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Down-regulation of some hepatic cytochrome P450s (CYP450s) was observed in patients and animals with ulcerative colitis (UC). This study examined changes of CYP450s activities in microsomes of liver (RLMs), intestine (RIMs) and kidney (RRMs) from rats with experimental acute colitis induced by 5% dextran sulfate sodium (DSS) for 7 days and those receiving DSS treatment followed by 7-d cessation through measuring 6α-(CYP1A1), 7α-(CYP2A1), 16α-(CYP2C11) and 2β-/6β-(CYP3A2) hydroxytestosterone (OHT) formed from testosterone. Both pro-(IL-1β, IL-6, TNF-α) and anti-(IL-4, IL-10) inflammatory cytokines were elevated in acute colitis, while the production of the former was enhanced and that of the latter declined by DSS withdrawal. In RLMs, the CYP2A1 activity was significantly increased at DSS stimulation and partially returned to normal level when DSS treatment was terminated. Activity of other CYP450s were decreased by acute colitis and remained after DSS withdrawal. In RRMs, formations of 6α-, 16α- and 2β-OHT significantly declined in acute colitis and DSS termination further potentiated the down-regulation, while 7α-OHT formation was suppressed at DSS stimulation and remained after DSS withdrawal. The formation of 6β-OHT only showed significant decrease after DSS withdrawal. Two metabolites (6α- and 6β-OHT) formed in RIMs and 6β-OHT formation was significantly decreased by DSS stimulation and continued after DSS treatment halted. These findings indicate that the alterations of CYP450s activities vary with organ, CYP isoforms and colitis status, which arouse cautions on efficacy and toxicity of drug therapy during disease progression. [ABSTRACT FROM AUTHOR]

Ultrasensitive detection of nucleic acid has attracted considerable attention recently in academic research and clinic diagnostics. Current approaches for DNA analysis involve complicated or expensive processes for labeling and often yield a high detection limit. In this study, a hydrogel electrode prepared from graphene oxide and fish sperm DNA is used for label−free mitochondrial DNA detection by impedimetric approach. The hydrogel has a bionic structure containing rich water and natural biomolecule fish sperm DNA that would benefit the adsorption and hybridization of DNA. Graphene oxide is a semiconductor and its conductivity can be improved by doping negatively charged DNA molecules. The result shows that the conductivity and impedance change of hydrogel electrode could be tuned by its length and component. The linear range for DNA detection by the optimized hydrogel is from 1.0 × 10−9 to 1.0 × 10−20 M with a detection limit of 1.0 × 10−20 M. The result is ascribed to the bionic structure and tunable conductivity of hydrogel electrode. The hydrogel electrode has been used to detect the real DNA samples from patients of ovarian cancer with satisfactory results. [ABSTRACT FROM AUTHOR]

The idea of structural art has gained an increase in interest due to the pioneering book by David Billington in 1983. With this, a paradigm shift is emerging with the belief that structural engineers can become artists in the design process by cooperatively integrating three tenets: economy, efficiency, and elegance. The objective of this up-to-date review is to present a broad perspective of structural art during the past three decades (1983–2013). Historical engineering projects and the stories of their structural engineers are discussed to identify the key conditions that have contributed to various works of structural art. Further, this review promotes the importance of the structural art concept and equips future engineers by discussing the potential resources and tools that can be utilized to learn more about structural art. [ABSTRACT FROM AUTHOR]

The buckling of cylindrical shells has long been regarded as an undesirable phenomenon, but increasing interests on the development of active and controllable structures open new opportunities to utilize such unstable behavior. In this paper, approaches for modifying and controlling the elastic response of axially compressed laminated composite cylindrical shells in the far postbuckling regime are presented and evaluated. Three methods are explored (1) varying ply orientation and laminate stacking sequence; (2) introducing patterned material stiffness distributions; and (3) providing internal lateral constraints. Experimental data and numerical results show that the static and kinematic response of unstable mode branch switching during postbuckling response can be modified and potentially tailored. [ABSTRACT FROM AUTHOR]

Medium- and long-span bridges of the high-speed rail (HSR) projects play a significant role when crossing certain obstacles, such as rivers, existing highways, etc. This paper provides a state-of-the-art review on the design practice of these special spans in the HSR projects of China. Given standard spans are usually smaller than 100m, special spans can be divided into two categories by the length of main span: medium length (100-200m) and large length (200-500m). For medium length, three structural forms are discussed as feasible design options, including steel arch, rigid frame and hybrid arch-girder. In addition, recently completed long-span bridges are reviewed to feature several innovative structural forms on the HSR of China, including steel truss arches and cable-stayed bridges with truss girder. Finally, the key technical features of long-span HSR bridges are summarized, and a discussion of the feasibility of longer spans is also included. [ABSTRACT FROM AUTHOR]

Anthraquinones naturally distribute in many plants including rhubarb and have widespread applications throughout industry and medicine. Recent studies provided new insights in potential applications of these traditional laxative constituents. Glucuronidation was the main metabolic pathway of rhubarb anthraquinones in vivo . This study examined the activity and regioselectivity of glucuronidation of rhubarb anthraquinones (aloe-emodin, emodin, chrysophanol, physcion, rhein) in liver and intestinal microsomes from rats and humans, by comparing with the core structure danthron. All anthraquinones formed mono-glucuronides and, except for rhein, the conjugation sites of the main metabolites were unambiguously identified. Two minor glucuronides of emodin were first reported together with the dominant emodin-3- O - β - d -glucuronide. The substitution on the anthraquinone ring was crucial to the activity and regioselectivity of glucuronidation. In general, the activity was decreased greatly with a β -COOH (rhein), while enhanced dramatically with a β -OH (emodin). Glucuronidation showed an absolute preference towards β -OH, followed by α -OH and β -alcoholic OH. The glucuronidation activity and regioselectivity also varied slightly with organs and species. All glucuronides of aloe-emodin, emodin, chrysophanol and physcion were formed by multiple human UGT isoforms with 1A9 being the most prominent in most cases. The UGT2B subfamily (2B7 and 2B15) only showed high activity towards a β -OH. In conclusion, the substitution at the anthraquinone ring was crucial to the rate and preference of glucuronidation. The high glucuronidation activity of UGT1A9 towards anthraquinones highlighted potential drug interactions. [ABSTRACT FROM AUTHOR]

A new video standard called High Efficiency Video Coding (HEVC) has been recently finalized. In comparison with the H.264/AVC video coding standard, HEVC further improves the video coding rate distortion (RD) performance, but at the price of significant increase in its encoding complexity, especially in its motion estimation (ME) due to large block sizes and complicated block partition. To reduce the ME complexity in HEVC while maintaining its RD performance, in this paper we first formulate ME at the integer pixel level as a statistical inference problem and then propose a confidence interval-based ME (CIME) method. The proposed CIME method can be applied either on top of the existing fast search implemented in HEVC or on its own to replace the existing fast search implemented in HEVC. Experiments show that for the low-delay main test configuration of HEVC: 1) when applied on top of the existing fast search in HEVC, the proposed CIME method further reduces, on average, the integer-level ME time by 70% with only 1.0% increase in bit rate while maintaining the same reconstruction quality in PSNR and 2) when applied on its own to replace the existing fast search implemented in HEVC, the proposed CIME method achieves performance comparable with that of the fast search in HEVC reference software and better than that of the dynamic system fast algorithm proposed recently in the literature. [ABSTRACT FROM AUTHOR]

