ABSTRACT
In patients with severe necrotizing pancreatitis, pancreatic necrosis and secondary infection of surrounding tissues can quickly spread to the whole retroperitoneal space. Treatment of pancreatic abscess complicating necrotizing pancreatitis is difficult and has a high mortality rate. The well-accepted treatment strategy is early debridement of necrotic tissues, drainage, and postoperative continuous retroperitoneal lavage. However, traditional open surgery has several disadvantages, such as severe trauma, interference with abdominal organs, a high rate of postoperative infection and adhesion, and hardness with repeated debridement. The retroperitoneal laparoscopic approach has the advantages of minimal invasion, a better drainage route, convenient repeated debridement, and avoidance of the spread of retroperitoneal infection to the abdominal cavity. In addition, retroperitoneal drainage leads to fewer drainage tube problems, including miscounting, displacement, or siphon. The debridement and drainage of pancreatic abscess tissue via the retroperitoneal laparoscopic approach plays an increasingly irreplaceable role in improving patient prognosis and saving healthcare resources and costs. The main procedures described here include laying the patient on the right side, raising the lumbar bridge and then arranging the trocar; establishing the pneumoperitoneum and cleaning the pararenal fat tissues; opening the lateral pyramidal fascia and the perirenal fascia outside the peritoneal reflections; opening the anterior renal fascia and entering the anterior pararenal space from the rear; clearing the necrotic tissue and accumulating fluid; and placing drainage tubes and performing postoperative continuous retroperitoneal lavage.
Subject(s)
Laparoscopy , Pancreatitis, Acute Necrotizing , Humans , Retroperitoneal Space/surgery , Debridement/methods , Abscess/etiology , Abscess/surgery , Pancreatitis, Acute Necrotizing/surgery , NecrosisABSTRACT
Aim: Limited data are available regarding ALI's clinical relevance and prognostic value in patients with hepatocellular carcinoma (HCC) after hepatectomy. Materials and methods: HCC patients who received hepatectomy at the Meizhou People's Hospital from May 2011 to February 2022 were enrolled in the study cohort. The ALI was calculated as follows: ALI = BMI (kg/m2) × ALB (g/dL)/(absolute neutrophil count/absolute lymphocyte count). The primary outcome was overall survival (OS). The secondary outcome was cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were performed, followed by nomogram construction and decision curve analysis (DCA). Results: 425 HCC patients were enrolled for analyses. Lower preoperative ALI was significantly correlated with incomplete tumor capsule and advanced tumor stage. Lower preoperative ALI was an adverse independent prognostic factor for OS (HR: 1.512, 95% CI: 1.122-2.039, P 0.007) and CSS (HR: 1.754, 95% CI: 1.262-2.438, P <0.001) in HCC patients. The nomogram plot was built based on three (including age, TNM stage, and ALI) and two (including TNM stage and ALI) independent prognostic factors for OS and CSS, respectively. Further analyses indicated that the nomogram had better predictive value and some net benefit than the traditional TNM stage alone, especially in long-term OS. Conclusions: Our study further indicated that ALI could be a prognostic marker for OS and CSS in HCC patients after hepatectomy, especially in long-term OS.
ABSTRACT
Meltblown nonwoven materials have gained attention due to their excellent filtration performance. The research on the performance of the intercalation meltblown preparation process is complex and a current research focus in the field of chemical production. Based on data related to intercalated and unintercalated meltblown materials under given process conditions, a product performance prediction model of intercalated meltblown materials was established under different process parameters (receiving distance, hot air velocity). The structural variables (thickness, porosity, and compressive resilience), the change in product performance, and the relationship between structural variables and product performance (filtration resistance, efficiency, air permeability) after intercalation were studied. Multiple regression analysis was used to analyze the structural variables, and evaluation of the regression results were made using R2, MSE, SSR, and SST. A BP neural network prediction model for product performance was established. The BP neural network model was used to find the maximum filtration efficiency. The study provides theoretical support for regulating product performance by solving the maximum filtration efficiency using BP neural network model.
