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Background: Mucosal-associated invariant T (MAIT) cells are unconventional T cells which recognize microbial metabolites presented by the major histocompatibility complex class I-related molecule MR1. Although MAIT cells have been shown to reside in human and murine skin, their contribution to atopic dermatitis (AD), an inflammatory skin disease associated with barrier dysfunction and microbial translocation, has not yet been determined. Methods: Genetic deletion of MR1 and topical treatment with inhibitory MR1 ligands, which result in the absence and functional inhibition of MAIT cells, respectively, were used to investigate the role of MR1-dependent immune surveillance in a MC903-driven murine model of AD. Results: The absence or inhibition of MR1 arrested AD disease progression through the blockade of both eosinophil activation and recruitment of IL-4- and IL-13-producing cells. In addition, the therapeutic efficacy of phototherapy against MC903-driven AD could be increased with prior application of folate, which photodegrades into the inhibitory MR1 ligand 6-formylpterin. Conclusion: We identified MAIT cells as sentinels and mediators of cutaneous type 2 immunity. Their pathogenic activity can be inhibited by topical application or endogenous generation, via phototherapy, of inhibitory MR1 ligands.

The ligand-activated aryl hydrocarbon receptor (AhR) is an important molecular regulator of immune function, whose activity can be modulated by dietary glucosinolate- and tryptophan-derived metabolites. In contrast, the potential use of polyphenols as dietary regulators of AhR-dependent immunity remains unclear. In this perspective, we discuss how cellular metabolism may alter the net effect of polyphenols on AhR, thus potentially reconciling some of the conflicting observations reported in the literature. We further provide a methodological roadmap, across the fields of immunology, metabolomics, and gut microbial ecology, to explore the potential effects of polyphenol-rich diets on AhR-regulated immune function in humans.

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.

As a member of the MicroRNA s (miRNAs) family, miR-421 has been widely studied in regulating the proliferation and apoptosis of cancer cells a. However, there are still no reports on miR-421 in regulating adipocyte differentiation and its related mechanisms. Accordingly, this study aimed to investigate the potential involvement of miR-421 in goat intramuscular preadipocytes (P_IMA). The expression level of miR-421 was measured via quantitative real-time PCR during goat P_IMA differentiation. And the effects of miR-421 on goat P_IMA differentiation were studied by liposome transfection, Oil red O staining and qRT-PCR. Furthermore, the miR-421 target was searched and the underlying mechanism was clarified by luciferase reporter assay and rescue experiment. Our results showed that inhibition of miR-421 could accumulation of lipid droplets by upregulation the expression level of AP2, LPL, C/EBPα and SREBP1. Further studies showed that fibroblast growth factor 13 (FGF13) was the direct target of miR-421. Knocking down of FGF13 expression could inhibit lipid droplet formation and down-regulated the expression of key adipogenic regulatory genes. In addition, the rescue experiment revealed that FGF13 is involved in miR-421-induced differentiation of goat P_IMA as a key factor. Overall, these findings indicate that miR-421 is a negative regulator in the progression of differentiation of goat P_IMA by inhibiting the expression of FGF13.

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.

Biological control agents and soil amendments have been applied to control tobacco bacterial wilt, but the mechanism is not well-known. In the present study, a field experiment was performed to investigate the soil physicochemical properties, disease index (DI) and disease incidence of tobacco bacterial wilt, and rhizosphere microbial community. The results show that the control efficacy of single application of antagonistic bacteria and calcium cyanamide was 46.43% and 51.92%, respectively. While the combined control efficacy of antagonistic bacteria and calcium cyanamide was 65.79%. Besides, the combined application of antagonistic bacteria and calcium cyanamide could increase soil pH, total N alkaline N, and exchangeable Ca, which were negatively associated with the microbial diversity, soil-borne pathogenic microorganisms, and incidence of tobacco bacterial wilt. Additionally, the combination of antagonistic bacteria and calcium cyanamide can improve the proportion of some antagonistic microbial species, and these antagonistic microbial species were inversely associated with the DI of tobacco bacterial wilt. In conclusion: The integrated measure may influence soil microbial communities through enhancing soil physicochemical properties and rebuild healthy soil microbial community structure to mitigate tobacco bacterial wilt. The current study presented valuable insights into the mechanisms enhancing soil health in the integrated measure.

A novel Gram-stain-negative, rod-shaped, aerobic, oxidase-positive and catalase-positive bacterium of the genus Pseudooceanicola , designated strain E2-1T, was isolated from surface water of Jiulong River Estuary, PR China. Cells of strain E2-1T grew in medium containing 0.5–12 % NaCl (w/v; optimum, 2–4 %), at 15–45 °C (optimum, 28–33 °C) and at pH 7.0–9.0 (optimum, pH 7.0–8.0). Comparative analyses of the 16S rRNA gene sequence revealed that strain E2-1T had the highest similarity to Pseudooceanicola nitratireducens JLT1210T (97.3 %) and Pseudooceanicola batsensis HTCC2597T (97.1 %), and had less than 97.0 % 16S rRNA gene sequence similarity to other type strains within the genus Pseudooceanicola . The DNA G+C content of strain E2-1T was 65.7 mol%. The average nucleotide identity and digital DNA–DNA hybridization relatedness values between E2-1T and related type strains were 75.0 and 20.1 % with P. nitratireducens JLT1210T and 75.6 and 20.4 % with P. batsensis HTCC2597T, respectively. The sole isoprenoid quinone was Q-10; the predominant polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, three unidentified phospholipids and six unidentified lipids; the major cellular fatty acids were C16 : 0 (17.5 %), C19 : 0 cyclo ω8c (22.7 %) and summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c; 10.1 %). According to the phylogenetic and genotypic results, strain E2-1T represents a novel species in the genus Pseudooceanicola , for which the name Pseudooceanicola aestuarii sp. nov. is proposed. The type strain is E2-1T (=MCCC 1K03742T=KCTC 72107T).

Glioblastoma (GBM) is the deadliest primary brain tumor that is highly resistant to current treatments. Polo-like kinase 1 (PLK1) and signal transducer and activator of transcription 3 (STAT3) are highly expressed in gliomas, especially GBM. Previous studies have shown reciprocal activation between PLK1 and STAT3 and that they regulate the same pools of MYC downstream. We have demonstrated that PLK1 and STAT3 levels are elevated in gliomas compared with those in normal brain tissues, and high expression of both PLK1 and STAT3 is associated with poor prognosis in TCGA. Moreover, there was direct or indirect reciprocal regulation between PLK1 and STAT3. Furthermore, we found that PLK1 and STAT3 can regulate the same pools of MYC downstream. Compared to monotherapy, combined treatment of glioma cells with PLK1 and STAT3 inhibitors, BI2536 and Stattic, respectively, showed lower expression of MYC, synergistic induction of cell invasion and apoptosis in vitro, and tumor inhibition in xenografts. PLK1 and STAT3 were able to directly regulate the expression of MYC and induce apoptosis of glioma cells through the regulation of MYC. These findings may help develop a therapeutic strategy for dual inhibition of PLK1 and STAT3 against the tumorigenesis of glioma.

