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Abstract: Background: Smad3 is a principal intracellular mediator of signaling for transforming growth factor β, a cytokine involved in pleiotropic pathophysiological processes including inflammation and immunity. The function of Smad3 in regulating inducible nitric oxide synthase (iNOS) expression and septic shock has not been characterized. Methods: Smad3−/−(referred hereafter as KO) and wild-type (WT) mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce the septic hypotension. Mortality, blood pressure, and plasma levels of nitrite were measured. The iNOS messenger RNA and protein levels in lung, kidney, and spleen were also analyzed. Results: Mice lacking functional Smad3 respond to LPS with greater mortality than their WT littermates. The high mortality of KO mice is accompanied by enhanced hypotension after intraperitoneal injection of LPS. Both KO and WT mice displayed an increase in plasma nitrite during the experimental period; however, LPS administration caused more dramatic changes in KO mice than WT mice. Likewise, the iNOS messenger RNA and protein levels in lung, kidney, and spleen were more strongly increased in KO mice than in WT mice after LPS administration. Conclusions: Defects in the Smad3 gene may increase susceptibility to the development of septic hypotension because of enhanced iNOS production. [Copyright &y& Elsevier]

Background: Many of these therapies have been compared against placebos, but have not been directly compared against each other. To evaluate the efficacy and safety of several commonly used drugs for AIS directly or indirectly. Methods: A systematic literature review was performed to identify randomized controlled trials (RCTs) published prior to April 2013 for AIS therapies. The primary outcome measures were the National Institutes of Health Stroke Scale (NIHSS) scores and the clinical effective rate. A fixed-effects meta-analysis and meta-regression are performed; lastly, performed a mixed treatment comparison was performed through the Bayesian methods. Results: Outcome of Efficacy of therapies for acute ischemic stroke are as followed: All of the therapies mentioned above yielded results a more effective result than placebo, Sodium ozagrel (RR 3.86, 95%CI 3.18–4.61); Sodium ozagrel + edaravone (RR 9.60, 95%CI 7.04–13.06); Edaravone (RR 4.07, 95%CI 3.30–5.01); Edaravone + Kininogenase (RR 15.33, 95%CI 10.03–23.05). The significant difference in efficacy between edaravone monotherapy and Sodium ozagrel + edaravone was evident (RR 0.43, 95%CI 0.08–0.61) and was also significant between efficacy of edaravone + Kininogenase and Sodium ozagrel (RR 4.00, 95%CI 2.47–6.24). The differences between the risk and benefit were not significant when comparing Sodium ozagrel and edaravone or edaravone + Kininogenase and Sodium ozagrel + Edaravone for AIS. Outcome of the defect of neurological function: Placebo served a significant difference in treating the defects of neurological function compared with Sodium ozagrel (WMD = −3.11, 95%CI −4.43 to −1.79), Sodium ozagrel + edaravone (WMD = −6.25, 95%CI −7.96 to −4.54) and Edaravone + Kininogenase (WMD =  −3.47, 95%CI −5.73 to −1.21). Conclusions: It provides that the efficacy of edaravone monotherapy in treatment was not more effective than Sodium ozagrel + edaravone.The efficacy of edaravone + Kininogenase monotherapy in treatment was more effective than Sodium ozagrel. Edaravone + Kininogenase and Sodium ozagrel + Edaravone appeared the most effective treatments. And Sodium ozagrel, Sodium ozagrel + edaravone, Edaravone + Kininogenase can improve the nerve dysfunction. [ABSTRACT FROM AUTHOR]

Abstract: The open reading frame of foot-and-mouth disease virus (FMDV) contains two authentic initiation codons and the second initiation codon is often selected in high frequency. In the study, we analyzed the effects of the host-cell synonymous codon usage and the overall tRNA concentration in the hosts on the region flanked by the two initiation codons (termed as the region 1) and the same length starting from the second initiation codon (defined as the region 2). We find that low-usage codons of hosts are more selected in the region 1 than the region 2; no obvious usage bias of codon with high C/G content exists in the region 1, and the latter part (ranging from the 13th codon position to the 28th codon position) of the region 1 generally contains the codon sites with the generally lower tRNA concentration than the counterpart of the region 2. The low-usage codons of the hosts with high selection in the region 1 and the cluster codon position with low tRNA concentration in the region 1 may serve as potential factors in decreasing the translation rate of the region 1 caused by initiation from the first start codon of FMDV. [Copyright &y& Elsevier]

Abstract: KMgF3 and KMgF3: Eu samples were firstly fabricated by molten salt synthesis (MSS) method in NH4HF2 flux without any surfactants. The NH4HF2 flux was utilized as both the reactant and the fluxing agent. The products with uniform and regular morphologies were characterized by X-ray diffraction (XRD), thermal stability (TG), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and photoluminescence (PL) spectra. The luminescent properties show that the obtained KMgF3 sample got a broad band blue emission at about 430nm arising from the trace oxygen and the color center, and the KMgF3: Eu sample exhibited fantastic emission under the excitation of different wavelengths. [Copyright &y& Elsevier]

Loganin, an iridoid glycoside, is one of the quality control indexes of Cornus officinalis Sieb. et Zucc. Increasing evidence emphasize the important role of inflammation in the pathology of depression, which links depression with other chronic diseases. Loganin prevents inflammatory response in multiple diseases and reverses depressive-like behaviors. However, the mechanisms underlying antidepressant-like effects of loganin for the treatment of inflammation-associated depression are not utterly understood. The present study was designed to predict the potential targets of loganin against inflammation-associated depression using a network pharmacology approach. Pharmmapper and Uniport were used to predict loganin-related targets. Targets of inflammation were identified through GeneCards databases and Online Mendelian Inheritance in Man (OMIM). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to identify the potential mechanism. Finally, qRT-PCR and ELISA were used to confirm the role of loganin on these targets. There were 15 nodes in the loganin-inflammation-depression intersection targets network. In the network, the degree value of CTNNB1 was above 3. Among top ten pathways identified by KEGG analysis, Th1/Th2 cell differentiation and IL-17 signaling pathways were related with both inflammation and depression. As indicated by qRT-PCR results, loganin increased CTNNB1 mRNA level. Moreover, loganin elevated M2 markers of microglia but decreased M1 markers of microglia against lipopolysaccharide (LPS), indicated by qRT-PCR results and ELISA results. CTNNB1 was the main target of loganin. Loganin alleviated LPS-induced inflammation through inhibiting M1 polarization of microglia. Our results provide a better understanding of loganin-induced antidepressant-like effects for the treatment of inflammation-associated depression. [Display omitted] [ABSTRACT FROM AUTHOR]

The development of a rapid-forming in-situ sprayable hydrogel with the functions of tumor treatment and wound healing is essential for eliminating residual tumor tissue and promoting wound healing caused by surgical resection. On account of its semiconductor properties, β-FeSi 2 (FS) was widely explored as a thermoelectric material. In this work, FS was first applied as a bioactive material for the application of tissue engineering. Excitedly, we found that FS could be used as a novel antitumor agent. It exhibited excellent photothermal performance, and the released Fe ions could generate •OH under the acidic conditions and excessive H 2 O 2 in the tumor microenvironment. Moreover, the sprayable β-FeSi 2 -incorporated sodium alginate (FS/SA) hydrogel was prepared as an instant gelation after spraying in situ , contributing to timely tumor-induced skin wound healing and efficiently suppressing tumors through photothermal and chemodynamic therapy (PTT and CDT). Furthermore, the released bioactive Fe and Si ions could promote the migration and differentiation of endothelial cells and the pro-angiogenesis of skin wounds. Accordingly, such sprayable hydrogel played an effective role in emergency wound treatment with the advantage of convenience and portability. Overall, with incorporation of FS into the sprayable FS/SA hydrogel, the composite hydrogel possessed dual functions of tumor therapy and skin wound healing. [ABSTRACT FROM AUTHOR]