ABSTRACT
Usually, the recognition of sex pheromone signals is restricted to adult moths. Here, our behavioral assay showed that fourth-instar Spodoptera litura larvae are attracted to cabbage laced with minor sex pheromones Z9,E12-tetradecadienyl acetate (Z9,E12-14:Ac) or Z9-tetradecenyl acetate (Z9-14:Ac). Seven odorant-binding proteins (OBPs) were upregulated after exposure to Z9,E12-14:Ac, and one OBP was upregulated after exposure to Z9-14:Ac. Fluorescence competitive binding assays showed that GOBP2 and OBP7 bound to sex pheromones. RNAi treatment significantly downregulated GOBP2 and OBP7 mRNA expression by 70.37 and 63.27%, respectively. The siOBP-treated larvae were not attracted to Z9,E12-14:Ac or Z9-14:Ac, and the corresponding preference indices were significantly lower than those in siGFP-treated larvae. Therefore, we concluded that GOBP2 and OBP7 are involved in the attraction of S. litura larvae to food containing Z9,E12-14:Ac and Z9-14:Ac. These results provide an important basis for exploring the olfactory mechanisms underlying sex pheromone attraction in moth larvae.
Subject(s)
Moths , Sex Attractants , Animals , Larva/genetics , Larva/metabolism , Moths/genetics , Odorants , Pheromones/metabolism , RNA, Messenger/metabolism , Sex Attractants/metabolism , Sex Attractants/pharmacology , Spodoptera/genetics , Spodoptera/metabolismABSTRACT
Athetis lepigone Möschler (Lepidoptera, Noctuidae) is a common maize pest in Europe and Asia. However, there is no long-term effective management strategy is available yet to suppress its population. Adults rely heavily on olfactory cues to locate their optimal host plants and oviposition sites. Pheromone-binding proteins (PBPs) are believed to be responsible for recognizing and transporting different odorant molecules to interact with receptor membrane proteins. In this study, the ligand-binding specificities of two AlepPBPs (AlepPBP2 and AlepPBP3) for sex pheromone components and host plant (maize) volatiles were measured by fluorescence ligand-binding assay. The results demonstrated that AlepPBP2 had a high affinity with two pheromones [(Z)-7-dodecenyl acetate, Ki = 1.11 ± 0.1 µM, (Z)-9-tetradecenyl acetate, Ki = 1.32 ± 0.15 µM] and ten plant volatiles, including (-)-limonene, α-pinene, myrcene, linalool, benzaldehyde, nonanal, 2-hexanone, 3-hexanone, 2-heptanone and 6-methyl-5-hepten-2-one. In contrast, we found that none of these chemicals could bind to AlepPBP3. Our results clearly show no significant differences in the functional characterization of the binding properties between AlepPBP2 and AlepPBP3 to sex pheromones and host plant volatiles. Furthermore, molecular docking was employed for further detail on some crucial amino acid residues involved in the ligand-binding of AlepPBP2. These findings will provide valuable information about the potential protein binding sites necessary for protein-ligand interactions which appear as attractive targets for the development of novel technologies and management strategies for insect pests.
Subject(s)
Moths , Receptors, Odorant , Sex Attractants , Animals , Carrier Proteins/metabolism , Female , Insect Proteins/metabolism , Ligands , Molecular Docking Simulation , Moths/metabolism , Pheromones/metabolism , Receptors, Odorant/metabolism , Sex Attractants/metabolism , Zea mays/metabolismABSTRACT
Spodoptera litura is an important pest that causes significant economic damage to numerous crops worldwide. Sex pheromones (SPs) mediate sexual communication in S. litura and show a characteristic degree of rhythmic activity, occurring mainly during the scotophase; however, the specific regulatory mechanisms remain unclear. Here, we employed a genome-wide analysis to identify eight candidate circadian clock genes in S. litura. Sequence characteristics and expression patterns were analyzed. Our results demonstrated that some circadian clock genes might regulate the biosynthesis and perception of SPs by regulating the rhythmic expression of SP biosynthesis-related genes and SP perception-related genes. Interestingly, all potential genes exhibited peak expression in the scotophase, consistent with the SP could mediate courtship and mating behavior in S. litura. Our findings are helpful in elucidating the molecular mechanism by which circadian clock genes regulate sexual communication in S. litura.
