Identification and validation of an immune-relevant risk signature predicting survival outcome and immune infiltration in uveal melanoma.

PURPOSE: The current study aimed to reveal a novel immune-related signature to evaluate immune infiltration status and the survival outcome for patients with uveal melanoma (UM). METHODS: Based on 80 UM samples from the Cancer Genome Atlas, the transcriptome gene expression and clinical characteristics were analyzed to identify immune-related genes that contributed most to prognosis based on LASSO Cox regression. By combining the gene expression level with the corresponding regression coefficient, a risk score was calculated and all patients were divided into high- and low-risk groups. Survival, tumor-infiltrating immune cell abundance, dysregulated signaling pathways, immunophenoscore and tumor mutation burden were compared between two groups. Validation of the risk signature was performed in GSE22138 and GSE44295 cohort. For evaluating the immunotherapy efficacy, 348 advanced urothelial cancer patients treated with immune checkpoint inhibitor (ICI) were used for external validation. RESULTS: Nine immune-related prognostic genes were identified under the LASSO Cox regression in the TCGA cohort; they are ACKR2, AREG, CCL5, CLEC11A, IGKV1-33, IL36B, NROB1, TRAV8-4 and TRBV28. Better prognosis, elevated immune cell infiltration, decreased immune-suppressive cell infiltration, immune response-related pathways and higher immunophenoscore were found in low-risk patients, with better ICI treatment response rate. CONCLUSION: The identified immune risk signature was demonstrated to be associated with the favorable immune infiltration, prognosis and immunotherapeutic efficacy, which may provide clues for survival evaluation and immune treatment.

F-box protein 17 promotes glioma progression by regulating glycolysis pathway.

F-box protein 17 (FBXO17) is associated with high-grade glioma and acted as a promotor of glioma development. This study investigated the effect and underlying pathway of FBXO17 on glioma. The Cancer Genome Atlas database was applied to analyze FBXO17 expression information in glioma. First, high FBXO17 expressions are associated with glioma and poor prognosis. Then, FBXO17 was upregulated in glioma cells. Meanwhile, knock-down of FBXO17 inhibited cell proliferation, migration, and invasion, but increased the cell apoptosis. Besides, knock-down of FBXO17 inhibited mitochondrial membrane potential and increased reactive oxygen species. Furthermore, knock-down of FBXO17 decreased level of adenosine triphosphate, glucose, lactate, GLUT1, HK2, PFKP, PKM2, and LDHA. In conclusion, FBXO17 was high expression in glioma, and FBXO17 regulates glioma by regulating glycolysis pathway, providing novel theoretical for the treatment of glioma.

MicroRNA-2861 and microRNA-5115 regulates myocardial ischemia-reperfusion injury through the GPR30/mTOR signaling pathway by binding to GPR30.

Myocardial ischemia-reperfusion (I/R) injury, a major contributor to morbidity and mortality, represents a combination of intrinsic cellular response to ischemia and the extrinsic acute inflammatory response. In the present study, microarray analysis of GSE67308 and GSE50885 identified differentially expressed GPR30 and upstream regulatory miR-2861 and miR-5115 in myocardial I/R. Furthermore, GPR30 was confirmed as a common target gene of miR-2861 and miR-5115, and miR-2861 and miR-5115 inhibited GPR30 expression. Poor expression of GPR30 was identified in the myocardial I/R injury mouse model. Overexpressed GPR30 led to alleviated the pathological conditions, diminished myocardial infarct size and apoptosis of myocardial tissue in mice. Moreover, miR-2861 and miR-5115 were found to be highly expressed in the myocardial I/R injury mouse model and to subsequently accelerate the disease progression. Notably, PR30 curtailed the development of myocardial I/R injury through activation of the mTOR signaling pathway. The key findings suggested that miR-2861 and miR-5115 blocked the activation of the GPR30/mTOR signaling pathway by targeting GPR30, thereby accelerating myocardial I/R injury in mice.

MMP9, CXCR1, TLR6, and MPO participant in the progression of coronary artery disease.

