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There are three main disadvantages including time-consuming task, high cost and complex detection procedures in the semen quality measurement to heighten the roosters’ reproductive capability in breeder flocks. Another solution is to select the breeder roosters with fine phenotypic characteristics by humans, while it is also a considerably labor-intensive task and even increases the risk of zoonoses at a poultry farm. To solve these problems, this paper proposes a strategy that effective promoting factors applied to Progressive Multi-Granularity (PMG) network ensures the accuracy of entire image and improves the accuracy of fine-grained image. This strategy allows the basic networks boost the classification performance in the case of specific combination. Given the same images inputted into our model, two groups of questionnaires for practitioners and non-practitioners judging the fertility by the rooster’s phenotypic traits, the experimental results show that our method has raised the accuracy by almost 10% by comparison with the results of questionnaire survey.

With the improvement of living standards, the problem of human obesity has been getting worse. It is important to classify human obesity and determine the relevant obesity factors. In this paper, Lasso feature selection method is used for feature selection of data set to further reduce the data dimension. In addition, because the traditional LightGBM algorithm has a certain randomness in parameter selection, it is difficult to determine the optimal combination of parameters. This paper uses genetic algorithm to optimize the parameters of LightGBM algorithm. It is worth mentioning that the use of data standardization reduces the runtime of LightGBM. The LightGBM based on GA optimization compared with other common machine learning algorithms obtains good results, compared with the traditional LightGBM algorithm, the average accuracy and the average runtime are improved by 0.5% and decreased by 72.12% respectively.

The liver is a metabolically active organ and is also 'tolerogenic', exhibiting sophisticated mechanisms of immune regulation that prevent pathogen attacks and tumorigenesis. How metabolism impacts the tumor microenvironment (TME) in hepatocellular carcinoma (HCC) remains understudied.We investigated the role of the metabolic regulator SIRT5 in HCC development by conducting metabolomic analysis, gene expression profiling, flow cytometry and immunohistochemistry analyses in oncogene-induced HCC mouse models and human HCC samples.We show that SIRT5 is downregulated in human primary HCC samples and that Sirt5 deficiency in mice synergizes with oncogenes to increase bile acid (BA) production, via hypersuccinylation and increased BA biosynthesis in the peroxisomes of hepatocytes. BAs act as a signaling mediator to stimulate their nuclear receptor and promote M2-like macrophage polarization, creating an immunosuppressive TME that favors tumor-initiating cells (TICs). Accordingly, high serum levels of taurocholic acid correlate with low SIRT5 expression and increased M2-like tumor-associated macrophages (TAMs) in HCC patient samples. Finally, administration of cholestyramine, a BA sequestrant and FDA-approved medication for hyperlipemia, reverses the effect of Sirt5 deficiency in promoting M2-like polarized TAMs and liver tumor growth.This study uncovers a novel function of SIRT5 in orchestrating BA metabolism to prevent tumor immune evasion and suppress HCC development. Our results also suggest a potential strategy of using clinically proven BA sequestrants for the treatment of patients with HCC, especially those with decreased SIRT5 and abnormally high BAs.Hepatocellular caricinoma (HCC) development is closely linked to metabolic dysregulation and an altered tumor microenvironment. Herein, we show that loss of the metabolic regulator Sirt5 promotes hepatocarcinogenesis, which is associated with abnormally elevated bile acids and subsequently an immunosuppressive microenvironment that favors HCC development. Targeting this mechanism could be a promising clinical strategy for HCC.

An ideal carbon-based supercapacitor electrode requires abundant micropores that are favorable for charge accumulation, and suitable mesopores that are beneficial for fast electrolyte ions transport. Herein, 3D porous carbon microspheres (carbon nanotube-ketjen black/activated carbon, CNT-KB/AC), where the CNT-KB microspheres (CKMS) as the framework providing mesopores and the activated carbon as the core providing micropores, have been constructed by spray drying and KOH activation. The obtained carbon composites exhibit a homogeneous spherical structure and high specific surface area (up to 1751 m2 g−1). The CNT-KB/AC electrode with an areal density of 3 mg cm−2 can achieve a high areal capacitance of 506.9 mF cm−2 at the current density of 0.2 A g−1 in 6 M KOH solution, which is much larger than that of the CNT/AC electrode (232.6 mF cm−2) and CNT-AB/AC electrode (179.5 mF cm−2). Besides, when the areal density is increased up to 9 mg cm−2, the areal capacitance of CNT-KB/AC is increased up to 998.9 mF cm−2 at 0.2 A g−1 and 724.9 mF cm−2 at 20 A g−1. Furthermore, it exhibits excellent long-term cycling stability (achieving capacitance retention of 94% after 10,000 cycles). These results indicate that the CNT-KB/AC composites are promising electrode materials for high-areal-density supercapacitors.

An ultrafine (6–7 nm) and well dispersed nano-SnO2/carbon nanotube hairball (SnO2/CNTH) composite material with a three-dimensional (3D) hierarchical structure is prepared by spray drying and solvo...

