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Significant Suppression of Non-small-cell Lung Cancer by Hydrophobic Poly(ester amide) Nanoparticles with High Docetaxel Loading
No full textNon-small-cell lung cancer (NSCLC) accounts for over 85% of clinical lung cancer cases, which is the leading cause of cancer-related death. To develop new therapeutic strategy for NSCLC, a library of L-phenylalanine-based poly(ester amide) (Phe-PEA) polymers was synthesized and assembled with docetaxel (Dtxl) to form Dtxl-loaded Phe-PEA nanoparticles (NPs). The hydrophobic Phe-PEA polymers were able to form NPs by nanoprecipitation method and the characterization results showed that the screened Dtxl-8P4 NPs have small particle size (similar to 100 nm) and high Dtxl loading (similar to 20 wt%). In vitro experiments showed that Dtxl-8P4 NPs were rapidly trafficked into cancer cells, then effectively escaped from lysosomal degradation and achieved significant tumor cell inhibition. In vivo results demonstrated that Dtxl-8P4 NPs with prolonged blood circulation could efficiently deliver Dtxl to A549 tumor sites, leading to reduced cell proliferation, block metastasis, and increase apoptosis, then persistent inhibition of tumor growth. Therefore, Phe-PEA NPs are able to load high amount of hydrophobic drugs and could be a promising therapeutic approach for NSCLC and other cancer treatments
Directly mining a fungal thermostable alpha-amylase from Chinese Nong-flavor liquor starter
No full textBackground: Chinese Nong-flavor (NF) liquor is continuously and stably produced by solid-state fermentation technology for 1000 years, resulting in enrichment of special microbial community and enzymes system in its starter. Based on traditional culture-dependent methods, these functional enzymes are hardly obtained. According to our previous metatranscriptomic analysis, which identifies plenty of thermostable carbohydrate-active enzymes in NF liquor starter, the aim of this study is to provide a direct and efficient way to mine these thermostable enzymes. Results: In present study, an alpha-amylase (NFAmy13A) gene, which showed the highest expression level of enzymes in starch degradation at high temperature stage (62 degrees C), was directly obtained by functional metatran-scriptomics from Chinese Nong-flavor liquor starter and expressed in Pichia pastoris. NFAmy13A had a typical signal peptide and shared the highest sequence identity of 64% with alpha-amylase from Aspergillus niger. The recombinant enzyme of NFAmy13A showed an optimal pH at 5.0-5.5 and optimal temperature at 60 degrees C. NFAmy13A was activated and stabilized by Ca2+, and its half-lives at 60 and 70 degrees C were improved significantly from 1.5 and 0.4 h to 16 and 0.7 h, respectively, in the presence of 10 mM CaCl2. Meanwhile, Hg2+, Co2+ and SDS largely inhibited its activity. NFAmy13A showed the maximum activity on amylopectin, followed by various starches, amylose, glycogen, and pullulan, and its specificity activity on amylopectin was 200.4 U/mg. Moreover, this alpha-amylase efficiently hydrolyzed starches (from corn, wheat, and potato) at high concentrations up to 15 mg/ml. Conclusions: This study provides a direct way to mine active enzymes from man-made environment of NF liquor starter, by which a fungal thermostable alpha-amylase (NFAmy13A) is successfully obtained. The good characteristics of NFAmy13A in degrading starch at high temperature are consistent with its pivotal role in solid-state fermentation of NF liquor brewing. This work would stimulate mining more enzymes from NF liquor starter and studying their potentially synergistic roles in NF liquor brewing, thus paving the way toward the optimization of liquor production and improvement of liquor quality in future
Correlates of ecological-niche diversity and extinction risk of amphibians in China under climate change
No full textIn the present study, we measured spatiotemporal properties of ecological niches of amphibians in China and tested the relative importance of various niche-diversity metrics for explaining the evolutionary distinctiveness-weighted extinction risk (EDGE) of amphibian species. We applied the hierarchical partitioning technique on the phylogenetically independent contrasts of the niche covariates and EDGE of amphibians, for the purpose of removing the influence of evolutionary inertia among species. As a comparison, phylogenetic least-square general regression (PLGS) was also conducted. The results showed that EDGE was high for those amphibian species of China identified as Critically Endangered or Endangered on the IUCN Red List. Niche fragmentation dimension (NFD) and niche position (NP) were the top two predictors across partial correlation analyses, hierarchical variation partitioning, PLGS and multiple regression analyses. Most temporal niche properties were not significantly associated with the EDGE index of amphibians. Variation partitioning analysis showed that the spatial component of niche measures explained the largest proportion of total variation in EDGE (similar to 31%), whereas the temporal component of niche properties explained similar to 8% of the variation. The significantly negative role of NFD and extinction risk of amphibians in China may be attributed to a reduced rescue effect, habitat geometry, and local extinction in species with large and continuous distributional ranges
Sex chromosomal dimorphisms narrated by X-chromosome translocation in a spiny frog (Quasipaa boulengeri)
No full textBackground: In the general model of sex chromosome evolution for diploid dioecious organisms, the Y (or W) chromosome is derived, while the homogametic sex presumably represents the ancestral condition. However, in the frog species Quasipaa boulengeri, heteromorphisms caused by a translocation between chromosomes 1 and 6 are not related to sex, because the same heteromorphic chromosomes are found both in males and females at the cytological level. To confirm whether those heteromorphisms are unrelated to sex, a sex-linked locus was mapped at the chromosomal level and sequenced to identify any haplotype difference between sexes. Results: Chromosome 1 was assigned to the sex chromosome pair by mapping the sex-linked locus. X-chromosome translocation was demonstrated and confirmed by the karyotypes of the progeny. Translocation heteromorphisms were involved in normal and translocated X chromosomes in the rearranged populations. Based on phylogenetic inference using both male and female sex-linked haplotypes, recombination was suppressed not only between the Y and normal X chromosomes, respectively the Y and translocated X chromosomes, but also between the normal and translocated X chromosomes. Both males and females shared not only the same translocation heteromorphisms but also the X chromosomal dimorphisms in this frog. Conclusions: The reverse of the typical situation, in which the X is derived and the Y has remained unchanged, is known to be very rare. In the present study, X-chromosome translocation has been known to cause sex chromosomal dimorphisms. The X chromosome has gone processes of genetic differentiation and/or structural changes by chance, which may facilitate sex chromosome differentiation. These sex chromosomal dimorphisms presenting in both sexes may represent the early stages of sex chromosome differentiation and aid in understanding sex chromosome evolution