Coronary artery disease (CAD) is the most frequent cardiovascular disease, which is induced by the decreased myocardial blood supply. The present study is conducted to understand the mechanisms of CAD. The GSE98583, GSE69587, and GSE71226 datasets from the Gene Expression Omnibus database were obtained. The differentially expressed genes (DEGs) were analyzed by the limma package, then the DEGs appeared in two or three datasets were selected as the coregulated genes using the VENNY tool, followed by enrichment analysis using DAVID tool. Protein-protein interaction (PPI) network, microRNA-transcription factor-target regulatory network, and drug-gene network were visualized. Finally, quantitative PCR and dual-luciferase reporter assay were conducted to validate the expression of key genes and the target relationship. There were 221 coregulated genes in GSE98583, GSE69587, and GSE71226. Besides, four pathways and 23 functional terms for co-upregulated genes, and 11 functional terms for co-downregulated genes were enriched. The degrees of PPI network nodes matrix metallopeptidase 9 (MMP9), C-X-C motif chemokine receptor 1 (CXCR1), toll-like receptor 6 (TLR6), and myeloperoxidase (MPO) were relatively higher. Moreover, MPO could interact with MMP9, CXCR1, and TLR6 in the PPI network. In the regulatory network, TLR6 and MMP9 separately were targeted by miR-3960 and v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA). Additionally, MMP9, CXCR1, and MPO were involved in the drug-gene network. The expression of MMP9, CXCR1, TLR6, and MPO were significantly upregulated in CAD samples than control, and miR-3960 could bind to TLR6 to inhibit its expression. CXCR1 and MPO might be involved in the progression of CAD. Besides, miR-3960 might function in the pathogenesis of CAD through targeting TLR6, and RELA might exert its role in CAD via targeting MMP9.

Atherosclerosis-associated endothelial cell apoptosis by miRNA let7-b-mediated downregulation of HAS-2.

MicroRNAs (miRNAs) play essential roles in the regulation and pathophysiology of various types of human diseases including atherosclerosis. Increasing numbers of miRNAs have been identified to be important regulators in the progression of atherosclerosis by regulating gene expression. However, functional miRNAs and the underlying mechanisms involved in atherosclerosis need fully elucidation. In the present study, the function of miRNA let-7b was investigated in human aortic endothelial cells (HAECs). The results showed that downregulation of let-7b in the high-fat diet mice and HAECs was inversely correlated with the expression level of HAS-2. upregulation of let-7b significantly reduced apoptosis of HAECs. The results also revealed that HAS-2 was a target gene of let-7b and HAS-2 reduction reversed the antiapoptotic effect of let-7b through regulation of the P13K/Akt pathway. These results together suggest the potential of regulating the let-7b expression and endothelial apoptosis against development and progression of atherosclerosis.

Synthesis and Antiproliferative Evaluation of Novel Longifolene-Derived Tetralone Derivatives Bearing 1,2,4-Triazole Moiety.

Seventeen novel 2-(5-amino-1-(substituted sulfonyl)-1H-1,2,4-triazol-3-ylthio)-6- isopropyl-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one compounds were synthesized from the abundant and naturally renewable longifolene and their structures were confirmed by FT-IR, NMR, and ESI-MS. The in vitro cytotoxicity of the synthesized compounds was evaluated by standard MTT assay against five human cancer cell lines, i.e., T-24, MCF-7, HepG2, A549, and HT-29. As a result, compounds 6d, 6g, and 6h exhibited better and more broad-spectrum anticancer activity against almost all the tested cancer cell lines than that of the positive control, 5-FU. Some intriguing structure-activity relationships were found and are discussed herein by theoretical calculation.

Influence of hemodynamics on myocardial cell cardiac index and its molecular mechanism.

