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Purpose: To evaluate the outcomes and toxicities of adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) in elderly (≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (LANPC, stage III‐IVa). Methods and Materials: Using an NPC‐specific database, 245 elderly patients with stage III‐IVa NPC, receiving CCRT +/− NAC, and an Adult Co‐morbidity Evaluation 27 (ACE‐27) score <2 were included. Recursive partitioning analysis (RPA) based on TNM stage and Epstein–Barr virus (EBV) DNA were applied for risk stratification. The primary end point was disease‐free survival (DFS). Results: Two risk groups were generated by the RPA model. In the high‐risk group (EBV DNA < 4000 copy/ml with stage IVa & EBV DNA ≥4000 copy/ml with stage III‐IVa), patients treated with NAC plus CCRT achieved improved 5‐year DFS rates compared to those who received CCRT alone (56.9% vs. 29.4%; p = 0.003). But we failed to observe the survival benefit of additional NAC in the low‐risk group (EBV DNA <4000 copy/ml with stage III). The most common severe acute toxic effects were leucopenia (46.8% vs. 24.4%) and neutropenia (43.7% vs. 20.2%) in the NAC plus CCRT group versus CCRT group with statistically significant differences. Conclusions: The addition of NAC to CCRT was associated with better DFS for the high‐risk group of elderly LANPC patients with ACE‐27 score <2. However, the survival benefit of additional NAC was not observed in low‐risk patients. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are well known for their immunoregulatory roles on allergic inflammation particularly by acting on T cells, B cells, and dendritic cells (DCs). MSC‐derived small extracellular vesicles (MSC‐sEV) are increasingly considered as one of the main factors for the effects of MSCs on immune responses. However, the effects of MSC‐sEV on DCs in allergic diseases remain unclear. MSC‐sEV were prepared from the induced pluripotent stem cells (iPSC)‐MSCs by anion‐exchange chromatography, and were characterized with the size, morphology, and specific markers. Human monocyte‐derived DCs were generated and cultured in the presence of MSC‐sEV to differentiate the so‐called sEV‐immature DCs (sEV‐iDCs) and sEV‐mature DCs (sEV‐mDCs), respectively. The phenotypes and the phagocytic ability of sEV‐iDCs were analyzed by flow cytometry. sEV‐mDCs were co‐cultured with isolated CD4+T cells or peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis. The levels of Th1 and Th2 cytokines produced by T cells were examined by ELISA and intracellular flow staining. And the following mechanisms were further investigated. We demonstrated that MSC‐sEV inhibited the differentiation of human monocytes to iDCs with downregulation of the expression of CD40, CD80, CD86, and HLA‐DR, but had no effects on mDCs with these markers. However, MSC‐sEV treatment enhanced the phagocytic ability of mDCs. More importantly, using anti‐IL‐10 monoclonal antibody or IL‐10Rα blocking antibody, we identified that sEV‐mDCs suppressed the Th2 immune response by reducing the production of IL‐4, IL‐9, and IL‐13 via IL‐10. Furthermore, sEV‐mDCs increased the level of Treg cells. Our study identified that mDCs treated with MSC‐sEV inhibited the Th2 responses, providing novel evidence of the potential cell‐free therapy acting on DCs in allergic airway diseases. [ABSTRACT FROM AUTHOR]

With the excessive consumption and pollution of water resources, the sustainable development of water resources poses a serious threat currently. How to perceive and prevent the degradation of water resource in advance is an urgent problem. The water resource carrying capacity (WRCC) is a significant indicator to reflect the condition of water resources in a region. Resounding to these circumstances, our research establishes a decision support framework to solve WRCC risk evaluation issues. First, hesitant probabilistic fuzzy sets (HPFSs) are selected as a representation for the evaluation information in the expert group. Aimed at existing studies of HPFSs, some limitations are overcome involving the distance and comparison rule. Secondly, a TODIM‐PROMETHEE II based multi‐criteria group decision making (MCGDM) method is developed to overcome the inherent restrictions of PROMETHEE II method and make it suitable for a practical decision‐making condition with bounded rationality. Subsequently, a case study is utilized to demonstrate the feasibility of our newly proposed decision support framework, followed by a sensitivity analysis and a comparison analysis. The outcome indicates that the framework has an excellent performance to solve this kind of MCGDM issues. [ABSTRACT FROM AUTHOR]

