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The purposes of this study were to construct a comprehensive nomogram for providing a simple, precise and personalized prediction of incident multidrug-resistant tuberculosis (MDR-TB) after completing pulmonary tuberculosis treatment (CPTBT). A matched case–control study (1:2 ratios) was performed between 2005 and 2018. A multivariable Cox regression analysis was used to evaluate independent predictors of incident MDR-TB after the CPTBT. A comprehensive nomogram was developed based on the multivariable Cox model. Overall, 1, 836 participants were included in this study. We developed and validated a simple-to-use nomogram that predicted the individualized risk of incident MDR-TB by using 10 parameters after the CPTBT. The concordance index of this nomogram was 0.833 [95% confidence interval (CI) 0.807–0.859] and 0.871 (95% CI 0.773–0.969) for the training and validation sets, respectively, which indicated adequate discriminatory power. The calibration curves for the risk of incident MDR-TB showed an optimal agreement between nomogram prediction and actual observation in the training and validation sets, respectively. The high sensitivity and specificity of nomogram was indicated by using a receiver operating characteristic curve analysis. Through this clinic tool, TB control executives could more precisely monitor, estimate and intervene the risk of incident MDR-TB among individuals with CPTBT.

Microhaplotypes are an emerging type of forensic genetic marker that are expected to support multiple forensic applications. Here, we developed a 124-plex panel for microhaplotype genotyping based on next-generation sequencing (NGS). The panel yielded intralocus and interlocus balanced sequencing data with a high percentage of effective reads. A full genotype was determined with as little as 0.1 ng of input DNA. Parallel mixture experiments and in-depth comparative analyses were performed with capillary-electrophoresis-based short tandem repeat (STR) and NGS-based microhaplotype genotyping, and demonstrated that microhaplotypes are far superior to STRs for mixture deconvolution. DNA from Han Chinese individuals (n = 256) was sequenced with the 124-plex panel. In total, 514 alleles were observed, and the forensic genetic parameters were calculated. A comparison of the forensic parameters for the 20 microhaplotypes with the top Ae values in the 124-plex panel and 20 commonly used forensic STRs showed that these microhaplotypes were as effective as STRs in identifying individuals. A linkage disequilibrium analysis showed that 106 of the 124 microhaplotypes were independently hereditary, and the combined match probability for these 106 microhaplotypes was 5.23 × 10−66. We conclude that this 124-plex microhaplotype panel is a powerful tool for forensic applications.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Two time-reversal quantum key distribution (QKD) schemes are the quantum entanglement based device-independent (DI)-QKD and measurement-device-independent (MDI)-QKD. The recently proposed twin field (TF)-QKD, also known as phase-matching (PM)-QKD, has improved the key rate bound from $O\left( \eta \right )$ to $O\left( \sqrt {\eta} \right )$ with $\eta$ the channel transmittance. In fact, TF-QKD is a kind of MDI-QKD but based on single-photon detection. In this paper, we propose a different PM-QKD based on single-photon entanglement, referred to as single-photon entanglement-based phase-matching (SEPM)-QKD, which can be viewed as a time-reversed version of the TF-QKD. Detection loopholes of the standard Bell test, which often occur in DI-QKD over long transmission distances, are not present in this protocol because the measurement settings and key information are the same quantity which is encoded in the local weak coherent state. We give a security proof of SEPM-QKD and demonstrate in theory that it is secure against all collective attacks and beam-splitting attacks. The simulation results show that the key rate enjoys a bound of $O\left( \sqrt {\eta} \right )$ with respect to the transmittance. SEPM-QKD not only helps us understand TF-QKD more deeply, but also hints at a feasible approach to eliminate detection loopholes in DI-QKD for long-distance communications., Comment: 7 pages, 3 figures

The round-robin differential-phase-shift quantum key distribution (RRDPS-QKD) protocol could provide an effective way to estimate the leakage information without monitoring the signal disturbance. Moreover, the self-compensating property of plug-and-play (P&P) setup can eliminate the variations of phase or polarization in QKD procedure. In the paper, we introduce the P&P concept into RRDPS-QKD, and propose a QKD protocol, named P&P RRDPS-QKD protocol, to make the RRDPS-QKD scheme more practical. We analyze the security, and discuss the key generation rate with infinite-intensity decoy state method. The results show that the proposed protocol is a good solution to RRDPS-QKD protocol with untrusted sources. It has a high security and its key generation rate could be as good as the protocol with trusted sources when the average input photon number N is greater than 106. In addition, the proposed protocol has a high noise tolerance in comparison with P&P BB84-QKD protocol.

