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• The activity of BN was highly improved by modulating the crystallinity of BN. • The high crystallinity could probably reduce the energy barrier for the activation of adsorbed O 2. • The activation of adsorbed O 2 is related to the formation of active site. In this work, we optimized the catalytic performances of h-BN in propane oxidative dehydrogenation by modulating the catalyst crystallinity. The propane conversion rate per unit specific surface area of the catalyst (-mol C 3 H 8 /m2/s) was improved by almost ten times by modulating the crystallinity of BN catalyst, gaining a propylene productivity of about 3.10 μmol g cat−1 s−1. The reaction activity presented a negative relationship with the specific surface area but positively related to the crystallinity of BN. High degree of crystallinity is proved to be beneficial for the binding of O 2 to BN by the O 2 -TPD results and zeta potentials of BN-T, which could probably reduce the energy barrier for the activation of O 2 and the formation of active sites. Additionally, the increase in propane conversion with the increase of reaction temperature tends to be gentle when the reaction temperature is above 530 °C, and it is almost equal to zero for O 2 /C 3 H 8 value increasing from 1.30 to 2.00, indicating an energy-efficient and economical route to convert C 3 H 8 over BN catalyst with high crystallinity. [ABSTRACT FROM AUTHOR]

The ubiquitous presence of microplastics in aquatic environments is considered a global threat to aquatic organisms. Species of the genus Daphnia provide an important link between aquatic primary producers and consumers of higher trophic levels; furthermore, these organisms exhibit high sensitivity to various environmental pollutants. Hence, the biological effects of microplastics on Daphnia species are well documented. This paper reviews the latest research regarding the ecotoxicological effects of microplastics on Daphnia , including the: 1) responses of individual, population, and community attributes of Daphnia to microplastics; 2) influence of the physical and chemical properties of microplastics; and 3) joint toxicity of microplastics and other pollutants on responses of Daphnia. Our literature review found that the published literature does not provide sufficient evidence to reveal the risks of microplastics at the population and community levels. Furthermore, we emphasized that high-level analysis has more general implications for understanding how individual-level research can reveal the ecological hazards of microplastics on Daphnia. Based on this review, we suggest avenues for future research, including microplastic toxicology studies based on both omics-based and community-level methods, especially the latter. [Display omitted] • This paper reviews ecotoxicological effects of microplastics (MP) on Daphnia. • Few studies reveal ecotoxicity of MP at population and community levels. • Influence of MP on Daphnia varies according to shape, size, color, etc. • The joint toxic effects of MP and other pollutants on Daphnia cannot be ignored. [ABSTRACT FROM AUTHOR]

Background Sepsis has high morbidity and mortality. The aim of this study was to investigate whether emodin, an anthraquinone derived from Chinese herb, exerts protective effects on lung injury in rat model of sepsis. Materials and methods Forty-eight male Wistar rats were randomly divided into four groups ( n = 12): normal group, sham-operated group, cecal ligation and puncture (CLP) model group, and emodin-treated group. Saline or emodin (25 mg/kg) was injected intraperitoneally 0.5 h before CLP. The rats were sacrificed 48 h after CLP. Lung wet-to-dry weight ratio and pathologic changes in the lung were examined, the contents of malondialdehyde and myeloperoxidase in lung tissue were detected, serum tumor necrosis factor alpha and interleukin 6 levels were measured by enzyme-linked immunosorbent assay, and the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was detected by Western blot analysis. Results Compared with control group, CLP group exhibited higher wet-to-dry weight ratio and water content in the lung ( P < 0.01), but these indexes were reduced and pathologic changes in the lung were relieved in the emodin-treated group. In addition, lung malondialdehyde and myeloperoxidase contents, serum levels of tumor necrosis factor alpha and interleukin 6, and phosphorylation of p38 MAPK increased in the CLP group but decreased in the emodin-treated group ( P < 0.05). Conclusions Emodin exerts protective effects on lung injury in septic rats, which is related to the inhibition of p38 MAPK pathway and the reduction of oxidative stress and inflammation response during sepsis. [ABSTRACT FROM AUTHOR]