A palladium‐catalyzed asymmetric intramolecular Heck reaction of aryl iodides with alkynyl carboxylic acids has been developed, delivering various indoline frameworks in moderate to excellent yields (up to 95 %) with excellent enantioselectivities (up to 96 % ee) and diastereoselectivities (>20 : 1) using BINOL‐based phosphoramidite as chiral ligand. This cascade annulation protocol, which tolerates a broad variety of functional groups and is conducted under an argon atmosphere, provides efficient and atom‐economical access to structurally diverse 2,3‐disubstituted indolines bearing vicinal tertiary and quaternary stereocenters. Additionally, the synthetic products could be converted to useful unique indoline derivatives without loss of enantiomeric excess. [ABSTRACT FROM AUTHOR]

Metazoans harbor a wealth of symbionts that are ever‐changing the environment by taking up resources and/or excreting metabolites. One such common environmental modification is a change in pH. Conventional wisdom holds that symbionts facilitate the survival and production of their hosts in the wild, but this notion lacks empirical evidence. Here, we report that symbiotic bacteria in the genus Enterococcus attenuate the oviposition avoidance of alkaline environments in Drosophila. We studied the effects of alkalinity on oviposition preference for the first time, and found that flies are robustly disinclined to oviposit on alkali‐containing substrates. This innate repulsion to alkaline environments is explained, in part, by the fact that alkalinity compromises the health and lifespan of both offspring and parent Drosophila. Enterococcus dramatically diminished or even completely reversed the ovipositional avoidance of alkalinity in Drosophila. Mechanistically, Enterococcus generate abundant lactate during fermentation, which neutralizes the residual alkali in an egg‐laying substrate. In conclusion, Enterococcus protects Drosophila from alkali stress by acidifying the ovipositional substrate, and ultimately improves the fitness of the Drosophila population. Our results demonstrate that symbionts are profound factors in the Drosophila ovipositional decision, and extend our understanding of the intimate interactions between Drosophila and their symbionts. [ABSTRACT FROM AUTHOR]

Group 2 innate lymphoid cells (ILC2s) are recently reported to play a more critical role in allergic diseases. We previously identified that mesenchymal stromal cells (MSCs) elicited therapeutic effects on allergic airway inflammation. Small extracellular vesicles (sEV) derived from MSCs possess striking advantages including low immunogenicity and high biosafety, and is extremely promising cell-free therapeutic agents. However, the effects of MSC-sEV on ILC2s are still unclear. Additionally, scalable isolation protocols are required for the mass production of homogenous MSC-sEV especially in clinical application. We previously reported that induced pluripotent stem cells-derived MSCs were the ideal cellular source for the large preparation of MSC-sEV. Here we developed a standardized scalable protocol of anion-exchange chromatography for isolation of MSC-sEV, and investigated the effects of MSC-sEV on ILC2 function from patients with allergic rhinitis and in a mouse ILC2-dominant asthma model. The characterization of MSC-sEV was successfully demonstrated in terms of size, morphology and specific markers. Using flow cytometry and human Cytokine Antibody Array, MSC-sEV but not fibroblasts-sEV (Fb-sEV) were found to significantly inhibit the function of human ILC2s. Similarly, systemic administration of MSC-sEV but not Fb-sEV exhibited an inhibition of ILC2 levels, inflammatory cell infiltration and mucus production in the lung, a reduction in levels of T helper 2 cytokines, and alleviation of airway hyperresponsiveness in a mouse model of asthma. Using RNA sequencing, miR-146a-5p was selected as the candidate to mediate the above effects of MSC-sEV. We next revealed the uptake of ILC2s to MSC-sEV, and that transfer of miR-146a-5p in MSC-sEV to ILC2s in part contributed to the effects of MSC-sEV on ILC2s in vitro and in a mouse model. In conclusion, we demonstrated that MSC-sEV were able to prevent ILC2-dominant allergic airway inflammation at least partially through miR-146a-5p, suggesting that MSC-sEV could be a novel cell-free strategy for the treatment of allergic diseases. [ABSTRACT FROM AUTHOR]

