Genome-wide analysis of ATP-binding cassette (ABC) transporter in Penaeus vannamei and identification of two ABC genes involved in immune defense against Vibrio parahaemolyticus by affecting NF-κB signaling pathway.

The ATP-binding cassette (ABC) transporters have crucial roles in various biological processes such as growth, development and immune defense in eukaryotes. However, the roles of ABC transporters in the immune system of crustaceans remain elusive. In this study, 38 ABC genes were systematically identified and characterized in Penaeus vannamei. Bioinformation analysis revealed that PvABC genes were categorized into ABC A-H eight subfamilies with 17 full-transporters, 11 half transporters and 10 soluble proteins, and multiple immunity-related cis-elements were found in gene promoter regions. Expression analysis showed that most PvABC genes were widely and highly expressed in immune-related tissues and responded to the stimulation of Vibrio parahaemolyticus. To investigate whether PvABC genes mediated innate immunity, PvABCC5, PvABCF1 and PvABCB4 were selected for dsRNA interference experiment. Knockdown of PvABCF1 and PvABCC5 not PvABCB4 increased the cumulative mortality of P. vannamei and bacterial loads in hepatopancreas after infection with V. parahaemolyticus. Further analysis showed that the PvABCF1 and PvABCC5 knockdown decreased expression levels of NF-κB pathway genes and antimicrobial peptides (AMPs). Collectively, these findings indicated that PvABCF1 and PvABCC5 might restrict V. parahaemolyticus challenge by positively regulating NF-κB pathway and then promoting the expression of AMPs, which would contribute to overall understand the function of ABC genes in innate immunity of invertebrates.

The Evolution and Transmission Dynamics of Multidrug-Resistant Tuberculosis in an Isolated High-Plateau Population of Tibet, China.

On the Tibetan Plateau, most tuberculosis is caused by indigenous Mycobacterium tuberculosis strains with a monophyletic structure and high-level drug resistance. This study investigated the emergence, evolution, and transmission dynamics of multidrug-resistant tuberculosis (MDR-TB) in Tibet. The whole-genome sequences of 576 clinical strains from Tibet were analyzed with the TB-profiler tool to identify drug-resistance mutations. The evolution of the drug resistance was then inferred based on maximum-likelihood phylogeny and dated trees that traced the serial acquisition of mutations conferring resistance to different drugs. Among the 576 clinical M. tuberculosis strains, 346 (60.1%) carried at least 1 resistance-conferring mutation and 231 (40.1%) were MDR-TB. Using a pairwise distance of 50 single nucleotide polymorphisms (SNPs), most strains (89.9%, 518/576) were phylogenetically separated into 50 long-term transmission clusters. Eleven large drug-resistant clusters contained 76.1% (176/231) of the local multidrug-resistant strains. A total of 85.2% of the isoniazid-resistant strains were highly transmitted with an average of 6.6 cases per cluster, of which most shared the mutation KatG Ser315Thr. A lower proportion (71.6%) of multidrug-resistant strains were transmitted, with an average cluster size of 2.9 cases. The isoniazid-resistant clusters appear to have undergone substantial bacterial population growth in the 1970s to 1990s and then subsequently accumulated multiple rifampicin-resistance mutations and caused the current local MDR-TB burden. These findings highlight the importance of detecting and curing isoniazid-resistant strains to prevent the emergence of endemic MDR-TB. IMPORTANCE Emerging isoniazid resistance in the 1970s allowed M. tuberculosis strains to spread and form into large multidrug-resistant tuberculosis clusters in the isolated plateau of Tibet, China. The epidemic was driven by the high risk of transmission as well as the potential of acquiring further drug resistance from isoniazid-resistant strains. Eleven large drug-resistant clusters consisted of the majority of local multidrug-resistant cases. Among the clusters, isoniazid resistance overwhelmingly evolved before all the other resistance types. A large bacterial population growth of isoniazid-resistant clusters occurred between 1970s and 1990s, which subsequently accumulated rifampicin-resistance-conferring mutations in parallel and accounted for the local multidrug-resistant tuberculosis burden. The results of our study indicate that it may be possible to restrict MDR-TB evolution and dissemination by prioritizing screening for isoniazid (INH)-resistant TB strains before they become MDR-TB and by adopting measures that can limit their transmission.

