Explore the vast range of titles available.

In this paper, we study the scenario in which the matter field is an electromagnetic field nonminimally coupled to the bumblebee vector field. We present exact charged spherically symmetric black hole solutions and slowly rotating charged solutions in bumblebee gravity with and without a cosmological constant. The static spherically symmetric solutions describe the Reissner–Nordström-like black hole and Reissner–Nordström-(anti) de Sitter-like black hole, while the stationary and axially symmetric solutions describe the Kerr–Newman-like black hole and Kerr–Newman–(anti) de Sitter-like black hole. We utilize the Hamilton–Jacobi formalism to study the shadows of the black holes. Additionally, we investigate the effect of the electric charge and Lorentz-violating parameters on the radius of the shadow reference circle and the distortion parameter. We find that the radius of the reference circle decreases with the Lorentz-violating parameter and the charge parameter, while the distortion parameter increases with the Lorentz-violating parameter and the charge parameter.

Background 3-Hydroxy butyrate dehydrogenase 2 (BDH2) is a short-chain dehydrogenase/reductase family member that plays a key role in the development and pathogenesis of human cancers. However, the role of BDH2 in gastric cancer (GC) remains largely unclear. Our study aimed to ascertain the regulatory mechanisms of BDH2 in GC, which could be used to develop new therapeutic strategies. Methods Western blotting, immunohistochemistry, and RT-PCR were used to investigate the expression of BDH2 in GC specimens and cell lines. Its correlation with the clinicopathological characteristics and prognosis of GC patients was analysed. Functional assays, such as CCK-8 and TUNEL assays, transmission electron microscopy, and an in vivo tumour growth assay, were performed to examine the proliferation, apoptosis, and autophagy of GC cells. Related molecular mechanisms were clarified by luciferase reporter, coimmunoprecipitation, and ubiquitination assays. Results BDH2 was markedly downregulated in GC tissues and cells, and the low expression of BDH2 was associated with poor survival of GC patients. Functionally, BDH2 overexpression significantly induced apoptosis and autophagy in vitro and in vivo. Mechanistically, BDH2 promoted Keap1 interaction with Nrf2 to increase the ubiquitination level of Nrf2. Ubiquitination/degradation of Nrf2 inhibited the activity of ARE to increase accumulation of reactive oxygen species (ROS), thereby inhibiting the phosphorylation levels of Akt Ser473 and mTOR Ser2448 . Conclusions Our study indicates that BDH2 is an important tumour suppressor in GC. BDH2 regulates intracellular ROS levels to mediate the PI3K/Akt/mTOR pathway through Keap1/Nrf2/ARE signalling, thereby inhibiting the growth of GC.

The mechanism by which miR‐605‐3p regulates hepatocellular carcinoma (HCC) metastasis has not been clarified. In this study, we found that miR‐605‐3p was down‐regulated in HCC and that low miR‐605‐3p expression was associated with tumour thrombus and tumour satellites. HCC patients with low miR‐605‐3p expression showed shorter overall survival and disease‐free survival after surgery. Overexpression of miR‐605‐3p inhibited epithelial‐mesenchymal transition and metastasis of HCC through NF‐κB signalling by directly inhibiting expression of TRAF6, while silencing of miR‐605‐3p had the opposite effect. We also found that SNHG16 directly bound to miR‐605‐3p as a competing endogenous RNA. Mechanistically, high expression of SNHG16 promoted binding to miR‐605‐3p and inhibited its activity, which led to up‐regulation of TRAF6 and sustained activation of the NF‐κB pathway, which in turn promoted epithelial‐mesenchymal transition and metastasis of HCC. TRAF6 increased SNHG16 promoter activity by activating NF‐κB, thereby promoting the transcriptional expression of SNHG16 and forming a positive feedback loop that aggravated HCC malignancy. Our findings reveal a mechanism for the sustained activation of the SNHG16/miR‐605‐3p/TRAF6/NF‐κB feedback loop in HCC and provide a potential target for a new HCC treatment strategy.

Background Critically ill patients in intensive care unit (ICU) are at high risk of venous thromboembolism (VTE). The standardized prophylaxis of VTE in these patients and the appropriate prevention protocols are not very clear. Method We enrolled 426 patients admitted to respiratory intensive care unit (RICU), all of them underwent Padua risk scoring and patients at high risk of VTE also underwent bleeding risk scoring. We compared the VTE prevention methods that followed the guidelines between two different bleeding risk groups and the VTE incidence of these two groups. We also analyzed the risk factors for VTE in RICU patients. Results In patients admitted to RICU, the rate of overall VTE prophylaxis was 71.3% (295/414), but the rate of standardized prophylaxis of VTE was only 32.6% (135/414). The standardized prophylaxis rate of VTE in high-risk bleeding patients was 40.3%, much higher than the 22.2% in low-risk bleeding patients (P < 0.001). There was also a significant difference in the incidence of VTE between the two groups (26.9%vs3.4%, P < 0.001). 70 (16.9%) patients in RICU developed VTE, the multivariable logistic regression analysis showed that immobilization time, pulmonary encephalopathy, oral or inject corticosteroids, trauma or surgery within 3 months were independent risk factors of VTE in patients admitted to RICU, while pharmacological prophylaxis was a protective factor for VTE. The receiver operating characteristic (ROC) curve showed that the above composite indicators had a higher predictive value for RICU patients with VTE, with a ROC area under the curve (AUC) of 0.925 (95%CI 0.894–0.956, P < 0.001). Conclusion Although the overall prophylaxis rate of VTE in patients admitted to RICU was high, the rate of standardized prevention was not ideal. Pharmacological prophylaxis may play an important role in preventing VTE in RICU patients and fruther studies are needed to explore the optimal thromboprophylaxis protocol for critically ill patients.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.

