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Lipoyltransferase 2 (LIPT2) acts as a key enzyme involved in fatty acid metabolism and cell membrane synthesis. However, the biological function of LIPT2 in various cancer types and its potential significance in prognosis continue to be unresolved. For this analysis, we evaluated the expression levels and the significance of prognosis of LIPT2 gene in all cancers by various bioinformatics methods. The results found that LIPT2 was dramatically overexpressed in the vast majority of cancers. The upregulated LIPT2 was related to bad prognosis in Brain Lower Grade Glioma (LGG), Glioma (GBMLGG), Glioblastoma multiforme (GBM), Kidney Chromophobe (KICH), and High-Risk Wilms Tumor (WT), while it had a favorable prognosis in Kidney renal clear cell carcinoma (KIRC), and Ovarian serous cystadenocarcinoma (OV), Pan-kidney cohort (KIPAN). Furthermore, we assessed the mutation status, methylation levels, and immune status of LIPT2 in pan-cancer. Single-cell sequencing results revealed the correlation of LIPT2 expression with various biological characteristics such as DNA lesion, tumor angiogenesis, cell apoptosis, metastasis, and invasion. Enrichment analysis unveiled potential molecular regulatory mechanisms. In conclusion, our research reveals a detailed key role of LIPT2 in the progression, prognosis, and immune efficacy of various forms of cancer. Therefore, we have reason to believe that LIPT2 has the potential to be a candidate biomarker for tumors. [ABSTRACT FROM AUTHOR]

WRKY transcription factors play a pivotal role in regulating stress signaling pathways, including those associated with salt stress response. The present work characterized the effects of two WRKY genes from Vigna unguiculata, namely VuWRKY21 and VuWRKY87, on enhancing plant salinity tolerance. Under salt stress conditions, Arabidopsis lines expressing VuWRKY21 or VuWRKY87 showed elevated expression of genes participating in saline stress response pathways and reduced oxidative stress induced by reactive oxygen species (ROS). Among the salt-responsive genes in Arabidopsis, AtP5CS1, AtNHX1, AtRD29A, AtSOS3, AtSOS2, and AtSOS1 exhibited modulated expression levels after stress imposition. Furthermore, compared to wild-type plants, at most evaluated times, transgenic lines, on average, presented lower H2O2 content while displaying higher content of SOD (EC: 1.15.1.1) and CAT (EC: 1.11.1.6) at early stages of salt stress. These findings suggest that the expression of both VuWRKY genes in Arabidopsis, particularly VuWRKY21, activated genes involved in salinity tolerance. [ABSTRACT FROM AUTHOR]

Background: An important stage in controlling gene expression is RNA alternative splicing (AS), and aberrant AS can trigger the development and spread of malignancies, including hepatocellular carcinoma (HCC). A crucial component of AS is cleavage and polyadenylation-specific factor 4 (CPSF4), a component of the CPSF complex, but it is unclear how CPSF4-related AS molecules describe immune cell infiltration in the total tumor microenvironment (TME). Methods: Using RNA-sequencing data and clinical data from TCGA-LIHC from the Cancer Genome Atlas (TCGA) database, the AS genes with differential expression were found. The univariate Cox analysis, KM analysis, and Spearman analysis were used to identify the AS genes related to prognosis. Screening of key AS genes that are highly correlated with CPSF4. Key genes were screened using Cox regression analysis and stepwise regression analysis, and prognosis prediction models and the topography of TME cell infiltration were thoroughly analyzed. Results: A model consisting of seven AS genes (STMN1, CLSPN, MDK, RNFT2, PRR11, RNF157, GHR) was constructed that was aimed to predict prognostic condition. The outcomes of the HCC samples in the high-risk group were considerably worse than those in the lower risk group (p < 0.0001), and different risk patient groups were formed. According to the calibration curves and the area under the ROC curve (AUC) values for survival at 1, 2, and 3 years, the clinical nomogram performs well in predicting survival in HCC patients. These values were 0.76, 0.70, and 0.69, respectively. Moreover, prognostic signature was markedly related to immune infiltration and immune checkpoint genes expression. Conclusion: By shedding light on the function of CPSF4 and the seven AS genes in the formation and progression of HCC, this research analysis contributes to the development of more useful prognostic, diagnostic, and possibly therapeutic biomarkers. [ABSTRACT FROM AUTHOR]