Transcriptomic analysis of gills in nitrite-tolerant and -sensitive families of Litopenaeus vannamei.

Nitrite stress is a major environmental factor that limits aquatic animal growth, reproduction and survival. Even so, some shrimps still can withstand somewhat high concentrations of nitrite environment. However, few studies have been conducted about the tolerance molecular mechanism of Litopenaeus vannamei in the high concentration nitrite. To identify the genes and pathways involved in the regulation of nitrite tolerance, we performed comparative transcriptomic analysis in the L. vannamei nitrite-tolerant (NT) and nitrite-sensitive (NS) families, and untreated shrimps were used as the control group. After 24 h of nitrite exposure (NaNO2, 112.5 mg/L), a total of 1521 and 868 differentially expressed genes (DEGs) were obtained from NT compared with NS and control group, respectively. Functional enrichment analysis revealed that most of these DEGs were involved in immune defense, energy metabolism processes and endoplasmic reticulum (ER) stress. During nitrite stress, energy metabolism in NT was significantly enhanced by activating the related genes expression of oxidative phosphorylation (OXPHOS) pathway and tricarboxylic acid (TCA) cycle. Meanwhile, some DEGs involved in innate immunity- related genes and pathways, and ER stress responses also were highly expressed in NT. Therefore, we speculate that accelerated energy metabolism, higher expression of immunity and ER related genes might be the important adaptive strategies for NT in relative to NS under nitrite stress. These results will provide new insights on the potential tolerant molecular mechanisms and the breeding of new varieties of nitrite tolerant L. vannamei.

Hg2+ Significantly Enhancing the Peroxidase-Like Activity of H2TCPP/ZnS/CoS Nanoperoxidases by Inducing the Formation of Surface-Cation Defects and Application for the Sensitive and Selective Detection of Hg2+ in the Environment.

Exploring excellent peroxidase mimics with enhanced peroxidase-like activity is important to the construction of a fast, low-cost, and convenient colorimetric sensing platform for heavy ions. In this work, 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (H2TCPP) was first used to modify ZnS/CoS and make it show better peroxidase-like activity. The metal-cation vacancies generated by Hg2+ contacting H2TCPP/ZnS/CoS further stimulate the catalytic activity. It is reported that the addition of Hg2+ usually causes a decrease of the peroxidase-like activity of metal sulfides. Oppositely, in our work, Hg2+ can trigger the colorimetric signal amplification because of lots of metal-cation vacancies generated on the surface of the nanocomposites (bimetallic sulfides). The peroxidase-like activity of ZnS/CoS was evaluated by virtue of the chromogenic substrate 3,3,5,5-tetramethylbenzidine (TMB) from colorless to blue in 3 min. The enhanced catalytic activity of H2TCPP/ZnS/CoS was attributed to lots of active sites from the metal-cation defects on the surface of H2TCPP/ZnS/CoS as well as the synergistic effect of porphyrin molecules and ZnS/CoS. The adsorption behavior of H2O2 on the H2TCPP/ZnS/CoS surface with defects was studied by density functional theory calculation. Thus, a colorimetric sensing platform based on Hg2+ trigger signal amplification has been successfully constructed, which can be used to sensitively and selectively determine Hg2+ in environmental samples.

Integrated analysis of physiological, transcriptomic and metabolomic responses and tolerance mechanism of nitrite exposure in Litopenaeus vannamei.

Nitrite accumulation in aquatic environments is a potential risk factor that disrupts multiple physiological functions in aquatic animals. In this study, the physiology, transcriptome and metabolome of the control group (LV-C), nitrite-tolerance group (LV-NT) and nitrite-sensitive group (LV-NS) were investigated to identify the stress responses and mechanisms underlying the nitrite tolerance of Litopenaeus vannamei. After LV-NT and LV-NS were subjected to nitrite stress, the hemocyanin contents were significantly decreased, and hepatopancreas showed severe histological damage compared with LV-C. Likewise, the antioxidant enzymes were also significantly changed after nitrite exposure. The transcriptome data revealed differentially expressed genes associated with immune system, cytoskeleton remodeling and apoptosis in LV-NT and LV-NS. The combination of transcriptomic and metabolomic analysis revealed nitrite exposure disturbed metabolism processes in L. vannamei, including amino acid metabolism, nucleotide metabolism and lipid metabolism. The multiple comparative analysis implicated that higher nitrite tolerance of LV-NT than LV-NS may be attributed to enhanced hypoxia inducible factor-1α expression to regulate energy supply and gaseous exchange. Moreover, LV-NT showed higher antioxidative ability, detoxification gene expression and enhanced fatty acids contents after nitrite exposure in relative to LV-NS. Collectively, all these results will greatly provide new insights into the molecular mechanisms underlying the stress responses and tolerance of nitrite exposure in L. vannamei.