A fast, simple and environmentally friendly method for the digestion of solid samples of Gentiana rigescens Franch. ex Hemsl. (G. rigescens) based on deep eutectic solvent (DES) was established, and inductively coupled plasma-optical emission spectrometry (ICP-OES) was used to quantify Ni, Zn, Co, Cr and Cu in DES digestion solution. Under optimized conditions, limits of detection (LOD) and limits of quantification (LOQ) ranged from 0.4 to 2.5 and 1.2-8.2 μg g

Inclusion of polymer additives is a known strategy to improve foam stability, but questions persist about the amount of polymer incorporated in the foam and the resulting structural changes that impact material performance. Here, we study these questions in sodium dodecyl sulfate (SDS)/hydroxypropyl methylcellulose (HPMC) foams using a combination of flow injection QTOF mass spectrometry and small-angle neutron scattering (SANS) measurements leveraging contrast matching. Mass spectrometry results demonstrate polymer incorporation and retention in the foam during drainage by measuring the HPMC-to-SDS ratio. The results confirm a ratio matching the parent solution and stability over the time of our measurements. The SANS measurements leverage precise contrast matching to reveal detailed descriptions of the micellar structure (size, shape, and aggregation number) along with the foam film thickness. The presence of HPMC leads to thicker films, correlating with increased foam stability over the first 15-20 min after foam production. Taken together, mass spectrometry and SANS present a structural and compositional picture of SDS/HPMC foams and an approach amenable to systematic study for foams, gathering mechanistic insights and providing formulation guidance for rational foam design.

Objective Patients with cardiac surgery–associated acute kidney injury are at risk of renal replacement therapy and in-hospital death. We aimed to develop and validate a novel predictive model for poor in-hospital outcomes among patients with cardiac surgery–associated acute kidney injury. Methods A total of 196 patients diagnosed with cardiac surgery–associated acute kidney injury were enrolled in this study as the training cohort, and 32 blood cytokines were measured. Least absolute shrinkage and selection operator regression and random forest quantile-classifier were performed to identify the key blood predictors for in-hospital composite outcomes (requiring renal replacement therapy or in-hospital death). The logistic regression model incorporating the selected predictors was validated internally using bootstrapping and externally in an independent cohort (n = 52). Results A change in serum creatinine (delta serum creatinine) and interleukin 16 and interleukin 8 were selected as key predictors for composite outcomes. The logistic regression model incorporating interleukin 16, interleukin 8, and delta serum creatinine yielded the optimal performance, with decent discrimination (area under the receiver operating characteristic curve: 0.947; area under the precision-recall curve: 0.809) and excellent calibration (Brier score: 0.056, Hosmer–Lemeshow test P = .651). Application of the model in the validation cohort yielded good discrimination. A nomogram was generated for clinical use, and decision curve analysis demonstrated that the new model adds more net benefit than delta serum creatinine. Conclusions We developed and validated a promising predictive model for in-hospital composite outcomes among patients with cardiac surgery–associated acute kidney injury and demonstrated interleukin-16 and interleukin-8 as useful predictors to improve risk stratification for poor in-hospital outcomes among those with cardiac surgery–associated acute kidney injury.

Although the relationship between trade and environment has been widely discussed in past studies, trade policy has been in a state of continuous change in recent years. Previous studies have focused on the impact of trade opening or liberalization on the environment, ignoring discussion of the dynamic changes of trade policy. Therefore, it is very important to explore the connection between trade policy changes and environmental pollution for future environmental protection. In order to realize the in-depth study of this mechanism, the paper will try to solve the following three problems: (1) What is the relationship between change in trade policy uncertainty and China’s environmental pollution? (2) What is the mechanism by which trade uncertainty changes environmental pollution? (3) Due to China’s vast territory and regional differences, will changes in trade policy uncertainty have heterogeneous effects due to regional differences? To solve these problems, based on China’s accession to the WTO at the end of 2001, this paper, for the first time, uses PM2.5 concentration data of 246 prefecture-level cities in China to explore the impact of trade policy uncertainty on China’s environmental pollution, then we make an in-depth analysis of the impact path and heterogeneity of urban spatial distribution and city size. We found that, after China’s accession to the WTO, the growth rate of PM2.5 concentration reduced in cities with lower trade policy uncertainty and the inhibition effect was different due to the spatial distribution of city size. A further mechanism test shows that reduction in trade policy uncertainty can improve environmental pollution through industrial, structural and technological effects.

With the development of human society, the shortage of traditional fossil fuels has intensified, and due to sustainable development and ecological environment, new green and pollution-free energy has entered the public’s field of vision. Thin-film solar cells have high photoelectric conversion efficiency, stable performance and low consumption of raw materials. However, some elements in raw materials are toxic and their reserves are small, which limits their large-scale popularization and use. Perovskite solar cells have attracted public attention because of their low cost and simple production process. The traditional energy content is limited, and the demand for energy is increasing with the development of the world economy, so the world is bound to face the dilemma that single fossil energy cannot meet the demand for energy for economic maintenance and development. As a clean energy, extensive use of solar energy is also an effective solution to the pollution caused by traditional energy utilization. This paper mainly analyzes the electrochemical preparation methods of perovskite solar cells, and studies its performance optimization.

MicroRNAs, a class of small and non-encoding RNAs that transcriptionally or post-transcriptionally modulate the expression of their target genes, have been implicated as critical regulatory molecules in ischemia-/reperfusion-induced cardiac injury. In the present study, we report on the role of miR-208a in myocardial I/R injury and the underlying cardio-protective mechanism. The gain-of-function and loss-of-function were used to explore the effects of miR-208a on cardiac injury induced by H2O2 in cardiomyocytes. As predicted, knockdown of endogenous miR-208a significantly decreased the level of cellular reactive oxygen species (ROS) and reduced cardiomyocyte apoptosis. In addition, miR-208a overexpression increased the ROS level and attenuated cell apoptosis in cardiomyocytes. Furthermore, protein tyrosine phosphatase receptor type G (PTPRG) and protein tyrosine phosphatase, non-receptor type 4 (PTPN4), which participate in regulating the level of cellular protein tyrosine phosphorylation balance, were predicted and verified as potential miR-208a targets using bioinformatics and luciferase assay. In summary, this study demonstrated that miR-208a plays a critical protective role in ROS-induced cardiac apoptosis.

