Schizophrenia is a complex psychiatric disorder with high genetic heterogeneity, however, the contribution of rare mutations to the disease etiology remains to be further elucidated. We herein ...performed exome sequencing in a Han Chinese schizophrenia family and identified a missense mutation (c.6724C>T, p.R2242C) in the teneurin transmembrane protein 4 (
) gene in the SCZD2 locus, a region previously linked to schizophrenia at 11q14-21. The mutation was confirmed to co-segregate with the schizophrenia phenotype in the family. Subsequent investigation of
exons 31, 32, and 33 adjacent to the p.R2242C mutation revealed two additional missense mutations in 120 sporadic schizophrenic patients. Residues mutated in these mutations, which are predicted to be deleterious to protein function, were highly conserved among vertebrates. These rare mutations were not detected in 1000 Genomes, NHLBI Exome Sequencing Project databases, or our in-house 1136 non-schizophrenic control exomes. Analysis of RNA-Seq data showed that
is expressed in the brain with high abundance and specificity. In line with the important role of
in central nervous system development, our findings suggested that increased rare variants in
could be associated with schizophrenia, and thus
could be a novel candidate gene for schizophrenia in the SCZD2 locus.
The Gram-negative phytopathogenic bacterium Xanthomonas campestris pv. campestris recruits the hrp/T3SS system to inject pathogenicity effector proteins into host cells and uses the rpf/DSF cell-cell ...signaling system to regulate the expression of virulence factors such as extracellular enzymes and polysaccharide. Whether these two systems have any connection is unknown.
Positive regulator candidates affecting hrpX expression were identified by sacB strategy. The transcriptional expression was determined by qRT-PCR and GUS activity analysis. Transcriptome analysis was performed by RNA deep-sequencing. The hypersensitive response (HR) was determined in the nonhost plant pepper ECW-10R and electrolyte leakage assay.
Mutation of the gene encoding the sensor RpfC of the rpf/DSF system significantly reduced the expression of hrpX, the key regulator of the hrp/T3SS system, all of the genes in the hrp cluster and most reported type III effector genes. Mutation of rpfG did not affect the expression of hrpX. The rpfC mutant showed a delayed and weakened HR induction.
RpfC positively regulates the expression of hrpX independent of RpfG, showing a complex regulatory network linking the rpf/DSF and hrp/T3SS systems.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this prospective study was to propose a new rating system using a risk model including conventional ultrasound (US) and acoustic radiation force impulse (ARFI) elastography for predicting ...central lymph node metastasis (LNM) in patients with papillary thyroid microcarcinoma (PTMC).A total of 252 patients with PTMCs were enrolled, who were preoperatively evaluated by US and ARFI elastography including virtual touch tissue imaging (VTI) and virtual touch tissue quantification (VTQ). Risk factors of independent variables for central LNM were analyzed by univariate and multivariate analyses. A multivariate analysis was performed to create a predicting model and rating system.Of the 252 patients, 72 (28.6%) had central LNMs. Multivariate analysis revealed that rare internal flow (odds ratio OR: 4.454), multiple suspicious foci on US (OR: 5.136), capsule involvement (OR: 20.632), and VTI area ratio (VAR) > 1 (OR: 5.621) were independent risk factors for central LNM. The final predicting model was obtained and the risk score (RS) was defined as 1.5 × (if rare internal flow) + 1.6 × (if multiple suspicious foci on US) + 1.7 × (if VAR > 1) + 3.0 × (if capsule involvement). The rating system was divided into 5 stages. Stage I, <1.5; Stage II, 1.5 to 3.0; Stage III, 3.1 to 4.7; Stage IV, 4.8 to 6.3; and Stage V, 6.4 to 7.8. The risk rates of central LNM were 3.4% (2/59) in Stage I, 13.3% (13/98) in Stage II, 54.2% (39/72) in Stage III, 72.2% (13/18) in Stage IV, and 100% (5/5) in Stage V (P < 0.001).The results indicated that rare internal flow, multiple suspicious foci, capsule involvement on US, and VAR > 1 on ARFI elastography are the risk factors for predicting central LNM. The risk model developed in the study clearly predicts the risk of central LNM in patients with PTMC and thus has a potential to avoid unnecessary central compartment node dissection.
