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Programmed death ligand 1 (PD-L1) is highly expressed in many cancers. We investigated the expression of PD-L1 and its relationship with vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 and KI-67 expression in 64 patients with primary glioma. The expression rate of PD-L1 in glioma patients was 78.12%. PD-L1 levels correlated with the tumor grade (p = 0.013), VEGF status (p = 0.002) and KI-67 status (p = 0.002). In addition, PD-L1 levels correlated positively with VEGF (r = 0.314, p = 0.011) and KI-67 (r = 0.391, p = 0.001) levels when the data were treated as continuous variables. This is the first report suggesting that PD-L1 is important for glioma angiogenesis and proliferation. Thus, further research should be conducted to assess the combination of targeted VEGF therapy and anti-PD-L1 immunotherapy for the treatment of glioma.

The entomopathogenic fungus Verticillium lecanii is a well-known biocontrol agent. V. lecanii produces subtilisin-like serine protease (Pr1), which is important in the biological control activity of some insect pests by degrading insect cuticles. In this study, a subtilisin-like serine protease gene VlPr1 was cloned from the fungus and the VlPr1 protein was expressed in Escherichia coli. The VlPr1 gene contains an open reading frame (ORF) interrupted by three short introns, and encodes a protein of 379 amino acids. Protein sequence analysis revealed high homology with subtilisin serine proteases. The molecular mass of the protease was 38 kDa, and the serine protease exhibited its maximal activity at 40°C and pH 9.0. Protease activity was also affected by Mg(2+) and Ca(2+) concentration. The protease showed inhibitory activity against several plant pathogens, especially towards Fusarium moniliforme.

To obtain the P8 protein of Rice gall dwarf virus (RGDV) with biological activity, its outer coat protein gene S8 was expressed in Spodoptera frugiperda (Sf9) insect cells using the baculovirus expression system. The S8 gene was subcloned into the pFastBac™1 vector, to produce the recombinant baculovirus transfer vector pFB-S8. After transformation, pFB-S8 was introduced into the competent cells (E. coli DH10Bac) containing a shuttle vector, Bacmid, generating the recombinant bacmid rbpFB-S8. After being infected by recombinant baculovirus rvpFB-S8 at different multiplicities of infection, Sf9 cells were collected at different times and analyzed by SDS-PAGE, Western blotting and immunofluorescence microscopy. The expression level of the P8 protein was highest between 48-72 h after transfection of Sf9 cells. Immunofluorescence microscopy showed that P8 protein of RGDV formed punctate structures in the cytoplasm of Sf9 cells.

Background: Type II diabetes mellitus (T2DM) is strongly linked with a heightened risk of coronary artery disease (CAD). Exploring biological targets common to T2DM and CAD is essential for CAD intervention strategies. Methods: RNA transcriptome data from CAD and T2DM patients and single-cell transcriptional data from myocardial tissue of CAD patients were used for bioinformatics analysis. Differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted to identify hub genes associated with the CAD Index (CADi) in these cells. We then intersected these genes with differentially expressed genes in the T2DM dataset to validate the key gene FGF7. Additional analyses included immune analysis, drug sensitivity, competing endogenous RNA (ceRNA) networks, and smooth muscle cell -related functional analysis. Results: An abnormally high proportion of smooth muscle cells was observed in CAD tissues compared to normal cardiomyocytes. The gene FGF7, which encodes the keratinocyte growth factor 7 protein, showed increased expression in both CAD and T2DM and was significantly positively correlated with the CADi (correlation = 0.24, p < 0.05). FGF7 expression was inversely correlated with CD4+ and CD8+ T-cell immune infiltration and correlated with the cardiovascular drugs. Overexpression of FGF7 in CAD samples enhanced interactions with mononuclear macrophages and influenced the metabolism of alanine, glutamate, nicotinamide, and retinol. We also identified that hsa-miR-15a-5p, hsa-miR-373-3p, hsa-miR-20a-5p, and hsa-miR-372-3p could regulate FGF7 expression. Conclusion: FGF7 serves as a critical shared biological target for T2DM and CAD, playing a significant role in CAD progression with potential therapeutic implications. [ABSTRACT FROM AUTHOR]

The arrest of neural crest‐derived sympathoadrenal neuroblast differentiation contributes to neuroblastoma formation, and overriding this blocked differentiation is a clear strategy for treating high‐risk neuroblastoma. A better understanding of neuroblast or neuroblastoma differentiation is essential for developing new therapeutic approaches. It has been proposed that Krueppel‐like factor 7 (KLF7) is a neuroblastoma super‐enhancer‐associated transcription factor gene. Moreover, KLF7 was found to be intensely active in postmitotic neuroblasts of the developing nervous system during embryogenesis. However, the role of KLF7 in the differentiation of neuroblast or neuroblastoma is unknown. Here, we find a strong association between high KLF7 expression and favorable clinical outcomes in neuroblastoma. KLF7 induces differentiation of neuroblastoma cells independently of the retinoic acid (RA) pathway and acts cooperatively with RA to induce neuroblastoma differentiation. KLF7 alters the GTPase activity and multiple differentiation‐related genes by binding directly to the promoters of neuroblast differentiation‐associated protein (AHNAK and AHNAK2) and glycerophosphodiester phosphodiesterase domain‐containing protein 5 (GDPD5) and regulating their expression. Furthermore, we also observe that silencing KLF7 in neuroblastoma cells promotes the adrenergic‐to‐mesenchymal transition accompanied by changes in enhancer‐mediated gene expression. Our results reveal that KLF7 is an inducer of neuroblast or neuroblastoma differentiation with prognostic significance and potential therapeutic value. [ABSTRACT FROM AUTHOR]

Background and aims: Liver regeneration retardation post partial hepatectomy (PH) is a common clinical problem after liver transplantation. Identification of key regulators in liver regeneration post PH may be beneficial for clinically improving the prognosis of patients after liver transplantation. This study aimed to clarify the function of junctional protein‐associated with coronary artery disease (JCAD) in liver regeneration post PH and to reveal the underlying mechanisms. Methods: JCAD knockout (JCAD‐KO), liver‐specific JCAD‐KO (Jcad△Hep) mice and their control group were subjected to 70% PH. RNA sequencing was conducted to unravel the related signalling pathways. Primary hepatocytes from KO mice were treated with epidermal growth factor (EGF) to evaluate DNA replication. Fluorescent ubiquitination‐based cell cycle indicator (FUCCI) live‐imaging system was used to visualise the phases of cell cycle. Results: Both global and liver‐specific JCAD deficiency postponed liver regeneration after PH as indicated by reduced gene expression of cell cycle transition and DNA replication. Prolonged retention in G1 phase and failure to transition over the cell cycle checkpoint in JCAD‐KO cell line was indicated by a FUCCI live‐imaging system as well as pharmacologic blockage. JCAD replenishment by adenovirus reversed the impaired DNA synthesis in JCAD‐KO primary hepatocyte in exposure to EGF, which was abrogated by a Yes‐associated protein (YAP) inhibitor, verteporfin. Mechanistically, JCAD competed with large tumour suppressor 2 (LATS2) for WWC1 interaction, leading to LATS2 inhibition and thereafter YAP activation, and enhanced expression of cell cycle‐associated genes. Conclusion: JCAD deficiency led to delayed regeneration after PH as a result of blockage in cell cycle progression through the Hippo–YAP signalling pathway. These findings uncovered novel functions of JCAD and suggested a potential strategy for improving graft growth and function post liver transplantation. Key Points: JCAD deficiency leads to an impaired liver growth after PH due to cell division blockage.JCAD competes with LATS2 for WWC1 interaction, resulting in LATS2 inhibition, YAP activation and enhanced expression of cell cycle‐associated genes.Delineation of JCADHippoYAP signalling pathway would facilitate to improve prognosis of acute liver failure and graft growth in living‐donor liver transplantation. [ABSTRACT FROM AUTHOR]