Background: Menin is a scaffold protein encoded by the Men1 gene, which interacts with various transcriptional proteins to activate or repress cellular processes and is a key mediator in multiple organs. Both liver-specific and hepatocyte-specific Menin deficiency promotes high-fat diet-induced liver steatosis in mice, as well as insulin resistance and type 2 diabetic phenotype. The potential link between Menin and hepatic metabolism homeostasis may provide new insights into the mechanism of fatty liver disease. Results: Disturbance of hepatic Menin expression impacts metabolic pathways associated with non-alcoholic fatty liver disease (NAFLD), including the FoxO signaling pathway, which is similar to that observed in both oleic acid-induced fatty hepatocytes model and biopsied fatty liver tissues, but with elevated hepatic Menin expression and inhibited FABP1. Higher levels of Menin facilitate glucose uptake while restraining fatty acid uptake. Menin targets the expression of FABP3/4/5 and also CD36 or GK, PCK by binding to their promoter regions, while recruiting and deploying the cellular localization of PPARγ and SIRT1 in the nucleus and cytoplasm. Accordingly, Menin binds to PPARγ and/or FoxO1 in hepatocytes, and orchestrates hepatic glucose and fatty acid uptake by recruiting SIRT1. Conclusion: Menin plays an orchestration role as a transcriptional activator and/or repressor to target downstream gene expression levels involved in hepatic energy uptake by interacting with the cellular energy sensor SIRT1, PPARγ, and/or FoxO1 and deploying their translocations between the cytoplasm and nucleus, thereby maintaining metabolic homeostasis. These findings provide more evidence suggesting Menin could be targeted for the treatment of hepatic steatosis, NAFLD or metabolic dysfunction-associated fatty liver disease (MAFLD), and even other hepatic diseases. Highlights: Higher Menin facilitates hepatic glucose uptake, but restrains hepatic fatty acid uptake. Conversely, lower Menin has the opposite effect. Menin interacts with PPARγ and/or FoxO1, as well as SIRT1, thereby targeting downstream gene expression. Through its recruitment of various proteins, Menin facilitates their translocations within the nucleus and cytoplasm. Menin serves as a key regulator of hepatic metabolism homeostasis. Menin expression is elevated in both induced fatty hepatocyte model and fatty liver tissues. [ABSTRACT FROM AUTHOR]

The cytotoxicity of micro/nanoplastics (MNPs) is known to be strongly influenced by particle size, but the mechanism is not clear so far. We reported the ability of polystyrene MNPs to be internalized by HeLa cells could be a reason for the size dependent cytotoxicity of MNPs. We found that small MNPs (10 nm and 15 nm in radius) could be efficiently internalized by HeLa cells, MNPs of 25 nm in radius could be slightly internalized by the cells, and larger MNPs could not enter the cells at all. We showed that only MNPs, which could be internalized by cells, had a toxic effect on cell activity in a dose-dependent manner. In contrast, MNPs, which could not be internalized by cells, showed no cytotoxicity even if at extremely high concentrations. We attributed the correlation between the size-dependent uptake of MNPs and the size-dependent cytotoxicity of MNPs to the enhanced reactive oxygen species (ROS) level and abnormal gene expression. Our study pointed out that cellular uptake is one of the most fundamental mechanisms for the cytotoxicity of MNPs. [ABSTRACT FROM AUTHOR]

