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Quantum teleportation plays a significant role in the field of quantum communication. This paper investigates quantum teleportation through a noisy environment by using GHZ state and non-standard W state as quantum channels. We analyze the efficiency of quantum teleportation by solving analytically a master equation in Lindblad form. Following the quantum teleportation protocol, we obtain the fidelity of quantum teleportation as a function of evolution time. The calculation results show that the teleportation fidelity using non-standard W is higher in comparison to GHZ state at the same evolution time. Moreover, we consider the efficiency of teleportation with weak measurements and reverse quantum measurement under amplitude damping noise. Our analysis suggests that the teleportation fidelity using non-standard W is also more robust to noise than GHZ state in the same conditions. Interestingly, we found that weak measurement and its reverse operation have no positive effect on the efficiency of quantum teleportation by using GHZ and non-standard W state in the amplitude damping noise environment. In addition, we also demonstrate the efficiency of quantum teleportation can be improved by making minor modifications to the protocol. [ABSTRACT FROM AUTHOR]

We investigated the effects of anti-CD80/86 antibodies in a murine high-risk corneal transplantation rejection model. A mixed lymphocyte reaction (MLR) assay was conducted with anti-CD80/86 antibodies. Inflammatory cytokine levels in the culture supernatant were measured using an enzyme-linked immunosorbent assay. Interferon (IFN)-γ-producing CD4+ T cell frequencies in the MLR were assessed using flow cytometry. In vivo, high-risk corneal allograft survival and IFN-γ-producing CD4+ T cell frequencies in corneal grafts were assessed with intraperitoneal injection of anti-CD80/86 antibodies compared to phosphate-buffered saline (PBS). RNA-sequencing was performed on corneal grafts 2 weeks post-transplantation. Anti-CD80/86 antibodies significantly decreased T-cell proliferation, IFN-γ+-producing CD4+ T cell frequencies, and IFN-γ, interleukin (IL)-1β, IL-2, IL-10, and tumor necrosis factor-α production in the MLR compared to PBS injection. Intraperitoneal injection of anti-CD80/86 antibodies significantly prolonged corneal graft survival and decreased IFN-γ+-producing CD4+ T cell frequencies compared to PBS injection. Gene set enrichment analysis showed that the gene sets mainly enriched in the control group were related to allograft rejection and inflammatory response compared to PBS injection. Anti-CD80/86 antibodies significantly prolonged corneal graft survival by inhibiting T-cell proliferation and inflammatory response. [ABSTRACT FROM AUTHOR]

This study aimed to construct and externally validate a user-friendly nomogram-based scoring model for predicting the risk of urinary tract infections (UTIs) in patients with acute ischemic stroke (AIS). A retrospective real-world cohort study was conducted on 1748 consecutive hospitalized patients with AIS. Out of these patients, a total of 1132 participants were ultimately included in the final analysis, with 817 used for model construction and 315 utilized for external validation. Multivariate regression analysis was applied to develop the model. The discriminative capacity, calibration ability, and clinical effectiveness of the model were evaluated. The overall incidence of UTIs was 8.13% (92/1132), with Escherichia coli being the most prevalent causative pathogen in patients with AIS. After multivariable analysis, advanced age, female gender, National Institute of Health Stroke Scale (NIHSS) score ≥ 5, and use of urinary catheters were identified as independent risk factors for UTIs. A nomogram-based SUNA model was constructed using these four factors (Area under the receiver operating characteristic curve (AUC) = 0.810), which showed good discrimination (AUC = 0.788), calibration, and clinical utility in the external validation cohort. Based on four simple and readily available factors, we derived and externally validated a novel and user-friendly nomogram-based scoring model (SUNA score) to predict the risk of UTIs in patients with AIS. The model has a good predictive value and provides valuable information for timely intervention in patients with AIS to reduce the occurrence of UTIs. [ABSTRACT FROM AUTHOR]

Although all wild-type bacterial populations exhibit antibiotic tolerance, bacterial mutants with higher or lower tolerant subpopulation sizes have been described. We recently showed that in mycobacteria, phenotypically-resistant subpopulations can grow in bulk-lethal concentrations of rifampicin, a first-line anti-tuberculous antibiotic targeting RNA polymerase. Phenotypic resistance was partly mediated by paradoxical upregulation of RNA polymerase in response to rifampicin. However, naturally occurring mutations that increase tolerance via this mechanism had not been previously described. Here, we used transposon insertional mutagenesis and deep sequencing (Tnseq) to investigate rifampicin-specific phenotypic resistance using two different in vitro models of rifampicin tolerance in Mycobacterium smegmatis. We identify multiple genetic factors that mediate susceptibility to rifampicin. Disruption of one gene, lepA, a translation-associated elongation factor, increased rifampicin tolerance in all experimental conditions. Deletion of lepA increased the subpopulation size that is able to grow in bulk-lethal rifampicin concentrations via upregulation of basal rpoB expression. Moreover, homologous mutations in lepA that are found in clinical Mycobacterium tuberculosis (Mtb) isolates phenocopy lepA deletion to varying degrees. Our study identifies multiple genetic factors associated with rifampicin tolerance in mycobacteria, and may allow correlation of genetic diversity of clinical Mtb isolates with clinically important phenotypes such as treatment regimen duration. [ABSTRACT FROM AUTHOR]

