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Antimicrobial peptides (AMPs), ancient scavengers of bacteria, are very poorly induced in macrophages infected by Mycobacterium tuberculosis (M. tuberculosis), but the underlying mechanism remains unknown. Here, we report that L-alanine interacts with PRSS1 and unfreezes the inhibitory effect of PRSS1 on the activation of NF-κB pathway to induce the expression of AMPs, but mycobacterial alanine dehydrogenase (Ald) Rv2780 hydrolyzes L-alanine and reduces the level of L-alanine in macrophages, thereby suppressing the expression of AMPs to facilitate survival of mycobacteria. Mechanistically, PRSS1 associates with TAK1 and disruptes the formation of TAK1/TAB1 complex to inhibit TAK1-mediated activation of NF-κB pathway, but interaction of L-alanine with PRSS1, disables PRSS1-mediated impairment on TAK1/TAB1 complex formation, thereby triggering the activation of NF-κB pathway to induce expression of AMPs. Moreover, deletion of antimicrobial peptide gene β-defensin 4 (Defb4) impairs the virulence by Rv2780 during infection in mice. Both L-alanine and the Rv2780 inhibitor, GWP-042, exhibits excellent inhibitory activity against M. tuberculosis infection in vivo. Our findings identify a previously unrecognized mechanism that M. tuberculosis uses its own alanine dehydrogenase to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis. In this work, authors mechanistically investigate the reduced induction of antimicrobial peptides in Mycobacterium tuberculosis infected macrophages. [ABSTRACT FROM AUTHOR]

Internal N6-methyladenosine (m6A) modifications are among the most abundant modifications of messenger RNA, playing a critical role in diverse biological and pathological processes. However, the functional role and regulatory mechanism of m6A modifications in the immune response to Mycobacterium tuberculosis infection remains unknown. Here, we report that methyltransferase-like 14 (METTL14)-dependent m6A methylation of NAPDH oxidase 2 (Nox2) mRNA was crucial for the host immune defense against M. tuberculosis infection and that M. tuberculosis-secreted antigen EsxB (Rv3874) inhibited METTL14-dependent m6A methylation of Nox2 mRNA. Mechanistically, EsxB interacted with p38 MAP kinase and disrupted the association of TAB1 with p38, thus inhibiting the TAB1-mediated autophosphorylation of p38. Interaction of EsxB with p38 also impeded the binding of p38 with METTL14, thereby inhibiting the p38-mediated phosphorylation of METTL14 at Thr72. Inhibition of p38 by EsxB restrained liquid–liquid phase separation (LLPS) of METTL14 and its subsequent interaction with METTL3, preventing the m6A modification of Nox2 mRNA and its association with the m6A-binding protein IGF2BP1 to destabilize Nox2 mRNA, reduce ROS levels, and increase intracellular survival of M. tuberculosis. Moreover, deletion or mutation of the phosphorylation site on METTL14 impaired the inhibition of ROS level by EsxB and increased bacterial burden or histological damage in the lungs during infection in mice. These findings identify a previously unknown mechanism that M. tuberculosis employs to suppress host immunity, providing insights that may empower the development of effective immunomodulators that target M. tuberculosis. [ABSTRACT FROM AUTHOR]

