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Tobacco bacterial wilt (TBW) is seriously damages the growth of tobacco. There is an urgent need to find a safer and more effective measure to control TBW. In this study, B. amyloliquefaciens ZM9 and marigold powder were applied to the tobacco roots alone or in combination, and the potential inhibition of TBW was assessed. On the other hand, the effects of these treatments on soil physicochemical properties, rhizosphere microbial community and soil metabolites were also evaluated. The results showed that the application of B. amyloliquefaciens ZM9 or marigold powder alone significantly reduced the abundance of R. solanacearum in rhizosphere soil, while the integrated treatment showed the strongest inhibitory effect. Moreover, the integrated treatment can inhibit the secretion of chemoattractants, and affect the change of rhizosphere soil microbial composition. In conclusion, the combination of antagonistic bacteria agent B. amyloliquefaciens ZM9 with marigold powder can enhance the suppression of TBW. Furthermore, B. amyloliquefaciens ZM9 and marigold have synergistic effects on suppressing TBW by regulation soil physicochemical properties, soil metabolites and microbial structure. This study provide a promising strategy for TBW control by integrated applying of B. amyloliquefaciens ZM9 and marigold powder.

Tobacco bacterial wilt (TBW) caused by Ralstonia solanacearum is the most serious soil-borne disease of tobacco. However, molecular mechanism information of R. solanacearum resistance is limited to tobacco, hindering better breeding of resistant tobacco. In this study, the expression profiles of the rootstalks of Yunyan87 (susceptible cultivar) and Fandi3 (resistant cultivar) at different stages after R. solanacearum infection were compared to explore molecular mechanisms of tobacco resistance against the bacterium. Findings from gene-expression profiling indicated that the number of upregulated differentially expressed genes (DEGs) at 3 and 7 days post-inoculation (dpi) increased significantly in the resistant cultivar. WRKY6 and WRKY11 family genes in WRKY transcription factors, ERF5 and ERF15 family genes in ERFs transcription factors, and genes encoding PR5 were significantly upregulated in the resistant cultivar response to the infection. For the first time, WRKY11 and ERF15 were found to be possibly involved in disease-resistance. The Kyoto Encyclopedia of Genes and Genomes analysis demonstrated glutathione metabolism and phenylpropane pathways as primary resistance pathways to R. solanacearum infection. In the resistant cultivar, DEGs encoding CYP450, TCM, CCoAOMT, 4CL, PAL, CCR, CSE, and CADH, involved in the synthesis of plant antitoxins such as flavonoids, stilbenoids, and lignins, enriched in the phenylpropane pathway were upregulated at 3 and 7 dpi. Furthermore, a pot experiment was performed to verify the role of flavonoids in controlling TBW. This study will strongly contribute to a better understanding of molecular interactions between tobacco plants and R. solanacearum.

Bacterial wilt as a soil-borne disease was caused by Ralstonia solanacearum, and seriously damages the growth of tobacco. Integrated biocontrol method was explored to control bacterial wilt. Nevertheless, the long-term effects of the integrated biocontrol method on soil bacterial community, soil physicochemical properties and the incidence of bacterial wilt are not well understood. In this study, B. amyoliquefaciens ZM9, calcium cyanamide and rice bran were applied to tobacco fields in different ways. The disease index and incidence of tobacco bacterial wilt (TBW), soil physicochemical properties, colonization ability of B. amyoliquefaciens ZM9, and rhizopshere bacterial community were investigated. The results showed that the integrated application of B. amyoliquefaciens ZM9, rice bran and calcium cyanamide had the highest control efficiency of TBW and bacteria community diversity. Additionally, the integrated biocontrol method could improve the colonization ability of B. amyoliquefaciens ZM9. Furthermore, the integrated biocontrol method could effectively suppress TBW by regulating soil physicochemical properties, promoting beneficial bacteria and antagonistic bacteria of rhizopshere soil. This strategy has prospect of overcoming the defects in application of a single antagonistic bacteria and provides new insights to understand how to improve the colonization capacity of antagonistic bacteria and control efficacy for TBW.

