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.

In insects, chitinases participate in the periodic shedding of old exoskeletons and the turnover of peritrophic membranes. Chitinase family members have been identified in dozens of species, including Tribolium castaneum, Drosophila melanogaster, and Anopheles gambiae. In this study, nine chitinases and three hypothetical chitinases have been identified in Bombyx mori L. (Lepidoptera: Bombycidae) through genome-wide searching. Phylogenetic analyses revealed that seven of them belong to the seven chitinase groups, respectively. BmCht25 and BmCht26 could not be grouped into the known chitinase groups, and might belong to two new groups of the chitinase family. BmCht10, BmCht25, and BmIDGF have glutamate amino acid substitutions in the active catalytic domain. Only BmCht5 and BmCht10 contain CBD domain and PEST sequences (rich in proline, glutamic acid, serine, and threonine). BmCht5 and BmCht26 are located on chromosome 7, and others (BmCht6, BmCht7, BmCht10, BmCht11, BmCht20, BmIDGF) are located on separate chromosomes of Bombyx mori, respectively. The present study provides important background information for future studies using Bombyx mori as a model organism for insect development and virus and host interaction.

ORCID ID: 0000-0002-7391-0246 (Y.F.).MicroRNAs (miRNAs) are a class of small regulatory RNAs that are found in almost all of the eukaryotes. Arabidopsis (Arabidopsis thaliana) miRNAs are processed from primary miRNAs (pri-miRNAs), mainly by the ribonuclease III-like enzyme DICER-LIKE1 (DCL1) and its specific partner, HYPONASTIC LEAVES1 (HYL1), a double-strand RNA-binding protein, both of which contain two doublestrand RNA-binding domains (dsRBDs). These dsRBDs are essential for miRNA processing, but the functions of them are not clear. Here, we report that the two dsRBDs of DCL1 (DCL1-D1D2), and to some extent the second dsRBD (DCL1-D2), complement the hyl1 mutant, but not the first dsRBD of DCL1 (DCL1-D1). DCL1-D1 is diffusely distributed throughout the nucleoplasm, whereas DCL1-D2 and DCL1-D1D2 concentrate in nuclear dicing bodies in which DCL1 and HYL1 colocalize. We show further that protein-protein interaction is mainly mediated by DCL1-D2, while DCL1-D1 plays a major role in binding of pri-miRNAs. These results suggest parallel roles between C-terminal dsRBDs of DCL1 and N-terminal dsRBDs of HYL1 and support a model in which Arabidopsis pri-miRNAs are recruited to dicing bodies through functionally divergent dsRBDs of microprocessor for accurate processing of plant pri-miRNAs.

We examine the relationship between atmospheric and water pollution, traffic congestion, access to parkland and personal well-being using a survey administered across six Chinese cities in 2007. In contrast to existing studies of well-being determinants by economists which typically employ single-item indicators, we use the Personal Well-being Index (PWI). We also employ the Job

In order to study the effects of different concentrations of sulfate on the strength of fly ash-based coal mine filling paste, using variable control, mechanical analysis, and other means, the changes in the uniaxial compressive strengths of filling paste blocks soaked in different concentrations of sodium sulfate solution for different durations are studied, and their stress-strain curves are discussed. e hydrated products of each block are analyzed at different stages by XRD, and the results indicate that different concentrations of sodium sulfate solution have different effects on the strength of the filling paste after soaking for different durations. A sodium sulfate solution with a concentration of 5% had an activator effect on the fly ash-based filling paste and enhanced the strength of the filling paste. A sodium sulfate solution with a concentration of 10% and 15% increased the early strength of the paste test block faster, but after 60 d, the strength decreased. e stress-strain curves for these blocks show that the elastic moduli of the filling paste test blocks change irregularly, and it was found that with the increase in soaking time, the blocks soaked in the 10% and 15% sodium sulfate solutions developed fissures in the later stage that adversely affected the strength of the filling paste. e XRD results show that the filling paste test block hydration products are hydrated calcium silicate (C-S-H) based and that ettringite (AFt), beneficial to strength of the filling paste in proper quantities, appeared in the main product of the filling paste test blocks that were soaked in the sodium sulfate solution. With the increase in the concentration of the sodium sulfate solution, the AFt is generated in larger quantities, and gypsum crystals begin to appear, which is not conducive to the filling paste block strength.

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InGaAs/InP single-photon detectors (SPDs) are the key devices for applications requiring near-infrared single-photon detection. Gating mode is an effective approach to synchronous single-photon detection. Increasing gating frequency and reducing module size are important challenges for the design of such detector system. Here we present for the first time an InGaAs/InP SPD with 1.25 GHz sine wave gating using a monolithically integrated readout circuit (MIRC). The MIRC has a size of 15 mm × 15 mm and implements the miniaturization of avalanche extraction for high-frequency sine wave gating. In the MIRC, low-pass filters and a low-noise radio frequency amplifier are integrated based on the technique of low temperature co-fired ceramic, which can effectively reduce the parasitic capacitance and extract weak avalanche signals. We then characterize the InGaAs/InP SPD to verify the functionality and reliability of MIRC, and the SPD exhibits excellent performance with 27.5 % photon detection efficiency, 1.2 kcps dark count rate, and 9.1 % afterpulse probability at 223 K and 100 ns hold-off time. With this MIRC, one can further design miniaturized high-frequency SPD modules that are highly required for practical applications. . InGaAs/InP SPAD can be operated either in free-running mode or in gating mode, aiming for asynchronous and synchronous single-photon detections, respectively.Free-running mode is suited for the applications in which photon arrival times are unknown. So far, various approaches have been implemented for free-running single-photon detection including passive quenching [2,3], passive quenching and active reset (PQAR) scheme [4,5], integrated circuit of active quenching [6,7], negative feedback avalanche diodes [8][9][10][11][12]. However, in the free-running schemes relatively long hold-off time settings are often required to further reduce the afterpulse probability, which may limit the maximum count rate of InGaAs/InP SPDs.For the applications in which photon arrival times are known, using gating mode can suppress both dark count rate (DCR) and afterpulse probability (P ap ). The challenge in this scheme is to extract avalanche signals superimposed on derivative signals due to the capacitive responses of SPAD. Gating frequency is one of the most important parameters, which determines the maximum count rate of SPD. In the early stage, gating frequencies were limited at the level of 10 MHz. After the invention of high-frequency gating techniques including sine wave gating (SWG) [13] and self-differencing [14], gating frequency has been rapidly increased up to GHz. In highfrequency gating schemes, ultrashort gating time extremely limits the quantity of charge created during avalanche process, which, therefore, results in effective suppression of the afterpulsing effect and significant increase of count rate. As a consequence of high-frequency gating, the amplitudes of avalanche signals are pretty small, i.e., at the level of mV. Therefore, the primary goal of readout circuit in the high-frequency gat...

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