EZH2 is a potential prognostic predictor of glioma.

The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. To evaluate the prognostic value of EZH2 in glioma, we analysed gene expression data and corresponding clinicopathological information from the Chinese Glioma Genome Atlas, the Cancer Genome Atlas and GTEx. Increased expression of EZH2 was significantly associated with clinicopathologic characteristics and overall survival as evaluated by univariate and multivariate Cox regression. Gene Set Enrichment Analysis revealed an association of EZH2 expression with the cell cycle, DNA replication, mismatch repair, p53 signalling and pyrimidine metabolism. We constructed a nomogram for prognosis prediction with EZH2, clinicopathologic variables and significantly correlated genes. EZH2 was demonstrated to be significantly associated with several immune checkpoints and tumour-infiltrating lymphocytes. Furthermore, the ESTIMATE and Timer Database scores indicated correlation of EZH2 expression with a more immunosuppressive microenvironment for glioblastoma than for low grade glioma. Overall, our study demonstrates that expression of EZH2 is a potential prognostic molecular marker of poor survival in glioma and identifies signalling pathways and immune checkpoints regulated by EHZ2, suggesting a direction for future application of immune therapy in glioma.

Histamine 2/3 receptor agonists alleviate perioperative neurocognitive disorders by inhibiting microglia activation through the PI3K/AKT/FoxO1 pathway in aged rats.

BACKGROUND: Microglia, the principal sentinel immune cells of the central nervous system (CNS), play an extensively vital role in neuroinflammation and perioperative neurocognitive disorders (PND). Histamine, a potent mediator of inflammation, can both promote and prevent microglia-related neuroinflammation by activating different histamine receptors. Rat microglia express four histamine receptors (H1R, H2R, H3R, and H4R), among which the histamine 1 and 4 receptors can promote microglia activation, whereas the role and cellular mechanism of the histamine 2 and 3 receptors have not been elucidated. Therefore, we evaluated the effects and potential cellular mechanisms of histamine 2/3 receptors in microglia-mediated inflammation and PND. METHODS: This study investigated the role of histamine 2/3 receptors in microglia-induced inflammation and PND both in vivo and in vitro. In the in vivo experiments, rats were injected with histamine 2/3 receptor agonists in the right lateral ventricle and were then subjected to exploratory laparotomy. In the in vitro experiments, primary microglia were pretreated with histamine 2/3 receptor agonists before stimulation with lipopolysaccharide (LPS). Cognitive function, microglia activation, proinflammatory cytokine production, NF-κb expression, M1/M2 phenotypes, cell migration, and Toll-like receptor-4 (TLR4) expression were assessed. RESULTS: In our study, the histamine 2/3 receptor agonists inhibited exploratory laparotomy- or LPS-induced cognitive decline, microglia activation, proinflammatory cytokine production, NF-κb expression, M1/M2 phenotype transformation, cell migration, and TLR4 expression through the PI3K/AKT/FoxO1 pathway. CONCLUSION: Based on our findings, we conclude that histamine 2/3 receptors ameliorate PND by inhibiting microglia activation through the PI3K/AKT/FoxO1 pathway. Our results highlight histamine 2/3 receptors as potential therapeutic targets to treat neurological conditions associated with PND.

Effect of tryptase on mouse brain microvascular endothelial cells via protease-activated receptor 2.

BACKGROUND: Mast cells (MCs), the 'first responders' in brain injury, are able to disrupt the blood-brain barrier (BBB), but the underlying mechanism is not well understood. Tryptase is the most abundant MC secretory product. Protease-activated receptor 2 (PAR-2) has been identified as a specific receptor for tryptase, which is abundantly expressed in brain microvascular endothelial cells. The BBB comprises brain microvascular endothelial cells that display specialised molecular properties essential for BBB function and integrity. Therefore, the purpose of the present study was to investigate the effects of tryptase on mouse brain microvascular endothelial cell line bEnd3 and its potential mechanisms of action. METHODS: Induction of mouse brain microvascular endothelial cell activation by tryptase was examined. Then, mouse brain microvascular endothelial cells were pretreated with a PAR-2 antagonist and stimulated with tryptase. Cellular activation, proinflammatory cytokine production, expression of PAR-2, Toll-like receptors (TLRs) and mitogen-activated protein kinases (MAPK), nuclear factor kappa B (NF-kappa B) phosphorylation were assessed. RESULTS: Tryptase upregulated the production of VCAM-1, MMPs (MMP9 and MMP2), TLR4 and TNF-α and downregulated the expression of the tight junction proteins occludin and claudin-5 in mouse brain microvascular endothelial cell. Among the MAPK and NF-kappa B pathway, ERK and NF-kappa B were activated by tryptase. All of these effects could be eliminated by the PAR-2 inhibitor. CONCLUSION: Based on our findings, we conclude that tryptase can trigger brain microvascular endothelial cell activation and proinflammatory mediator release. These findings may further clarify the involvement and mechanism of tryptase in BBB disruption.