Uromodulin is recognized as a protective factor during AKI-to-CKD progression, but the mechanism remains unclear. We previously reported that uromodulin interacts with complement factor H (CFH) in vitro, and currently aimed to study the expression and interaction evolution of uromodulin and CFH during AKI-to-CKD transition. We successfully established a rat model of AKI-to-CKD transition induced by a four-time cisplatin treatment. The blood levels of BUN, SCR, KIM-1 and NGAL increased significantly during the acute injury phase and exhibited an uptrend in chronic progression. PAS staining showed the nephrotoxic effects of four-time cisplatin injection on renal tubules, and Sirius red highlighted the increasing collagen fiber. Protein and mRNA levels of uromodulin decreased while urine levels increased in acute renal injury on chronic background. An extremely diminished level of uromodulin correlated with severe renal fibrosis. RNA sequencing revealed an upregulation of the alternative pathway in the acute stage. Renal CFH gene expression showed an upward tendency, while blood CFH localized less, decreasing the abundance of CFH in kidney and following sustained C3 deposition. A co-IP assay detected the linkage between uromodulin and CFH. In the model of AKI-to-CKD transition, the levels of uromodulin and CFH decreased, which correlated with kidney dysfunction and fibrosis. The interaction between uromodulin and CFH might participate in AKI-to-CKD transition. [ABSTRACT FROM AUTHOR]

Mental health disorders are responsible for 125.3 million disability-adjusted life years (DALYs) lost globally, with depression in adolescents rising faster than in adults. In total, more than 90% of the 1.2 billion adolescents in the world live in low- and middle-income countries (LMICs). Despite the rise in teenage marriage and pregnancy in LMICs, there is a paucity of research on the role of pregnancy as a risk factor for adolescent mental health, and the role of spousal connectedness as a potential protective factor. This study aims to address this gap. A total of 2408 currently married adolescent (aged 15–19 years) women from the Bangladesh Adolescent Health and Wellbeing Survey 2019–2020 were analysed. Multivariable models were used to assess the factors associated with depression symptoms and major depressive disorder (MDD). The prevalence of moderate/severe depressive symptoms or MDD among adolescents was 14.6%, well ahead of south Asian levels. The odds of having moderate/severe depressive symptoms (adjusted odds ratio [AOR]=1.94, 95% confidence interval [CI] 1.37–2.76) or MDD (AOR=1.63, 95%CI 1.18–2.25) were higher in pregnant adolescent women than in non-pregnant adolescent women. A closer relationship with one's husband reduced the risk of developing moderate/severe depressive symptoms (AOR=0.90, 95% CI 0.84–0.96) or MDD (AOR=0.91, 95% CI 0.86–0.97). Pregnancy and connectedness had no statistically significant interaction effect on depression. There is an urgent need for affordable and scalable interventions to reduce the risk of mental health morbidity in pregnant adolescent women especially in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Corn is one of the main food crops in China, and its area ranks in the top three in the world. However, the corn leaf disease has seriously affected the yield and quality of corn. To quickly and accurately identify corn leaf diseases, taking timely and effective treatment to reduce the loss of corn yield. We proposed identifying corn leaf diseases using the Mobilenetv3 (CD-Mobilenetv3) model. Based on the Mobilenetv3 model, we replaced the model's cross-entropy loss function with a bias loss function to improve accuracy. Replaced the model's squeeze and excitation (SE) module with the efficient channel attention (ECA) module to reduce parameters. Introduced the cross-layer connections between Mobile modules to utilize features synthetically. Then we Introduced the dilated convolutions in the model to increase the receptive field. We integrated a hybrid open-source corn leaf disease dataset (CLDD). The test results on CLDD showed the accuracy reached 98.23%, the precision reached 98.26%, the recall reached 98.26%, and the F1 score reached 98.26%. The test results are improved compared to the classic deep learning (DL) models ResNet50, ResNet101, ShuffleNet_x2, VGG16, SqueezeNet, InceptionNetv3, etc. The loss value was 0.0285, and the parameters were lower than most contrasting models. The experimental results verified the validity of the CD-Mobilenetv3 model in the identification of corn leaf diseases. It provides adequate technical support for the timely control of corn leaf diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • Six kinds of implants with customized irregular shapes were designed and fabricated via FDM 3D printing technology and the printing accuracy were evaluated. • Two kinds of implants with customized dosages were designed by controlling the volume size of the implant and regulating the grid widths of each layer respectively, and were then fabricated via SSE 3D printing technology and the accuracy of dosage control were clearly verified. • Three kinds of implants with customized internal structures were designed and fabricated via FDM 3D and SSE 3D printing technologies, respectively, and the in vitro drug release behaviors were then analyzed. • The in vitro antibacterial effects, in vitro and in vivo biocompatibility of customized implants printed via FDM 3D and SSE 3D printing technologies were explored. A customized implantable drug delivery system with the dual functions of playing a supporting role and providing continuous bacteriostasis is of great importance during the treatment of bone defect diseases. The main objective of this study was to explore the potential of using three-dimensional (3D) printing technologies to fabricate customized implants. Ciprofloxacin hydrochloride (Cipro) was chosen as the model drug, and two printing technologies, semisolid extrusion (SSE) and fused deposition modeling (FDM) were introduced. Six kinds of implants with customized irregular shapes were printed via FDM technology. Two kinds of implants with customized dosages were constructed via SSE technology. In addition, three kinds of implants with customized internal structures were produced via FDM and SSE technologies. The data for morphology, dimensions and mechanical properties demonstrated satisfactory printability and good printing accuracy when applying SSE and FDM technologies to produce the customized implants. The dissolution curves indicated that the desired customized drug release could be achieved by designing the specific internal structures. The biocompatibility examination showed that the printed implants possessed outstanding biocompatibility. In conclusion, all results suggested that 3D printing technologies provide a feasible method and novel strategy to fabricate customized implantable drug delivery systems. [ABSTRACT FROM AUTHOR]

Tongmai granules (TMG) is composed of Salvia miltiorrhiza Bge. , Radix puerariae Lobata., and Ligusticum chuanxiong hort. TMG is mainly used for ischemic cardiovascular, cerebrovascular diseases, atherosclerosis, coronary heart disease, cerebral infarction and cerebral ischemia. TMG is a kind of traditional compound granule, which has a protective effect on brain injury. However, the potential protective mechanism of the TMG has not been elucidated. TMG has a good effect on brain injury, but its brain protective mechanism is still unclear. The purpose of this study was to confirm the neuroprotective mechanism of TMG, reveal its target genes and identify the active components of TMG. High-performance liquid chromatography (HPLC) was used to identify the fingerprint of TMG. UPLC-Q-TOF-MSE was used to analyze the base peak intensity (BPI) chromatograms of TMG. TMG was pre-administered for one week, brain injury and edema were induced by injection of glutamate (Glu) into the lateral ventricles of rats. HE staining was used to investigate the pathological damage caused by Glu in the hippocampus of rats, and the RNA-seq was used to analyze the changes of different genes before and after TMG treatment. Finally, changes of related proteins were analyzed by qRT-PCR, Western blot, and other molecular biological methods. Dosage of TMG were set to 0.6 g/kg, 1.2 g/kg and 2.4 g/kg. We found that TMG contained many active components, including salvianolic acid, puerarin, ferulic acid, etc. TMG could improve cerebral edema and brain injury induced by Glu. After TMG treatment, differential gene analysis showed that differential genes were significantly enriched in toll-like receptor signaling pathway. qRT-PCR validation results were consistent with RNA-Seq analysis results. Combined with Western blot analysis, we found that TMG ultimately regulated the expression of inflammatory cytokines by affecting the TLR4/MyD88/AP-1 pathway. In this study, we combined TMG with RNA-seq analysis to demonstrate that TMG may play a neuroprotective role by regulating Toll-like receptor signaling pathway and down-regulating the expression of inflammatory cytokine. TMG may become a kind of traditional Chinese medicine with neuroprotective potential. [Display omitted] [ABSTRACT FROM AUTHOR]