In the multi‐criteria group decision‐making (MCGDM) problems with great uncertainty, making full use of participants' evaluation information could help improve the accuracy and reliability of decision results. Probabilistic linguistic term set (PLTS) is an effective tool to represent qualitative data and can fully express the hesitation and preference of decision makers. Therefore, this paper aims to propose an MCGDM method based on PLTSs. In the proposed method, the projection of PLTSs is explored to measure the distance and angle differences between two objects, and Bayesian best–worst method (Bayesian BWM) is used to determine the aggregated final weights of criteria. Besides, the elimination and choice translating reality III (ELECTRE III) method combined with distillation algorithm deals with the projection of PLTSs to obtain the alternatives' ranking of each decision maker. Then, the weighted convex median voting rule is developed to integrate the rankings results regarding all decision makers, which can solve the conflict of ranking results among experts and ensure that the comprehensive ranking results are reasonable and practical. Finally, a case study of health‐care waste management is designed and comparative analyses are implemented to show the effectiveness and advantages of the proposed method. [ABSTRACT FROM AUTHOR]

Direct sulfonamidation of quinoxalin‐2(1H)‐one derivatives has been developed using a readily available Cu salt as the catalyst and inexpensive ammonium persulfate as the oxidant in moderate conditions. Owing to the feature of handy operation and good functional group tolerance, this method provides a convenient and efficient access to curative 3‐sulfonamidated quinoxalin‐2(1H)‐one scaffolds. [ABSTRACT FROM AUTHOR]

Background: Genetics is best dedicated to interpreting pathogenesis and revealing gene functions. The past decade has witnessed unprecedented progress in genetics, particularly in genome‐wide identification of disorder variants through Genome‐Wide Association Studies (GWAS) and Phenome‐Wide Association Studies (PheWAS). However, it is still a great challenge to use GWAS/PheWAS‐derived data to elucidate pathogenesis. Methods: In this study, we used HotNet2, a heat diffusion‐based systems genetics algorithm, to calculate the networks for disease genes obtained from GWAS and PheWAS, with an attempt to get deeper insights into disease pathogenesis at a molecular level. Results: Through HotNet2 calculation, significant networks for 202 (for GWAS) and 167 (for PheWAS) types of diseases were identified and evaluated, respectively. The GWAS‐derived disease networks exhibit a stronger biomedical relevance than PheWAS counterparts. Therefore, the GWAS‐derived networks were used for pathogenesis interpretation by integrating the accumulated biomedical information. As a result, the pathogenesis for 64 diseases was elucidated in terms of mutation‐caused abnormal transcriptional regulation, and 47 diseases were preliminarily interpreted in terms of mutation‐caused varied protein‐protein interactions. In addition, 3,802 genes (including 46 function‐unknown genes) were assigned with new functions by disease network information, some of which were validated through mice gene knockout experiments. Conclusions: Systems genetics algorithm HotNet2 can efficiently establish genotype‐phenotype links at the level of biological networks. Compared with original GWAS/PheWAS results, HotNet2‐calculated disease‐gene associations have stronger biomedical significance, hence provide better interpretations for the pathogenesis of genome‐wide variants, and offer new insights into gene functions as well. These results are also helpful in drug development. [ABSTRACT FROM AUTHOR]

Three (R,R)‐3,4‐diaminopyrrolidine‐based chiral N4 ligands and corresponding iron complexes were synthesized. The complexes were applied to the asymmetric epoxidation of various α,β‐unsaturated ketones with H2O2 as an oxidant and carboxylic acid as auxiliary. Good to excellent enantioselectivity (up to 97%) was achieved in the case of 2,2‐dimethylbutyric acid as an auxiliary. [ABSTRACT FROM AUTHOR]

A novel highly efficient, environmentally benign Lewis acid‐catalyzed, and protection‐free protocol for the construction of valuable polycyclic products bearing a 1H‐pyrrolo[1,2‐a]indole scaffold is described, starting from readily available propargylic alcohols and 2‐ethynylanilines. The one‐pot transformation entails the cleavage of one C−O bond, and the construction of two C−N bonds and one C−C double bond. This unique operationally simple method is performed under mild conditions and in air, producing water as the only byproduct; it is scalable and demonstrates good functional group compatibility and broad scope. [ABSTRACT FROM AUTHOR]