Urinary extracellular vesicles (uEVs) are rich in valuable biomolecule information which are increasingly recognized as potential biomarkers for various diseases. uEV long RNAs are among the critical cargos capable of providing unique transcriptome information of the source cells. However, consensus regarding ideal reference genes for relative long RNAs quantification in uEVs is not available as of date. Here we explored stable reference genes through profiling the long RNA expression by RNA‐seq following unsupervised analysis and validation studies. Candidate reference genes were identified using four algorithms: NormFinder, GeNorm, BestKeeper and the Delta Ct method, followed by validation. RNA profile showed uEVs contained abundant long RNAs information and the core transcriptome was related to cellular structures, especially ribosome which functions mainly as translation, protein and RNA binding molecules. Analysis of RNA‐seq data identified RPL18A, RPL11, RPL27, RACK1, RPSA, RPL41, H1‐2, RPL4, GAPDH, RPS27A as candidate reference genes. RT‐qPCR validation revealed that RPL41, RPSA and RPL18A were reliable reference genes for long RNA quantification in uEVs from patients with diabetes mellitus (DM), diabetic nephropathy (DN), IgA nephropathy (IgAN) and prostate cancer (PCA). Interestingly, RPL41 also outperformed traditional reference genes in renal tissues of DN and IgAN, as well as in plasma EVs of several types of cancers. The stable reference genes identified in this study may facilitate development of uEVs as novel biomarkers and increase the accuracy and comparability of biomarker studies. [ABSTRACT FROM AUTHOR]

Background: This work aimed to reveal the expression profiles of tRNA-derived small RNAs (tsRNAs) in diabetes. Methods: Thirty-five diabetes patients and thirty-three controls were enrolled. The serum samples of 4 diabetes patients and 4 controls were subjected to tRF and tiRNA polymerase chain reaction (PCR) Array analysis. Then quantitative PCR (qPCR) validation was performed on all the samples. Bioinformatics analyses were conducted to explore their functions. Results: We found 115 tsRNAs that significantly differed between the two groups. 3'tiR- 080-ProTGG(mt) was selected for further qPCR validation in all participants, and it was significantly decreased in diabetes patients compared with controls. Bioinformatics analysis indicated that 3'tiR-080-ProTGG(mt) may play regulatory roles via the cyclic adenosine monophosphate (cAMP) signaling pathway in the pathogenesis and progression of diabetes. Conclusion: Hence, we report that circulating tsRNAs are dysregulated that could be involved in the pathogenesis of diabetes. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis risk stratification is crucial for the surgical decision‐making of thyroid cancer. This study investigated whether the integrated gene profiling (combining expression, SNV, fusion) of Fine‐Needle Aspiration (FNA) samples can improve the prediction of lymph node metastasis in patients with papillary thyroid cancer. Methods: In this retrospective cohort study, patients with papillary thyroid cancer who went through thyroidectomy and central lymph node dissection were included. Multi‐omics data of FNA samples were assessed by an integrated array. To predict lymph node metastasis, we built models using gene expressions or mutations (SNV and fusion) only and an Integrated Risk Stratification (IRS) model combining genetic and clinical information. Blinded histopathology served as the reference standard. ROC curve and decision curve analysis was applied to evaluate the predictive models. Results: One hundred and thirty two patients with pathologically confirmed papillary thyroid cancer were included between 2016–2017. The IRS model demonstrated greater performance [AUC = 0.87 (0.80–0.94)] than either expression classifier [AUC = 0.67 (0.61–0.74)], mutation classifier [AUC = 0.61 (0.55–0.67)] or TIRADS score [AUC = 0.68 (0.62–0.74)] with statistical significance (p < 0.001), and the IRS model had similar predictive performance in large nodule [>1 cm, AUC = 0.88 (0.79–0.97)] and small nodule [≤1 cm, AUC = 0.84 (0.74–0.93)] subgroups. The genetic risk factor showed independent predictive value (OR = 10.3, 95% CI:1.1–105.3) of lymph node metastasis in addition to the preoperative clinical information, including TIRADS grade, age, and nodule size. Conclusion: The integrated gene profiling of FNA samples and the IRS model developed by the machine‐learning method significantly improve the risk stratification of thyroid cancer, thus helping make wise decisions and reducing unnecessary extensive surgeries. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic cardiomyopathy (HCM) is a grave hazard to human health. Circular RNA (circRNAs) and micro RNA (miRNAs), which are competitive endogenous RNA, have been shown to play a critical role inHCM pathogenicity. However, to a great extent, the biological activities of ceRNA in HCM pathophysiology and prognosis remain to be investigated. Materials and methods: By analyzing the expression files in the Gene Expression Comprehensive (GEO) database, differentially expressed (DE) circRNAs, miRNAs, and mRNAs in HCM were identified, and the target molecules of circRNAs and miRNAs were predicted. The intersection of the differentially expressed RNA molecules and the expected target was then calculated, and a ceRNA network was subsequently constructed using RNA molecules. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the potential etiology was elucidated. qPCR was used to validate a portion of the hub gene using Angiotensin II to generate a cell hypertrophy model. Results: Three large-scale HCM sample datasets were extracted from the GEO database. After crossing these molecules with their expected targets, the circRNA-miRNA-mRNA network had two DEcircRNAs, two DEmiRNAs, and thirty DEmRNAs, compared to normal tissues. Functional enrichment analysis of GO and KEGG demonstrated that many of the HCM pathways and mechanisms were associated with calcium channel release, which is also the primary focus of future research. The qPCR results revealed that circRNA, miRNA, and mRNA expression levels were different. They may include novel noninvasive indicators for the early screening and prognostic prediction of HCM. Conclusion: In this study, we hypothesized a circRNA-miRNA-mRNA regulation network that is closely related to the progression and clinical outcomes of HCM and may contain promising biomarkers and treatment targets for HCM. [ABSTRACT FROM AUTHOR]

Summary: Submergence is an abiotic stress that limits agricultural production world‐wide. Plants sense oxygen levels during submergence and postsubmergence reoxygenation and modulate their responses. Increasing evidence suggests that completely submerged plants are often exposed to low‐light stress, owing to the depth and turbidity of the surrounding water; however, how light availability affects submergence tolerance remains largely unknown.Here, we showed that Arabidopsis thaliana MYB DOMAIN PROTEIN30 (MYB30) is an important transcription factor that integrates light signaling and postsubmergence stress responses.MYB DOMAIN PROTEIN30 protein abundance decreased upon submergence and accumulated during reoxygenation. Under submergence conditions, CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), a central regulator of light signaling, caused the ubiquitination and degradation of MYB30. In response to desubmergence, however, light‐induced MYB30 interacted with MYC2, a master transcription factor involved in jasmonate signaling, and activated the expression of the VITAMIN C DEFECTIVE1 (VTC1) and GLUTATHIONE SYNTHETASE1 (GSH1) gene families to enhance antioxidant biosynthesis. Consistent with this, the myb30 knockout mutant showed increased sensitivity to submergence, which was partially rescued by overexpression of VTC1 or GSH1.Thus, our findings uncover the mechanism by which the COP1‐MYB30 module integrates light signals with cellular oxidative homeostasis to coordinate plant responses to postsubmergence stress. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a type of systemic immune disease characterized by chronic inflammatory disease of the joints. However, the aetiology and underlying molecular events of RA are unclear. Here, we applied bioinformatics analysis to identify potential immune effector molecules involved in RA. The three microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. We used the R software screen 115 overlapping differentially expressed genes (DEGs). Subsequently, we constructed a protein–protein interaction (PPI) network encoded by these DEGs and identified 10 genes closely associated with RA – LCK, GZMA, GZMB, CD2, LAG3, IL-15, TNFRSF4, CD247, CCR5 and CCR7. Furthermore, in the miRNA–hub gene networks, we screened out hsa-miR-146a-5p, which is the miRNA controlling the largest number of hub genes. Finally, we found some transcription factors that closely interact with hub genes, such as FOXC1, GATA2, YY1, RUNX2, SREBF1, CEBPB and NFIC. This study successfully predicted that LCK, FOXC1 and hsa-miR-146a-5p can be used as potential immune effector molecules of RA. Our study may have potential implications for future prediction of disease progression in patients with symptomatic RA, and has important significance for the pathogenesis and targeted therapy of RA. [ABSTRACT FROM AUTHOR]