We study the genuine tripartite nonlocality of some qubit states in a triple JCM. In this model, each atom state (A, B or C) was initially prepared with an independent cavity (a, b or c). By using two kinds of GHZ-like states as the atomic initial states, we investigate the genuine tripartite nonlocality as the time evolutions for the non-interaction three-qubit subsystems. We also study the genuine tripartite nonlocality of the subsystems by using the Svetlichny inequality. For the subsystems of three atoms ABC and three cavity modes abc, we show that they are genuinely nonlocal at certain period intervals of time. The states of all the other inequivalent subsystems satisfy the Svetlichny inequality for two types of GHZ-like states. [ABSTRACT FROM AUTHOR]

A DMA (dynamic mechanical analysis)-like device based on the principle of classical viscoelasticity testing is invented to investigate the in-situ/in-vivo shear-bearing mechanism of plantar soft tissue. Forty-three volunteers were recruited for the shear-strain test in the longitudinal and transverse directions at five anatomical spots on the plantar surface. Several encouraging observations indicated significant variances among different spots and individuals, implying that the outer forefoot surrounding the second, fifth metatarsal head is a more intensive shear-bearing region on the plantar surface compared to the inner forefoot under the first metatarsal head, and drawing the hypothesis of a significant effect of BMI on the shear-bearing property. The speculations agree with our expectations and other previous research. The feasibility and practical value of this novel approach are substantiated, and these intriguing discoveries provide foundational underpinnings for further in-depth investigations. [ABSTRACT FROM AUTHOR]

Hyposalivation is a complication of hypertension. However, little is known about the role of long non-coding RNAs (lncRNAs) in salivary glands in hypertension. This study aimed to compare the lncRNA and mRNA expression profiles between spontaneous hypertension rats (SHRs) and Wistar-Kyoto (WKY) rats through microarray analysis and apple bioinformatics methods to analyse their potential roles in hyposalivation. The differentially expressed (DE) lncRNAs and mRNAs were confirmed by quantitative real-time PCR (qRT-PCR). Compared with WKY rats, 225 DE lncRNAs and 473 DE mRNAs were identified in the SMG of SHRs. The pathway analyses of DE mRNAs showed that inflammatory mediator regulation of transient receptor potential channels was involved in hyposalivation in SHRs. Ten DE lncRNAs were chosen for further research. A coding-non-coding gene co-expression (CNC) network and competing endogenous RNA (ceRNA) network analysis revealed that the potential functions of these 10 DE lncRNAs were closely connected with the processes of the immune response. This study showed abundant DE lncRNAs and mRNAs in hypertensive SMGs. Furthermore, our results indicated strong associations between the immune response and hyposalivation and showed the potential of immune-related genes as novel and therapeutic targets for hyposalivation. [ABSTRACT FROM AUTHOR]

Misfolding of translated proteins occurs in all domains of life. In most cells, misfolded proteins coalesce in discrete aggregates at distinct cellular locations. In many bacteria, including mycobacteria, protein aggregates are located at the cellular pole. Yet the mechanism by which aggregates are sorted to the mycobacterial pole is not known. Here, we show that in Mycobacterium smegmatis, the small heat shock protein HspX plays a critical role in the polar localization of aggregates of a model fluorescent misfolded protein, GLR103. HspX itself has a polar localization, which is dependent on its N-terminal domain. In a strain deleted for hspX, GLR103 is less liable to aggregation and no longer localizes to the pole, and redirecting HspX to the septum radically disrupts the normal polar localization of GLR103 aggregates. To further investigate the role of HspX in native protein aggregation, we performed semi-quantitative mass-spectrometry of mycobacterial protein aggregates in wild-type, hspX-deleted and hspX-overexpressing strains. We identified a subset of proteins that appeared to be HspX-dependent for aggregate formation. Furthermore, we demonstrate that for validated native protein aggregates, sorting to the cellular pole following proteotoxic stress required HspX. In summary, we have identified the cellular function of HspX in Mycobacterium smegmatis as both a pro-aggregase and polar sortase. [ABSTRACT FROM AUTHOR]

To determine whether the nationwide program 'Reducing maternal mortality and eliminating neonatal tetanus' contributed to the rapid decline in China's maternal mortality ratio (MMR) and neonatal tetanus elimination by enhancing hospital delivery, we compared MMR and neonatal tetanus incidence rate (NTR) reductions by province from 2000 to 2013. The difference-in-difference method was used to analyze the program effect. Long-term effects were analyzed relative to MMR and NTR in 2000 and 2002, respectively, while short-term effects in a given year were analyzed relative to MMR and NTR in the preceding year. The national program was associated with a faster decline in MMR in the long term. The rate of decline showed an inverse 'U' shape from 2000 to 2013, peaking in 2009. The program had a short-term effect in MMR reduction in 2005, 2007, and 2009. The program was also associated with faster decline in NTR in the short term at some time points, but this association was not consistent and was not found in the long term. In conclusion, the program accelerated decline of MMR from 2000 to 2013 but did not clearly reduce NTR at the province level. Therefore, this targeted program worked efficiently in resource-poor areas. [ABSTRACT FROM AUTHOR]

