The psychometric properties of the quick inventory of depressive symptomatology-self-report (QIDS-SR) in patients with HBV-related liver disease

Background: Comorbid depression in Hepatitis B virus (HBV) is common. Developing accurate and time efficient tools to measure depressive symptoms in HBV is important for research and clinical practice in China. Aims: This study tested the psychometric properties of the Chinese version of the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR) in HBV patients. Methods: The study recruited 245 depressed patients with HBV and related liver disease. The severity of depressive symptoms was assessed with the Montgomery-Asberg Depression Rating Scale (MADRS) and the QIDS-SR. Results: Internal consistency (Cronbach’s alpha) was 0.796 for QIDS-SR. The QIDS-SR total score was significantly correlated with the MADRS total score (r=0.698, p. Conclusions: The QIDS-SR (Chinese version) has good psychometric properties in HBV patients and appears to be useful in assessing depression in clinical settings

Characterization of protein-protein interactions between the nucleocapsid protein and membrane protein of the avian infectious bronchitis virus

Avian infectious bronchitis virus (IBV) is one of the major viral respiratory diseases of chickens. Better understanding of the molecular mechanism of viral pathogenesis may contribute significantly to the development of prophylactic, therapeutic and diagnostic reagents as well as help in infection control. Avian IBV belongs to the Coronaviridaes and is similar to the other known coronaviruses. Previous studies have indicated that protein–protein interactions between nucleocapsid (N) and the membrane (M) proteins in coronavirus are related to coronavirus viral assembly. However, cases of IBV are seldom reported. In this study, yeast two-hybrid and  co-immunoprecipitation techniques were applied to investigate possible interactions between IBV N and M proteins. We found that interaction of the N and M proteins took place in vivo and the residues 168 – 225 of the M protein and the residues 150 - 210 of the N protein were determined to be involved in their interaction. These results may provide some useful information on the molecular mechanism of IBV’s N and M proteins, which will facilitate therapeutic strategies aiming at the disruption of the association between membrane and nucleocapsid proteins and indicate a new drug target for IBV.Key words: Co-immunoprecipitation, membrane protein, nucleocapsid protein, protein-protein interaction, yeast two-hybrid

Pulsed Laser Beam Welding of Pd\u3csub\u3e43\u3c/sub\u3eCu\u3csub\u3e27\u3c/sub\u3eNi\u3csub\u3e10\u3c/sub\u3eP\u3csub\u3e20\u3c/sub\u3e Bulk Metallic Glass

We used pulsed laser beam welding method to join Pd43Cu27Ni10P20 (at.%) bulk metallic glass and characterized the properties of the joint. Fusion zone and heat-affected zone in the weld joint can be maintained completely amorphous as confirmed by X-ray diffraction and differential scanning calorimetry. No visible defects were observed in the weld joint. Nanoindentation and bend tests were carried out to determine the mechanical properties of the weld joint. Fusion zone and heat-affected zone exhibit very similar elastic moduli and hardness when compared to the base material, and the weld joint shows high ductility in bending which is accomplished through the operation of multiple shear bands. Our results reveal that pulsed laser beam welding under appropriate processing parameters provides a practical viable method to join bulk metallic glasses

Interleukin-33 Contributes to the Induction of Th9 Cells and Antitumor Efficacy by Dectin-1-Activated Dendritic Cells

We recently discovered that dectin-1-activated dendritic cells (DCs) drive potent T helper (Th) 9 cell responses and antitumor immunity. However, the underlying mechanisms need to be further defined. The cytokine microenvironment is critical for Th cell differentiation. Here, we show that dectin-1 activation enhances interleukin (IL)-33 expression in DCs. We found that blocking IL-33/ST2 inhibits dectin-1-activated DC-induced Th9 cell differentiation. More importantly, the addition of IL-33 further promotes Th9 cell priming and antitumor efficacy induced by dectin-1-activated DCs. Mechanistically, in addition to the promotion of Th9 and Th1 cells, dectin-1-activated DCs combined with IL-33 abolish the activity of IL-33 in the induction of regulatory T cells. Furthermore, the combined treatment of dectin-1-activated DCs and IL-33 increases the frequencies of CD4+ T cells by fostering their proliferation and inhibiting their exhaustive differentiation. Thus, our results demonstrate the important role of IL-33 in dectin-1-activated DC-induced Th9 cell differentiation and antitumor efficacy, and suggest that the combination of dectin-1-activated DCs and IL-33 may present a new effective modality of DC-based vaccines in tumor immunotherapy