Background: To understand how Plasmodium falciparum malaria is controlled, it is essential to elucidate the transcriptomic responses of the human host in naturally-exposed populations. Various individual studies of the human transcriptomic responses to naturally transmitted P. falciparum infections have been reported with varying results. Multicohort gene expression analysis by aggregating data from diverse populations into a single analysis will increase the reproducibility and reliability of the results. Methods: In this study, discovery cohorts GSE1124-GPL96, GSE34404, GSE117613, and validation cohort GSE35858 were obtained from the Gene Expression Omnibus. A meta-analysis using data from the multicohort studies was performed to identify the differentially expressed genes (DEGs) between malaria-infected and noninfected individuals using the MetaIntegrator R package. Subsequently, the protein–protein interaction (PPI) networks of the DEGs were constructed using Cytoscape software. Significant modules were selected, and the hub genes were identified using the CytoHubba and MCODE plug-ins. Multicohort WGCNA was conducted to find a correlation between modules and malaria infection. Furthermore, the immune cell profile of the peripheral blood in different groups was identified using ssGSEA. Results: These analyses reveal that neutrophil activation, neutrophil-mediated immunity, and neutrophil degranulation are involved in the human response to natural malaria infection. However, neutrophil cell enrichment and activation were not significantly different between mild malaria and severe malaria groups. Malaria infection also downregulates host genes in ribosome synthesis and protein translation and upregulates host cell division-related genes. Furthermore, immune cell profiling analysis shows that activated dendritic cells and type 2 T helper cells are upregulated, while activated B cells, immature B cells, and monocytes are downregulated in the malaria-infected patients relative to the noninfected individuals. Significantly higher enrichment of activated dendritic cell-related genes and significantly lower enrichment of monocyte-related genes are also observed in the peripheral blood of the severe malaria group than in the mild malaria group. Conclusion: These results reveal important molecular signatures of host responses to malaria infections, providing some bases for developing malaria control strategies and protective vaccines. [ABSTRACT FROM AUTHOR]

Background: Abnormal glycosylation of proteins has been identified in almost all types of cancers and is closely related to the cancer progression, metastasis, and survival of cancer patients. This study was to explore the values of serum tumor abnormal protein (TAP), an abnormal glycochain protein, in the diagnosis and prognosis of gastric cancer (GC). Methods: A total of 335 GC patients were included as the study group, and another 335 subjects served as the control group. Tumor abnormal protein expression was compared between the 2 groups. Correlation analysis was used to assess the correlations of TAP with clinicopathological factors. Gastric cancer patients were divided into training set and test set at a ratio of 2:1. Univariate and multivariate Cox regression analyses in training set were used to evaluate the prognostic significance of TAP in GC patients and explore the independent risk factors for overall survival (OS) and disease-free survival (DFS) to establish a prognostic model, followed by testing of the model. According to the median of TAP, 335 GC patients were divided into 2 groups to plot the survival curves of OS and DFS. Results: Tumor abnormal protein expression in the study group was significantly higher than in the control group. Taking the best cut-off value of TAP (110.128 μm2) as the diagnostic criteria for GC, the sensitivity and specificity of TAP were 83.58% and 97.61%, respectively, and the area under the receiver operating characteristics (ROC) curve was 0.935, which was not inferior to computed tomography (CT). Tumor abnormal protein expression was an independent risk factor for OS and DFS. The prognostic predictive value of TAP was better than that of pathological stage in GC patients. The model with TAP was effective in predicting prognosis. Conclusion: Tumor abnormal protein is an effective indicator for early screening and prognostic evaluation of GC and can also assist the clinical diagnosis and treatment of GC. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the diagnostic and prognostic role of tumor‐educated leukocytes (TELs) mRNA in Chinese patients with non‐small cell lung cancer (NSCLC). Methods: The TELs collected underwent total RNA isolation. RNA‐sequencing (RNA‐seq) technology was used to analyze the transcriptome of the TELs. The mRNA expression levels of differential genes were analyzed by RT‐qPCR. Statistical analyses were performed using Prism and SPSS by Mann–Whitney nonparametric test, Kruskal‐Wallis test and one‐way ANOVA. Results: We used RNA‐seq technology to screen 95 differential genes (DEGs) from seven NSCLC and four controls, wherein 15 genes were upregulated, and 80 were downregulated. Of these, four genes were selected for further analysis, wherein one was upregulated (GPX1) and three were downregulated (BCL9L, MAP3K7CL, PCSK7). RT‐qPCR was performed in 431 samples (237 NSCLC, 194 healthy donors). The four‐gene panel showed significant differences (p < 0.001) in the expression levels between NSCLC and healthy samples. ROC curves of the panel revealed an AUC of 0.803, with a sensitivity of 73.8% and specificity of 75.3%. GPX1, BCL9L and PCSK7 genes distinguished early‐stage NSCLC patients from healthy group (p < 0.05). When the three genes were combined to diagnose early‐stage NSCLC, the diagnostic efficacy was 0.772, sensitivity was 73.7%, and specificity was 72.2%. In addition, the downregulated gene BCL9L was associated with chemotherapeutic effect. Conclusions: The present study provided a systematic description of gene expression profiling in the TELs. It is worth noting that these four genes may be potential candidate genes for NSCLC diagnostic biomarkers and provide a basis for further biological and functional studies. [ABSTRACT FROM AUTHOR]

Background: Despite the emerging insights into many snoRNAs (small nucleolar RNAs) which are detectable in body fluids and serve as noninvasive biomarkers, few studies have previously discussed the role of snoRNAs in tumor‐educated platelets (TEPs). Herein, we systematically estimated dysregulation of snoRNAs in non‐small cell lung cancer (NSCLC) and clarified the biomarker potential of SNORD55 in platelets. Methods: We compared expression of snoRNAs between NSCLC and normal tissues using SNORic datasets. Platelets were isolated from plasma using low‐speed centrifugation and subjected to quantitative polymerase chain reaction (qPCR) for SNORD55 detection. Results: SNORD55 was significantly decreased in TEPs from NSCLC patients especially in early‐stage patients compared with healthy controls. Importantly, we validated that TEP SNORD55 was capable of acting as a promising biomarker for NSCLC. It exerted diagnostic performance for NSCLC diagnosis, possessing an AUC of 0.803, as well as for early NSCLC diagnosis, possessing an AUC of 0.784. Moreover, the combination of TEP SNORD55 and carcinoembryonic antigen (CEA) improved the diagnostic efficiency of cancer progression. In addition, TEP SNORD55 also potentially acts as a noninvasive early biomarker for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) with favorable diagnostic efficiencies. Conclusions: In summary, TEP SNORD55 could potentially serve as a noninvasive biomarker for NSCLC diagnosis and early diagnosis. Key points: SNORD55 was significantly decreased in TEPs from NSCLC patients compared to healthy controls and acted as a novel biomarker for early NSCLC. [ABSTRACT FROM AUTHOR]

