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.

Gut microbiota regulates chronic ethanol exposure-induced depressive-like behavior through hippocampal NLRP3-mediated neuroinflammation.

Chronic ethanol exposure (CEE), which can lead to neuroinflammation, is an increasing risk factor for depression disorder, but the underlying mechanism is not clear. Recent observations have revealed the associations among psychiatric disorders, ethanol exposure and alterations of the gut microbiota. Here, we found that CEE induced depressive-like behavior, which could be alleviated by probiotics and transferred from donor to recipient mice by fecal microbiota transplantation (FMT). Neuroinflammation and the activation of the NLRP3 inflammasome were also observed in recipient mice. The downregulation of NLRP3 in the hippocampus mitigated CEE-induced depressive-like behavior and neuroinflammation but had no significant effect on FMT recipient mice. Moreover, elevated serum inflammatory factors in recipient mice showed a significant mediation effect between the gut microbiota and depressive-like behavior. Together, our study findings indicate that the gut microbiota contributes to both hippocampal NLRP3-mediated neuroinflammation and depressive-like behavior induced by CEE, which may open avenues for potential interventions against CEE-associated psychiatric disorders.

Clinical and ultrasonic risk factors for high-volume central lymph node metastasis in cN0 papillary thyroid microcarcinoma: A retrospective study and meta-analysis.

OBJECTIVE: Papillary thyroid microcarcinoma (PTMC) comprises more than 50% of all newly detected cases of papillary thyroid carcinoma (PTC). High-volume lymph node metastasis (involving >5 lymph nodes) (hv-LNM) is associated with PTMC recurrence. In half of the clinically node-negative (cN0) PTMC patients, central lymph node metastasis (CLNM) is pathologically present. However, clinical risk factors for high-volume CLNM (hv-CLNM) in cN0 PTMC have not been defined well. Therefore, we aimed to obtain evidence for hv-CLNM risk factors in cN0 PTMC. DESIGN: Data on patients who visited our hospital between January 2020 and December 2021 were collected; a preoperative diagnosis of cN0 and a postoperative pathological confirmation of PTMC were obtained. After filtering by inclusion versus exclusion criteria, the obtained data (N = 2268) were included in the meta-analysis. Relevant studies published as of 10 April 2022, were identified from the Web of Science, PubMed, WANFANG, and CNKI databases. These eligible studies were included in the meta-analysis and the association between clinicopathological factors and hv-CLNM in cN0 PTMC was assessed. SPSS and MetaXL were used for statistical analyses. RESULTS: The meta-analysis included 10 previous studies (11,734 patients) and 2268 patients enroled in our hospital for a total of 14,002 subjects. The results of which suggested that younger age (<40, odds ratio [OR] = 3.28, 95% confidence interval [CI] = 2.75-3.92, p < .001 or <45 odds ratio [OR] = 2.93, 95% CI = 2.31-3.72, p < .001), male sex (OR = 2.81, 95% CI = 2.25-3.52, p < .001), tumour size >5 mm (OR = 1.85, 95% CI = 1.39-2.47, p < .001), multifocality (OR = 1.88, 95% CI = 1.56-2.26, p < .001), extrathyroidal extension (OR = 2.58, 95% CI = 2.02-3.30, p < .001), capsule invasion (OR = 2.02, 95% CI = 1.46-2.78, p < .001), microcalcification (OR = 3.25, 95% CI = 2.42-4.36, p < .001) and rich blood flow (OR = 1.65, 95% CI = 1.21-2.25, p = .002) were the significant factors related to an elevated hv-CLNM risk in cN0 PTMC patients. Hashimoto thyroiditis (OR = 0.76, 95% CI = 0.55-1.07, p = .114), irregular margin (versus regular margin, OR = 0.96, 95% CI = 0.68-1.33, p = .787) and hypoechoic (versus nonhypoechoic, OR = 1.27, 95% CI = 0.84-1.92, p = .261) showed no significant association with hv-CLNM. CONCLUSIONS: Younger age, tumour size >5 mm, males, extrathyroidal extension, multifocality, microcalcification, capsular invasion, and rich blood flow were the significant clinicopathological risk factors for hv-CLNM risk in cN0 PTMC patients. These predictors may compensate for the sensitivity of imaging diagnosis in the preoperative period, thus helping in the effective identification of PTMCs with an invasive phenotype.

A Practical Statin Recommendation System Based on Real-World Data to Improve LDL-C Management in Secondary Prevention.