Most of the genome-wide association studies (GWASs) for human complex diseases have ignored dominance, epistasis and ethnic interactions. We conducted comparative GWASs for total cholesterol using full model and additive models, which illustrate the impacts of the ignoring genetic variants on analysis results and demonstrate how genetic effects of multiple loci could differ across different ethnic groups. There were 15 quantitative trait loci with 13 individual loci and 3 pairs of epistasis loci identified by full model, whereas only 14 loci (9 common loci and 5 different loci) identified by multi-loci additive model. Again, 4 full model detected loci were not detected using multi-loci additive model. PLINK-analysis identified two loci and GCTA-analysis detected only one locus with genome-wide significance. Full model identified three previously reported genes as well as several new genes. Bioinformatics analysis showed some new genes are related with cholesterol related chemicals and/or diseases. Analyses of cholesterol data and simulation studies revealed that the full model performs were better than the additive-model performs in terms of detecting power and unbiased estimations of genetic variants of complex traits. [ABSTRACT FROM AUTHOR]

Regulation of intron retention (IR), a form of alternative splicing, is a newly recognized checkpoint in gene expression. Since there are numerous abnormalities in gene expression in the prototypic autoimmune disease systemic lupus erythematosus (SLE), we sought to determine whether IR was intact in patients with this disease. We, therefore, studied global gene expression and IR patterns of lymphocytes in SLE patients. We analyzed RNA-seq data from peripheral blood T cell samples from 14 patients suffering from systemic lupus erythematosus (SLE) and 4 healthy controls and a second, independent data set of RNA-seq data from B cells from16 SLE patients and 4 healthy controls. We identified intron retention levels from 26,372 well annotated genes as well as differential gene expression and tested for differences between cases and controls using unbiased hierarchical clustering and principal component analysis. We followed with gene-disease enrichment analysis and gene-ontology enrichment analysis. Finally, we then tested for significant differences in intron retention between cases and controls both globally and with respect to specific genes. Overall decreased IR was found in T cells from one cohort and B cells from another cohort of patients with SLE and was associated with increased expression of numerous genes, including those encoding spliceosome components. Different introns within the same gene displayed both up- and down-regulated retention profiles indicating a complex regulatory mechanism. These results indicate that decreased IR in immune cells is characteristic of patients with active SLE and may contribute to the abnormal expression of specific genes in this autoimmune disease. [ABSTRACT FROM AUTHOR]

To provide evidence-based medicine references for formulating prevention and control policies in plateau areas, we explore the characteristics of anemia patients in Tibet (the plateau areas of China), especially those located at an altitude above 4500 m. We collected clinical data from 379 Tibetan anemia patients over the age of 18 years. We found those female patients accounted for the majority of Tibetan anemia patients. Almost half of the anemia patients aged from 28 to 47 years. The percentage of severe anemia and extremely severe anemia was 45.4% and 2.4%, respectively. 88.7% of patients are engaged in agriculture and animal husbandry, and 81.5% of patients just graduated from primary school or below. The most common causes of anemia were nutritional anemia, especially iron-deficiency anemia. At high-altitude localities, folic acid-deficiency anemia needs more attention. Overall, this study showed that altitude influences the incidence, severity, and cause of anemia. Peasants and herdsmen, low education levels, young and middle-aged women, and nutrition status should be paid attention to in future anemia control. [ABSTRACT FROM AUTHOR]

Lymphoblastoid cell lines (LCLs) provide an unlimited source of genomic DNA for genetic studies. Here, we compared mtDNA sequence variants, heteroplasmic or homplasmic, between LCL (sequenced by mitoRCA-seq method) and whole blood samples (sequenced through whole genome sequencing approach) of the same 130 participants in the Framingham Heart Study. We applied harmonization of sequence coverages and consistent quality control to mtDNA sequences. We identified 866 variation sites in the 130 LCL samples and 666 sites in the 130 blood samples. More than 94% of the identified homoplasmies were present in both LCL and blood samples while more than 70% of heteroplasmic sites were uniquely present either in LCL or in blood samples. The LCL and whole blood samples carried a similar number of homoplasmic variants (p = 0.45) per sample while the LCL carried a greater number of heteroplasmic variants than whole blood per sample (p < 2.2e−16). Furthermore, the LCL samples tended to accumulate low level heteroplasmies (heteroplasmy level in 3–25%) than their paired blood samples (p = 0.001). These results suggest that cautions should be taken in the interpretation and comparison of findings when different tissues/cell types or different sequencing technologies are applied to obtain mtDNA sequences. [ABSTRACT FROM AUTHOR]

Interferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu's arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P < 0.05). The percentage of CD3+IFN-γ+ cells in peripheral blood CD3+ cells was significantly higher in TAK patients than that of healthy control group (P = 0.002). A higher proportion of CD3+CD8+IFN-γ+ cells/CD3+IFN-γ+ cells (40.23 ± 11.98% vs 35.12 ± 11.51%, P = 0.049), and a significantly lower CD3+CD4+IFN-γ+/ CD3+CD8+IFN-γ+ ratio (1.34 ± 0.62% vs 1.80 ± 1.33%, P = 0.027) were showed in the TAK group than that of control group. The CD3+CD8+IFN-γ+/CD3+IFN-γ+ ratio was positively correlated with CD3+IFN-γ+cells/ CD3+cells ratio (r = 0.430, P = 0.001), serum IFN-γ level (r = 0.318, P = 0.040) and IL-17 level (r = 0.326, P = 0.031). It was negatively correlated with CD3+CD4+IFN-γ+/CD3+IFN-γ+ ratio (r = − 0.845, P < 0.001). IFN-γ secreted by CD3+CD8 + T cells is an important source of serum IFN-γ in TAK patients. [ABSTRACT FROM AUTHOR]