Subject(s)
Circadian Clocks , Sex Attractants , Animals , Circadian Clocks/genetics , Communication , Sex Attractants/metabolism , Spodoptera/physiologyABSTRACT
BACKGROUND: Athetis lepigone, a noctuid moth feeding on more than 30 different crops worldwide, has evolved a sophisticated, sensitive, and specific chemosensory system to detect and discriminate exogenous chemicals. Odorant-binding proteins (OBPs) are the most important agent in insect chemosensory systems to be explored as an alternative target for environmentally friendly approaches to pest management. RESULTS: To investigate the olfactory function of A. lepigone OBPs (AlepOBPs), AlepOBP6 was identified and expressed in Escherichia coli. The binding affinity of the recombinant OBP to 20 different ligands was then examined using a competitive binding approach. The results revealed that AlepOBP6 can bind to two sex pheromones and ten maize volatiles, and its conformation stability is pH dependent. We also carried out a structure-function study using different molecular approaches, including structure modeling, molecular docking, and a mutation functional assay to identify amino acid residues (M39, V68, W106, Q107, and Y114) involved in the binding of AlepOBP6 to both sex pheromones and maize volatiles in A. lepigone. CONCLUSION: These results suggest that AlepOBP6 is likely involved in mediating the responses of A. lepigone to sex pheromones and maize volatiles, which may play a pivotal function in mating, feeding, and oviposition behaviors. This study not only provides new insight into the binding mechanism of OBPs to sex pheromones and host volatiles in moths, but also contributes to the discovery of novel target candidates for developing efficient behavior disruptors to control A. lepigone in the future. © 2021 Society of Chemical Industry.
Subject(s)
Moths , Receptors, Odorant , Sex Attractants , Animals , Female , Insect Proteins/genetics , Ligands , Molecular Docking Simulation , Pheromones , Receptors, Odorant/genetics , Zea maysABSTRACT
INTRODUCTION: One of the most common cancers is hepatocellular carcinoma (HCC), which is an aggressive cancer that is associated with high mortality. The expression and role of ARHGAP20 in HCC remain unclear. MATERIALS AND METHODS: The expression and clinical role of ARHGAP20 were investigated using online databases and HCC samples from Meizhou People's Hospital. Wound healing assays, transwell migration/invasion assays, and lung metastasis models were performed using nude mice. Gene set enrichment analyses were used to further explore the potential mechanisms. RESULTS: Inspired by expression analyses of three different public databases (ie, TIMER, Oncomine, and HCCDB database), we confirmed that ARHGAP20 was downregulated in clinical HCC tumors compared with normal controls. ARHGAP20 expression inhibited HCC migration and invasion in vitro and in vivo. Based on GSEA results, we tested markers of the PI3K-AKT signaling pathway. Interestingly, while ARHGAP20 upregulation suppressed HCC migration/invasion and phosphorylation of AKT/PI3K molecules, exposure to the PI3K-AKT pathway agonist rhIGF-1 partially rescued these phenomena. ARHGAP20 also showed a close correlation with certain components in the HCC immune microenvironment. Furthermore, we revealed that downregulated ARHGAP20 was significantly correlated with larger tumor size and vascular invasion, and could be used as an adverse independent prognostic factor for HCC OS but not RFS. CONCLUSION: ARHGAP20 was identified for the first time as a tumor suppressor gene that could inhibit HCC progression by regulating the PI3K-AKT signaling pathway and the immune microenvironment in HCC.
ABSTRACT
The tobacco cutworm Spodoptera litura (Lepidoptera: Noctuidae) is a polyphagous pest with a highly selective and sensitive chemosensory system involved in complex physiological behaviors such as searching for food sources, feeding, courtship, and oviposition. However, effective management strategies for controlling the insect pest populations under threshold levels are lacking. Therefore, there is an urgent need to formulate eco-friendly pest control strategies based on the disruption of the insect chemosensory system. In this study, we identified 158 putative chemosensory genes based on transcriptomic and genomic data for S. litura, including 45 odorant-binding proteins (OBPs, nine were new), 23 chemosensory proteins (CSPs), 60 odorant receptors (ORs, three were new), and 30 gustatory receptors (GRs, three were new), a number higher than those reported by previous transcriptome studies. Subsequently, we constructed phylogenetic trees based on these genes in moths and analyzed the dynamic expression of various genes in head capsules across larval instars using quantitative real-time polymerase chain reaction. Nine genes-SlitOBP8, SlitOBP9, SlitOBP25, SlitCSP1, SlitCSP7, SlitCSP18, SlitOR34, SlitGR240, and SlitGR242-were highly expressed in the heads of 3- to 5-day-old S. litura larvae. The genes differentially expressed in olfactory organs during larval development might play crucial roles in the chemosensory system of S. litura larvae. Our findings substantially expand the gene inventory for S. litura and present potential target genes for further studies on larval feeding in S. litura.