With the improvement of people's living standards and change of lifestyles, the morbidity of the cardiovascular and cerebrovascular diseases (cardiovascular and cerebrovascular diseases, CCVD), especially the atherosclerosis (atherosclerosis, AS), presents a rising tendency year by year. The injury and inflammatory reaction of endothelial cells is one of the important factors causing AS. However, its molecular mechanism still needs further studying. This paper will discuss the influence of hemodynamics on the cardiac muscle cells cardiac index and its molecular mechanism. The Human umbilical vein endothelial cells (Human umbilical vein endothelial cells, HUVEC) were cultivated and separated and processed by 100ng Lipopolysaccharide (Lipopolysaccharide, LPS) to simulate the injury and inflammation state of the vascular endothelial cells. The hemodynamic state was simulated by the Parallel-Plate Flow Chamber in laboratory. And the MTT was adopted to detect HUVEC growth and the flow cytometry (flow cytometry, FCT) to detect HUVEC apoptosis. And the cardiac index was tested by RT-PCR and western blot. And the cell apoptosis caused by LPS was tested when the cardiac index was over-expressed and reduced. LPS could inhabit HUVEC growth and lead to its apoptosis. Hemodynamics (16dyn/cm2) could reduce HUVEC growth inhibition and apoptosis caused by LPS. And the dose-dependent LPS reduced HUVEC cardiac index, while when it was processed by the hemodynamics (16dyn/cm2), the HUVEC cardiac index would increase. And the over-expression of the cardiac index could inhabit the cell apoptosis caused by LPS, and the interference technology was adopted to deal with the cardiac index, which could enhance the cell apoptosis caused by LPS. Hemodynamics could inhabit the HUVEC apoptosis caused by LPS, which might be one of the reasons causing AS, through enhancing the cardiac index.

Transcriptome analysis reveals the effects of Schizochytrium sp. on the meat quality attributes of Tan lambs.

Schizochytrium sp., a feed additive, positively affects the quality of animal meat. In this study, the molecular mechanisms through which dietary Schizochytrium sp. affects the meat quality characteristics of Tan lambs were investigated using transcriptomic techniques. The findings demonstrate that the lambs supplemented with Schizochytrium sp. had a larger loin eye area and a higher average daily gain and intramuscular fat content (P < 0.05). They also had lower drip loss (at 24 and 48 h) and shear force (P < 0.05). Further, 745 genes were differentially expressed between lambs supplemented with Schizochytrium and the control group. Moreover, KEGG pathway analysis showed that the ECM-receptor interaction pathway, which is related to muscle generation and intramuscular fat deposition, was significantly enriched in the lambs administered a diet containing Schizochytrium sp. Herein, we identified some pivotal genes linked to muscular system development and lipid metabolism. Thus, using Schizochytrium sp. may boost the meat quality of Tan lambs by modifying the expression of genes related to hub pathways. The results supply a new basis to determine the molecular mechanisms through which Schizochytrium sp. supplementation regulates the meat quality characteristics of sheep.

Expression of MAF bZIP transcription factor B protects against ulcerative colitis through the inhibition of the NF-κB pathway.

PURPOSE: The aim of this study was to explore whether MAF bZIP transcription factor B (MAFB) might alleviate ulcerative colitis (UC) in dextran sulfate sodium (DSS)-induced mice and LPS-induced IEC-6 cells. METHODS: UC in vivo and in vitro model was established by using DSS and LPS, respectively. The mice body weight and disease activity index (DAI) score were recorded daily, and colon length was measured. Moreover, the permeability was evaluated utilizing a fluorescein isothiocyanate dextran (FITC-Dextran) probe. Histopathological changes of DSS-induced colitis mice was assessed utilizing H&E staining. Next, qRT-PCR was performed to detect IL-1ß, IL-6, TNF-α, and IL-10 level in in vivo and in vitro. Furthermore, the level of MDA, SOD, CAT, and GSH were evaluated in colon tissues. Besides, the expressions of tight junction proteins and NF-κB pathway relative proteins were examined in colitis mice and IEC-6 cells using western blot, immunohistochemistry and immunofluorescence. RESULTS: MAFB level was downregulated in DSS-induced colitis mice. Moreover, the upregulation of MAFB protected mice from DSS-induced colitis by suppressing DSS-induced inflammation, oxidative stress, and intestinal barrier impairment. We also demonstrated that the upregulation of MAFB inactivated NF-κB pathway in DSS-caused colitis mice. Subsequently, we observed that MAFB upregulation could inhibit LPS-caused epithelial barrier impairment and inflammation in IEC-6 cells. Additionally, MAFB overexpression could suppress the activation of NF-κB pathway in IEC-6 cells. CONCLUSION: The upregulation of MAFB could protect against UC via the suppression of inflammation and the intestinal barrier impairment through inhibiting the NF-κB pathway.

Spatial-Temporal Kinetic Behaviors of Micron-Nano Dust Adsorption along Epoxy Resin Insulator Surfaces and the Physical Mechanism of Induced Surface Flashover.