Interest in the use of enhanced-efficiency nitrogen (N) fertilizers (EENFs) has increased in recent years due to their potential to increase crop yield and reduce environmental N loss. Drip-fertigation is widely used for crop production in arid regions to improve water and nutrient use efficiency whereas the effectiveness of EENFs with drip irrigation remains unclear. A field experiment was conducted in 2015 and 2016 to examine the effects of EENFs on yield, N use and quality of cotton (Gossypium hirsutum) grown under drip-fertigation in arid NW China. Treatments included an unfertilized control and application of 240 kg N ha−1 by polymer-coated urea (ESN), urea alone, or urea plus urease (NBPT) and nitrification (DCD) inhibitors. ESN was all banded in the plant row at planting, whereas urea was applied with 20% N banded at planting and 80% N by six fertigation events over the growing season. Results showed there was generally no treatment effect on seed and lint yield, N concentration or allocations, N recovery efficiency and fiber quality index of cotton. A lack of treatment effect could be due to N supplied with drip-fertigation better synthesized with crop N needs and the relatively high soil native NO3− availability, which hindered the effect of polymer-coated urea and double inhibitors. These results highlight the challenge of the employment of EENFs products for drip-fertigation system in arid area. Further research is required to define the field conditions under which the agronomic efficiency of EENFs products may be achieved in accordance with weather conditions.

Sinusoidal dedifferentiation is a complicated process induced by several factors, and exists in early stage of diverse liver diseases. The mechanism of sinusoidal dedifferentiation is poorly unknown. In this study, we established a NaAsO2-induced sinusoidal dedifferentiation mice model. Liver sinusoidal endothelial cells were isolated and isobaric tag for relative and absolute quantitation (iTRAQ) based proteomic approach was adopted to globally examine the effects of arsenic on liver sinusoidal endothelial cells (LSECs) during the progression of sinusoidal dedifferentiation. In all, 4205 proteins were identified and quantified by iTRAQ combined with LC-MS/MS analysis, of which 310 proteins were significantly changed in NaAsO2 group, compared with the normal control. Validation by western blot showed increased level of clathrin-associated sorting protein Disabled 2 (Dab2) in NaAsO2 group, indicating that it may regulate receptor endocytosis, which served as a mechanism to augment intracellular VEGF signaling. Moreover, we found that knockdown of Dab2 reduced the uptake of VEGF in LSECs, furthermore blocking VEGF-mediated LSEC dedifferentiation and angiogenesis.

Occasional beer spoilage incidents caused by false-negative isolation of lactic acid bacteria (LAB) in the viable but non-culturable (VBNC) state, result in significant profit loss and pose a major concern in the brewing industry. In this study, both culturable and VBNC cells of an individual Lactobacillus harbinensis strain BM-LH14723 were identified in one spoiled beer sample by genome sequencing, with the induction and resuscitation of VBNC state for this strain further investigated. Formation of the VBNC state was triggered by low-temperature storage in beer (175 ± 1.4 days) and beer subculturing (25 ± 0.8 subcultures), respectively, and identified by both traditional staining method and PMA-PCR. Resuscitated cells from the VBNC state were obtained by addition of catalase rather than temperature upshift, changing medium concentration, and adding other chemicals, and both VBNC and resuscitated cells retained similar beer-spoilage capability as exponentially growing cells. In addition to the first identification of both culturable and VBNC cells of an individual L. harbinensis strain from spoiled beer, this study also for the first time reported the VBNC induction and resuscitation, as well as verification of beer-spoilage capability of VBNC and resuscitated cells for the L. harbinensis strain. Genes in association with VBNC state were also identified by the first genome sequencing of beer spoilage L. harbinensis. The results derived from this study suggested the contamination and spoilage of beer products by VBNC and resuscitated L. harbinensis strain BM-LH14723.