Background Lysine demethylase 3A (KDM3A) has been increasingly recognized as an important epigenetic regulator involved in cancer development. This study aims to explore the relevance of KDM3A to cervical cancer (CC) progression and the molecules involved. Materials and methods Tumor and the adjacent tissues from CC patients were collected. KDM3A expression in tissues and CC cell lines and its correlation with the survival and prognosis of patients were determined. Malignant potentials of CC cells and the angiogenesis ability of HUVECs were measured to evaluate the function of KDM3A on CC progression. The interactions among KDM3A, H3K9me2 and ETS1, and the binding between ETS1 and KIF14 were validated through ChIP and luciferase assays. Altered expression of ETS1 and KIF14 was introduced to explore their roles in CC development. Results KDM3A was abundantly expressed in CC tissues and cells and linked to dismal prognosis of CC patients. Knockdown of KDM3A suppressed malignant behaviors of CC cells. KDM3A was found to increase ETS1 expression through the demethylation of H3K9me2. Overexpression of ETS1 blocked the inhibiting roles of sh-KDM3A. ETS1 could bind to the promoter region of KIF14 to trigger its transcription. Overexpression ofKIF14aggravated the malignant behaviors of CC cells and the angiogenesis ability of HUVECs, and it activated the Hedgehog signaling pathway. Artificial activation of Hedgehog by Sag1.5 diminished the effects of sh-KDM3A. These changes were reproduced in vivo. Conclusion This study evidenced that KDM3A promotes ETS1-mediated KIF14 transcription to promote CC progression with the involvement of the Hedgehog activation.

NONCODE (http://www.noncode.org/) is a comprehensive database of collection and annotation of noncoding RNAs, especially long non-coding RNAs (lncRNAs) in animals. NONCODEV6 is dedicated to providing the full scope of lncRNAs across plants and animals. The number of lncRNAs in NONCODEV6 has increased from 548 640 to 644 510 since the last update in 2017. The number of human lncRNAs has increased from 172 216 to 173 112. The number of mouse lncRNAs increased from 131 697 to 131 974. The number of plant lncRNAs is 94 697. The relationship between lncRNAs in human and cancer were updated with transcriptome sequencing profiles. Three important new features were also introduced in NONCODEV6: (i) updated human lncRNA-disease relationships, especially cancer; (ii) lncRNA annotations with tissue expression profiles and predicted function in five common plants; iii) lncRNAs conservation annotation at transcript level for 23 plant species. NONCODEV6 is accessible through http://www.noncode.org/.

Leaf rust is an important wheat disease that is a significant hindrance for wheat production in most areas of the world. Breeding resistant cultivars can effectively and economically control the disease. In the present study, a wheat collection consisting of 100 cultivars from China and 18 improved germplasms from global landrace donors together with 36 known single Lr gene lines were tested with 20 strains of Puccinia triticina Eriks. in the seedling stage to postulate the Lr gene in the cultivars and germplasms. In addition, 12 diagnostic molecular markers specific to 10 Lr genes were used to detect the presence of the Lr genes in the wheat collection. Resistance to leaf rust of these cultivars at the adult plant stage was tested in fields under natural infection during the 2016 to 2018 cropping seasons in Baoding, Hebei Province. The gene postulation combined with molecular marker detection showed that six Lr genes (Lr1, Lr26, Lr33, Lr34, Lr45, and Lr46) were identified in 44 wheat accessions, including 37 cultivars and seven improved germplasms. Among the 44 wheat accessions postulated with Lr genes, Lr1 was present in four accessions, Lr26 in 12 accessions, Lr33 in two accessions, Lr34 in 14 accessions, Lr45 in three accessions, and Lr46 in 16 accessions. In the collection of 118 cultivars/germplasms, 34 wheat lines displayed adult-plant resistance carrying Lr34, Lr46, and/or underdetermined genes. Therefore, a high level of leaf rust resistance can be achieved through the combination of all-stage resistance and adult-plant resistance genes together in wheat cultivars.

Background In this study, Malus doumeri leaf flavonoids (MDLF) were used as the research object to observe their in vitro antioxidant stress ability. Hydrogen peroxide (H2O2) was used to induce oxidative stress in 293 T cells. Methods MTT, flow cytometry, and qPCR were used to verify the effect of MDLF. Results In vitro cell experiments showed that at a concentration of 0–160 μg/mL, MDLF did not affect the normal proliferation of human embryonic kidney 293 T cells (HEK 293 T cells), and MDLF had no cytotoxic effect in this concentration range. It was found that MDLF could maintain the survival of HEK 293 T cells (82.6%) at a high concentration (160 μg/mL). Morphological observation also found that MDLF can inhibit the cell structure imperfection caused by H2O2. It was also observed that MDLF could significantly increase the levels of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) and reduce the level of malondialdehyde (MDA). The results of quantitative polymerase chain reaction (qPCR) showed that MDLF could significantly up-regulate the mRNA expression levels of CAT, SOD, GSH, GSH-Px, B-cell lymphoma-2 (Bcl-2) and downregulate the expression levels of B-cell lymphoma-2 associated x protein (Bax), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-B (NF-κB) in oxidative stress-injured cells. The HPLC analysis showed that MDLF contained hyperin, isoquercetin, quercitrin, hesperidin, myricetin, baicalin and quercetin. Conclusion From the experimental results, it was observed that MDLF has a strong anti-oxidation ability in vitro, and it can interfere with the oxidative stress damage caused by H2O2 in 293 T cells. Therefore, MDLF is a type of natural substance with good anti-oxidant effect, and it has the potential to interfere with many diseases.

This pilot study aimed to potentially increase the consumption of cancer-preventative sulforaphane, available in broccoli, by introducing this vegetable in novel kimchi products. A panel of mostly ...

