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Background: Whole-genome approaches are widely preferred for species delineation in prokaryotes. However, these methods require pairwise alignments and calculations at the whole-genome level and thus are computationally intensive. To address this problem, a strategy consisting of sieving (pre-selecting closely related genomes) followed by alignment and calculation has been proposed.Results: Here, we initially test a published approach called "genome-wide tetranucleotide frequency correlation coefficient" (TETRA), which is specially tailored for sieving. Our results show that sieving by TETRA requires > 40% completeness for both genomes of a pair to yield > 95% sensitivity, indicating that TETRA is completenessdependent. Accordingly, we develop a novel algorithm called "fragment tetranucleotide frequency correlation coefficient" (FRAGTE), which uses fragments rather than whole genomes for sieving. Our results show that FRAGTE achieves~100% sensitivity and high specificity on simulated genomes, real genomes and metagenome-assembled genomes, demonstrating that FRAGTE is completeness-independent. Additionally, FRAGTE sieved a reduced number of total genomes for subsequent alignment and calculation to greatly improve computational efficiency for the process after sieving. Aside from this computational improvement, FRAGTE also reduces the computational cost for the sieving process. Consequently, FRAGTE extremely improves run efficiency for both the processes of sieving and after sieving (subsequent alignment and calculation) to together accelerate genome-wide species delineation.Conclusions: FRAGTE is a completeness-independent algorithm for sieving. Due to its high sensitivity, high specificity, highly reduced number of sieved genomes and highly improved runtime, FRAGTE will be helpful for whole-genome approaches to facilitate taxonomic studies in prokaryotes.

As an endogenous gaseous mediator, H S exerts antioxidative, antiapoptotic, and cytoprotective effects in livers. This study was designed to investigate the protective role of H S against uranium-induced hepatotoxicity in adult SD male rats after in vivo effect of uranium on endogenous H S production was determined in livers. The levels of endogenous H S and H S-producing enzymes (CBS and CSE) were measured in liver homogenates from uranium -intoxicated rats. In rats injected intraperitoneally (i.p.) with uranyl acetate or NaHS (an H S donor) alone or in combination, we examined biochemical parameters to assess liver function, revealed hepatic histopathological alteration, investigated oxidative stress markers, and explored apoptotic signaling in liver homogenates. The results suggest that uranium-intoxication in rats decreased CBS and CSE protein expression, H S synthesis capacity, and endogenous H S generation. NaHS administration in uranium-intoxicated rats produced amelioration in liver biochemical indices and histopathological effects, decreased MDA content, and increased GSH level and antioxidative enzymes activities like SOD, CAT, GPx, and GST. NaHS administration in uranium-intoxicated rats attenuated uranium-activated phosphorylation state of JNK. NaHS treatment in uranium-intoxicated rats increased antiapoptotic Bcl-2 but decreased pro-apoptotic Bax, resulting in the rise of Bcl-2/Bax ratio. NaHS treatment in uranium-intoxicated rats reduced the apoptosis mediator caspase-3 and cytochrome c release and elevated ATP contents. Taken together, these data implicate that H S can afford protection to rat livers against uranium-induced adverse effects mediated by up-regulation of antioxidant and antiapoptotic signaling. The anti-apoptotic property of H S may be involved, at least in part, in inhibiting JNK signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 581-593, 2017.