EPR spectroscopy was used to monitor formation of free radicals in human hair upon UV irradiation. While the EPR spectra of brown hair were dominated by melanin signal, those of white hair were keratin-derived. The decay of UV induced keratin radicals was enhanced at increased ambient humidity. We argue that at higher humidity the swollen hair provides a more liquid-like environment, and higher molecular mobility in this environment leads to faster radical reactions. This interpretation is consistent with the increased UV-triggered protein damage in hair at high humidity as demonstrated by the protein loss, MALDI-TOF and FT-IR data.

In this work, switchable hydrophilicity solvent-based ultrasound-assisted liquid phase microextraction (SHS-UA-LPME) was combined with micro-volume UV-vis spectrophotometry for the determination of trace nickel in the medicinal plant Gentiana rigescens Franch. ex Hemsl. (G. rigescens) samples for the first time. Micro-volume spectrophotometry has the characteristics of microanalysis, economy and low operation cost, which is feasible to be combined with miniaturized enrichment method. Dipropylamine (DPA) as a switchable solvent completed the extraction during the phase conversion process. It was changed from hydrophobic to hydrophilic under the action of HCl, and then completed phase transition under the action of NaOH. The parameters influencing the extraction efficiency were investigated. Under the optimal conditions, the enhancement factor (EF), the limit of detection (LOD), the limit of quantitation (LOQ) and relative standard deviation (RSD, n = 7) were 28, 0.02 µg/L, 0.067 µg/L and 1.4%, respectively. The established method was applied to the determination of G. rigescens samples collected from the local field with satisfactory results.

There is a need to investigate the role of nuclear factor kappa B in the regulation of cyclooxygenase-2 expression in the epileptic rat brain and cultured hippocampal neurons. Immunofluorescence and polymerase chain reaction was used to detect the expression of nuclear factor kappa B and cyclooxygenase-2. In cultured hippocampal neurons and rat brain: the control group compared with the normal group, nuclear factor kappa B expression in the hippocampal dentate gyrus, cerebral cortex, the piriform cortex brain regions were significantly increased (P < 0.01). This is accompanied by a significant increase in cyclooxygenase-2 protein and mRNA expressions in the hippocampus (P < 0.01). In the experimental group compared to the control group, the nuclear factor-kappa B expression in the hippocampal dentate gyrus, cerebral cortex, piriform cortex, and other brain regions was significantly lower (P < 0.01), with the accompanying decrease in cyclooxygenase-2 protein and mRNA expression (P < 0.01) in the hippocampus. In conclusion, κB-decoy can inhibit nuclear factor kappa B activation in epileptic rat brain and cyclooxygenase-2 overexpression.

G protein-coupled receptor 50 (GPR50) belongs to the G protein-coupled receptor which is highly homologous with the sequence of melatonin receptor MT1 and MT2. GPR50 expression has previously been reported in many brain regions, like cortex, midbrain, pons, amygdala. But, the distribution of GPR50 in the hippocampus and cortex and the cell types expressing GPR50 is not yet clear. In this study, we examined the distribution of GPR50 in adult male mice by immunofluorescence. Our results showed that GPR50 was localized in the CA1-3 pyramidal cells and the granule cells of the dentate gyrus. GPR50 was also expressed in excitatory and inhibitory neurons. As inhibitory neurons also contain many types, we found that GPR50 was localized in some interneurons in which it was co-expressed with the calcium-binding proteins calbindin, calretinin, and parvalbumin. Besides, similar results were seen in the cortex. The widespread expression of GPR50 in the hippocampus and cortex suggests that GPR50 may be associated with synaptic plasticity and cognitive function.

Non-rigid object tracking is an important yet challenging task in computer vision. In this paper, a multi-patch neural network (MPNet) model is presented to address the problem of non-rigid object tracking. The model learns a multiple patch based framework, which mainly consists of two branches of neural networks. One branch is to track the global target and the other branch partitions the target into multiple patches which are tracked separately. The global tracking and the multiple patch tracking are combined to compute the final tracking results. Compared with the existing methods, our model exploits the trajectories of various parts of a non-rigid object and therefore can accurately track the non-rigid object. Experiments on visual tracking datasets prove the strength of the proposed method.

Chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans (PGs) are major extracellular matrix (ECM) components of the central nervous system (CNS). A large body of evidence has shown that CSPGs/DSPGs play critical roles in neuronal growth, axon guidance, and plasticity in the developing and mature CNS. It has been proposed that these PGs exert their function through specific interaction of CS/DS chains with its binding partners in a manner that depends on the sulfation patterns of CS/DS. It has been reported that dermatan 4-O-sulfotransferase-1 (Chst14/D4st1) specific for DS, but not chondroitin 4-O-sulfotransferase-1 (Chst11/C4st1) specific for CS, regulates proliferation and neurogenesis of neural stem cells (NSCs), indicating that CS and DS play distinct roles in the self-renewal and differentiation of NSCs. However, it remains unknown whether specific sulfation profiles of DS has any effect on CNS plasticity. In the present study, Chst14/D4st1-deficient (Chst14−/−) mice was employed to investigate the involvement of DS in synaptic plasticity. First, behavior study using Morris Water Maze (MWM) showed that the spatial learning and memory of Chst14−/− mice was impaired when compared to their wild type (WT) littermates. Corroborating the behavior result, long-term potentiation (LTP) at the hippocampal CA3-CA1 connection was reduced in Chst14−/− mice compared to the WT mice. Finally, the protein levels of N-Methyl-D-aspartate (NMDA) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, postsynaptic density 95 (PSD95), growth associated protein 43 (GAP-43), synaptophysin (SYN) and N-ethylmaleimide sensitive factor (NSF) which are important in synaptic plasticity were examined and Chst14/D4st1 deficiency was shown to significantly reduce the expression of these proteins in the hippocampus. Further studies revealed that Akt/mammalian target rapamycin (mTOR) pathway proteins, including protein kinase B (p-Akt), p-mTOR and p-S6, were significantly lower in Chst14−/− mice, which might contribute to the decreased protein expression. Together, this study reveals that specific sulfation of DS is critical in synaptic plasticity of the hippocampus and learning and memory, which might be associated with the changes in the expression of glutamate receptors and other synaptic proteins though Akt/mTOR pathway.