This study tested whether a medicinal plant, Vasaka, typically consumed as a tea to treat respiratory malaise, could protect airway epithelial cells (AECs) from wood smoke particle-induced damage and prevent pathological mucus production. Wood/biomass smoke is a pneumotoxic air pollutant. Mucus normally protects the airways, but excessive production can obstruct airflow and cause respiratory distress. Vasaka tea pre- and co-treatment dose-dependently inhibited mucin 5AC (MUC5AC) mRNA induction by AECs treated with wood smoke particles. This correlated with transient receptor potential ankyrin-1 (TRPA1) inhibition, an attenuation of endoplasmic reticulum (ER) stress, and AEC damage/death. Induction of mRNA for anterior gradient 2, an ER chaperone/disulfide isomerase required for MUC5AC production, and TRP vanilloid-3, a gene that suppresses ER stress and wood smoke particle-induced cell death, was also attenuated. Variable inhibition of TRPA1, ER stress, and MUC5AC mRNA induction was observed using selected chemicals identified in Vasaka tea including vasicine, vasicinone, apigenin, vitexin, isovitexin, isoorientin, 9-oxoODE, and 9,10-EpOME. Apigenin and 9,10-EpOME were the most cytoprotective and mucosuppressive. Cytochrome P450 1A1 (CYP1A1) mRNA was also induced by Vasaka tea and wood smoke particles. Inhibition of CYP1A1 enhanced ER stress and MUC5AC mRNA expression, suggesting a possible role in producing protective oxylipins in stressed cells. The results provide mechanistic insights and support for the purported benefits of Vasaka tea in treating lung inflammatory conditions, raising the possibility of further development as a preventative and/or restorative therapy. [ABSTRACT FROM AUTHOR]

Neuropeptides function as central neuromodulators and circulating hormones that modulate insect behavior and physiology. Leucokinin (LK) is an intercellular signaling molecule that mediates many physiological and behavioral processes. However, the functions of LK associated with environmental stress and feeding behavior in the fall webworm, Hyphantria cunea , is little known. Our primary objective is to understand the function of LK and LK receptor (LKR) neuroendocrine system in H. cunea. In the present study, the results showed that LK/LKR are expressed at different developmental stages and in various tissues of H. cunea. A candidate receptor–ligand pairing for LK was identified in the larval transcriptome of H. cunea. In a heterologous expression system, the calcium assay was used to demonstrate that LKR is activated by HcLKs in a dose-dependent manner, with 50% effective concentration (EC50) values of 8.44–90.44nM. Knockdown of HcLK and HcLKR by microinjecting target-specific dsRNA leads to several effects in H. cunea , including feeding promotion, increase in resistance to desiccation and starvation stress, and regulation of water homeostasis. The transcript levels of HILP2 (except in the LK knockdown group), HILP5 , and HILP8 increased, whereas those of HILP3 , HILP4 , and HILP6 decreased; HILP1 , HILP2 (in the LK knockdown group), and HILP7 gene expression was not influenced after LK and LKR knockdown. Variations in mRNA expression levels in insulin-like peptide genes in the knockdown larvae suggest an essential role of these genes in survival in H. cunea. To our knowledge, the present study is the first comprehensive study of LK and LKR – from gene to behavior – in H. cunea. [ABSTRACT FROM AUTHOR]

Background: Type 1 Diabetes (T1D) is a T cell-mediated autoimmune disorder caused by the destruction of insulin-secreting cells. B7-H3 (CD276) plays a vital role in T cell response. However, B7-H3 expression and its clinical significance in T1D remain unclear. The aim of this study was to investigate the correlations between the expression of B7-H3 and clinical parameters in T1D patients. The possible role of B7-H3 gene variants with T1D was also discussed. Methods: Four B7-H3 single nucleotide polymorphisms (SNPs) were genotyped in 121 T1D patients and 120 healthy controls by polymerase chain reaction (PCR) direct sequencing. Expression of membrane B7-H3 (mB7-H3) in peripheral blood lymphocytes was determined by flow cytometry. Levels of soluble B7-H3 (sB7-H3) in serum were analyzed by enzyme linked immunosorbent assay (ELISA). Results: The B7-H3 haplotype T-A-C-T was less frequently observed in T1D patients compared to the controls (OR: 0.31, 95% CI: 0.16–0.61). B7-H3 expression on monocytes showed significant upregulation in T1D patients and was positively correlated with several clinical features including ALT, fast C-peptide 120 min, HbAlc, IFN-γ, IL-6 and TNF-α (P < 0.05). The concentration of sB7-H3 in serum increased in T1D patients (P < 0.0001). We also observed that B7-H3-T-A-C-T was associated with the decreased release of sB7-H3 but not the membrane form. Conclusions: B7-H3 may act as a potential biomarker related to the pathogenesis of T1D. The B7-H3-T-A-C-T polymorphism variant is associated with the low risk of T1D as well as less release of sB7-H3. [ABSTRACT FROM AUTHOR]