The advanced Gas Insulated Switchgear/Gas Insulated Lines (GIS/GIL) transmission equipment serves as an essential physical infrastructure for establishing a new energy power system. An analysis spanning nearly a decade on faults arising from extra/ultra-high voltage discharges reveals that over 60% of such faults are attributed to the discharge of metal particles and dust. While existing technical means, such as ultra-high frequency and ultrasonic sensing, exhibit effectiveness in online monitoring of particles larger than sub-millimeter dimensions, the inherent randomness and elusive nature of micron-nano dust pose challenges for effective characterization through current technology. This elusive micron-nano dust, likely concealed as a latent threat, necessitates special attention due to its potential as a "safety killer". To address the challenges associated with detecting micron-nano dust and comprehending its intricate mechanisms, this paper introduces a micron-nano dust adsorption experimental platform tailored for observation and practical application in GIS/GIL operations. The findings highlight that micron-nano dust's adsorption state in the electric field predominantly involves agglomerative adsorption along the insulator surface and diffusive adsorption along the direction of the ground electrode. The pivotal factors influencing dust movement include the micron-nano dust's initial position, mass, material composition, and applied voltage. Further elucidation emphasizes the potential of micron-nano dust as a concealed safety hazard. The study reveals specific physical phenomena during the adsorption process. Agglomerative adsorption results in micron-nano dust speckles forming on the epoxy resin insulator's surface. With increasing voltage, these speckles undergo an "explosion", forming an annular dust halo with deepening contours. This phenomenon, distinct from the initial adsorption, is considered a contributing factor to flashovers along the insulator's surface. The physical mechanism behind flashovers triggered by micron-nano dust is uncovered, highlighting the formation of a localized short circuit area and intense electric field distortion constituted by dust speckles. These findings establish a theoretical foundation and technical support for enhancing the safe operational performance of AC and DC transmission pipelines' insulation.

Identification of key genes related to heart failure by analysis of expression profiles.

Introduction: To elucidate the candidate biomarkers involved in the pathogenesis process of heart failure (HF) via analysis of differentially expressed genes (DEGs) of the dataset from the Gene Expression Omnibus (GEO). Material and methods: The GSE76701 gene expression profiles regarding the HF and control subjects were respectively analysed. Briefly, DEGs were firstly identified and subjected to Cytoscape plug-in ClueGO + CluePedia and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A protein-protein interaction (PPI) network was then built to analyse the interaction between DEGs, followed by the construction of an interaction network by combining with hub genes with the targeted miRNA genes of DEGs to identify the key molecules of HF. In addition, potential drugs targeting key DEGs were sought using the drug-gene interaction database (DGIdb), and a drug-mRNA-miRNA interaction network was also constructed. Results: A total of 489 DEGs were verified between HF and control, which mainly enriched in type I interferon and leukocyte migration according to molecular function. Significantly increased levels of GAPDH, GALM1, MMP9, CCL5, and GNAL2 were found in the HF setting and were identified as the hub genes based on the PPI network. Furthermore, according to the drug-mRNA-miRNA network, FCGR2B, CCND1, and NF-κb, as well as corresponding miRNA-605-5p, miRNA-147a, and miRNA-671-5p were identified as the drug targets of HF. Conclusions: The hub genes GAPDH, GALM1, MMP9, CCL5, and GNAL2 were significantly increased in HF. miRNA-605-5p, miRNA-147a, and miRNA-671-5p were predicted as the drug target-interacted gene-miRNA of HF.

Correction: The thalamic clustering coefficient moderates the vigor-sleep quality relationship.

[This corrects the article DOI: 10.1007/s41105-023-00456-2.].

The thalamic clustering coefficient moderates the vigor-sleep quality relationship.