ABSTRACT: Statins are considered the cornerstone of secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD). However, many patients fail to achieve the guide-recommended goal of low-density lipoprotein cholesterol (LDL-C) after statin monotherapy, leading to a high residual risk of cardiovascular events. Owing to individual differences in statin therapy, it is possible first to consider changing the type of statin before adding nonstatin medications in certain patients to improve LDL-C management. We developed and evaluated a statin recommendation system using real-world data. Ensemble learning was performed to develop the recommendation system that integrated the output results of support vector machines (SVM) and the similarity of patients. Model performance was assessed to investigate whether treatment according to the recommended model would increase the proportion of patients with the primary end point. Finally, a total of 3510 patients were enrolled in the development and validation of the recommender system. Of them, 1240 patients received atorvastatin (35.3%), 1714 patients received rosuvastatin (48.8%), and 556 patients received pitavastatin (15.8%). The statin recommendation system could significantly improve LDL-C target rate achievement in the recommended treatment group compared with the nonrecommended treatment group in the validation set (50.8% vs. 31.5%, P < 0.001). This study demonstrated that the statin recommendation system could significantly improve the achievement of LDL-C goals in ASCVD patients, providing a new approach to improve LDL-C management.

A four-enhancer RNA-based prognostic signature for thyroid cancer.

Enhancer RNAs (eRNAs) can serve as an independent prognostic factor for poor outcomes of cancer patients. The purpose of this study was to identify a vital eRNA signature that has prognostic value for thyroid cancer based on GTEx and TCGA screening. We downloaded gene expression data and clinical data of thyroid cancer included in the GTEx and TCGA databases and conducted data consolidation. eRNA expression data were extracted, and subjected to differential analysis and cluster analysis. Univariate Cox regression was used to screen the prognostic factors of thyroid cancer. Multivariate Cox regression was applied for prognostic risk assessment model construction, with the efficacy evaluated by receiver operating characteristic (ROC) curve. Downstream regulatory genes of candidate eRNAs were determined using correlation analysis. There were 79 differentially expressed eRNAs associated with thyroid cancer. These differentially expressed eRNAs could assign all thyroid cancer samples into three molecular subtypes, which showed a strong link to lymph node metastasis (N stage) of thyroid cancer patients. Additionally, four key eRNAs AC141930.1, NBDY, MEG3 and AP002358.1 closely related to the prognosis of thyroid cancer patients. The risk model based on the four eRNAs predicted the prognosis of thyroid cancer patients effectively. TPO, MGST2, THBS2 and SLC25A47P1 were potential downstream regulators of the four eRNAs involved in the development of thyroid cancer. Collectively, our data suggest that a four-eRNA signature consisting of AC141930.1, NBDY, MEG3 and AP002358.1 can accurately predict the prognosis of thyroid cancer patients.

Programmable Bispecific Nano-immunoengager That Captures T Cells and Reprograms Tumor Microenvironment.

Immune checkpoint blockade (ICB) therapy has revolutionized clinical oncology. However, the efficacy of ICB therapy is limited by the ineffective infiltration of T effector (Teff) cells to tumors and the immunosuppressive tumor microenvironment (TME). Here, we report a programmable tumor cells/Teff cells bispecific nano-immunoengager (NIE) that can circumvent these limitations to improve ICB therapy. The peptidic nanoparticles (NIE-NPs) bind tumor cell surface α3ß1 integrin and undergo in situ transformation into nanofibrillar network nanofibers (NIE-NFs). The prolonged retained nanofibrillar network at the TME captures Teff cells via the activatable α4ß1 integrin ligand and allows sustained release of resiquimod for immunomodulation. This bispecific NIE eliminates syngeneic 4T1 breast cancer and Lewis lung cancer models in mice, when given together with anti-PD-1 antibody. The in vivo structural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics to greatly enhance ICB therapy against cancers.

NUSAP1 Binds ILF2 to Modulate R-Loop Accumulation and DNA Damage in Prostate Cancer.

Increased expression of NUSAP1 has been identified as a robust prognostic biomarker in prostate cancer and other malignancies. We have previously shown that NUSAP1 is positively regulated by E2F1 and promotes cancer invasion and metastasis. To further understand the biological function of NUSAP1, we used affinity purification and mass spectrometry proteomic analysis to identify NUSAP1 interactors. We identified 85 unique proteins in the NUSAP1 interactome, including ILF2, DHX9, and other RNA-binding proteins. Using proteomic approaches, we uncovered a function for NUSAP1 in maintaining R-loops and in DNA damage response through its interaction with ILF2. Co-immunoprecipitation and colocalization using confocal microscopy verified the interactions of NUSAP1 with ILF2 and DHX9, and RNA/DNA hybrids. We showed that the microtubule and charged helical domains of NUSAP1 were necessary for the protein-protein interactions. Depletion of ILF2 alone further increased camptothecin-induced R-loop accumulation and DNA damage, and NUSAP1 depletion abolished this effect. In human prostate adenocarcinoma, NUSAP1 and ILF2 mRNA expression levels are positively correlated, elevated, and associated with poor clinical outcomes. Our study identifies a novel role for NUSAP1 in regulating R-loop formation and accumulation in response to DNA damage through its interactions with ILF2 and hence provides a potential therapeutic target.