Magnetite-functionalized biochar (MBC) is a promising engineered material for remediation of antibiotic-contaminated fields. However, sorption mechanisms of ionizable organic compounds such as sulfonamide antibiotics (SAs) on MBC are still unclear. This study employed four representative SAs including sulfamethazine (SMT), sulfamerazine (SMR), sulfadiazine (SDZ), and sulfamethoxazole (SMX), to compare the difference in sorption on MBC. Results showed that the sorption capacities and affinities of the four SAs varied with their substituents, hydrophobic properties, and dissociation constants (pKa). Synergistic effect during co-pyrolysis with Fe3+ enhanced the sorption performance of MBC towards SAs compared to original BC. Spectral methods confirmed structural changes of MBC such as the variance in oxygen-containing groups and defective/graphitized phases. Results of modeling pH-dependent sorption revealed that H-bonding or π-bond assisted H-bonding determined the sorption affinities and capacities of SAs. In particular, the SAs with lower pKa were thermodynamically favorable to form H-bonding with MBC via proton exchange with water molecules. Quantum calculation results quantified the contributions of H-bonding strengths and found that the energies of H-bonding were correlated with affinities of SAs. Moreover, contributions of oxygen-containing groups instead of minerals dominated the H-bonding energies. Mechanistic insights from this study can be valuable in exploring engineered BC composites for practical application in field remediation. Highlights: Sorption capacity and affinity of four SAs varied with substituents, Kow, and pKa Copyrolyzed carbon matrix and Fe3+ synergistically enhanced SA sorption performance H-bonding or π-bond assisted H-bonding determined SA sorption affinity and capacity Contributions of O-containing groups instead of minerals dominated H-bonding energy [ABSTRACT FROM AUTHOR]

Background: Habitat degradation and flow regime alterations are two of the most prominent and common impact factors to freshwater mussel populations. Knowledge of the correlation between freshwater mussel distribution, density and habitat characteristics is important for maintaining and restoring their biodiversity and ecological functions. Information on predicting habitat suitability of freshwater mussels is lacking in China. Here, we aimed to analyze the correlation between freshwater mussel density and complex hydraulic and physicochemical variables to predict habitat suitability. Results: The results showed that four complex hydraulic variables (boundary Reynolds number, critical shear stress, bed roughness and mean sediment particle size) and four physicochemical variables (water temperature, chlorophyll-a, transparency and pH) were key factors for predicting habitat suitability of freshwater mussels. Freshwater mussel density was significantly correlated with Froude number, water temperature and chlorophyll-a. Conclusions: Our results confirmed that higher freshwater mussel density would be associated with areas that are stable in complex hydraulic and physicochemical variables. These results provide an important insight into the conservation of freshwater mussel diversity and their habitat restoration in China and globally. [ABSTRACT FROM AUTHOR]

Primordial germ cells (PGCs) are the undifferentiated progenitors of the gametes. Unlike the poor maintenance of cultured mammalian PGCs, the avian PGCs can be expanded in vitro indefinitely while preserving pluripotency and germline competence. In mammals, the Oct4 is the master transcription factor that ensures the stemness of pluripotent cells such as PGCs, but the specific function of Oct4 in chicken PGCs remains unclear. As expected, the loss of Oct4 in chicken PGCs reduced the expression of key pluripotency factors and promoted the genes involved in endoderm and ectoderm differentiation. Furthermore, the global active chromatin was reduced as shown by the depletion of the H3K27ac upon Oct4 suppression. Interestingly, the de-activated chromatin caused the down-regulation of adjacent genes which are mostly known regulators of cell junction, chemotaxis and cell migration. Consequently, the Oct4-deficient PGCs show impaired cell migration and could not colonize the gonads when re-introduced into the bloodstream of the embryo. We propose that, in addition to maintaining pluripotency, the Oct4 mediated chromatin activation is dictating chicken PGC migration. [ABSTRACT FROM AUTHOR]

Pathogenic mycobacteria induce the formation of hypoxic granulomas during latent tuberculosis (TB) infection, in which the immune system contains, but fails to eliminate the mycobacteria. Fatty acid metabolism-related genes are relatively overrepresented in the mycobacterial genome and mycobacteria favor host-derived fatty acids as nutrient sources. However, whether and how mycobacteria modulate host fatty acid metabolism to drive granuloma progression remains unknown. Here, we report that mycobacteria under hypoxia markedly secrete the protein Rv0859/MMAR_4677 (Fatty-acid degradation A, FadA), which is also enriched in tuberculous granulomas. FadA acts as an acetyltransferase that converts host acetyl-CoA to acetoacetyl-CoA. The reduced acetyl-CoA level suppresses H3K9Ac-mediated expression of the host proinflammatory cytokine Il6, thus promoting granuloma progression. Moreover, supplementation of acetate increases the level of acetyl-CoA and inhibits the formation of granulomas. Our findings suggest an unexpected mechanism of a hypoxia-induced mycobacterial protein suppressing host immunity via modulation of host fatty acid metabolism and raise the possibility of a novel therapeutic strategy for TB infection. [ABSTRACT FROM AUTHOR]