Marigold is reported to have antibacterial activity, and effectively protect crops against soil-borne diseases. However, it is not known whether and how tobacco bacterial wilt (TBW) could be mitigated via intercropping with marigold under field conditions. In this study, a field experiment was performed to measure and compare the occurrence of TBW, the soil chemical properties, and soil microbial composition and diversity between a tobacco-marigold intercropping system and a tobacco monocropping system. At 100 days (d) post-transplantation, the incidence (I) and disease index (DI) for the tobacco-marigold intercropping system were 30.12% and 58.25% lower than that for tobacco monocropping system, respectively. The results showed that Sobs, Shannon and Chao 1 index of soil bacterial communities in the tobacco-marigold intercropping system were 10.34%, 1.41% and 5.13% higher than that in the tobacco monocropping system at 100 d post-transplantation, respectively. It exhibited a higher richness and diversity of soil bacterial communities in the tobacco-marigold intercropping system. The relative abundance of some beneficial genera in tobacco-marigold intercropping system, such as Lysobacter, Burkholderia, Trichoderma, Mortierella, Chaetomium, Penicillium, was 1.50, 1.61, 3.35, 1.67, 4.40 and 4.50 fold higher than that in tobacco monocropping system. The presence of the intercropping system inhibited soil acidification and loss of soil calcium ions. The redundancy analysis (RDA) indicated that soil pH and exchange Ca2+ were the main environmental factors which seemed to influence the bacterial and fungal community. The results from this study provided valuable insight into the possible mechanisms enhancing soil health in the tobacco-marigold intercropping system.

Brown spot disease, caused by Alternaria alternate, is one of the most destructive leaf spot diseases that made a major impact on tobacco growing. Biocontrol has attracted increasing attentions as its features of environmental friendship, promoting plant growth, etc. Iturin A, with broad spectrum antifungal activity, is a kind of biosurfactant that mainly produced by Bacillus. In this study, the promoter of iturin A synthetase cluster of Bacillus amyloliquefaciens HZ-12 was respectively replaced by promoters P43, PbacA, PsrfA and Pylb, our results implied that transcriptional level of gene ituD and iturin A titer showed consistent change trends, and PbacA was proven as the most efficient promoter, iturin A titer of which reached 950.08 ± 19.43 mg/L. Furthermore, regulator gene abrB was deleted to release the repression effect of AbrB on PbacA, ituD transcriptional level and iturin A titer were increased by 133.25 % and 20.88 %, respectively. Then, the maximum iturin A titer reached 2013.43 ± 32.86 mg/L by optimizing fermentation medium, increased by 392.15 % compared to the original (408.97 ± 21.35 mg/L). Finally, our results demonstrated that enhancing iturin A synthetic capability benefited the suppression of A. alternate. Collectively, this study provided a promising strain with an efficient fermentation medium for large-scale industrial production of iturin A.

Diabetic nephropathy (DN) is one of the most important renal complications associated with diabetes, and the mechanisms are yet to be fully understood. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin-D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The aim of the present study was to explore the potential mechanism by which 1,25(OH)2D3 reduced oxidative stress in diabetic rat kidneys. In this study, we established a vitamin D-deficient spontaneous diabetes model: 5–6 wk of age Zucker diabetic fatty (ZDF) rats were treated with or without 1,25(OH)2D3 for 7 wk, age-matched Zucker lean rats served as control. Results showed that ZDF rats treated with 1,25(OH)2D3 had decreased body mass, food intake, water intake, and urine volume. 1,25(OH)2D3 ameliorated urine glucose, blood glucose and abnormal glucose tolerance. Additionally, 1,25(OH)2D3 significantly lowered microalbuminuria, decreased the glomerular basement membrane thickness, and in some degree inhibited glomerular hypertrophy, mesangial expansion, and tubular dilatation. Furthermore, 1,25(OH)2D3 attenuated renal oxidative damage, as reflected by the levels of malondialdehyde, reduced glutathione, 4-hydroxynonenal, 8-hydroxy-2'-deoxyguanosine, and reactive oxygen species production, and notably inhibited poly(ADP-ribose) polymerase-1 (PARP1), activated sirtuin 1 (SIRT1), and decreased the expression of NADPH oxidase 4 (NOX4). Of interest, the abovementioned proteins could be involved in the antioxidant mechanism of 1,25(OH)2D3 in diabetic rat kidneys. Our study showed that oxidative stress might be a major contributor to DN pathogenesis and uncovered the antioxidant role of 1,25(OH)2D3 in diabetic nephropathy that was associated with the PARP1/SIRT1/ NOX4 pathway.

The ECM protein EFEMP1 (fibulin‐3) is associated with all types of solid tumor through its cell context‐dependent dual function. A variant of fibulin‐3 was engineered by truncation and mutation to alleviate its oncogenic function, specifically the proinvasive role in glioblastoma multiforme (GBM) cells at stem‐like state. ZR30 is an in vitro synthesized 39‐kDa protein of human fibulin‐3 variant. It has a therapeutic effect in intracranial xenograft models of human GBM, through suppression of epidermal growth factor receptor/AKT and NOTCH1/AKT signaling in GBM cells and extracellular MMP2 activation. Glioblastoma multiforme is highly vascular, with leaky blood vessels formed by tumor cells expressing endothelial cell markers, including CD31. Here we studied GBM intracranial xenografts, 2 weeks after intratumoral injection of ZR30 or PBS, by CD31 immunohistochemistry. We found a 70% reduction of blood vessel density in ZR30‐treated xenografts compared with that of PBS‐treated ones. Matrigel plug assays showed the effect of ZR30 on suppressing angiogenesis. We further studied the effect of ZR30 on genes involved in endothelial transdifferentiation (ETD), in 7 primary cultures derived from 3 GBMs under different culture conditions. Two GBM cultures formed mesh structures with upregulation of ETD genes shortly after culture in Matrigel Matrix, and ZR30 suppressed both. ZR30 also downregulated ETD genes in two GBM cultures with high expression of these genes. In conclusion, multifaceted tumor suppression effects of human fibulin‐3 variant include both suppression of angiogenesis and vasculogenic mimicry in GBM., Vascularization in glioblastoma multiforme intracranial xenograft was reduced by intratumoral injection of ZR30, an in vitro synthesized 39‐kDa protein of human fibulin‐3 variant.

REV3L, the catalytic subunit of DNA polymerase ζ (Pol ζ), is indispensable for translesion DNA synthesis, which protects cells from deleterious DNA lesions resulting from various intrinsic and environmental sources. However, REV3L lacks a proofreading exonuclease activity and consequently bypasses DNA lesions at the expense of increased mutations, which poses a severe threat to genome stability. Here we report a site-specific proteolytic event of human REV3L. We show that REV3L is cleaved by a threonine aspartase, Taspase1 (TASP1), to generate an N-terminal 70-kDa fragment (N70) and a polypeptide carrying the C-terminal polymerase catalytic domain in human cells. Strikingly, such a post-translational cleavage event plays a vital role in controlling REV3L stability by preventing ubiquitination and proteasome-mediated degradation of REV3L. Indicative of the biological importance of the above REV3L post-translational processing, cellular responses to UV and cisplatin-induced DNA lesions are markedly impaired in human HCT116 cell derivatives bearing defined point mutations in the endogenous REV3L gene that compromise REV3L cleavage. These findings establish a new paradigm in modulating the abundance of REV3L through site-specific proteolysis in human cells.