Novel heavy atom free 5,5-dioxoyphenothiazine-based “D–A–D” emitters with aggregation-induced emission (AIE), room-temperature phosphorescence (RTP), white light emission and dual-mode mechanochromic luminescence (MCL) characteristics have been designed and synthesized. Impressively, DCzCs and DCzCs-Et showed persistent RTP (pRTP) in the crystalline state with lifetimes of 528 ms and 137 ms in air, respectively. DCzCs-Ac exhibited white light emission with a CIE coordinate of (0.25, 0.26), due to the dual emission of fluorescence and phosphorescence. Detailed studies have shown that through simply functional group modification on the acceptor skeleton to modulate the molecular structure and intermolecular interactions, we fine-tuned the optical properties of the luminogens and realized white light emission. The dense crystal packing was proved to be closely related to the phosphorescence of the system and the special dual-mode MCL behavior was attributed to the conversion of crystalline-amorphous state under external force.

Two novel aggregation-induced emission (AIE) based fluorescent probes, TPANI-DNs and PCZNI-DNs, have been designed and synthesized for “turn-on” detection of H2S. Chromophore napthalimide fused triphenylamine (or phenylcarbazole) unit as fluorophore in combination with 2,4-dinitrobenzenesulfonyl as recognition moiety constructed probes. The design strategy of the twisted D-π-A structure can efficiently transform the aggregation-caused quenching (ACQ) system into the AIE system by strengthening the restriction of intramolecular motion and preventing the intermolecular π-π stacking. The consequences showed that both TPANI-DNs and PCZNI-DNs displayed large stokes shift (135 nm and 120 nm, respectively), high selective and sensitive detection. The response mechanisms and fluorescent properties were further investigated through the time-dependent density functional theory (TDDFT). Importantly, since the strong AIE properties, a H2S test board has been prepared and used to detect H2S onsite easily and sensitively, displaying potential practical applications.

Surface coating is an efficient strategy to enhance the interfacial stability of the electrode. Graphene quantum dots (GQDs) have advantages of excellent dispersion in water, outstanding electron and ion conductivities and high specific surface area. In this work, GQDs were coated directly on the surface of LiCoO2 particles (GQDs-LiCoO2) through liquid phase method. Compared to bare LiCoO2, the cycling performance, rate capacity and thermo-stability of the GQDs-LiCoO2 have been significantly improved in the voltage range of 3.04.5 V. GQDs-LiCoO2 showed a much higher capacity retention than that of bare LiCoO2 (82.8 % vs 46.1 %) after 100 cycles at 0.5 C. The excellent improvement of the GQDs-LiCoO2 was mainly attributed to the formation of a uniform, stable, dense and well-conductive protective layer on the surface of LiCoO2 particles by the surface coating of GQDs. The detailed analysis of the cycled electrodes reveals that the GQDs coating stabilizes the crystal structure of LiCoO2 and suppresses undesirable interfacial side reactions between the cathode and electrolyte, leading to the improvement of battery performance.

Anomaly detection on system logs is to report system failures with utilization of console logs collected from devices, which ensures the reliability of systems. Most previous researches split logs into sequential time windows and regarded each window as an independent instance for classification using popular machine learning methods like support vector machine(SVM), however, neglected the time patterns under logs. Those approaches also suffer from information loss due to the vector representation, and high dimensionality if there is a large number of log events. To make up these deficiencies, unlike most traditional methods that used a vector to represent a period behavior at the macro level, we construct a 2D matrix to reveal more detailed system behaviors in the time period by dividing each window into sequential subwindows. To provide a more efficient representation, we further use the ant colony optimization algorithm to find a highly-coupled event template as the horizontal index of the 2D window matrix to replace the disordered one. To capture time dependencies, a multi-module convolutional auto-encoder is configured as that different paralleled modules scan among different time intervals to extract information respectively. These features are then concatenated in latent space as the final input, which contains diversified time information, for classification by SVM. The experiments on Blue Gene/L log dataset showed that our proposed method outperforms the state-of-art SVM method.

To study the reactivity of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) with the cationically charged agents cetylpyridinium chloride, stannous fluoride, and the non-cationic agent triclosan. We also assessed the effect of these agents to inhibit LPS and LTA binding to cellular Toll-like Receptors (TLRs) in vitro.The ability of these antimicrobials to bind with LPS and/or LTA was assessed in both the Limulus amebocyte lysate and BODIPY-TR-cadaverine dye assays. Mass spectroscopy was then used to confirm that stannous fluoride directly binds with LPS and to determine stoichiometry. Lastly, we looked for possible inhibitory effects of these antimicrobial agents on the ability of fluorescently conjugated LPS to bind to TLR4 expressed on HEK 293 cells.Cetylpyridinium chloride (CPC) and stannous salts including stannous fluoride interfered with LPS and LTA reactivity in both dye assays, while triclosan had no effect. Mass spectroscopy revealed direct binding of stannous fluoride with E. Coli LPS at 1:1 stoichiometric ratios. In the cellular assay, cetylpyridinium chloride and stannous fluoride, but not triclosan, inhibited LPS binding to TLR4.These results support a potential mechanism of action for stannous fluoride and CPC formulated in oral products in which these ingredients bind bacterial toxins and potentially render them less toxic to the host. These results may influence home care recommendations for patients at risk for plaque-related diseases.

