high-throughput screening formats are prevalent. While a multitude of assays have been reported and validated for high-throughput imaging (HTI) and high-content screening (HCS) for novel drug discovery and toxicology, limited HTI/HCS with large compound libraries have been reported. Nonetheless, 3D HTI instrumentation technology is advancing and this technology is now on the verge of allowing for 3D HCS of thousands of samples. This review focuses on the state-of-the-art high-throughput imaging systems, including hardware and software, and recent literature examples of 3D organotypic culture models employing this technology for drug discovery and toxicology screening. [ABSTRACT FROM AUTHOR]

Toll-like receptor 4 (TLR4) is involved in multiple malignancies; however, the role of TLR4 in the pathogenesis of malignant pleural effusion (MPE) remains unknown. The objectives of this study were to explore the impact of TLR4 signaling on the development of MPE in a murine model and to define the underline mechanisms by which TLR works. Development of MPE as well as proliferation and angiogenesis of pleural tumor were determined in TLR4-/- and wild type mice. Differentiation of Th1 and Th17 cells as well as their signal transductions was explored. The effects of TLR4 signaling on survival of mice bearing MPE were also investigated. Compared with wild type mice, Th1 cells were augmented, and Th17 cells were suppressed in MPE from TLR4-/- mice. The in vitro experiments showed that TLR4 deficiency promoted Th1 cell differentiation via enhancing STAT1 pathway and inhibited Th17 cell differentiation via suppressing STAT3 pathway. TLR4 deficiency promoted MPE formation and, thus, accelerated the death of mice bearing MPE, whereas intraperitoneal injection of anti-IFN-γ mAb or recombinant mouse IL-17 protein into TLR4-/- mice was associated with improved survival. Our data provides the first definitive evidence of a role for TLR4 signaling in protective immunity in the development of MPE. Our findings also demonstrate that TLR4 deficiency promotes MPE formation and accelerates mouse death by enhancing Th1 and suppressing Th17 response. [ABSTRACT FROM AUTHOR]

Tempo-spatial patterns of mercury bioaccumulation and tropho-dynamics, and the potential for a reservoir effect were evaluated in the Three Gorges Reservoir (TGR, China) from 2011 to 2012, using total mercury concentrations (THg) and stable isotopes (δ 13 C and δ 15 N) of food web components (seston, aquatic invertebrates and fish). Hg concentrations in aquatic invertebrates and fish indicated a significant temporal trend associated with regular seasonal water-level manipulation. This includes water level lowering to allow for storage of water during the wet season (summer); a decrease of water levels from September to June providing a setting for flood storage. Hg concentrations in organisms were the highest after flooding. Higher Hg concentrations in fish were observed at the location farthest from the dam. Hg concentrations in water and sediment were correlated. Compared with the reservoirs of United States and Canada, TGR had lower trophic magnification factors (0.046–0.066), that are explained primarily by organic carbon concentrations in sediment, and the effect of “growth dilution”. Based on comparison before and after the impoundment of TGR, THg concentration in biota did not display an obvious long-term reservoir effect due to (i) short time since inundation, (ii) regular water discharge associated with water-level regulation, and/or (iii) low organic matter content in the sediment. [ABSTRACT FROM AUTHOR]