Background: The N -acetyltransferase 1 (NAT1) gene is downregulated in several cancers and associated with patient survival. In this study, we sought to examine the prognostic value and clinical significance of NAT1 methylation in colon adenocarcinoma (COAD). Methods: Data relating to NAT1 mRNA expression and methylation and clinicopathological features of COAD were extracted from the database of The Cancer Genome Atlas. We compared the mRNA expression and methylation of NAT1 between COAD and normal tissues and performed correlation analysis to assess the association between NAT1 mRNA expression and methylation. Furthermore, we assessed patient survival based on CpG sites in the promoter region of NAT1 and analyzed the association between the NAT1 mRNA expression and CpG site methylation and clinicopathological features. An independent Gene Expression Omnibus (GEO) dataset was used to validate the results. Results: We found that the expression of NAT1 mRNA was reduced in COAD compared with normal tissues and that mean methylation of the eight CpG sites in the promoter region of NAT1 was higher in COAD tissues than in normal tissues. Furthermore, five CpG sites were demonstrated to be significantly negatively correlated with NAT1 mRNA expression in COAD. Survival analysis indicated that NAT1 mRNA expression and the cg15797286 and cg18509990 sites were associated with the overall survival of COAD patients. Combined survival analysis revealed that combinations of NAT1 mRNA expression with five CpG sites were significantly associated with the overall survival of COAD patients. Both NAT1 mRNA and cg15797286 were associated with the T, N, and clinical stages of COAD. The GEO data indicated that cg15797286 was hypermethylated in recurrent colorectal adenomas. Conclusions: Methylation of NAT1 is associated with the development of COAD, and may serve as prognostic and treatment biomarkers for COAD. [ABSTRACT FROM AUTHOR]

Acute alcohol exposure induces unconscious condition such as coma whose main physical manifestation is the loss of righting reflex (LORR). Xingnaojing Injection (XNJI), which came from Chinese classic formula An Gong Niu Huang Pill, is widely used for consciousness disorders in China, such as coma. Although XNJI efficiently shortened the duration of LORR induced by acute ethanol, it remains unknown how XNJI acts on ethanol-induced coma (EIC). We performed experiments to examine the effects of XNJI on orexin and adenosine (AD) signaling in the lateral hypothalamic area (LHA) in EIC rats. Results showed that XNJI reduced the duration of LORR, which implied that XNJI promotes recovery form coma. Microdialysis data indicated that acute ethanol significantly increased AD release in the LHA but had no effect on orexin A levels. The qPCR results displayed a significant reduction in the Orexin-1 receptors (OX1R) expression with a concomitant increase in the A1 receptor (A1R) and equilibrative nucleoside transporter type 1 (ENT1) expression in EIC rats. In contrast, XNJI reduced the extracellular AD levels but orexin A levels remained unaffected. XNJI also counteracted the downregulation of the OX1R expression and upregulation of A1R and ENT1 expression caused by EIC. As for ADK expression, XNJI but not ethanol, displayed an upregulation in the LHA in EIC rats. Based on these results, we suggest that XNJI promotes arousal by inhibiting adenosine neurotransmission via reducing AD level and the expression of A1R and ENT1. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the mechanism of Liuwei Dihuang Pill (六味地黄丸, LDP) in treating postmenopausal osteoporosis (PMOP) with Shen (Kidney) yin deficiency.Methods: In this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group (Group A), PMOP Shen-yang deficiency group (Group B), PMOP without Shen deficiency group (Group C), and control group (Group N). Real-time polymerase chain reaction (RT-PCR) and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 (CLCF1), ankyrin repeat and SOCS box containing 1 (ASB1), and prokineticin 2 (PROK2) genes and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway.Results: The mRNA (P<0.05) and protein (P<0.01) expression levels of the CLCF1 gene in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gene were obviously up-regulated (P<0.01). After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated (both P<0.01), and the average bone density of the top femur had significantly increased (P<0.05). In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3.Conclusions: The CLCF1 gene is an important gene associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gene expression and activation of the JAK/STAT signaling pathway. [ABSTRACT FROM AUTHOR]

The global atmospheric CO concentration is currently (2012) 393.1 μmol mol, an increase of approximately 42 % over pre-industrial levels. In order to understand the responses of metabolic enzymes to elevated CO concentrations, an experiment was conducted using the Free Air CO Enrichment (FACE )system. Two conventional japonica rice varieties ( Oryza sativa L. ssp. japonica) grown in North China, Songjing 9 and Daohuaxiang 2, were used in this study. The activities of ADPG pyrophosphorylase, soluble and granule-bound starch synthases, and soluble and granule-bound starch branching enzymes were measured in rice grains, and the effects of elevated CO on the amylose and protein contents of the grains were analyzed. The results showed that elevated CO levels significantly increased the activity of ADPG pyrophosphorylase at day 8, 24, and 40 after flower, with maximum increases of 56.67 % for Songjing 9 and 21.31 % for Daohuaxiang 2. Similarly, the activities of starch synthesis enzymes increased significantly from the day 24 after flower to the day 40 after flower, with maximum increases of 36.81 % for Songjing 9 and 66.67 % for Daohuaxiang 2 in soluble starch synthase (SSS), and 25.00 % for Songjing 9 and 36.44 % for Daohuaxiang 2 in granule-bound starch synthase (GBSS), respectively. The elevated CO concentration significantly increased the activity of soluble starch branching enzyme (SSBE) at day 16, 32, and 40 after flower, and also significantly increased the activity of granule-bound starch branching enzyme (GBSBE) at day 8, 32, and 40 after flower. The elevated CO concentration increased the peak values of enzyme activity, and the timing of the activity peaks for SSS and GBSBE were earlier in Songjing 9 than in Daohuaxiang 2. There were obvious differences in developmental stages between the two varieties of rice, which indicated that the elevated CO concentration increased enzyme activity expression and starch synthesis, affecting the final contents of starch and protein in the rice grains. Our results will provide a foundation for understanding the physiological mechanisms of rice yield under elevated atmospheric CO concentrations. [ABSTRACT FROM AUTHOR]

NSP4 and VP7 are important functional proteins of rotavirus. Proper combination of viral gene expression is favorable to improving the protection effect of subunit vaccine. In the present study, We evaluated the immunogenicity and efficacy of the bicistronic recombinant adenovirus (rAd-NSP4-VP7) and two single-gene expressing adenoviruses (rAd-NSP4, rAd-VP7). The three adenovirus vaccines were used to immunize mice by intramuscular or intranasal administration. The data showed significant increases in serum antibodies, T lymphocyte subpopulations proliferation, and cytokine secretions of splenocyte in all immunized groups. However, the serum IgA and neutralizing antibody levels of the rAd-NSP4-VP7 or rAd-VP7 groups were significantly higher than those of the rAd-NSP4, while the splenocyte numbers of IFN-γ secretion in the rAd-NSP4-VP7 or rAd-NSP4 groups was greater than that of the rAd-VP7. Furthermore, the efficacy evaluation in a suckling mice model indicated that only rAd-NSP4-VP7 conferred significant protection against rotavirus shedding challenge. These results suggest that the co-expression of NSP4 and VP7 in an adenovirus vector induce both humoral and cell-mediated immune responses efficiently, and provide potential efficacy for protection against rotavirus disease. It is possible to represent an efficacious subunits vaccine strategy for control of rotavirus infection and transmission. [ABSTRACT FROM AUTHOR]