The fall webworm, Hyphantria cunea (Drury) (Lepidoptera: Noctuidae), is a major pest found in forests. In this study, the effects of Hyphantria cunea nucleopolyhedrovirus (HcNPV) infection on the transcription levels and activities of glutathione S -transferases (GSTs) in H. cunea were determined. In the present study, 18 GST family genes were identified from the H. cunea transcriptome dataset by using bioinformatic analyses. These GST genes were classified into cytosolic (15 genes) and microsomal (three genes) classes. The 15 cytosolic GST genes belonged to four different subclasses (epsilon, sigma and delta). The all GST genes, especially GSTe4 , showed high expression levels in egg and 1st~4th instar larval stage while their low expression levels in 5th~7th instar larvae using real-time quantitative PCR analysis. However, the expression levels of the 18 GST genes were varied after exposure to sublethal doses of HcNPV. The expression levels of most GSTs were downregulated and upregulated at low and high concentrations of HcNPV, respectively. The corresponding total GST activities also showed similar patterns. In H. cunea , changes in the expression levels and enzymatic activities of GSTs after exposure to HcNPV indicated that they may have important functions in the defense against HcNPV, and the stress, which may be reflected by the high GST enzymatic activities. The 18 GST family genes were firstly identified from H. cunea transcriptome dataset by bioinformatics analysis. The changes in H. cunea GSTs gene expression levels and enzymatic activity exposed to HcNPV contribute to understand HcNPV defense. Unlabelled Image • Eighteen GST family genes were identified from the H. cunea transcriptome dataset by using bioinformatic analyses. • The HcNPV causes variation of expression levels of GST genes along with total GST activities. • Changes in mRNA and activity of GSTs in H. cunea indicated important functions in the defense against HcNPV. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to explore the miR‐342‐3p expression in pre‐eclampsia (PE) placentas and confirm whether miR‐342‐3p exerts effects on proliferation and migration of HTR‐8/SVneo trophoblastic cells. Methods: The PE placentas (n = 8) were taken from gravidas complicated by PE and delivered after 34 weeks. The chorionic plates and the basal plates were separately taken from the placenta disc near the position of umbilical cord insertion. RT‐qPCR was used to measure the expression of miR‐342‐3p in the chorionic plates and the basal plates. Cell invasion assay and MMT assay were used to assess the effects of miR‐342‐3p on proliferation and migration of HTR‐8/SVneo trophoblastic cells. Luciferase reporter assay and Western blotting were used to analyze the target of miR‐342‐3p and investigate the detailed mechanisms. Results: The expression of miR‐342‐3p was upregulated in both basal plates and chorionic plates in patients with PE compared with healthy pregnant individuals. MiR‐342‐3p inhibitor suppressed the cell viability and invasion, and induced apoptosis in trophoblast cells. Furthermore, inhibitor of DNA binding (ID)‐4 (ID4) was a direct target of miR‐342‐3p, and knockdown of ID4 abrogated the regulation effect of miR‐342‐3p on cell viability, apoptosis and invasion. Conclusion: Inhibition of miR‐342‐3p expression may suppress the occurrence of PE by targeting ID4 in vitro. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To investigate the association of matrix metalloproteinase (MMP)‐7 and MMP‐9 with pelvic lymph node and para‐aortic lymph node metastasis in early cervical cancer. Methods: A total of 137 patients with early cervical cancer (Stage Ia2‐IIa2) were recruited from the Department of Gynecology and Obstetrics, Tumor Hospital of Liaoning Province from January 2009 to May 2014. We evaluated the expression of MMP‐7 and MMP‐9 by immunohistochemistry and their association with the clinicopathological parameters such as pelvic, common iliac and para‐aortic lymph node metastasis. Spearman correlation was performed to analyze the correlation between MMP‐7 and MMP‐9 in cervical cancer. Finally, the areas under the receiver operating characteristic curve (ROC) of MMP‐7 and MMP‐9 in pelvic lymph node metastasis were assessed. Results: MMP‐7 expression was significantly higher in patients with adenocarcinomas and adenosquamous carcinomas (P = 0.014), vascular cancer embolus (P = 0.041), pelvic lymph node metastasis (P = 0.000) and a higher level of Ki‐67 (P = 0.000). MMP‐9 expression was significantly associated with vascular cancer embolus (P = 0.003), depth of stromal invasion (P = 0.001), pelvic lymph node metastasis (P = 0.003), common iliac lymph node metastasis (P = 0.001) and para‐aortic lymph nodes metastasis (P = 0.004). Coexpression of MMP‐7 and MMP‐9 was significantly associated with vascular cancer embolus (P < 0.001), higher expression of Ki‐67 (P < 0.001) and pelvic lymph node metastasis (P < 0.001). Spearman correlation analysis indicated a positive correlation between MMP‐7 and MMP‐9 (r = 0.263, P = 0.002). Areas under the ROC of MMP‐7 and MMP‐9 were 0.707 and 0.646, respectively. Conclusion: MMP‐7 and MMP‐9 expressions were associated with lymph node metastasis in patients with early cervical cancers, suggesting a positive correlation of MMP‐7 and MMP‐9 with invasive potential in early cervical cancers. [ABSTRACT FROM AUTHOR]