• The powders after MA consisted of large- and small-Cu grain layers due to inhomogeneous distribution of yttrium atoms. • Areal fraction of small Cu grain layer increases with increasing MA duration. • The powders after ball-milled have exothermic reaction at around 310°C, which may be recrystallization and grain growth of Cu grains. • During heat treatment above 300°C after MA, yttrium atoms are diffused into the outer peripheral region and forms a new small-Cu grain area. Oxide dispersion strengthened Cu alloys (ODS-Cu) having dispersed yttria (Y 2 O 3) fabricated using hot isostatic pressing (HIP) of mechanically alloyed (MA) Cu-Y powders. They exhibited a heterogeneous mixed grain structure, which were composed of a large and small Cu grain area. In the small Cu grain regions, Y₂O₃ particles were segregated along the grain boundaries, and acted as a crack propagation path, leading to brittle fracture. Therefore, we investigated the microstructural changes by the MA and heat treatment processes for the microstructure optimization. The powders of 4 to 32 MA hours formed a nested crust-like layered structure with large and small Cu grains. The layers were destroyed by heat treatment at 500°C, because recrystallization and grain growth of Cu occurred in the temperature range of 310 - 330°C. It was considered that Y 2 O 3 was moved out to the circumferential area of the powders. Based on these results, it was suggested that the structural changes inside MA powders during HIP are the essential factor of the Y 2 O 3 distribution within the Y 2 O 3 -added ODS-Cu alloys. [ABSTRACT FROM AUTHOR]

• Foamed geopolymer was successfully produced from industrial wastes. • Foamed geopolymer consisted of geopolymer binders, unreacted and nonreactive phases. • The factors influencing the mechanical properties of geopolymer were studied. The characteristics of strong alkalinity and concentrated heavy metals make it difficult to dispose and re-utilize Bayer red mud (RM). As for another industrial waste, ZSM-5 (Zeolite Socony Mobil-5) waste is deactivated ZSM-5 catalysts that was formed from the industrial cycles. Herein, a new kind of foamed geopolymer composite (containing various ratios of RM/FA) with micropores was fabricated at elevated temperature from three industrial wastes: Bayer red mud (RM), fly ash (FA) and ZSM-5 waste. The final geopolymer products were characterized by compressive strength tests, X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, FT-IR spectral analysis, and mercury intrusion porosimetry to evaluate the relationship between their microstructure, geopolymerization reactions and mechanical properties. ZSM-5 waste has the strong ability to foam because it contains ZSM-5 that possesses numerous mesoporous. The addition of ZSM-5 waste generates a microporous structure. Higher RM/FA ratios generally result in a lower compressive strength owing to the lower reactivity of the RM; however, excessive RM particles may cause the negative effect. The compressive strength in overall decreases from 10.7 to 8.0 MPa and the bulk density increases from 1.04 to 1.26 g/cm−1 with the increased RM/FA ratios of 0.4–1.0, respectively. Microscopic morphology analysis demonstrates that the final products are composites consisting of geopolymer gels and unreacted phases, such as mullite and hematite phases, as fillers. This research can shed light on the utilization and mechanisms of industrial RM and ZSM-5 waste into the construction and building materials. [ABSTRACT FROM AUTHOR]

• M1 and M3 alite along the same pseudo-hexagonal subcell direction were determined. • A new one-dimensional incommensurate modulation structure was found in M1-alite. • The relationship between SO 3 /MgO and M1 alite content in C 3 S was determined. • Compressive strength of clinker was related to the polymorph and content of alite. This paper explored the structural modulation of alite in cement clinkers doped with high content of MgO and a series amount of SO 3. The effect of alite polymorph on compressive strength had also been studied. The results showed that high content of MgO stabilized M3 type alite while the increase of doped SO 3 could gradually modulated the polymorph to M1 type. M1 type alite had an incommensurate modulation along pseudo-hexagonal subcell [ 2 - 10 ] H * direction while M3 type alite hadn't appeared this characteristic. A new incommensurate modulation was found in M1-type alite along the pseudo-hexagonal subcell [ 01 7 - ] H * direction. Quantitative analysis results showed there was a nonlinear correlation between SO 3 /MgO and alite content in clinkers which could be well fitted by the parabola curve. SO 3 /MgO and M1 alite content in C 3 S ( M1 - C 3 S M1 - C 3 S + M3 - C 3 S × 100 %) showed a linear relationship. The compressive strength of clinkers was affected by both polymorph and content of alite. The correlation between the polymorph, content of alite and compressive strength of clinkers was determined by Multiple linear regression analysis. [ABSTRACT FROM AUTHOR]

Piedmont alluvial fans have, for a long time, supported clean groundwater for human development worldwide. Rapid urbanization in China has over-exploited groundwater and resulted in severe groundwater nitrate pollution in piedmont alluvial fans, which has led to both human health concerns and clean water shortages, especially in rural residential areas where drinking water is mainly derived from shallow groundwater. However, sources of nitrate in groundwater and their pathways are still unclear. In this study, we hypothesized that untreated manure and domestic sewage are the primary nitrate sources in a residential area, and that an unconfined aquifer would be more vulnerable to nitrate pollution than a confined aquifer due to nitrate infiltration via the vadose zone. To verify this hypothesis, groundwater nitrate pollution in a well-characterized piedmont alluvial fan was studied through hydrochemical composition and multi-isotope (δ 15N NO3 , δ 34S SO4 , δ 18O SO4 , δ 13C DIC) data over four seasons. Seasonal variations for both NO 3 − concentrations and δ 15N NO3 values in unconfined groundwater (UGW) and confined groundwater (CGW) were observed. Mixing of nitrate sourced from manure/sewage, precipitation, soil nitrogen, and synthetic fertilizer controlled the groundwater nitrate level, and manure/sewage contributed 52.4%, 32.4%, and 33.7% nitrate to UGW, CGW, and surface water (SFW), respectively, based on Stable Isotope Mixing Models in R (SIMMR) analysis. Denitrification had a minor effect on groundwater nitrate levels in a residential area, and nitrate pollution in CGW was partly due to nitrate migration through geological faults and fracture zones in a piedmont alluvial fan. Nitrate pollution sources and pathways in residential areas were confirmed through multiple isotopes (δ 15N NO3 , δ 13C DIC , δ 34S SO4 , and δ 18O SO4). Collectively, these results highlight the roles of the hydrogeological setting and anthropogenic activities in groundwater N pollution beneath piedmont alluvial fans. • Hydrogeological controls play a key role in nitrate levels in groundwater. • Elevated nitrate levels in groundwater are closely linked with manure/sewage. • Unconfined groundwater is more vulnerable to nitrate pollution than confined groundwater. • Multiple isotope data confirms nitrate sources and transformations in groundwater. [ABSTRACT FROM AUTHOR]

Abstract: Background: The liver is one of the organs most frequently affected by trauma and hemorrhagic shock; the exact role of p38 mitogen-activated protein kinase (MAPK) activation in response to hepatic hemorrhagic shock/resuscitation (HS/R) remains unclear. Materials and methods: C57Bl/6 mice were divided into four groups: sham-operated group, SB-only group, control group, and SB + HS/R group. Hepatocellular injury (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and tumor necrosis factor (TNF-α) and interleukin (IL-1β) messenger ribonucleic acid (mRNA) expression in the liver were assessed 6 h after resuscitation, p38 MAPK activation in the liver was assessed at 30 min after resuscitation. Results: p38 MAPK activation was higher in the control group than other groups 30 min after resuscitation. p38 MAPK activation level in the SB + HS/R group did not change significantly compared with that of sham and SB-only groups, but was significantly lower than that in the control group. The TNF-α mRNA expression in the control group was significantly higher than that in the sham group. The TNF-α mRNA levels after HS/R in the SB + HS/R group were significantly lower than those in the control group and were roughly the same as those in the sham and SB-only groups. IL-1β mRNA expression showed similar changes in the four groups. Serum ALT and AST levels in the control group were significantly higher than those in the sham group. The increase in serum ALT and AST levels after HS/R in the SB + HS/R group was significantly less pronounced than that in the control group and markedly higher than that in the sham group. Conclusions: p38 MAPK was phosphorylated during the HS/R process. Inhibiting the activation of p38 MAPK may attenuate HS/R injury to the liver. [Copyright &y& Elsevier]