The effects of ambient atmospheres on the arc erosion behaviors of Ti3SiC2 cathodes were investigated at 5.5 kV in argon, nitrogen, air, and oxygen. The mass loss of the cathodes increased in the order of argon, nitrogen, air, and oxygen and the morphologies were measured by 3D laser scanning confocal microscope with a gradual blooming phenomenon. Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy were employed to detect the components of erosion regions. The erosion-chemical products mainly consisted of TiNx in nitrogen, TiNx, TiO2 and SiO2 in air, TiO2 and SiO2 in oxygen. The arc energy was responsible for the arc erosion characteristics in different atmospheres. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis is an intracellular pathogen that uses several strategies to interfere with the signalling functions of host immune molecules. Many other bacterial pathogens exploit the host ubiquitination system to promote pathogenesis1,2, but whether this same system modulates the ubiquitination of M. tuberculosis proteins is unknown. Here we report that the host E3 ubiquitin ligase ANAPC2—a core subunit of the anaphase-promoting complex/cyclosome—interacts with the mycobacterial protein Rv0222 and promotes the attachment of lysine-11-linked ubiquitin chains to lysine 76 of Rv0222 in order to suppress the expression of proinflammatory cytokines. Inhibition of ANAPC2 by specific short hairpin RNA abolishes the inhibitory effect of Rv0222 on proinflammatory responses. Moreover, mutation of the ubiquitination site on Rv0222 impairs the inhibition of proinflammatory cytokines by Rv0222 and reduces virulence during infection in mice. Mechanistically, lysine-11-linked ubiquitination of Rv0222 by ANAPC2 facilitates the recruitment of the protein tyrosine phosphatase SHP1 to the adaptor protein TRAF6, preventing the lysine-63-linked ubiquitination and activation of TRAF6. Our findings identify a previously unrecognized mechanism that M. tuberculosis uses to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis. Mycobacterium tuberculosis suppresses the production of inflammatory cytokines by host cells through the host-mediated ubiquitination of a mycobacterial protein, enhancing the interaction of a host signalling inhibitor with another signalling molecule. [ABSTRACT FROM AUTHOR]

Quite a number of studies have examined the effects of fish oil supplementation on cognitive performance in different transgenic animal models of Alzheimer’s disease (AD). However, inconsistent and controversial outcomes have been derived from these experiments. In order to investigate whether the beneficial effect of fish oil supplementation on cognition was dietary VE status associated, fish oil dietary intervention was carried out in transgenic APPswe/PS1dE9 (APP/PS1) mice. Control mice (C57BL/6J mice) were fed a normal control diet. APP/PS1 mice were assigned to a normal control diet group and low VE diet + fish oil supplement, normal VE diet + fish oil supplement, and high VE diet + fish oil supplement groups, respectively. After 7 months of dietary intervention, we found that fish oil supplementation improved behavioral performance, alleviated brain beta-amyloid (Aβ) plaque burden, and attenuated the oxidative stress in APP/PS1 mice by increasing cortical GSH content and total antioxidant capacity, as well as by decreasing MDA level. Fish oil treatment increased cortical n-3 PUFA concentration and decreased n-6/n-3 PUFA ratio in APP/PS1 mice. Fatty acid transporters, Nrf2 and downstream targets involved in cortical and hippocampal antioxidant system were also modulated by fish oil-supplemented diet. Our data demonstrate that fish oil supplementation exerts an enhanced modulatory effect on the antioxidant system and fatty acid concentrations in APP/PS1 mice fed on lowly or averagely concentrated level of VE-containing diet than in mice fed with VE-rich diet. The current data do support previous findings that already dictate the beneficial effect of n-3 PUFAs on cognitive function. Moreover, the cognition promoting effects of n-3 PUFAs may be dietary VE status related. [ABSTRACT FROM AUTHOR]