Purpose Members of the aaRS (aminoacyl-tRNA synthetase) family are proteins controlling the aminoacylation process, in which YARS (tyrosyl-tRNA synthetase) catalyzes the binding of tyrosine to its cognate tRNA and plays an important role in basic biosynthesis. Several studies have demonstrated the association between YARS mutation and certain developmental abnormalities/diseases, yet YARS’s linkage with cancer remains uncategorized. In this study, by combining in silico, in vitro, and in vivo studies, we explored the expressions and functions of YARS in gastric cancer (GC). Methods We evaluated YARS’s distribution in tumor and paired normal tissues/specimens of GC by referring to large cohort online datasets and patient-derived tissue specimens. YARS-related changes were assessed by phenotypical/molecular experiments and RNA-sequencing analysis in GC cell lines harboring YARS knockdown or overexpression. Results Both the transcript and protein levels of YARS were evidently higher in gastric cancer tissues than in paired normal tissues. YARS knockdown induced repressed proliferation and invasiveness, as well as enhanced apoptosis in GC cell lines, while abnormally upregulating YARS expression promoted gastric cancer growth in vivo. We inferred based on RNA-sequencing that YARS modulates multiple cancerous signaling pathways and proved through cellular experiments that YARS promoted GC progression, as well as homologous recombination by activating PI3K-Akt signaling. Conclusions By revealing the existence of a YARS-PI3K-Akt signaling axis in gastric cancer, we discovered that tRNA synthetase YARS is a novel tumorigenic factor, characterized by its upregulation in tumor-derived specimens, as well as its functions in promoting gastric cancer progression.

Methylglyoxal (MGO) is the main antimicrobial determinant associated with using Mānuka Honey as a topical dressing. While direct mechanisms of Mānuka honey MGO's antimicrobial activity have been demonstrated, such as disruption of bacterial fimbria and flagella, no interaction of Mānuka honey-derived MGO with antimicrobial effector cells of the immune system, such as mucosal-associated invariant T cells (MAIT cells), has yet been reported. MAIT cells are an abundant subset of human T cells, critical for regulating a diverse range of immune functions, including antimicrobial defense mechanisms but also mucosal barrier integrity. MAIT cells become activated by recognition of an important microbial metabolite, 5-amino-6-d-ribitylaminouracil (5-A-RU), which is produced by a wide range of microbial pathogens and commensals. Recognition is afforded when 5-A-RU condenses with mammalian-cell derived MGO to form the potent MAIT cell activator, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU). Formation of 5-OP-RU and its subsequent presentation to MAIT cells by major histocompatibility (MHC)-related molecule 1 (MR1) facilitates host-pathogen and host-commensal interactions. While MGO is a metabolite naturally present in mammalian cells, it is unclear whether exogenous dietary MGO sources, such as those obtained from Mānuka honey intake, can contribute to 5-OP-RU formation and enhance MAIT cell activation. In this work, we report that endogenous MGO is the rate-limiting substrate for converting microbial 5-A-RU to 5-OP-RU and that Mānuka honey-derived MGO significantly enhances MAIT cell activation in vitro. Our findings posit a novel mechanism by which intake of a food item, such as Mānuka honey, can potentially support immune homeostasis by enhancing MAIT cell-specific microbial sensing.

Human pancreatic stellate cells (PSCs) play a critical role in fibrogenesis during chronic pancreatitis (CP). However, primary PSCs have a short lifespan in vitro, which seriously affects their use in various applications. We have established a stable immortalized human PSC line (HP-1) by RSV promoter/enhancer-driven SV40 T antigen expression in primary activated human PSCs. HP-1 cells express cytoskeleton proteins including glial fibrillary acidic protein (GFAP), α-smooth muscle actin (α-SMA), vimentin and desmin, and are typical of PSCs, which are high transfeciability and viable in 0.5% serum. The cells express receptors such as TGFβR2, PDGFR, TGF-β pseudoreceptor Bambi and PPRPγ that are commonly found in PSCs. HP-1 cells are similar to activated human PSCs in that they have enhanced expression of α-SMA, CTGF, Col1 and TIMP-2 mRNAs or proteins, as well as decreased expression of MMP-1/2 mRNAs or proteins in response to TGF-β1 stimulation. Comparative proteomics revealed 4,537 shared proteins between HP-1 cells and PSCs and no single protein in HP-1 cells versus PSCs. Statistical analysis reveals no significantly difference between HP-1 cells and PSCs in their expression of proteins associated with matrix and matrix remodeling. The similarity between HP-1 cell and PSC is further shown by the finding that only 9 proteins are differentially up-regulated > ± 2-fold in HP-1 cells and 13 proteins are up-regulated > ± 2-fold in PSCs and none of these proteins include ECM proteins, cytokines, growth factors or matrix remodeling regulatory proteins. Therefore, HP-1 cells can be used as an effective tool for the study of PSC-mediated pancreatic fibrosis.

Gram-positive bacteria (e.g. Firmicutes) and their mobile genetic elements (plasmids, bacteriophages) encode peptide-based quorum sensing systems (QSSs) that regulate behavioral transitions in a density-dependent manner. In their simplest form, termed “RRNPP”, these QSSs are composed of two adjacent genes: a communication propeptide and its cognate intracellular receptor. Despite the prime importance of RRNPP QSSs in the regulation of key biological pathways such as virulence, sporulation or biofilm formation in bacteria, conjugation in plasmids or lysogeny in temperate bacteriophages, no tools exist to predict their presence in target genomes/mobilomes. Here, we introduce RRNPP_detector, a software to predict RRNPP QSSs in chromosomes, plasmids and bacteriophages of gram-positive bacteria, available at https://github.com/TeamAIRE/RRNPP_detector. RRNPP_detector does not rely on homology searches but on a signature of multiple criteria, which are common between distinct families of experimentally-validated RRNPP QSSs. Because this signature is generic while specific to the canonical mechanism of RRNPP quorum sensing, it enables the discovery of novel RRNPP QSSs and thus of novel “languages” of biocommunication. Applying RRNPP_detector against complete genomes of viruses and Firmicutes available on the NCBI, we report a potential 7.5-fold expansion of RRNPP QSS diversity, alternative secretion-modes for certain candidate QSS propeptides, ‘bilingual’ bacteriophages and plasmids, as well as predicted chromosomal and plasmidic Biosynthetic-Gene-Clusters regulated by QSSs.