Incidental T1 stage medullary thyroid carcinoma: The effect of tumour diameter on prognosis and therapeutic implications.

OBJECTIVE: The definition of the tumour diameter of micro-medullary thyroid carcinoma (micro-MTC) is insufficient. It is controversial to perform a completion thyroidectomy immediately for incidental T1 stage MTC. DESIGN: We used the Surveillance, Epidemiology and End Results (SEER) registry to retrospectively analyze all patients with T1 stage MTC diagnosed between 2004 and 2015. The tumour diameter 1.0 and 0.5 cm were used as the cut-off points to group and analyze the differences of clinicopathological features. We analyzed the prognosis of patients with less than total thyroidectomy. METHODS: The disease-specific survival was the main outcome. Survival was estimated with Kaplan-Meier curves and Cox regression models estimated hazard ratios for tumour characteristics. RESULTS: A total of 908 patients diagnosed with T1 stage MTC in the SEER database were included. Our study found that tumour diameter 1.0 cm is a key point affecting the prognosis of T1 stage MTC patients, although patients with tumour diameter ≤ 0.5 cm had a lower rate of lymph node metastasis and no distant metastasis. Cox proportional hazard multivariate analysis showed that distant metastasis was the only risk factor for survival in patients with T1 stage MTC. Kaplan-Meier survival analysis showed that, regardless of tumour diameter, there was no significant difference between less than total thyroidectomy and total thyroidectomy in T1 stage patients. CONCLUSIONS: For incidental MTC with tumour diameter ≤ 1.0 cm and without distant metastasis, if there is no significant increase in serum calcitonin level after surgery and ret proto-oncogene (RET) gene mutation is negative, it may be not necessary to perform completion thyroidectomy immediately.

AMPAkine CX516 alleviated chronic ethanol exposure-induced neurodegeneration and depressive-like behavior in mice.

Chronic ethanol exposure (CEE) is associated with greater neurodegenerative effects and an increased risk of depression disorder. The AMPAR is thought to be involved in depression and a reduction in its GluA1 subunit was observed in the mouse hippocampus after CEE. AMPAkines are positive allosteric modulators of the AMPA receptor and have improved depressive-like behavior. However, the role of AMPARs in CEE-induced depressive-like behavior is not clear. It is unclear whether AMPAkines, positive allosteric agonists of AMPARs, protect against ethanol-induced depression. We investigated the effects of CX516 on ethanol-induced depressive-like behavior in a mouse model. CX516 (5 mg/kg) administration alleviated 20% (m/V) ethanol-induced depressive-like behavior in mice. Furthermore, CX516 significantly diminished the inhibition of the ERK1/2-BDNF-TrkB pathway in the hippocampus of ethanol-exposed mice. In addition, CX516 attenuated the levels of pro-inflammatory (IL-6, IL-1ß), apoptosis (BAX, BCL-2), and neurodegeneration (FJC) in the mouse hippocampus induced by CEE.

Chronic ethanol exposure induced anxiety-like behaviour by altering gut microbiota and GABA system.

Ethanol, also known as alcohol, is one of the most common drinks in the world. Chronic ethanol exposure has been reported to induce mental disorders. Ethanol also has a strong effect on the gut microbiota. The gut microbiota has been reported to affect the brain via multiple pathways, including changes in γ-aminobutyric acid (GABA) system, and cause a variety of mental disorders. The GABA system in the cortex is associated with anxiety. However, the role of gut microbiota played in ethanol exposure-induced changes in the GABA system and anxiety is still not clear. We established a 30-day ethanol exposure mouse model and investigated the effects of microbiota using the antibiotic minocycline. Minocycline alleviated ethanol-induced anxiety-like behaviour, dysbiosis of microbiota, intestinal barrier disruption, increased serum endotoxin and interleukin (IL)-6. Minocycline also attenuated ethanol-induced apoptosis and decreased expression of glutamate decarboxylases (GADs) and GABRA1 in the prefrontal cortex. Our results indicated that gut microbiota plays an important role in ethanol-induced anxiety-like behaviour by altering the function of GABA system. In addition, causal mediation analysis showed that endotoxin and IL-6 may mediate the connection between the gut microbiota and the expression of GABAA receptor in the prefrontal cortex.