Natural killer (NK) cell‐based immunotherapy holds prominent potential for cancer treatment. However, its application in solid tumors is limited by a rapid decline in viability and function, as well as inadequate homing and infiltration. Herein, a generalized strategy is offered to construct a bio‐orthogonal targeted live‐cell nanocarrier (N3‐NK‐NPs) by coupling with responsive released interleukin‐21 (IL‐21) nanoparticles (ILNPs) on glyco‐engineered NK cell surfaces. Complementary bio‐orthogonal groups (azide (N3)/bicyclo [6.1.0] nonyne (BCN), serving as an artificial ligand receptor are separately implanted into NK cells (N3‐NK) and tumor cells (BCN‐Raji) via nondestructive metabolic glycoengineering. The bio‐orthogonal strategy effectively promotes the specific recognition and migration of NK cells, showing nearly fourfold deeper infiltration in tumor than control groups. Compared with traditional systemic administration, ILNPs hitchhiking on cell vectors selectively in situ releases the IL‐21 adjuvant in the tumor to produce effective and continuous “pseudo‐autocrine” stimulation surrounding NK cells under a low dose (5 µg kg–1), which greatly promotes proliferation and activation of NK cells, resulting in enhanced therapeutic potential while limiting systemic toxicity. Importantly, live‐cell nanocarrier effectively activates innate immune system through IL‐21 triggered recruitment of multiple immunocytes, significantly improving tumor immune microenvironment. This in situ activated NK cell nanocarrier with bio‐orthogonal targeting provides a universal and powerful strategy for immune cells activation and solid tumor immunotherapy.

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Hydrogen sulfide (HS) shows antioxidative, anti-inflammatory, antiapoptotic, and cytoprotective effects in kidneys. Recently, HS has been reported to alleviate uranium-induced rat nephrotoxicity through oxidative stress and inflammatory response via Nrf2-NF-κB pathways. Here, the protective effect and molecular mechanism of HS on uranium-induced apoptosis were examined in normal rat kidney proximal cells (NRK-52) in vitro. The results indicate that NaHS (an HS donor) administration in uranium-intoxicated kidney cells ameliorated uranium-induced reactive oxygen species generation, caspase-3-dependent apoptosis, and endoplasmic reticulum (ER) stress identified through several key markers including GRP78, C/EBP homologous protein (CHOP), and caspase-12. NaHS treatment in uranium-intoxicated kidney cells abolished the effects of uranium on Akt phosphorylation, GSK-3β activation, increased Fyn nuclear expression, and concomitantly decreased Nrf2 nuclear expression. NaHS administration in uranium-treated kidney cells resorted uranium-decreased the expression of two key subunit PSMA6 and PSMB7 in 20S proteasome. But, DRB (an Nrf2 inhibitor) administration abrogated the effects of NaHS on PSMA6 and PSMB7 expression in uranium-contaminated kidney cells. Bortezomib (a proteasome inhibitor) treatment in NaHS pulsing uranium cotreated kidney cells reversed the effects of NaHS on not only PSMA6 and PSMB7 but also GRP78 and CHOP. Taken together, all data suggest that HS can attenuate uranium-induced kidney cell apoptosis mediated by ER stress via 20S proteasome involving in Akt/GSK-3β/Fyn-Nrf2 signaling axis.

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Members of the Sox gene family are characterized by an HMG-box that shows sequence similarity with that of the mouse testis-determining gene Sry. Using degenerate primers PCR, seven and eight HMG-box motifs of Sry-related genes were cloned and sequenced from genomic DNA of Trionyx sinensis (termed TS41-47) and Alligator sinensis (AS41-48) with TSD (temperature-dependent sex determination). Among 15 Sry-related genes, TS41, TS42, AS41, and AS42 shared 80, 72, 81, and 79% amino acid identity, respectively, with each HMG-box domain of the mouse Sox-1, -2, and -3 genes by Blast analysis. Molecular phylogenetic analysis showed that the clustering of TS41-42 and AS41-42 was distant to the clustering of the nonreptilian vertebrate Sox-1, -2, -3 homologs, including fish, amphibian, bird, and mammals. The amino acid identity among TS41-42, AS41-42, and the nonreptilian vertebrate Sox-1, -2, -3 homologs is lower than identities among the Sox-1, -2, -3 homologs, suggesting that the sequence changes in TS41-42 of Trionyx sinensis and AS41-42 of Alligator sinensis might have occurred after the diversification of amniotes.