Background: HMGA2 encodes a small non histone chromatin-associated protein that has no intrinsic transcriptional activity, but can modulate transcription by altering the chromatin architecture. HMGA2 was found overexpressed in a variety of epithelial and mesenchymal tumors and promoted invasion and metastasis in most malignant epithelial tumors. A recent study showed that P53 inhibited CRC progression by targeting HMGA2. However, the mechanism by which HMGA2 affect angiogenesis in CRC has not been clarified. Methods: The expression of HMGA2 was analyzed by IHC, WB and bio infomatic analysis. Cbioportal and mexpress online tools were applied to explore the CNV and methylation of HMGA2 in CRC patients. Single cell data from GEO was used to examine the specific cell type that contribute to the high HMGA2 expression in CRC. Lentivirus was used to knock down HMGA2 in CRC cells and HUVECs was used to study angiogenesis. Results: In the current study, we first detected the expression pattern of HMGA2 in CRC patients and evaluated its clinical values and CNV amplification could possibly contribute to the up regulation of HMGA2 in CRC patients. By analyzing CRC single cell data we found that HMGA2 was specifically up regulated in the colorectal epithelial cells. Furthermore, knocking down of HMGA2 suppresses angiogenesis via dual regulation of VEGF-A and SEMA3A in CRC through inactivating VEGRR2 pathway in HUVECs. Conclusions: HMGA2 might be a promising prognostic marker and target for treating advanced CRC patients.

Environmental health and food safety issues potentially caused by the dinitroaniline herbicide pendimethalin (PM) are a worldwide concern. The toxicity response of ginger and tissue accumulation effects of PM on ginger biomass were studied by utilizing PM (CK (clean water), PM1 (0.4%), PM2 (0.67%), PM3 (1.0%), and PM4 (1.67%)) in a dose–response study. It significantly reduced the biomass of ginger under PM4, which is attributed to root damage. The net photosynthetic rate of ginger under PM4 was 11.37% lower than that of CK, which is mainly caused by stomatal limitation. In addition, the ultrastructure of chloroplasts has changed. PM4 caused the accumulation of reactive oxygen species (ROS) in ginger. The activity of superoxide dismutase (SOD) and peroxidase (POD) increased accordingly, maintaining the dynamic balance of ROS content. PM had no significant effect on the expression of ginger α-tubulin genes. PM was significantly accumulated in ginger roots, but not rhizomes. Si increased the productivity of ginger under PM4, which is mainly related to the increase of root development (root application of silicon) and photosynthetic efficiency (foliar application of silicon). Si reduced the ROS content due to the increase in SOD, POD, and catalase (CAT) activity and photosynthetic efficiency.

Background: Lipid metabolism has a profound impact on gastric cancer (GC) progression and is a newly targetable vulnerability for cancer therapy. Given the importance of lipids in cancer cellular processes, in this study we employed lipidomic clinical and transcriptomic data of GC to connect the variations of lipid metabolism changes.Method: We constructed a clinical nomogram based on the lipid factors and other clinical items. Then by using multi-omics techniques, we established a lipid-related gene signature for individualized prognosis prediction in patients with GC. Moreover, a total of 1357 GC cases were then applied to evaluate the robustness of this model. WGCNA was used to identify co-expression modules and enriched genes associated with GC lipid metabolism. The role of key genes ACLY in GC was further investigated.Results: The prognostic value of the lipidomic signature was analyzed using Cox regression model, and clinical nomogram was established. Among them, we observed overexpression of ACLY significantly increased the levels of intracellular free fatty acid and triglyceride, and activate AKT/mTOR pathway to promote cancer development.Conclusions: In conclusion, our findings delineated a GC clinical and lipidomic signature and revealed that GC exhibited a reprogramming of lipid metabolism in association with an altered expression of lipid metabolism-associated genes. Among them, ACLY significantly promoted GC lipid metabolism and increased cancer cell proliferation, suggesting that this pathway can be targetable as a metabolic vulnerability in future GC therapy.

In this study, the complete chloroplast genome of Michelia chartacea B. L. Chen & S. C. Yang was 160,138 bp in length. It includes a large single-copy (LSC) region of 88,164 bp, a small single-copy region (SSC) of 18,824 bp, and with a pair of inverted repeats (IRs) of 26,575 bp. The GC content in the chloroplast genome was 39.23%. In total, 130 genes in the chloroplast genome of Michelia chartacea were annotated, including 83 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The phylogenetic analysis showed that M. chartacea was closely related with M. martini and M. maudiae, forming a clade included in Michelia.

Integrative analysis was performed in the Chinese Glioma Genome Atlas and The Cancer Genome Atlas to describe the pyroptosis-associated molecular classification and prognostic signature in glioma. Pyroptosis-related genes were used for consensus clustering and to develop a prognostic signature. The immune statuses, molecular alterations and clinical features of differentially expressed genes were analyzed among different subclasses and risk groups. A lncRNA-miRNA-mRNA network was built, and drug sensitivity analysis was used to identify small molecular drugs for the identified genes. Glioma can be divided into two subclasses using 30 pyroptosis-related genes. Cluster 1 displayed high immune signatures and poor prognosis as well as high immune-related function scores. A prognostic signature based on 15 pyroptosis-related genes of the CGGA cohort can predict the overall survival of glioma and was well validated in the TCGA cohort. Cluster 1 had higher risk scores. The high-risk group had high immune cell and function scores and low DNA methylation of pyroptosis-related genes. The differences in pyroptosis-related gene mutations and somatic copy numbers were significant between the high-risk and low-risk groups. The ceRNA regulatory network uncovered the regulatory patterns of different risk groups in glioma. Nine pairs of target genes and drugs were identified. In vitro, CASP8 promotes the progression of glioma cells. Pyroptosis-related genes can reflect the molecular biological and clinical features of glioma subclasses. The established prognostic signature can predict prognosis and distinguish molecular alterations in glioma patients. Our comprehensive analyses provide valuable guidelines for improving glioma patient management and individualized therapy.

Communication between viruses supported by quorum sensing systems (QSSs) were found to optimize the fitness of temperate bacteriophages of Bacilli by guiding the transition from the host-destructive lytic cycle to the host-protective lysogenic cycle in a density-dependent manner. All known phage-encoded QSSs consist of a communication propeptide and a cognate intracellular receptor that regulates the expression of adjacent target genes upon recognition of the matured peptide, a signature known as RRNPP and found in chromosomes, plasmids and phages of Firmicutes bacteria. Recently, we have introduced the RRNPP_detector software to detect novel genetic systems matching the RRNPP signature, which unearthed many novel phage-encoded candidate QSSs. Here, by looking at the adjacent genes likely regulated by these viral candidate QSSs, we identified an unsuspected clustering of viral QSSs with viral genes whose bacterial homologs are key regulators of the last-resort bacterial sporulation initiation pathway (rap, spo0E or abrB). Consistently, we found evidence in published data that certain of these QSSs encoded by prophages (phage genomes inserted within a bacterial genome) dynamically manipulate the timing of sporulation in the host. Because these viral QSSs are genetically diverse and are found associated with different sporulation regulators, this suggests a convergent evolution in bacteriophages of density-dependent sporulation-hijacking mechanisms.SIGNIFICANCECommunication between viruses supported by quorum sensing systems (QSSs) is a brand new research area that has transformed our views of viral adaptation and virus-host co-evolution. The viral QSSs discovered so far were found to guide the lysis-lysogeny decision in temperate bacteriophages as a function of phage density. Here, we identified that quorum sensing-mediated communication between phages can not only guide the regulation of viral processes but also the manipulation of the bacterial sporulation pathway. Our finding introduces the new view that not only bacteria decide when it is time to sporulate, some bacteriophages are also key stakeholders in this dynamical decision-making process. Considering that spores are the transmissive form of many pathogens, these new insights have important applied implications.