In vitro corrosion of pure Mg in phosphate buffer solution-Influences of isoelectric point and molecular structure of amino acids.

Influences of proteins on degradation of magnesium alloys are of great significance but not well understood. In particular the roles of amino acids, the basic unit of proteins in regulating the progress of biodegradation of magnesium based materials remain unclear. This study aims to investigate the impacts of alanine, glutamic acid and lysine on degradation of pure magnesium in phosphate buffer solution through SEM, XPS, FTIR, potentiodynamic polarisation curves, electrochemical impedance spectroscopy and immersion tests. The changed contents of amino acids in solutions were detected by UV-vis spectrophotometer. Results demonstrate that the charges of the selected amino acids imposed significant contribution to suppressing the degradation of pure magnesium in phosphate buffer solution. The presence of amino acids led to the formation of phosphate-based corrosion products, increasing free corrosion potential, and reduction in corrosion current density and solution pH depending on their isoelectric points and molecular structures. A plausible corrosion mechanism organised by amino acids on pure magnesium was proposed.

Hierarchical multi-shell 66-nuclei silver nanoclusters trapping subvalent Ag6 kernels.

Hierarchical nano structures are hard to fabircate. Here, we present three novel hierarchical multi-shell 66-nuclei silver nanoclusters, trapping ultrasmall Ag64+ nano-fragments by nine MoO42- ions. This Ag6@(MoO4)9 core is further wrapped by an outer Ag60 shell. The Ag6 kernel evolves from reduction involving DMF solvent. Carboxylate ligands are very important in the modulation of the polygon patterns on the Ag60 shell.

Carboxylic acid stimulated silver shell isomerism in a triple core-shell Ag84 nanocluster.

Isomerization is highly important in all aspects of science, yet it is rarely observed in nanoscience. Here, we synthesized a unique triple core-shell Ag84 nanocluster displaying isomerism, which is controlled by different carboxylic acids and a one-way transformation (SD/Ag84a → SD/Ag84b). The innermost core is a rare Ag10 nanocluster which comprises an Ag6 octahedral unit as seen in face-centred cubic (fcc) silver metal and four capped Ag atoms. It templates two crescent-shaped polyoxometalate (W7O26)10- shells which are then enclosed in a shell of silver shaped as rugby balls. The organic ligands (iPrS-, n PrCOO- and PhCOO-) finally shield the metallic clusters. Due to slight differences in structure at two poles and the steric hindrance of n PrCOO- and PhCOO-, SD/Ag84a and SD/Ag84b adopt the shapes of flat-headed and cuspidal prolate spheres, respectively. Interestingly, PhCOOH is dominant over n PrCOOH whereby crystals of SD/Ag84b were isolated if PhCOOH is added during the synthesis of SD/Ag84a. This demonstrates that PhCOOH not only alters the organic coats but also induces metal shell re-organization. This work reveals carboxylate-controlled skeletal isomerism in silver nanoclusters for the first time, thus deepening the understanding of silver nanocluster assembly, flexibility and reactivity.

Enclosing classical polyoxometallates in silver nanoclusters.