Electron work function (EWF) is correlated to intrinsic properties of metallic materials and can be an alternative parameter to obtain supplementary clues for guiding material design and modification. A higher EWF corresponds to a more stable electronic state, leading to higher resistance to any attempt to change the material structure and properties. In this study, effects of Ni as a solute with a higher EWF on mechanical, electrochemical, and tribological properties of low-carbon steel were investigated. Added Ni, which has more valence electrons, enhanced the electrons-nuclei interaction in the steel, corresponding to higher EWF. As a result, the Ni-added steel showed increased mechanical strength and corrosion resistance, resulting in higher resistances to wear and corrosive wear. Mechanism for the improvements is elucidated through analyzing EWF-related variations in Young’s modulus, hardness, corrosion potential, and tribological behavior. [ABSTRACT FROM AUTHOR]

Harmful algal blooms in eutrophic waters pose a serious threat to freshwater ecosystems and human health. In-situ light availability control is one of the most commonly used technologies to suppress algae in lakes and reservoirs. To develop a better understanding of the effects of light on algal growth, specific density, colony size and sinking loss, Anabaena flos-aquae (cyanobacteria) and Scenedesmus obliquus (green algae) were evaluated in varying light scenarios. The results showed that the specific density and colony size of these two species varied during growth, and there were obvious differences among the light scenarios. At the end of exponential phase, S. obliquus incubated under light-limited condition maintained a higher specific density and formed larger aggregates, whereas A. flos-aquae formed a longer filament length. Both species exhibited higher sinking loss rates with lower light availability. These results implied that the sinking loss rate was not always constant but should be considered as a variable response to the change of light availability, and in-situ light availability control might result in a significant increase of the sinking loss of algae due to the change of size and specific density, thereby further affecting the algal biomass in the water column. [ABSTRACT FROM AUTHOR]

Arbuscular mycorrhizal (AM) fungi play an important role in plant tolerance of heavy metal contamination. In this study, a pot experiment was conducted to illustrate the effects of the two AM fungi species Funneliformis mosseae (Fm) and Rhizophagus irregularis (Ri) on plant growth of Oryza sativa L. either with or without ethylenediamine tetraacetate (EDTA) addition and during exposure to five Cd concentrations (in the range of 0-5 mg kg−1). The results showed that Fm inoculation achieved greater mycorrhizal colonization and mycorrhizal dependency indexes than Ri inoculation. In addition, the effects of AM fungi on Cd biosorption and translocation in rice were also investigated in the presence of EDTA. Despite cooperative adsorption, the Freundlich isotherm could describe the biosorption effects of Cd on rice roots regardless of AM fungi inoculation or EDTA addition. Cd concentrations in mycorrhizal roots increased but decreased in mycorrhizal shoots in contrast to the control treatment. Although EDTA addition negatively inhibited the uptake of Cd to mycorrhizal shoots, lower translocation factor (TF) and bioconcentration factor (BCF) were still observed in treatments with EDTA compared to control treatment. Our findings suggest that Ri and Fm inoculation enhanced Cd immobilization in the roots, thus preventing Cd entry into the food chain during exposure to low and high Cd stress, respectively. [ABSTRACT FROM AUTHOR]

The arc corrosion evolution of Cu-20 vol.% Ti3AlC2 cathodes is presented here. After eroded by 3, 4, 5, 6, 7, 8, 9, 10 kV DC voltage, respectively, the surface morphologies were characterized by field emission scanning electron microscope with craters and protrusions. Compared to small craters and dense protrusions of the morphology by high voltage, the eroded surface was covered with bigger craters and sparse protrusions at low voltage. No crack was discovered on the surface even at 10 kV. By means of energy dispersive spectroscopy and Raman spectroscopy, the decomposition of Cu-20 vol.% Ti3AlC2 cathode to CuO, Al2O3 and TiO2 were proved. Meanwhile, W anode is oxidized to WO2. The peak current increases with the increasing breakdown voltage, which is recorded by a digital memory oscilloscope. [ABSTRACT FROM AUTHOR]