Responses of soil respiration and its components to experimental warming in an alpine scrub ecosystem on the eastern Qinghai-Tibet Plateau
No full textThe responses of soil respiration (R-s) to warming are driven by its components, that is, heterotrophic respiration (R-h) and rhizosphere respiration (R-r, including fine root respiration [R-fr] and rhizomicrobial respiration [R-z]). However, the effects of warming on R-s and its components are rarely studied in alpine scrub ecosystems on the Qinghai-Tibet Plateau. Here, we conducted a warming experiment to examine how R-s and its components respond to experimental warming. We found that one-year experimental warming (increased by 1.3 degrees C) significantly stimulated the rates of R-s, R-h and R-r by 21.6, 23.8, and 21.1%, respectively. The annual cumulative C effluxes of R-s increased by 87.87 g m(-2) with nearly equal contributions from R-h (46.84 g m(-2)) and R-r (41.03 g m(-2)) under warming. Moreover, warming-induced increase in R-r mainly resulted from increased R-fr rather than R-z due to the significant increase in fine root biomass and R-fr rate. In addition, the Q(10) values for R-s, R-h and R-r were also increased by experimental warming, while the contribution of R-h to R-s was not altered by experimental warming. Collectively, our results suggest that future climatic warming will stimulate more C releases from soil to the atmosphere through an enhancement of both R-h and R-r in these alpine scrub ecosystems on the Qinghai-Tibet Plateau. (C) 2018 Elsevier B.V. All rights reserved
Hydrochloric Acid-Promoted Copper/Iron-Cocatalyzed Deesterificative Oxyphosphorylation of 2-Substituted Acrylates with H-Phosphine Oxides
No full textAn unprecedented method for the transformation of 2-substituted acrylates into beta-ketophosphine oxides has successfully been developed via hydrochloric acid-promoted copper/iron-cocatalyzed deesterificative oxyphosphorylation under dioxygen atmosphere, simultaneously inhibiting the formation of the preceding hydroxyphosphorylation products. Through this convenient and practical process, a library of structurally diverse beta-ketophosphine oxides could be selectively and effectively obtained with broad substrate scope and good functional group tolerance under mild conditions, accompanied by chemoselective cleavage of C(sp(2))-C(C=O) bonds
Oxadiazepine Synthesis by Formal [4+3] Cycloaddition of o-Chloromethyl Arylsulfonamides with Nitrones Promoted by NaHCO3
No full textAn effective and facile method for the synthesis of highly substituted 1,2,3,5-tetrahydrobenzo[e][1,2,4]-oxadiazepines is described. A formal [4+3] cycloaddition of N-(2-(chloromethyl) phenyl) amides with nitrones afforded benzo[e][1,2,4]-oxadiazepine derivatives with high atom economy and excellent yields (up to 97%)
Profiling the origin, dynamics, and function of traction force in B cell activation
No full textB lymphocytes use B cell receptors (BCRs) to recognize membrane-bound antigens to further initiate cell spreading and contraction responses during B cell activation. We combined traction force microscopy and live-cell imaging to profile the origin, dynamics, and function of traction force generation in these responses. We showed that B cell activation required the generation of 10 to 20 nN of traction force when encountering antigens presented by substrates with stiffness values from 0.5 to 1 kPa, which mimic the rigidity of antigen-presenting cells in vivo. Perturbation experiments revealed that F-actin remodeling and myosin- and dynein-mediated contractility contributed to traction force generation and B cell activation. Moreover, membrane-proximal BCR signaling molecules (including Lyn, Syk, Btk, PLC-gamma 2, BLNK, and Vav3) and adaptor molecules (Grb2, Cbl, and Dok-3) linking BCR microclusters and motor proteins were also required for the sustained generation of these traction forces. We found a positive correlation between the strength of the traction force and the mean fluorescence intensity of the BCR microclusters. Furthermore, we demonstrated that isotype-switched memory B cells expressing immunoglobulin G (IgG)-BCRs generated greater traction forces than did mature naive B cells expressing IgM-BCRs during B cell activation. Last, we observed that primary B cells from patients with rheumatoid arthritis generated greater traction forces than did B cells from healthy donors in response to antigen stimulation. Together, these data delineate the origin, dynamics, and function of traction force during B cell activation
Evaluation of the estimate bias magnitude of the Rao's quadratic diversity index
No full textRao's quadratic diversity index is one of the most widely applied diversity indices in functional and phylogenetic ecology. The standard way of computing Rao's quadratic diversity index for an ecological assemblage with a group of species with varying abundances is to sum the functional or phylogenetic distances between a pair of species in the assemblage, weighted by their relative abundances. Here, using both theoretically derived and observed empirical datasets, we show that this standard calculation routine in practical applications will statistically underestimate the true value, and the bias magnitude is derived accordingly. The underestimation will become worse when the studied ecological community contains more species or the pairwise species distance is large. For species abundance data measured using the number of individuals, we suggest calculating the unbiased Rao's quadratic diversity index