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

End-Use Quality of Historical and ModernWinter Wheats Adapted to the Great Plains of the United States

Improving milling and baking properties is important during wheat breeding. To determine changes in milling and baking quality of hard winter wheat, 23 adapted cultivars released in the Great Plains between 1870 and 2013 were grown in triplicate in a single location (Mead, NE, USA) over two crop years (2018 and 2019). Grain yield and kernel hardness index increased by release year (p \u3c 0.05). The observed increase in hardness index was accompanied by a decrease in percent soft kernels (p \u3c 0.05). Diameter and weight decreased with release year in 2019 (p \u3c 0.05), and their standard deviation increased with the release year (p \u3c 0.05). Flour protein content decreased with release year (p \u3c 0.05) and dough mixing quality increased (p \u3c 0.05). No significant relationship was found for baking property variables, but bran water retention capacity (BWRC), which is correlated with whole wheat bread quality, increased with release year (p \u3c 0.05). In conclusion, wheat kernels have become harder but more variable in shape over a century of breeding. Mixing quality showed significant improvements, and loaf volume and firmness remained constant, even in the presence of a decrease in protein concentration. Bran quality decreased across release year, which may have implications for whole grain baking quality and milling productivity

M2-like macrophages in the fibrotic liver protect mice against lethal insults through conferring apoptosis resistance to hepatocytes.

Acute injury in the setting of liver fibrosis is an interesting and still unsettled issue. Most recently, several prominent studies have indicated the favourable effects of liver fibrosis against acute insults. Nevertheless, the underlying mechanisms governing this hepatoprotection remain obscure. In the present study, we hypothesized that macrophages and their M1/M2 activation critically involve in the hepatoprotection conferred by liver fibrosis. Our findings demonstrated that liver fibrosis manifested a beneficial role for host survival and apoptosis resistance. Hepatoprotection in the fibrotic liver was tightly related to innate immune tolerance. Macrophages undertook crucial but divergent roles in homeostasis and fibrosis: depleting macrophages in control mice protected from acute insult; conversely, depleting macrophages in fibrotic liver weakened the hepatoprotection and gave rise to exacerbated liver injury upon insult. The contradictory effects of macrophages can be ascribed, to a great extent, to the heterogeneity in macrophage activation. Macrophages in fibrotic mice exhibited M2-preponderant activation, which was not the case in acutely injured liver. Adoptive transfer of M2-like macrophages conferred control mice conspicuous protection against insult. In vitro, M2-polarized macrophages protected hepatocytes against apoptosis. Together, M2-like macrophages in fibrotic liver exert the protective effects against lethal insults through conferring apoptosis resistance to hepatocytes

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

Vitamin D Signaling through Induction of Paneth Cell Defensins Maintains Gut Microbiota and Improves Metabolic Disorders and Hepatic Steatosis in Animal Models.

Metabolic syndrome (MetS), characterized as obesity, insulin resistance, and non-alcoholic fatty liver diseases (NAFLD), is associated with vitamin D insufficiency/deficiency in epidemiological studies, while the underlying mechanism is poorly addressed. On the other hand, disorder of gut microbiota, namely dysbiosis, is known to cause MetS and NAFLD. It is also known that systemic inflammation blocks insulin signaling pathways, leading to insulin resistance and glucose intolerance, which are the driving force for hepatic steatosis. Vitamin D receptor (VDR) is highly expressed in the ileum of the small intestine, which prompted us to test a hypothesis that vitamin D signaling may determine the enterotype of gut microbiota through regulating the intestinal interface. Here, we demonstrate that high-fat-diet feeding (HFD) is necessary but not sufficient, while additional vitamin D deficiency (VDD) as a second hit is needed, to induce robust insulin resistance and fatty liver. Under the two hits (HFD+VDD), the Paneth cell-specific alpha-defensins including α-defensin 5 (DEFA5), MMP7 which activates the pro-defensins, as well as tight junction genes, and MUC2 are all suppressed in the ileum, resulting in mucosal collapse, increased gut permeability, dysbiosis, endotoxemia, systemic inflammation which underlie insulin resistance and hepatic steatosis. Moreover, under the vitamin D deficient high fat feeding (HFD+VDD), Helicobacter hepaticus, a known murine hepatic-pathogen, is substantially amplified in the ileum, while Akkermansia muciniphila, a beneficial symbiotic, is diminished. Likewise, the VD receptor (VDR) knockout mice exhibit similar phenotypes, showing down regulation of alpha-defensins and MMP7 in the ileum, increased Helicobacter hepaticus and suppressed Akkermansia muciniphila. Remarkably, oral administration of DEFA5 restored eubiosys, showing suppression of Helicobacter hepaticus and increase of Akkermansia muciniphila in association with resolving metabolic disorders and fatty liver in the HFD+VDD mice. An in vitro analysis showed that DEFA5 peptide could directly suppress Helicobacter hepaticus. Thus, the results of this study reveal critical roles of a vitamin D/VDR axis in optimal expression of defensins and tight junction genes in support of intestinal integrity and eubiosis to suppress NAFLD and metabolic disorders

Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing Endotoxemia.