Abstract: The 3C-like main peptidase 3CLpro is a viral polyprotein processing enzyme essential for the viability of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). While it is generalized that 3CLpro and the structurally related 3Cpro viral peptidases cleave their substrates via a mechanism similar to that underlying the peptide hydrolysis by chymotrypsin-like serine proteinases (CLSPs), some of the hypothesized key intermediates have not been structurally characterized. Here, we present three crystal structures of SARS 3CLpro in complex with each of two members of a new class of peptide-based phthalhydrazide inhibitors. Both inhibitors form an unusual thiiranium ring with the nucleophilic sulfur atom of Cys145, trapping the enzyme''s catalytic residues in configurations similar to the intermediate states proposed to exist during the hydrolysis of native substrates. Most significantly, our crystallographic data are consistent with a scenario in which a water molecule, possibly via indirect coordination from the carbonyl oxygen of Thr26, has initiated nucleophilic attack on the enzyme-bound inhibitor. Our data suggest that this structure resembles that of the proposed tetrahedral intermediate during the deacylation step of normal peptidyl cleavage. [Copyright &y& Elsevier]

Abstract: We have solved the crystal and molecular structures of hepatitis A viral (HAV) 3C proteinase, a cysteine peptidase having a chymotrypsin-like protein fold, in complex with each of three tetrapeptidyl-based methyl ketone inhibitors to resolutions beyond 1.4 Å, the highest resolution to date for a 3C or a 3C-Like (e.g. SARS viral main proteinase) peptidase. The residues of the β-hairpin motif (residues 138–158), an extension of two β-strands of the C-terminal β-barrel of HAV 3C are critical for the interactions between the enzyme and the tetrapeptide portion of these inhibitors that are analogous to the residues at the P4 to P1 positions in the natural substrates of picornaviral 3C proteinases. Unexpectedly, the Sγ of Cys172 forms two covalent bonds with each inhibitor, yielding an unusual episulfide cation (thiiranium ring) stabilized by a nearby oxyanion. This result suggests a mechanism of inactivation of 3C peptidases by methyl ketone inhibitors that is distinct from that occurring in the structurally related serine proteinases or in the papain-like cysteine peptidases. It also provides insight into the mechanisms underlying both the inactivation of HAV 3C by these inhibitors and on the proteolysis of natural substrates by this viral cysteine peptidase. [Copyright &y& Elsevier]

Hepatitis A virus (HAV) 3C proteinase is a member of the picornain cysteine proteases responsible for the processing of the viral polyprotein, a function essential for viral maturation and infectivity. This and its structural similarity to other 3C and 3C-like proteases make it an attractive target for the development of antiviral drugs. Previous solution NMR studies have shown that a Cys24Ser (C24S) variant of HAV 3C protein, which displays catalytic properties indistinguishable from the native enzyme, is irreversibly inactivated by N-benzyloxycarbonyl-l-serine-β-lactone (1a) through alkylation of the sulfur atom at the active site Cys172. However, crystallization of an enzyme–inhibitor adduct from the reaction mixture followed by X-ray structural analysis shows only covalent modification of the ε2-nitrogen of the surface His102 by the β-lactone with no reaction at Cys172. Re-examination of the heteronuclear multiple quantum coherence (HMQC) NMR spectra of the enzyme–inhibitor mixture indicates that dual modes of single covalent modification occur with a ≥3:1 ratio of S-alkylation of Cys172 to N-alkylation of His102. The latter product crystallizes readily, probably due to the interaction between the phenyl ring of the N-benzyloxycarbonyl (N-Cbz) moiety and a hydrophobic pocket of a neighboring protein molecule in the crystal. Furthermore, significant structural changes are observed in the active site of the 3C protease, which lead to the formation of a functional catalytic triad with Asp84 accepting one hydrogen bond from His44. Although the 3C protease modified at Cys172 is catalytically inactive, the singly modified His102 Nε2-alkylated protein displays a significant level of enzymatic activity, which can be further modified/inhibited by N-iodoacetyl-valine-phenylalanine-amide (IVF) (in solution and in crystal) or excessive amount of the same β-lactone inhibitor (in solution). The success of soaking IVF into HAV 3C–1a crystals demonstrates the usefulness of this new crystal form in the study of enzyme–inhibitor interactions in the proteolytic active site. [Copyright &y& Elsevier]