Background: Splanchnic ischemia is common in critically ill patients, and it can result in injury not only of the intestine but also in distant organs, particularly in the lung. Local inflammatory changes play a pivotal role in the development of acute lung injury after intestinal ischemia, but the underlying molecular mechanisms are not fully understood. We sought to examine the role of Toll-like receptor 4 (TLR4) in the mouse model of intestinal ischemia-reperfusion (I/R)-induced lung injury and inflammation. Materials and Methods: Adult male TLR4 mutant (C3H/HeJ) mice and TLR4 wild-type (WT) (C3H/HeOuJ) mice were subjected to 40 min of intestinal ischemia by clamping the superior mesenteric artery followed by 6 h of reperfusion. Lung histology was assessed and parameters of pulmonary microvascular permeability, inflammatory cytokine expression, and neutrophil infiltration were measured. Activation of mitogen-activated protein kinases (MAPKs) and the transcription factors nuclear factor κB (NF-κB) and activator protein-1 (AP-1) in the lungs were also detected. Results: After intestinal I/R, lungs from TLR4 mutant mice demonstrated a significantly lower histological injury, a marked reduction of epithelial apoptosis associated with the decreased level of cleaved caspase-3 and the increased ratio of Bcl-xL to Bax proteins, and a large reduction in pulmonary vascular permeability and myeloperoxidase (MPO) activity in comparison with WT mice. TLR4 mutant mice also displayed marked decreases in tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2) expression. Following intestinal I/R, phosporylation of p38 MAPK and activation of NF-κB and AP-1 were significantly inhibited in lung tissue from TLR4 mutant mice compared with WT controls. Conclusions: These data suggest that TLR4 plays an important role in the pathogenesis of intestinal I/R-induced acute lung injury and inflammation and that p38 kinase and NF-κB may be involved in TLR4 signaling-mediated lung inflammatory processes during intestinal I/R. [Copyright &y& Elsevier]

Background: The effect of storage conditions on the microbiome and metabolite composition of human biological samples has not been thoroughly investigated as a potential source of bias. We evaluated the effect of two common storage conditions used in clinical trials on the bacterial and metabolite composition of the vaginal microbiota using pyrosequencing of barcoded 16S rRNA gene sequencing and 1H-NMR analyses. Methodology/Principal Findings: Eight women were enrolled and four mid-vaginal swabs were collected by a physician from each woman. The samples were either processed immediately, stored at -80°C for 4 weeks or at -20°C for 1 week followed by transfer to -80°C for another 4 weeks prior to analysis. Statistical methods, including Kolmogorovo-Smirnov and Wilcoxon tests, were performed to evaluate the differences in vaginal bacterial community composition and metabolites between samples stored under different conditions. The results showed that there were no significant differences between samples processed immediately after collection or stored for varying durations. 1H-NMR analysis of the small molecule metabolites in vaginal secretions indicated that high levels of lactic acid were associated with Lactobacillusdominated communities. Relative abundance of lactic acid did not appear to correlate with relative abundance of individual Lactobacillus sp. in this limited sample, although lower levels of lactic acid were observed when L. gasseri was dominant, indicating differences in metabolic output of seemingly similar communities. Conclusions/Significance: These findings benefit large-scale, field-based microbiome and metabolomic studies of the vaginal microbiota. [ABSTRACT FROM AUTHOR]

Abstract: Aims: P311 is an 8kDa protein that has been shown to be of importance in the process of myofibroblast transformation, glioblastoma invasion and nerve regeneration. However, the interaction protein of P311 has yet to be found. The purpose of this study was to find the interactive protein of P311. Main methods: The yeast two-hybrid system was used for screening the potential interaction proteins of P311. Joint expression of the potential interactive protein and P311 was immunohistochemically stained. The interaction between P311 and the selected protein was further confirmed by fluorescence resonance energy transfer (FRET) in pulmonary adenocarcinoma tissue sections, and by coimmunoprecipitation in HEK293. Key findings: Integrin β4 binding protein (ITGB4BP) was confirmed as the interaction protein of P311. Co-expression and interaction of ITGB4BP and P311 were demonstrated in pulmonary adenocarcinoma by both immunohistochemistry and FRET. Moreover the interaction between P311 and ITGB4BP was demonstrated by coimmunoprecipitation in HEK293. Significance: The interactions between P311 and ITGB4BP may be very important in the process of tumor cell differentiation and metastasis. ITGB4BP may provide a potential new target for the therapy of tumors. [Copyright &y& Elsevier]

Background and Aim: Hepatitis B surface antigen (HBsAg) clearance is the closest cure outcome in hepatitis B. The goal of this study was to investigate clinical features in chronic hepatitis B patients achieving seroconversion of HBsAg after treatment with α-interferon (IFN-α) and a nucleos(t)ide analog. Methods: This retrospective study enrolled 38 chronic hepatitis B patients treated with IFN-α plus a nucleos(t)ide analog who achieved HBsAg seroconversion during the period from June 2001 to May 2009. Clinical and laboratory data of the patients were collected before and after treatment every 3 months. All patients with HBsAg seroconversion in this study were followed up for at least 12 months post-treatment. Results: A total of 38 out of 142 patients achieved HBsAg seroconversion after treatment with IFN-α and a nucleos(t)tide analog for a prolonged period of time (medium 31 months). The median time to hepatitis B e antigen seroconversion and to HBsAg seroconversion was 19.5 months (range 3-60 months) and 25.5 months (range 9-63 months), respectively. Thirty-six patients (95%) sustained HBsAg seroconversion during the post-treatment follow up. Three different HBsAg response patterns were observed with classical model accounting for 57.9% (22/38 cases), simultaneous transition mode accounting for 23.7% (9/38 cases), and HBsAg prior transition model accounting for 18.4% (7/38 cases). Conclusions: Extended treatment with IFN-α in combination with a nucleos(t)ide analog in patients with hepatitis-B-e-antigen-positive appears to be a promising approach for achieving a high rate of HBsAg clearance-the closest outcome to cure. [ABSTRACT FROM AUTHOR]

Abstract: The microhardness, grain size and distribution of the precipitates in various zones of a 2519-T87 aluminum alloy welded joint welded by friction stir welded were investigated. The dynamic recrystallization occurred in the weld nugget zone and the size of recrystallized grains was smaller than that in the thermo-mechanically affected zone, besides, θ′ and θ phase precipitated. The thermo-mechanically affected zone was divided into three ones: the zone close to the thermo-mechanically affected zone, where coarse θ′ precipitates were observed; the middle zone, where the mainly θ precipitates appeared; and the zone close to the heat-affected zone, where both thin θ′ and θ precipitates were observed. In the heat-affected zone, the size of θ′ precipitates was less than those in the base metal zone. On the transverse cross-section of welded joint the microhardness curve shows a W-shape. [Copyright &y& Elsevier]