Establishing an efficient and eco-friendly extraction method of bioactive ingredients from plant materials is highly needed to insure a better human health by combating different diseases. In this ...work, a two-phase system formed by green and recyclable menthol-based hydrophobic deep eutectic solvent (DES) aqueous was synthesized and evaluated its application for simultaneous extraction of seven main target taxanes in the Taxus chinese needles. The formation of micelles from two-phase system in the menthol-based DES aqueous simultaneously enhanced the mass transfer and enrichment for target taxanes. Under the optimal conditions of menthol/1-butanol ratio 1:1 (mol/mol), water content 50%, solid-liquid ratio 1:30 g/mL, extraction time 30 min and ultrasonic power 250 W, the extraction yields of seven main taxanes were 1.27–2.65 folds higher than the conventional organic solvents. The recovery yields after enrichment with the two-phase system of the menthol-based DES aqueous were higher than 95.31%. Furthermore, the menthol-based DES aqueous could be recycled at least three times with perfect extraction efficiency for target compounds. This work proved that the natural menthol-based DES aqueous solution is an effective and non-toxic green extraction solvent, which has the potential to effectively extract phytochemicals from plant materials in the future.
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•Some menthol-based DES aqueous were prepared as green solvents.•Extraction and enrichment of taxanes could be conducted simultaneously.•The DES aqueous possessed higher reusability.•The kinetics of DES aqueous extraction process for taxanes was studied firstly.
Data on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg)-positive (HBsAg+) donors to HBsAg-negative (HBsAg-) recipients D(HBsAg+)/R(HBsAg-) are limited. We aimed to report the ...outcomes of D(HBsAg+)/R(HBsAg-) KTx in recipients with or without hepatitis B surface antibody (HBsAb).
Eighty-three D(HBsAg+)/R(HBsAg-) living KTx cases were retrospectively identified. The 384 cases of KTx from hepatitis B core antibody-positive (HBcAb+) living donors to HBcAb-negative (HBcAb-) recipients D(HBcAb+)/R(HBcAb-) were used as the control group. The primary endpoint was posttransplant HBsAg status change from negative to postive (-- →+).
Before KTx, 24 donors (28.9%) in the D(HBsAg+)/R(HBsAg-) group were hepatitis B virus (HBV) DNA positive, and 20 recipients were HBsAb-. All 83 D(HBsAg+)/R(HBsAg-) recipients received HBV prophylaxis, while no D(HBcAb+)/R(HBcAb-) recipients received prophylaxis. After a median follow-up of 36 months (range, 6-106) and 36 months (range, 4-107) for the D(HBsAg+)/R(HBsAg-) and D(HBcAb+)/R(HBcAb-) groups, respectively, 2 of 83 (2.41%) D(HBsAg+)/R(HBsAg-) recipients and 1 of 384 (0.26%) D(HBcAb+)/R(HBcAb-) became HBsAg+, accompanied by HBV DNA-positive (P = .083). The 3 recipients with HBsAg-→+ were exclusively HBsAb-/HBcAb- before KTx. Recipient deaths were more frequent in the D(HBsAg+)/R(HBsAg-) group (6.02% vs 1.04%, P = .011), while liver and graft function, rejection, infection, and graft loss were not significantly different. In univariate analyses, pretransplant HBsAb-/HBcAb- combination in the D(HBsAg+)/R(HBsAg-) recipients carried a significantly higher risk of HBsAg-→+, HBV DNA-→+, and death.
Living D(HBsAg+)/R(HBsAg-) KTx in HBsAb+ recipients provides excellent graft and patient survivals without HBV transmission. HBV transmission risks should be more balanced with respect to benefits of D(HBsAg+)/R(HBsAg-) KTx in HBsAb-/HBcAb- candidates.