Rice is the staple food of almost half of the world population, and in excess 90% of it is grown and consumed in Asia, but the disposal of rice straw poses a problem for farmers, who often burn it in the fields, causing health and environmental problems. However, with increased focus on the development of sustainable biofuel production, rice straw has been recognized as a potential feedstock for non-food derived biofuel production. Currently, the commercial realization of rice as a biofuel feedstock is constrained by the high cost of industrial saccharification processes needed to release sugar for fermentation. This study is focused on the alteration of lignin content, and cell wall chemotypes and structures, and their effects on the saccharification potential of rice lignocellulosic biomass. A recombinant inbred lines (RILs) population derived from a cross between the lowland rice variety IR1552 and the upland rice variety Azucena with 271 molecular markers for quantitative trait SNP (QTS) analyses was used. After association analysis of 271 markers for saccharification potential, 1 locus and 4 pairs of epistatic loci were found to contribute to the enzymatic digestibility phenotype, and an inverse relationship between reducing sugar and lignin content in these recombinant inbred lines was identified. As a result of QTS analyses, several cell-wall associated candidate genes are proposed that may be useful for marker-assisted breeding and may aid breeders to produce potential high saccharification rice varieties. [ABSTRACT FROM AUTHOR]

The ocular albinism type 1 gene, named OA1 , is a coding pigment cell-specific G protein-coupled receptor exclusively localized in intracellular organelles. However, the function of OA1 in insects remains generally unknown. In the present study, we explore for the first time the function of LdOA1 in the Asian gypsy moth, Lymantria dispar . To identify the function of LdOA1 gene in the development and growth of the Asian gypsy moth, the LdOA1 gene in third instar larvae was knocked down by RNAi. Compared with the controls, the knockdown of LdOA1 increased larval mortality but did not significantly affect their utilization of nutrition. Moreover, LdOA1 was stably transformed into the third chromosome of Drosophila melanogaster . The LdOA1 gene in the transformed D. melanogaster modulated the expression of heat-shock protein ( hsp ) and increased the expression of hsp genes under deltamethrin stress, which indicates that LdOA1 is involved in the regulation of hsp gene expression. These results deepen our understanding of the molecular function of OA1 in insects. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is currently one of the top lethal cancers with an increasing trend. Deregulation of MYC in HCC is frequently detected and always correlated with poor prognosis. As the zebrafish genome contains two differentially expressed zebrafish myc orthologs, myca and mycb, it remains unclear about the oncogenicity of the two zebrafish myc genes. In the present study, we developed two transgenic zebrafish lines to over-express myca and mycb respectively in the liver using a mifepristone-inducible system and found that both myc genes were oncogenic. Moreover, the transgenic expression of myca in hepatocytes caused robust liver tumors with several distinct phenotypes of variable severity. ~5% of myca transgenic fish developing multinodular HCC with cirrhosis after 8 months of induced myca expression. Apoptosis was also observed with myca expression; introduction of homozygous tp53-/- mutation into the myca transgenic fish reduced apoptosis and accelerated tumor progression. The malignant status of hepatocytes was dependent on continued expression of myca; withdrawal of the mifepristone inducer resulted in a rapid regression of liver tumors, and the tumor regression occurred even in the tp53-/- mutation background. Thus, our data demonstrated the robust oncogenicity of zebrafish myca and the requirement of sustained Myc overexpression for maintenance of the liver tumor phenotype in this transgenic model. Furthermore, tumor regression is independent of the function of Tp53. [ABSTRACT FROM AUTHOR]