Background: Several studies have indicated that prostaglandin E2 and E-prostanoid (EP) receptors play a role in the pathogenesis of chronic rhinosinusitis (CRS) in white populations. However, until now there was no report about EP receptor expression and its role in the pathophysiology of CRS in Chinese patients. Objective: To investigate the expression profiles of EP receptors, including EP1, EP2, EP3, and EP4 receptors in different Chinese patients with CRS with aspirin tolerance. Methods: Nasal biopsy specimens were obtained from 12 controls, 12 patients with CRS without nasal polyps (CRSsNP), 12 with eosinophilic CRS with nasal polyps (CRSwNP), and 16 with noneosinophilic CRSwNP. Histopathologic characteristics were observed under a light microscope. Immunostaining was used to examine tissue localization of EP receptors. Messenger RNA and protein expression of EP receptors were examined by means of quantitative RT-polymerase chain reaction and Western blot, respectively. Results: Different types of CRS presented different histopathologic hallmarks. EP receptors were expressed mainly on epithelium, glands, and infiltrating inflammatory cells in nasal tissue. In controls, patients with CRSsNP, and those with noneosinophilic CRSwNP, EP4 mRNA levels were higher than EP1, EP2, and EP3 receptors. EP2 was downexpressed, and EP1 was upexpressed in patients with eosinophilic CRSwNP. When comparing EP receptor expression among different groups, Messenger RNA and protein of EP1 receptor were significantly enhanced in eosinophilic CRSwNP, but EP2, EP3, and EP4 receptors did not show significant differences. Conclusion: EP receptor expressions present different features in healthy subjects and patients with CRS. The upregulated EP1 receptor in eosinophilic CRSwNP might be associated with excessive infiltrations of eosinophils and other inflammatory cells. The accurate role of the four EP receptors in the pathogenesis of different CRS remains to be further explored. [ABSTRACT FROM AUTHOR]

Ribosomal S6 Kinase 2 (RSK2) is a member of the p90RSK family of serine/threonine kinases, which are widely expressed and respond to many growth factors, peptide hormones, and neurotransmitters. Loss-of function mutations in the RPS6KA3 gene, which encodes the RSK2 protein, have been implicated in Coffin-Lowry Syndrome (CLS), an X-linked mental retardation disorder associated with cognitive deficits and behavioral impairments. However, the cellular and molecular mechanisms underlying this neurological disorder are not known. Recent evidence suggests that defective DNA damage signaling might be associated with neurological disorders, but the role of RSK2 in the DNA damage pathway remains to be elucidated. Here, we show that Adriamycin-induced DNA damage leads to the phosphorylation of RSK2 at Ser227 and Thr577 in the chromatin fraction, promotes RSK2 nuclear translocation, and enhances RSK2 and Atm interactions in the nuclear fraction. Furthermore, using RSK2 knockout mouse fibroblasts and RSK2-deficient cells from CLS patients, we demonstrate that ablation of RSK2 impairs the phosphorylation of Atm at Ser1981 and the phosphorylation of p53 at Ser18 (mouse) or Ser15 (human) in response to genotoxic stress. We also show that RSK2 affects p53-mediated downstream cellular events in response to DNA damage, that RSK2 knockout relieves cell cycle arrest at the G2/M phase, and that an increased number of γH2AX foci, which are associated with defects in DNA repair, are present in RSK2-deficient cells. Taken together, our findings demonstrated that RSK2 plays an important role in the DNA damage pathway that maintains genomic stability by mediating cell cycle progression and DNA repair. [ABSTRACT FROM AUTHOR]

PURPOSE: To investigate the level of miR-146a in peripheral blood mononuclear cells (PBMCs) from patients with primary Sjogren's syndrome (pSS). METHODS: PBMCs from patients with pSS were studied. The expression of miR-146a in PBMCs from 17 active pSS patients, 28 inactive pSS patients and 14 controls were determined by using real-time PCR. Statistical analysis was performed with SPSS16.0 software package. RESULTS: miR-146a level was significantly higher in active pSS patients than control subjects (P<0.05), whereas miR-146a level was not significantly different between inactive pSS patients and controls (P>0.05). miR-146a level was significantly higher in active pSS patients than in inactive pSS patients (P<0.05). CONCLUSION: It is concluded that miR-146a level is up-regulated in the PBMCs of active pSS patients. Supported in part by National Natural Science Foundation of China (81100766), Research Fund of Science and Technology Commission of Shanghai Municipality (08DZ2271100, 10411964400), Program for Innovative Research Team of Shanghai Municipal Education Commission, and Medical Foundation of Shanghai Jiao Tong University(YZ1024). [ABSTRACT FROM AUTHOR]

Purpose: EphA2 receptor tyrosine kinase is frequently overexpressed and functionally altered in a variety of human cancers. The study aimed to assess EphA2 expression and to explore its roles in squamous-cell carcinoma of the head and neck (SCCHN). Methods: EphA2 expression in 98 primary SCCHN tissue specimens was analyzed by immunohistochemistry and correlated with clinicopathological parameters. Additionally, 13 paired SCCHN tissues and 6 SCCHN cell lines were evaluated for EphA2 expression by RT-PCR and immunoblotting. Results: EphA2 overexpressed in SCCHN tissues and SCCHN cell lines. More importantly, high EphA2 expression was significantly associated with tumor site, T classification, clinical stage, recurrence, and lymph node metastasis, respectively. Patients with high EphA2 expression had both poorer disease-free survival and overall survival than patients with low EphA2 expression. Multivariate Cox regression analysis revealed that EphA2 overexpression was an independent prognostic factor for patients with SCCHN. Conclusions: These findings suggested that EphA2 may contribute to SCCHN progression and represent a novel prognostic indicator for patients with SCCHN. [ABSTRACT FROM AUTHOR]

Abstract: Objectives : The study was trying to figure out the possible role of cell-free miR-24 and miR-30d as diagnostic biomarkers for malignant effusions. Methods : A total of 110 effusion samples (28 benign and 82 malignant) were collected and cell-free total RNA was extracted. Quantitative RT-PCR was carried out to measure the expression levels of miR-24 and miR-30d, with an exogenous supplemented plant miRNA, ath-miR156a as the reference RNA. Results : Malignant pleural effusions had higher expression levels of cell-free miR-24 and miR-30d than benign effusions. In the ascites group, only miR-30d was found to be significantly up-regulated in the supernatant of effusions. Combination of cell-free miR-24 and miR-30d could discriminate malignant ascites from benign with improved potency comparing to single miR-30d. Conclusions : Cell-free miR-30d and miR-24 are potential diagnostic biomarkers for malignant and benign effusions. [Copyright &y& Elsevier]