Latent heat thermal energy storage (LHTES) using phase change materials (PCM) has been considered a promising technique for improving the energy efficiency of thermal systems. However, a LHTES unit often suffers from low power density, e.g., low energy charging rates, because of the low thermal conductivity of common PCM like paraffin. Close-contact melting (CCM) has long been studied as a special melting process featuring very high heat transfer rates as a result of the low thermal resistance across the thin melt film between the PCM and the heating surface. It was shown in the literature that utilization of CCM could reduce the charging time of a well-designed LHTES container by even 4 times. Towards increasing the power density of LHTES units, this review paper focuses on the progress of CCM studies, including fundamental mechanisms, applications, and enhancement methods. Available theoretical models, experimental observations, as well as numerical approaches were reviewed systematically. The research gaps between investigations and applications were discussed, and the main challenges on both mechanistic understanding and utilization of CCM were also outlined. Last, some recommendations for future researches on CCM as a pathway for realizing rapid energy charging of PCM-based LHTES units were proposed. • Close-contact melting (CCM) is deemed to be a pathway for highly efficient melting. • A review of CCM studies for charging of latent heat thermal storage was performed. • CCM can reduce charging time by 4 or more times in a well-designed container. • Main challenges and approaches on cold CCM applications were identified. • Directions towards realizing CCM for rapid charging of latent heat were outlined. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine Qianghuo Shengshi decoction (QSD) is widely used in the treatment of nervous headache, rheumatoid arthritis, sciatica, allergic purpura, and other clinical diseases in China. However, the underlying mechanisms of its anti-inflammatory and analgesic effects has not been elucidated. The aim of this study was to confirm the anti-inflammatory and analgesic effects and the underlying mechanism of QSD in vivo. In addition, this study was also to isolate and analyze the main active components of QSD by high performance liquid chromatography (HPLC). In this study, the acetic acid writhing test, hot plate test and ear swelling test and formalin test were carried out to explore the anti-inflammatory and analgesic effects of QSD. The doses were set to 7.8 g/kg, 15.6 g/kg and 31.2 g/kg body weight. Western blot was utilized to study further possible mechanisms of QSD. Moreover, the HPLC method was used to isolate and identify the components in the extraction of QSD. Twelve characteristic peaks were recognized in the HPLC spectrum, which all were the known compounds. The QSD exhibited dose-dependent effects in anti-inflammatory and analgesic aspects. Compared with model group, the writhing times of in groups of different doses of QSD (15.6 g/kg and 31.2 g/kg (oral administration = p.o.)) were reduced by 33.0% and 45.8% and indicated the QSD showed significant (p < 0.05) peripheral analgesic effect. QSD ((31.2 g/kg), p.o.) showed significant(p < 0.05) analgesic effect in the hot plate test. Inhibition rates of QSD ((15.6 g/kg and 31.2 g/kg), p.o.) in ear swelling test induced by p-xylene were 27.5% and 54.6% and demonstrated the significant (p < 0.05) anti-inflammatory activity. QSD ((31.2 g/kg), p.o.) significantly (p < 0.05) reduced times of paw licking in formalin test, and its inhibition rates were 34.3% and 28.0% in Phase I and Phase Ⅱ response, respectively. Western blot results showed that QSD inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) protein and cAMP response element-binding protein (CREB). These results of this study undoubtedly confirmed that QSD expressed obvious analgesic and anti-inflammatory activities. Anti-inflammatory and analgesic effects of QSD may be achieved by regulating the MAPKs protein and further regulating the expression of CREB. In all, QSD may play an anti-inflammatory and analgesic role through a variety of active ingredients. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Propose an evaluation index for the distillation process with multiple factors. • Propose three total distillation schemes for separating DMA/HAc/water. • Three heat integrated configurations further improve energy efficiency. Industrial wastewater containing N,N-Dimethylacetamide (DMA) and acetic acid (HAC) will be produced in the production of DMA by acetic acid method. The binary mixture of HAc and DMA has maximum-boiling azeotropic point, and the relative volatility of HAc and water is small. Therefore, high purity separation cannot be realized by traditional distillation. By analyzing the separation methods of binary mixture, three processes of extractive-pressure swing distillation, azeotropic-pressure swing distillation, and azeotropic-extractive distillation are proposed to separate DMA-HAc-water ternary mixtures. The heat integration enhancement configuration is completed according to the process characteristics. The results show that compared with the conventional processes, the TAC of the three heat integration processes is reduced by more than 25%, and the energy consumption is reduced by more than 40%. The process quality index (PQI), which integrates TAC, energy consumption, environment and thermodynamic efficiency, is proposed and applied to the evaluation of all processes. The results indicate that the heat integrated azeotropic-extractive distillation (HIAED) process shows more significant industrial application potential. [ABSTRACT FROM AUTHOR]

Background/Aims: Neuronostatin, derived from the somatostatin preprohormone, was recently identified to be produced by several tissues exerting a role in cardiovascular regulation and metabolism. Nonetheless, the precise mechanism behind neuronostatin-elicited myocardial responses remains elusive. Methods: This study was designed to elucidate the impact of neuronostatin on cardiac contractile function and the underlying mechanism of action involved. Adult male C57 BL/6 mice were subjected to a bolus injection of neuronostatin (50 μg/kg, i.p.). Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ handling properties were monitored to evaluate the effect of neuronostatin on cardiac function. Western blot analysis was used to examine potential signaling mechanisms involved. Results: Neuronostatin administration suppressed myocardial and cardiomyocyte contractile function and disturbed intracellular Ca2+ homeostasis. We observed enlarged LVESD (with unchanged LVEDD), reduced fractional shortening, depressed peak shortening, maximal velocity of shortening/relengthening, resting and electrically-stimulated rise in intracellular Ca2+, and prolonged relengthening duration in hearts from neuronostatin-treated mice. These effects were accompanied by downregulation of phosphorylation of sarcoplasmic reticulum Ca2+-ATPase (SERCA) and phospholamban (PLB) and activation of AMPK. Conclusion: Our data suggest that the cardiac depressant properties of neuronostatin possibly associated with loss of SERCA phosphorylation and AMPK activation. These findings revealed a potent inhibitory capacity for neuronostatin on cardiac function, the physiological relevance of which deserves further study. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Differential gene expression in CD177+ and CD177− neutrophils was investigated, in order to detect possible differences in neutrophil function which could be related to the pathogenesis of ANCA-associated Vasculitides (AAV). Methods: Neutrophils were isolated from healthy controls (HC) with high, negative or bimodal CD177 expression, and sorted into CD177+ and CD177− subpopulations. Total RNA was screened for expression of 24,000 probes with Illumina Ref-8 Beadchips. Genes showing differential expression between CD177+ and CD177− subsets in microarray analysis were re-assessed using quantitative-PCR. CD177 expression on neutrophil precursors in bone marrow was analyzed using quantitative PCR and flowcytometry. Results: The proportion of CD177+ cells increased during neutrophil maturation in bone marrow. Fold change analysis of gene expression profile of sorted CD177+ and CD177− neutrophils resulted in 14 genes with fold change (fc) >3 difference in expression. Interestingly, 10 of these genes have been reported to change significantly in expression during neutrophil maturation, and most of these genes were granule protein (GP) coding genes. mRNA expression levels measured by RT-PCR of a number of these GP, and of PR3 and MPO were higher in the CD177− neutrophil subset in HC, however, particular granule protein amounts were comparable between CD177+ and CD177− neutrophil subsets. AAV patients had higher amounts of CD177+ neutrophils, but contrary to neutrophils from HC expression of GP-genes was increased, possibly due to activation. Conclusion: The neutrophil population can be distinguished by membrane expression of CD177 into subsets that are different in expression of GP mRNA but not in GP protein production. GP gene expression is also elevated in AAV patients, which is not explained by skewed distribution of CD177+ and CD177− subsets but may be associated with neutrophil activation during on-going inflammation. [ABSTRACT FROM AUTHOR]