Danggui Buxue Decoction (DBT) is classical prescriptions, which contains two Traditional Chinese Medicines of Angelicae sinensis radix and Astragali radix. According to the preliminary work of our laboratory and numerous studies, it has been found that DBT has a therapeutic effect on diabetic nephropathy (DN). However, the mechanisms underlying its action remain unclear. The aim of this study was to evaluate the impact of DBT on kidney disease in diabetic mice and further explore its protective mechanism. DN mice model was induced by high-fat fodder and streptozotocin (STZ). Qualitative and quantitative analysis of 6 compounds in DBT was carried out by HPLC, including calycosin-7-glucoside, ferulic acid, ononin, calycosin, formononetin, and levostilide A. Hematoxylin-Eosin (HE) staining was used to determine the degree of kidney pathological damage. The UPLC-Q Exactive MS technique was used to analyze the lipids metabolism profile of kidneys samples and multiple statistical analysis methods were used to screen and identify biomarkers. Transcriptomics analyses were carried out using RNAseq. The possible molecular mechanism was unraveled by network pharmacology. Thirty-one significantly altered lipid metabolites were identified in the model group comparing with the control group. DBT improved aberrant expression of several pathways related to lipidomics, including glycerophospholipid metabolism and sphingolipid metabolism. Comprehensive analysis indicated that DBT intervention reduced the content of Cers, phosphatidylethanolamines and phosphatidylcholines in mouse kidneys by downregulating the transcription level of Degs2 and Cers , reducing lipid accumulation and promoting Akt phosphorylation by upregulating the expression of Acers and Pdk1. Network pharmacology analysis showed that components in DBT, such as kaempferol, ferulic acid and astragaloside IV, could be responsible for the pharmacological activity of DN by regulating the AGE-RAGE, PI3K/Akt, MAPK and NF-κB signaling pathways in diabetic complications. These results showed that DBT may improve DN by affecting insulin resistance, chronic inflammation and lipid accumulation. [Display omitted] • DBT treatment mainly affected glycerophospholipid and sphingolipid metabolism. • DBT improved DN by affecting the expression of the Degs2 and Cers genes. • Ceramides were important biomarkers of DN. [ABSTRACT FROM AUTHOR]

• The TUB , AK , RPS15 are best candidate reference genes for developmental stages. • The RPS3 and GAPDH are best candidate reference genes for insecticide stress. • The EF1-α and TUB are preferential housekeeping genes under various conditions. The quantitative real-time polymerase chain reaction (qRT-PCR) has rapidly become the most sensitive and accurate method for the quantitative analysis of gene expression. Normalization of gene expression to that of relatively stably expressed housekeeping genes is required to facilitate the study of gene expression and to obtain more accurate RT-PCR data. However, no studies of the stability of expression of housekeeping genes in Lymantria dispar have been reported. In the present study, BestKeeper, GeNorm and NormFinder statistical software was used to evaluate the expression of thirteen candidate reference genes in L. dispar under different conditions. The expression levels of candidate reference genes were determined for two biological factors (developmental stages and tissues) and four abiotic treatments (temperature, insecticide, CO 2 and starvation). The results showed that the best candidate reference genes in L. dispar were TUB , AK , RPS15 for developmental stages, RPL32 and GAPDH for tissues, ACTB and EF1-α for CO 2 stress, GAPDH and RPL32 for temperature stress, RPS3 and GAPDH for insecticide stress, and GAPDH and RPS3 for starvation stress. In summary, EF1-α and TUB are preferential housekeeping genes in L. dispar under various conditions. These results provide a basis for the further study of functional genes of L. dispar. [ABSTRACT FROM AUTHOR]

