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Background: To investigate the factors associated with acute kidney injury (AKI) in postoperative colorectal cancer (CRC) patients and develop a risk prediction model. Methods: The clinical data of 389 CRC patients were retrospectively analyzed. The patients were divided into AKI (n = 30) and non-AKI groups (n = 359) according to KDIGO diagnostic criteria. Demographic data, the presence of underlying diseases, perioperative conditions and related examination results were compared between the two groups. Binary logistic regression was used to analyze the independent risk factors for postoperative AKI, and a risk prediction model was established. And a verification group (94 patients) was used to verify the model. Results: 30 patients (7.71%) with CRC had postoperative AKI. Binary logistic regression analysis showed that preoperative combined hypertension, preoperative anemia, inadequate intraoperative crystalloid infusion, low intraoperative minimum mean arterial pressure (MAP) and moderate to severe postoperative decline in hemoglobin (Hb) levels were independent risk factors. The risk prediction model developed was expressed as Logit P = − 0.853 + 1.228 * preoperative combined hypertension + 1.275 *preoperative anemia − 0.002 * intraoperative crystalloid infusion (ml) − 0.091 * intraoperative minimum MAP (mmHg) + 1.482 * moderate to severe postoperative decline in Hb levels. In Hosmer–Lemeshow test, χ2 = 8.157, P = 0.718 showed that the fitting effect was good. The area under ROC curve was 0.776 (95% CI 0.682–0.871, P < 0.001), with a prediction threshold of 1.570, a sensitivity of 63.3% and a specificity of 88.9%. The sensitivity and specificity of the verification group were 65.8% and 86.1%. Conclusions: Preoperative combined hypertension, preoperative anemia, inadequate intraoperative crystalloid infusion, low intraoperative minimum MAP, and moderate to severe postoperative decline in Hb levels were independent risk factors for AKI development in CRC patients. The prediction model can effectively predict the occurrence of postoperative AKI in patients with CRC. [ABSTRACT FROM AUTHOR]

Eugenol, a plant-derived component possessing small side effects, has an insecticidal activity to Tribolium castaneum; however, the underlying molecular mechanisms of eugenol acting on T. castaneum are currently unclear. Here, a nerve conduction carboxylesterase and a detoxifying glutathione S-transferase were significantly inhibited after eugenol exposure, resulting in the paralysis or death of beetles. Then, RNA-sequencing of eugenol-exposed and control samples identified 362 differentially expressed genes (DEGs), containing 206 up-regulated and 156 down-regulated genes. RNA-seq data were validated further by qRT-PCR. GO analysis revealed that DEGs were associated with 1308 GO terms of which the most enriched GO terms were catalytic activity, and integral component of membrane; KEGG pathway analysis showed that these DEGs were distributed in 151 different pathways, of which some pathways associated with metabolism of xenobiotics or drug were significantly enriched, which indicated that eugenol most likely disturbed the processes of metabolism, and detoxication. Moreover, several DEGs including Hexokinase type 2, Isocitrate dehydrogenase, and Cytochrome b-related protein, might participate in the respiratory metabolism of eugenol-exposed beetles. Some DEGs encoding CYP, UGT, GST, OBP, CSP, and ABC transporter were involved in the xenobiotic or drug metabolism pathway, which suggested that these genes of T. castaneum participated in the response to eugenol exposure. Additionally, TcOBPC11/ TcGSTs7, detected by qRT-PCR and RNA-interference against these genes, significantly increased the mortality of eugenol-treated T. castaneum, providing further evidence for the involvement of OBP/GST in eugenol metabolic detoxification in T. castaneum. These results aid eugenol insecticidal mechanisms and provide the basis of insect control. [ABSTRACT FROM AUTHOR]

Here, we report the complete genome sequence and organization of a novel virus detected in rubber trees (Hevea brasiliensis). Because the infected plants were asymptomatic, this virus was tentatively named "rubber tree latent virus 1" (RTLV1). The full genome of RTLV1 is 9,422 nt in length and contains three open reading frames with a 157-nt 5' untranslated region (UTR) and a 316-nt 3' UTR. The replicase shares the highest amino acid (aa) sequence identity (32.62%), with only 31% query coverage, with the replicase of Hubei virga-like virus 11. Phylogenetic analysis based on the aa sequence of ORF1 showed that RTLV1 clustered with unclassified members of the family Virgaviridae in a clade that was not closely related to any genus in this family. [ABSTRACT FROM AUTHOR]