Background: Goats are popular in China because of their superior meat quality, delicate flesh, and unique flavor. Long noncoding RNAs (lncRNAs) play important roles in transcriptional and post-transcriptional regulation of gene expression. However, the effects of lncRNAs on the meat quality of goat hasn’t been fully elucidated yet. Results: In this investigation, we performed RNA-Seq analysis of intramuscular and subcutaneous adipocytes from Jianzhou Daer goat before and after differentiation, including both intramuscular preadipocytes (IMPA) vs intramuscular adipocytes (IMA) and subcutaneous preadipocytes (SPA) vs subcutaneous adipocytes (SA). A total of 289.49 G clean reads and 12,519 lncRNAs were obtained from 20 samples. In total, 4,121 differentially expressed RNAs (388 miRNAs, 182 lncRNAs and 3,551 mRNAs) were identified by pairwise comparison. There were 135 differentially expressed lncRNAs specific to intramuscular adipocytes, 39 DELs specific to subcutaneous adipocytes, and 8 DELs common to both adipocytes in these 182 DELs. Some well-known and novel pathways associated with preadipocyte differentiation were identified: fat acid metabolism, TGF-beta signaling pathway and PI3K-Akt signaling pathway. We also identified hub miRNAS in both types of fat cells and visualized them in Cytoscape. Conclusions: Our analysis revealed the unique and common lncRNA-miRNA-mRNA networks of two kinds of adipocytes. Several lncRNAs that regulate goat meat quality were screened out, such as XR_001918647.1, XR_001917728.1, XR_001297263.2 and LNC_004191. Our study utilized RNA-seq analysis to predict the functions of lncRNA on goat meat quality. Furthermore, our findings of lncRNA-miRNA-mRNA network, may contribute to a better understanding of the molecular mechanisms underlying in goat meat quality and provide a theoretical basis for further goat molecular breeding.

Ribosome-inactivating proteins (RIPs) are toxic proteins that can inhibit protein synthesis. RIPs purified from Bougainvillea have low nonspecific toxicity, showing promise for processing applications in the agricultural and medical fields. However, systematic research on the polymorphism of Bougainvillea RIPs is lacking, and it is worth exploring whether different isoforms differ in their active characteristics. The transcriptional and translational expression of type I RIPs in Bougainvillea glabra leaves was investigated in this study. Seven RIPs exhibited seasonal variation at both the mRNA and protein levels. The isoforms BI4 and BI6 showed the highest transcriptional expression in both the summer and autumn samples. Interestingly, BI6 was not detected in the protein level in any of the samples. However, the bioinformatics analysis showed that RIPs derived from the same species were gathered in a different cluster, and that the active sites changed among the isoforms during evolution. The significant discrepancy in Bougainvillea RIPs mainly locates at both termini of the amino acid sequence, particularly at the C terminus. Post-translational modifications may also exist in Bougainvillea RIPs. It is concluded that the reason for the polymorphism of Bougainvillea RIPs may be that these proteins are encoded by multiple genes due to genetic processes such as gene duplication and mutation. According to the results of sequence analysis, the possible functional differences of B. glabra RIP isoforms are discussed with regard to the observed discrepancy in both active sites and structures.

Manglietia yuyuanensis is an important afforestation and excellent broad-leaved tree species in southern China. In this study, we assembled the complete chloroplast genome of M. yuyuanensis based o...

Background: Immune cells recognize tumor antigens presented on major histocompatibility complex class I (MHC-I) molecule. Increase of MHC-I molecular expression makes tumor cells more susceptible to lysis by immune cells. Methods: Tumor lysate vaccine was prepared to damage glioma cells including cell lines and primary cultured cells from surgical samples. The enhanced effect of histone deacetylase inhibitors (HDACi) to tumor lysate vaccine was observed. The expressions of MHC-I pathway molecules were detected by flow cytometry and western blot after HDACi treatment. Cell apoptosis and cell lysis were measured following blocking cytotoxic T lymphocyte (CTL) pathway. Tumor size and mice survival were analyzed in combinative treatment with HDACi and tumor lysate. Results: HDACi up-regulated the expressions of MHC-I pathway molecules, and enhanced the recognition and killing of immune cells, which was activated by tumor lysate. Activated antigen specific immune responses regulated CTL activity, and HDACi promoted immune response through cytotoxic effect of CTL. Anti-tumor effect of tumor lysate pulse immunogenicity in vivo was elevated by HDACi due to up-regulation of antigen presentation. Conclusions: Our study showed that HDACi enhanced recognition of glioma cell by immune cells and sensitivity of tumor immunotherapy, and improved the anti-tumor effect of tumor lysate vaccine through activating CTL immune response. These pharmacological molecular mechanisms of increasing immune recognition suggest that epigenetic modulation is a promising strategy for sensitizing immunotherapy for glioma treatment.

WITHDRAWAL NOTICE In our paper entitled ROC and Anova Analysis on Human Macrophage THP 1 Gene, where the corresponding author is Qingqing Li, which was published in Journal of Medical Imaging and Health Informatics, 2019, Volume 9, pp.1246–1253, there is a conflict of interest between the authors of the article. We have found that the results in Figures 1 and 2 of the article may be unreliable under different growth states of the cells. Therefore, after careful consideration, we have decided to withdraw this paper with great regret. After resolution of the problematic results, we will resubmit the manuscript. We sincerely apologize for any inconvenience caused by the withdrawal of this article from the journal.

Low temperature is a major factor limiting seedling growth and the production of cotton (Gossypium hirsutum L.). However, enhancing chilling tolerance is typically negatively correlated with yield in agricultural production. Here, we demonstrate that transgenic cotton expressing Atriplex hortensis choline monooxygenase (AhCMO) greatly enhanced resistance to chilling stress. The promotion of chilling tolerance is mainly due to an increase in the content of osmoprotectants, especially glycine betaine and proline. The increased chilling tolerance was further verified at the molecular level using genome-wide expression profiling by RNA-sequencing. Further detailed analysis showed that the number of genes involved in scavenging of reactive oxygen species (ROS) was down-regulated and the activity of superoxide dismutase (SOD) and catalase (CAT) were decreased in AhCMO transgenic cotton compared with wild type after low temperture treatment. More importantly, overexpression of AhCMO in cotton moderately improved cotton fiber yield in normal growth condition. These data show that AhCMO transgenic cotton enhances low temperature tolerance via directly accumulating cellular osmoprotectants. Manipulating the expression of AhCMO by biotechnological tools could be a powerful method to enhance chilling tolerance in cotton.