Gamma‐proteobacteria Xanthomonas spp. cause at least 350 different plant diseases among important agricultural crops, which result in serious yield losses. Xanthomonas spp. rely mainly on the type III secretion system (T3SS) to infect their hosts and induce a hypersensitive response in nonhosts. HrpG, the master regulator of the T3SS, plays the dominant role in bacterial virulence. In this study, we used chromatin immunoprecipitation followed by sequencing (ChIP‐seq) and tandem affinity purification (TAP) to systematically characterize the HrpG regulon and HrpG interacting proteins in vivo. We obtained 186 candidate HrpG downstream genes from the ChIP‐seq analysis, which represented the genomic‐wide regulon spectrum. A consensus HrpG‐binding motif was obtained and three T3SS genes, hpa2, hrcU, and hrpE, were confirmed to be directly transcriptionally activated by HrpG in the inducing medium. A total of 273 putative HrpG interacting proteins were identified from the TAP data and the DNA‐binding histone‐like HU protein of Xanthomonas campestris pv. campestris (HUxcc) was proved to be involved in bacterial virulence by increasing the complexity and intelligence of the bacterial signalling pathways in the T3SS. [ABSTRACT FROM AUTHOR]

A direct C–H alkylation of quinoxalinones at the C‐3 position with sodium alkylsulfinates and phenyliodine(III) dicarboxylates has been developed under catalyst‐free conditions. A series of 3‐alkylquinoxalinones were afforded in moderate to excellent yields in this protocol, which offers a practical and efficient access to biologically interesting 3‐alkylquinoxalin‐2(1H)‐one derivatives. [ABSTRACT FROM AUTHOR]

Actual stochastic multicriteria decision‐making (MCDM) problems usually exhibit two forms of information loss: criteria value uncertainty and criteria weight uncertainty. In this paper, extended gray numbers (EGNs), integrated with discrete gray numbers and interval gray numbers are used to express the uncertainty of stochastic MCDM problems. Stochastic multicriteria acceptability analysis (SMAA) and ELECTRE III are combined to solve stochastic MCDM problems with uncertain weight information. First, the outranking relations on interval gray numbers and EGNs are defined. Then, a SMAA‐ELECTRE model for dealing with gray stochastic MCDM problems is constructed. Finally, an illustrative example and two comparative analyses are provided to verify the feasibility and usability of the proposed approach. The proposed approach provides recommendations for alternatives based on uncertain preference information. It therefore contributes a new way to solve stochastic MCDM problems with uncertain, imprecise, and/or missing preference information. [ABSTRACT FROM AUTHOR]

A copper‐catalyzed direct C−H difluoroacetylation of quinoxalinones at the C‐3 position with ethyl bromodifluoroacetate has been developed. In this reaction, diverse difluoroacetylated quinoxalin‐2(1H)‐ones with a wide range of functional groups could be obtained in moderate to good yields, using cheap, commercially available reagents. This protocol would offer a meaningfully synthetic method for pharmacologically interesting difluoroacetylated quinoxalin‐2(1H)‐one derivatives. [ABSTRACT FROM AUTHOR]

Transcriptional regulation involves a series of sophisticated protein–protein and protein–DNA interactions (PPI and PDI). Some transcriptional complexes, such as c‐Fos/c‐Jun and their binding DNA fragments, have been conserved over the past one billion years. Considering the thermodynamic principle for transcriptional complex formation, we hypothesized that the c‐Fos/c‐Jun complex may represent a thermodynamic summit in the evolutionary space. To test this, we invented a new method, termed One‐Pot‐seq, which combines cDNA display and proximity ligation to analyse PPI/PDI complexes simultaneously. We found that the wild‐type c‐Fos/c‐Jun complex is indeed the most thermodynamically stable relative to various mutants of c‐Fos/c‐Jun and binding DNA fragments. Our method also provides a universal approach to detect transcriptional complexes and explore transcriptional regulation mechanisms. [ABSTRACT FROM AUTHOR]

