WD-repeat protein 79 (WDR79), a member of the WD-repeat protein family, acts as a scaffold protein, participating in telomerase assembly, Cajal body formation and DNA double-strand break repair. Here, we first report that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung cancer (NSCLC). Knockdown of WDR79 significantly inhibited the proliferation of NSCLC cells in vitro and in vivo by inducing cell cycle arrest and apoptosis. WD-repeat protein 79 -induced cell cycle arrest at the G0/G1 phase was associated with the expression of G0/G1-related cyclins and cyclin-dependent kinase complexes. We also provide evidence that WDR79 knockdown induces apoptosis via a mitochondrial pathway. Collectively, these results suggest that WDR79 is involved in the tumorigenesis of NSCLC and is a potential novel diagnostic marker and therapeutic target for NSCLC.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease affecting predominantly females. To discover additional genetic risk variants for SLE on the X chromosome, we performed a follow-up study of our previously published genome-wide association study (GWAS) data set in this study.

Poly-γ-glutamic acid (γ-PGA) is an important natural biopolymer that is used widely in fields of foods, medicine, cosmetics, and agriculture. Several B. amyloliquefaciens LL3 mutants were constructed to improve γ-PGA synthesis via single or multiple marker-less in-frame deletions of four gene clusters (itu, bae, srf, and fen) encoding antibiotic substances. γ-PGA synthesis by the Δsrf mutant showed a slight increase (4.1 g/L) compared with that of the wild-type strain (3.3 g/L). The ΔituΔsrf mutant showed increased γ-PGA yield from 3.3 to 4.5 g/L, with an increase of 36.4%. The γ-PGA yield of the ΔituΔsrfΔfen and ΔituΔsrfΔfenΔbae mutants did not show a further increase. The four gene clusters' roles in swarming motility and biofilm formation were also studied. The Δsrf and Δbae mutant strains were both significantly defective in swarming, indicating that bacillaene and surfactin are involved in swarming motility of B. amyloliquefaciens LL3. Furthermore, Δsrf and Δitu mutant strains were obviously defective in biofilm formation; therefore, iturin and surfactin must play important roles in biofilm formation in B. amyloliquefaciens LL3.

Compost habitats sustain a vast ensemble of microbes specializing in the degradation of lignocellulosic plant materials and are thus important both for their roles in the global carbon cycle and as potential sources of biochemical catalysts for advanced biofuels production. Studies have revealed substantial diversity in compost microbiomes, yet how this diversity relates to functions and even to the genes encoding lignocellulolytic enzymes remains obscure. Here, we used a metagenomic analysis of the rice straw-adapted (RSA) microbial consortia enriched from compost ecosystems to decipher the systematic and functional contexts within such a distinctive microbiome.

Legionella pneumophila is the causative agent of Legionnaires' disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication of L. pneumophila, however the contributions of other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods to characterise the major inflammatory cells in lung after acute respiratory infection of mice with L. pneumophila. We observed that the numbers of alveolar macrophages rapidly decreased after infection coincident with a rapid infiltration of the lung by monocyte-derived cells (MC), which, together with neutrophils, became the dominant inflammatory cells associated with the bacteria. Using mice in which the ability of MC to infiltrate tissues is impaired it was found that MC were required for bacterial clearance and were the major source of IL12. IL12 was needed to induce IFNγ production by lymphoid cells including NK cells, memory T cells, NKT cells and γδ T cells. Memory T cells that produced IFNγ appeared to be circulating effector/memory T cells that infiltrated the lung after infection. IFNγ production by memory T cells was stimulated in an antigen-independent fashion and could effectively clear bacteria from the lung indicating that memory T cells are an important contributor to innate bacterial defence. We also determined that a major function of IFNγ was to stimulate bactericidal activity of MC. On the other hand, neutrophils did not require IFNγ to kill bacteria and alveolar macrophages remained poorly bactericidal even in the presence of IFNγ. This work has revealed a cooperative innate immune circuit between lymphoid cells and MC that combats acute L. pneumophila infection and defines a specific role for IFNγ in anti-bacterial immunity.

