SHP2 Drives Adaptive Resistance to ERK Signaling Inhibition in Molecularly Defined Subsets of ERK-Dependent Tumors

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Expanded Expression Landscape and Prioritization of Circular RNAs in Mammals

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Comparative expression analysis of heavy metal ATPase subfamily genes between Cd-tolerant and Cd-sensitive turnip landraces

The heavy metal ATPase(HMA)subfamily is mainly involved in heavy metal(HM)tolerance and transport in plants,but an understanding of the definite roles and mechanisms of most HMA members are still limited.In the present study,we identified 14 candidate HMA genes named BrrHMAl—BrrHMA8 from the turnip genome and analyzed the phylogeny,gene structure,chromosome distribution,and conserved domains and motifs of HMAs in turnip(Brassica rapa var.rapa).According to our phylogenetic tree,the BrrHMAs are divided into a Zn/Cd/Co/Pb subclass and Cu/Ag subclass.The BrrHMA members show similar structural characteristics within subclasses.To explore the roles of BrrHMAs in turnip,we compared the gene sequences and expression patterns of the BrrHMA genes between a Cd-tolerant landrace and a Cd-sensitive landrace.Most BrrHMA genes showed similar spatial expression patterns in both Cd-tolerant and Cd-sensitive turnip landraces;some BrrHMA genes,however,were differentially expressed in specific tissue in Cd-tolerant and Cd-sensitive turnip.Specifically,BrrHMA genes in the Zn/Cd/Co/Pb subclass shared the same coding sequence but were differentially expressed in Cd-tolerant and Cd-sensitive turnip landraces under Cd stress.Our findings suggest that the stable expression and up-regulated expression of BrrHMA Zn/Cd/Co/Pb subclass genes under Cd stress may contribute to the higher Cd tolerance of turnip landraces.     

Fullerene nanoparticles for the treatment of ulcerative colitis

Ulcerative colitis (UC) is a long-term, recurrent inflammatory bowel disease for which no effective cure is yet available in the clinical setting. Repairing the barrier dysfunction of the colon and reducing intestinal inflammation are considered key objectives to cure UC. Here we demonstrate a novel therapeutic strategy based on a C₆₀ fullerene suspension (C₆₀FS) to treat dinitrobenzene sulfonic acid-induced UC in an animal model. C₆₀FS can repair the barrier dysfunction of UC and effectively promote the healing of ulcers; it also manifests better treatment effects compared with mesalazine enema. C₆₀FS can reduce the numbers of basophils in the blood of UC rats and mast cells in the colorectal tissue, thereby effectively alleviating inflammation. The expression of H1R, H4R, and VEGFR2 receptors in colorectal tissues is inhibited by C₆₀FS, and the levels of histamine and prostaglandin in the rat blood are reduced. This work presents a reliable strategy based on fullerene to cure UC and provides a novel guide for UC treatment.

     

Melatonin inhibits Gram-negative pathogens by targeting citrate synthase

Bacterial infections caused by Gram-negative pathogens represent a growing burden for public health worldwide. Despite the urgent need for new antibiotics that effectively fight against pathogenic bacteria, very few compounds are currently under development or approved in the clinical setting. Repurposing compounds for other uses offers a productive strategy for the development of new antibiotics. Here we report that the multifaceted melatonin effectively improves survival rates of mice and decreases bacterial loads in the lung during infection. Mechanistically, melatonin specifically inhibits the activity of citrate synthase of Gram-negative pathogens through directly binding to the R300, D363, and H265 sites, particularly for the notorious Pasteurella multocida. These findings highlight that usage of melatonin is a feasible and alternative therapy to tackle the increasing threat of Gram-negative pathogen infections via disrupting metabolic flux of bacteria.

     

Fruit and vegetable consumption,cardiovascular disease,and all-cause mortality in China

Science China Life Sciences - Evidence about the response patterns of fruit and vegetable consumption with the risk of cardiovascular disease (CVD) and all-cause mortality was inconsistent. These...     

Effects of 5-aminolevulinic acid on the inflammatory responses and antioxidative capacity in broiler chickens challenged with lipopolysaccharide