Non-muscle myosin IIA (NMIIA) protein plays an important role in cell cytokinesis and cell migration. The role and underlying regulatory mechanisms of NMIIA in pancreatic cancer (PC) remain elusive. We found that NMIIA is highly expressed in PC tissues and contributes to PC poor progression by using open microarray datasets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and PC tissue arrays. NMIIA regulates β-catenin mediated EMT to promote the proliferation, migration, invasion, and sphere formation of PC cells in vitro and in vivo. NMIIA controls the β-catenin transcriptional activity by interacting with β-catenin. Moreover, MEK/ERK signaling is critical in MLC2 (Ser19) phosphorylation, which can mediate NMIIA activity and regulate Wnt/β-catenin signaling. These findings highlight the significance of NMIIA in tumor regression and implicate NMIIA as a promising candidate for PC treatment.

The gap junction protein plays an important role in the bone formation and alteration of these proteins leading to cause bone development. Aim to determine the effects of different concentration of fluoride on gap-junctional intercellular communication (GJIC) related genes and proteins in the rats' osteoblast cells. We treated the osteoblast cells with various concentrations (0, 0.01, 0.1, 0.5, and 1.0 mM) NaF for 24 and 72 h. We used the scrape loading and dye transfer technique to research the intracellular connectivity. Moreover, the mRNA expression levels of connexin 43 (Cx43), connexin45 (Cx45), collagen I, and osteocalcin (OCN) were analyzed by qRT-PCR, the protein expression levels of connexin43 (Cx43) were analyzed by western blotting and immunofluorescence. Our results suggested that the osteoblast proliferations were decreased in the 0.5 and 1 mM NaF groups, after 24 and 72 treatments. The scrape loading and dye transfer experiment showed that the GJIC were increased in the 0.01 mM NaF group and decreased in the 0.5 and 1 mM NaF groups. In addition, the mRNA expressions of Cx43, Cx45, and OCN, and the protein expressions of Cx43 were increased in the 0.01 mM NaF group and decreased in the 0.5 and 1 mM NaF groups. In summary, these results suggest that the low concentration NaF is good for the GJIC, but the high concentration NaF damages the GJIC.

Rhesus and several other species of monkeys are susceptible to genotypes of hepatitis E virus (HEV), and these species are thus commonly used as animal models for experimental HEV infection. However, information regarding HEV infection in monkeys in nature or at monkey farms is limited. To investigate the status of HEV infection in rhesus monkeys at farms, we collected 548 serum and 48 fecal samples from a rhesus monkey farm in China, and analyzed their levels of anti-HEV IgG antibodies and HEV RNAs. An enzyme-linked immunosorbent assay using genotype 3 HEV-like particles as antigen revealed anti-HEV IgG-positivity in 388 (70.8%) monkeys. The antibody-positive rates in the 1-year-old and 2-year-old monkeys were significantly lower than those in monkeys >3 years old. The antibody-positive rate was greatly increased from 7.4% in the 2-year-old monkeys to 100% in the 3-year-olds, suggesting that the latter received HEV infection at a high frequency. HEV RNA was detected in one of 88 sera from 1- and 2-year-old monkeys and 10 of 48 fecal specimens from 3-year-old monkeys by reverse transcription-polymerase chain reaction. Phylogenetic analyses revealed that the HEV strain RmKM15 was present in a serum sample that belonged to subtype 4b in genotype 4, whereas 10 strains detected in the fecal specimens belonged to subtype 4 h, suggesting that two genetically different strains were circulating at the farm. However, no significant clinical signs were observed in these monkeys. Further studies are required to identify the source of infection and to evaluate the pathogenicity of HEV in rhesus monkeys.

Background Angiopoietin-like protein 8 (ANGPTL8), a newly identified hormone, has been recently characterized as a metabolic regulator which can affect energy homeostasis and has interesting potentials as a metabolic disease therapy. However, little is as yet known as to whether circulating ANGPTL8 levels are altered in thyroid dysfunction. This study measured serum ANGPTL8 levels in patients with Graves’ disease and explored the correlations between its serum levels and thyroid index in Graves’ disease. Methods The concentration of ANGPTL8 was analyzed in blood samples of 128 well-characterized individuals whose anthropometric parameters, biochemical parameters, and thyroid index were measured. The participants were divided into Graves’ disease patients (n = 60) and healthy control subjects (n = 68). Logistic regression was used to evaluate the relationship between ANGPTL8 and Graves’ disease. Results Serum ANGPTL8 levels were more significantly decreased in Graves’ disease patients than in healthy control subjects (177.67 ± 135.07 vs 326.41 ± 194.72 pg/mL; p

microRNAs (miRNAs) are small non-coding RNAs that regulate various biological processes by targeting mRNAs and affecting their stability or translation. miR-122 is a major miRNA in mammalian liver but its function in poultry liver has not been studied. Therefore, the objective of the current study was to determine the function of miR-122 in the chicken liver. Through bioinformatics, we found P4HA1 was a candidate target of miR-122. P4HA1 mRNA and protein expression were increased in hepatocytes when miR-122 was knocked down by locked nucleic acid (LNA)-antisense-miR-122 (LNA-122). Reporter gene analyses confirmed that P4HA1 was a target of miR-122. Because P4HA1 is known to play an important role in liver metabolism, these findings suggest that miR-122 may be involved in liver metabolism in the chicken by regulating the P4HA1 expression.Highlights The predicted target site of miR-122 in chicken P4HA1 is conserved among species. P4HA1 mRNA and protein are upregulated in miR-122 knockdown chicken hepatocytes. miR-122 targets P4HA1 in chicken.

In order to improve the spore yield of compound Bacillus spp. (B. amyloliquefaciens, B. laterosporus and B. megaterium), the effects of nutrient conditions including carbon source, nitrogen source, mineral salt and fermentation conditions including the inoculum age, inoculation amount, loading volume of liquid and initial pH on the spore yield were studied. The results indicated that the optimized medium was glucoses 20 g/L, soybean meal 30.0 g/L, K2HPO4 1.0 g/L; fermentation temperature is 37℃, the inoculum age 12 h, initial pH 7.0, 2% inoculation amount, loading volume of liquid 20 mL/250 mL. Under the optimized conditions of culture medium and fermentation for compound Bacillus spp., spore yield was 10.24 times more than the initial medium, and the spore formation rate reached more than 90%.