[Purpose/Significance] A future learning center (FLC), a ground-breaking novel education model crafted in response to the burgeoning demands of a rapidly digitized and intelligent society, will undeniably spearhead the new wave of intelligent construction in contemporary university libraries. As this evolution unfolds, libraries urgently need to clarify and solidify their roles in the meticulous construction of future learning centers. Doing so will promote vibrant knowledge exchange, robustly stimulate cross-disciplinary cooperation, and also guide and embolden libraries to proactively seize unprecedented development opportunities and to collaboratively face the emerging challenges ahead. [Method/Process] To comprehend the genesis and potential of the FLC, this research undertakes a meticulous examination of its foundational concepts, overarching objectives, inherent tasks, and structural framework. It delves deep into the libraries' pivotal role in nurturing these centers, especially through the lens of role delineation and functional metamorphosis. Gleaning insights from real-world examples such as the Beijing Institute of Technology Library and the Shanghai University of Finance and Economics Library, this investigation seeks to capture a snapshot of the current operational landscape, along with its associated tribulations and challenges. Through this way, the research hopes to chart a roadmap, offering invaluable reference and actionable guidance for libraries poised to embark on their journey of creating FLCs. [Results/Conclusions] The future learning center encompasses an intelligent learning environment that melds information services with learning and teaching support. Such spaces are poised to emerge as novel grassroots learning organizations underpinning evolution in learning techniques and the genesis of knowledge. Crafting these future learning centers necessitates a systematic approach, calling for collaboration from various stakeholders. Within this context, libraries serve dual roles as both initiators and active contributors. While libraries' involvement in developing future learning centers remains in nascent stages of growth, the core challenge lies in pioneering a human-centric model that harmoniously fuses space, resources, and services to offer students an enriched, tailored, and novel learning journey. As educational paradigms shift, libraries must capitalize on this momentum, drawing from their foundational expertise in intelligent library development, to resonate with the evolving criteria of talent development. Confronted with myriad challenges-- ranging from role definition, conceptual alignment, and overcoming educational reform resistance to enhancing professional acumen and navigating spatial constraints -- libraries are suggested to strategically assimilate educational assets, reconfigure spatial methodologies, and proffer intelligent solutions. They should aim at fostering students' proficiency in autonomous, participatory, and investigative learning through diverse resources. In essence, libraries should evolve into hubs for information services, focal points for student learning, and pillars for teaching assistance. [ABSTRACT FROM AUTHOR]

Objective: Growing evidence indicates that the activation of c-Jun N-terminal kinase (JNK) is implicated in the multiple major pathological features of Alzheimer disease (AD). However, whether specific inhibition of JNK activation could prevent disease progression in adult transgenic AD models at moderate stage remains unknown. Here we first investigated the potential disease-modifying therapeutic effect of systemic administration of SP600125, a small-molecule JNK-specific inhibitor, in middle-aged APPswe/PS1dE9 mice.Methods: Using behavioral, histological, and biochemical methods, outcomes of SP600125 treatment on neuropathology and cognitive deficits were studied in APPswe/PS1dE9 mice.Results: Compared with vehicle-treated APPswe/PS1dE9 mice, chronic treatment of SP600125 for 12 weeks potently inhibited JNK activation, which resulted in a marked improvement of behavioral measures of cognitive deficits and a dramatic reduction in amyloid plaque burden, β-amyloid production, tau hyperphosphorylation, inflammatory responses, and synaptic loss in these transgenic animals. In particular, we found that SP600125 treatment strongly promoted nonamyloidogenic amyloid precursor protein (APP) processing and inhibited amyloidogenic APP processing via regulating APP-cleavage secretase expression (ie, ADAM10, BACE1, and PS1) in APPswe/PS1dE9 mice.Interpretation: Our findings demonstrate that chronic SP600125 treatment is powerfully effective in slowing down disease progression by markedly reducing multiple pathological features and ameliorating cognitive deficits associated with AD. This study highlights the concept that active JNK actually contributes to the development of the disease, and provides critical preclinical evidence that specific inhibition of JNK activation by SP600125 treatment may be a novel promising disease-modifying therapeutic strategy for the treatment of AD. [ABSTRACT FROM AUTHOR]

Objective Growing evidence indicates that the activation of c-Jun N-terminal kinase (JNK) is implicated in the multiple major pathological features of Alzheimer disease (AD). However, whether specific inhibition of JNK activation could prevent disease progression in adult transgenic AD models at moderate stage remains unknown. Here we first investigated the potential disease-modifying therapeutic effect of systemic administration of SP600125, a small-molecule JNK-specific inhibitor, in middle-aged APPswe/PS1dE9 mice. Methods Using behavioral, histological, and biochemical methods, outcomes of SP600125 treatment on neuropathology and cognitive deficits were studied in APPswe/PS1dE9 mice. Results Compared with vehicle-treated APPswe/PS1dE9 mice, chronic treatment of SP600125 for 12 weeks potently inhibited JNK activation, which resulted in a marked improvement of behavioral measures of cognitive deficits and a dramatic reduction in amyloid plaque burden, β-amyloid production, tau hyperphosphorylation, inflammatory responses, and synaptic loss in these transgenic animals. In particular, we found that SP600125 treatment strongly promoted nonamyloidogenic amyloid precursor protein (APP) processing and inhibited amyloidogenic APP processing via regulating APP-cleavage secretase expression (ie, ADAM10, BACE1, and PS1) in APPswe/PS1dE9 mice. Interpretation Our findings demonstrate that chronic SP600125 treatment is powerfully effective in slowing down disease progression by markedly reducing multiple pathological features and ameliorating cognitive deficits associated with AD. This study highlights the concept that active JNK actually contributes to the development of the disease, and provides critical preclinical evidence that specific inhibition of JNK activation by SP600125 treatment may be a novel promising disease-modifying therapeutic strategy for the treatment of AD. Ann Neurol 2015;77:637-654 [ABSTRACT FROM AUTHOR]