Multifunctional role of oral bacteria in the progression of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders of varying severity, ultimately leading to fibrosis. This spectrum primarily consists of NAFL and non-alcoholic steatohepatitis. The pathogenesis of NAFLD is closely associated with disturbances in the gut microbiota and impairment of the intestinal barrier. Non-gut commensal flora, particularly bacteria, play a pivotal role in the progression of NAFLD. Notably, Porphyromonas gingivalis, a principal bacterium involved in periodontitis, is known to facilitate lipid accumulation, augment immune responses, and induce insulin resistance, thereby exacerbating fibrosis in cases of periodontitis-associated NAFLD. The influence of oral microbiota on NAFLD via the "oral-gut-liver" axis is gaining recognition, offering a novel perspective for NAFLD management through microbial imbalance correction. This review endeavors to encapsulate the intricate roles of oral bacteria in NAFLD and explore underlying mechanisms, emphasizing microbial control strategies as a viable therapeutic avenue for NAFLD.

Identification of chitinase genes and roles in the larval-pupal transition of Leptinotarsa decemlineata.

BACKGROUND: Insect chitinases play crucial roles in degrading chitin in the extracellular matrix, affecting insect development and molting. However, our understanding of the specific functions of various chitinases in Leptinotarsa decemlineata is limited, hindering the deployment of novel gene-targeting technologies as pest management strategies. RESULTS: We identified and characterized 19 full-length complementary DNA (cDNA) sequences of chitinase genes (LdChts) in Leptinotarsa decemlineata. Despite having varying domain architectures, all these chitinases contained at least one chitinase catalytic domain. Phylogenetic analysis classified the chitinase proteins into ten distinct clusters (groups I-X). Expression profiles showed the highest expression in chitin-rich tissues or during specific developmental stages from the larva-to-pupa transition. Gene-specific RNA interference (RNAi) experiments provided valuable insight into chitinase gene function. Silencing of group II LdCht10 prevented larval-larval molting, larval-prepupal, and prepupal-pupal processes. Moreover, our study revealed that LdCht5, LdCht2, LdCht11, LdCht1, and LdCht3 from groups I and VII-X were specifically essential for the transition from prepupal to pupal stage, whereas LdIDGF2 from group V was necessary for the larval-prepupal metamorphic process. The chitinase gene LdCht7 from group III and LdIDGF4 from group V were involved in both the larva-to-prepupa and the prepupa-to-pupa shift. Additionally, our findings also shed light on the exclusive expression of nine chitinase genes within group IV in the digestive system, suggesting their potential role in regulating larval body weight and larva-to-pupa transition. CONCLUSION: Our results provide a comprehensive understanding of the functional specialization of chitinase genes during the molting process of various stages and identify potential targets for RNAi-based management of Leptinotarsa decemlineata. © 2023 Society of Chemical Industry.

SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence.

Thoracic aortic aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments. The current understanding of the pathogenesis of TAA is still limited, especially for sporadic TAAs without known genetic mutation. Sirtuin 6 (SIRT6) expression was significantly decreased in the tunica media of sporadic human TAA tissues. Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture, reduced survival, and increased vascular inflammation and senescence after angiotensin II infusion. Transcriptome analysis identified interleukin (IL)-1ß as a pivotal target of SIRT6, and increased IL-1ß levels correlated with vascular inflammation and senescence in human and mouse TAA samples. Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation. Genetic knockout of Il1b or pharmacological inhibition of IL-1ß signaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation, senescence, TAA formation and survival in mice. The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence, providing insight into potential epigenetic strategies for TAA treatment.

Gliosarcoma: The Distinct Genomic Alterations Identified by Comprehensive Analysis of Copy Number Variations.