Subject(s)
Genes, Insect , Insect Proteins/genetics , Receptors, Odorant/genetics , Spodoptera/genetics , Animals , Female , Head , Insect Proteins/metabolism , Larva/metabolism , Male , Receptors, Odorant/metabolism , Spodoptera/metabolism , TranscriptomeABSTRACT
INTRODUCTION: N6-methyladenosine (m6A), the most prominent mRNA modification, plays a critical role in many physiological and pathological processes. However, the roles of m6A RNA modification in hepatocellular carcinoma (HCC) remain largely unknown. MATERIALS AND METHODS: We investigated the mRNA expression and clinical significance of m6A-related genes using data from The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma cohort. Mutation, copy number variation (CNV), methylation, differential expression, and gene ontology analyses, gene set enrichment analysis and the construction of a competing endogenous RNA (ceRNA) regulatory network were performed to investigate the underlying mechanisms of the aberrant expression of m6A-related genes. RESULTS: m6A-related genes were frequently dysregulated in cancers but with a cancer-specific pattern. METTL3, YTHDF2, and ZC3H13 were found to be independent prognostic factors of overall survival (OS); however, only METTL3 was found to be an independent prognostic factor of recurrence-free survival (RFS). Joint effects analysis showed the predictive capacity of combining METTL3, YTHDF2, and ZC3H13 for HCC OS. Then the potential mechanisms of METTL3 were further explored due to its prognostic role in both OS and RFS. CNV and DNA methylation, but not somatic mutations, might contribute to the abnormal upregulation of METTL3 in HCC. Significantly altered genes, microRNAs, and lncRNAs were identified, and a ceRNA regulatory network was constructed to explain the upregulation of METTL3 in HCC. CONCLUSIONS: Our study identified several m6A-related genes, especially METTL3, that could be potential prognostic biomarkers in HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Methyltransferases , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Databases, Genetic/statistics & numerical data , Disease Progression , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Methyltransferases/genetics , Methyltransferases/metabolism , Prognosis , Up-RegulationABSTRACT
Insect resistance to insecticides is an increasingly serious problem, and the resistant mechanisms are complicated. The resistance research based on the chemosensory pathway is one of the hot problems at present, but the specific binding mechanism of chemosensory genes and insecticides remains elusive. The binding mechanism of AlepGOBP2 (belong to insect chemosensory gene) with two insecticides was investigated by computational and experimental approaches. Our calculation results indicated that four key residues (Phe12, Ile52, Ile94, and Phe118) could steadily interact with these two insecticides and be assigned as hotspot sites responsible for their binding affinities. The significant alkyl-π and hydrophobic interactions involved by these four hotspot residues were found to be the driving forces for their binding affinities, especially for two residues (Phe12 and Ile94) that significantly contribute to the binding of chlorpyrifos, which were also validated by our binding assay results. Furthermore, we also found that the AlepGOBP2-chlorpyrifos/phoxim complexes can be more efficiently converged in the residue-specific force field-(RSFF2C) and its higher accuracy and repeatability in protein dynamics simulation, per-residue free energy decomposition, and computational alanine scanning calculations have also been achieved in this paper. These findings provided useful insights for efficient and reliable calculation of the binding mechanism of relevant AlepGOBPs with other insecticides, facilitating to develop new and efficient insecticides targeting the key sites of AlepGOBP2.
Subject(s)
Chlorpyrifos/chemistry , Insect Proteins/chemistry , Moths/metabolism , Organothiophosphorus Compounds/chemistry , Receptors, Odorant/chemistry , Receptors, Odorant/metabolism , Animals , Chlorpyrifos/metabolism , Insect Proteins/metabolism , Molecular Dynamics Simulation , Moths/chemistry , Organothiophosphorus Compounds/metabolism , Protein BindingABSTRACT
Insects employ a sensitive chemosensory system to accurately recognize external odorants, which help them to make a behavioral response quickly. Semiothisa cinerearia has caused serious damages to Sophora japonica L. in recent years, and there is still a lack of effective strategy to control the pest. Although the two type-II sex pheromones of S. cinerearia, 6Z,9Z-cis-3,4-epoxy-17:H and 3Z,6Z,9Z-17:H, have been identified for 30 years, the molecular mechanisms underlying the chemosensation of the two sex pheromones are still unknown. Here, we found that there are differences in the types of antennae sensilla between sexes, and revealed 146 putative chemosensory genes in the antennal transcriptome. Among these genes, 11 and 40 of them displayed male-biased and female-biased expression, respectively. Our findings greatly improve the chemosensory gene resources for S. cinerearia and provide a foundation for functional studies of these sex-biased genes on the chemosensation of sex pheromones and on other sex-related behaviors.