Sleep disorders affect more than one-quarter of the world's population, resulting in reduced daytime productivity, impaired immune function, and an increased risk of cardiovascular disease. It is important to identify the physiological and psychological factors related to sleep for the prevention and treatment of sleep disorders. In this study, we correlated measurements of emotional state, sleep quality, and some brain neural activity parameters to better understand the brain and psychological factors related to sleep. Resting-state functional magnetic resonance imaging (rs-fMRI) of 116 healthy undergraduates were analyzed using graph theory to assess regional topological characteristics. Among these, the left thalamic cluster coefficient proved to be the ablest to reflect the characteristics of the sleep neural graph index. The Profile of Mood States (POMS) was used to measure vigor, and the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. The results showed that the left thalamic clustering coefficient was negatively correlated with sleep quality and vigor. Further, the left thalamic clustering coefficient moderated the relationship between vigor and sleep quality. When the left thalamic clustering coefficient was very low, there was a significant positive correlation between vigor and sleep quality. However, when the left thalamic clustering coefficient was high, the correlation between vigor and sleep quality became insignificant. The relationship between vigor and sleep quality is heterogeneous. Analyzing the function of the left thalamic neural network could help understand the variation in the relationship between vigor and sleep quality in different populations. Such observations may help in the development of personalized interventions for sleep disorders.

Phase driven topological states in correlated Haldane model on a honeycomb lattice.

Using mean field method and random phase approximation, we studied the phase driven topological exotic states in correlated Haldane model on a honeycomb lattice. It is found that topological spin density waves emerge with the phase change of next-nearest-neighbor hopping. We also investigated the topological properties of these spin density waves, including Chern number, edge state and Hall conductivity. Our work provides a new insight for topological phase transitions in correlated quantum anomalous Hall insulators.

Enhanced N-Type Bismuth-Telluride-Based Thermoelectric Fibers via Thermal Drawing and Bridgman Annealing.

N-type bismuth telluride (Bi2Te3) based thermoelectric (TE) fibers were fabricated by thermal drawing and Bridgman annealing, and the influence of Bridgman annealing on the TE properties of n-type Bi2Te3-based TE fibers was studied. The Bridgman annealing enhanced the electrical conductivity and Seebeck coefficient because of increasing crystalline orientation and decreasing detrimental elemental enrichment. The TE performance of n-type Bi2Te3-based TE fibers was improved significantly by enhancing the power factor. Hence the power factor increased from 0.14 to 0.93 mW/mK2, and the figure-of-merit value is from 0.11 to 0.43 at ~300 K, respectively.

Surface Flashover Induced by Metal Contaminants Adhered to Tri-Post Epoxy Insulators under Superimposed Direct and Lightning Impulse Voltages.

Metal contaminants can distort the surface electric field of the tri-post epoxy insulator and cause serious surface charge accumulation, significantly reducing the insulation performance of the insulator under the superimposed DC and lightning impulse voltage. In this paper, an experimental platform for charge accumulation and surface flashover of tri-post epoxy insulators under the superimposed DC and lightning impulse voltage was built, by surface point measurement and charge inversion calculation, the surface charge distribution characteristics of tri-post insulators with attached particles was experimentally explored and the influence law of attached metal particles on the charge accumulation was discussed. The results show that metal particles can cause a surge in the surface charge density of the tri-post epoxy insulator, forming bipolar charge spots whose polarity is opposite to that of the adjacent electrodes. The adsorbed metal dust can cause the polarity reversal of adjacent surface charges, forming a large-area unipolar charge spot. Moreover, the flashover voltage of a tri-post insulator under DC superimposed lightning impulse voltage with a clean surface and attached metal particle was measured, and the synergistic induction mechanism of charge spot accumulation and metal particle discharge on the flashover along the face of the tri-post insulator is thereby revealed. Compared with the clean insulators, the surface flashover voltages of tri-post epoxy insulators with metal contaminants adhered decrease under the superimposed voltages of different polarities, but the decline amplitude is greater under the heteropolar composite voltage. When adhered to the middle of the insulator leg, the distribution range of bipolar charge spots is the widest, and the surface flashover voltage decreases sharply, which can drop by 32% compared with the absence of particles. In addition, when the metal dust adsorbed by the tri-post epoxy insulator has a wide distribution range, the impact of metal dust on the flashover voltage is greater than that of the attached metal particles, and its hazard cannot be ignored. The research results can provide a reference for the insulation test method and optimal design of the DC tri-post epoxy insulator.

Obstructive Sleep Apnea Affects Lacrimal Gland Function.