The present study aims to define the trend of time related changes with local bacterial alteration of bacterial resistance in severe burns in our burn center during a 12-year period. Retrospective analysis of microbiological results on severely burned wounds between 1998 and 2009 was carried out. A study of 3615 microbial isolates was performed. Staphylococcus aureus was the most commonly isolated pathogen (38.2%) followed by A. baumannii (16.2%), Streptococcus viridans (11.4%), Pseudomonas aeruginosa (10.4%), coagulase-negative staphylococci (CNS, 9.2%). The species ratios of S. aureus and A. baumannii increased significantly from 1st to 8th week of hospitalization, while those of Streptococcus viridans, P. aeruginosa and coagulase-negative staphylococci decreased during the same period. Bacterial resistance rates were compared between the periods 1998–2003 and 2004–2009. Vancomycin remained as the most sensitive antibiotic in S. aureus including methicillin-resistant S. aureus (MRSA). It was very likely that the majority of infections caused by Streptococcus viridans, P. aeruginosa and coagulase-negative staphylococci occurred in the early stage of burn course and the majority of infections caused by A. baumannii occurred 4weeks after admission. The use of different antibiotics was probably the major contributor to these trends. [Copyright &y& Elsevier]

Abstract: Due to the importance of aldose reductase (ALR2) as a potential drug target in the treatment of diabetic complications, there are increasing interests in design and synthesis of ALR2 inhibitors. Here, we prepared 1,2-benzothiazine 1,1-dioxide acetic acid derivatives and investigated their inhibition activity. Most of these derivatives were found to be active with IC50 values ranging from 0.11μM to 10.42μM, and compound 8d, 2-[2-(4-bromo-2-fluorobenzyl)-1,1-dioxido-2H-1,2-benzothiazin-4(3H)-ylidene]acetic acid, showed the most potent inhibition activity. Further, SAR and docking studies suggest that in comparison with the α,β-unsaturated derivatives, the saturated carboxylic acid derivatives had a greater binding affinity with the enzyme and thus an enhanced inhibition activity. Therefore, development of more powerful ARIs based on benzothiazine 1,1-dioxide by stereo-controlled synthesis could be expected. [Copyright &y& Elsevier]

The structure, electronic property, and infrared spectroscopy of endohedral metallofullerenes TM@C20 (TM = Ce and Gd) have been systematically investigated with the aid of the hybrid DFT-B3LYP functional. It is found that in the endohedral metallofullerenes the average CC bond lengths are obvious longer than those of empty cage. The frontier orbital analyses show that the endohedral metallofullerene Gd@C20 has the high-thermodynamic stability. Natural population analysis also tells us that only in the Ce@C20, the Ce atom acts as an electron acceptor with the negative charges, and the 4f orbitals of Ce and Gd atoms have a significant contribution in the formation of chemical bonding. Additionally, the analyses of harmonic vibrational frequencies reveal that when the TM atoms are encapsulated into the C20 cage, the strongest absorption peaks are characterized by a mixture of TM−C bending and CC stretching vibrations. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011 [ABSTRACT FROM AUTHOR]

Liesegang rings, periodical bands or ring patterns formed by inorganic precipitation in polymer gel medium, have attracted lots of interest of researchers aiming to construct ordered structures. Inspired by the Liesegang ring phenomena, chitosan, instead of inorganic species, was used as building block to construct a chitosan hydrogel with concentric multilayers in a protonated chitosan/NaOH reaction system by alternate soaking in NaOH solution and water. The morphology of concentric multilayers structure was characterized by environmental scanning electron microscopy. The upload and release behavior of isoniazid was also investigated. The quantitive rules of the concentric layer position/the square root of reaction time and the position of the consecutive concentric layer coincide with the time law and space law of the classical Liesegang ring phenomena, respectively. The chitosan solution converts into a hydrogel accompanied by remarkable volume shrinkage due to hydrogen bonds reconstruction and electrostatic repulsion disappearance. The separated concentric multilayers can be formed due to the fluctuation of hydroxide ions concentration when the neutralization is interrupted by alternate soaking in NaOH solution and water. The major difference of the concentric multilayers in chitosan hydrogel from the classical Liesegang ring phenomena occurring in inorganic precipitation systems is that chitosan not only plays the role of reactant in chitosan hydrogel formation, but also acts as supporting reaction medium to control the diffusion behavior of hydroxide ions. The porosity and equilibrium swelling ratio of the chitosan xerogel are 63% and 1100%, respectively, which is feasible for drug uploading through diffusion or absorption. The isoniazid release kinetics are dominated by the diffusion-erosion model. The chitosan hydrogel with concentric multilayers structure loaded with isoniazid will have wide applications in treatment of bone tuberculosis. [ABSTRACT FROM AUTHOR]

A series of novel benzothiadiazine 1,1-dioxide derivatives were synthesized and tested for their inhibitory activity against aldose reductase. Of these derivatives, 17 compounds, having a substituted N2-benzyl group and a N4-acetic acid group on the benzothiadiazine, were found to be potent and selective aldose reductase inhibitors in vitro with IC50 values ranging from 0.032 to 0.975 μM. 9m proved to be the most active in vitro. The eight top-scoring compounds coming from the in vitro test for ALR2 inhibition activity were then tested in vivo, whereby three derivatives, 9i, 9j, and 9m, demonstrated a significantly preventive effect on sorbitol accumulation in the sciatic nerve in the 5-day streptozotocin-induced diabetic rats in vivo. Structure−activity relationship and molecular docking studies highlighted the importance of substitution features of N4-acetic acid group and halogen-substituted N2-benzyl group in the benzothiadiazine scaffold and indicated that substitution with hallogen at C-7 had a remarkably strong effect on ALR2 inhibition potency. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression and cellular distribution of regulated upon activation normal T-cell expressed and secreted (RANTES) in the male reproductive system. Design: Basic research. Setting: University academic medical center. Patient(s): Three adult male organ donors. Intervention(s): None. Main Outcome Measure(s): Reverse transcriptase–polymerase chain reaction (RT-PCR), in situ hybridization, immunohistochemical staining, and immunofluorescence staining were used to examine the distribution of RANTES in human and mouse epididymis. Western blot was used to quantitate the levels of RANTES expression in mouse epididymis on postnatal days. Immunofluorescence staining was applied to detect RANTES association with spermatozoa from mouse epididymis. Result(s): The location of RANTES was restricted to ciliated cells of the efferent duct and apical, narrow, and basal cells of the epididymal ducts, in both humans and mouse. RANTES-positive basal cells were only identified in the epididymal ducts in humans. The signals of RANTES were first detected on day 28 and increased during mouse sexual maturation. We also observed that RANTES was bound on both normal and defective epididymal sperm, but in different patterns. Conclusion(s): RANTES is constitutively expressed in the epididymis and secreted into the lumen of epididymis throughout sexual maturity, and differentially associates with viable and defective spermatozoa. [Copyright &y& Elsevier]

Abstract: Objective: To identify treatment-related factors associated with mortality in massively burned adult patients. Methods: This retrospective cohort study examined survival outcomes at a burn unit of 54 beds and 10 burn ICU beds, totaling 900 admissions per year. The cases of 102 adult patients, admitted consecutively from January 1993 to October 2007, with massive burns (burn area>70% of the total body surface area, TBSA) were studied. Relevant variables were recorded from the initial injury and throughout the hospital course. Survival analysis, based on univariate and stepwise multivariate Cox proportional hazards regression, was performed to determine which variables predicted mortality. Results: The overall mortality rate was 30.4%. Burn size, severe inhalation injury, full-thickness burns, serum creatinine levels, inotropic support, platelet counts<20,000 per mm3, sepsis and ventilator dependency were significantly associated with mortality as determined by univariate analysis. Only sepsis, ventilator dependency and platelet counts were significant independent predictors of mortality as determined by multivariate analysis. Conclusions: Sepsis, ventilator dependence (indicating severe respiratory complications), and low platelet counts (indicating thrombocytopenia) are associated with increased mortality risk in adult patients with massive burns. Methods should be sought to ameliorate these complications during treatment in burn-care units. [Copyright &y& Elsevier]