A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic fatty liver disease, and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low-cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine, but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to 1) reduced plasma endotoxin levels, 2) resolved systemic inflammation and hepatic steatohepatitis, and 3) improved insulin sensitivity. Gut dysbiosis, characterized as an increase of the phylum Firmicutes and a decrease of Bacteroidetes and Akkermansia muciniphila, was fully corrected by cholestyramine, indicating that the negatively charged components in the gut are critical for the dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine-treated animals, was sufficient to antagonize the metabolic disorders of the recipient mice. These results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis

An aldehyde dehydrogenase gene, GhALDH7B4_A06, positively regulates fiber strength in upland cotton (Gossypium hirsutum L.)

High fiber strength (FS) premium cotton has significant market demand. Consequently, enhancing FS is a major objective in breeding quality cotton. However, there is a notable lack of known functionally applicable genes that can be targeted for breeding. To address this issue, our study used specific length–amplified fragment sequencing combined with bulk segregant analysis to study FS trait in an F2 population. Subsequently, we integrated these results with previous quantitative trait locus mapping results regarding fiber quality, which used simple sequence repeat markers in F2, F2:3, and recombinant inbred line populations. We identified a stable quantitative trait locus qFSA06 associated with FS located on chromosome A06 (90.74–90.83 Mb). Within this interval, we cloned a gene, GhALDH7B4_A06, which harbored a critical mutation site in coding sequences that is distinct in the two parents of the tested cotton line. In the paternal parent Ji228, the gene is normal and referred to as GhALDH7B4_A06O; however, there is a nonsense mutation in the maternal parent Ji567 that results in premature termination of protein translation, and this gene is designated as truncated GhALDH7B4_A06S. Validation using recombinant inbred lines and gene expression analysis revealed that this mutation site is correlated with cotton FS. Virus-induced gene silencing of GhALDH7B4 in cotton caused significant decreases in FS and fiber micronaire. Conversely, GhALDH7B4_A06O overexpression in Arabidopsis boosted cell wall component contents in the stem. The findings of our study provide a candidate gene for improving cotton fiber quality through molecular breeding

Carbohydrate utilization by the gut microbiome determines host health responsiveness to whole grain type and processing methods

Little is known about how interactions among grain processing, grain type, and carbohydrate utilization (CU) by the microbiome influence the health benefits of whole grains. Therefore, two whole grains – brown rice and whole wheat – and two processing methods – boiling (porridge) and extrusion – were studied for their effects on host metabolic outcomes in mice harboring human microbiomes previously shown in vitro to have high or low CU. Mice carrying either microbiome experienced increases in body weight and glycemia when consuming Western diets supplemented with extruded grains versus porridge. However, mice with the high but not low CU microbiome also gained more weight and fat over time and were less glucose tolerant when consuming extruded grain diets. In high CU microbiome mice, the exacerbated negative health outcomes associated with extrusion were related to altered abundances of Lachnospiraceae and Ruminococcaceae as well as elevated sugar degradation and colonic acetate production. The amplicon sequence variants (ASVs) associated with extruded and porridge diets in this in vivo study were not the same as those identified in our prior in vitro study; however, the predicted functions were highly correlated. In conclusion, mice harboring both high and low CU microbiomes responded to the whole grain diets similarly, except the high CU microbiome mice exhibited exacerbated effects due to excessive acetate production, indicating that CU by the microbiome is linked to host metabolic health outcomes. Our work demonstrates that a greater understanding of food processing effects on the microbiome is necessary for developing foods that promote rather than diminish host health

Genomic analysis of estrogen cascade reveals histone variant H2A.Z associated with breast cancer progression

We demonstrate an integrated approach to the study of a transcriptional regulatory cascade involved in the progression of breast cancer and we identify a protein associated with disease progression. Using chromatin immunoprecipitation and genome tiling arrays, whole genome mapping of transcription factor-binding sites was combined with gene expression profiling to identify genes involved in the proliferative response to estrogen (E2). Using RNA interference, selected ERα and c-MYC gene targets were knocked down to identify mediators of E2-stimulated cell proliferation. Tissue microarray screening revealed that high expression of an epigenetic factor, the E2-inducible histone variant H2A.Z, is significantly associated with lymph node metastasis and decreased breast cancer survival. Detection of H2A.Z levels independently increased the prognostic power of biomarkers currently in clinical use. This integrated approach has accelerated the identification of a molecule linked to breast cancer progression, has implications for diagnostic and therapeutic interventions, and can be applied to a wide range of cancers