Broad dysregulation of gene expression control is a hallmark of cancer progression. Identifying the underlying master regulators that drive pathological gene expression is a key challenge in precision oncology. Here, we have developed a network analytical framework, named PRADA, that identifies oncogenic RNA-binding proteins through the systematic detection of coordinated changes in their target regulons. Application of this approach to data collected from clinical samples, patient-derived xenografts, and cell line models of colon cancer metastasis revealed the RNA-binding protein RBMS1 as a suppressor of colon cancer progression. We observed that silencing RBMS1 results in increased metastatic capacity in xenograft mouse models, and that restoring its expression blunts metastatic liver colonization. We have found that RBMS1 functions as a post-transcriptional regulator of RNA stability by directly binding and stabilizing ~80 target mRNAs. Measurements in more than 180 clinical samples as well as survival analyses in publicly available datasets, have shown that RBMS1 silencing and the subsequent downregulation of its targets are strongly associated with disease progression and poor survival in colon cancer patients. Together, our findings establish a role for RBMS1 as a previously unknown regulator of RNA stability and as a suppressor of colon cancer metastasis with clinical utility for risk stratification of patients. SignificanceBy applying a new analytical approach to transcriptomic data from clinical samples and models of colon cancer progression, we have uncovered RBMS1 as a suppressor of metastasis and as a posttranscriptional regulator of RNA stability. Notably, RBMS1 silencing and downregulation of its targets are negatively associated with patient survival. MainMetastatic progression in colorectal cancer (CRC) is accompanied by widespread gene expression reprogramming. Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve

Highlights d A large collection of cancer cell line protein responses to drug perturbations d Perturbed protein responses greatly increase predictive power for drug sensitivity d A systematic map of protein-drug connectivity was built based on response profiles d A user-friendly, interactive data portal was developed for community use Authors

Myxobolus turpisrotundus Zhang, 2009, infects allogynogenetic gibel carp Carassius auratus gibelio (Bloch) and is always regarded as synonymous with Myxobolus rotundus Nemeczek, 1911, since its first report in goldfish Carassius auratus auratus (L.) in China in 1955. In this study, it was comprehensively examined by morphological and molecular biological methods. The round spores of M. turpisrotundus are similar to those of M. rotundus from common bream Abramis brama (L.) in morphology; however, we detected slight differences in morphometry. The ratios of the length and width of the spore to the length and width of the polar capsule of M. turpisrotundus are usually below 2.0 and 1.9, respectively, however these ratios are always above 2.0 and 1.9 in M. rotundus. The plasmodium size of M. turpisrotundus is 600-6,200 microm in diameter and that of M. rotundus is 60-180 microm in diameter. Scanning observation showed the spore surface of M. turpisrotundus was generally pitted. Yet the surface of M. rotundus is smooth. Sequence comparison revealed the small subunit ribosomal RNA gene sequence of M. turpisrotundus did not match any published sequences of M. rotundus (EU710583, 85% over 742 bp; FJ851447, 85% over 742 bp, FJ851448, 85% over 742 bp; FJ851449, 85% over 742 bp). Moreover, phylogenetic analysis showed M. turpisrotundus clustered with the species from allogynogenetic gibel carp with high bootstrap values (100% neighbor-joining, NJ; 100% maximum parsimony, MP) and M. rotundus from common bream composed a new cluster with high bootstrap values (100% NJ, 100% MP). From the morphological and molecular biological data, we gain enough evidences to support the validity of M. turpisrotundus.

Bacillus subtilis is widely used in aquaculture as a probiotic. However, few studies have been conducted to examine the effect of B. subtilis on liver lipid metabolism. A total of 135 healthy grass carp (50.24 ± 1.38 g) were randomly divided into three groups: control (Con), high-fat diet (HF), and high-fat diet + B. subtilis (HF + B. subtilis), and fed for 8 weeks. The results showed that compared with the HF group, the weight gain rate (WGR) significantly increased (P < 0.05) and the hepatic lipid content, serum low-density lipoprotein cholesterol (LDL-C), and aspartate aminotransferase (AST) decreased in the group supplemented with B. subtilis (P < 0.05). Moreover, the hepatic mRNA expression of fatty acid synthase (FAS) was significantly down-regulated and the carnitine palmitoyl transferases (CPT1α1a) were up-regulated in the HF + B. subtilis group compared to the HF group (P < 0.05), respectively. Additionally, in the HF + B. subtilis group, glutathione (GSH) significantly increased (P < 0.05), while hydrogen peroxide (H 2 O 2) and malondialdehyde (MDA) contents significantly decreased compared to the HF group (P < 0.05). B. subtilis may reduce the hepatic lipid content by inhibiting its synthesis and promoting β-oxidation of fatty acids. B. subtilis may also alleviate dyslipidaemia and prevent oxidative damage in the liver caused by the high-fat diet of grass carp. Hence, dietary supplementation with B. subtilis shows promise as a therapeutic or preventive tool against fatty liver disease.