Purpose: A novel systemic immune-inflammation index (SII) based on platelet ( P), neutrophil ( N), and lymphocyte ( L) counts has been reported to be associated with clinical outcomes in several solid tumors. We aimed to investigate its prognostic value in esophageal squamous cell carcinoma (ESCC) and the potential relationship with quality of life (QOL). Methods: A total of 280 ESCC patients who underwent esophagectomy were enrolled. SII (SII = P × N/ L) was calculated on the basis of data obtained within 1 week before surgery. An optimal cut-off value stratified patients into high (≥560) and low (<560) preoperative SII groups. The widely used EORTC QLQ-C30 and QLQ-OES18 were utilized to assess QOL at cancer diagnosis and 36 months after surgery. Generalized estimating equations (GEEs) were used to evaluate the association of SII with QOL. Kaplan-Meier method and Cox proportional regression were used to analyze the prognostic value of SII. Results: Kaplan-Meier analyses revealed that higher SII correlated significantly with poorer overall survival (OS) ( p < 0.001) and disease-free survival (DFS) ( p < 0.001) in patients with ESCC. Multivariate analysis identified SII as an independent prognostic factor for OS ( p < 0.001; HR 2.578; 95% CI 1.625-4.088) and DFS ( p < 0.001; HR 2.699; 95% CI 1.726-4.223). In addition, patients with high SII exhibited notably deteriorating QOL ( p < 0.05). Conclusions: The preoperative SII is a promising biomarker for predicting survival and QOL of patients with ESCC. It may help to identify the high-risk patients for treatment strategy decisions. [ABSTRACT FROM AUTHOR]

Arbuscular mycorrhizal (AM) fungi have been used to alleviate heavy metal stress on plant growth and uptake of micro- and macroelements. A greenhouse pot experiment was conducted to verify the effects of AM fungus Rhizophagus irregularis on the growth, physiological characteristics, total Cd, and element uptake of Phragmites australis under different Cd stress (in the range of 0-20 mg L). The results showed that the symbiosis could effectively alleviate Cd toxicity with greater root biomass, higher photosynthesis rate, and lower levels of malonaldehyde (MDA) and proline than non-mycorrhizal plants could. However, reduced transpiration rate (Tr) and stomatal conductance ( g ) indicated R. irregularis protected host plants from Cd stress (≥5 mg L) via the stomatal closure. Although micro- and macroelements displayed differently in the presence of Cd, higher concentrations were still detected in mycorrhizal plants in contrast to non-mycorrhizal plants. Moreover, step multiple regression significantly demonstrated Pn, stem diameter (Sd), and g were the important factors with regard to total Cd uptake in the symbiosis, but Mn affected to non-mycorrhizal plants. These results suggested R. irregularis could alleviate the competition between Mn and Cd by altering plant physiology. This work clearly demonstrated that R. irregularis can be able to support P. australis growth better even though under high Cd stress (>1 mg L), suggesting its good potential for practical use in high Cd-contaminated areas. [ABSTRACT FROM AUTHOR]