HYOU1 facilitates proliferation, invasion and glycolysis of papillary thyroid cancer via stabilizing LDHB mRNA.

HYOU1 is upregulated in many kinds of cancer cells, and its high expression is associated with tumour invasiveness and poor prognosis. However, the role of HYOU1 in papillary thyroid cancer (PTC) development and progression remains to be elucidated. Here, we reported that HYOU1 was highly expressed in human PTC and associated with poor prognosis. HYOU1 silencing suppressed the proliferation, migration and invasion of PTC cells. Mechanistic analyses showed that HYOU1 silencing promoted oxidative phosphorylation while inhibited aerobic glycolysis via downregulating LDHB at the posttranscriptional level. We further confirmed that the 3'UTR of LDHB mRNA is the indirect target of HYOU1 silencing and HYOU1 silencing increased miR-375-3p levels. While LDHB overexpression significantly suppressed the inhibitory effects of HYOU1 silencing on aerobic glycolysis, proliferation, migration and invasion in PTC cells. Taken together, our findings suggest that HYOU1 promotes glycolysis and malignant progression in PTC cells via upregulating LDHB expression, providing a potential target for developing novel anticancer agents.

Novel vaccine design based on genomics data analysis: A review.

Modification of pathogenic strains with the passage of time is responsible for evolution in the timeline of vaccine development for last 30 years. Recent advancements in computational vaccinology on the one hand and genome sequencing approaches on the other have generated new hopes in vaccine development. The aim of this review was to discuss the evolution of vaccines, their characteristics and limitations. In this review, we highlighted the evolution of vaccines, from first generation to the current status, pointing out how different vaccines have emerged and different approaches that are being followed up in the development of more rational vaccines against a wide range of diseases. Data were collected using Google Scholar, Web of Science, Science Direct, Web of Knowledge, Scopus and Science Hub, whereas computational tools such as NCBI, GeneMANIA and STRING were used to analyse the pathways of vaccine action. Innovative tools, such as computational tools, recombinant technologies and intra-dermal devices, are currently being investigated in order to improve the immunological response. New technologies enlightened the interactions of host proteins with pathogenic proteins for vaccine candidate development, but still there is a need of integrating transcriptomic and proteomic approaches. Although immunization with genomics data is a successful approach, its advantages must be assessed case by case and its applicability depends on the nature of the agent to be immunized, the nature of the antigen and the type of immune response required to achieve effective protection.

Clinicopathological Characteristics and Prognosis of Poorly Differentiated Thyroid Carcinoma Diagnosed According to the Turin Criteria.

OBJECTIVE: Poorly differentiated thyroid carcinoma (PDTC) is the primary cause of death in patients with nonanaplastic follicular cell-derived thyroid carcinoma. We purposed to identify the clinical and pathological characteristics of PDTC and their relationship with prognosis. METHODS: A retrospective analysis was conducted on patients diagnosed with PDTC at our institution from 2010 to 2018. All of their histopathology slides were reviewed by 2 experienced pathologists based on the Turin criteria. Furthermore, information regarding clinical characteristics, pathological characteristics, treatment strategy, and follow-up events were collected. The Kaplan-Meier method was used for survival analysis, while the log-rank test was used to compare survival curves. Then, the Cox proportional hazards model was used to perform univariate and multivariate analyses. RESULTS: Twenty-six patients with PDTC who met the Turin criteria were enrolled in this study. The median follow-up period of the included 26 patients was 76 months, while the 3- and 5-year survival rates were 40% and 18%, respectively. Notably, univariate analysis revealed that tumor size >4 cm (P = .038), extrathyroidal extension (ETE) (P = .020), distant metastases (P = .047), poorly differentiated areas >60% (P = .049), and Ki-67 labeling index >30% (P = .040) were associated with poor prognosis. On the other hand, multivariate analysis identified ETE (P = .007) and distant metastases (P = .031) as independent risk factors for poor prognosis. CONCLUSION: PDTC is a rare carcinoma with high invasiveness and poor prognosis. Patients with ETE or distant metastases may have adverse outcomes.

Unilateral Tnm T1 And T2 Papillary Thyroid Carcinoma With Lateral Cervical Lymph Node Metastasis: Total Thyroidectomy or Lobectomy?