Gliosarcoma (GSM), a histologic variant of glioblastoma (GBM), carries a poor prognosis with less than one year of median survival. Though GSM is similar with GBM in most clinical and pathological symptoms, GBM has unique molecular and histological features. However, as the rarity of GSM samples, the genetic information of this tumor is still lacking. Here, we take a comprehensive analysis of DNA copy number variations (CNV) in GBM and GSM. Whole genome sequencing was performed on 21 cases of GBM and 15 cases of GSM. CNVKIT is used for CNV calling. Our data showed that chromosomes 7, 8, 9, and 10 were the regions where CNV frequently happened in both GBM and GSM. There was a distinct CNV signal in chromosome 2 especially in GSM. The pathway enrichment of genes with CNV was suggested that the GBM and GSM shared the similar mechanism of tumor development. However, the CNV of some screened genes displayed a disparate form between GBM and GSM, such as AMP, BEND2, HDAC6, FOXP3, ZBTB33, TFE3, and VEGFD. It meant that GSM was a distinct subgroup possessing typical biomarkers. The pathways and copy number alterations detected in this study may represent key drivers in gliosarcoma oncogenesis and may provide a starting point toward targeted oncologic analysis with therapeutic potential.

Multiphase convolutional dense network for the classification of focal liver lesions on dynamic contrast-enhanced computed tomography.

BACKGROUND: The accurate classification of focal liver lesions (FLLs) is essential to properly guide treatment options and predict prognosis. Dynamic contrast-enhanced computed tomography (DCE-CT) is still the cornerstone in the exact classification of FLLs due to its noninvasive nature, high scanning speed, and high-density resolution. Since their recent development, convolutional neural network-based deep learning techniques has been recognized to have high potential for image recognition tasks. AIM: To develop and evaluate an automated multiphase convolutional dense network (MP-CDN) to classify FLLs on multiphase CT. METHODS: A total of 517 FLLs scanned on a 320-detector CT scanner using a four-phase DCE-CT imaging protocol (including precontrast phase, arterial phase, portal venous phase, and delayed phase) from 2012 to 2017 were retrospectively enrolled. FLLs were classified into four categories: Category A, hepatocellular carcinoma (HCC); category B, liver metastases; category C, benign non-inflammatory FLLs including hemangiomas, focal nodular hyperplasias and adenomas; and category D, hepatic abscesses. Each category was split into a training set and test set in an approximate 8:2 ratio. An MP-CDN classifier with a sequential input of the four-phase CT images was developed to automatically classify FLLs. The classification performance of the model was evaluated on the test set; the accuracy and specificity were calculated from the confusion matrix, and the area under the receiver operating characteristic curve (AUC) was calculated from the SoftMax probability outputted from the last layer of the MP-CDN. RESULTS: A total of 410 FLLs were used for training and 107 FLLs were used for testing. The mean classification accuracy of the test set was 81.3% (87/107). The accuracy/specificity of distinguishing each category from the others were 0.916/0.964, 0.925/0.905, 0.860/0.918, and 0.925/0.963 for HCC, metastases, benign non-inflammatory FLLs, and abscesses on the test set, respectively. The AUC (95% confidence interval) for differentiating each category from the others was 0.92 (0.837-0.992), 0.99 (0.967-1.00), 0.88 (0.795-0.955) and 0.96 (0.914-0.996) for HCC, metastases, benign non-inflammatory FLLs, and abscesses on the test set, respectively. CONCLUSION: MP-CDN accurately classified FLLs detected on four-phase CT as HCC, metastases, benign non-inflammatory FLLs and hepatic abscesses and may assist radiologists in identifying the different types of FLLs.

Stereoselective hydrogenation on the exocyclic and conjugated double bond of sesquiterpene lactones by Aspergillus versicolor D-1.

Aspergillus versicolor D-1 was employed to convert dehydrocostuslactone (1) and 3-hydroxy-1(10),3,11(13)-guaiatriene-12,6-olide-2-one (5) stereoselectively. The reactions occurring were specific hydrogenation on the exocyclic alpha,beta-double bond of sesquiterpene lactones with excellent conversion. Products were identified by the analysis of their spectra such as UV, IR, MS, (1)H, (13)C NMR, and NOESY, and the structure of one new compound was elucidated. The characteristic of the stereoselective hydrogenation was also discussed and suggested.

Prognostic value of metabolic tumour volume and total lesion glycolysis measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography in small cell lung cancer: A systematic review and meta-analysis.