Background: Barrett's esophagus (BE) is a metaplastic precursor lesion of esophageal adenocarcinoma (EA), the most rapidly increasing cancer in western societies. While the prevalence of BE is increasing, the vast majority of EA occurs in patients with undiagnosed BE. Thus, we sought to identify genes that are altered in BE compared to the normal mucosa of the esophagus, and which may be potential biomarkers for the development or diagnosis of BE. Design: We performed gene expression analysis using HG-U133A Affymetrix chips on fresh frozen tissue samples of Barrett's metaplasia and matched normal mucosa from squamous esophagus (NE) and gastric cardia (NC) in 40 BE patients. Results: Using a cut off of 2-fold and P<1.12E-06 (0.05 with Bonferroni correction), we identified 1324 differentially-expressed genes comparing BE vs NE and 649 differentially-expressed genes comparing BE vs NC. Except for individual genes such as the SOXs and PROM1 that were dysregulated only in BE vs NE, we found a subset of genes (n = 205) whose expression was significantly altered in both BE vs NE and BE vs NC. These genes were overrepresented in different pathways, including TGF-β and Notch. Conclusion: Our findings provide additional data on the global transcriptome in BE tissues compared to matched NE and NC tissues which should promote further understanding of the functions and regulatory mechanisms of genes involved in BE development, as well as insight into novel genes that may be useful as potential biomarkers for the diagnosis of BE in the future. [ABSTRACT FROM AUTHOR]

Amphibian skin secretions contain a broad spectrum of biologically active compounds, particularly antimicrobial peptides, which are considered to constitute a first line of defence against bacterial infection. Here we describe the identification of two prototype peptides representing a novel structural class of antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii. Named hylaranin-L1 (GVLSAFKNALPGIMKIIVamide) and hylaranin-L2 (GVLSVIKNALPGIMRFIAamide), both peptides consist of 18 amino acid residues, are C-terminally amidated and are of unique primary structures. Their primary structures were initially deduced by MS/MS fragmentation sequencing from reverse-phase HPLC fractions of skin secretion that demonstrated antimicrobial activity. Subsequently, their precursor-encoding cDNAs were cloned from a skin secretion-derived cDNA library and their primary structures were confirmed unequivocally. Synthetic replicates of both peptides exhibited broad-spectrum antimicrobial activity with mean inhibitory concentrations (MICs) of 34 μM against Gram-negative Escherichia coli, 4.3 μM against Gram-positive Staphylococcus aureus and 4-9 μM against the yeast, Candida albicans. Both peptides exhibited little haemolytic activity (<6 %) at the MICs for S. aureus and C. albicans. Amphibian skin secretions thus continue to provide novel antimicrobial peptide structures that may prove to be lead compounds in the design of new classes of anti-infection therapeutics. [ABSTRACT FROM AUTHOR]

Highlights: [•] We examined the effect of metallothionein on ER stress-induced heart dysfunction. [•] Metallothionein rescues against ER stress-induced cardiac dysfunction. [•] The beneficial effect of metallothionein was related to attenuated autophagy. [Copyright &y& Elsevier]

Highlights: [•] Recently, GWASs have identified CD33 gene as a genetic locus for AD. [•] Our results showed that CD33 expressions in PBMCs were decreased in AD patients. [•] CD33 may contribute to AD pathogenesis by involving inflammatory response. [•] CD33 combining additional parameters may make an useful adjunct to future AD diagnosis. [Copyright &y& Elsevier]

The idea of block-sparse signal reconstruction, as an alternative perspective compared with the conventional approach, is exploited to formulate the problem of direction-of-arrival (DOA) estimation for wideband signals. Prolate spheroidal wave functions (PSWFs) are used to form the block-wise bases for this problem, due to its excellent performance in extrapolating bandlimited signals, and the block orthogonal matching pursuit (BOMP) algorithm is directly employed to verify its efficiency. Simulation results show that the proposed method yields better performance when the number of samples is highly limited. [ABSTRACT FROM AUTHOR]

Abstract: The underlying causes of postoperative cognitive decline (POCD) in old patients remained unelucidated, and there are little descriptions on mechanisms associated with the blood–brain barrier (BBB) disruption during POCD. We therefore tested the effects of orthopedic surgery with different concentrations of sevoflurane for 2h on the behavior test and the BBB permeability in aged rats. 18-month rats were divided into control group and surgical group with propofol anesthesia (0.7mgkg−1 min−1) and 1.0MAC, 1.3MAC, and 1.5MAC sevoflurane inhalation for 2h. We assessed their cognitive function via Y-maze and fear conditioning test on day 1, 3, and 7 after experiments. Animals were then assigned to control group, propofol (2h, 0.7mgkg−1 min−1) group, surgery plus propofol group and surgery plus 1.5MAC sevoflurane inhalation for 2h. Their hippocampal BBB permeability was detected with Evans blue quantification. Alterations of tight junctions in hippocampus were measured with occludin and claudin-5 western blot. Then we assessed matrix metalloproteinase-2,9 (MMP-2,9) via western blot and immunohistochemistry staining at day 1, 3, 7, and 14 after experiments. Surgery impaired cognitive function and increased Evans blue leakage into the hippocampus in aged rats while 2h of 1.5MAC sevoflurane inhalation potentiated these effects. Surgery induced occludin protein expression decreases and MMP-2,9 proteins increase and these influences can be enhanced by high concentration of sevoflurane inhalation. In conclusion, 1.5MAC sevoflurane for 2h exacerbated cognitive impairment induced by orthopedic surgery in aged rats and the breach in BBB may be involved in this process. [Copyright &y& Elsevier]

Abstract: A field investigation was conducted for the vegetation composition and 226Ra uptake by native plant species at a uranium mill tailings impoundment in South China. 80 species belonging to 67 genera in 32 families were recorded in the sampling sites. The Poaceae and Asteraceae were the dominant families colonizing the impoundment. The number of the plant species and vegetation community composition in the sampling sites seemed most closely related to the activities of 226Ra and the pH value of the uranium tailings. The plant species in the sampling sites with relatively low activities of 226Ra and relatively high pH value formed a relatively stable vegetation community. The plant species in the sampling sites with medium activities of 226Ra and medium pH value formed the transitional vegetation community. The plant species in the sampling sites with relatively high activities of 226Ra and relatively low pH value formed a simple unstable vegetation community that was similar to that on the unused grassland. The activities of 226Ra and transfer factors (TFs) varied greatly with the plant species. The high activities of 226Ra and TFs were found in the leaves of Pteris multifida (150.6 Bq/g of AW; 9.131), Pteridium aquilinum (122.2 Bq/g of AW; 7.409), and Dryopteris scottii (105.7 Bq/g of AW; 6.408). They satisfied the criteria for a hyperaccumulator for 226Ra. They may be the candidates for phytoremediation of 226Ra in the uranium mill tailings impoundment areas and the contaminated soils around. [Copyright &y& Elsevier]