Genipin is the major active component of Gardeniae fructus and has been shown to ameliorate diabetes and insulin resistance in rat models. In this study, we first investigated the effect of genipin on obesity and the related lipid metabolism mechanisms in diet-induced obese rats. Our results showed that genipin reduced body weight, food intake, and visceral fat mass; ameliorated dyslipidemia, glucose intolerance, insulin intolerance, adipocyte hypertrophy, and hepatic steatosis; and reduced serum tumor necrosis factor-α level in diet-induced obese rats. Quantitative real-time reverse-transcription polymerase chain reaction results further illustrated that genipin promoted lipolysis and β-oxidation of fatty acid by upregulating gene expressions of hormone-sensitive lipase and adipose triglyceride lipase in white adipose tissue (WAT) and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1α in hepatic tissue. Moreover, genipin promoted browning of WAT by upregulating the mRNA and protein levels of uncoupling protein 1 and PRD1-BF1-RIZ1 homologous domain containing 16 in WAT. Additionally, genipin inhibited gene expressions of activin receptor-like kinase 7, tumor necrosis factor-α, and interlukin-6 in WAT. These results indicated that genipin had a potential therapeutic role in obesity, in which regulation of lipid mobilization and browning of WAT were involved.

The protective effects of dioscin, a natural steroidal saponin from some medicinal plants including Dioscorea nipponica Makino, against lipopolysaccharide (LPS)- induced acute liver and renal damages have been reported in our previous works. However, its effect on LPS-induced acute lung injury (ALI) remains unknown. In the present study, the effects and possible mechanisms of dioscin against LPS-induced ALI in vitro and in vivo were investigated. The results showed that dioscin effectively inhibited cell proliferation and markedly decreased reactive oxidative species (ROS) level in 16HBE cells treated by LPS. In addition, dioscin significantly attenuated LPS-induced histological alterations, suppressed the infiltration of inflammatory cells, as well as decreased the levels of MDA, SOD, NO and iNOS in mice and rats (p < 0.05). Mechanistically, dioscin significantly decreased the protein levels of TLR4, MyD88, TRAF6, TKB1, TRAF3, phosphorylation levels of PI3K, Akt, IκBα, NF-κB, and the mRNA levels of IL-1β, IL-6 and TNF-α against oxidative stress and inflammation (p < 0.05). TLR4 overexpression was also decreased by dioscin, leading to the markedly decreased the levels of MyD88, TRAF6, TKB1, TRAF3, p-PI3K, p-Akt, p-IκBα and p-NF-κB. These findings provide new insights that dioscin exhibited protective effect against LPS-induced ALI via adjusting TLR4/MyD88- mediated oxidative stress and inflammation, which should be developed as one potent candidate for the treatment of ALI in the future.

SynopsisObjective The objective of this work was to identify whether low levels of redox metals such as copper will accelerate damage to hair on exposure to UV irradiation and whether this damage can be prevented. Methods The methods used were proteomics to measure the protein damage via protein loss after different periods of exposure and mass spectroscopy methods to identify specific marker peptides that are specifically created by this type of damage. Results In this work, we have developed new insights into the mechanism of UV damage using these proteomic methods. A marker fragment in the hair protein loss extract was identified (m/z = 1279) that is unique to UV exposure and increases with time of UV exposure. We have also identified for the first time in hair the role of exogenous copper in increasing UV damage both in terms of total protein degradation and also increased formation of the marker fragment and proposed a mechanism of action. It has been demonstrated that shampoo treatment containing a chelant such as N,N'-ethylenediamine disuccinic acid (EDDS) reduced copper accumulation in hair. Conclusion This work provides evidence for the role of copper in UV-induced damage to hair and strategies to reduce copper levels in hair using a chelant such as EDDS.

Introduction Ataluren functions by interacting with ribosomes to promote read-through of nonsense mutations in CF. Ataluren9s activity was shown to be inhibited by certain aminoglycosides such as tobramycin that also bind to the ribosome. Aim To investigate the effect of ataluren on lung function (LF) and pulmonary exacerbations. Methods A post-hoc analysis was performed on a recent randomized, double-blind, placebo-controlled, phase 3 study to determine the efficacy and safety of ataluren in patients with nonsense mutation cystic fibrosis (nmCF) (Kerem E, et al. Lancet Respir Med. 2014;2:539-47) on %-predicted FEV 1 (ppFEV 1 ) and exacerbations by use of chronic inhaled tobramycin at baseline. Results Patients not receiving chronic inhaled tobramycin (non-TOBI; n=146), showed a 5.7% difference in relative ppFEV 1 between ataluren and placebo (−0.7% vs −6.4%; p=0.0082) and 40% fewer exacerbations (1.42 vs 2.18; p=0.0061). Non-TOBI patients ≥6 to 1 between ataluren and placebo (4.9% vs −3.3%; p=0.026) and a 60% lower exacerbation rate favoring ataluren (p=0.030). In all intent-to-treat patients (N=232) at week 48, including tobramycin patients, neither relative change from baseline in ppFEV 1 (−2.5% vs −5.5%; p=0.12), nor number of exacerbations (1.42 vs 1.78; p=0.099) significantly differed between ataluren and placebo. Conclusions Ataluren significantly reduced exacerbations and improved LF in nmCF patients not receiving chronic inhaled tobramycin, with markedly improved treatment effect in children and adolescents. Ataluren thus shows promise as a disease-modifying therapy in nmCF.