Anthurium is an important ornamental crop in the world market and its floral scent can enhance its ornamental value. To date, studies of the components and formation mechanism of the floral scent of Anthurium are relatively few. In this study, the scent profiles of two Anthurium varieties were measured by gas chromatograph-mass spectrometer (GC-MS). There were 32 volatile organic compounds (VOCs) identified in Anthurium 'Mystral', and the most abundant compound was eucalyptol (57.5%). Extremely small amounts of VOCs were detected in Anthurium 'Alabama'. Compared with A. 'Alabama', most genes related to floral scent synthesis exhibited a higher expression in A.'Mystral', including AaDXS, AaDXR, AaMDS, AaHDS, AaTPS, AaDAHPS, AaADT2, AaPAL1, and AaPAL2. In order to produce new varieties of Anthurium with fragrance, 454 progenies of two crossbred combinations of A. 'Mystral' and A. 'Alabama' were obtained. Four F1 generation plants with different floral scent intensities were selected for further study. The major components of floral scent in the progenies were similar to that of the parental A.'Mystral' plant. The expression patterns of genes related to floral scent synthesis were consistent with the relative contents of different types of VOCs. This study revealed the profiles of volatile compounds and associated gene expression in two Anthurium cultivars and their F1 hybrids, which provided a basis for the floral scent inheritance of Anthurium andraeanum. [ABSTRACT FROM AUTHOR]

Huyang Yangkun Formula (HYF) has been prescribed for premature ovarian insufficiency (POI) for decades in the clinical setting. Little is known regarding its underlying molecular mechanism. This study was conducted to elucidate the possible mechanism of the protective potential of HYF against POI induced by the industrial chemical 4-vinylcyclohexene diepoxide (VCD) in rats. Quality control of HYF was conducted via HPLC and UPLC-MS. Female rats were injected with VCD (160 mg/kg) daily for 15 days. Then, 1.35 g/kg (low dose) or 0.235 g/kg (high dose) HYF was administered once/day for 25 days. Serum AMH, FSH, E2, ALT, AST, BUN and Cr levels were detected through ELISA and HE-stained follicles were counted in ovarian sections. Additionally, RNA-seq profiling analysis and functional assays were used to screen for differentially expressed genes and key regulators with potentially important roles associated with HYF. The ovaries of POI rats contained fewer antral and maturing follicles (p < 0.05) than those of control rats, whereas atretic follicles were increased significantly (p < 0.05), and AMH levels were significantly lower in the VCD group than in the control group (p < 0.05). These conditions showed some improvement after low- and high-dose HYF treatment. Low- and high-dose HYF increased AMH levels by 42.4% and 25.9% and decreased FSH levels by 17.5% and 24.1%, respectively, in comparison to the VCD group. The two HYF dosage groups showed significantly increased numbers of antral and maturing follicles but a reduced number of atretic follicles (p < 0.05). HYF down-regulation of JAK, Lats2 and YAP mRNA expression gene expression (p < 0.05) compared with the VCD group. HYF resulted in a strongly attenuated VCD-induced phosphorylation of JAK2 and STAT3 (p < 0.01) and YAP (p < 0.001), but induced an increase in protein levels of LATS2 (p < 0.05). Our findings demonstrated the treatment efficacy of HYF in POI rats and showed that HYF repairs the dysfunction and enhances the ovarian function of POI rats through the Hippo–JAK2/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

The water flea Daphnia magna is a keystone species in freshwater ecosystems and has been widely used as a model organism in environmental ecotoxicology. This aquatic crustacean is sensitive to environmental stressors and displays considerable plasticity in adapting to changing environmental conditions. Part of this plasticity may be due to epigenetic regulation of gene expression, including changes to DNA methylation and histone modifications. Because of the generally hypomethylated genome of this species, we hypothesized that the histone code may have an essential role in the epigenetic control and that histone modifications might be an early marker for stress. This study aims to characterize the epigenetic, transcriptional and phenotypic responses and their causal linkages in directly exposed adult (F0) Daphnia and peritoneal exposed neonates (F1) after a chronic (7-day) exposure to a sublethal concentration (10 mg/l) of 5-azacytidine, a well-studied vertebrate DNA methylation inhibitor. Exposure of the F0 generation significantly reduced the cumulative fecundity, accompanied with differential expression of genes in the one-carbon-cycle metabolic pathway. In the epigenome of the F0 generation, a decrease in global DNA methylation, but no significant changes on H3K4me3 or H3K27me3, were observed. In the F1 offspring generation, changes in gene expression, a significant reduction in global DNA methylation and changes in histone modifications were identified. The results indicate that exposure during adulthood may result in more pronounced effects on early development in the offspring generation, though interpretation of the data should be carefully done since both the exposure regime and developmental period is different in the two generations examined. The obtained results improve our understanding of crustacean epigenetics and the tools developed may promote use of epigenetic markers in hazard assessment of environmental stressors. [ABSTRACT FROM AUTHOR]

Agave species are important crassulacean acid metabolism (CAM) plants and widely cultivated in tropical areas for producing tequila spirit and fiber. The hybrid H11648 of Agave ((A. amaniensis × A. angustifolia) × A. amaniensis) is the main cultivar for fiber production in Brazil, China, and African countries. Small Auxin Up-regulated RNA (SAUR) genes have broad effect on auxin signaling-regulated plant growth and development, while only few SAUR genes have been reported in Agave species. In this study, we identified 43, 60, 24, and 21 SAUR genes with full-length coding regions in A. deserti, A. tequilana, A. H11648, and A. americana, respectively. Although phylogenetic analysis revealed that rice contained a species-specific expansion pattern of SAUR gene, no similar phenomena were observed in Agave species. The in silico expression indicated that SAUR genes had a distinct expression pattern in A. H11648 compared with other Agave species; and four SAUR genes were differentially expressed during CAM diel cycle in A. americana. Additionally, an expression analysis was conducted to estimate SAUR gene expression during different leaf developmental stages, abiotic and biotic stresses in A. H11648. Together, we first characterized the SAUR genes of Agave based on previously published transcriptome datasets and emphasized the potential functions of SAUR genes in Agave's leaf development and stress responses. The identification of which further expands our understanding on auxin signaling-regulated plant growth and development in Agave species. [ABSTRACT FROM AUTHOR]

Agave plants are important crassulacean acid metabolism (CAM) plants with multiple agricultural uses, such as being used in tequila and fiber production. Agave hybrid H11648 ((A. amaniensis Trel. and Nowell × A. angustifolia Haw.) × A. amaniensis) is the main cultivated Agave species for fiber production in large tropical areas around the world. In this study, we conducted a transcriptome analysis of A. H11648. About 49.25 million clean reads were obtained by Illumina paired-end sequencing. De novo assembly produced 148,046 unigenes with more than 40% annotated in public databases, or matched homologs in model plants. More homologous gene pairs were found in Asparagus genome than in Arabidopsis or rice, which indicated a close evolutionary relationship between Asparagus and A. H11648. CAM-related gene families were also characterized as previously reported in A. americana. We further identified 12 cellulose synthase genes (CesA) in Asparagus genome and 38 CesA sequences from A. H11648, A. americana, A. deserti and A. tequilana. The full-length CesA genes were used as references for the cloning and assembly of their homologs in other Agave species. As a result, we obtained CesA1/3/4/5/7 genes with full-length coding region in the four Agave species. Phylogenetic and expression analysis revealed a conserved evolutionary pattern, which could not explain the distinct fiber traits in different Agave species. We inferred that transcriptional regulation might be responsible for Agave fiber development. This study represents the transcriptome of A. H11648, which would expand the number of Agave genes and benefit relevant studies of Agave fiber development. [ABSTRACT FROM AUTHOR]