We aimed to describe the characteristics of adolescent pregnancy, determine its effect on adverse maternal and perinatal outcomes and explore whether that association varies with gestational age with the goal of proposing specific recommendations for adolescent health in China. This study included 2,366,559 women aged 10–24 years who had singleton pregnancies between 2012 and 2019 at 438 hospitals. Adolescent pregnancy was defined as younger than 20 years of age. We used multivariable logistic regression to estimate the effects. Women aged 20–24 years served as the reference group in all analyses. The proportion of rural girls with adolescent pregnancies rebounded after 2015 even though common-law marriage in rural areas decreased. Higher risks of eclampsia (adjusted odds ratio (aOR) 1.87, 95% confidence interval (CI) 1.57 ~ 2.23), severe anaemia (aOR 1.18, 95% CI 1.09 ~ 1.28), maternal near miss (MNM; aOR 1.24, 95% CI 1.12 ~ 1.37), and small for gestational age (SGA; aOR 1.30, 95% CI 1.28 ~ 1.33) were observed when gestational age was > 37 weeks. Adolescent pregnancy was independently associated with increased risks of other perinatal outcomes. Further implementation of pregnancy prevention strategies and improved health care interventions are needed to reduce adolescent pregnancies and prevent adverse fertility outcomes among adolescent women in China at a time when adolescent fertility rate is rebounding. [ABSTRACT FROM AUTHOR]

Corneal neovascularization (CNV) causes higher-order aberrations, corneal edema, ocular inflammation, and corneal transplant rejection, thereby decreasing visual acuity. In this study, we investigated the effects of topical administration of the kappa opioid receptor agonist nalfurafine (TRK-820) on CNV. To induce CNV, intrastromal corneal sutures were placed on the corneal stroma of BALB/c mice for 2 weeks. Nalfurafine (0.1 µg/2 μL/eye) was topically administered to the cornea once or twice daily after CNV induction. The CNV score, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in neovascularized corneas were evaluated using slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. The mRNA expression of the kappa opioid receptor gene Oprk1 was significantly upregulated following CNV induction. Topical administration of nalfurafine twice daily significantly suppressed CNV and lymphangiogenesis, as well as reduced the mRNA levels of angiogenic and pro-inflammatory factors in the neovascularized corneas. Moreover, nalfurafine administration twice daily reduced the numbers of infiltrating leukocytes, neutrophils, macrophages, and interferon-γ-producing CD4+ T cells in the neovascularized corneas. In this study, we demonstrated that topical administration of nalfurafine suppressed local CNV in a mouse model along with the activation of KOR, suggesting that nalfurafine may prevent and control CNV in humans. [ABSTRACT FROM AUTHOR]

Corneal allograft survival is mediated by the variety of immunological reactions and wound healing process. Our aim was to explore the effects of topical administration of ripasudil, a selective Rho-associated coiled-coil protein kinase inhibitor, on corneal allograft survival. Ripasudil was administered to mice thrice a day after allogeneic corneal transplantation. Corneal graft survival, opacity, neovascularization, re-epithelization, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in the grafted cornea and draining lymph nodes (dLNs) were evaluated with slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. Graft survival was significantly prolonged with lower graft opacity and neovascularization scores in 0.4% and 2.0% ripasudil-treated groups, and mRNA levels of angiogenic and pro-inflammatory factors in ripasudil-treated grafted corneas were reduced. Moreover, 0.4% and 2.0% ripasudil reduced CD45+-infiltrated leukocyte frequency, Cd11b and Cd11c mRNA levels, and the frequencies of mature dendritic cells, IFNγ-, and IL-17- producing CD4+T cells in the dLNs of recipients. Re-epithelization rate of the grafted cornea was significantly higher in the 0.4% and 2.0% ripasudil groups than in the control. Topically applied ripasudil prolonged graft survival by downregulating neovascularization and inflammation factors, while promoting corneal re-epithelization, suggesting that ripasudil may be useful for suppressing immunological rejection in corneal transplantation. [ABSTRACT FROM AUTHOR]

To reveal the impacts of smoking on genetic architecture of human body weight, we conducted a genome-wide association study on 5,336 subjects in four ethnic populations from MESA (The Multi-Ethnic Study of Atherosclerosis) data. A full genetic model was applied to association mapping for analyzing genetic effects of additive, dominance, epistasis, and their ethnicity-specific effects. Both the unconditional model (base) and conditional model including smoking as a cofactor were investigated. There were 10 SNPs involved in 96 significant genetic effects detected by the base model, which accounted for a high heritability (61.78%). Gene ontology analysis revealed that a number of genetic factors are related to the metabolic pathway of benzopyrene, a main compound in cigarettes. Smoking may play important roles in genetic effects of dominance, dominance-related epistasis, and gene-ethnicity interactions on human body weight. Gene effect prediction shows that the genetic effects of smoking cessation on body weight vary from different populations. [ABSTRACT FROM AUTHOR]