Subject(s)
Moths/genetics , Receptors, Odorant/genetics , Sex Attractants/physiology , Animals , Female , Gene Expression Profiling , Male , Moths/physiology , Phylogeny , TranscriptomeABSTRACT
Athetis lepigone is a polyphagous pest found around the world that feeds on maize, wheat, and various other important crops. Although it exhibits a degree of resistance to various chemical insecticides, an effective pest-control method has not yet been developed. The sex pheromone communication system plays an essential role in the mating and reproduction of moths, in which pheromone-binding proteins (PBPs) are crucial genes. In this study, we cloned and purified the protein AlepPBP1 using an E. coli expression system and found it had a higher binding affinity to two sex pheromones of A. lepigone, namely, Z7-12:Ac and Z9-14:Ac (with Ki 0.77 ± 0.10 and 1.10 ± 0.20 µM, respectively), than to other plant volatiles. The binding-mode analysis of protein conformation with equilibrium stabilization was obtained using molecular dynamics (MD) simulation and indicated that hydrophobic interactions involving several nonpolar residues were the main driving force for the binding affinity of AlepPBP1 with sex pheromones. Computational alanine scanning (CAS) was performed to further identify key amino acid residues and validate their binding contributions. Each key residue, including Phe36, Trp37, Val52, and Phe118, was subsequently mutated into alanine using site-directed mutagenesis. Binding assays showed that the efficient binding abilities to Z7-12:Ac (F36A, W37A, and F118A) and Z9-14:Ac (F36A, W37A, V52A, and F118A) were almost lost in the mutated proteins. Our results demonstrated that these key amino acid residues are crucial for determining the binding ability of AlepPBP1 to sex pheromones. These findings provide a basis for the use of AlepPBP1 in the studies as a specific target for the development of novel behavioral antagonists with marked inhibition or mating-disruption abilities using computer-aided drug design (CADD).
Subject(s)
Carrier Proteins/metabolism , Insect Proteins/metabolism , Moths/metabolism , Sex Attractants/metabolism , Amino Acid Motifs , Animals , Carrier Proteins/chemistry , Carrier Proteins/genetics , Female , Insect Proteins/chemistry , Insect Proteins/genetics , Kinetics , Male , Molecular Docking Simulation , Moths/chemistry , Moths/drug effects , Moths/genetics , Protein Binding , Sex Attractants/chemistry , Sex Attractants/pharmacologyABSTRACT
Athetis lepigone is one of the most severe polyphagous pests, and it has developed resistance to different chemical insecticides. Insects primarily rely on the olfactory system to recognize various environmental chemicals, including xenobiotics such as insecticides. Here, we expressed two A. lepigone pheromone-binding proteins (AlepPBP2 and AlepPBP3), and observed they had higher binding affinities to phoxim than other insecticides, with Ki was 3.30⯱â¯0.38⯵M and 3.27⯱â¯0.10⯵M, respectively. Molecular dynamics simulation, binding mode analysis, and computational alanine scanning showed that six residues (Phe15, Phe39, Ile55, Leu65, Ile97, and Phe122) of AlepPBP2 and three residues (Phe12, Ile52, and Ile134) of AlepPBP3 maybe as potential residues that can change protein ability to bind an organophosphorus insecticide phoxim. Then, we used site-directed mutagenesis assay to mutate these residues into alanine, respectively. Subsequently, the binding assays displayed that Phe15, Phe39, and Ile97 of AlepPBP2, Phe12 and Ile134 of AlepPBP3 caused a significant decrease of AlepPBPs binding ability to phoxim, suggesting they should play crucial roles in the AlepPBPs/phoxim interactions. Our findings could further advance in using PBPs as unique targets to design and develop precise and environmentally-friendly pest control agents with high insecticidal potential using a computer-aided drug design (CADD) approach.