[Display omitted] • UBE4B overexpression inhibits the apoptosis of SH-SY5Y cells via the AKT pathway. • Syringaresinol promotes the repair of spinal cord injury in rats via UBE4B overexpression, increases AKT phosphorylation, and reduces neuronal apoptosis. Spinal cord injury (SCI) is a serious traumatic disease with no effective treatment. This study aimed to explore the therapeutic effect of syringaresinol on SCI. First, the potential targets and associated signaling pathways of syringaresinol were predicted by bioinformatics analysis and molecular docking. Second, MTT was employed to evaluate cell proliferation rate, Western blot was performed to detect protein expression, RT-qPCR was conducted to detect mRNA expression levels, flow cytometry and 5-ethynyl-2′-deoxyuridine (EDU) staining were used to determine cell apoptosis, and immunofluorescence and immunohistochemistry were used to estimate the expression of RNA binding fox-1 homolog 3 and clipped caspase 3. Basso–Beattie–Bresnahan scores and inclined plate tests were conducted to analyze hindlimb locomotor function. Results showed that syringaresinol could inhibit the apoptosis of glutamate-treated SHSY5Y cells by upregulating the expression of ubiquitination factor E4B (UBE4B) and activating the AKT serine/threonine kinase (AKT) signaling pathway. This effect can be rescued by UBE4B knockdown or AKT pathway inhibition. Syringaresinol remarkably improved locomotor function and increased neuronal survival in SCI rats. Our results suggested that syringaresinol could promote locomotor functional recovery by reducing neuronal apoptosis by activating the UBE4B/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

We aim to identify the potential genes and signaling pathways associated with the nasopharyngeal carcinoma (NPC) prognosis using Weighted Gene Co-Expression Network Analysis (WGCNA). Gene Expression Omnibus (GEO) query was utilized to download two NPC mRNA microarray data. WGCNA was conducted on differentially expressed genes (DEGs) to obtain tumor-associated gene modules. Genes in core modules were intersected with DEGs for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. GSE102349 dataset was devoted to identifying prognostic hub genes by survival analysis and the results were confirmed by quantitative polymerase chain reaction (qPCR). Co-expression networks were built, and we detected 12 gene modules. The Brown module and Magenta module were extremely associated with NPC samples. GO functional analysis and KEGG pathway analysis was carried out to the genes in the Brown and Magenta modules. Our data indicated that DEGs in Brown module and Magenta module were correlated with the biological regulation, metabolic process, reproduction, and cellular proliferation. Twenty-six hub genes were obtained and were considered to be closely related to NPC. GSE102349 dataset was devoted to identifying prognostic hub genes by survival analysis. The expression of IL33, MPP3 and SLC16A7 in GSE102349 dataset was significantly correlated with the progression-free survival (PFS). The results of qPCR indicated a strong correlation between SLC16A7 expression and the overall survival (OS). WGCNA contributed to the detection of gene modules and identification of hub genes and crucial genes. These crucial genes might be potential targets for pharmaceutic therapies with potential clinical significance. [ABSTRACT FROM AUTHOR]

The teosinte branched1, cycloidea, and proliferating cell factor family (TCP) proteins are plant-specific transcription factors that play crucial roles in regulating plant development and stress responses. However, information on the TCP family in Chrysanthemum indicum is limited. In this study, we identified 35 CiTCP family members and characterized their structural features, phylogenetic relationships, and expression patterns across various tissues and in response to different stress treatments. Phylogenetic analysis classified the CiTCP family members into three distinct subfamilies: PCF, CYC/TB1, and CIN. This classification was corroborated by the exon-intron structures and conserved motifs. Expression level analysis demonstrated that PCF type genes were broadly expressed in different tissues, while most CYC/TB1 and CIN type genes exhibited predominant expression in specific tissues. Most CiTCPs responded to abiotic stress treatments, with their response to salt stress occurring primarily within one hour of exposure. Notably, Arabidopsis plants overexpressing CiTCP23 showed insensitivity to salt stress, as evidenced by higher germination rates, longer seedling roots, and significantly improved salt stress resistance compared to wild-type (WT) plants. Quantitative RT-PCR (qRT-PCR) analysis showed that several salt-responsive genes, such as AtSOS1 , AtSOS2 , AtSOS3 , AtABF3 , AtCOR15A, AtADH, AtCBF4, AtRD29A , and AtRD29B , were significantly upregulated in CiTCP23 overexpressing plants. Collectively, these findings suggest that CiTCP23 positively regulates salt tolerance in Arabidopsis by modulating the expression of key genes involved in the salt response. • A total of 35 CiTCPs were identified in chrysanthemum, and their key characteristics were analyzed. • The expression patterns of CiTCP genes were examined across different tissues and under various stress treatments. • The role of CiTCP23 in the response to salt stress was preliminary investigated. [ABSTRACT FROM AUTHOR]

Tripartite motif-containing protein 29 (TRIM29) is a member of TRIM family protein which has been reported to play a role in the progress of inflammatory and cancer diseases. However, its specific role in gastric cancer (GC) has yet to be fully understood. Here, we investigated the expression of TRIM29 in gastric cancer and its functions in the antitumor immunity. TRIM29 expression was lower in tumor tissues than that in paired normal tissues. Lower expression of TRIM29 was related to aberrant hypermethylation of CpG islands in TRIM29 gene. Comprehensive proteomics and immunoprecipitation analyses identified IGF2BP1 as TRIM29 interactors. TRIM29 interacted with IGF2BP1 and induced its ubiquitination at Lys440 and Lys450 site by K48-mediated linkage for protein degradation. IGF2BP1 promoted PD-L1 mRNA stability and expression in a 3′UTR and m6A-dependent manner. Functionally, TRIM29 enhanced antitumor T-cell immunity in gastric cancer dependent on the IGF2BP1/PD-L1 axis in vivo and in vitro. Clinical correlation analysis revealed that TRIM29 expression in patient samples was associated with CD8+ immune cell infiltration in the GC microenvironment and the overall survival rates of GC patients. Our findings revealed a crucial role of TRIM29 in regulating the antitumor T-cell immunity in GC. We also suggested that the TRIM29/IGF2BP1/PD-L1 axis could be used as a diagnostic and prognostic marker of gastric cancer and a promising target for GC immunotherapy. In the study, "TRIM29 promotes antitumor immunity through enhancing IGF2BP1 ubiquitination and subsequent PD-L1 downregulation in gastric cancer," we explored for the first time the role of the E3 ubiquitin ligase TRIM29 in antitumor T-cell immunity and showed that this role is dependent on the IGF2BP1/PD-L1 signaling axis. • Through a gastric cancer cell-T cell co-culture model, we found that TRIM29 enhanced anti-tumor T cell immunity. Further exploring its molecular mechanism, we confirmed that TRIM29 induces K48-linked ubiquitination degradation of the IGF2BP1 K440 and K450 sites through its C-terminal structural domain binding to the KH3/4 structural domain of IGF2BP1, which further mediates the effect of IGF2BP1 in a 3′UTR- and m6A-dependent manner on the PD-L1 mRNA stability and expression. • In animal models with different immune systems, we also found that specific antagonism of TRIM29 could synergize with PD-1 monoclonal antibody to exert anti-tumor effects, and clinical samples also verified that the expression of TRIM29 in gastric cancer was significantly correlated with the infiltration of CD8+ T-cells and the overall survival of gastric cancer patients. • This study provides new ideas for the immunotherapy of gastric cancer, and TRIM29 may be a potential prognostic predictor and therapeutic target for gastric cancer patients. The expression of TRIM29 can improve the prediction accuracy of PD-L1 histochemical scores, a predictive target for the efficacy of immunotherapy in gastric cancer, and the combination of TRIM29 specific antagonist and PD-1 monoclonal antibody can enhance the efficacy of immunotherapy for gastric cancer by increasing the activity of CD8+ T-cells. The combination of TRIM29-specific antagonist and PD-1 monoclonal antibody can improve the immunotherapeutic effect of gastric cancer by enhancing CD8+ T cell activity. [ABSTRACT FROM AUTHOR]