This multicenter, randomized, double-blind, parallel-controlled trial aimed to compare the pharmacokinetics (PK) of IBI301 with rituximab in patients with CD20-positive (CD20+) B-cell lymphoma, who achieved a complete response/unconfirmed complete response after standard treatments. Patients were randomized (1:1) to receive IBI301 or rituximab (375 mg/m2, IV). Patients who continuously benefitted from the trial after the PK phase underwent the extension phase to receive up to three cycles of 3-month-cycle of rituximab/IBI301 maintenance therapy. PK was described using the area under the serum concentration–time curve from time zero to infinity (AUC0-inf), AUC from time zero to last quantifiable concentration (AUC0-t), and maximum serum concentration (Cmax). Pharmacodynamics (PD), incidence of adverse events and immunogenicity were evaluated. PK was defined equivalent, if 90% confidence intervals (CIs) for geometric mean ratios of PK endpoints fell within the margin of 0.8–1.25. Overall, 181 patients were enrolled in IBI301 (n = 89) and rituximab (n = 92) groups. Geometric mean ratios of AUC0-inf, AUC0-t, and Cmax were 0.91 (90% CI 0.85, 0.97), 0.91 (90% CI 0.86, 0.97), and 0.96 (90% CI 0.92, 1.01) between treatment groups, all within the bioequivalence range. Peripheral CD19+ and CD20+ B-cell counts were similar at each prespecified time point between the groups. No difference in immunogenicity was observed. The incidences of treatment-emergent adverse events (84.3% vs. 83.5%) and treatment-related AEs (56.2% vs. 61.5%) were comparable (IBI301 vs. rituximab). IBI301 was PK bioequivalent to rituximab in patients with CD20+ B-cell lymphoma. The PD, safety, and immunogenicity profiles of IBI301 were similar to those of rituximab. [ABSTRACT FROM AUTHOR]

Rhizoctonia solani is a fungal species complex that causes necrotrophic crop diseases. It comprises several anastomosis groups, some of which include intra-subgroups, such as AG-1 IA and AG-1 IB, exhibiting varying pathogenicity. Owing to its heterozygous and multinucleate features, genomic analyses of R. solani are still challenging, and understanding of its genetic diversity and genic components is limited. In this study, in order to elucidate the molecular basis of this phytopathogen complex, an integrated transcriptome analysis was undertaken for three subgroups of AG-1, i.e. AG-1 IA, AG-1 IB, and AG-1 IC. Sequence variations suggested substantial evolutionary distances within AG-1. Transcript simple sequence repeats showed comparable characteristics among AG-1, but contained polymorphic sites. Intra-subgroup polymorphisms suggested varying genic heterozygosity within AG-1, suggesting their independent evolutionary trajectory. Sequences of pathogenic factors, phytotoxin biosynthesis pathway enzymes, secreted lignocellulosic enzymes, secreted reactive oxygen species detoxification enzymes, apoplastic/cytoplasmic effector candidates, were conserved among those subgroups. dN/dS ratios of a secretome subset suggested core secreted proteins in AG-1 and distinct evolution of Cys-rich small secreted proteins after differentiation of AG-1 subgroups. Identification of likely pathogenic factors including allergen protein homologues, oxidative phosphorylation and ethylene biosynthesis pathways, and diversification of polysaccharide monooxygenases provides molecular insight into key genomic components that play a role in R. solani pathogenesis. [ABSTRACT FROM AUTHOR]

To date, there have been very limited studies regarding the clinical epidemiology of attempted suicide in Chinese individuals with heroin-dependence. The objective of this study was to examine the prevalence and correlates of suicide attempt in Chinese individuals receiving methadone maintenance treatment for heroin dependence. Demographic, clinical, and psychosocial data of 603 methadone-maintained patients with heroin dependence were collected with a standardized self-administered questionnaire. The presence of suicide attempt and antisocial personality disorder was assessed by using a single question and the Mini-International Neuropsychiatric Interview 5.0. The one-month and lifetime prevalence rates of suicide attempt were 9.5% and 34.2%, respectively. In multivariable logistic regression, lifetime suicide attempt was significantly associated with female gender (OR = 2.81), being 20–39 years old (OR = 2.73), an education level of primary school or lower (OR = 2.07), poor economic status (OR = 3.06), injecting heroin before methadone maintenance treatment (OR = 2.92), depressive symptoms (OR = 3.46), anxiety symptoms (OR = 1.88), and antisocial personality disorder (OR = 2.85). Suicide attempt is very prevalent among Chinese individuals receiving methadone maintenance treatment for heroin dependence. Services for patients with heroin dependence in methadone maintenance treatment clinics in China should include psychosocial supports, periodic screening for suicide attempt and other suicidal behaviors and, when needed, psychiatric treatment and crisis intervention. [ABSTRACT FROM AUTHOR]

In this study we characterized the TCR repertoire profiles in patients with chronic progressive inflammatory neurological disorders including HAM/TSP, associated with human T-cell lymphotropic virus type I (HTLV-I) infection, and multiple sclerosis (MS), an inflammatory, demyelinating disease of the CNS of unknown etiology. We hypothesized that a T-cell receptor (TCR) clonal repertoire 'signature' could distinguish HAM/TSP patients from healthy controls, as well as from patients with a more heterogeneous CNS-reactive inflammatory disease such as MS. In this study, we applied an unbiased molecular technique - unique molecular identifier (UMI) library-based strategy to investigate with high accuracy the TCR clonal repertoire by high throughput sequencing (HTS) technology. cDNA-TCR β-chain libraries were sequenced from 2 million peripheral mononuclear cells (PBMCs) in 14 HAM/TSP patients, 34 MS patients and 20 healthy controls (HC). While HAM/TSP patients showed a higher clonal T-cell expansion compared to MS and HC, increase of the TCR clonal expansion was inversely correlated with the diversity of TCR repertoire in all subjects. In addition, longitudinal analysis of TCR repertoires from HAM/TSP patients demonstrated a correlation of the TCR clonal expansion with HTLV-I proviral load. Surprisingly, MS patients showed a higher diversity of TCR repertoires than other groups. Despite higher TCR clonal expansions in HAM/TSP patients, no disease-specific TCRs were shared among patients. Only non-shared or "private" TCR repertoires was observed. While no clones that shared the same CDR3 amino acid sequences were seen in either HC or MS patients, there was a cluster of related CDR3 amino acid sequences observed for 18 out of 34 MS patients when evaluated by phylogenetic tree analysis. This suggests that a TCR-repertoire signature may be identified in a subset of patients with MS. [ABSTRACT FROM AUTHOR]