A reflective beam shaper is designed for the purpose of compensation of the low-order aberrations in high-power slab lasers. A proportional-integral-derivative (PID) control algorithm is used to control the optical parameters of a beam shaper for active compensation of low-order aberrations. Simulations of the PID algorithm show that different combinations of defocus, 0-deg astigmatism, and 45-deg astigmatism, which are the main contributors of beam aberrations in slab lasers, can be well compensated by variation of distance and rotation angle of mirrors. For a beam with large wave aberrations [peak-to-valley (PtV) = 87.7λ, root-mean-square (RMS) = 19λ], the adjustment of distance between mirrors is less than 100 mm, and the rotation angle about the z-axis is <3.2 deg, and the wavefront distortion is reduced to a level (PtV = 0.50λ, RMS = 0.09λ) that can be further corrected with one deformable mirror. The effectiveness and performance of low-order aberration compensation with the reflective beam shaper are also verified by experiments. [ABSTRACT FROM AUTHOR]

Background and Purpose Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion. Experimental Approach We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion ( BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses. Key Results BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin. Conclusion and Implications Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion (MPE) is an exudative effusion caused by primary or metastatic pleural carcinosis. Th17 cells and their cytokines are critical components in various disease including MPE. In this review, we summarize current published articles regarding the multifunctional roles of Th17 cells and their related cytokines in MPE. Th17 cells are accumulated in MPE compared with paired serum via certain manners. The upregulation of Th17 cells and the interactions between Th17 cells and other immune cells, such as Th1 cells, Th9 cells, regulatory T cells and B cells, are reported to be involved in the formation and development of MPE. In addition, cytokines, which are elaborated by Th17 cells, including IL-17A, IL-17F, IL-21, IL-22, IL-26, GM-CSF, or associated with Th17 cells differentiation, including IL-1β, IL-6, IL-23, TGF-β, are linked to the pathogenesis of MPE through exerting pro- or anti-tumorigenic functions on their own as well as regulating the generation and differentiation of Th17 cells in MPE. Based on these findings, we proposed that Th17 cells and their cytokines might be diagnostic or prognostic tools and potential therapeutic targets for MPE. [ABSTRACT FROM AUTHOR]

Highlights: [•] An epoxy resin-Q345 system with a sandwich structure was prepared. [•] Cl− ions permeated into epoxy resin coating prior to K+ ions. [•] Free volume size and PAL increased when the coating was immersed into the solution. [Copyright &y& Elsevier]

Highlights: [•] Th17 cells express the highest levels of TNF than other Th subsets. [•] Th17 cells most potently stimulate co-transferred Tregs in Rag1 KO mice. [•] This effect of Th17 cells is TNF- and IL-2-dependent. [•] TNF–TNFR2 plays crucial role in reciprocal stimulation of Th17 cells and Tregs. [Copyright &y& Elsevier]

Background: Although the prognosis of patients with small (≤1cm) tumors is generally favorable, emerging data suggests that biological behavior varies between intrinsic subtypes in such patients. Furthermore, it still remains unclear whether HER2-positive pT1a-bN0M0 patients could benefit from adjuvant trastuzumab. For further evaluation, we sought to conduct a meta-analysis so as to get a better understanding of the prognosis for HER2-positive pT1a-bN0M0 patients and their survival benefit from adjuvant trastuzumab, accordingly, offering the implications for current practice. Methods: The PubMed database, the online proceedings of the American Society of Clinical Oncology (ASCO) Annual Meetings, the online proceedings of the San Antonio Breast Cancer Symposium, and the CD proceedings of the International St. Gallen Breast Cancer Conference were searched for all relevant studies published before September 2012. Relative risks (RRs) were used to compare the prognosis of different intrinsic subtypes for pT1a-bN0M0 breast cancer. Analyses were also performed to estimate the association between adjuvant trastuzumab and various survival outcomes. Results: With eight eligible studies identified, this meta-analysis demonstrated a deleterious effect of HER2+ phenotype on disease-free survival (DFS; RR = 3.677, 95% CI 2.606–5.189, p <0.001) and distant disease-free survival (DDFS; RR = 3.824, 95% CI 2.249–6.501, p<0.001) as compared to HR+/HER2- subgroup. However, significant difference failed to be achieved in terms of any endpoint between HER2+ and triple negative breast cancer (TNBC). Besides, a marked improvement in DFS was observed with the addition of trastuzumab for HER2-positive pT1a-bN0M0 patients (RR = 0.323, 95% CI 0.191–0.547, p<0.001). Conclusion: This meta-analysis clarifies that intrinsic subtypes might be a reliable marker to predict the prognosis in pT1a-bN0M0 breast cancer. Besides, even for such early stage HER2-positive patients, adjuvant trastuzumab might bring significant survival benefit. [ABSTRACT FROM AUTHOR]