OBJECTIVE: The aim of this study was to explore the effect of total thyroidectomy (TT) and lobectomy (LT) on the prognosis of unilateral papillary thyroid carcinoma (PTC) with lateral cervical lymph node metastasis. METHODS: Patients with PTC and lateral cervical lymph node metastasis who underwent lateral cervical lymph node dissection between January 2007 and December 2016 were retrospectively reviewed. To investigate the effect of surgical procedure on the prognosis of lymph node metastasis patients, other high-risk factors such as extrathyroidal invasion and large tumor size were excluded. All patients were in Tumor-Node-Metastasis (TNM) stage T1 and T2. Primary end point was recurrence-free survival (RFS). RESULTS: Among 264 PTC patients, 104 (39.4%) patients received TT and 160 (60.6%) patients received LT. With a median follow-up of 50 months (interquartile range, 34 to 74 months), 7 patients (2.65%) experienced recurrence. The 5-year RFS in the TT and LT groups was 96.1% and 97.7%, respectively, and was not significantly different (P = .765). Similar results were found when excluding patients who received radioiodine ablation, which were 97.7% and 97.4%, respectively (P = .752). Age ≥55 years (hazard ratio, 7.368; P = .018) and multifocality in the ispi-lateral lobe (hazard ratio, 10.059; P =.006) were identified as independent risk factors of recurrence. CONCLUSION: For unilateral TNM T1 and T2 PTC patients with lateral lymph node metastasis, there was no significant difference in the effect of TT and LT for RFS in the absence of other risk factors during the follow-up period. Patient age ≥55 years with multifocality in the unilateral lobe might be independent risk factors for prognosis.

Comparison of Outcomes Following Thyroid Isthmusectomy, Unilateral Thyroid Lobectomy, and Total Thyroidectomy in Patients with Papillary Thyroid Microcarcinoma of the Thyroid Isthmus: A Retrospective Study at a Single Center.

BACKGROUND Papillary thyroid microcarcinoma (PTMC) measures less than 10 mm in diameter, is more common in the thyroid lobes, but rarely presents in the thyroid isthmus. This retrospective study aimed to compare patient outcomes following various types of surgery in patients with PTMC of the thyroid isthmus, at a single center in China. MATERIAL AND METHODS We analyzed the clinical data of patients with isthmus thyroid cancer treated at the First Hospital of China Medical University. Patients were divided into 2 groups according to the tumor diameter-PTMC of the thyroid isthmus and papillary thyroid carcinoma >10 mm. The clinicopathological features between the 2 groups were compared, and the effects of various surgical methods on the prognosis of patients were analyzed. RESULTS A total of 70 patients were included in this study: 29 with PTMC of the thyroid isthmus (41.4%) and 41 with papillary thyroid carcinoma >10 mm (58.6%). The rates of lymph node metastasis (10.3% vs. 34.1%) and extrathyroid extension (0% vs. 14.6%) in the PTMC of the thyroid isthmus were significantly lower than those in the papillary thyroid carcinoma >10 mm. The recurrence-free survival (RFS) rate was 97.1%. Survival analysis showed that there was no significant difference in RFS among patients with PTMC of the thyroid isthmus undergoing isthmusectomy, unilateral lobectomy, and total thyroidectomy. CONCLUSIONS These findings from a single center showed that for patients with PTMC of the thyroid isthmus, who had no comorbidities, there was no significant difference in outcome between the 3 types of thyroid surgery.

Disruption of TAB1/p38α interaction using a cell-permeable peptide limits myocardial ischemia/reperfusion injury.

Targeting the adaptor protein (transforming growth factor-ß (TGF-ß)-activated protein kinase 1 (TAK1)-binding protein 1) (TAB1)-mediated non-canonical activation of p38α to limit ischemia/reperfusion (I/R) injury after an acute myocardial infarction seems to be attractive since TAB1/p38α interaction occurs specifically in very limited circumstances and possesses unique structural basis. However, so far no TAB1/p38α interaction inhibitor has been reported due to the limited knowledge about the interfaces. In this study, we sought to identify key amino acids essential for the unique mode of interaction with computer-guided molecular simulations and molecular docking. After validation of the predicted three-dimensional (3-D) structure of TAB1/p38α complex, we designed several peptides and evaluated whether they could block TAB1/p38α interaction with selectivity. We found that a cell-permeable peptide worked as a selective TAB1/p38α interaction inhibitor and decreased myocardial I/R injury. To our knowledge, this is the first TAB1/p38α interaction inhibitor.

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.