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Macrophages have a defensive function against bacteria through phagocytosis and the secretion of cytokines. Histone modifications play an essential role in macrophage functions. Here, we report that Cxxc finger protein 1 (CFP1), a key component of the SETD1 histone methyltransferase complex, promoted the phagocytic and bactericidal activity of GM-CSF-derived macrophages. CFP1-deficient mice were more susceptible to bacterial infection due to the decreased expression of Csf2rα, a subunit of the GM-CSF receptor essential for inflammation and alveolar macrophage development, through the loss of H3K4 modifications in the promoter of the Csf2rα gene. In addition, the lung tissues of CFP1-deficient mice exhibited spontaneous inflammatory symptoms, including both the infiltration of inflammatory cells and the accumulation of surfactant phospholipids and proteins. Furthermore, we showed that Csf2rα and PU.1 can partially rescue the defects in phagocytosis and in the intracellular killing of bacteria. Collectively, our data highlight the importance of CFP1 in the phagocytic and bactericidal activity of macrophages.

The pharmacokinetics and residue elimination of florfenicol (FFC) and its metabolite florfenicol amine (FFA) were studied in healthy blunt‐snout bream (Megalobrama amblycephala, 50 ± 10 g). The study was conducted with a single‐dose (25 mg/kg) oral administration at a water temperature of 18 or 28°C, while in the residue elimination study, fish were administered at 25 mg/kg daily for three consecutive days by oral gavage to determine the withdrawal period (WDT) at 28°C. The FFC and FFA levels in plasma and tissues (liver, kidneys and muscle) were analysed using high‐performance liquid chromatography (HPLC). A no‐compartment model was used to analyse the concentration versus time data of M. amblycephala. In the two groups at 18 and 28°C, the maximum plasma concentration (Cmax) of FFC was 5.89 and 6.21 μg/ml, while the time to reach Cmax (Tmax) was 5.97 and 2.84 hr, respectively. These suggested that higher temperature absorbed more drug and more quickly at M. amblycephala. And the elimination half‐life (T1/2kβ) of FFC was calculated as 26.75 and 16.14 hr, while the total body clearance (CL) was 0.09 and 0.15 L kg−1 hr−1, and the areas under the concentration–time curves (AUCs) were 265.87 and 163.31 μg hr/ml, respectively. The difference demonstrated that the elimination rate of FFC in M. amblycephala at 28°C was more quickly than that at 18°C. The results of FFA showed the same trend in tissues of M. amblycephala. After multiple oral doses (25 mg/kg daily for 3 days), the k (eliminate rate constant) of FFA in M. amblycephala muscle was 0.017, the C0 (initial concentration) was 3.07 mg/kg, and the WDT was 10 days (water temperature 28°C).

For screening bilobalide (BB)-producing endophytic fungi from medicinal plant Ginkgo biloba, a total of 57 fungal isolates were isolated from the internal stem, root, leaf, and bark of the plant G. biloba. Fermentation processes using BB-producing fungi other than G. biloba may become a novel way to produce BB, which is a terpene trilactones exhibiting neuroprotective effects. In this study, a BB-producing endophytic fungal strain GZUYX13 was isolated from the leaves of G. biloba grown in the campus of Guizhou University, Guiyang city, Guizhou province, China. The strain produced BB when grown in potato dextrose liquid medium. The amount of BB produced by this endophytic fungus was quantified to be 106 μg/L via high-performance liquid chromatography (HPLC), substantially lower than that produced by the host tissue. The fungal BB which was analyzed by thin layer chromatography (TLC) and HPLC was proven to be identical to authentic BB. The strain GZUYX13 was identified as Pestalotiopsis uvicola via morphology and ITS rDNA phylogeny. To the best of our knowledge, this is the first report concerning the isolation and identification of endophytic BB-producing Pestalotiopsis spp. from the host plant, which further proved that endophytic fungi have the potential to produce bioactive compounds.