Abstract: Angiotensin II is able to trigger inflammatory responses through an angiotensin II type 1 (AT1) receptor. The role of AT1 receptor in acute lung injury (ALI) is poorly understood. Mice were randomly divided into three groups (n =40 each groups): NS group; LPS group (2mg/kg LPS intratracheally); and LPS+ZD 7155 group, 10mg/kg ZD 7155 (an AT1 receptor antagonist) intraperitoneally 30min prior to LPS exposure. Samples from the lung were isolated and assayed for histopathology analyses or proinflammatory gene expressions, angiotensin II receptors expressions and nuclear factors activities. LPS exposure resulted in severe ALI, elevated levels of TNF-α and IL-1β mRNA expressions, and increased activities of NF-κB and activated protein (AP)-1. Upregulation of AT1 receptor and down-regulation of AT2 receptor were also observed after LPS challenge. Pretreatment with ZD 7155 significantly inhibited the increase of AT1 receptor expression and upregulated AT2 receptor expression. ZD 7155 also reduced the mRNA expression of TNF-α and IL-1β, inhibited the activation of NF-κB and AP-1, and improved lung histopathology. These findings suggest that antagonism of AT1 receptor inhibits the activation of NF-κB and AP-1 in the lung, which may mediate the release of TNF-α and IL-1β and contribute to LPS-induced ALI. [Copyright &y& Elsevier]

Abstract: A comparative analysis of electronic structure and stability of endohedral metallofullerenes TM@C24 and TM@C24H12 (TM=Ti, Zr and Hf) is systematically performed with the aid of quantum chemical DFT-B3PW91 approach. Our calculated results show that TM@C24H12 display higher symmetry compared with TM@C24, and all of endohedral metallofullerenes are in a singlet spin state. Thermodynamic data reflect that endohedral metallofullerenes TM@C24 are more stable than TM@C24H12 and the Ti atom is energetically favorable to be encapsulated. However, these TM@C24H12 have higher kinetic stability. The analyses of the vertical electron affinities (VEAs) and vertical ionization potentials (VIPs) indicate the possibilities of accepting electrons of TM@C24H12 become weaker and the possibilities of denoting electrons become stronger. Additionally, natural population analysis presents that the natural charge on TM atoms dramatically increases along with increasing atomic number, and the 5d orbitals of Zr atom and 6d orbitals of Hf atom are significantly involved in their chemical bonding. [Copyright &y& Elsevier]

Abstract: Angiotensin II is critically involved in skin wound healing, but the underlying mechanism remains unclear. This study investigated the effect of angiotensin II on type I collagen gene activation in human dermal fibroblasts and the possible mechanism involved. Angiotensin II stimulated the mRNA and protein expression of type I collagen and TGF-β1. Effects were abolished by the angiotensin AT1 receptor antagonist ZD7155 but not by the AT2 blocker PD123319. Blockade of TGF-β1 markedly inhibited angiotensin II-induced type I collagen gene expression. Activator protein-1 (AP-1) decoy ODNs transfection suppressed angiotensin II-induced TGF-β1 expression, and also, diminished type I collagen expression. These data indicated that angiotensin II induces collagen gene activation in human dermal fibroblasts through an AT1-mediated AP-1/TGF-β1 signaling pathway. [Copyright &y& Elsevier]

To evaluate the antibacterial effect of multivalent silver ion carried by zirconium phosphate (ZP-Ag) both in vitro and in an experimental rat burn wound compared with that of sulfadiazine silver (SD-Ag). Firstly, the minimal inhibition concentration and the minimal bactericidal concentration of ZP-Ag to three different strains of bacteria ( Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli) were compared with those of SD-Ag in vitro. Following this dressings containing the same mass of ZP-Ag or SD-Ag were applied to wounds in a rat burn model and their antimicrobial activity assayed. The inflammatory response of the wounds managed with the two kinds of dressings was compared. Both the minimal inhibition concentration and minimal bactericidal concentration of ZP-Ag to S. aureus, P. aeruginosa, and E. coli were two to four times lower than those of SD-Ag. In vivo ZP-Ag had a more effective antibacterial action inhibiting the growth of the above three bacterial strains under burn scar, compared with dressings made from the same mass of SD-Ag. Moreover, the antibacterial effect was unchanged after the ZP-Ag dressings were washed 20 times, while it dramatically decreased after the dressings with SD-Ag were washed 20 times. When covered by either regular or washed ZP-Ag dressings, the wounds showed integrity with no visible inflammatory reaction. However, various extents of inflammatory reactions on or around the wounds covered with regular SD-Ag dressing were observed. This study showed that dressings with ZP-Ag had a prominent and relative long-term antibacterial effect. ZP-Ag dressings could be an effective, low-cost management option for burn wounds. [ABSTRACT FROM AUTHOR]

Simple Summary: Red palm weevil (RPW), Rynchophorus ferrugineus Olivier, is a destructive pest that often seriously infests palm plants. Because of the negative environmental effect and pesticide resistance caused by insecticide applications, it is important to develop novel green control strategies for this pest. The intestinal tracts of RPW are often colonized by multiple bacterial species that have promoting effects on the growth, development and immunity of RPW larvae. This review summarized the current understanding on the crosstalk between RPW larvae and their gut microbiota and pointed out the great potential of the development of microbial resource-based management methods for this pest. Red Palm Weevil (RPW), Rhynchophorus ferrugineus Olivier, is a notorious pest, which infests palm trees and has caused great economic losses worldwide. At present, insecticide applications are still the main way to control this pest. However, pesticide resistance has been detected in the field populations of RPW. Thus, future management strategies based on the novel association biological control need be developed. Recent studies have shown that the intestinal tract of RPW is often colonized by multiple microbial species as mammals and model insects, and gut bacteria have been found to promote the growth, development and immune activity of RPW larvae by modulating nutrient metabolism. Furthermore, two peptidoglycan recognition proteins (PGRPs), PGRP-LB and PGRP-S1, can act as the negative regulators to modulate the intestinal immunity to maintain the homeostasis of gut bacteria in RPW larvae. Here, we summarized the current knowledge on the gut bacterial composition of RPW and their impact on the physiological traits of RPW larvae. In contrast with metazoans, it is much easier to make genetic engineered microbes to produce some active molecules against pests. From this perspective, because of the profound effects of gut bacteria on host phenotypes, it is promising to dissect the molecular mechanisms behind their effect on host physiology and facilitate the development of microbial resource-based management methods for pest control. [ABSTRACT FROM AUTHOR]

OBJECTIVE. This review was an effort to systematically examine the nationwide data available on pediatric burns requiring hospitalization to reveal burn epidemiology and guide future education and prevention. METHODS. The China Biomedical Disk Database, Chongqing VIP Database, and China Journal Full-Text Database were searched for articles reporting data on children and their burns from January 2000 through December 2005. Studies were included that systematically investigated the epidemiology of pediatric burns requiring hospitalization in China. Twenty-eight articles met the inclusion criteria, all of which were retrospective analyses. For each study included, 2 investigators independently abstracted the data related to the population description by using a standard form and included the percentage of patients with burn injury who were <15 years old; gender and distribution of age; type of residential area; place of injury; distribution of months and time; reasons for burn; anatomical sites of burn; severity of burn; and mortality and cause of death. These data were extracted, and a retrospective statistical description was performed with SPSS11.0 (SPSS Inc. Chicago, IL). RESULTS. Of the pediatric patients studied, the proportion of children with burn injury ranged from 22.50% to 54.66%, and the male/female ratio ranged from 1.25:1 to 4.42:1. The ratio of children aged ≤3 years to those >3 years was 0.19:1 to 4.18:1. The rural/urban ratio was 1.60:1 to 12.94:1. The ratio of those who were burned indoors versus outdoors was 1.62 to 17.00, and there were no effective hints on the distribution of seasons and anatomical sites of burn that could be found. The peak hours of pediatric burn were between 17:00 and 20:00. Most articles reported the sequence of reasons as hot liquid > flame > electricity > chemical, and scalding was, by far, the most predominant reason for burn. The majority of the studies reported the highest proportion involved in moderate burn, and the lowest proportion was for critical burn. The mortality rate ranged from 0.49% to 9.08%, and infection, shock, and multiple organ dysfunction syndrome were the most common causes of death. CONCLUSIONS. Considering the national proportion of children, a high proportion of hospitalized patients with burn injury were children; those who were male, aged ≤3 years, and lived most of the time indoors were especially susceptible. Great attention should be paid when hot water is used or during suppertime. This compilation and analysis of hospitalization-based information has proved useful in establishing the rational priorities tor prevention; a family-school-factory-government mode of preventive strategy has come into being and was performed effectively. [ABSTRACT FROM AUTHOR]