A lot of literature show that social isolation stress could be a key reason that leads to cognitive deficits for both humans and rodent models; however, the detailed mechanisms are still not clear completely. ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function. We hypothesize that social isolation stress may impact the expression of ADAR1, leading to cognitive deficits. To prove our hypothesis, we evaluated the cognition ability of the mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expressions in hippocampus and cortex using immunohistochemistry and western blot. Our study showed that social isolation stress significantly induced spatial and non-spatial cognition deficits. In addition, social isolation significantly increased both the immuno reactivity and protein expressions of ADAR1 in the hippocampus and frontal cortex. Furthermore, we found that adolescent re-socialization recovered not only the cognition deficits but also the increased ADAR1 protein expression in hippocampus and the increased number of ADAR1 positive cells in frontal cortex of the isolated mice. In conclusion, social isolation stress significantly increased ADAR1 expressions in the hippocampus and cortex, leading to cognitive deficits.

Adenosine deaminase acting on RNA (ADAR) activity increases in response to inflammation. Social isolation stress is related to neuroinflammation; however, it remains unclear whether ADAR1 is altered in response to social isolation stress-induced cognitive deficits. To investigate our hypothesis that ADAR1 displayed patterns of change in response to social isolation stress, we addressed this issue systemically by isolating Kunming mice for 2, 4 and 8 weeks individually since postnatal 21 days to set up isolation mouse model. Furthermore, we arranged re-socialization group to evaluate the alterations of ADAR1 in the cognitive deficits recovery. The results of behavior tests showed that social isolation stress resulted in cognitive dysfunction, which was recovered by re-socialization in re-gregarious rearing group. Furthermore, the immunohistochemistry and western blot results displayed that both the immunoreactivity and protein expression of ADAR1 in the hippocampus and frontal cortex increased obviously as compared to the same age mice without isolation. The above abnormal alterations of ADAR1 were recovered by re-socialization in re-gregarious rearing group. Our study supports the hypothesis that ADAR1 is altered in mice affected by social isolation stress-induced cognitive deficits.

This paper develops a new nonparametric test for the location shift between two populations based on order restricted randomized design (ORRD). The ORRD exploits the use of subjective, imprecise or rough information among experimental units to create a blocking factor. The blocking factor, in a given set of H experimental units, is constructed by ranking the units from smallest to largest and then assigning them into H ranking classes (judgment blocks). The design then uses a restricted randomization to assign the treatment regimes to experimental units across these judgment blocks. This randomization scheme induces a positive correlation structure among within-set response measurements. The positive correlation structure then acts as a variance reduction technique in the inference of a contrast parameter in an ORRD. The paper develops a rank-sum test to test the difference between two treatment medians. It is shown that the test performs better than its competitors regardless of the accuracy of the ranking information of within-set units. The paper also constructs point and interval estimators for the contrast parameter. For set sizes H > 2, there are more than one ORRDs. The paper constructs an optimal design that maximizes the asymptotic Pitman efficacy of the proposed test among all possible ORRDs. The proposed test is applied to ACTG 320 clinical trial data.

Background Myocardial infarction (MI) remains the most common cause of heart failure (HF) worldwide. For almost 50 years, HF has been recognized as a determinant of adverse prognosis after MI, but efforts to promote myocardial repair have failed to be translated into clinical therapies. Aims In this study, we investigated the effects of BRD4 on cardiac function and the underlying mechanism. Material and methods The in vivo rat model of AMI and in vitro neonatal cardiomyocytes were established and cultured respectively, the BRD4 and NPPA/NPPB expression levels were detected by qPCR and Western blot, and interaction of BRD4 with acetylation RelA or NPPA/B promoters were examined by co-immunoprecipitation and chromatin immunoprecipitation assays, respectively. Results We found that BRD4 protein expression was significantly increased in cardiomyocytes of MI rat model and cardiomyocytes under hypoxia, accompanied by the expression of natriuretic peptide A (NPPA) and natriuretic peptide B (NPPB). Functionally, knockdown of BRD4 greatly downregulated the NPPA and NPPB in vivo and in vitro, improved the hemodynamic and biometric parameters in rat with heart failure, as well as decreased the apoptosis occurrence. In vitro studies further demonstrated that BRD4 bound with acetylated RelA to enhance the activation of NF-κb signaling, which resulted in activation of NPPA and NPPB transcriptions. Conclusions Taken together, our findings suggest that inhibition of BRD4 attenuated cardiomyocyte apoptosis via NF-κB pathway in myocardial infarction, and this study sheds light on developing new strategies to overcome myocardial damage.

Introduction Social isolation enhances the aggressive behavior of animals, but the detailed mechanism remains unclear. Epigenetic studies have suggested that Htr2c RNA editing is closely related to aggressive behavior. This study aims to obtain a fundamental understanding of how social isolation impacts adenosine deaminase acting on RNA 1 (ADAR1, RNA editing enzyme) and Htr2c RNA editing, leading to aggressive behavior, and explore the effective solutions for the recovery of this behavior. Methods We evaluated 21-day-old BALB/c mice with and without isolation for aggressive behavior using a resident-intruder test. Immune-reactivity and protein expression of ADAR1 (p110) were measured using immunohistochemistry and Western blotting. Htr2c RNA editing was evaluated using pyrosequencing. In addition, the 5-HT 2C R antagonist SB243213/5-HT 2C R inverse agonist SB206553 was used to treat the isolated mice, and the performance of both treatments on the behavior, ADAR1 (p110) expression, and Htr2c RNA editing in isolated mice was examined. Results Both the protein expression and immune-reactivity of ADAR1 (p110) in the amygdala decreased, but the percentage of Htr2c RNA editing at A and B sites of amygdala only showed a moderate increase in isolated BALB/c mice with enhanced aggressive behavior compared to the age-matched group-housed BALB/c mice. Additionally, treatment with the 5-HT 2C R antagonist SB243213/5-HT 2C R inverse agonist SB206553 recovered the enhanced aggressive behavior of isolated mice and returned the protein expression and immune-reactivity of ADAR1 (p110) back to the normal level. Moreover, compared to the age-matched isolated mice treated with physiological saline, isolated mice treated with 5-HT 2C R inverse agonist SB206553 showed a lower percentage of Htr2c RNA editing at both A and B sites, and the same result occurred in isolated mice treated with 5-HT 2C R antagonist SB243213 at B site of Htr2c RNA editing. Conclusions The 5-HT 2C R antagonist SB243213/5-HT 2C R inverse agonist SB206553 recovered increased aggressive behavior of isolated BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing.