Background: Our previous data have demonstrated that the number of IL-9-producing CD4 T cells (Th9 cells) in malignant pleural effusion (MPE) was significantly increased when compared with that in blood. The aim of the present study was to investigate the mechanism by which Th9 cells were recruited into MPE and the phenotypic characteristics of pleural Th9 cells. Methods: The expression patterns of chemokine receptors (CCRs) on Th9 cells and the chemoattractant activity of chemokine CCL20 for Th9 cells in vitro were observed. The phenotypic features of Th9 cells in MPE were determined by flow cytometry. Results: We found that Th9 cells in both MPE and blood expressed a high level of CCR6 on their surface. An in vitro migration assay confirmed that both MPE and supernatants of cultured pleural mesothelial cells could induce the migration of Th9 cells, and anti-CCL20 mAb significantly inhibited the ability of MPE or supernatants to stimulate Th9 cell chemotaxis. We also noted that pleural Th9 cells expressed high levels of CD45RO and very low levels of CD45RA and CD62L, displaying the phenotype of effector memory cells. Conclusions: Our data revealed that recruitment of Th9 cells into MPE could be induced by pleural CCL20 and that the majority of Th9 cells in MPE displayed the phenotype of effector memory cells. [ABSTRACT FROM AUTHOR]

The gradient composite TiAlSiN coatings were prepared by the cathodic arc ion technology. The tribological properties of TiAlSiN coating were investigated by the ball on disc tribological test in the humid atmosphere against various friction pairs. The results show that the TiAlSiN coating exhibited excellent mechanical properties. The corresponding wear mechanism varied with different friction pair under loads (2 N, 15 N, 25 N). The wear mechanisms of the coatings against stainless steel ball and ZrO 2 ball were the adhesive wear and the abrasive wear, respectively. The wear rate and the friction coefficient of coating against Si 3 N 4 ball were significantly decreased due to the generation of SiO 2 •nH 2 O layer. However, the SiO 2 •nH 2 O layer was weakened with the increasing of the load. Results show that the tribological properties of TiAlSiN coating are affected by the material of friction pairs. Lubrication film can be formed in a humid environment to improve the tribological properties of the coating. • The soft SUS friction pair transferred to the surface of TiAlSiN coating. • The stable SiO 2. nH 2 O lubrication film required certain Si content, appropriate contact stress and temperature. [ABSTRACT FROM AUTHOR]

Highlights: [•] The PEO film contains a ring at the edge and a volcano-like profile in the middle. [•] A special ring-like nucleation provides a visual mark of Marangoni convection. [•] The decreasing viscous stress is the key point of contact line recession. [Copyright &y& Elsevier]

Abstract: The phase aberration caused by thermal deformations in a high power inner optical system is simulated and the wavefront pre-compensation for correcting the aberration is studied experimentally. Choosing Strehl ratio (SR) and the root-mean-square (RMS) of distorted phase as the characteristic parameters, the beam quality of outgoing laser is calculated when the wavefront of incident laser is compensated. Based on the computed results, the laboratory experiment is designed to model the thermal deformations aberration and the correction process by using two Liquid Crystal on Silicon Spatial Light Modulators (LCoS-SLM). The negative influence of astigmatism and defocusing on laser beam quality in far field is obvious and the astigmatism induces the non-axisymmetrical divergence of intensity distribution. After wavefront pre-compensation the power in the bucket (PIB) value of outgoing laser beam is close to the flat wavefront laser source. Both simulated and experimental results indicate that the method of wavefront pre-compensation can greatly correct the aberrations caused from thermal deformation, and the laboratory experiment is a feasible method to modeling the inner optical system with phase aberration. [Copyright &y& Elsevier]