Abstract: Piperazine-based polyurethane ureas (P-PUUs) with piperazine (PP) units as the functional ingredients have been designed to explore a novel polymeric biomaterial with the controllable degradation for bone repair in this study. P-PUUs were prepared upon the chain-growth polymerization of poly (d, l -lactic acid) diol (PDLLA diol), 1, 6-hexamethylene diisocyanate (HDI) where PP functioned as the chain extender. The investigation of in vitro degradation of P-PUUs was performed and the mechanical properties of P-PUUs during degradation were calculated. The results revealed that manipulating the ratio of PDLLA diol: HDI: PP could obtain the precise number of PP units (Num(pp)) in P-PUUs which may significantly impact the degradation stability and the degradation rate of P-PUUs. The negative linear correlation between the degradation rate and the Num(pp) of P-PUUs has been proved, suggesting the P-PUUs were endowed with controllable degradation. Such a linear correlation is expected to be applied to bone repair where the specific degradation rate of P-PUUs for the specific bone defect can be precisely predicted once the Num(pp) and the bone repairing period are known. Additionally, P-PUUs with higher Num(pp) exhibited remarkable mechanical properties during degradation which allowed polymers to provide more persistent mechanical support to bone repair. [Copyright &y& Elsevier]

TREM2 has been reported to be associated with Alzheimer's disease (AD). Here, we evaluated TREM2 mRNA and protein expressions in peripheral blood from AD patients and healthy controls. Higher levels of TREM2 mRNA (p = 0.002) and protein (p < 0.001) were identified in AD patients. We observed a significant correlation between TREM2 expressions and MMSE score (mRNA: r = -0.482, protein: r = -0.582; p < 0.01). According to ROC curve analysis, the diagnostic accuracy for TREM2 protein levels on monocytes was 70%, with the sensitivity and specificity 68% and 72%, respectively. Our results indicate that TREM2 might serve as a novel noninvasive biomarker for AD diagnosis. [ABSTRACT FROM AUTHOR]

Werner syndrome is caused by mutations in the DNA repair Werner helicase (WRN) gene and characterized by accelerated aging including cataracts. Age-related cataract (ARC) cases ( N = 504) and controls ( N = 244) were recruited from a population-based study to evaluate the association of single-nucleotide polymorphisms (SNPs) of WRN and another DNA repair gene (human 8-oxoguanine DNA N-glycosylase 1) with ARC. Among the five SNPs tested, only WRN rs1346044 was found to be significantly associated between cases and controls before multiple-testing adjustment. The minor C allele of rs1346044 was associated with ARC with an odds ratio (OR) of 0.66, suggesting a protective role of the C allele for developing ARC. The stratification analysis on the subtypes of ARC showed that rs1346044 was significantly associated with cortical cataract, but not with nuclear, posterior subcapsular, and mixed types after multiple-testing adjustment (OR = 0.51, p < 0.01). The genetic model analysis showed that the results fit the dominant model (OR = 0.44, p < 0.001). The comet assay used to assess the extent of DNA damage in peripheral lymphocytes of ARC cases found that the DNA damage in lymphocytes from patients with CC genotype was significantly less than that in patients with TT genotype. We concluded that the C allele of rs1346044, a non-synonymous SNP resulting in the conversion of Cys to Arg at amino acid position 1367 of WRN, alters susceptibility to ARC, especially the cortical type of the disease, in the Han Chinese. The underlying mechanism of its protective role might be related to the improved DNA repair function. [ABSTRACT FROM AUTHOR]

[Display omitted] Traumatic brain injury (TBI) is a brain injury resulting from blunt mechanical external forces, which is a crucial public health and socioeconomic problem worldwide. TBI is one of the leading causes of death or disability. The primary injury of TBI is generally irreversible. Secondary injury caused by neuroinflammation could result in exacerbation of patients, which indicated that anti-inflammation and immunomodulatory were necessary for the treatment of TBI. Accumulated evidence reveals that the transplantation of umbilical cord mesenchymal stem cells (UCMSCs) could regulate the microenvironment in vivo and keep a balance of helper T 17(Th17)/ regulatory T cell (Treg). Therefore, it is reasonable to hypothesize that the UCMSCs could repair neurological impairment by maintaining the balance of Th17/Treg after TBI. In the study, we observed the phenomenon of trans-differentiation of T lymphocytes into Th17 cells after TBI. Rats were divided into Sham, TBI, and TBI + UCMSCs groups to explore the effects of the UCMSCs. The results manifested that trans-differentiation of Th17 into Treg was facilitated by UCMSCs, which was followed by promotion of neurological recovery and improvement of learning and memory in TBI rats. Furthermore, UCMSCs decreased the phosphorylation of nuclear factor-kappa B (NF-κB) and increased the expression of mothers against decapentaplegic homolog 3 (Smad3) in vivo and vitro experiments. In conclusion, UCMSCs maintained Th17/Treg balance via the transforming growth factor-β (TGF-β)/ Smad3/ NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

The novel power generation system based on coal gasification in supercritical water (SCW) holds great promise to meet the increasing energy demands in China, with less emissions in comparison to the traditional coal-fired power generation. The stable and complete oxidation of hydrogen occurring in the supercritical water oxidation (SCWO) reactor is paramount to the safety and overall energy efficiency of the system. In order to better understand and improve the performance of this reactor, optimal design and thermodynamic analysis were conducted using Aspen Plus. The outlet hydrogen concentration and the internal temperature of the reactor were taken as the two key indicators of the optimal design. The optimized results for the reactor were found to be the reactor diameter of 90 mm, axial length of 10.75 m, oxygen inlet number of 3 with the oxygen ratio of 11.0%/39.9%/49.1%, under the given inlet working fluid components and flow rates. The three-stage reactor design was confirmed to have good robustness when different types of coals are adopted for generating syngas. In addition, by analyzing the enthalpy and exergy flow distributions in the reactor, it was revealed that the total exergy destruction for the whole three-stage reactor is only about 6.29%, and that the exergy destruction is consistent with the oxidation process. These findings could be used as guidelines for the design and implementation of the SCWO reactor towards higher safety margin and energy efficiency for this new coal-boiled power generation technique. [Display omitted] • An optimal design method for operating the hydrogen oxidation reactor was proposed. • Thermodynamic analysis of the exergy distribution and destruction was also conducted. • The optimized reactor has a good robustness for syngas produced from different coals. • The exergy loss is consistent with the process of oxidation reaction in the reactor. • The reactor optimization can help improve system safety margin and energy efficiency. [ABSTRACT FROM AUTHOR]

The heart is a high energy demand organ and enhancing mitochondrial function is proposed as the next-generation therapeutics for heart failure. Our previous study found that anthelmintic drug niclosamide enhanced mitochondrial respiration and increased adenosine triphosphate (ATP) production in cardiomyocytes, therefore, this study aimed to determine the effect of niclosamide on heart failure in mice and the potential molecular mechanisms. The heart failure model was induced by transverse aortic constriction (TAC) in mice. Oral administration of niclosamide improved TAC-induced cardiac hypertrophy, cardiac fibrosis, and cardiac dysfunction in mice. Oral administration of niclosamide reduced TAC-induced increase of serum IL-6 in heart failure mice. In vitro , niclosamide within 0.1 μM increased mitochondrial respiration and ATP production in mice heart tissues. At the concentrations more than 0.1 μM, niclosamide reduced the increased interleukin- 6 (IL-6) mRNA expression in lipopolysaccharide (LPS)-stimulated RAW264.7 and THP-1 derived macrophages. In cultured primary cardiomyocytes and cardiac fibroblasts, niclosamide (more than 0.1 μM) suppressed IL-6- and phenylephrine-induced cardiomyocyte hypertrophy, and inhibited collagen secretion from cardiac fibroblasts. In conclusion, niclosamide attenuates heart failure in mice and the underlying mechanisms include enhancing mitochondrial respiration of cardiomyocytes, inhibiting collagen secretion from cardiac fibroblasts, and reducing the elevated serum inflammatory mediator IL-6. The present study suggests that niclosamide might be therapeutic for heart failure. [ABSTRACT FROM AUTHOR]