Serum HBsAg and HBcrAg is associated with inflammation in HBeAg-positive chronic hepatitis B patients

Backgrounds & aimsLiver inflammation is the main risk factor for developing liver fibrosis, cirrhosis, and even hepatocellular carcinoma in chronic hepatitis B (CHB) patients. To replace biopsy, additional non-invasive biomarkers to diagnose and grade liver necroinflammation are urgently required in clinical practice.MethodNinety-four CHB patients, including 74 HBeAg-positive and 20 HBeAg-negative patients, were enrolled and started entecavir or adefovir therapy. Serum HBV RNA, HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), ALT and AST levels, as well as intrahepatic HBV DNA and cccDNA were measured at baseline and during treatment. Liver inflammation was assessed at baseline and month 60 by liver biopsy. Inflammation regression was defined as a ≥1-grade decrease according to the Scheuer scoring system.ResultsIn HBeAg-positive CHB patients, at baseline, serum HBsAg and HBcrAg levels negatively correlated with inflammation grade, while ALT and AST levels positively correlated with inflammation grade. AST plus HBsAg exhibited excellent diagnostic ability for significant inflammation with an AUROC of 0.896. After 60 months of antiviral treatment, almost all the patients’ liver inflammation ameliorated to G1, and no patients had inflammation progression.ConclusionBesides ALT and AST, serum HBsAg and HBcrAg correlated with inflammation grade in HBeAg-positive CHB patients before NAs treatment. Moreover, the combination of HBsAg and AST exhibited excellent diagnostic ability for significant inflammation

Morphological diversity of single neurons in molecularly defined cell types.

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits

The 5-Hydroxymethylcytosine Landscape of Prostate Cancer

Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first study integrating whole-genome 5hmC with DNA, 5mC, and transcriptome sequencing in clinical samples of benign, localized, and advanced prostate cancer. 5hmC is shown to mark activation of cancer drivers and downstream targets. Furthermore, 5hmC sequencing revealed profoundly altered cell states throughout the disease course, characterized by increased proliferation, oncogenic signaling, dedifferentiation, and lineage plasticity to neuroendocrine and gastrointestinal lineages. Finally, 5hmC sequencing of cell-free DNA from patients with metastatic disease proved useful as a prognostic biomarker able to identify an aggressive subtype of prostate cancer using the genes TOP2A and EZH2, previously only detectable by transcriptomic analysis of solid tumor biopsies. Overall, these findings reveal that 5hmC marks epigenomic activation in prostate cancer and identify hallmarks of prostate cancer progression with potential as biomarkers of aggressive disease. SIGNIFICANCE: In prostate cancer, 5-hydroxymethylcytosine delineates oncogene activation and stage-specific cell states and can be analyzed in liquid biopsies to detect cancer phenotypes. See related article by Wu and Attard, p. 3880.publishedVersionPeer reviewe

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Microstructure and Mechanical Properties of Friction Welding Joints with Dissimilar Titanium Alloys

Titanium alloys, which are important in aerospace application, offer different properties via changing alloys. As design complexity and service demands increase, dissimilar welding of the titanium alloys becomes a particular interest. Linear friction welding (LFW) is a relatively novel bond technique and has been successfully applied for joining titanium alloys. In this paper, dissimilar joints with Ti-6Al-4V and Ti-5Al-2Sn-2Zr-4Mo-4Cr alloys were produced by LFW process. Microstructure was studied via optical microscopy and scanning electron microscopy (SEM), while the chemical composition across the welded samples was identified by energy dispersive X-ray spectroscopy. Mechanical tests were performed on welded samples to study the joint mechanical properties and fracture characteristics. SEM was carried out on the fracture surface to reveal their fracture modes. A significant microstructural change with fine re-crystallization grains in the weld zone (WZ) and small recrystallized grains in the thermo-mechanically affected zone on the Ti-6Al-4V side was discovered in the dissimilar joint. A characteristic asymmetrical microhardness profile with a maximum in the WZ was observed. Tensile properties of the dissimilar joint were comparable to the base metals, but the impact toughness exhibited a lower value