Physicochemical properties such as AM content, morphology, gelatinization, crystallography and pasting behavior of an under utilized yam starch from Dioscoreae zingiberensis C.H. Wright were characterized by SEM, particle size analysis, X-ray powder diffraction, DSC, and Brabender viscoamylograph, and compared to commercial potato and maize starches. D. zingiberensis starch had an AM content of 23.62% and exhibited a flattened ovoid shaped granules with majority (87.4%) of them having diameter in the range of 10-50 µm and centering at 21.192 µm. The X-ray powder diffraction showed A-type crystalline patterns of D. zingiberensis. Higher values in onset temperature ( To, 70.49°C), peak temperature ( Tp, 78.53°C) and conclusion temperature ( Tc, 85.96°C) of D. zingiberensis. Unlike potato starch, pasting properties of D. zingiberensis starch were somewhat similar to that of maize starch. Pasting onset temperature, maximum, breakdown, and setback viscosity of D. zingiberensis starch were 73.4°C, 309, 46, and 161 BU, respectively. Interestingly, a very stable paste viscosity was observed during high temperature (5 min for D. zingiberensis starch. [ABSTRACT FROM AUTHOR]

Abstract: Th22 cells have been reported to be involved in human cancers. However, differentiation and immune regulation of Th22 cells in malignant pleural effusion (MPE) remain unknown. We noted that Th22 cell numbers were increased in MPE, and that IL-22 substantially promoted the proliferation and migratory activity of A549 cells. Moreover, IL-22 could strongly facilitate intercellular adhesion of A549 cells to pleural mesothelial cell monolayers. Our data revealed that the increase in Th22 cells in MPE was due to pleural cytokines and chemokines, and that Th22 exerted an important immune regulation on cancer cells in human pleural malignant environment. [Copyright &y& Elsevier]

Abstract: Benzoylformic acid was synthesized from the hydrolysis of benzoyl cyanide by a newly isolated Rhodococcus sp. CCZU10-1. In this study, an aqueous–toluene biphasic system was developed for highly efficient production of benzoylformic acid from the hydrolysis of benzoyl cyanide. In the aqueous–toluene biphasic system, the phase volume ratio, buffer pH and reaction temperature were optimized. Using fed-batch method, a total of 932mM benzoylformic acid accumulated in the reaction mixture after the 10th feed. Moreover, enzymatic hydrolysis of benzoyl cyanide using calcium alginate entrapped resting cells was carried out in the aqueous–toluene biphasic system, and efficient biocatalyst recycling was achieved as a result of cell immobilization in calcium alginate, with a product-to-biocatalyst ratio of 14.26g benzoylformic acid g−1 dry cell weight (DCW) cell after 20 cycles of repeated use. [Copyright &y& Elsevier]

Two new quaternary protoberberine alkaloids, namely corydayanine (1) and yanhusuine (2), were isolated from the tubers of Corydalis yanhusuo. On the basis of extensive chemical and spectroscopic evidences, especially 1D and 2D NMR and HRMS experiments, their structures were elucidated as 5,6-dihydro-3,9-dihydroxy-2,10-dimethoxy-13-methyl-dibenzo[a,g] quinolizinium alkaloid and 5,6-dihydro-12-hydroxy-2,3,9-trimethoxy-13-methyl-dibenzo[a,g] quinolizinium alkaloid, respectively. [ABSTRACT FROM AUTHOR]

Air blowers are widely used in industry. The vibration of the rolling bearing-rotor is a key factor in the blower's performance because it significantly influences the security and working life of the whole system. In previous research on the vibration characteristics of the air blower, the supporting rolling element bearing was always simplified as a particle on a shaft with radial stiffness and damping coefficient. Such simplification neglects the effects of the bearing structure on the vibration performance of the rotor system. In this paper, a numerical model of the bending stiffness of the tapered roller bearing was established through mechanics and deformation analysis. On the base of the model, a new TMM (transfer matrix method) for bearing-rotor system was established; the new TMM considers the influences of the bearing structure on the vibration of the rotor system. Furthermore, modal analysis on an air blower rotor system was carried out by using the new TMM, and the mode shape, critical speed and unbalance response of the air blower system were obtained. The same blower rotor was also analyzed by FEM to verify the validation of the new TMM, showing that the new method proposed in this paper for vibration characteristics calculation of an air blower is credible. [ABSTRACT FROM AUTHOR]