Background: This retrospective study was designed to estimate the efficacy and toxicity of definitive radiotherapy with concurrent or sequential docetaxel/S-1 for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Of the 62 eligible patients enrolled in this study during January 1, 2010 to December 31, 2014 from Qilu Hospital, Shandong University, Shandong Province, 39 patients received 3 cycles of docetaxel/S-1 during and after radiotherapy (concurrent chemoradiotherapy, CCRT), and 23 patients had radiotherapy followed by 3 cycles of docetaxel and S-1 (sequential chemoradiotherapy, SCRT). Results: The CR of CCRT and SCRT groups were 48.72 and 21.74 %, respectively ( p = 0.035). The median progress-free survival (PFS) of CCRT group (23.5 months) was significantly higher than SCRT group (11.7 months; p = 0.004). The median overall survival (OS) of CCRT group (33.5 months) also was significantly higher than SCRT group (24.0 months; p = 0.004). At 2 years, in this patient population, the rate of PFS of CCRT group was (44.2 ± 8.2 %), significantly higher than SCRT group (11.9 ± 9.6 %; p = 0.002). The 2-year OS rate of CCRT (68.6 ± 7.5 %) was significantly higher than SCRT group as well (42.0 ± 14.0 %; p = 0.002). The incidence of adverse events was higher in CCRT than SCRT group. No grade 4 or grade 5 adverse events occurred in our study. Conclusions: Definitive radiotherapy with concurrent or sequential docetaxel and S-1 for inoperable locally advanced ESCC was very well tolerated and remarkably active. In both CCRT and SCRT groups, acute toxicities were manageable. This regimen holds promises for treatment of esophageal carcinoma and warrants further investigation. [ABSTRACT FROM AUTHOR]

MicroRNA-613 (miR-613) plays important roles in tumorigenesis and cancer progression. We aimed to evaluate its expression level and potential for diagnosis and prognosis in esophageal squamous cell cancer (ESCC). We examined miR-613 expression in 60 pairs of ESCC cancerous and matched paracancerous tissues, serum samples from 75 ESCC patients and 75 healthy volunteers, and 105 formalin-fixed paraffin-embedded (FFPE) tissue samples using quantitative reverse transcription polymerase chain reaction. Receiver-operating characteristic (ROC) curve analysis, Kaplan-Meier method, and Cox regression were applied to analyze its diagnostic and prognostic value. MiR-613 was significantly decreased in ESCC tissue compared with paracancerous tissue ( P < 0.001). Moreover, the expression level of miR-613 was significantly reduced with increased T stage of ESCC. Statistically significant difference between ESCC patients and healthy controls in expression level of miR-613 (0.89 ± 0.73 vs. 1.71 ± 1.03, P < 0.001) was found. The area under the ROC curve (AUC) based on serum miR-613 was 0.767 ± 0.040. We also performed analysis on early-stage patients and revealed that the AUC value was 0.728 ± 0.052 ( P < 0.001). The Kaplan-Meier curve revealed that the downregulation of miR-613 was related to worse overall survival (OS) and progression-free survival (PFS) of ESCC patients ( P = 0.018 and P = 0.035, respectively). Furthermore, the multivariate analysis identified miR-613 to be an independent prognostic factor for OS and PFS ( P = 0.031 and P = 0.006, respectively) In conclusion, miR-613 is significantly reduced in cancerous tissue and serum samples of ESCC patients. It can serve as an ideal indicator for the diagnosis and prognosis of ESCC. [ABSTRACT FROM AUTHOR]

Background: Typhae Pollen (TP) and Trogopterus Feces (TF) are well-known traditional medicine in china which widely used for thousands of years as drug pair called Shixiao San for treatment of blood stasis syndrome, specially shown great efficacy in gynecological disease. Typhaneoside, vanillic acid and p-coumaric acid are the main bioactive components of Typhae Pollen. This study was carried out for comparing the pharmacokinetic profile of these three major bioactive components in rats after oral administration of Typhae Pollen-Trogopterus Feces (TP-TF) drug pair before and after compatibility. Methods: A sensitive and rapid UPLC-TQ/MS method has been developed for simultaneous quantification of the three main bioactive compounds in blood at different time points after oral administration of Typhae Pollen (TP) and the combination with Trogopterus Feces (TF). Results: There were significant differences of C, T, T and AUC for three bioactive compounds among the groups, for typhaneoside with the most highest plasma concentration of 370.86 ± 315.71 ng/mL and more longer T in TP-TF co-decoction group (C); for vanillic acid, TP-TF co-decoction group (C) had a good absorption with C (3870.99 ± 2527.99 ng/mL) and T (1.47 ± 3.20 h); for p-coumaric acid, it had similar pharmacokinetic characteristics with vanillic acid. Conclusions: The three bioactive components in Typhae Pollen (TP) were simultaneously determined by UPLC-TQ/MS and had a good absorption in rat plasma after the combination with Trogopterus Feces (TF). [ABSTRACT FROM AUTHOR]