T-bet, a Th1-specific transcription factor, can promote the production of IFN-γ. IFN-γ is the principal Th1 effector cytokine and it has a crucial role in Th1 differentiation, which can drive the differentiation of naïve CD4+T cells into T-helper 1 (Th1) cells. In our study, a human T-bet gene was fused with a gene fragment encoding HIV-1 protein transduction domain in a bacterial expression vector to produce a Tat/T-bet fusion protein. The expressed and purified Tat/T-bet proteins were transduced efficiently into THP-1 cells in a time- and dose-dependent manner; when Tat/T-bet pretreated THP-1 cells were co-cultured with CD4+T cells, the IFN-γ level increased higher to about 7 pg/ml, 10-folds as compared with the normal level when tested at 48 hours. The results demonstrated that the Tat/T-bet fusion protein can be efficiently transduced into antigen-presenting cells (APCs) like THP-1 cells and then regulated Th1/Th2 balance, which may act as a potential tool for gene therapy. [ABSTRACT FROM AUTHOR]

Abstract: The special design considerations for a unique high-power multiple-pulse induction module at megahertz repetition rate burst mode are presented and a prototype triple-pulse induction module has been constructed to verify the engineering feasibility of such a scheme. In the prototype module, three single pulses produced independently by three Marx-charged Blumlein pulse forming lines are isolated and merged by six high-voltage rectifier diodes. Experiments conducted with an iron-based metallic glass (1K101) test induction cell demonstrate that a train of three ∼250kV pulses separated by 800ns can be obtained in the induction gap of the cell without resetting the magnetic cores between pulses. A pulse with a rise time of 35ns, ±1% flat top of 60ns, and full-width at half-maximum of 120ns was obtained when tested with a formal linear induction cell and finely tuned. It appears that nonlinear characterization of magnetic cores results in an increase in magnetization current and voltage drop pulse by pulse; the distortion of voltage waveform is not observed in the module if the voltage-seconds of the magnetic cores are sufficient. Because 1K101 metallic glass core has two times the equivalent flux swing of that of NiZn ferrite, metallic glass is advantageous for designing a compact multiple-pulse induction cell. The maximum amplitude of the voltage reversal is about 26% of that of the incident pulse when the cores are saturated. [Copyright &y& Elsevier]

VEGF, nitric oxide (NO), inflammation, and vascular- and extravascular remodeling coexist in asthma and other disorders. In these responses, VEGF regulates angiogenesis. VEGF also induces inflammation and remodeling. The mechanisms of the latter responses have not been defined, however. We hypothesized that VEGF-induces extravascular tissue responses via NO-dependent mechanisms. To evaluate this hypothesis, we compared the effects of transgenic VEGF165 in lungs from normal mice, mice treated with pan-NO synthase (NOS) or endothelial NOS (eNOS) inhibitors, and mice with null mutations of inducible NOS (iNOS) or eNOS. These studies demonstrate that VEGF selectively stimulates eNOS and iNOS. They also demonstrate that VEGF induces pulmonary alterations via NO-dependent and -independent mechanisms with angiogenesis, edema, mucus metaplasia, airway hyperresponsive- ness, lymphocyte accumulation, dendritic cell hyperplasia and S-nitrosoglutathione reductase stimulation being NO-dependent and dendritic cell activation being NO-independent. Furthermore, they demonstrate that eNOS and iNOS both contribute to these responses. NO/NOS-based interventions may be therapeutic in VEGF-driven inflammation and remodeling. [ABSTRACT FROM AUTHOR]

IL-13 dysregulation plays a critical role in the pathogenesis of a variety of inflammatory and remodeling diseases. In these settings, STAT6 is believed to be the canonical signaling molecule mediating the tissue effects of IL-13. Signaling cascades involving MAPKs have been linked to inflammation and remodeling. We hypothesized that MAPKs play critical roles in effector responses induced by IL-13 in the lung. We found that Tg IL-13 expression in the lung led to potent activation of ERK1/2 but not JNK1/2 or p38. ERK1/2 activation also occurred in mice with null mutations of STAT6. Systemic administration of the MAPK/ERK kinase 1 (MEK1) inhibitor PD98059 or use of Tg mice in which a dominant-negative MEK1 construct was expressed inhibited IL-13-induced inflammation and alveolar remodeling. There were associated decreases in IL-13-induced chemokines (MIP-1alpha/CCL-3, MIP-1beta/CCL-4, MIP-2/CXCL-1, RANTES/CCL-5), MMP-2, -9, -12, and -14, and cathepsin B and increased levels of alpha1-antitrypsin. IL-13-induced tissue and molecular responses were noted that were equally and differentially dependent on ERK1/2 and STAT6 signaling. Thus, ERK1/2 is activated by IL-13 in the lung in a STAT6-independent manner where it contributes to IL-13-induced inflammation and remodeling and is required for optimal IL-13 stimulation of specific chemokines and proteases as well as the inhibition of specific antiproteases. ERK1/2 regulators may be useful in the treatment of IL-13-induced diseases and disorders. [ABSTRACT FROM AUTHOR]

Functionalized arylcopper reagents have been produced in good yields at 25 °C from activated copper and the corresponding functionalized aryl iodides without the need of traditional organolithium or Grignard precursors. These organocopper compounds will undergo carboxylation with CO2 to form the corresponding copper benzoates. In turn, these salts can be acidified to produce the functionalized aryl acids or treated with appropriate alkyl halides in the presence of a dipolar aprotic solvent to generate the corresponding aryl esters. This methodology permits the formation of functionalized organic acids and esters that could not be generated by the carboxylation of organomagnesium compounds. [ABSTRACT FROM AUTHOR]

Hyperoxic acute lung injury (HALI) is characterized by a cell death response with features of apoptosis and necrosis that is inhibited by IL-11 and other interventions. We hypothesized that Bfl-1/A1, an antiapoptotic Bcl-2 protein, is a critical regulator of HALI and a mediator of IL-11-induced cytoprotection. To test this, we characterized the expression of A1 and the oxygen susceptibility of WT and IL-11 Tg(+) mice with normal and null A1 loci. In WT mice, 100% O(2) caused TUNEL(+) cell death, induction and activation of intrinsic and mitochondrial-death pathways, and alveolar protein leak. Bcl-2 and Bcl-xl were also induced as an apparent protective response. A1 was induced in hyperoxia, and in A1-null mice, the toxic effects of hyperoxia were exaggerated, Bcl-2 and Bcl-xl were not induced, and premature death was seen. In contrast, IL-11 stimulated A1, diminished the toxic effects of hyperoxia, stimulated Bcl-2 and Bcl-xl, and enhanced murine survival in 100% O(2). In A1-null mice, IL-11-induced protection, survival advantage, and Bcl-2 and Bcl-xl induction were significantly decreased. VEGF also conferred protection via an A1-dependent mechanism. In vitro hyperoxia also stimulated A1, and A1 overexpression inhibited oxidant-induced epithelial cell apoptosis and necrosis. A1 is an important regulator of oxidant-induced lung injury, apoptosis, necrosis, and Bcl-2 and Bcl-xl gene expression and a critical mediator of IL-11- and VEGF-induced cytoprotection. [ABSTRACT FROM AUTHOR]