[Display omitted] • Foam separation was used to recover the protein from perilla seed meal (PSM). • Glycine betaine (GB) engaged in cation-π interaction with PSM protein (PSMP). • GB enhanced the adsorption of PSMP at the gas-liquid interface. • Two regular-hexagon hollow prismoids intensified the enrichment of PSMP. • PSMP with high purity and yields was obtained using two-stage foam separation. The utilization of agro-food waste into protein products is an alternative solution for global protein shortage and waste management. Perilla (Perilla frutescens L.) seed meal (PSM) is abundant and protein-rich by-products from the oilseed industry. To achieve the industrial production of valuable PSM protein (PSMP), a two-stage foam separation with a low cost and a high efficiency was developed to fractionate the high-concentration PSMP (1.3 times its critical micelle concentration (CMC)) from its crude extract. In the first-stage, glycine betaine (GB), a naturally occurring osmolyte, was used as a green enhancer for the recovery of PSMP. The result of SEM, FTIR, UV–vis and fluorescence spectra demonstrated that GB engaged in cation-π interactions with aromatic residues of PSMP, which made the protein structure unfold and enabled its hydrophobic groups of PSMP to be more exposed. These factors, plus protein aggregation, were responsible for the enhanced interfacial adsorption of PSMP. Its recovery percentage with 0.3 g/L GB (pH 7.0) increased by 52.9% compared to that without GB. Furthermore, an internal component of regular-hexagon hollow prismoid (RHP) was also designed to intensify the foam drainage and raise PSMP enrichment to 7.1 ± 0.3. In the second-stage, PSMP could be further recovered and its total recovery percentage reached 94.5 ± 4.7%. After foam separation, the amino acid composition of PSMP was analyzed by SDS-PAGE and HPLC–UV and its functional properties was also evaluated. These results provide a new insight into enhancing the protein separation from agro-food waste. [ABSTRACT FROM AUTHOR]

Herein, we aimed to determine the clinical efficacy of recombinant human thrombopoietin (rhTPO) combined with glucocorticoids for treating immune thrombocytopenia (ITP). Clinical data of 87 patients with ITP admitted to our hospital were retrospectively analyzed, and patients were divided into two groups according to the treatment employed: 42 patients in the control group (CG) were prescribed glucocorticoids, and 45 patients in the study group (SG) received rhTPO combined with glucocorticoids. The total effective treatment rate in the SG (95.56%) was higher than that in the CG (76.19%) (P < 0.05). The SG achieved a platelet (PLT) count > 50 × 109/L faster and required fewer PLT transfusions than the CG (P < 0.05). At 1, 7, and 14 days after treatment, the PLT count increased in both groups and was higher in the SG than in the CG (P < 0.05). After treatment, CD3+, CD4+, and CD4+/CD8+ T cells increased, whereas CD8 + decreased in both groups, with the SG exhibiting a superior improvement to the CG (P < 0.05). Considering prothrombin time, activated partial thromboplastin time, and fibrinogen, differences between the two groups were not statistically significant, both before and after treatment (P > 0.05). rhTPO combined with glucocorticoids for treating ITP can effectively enhance the therapeutic effect, regulate the T lymphocyte subpopulation, rapidly increase the PLT level, and induce no significant effect on the coagulation function of patients, with good safety and high clinical promotion value. [ABSTRACT FROM AUTHOR]

Aqueous zinc ion batteries (AZIBs) are receiving increasing attention for large‐scale energy storage systems owing to their appealing features with intrinsic safety, low cost, and scalability. Unfortunately, the water‐induced parasitic reactions and dendrite growth on the Zn anode severely impede the further development of AZIBs. Herein, a thiourea additive is introduced into ZnSO4 electrolyte to construct unique metal‐molecule interface for simultaneously regulating the Zn anode interface chemistry and the bulk electrolyte environment. Experimental results and theoretical calculations reveal that the formed metal‐molecule interface can not only serve as a corrosion inhibitor for alleviating the water‐induced side reactions, but also act as a Zn2+ ion regulator for promoting the homogenous Zn deposition, thus achieving a corrosion‐free and dendrite‐free Zn anode. Consequently, the Zn|Zn symmetric cell exhibits an extended lifespan of 1200 h at 1 mA cm–2, 1mAh cm–2, and a high cumulative capacity of 3000 mAh cm–2 at 10 mA cm–2. When paired with V2O5 cathode, the Zn|V2O5 full cell delivers a high capacity retention of 76.0% after 1000 cycles at 1 A g–1. This study paves a new way to modulate Zn electrode interface chemistry by the novel design of metal‐molecule interface for advanced rechargeable Zn metal batteries and beyond. [ABSTRACT FROM AUTHOR]

For p-(dimethylamino)chalcone ( p-DMAC), the N atom is the most basic site in the liquid phase, whereas the O atom possesses the highest proton affinity in the gas phase. A novel and interesting observation is reported that the N- and O-protonated p-DMAC can be competitively produced in atmospheric pressure chemical ionization (APCI) with the change of solvents and ionization conditions. In neat methanol or acetonitrile, the protonation is always under thermodynamic control to form the O-protonated ion. When methanol/water or acetonitrile/water was used as the solvent, the protonation is kinetically controlled to form the N-protonated ion under conditions of relatively high infusion rate and high concentration of water in the mixed solvent. The regioselectivity of protonation of p-DMAC in APCI is probably attributed to the bulky solvent cluster reagent ions (SH) and the analyte having different preferred protonation sites in the liquid phase and gas phase. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: Maternal nutrient restriction during pregnancy is associated with the development of a “thrifty phenotype” in offspring, conferring increased prevalence of metabolic diseases in adulthood. To explore the possible mechanisms behind heart diseases in adulthood following maternal nutrient restriction, dams were fed a nutrient-restricted (NR: 50%) or control (100%) diet from 28 to 78 days of gestation. Both groups were then fed 100% of requirements to lambing. At 6 years of age, female offspring of NR and control ewes of similar weight and body condition were subjected to ad libitum feeding of a highly palatable diet for 12 weeks. Cardiac geometry, post-insulin receptor signaling, autophagy and proinflammatory cytokines were evaluated in hearts from adult offspring. Our results indicated that maternal nutrient restriction overtly increased body weight gain and triggered cardiac remodeling in offspring following the 12-week ad libitum feeding. Phosphorylation of insulin receptor substrate-1 (IRS1) was increased in left but not right ventricles from NR offspring. Levels of signal transducer and activator of transcription-3 were up-regulated in left ventricles, whereas expression of tumor necrosis factor-α and toll-like receptor-4 was enhanced in right ventricles, in adult offspring of maternal nutrition-restricted ewes. No significant differences were found in pan-IRS1, pan-AMP-dependent protein kinase (AMPK), pan-Akt, phosphorylated AMPK, phosphorylated Akt, glucose transporter 4, phosphorylated mammalian target of rapamycin, Beclin-1 and microtubule-associated protein 1 light-chain 3 II proteins in left and right ventricles between the control and NR offspring. These data revealed that maternal nutrient restriction during early to mid gestation may predispose adult offspring to cardiac remodeling possibly associated with phosphorylation of IRS1 as well as proinflammatory cytokines but not autophagy. [Copyright &y& Elsevier]

