AZGP1 deficiency promotes angiogenesis in prostate cancer.

BACKGROUND: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. METHOD: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. RESULT: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. CONCLUSION: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

A multi-feature spatial-temporal fusion network for traffic flow prediction.

The traffic flow prediction is the key to alleviate traffic congestion, yet very challenging due to the complex influence factors. Currently, the most of deep learning models are designed to dig out the intricate dependency in continuous standardized sequences, which are dependent to high requirements for data continuity and regularized distribution. However, the data discontinuity and irregular distribution are inevitable in the real-world practical application, then we need find a way to utilize the powerful effect of the multi-feature fusion rather than continuous relation in standardized sequences. To this end, we conduct the prediction based on the multiple traffic features reflecting the complex influence factors. Firstly, we propose the ATFEM, an adaptive traffic features extraction mechanism, which can select important influence factors to construct joint temporal features matrix and global spatial features matrix according to the traffic condition. In this way, the feature's representation ability can be improved. Secondly, we propose the MFSTN, a multi-feature spatial-temporal fusion network, which include the temporal transformer encoder and graph attention network to obtain the latent representation of spatial-temporal features. Especially, we design the scaled spatial-temporal fusion module, which can automatically learn optimal fusion weights, further adapt to inconsistent spatial-temporal dimensions. Finally, the multi-layer perceptron gets the mapping function between these comprehensive features and traffic flow. This method helps to improve the interpretability of the prediction. Experimental results show that the proposed model outperforms a variety of baselines, and it can accurately predict the traffic flow when the data missing rate is high.

A Label-Free Fluorescent Amplification Strategy for High-Sensitive Detection of Pseudomonas aeruginosa based on Protective-EXPAR (p-EXPAR) and Catalytic Hairpin Assembly.

This study presents a fluorescent mechanism for two-step amplification by combining two widely used techniques, exponential amplification reaction (EXPAR) and catalytic hairpin assembly (CHA). Pseudomonas aeruginosa (P. aeruginosa) engaged in competition with the complementary DNA in order to attach to the aptamer that had been fixed on the magnetic beads. The unbound complementary strand in the liquid above was utilized as a trigger sequence to initiate the protective-EXPAR (p-EXPAR) process, resulting in the generation of a substantial quantity of short single-stranded DNA (ssDNA). The amplified ssDNA can initiate the second CHA amplification process, resulting in the generation of many double-stranded DNA (dsDNA) products. The CHA reaction was initiated by the target/trigger DNA, resulting in the release of G-quadruplex sequences. These sequences have the ability to bond with the fluorescent amyloid dye thioflavin T (ThT), generating fluorescence signals. The method employed in this study demonstrated a detection limit of 16 CFU/ml and exhibited a strong linear correlation within the concentration range of 50 CFU/ml to 105 CFU/ml. This method of signal amplification has been effectively utilized to create a fluorescent sensing platform without the need for labels, enabling the detection of P. aeruginosa with high sensitivity.

Exploring the bidirectional relationship between metabolic syndrome and thyroid autoimmunity: a Mendelian randomization study.

Background: Observational studies have reported a possible association between metabolic syndrome (MetS) and thyroid autoimmunity. Nevertheless, the relationship between thyroid autoimmunity and MetS remains unclear. The objective of this research was to assess the causal impact of MetS on thyroid autoimmunity through the utilization of Mendelian randomization (MR) methodology. Methods: We performed bidirectional MR to elucidate the causal relationship between MetS and their components and thyroid autoimmunity (positivity of TPOAb). Single nucleotide polymorphisms (SNPs) of MetS and its components were obtained from the publicly available genetic variation summary database. The Thyroidomics Consortium conducted a genome-wide association analysis, which provided summary-level data pertaining to thyroid autoimmunity. The study included several statistical methods, including the inverse variance weighting method (IVW), weighted median, simple mode, weight mode, and MR-Egger methods, to assess the causal link. In addition, to ensure the stability of the results, a sensitivity analysis was conducted. Results: IVW showed that MetS reduced the risk of developing thyroid autoimmunity (OR = 0.717, 95% CI = 0.584 - 0.88, P = 1.48E-03). The investigation into the causative association between components of MetS and thyroid autoimmune revealed a statistically significant link between triglycerides levels and the presence of thyroid autoimmunity (IVW analysis, OR = 0.603, 95%CI = 0.45 -0.807, P = 6.82E-04). The reverse analysis did not reveal any causal relationship between thyroid autoimmunity and MetS, including its five components. Conclusions: We have presented new genetic evidence demonstrating that MetS and its triglyceride components may serve as potential protective factors against thyroid autoimmunity.

Cross-modal credibility modelling for EEG-based multimodal emotion recognition.

Objective.The study of emotion recognition through electroencephalography (EEG) has garnered significant attention recently. Integrating EEG with other peripheral physiological signals may greatly enhance performance in emotion recognition. Nonetheless, existing approaches still suffer from two predominant challenges: modality heterogeneity, stemming from the diverse mechanisms across modalities, and fusion credibility, which arises when one or multiple modalities fail to provide highly credible signals.Approach.In this paper, we introduce a novel multimodal physiological signal fusion model that incorporates both intra-inter modality reconstruction and sequential pattern consistency, thereby ensuring a computable and credible EEG-based multimodal emotion recognition. For the modality heterogeneity issue, we first implement a local self-attention transformer to obtain intra-modal features for each respective modality. Subsequently, we devise a pairwise cross-attention transformer to reveal the inter-modal correlations among different modalities, thereby rendering different modalities compatible and diminishing the heterogeneity concern. For the fusion credibility issue, we introduce the concept of sequential pattern consistency to measure whether different modalities evolve in a consistent way. Specifically, we propose to measure the varying trends of different modalities, and compute the inter-modality consistency scores to ascertain fusion credibility.Main results.We conduct extensive experiments on two benchmarked datasets (DEAP and MAHNOB-HCI) with the subject-dependent paradigm. For the DEAP dataset, our method improves the accuracy by 4.58%, and the F1 score by 0.63%, compared to the state-of-the-art baseline. Similarly, for the MAHNOB-HCI dataset, our method improves the accuracy by 3.97%, and the F1 score by 4.21%. In addition, we gain much insight into the proposed framework through significance test, ablation experiments, confusion matrices and hyperparameter analysis. Consequently, we demonstrate the effectiveness of the proposed credibility modelling through statistical analysis and carefully designed experiments.Significance.All experimental results demonstrate the effectiveness of our proposed architecture and indicate that credibility modelling is essential for multimodal emotion recognition.