Lasso peptides are ribosomally synthesized and post-translationally modified peptides produced by bacteria. They are characterized by an unusual lariat-knot structure. Targeted genome scanning revealed a wide diversity of lasso peptides encoded in actinobacterial genomes, but cloning and heterologous expression of these clusters turned out to be problematic. To circumvent this, we developed an orthogonal expression system for heterologous production of actinobacterial lasso peptides in Streptomyces hosts based on a newly-identified regulatory circuit from Actinoalloteichus fjordicus. Six lasso peptide gene clusters, mainly originating from marine Actinobacteria, were chosen for proof-of-concept studies. By varying the Streptomyces expression hosts and a small set of culture conditions, three new lasso peptides were successfully produced and characterized by tandem MS. The newly developed expression system thus sets the stage to uncover and bioengineer the chemo-diversity of actinobacterial lasso peptides. Moreover, our data provide some considerations for future bioprospecting efforts for such peptides. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre- ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per- mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ © The Author(s) 2018

Numerous studies have investigated the prognostic values of MYC and/or BCL2 protein overexpression in diffuse large B-cell lymphoma (DLBCL). However, the results still demonstrate discrepancies among different studies. We aimed to do a systematic review and meta-analysis on the relationships between overexpression MYC and/or BCL2 and DLBCLs treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). This study followed the guidelines of PRISMA and Cochrane handbook. The hazard ratios (HRs) for overall survival (OS) were pooled to estimate the main effect size. Twenty studies recruited a total of 5576 patients were available for this meta-analysis. The results showed that MYC (HR = 1.96, 95%CI (confidence interval) = 1.69–2.27)without heterogeneity(I2 = 17.2%, P = 0.280), BCL2 (HR = 1.65, 95%CI = 1.43–1.89, I2 = 20.7%, P = 0.234) protein overexpression, and co-overexpression (HR = 2.58, 95%CI = 2.19–3.04, I2 = 17.2%, P = 0.275) had a poor prognosis in R-CHOP treated DLBCL patients, respectively. The current analysis indicated that MYC and/or BCL2 protein overexpression, and particularly co-overexpression was related to short overall survival in R-CHOP treated DLBCL patients, showing that application of the two new biomarkers can help to better stratify DLBCL patients and guide targeted treatment.

Toward the elucidation of the advanced mechanism of l-valine production by Corynebacterium glutamicum, a highly developed industrial strain VWB-1 was analyzed, employing the combination of transcriptomics and proteomics methods. The transcriptional level of 1155 genes and expression abundance of 96 proteins were changed significantly by the transcriptome and proteome comparison of VWB-1 and ATCC 13869. It was indicated that the key genes involved in the biosynthesis of l-valine, ilvBN, ilvC, ilvD, ilvE were up-regulated in VWB-1, which together made prominent contributions in improving the carbon flow towards l-valine. The l-leucine and l-isoleucine synthesis ability were weakened according to the down-regulation of leuB and ilvA. The up-regulation of the branched chain amino acid transporter genes brnFE promoted the l-valine secretion capability of VWB-1. The NADPH and ATP generation ability of VWB-1 were strengthened through the up-regulation of the genes involved in phosphate pentose pathway and TCA pathway. Pyruvate accumulation was achieved through the weakening of the l-lactate, acetate and l-alanine pathways. The up-regulation of the genes coding for elongation factors and ribosomal proteins were beneficial for l-valine synthesis in C. glutamicum. All information acquired were useful for the genome breeding of better industrial l-valine producing strains.