Postterm births are associated with an increased risk of adverse perinatal outcomes, but few studies have investigated the epidemiological characteristics of postterm births. We aimed to estimate the prevalence of postterm births and examine the potential association between maternal sociodemographic and obstetric characteristics and postterm births. Data were collected from China's National Maternal Near Miss Surveillance System, 2012-2016. A logistic regression was used to assess the association between sociodemographic and obstetric characteristics and postterm births. A Poisson regression was used to determine the crude and adjusted trends of postterm births over time across regions. Among the 6,240,830 singleton births with gestational periods of 37 weeks or longer, 1.16% were postterm. The prevalence of postterm births was significantly higher in the western region and among mothers who delivered at a level ≤2 hospital, had a lower education, or were younger. A reduced risk of postterm births was observed among primiparous women, mothers who previously had a caesarean section, mothers with pregnancy complications, and mothers with ten or more antenatal visits. The risk of postterm births decreased as the number of antenatal visits increased. The overall postterm birth rates significantly decreased from 1.49% in 2012 to 0.70% in 2016. The postterm birth rates were markedly reduced in the east, central, and west regions, and the rate of the decrease was greater in the east than in the west. Furthermore, substantial decreases were observed across regions in 2014 and 2016. In conclusion, multiple sociodemographic and obstetric factors are associated with the prevalence of postterm births. A significant decreasing trend in postterm birth rates was observed in China. [ABSTRACT FROM AUTHOR]

Tilletia horrida is a soil-borne, mononucleate basidiomycete fungus with a biotrophic lifestyle that causes rice kernel smut, a disease that is distributed throughout hybrid rice growing areas worldwide. Here we report on the high-quality genome sequence of T. horrida; it is composed of 23.2 Mb that encode 7,729 predicted genes and 6,973 genes supported by RNA-seq. The genome contains few repetitive elements that account for 8.45% of the total. Evolutionarily, T. horrida lies close to the Ustilago fungi, suggesting grass species as potential hosts, but co-linearity was not observed between T. horrida and the barley smut Ustilago hordei. Genes and functions relevant to pathogenicity were presumed. T. horrida possesses a smaller set of carbohydrate-active enzymes and secondary metabolites, which probably reflect the specific characteristics of its infection and biotrophic lifestyle. Genes that encode secreted proteins and enzymes of secondary metabolism, and genes that are represented in the pathogen-host interaction gene database genes, are highly expressed during early infection; this is consistent with their potential roles in pathogenicity. Furthermore, among the 131 candidate pathogen effectors identified according to their expression patterns and functionality, we validated two that trigger leaf cell death in Nicotiana benthamiana. In summary, we have revealed new molecular mechanisms involved in the evolution, biotrophy, and pathogenesis of T. horrida. [ABSTRACT FROM AUTHOR]

Mutations in the gene encoding phenylalanine hydroxylase (PAH) are associated with various degrees of phenylketonuria (PKU). The aim of our study was to define the genotype-phenotype correlations of mutations in the PAH gene that cause phenylketonuria (PKU) among the Chinese mainland population. Mutations in the PAH gene were analysed by next-generation sequencing, and a genotype-phenotype correlation analysis was performed in 1079 patients. Fifteen “null + null” genotypes, including four homoallelic and eleven heteroallelic genotypes, were clearly associated with classic PKU. Five functionally hemizygous (p.E280K, p.R252Q, p.E56D, p.S310F and p.T372R) and four compound heterozygous (p.T278I/p.S359L, p.R408W/p.R243Q, p.F161S/p.R243Q and p.F161S/p.R413P) genotypes were clearly associated with classic PKU. Ten functionally hemizygous genotypes, p.G257V, p.R158W, p.L255S, p.G247V, p.F161S, p.R158Q, p.V388M, p.I65T, p.I324N and p.R400K, were frequently associated with classic PKU. Three functionally hemizygous genotypes, p.P147L, p.I95del and p.F331S, and four compound heterozygous genotypes, p.G257V/p.R408Q, p.A434D/p.R413P, p.R243Q/p.A47E and p.R241C/p.G239D, were consistently correlated with mild PKU. Three functionally hemizygous genotypes, p.H107R, p.Q419R and p.F392I, and nine compound heterozygous genotypes (p.G312V/p.R241C, p.R243Q/p.V230I, p.R243Q/p.A403V, p.R243Q/p.Q419R, p.R243Q/p.R53H, p.R243Q/p.H107R, p.R241C/p.R408Q, p.R241C/p.H220P and p.R53H/p.R400K) were consistent with mild hyperphenylalaninaemia (MHP). Our study provides further support for the hypothesis that the PAH genotype is the main factor that determines the phenotype of PKU. [ABSTRACT FROM AUTHOR]