A convenient C−H amination of quinoxalin‐2‐ones has been developed. This transformation provides concise access to 3‐aminoquinoxalin‐2(1H)‐ones with a broad tolerance of functional groups, utilizing TMSN3 as an amino source under simple and mild conditions. The target 3‐aminoquinoxalin‐2(1H)‐ones are important intermediates for the synthesis of biologically active 3‐N‐substituted quinoxalin‐2‐one derivatives. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) regulate various biological processes during insect development; however, their role in larval–pupal development in oriental fruit fly, Bactrocera dorsalis (Hendel) remains unknown. In the current study, we address the biological function of a conserved miRNA, Bdo‐Let‐7 in the regulation of BdE75 gene, which belongs to the ecdysone signaling pathway and participates in the larval–pupal development in B. dorsalis. Using dual luciferase reporter assay in HEK293T cells we show that Bdo‐Let‐7 miRNA interacts with the 3′ untranslated region of BdE75 gene and suppresses its expression. The Bdo‐Let‐7 and BdE75 are also co‐expressed in the larval–pupal stages and in different tissues of B. dorsalis. In in vivo experiments, the injection of Bdo‐Let‐7 agomir and antagomir in third instar larvae down‐ and up‐regulated the expression of BdE75, respectively. The 20‐hydroxyecdysone (20E) injection assay shows that 20E up‐regulated the expression of Bdo‐Let‐7 on the 5th day of the larvae. Moreover, abnormal pupation and eclosion were observed after larval Bdo‐Let‐7 antagomir injection. Based on these results, we show that Bdo‐Let‐7 regulates the ecdysone signaling pathway through the exact dose of BdE75 gene, and is indispensable for normal larval–pupal development in B. dorsalis. [ABSTRACT FROM AUTHOR]

Interleukin (IL)‐17A is pro‐inflammatory cytokine which has been identified as a noninvasive marker of the pathogenesis of non‐alcoholic steatohepatitis (NASH). However, the underlying role of IL‐17A in NASH progression remains unclear. This study was designed to investigate the biological function and molecular mechanism of IL‐17A in the induction of NASH. The results showed that IL‐17A was highly expressed in high‐fat diet (HFD)‐induced NASH mouse model. Intravenous injection of IL‐17A exacerbated steatohepatitis process via promoting hepatocyte apoptosis. Furthermore, IL‐17A‐induced apoptosis was mediated by ERK1/2/p65 signaling pathway. In conclusion, we demonstrated that IL‐17A‐mediated ERK1/2/p65 signaling pathway was a promising target for the treatment of NASH. © 2018 IUBMB Life, 71(3):302–309, 2019 [ABSTRACT FROM AUTHOR]

A convenient and efficient protocol for the synthesis of thetetrazolo[1,5‐a]quinoxalin‐4(5H)‐ones via copper‐catalyzed [3+2] cyclization of azidotrimethylsilane with quinoxalin‐2(1H)‐ones under mild conditions has been disclosed. This practical protocol is compatible with a variety of functional groups and provides an access to functionalized tetrazolo[1,5‐a]quinoxalin‐4(5H)‐ones from readily available and safe starting materials. [ABSTRACT FROM AUTHOR]

The main objective of this work was to investigate the uptake channels of skin cells through which coumarin 6, transported by deoxycholate‐mediated liposomes (DOC‐LS), was internalised; this was also compared against the action of conventional LS. Coumarin 6‐loaded DOC‐LS and LS were characterised for size distribution, zeta potential, and shape, and analysed in vitro in human epidermal immortal keratinocyte (HaCaT) (epidermal) and human embryonic skin fibroblast (CCC‐ESF‐1) (dermal) cell lines. Various endocytosis inhibitors were incubated with cells treated with the nanocarriers. Flow cytometry results indicated that HaCaT and CCC‐ESF‐1 cells internalise the tested preparations through pinocytotic vesicles, macropinocytosis, clathrin‐mediated endocytic pathways, and via lysosomes, which consume a considerable amount of energy. The endocytosis pathways of DOC‐LS and LS showed no difference. This study provides a basis for the application of LS being combined with a microneedle system for efficient intracellular drug delivery, targeting cutaneous histocyte disorders. [ABSTRACT FROM AUTHOR]

Disclosed herein is a direct C−H trifluoromethylation of quinoxalin‐2(1H)‐ones with sodium trifluoromethanesulfinate. This protocol affords a series of 3‐trifluoromethylquinoxalin‐2(1H)‐one derivatives in moderate to excellent yields under transition‐metal‐free conditions. The present methodology features utilization of the inexpensive trifluoromethyl source without transition‐metal‐catalysts, mild reaction conditions and high functional group tolerance, which promises a convenient and efficient access to pharmaceutically interesting quinoxalinones. [ABSTRACT FROM AUTHOR]