In this paper, we present an effective way for simulating oceanic turbulence channel on the beam carrying orbital angular momentum (OAM). The influence caused by oceanic turbulence channel on the phase and intensity of the propagation beam is equivalent to that the beam passing through several individual phase screens generated by power spectrum inversion method at regular intervals. A modified subharmonic compensation method is then further balance the phase screen for the losses of lower frequency components in the power spectrum inversion method. The feasibility is verified by the theoretical phase structure function and the propagation characteristics of an OAM beam in underwater environment. The results show that the phase structure function and the propagation characteristics of the OAM beam evaluated by the phase screen model all coincide with those theoretical results at high spatial frequency. Simultaneously, the low frequency components could be effectively compensated by the modified subharmonic method. With the increase of the subharmonic order and sample level, the performance evaluated by the phase screen model are closer to the theoretical ones. It has provided an effective way for simulating oceanic turbulence channel for the underwater optical communications.

Radopholus similis is an important migratory endoparasitic nematode, severely harms banana, citrus and many other commercial crops. Little is known about the molecular mechanism of infection and pathogenesis of R. similis. In this study, 64761 unigenes were generated from eggs, juveniles, females and males of R. similis. 11443 unigenes showed significant expression difference among these four life stages. Genes involved in host parasitism, anti-host defense and other biological processes were predicted. There were 86 and 102 putative genes coding for cell wall degrading enzymes and antioxidase respectively. The amount and type of putative parasitic-related genes reported in sedentary endoparasitic plant nematodes are variable from those of migratory parasitic nematodes on plant aerial portion. There were no sequences annotated to effectors in R. similis, involved in feeding site formation of sedentary endoparasites nematodes. This transcriptome data provides a new insight into the parasitic and pathogenic molecular mechanisms of the migratory endoparasitic nematodes. It also provides a broad idea for further research on R. similis.

In this paper, we report on experimental demonstration of the propagation and self-healing property of Bessel-Gaussian (BG) beam carrying orbital angular momentum (OAM) in an underwater environment. Especially, the effects of topological charge, temperature gradient, and salinity on the transmission and self-reconstruction of BG beam in underwater turbulence are analyzed. The results show that the detection probabilities both for propagation and self-healing greatly decrease with temperature gradient, and gradually decrease with salinity. BG beam has a self-healing property in the underwater environment when the obstruction is quite small. The detection probability greatly decreases with obstruction size, while it gradually decreases with salinity fluctuations for different obstruction sizes. For the same blockage ratio, the smaller topological charge of BG beam is, the better self-healing characteristics the BG beam has.

Oil palm (Elaeis guineensis Jacq.) is the leading oil-producing crops and the most important edible oil resource worldwide. DNA markers and genetic linkage maps are essential resources for marker-assisted selection to accelerate genetic improvement. We conducted RAD-seq on an Illumina NextSeq500 to discover genome-wide SNPs, and used the SNPs to construct a linkage map for an oil palm (Tenera) population derived from a cross between a Deli Dura and an AVROS Pisifera. The RAD-seq produced 1,076 million single-end reads across the breeding population containing 155 trees. Mining this dataset detected 510,251 loci. After filtering out loci with low accuracy and more than 20% missing data, 11,394 SNPs were retained. Using these SNPs, in combination with 188 anchor SNPs and 123 microsatellites, we constructed a linkage map containing 10,023 markers covering 16 chromosomes. The map length is 2,938.2 cM with an average marker space of 0.29 cM. The large number of SNPs will supply ample choices of DNA markers in analysing the genetic diversity, population structure and evolution of oil palm. This high-density linkage map will contribute to mapping quantitative trait loci (QTL) for important traits, thus accelerating oil palm genetic improvement.

3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a pivotal regulator in the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway that have been shown to play key roles in the functional development of B and T cells via activation of AGC protein kinases during hematopoiesis. However, the role of PDK1 in HSCs has not been fully defined. Here we specifically deleted the PDK1 gene in the hematopoietic system and found that PDK1-deficient HSCs exhibited impaired function and defective lineage commitment abilities. Lack of PDK1 caused HSCs to be less quiescent and to produce a higher number of phenotypic HSCs and fewer progenitors. PDK1-deficient HSCs were also unable to reconstitute the hematopoietic system. Notably, HSC function was more dependent on PDK1 than on mTORC2, which indicates that PDK1 plays a dominant role in the Akt-mediated regulation of HSC function. PDK1-deficient HSCs also exhibited reduced ROS levels, and treatment of PDK1-deficient HSCs with L-butathioninesulfoximine in vitro elevated the low ROS level and promoted colony formation. Therefore, PDK1 appears to contribute to HSC function partially via regulating ROS levels.