Hyperoxic acute lung injury (HALI) is characterized by a cell death response with features of apoptosis and necrosis that is inhibited by IL-11 and other interventions. We hypothesized that Bfl-1/A1, an antiapoptotic Bcl-2 protein, is a critical regulator of HALI and a mediator of IL-11-induced cytoprotection. To test this, we characterized the expression of Al and the oxygen susceptibility of WT and IL-11 Tg(+) mice with normal and null A1 loci. In WT mice, 100% O2 caused TUNEL+ cell death, induction and activation of intrinsic and mitochondrial-death pathways, and alveolar protein leak. Bcl-2 and Bcl-xl were also induced as an apparent protective response. Al was induced in hyperoxia, and in Al-null mice, the toxic effects of hyperoxia were exaggerated, Bcl-2 and Bcl-xl were not induced, and premature death was seen. In contrast, IL-11 stimulated A1, diminished the toxic effects of hyperoxia, stimulated Bcl-2 and Bcl-xl, and enhanced murine survival in 100% O2. In A1-null mice, IL-11-induced protection, survival advantage, and Bcl-2 and Bcl-xl induction were significantly decreased. VEGF also conferred protection via an A1-dependent mechanism. In vitro hyperoxia also stimulated A1, and A1 overexpression inhibited oxidant-induced epithelial cell apoptosis and necrosis. A1 is an important regulator of oxidant-induced lung injury, apoptosis, necrosis, and Bcl-2 and Bcl-xl gene expression and a critical mediator of IL-11- and VEGF-induced cytoprotection. [ABSTRACT FROM AUTHOR]

Presents a study which compared the remodeling and inflammatory effects of an interleukin-13 (IL-13) transgene in lungs of wild-type, matrix metalloproteinases(MMP)-90-deficient, or matrix metalloproteinases-12-deficient mice. Discussion on tissue remodeling responses; Role of MMP in IL-13-induced alterations in lung volume and alveolar size; Role of MMP-12 in IL-13-induced tissue fibrosis; Effects of MMP deficiency on IL-13 induction of lung proteases.

IL-13 potently stimulates eosinophilic and lymphocytic inflammation and alveolar remodeling in the lung, effects that depend on the induction of various matrix metalloproteinases (MMPs). Here, we compared the remodeling and inflammatory effects of an IL-13 transgene in lungs of wild-type, MMP-9-deficient, or MMP-12-deficient mice. IL-13-induced alveolar enlargement, lung enlargement, compliance alterations, and respiratory failure and death were markedly decreased in the absence of MMP-9 or MMP-12. Moreover, IL-13 potently induced MMPs-2, -12, -13, and -14 in the absence of MMP-9, while induction of MMPs-2, -9, -13, and -14 by IL-13 was diminished in the absence of MMP-12. A deficiency in MMP-9 did not alter eosinophil, macrophage, or lymphocyte recovery, but increased the recovery of total leukocytes and neutrophils in bronchoalveolar lavage (BAL) fluids from IL-13 transgenic mice. In contrast, a deficiency in MMP-12 decreased the recovery of leukocytes, eosinophils, and macrophages, but not lymphocytes or neutrophils. These studies demonstrate that IL-13 acts via MMPs-9 and -12 to induce alveolar remodeling, respiratory failure, and death and that IL-13 induction of MMPs-2, -9, -13, and -14 is mediated at least partially by an MMP-12-dependent pathway. The also demonstrate that MMPs-9 and -12 play different roles in the generation of IL-13-induced inflammation, with MMP-9 inhibiting neutrophil accumulation and MMP-12 contributing to the accumulation of eosinophils and macrophages. [ABSTRACT FROM AUTHOR]

An alternative vaccine design approach and diagnostic kits are highly required against the anticipated pandemicity caused by the South African Territories type 2 (SAT2) Foot and Mouth Disease Virus (FMDV). However, the distinct antigenicity and immunogenicity of VP1, VP0, and VP3 of FMDV serotype SAT2 are poorly understood. Similarly, the particular roles of the three structural proteins in novel vaccine design and development remain unexplained. We therefore constructed VP1, VP0, and VP3 encoding gene (SAT2:JX014256 strain) separately fused with His-SUMO (histidine-small ubiquitin-related modifier) inserted into pET-32a cassette to express the three recombinant proteins and separately evaluated their antigenicity and immunogenicity in mice. The fusion protein was successfully expressed and purified by the Ni-NTA resin chromatography. The level of serum antibody, spleen lymphocyte proliferation, and cytokines against the three distinct recombinant proteins were analyzed. Results showed that the anti-FMDV humoral response was triggered by these proteins, and the fusion proteins did enhance the splenocyte immune response in the separately immunized mice. We observed low variations among the three fusion proteins in terms of the antibody and cytokine production in mice. Hence, in this study, results demonstrated that the structural proteins of SAT2 FMDV could be used for the development of immunodiagnostic kits and subunit vaccine designs. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is resulted from activations of polyol pathway and oxidative stress by abnormal metabolism of glucose, and no specific medication is available. We designed a novel class of benzoxazolone derivatives, and a number of individuals were found to have significant antioxidant activity and inhibition of aldose reductase of the key enzyme in the polyol pathway. The outstanding compound (E)-2-(7-(4-hydroxy-3-methoxystyryl)-2-oxobenzo[d]oxazol-3(2H)-yl)acetic acid was identified to reduce urinary proteins in diabetic mice suggesting an alleviation in the diabetic nephropathy, and this was confirmed by kidney hematoxylin-eosin staining. Further investigations showed blood glucose normalization, declined in the polyol pathway and lipid peroxides, and raised glutathione and superoxide dismutase activity. Thus, we suggest a therapeutic function of the compound for DN which could be attributed to the combination of hypoglycemic, aldose reductase inhibition and antioxidant. [Display omitted] • A novel class of benzoxazolone derivatives had significant activities in antioxidant and inhibition of aldose reductase. • Most potent one of them showed the activities in diabetic mice and also in blood glucose normalization. • An alleviation in diabetic nephropathy was confirmed by urinary proteins reduction and kidney hematoxylin-eosin staining. [ABSTRACT FROM AUTHOR]

A recently discovered human glycoprotein, chitinase 3-like 1 (Chi3L1), may play a role in inflammation, tissue remodeling, and visceral fat accumulation. We hypothesize that Chi3L1 gene expression is important in the development of hepatic insulin resistance characterized by the generation of pAKT, pGSK, and pERK in wild type and Chi3L1 knockout (KO) murine liver following insulin stimulation. The Chi3L1 gene and protein expression was evaluated by Real Time PCR and ELISA; lipid accumulation in hepatocytes was also assessed. To alter Chi3L1 function, three different anti-Chi3L1 monoclonal antibodies (mAbs) were administered in vivo and effects on the insulin signaling cascade and hepatic lipid deposition were determined. Transmission of the hepatic insulin signal was substantially improved following KO of the CHi3L1 gene and there was reduced lipid deposition produced by a HFD. The HFD-fed mice exhibited increased Chi3L1 expression in the liver and there was impaired insulin signal transduction. All three anti-Chi3L1 mAbs partially restored hepatic insulin sensitivity which was associated with reduced lipid accumulation in hepatocytes as well. A KO of the Chi3L1 gene reduced lipid accumulation and improved insulin signaling. Therefore, Chi3L1 gene upregulation may be an important factor in the generation of NAFLD/NASH phenotype. [ABSTRACT FROM AUTHOR]