The aim of this study was to evaluate the prognostic value of metabolic tumour volume (MTV) and total lesion glycolysis (TLG) for small cell lung cancer (SCLC). MEDLINE, EMBASE and Cochrane Library databases were systematically searched. The pooled hazard ratio (HR) was used to measure the influence of MTV and TLG on survival. The subgroup analysis according to VALSG stage and the measured extent of MTV was performed. Patients with high MTV values experienced a significantly poorer prognosis with a HR of 2.42 (95% CI 1.46-4.03) for overall survival (OS) and a HR of 2.78 (95% CI 1.39-5.53) for progression-free survival (PFS) from the random effect model, and the pooled HR from the fixed effect model was 2.10 (95% CI 1.77-2.50) for OS and 2.27 (95% CI 1.83-2.81) for PFS. Patients with high TLG experienced a poorer prognosis with a HR of 1.61 (95% CI: 1.24-2.07) for OS from the random effect model, and the pooled HR from the fixed effect model was 1.64 (95% CI 1.37-1.96). Heterogeneity among studies was high for MTV in both OS and PFS meta-analyses (I2  = 87% and 88% respectively). After removing one outlier study the heterogeneity was substantially reduced (I2  = 0%) and the pooled HR for the effect of MTV on OS was 1.80 (1.51-2.16, P < 0.00001), and on PFS it was 1.86 (1.49-2.33, P < 0.00001), using either the fixed or random effects model. High MTV is associated with a significantly poorer prognosis OS and PFS, and high TLG is associated with a significantly poorer prognosis regarding OS for SCLC.

[Characteristics of a novel human testis-specific gene, HSD-9, and its encoding protein].

OBJECTIVE: To study the characteristics of a novel human testis-specific gene, HSD-9, and its encoding protein. METHODS: HSD-9 was a novel gene from a human germ cells-specific ESTs library established in our laboratory. We used an electronic cloning method to obtain HSD-9 gene, and analyzed the characteristics of this novel gene and encoding product by bioinformatics methods, detected its expressing profile using a Northern blot assay, prepared specific rabbit polyclonal antibodies against HSD-9 protein, observed the localization of this protein in the germ cells and some somatic cells with confocal microscopy. RESULTS: HSD-9 was expressed in human testes, and its rat homolog was found in the varying germ cells. HSD-9 protein could partly be colocalized with clathrin. CONCLUSIONS: HSD-9 is specific in human testes, and the expression pattern of its encoding product is similar to those of some endocytosis proteins. It is speculated that HSD-9 protein may function in the endocytosis.

[Compositions, Sources and Health Risks of Polycyclic Aromatic Hydrocarbons (PAHs) in Surface Dusts from Driving-schools in a City of Henan Province, China].

The contamination of polycyclic aromatic hydrocarbons (PAHs) in surface dusts attracts great attentions due to their properties of threatening human health. Twenty-nine surface dust samples were collected from driving-schools in a city of Henan. Concentrations of 16 priority PAHs were analyzed by gas chromatography-mass spectrometry (GC-MS). The health risks exposed to dust PAHs for three different scenarios (working for 5 a, 10 a and 20 a in driving-school) were estimated by the health risk assessment model (ILCRs). Source identification was analyzed by diagnostic ratio, composition analysis, and principal component analysis. The results showed that concentrations of the ∑PAHs in dusts ranged from 198.21 to 3400.89 µg·kg-1, with a mean of 908.72 µg·kg-1. Among individual PAHs, the contents of naphthalene (Nap), phenanthrene (Phe), anthracene (Ant) and fluoranthene (Flu) were higher, and the content of dibenzo[a, h]anthracene (DBA) was the lowest. The dominant compounds were 2-3 ring PAHs, which accounted for 55.79%, while the 4-6 ring PAHs accounted for 44.21%. The health risks exposed to PAHs in dust in three different scenarios were 9.27×10-8, 1.85×10-7, and 3.71×10-7 respectively; only sample J11 was with potential health risk in scenario 3, and the other samples were all without risks. Average daily doses by dermal contact of dust particles for the PAHs was the main exposure way. PAHs in dusts of driving-school were mainly originated from the combustion of fossil fuels and mixture combustion. The major sources of dust PAHs in farmland area driving-schools were natural gas and diesel combustion (56.44%), coal combustion (26.55%), gasoline combustion and the leakage (17.01%); dust PAHs in industrial area driving-schools were from mixture combustion (76.26%), gasoline combustion and the leakage (22.85%), coking and coal combustion (0.89%); and dust PAHs in mixed area driving-schools were from coal combustion (45.57%), natural gas and diesel combustion (45.41%), gasoline combustion and the leakage (9.02%). The concentrations and health risks of heavy metals in dusts were closely related to the surroundings around driving-schools and the previous land use status.