Subject(s)
Insecticides , Olfaction Disorders , Animals , Carrier Proteins , Insect Proteins/genetics , Insect Proteins/metabolism , Insecticides/toxicity , PheromonesABSTRACT
Athetis lepigone (Alep) is a polyphagous pest native to Europe and Asia that has experienced major outbreaks in the summer maize area of China since 2011 and has shown evidence of resistance to some insecticides. Insect olfaction is crucial for recognition of sex pheromones, host plant volatiles and even insecticides, in which two general-odorant binding proteins (GOBPs) play important roles. To elucidate the functions of GOBPs in A. lepigone, we first expressed the two AlepGOBP proteins in the E. coli expression system. Then, the results of fluorescence competitive binding assays demonstrated that the high binding affinity of AlepGOBP2 with sex pheromones [(Z)-7-dodecenyl acetate (Z7-12:Ac), Ki = 0.65 µM; (Z)-9-tetradecenyl acetate (Z9-14:Ac), Ki = 0.83 µM], two maize plant volatiles [Ocimene, Ki = 9.63 µM; (E)-ß-Farnesene, Ki = 4.76 µM] and two insecticides (Chlorpyrifos Ki =5.61 µM; Phoxim, Ki = 4.38 µM). However, AlepGOBP1 could only bind Ocimene (Ki = 13.0 µM) and two insecticides (Chlorpyrifos Ki =4.46 µM; Phoxim, Ki = 3.27 µM). These results clearly suggest that AlepGOBP1 and AlepGOBP2 differentiate among odorants and other ligands. The molecular docking results further revealed different key residues involved in the ligand binding of AlepGOBPs. In summary, this study provides a foundation for exploring the olfactory mechanism of A. lepigone and identified two potential target genes for the development of highly effective insecticides in the future.
Subject(s)
Insecticides , Moths , Sex Attractants , Animals , China , Escherichia coli , Insect Proteins , Molecular Docking Simulation , Odorants , PheromonesABSTRACT
While hundreds of consistently altered metabolic genes had been identified in hepatocellular carcinoma (HCC), the prognostic role of them remains to be further elucidated. Messenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma and GSE14520 data set from the Gene Expression Omnibus database. Univariate Cox regression analysis and lasso Cox regression model established a novel four-gene metabolic signature (including acetyl-CoA acetyltransferase 1, glutamic-oxaloacetic transaminase 2, phosphatidylserine synthase 2, and uridine-cytidine kinase 2) for HCC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was significantly correlated with other negative prognostic factors such as higher α-fetoprotein. The signature was found to be an independent prognostic factor for HCC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. Furthermore, gene set enrichment analyses revealed several significantly enriched pathways, which might help explain the underlying mechanisms. Our study identified a novel robust four-gene metabolic signature for HCC prognosis prediction. The signature might reflect the dysregulated metabolic microenvironment and provided potential biomarkers for metabolic therapy and treatment response prediction in HCC.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Transcriptome/genetics , Acetyl-CoA C-Acetyltransferase/genetics , Acetyl-CoA C-Acetyltransferase/metabolism , Adult , Aged , Aspartate Aminotransferases/genetics , Aspartate Aminotransferases/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/mortality , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/metabolism , Liver Neoplasms/mortality , Male , Middle Aged , Nitrogenous Group Transferases/genetics , Nitrogenous Group Transferases/metabolism , Nomograms , Prognosis , Uridine Kinase/genetics , Uridine Kinase/metabolismABSTRACT
Accumulating evidence indicates a strong correlation between type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC), but the underlying pathophysiology is still elusive. We aimed to identify unrecognized but important genes and pathways related to T2DM and HCC by bioinformatic analysis. The GSE64998 and GSE15653 datasets (for T2DM), the GSE121248 dataset and the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset (for HCC) were downloaded. Differential expression analysis, functional and pathway enrichment analysis, protein-protein interaction (PPI) network construction, survival analysis, transcription factor (TF) prediction, and correlation of gene expression with methylation and tumour-infiltrating immune cells were conducted. Nine genes, namely, CDNF, CRELD2, DNAJB11, DTL, GINS2, MANF, PDIA4, PDIA6, and VCP, were recognized as hub genes. Enrichment analysis revealed several enriched terms and pathways. Transcription factors such as Kruppel-like factor 6, abnormal methylation and immune dysregulation might help explain the dysregulation of hub genes. Our study identified nine hub genes that might play a critical role in both T2DM and HCC. However, more studies are warranted to clarify the mechanisms of these genes.