Chronic ototoxicity of β-diketone antibiotics (DKAs) to zebrafish (Danio rerio) was explored in detail by following abnormal expressions of two hearing-related miRNAs. Dose-dependent down-regulation of miR-96 and miR-184 was observed in otoliths during embryonic-larval development. Continuous DKA exposure to 120-hpf larva decreased sensitivity to acoustic stimulation. Development of otolith was delayed in treatment groups, showing unclear boundaries and vacuolization at 72-hpf, and utricular enlargement as well as decreased saccular volume in 96-hpf or latter larval otoliths. If one miRNA was knocked-down and another over-expressed, only a slight influence on morphological development of the otic vesicle occurred, but knocked-down or over-expressed miRNA both significantly affected zebrafish normal development. Injection of miR-96, miR-184 or both micRNA mimics to yolk sac resulted in marked improvement of otic vesicle phenotype. However, hair cell staining showed that only the injected miR-96 mimic restored hair cell numbers after DKA exposure, demonstrating that miR-96 played an important role in otic vesicle development and formation of hearing, while miR-184 was only involved in otic vesicle construction during embryonic development. These observations advance our understanding of hearing loss owing to acute antibiotic exposure and provide theoretical guidance for early intervention and gene therapy for drug-induced diseases.

Background Lactobacillus plantarum, a versatile lactic acid-fermenting bacterium, isolated from the traditional pickles in Ningbo of China, was chosen for grass carp fermentation, which could also improve the flavor of grass carp. We here explored the central metabolic pathways of L. plantarum by using metabolomic approach, and further proved the potential for metabolomics combined with proteomics approaches for the basic research on the changes of metabolites and the corresponding fermentation mechanism of L. plantarum fermentation. Results This study provides a cellular material footprinting of more than 77 metabolites and 27 proteins in L. plantarum during the grass carp fermentation. Compared to control group, cells displayed higher levels of proteins associated with glycolysis and nucleotide synthesis, whereas increased levels of serine, ornithine, aspartic acid, 2-piperidinecarboxylic acid, and fumarate, along with decreased levels of alanine, glycine, threonine, tryptophan, and lysine. Conclusions Our results may provide a deeper understanding of L. plantarum fermentation mechanism based on metabolomics and proteomic analysis and facilitate future investigations into the characterization of L. plantarum during the grass carp fermentation. Electronic supplementary material The online version of this article (10.1186/s12866-018-1354-x) contains supplementary material, which is available to authorized users.

The intestinal microbiome is essential for human health. Significant differences in microbiota compositions have been found between individuals, but the impact that sex has on the gut microbiota alterations during obesity alleviation via fish oil and krill oil treatments is unknown. In this study, male and female high-fat-diet induced obese ICR mice received 600 μg g −1 d −1 fish oil, krill oil, or a mixture of both (1:1, 600 μg g −1 d −1 ) continuously for 12 weeks. Our results indicated that the oil treatment had a greater efficacy in alleviating obesity in male mice compared with female mice, and the overall structures of the gut microbiota were notably different. Three operational taxonomic units (OTUs) were identified that were highly associated with the obesity phenotype in male mice, while 14 such OTUs were identified in female mice. These findings demonstrated that the alteration of the gut microbiota after fish and krill oil supplementation in mice is sex-associated.

Feasibility of subcriticality monitoring with a digital reactivity meter based on inverse kinetics method has been investigated at the lead-based zero power reactor VENUS-II. A series of control rod drop experiments have been carried out in this work. The subcriticality before and after the rod drop were estimated considering the effect of external neutron source. The control rod worth was also extracted from the rod drop experiments. The measurement results exhibited obvious spatial dependence induced by the control rod insertion, and they could be corrected by correction factors calculated with MCNP code. The corrected values of control rod worth were found to be consistent with the reference ones predetermined at critical condition. Moreover, this method could also provide real time subcriticality without any correction when the detectors were placed at appropriate positions at slightly subcritical state. Based on these measurements, it has been proved that the digital reactivity meter could be a useful tool for continuous reactivity monitoring in the operation of ADS in future.

The gC1qR is a ubiquitously expressed cell protein that interacts with the globular heads of C1q (gC1q) and many other ligands. In this study, one gC1qR homolog gene was obtained from Exopalaemon carinicauda and named EcgC1qR. The complete nucleotide sequence of EcgC1qR contained a 774 bp open reading frame (ORF) encoding EcgC1qR precursor of 257 amino acids. The deduced amino acid sequence of EcgC1qR revealed a 55-amino-acid-long mitochondrial targeting sequence at the N-terminal and a mitochondrial acidic matrix protein of 33 kDa (MAM33) domain. The genomic organization of EcgC1qR gene showed that EcgC1qR gene contained five exons and four introns. EcgC1qR could express in all of the detected tissues and its expression was much higher in hepatopancreas and hemocytes. The expression of EcgC1qR in the hepatopancreas of prawns challenged with Vibrio parahaemolyticus and Aeromonas hydrophila changed in a time-dependent manner. The expression of EcgC1qR in prawns challenged with V. parahaemolyticus was up-regulated at 6 h (p 0.05), and significantly up-regulated at 12 h and 24 h (p 0.01), and then returned to the control levels at 48 h post-challenge (p 0.05). At the same time, the expression in Aeromonas-challenged group was significantly up-regulated at 6, 12 and 24 h. The recombinant EcgC1qR could inhibit the growth of two tested bacteria. In addition, we successfully deleted EcgC1qR gene through CRISPR/Cas9 technology and it was the first time to obtain the mutant of gC1qR homolog gene in crustacean. It's a great progress to study the biological function of gC1qR in crustacean in future.

PIWI-interacting RNAs are a class of small RNAs that is most abundantly expressed in animal germline. Substantial research is going on to reveal the functions of piRNAs in the epigenetic and post-transcriptional regulation of transposons and genes. To collect and annotate these data, we developed piRBase, a database assisting piRNA functional study. Since its launch in 2014, piRBase has integrated 264 data sets from 21 organisms, and the number of collected piRNAs has reached 173 million. The latest piRBase release (v2.0, 2018) was more focused on the comprehensive annotation of piRNA sequences, as well as the increasing number of piRNAs. In addition, piRBase release v2.0 also contained the potential information of piRNA targets and disease related piRNA. All datasets in piRBase is free to access, and available for browse, search and bulk downloads at http://www.regulatoryrna.org/database/piRNA/.

Tsukushi (TSK), a newly identified hepatokine, is a member of the small leucine-rich proteoglycans (SLRPs) family. TSK was originally isolated and identified in the lens of the chicken. Preliminary research on TSK has focused on its role in various physiological processes such as growth and development, wound healing, and cartilage formation. In recent years, the role of TSK in regulating cell signaling pathways, cell proliferation, and differentiation has been studied. In addition, the research has gradually expanded to the fields of glycolipid metabolism and energy balance. This article briefly reviews the role of TSK in the physiological and pathological process.