Abnormal dopaminergic transmission has been implicated as a risk determinant of HIV-1-associated neurocognitive disorders. HIV-1 Tat protein increases synaptic dopamine (DA) levels by directly inhibiting DA transporter (DAT) activity, ultimately leading to dopaminergic neuron damage. Through integrated computational modeling prediction and experimental validation, we identified that histidine547 on human DAT (hDAT) is critical for regulation of basal DA uptake and Tat-induced inhibition of DA transport. Compared to wild type hDAT (WT hDAT), mutation of histidine547 (H547A) displayed a 196% increase in DA uptake. Other substitutions of histidine547 showed that DA uptake was not altered in H547R but decreased by 99% in H547P and 60% in H547D, respectively. These mutants did not alter DAT surface expression or surface DAT binding sites. H547 mutants attenuated Tat-induced inhibition of DA transport observed in WT hDAT. H547A displays a differential sensitivity to PMA- or BIM-induced activation or inhibition of DAT function relative to WT hDAT, indicating a change in basal PKC activity in H547A. These findings demonstrate that histidine547 on hDAT plays a crucial role in stabilizing basal DA transport and Tat-DAT interaction. This study provides mechanistic insights into identifying targets on DAT for Tat binding and improving DAT-mediated dysfunction of DA transmission. [ABSTRACT FROM AUTHOR]

Predation by bacteriophages can significantly influence the population structure of bacterial communities. Vibrio cholerae the causative agent of cholera epidemics interacts with numerous phages in the aquatic ecosystem, and in the intestine of cholera patients. Seasonal epidemics of cholera reportedly collapse due to predation of the pathogen by phages. However, it is not clear how sufficient number of the bacteria survive to seed the environment in the subsequent epidemic season. We found that bacterial cell density-dependent gene expression termed 'quorum sensing' which is regulated by signal molecules called autoinducers (AIs) can protect V. cholerae against predatory phages. V. cholerae mutant strains carrying inactivated AI synthase genes were significantly more susceptible to multiple phages compared to the parent bacteria. Likewise when mixed cultures of phage and bacteria were supplemented with exogenous autoinducers CAI-1 or AI-2 produced by recombinant strains carrying cloned AI synthase genes, increased survival of V. cholerae and a decrease in phage titer was observed. Mutational analyses suggested that the observed effects of autoinducers are mediated in part through the quorum sensing-dependent production of haemaglutinin protease, and partly through downregulation of phage receptors. These results have implication in developing strategies for phage mediated control of cholera. [ABSTRACT FROM AUTHOR]

Phenylketonuria (PKU) is an inherited autosomal recessive disorder of phenylalanine metabolism, mainly caused by a deficiency of phenylalanine hydroxylase (PAH). The incidence of various PAH mutations differs among race and ethnicity. Here we report a spectrum of PAH mutations complied from 796 PKU patients from mainland China. The all 13 exons and adjacent intronic regions of the PAH gene were determined by next-generation sequencing. We identified 194 different mutations, of which 41 are not reported before. Several mutations reoccurred with high frequency including p.R243Q, p.EX6-96A > G, p.V399V, p.R241C, p.R111*, p.Y356*, p.R413P, and IVS4-1G > A. 76.33% of mutations were localized in exons 3, 6, 7, 11, 12. We further compared the frequency of each mutation between populations in northern and southern China, and found significant differences in 19 mutations. Furthermore, we identified 101 mutations that are not reported before in Chinese population, our study thus broadens the mutational spectrum of Chinese PKU patients. Additionally, 41 novel mutations will expand and improve PAH mutation database. Finally, our study offers proof that NGS is effective, reduces screening times and costs, and facilitates the provision of appropriate genetic counseling for PKU patients. [ABSTRACT FROM AUTHOR]

CCAAT/enhancer-binding protein α (C/ebpα) is a transcription factor that plays important roles in the regulation of hepatogenesis, adipogenesis and hematopoiesis. Disruption of the C/EBPα gene in mice leads to disturbed liver architecture and neonatal death due to hypoglycemia. However, the precise stages of liver development affected by C/ebpα loss are poorly studied. Using the zebrafish embryo as a model organism, we show that inactivation of the cebpa gene by TALENs results in a small liver phenotype. Further studies reveal that C/ebpα is distinctively required for hepatic outgrowth but not for hepatoblast specification. Lack of C/ebpα leads to enhanced hepatic cell proliferation and subsequent increased cell apoptosis. Additional loss of p53 can largely rescue the hepatic defect in cebpa mutants, suggesting that C/ebpα plays a role in liver growth regulation via the p53 pathway. Thus, our findings for the first time demonstrate a stage-specific role for C/ebpα during liver organogenesis. [ABSTRACT FROM AUTHOR]

Mutations in mitochondrial DNA (mtDNA) can lead to a wide range of human diseases. We have developed a deep sequencing strategy, mitoRCA-seq, to detect low-frequency mtDNA point mutations starting with as little as 1 ng of total DNA. It employs rolling circle amplification, which enriches the full-length circular mtDNA by either custom mtDNA-specific primers or a commercial kit, and minimizes the contamination of nuclear encoded mitochondrial DNA (Numts). By analyzing the mutation profiles of wild-type and Polg (mitochondrial DNA polymerase γ) mutant mice, we found that mice with the proofreading deficient mtDNA polymerase have a significantly higher mutation load by expanding the number of mutation sites and to a lesser extent by elevating the mutation frequency at existing sites even before the premature aging phenotypes appear. Strikingly, cytocine (C) to thymine (T) transitions are found to be overrepresented in the mtDNA of Polg mutated mice. The C → T transition, compared to other types of mutations, tends to increase the hydrophobicity of the underlying amino acids, and may contribute to the impaired protein function of the Polg mutant mice. Taken together, our findings may provide clues to further investigate the molecular mechanism underlying premature aging phenotype in Polg mutant mice. [ABSTRACT FROM AUTHOR]