Considering the relationship between inhomogeneous plastic deformation and fatigue damage, deformation inhomogeneity evolution and fatigue failure of superalloy GH4169 under temperature 500 °C and ...macro tension compression cyclic loading are studied, by using crystal plasticity calculation associated with polycrystalline representative Voronoi volume element (RVE). Different statistical standard deviation and differential entropy of meso strain are used to measure the inhomogeneity of deformation, and the relationship between the inhomogeneity and strain cycle is explored by cyclic numerical simulation. It is found from the research that the standard deviations of each component of the strain tensor at the cyclic peak increase monotonically with the cyclic loading, and they are similar to each other. The differential entropy of each component of the strain tensor also increases with the number of cycles, and the law is similar. On this basis, the critical values determined by statistical standard deviations of the strain components and the equivalent strain, and that by differential entropy of strain components, are, respectively, used as fatigue criteria, then predict the fatigue–life curves of the material. The predictions are verified with reference to the measured results, and their deviations are proved to be in a reasonable range.
•The molecular structures of two compounds were confirmed by their crystal structures.•The thermal behaviors and decomposition mechanisms of two compounds were described, respectively.•Some ...parameters were calculated to evaluate the thermal stability and safety of two compounds.
In this contribution, two metal energetic complexes Co(HCONHNH2)2(AFT)2·H2O (1) and Pb(HCONHNH2)2(AFT)2n (2) (HCONHNH2=formyl hydrazide and HAFT = 4-amino-3-(5-tetrazolate)-furazan) have been synthesized and characterized. The structures of compound 1 and 2 are characterized by single crystal X-ray diffraction. The tests show that 1 possesses One-dimensional (1D) chain structure and 2 exhibits two-dimensional (2D) energetic metal-organic framework (MOF). The thermal decomposition processes of compounds have been investigated by MS-FTIR-DSC-TG coupling technique. It's worth noting that both of them exhibit higher thermal stabilities. Moreover, gaseous products generated after thermal decomposition of compound 1 and 2 are CO2, NO2, N2O, CO, HCN, NH3, H2O, N2. The standard molar enthalpies of formation of 1 and 2 are calculated to be -4501.25 kJ·mol-1 and -1091.13 kJ·mol-1, respectively. Detonation velocity and detonation pressure are respectively 9.32 km·s−1, 42.13 GPa for 1 and 5.62 km·s−1, 18.36 GPa for 2. Surprisingly, compound 2 exhibits promising detonation velocity and detonation pressure, which are higher than those of TNT, RDX and HMX. The above-mentioned information on thermal behavior is available to analyze and evaluate the stability and thermal safety of 1 and 2. The sensitivity tests reveal they possess excellent insensitivities to impact and friction. All the characterizations show that they can be used as potential energetic materials.
A Ni–oxazoline complex-catalyzed asymmetric decarboxylative aldol reaction between malonic acid half-oxyesters and various carbonyls with carboxylate assistance was developed, affording structurally ...diverse β-hydroxy esters with good yields and enantioselectivities under mild conditions. Importantly, the broad substrate scope of this methodology enabled rapid accesses to several natural products and their analogues as exemplified by phenylpropanoid, phaitanthrin B, and phthalide.
CD4
T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4
T cell exhaustion and how it contributes to the immune ...response and disease progression in human gastric cancer (GC) remain largely unknown.
A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4
T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4
T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity.
In comparison with CD4
T cells from the non-tumor tissues, significantly more GC-infiltrating CD4
T cells expressed CD39. Most GC-infiltrating CD39
CD4
T cells exhibited CD45RA
CCR7
effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39
CD4
counterparts. Moreover,
inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39
CD4
T cells were positively associated with disease progression and patients' poorer overall survival.
Our study demonstrates that CD39 expression defines GC-infiltrating CD4
T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.
The relation between deformation inhomogeneity and low-cycle-fatigue failure of T2 pure copper and the nickel-based superalloy GH4169 under symmetric tension-compression cyclic strain loading is ...investigated by using a polycrystal representative volume element (RVE) as the material model. The anisotropic behavior of grains and the strain fields are calculated by crystal plasticity, taking the Bauschinger effect into account to track the process of strain cycles of metals, and the Shannon's differential entropies of both distributions of the strain in the loading direction and the first principal strain are employed at the tension peak of the cycles as measuring parameters of strain inhomogeneity. Both parameters are found to increase in value with increments in the number of cycles and they have critical values for predicting the material's fatigue failure. Compared to the fatigue test data, it is verified that both parameters measured by Shannon's differential entropies can be used as fatigue indicating parameters (FIPs) to predict the low cycle fatigue life of metal.
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