Among aquatic organisms, invertebrate species such as the freshwater crustacean Daphnia magna are believed to be sensitive to gamma radiation, although information on responses at the individual, biochemical and molecular level is scarce. Following gamma radiation exposure, biological effects are attributed to the formation of free radicals, formation of reactive oxygen species (ROS) and subsequently oxidative damage to lipids, proteins and DNA in exposed organisms. Thus, in the present study, effects and modes of action (MoA) have been investigated in D . magna exposed to gamma radiation (dose rates: 0.41, 1.1, 4.3, 10.7, 42.9 and 106 mGy/h) after short-term exposure (24 and 48 h). Several individual, cellular and molecular endpoints were addressed, such as ROS formation, lipid peroxidation, DNA damage and global transcriptional changes. The results showed that oxidative stress is one of the main toxic effects in gamma radiation exposed D . magna , mediated by the dose-dependent increase in ROS formation and consequently oxidative damage to lipids and DNA over time. Global transcriptional analysis verified oxidative stress as one of the main MoA of gamma radiation at high dose rates, and identified a number of additional MoAs that may be of toxicological relevance. The present study confirmed that acute exposure to gamma radiation caused a range of cellular and molecular effects in D . magna exposed to intermediate dose rates, and highlights the need for assessing effects at longer and more environmentally relevant exposure durations in future studies. [ABSTRACT FROM AUTHOR]

Despite many advances in treatment over the past few years, the poor 5-year survival rate and high recurrence rate of gastric cancer (GC) remain unsatisfactory. As the most abundant epigenetic modification in the eukaryotic mRNA, N6-methyladenosine (m6A) methylation participates in tumor progression and tissue development. During tumor progression, DNA damage repair mechanisms can be reprogrammed to give new growth advantages on tumor clones whose genomic integrity is disturbed. Here we detected the elevated SUV39H2 expression in GC tissues and cell lines. Functionally, SUV39H2 promoted GC proliferation and inhibited apoptosis in vitro and in vivo. Mechanistically, METTL3-mediated m6A modification promotes mRNA stability of SUV39H2 in an IGF2BP2 dependent manner, resulting in upregulated mRNA expression of SUV39H2. As a histone methyltransferase, SUV39H2 was verified to increase the phosphorylation level of ATM through transcriptional repression of DUSP6, thereby promoting HRR and ultimately inhibiting GC chemosensitivity to cisplatin. Collectively, these results indicate the specific mechanism of m6A-modified SUV39H2 as a histone methyltransferase promoting HRR to inhibit the chemosensitivity of GC. SUV39H2 is expected to become a key target in the precision targeted therapy of GC. • METTL3-mediated m6A methylation promotes SUV39H2 mRNA stability in an IGF2BP2-dependent manner. • SUV39H2 transcriptionally represses DUSP6 expression by catalyzing its H3K9 tri-methylation. • SUV39H2 promotes homologous recombination through DUSP6/ATM axis and inhibits chemosensitivity of gastric cancer. [ABSTRACT FROM AUTHOR]

• Investigating the underlying molecular mechanisms of Cutaneous Leishmaniasis. • Screening for diagnostic markers related to immune cells by bioinformatics analysis. • Uncovering the important roles of immune response in Cutaneous Leishmaniasis. Cutaneous Leishmaniasis (CL) is the most common clinical form of leishmaniasis. Despite its low mortality, CL deserves further attention because its pathogenesis is currently no well-known or well-researched. We downloaded the gene expression datasets of GSE55664 and GSE63931 with respect to leishmaniasis from the Gene Expression Synthesis (GEO) database. Additionally, the differentially expressed genes (DEGs) in the infection and control groups were identified by packages of R software. The Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) pathway were utilized for the biological functional analysis. Subsequently, we identified the top ten hub genes from protein-protein interaction (PPI) networks based on STRING and Cytoscape software. The hub genes were validated in GraphPad Prism 8.0 using the GSE162760 dataset. Further, CIBERSORT was used to evaluate the immune cell infiltration proportions between the CL infection samples and the control samples based on the GSE43880 and GSE55664 datasets. The enrichment analysis revealed that DEGs were significantly involved in cell-mediated immune responses, such as leukocyte cell-cell adhesion and T-cell activation. STAT1, CCR7, CCR2, and CXCL10 were identified as hub genes with statistical significance. These hub genes showed close correlations with various immune cells, such as M1 cells and CD4-activated memory T-cells. In our research, we used bioinformatics analysis to identify some molecular biomarkers and significant pathways in CL infection. These hub genes may provide new options for future diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Abstract: RNA activation is a promising discovery that promoter-targeted double-stranded small RNAs, termed small activating RNAs (saRNAs), can induce gene expression, which represents a novel approach to gene over-expression without traditional vector-based systems. PAWR is a tumor suppressing gene essential for apoptosis and a cancer-selective target for cancer therapeutics. Here our study identified synthetic saRNAs that could activate the expression of PAWR in human cancer cells. Functional analysis of PAWR induction revealed that saRNA treatment induced growth inhibition and apoptosis of cancer cells, and predictably modulated the expression of known downstream target gene Bcl-2. New functional saRNAs can also be harvested by one or two-base shifting of the original target sites. Chromatin immunoprecipitation assays indicated that activation of PAWR is accompanied by reduced dimethylation at histone H3K9 and increased dimethylation at histone H3K4. Moreover, the existence of transcripts in PAWR promoter was detected but its relationship with RNA activation needs more lucubration. These data have enlarged the gene pool of RNAa and hold great promise as an alternative for PAWR-targeted therapeutics. [Copyright &y& Elsevier]

Helicobacter pylori is a pathogen involved in several gastroduodenal diseases, whose infection mechanisms have not been completely confirmed. To study the specific mechanism of gastropathy caused by H. pylori , we analyzed the gene microarray of gastric mucosa and gastric cells infected by H. pylori through bioinformatics analysis. We downloaded GSE60427 and GSE74492 from the Gene Expression Omnibus (GEO) database, screened differentially expressed genes (DEGs), and identified the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) through R software. The Search Tool for the Retrieval of Interacting Genes (STRING) was applied to establish a protein–protein interaction (PPI) network and Cytoscape was used to identify the top seven hub genes. Besides, we also constructed the gene–microRNA(gene–miRNA) interaction through the miRTarBase v8.0 database by using the NetworkAnalyst tool. One hundred and fifteen DEGs were screened out, with 54 genes up-regulated and 61 genes down-regulated, among which seven hub genes, including "IGF1R," "APOE," "IRS1," "ATF3," "LCN2," "IL2RG," and "PI3," were considered as the main regulatory proteins in gastric cells when infected by H. pylori. In this study, hub genes and related signal enrichment pathways of gastropathy infected by H. pylori were analyzed through bioinformatics analysis based on the GSE60427 and GSE74492 datasets. • Bioinformatics revealed the signaling pathways related to Helicobacter pylori infection in gastric cells. • Bioinformatics revealed the main differential genes of Helicobacter pylori infection in gastric cells. • The study first found that IGF1R was down regulated in Helicobacter pylori with proper conjecture. [ABSTRACT FROM AUTHOR]