Abstract: In the modern drug discovery pipeline, identification of novel drug targets is a critical step. Despite rapid progress in developing biomedical techniques, it is still a great challenge to find promising new targets from the ample space of human genes. This fact is partially responsible for the situation of “more investments, fewer drugs” in the pharmaceutical industry. A series of recent researches revealed that successfully targeted genes share some common evolutionary and genetic features, which means that the knowledge accumulated in modern evolutionary biology and genetics is very helpful to identify potential drug targets and to find new drugs as well. In this article, we comprehensively summarize the links between human drug targets and genetic diseases and their evolutionary origins, with an attempt to introduce these novel concepts and their medical implications to the biomedical community. [ABSTRACT FROM AUTHOR]

Abstract: A convenient and efficient manganese‐catalyzed trifluoromethylazidation of alkenes has been developed by utilizing inexpensive and readily available CF3SO2Na under mild conditions. The various β‐trifluoromethylated alkyl azides were directly obtained from corresponding allyl, vinyl, chain terminal and internal alkenes, and easily further transformed into other CF3‐containing compounds. [ABSTRACT FROM AUTHOR]

We reconstructed the first genome-scale metabolic network of the plant pathogen Pectobacterium carotovorum subsp. carotovorum PC1 based on its genomic sequence, annotation, and physiological data. Metabolic characteristics were analyzed using flux balance analysis (FBA), and the results were afterwards validated by phenotype microarray (PM) experiments. The reconstructed genome-scale metabolic model, iPC1209, contains 2235 reactions, 1113 metabolites and 1209 genes. We identified 19 potential bactericide targets through a comprehensive in silico gene-deletion study. Next, we performed virtual screening to identify candidate inhibitors for an important potential drug target, alkaline phosphatase, and experimentally verified that three lead compounds were able to inhibit both bacterial cell viability and the activity of alkaline phosphatase in vitro. This study illustrates a new strategy for the discovery of agricultural bactericides. [ABSTRACT FROM AUTHOR]

A new 1,3-dihydroisobenzofuran derivative ( 1), together with its epimer ( 2), was isolated from marine Streptomyces sp. W007. The structure of the two compounds was established by extensive spectroscopic analysis and comparison with reported data. The absolute configurations of 1 and 2 were determined by a combination of experimental and computational means, including J-coupling analysis and nuclear Overhauser effect spectroscopy (NOESY) spectra, (NMR) calculations, electronic circular dichroism (ECD), and optical rotation (OR) calculations. Compound 1 had no cytotoxicity against human lung adenocarcinoma cell line A549, while compound 2 exhibited weak activity, suggesting that the depends on the configuration of a single chirality center. Chirality 27:82-87, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A series of triarylboranes, in which different substituents are introduced at the para position of the dimethylamino group of a 2-dimesitylboryl-2'-( N, N-dimethylamino)biphenyl core unit, have been comprehensively investigated to explore the effect of structural modification on photophysical properties. The introduction of electron-accepting substituents would facilitate the HOMO→LUMO charge transfer (CT) transition. In contrast, the intramolecular CT transition is significantly prohibited when electron-donating substituents are incorporated. Notably, the HOMO→LUMO CT transition mainly consists of the transition from the electron-donating amino group to an electron acceptor other than boryl when a strong electron acceptor such as the dicyanovinyl group is present. This dicyanovinyl-substituted compound displays sensing abilities to discriminate fluoride and cyanide ions. In solution in THF, the fluoride ions first bind to the boron center, then attack the α-carbon atom of the dicyanovinyl group, whereas the cyanide anion acts on the electron-accepting centers in the reverse sequence. As a result, the absorption and emission change in different manners upon addition of fluoride and cyanide ions. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSPs) are known as chaperones that help with folding of other proteins when cells are under environmental stresses. The upregulation of HSPs is essential for cold survival during insect diapause. The ectoparasitoid Habrobracon hebetor, a potential biological control agent, can enter reproductive diapause when reared at low temperature and short photoperiod. However, the expression of HSPs during diapause of H. hebetor has not been studied. In this study, we sequenced and characterized the full-length complementary DNAs of three Hsp70 genes ( HhHsp70I, HhHsp70II and HhHsp70III) from H. hebetor. Their deduced amino acid sequences showed more than 80% identities to their counterparts from other insect species. However, the multiple sequence alignment among the three deduced amino acid sequences of HhHsp70s showed only 46% identities. A phylogenetic analysis of the three HhHsp70s and all other known Hsp70 sequences from Hymenoptera clustered all the Hsp70s into four groups, and the three HhHsp70s were distributed into three different groups. Real-time quantitative polymerase chain reaction analysis showed that the expression of the three HhHsp70 genes in H. hebetor reared at different conditions was quite different. HhHsp70I showed higher relative expression when H. hebetor were reared at 27.5°C than at two lower temperatures (17.5°C and 20°C) regardless of the photoperiod, whereas HhHsp70II showed higher expression when H. hebetor were reared at 20°C and 10 : 14 L : D than when reared at 17.5°C and either 16 : 8 L : D or 10 : 14 L : D. In contrast, HhHSP70III was expressed at similar levels regardless of the rearing conditions. These results may suggest functional differences among the three HhHsp70 genes in H. hebetor. [ABSTRACT FROM AUTHOR]