Background: Regulated in development and DNA damage response (REDD1), a gene responding to hypoxia or multiple DNA damage events, was recently implicated in cancer development and progression. Previously, in vivo and in vitro experiments indicated that REDD1 functions as an oncogene in ovarian cancer cells. However, the role of REDD1 in cancer cell migration and invasion and in clinical significance of prognostic values is not examined in detail. Methods: We detected the REDD1 protein expression by immunohistochemistry in 18 normal ovarian surface epithelium or fallopian tube epithelium specimens, 24 ovarian borderline tumors, and 229 ovarian cancers. Fisher's exact test, logistic regression analysis, the Kaplan–Meier method, and the log-rank test were used to evaluate the association of REDD1 with clinical factors, overall survival and disease-free survival. The prognostic predictive value of REDD1 for ovarian cancer patients was evaluated using multivariate Cox proportional hazard regression models. REDD1 expression in HEY, HEY A8, SKOV3, SKOV3 ip1, OVCA429, OVCA433 and A2780 human ovarian epithelial cancer cell lines was detected by western blotting. The role of REDD1 in cell invasion and migration was assessed by transwell migration and invasion assays using SKOV3, A2780, HEY, HEYA8, and SKOV3-REDD1 with parental A2780-REDD1 HEY-REDD1i and HEY A8-REDD1i. Results: High expression of REDD1 was observed in 35.4% of primary ovarian carcinoma samples. Overexpression of cytoplasmic REDD1 in ovarian cancer was significantly associated with serous carcinoma (P < 0.001), late-stage disease (P < 0.001), ascites (P < 0.001), and partial or non-response to chemotherapy (P < 0.001). High cytoplasmic expression of REDD1 was correlated with poorer overall survival (P < 0.001) and disease-free survival (P < 0.001). The multivariate Cox proportional hazards regression analysis indicated that patients with high cytoplasmic REDD1 expression had a high risk of death (P < 0.001) and high risk of an event (i.e., recurrence, progression, or death) (P < 0.001). REDD1 was first reported as an independent prognostic factor in ovarian cancer patients. In addition, REDD1 overexpression enhanced ovarian cancer cell migration and invasion. Conclusion: REDD1 is an independent unfavorable prognostic factor in ovarian carcinoma and may promote ovarian cancer metastasis. [ABSTRACT FROM AUTHOR]

The amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer's disease (AD). Despite extensive studies, little is known about the regulation of APP's functions in vivo. Here we report that expression of human APP in Drosophila, in the same temporal-spatial pattern as its homolog APPL, induced morphological defects in wings and larval NMJ, larva and adult locomotion dysfunctions, male choice disorder and lifespan shortening. To identify additional genes that modulate APP functions, we performed a genetic screen and found that loss of Polo, a key regulator of cell cycle, partially suppressed APP-induced morphological and behavioral defects in larval and adult stages. Finally, we showed that eye-specific expression of APP induced retina degeneration and cell cycle re-entry, both phenotypes were mildly ameliorated by loss of Polo. These results suggest Polo is an important in vivo regulator of the pathological functions of APP, and provide insight into the role of cell cycle re-entry in AD pathogenesis. [ABSTRACT FROM AUTHOR]

The Asian spongy moth, Lymantria dispar , is a worldwide forest pest that damages >500 plant species. Nowadays, chemical control is the most widely used method because of its rapidity and effectiveness, but the insecticide resistance is a growing concern for spongy moth. As important post-transcriptional regulators of gene expression, whether microRNAs (miRNAs) are involved in insecticide tolerance is little known in spongy moth. Therefore, an integrated analysis of miRNA and mRNA was performed on L. dispar larvae treated with cyantraniliprole. Compared to the control group, a total of 432 differentially expressed genes (DEGs) and 23 differentially expressed miRNAs (DEMs) were identified in L. dispar larvae under cyantraniliprole exposure. Among them, twelve DEGs encoding detoxification enzymes/proteins were further analyzed. Twenty-one genes related to insecticide tolerance were predicted by 11 DEMs, of which 25 miRNA-mRNA interactions were identified. In the miRNA-mRNA network, novel-miR-4 and mmu-miR-3475-3p were involved in the response of L. dispar to cyantraniliprole stress by regulating five genes associated with detoxification, respectively. The P450 gene CYP4C1 (c34384.graph_c0) was the only DEG related to detoxification in the network, which was regulated by novel-miR-4. The expression levels of ten DEMs were confirmed by quantitative reverse transcription PCR (RT-qPCR) and the trends were consistent with miRNA-seq. This study identified some candidate miRNAs and mRNAs related to cyantraniliprole tolerance in L. dispar , which provides valuable transcriptomic information for revealing the molecular mechanisms of insect tolerance and developing novel insecticides. [Display omitted] • 432 mRNAs were differentially expressed in L. dispar treated with cyantraniliprole. • 23 miRNAs were differentially expressed in L. dispar treated with cyantraniliprole. • 12 differentially expressed mRNAs up-regulated related to detoxification of cyantraniliprole. • 25 miRNA-mRNA interactions related to insecticide tolerance were predicted. [ABSTRACT FROM AUTHOR]