Subject(s)
Carcinoma, Hepatocellular/genetics , Diabetes Mellitus/genetics , Liver Neoplasms/genetics , Computational Biology , Databases, Genetic , HumansABSTRACT
Chemosensory systems play an important role in insect behavior, and some key associated genes have potential as novel targets for pest control. Cacopsylla chinensis is an oligophagous pest and has become one of the main pests of pear trees, but little is known about the molecular-level means by which it locates its hosts. In this study, we assembled the head transcriptome of C. chinensis using Illumina sequencing, and 63,052 Unigenes were identified. A total of 36 candidate chemosensory genes were identified, including five different families: 12 odorant binding proteins (OBPs), 11 chemosensory proteins (CSPs), 7 odorant receptors (ORs), 4 ionotropic receptors (IRs), and 2 gustatory receptors (GRs). The number of chemosensory gene families is consistent with that found in other Hemipteran species, indicating that our approach successfully obtained the chemosensory genes of C. chinensis. The tissue expression of all genes using quantitative real-time PCR (qRT-PCR) found that some genes displayed male head, female head, or nymph-biased specific/expression. Our results enrich the gene inventory of C. chinensis and provide valuable resources for the analysis of the functions of some key genes. This will help in developing molecular targets for disrupting feeding behavior in C. chinensis.
ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) remains a major challenge for public health worldwide. Considering the great heterogeneity of HCC, more accurate prognostic models are urgently needed. To identify a robust prognostic gene signature, we conduct this study. MATERIALS AND METHODS: Level 3 mRNA expression profiles and clinicopathological data were obtained in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC). GSE14520 dataset from the gene expression omnibus (GEO) database was downloaded to further validate the results in TCGA. Differentially expressed mRNAs between HCC and normal tissue were investigated. Univariate Cox regression analysis and lasso Cox regression model were performed to identify and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier curve, multivariate Cox regression analysis, nomogram, and decision curve analysis (DCA) were used to assess the prognostic capacity of the six-gene signature. The prognostic value of the gene signature was further validated in independent GSE14520 cohort. Gene Set Enrichment Analyses (GSEA) was performed to further understand the underlying molecular mechanisms. The performance of the prognostic signature in differentiating between normal liver tissues and HCC were also investigated. RESULTS: A novel six-gene signature (including CSE1L, CSTB, MTHFR, DAGLA, MMP10, and GYS2) was established for HCC prognosis prediction. The ROC curve showed good performance in survival prediction in both the TCGA HCC cohort and the GSE14520 validation cohort. The six-gene signature could stratify patients into a high- and low-risk group which had significantly different survival. Cox regression analysis showed that the six-gene signature could independently predict OS. Nomogram including the six-gene signature was established and shown some clinical net benefit. Furthermore, GSEA revealed several significantly enriched oncological signatures and various metabolic process, which might help explain the underlying molecular mechanisms. Besides, the prognostic signature showed a strong ability for differentiating HCC from normal tissues. CONCLUSIONS: Our study established a novel six-gene signature and nomogram to predict overall survival of HCC, which may help in clinical decision making for individual treatment.
ABSTRACT
Sex pheromone biosynthesis in moths relies on the activity of multiple enzymes, including Δ9 desaturase, which plays an important role in catalyzing desaturation at the Δ9 position of the carbon chain. However, the physiological function of moth Δ9 desaturase has not been elucidated in vivo. In this study, we used the CRISPR/Cas9 system to knockout the Δ9 desaturase gene (SlitDes11) of Spodoptera litura to analyze its role in sex pheromone biosynthesis. First, through the direct injection of SlitDes11-single guide RNA (sgRNA)/Cas9 messenger RNA into newly laid eggs, gene editing was induced in around 30% of eggs 24â¯h after injection and was induced in 20.8% of the resulting adult moths. Second, using a sibling-crossing strategy, insects with mutant SlitDes11 (bearing a premature stop codon) were selected, and homozygous mutants were obtained in the G5 generation. Third, pheromone gland extracts of adult female homozygous SlitDes11 mutants were analyzed using Gas chromatography (GC). The results showed that titers of all three ester sex pheromone components; Z9, E11-14:Ac, Z9,E12-14:Ac, and Z9-14:Ac; were reduced by 62.40%, 78.50%, and 72.50%, respectively. This study provides the first direct evidence for the role of SlitDes11 in sex pheromone biosynthesis in S. litura, and indicates the gene could be as potential target to disrupt sexual communication in S. litura for developing a new pollution-free insecticide.