BackgroundHistone deacetylases (HDACs) have been shown to be involved in tumorigenesis, but their precise role and molecular mechanisms in gastric cancer (GC) have not yet been fully elucidated.MethodsBioinformatics screening analysis, qRT-PCR, and immunohistochemistry (IHC) were used to identify the expression of HDAC4 in GC. In vitro and in vivo functional assays illustrated the biological function of HDAC4. RNA-seq, GSEA pathway analysis, and western blot revealed that HDAC4 activated p38 MAPK signalling. Immunofluorescence, western blot, and IHC verified the effect of HDAC4 on autophagy. ChIP and dual-luciferase reporter assays demonstrated that the transcriptional regulation mechanism of HDAC4 and ATG4B.ResultsHDAC4 is upregulated in GC and correlates with poor prognosis. In vitro and in vivo assays showed that HDAC4 contributes to the malignant phenotype of GC cells. HDAC4 inhibited the MEF2A-driven transcription of ATG4B and prevented MEKK3 from p62-dependent autophagic degradation, thus activating p38 MAPK signalling. Reciprocally, the downstream transcription factor USF1 enhanced HDAC4 expression by regulating HDAC4 promoter activity, forming a positive feedback loop and continuously stimulating HDAC4 expression and p38 MAPK signalling activation.ConclusionHDAC4 plays an oncogenic role in GC, and HDAC4-based targeted therapy would represent a novel strategy for GC treatment.

Peripheral blood lymphocyte subsets have been reported to be useful as prognostic and/or diagnostic markers for patients with cancer. However, the clinical value of peripheral blood lymphocyte subsets in gastric cancer (GC) has remained elusive. In the present study, peripheral CD3+, CD4+ and CD8+ T lymphocytes, B cells (CD19+), regulatory T cells (Tregs; CD4+CD25+CD127-) and natural killer (NK) cells (CD3-CDl6+CD56+) were detected by flow cytometry in 122 patients with GC, 80 healthy donors (HDs) and 80 patients with gastric ulcer (GU). NK cells (CD56+) were detected by immunohistochemical (IHC) analysis in 20 GC and three GU tissue samples. A receiver-operating characteristic (ROC) curve was used to determine the threshold of the peripheral NK cell level and survival analysis was performed to assess its prognostic value in patients with GC. The results indicated that the peripheral NK cell proportion in patients with GC (18.77%) was significantly higher than that in the HD (12.19%) and GU (12.74%) groups. IHC analysis suggested that the NK level in GC tumor samples was correlated with that in paired serum samples. ROC curve analysis indicated that the peripheral NK cell level (15.16%) was able to effectively identify patients with GC, a diagnostic sensitivity of 75.41% and a specificity of 77.45% were determined. Multivariate logistic regression analysis revealed that the peripheral NK cell level was independently associated with the T stage and survival analysis demonstrated that high levels of peripheral NK cells were associated with poor prognosis of patients with GC. In conclusion, the peripheral NK cell level may be a diagnostic and prognostic marker for patients with GC.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0) patients experienced prostate-specific antigen (PSA) response and 11 (44.0) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.

Due to their excellent electrical properties and compatibility with room-temperature deposition/printing processing, high-purity single-walled semiconducting carbon nanotubes hold great potential for macroelectronic applications such as in thin-film transistors and display back-panel electronics. However, the relative advantages and disadvantages of various nanotubes for macroelectronics remains an open issue, despite the great significance. Here in this paper, we report a com- parative and systematic study of three kinds of mainstream carbon nanotubes （arc-discharge, HiPCO, CoMoCAT） separated using low-cost gel-based column chromatography for thin-film transistor applications, and high performance transistors--which satisfy the requirements for transistors used in active matrix organic light-emitting diode displays--have been achieved. We observe a trade-off between transistor mobility and on/off ratio depending on the nanotube diameter. While arc-discharge nanotubes with larger diameters lead to high device mobility, HiPCO and CoMoCAT nanotubes with smaller diameters can provide high on/off ratios （〉 106） for transistors with comparable dimensions. Furthermore, we have also compared gel-based separated nanotubes with nanotubes separated using the density gradient ultracentrifuge （DGU） method, and find that gel-separated nanotubes can offer purity and thin-film transistor performance as good as DGU-separated nanotubes. Our approach can serve as the critical foundation for future carbon nanotube-based thin-film macroelectronics.

Dear Editor, Flowering adaptability of cultivars to growth condi- tions should be one of the most important targets in crop domestication and selection. We report here the position- al cloning of a major pleiotropic QTL, Ghd7.1, which encodes a PSEUDO-RESPONSE REGULATOR 7-like protein. Under long-day conditions, Ghd7.1 greatly de- lays rice heading and enhances grain productivity.