Obesity is a public health problem in the US. Diet tracking helps control obesity but manual entry is tedious. Proposed solutions such as food recognition from photographs and scanning barcodes have limitations. We investigate the use of speech recognition for diet recording. We improved the accuracy of food order recognition at restaurants by (1) limiting words in the speech recognizer's corpus to only items on the menus of nearby restaurants (2) implementing an acoustic model to recognize the speaking style of the smartphone owner. Building on these mechanisms, we propose DietRecord, a smartphone application that automatically recognizes and records restaurant orders. Results of our user studies to evaluate DietRecord were encouraging. [ABSTRACT FROM AUTHOR]

Microscopy of direct smear with the Ziehl-Neelsen stain is still broadly used in tuberculosis diagnosis. However, this method suffers from low specificity and is difficult to distinguish Mycobacterium tuberculosis (MTB) from nontuberculosis mycobacterial (NTM), since all mycobacterial species are positive in Ziehl-Neelsen stain. In this study, we utilized whole cell SELEX to obtain species-specific aptamers for increasing the specificity of MTB detection. Whole cell SELEX was performed in MTB reference strain HRv by two selection processes based on enzyme-linked plate or Eppendorf tube, respectively. To increase success rate of generating aptamers, the selection processes were systematically monitored to understand the dynamic evolution of aptamers against complex structure of target bacteria. Two preponderant groups and ten high-affinity aptamers were obtained by analyzing the dynamic evolution. Preponderant aptamer MA1 from group I showed relatively high binding affinity with apparent dissociation constant (K value) of 12.02 nM. Sandwich ELISA assay revealed five aptamer combinations effectively bound MTB strains in preliminary evaluation, especially the combination based on aptamer MA2 (another preponderant aptamer from group II) and MA1. Further evaluated in many other strains, MA2/MA1 combination effectively identified MTB from NTM or other pathogenic bacteria, and displayed the high specificity and sensitivity. Binding analysis of aptamer MA1 or MA2 by fluorescence microscopy observation showed high binding reactivity with HRv, low apparent cross-reactivity with M. marinum, and no apparent cross-reactivity with Enterobacter cloacae. Taken together, this study provides attractive candidate species-specific aptamers to effectively capture or discriminate MTB strains. [ABSTRACT FROM AUTHOR]