Precise prediction for genetic architecture of complex traits is impeded by the limited understanding on genetic effects of complex traits, especially on gene-by-gene (GxG) and gene-by-environment (GxE) interaction. In the past decades, an explosion of high throughput technologies enables omics studies at multiple levels (such as genomics, transcriptomics, proteomics, and metabolomics). The analyses of large omics data, especially two-loci interaction analysis, are very time intensive. Integrating the diverse omics data and environmental effects in the analyses also remain challenges. We proposed mixed linear model approaches using GPU (Graphic Processing Unit) computation to simultaneously dissect various genetic effects. Analyses can be performed for estimating genetic main effects, GxG epistasis effects, and GxE environment interaction effects on large-scale omics data for complex traits, and for estimating heritability of specific genetic effects. Both mouse data analyses and Monte Carlo simulations demonstrated that genetic effects and environment interaction effects could be unbiasedly estimated with high statistical power by using the proposed approaches. [ABSTRACT FROM AUTHOR]

Enrichment of glycopeptides by hydrazide chemistry (HC) is a popular method for glycoproteomics analysis. However, possible side reactions of peptide backbones during the glycan oxidation in this method have not been comprehensively studied. Here, we developed a proteomics approach to locate such side reactions and found several types of the side reactions that could seriously compromise the performance of glycoproteomics analysis. Particularly, the HC method failed to identify N-terminal Ser/Thr glycopeptides because the oxidation of vicinal amino alcohol on these peptides generates aldehyde groups and after they are covalently coupled to HC beads, these peptides cannot be released by PNGase F for identification. To overcome this drawback, we apply a peptide N-terminal protection strategy in which primary amine groups on peptides are chemically blocked via dimethyl labeling, thus the vicinal amino alcohols on peptide N-termini are eliminated. Our results showed that this strategy successfully prevented the oxidation of peptide N-termini and significantly improved the coverage of glycoproteome. [ABSTRACT FROM AUTHOR]

Suberoylanilide hydroxamic acid (SAHA) is a well-known histone deacetylase (HDAC) inhibitor and has been used as practical therapy for breast cancer and non-small cell lung cancer (NSCLC). It is previously demonstrated that SAHA treatment could extensively change the profile of acetylome and proteome in cancer cells. However, little is known about the impact of SAHA on other protein modifications and the crosstalks among different modifications and proteome, hindering the deep understanding of SAHA-mediated cancer therapy. In this work, by using SILAC technique, antibody-based affinity enrichment and high-resolution LC-MS/MS analysis, we investigated quantitative proteome, acetylome and ubiquitylome as well as crosstalks among the three datasets in A549 cells toward SAHA treatment. In total, 2968 proteins, 1099 acetylation sites and 1012 ubiquitination sites were quantified in response to SAHA treatment, respectively. With the aid of intensive bioinformatics, we revealed that the proteome and ubiquitylome were negatively related upon SAHA treatment. Moreover, the impact of SAHA on acetylome resulted in 258 up-regulated and 99 down-regulated acetylation sites at the threshold of 1.5 folds. Finally, we identified 55 common sites with both acetylation and ubiquitination, among which ubiquitination level in 43 sites (78.2%) was positive related to acetylation level. [ABSTRACT FROM AUTHOR]

The concept of aromaticity has long played an important role in chemistry and continues to fascinate both experimentalists and theoreticians. Among the archetypal aromatic compounds, heteroaromatics are particularly attractive. Recently, substitution of a transition-metal fragment for a carbon atom in the anti-aromatic hydrocarbon pentalene has led to the new heteroaromatic osmapentalenes. However, construction of the aza-homolog of osmapentalenes cannot be accomplished by a similar synthetic manipulation. Here, we report the synthesis of aza-osmapentalenes by sequential ring contraction/annulation reactions of osmabenzenes via osmapentafulvenes. Nuclear magnetic resonance spectra, X-ray crystallographic analysis, and DFT calculations all suggest that these aza-osmapentalenes exhibit aromatic character. Thus, the stepwise transformation of metallabenzenes to metallapentafulvenes and then aza-metallapentalenes provides an efficient and facile synthetic route to these bicyclic heteroaromatics. [ABSTRACT FROM AUTHOR]

The small ubiquitin-related modifier (SUMO) participates in various cellular processes, including maintenance of genome integrity, nuclear transport, transcription and signal transduction. However, the biological function of sumoylation in hematopoiesis has not been fully explored. We show here that definitive hematopoietic stem/progenitor cells (HSPCs) are depleted in SUMO-deficient zebrafish embryos. Impairment of sumoylation attenuates HSPC generation and proliferation. The hyposumoylation triggered HSPC defects are CCAAT/enhancer-binding protein α (C/ebpα) dependent. Critically, a SUMO-C/ebpα fusion rescues the defective hematopoiesis in SUMO-deficient embryos, at least in part through restored runx1 expression. While C/ebpα-dependent transcription is involved in myeloid differentiation, our studies here reveal that C/ebpα sumoylation is essential for HSPC development during definitive hematopoiesis. [ABSTRACT FROM AUTHOR]