Group-living animals can affect each other's behaviour, causing changes in the rate or type of behaviours performed (social facilitation), or convergence in behaviour to that displayed by the majority of neighbours (social conformity). Facilitation and conformity effects can act to reduce direct competition and/or enable social coordination, and the degree to which individuals can affect each other's behaviour can depend upon the identities and traits of those interacting. To investigate the effect of social partners on individual behaviour, we studied the activity of Java sparrows, Lonchura oryzivora , in three contexts (alone, in the presence of three males or in the presence of three females) and in two conditions (novel environment and novel object tests). A significant proportion of variation in bird activity across trials was attributed to variation among individuals, indicating a personality trait. However, activity varied systematically according to whether birds were tested alone or in the presence of companions. We found that irrespective of the focal bird's sex, individuals were more active in a social context than when alone, and this effect was greatest when focal birds were in the presence of male companions. Overall, our findings demonstrate facilitative effects of social partners on Java sparrow activity, and the magnitude of this effect depended on the sex of the companions. These results therefore support the hypothesis that social isolation causes behavioural inhibition (which may be caused by increased perception of risk), and future studies should carefully assess the need to consider the social context when studying personality and its ecological and evolutionary processes across different species and contexts. • Social facilitation occurs when an individual's behaviour increases that of others. • Social facilitation depends on the identities and traits of companions. • Social isolation causes behavioural inhibition. • Java sparrows were more active in a social context than when alone. • Social facilitation was greatest when male companions were present. [ABSTRACT FROM AUTHOR]

Breast cancer is the most frequently diagnosed tumor type and the primary leading cause of cancer deaths in women worldwide. Drug resistance is the major obstacle for breast cancer treatment improvement. TRAIL-inducing compound 10 (Tic10), a novel activator of FOXO3, exhibits potent antitumor efficacy both in vitro and in vivo. In the present study, we investigated the resistance reversal effect of Tic10 on multidrug-resistant breast cancer cells T47D/5Fu derived from T47D breast cancer cells. We found that FOXO3a was significantly decreased in T47D/5-Fu cells, whereas treatment of Tic10 enhances FOXO3a expression and nuclear translocation. Moreover, treatment of Tic10 could reverses 5-Fluorouracil resistance of T47D/5-Fu cells via induction of G0/G1 cell cycle arrest and apoptosis. Furthermore, we found that Tic10 decreased the expression of CDK4 via FOXO3a-dependment mechanism. In addition, our data showed that Tic10 could sensitize drug resistant T47D/5-Fu cells to 5-Fu in vivo. Taken together, these data suggested Tic10 as capable of restoring sensitivity for drug-resistant breast cancer cells. [ABSTRACT FROM AUTHOR]

Visible-light photcatalysts of BiNbO4 and BiTaO4 powders have been successfully synthesized by a citrate method. The formation of pure triclinic phase of BiNbO4 and BiTaO4 at low temperature of 700°C can be attributed to the advantage of the citrate method. The photocatalytic activity and possible mechanism were investigated deeply. For BiNbO4 particles, the mechanism of methyl violet (MV) degradation under visible light irradiation involves photocatalytic and photosensitization pathways and the catalyst specific surface area has dominant influence. While for BiTaO4 particles, the dominant mechanism arises from photosensitization pathways and a trade off between high specific surface area and good crystallinity is achieved. BiNbO4 powder calcined at 700°C shows the best photocatalytic efficiency among these catalysts, which is ascribed to its large surface area and more positive conduction band level. The optimal catalyst loading, additive H2O2 concentration and pH value is around 1g/L, 2mmol/L and 8mmol/L, respectively. [ABSTRACT FROM AUTHOR]