The 14-3-3 family, which is composed of seven distinct members in humans, plays important roles in the cell cycle, apoptosis, synaptic plasticity and neuronal differentiation and migration. Previous genetic and post-mortem gene expression studies have linked this family to schizophrenia. However, the direction of gene expression changes in these studies has been inconsistent, and reports of 14-3-3 gene expression in living schizophrenic patients are still lacking. Here, we assessed 14-3-3 gene and protein expression levels in peripheral blood leukocytes from drug-naïve first-episode schizophrenic patients and matched controls. mRNA and protein expression levels were quantified by qRT-PCR and UPLC-MRM/MS, respectively. Expression analysis revealed four downregulated and one upregulated mRNA transcripts as well as five downregulated protein levels of 14-3-3 isoforms in schizophrenia. Moreover, significant positive correlations between 14-3-3 mRNA and protein expression levels were found in schizophrenia, and we also identified negative correlations between ε, θ and ζ isoform expression levels and positive symptoms of schizophrenia. Our results suggest that gene and protein expression levels for the 14-3-3 family are dysregulated in schizophrenia, perhaps owing to specific regulatory mechanisms, and we also suggest that expression of the 14-3-3ε, θ and ζ isoform genes could be useful indicators of disease severity.

The DNA-binding protein AT-Rich Interactive Domain 3B (ARID3B) is elevated in ovarian cancer and increases tumor growth in a xenograft model of ovarian cancer. However, relatively little is known about ARID3B's function. In this study we perform the first genome wide screen for ARID3B direct target genes and ARID3B regulated pathways. We identified and confirmed numerous ARID3B target genes by chromatin immunoprecipitation (ChIP) followed by microarray and quantitative RT-PCR. Using motif-finding algorithms, we characterized a binding site for ARID3B, which is similar to the previously known site for the ARID3B paralogue ARID3A. Functionality of this predicted site was demonstrated by ChIP analysis. We next demonstrated that ARID3B induces expression of its targets in ovarian cancer cell lines. We validated that ARID3B binds to an epidermal growth factor receptor (EGFR) enhancer and increases mRNA expression. ARID3B also binds to the promoter of Wnt5A and its receptor FZD5. FZD5 is highly expressed in ovarian cancer cell lines, and is upregulated by exogenous ARID3B. Both ARID3B and FZD5 expression increase adhesion to extracellular matrix (ECM) components including collagen IV, fibronectin and vitronectin. ARID3B-increased adhesion to collagens II and IV require FZD5. This study directly demonstrates that ARID3B binds target genes in a sequence-specific manner, resulting in increased gene expression. Furthermore, our data indicate that ARID3B regulation of direct target genes in the Wnt pathway promotes adhesion of ovarian cancer cells.

In this work, we have developed a truncated DNA aptamer, termed XQ-2d, with high affinity and specificity for pancreatic ductal adenocarcinoma (PDAC). Aptamer XQ-2d selectively binds to PL45 cells with a dissociation constant in the nanomolar range, as determined by its recognition of PL45 tumor cells in mice. Moreover, XQ-2d shows better recognition ratio for 40 tissue sections of clinical PDAC samples (82.5%) compared to the initial cell-SELEX selection library (5%). Therefore, XQ-2d can be considered a promising candidate as a tool for PDAC diagnosis and treatment.

To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn's disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.

Chailong Jieyu Pill (CJP) is composed of Radix Bupleuri, Radix Scutellariae, Rhizoma Pinelliae Preparata, Radix Codonopsis, Radix Glycyrrhizae preparata, keel, Concha Ostreae, Concha Margaritifera Usta, Rhizoma Zingiberis Recens, and Fructus Jujubae. CJP has shown good clinical effects on improving anxiety disorders. However, as the mechanism underlying such benefits remains unclear, the aim of this study was to investigate the mechanism of action for CJP on anxiety-related behaviors in a rat model of anxiety disorder. After establishing a rat model of anxiety disorder using uncertain empty bottle stimulation, rats were divided into control, model, citalopram, low-dose CJP, and high-dose CJP groups. After 1 month of administration, effects of treatments on rat appearance, body weight, and open-field test scores were observed. In addition, hippocampal monoamine neurotransmitter (5-hydroxytryptamine, dopamine, and norepinephrine) contents were measured with an enzyme-linked immunosorbent assay, and mRNA expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) were measured with reverse transcription-polymerase chain reaction. CJP increased rat weight, and this effect was increased in the high-dose CJP group compared with the citalopram group (P < 0.05). CJP also elevated open-field test scores compared with the citalopram group (P < 0.05). While CJP decreased monoamine neurotransmitter contents in rat hippocampus, the regulatory effect of CJP on 5-hydroxytryptamine was reduced compared with citalopram (P < 0.01). CJP upregulated GR mRNA expression in both low-dose (P < 0.05) and high-dose (P < 0.01) CJP groups, but only the latter significantly downregulated MR mRNA expression and showed enhanced effects compared with citalopram (P < 0.05). Thus, CJP likely exerted its significant antianxiety effect by diminishing monoamine neurotransmitters and regulating mRNA expression of MR and GR in the hippocampus of our rat model of anxiety disorder.