Delay in diagnosis of leprosy can increase the risk of nerve function impairments and promote the transmission of the infection in a community. In order to understand the factors associated with the delays in diagnosis of leprosy, a questionnaire-based interview was conducted to collect information on the delays among 88 newly diagnosed leprosy patients. The results showed that delay was common and associated with the high rate of disability in the study population. The total mean delay was 50.18 months (median 36 months). The mean patient delay was 24-4 months (median 9.5 months) and the mean health service delay was 257 months (median 12 months). Patients with leprosy reported a variety of symptoms/signs at an early stage of the disease, particularly numbness and tingling. Ignorance of the illness was reported to be the main reason for the patient's delay. Health seeking actions ranged from 1 to 50 with a mean of 7.2 after becoming aware of the first symptom/sign. The effectiveness of early diagnosis of leprosy through health promotion in the population needs to be validated and continuous training on leprosy among healthcare providers is needed.

This study aimed to investigate the protective effect of nicotine on dopaminergic neurons and its mechanisms in mice with Parkinson disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). C57BL/6J mice were injected with MPTP for 8 days to establish a PD model. Nicotine was given for 10 days in the nicotine therapeutic group. Animals were examined behaviorally with the pole test and traction test. Tyrosine hydroxylase (TH) and γ-aminobutyric acid (GABA) were determined by using the immunocytochemistry (ICC) method. The ultrastructural changes of the caudate nucleus (CN) were observed under electron microscopy. The results showed that pretreatment with nicotine could improve the dyskinesia of PD mice markedly. Simultaneously, TH-positive (P

The competitive adsorption of the Na salt of phytic acid (PA) and 4-methyl-4H-1,2,4-triazole-3-thiol (4-MTTL) was investigated by using the surface-enhanced Raman scattering (SERS) technique and electrochemical measurements. On the basis of the recorded SERS spectra, it was found that PA molecules could competitively occupy the silver surface modified with 4-MTTL monolayers and that the competitive adsorption of 4-MTTL at the silver surface with the PA monolayers also happened, but the effect of coadsorption of PA on the structure of 4-MTTL monolayers was smaller than that of 4-MTTL on the PA monolayers. In addition, according to the electrochemical measurements, the only 4-MTTL monolayers or the only PA monolayers at the silver surface exhibited a reasonable stability. The coadsorption of 4-MTTL and PA formed a mixed film at the silver surface immersed in the solution with the coexistence of 4-MTTL and PA, and the film was unstable when a potential was applied.

Monolayers of sulfanilamide on metallic surface can serve as an ideal model for understanding the interaction mechanism between the metal and the sulfanilamide molecule. In the present paper, the surface-enhanced Raman scattering (SERS) technique was employed to obtain the SERS spectra of sulfanilamide monolayers formed on the silver surface under different pH values. Assignments of the spectra were carried out with the aid of density functional theory (DFT) calculations (BLYP/6-311G). It can be found that the adsorption function of sulfanilamide on the silver surface was influenced by the pH value. The fully protonated sulfanilamide molecule adsorbed on the silver surface through N13H2 group and the benzene ring anchored in a relatively perpendicular manner leading to N7H2 and S10O2 groups near the surface, while the completely deprotonated sulfanilamide molecule attached on the silver surface via N7H2 and the benzene ring was perpendicular to, and the N13H2 and S10O2 groups were far from the silver surface. Copyright © 2009 John Wiley & Sons, Ltd.

Electrochemically anticorrosive behavior of 4-methyl-4H-1,2, 4-triazole-3-thiol (MTTL) self-assembled monolayers (SAMs) on the silver electrode was studied by means of electrochemical impedance spectroscopy (EIS) and polarization measurements. The promising inhibition effect of the MTTL for silver had been affirmed. Results of surface-enhanced Raman scattering (SERS) experiments indicated that the MTTL molecule in a tilted orientation was self-assembled on the silver surface through S' and N(2) atoms to form monolayers. An in situ electrochemical SERS experiment implied the changes of adsorption fashion of MTTL momolayers on the silver surface with the potential shifted to more negative direction. Copyright (C) 2009 John Wiley & Sons, Ltd.

The pH-dependent structures of the 2-amino-5-mercapto-1,3,4-thiadiazole (AMT) self-assembled monolayers (SAMs) on the silver surface were studied by surface enhanced Raman scattering (SERS) spectroscopy. The resulting SERS spectra show that the adsorption fashion of AMT monolayers formed at pH 1 could exhibit the strongest interaction with the silver surface among the investigated pH values at 1, 7, and 13. Electrochemical impedance spectroscopy (EIS) illuminates that the anticorrosive effect of AMT monolayers formed under pH 1 is the best. The inhibition efficiencies of AMT SAMs formed under pH 1, 7 and 13 are 72.2, 39.1 and 4.97%, respectively, according to experimental results of their Tafel plots.