Abstract: 5-Fluorouracil (5-FU) is commonly used to treat breast cancer; however, it becomes increasingly ineffective with tumor progression. Epithelial-to-mesenchymal transition (EMT) is a process whereby cells acquire morphologic and molecular alterations facilitating tumor metastasis and progression. Emerging evidence associates chemoresistance with acquisition of EMT in cancer. However, it is not clear whether this phenomenon is involved in acquired resistance to 5-FU. Using a previously established in vitro cell model of 5-fluorouracil-resistant MCF7 cells (MCF7/5-FU), we assessed the cellular morphology, molecular changes, migration and invasion consistent with EMT. We found that silencing of Snail by stable RNA interference reversed the EMT and greatly abolished invasion behavior of MCF7/5-FU cells. We also showed that inhibition of Snail increased the sensitivity of 5-FU-resistant cells to 5-FU. Our study provided a new insight into EMT-like phenotypic changes associated with 5-FU resistance in MCF7 cells. We believed that down-regulation of Snail could be a potential novel therapeutic approach to overcoming chemoresistance and preventing metastasis during 5-FU chemotherapy. [Copyright &y& Elsevier]

The autophagy/apoptosis interaction has always been a focus of study in pathogenicity models. Neuritin is a neurotrophic factor that is highly expressed primarily in the central nervous system. Our previous study revealed that it protects against apoptosis in cortical neurons subjected to oxygen-glucose deprivation (OGD)/reoxygenation (OGD/R), and later animal experiments revealed that it can increase the expression of the autophagy-related protein LC3. Whether this neuroprotective effect is closely related to autophagy is still unclear. In this study, we hypothesized that neuritin can promote autophagic flux to protect nerve cells after OGD/R. To verify this hypothesis, we induced OGD/R in primary cortical neurons and assessed cell viability by the CCK8 and LDH assays. Cell apoptosis was assessed by Annexin V-FITC/PI, staining, and the contents and mRNA abundances of the autophagy-related proteins LC3 and p62, the apoptotic protein Caspase3 were quantified by Western blotting and RT-PCR. Autophagic flux was assessed by immunofluorescence after RFP-GFP-LC3 virus transfection, and ultrastructural changes in autophagosomes were observed by transmission electron microscopy (TEM). The results showed that cell viability was decreased, apoptosis was increased and autophagy was enhanced after OGD/R. Neuritin significantly increased cell viability, decreased apoptosis, further increased the expression of the autophagic flux-related protein LC3, further decreased p62 expression, and significantly increased the autophagosome number and autophagosome to lysosome ratio. Bafilomycin A1 (BafA1) is a late autophagy inhibitor, aggravated cell damage and apoptosis and counteracted the enhancement of autophagy activation and protective effects of neuritin. In conclusion, neuritin may promote the completion of autophagic flux by ameliorating neuronal damage after OGD/R. • Neuritin promotes the activation of autophagic flux. • Treatment with OGD/R increased LC3 conversion, the expression level of p62 and decreased the fusion of autophagosomes and lysosomes. • OGD/R represented decreased autophagic flux. • Treatment with neuritin recovered the autophagic flux inhibited by OGD/R. [ABSTRACT FROM AUTHOR]

Abstract: The severe acute respiratory syndrome (SARS) virus depends on a chymotrypsin-like cysteine proteinase (3CLpro) to process the translated polyproteins to functional viral proteins. This enzyme is a target for the design of potential anti-SARS drugs. A series of ketones and corresponding mono- and di-fluoro ketones having two or three aromatic rings were synthesized as possible reversible inhibitors of SARS 3CLpro. The design was based on previously established potent inhibition of the enzyme by oxa analogues (esters), which also act as substrates. Structure–activity relationships and modeling studies indicate that three aromatic rings, including a 5-bromopyridin-3-yl moiety, are key features for good inhibition of SARS 3CLpro. Compound 11d, 2-(5-bromopyridin-3-yl)-1-(5-(4-chlorophenyl)furan-2-yl)ethanone and its α-monofluorinated analogue 12d, gave the best reversible inhibition with IC50 values of 13μM and 28μM, respectively. In contrast to inhibitors having two aromatic rings, α-fluorination of compounds with three rings unexpectedly decreased the inhibitory activity. [Copyright &y& Elsevier]