Highlights • Addition of either sulphur or T. thioparus controls nitrogen losses. • Addition of T. thioparus enhances expression of AOA and nxrA. • Addition of T. thioparus positively correlates with nxrA and NO 3 -N. • Combined use of sulphur and T. thioparus controls nitrogen losses more effectively. • Combined use of sulphur and T. thioparus affects all six nitrogen-related genes. Abstract Severe nitrogen (N) loss is a barrier for composting treatment. Since N transformation during composting is closely related to nitrogen loss, the impacts of adding sulphur and Thiobacillus thioparus 1904 to N transformation during composting were investigated in this work. Physicochemical properties and the expression of genes encoding N-related proteins were analysed to evaluate microbiological processes associated with N dynamics. The results indicated that (1) sulphur addition reduced the pH and cumulative NH 3 emission, and decreased N losses by 44.23%, while no significant differences were observed in the expression of N cycle-associated genes compared with the control treatment; (2) the application of T. thioparus 1904 increased NO 3 −-N content, reduced N loss by 28.20%, and significantly enhanced the expression of ammonia monooxygenase A (archaeal amoA; AOA) and nitrite oxidoreductase A (nxrA) during the mature phase; (3) the combined application of sulphur and T. thioparus 1904 significantly affected the expression of functional genes related to nitrification and denitrification, which contributed to a reduction in accumulated NH 3 emission, an increase in NO 4 +-N content, and a decrease in N losses by 70.94%. Expression of ammonia monooxygenase A (bacterial amoA; AOB) , nxrA and nitrous oxide reductase Z (nosZ) genes in the combined treatment was positively correlated with NO 3 −-N, whereas expression of AOA and accumulation of NH 3 were negatively correlated with NO 3 −-N. These results indicate that the combined application of sulphur and T. thioparus 1904 had a significant regulatory effect on N cycle genes and effectively reduced the N loss during composting. [ABSTRACT FROM AUTHOR]

To date, elevated CO 2 concentrations in the environment caused by various human activities influence diverse areas of life, including the interactions between insects and plants. The Lymantria dispar is one of the most severely destructive pests, which further could inflict ecological and economical damage. In this experiment, one-year-old Populus davidiana × P. bolleana plants were grown in CO 2 -enhanced environments for one month at three different CO 2 concentrations: 397 ppm (atmospheric CO 2 concentration), 550 ppm and 750 ppm (two predicted elevated CO 2 concentrations). The 3rd instar L. dispar larvae then fed on the treated poplar seedlings covered in a nylon bag. The L. dispar larvae fed on poplar seedling treated for 96 h showed the highest growth rate at all CO 2 concentrations. Enzymatic activity of treated larvae showed the highest GST and P450 activity at 750 ppm CO 2. The relative expressions of seven CYP and ten GST genes in L. dispar larvae were analyzed quantitatively using real-time RT-PCR, which the results were expressed variably. Compared to 397 ppm CO 2 , the expression of CYP4L23 was down-regulated, while the expressions of other CYP genes were up-regulated. Meanwhile, only GSTo1 gene showed down-regulated at 48 h and 96 h in 750 ppm CO 2 treatment, while GST expression level for the other nine GST genes showed up-regulated at 48 h and 72 h. These results offer the insight into plant-insect interactions under global climate change and furthermore will provide essential information for strategic pest control based on biochemical and molecular levels changes in gypsy moths. [Display omitted] • Poplar treated by CO 2 affected the growth rate of L. dispar larvae. • Activities of GST and P450 in L. dispar larvae were induced by indirect high CO 2 stress. • Expressions of GST and P450 genes in L. dispar larvae were affected indirectly by CO 2 stress. • Poplar treated CO 2 regulated the functions of GST and P450 in L. dispar larvae. [ABSTRACT FROM AUTHOR]