5-Aminolevulinic acid (5-ALA) is an intermediate in haem biosynthesis and has anti-apoptotic, anti-inflammatory, antioxidant, and other pharmacological effects. This study aimed to investigate the effect of dietary supplementation with 5-ALA on growth performance, antioxidant capacity, and inflammatory response of the lipopolysaccharide (LPS)-challenged broiler chickens. The experiment was designed as a 2 × 2 factorial arrangement with dietary 5-ALA (0 or 60 mg/kg) and LPS (injection of saline or 0.5 mg/kg BW) levels as treatments. A total of 240 one-day-old Arbor Acres broilers were distributed into four treatments consisting of six replicates of 10 birds. All the experimental broilers were intraperitoneally injected with LPS or sterile saline at 16, 18, and 20 days of age. Our results showed that dietary 5-ALA supplementation reduced (P < 0.05) the feed to gain before broilers were stimulated with LPS (days 1–15). LPS challenge decreased (P < 0.05) the catalase (CAT), total superoxide dismutase activities and increased the content of malondialdehyde (MDA) in the serum of broiler chickens. However, 5-ALA supplementation had a tendency to increase (P = 0.08) the activity of CAT and decreased (P < 0.05) the content of MDA. LPS challenge showed higher (P < 0.05) interleukin (IL)-1β, IL-6, and IL-10 concentrations in the serum, whereas dietary 5-ALA supplementation decreased (P < 0.05) the levels of IL-1β and IL-6. Additionally, dietary 5-ALA supplementation significantly attenuated (P < 0.05) the upregulation of mRNA expression levels of hepatic toll-like receptor 4 (TLR4), IL-1β, and IL-2 induced by LPS challenge. Moreover, dietary 5-ALA supplementation also enhanced the mRNA expression of 5-aminolevulinate dehydratase, ferrochelatase, and haem oxygenase-1 (HO-1) as compared to the unsupplemented groups. In conclusion, our results suggested that supplementation of 60 mg/kg 5-ALA exhibited LPS-induced anti-inflammatory and antioxidant properties by enhancing the HO-1 expression and inhibiting the TLR4/NF-κB signalling pathway.     

Bovine colostrum promoted ileal health in newborn lambs at 24 h after birth: insight from intestinal morphology and innate immunity

The contribution of colostrum to passive immunity transfer and intestinal protection in newborn ruminants is well known; however, it is currently unclear how colostrum intake affects intestinal innate immunity. We investigated the effects of bovine colostrum intake on ileal morphology, expression of genes involved in intestinal innate immunity, and serum concentrations of inflammatory cytokines in newborn lambs. Twenty-seven newborn male Hu lambs were used, of which 18 were bottle-fed either bovine colostrum (C24h; n = 9) or bovine mature milk (M24h; n = 9) within the first 2 h after birth at an intake of approximately 8% of BW; the remaining nine lambs did not receive any feeding (N24h). Blood and ileal tissue samples were collected after the lambs were slaughtered at 24 h after birth. Ileal villus height and villus height-to-crypt depth ratio were significantly higher in C24h than those in N24h and M24h lambs (P < 0.01). Messenger RNA (mRNA) abundance of toll-like receptor (TLR)-2, TLR3, TLR4, TLR6, TLR7, TLR8 and tumour necrosis factor alpha in the ileum was lower in C24h than that in N24h lambs (P < 0.05). Moreover, C24h lambs had a lower TLR3 mRNA abundance (P < 0.01) and a trend of lower TLR6 (P = 0.06) and interleukin 1 beta (P = 0.08) expression compared with those in M24h lambs. We also observed strong positive correlations of tumour necrosis factor alpha expression with that of TLR2 (r = 0.71; P < 0.001), TLR4 (r = 0.88; P < 0.001) and TLR8 (r = 0.83; P < 0.001). Interestingly, the expression of barrier-related molecules, including mucin-13, lysozyme, claudin (CLDN)-1, CLDN2, CLDN4, CLDN7, CLDN12, occludin, zonula occluden-1 and junctional adhesion molecule-1, was consistently lower in C24h lambs than that in N24h and M24h lambs (P < 0.05). These results indicated that the beneficial roles of colostrum intake on intestinal protection in newborn lambs were associated with low TLR expression, which was reflected by improved intestinal development and reduced inflammatory response. Further studies using fluorescence in situ hybridisation and immunohistochemical methods are needed to further explore the mechanisms underlying the lower expression of intestinal barrier-related molecules due to colostrum feeding.     

Biocontrol: Endophytic bacteria could be crucial to fight soft rot disease in the rare medicinal herb,Anoectochilus roxburghii

Microbial destabilization induced by pathogen infection has severely affected plant quality and output, such as Anoectochilus roxburghii, an economically important herb. Soft rot is the main disease that occurs during A. roxburghii culturing. However, the key members of pathogens and their interplay with non-detrimental microorganisms in diseased plants remain largely unsolved. Here, by utilizing a molecular ecological network approach, the interactions within bacterial communities in endophytic compartments and the surrounding soils during soft rot infection were investigated. Significant differences in bacterial diversity and community composition between healthy and diseased plants were observed, indicating that the endophytic communities were strongly influenced by pathogen invasion. Endophytic stem communities of the diseased plants were primarily derived from roots and the root endophytes were largely derived from rhizosphere soils, which depicts a possible pathogen migration image from soils to roots and finally the stems. Furthermore, interactions among microbial members indicated that pathogen invasion might be aided by positively correlated native microbial members, such as Enterobacter and Microbacterium, who may assist in colonization and multiplication through a mutualistic relationship in roots during the pathogen infection process. Our findings will help open new avenues for developing more accurate strategies for biological control of A. roxburghii bacterial soft rot disease.