Monocytes infiltrate damaged liver tissue during noninfectious liver injury and often have dual roles, perpetuating inflammation and promoting resolution of inflammation and fibrosis. However, how monocyte subsets distribute and are differentially recruited in the liver remain unclear. In the current study, the subpopulations of infiltrating monocytes were examined following liver ischemia/reperfusion (I/R) injury in mice using flow cytometry. CD11b+Ly6C high (Ly6Chi) cells (inflammatory monocytes) and CD11b+Ly6C low cells (reparative monocytes) were recruited into the liver following I/R injury. Treatment with clodronate‑loaded liposomes, which transiently deplete systemic macrophages, alleviated hepatic damage. Mice genetically deficient in C‑C motif chemokine ligand 2 (CCL2), or its receptor C‑C chemokine receptor 2 (CCR2), exhibited diminished hepatic damage compared with wild‑type mice following I/R, by controlling intrahepatic inflammatory Ly6Chi monocyte accumulation. In addition, the CCR2 specific inhibitor RS504393 alleviated hepatic I/R injury. The results suggest that the CCR2/CCL2 axis has an important role in monocyte infiltration and may represent a novel target for the treatment of liver I/R injury.

The association between normal thyroid function and diabetic kidney disease (DKD) has gained increasing attention. The present study evaluated the relationship between normal thyroid hormone levels and DKD in type 2 diabetes mellitus (T2DM) patients. A total of 862 type 2 diabetes patients were enrolled in this cross-sectional study in Xi'an, Shaanxi Province, China. The subjects were evaluated for anthropometric measurements, thyroid function and DKD. Of 862 patients, 246 (28.5%) suffered from DKD, and the prevalence of DKD did not differ between men and women. The prevalence of DKD showed a significantly decreasing trend across the quartiles based on free triiodothyronine (FT3) levels (41.1%, 30.6%, 23.8%, and 18.9%, P < 0.001). In comparison with all participants categorized in the first FT3 quartile group (FT3-Q1) (<4.380), the adjusted odds ratio of DKD in the second FT3 quartile group (FT3-Q2), the third FT3 quartile group (FT3-Q3), and the fourth FT3 quartile group (FT3-Q4) were 0.655(95%CI: 0.406-1.057), 0.493(95%CI: 0.299-0.813), 0.406(0.237-0.697) (P < 0.05). Also, similar results were observed in men. Conversely, none of the FT3 groups was associated with DKD in women. The present study showed that FT3 within normal range was negatively correlated with DKD in T2DM patients.

Obesity is causally associated with atherosclerosis, and adipose tissue (AT)-derived exosomes may be implicated in the metabolic complications of obesity. However, the precise role of AT-exosomes in atherogenesis remains unclear. We herein aimed to assess the effect of AT-exosomes on macrophage foam cell formation and polarization and subsequent atherosclerosis development.

The characteristic of carcinoma is cell migration and invasion, which involve in strong actin dynamics. Regulations of actin dynamics have been implicated in cancer cell migration and tumor progression. WDR1 (WD-repeat domain 1) is a major cofactor of the actin depolymerizing factor (ADF)/cofilin, strongly accelerating ADF/cofilin-mediated actin disassembly. The role of WDR1 in non-small cell lung cancer (NSCLC) progression has been unknown. Here, we show that the expression levels of WDR1 are increased in human NSCLC tissues compared with adjacent non-tumor tissues, and high WDR1 level correlates with poor prognosis in NSCLC patients. Knockdown of WDR1 in NSCLC cells significantly inhibits cell migration, invasion, EMT process and tumor cell growth in vitro and in vivo. Otherwise, overexpression of WDR1 promotes NSCLC cell proliferation and migration. Mechanically, our data suggested WDR1 regulated tumor cells proliferation and migration might through actin cytoskeleton-mediated regulation of YAP, and we demonstrated that WDR1 contributes to NSCLC progression through ADF/cofilin-mediated actin disassembly. Our findings implicate that the ADF/cofilin-WDR1-actin axis as an activator of malignant phenotype that will be a promising therapeutic target in lung cancer.