Zfp637 is a recently identified zinc finger protein and its functions remain largely unknown. Here, we innovatively demonstrate the effects of Zfp637 on the differentiation of mouse spermatogonia and on its downstream target gene SOX2 in vitro. Obesity has been recognized as a chronic inflammatory disease that leads to decreased sexual function and sexual development disorders. We observed higher levels of IL-6 in serum and testis homogenates from obese mice compared with control mice. We also demonstrated that high levels of IL-6 inhibited Zfp637 expression and we elucidated the underlying mechanisms. SOCS3 overexpression and STAT3 phosphorylation inhibitor (AG490) were used to investigate the function of the SOCS3/STAT3 pathway during this process. Our results showed that exposure of mouse spermatogonial cells to high levels of IL-6 inhibited Zfp637 expression by increasing SOCS3 expression and inhibiting the phosphorylation of STAT3, further reducing cellular differentiation. Consistent with the in vitro results, we observed increasing expression levels of SOCS3 and SOX2, but a reduction of Zfp637 expression, in obese mouse testes. In conclusion, Zfp637 plays a crucial role in spermatogenesis by downregulating SOX2 expression and IL-6 can decrease the expression of Zfp637 through the SOCS3/STAT3 signaling pathway.

The impact of anemia on the outcome of patients with stroke remains inconsistent. We performed a meta-analysis of cohort studies to assess the mortality risk in stroke patients with and without anemia. Systematic searches were conducted in the PubMed, China National Knowledge Infrastructure, Web of Science and Wanfang databases to identify relevant studies from inception to November 2015. The estimated odds ratio with a 95% confidence interval was pooled. subgroup analyses and sensitivity analyses were also conducted. We used Begg’s funnel plot and Egger’s test to detect the potential publication bias. Thirteen cohort studies with a total of 19239 patients with stroke were included in this meta-analysis. The heterogeneity among studies was slight (I2 = 59.0%, P = 0.031). The results from a random-effect model suggest that anemia is associated with an increased mortality risk in patients with stroke (adjusted odds ratio = 1.39, 95% confidence interval: 1.22–1.58, P

In conventional neonatal MRI, the T2 hyperintensity (T2h) in cerebral white matter (WM) at term-equivalent age due to immaturity or impairment is still difficult to identify. To clarify such issue, this study used the metrics derived from a two-compartment WM model of diffusional kurtosis imaging (WM-DKI), including intra-axonal, extra-axonal axial and radial diffusivities (Da, De,// and De,⊥), to compare WM differences between the simple T2h and normal control for both preterm and full-term neonates, and between simple T2h and complex T2h with hypoxic-ischemic encephalopathy (HIE). Results indicated that compared with control, the simple T2h showed significantly increased De,// and De,⊥, but no significant change in Da in multiple premyelination regions, indicative of expanding extra-axonal diffusion microenvironment; while myelinated regions showed no changes. However, compared with simple T2h, the complex T2h with HIE had decreased Da, increased De,⊥ in both premyelination and myelinated regions, indicative of both intra- and extra-axonal diffusion alterations. While diffusion tensor imaging (DTI) failed to distinguish simple T2h from complex T2h with HIE. In conclusion, superior to DTI-metrics, WM-DKI metrics showed more specificity for WM microstructural changes to distinguish simple T2h from complex T2h with HIE.

Pseudomonas aeruginosa is a gram-negative bacterium and one of the leading causes of nosocomial infection worldwide, however, no effective vaccine is currently available in the market. Here, we demonstrate that inactivation of the bacteria by X-ray irradiation inhibits its replication capability but retained antigenic expression functionally thus allowing its use as a potential vaccine. Mice immunized by this vaccine were challenged by the parental strain, the O-antigen-homologous strain PAO-1 (O2/O5) and heterologous strain PAO-6 (O6) in an acute pneumonia model. We further measured the protective effect of the vaccine, as well as host innate and cellular immunity responses. We found immunized mice could protect against both strains. Notably, the antiserum only had significant protective role against similar bacteria, while adoptive transfer of lymphocytes significantly controlled the spread of the virulent heterologous serogroup PAO-6 infection and the protective role could be reversed by CD4 rather than CD8 antibody. We further revealed that vaccinated mice could rapidly recruit neutrophils to the airways early after intranasal challenge by PAO-6 and the irradiated vaccine was proved to be protective by the generated CD4+ IL-17+ Th17 cells. In conclusion, the generation of inactivated but metabolically active microbes is a promising strategy for safely vaccinating against Pseudomonas aeruginosa.