Due to the elusive nature of polyoxometallates (POMs) in the assembly of silver clusters, POMs trapped by silver clusters are usually different from the pristine form, which surely increases the novelty of the assembly results but makes the final structure predictability challenging. Herein, three novel high-nuclearity silver-thiolate clusters trapping two kinds of classical POMs, Lindqvist-Mo6O192- and V10O286-, are reported. They are identified to be [(V10O28)@Ag44] (SD/Ag44a), [(V10O28)@Ag46] (SD/Ag46), and [(Mo6O19)@Ag44] (SD/Ag44b) clusters, which are further extended to 1D chain, 2D sql layer, and 3D pcu framework, respectively. Of note, SD/Ag44b contains a regular cubic Mo6O19 core sealed by an Ag44(EtS)24 shell in a pseudo-sodalite unit and six SCl4 planar squares connecting the respective adjacent silver tetragonal faces. This structure is a novel zeolite closely related to the natural alumino-silicate 'sodalite' but exceptionally made of core-shell silver clusters. Moreover, the Oh symmetric Mo6O192- templates an Oh symmetric Ag44 cluster in SD/Ag44b, realizing authentic symmetry delivery from guest to host in this system. This is a rare silver cluster family with classical POMs encapsulated.

Stress response and tolerance mechanisms of ammonia exposure based on transcriptomics and metabolomics in Litopenaeus vannamei.

Ammonia, one of the major limiting environment factors in aquaculture, may pose a threat to the shrimp growth, reproduction and survival. In this study, to understand molecular differences of transcriptomic and metabolomic responses and investigate the tolerance mechanisms underlying ammonia stress in Litopenaeus vannamei, ammonia-tolerant family (LV-AT) and ammonia-sensitive family (LV-AS) of these two extreme families were exposed to high-concentration (NH4Cl, 46 mg/L) ammonia for 24 h. The comparative transcriptome analysis between ammonia-treated and control (LV-C) groups revealed involvement of immune defense, cytoskeleton remodeling, antioxidative system and metabolic pathway in ammonia-stress response of L. vannamei. Likewise, metabolomics analysis showed that ammonia exposure could disturb amino acid metabolism, nucleotide metabolism and lipid metabolism, with metabolism related-genes changed according to RNA-seq analysis. The comparison of metabolite and transcript profiles between LV-AT and LV-AS indicated that LV-AT used the enhanced glycolysis and tricarboxylic acid (TCA) cycle strategies for energy supply and ammonia excretion to adapt high-concentration ammonia. Furthermore, some of genes involved in the detoxification and ammonia excretion were highly expressed in LV-AT. We speculate that the higher ability of ammonia excretion and detoxification and the accelerated energy metabolism for energy supplies might be the adaptive strategies for LV-AT relative to LV-AS after ammonia stress. Collectively, the combination of transcriptomics and metabolomics results will greatly contribute to incrementally understand the stress responses on ammonia exposure to L. vannamei and supply molecular level support for evaluating the environmental effects of ammonia on aquatic organisms. The results further constitute new sights on the potential molecular mechanisms of ammonia adaptive strategies in shrimps at the transcriptomics and metabolomics levels.

Space Craft-like Octanuclear Co(II)-Silsesquioxane Nanocages: Synthesis, Structure, Magnetic Properties, Solution Behavior, and Catalytic Activity for Hydroboration of Ketones.

Two novel space craft-like octanuclear Co(II)-silsesquioxane nanocages, {Co8[(MeSiO2)4]2(dmpz)8} (SD/Co8a) and {Co8[(PhSiO2)4]2(dmpz)8} (SD/Co8b) (SD = SunDi; Hdmpz = 3,5-dimethylpyrazole), have been constructed from two similar multidentate silsesquioxane ligands assisted with a pyrazole ligand. The Co8 skeleton consists of eight tetrahedral Co(II) ions arranged in a ring and is further capped by two (MeSiO2)4 ligands up and down. The auxiliary dmpz- ligands seal the ring finally. Electrospray ionization mass spectrometry revealed SD/Co8a and SD/Co8b are highly stable in CH2Cl2. Magnetic analysis implies that SD/Co8a announces antiferromagnetic interactions between Co(II) ions. Moreover, both of them display good homogeneous catalytic activity for hydroboration of ketones in the presence of pinacolborane under mild conditions.

Three Chiral Cyanide-Bridged Cr-Cu Complexes: Synthesis, Crystal Structures and Magnetic Properties.