Drug-induced cholestasis is a leading cause of drug withdrawal. However, the use of primary human hepatocytes (PHHs), the gold standard for predicting cholestasis in vitro, is limited by their high cost and batch-to-batch variability. Mature hepatocyte characteristics have been observed in human induced hepatocytes (hiHeps) derived from human fibroblast transdifferentiation. Here, we evaluated whether hiHeps could biosynthesize and excrete bile acids (BAs) and their potential as PHH alternatives for cholestasis investigations. Quantitative real-time PCR (qRT-PCR) and western blotting indicated that hiHeps highly expressed BA synthases and functional transporters. Liquid chromatography tandem mass spectrometry (LC-MS/MS) showed that hiHeps produced normal intercellular unconjugated BAs but fewer conjugated BAs than human hepatocytes. When incubated with representative cholestatic agents, hiHeps exhibited sensitive drug-induced bile salt export pump (BSEP) dysfunction, and their response to cholestatic agent-mediated cytotoxicity correlated well with that of PHHs (r2 = 0.8032). Deoxycholic acid (DCA)-induced hepatotoxicity in hiHeps was verified by elevated aspartate aminotransferase (AST) and γ-glutamyl-transferase (γ-GT) levels. Mitochondrial damage and cell death suggested DCA-induced toxicity in hiHeps, which were attenuated by hepatoprotective drugs, as in PHHs. For the first time, hiHeps were reported to biosynthesize and excrete BAs, which could facilitate predicting cholestatic hepatotoxicity and screening potential therapeutic drugs against cholestasis.

Sexual dimorphism is an interesting biological phenomenon. Previous studies showed that DNA methylation might play a role in sexual dimorphism. However, the overall picture of the genome-wide methylation landscape in sexually dimorphic species remains unclear. We analyzed the DNA methylation landscape and transcriptome in hybrid tilapia (Oreochromis spp.) using whole genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq). We found 4,757 sexually dimorphic differentially methylated regions (DMRs), with significant clusters of DMRs located on chromosomal regions associated with sex determination. CpG methylation in promoter regions was negatively correlated with the gene expression level. MAPK/ERK pathway was upregulated in male tilapia. We also inferred active cis-regulatory regions (ACRs) in skeletal muscle tissues from WGBS datasets, revealing sexually dimorphic cis-regulatory regions. These results suggest that DNA methylation contribute to sex-specific phenotypes and serve as resources for further investigation to analyze the functions of these regions and their contributions towards sexual dimorphisms.

Asian seabass has suffered from viral nervous necrosis (VNN) disease. Our previous study has mapped quantitative trait loci (QTL) for resistance to VNN disease. To fine map these QTL and identify causative genes, we identified 6425 single nucleotide polymorphisms (SNPs) from 85 dead and 94 surviving individuals. Combined with 155 microsatellites, we constructed a genetic map consisting of 24 linkage groups (LGs) containing 3000 markers, with an average interval of 1.27 cM. We mapped one significant and three suggestive QTL with phenotypic variation explained (PVE) of 8.3 to 11.0%, two significant and two suggestive QTL with PVE of 7.8 to 10.9%, for resistance in three LGs and survival time in four LGs, respectively. Further analysis one QTL with the largest effect identified protocadherin alpha-C 2-like (Pcdhac2) as the possible candidate gene. Association study in 43 families with 1127 individuals revealed a 6 bp insertion-deletion was significantly associated with disease resistance. qRT-PCR showed the expression of Pcdhac2 was significantly induced in the brain, muscle and skin after nervous necrosis virus (NNV) infection. Our results could facilitate marker-assisted selection (MAS) for resistance to NNV in Asian seabass and set up the basis for functional analysis of the potential causative gene for resistance.

Transition metal oxides host an array of exotic electronic phases, including superconductivity, ferroelectricity, quantum spin liquid and Mott insulators. Their extreme sensitivity to external stimuli enables various routes to manipulate the ground state, which greatly improves our understanding of the physics involved. Here, we report the competition between strain and dimensionality effects on the phase evolution in high quality NdNiO3 films down to several unit cells. While both compressive and tensile strains increase the Ni 3d band width and favor the metallic phase, reducing dimensionality, on the other hand, decreases the covalent band width and favors the insulating phase in NdNiO3. The experimental observations are well supported by ab initio calculations and improve our understanding of the electronic behavior in strongly correlated electron systems.

A high-density genetic map is essential for comparative genomic studies and fine mapping of QTL and can also facilitate genome sequence assembly. Here, a high density genetic map of Asian seabass was constructed with 3321 SNPs generated by sequencing 144 individuals in a F2 family. The length of the map was 1577.67 cM with an average marker interval of 0.52 cM. A high level of genomic synteny among Asian seabass, European seabass, Nile tilapia and stickleback was detected. Using this map, one genome-wide significant and five suggestive QTL for growth traits were detected in six linkage groups (i.e. LG4, LG5, LG11, LG13, LG14 and LG15). These QTL explained 10.5–16.0% of phenotypic variance. A candidate gene, ACOX1 within the significant QTL on LG5 was identified. The gene was differentially expressed between fast- and slow-growing Asian seabass. The high-density SNP-based map provides an important tool for fine mapping QTL in molecular breeding and comparative genome analysis.