We determined the complete genome sequence of a soil bacterium, Streptomyces albulus NK660. It can produce ε-poly-l-lysine, which has antimicrobial activity against a spectrum of microorganisms. The genome of S. albulus NK660 contains a 9,360,281-bp linear chromosome and a 12,120-bp linear plasmid.

Objective. This study aimed to determine the influence of Tang Wang One Decoction (TWOD) on the retinal vessels of diabetic rats. Methods. The hemorheology of diabetic rats was observed. Morphological studies of retinal vessels were conducted using optical microscopy and electron microscopy. Immunological histochemistry assay was used to measure the expression levels of MMP-9, occludin, and claudin-5. Results. Obvious pathological damage was observed in the retinal vessels of diabetic rats. TWOD positively affected the hemorheology and morphology of retinal vessels. The decoction also decreased the expression of MMP-9 and increased the expression of occludin and claudin-5. Conclusions. The results suggest that the retinal protective effects of TWOD might be related to downregulation of MMP-9 and upregulation of occludin and claudin-5.

To explore the repairing effect of combination of adipose stem cells (ASCs) and composite scaffolds on CWR, the electrospun Poly 1, 8-octanediol-co-citric acid (POC)-poly-L-lactide acid (PLA) composite scaffolds were prepared, followed by in vitro and in vivo biocompatibility evaluation of the scaffolds. Afterwards, ASCs were seeded on POC-PLA to construct the POC-PLA-ASCs scaffolds, and the POC-PLA, POC-PLA-ASCs, and traditional materials expanded polytetrafluoroethylene (ePTFE) were adopt for CWR in New Zealand white (NZW) rabbit models. As results, the POC-PLA-ASCs patches possessed good biocompatibility as the high proliferation ability of cells surrounding the patches. Rabbits in POC-PLA-ASCs groups showed better pulmonary function, less pleural adhesion, higher degradation rate and more neovascularization when compared with that in other two groups. The results of western blot indicated that POC-PLA-ASCs patches accelerated the expression of VEGF and Collagen I in rabbit models. From the above, our present study demonstrated that POC-PLA material was applied for CWR successfully, and ASCs seeded on the sheets could improve the pleural adhesions and promote the reparation of chest wall defects.

Combining experimental and computational screening methods has been of keen interest in drug discovery. In the present study, we developed an efficient screening method that has been used to screen 2100 small-molecule compounds for alanine racemase Alr-2 inhibitors.

It is essential to analyze rare mutations in many fields of biomedical research. However, the detection of rare mutations is usually failed due to the interference of predominant wild-type DNA surrounded. Herein we describe a sensitive and facile method of detecting rare point mutation on the basis of allele-specific amplification in emulsion PCR. The identification and selective amplification of rare mutation are accomplished in one-pot reaction. The allele-specific primers coupled on magnetic beads allow the exclusive amplification and enrichment of the mutant amplicons. The productive beads bearing mutant amplicons are subsequently stained with the fluorescent dyes. Thus, the rare point mutations with a percentage as low as 0.1%, can be detected by fluorescent analysis. The relative percentages of mutation among different samples can be roughly accessed by counting the fraction of fluorescent positive beads through flow cytometry.

Ethylene plays essential roles in adaptive growth of rice plants in water-saturating environment; however, ethylene signaling pathway in rice is largely unclear. In this study, we report identification and characterization of ethylene-response mutants based on the specific ethylene-response phenotypes of etiolated rice seedlings, including ethylene-inhibited root growth and ethylene-promoted coleoptile elongation, which is different from the ethylene triple-response phenotype in Arabidopsis. We establish an efficient system for screening and a set of rice mutants have been identified. Genetic analysis reveals that these mutants form eight complementation groups. All the mutants show insensitivity or reduced sensitivity to ethylene in root growth but exhibit differential responses in coleoptile growth. One mutant group mhz7 has insensitivity to ethylene in both root and coleoptile growth. We identified the corresponding gene by a map-based cloning method. MHZ7 encodes a membrane protein homologous to EIN2, a central component of ethylene signaling in Arabidopsis. Upon ethylene treatment, etiolated MHZ7-overexpressing seedlings exhibit enhanced coleoptile elongation, increased mesocotyl growth and extremely twisted short roots, featuring enhanced ethylene-response phenotypes in rice. Grain length was promoted in MHZ7-transgenic plants and 1000-grain weight was reduced in mhz7 mutants. Leaf senescent process was also affected by MHZ7 expression. Manipulation of ethylene signaling may improve adaptive growth and yield-related traits in rice.