Two trans-dicyanidochromium(III)-containing building blocks and one chiral copper(II) compound have been employed to assemble cyanide-bridged heterometallic complexes, resulting in three chiral cyanide-bridged Cr(III)-Cu(II) complexes, [Cu(L1)2Cr(L3)(CN)2]ClO42 · CH3OH · H2O (1a, L1 = (S,S)-1,2-diaminocyclohexane, H2L3 =1,2-bis(pyridine- 2-carboxamido)benzene), [Cu(L2)2Cr(L2)(CN)2]ClO42 · CH3OH · H2O (1b, L2 = (R,R)-1,2-diaminocyclohexane) [Cu(L3)2Cr(L4)(CN)2][Cr(L4)(CN)2] · CH3OH · 2H2O (2), (H2L4 = 1,2-bis(pyridine-2-carboxamido)-4-chlorobenzene). All the three complexes have been characterized by elemental analysis, IR spectroscopy and X-ray structure determination. Single-crystal X-ray diffraction analysis shows that the two enantiomeric complexes 1a, 1b and the complex 2 belong to cyanide-bridged cationic binuclear structure type with ClO4 - or the anionic cyanide building block as balance anion for complexes 1a, 1b or 2, respectively. Investigation of the magnetic properties of the complexes 1a and 2 reveals the weak ferromagnetic coupling between the neighboring Cr(III) and Cu(II) ions through the bridging cyanide group.

Preparation of oxazolines and oxazoles via a PhI(OAc)2-promoted cyclization of N-propargylamides.

A metal-free cyclization of N-propargylamides for the synthesis of various oxazolines and oxazoles via a 5-exo-dig process is presented. Using (diacetoxyiodo)benzene (PIDA) as a reaction promoter and lithium iodide (LiI) as an iodine source, intramolecular iodooxygenation of N-propargylamides proceeded readily, leading to the corresponding (E)-5-iodomethylene-2-oxazolines in good to excellent isolated yields. In addition, using the PhI(OAc)2/LiI system, N-propargylamides can be converted to the corresponding oxazole-5-carbaldehydes in the presence of oxygen under visible light irradiation. The resulting products can be further converted into various oxazoline and oxazole derivatives after simple derivatizations, and this method ultimately offers an efficient route to a variety of biologically active structures.

Preparation of polysubstituted dihydrofurans through a PhI(OAc)2-promoted haloenolcyclization of olefinic dicarbonyl compounds.

A metal-free cyclization of olefinic dicarbonyl compounds for the synthesis of various 5-halomethyl-4,5-dihydrofurans is presented. Using (diacetoxyiodo)benzene as the reaction promoter and halotrimethylsilane as the halogen source, the intramolecular haloenolcyclization of the 2-allyl-1,3-dicarbonyl compounds smoothly proceeded, leading to the corresponding 5-halomethyl-4,5-dihydrofurans in good to excellent isolated yields. Moreover, the resulting 5-iodomethyl products could be converted to functionalized furans in almost quantitative yields by treatment with DBU followed by acid-catalyzed rearrangement. The reactions could be carried out on a gram scale and did not require harsh reaction conditions. The good isolated yields, mild conditions, and operational simplicity make this reaction a viable method for the construction of different dihydrofuran and furan structures.

A New Member of the Inverted Cucurbit[n]uril Family.

A new inverted cucurbituril, namely inverted hexamethylcucurbit[3,3]uril (iMe6 Q[3,3]), has been isolated and characterized. It incorporates a single inverted un-substituted glycoluril unit oriented towards the interior of the cavity, shows good solubility in water and organic solvents (DMSO), and exhibits different selectivity for guests to those of iQ[6] and other known Q[6]s.

Association between Th17-related cytokines and risk of non-small cell lung cancer among patients with or without chronic obstructive pulmonary disease.