Aim To investigate the mechanism of endoplasmic reticulum (ER) stress-induced apoptosis as well as the protective action of basic fibroblast growth factor ( bFGF) both in vivo and in vitro. Methods and Results ER stress-induced apoptosis was involved in the injuries of spinal cord injury (SCI) model rat. bFGF administration improved the recovery and increased the survival of neurons in spinal cord lesions in model rat. The protective effect of bFGF is related to the inhibition of CHOP, GRP78 and caspase-12, which are ER stress-induced apoptosis response proteins. bFGF administration also increased the survival of neurons and the expression of growth-associated protein 43 (GAP43), which is related to neural regeneration. The protective effect of bFGF is related to the activation of downstream signals, PI3K/Akt/GSK-3β and ERK1/2, especially in the ER stress cell model. Conclusions This is the first study to illustrate that the role of bFGF in SCI recovery is related to the inhibition of ER stress-induced cell death via the activation of downstream signals. Our work also suggested a new trend for bFGF drug development in central neural system injuries, which are involved in chronic ER stress-induced apoptosis. [ABSTRACT FROM AUTHOR]

The bacterial cellulose-poly(vinyl alcohol) (BC/PVA) nanocomposite hydrogels using BC as the reinforcement and PVA as the matrix materials were formed in coagulating bath and crosslinked with formaldehyde, and characterized by attenuated total reflection Fourier transform infrared spectroscopy, mechanical properties tests, thermogravimetric analysis, and scanning electron microscope analysis. It was known that the chemical cross-linked BC/PVA nanocomposite hydrogels exhibited some promising characteristics, such as appropriate mechanical strength and excellent thermal properties. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]

Cellulose and hemicelluloses are the most prevalent sources of carbon in nature. Currently many approaches employ micro-organisms and their enzyme products to degrade plant feedstocks for production of bioenergy. Scarab larvae are one such model. They consume celluloses from a variety of sources including plant roots, soil organic matter and decaying wood, and are able to extract nutrients and energy from these sources. In this paper, we review the physicochemical properties of the scarab larval gut, the diversity and digestive role that microflora play in the scarab gut and discuss the potential for applying these digestive processes in bioreactors for improving bio-fuel production. Scarab larvae are characterised by their highly alkaline midgut which is dominated by serine proteinase enzymes, and a modified hindgut which harbors the majority of the intestinal microbiota under anaerobic conditions. Evidence suggests that digestion of recalcitrant organic matter in scarab larvae likely results from a combination of endogenous gut proteinases and cellulolytic enzymes produced by symbiotic micro-organisms. Most of the easily digestible proteins are mobilized and absorbed in the midgut by endogenous proteinases. The hindgut contents of scarab larvae are characterized by high concentrations of volatile fatty acids, the presence of fermenting bacteria, and typical anaerobic activities, such as methanogenesis. The hindgut typically contains a wide diversity of micro-organisms, some of which appear to be obligate symbionts with cellulolytic potential. As a result, the scarab larval gut can be regarded as a small bioreactor resembling the rumen of sheep or cattle, where solid food particles composed of cellulose, hemicellulose, pectin and polysaccharides are degraded through enzymatic and fermentation processes. Together these observations suggest scarab larvae have potential to assist the bio-fuel industry by providing new sources of (hemi)cellulolytic bacteria and bacterial (hemi)cellulolytic enzymes. [ABSTRACT FROM AUTHOR]