Valosine containing protein (VCP/p97), which involves in several important cellular functions and plays an important role in ubiquitin-mediated misfolding protein degradation, has been found to be a novel target for the treatment of a range of cancers, such as lung cancer and breast cancer. In this study, the atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR) and docking models were developed using PHASE and GLIDE modules of Schrödinger software, respectively. The theoretical models were generated from 38 N-benzylpyrimidin-4-amine inhibitors of p97. An AADRRR model consisting of two hydrogen bond acceptors (A), one hydrogen bond donor (D), and three aromatic rings (R) was obtained. Thirty eight derivatives were divided into a training set with 27 molecules to generate 3D-QSAR models and a test set with 11 molecules to validate 3D-QSAR model. A robust QSAR model with good prediction in internal and external verification was constructed, where R2, Q2, and Pearson-R were 0.924, 0.701, and 0.8783, respectively. QSAR model showed the hydrogen bond donor, electron-withdrawing group, and hydrophobic characteristics affecting the p97 activity. Molecular docking studies indicated that the H-bond and hydrophobic interactions existed between the inhibitors and p97, which was consistent with the results of 3D-QSAR. These results provided some useful information for designing new and effective p97 inhibitors. [ABSTRACT FROM AUTHOR]

Protease-activated receptors (PARs) are G protein-coupled receptors of which four members PAR1, PAR2, PAR3, and PAR4 have been identified, characterized by a typical mechanism of activation involving various related proteases. The amino-terminal sequence of PARs is cleaved by a broad array of proteases, leading to specific proteolytic cleavage which forms endogenous tethered ligands to induce agonist-biased PAR activation. The biological effect of PARs activated by coagulation proteases to regulate hemostasis and thrombosis plays an enormous role in the cardiovascular system, while PAR4 can also be activated by trypsin, cathepsin G, the activated factor X of the coagulation cascade, and trypsin IV. Irrespective of its role in thrombin-induced platelet aggregation, PAR4 activation is believed to be involved in inflammatory lesions, as show by investigations that have unmasked the effects of PAR4 on neutrophil recruitment, the regulation of edema, and plasma extravasation. This review summarizes the roles of PAR4 in coagulation and other extracellular protease pathways, which activate PAR4 to participate in normal regulation and disease. [ABSTRACT FROM AUTHOR]

Certain long non-coding RNAs (lncRNAs) have potential peptide-coding abilities. Here, the role and molecular basis of the RNF217-AS1-encoded peptide in stomach cancer (SC) tumorigenesis were explored. Here, lncRNAs associated with SC pathogenesis and macrophage infiltration and lncRNAs with peptide-coding potential were searched by bioinformatics analysis. The gene mRNA and protein levels were examined by RT-qPCR and western blot assays, respectively. Cell viability, migratory, and invasive abilities were measured by CCK-8, Transwell migration, and Transwell invasion assays, respectively. The potential biological processes related to lncRNA RNF217-AS1 were identified by single-gene GSEA analysis. The effect of RNF217-AS1-encoded peptide on SC tumorigenesis was examined by mouse xenograft experiments. The results showed that lncRNA NR2F1-AS1 and RNF217-AS1 were differentially expressed and associated with macrophage infiltration in SC, and they had the ability to translate into short peptides. The RNF217-AS1 ORF-encoded peptide could reduce SC cell viability, inhibit cell migration and invasion, as well as hinder the development of SC xenograft tumors. The RNF217-AS1 ORF-encoded peptide in human SC AGS cells suppressed THP-1 cell migration, triggered the differential expression of CXCL1/CXCL2/CXCL8/CXCL12, and inactivated the TLR4/NF-κB/STAT1 signaling pathways. As a conclusion, the RNF217-AS1 ORF-encoded peptide hindered SC progression in vitro and in vivo and suppressed macrophage recruitment and pro-inflammatory responses in SC. [ABSTRACT FROM AUTHOR]