Hit to lead (H2L) optimization is a key step for drug and agrochemical discovery. A critical challenge for H2L optimization is the low efficiency due to the lack of predictive method with high accuracy. We described a new computational method called Computational Substitution Optimization (CSO) that has allowed us to rapidly identify compounds with cytochrome bc1 complex inhibitory activity in the nanomolar and subnanomolar range. The comprehensively optimized candidate has proved to be a slow binding inhibitor of bc1 complex, ~73-fold more potent (Ki = 4.1 nM) than the best commercial fungicide azoxystrobin (AZ; Ki = 297.6 nM) and shows excellent in vivo fungicidal activity against downy mildew and powdery mildew disease. The excellent correlation between experimental and calculated binding free-energy shifts together with further crystallographic analysis confirmed the prediction accuracy of CSO method. To the best of our knowledge, CSO is a new computational approach to substitution-scanning mutagenesis of ligand and could be used as a general strategy of H2L optimisation in drug and agrochemical design.

Vertical interfaces in vertically aligned nanocomposite thin films have been approved to be an effective method to manipulate functionalities. However, several challenges with regard to the understanding on the physical process underlying the manipulation still remain. In this work, because of the ordered interfaces and large interfacial area, heteroepitaxial (BaTiO3)1-x:(Sm2O3)x thin films have been fabricated and used as a model system to investigate the relationship between vertical interfaces and dielectric properties. Due to a relatively large strain generated at the interfaces, vertical interfaces between BaTiO3 and Sm2O3 are revealed to become the sinks to attract oxygen vacancies. The movement of oxygen vacancies is confined at the interfaces and hampered by the misfit dislocations, which contributed to a relaxation behavior in (BaTiO3)1-x:(Sm2O3)x thin films. This work represents an approach to further understand that how interfaces influence on dielectric properties in oxide thin films.

Natural selection and selective breeding for genetic improvement have left detectable signatures within the genome of a species. Identification of selection signatures is important in evolutionary biology and for detecting genes that facilitate to accelerate genetic improvement. However, selection signatures, including artificial selection and natural selection, have only been identified at the whole genome level in several genetically improved fish species. Tilapia is one of the most important genetically improved fish species in the world. Using next-generation sequencing, we sequenced the genomes of 47 tilapia individuals. We identified a total of 1.43 million high-quality SNPs and found that the LD block sizes ranged from 10–100 kb in tilapia. We detected over a hundred putative selective sweep regions in each line of tilapia. Most selection signatures were located in non-coding regions of the tilapia genome. The Wnt signaling, gonadotropin-releasing hormone receptor and integrin signaling pathways were under positive selection in all improved tilapia lines. Our study provides a genome-wide map of genetic variation and selection footprints in tilapia, which could be important for genetic studies and accelerating genetic improvement of tilapia.

Ferroelectric random access memory is still challenging in the feature of combination of room temperature stability, non-destructive readout and high intensity storage. As a non-contact and non-destructive information readout method, surface potential has never been paid enough attention because of the unavoidable decay of the surface potential contrast between oppositely polarized domains. That is mainly due to the recombination of the surface movable charges around the domain walls. Here, by introducing a laser beam into the combination of piezoresponse force microscopy and Kelvin probe force microscopy, we demonstrate that the surface potential contrast of BiFeO3 films can be recovered under light illumination. The recovering mechanism is understood based on the redistribution of the photo-induced charges driven by the internal electric field. Furthermore, we have created a 12-cell memory pattern based on BiFeO3 films to show the feasibility of such photo-assisted non-volatile and non-destructive readout of the ferroelectric memory.

Oxygen vacancies (V(O)) effects on magnetic ordering in Eu₀.₅Ba₀.₅TiO₃₋δ (EBTO₃₋δ) thin films have been investigated using a combination of experimental measurements and first-principles density-functional calculations. Two kinds of EBTO₃₋δ thin films with different oxygen deficiency have been fabricated. A nuclear resonance backscattering spectrometry technique has been used to quantitatively measure contents of the V(O). Eu₀.₅Ba₀.₅TiO₃ ceramics have been known to exhibit ferroelectric (FE) and G-type antiferromagnetic (AFM) properties. While, a ferromagnetic (FM) behavior with a Curie temperature of 1.85 K has been found in the EBTO₃₋δ thin films. Spin-polarized Ti(3+) ions, which originated from the V(O), has been proven to mediate a FM coupling between the local Eu 4f spins and were believed to be responsible for the great change of the magnetic ordering. Considering the easy formation of V(O), our work opens up a new avenue for achieving co-existence of FM and FE orders in oxide materials.