The suitability of combining microbial pesticides and an insect parasitoid for pest management of stored cereal in China was evaluated using laboratory assays. For this purpose, interactions between Bacillus thuringiensis ( Bt), Bt-intoxicated host larvae and the parasitoid Habrobracon hebetor (Say) (Hymenoptera: Braconidae) were tested against Plodia interpunctella Hübner (Lepidoptera: Pyralidae) . Bt or H. hebetor alone caused 41.67% and 35.35% P. interpunctella larval mortality respectively. The Bt–parasitoid combined treatment significantly increased mortality of P. interpunctella (86%). Progeny development of H. hebetor was dependent upon its susceptibility to Bt. Fewer parasitoids emerged from Bt–parasitoid combined treatment than in non- Bt treatments. However, since Bt did not prevent parasitoid development, a combined treatment with Bt and parasitoid release could produce better protection against P. interpunctella than either treatments when used singly, because their lethal effects were additive to each other. [ABSTRACT FROM AUTHOR]

Plant mechanical strength is an important agronomic trait of rice. An ethyl methane sulfonate (EMS) -induced rice mutant, fragile plant 2 ( fp2), showed morphological changes and reduced mechanical strength. Genetic analysis indicated that the brittle of fp2 was controlled by a recessive gene. The fp2 gene was mapped on chromosome 10. Anatomical analyses showed that the fp2 mutation caused the reduction of cell length and cell wall thickness, increasing of cell width, and the alteration of cell wall structure as well as the vessel elements. The consequence was a global alteration in plant morphology. Chemical analyses indicated that the contents of cellulose and lignin decreased, and hemicelluloses and silicon increased in fp2. These results were different from the other mutants reported in rice. Thus, fp2 might affect the deposition and patterning of microfibrils, the biosynthesis and deposition of cell wall components, which influences the formation of primary and secondary cell walls, the thickness of cell walls, cell elongation and expansion, plant morphology and plant strength in rice. [ABSTRACT FROM AUTHOR]

Abstract: To explore whether there exist correlations between human gene expressions and corresponding sequence features, the expression levels for 81 oncogenes in 24 human tissues were collected and correlated with 159 sequence features. It was found that there do exist significant correlations between them, some of which are of significance to understanding translational selection on sequence features of human genes and some have important implications for diagnosing cancers. [Copyright &y& Elsevier]

Discovering the mechanism of protein folding, in molecular biology, is a great challenge. A key step to this end is to find factors that correlate with protein folding rates. Over the past few years, many empirical parameters, such as contact order, long-range order, total contact distance, secondary structure contents, have been developed to reflect the correlation between folding rates and protein tertiary or secondary structures. However, the correlation between proteins' folding rates and their amino acid compositions has not been explored. In the present work, we examined systematically the correlation between proteins' folding rates and their amino acid compositions for two-state and multistate folders and found that different amino acids contributed differently to the folding progress. The relation between the amino acids' molecular weight and degeneracy and the folding rates was examined, and the role of hydrophobicity in the protein folding process was also inspected. As a consequence, a new indicator called composition index was derived, which takes no structure factors into account and is merely determined by the amino acid composition of a protein. Such an indicator is found to be highly correlated with the protein's folding rate ( r > 0.7). From the results of this work, three points of concluding remarks are evident. (1) Two-state folders and multistate folders have different rate-determining amino acids. (2) The main determining information of a protein's folding rate is largely reflected in its amino acid composition. (3) Composition index may be the best predictor for an ab initio protein folding rate prediction directly from protein sequence from the standpoint of practical application. Proteins 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: The present one-drug-one-target paradigm in drug discovery has been considered partially responsible for the more-funding-less-drug predicament in modern pharmaceutical industry. To hit the multiple targets implicated in complex diseases, two strategies, based on multicomponent or single-ingredient, are conceivable. Although the latter is more difficult to be fulfilled than the former, the recent progress made in the fight against Alzheimer’s disease (AD) has brought us the first light of success of the latter strategy. In this review, both synthetic and natural multipotent agents are described, which hit two or more targets implicated in AD, e.g., acetylcholinesterase, monoamine oxidase, amyloid-β, τ protein, metal ions and reactive oxygen species. Nevertheless, due to the potential risks in safety, absorbability and pharmacokinetics of synthetic multipotent agents, natural counterparts seem more promising in the future development. [Copyright &y& Elsevier]