ZNF32 is a recently identified zinc finger protein and its functions remain largely unknown. Autophagy has been shown to affect cell proliferation and survival. Here, we innovatively show the effect of ZNF32 on cell autophagy and autophagy-associated cell death in breast carcinoma cells and also elucidate its underlying mechanisms. We examined the autophagic activity and LC3 II expression in human carcinoma cell lines with increased or decreased ZNF32 expression. Pharmacological inhibition (rapamycin) or activation (EGF) assays were used to investigate the function of the AKT/mTOR pathway during this process. H2O2- and diamide-induced MCF-7 cell death models were used to elucidate the role of ZNF32-associated autophagy in breast carcinoma cell death. Our results show that increasing ZNF32 expression in MCF-7 cells inhibits autophagy initiation by activating the AKT/mTOR pathway and further reduced autophagy-associated cell death and maintained MCF-7 cell survival. Conversely, impairing ZNF32 expression by transfecting ZNF32 siRNA strongly promoted autophagy, further augmenting autophagy-associated cell death. Furthermore, correlations between ZNF32 and autophagy were observed in both MCF-7 xenograft tumors and in breast cancer patients. In conclusion, ZNF32 acts as an effective autophagy inhibitor to protect breast cancer cells from excessive stimulus-autophagy-induced cell death.

The patient-derived tumor xenograft (PDTX) model has become the most realistic model for preclinical studies. PDTX models of gastric cancer using surgical tissues are reported occasionally; however, the PDTX models using gastroscopic biopsies, which are best for evaluating new drugs, are unreported. In our study, a total of 185 fresh gastroscopic biopsies of gastric cancer were subcutaneously transplanted into NOD/SCID (Nonobese Diabetic/Severe Combined Immunodeficiency) mice. Sixty-three PDTX models were successfully established (34.1%, 63/185) and passaged to maintain tumors in vivo and the mean latency period of xenografts was 65.86 ± 32.84 days (11–160 days). Biopsies of prior chemotherapy had a higher transplantation rate (52.1%, 37/71) than biopsies after chemotherapy (21.9%, 25/114; P = 0.000). No differences were found between the latency period of xenografts and characteristics of patients. The pathological and molecular features of PDTX as well as chemosensitivity were highly consistent with those of primary tumors of patients. The genetic characteristics were stable during passaging of PDTX models. In summary PDTX models using gastroscopic biopsies in gastric cancer were demonstrated for the first time and the biological characteristics of the PDTX models were highly consistent with patients, which provided the best preclinical study platform for gastric cancer.

We assessed whether red cell distribution width (RDW) is associated with serum uric acid (UA) level in a group of 512 patients with newly diagnosed hypertension, recruited in Beijing. Patients were divided into high uric acid group and low uric acid group according to the median (334.9 μmol/L) of serum uric acid. Compared with the low uric acid group, the patients with high uric acid had higher red blood cell count (P < 0.001) and RDW (P = 0.032). The multiple linear regression analysis showed that RDW (P = 0.001) was positively correlated with uric acid level after the adjustment of related factors. Stepwise multiple logistic regression model confirmed that RDW (odds ratio: OR = 1.75) was independent determinants of high serum uric acid as well as sex (OR = 6.03), triglycerides (OR = 1.84), and Blood Urea Nitrogen (BUN, OR = 1.30). RDW may be independently associated with serum UA level in patients with newly diagnosed hypertension. To firmly establish the causal role of RDW in the incidence of high uric acid level among hypertensive patients, large cohort studies are needed.