BACKGROUND: CD4 (+) T helper 17 (Th17) cells play critical roles in inflammation and tumor development. The involvement of Th17 cells in chronic obstructive pulmonary disease (COPD)-type inflammation-associated lung cancer has also been confirmed in animal models. However, to the authors' knowledge, it is unknown whether the role of Th17 cells is different in patients with lung cancer complicated with COPD compared with those without COPD. In the current study, the authors attempted to determine the association between the circulating levels of Th17-related cytokines and the clinical characteristics of non-small cell lung cancer (NSCLC) in patients with or without COPD. METHODS: The authors designed a matched case-control study that included 70 patients with NSCLC with COPD, 148 patients with NSCLC without COPD, and 148 healthy controls. The data regarding the clinicopathological features of these participants were collected. Circulating levels of Th17-related cytokines, including interleukin (IL) 23 (IL-23), IL-17A, IL-17F, IL-22, and tumor necrosis factor-α, were measured. RESULTS: The circulating levels of IL-23, IL-17A, IL-17F, IL-22, and tumor necrosis factor-α were found to be significantly higher in the patients with NSCLC compared with the healthy controls (P<.05). The elevated levels were found to be significantly associated with lung cancer risk (P<.05). However, no significant differences were found between patients with NSCLC with COPD and patients without COPD. It is interesting to note that, among patients with NSCLC without COPD, the levels of these cytokines were consistently higher among patients with stage I to stage IIIA disease compared with those with stage IIIB to stage IV disease (P<.05). In addition, the 5 Th17-related cytokines demonstrated pairwise correlations, with Spearman rank correlation coefficients of 0.646 to 0.888 (P<.05). CONCLUSIONS: The results of the current study indicate a clear association between the Th17-related cytokine profile and the risk of NSCLC complicated by the presence or absence of COPD.

[Normative research on bacteriostasis and relieving itching external therapeutic function of kochiae fructus].

OBJECTIVE: To normalize bacteriostasis and relieving itching external therapeutic function of Kochiae Fructus. METHODS: Itching guinea pig model caused by histamine, itching mice model, eczema guinea pig model caused by OVA, and inhibitory effect on pathogens in vitro were used to observe the itching threshold, symptoms and other related physiological index, as well as the inhibitory effect on the normal skin fungi by water extraction of Kochiae Fructus to evaluate the external therapeutic function of Kochiae Fructus. RESULTS: The itching threshold of guinea pig itching model treated by water extraction of Kochiae Fructus at high, medium and low three dosage level, could be significantly increased when compared with negative control group (P < 0.05 or P < 0.01); Red speckle of OVA guinea pig model treated by water extraction of Kochiae Fructus at high, medium and low three dosage level, could be significantly decreased when compared with negative control group (P < 0.05 or P < 0.01); The number of itching and total time of itching within 30 minutes of mice model caused by R-glycose anhydride treated by water extraction of Kochiae Fructus at high, medium and low three dosage level, could be significantly decreased when compared with negative control group (P < 0.05 or P < 0.01); Several common skin fungi could be significantly inhibited by the water extraction of Kochiae Fructus. MIC of the water extraction of Kochiae Fructus on Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis, Trichophyton violaceum, and Trichophyton schoenleini were 3.12%, 0.78%, 0.78%, 0.78%, 0.78%, respectively. CONCLUSION: Kochiae fructus has the effect of bacteriostasis and relieving itching.

Perchloratobis[1-(1,10-phenanthrolin-2-yl)-2-pyridone]zinc(II) perchlorate.

In the title mononuclear complex, [Zn(ClO(4))(C(17)H(11)N(3)O)(2)]ClO(4), the Zn(II) ion is coordinated in a distorted octa-hedral geometry. The dihedral angles between the pyridine rings and the mean planes of the 1,10-phenanthroline ring system in each of the 1-(1,10-phenanthrolin-2-yl)-2-pyridone (PP) ligands is 24.51 (10)° for the tridendate PP ligand and 73.55 (6)° for the bidentate PP ligand. Within the mol-ecule there is a weak π-π inter-action between the pyridine ring of the bidentate ligand and the 1,10-phenanthroline ring system of the tridendate ligand with a centroid-centroid distance of 3.6383 (19) Å.

Diaqua-(1,10-phenanthrolin-2-ol)nickel(II) dinitrate.

In the mononuclear title complex, [Ni(C(12)H(8)N(2)O)(2)(H(2)O)(2)](NO(3))(2), the Ni(II) ion is coordinated in a distorted octa-hedral geometry. The dihedral angle between the two mean planes defined by the phenanthroline ligands is 88.26 (6)°. Intra- and intermolecular O-H⋯O hydrogen bonds between the cation and the anions lead to the formation of a layered arrangement parallel to (010).