[Analysis of the degrading products of carbofuran by Sphingomonas sp. with GC/MS and GC/FTIR].

In different degrading phases, the degrading products of carbofuran by CDS-1(Sphingomonas sp. ) were extracted by acetone. According to the analysis of gas chromatography/mass spectrometry (GC/MS), carbofuran-7-phenol was identified as the initial degrading product, and an unknown metabolite with molecular weight of 182 was determined as 2-hydroxyl-3-tertiarybutylalcohol-phenol, which was the next degrading product of carbofuran-7-phenol. According to the analysis of GC/MS and gas chromatography/Fourier transform infrared spectrum (GC/FTIR), the main component of the compounds that appeared in the final phase of degradation which could produce volatile pungent odor, was identified as carvone.

Prognostic value of tissue inhibitor of metalloproteinase-2 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Tissue inhibitor of metalloproteinase-2 (TIMP-2) is a small secretory glycoprotein with anti-matrix metalloproteinase activity. Data on the value of TIMP-2 as a prognostic factor in non-small cell lung cancer (NSCLC) are discordant and remain controversial. A systematic review and meta-analysis was performed to explore this issue. METHODS: We identified the relevant literature by searching the PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang Data databases (search terms: "non-small cell lung cancer" or "NSCLC" or "Lung Carcinoma, Non-Small-Cell", "Tissue Inhibitor of Metalloproteinase-2" or "TIMP-2", and "prognosis" or "prognostic" or "survive") for updates prior to March 1, 2014. The pooled hazard ratio (HR) of overall survival with a 95% confidence interval (95% CI) was used to evaluate the strength of the association between positive TIMP-2 expression and survival in patients with NSCLC. RESULTS: We included 12 studies in our systematic review; five studies involving 399 patients with NSCLC were meta-analyzed. The pooled HR of all included patients was 0.57 (95% CI: 0.43-0.77), and the HRs of subgroup analysis according to stage (I-IV), testing method (immunohistochemistry) and high TIMP-2 expression percentage (<50%) were 0.63 (95% CI: 0.43-0.92), 0.55 (95% CI: 0.41-0.74), and 0.50 (95% CI: 0.28-0.88), respectively. These data suggested that high TIMP-2 expression is associated with favorable prognosis in NSCLC. The meta-analysis did not reveal heterogeneity or publication bias. CONCLUSIONS: TIMP-2 expression indicates favorable prognosis in patients with NSCLC; as a protective factor, it could help predict outcome and may guide clinical therapy in the future.

The effectiveness of multimedia visual perceptual training groups for the preschool children with developmental delay.

This study compared the effectiveness of three approaches to improving visual perception among preschool children 4-6 years old with developmental delays: multimedia visual perceptual group training, multimedia visual perceptual individual training, and paper visual perceptual group training. A control group received no special training. This study employed a pretest-posttest control group of true experimental design. A total of 64 children 4-6 years old with developmental delays were randomized into four groups: (1) multimedia visual perceptual group training (15 subjects); (2) multimedia visual perceptual individual training group (15 subjects); paper visual perceptual group training (19 subjects); and (4) a control group (15 subjects) with no visual perceptual training. Forty minute training sessions were conducted once a week for 14 weeks. The Test of Visual Perception Skills, third edition, was used to evaluate the effectiveness of the intervention. Paired-samples t-test showed significant differences pre- and post-test among the three groups, but no significant difference was found between the pre-test and post-test scores among the control group. ANOVA results showed significant differences in improvement levels among the four study groups. Scheffe post hoc test results showed significant differences between: group 1 and group 2; group 1 and group 3; group 1 and the control group; and group 2 and the control group. No significant differences were reported between group 2 and group 3, and group 3 and the control group. The results showed all three therapeutic programs produced significant differences between pretest and posttest scores. The training effect on the multimedia visual perceptual group program and the individual program was greater than the developmental effect Both the multimedia visual perceptual group training program and the multimedia visual perceptual individual training program produced significant effects on visual perception. The multimedia visual perceptual group training program was more effective for improving visual perception than was multimedia visual perceptual individual training program. The multimedia visual perceptual group training program was more effective than was the paper visual perceptual group training program.