The epidermal growth factor receptor (EGFR) signaling pathway regulates cell proliferation, differentiation, and survival, and is frequently dysregulated in esophageal and gastric cancers. Few studies have comprehensively examined the association between germline genetic variants in the EGFR pathway and risk of esophageal and gastric cancers. Based on a genome-wide association study in a Han Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for 1942 esophageal squamous cell carcinomas (ESCCs), 1758 gastric cancers (GCs), and 2111 controls. SNP-level analyses were conducted using logistic regression models. We applied the resampling-based adaptive rank truncated product approach to determine the gene- and pathway-level associations. The EGFR pathway was significantly associated with GC risk (P = 2.16×10−3). Gene-level analyses found 10 genes to be associated with GC, including FYN, MAPK8, MAP2K4, GNAI3, MAP2K1, TLN1, PRLR, PLCG2, RPS6KB2, and PIK3R3 (P<0.05). For ESCC, we did not observe a significant pathway-level association (P = 0.72), but gene-level analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and ESCC (P<0.05). Our data suggest an association between specific genes in the EGFR signaling pathway and risk of GC and ESCC. Further studies are warranted to validate these associations and to investigate underlying mechanisms. [ABSTRACT FROM AUTHOR]

The DNA repair pathways help to maintain genomic integrity and therefore genetic variation in the pathways could affect the propensity to develop cancer. Selected germline single nucleotide polymorphisms (SNPs) in the pathways have been associated with esophageal cancer and gastric cancer (GC) but few studies have comprehensively examined the pathway genes. We aimed to investigate associations between DNA repair pathway genes and risk of esophageal squamous cell carcinoma (ESCC) and GC, using data from a genome-wide association study in a Han Chinese population where ESCC and GC are the predominant cancers. In sum, 1942 ESCC cases, 1758 GC cases and 2111 controls from the Shanxi Upper Gastrointestinal Cancer Genetics Project (discovery set) and the Linxian Nutrition Intervention Trials (replication set) were genotyped for 1675 SNPs in 170 DNA repair-related genes. Logistic regression models were applied to evaluate SNP-level associations. Gene- and pathway-level associations were determined using the resampling-based adaptive rank-truncated product approach. The DNA repair pathways overall were significantly associated with risk of ESCC (P = 6.37 × 10−4), but not with GC (P = 0.20). The most significant gene in ESCC was CHEK2 (P = 2.00 × 10−6) and in GC was CLK2 (P = 3.02 × 10−4). We observed several other genes significantly associated with either ESCC (SMUG1, TDG, TP53, GTF2H3, FEN1, POLQ, HEL308, RAD54B, MPG, FANCE and BRCA1) or GC risk (MRE11A, RAD54L and POLE) (P < 0.05). We provide evidence for an association between specific genes in the DNA repair pathways and the risk of ESCC and GC. Further studies are warranted to validate these associations and to investigate underlying mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: Sepsis is characterized by systematic inflammation and contributes to cardiac dysfunction. This study was designed to examine the effect of protein kinase B (Akt) activation on lipopolysaccharide-induced cardiac anomalies and underlying mechanism(s) involved. Mechanical and intracellular Ca2+ properties were examined in myocardium from wild-type and transgenic mice with cardiac-specific chronic Akt overexpression following LPS (4mg/kg, i.p.) challenge. Akt signaling cascade (Akt, phosphatase and tensin homologue deleted on chromosome ten, glycogen synthase kinase 3 beta), stress signal (extracellular-signal-regulated kinases, c-Jun N-terminal kinases, p38), apoptotic markers (Bcl-2 associated X protein, caspase-3/-9), endoplasmic reticulum (ER) stress markers (glucose-regulated protein 78, growth arrest and DNA damage induced gene-153, eukaryotic initiation factor 2α), inflammatory markers (tumor necrosis factor α, interleukin-1β, interleukin-6) and autophagic markers (Beclin-1, light chain 3B, autophagy-related gene 7 and sequestosome 1) were evaluated. Our results revealed that LPS induced marked decrease in ejection fraction, fractional shortening, cardiomyocyte contractile capacity with dampened intracellular Ca2+ release and clearance, elevated reactive oxygen species (ROS) generation and decreased glutathione and glutathione disulfide (GSH/GSSG) ratio, increased ERK, JNK, p38, GRP78, Gadd153, eIF2α, BAX, caspase-3 and -9, downregulated B cell lymphoma 2 (Bcl-2), the effects of which were significantly attenuated or obliterated by Akt activation. Akt activation itself did not affect cardiac contractile and intracellular Ca2+ properties, ROS production, oxidative stress, apoptosis and ER stress. In addition, LPS upregulated levels of Beclin-1, LC3B and Atg7, while suppressing p62 accumulation. Akt activation did not affect Beclin-1, LC3B, Atg7 and p62 in the presence or absence of LPS. Akt overexpression promoted phosphorylation of Akt and GSK3β. In vitro study using the GSK3β inhibitor SB216763 mimicked the response elicited by chronic Akt activation. Taken together, these data showed that Akt activation ameliorated LPS-induced cardiac contractile and intracellular Ca2+ anomalies through inhibition of apoptosis and ER stress, possibly involving an Akt/GSK3β-dependent mechanism. [Copyright &y& Elsevier]

Objective: To profile RNA expression in gastric cancer by anatomic subsites as an initial step in identifying molecular subtypes and providing targets for early detection and therapy. Methods: We performed transcriptome analysis using the Affymetrix GeneChip U133A in gastric cardia adenocarcinomas (n = 62) and gastric noncardia adenocarcinomas (n = 72) and their matched normal tissues from patients in Shanxi Province, and validated selected dysregulated genes with additional RNA studies. Expression of dysregulated genes was also related to survival of cases. Results: Principal Component Analysis showed that samples clustered by tumor vs. normal, anatomic location, and histopathologic features. Paired t-tests of tumor/normal tissues identified 511 genes whose expression was dysregulated (P<4.7E-07 and at least two-fold difference in magnitude) in cardia or noncardia gastric cancers, including nearly one-half (n = 239, 47%) dysregulated in both cardia and noncardia, one-fourth dysregulated in cardia only (n = 128, 25%), and about one-fourth in noncardia only (n = 144, 28%). Additional RNA studies confirmed profiling results. Expression was associated with case survival for 20 genes in cardia and 36 genes in noncardia gastric cancers. Conclusions: The dysregulated genes identified here represent a comprehensive starting point for future efforts to understand etiologic heterogeneity, develop diagnostic biomarkers for early detection, and test molecularly-targeted therapies for gastric cancer. [ABSTRACT FROM AUTHOR]

Objectives: The endoplasmic reticulum (ER) chaperone tauroursodeoxycholic acid (TUDCA) has exhibited promises in the treatment of obesity, although its impact on obesity-induced cardiac dysfunction is unknown. This study examined the effect of TUDCA on cardiomyocyte function in high-fat diet-induced obesity. Methods: Adult mice were fed low or high fat diet for 5 months prior to treatment of TUDCA (300 mg/kg. i.p., for 15d). Intraperitoneal glucose tolerance test (IPGTT), cardiomyocyte mechanical and intracellular Ca2+ property, insulin signaling molecules including IRS-1, Akt, AMPK, ACC, GSK-3β, c-Jun, ERK and c-Jun N terminal kinase (JNK) as well as ER stress and intracellular Ca2+ regulatory proteins were examined. Myocardial ultrastructure was evaluated using transmission electron microscopy (TEM). Results: High-fat diet depressed peak shortening (PS) and maximal velocity of shortening/relengthenin as well as prolonged relengthening duration. TUDCA reversed or overtly ameliorated high fat diet-induced cardiomyocyte dysfunction including prolongation in relengthening. TUDCA alleviated high-fat diet-induced decrease in SERCA2a and phosphorylation of phospholamban, increase in ER stress (GRP78/BiP, CHOP, phosphorylation of PERK, IRE1α and eIF2α), ultrastructural changes and mitochondrial permeation pore opening. High-fat diet feeding inhibited phosphorylation of AMPK and promoted phosphorylation of GSK-3β. TUDCA prevented high fat-induced dephosphorylation of AMPK but not GSK-3β. High fat diet promoted phosphorylation of IRS-1 (Ser307), JNK, and ERK without affecting c-Jun phosphorylation, the effect of which with the exception of ERK phosphorylation was attenuated by TUDCA. Conclusions: These data depict that TUDCA may ameliorate high fat diet feeding-induced cardiomyocyte contractile and intracellular Ca2+ defects through mechanisms associated with mitochondrial integrity, AMPK, JNK and IRS-1 serine phosphorylation. [ABSTRACT FROM AUTHOR]