The freshwater mussel Ptychorhynchus pfisteri is a threatened and endemic species in China. In this study, the complete maternal mitochondrial genome of P. pfisteri was firstly determined (GenBank accession no. KY067440). The circle genome is 16,040 bp in length. It consists of 14 protein-coding genes ( cox1-3, nad1-6, nad4L, cob, atp6, atp8 and FORF), 22 tRNA genes, two rRNA genes and a putative control region. The gene order of P. pfisteri is not identical to other unionoid bivalves except Gonideinae species. Maximum likelihood analyses reveal that P. pfisteri belongs to the subfamily Gonideinae. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb, the role of calcium (Ca2+) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb-infected mice and macrophages. The target of miR-27a is the ER-located Ca2+ transporter CACNA2D3. Targeting of this transporter leads to the downregulation of Ca2+ signaling, thus inhibiting autophagosome formation and promoting the intracellular survival of Mtb. Mice lacking of miR-27a and mice treated with an antagomir to miR-27a are more resistant to Mtb infection. Our findings reveal a strategy for Mtb to increase intracellular survival by manipulating the Ca2+-associated autophagy, and may also support the development of host-directed anti-TB therapeutic approaches. How Mycobacterium tuberculosis (Mtb) escapes autophagy-mediated clearance is poorly understood. Here, Liu et al. show that Mtb-induced MicroRNA-27a targets the ER-associated calcium transporter CACNA2D3, leading to suppression of antimicrobial autophagy and to enhanced intracellular survival of Mtb. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), and remains a leading public health problem. Previous studies have identified host genetic factors that contribute to Mtb infection outcomes. However, much of the heritability in TB remains unaccounted for and additional susceptibility loci most likely exist. We perform a multistage genome-wide association study on 2949 pulmonary TB patients and 5090 healthy controls (833 cases and 1220 controls were genome-wide genotyped) from Han Chinese population. We discover two risk loci: 14q24.3 (rs12437118, Pcombined = 1.72 × 10−11, OR = 1.277, ESRRB) and 20p13 (rs6114027, Pcombined = 2.37 × 10−11, OR = 1.339, TGM6). Moreover, we determine that the rs6114027 risk allele is related to decreased TGM6 transcripts in PBMCs from pulmonary TB patients and severer pulmonary TB disease. Furthermore, we find that tgm6-deficient mice are more susceptible to Mtb infection. Our results provide new insights into the genetic etiology of TB. Genetic risk loci for tuberculosis (TB) have so far been identified in African and Russian populations. Here, the authors perform a three-stage GWAS for TB in Han Chinese populations and find two risk loci near ESRRB and TGM6 and further demonstrate that tgm6 protects mice from Mtb infection. [ABSTRACT FROM AUTHOR]

Vitamin D can exert anticancer effect beyond bone and calcium metabolism. We aimed to investigate whether postoperative vitamin D supplementation affects quality of life (QOL) and survival in esophageal cancer (EC) patients. We utilized the widely used EORTC QLQ-C30 and QLQ-OES18 to assess QOL at EC diagnosis and 24 months after surgery. Generalized estimating equations (GEEs) were used to analysis the association of vitamin D supplement use with QOL. Kaplan-Meier method and Cox regression model were used to evaluate the prognostic value of vitamin D supplementation. The notably improved QOL were found among vitamin D supplementation users compared with non-users (p < 0.05). Kaplan-Meier analysis revealed that vitamin D supplement use was significantly associated with improved disease-free survival (DFS) (p = 0.030), but not related to overall survival (OS) (p = 0.303). The multivariable analysis further demonstrated vitamin D supplement use as an independent prognostic factor for DFS (p = 0.040; HR 0.610; 95% CI 0.381-0.978). In conclusion, these results showed that vitamin D supplement use could serve as a promising intervention to enhancing QOL and prolonging DFS in EC. [ABSTRACT FROM AUTHOR]

A correction to the article "Frankincense and myrrh suppress inflammation via regulation of the metabolic profiling and the MAPK signaling pathway" that was published online in the September 2, 2015 issue is presented.

Frankincense and myrrh are highly effective in treatment of inflammatary diseases, but lacking of the therapy mechanisms. We undertook this stuty to evaluate the effects on Adjuvant-induced Arthritis (AIA) rats and to explore the underlying mechanisms by analyzing the metabolic profiling and signaling pathway evaluated by expression of inflammatory cytokines, c-jun and c-fos and corresponding phosphorylation levels. The results stated the elevated expression levels of TNFα, PGE2, IL-2, NO, and MDA in serum and swelling paw of AIA rats were significantly decreased after treatment, which exerted more remarkable inhibitive effects of combined therapy. The metbolic profiling of plasma and urine were clearly improved and twenty-one potential biomarkers were identified. Moreover, the inhibited effects of five bioactive components on cytokine transcription in PHA stimulated-PBMC showed the MAPK pathway might account for this phenomenon with considerable reduction in phosphorylated forms of all the three MAPK (ERK1/2, p38 and JNK) and down regulation of c-jun and c-fos. [ABSTRACT FROM AUTHOR]