PURPOSE: To determine the effect of obstructive sleep apnea syndrome (OSA) on lacrimal gland function and its mechanism. METHODS: Male mice aged seven to eight weeks were housed in cages with cyclic intermittent hypoxia to mimic OSA, and the control group was kept in a normal environment. Slit-lamp observation, fluorescein staining, and corneal sensitivity detection are used to assess cornea changes. Tear secretion was detected by phenol red cotton thread, and the pathological changes of lacrimal gland were observed by hematoxylin and eosin staining, oil red O staining, cholesterol and triglyceride kits, immunofluorescence staining, immunohistochemical staining, real-time polymerase chain reaction, transmission electron microscopy, and Western blot. RESULTS: Studies revealed a decreased tear secretion, corneal epithelial defects and corneal hypersensitivity. Myoepithelial cell damage, abnormal lipid accumulation, reduced cell proliferation, increased apoptosis and inflammatory cell infiltration in the lacrimal gland were also seen. Hifα and NF-κB signaling pathways, moreover, were activated, while Pparα was downregulated, in the lacrimal glands of OSA mice. Fenofibrate treatment significantly alleviated pathological changes of the lacrimal gland induced by OSA. CONCLUSION: OSA disturbs the Hifα/Pparα/NF-κB signaling axis, which affects lacrimal gland structure and function and induces dry eye.

Competition between spin density wave and charge density wave driven by interactions of spinful Haldane model on honeycomb lattices.

We investigate the interacting spinful Haldane model with on-site and nearest-neighbor repulsions on honeycomb lattices. Interactions drive spin-density and charge-density waves competing with each other. This competition enriches the phase diagram of the system greatly, where both topological and non-topological coexistence phases emerge with spin-density and charge-density wave orders. Moreover, the topological phase transition accompanied by the energy gap closure in coexistence phases is of third order. Finally, we study the topological properties consisting ofChernnumbers and edge states for different phases.

Inhibition Effect of Solid Products and DC Breakdown Characteristics of the HFO1234Ze(E)-N2-O2 Ternary Gas Mixture.

HFO1234ze(E) is an environmentally friendly SF6 substitute gas with prominent application potential. To suppress the generation of the HFO1234ze(E) solid decomposition products, which may cause great hazards to the gas-solid insulation strength, a gas mixing scheme screening method based on the reactive force field (ReaxFF) molecular dynamics (MD) simulation was innovatively proposed. The simulation results show that the inhibitory effect of O2 on the formation of HFO1234ze(E) solid products is better than those of CO2 and CF4. Further study shows that when O2 accounts for 3.33% of the gas mixture, the solid precipitate content is reduced by 48%. The experimental study shows that an O2 content of 3.33% can inhibit the generation of solid products by more than 50%. Besides, compared with HFO1234ze(E)-N2, the DC breakdown voltage of HFO1234ze(E)-N2-O2 is slightly increased, and the breakdown voltage dispersion degree and continuous breakdown voltage drop rate are decreased. This work gives a feasible solution for the suppression of HFO1234ze(E) solid decomposition products and provides an efficient method for solving similar problems of environmentally friendly insulating gas in C/F/O/N systems.

Thermal Decomposition Mechanism of GIS Basin Insulator and Kinetic Parameters-Based Lifetime Prediction Methodology.

To reliably detect the latent defects and accurately evaluate the remaining life of gas insulated switchgear (GIS) basin insulators, more effective detection and characterization methods need to be explored. The study of pyrolysis kinetic parameters based on the intrinsic characteristics of materials provides a new way to solve this problem. First, an integral expression model of the reaction mechanism function with four parameters is proposed in this paper, which can represent various existing reaction mechanism functions with better universality and more application fields. Then, on the basis of the temperature transformation equation, an improved method for calculating the activation energy is presented, which shows higher computational accuracy than the existing methods. Further, based on a non-isothermal kinetic equation, the structure of the experimental function is given. It is a method for solving the pyrolysis reaction mechanism function of insulating materials, which can also be used to calculate the pre-exponential factor simultaneously. The thermogravimetric analysis experiment is carried out on a certain basin insulator sample at different heating rates. The pyrolysis kinetic state parameters, including the activation energy, reaction mechanism function and pre-exponential factor of the basin insulator, are calculated. Finally, the life prediction method of basin insulators is established, and the key factors affecting the life of insulators are discussed.