The problem of direction-of-arrival (DOA) estimation for sparse array is addressed. The perspective that DOA estimation in virtual array response model can be cast as the problem of sparse recovery is introduced. Two methods are proposed, based on different optimization problems, which are solvable using second-order cone (SOC) programming. Without the knowledge of the number of sources, the proposed methods yield superior performances, which are verified by numerical simulations. [ABSTRACT FROM AUTHOR]

Abstract: A new method is proposed for sources number detection in array signal processing. This method is based on the orthogonality of signal subspace and noise subspace. At first obtain a set of bootstrap snapshots from original snapshots. Then estimate the direction of an arbitrary incident source, make eigen-decomposition of the covariance matrix and compute the weighted inner product vector. Subsequently repeat the above procedures many times to get weighted inner product vectors and calculate the average of them. Finally employ a clustering algorithm to determine the number of sources. The simulation results show the superiority of the proposed method at small number of snapshots and/or low signal-to-noise ratio (SNR). [Copyright &y& Elsevier]

Objectives: Second hand cigarette smoke is an independent risk factor for cardiovascular disease. Although a tie between smoking and cardiovascular disease is well established, the underlying mechanisms still remains elusive due to the lack of adequate animal models. This study was designed to use a mouse model of exposure to cigarette smoke, a surrogate of environmental tobacco smoke, to evaluate the impact of cardiac overexpression of heavy metal scavenger metallothionein on myocardial geometry, contractile and intracellular Ca2+ properties and apoptosis following side-stream smoke exposure. Methods: Adult male wild-type FVB and metallothionein transgenic mice were placed in a chamber exposed to cigarette smoke for 1 hour daily for 40 days. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties, fibrosis, apoptosis and mitochondrial damage were examined. Results: Our data revealed that smoke exposure enlarged ventricular end systolic and diastolic diameters, reduced myocardial and cardiomyocyte contractile function, disrupted intracellular Ca2+ homeostasis, facilitated fibrosis, apoptosis and mitochondrial damage (cytochrome C release and aconitase activity), the effects of which were attenuated or mitigated by metallothionein. In addition, side-stream smoke expose enhanced phosphorylation of Akt and GSK3β without affecting pan protein expression in the heart, the effect of which was abolished or ameliorated by metallothionein. Cigarette smoke extract interrupted cardiomyocyte contractile function and intracellular Ca2+ properties, the effect of which was mitigated by wortmannin and NAC. Conclusions: These data suggest that side-stream smoke exposure led to myocardial dysfunction, intracellular Ca2+ mishandling, apoptosis, fibrosis and mitochondrial damage, indicating the therapeutic potential of antioxidant against in second smoking-induced cardiac defects possibly via mitochondrial damage and apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: Despite great progress in the fields of tissue engineering and stem cell therapy, the translational and preclinical studies are required to accelerate the clinical application of tissue engineered nerve grafts, as an alternative to autologous nerve grafts, for peripheral nerve repair. Rhesus monkeys (non-human primates) are more clinically relevant and more suitable for scaling up to humans as compared to other mammalians. Based on this premise, and considering a striking similarity in the anatomy and function between human and monkey hands, here we used chitosan/PLGA-based, autologous marrow mesenchymal stem cells (MSCs)-containing tissue engineered nerve grafts (TENGs) for bridging a 50-mm long median nerve defect in rhesus monkeys. At 12 months after grafting, locomotive activity observation, electrophysiological assessments, and FG retrograde tracing tests indicated that the recovery of nerve function by TENGs was more efficient than that by chitosan/PLGA scaffolds alone; histological and morphometric analyses of regenerated nerves further confirmed that the morphological reconstruction by TENGs was close to that by autografts and superior to that by chitosan/PLGA scaffolds alone. In addition, blood test and histopathological examination demonstrated that TENGs featured by addition of autologous MSCs could be safely used in the primate body. These findings suggest the efficacy of our developed TENGs for peripheral nerve regeneration and their promising perspective for clinical applications. [Copyright &y& Elsevier]

A novel extracellular exoinulinase was purified and characterized from a new yeast strain KRF1, and the gene encoding the enzyme was successfully cloned. The enzyme was stable at low pH between 3.0 and 6.5. The K and V values of the purified enzyme for inulin were 2.3 mg/mL and 4.8 mg/min, respectively. The optimum temperature of the inulinase was 50 °C, and the enzyme remained 78 % of activity at 60 °C for 2 h. The inulinase showed an amino acid sequence identity of 58 % to its closest homolog in Meyerozyma ( Pichia) guilliermondii. In the secondary structure, the domain G (VMEVH) of the enzyme contained three unique residues (V, M, and H). Compared with previously reported inulinases, the enzyme from strain KRF1 displayed strong acid resistance, notable thermostability, and high affinity for the substrate of inulin. Based on sequence analysis of the 26S rDNA D1/D2 domain and phenotypic characterization, the yeast strain KRF1 was found to represent a novel anamorphic, ascomycetous yeast species. A complete description of the species is given and the name Candida kutaonensis sp. nov (type strain = KRF1 = AS 2.4027 = CBS 11388) is proposed. [ABSTRACT FROM AUTHOR]

Abstract: A new algorithm involving sparse recovery is proposed to address the problem of direction-of-arrival (DOA) estimation using weighted subspace fitting (WSF). The proposed algorithm proves to be a modified version of ℓ 1-SVD by using an optimal weighting matrix, wherein a scheme of regularization between sparsity penalty and subspace fitting error is also given for all SNR range. Numerical simulations verify the efficiency of the proposed algorithm and illustrate the performance improvement in low SNR. [Copyright &y& Elsevier]

Thermotolerant inulin-utilizing yeast strains are desirable for ethanol production from Jerusalem artichoke tubers by consolidated bioprocessing (CBP). To obtain such strains, 21 naturally occurring yeast strains isolated by using an enrichment method and 65 previously isolated Saccharomyces cerevisiae strains were investigated in inulin utilization, extracellular inulinase activity, and ethanol fermentation from inulin and Jerusalem artichoke tuber flour at 40 °C. The strains Kluyveromyces marxianus PT-1 (CGMCC AS2.4515) and S. cerevisiae JZ1C (CGMCC AS2.3878) presented the highest extracellular inulinase activity and ethanol yield in this study. The highest ethanol concentration in Jerusalem artichoke tuber flour fermentation (200 g L) at 40 °C achieved by K. marxianus PT-1 and S. cerevisiae JZ1C was 73.6 and 65.2 g L, which corresponded to the theoretical ethanol yield of 90.0 and 79.7 %, respectively. In the range of 30 to 40 °C, temperature did not have a significant effect on ethanol production for both strains. This study displayed the distinctive superiority of K. marxianus PT-1 and S. cerevisiae JZ1C in the thermotolerance and utilization of inulin-type oligosaccharides reserved in Jerusalem artichoke tubers. It is proposed that both K. marxianus and S. cerevisiae have considerable potential in ethanol production from Jerusalem artichoke tubers by a high temperature CBP. [ABSTRACT FROM AUTHOR]