Anticorrosive behaviors of 2-mercaptobenzothiazole (MBT) self-assembled monolayers (SAMs) on silver and zinc electrodes were comparatively studied by means of electrochemical impedance spectroscopy (EIS). The promising inhibition effect of the MBT for silver and zinc from corrosion had been confirmed. The adsorption geometries of MBT monolayers on zinc and silver electrodes were observed by surface enhanced Raman scattering (SERS) technique. The SERS spectra implied that monolayers of MBT could be self-assembled on Ag surface through S 10 and N 3 atoms and the molecular plane should be tilted with respect to the surface. On Zn surface, MBT molecules formed monolayers via both S atoms and the other moieties of the molecule away from the surface. From the in situ electrochemical SERS results it can be found that MBT monolayers on both Ag and Zn surfaces experienced the changes of adsorption fashions as the potential shifting to more negative direction.

Surface-enhanced Raman scattering (SERS) spectroscopy was applied to observe the process and structure of N-acetylalanine molecules self-assembled at the silver surface. SERS data show that the N-acetylalanine molecules adsorb at the silver surface through the amino group and the entire carboxyl group in a perpendicular way after a self-reorganization. Results of SERS and X-ray photoelectron spectroscopic experiments indicate that the Ce3+ affects the structure of monolayers because of the binding reaction between the Ce3+ and the carbonyl along with the amino groups in N-acetylalanine. The Ce3+ capped by N-acetylalanine monolayers can be removed by adding EDTA solution and the original structure of monolayers is recovered. However, the impact of K+ on the structure of N-acetylalanine monolayers is slight and can be ignored.

SynopsisObjective Damage to hair from UV exposure has been well reported in the literature and is known to be a highly complex process involving initiation via absorption of UV light followed by formation and propagation of reactive oxygen species (ROS). The objective of this work was to understand these mechanisms, explain the role of copper in accelerating the formation of ROS and identify strategies to reduce the hair damage caused by these reactive species. Methods The location of copper in hair was measured by Transmission electron microscopy–(TEM) X-ray energy dispersive spectroscopy (XEDS) and levels measured by ICP-OES. Protein changes were measured as total protein loss via the Lowry assay, and MALDI ToF was used to identify the biomarker protein fragments. TBARS assay was used to measure lipid peroxide formation. Sensory methods and dry combing friction were used to measure hair damage due to copper and UV exposure and to demonstrate the efficacy of N,N' ethylenediamine disuccinic acid (EDDS) and histidine chelants to reduce this damage. Results In this work, a biomarker protein fragment formed during UV exposure is identified using mass spectrometry. This fragment originates from the calcium-binding protein S100A3. Also shown is the accelerated formation of this peptide fragment in hair containing low levels of copper absorbed from hair during washing with tap water containing copper ions. Transmission electron microscopy (TEM) X-ray energy dispersive spectroscopy (XEDS) studies indicate copper is located in the sulphur-poor endo-cuticle region, a region where the S100A3 protein is concentrated. A mechanism for formation of this peptide fragment is proposed in addition to the possible role of lipids in UV oxidation. A shampoo and conditioner containing chelants (EDDS in shampoo and histidine in conditioner) is shown to reduce copper uptake from tap water and reduce protein loss and formation of S100A3 protein fragment. In addition, the long-term consequences of UV oxidation and additional damage induced by copper are illustrated in a four-month wear study where hair was treated with a consumer relevant protocol of hair colouring treatments, UV exposure and regular shampoo and conditioning. Conclusions The role of copper in accelerating UV damage to hair has been demonstrated as well as the ability of chelants such as EDDS and histidine in shampoo and conditioner products to reduce this damage.

Advanced renal cell carcinoma (RCC) is resistant to cytotoxic chemotherapy, and immunotherapy has modest activity. Proteasome inhibitors represent a novel class of anticancer agents that have activity across a wide spectrum of tumor types. We investigated the efficacy of the proteasome inhibitor bortezomib (VELCADE, formerly known as PS-341) in RCC and found that bortezomib potently induces apoptosis of RCC cell lines. Blockade of the nuclear factor-κB (NF-κB) pathway is considered a crucial effect in bortezomib-induced apoptosis, but the dependence on NF-κB inhibition for bortezomib-mediated death has not been formally demonstrated. Thus, we also studied the contribution of NF-κB inhibition as a mechanism of bortezomib-induced apoptosis in RCC cells, which display constitutive NF-κB activation. Ectopic expression of the NF-κB family members, p65 (Rel A) and p50 (NF-κB1), markedly reduced bortezomib-induced apoptosis. However, when we used selective genetic and chemical inhibitors of NF-κB, we found that NF-κB blockade was not sufficient to induce apoptosis of RCC cells. Thus, we conclude that maximal bortezomib-induced apoptosis is dependent on its NF-κB inhibitory effect, but NF-κB-independent effects also play a critical role in the induction of apoptosis by bortezomib. This represents the first report to formally demonstrate that bortezomib-induced NF-κB blockade is required to achieve the maximum degree of apoptosis by this drug.

Protein protease inhibitors could potentially be used to stabilize proteases in commercial products such as liquid laundry detergents. However, many protein protease inhibitors are susceptible to hydrolysis inflicted by the protease. We have engineered Streptomyces subtilisin inhibitor (SSI) to resist proteolysis by adding an interchain disulfide bond and removing a subtilisin cleavage site at leucine 63. When these stabilizing changes were combined with changes to optimize the affinity for subtilisin, the resulting inhibitor provided complete protease stability for at least 5 months at 31 degrees C in a subtilisin-containing liquid laundry detergent and allowed full recovery of the subtilisin activity upon the dilution that occurs in a North American washing machine.