The treatment of chronic wounds is a major challenge in regenerative medicine, and angiogenesis is known to be critical for chronic wound healing. Hot springs with temperature in the range of 30–45 °C can promote blood circulation, and some hot spring elements including iron and silicon are also known to be active in promoting angiogenesis. Inspired by the hot spring function, we designed a novel bioactive photothermal hydrogel with "hot spring effect" based on fayalite (FA) and N, O-carboxymethyl chitosan (NOCS), which releases bioactive ions and has heating function to create hot ion environment in wound area. The hot spring-mimetic hydrogel showed significant enhancement of angiogenesis and chronic wound healing in vivo due to the in situ heating through photothermal effect combined with the bioactive ions (Fe2+ and SiO 4 4−) released from the hydrogel. It is further confirmed that the synergetic effect of the mild heating and bioactive ions on angiogenesis was mainly because of the activation of different angiogenic factors and signaling pathways. Our study suggests that the hot spring-mimetic approach may be an effective strategy to design bioactive materials for promoting angiogenesis and tissue regeneration. [ABSTRACT FROM AUTHOR]

• A test bench with function of dynamic load self-balancing was designed to facilitate full-scale fatigue test for sticks indoors. The fatigue life of bolt connections was predicted. The predicted fatigue lives were mostly in line with actual lives, which proved the feasibility of prediction method. • The force distribution of bolt group was non-uniform. In other words, bolts of different materials and sizes should be selected to match fatigue bench test of components. • In terms of SEM results, high quality bolts should be selected. In this study, a new bench device with full-scale fatigue test for excavator stick was designed. The test bench has the function of dynamic load self-balancing, because a part of the load applied to the specimen of stick is directly transferred to the pillars of the test machine through the high-strength bolts connection. Accordingly, the ground under the test machine was not affected by the test load. However, some bolts located on the fatigue test bench failed and fractured during fatigue testing for excavator stick. To determine the failure reasons of bolts, mechanical and scanning electron microscope (SEM) analyses were conducted. The tensile stress of bolt group under ultimate load was evaluated via finite element model (FEM) of test bench according to test load spectrum. Moreover, under the test load spectrum, the stress range of bolt group was obtained and the fatigue life prediction of bolts was conducted by referring to Eurocode 3. It should be noted that the results of numerical simulation of fatigue lives for failure bolts were consistent with the actual lives of failure bolts during test. A fractured surface on one of the failed bolts was examined by SEM observation to determine the failure initiation and failure mode. [ABSTRACT FROM AUTHOR]

Hot film sensors detect the flow shear stress based on the forced convection heat transfer to the fluid. Current hot film sensors have been significantly hindered by the relatively low sensitivity due to the massive heat conduction to the substrate. This paper describes the design, fabrication, simulation, and testing of a novel flow sensor with dual-layer hot film structures. More specifically, the heat conduction was insulated from the sensing heater to the substrate by controlling both sensing and guarding heaters working at the same temperature, resulting in a higher sensitivity. The experiment and simulation results showed that the sensitivity of the dual-layer hot film sensor was significantly improved in comparison to the single-layer sensor. Additionally, the dual-layer sensor was designed and fabricated in an integrated, flexible, and miniaturized manner. Its small size makes it an excellent candidate for flow detection. [ABSTRACT FROM AUTHOR]

As rate-limited enzyme of polyol pathway, aldose reductase (ALR2) is one of the key inhibitory targets for alleviating diabetic complications. To reduce the toxic side effects of the inhibitors and to decrease the level of oxidative stress, the inhibitory selectivity towards ALR2 against detoxicating aldehyde reductase (ALR1) and antioxidant activity are included in the design of multifunctional ALR2 inhibitors. Hydroxypyridinone derivatives were designed, synthesized and evaluated their inhibitory behavior and antioxidant activity. Notably, {2-[2-(3,4-dihydroxy-phenyl)-vinyl]-5-hydroxy-4-oxo-4H-pyridin-1-yl}-acetic acid (7l) was the most potent, with IC50 values of 0.789 μM. Moreover, 7l showed excellent selectivity towards ALR2 with selectivity index 25.23, which was much higher than that of eparlestat (17.37), the positive control. More significantly, 7l performed powerful antioxidative action. At a concentration of 1 μM, phenolic compounds 7l scavenged DPPH radical with an inhibitory rate of 41.48%, which was much higher than that of the well-known antioxidant Trolox, at 11.89%. Besides, 7l remarkably suppressed lipid peroxidation with a rate of 88.76% at a concentration of 100 μM. The binding mode derived from molecular docking proved that the derivatives were tightly bound to the activate site, suggesting strongly inhibitory action of derivatives against ALR2. Therefore, these results provided an achievement of multifunctional ALR2 inhibitors capable with potency for both selective ALR2 inhibition and as antioxidants. [ABSTRACT FROM AUTHOR]

Dihydrobenzoxazinone derivatives revealed potent activities of aldose reductase inhibition and antioxidant against diabetic complications. Dihydrobenzoxazinone based design and synthesis produced two series of compounds as aldose reductase (ALR2) inhibitor candidates. In particular, phenolic residues were embodied into the compounds for the combination of strengthening the inhibitory acitvity and antioxidant ability to retard the progression of diabetic complications. Most of the derivatives with styryl side chains exhibited excellent activities on selective ALR2 inhibition with IC 50 values ranging from 0.082 to 0.308 μM, and {8-[2-(4-hydroxy-phenyl)-vinyl]-2-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl}-acetic acid (3a) was the most potent. More significantly, most of dihydrobenzoxazinone compounds revealed not only good inhibitory effect on ALR2, but also showed powerful antioxidant activity. Notably, phenolic compound 3a was even comparable to the well-known antioxidant Trolox, confirming that the C8 p-hydroxystyryl substitution was key structure of lowering oxidative stress. Therefore, these results provided an achievement of multifunctional ALR2 inhibitors possessing capacities for both ALR2 inhibition and as antioxidants. [ABSTRACT FROM AUTHOR]

A colorimetric logic gate based on free gold nanoparticles is presented with melamine and Hg2+, as well as its colorimetric detection of Hg2+ with good selectivity and sensitivity. [ABSTRACT FROM AUTHOR]

Increasing evidences support that glial connexins are involved in the demyelination pathology of multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. Here, we review the data from patients with MS and animal models of MS that implicate connexins in demyelination. Connexins expressed in oligodendrocytes and astrocytes show diverse changes at the different phases of MS. Loss of oligodendrocyte or astrocyte connexins contributes to demyelination and exaggerates the pathology of MS. Channel-dependent and –independent connexins are involved in the pathology of demyelination, which is related with myelin integrity, metabolic homeostasis, the brain-blood barrier, the immune cell infiltration, and the inflammatory response. A comprehensive understanding of connexin function in demyelination may provide new therapeutic targets for MS. • Connexins in oligodendrocytes and astrocytes play an essential role in the development and maintenance of myelin. • The function of connexins in oligodendrocytes and astrocytes is important in MS pathology. • Role of connexins in demyelination phase may provide novel therapeutic targets for MS. [ABSTRACT FROM AUTHOR]

The systematic separation strategy has long and widely been applied in the research and development of herbal medicines. However, the pharmacological effects of many bioactive constituents are much weaker than those of the corresponding herbal extracts. Thus, there is a consensus that purer herbal extracts are sometimes less effective. Pharmacological loss of purified constituents is closely associated with their significantly reduced intestinal absorption after oral administration. In this review, pharmacokinetic synergies among constituents in herbal extracts during intestinal absorption were systematically summarized to broaden the general understanding of the pharmaceutical nature of herbal medicines. Briefly, some coexisting constituents including plant-produced primary and secondary metabolites, promote the intestinal absorption of active constituents by improving solubility, inhibiting first-pass elimination mediated by drug-metabolizing enzymes or drug transporters, increasing the membrane permeability of enterocytes, and reversibly opening the paracellular tight junction between enterocytes. Moreover, some coexisting constituents change the forms of bioactive constituents via mechanisms including the formation of natural nanoparticles. This review will focus on explaining this new synergistic mechanism. Thus, herbal extracts can be considered mixtures of bioactive compounds and pharmacokinetic synergists. This review may provide ideas and strategies for further research and development of herbal medicines. [ABSTRACT FROM AUTHOR]