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Colorectal cancer (CRC) is one of the leading cancers worldwide, with metastasis being a major cause of high mortality rates among patients. In this study, dysregulated gene Tweety homolog 3 (TTYH3) was identified by Gene Expression Omnibus database. Public databases were used to predict potential competing endogenous RNAs (ceRNAs) for TTYH3. Quantitative real‐time polymerase chain reaction, western blot, and immunohistochemistry were utilized to analyze TTYH3 and histone deacetylase 7 (HDAC7) levels. Luciferase assays confirmed miR‐1271‐5p directly targeting the 3′ untranslated regions of TTYH3 and HDAC7. In vitro experiments such as transwell and human umbilical vein endothelial cell tube formation, as well as in vivo mouse models, were conducted to assess the biological functions of TTYH3 and HDAC7. We discovered that upregulation of TTYH3 in CRC promotes cell migration by affecting the Epithelial–mesenchymal transition pathway, which was independent of its ion channel activity. Mechanistically, TTYH3 and HDAC7 functioned as ceRNAs, reciprocally regulating each other's expression. TTYH3 competes for binding miR‐1271‐5p, increasing HDAC7 expression, facilitating CRC metastasis and angiogenesis. This study reveals the critical role of TTYH3 in promoting CRC metastasis through ceRNA crosstalk, offering new insights into potential therapeutic targets for clinical intervention. [ABSTRACT FROM AUTHOR]

Background and Objectives. Timely identification of developing severe respiratory failure in patients with autoimmune encephalitis (AE) is crucial to ensure prompt treatment with invasive mechanical ventilation (IMV), which can potentially improve the outcome. We aimed to develop a nomogram for requiring IMV based on easily available clinical characteristics. Methods. A multivariate predictive nomogram model was developed using the risk factors identified by LASSO regression and assessed by receiver operator characteristics (ROC) curve, calibration curve, and decision curve analysis. Results. The risk factors predictive of severe respiratory failure were male gender, impaired hepatic function, elevated intracranial pressure, and higher neuron-specific enolase. The final nomogram achieved an AUC of 0.770. After validation by bootstrapping, a concordance index of 0.748 was achieved. Conclusions. Our nomogram accurately predicted the risk of developing respiratory failure needing IMV in AE patients and provide clinicians with a simple and effective tool to guide treatment interventions in the AE patients. [ABSTRACT FROM AUTHOR]

To conclude, we demonstrated that increases in air pollutant concentrations and changes in meteorological conditions are associated with number of outpatient visits for AR. Keywords: air pollutants; allergic rhinitis; distributed non-linear lag model; generalized additive model; meteorological factors EN air pollutants allergic rhinitis distributed non-linear lag model generalized additive model meteorological factors 1656 1659 4 06/02/23 20230601 NES 230601 Allergic rhinitis (AR) is characterized by nasal obstruction, pruritus, rhinorrhea, and sneezing, and it affects 10% to 40% of the population.[1] The prevalence of self-reported AR has been reported increasingly from 11.1% to 17.6% in China.[2] Climate change and air pollution are thought to be responsible for the global increase in allergic diseases.[[3]] However, most previous studies on air pollution or meteorological factors affecting AR have been conducted in a single- and medium-latitude city.[[5]] To find the association between daily air pollutants and meteorological factors and the incidence of AR, we conducted this low-latitude multi-city study in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA), China. (B) Percent change (95% CI) of daily AR outpatient visits for each ten units increase in concentrations of six pollutants using different lag structures in GBA. [Extracted from the article]

Histone deacetylases (HDACs) are involved in many processes including tumor cell growth and proliferation and regulation of gene expression. To clarify the role of class IIa HDACs in the metastasis of colon adenocarcinoma, we used the class IIa HDAC inhibitor TMP269 and found that it effectively inhibited the migration ability of colon adenocarcinoma cells. Next, we silenced the member of class IIa HDACs and confirmed that the migratory ability of colon adenocarcinoma cells was significantly inhibited by silencing HDAC5 or HDAC7. HDAC5 plays a variety of roles in human cancers. Here, we examined the role of HDAC5 in colon adenocarcinoma. The results indicated that HDAC5 was highly expressed in tumor tissues and negatively correlated with the expression of miR‐148a‐3p. Moreover, the expression of HDAC5 was correlated with tumor progression. HDAC5 markedly increased the invasion and migration of cancer cells in vitro, an effect that could be inhibited by overexpression of miR‐148a‐3p. Following an intraperitoneal injection of colon adenocarcinoma cells in athymic nude mice, HDAC5 promoted tumor implant. Together, these findings showed that HDAC5 overexpression in colon adenocarcinoma is consistent with tumor progression and tumor cell migration and the impact of HDAC5 overexpression is reduced by miR‐148a‐3p. [ABSTRACT FROM AUTHOR]

The present study incorporated a moderated mediation model to explore the role of attitude towards condom use in mediating the link between sexual sensation seeking (SSS) and condom use and whether this indirect link was modified by HIV-related knowledge among Chinese YMSM. Survey data were collected from a cross-sectional study conducted in Wuhan, China and 373 YMSM were recruited. The mediation and moderated mediation modelling analyses were performed with the software SPSS PROCESS macro. Mediation analysis indicated that attitude towards condom use partly mediated the link between SSS and condom use (indict effect = −0.158, P < 0.001). Moderation analysis found HIV-related knowledge acted as a moderator in the relationship between SSS and attitude towards condom use (interact effect = 0.089, P = 0.001). Final moderated mediation analysis demonstrated that the indirect effect from SSS to condom use through attitude towards condom use was moderated by HIV-related knowledge, that is the interaction between HIV-related knowledge and SSS was positively associated with attitude towards condom use (β = 0.101, P < 0.001). Therefore, increased YMSM-specific HIV-related knowledge education programs need to be conducted. Further longitudinal research is required to verify the findings of this study. [ABSTRACT FROM AUTHOR]

The apolipoprotein C3 (APOC3) gene, which is a member of the APOA1/C3/A4/A5 gene cluster, plays a crucial role in lipid metabolism. Dyslipidemia is an important risk factor for ischemic stroke. In the present study, we performed a hospital-based case—control study of 895 ischemic stroke patients and 883 control subjects to examine the effects of four APOC3 single nucleotide polymorphisms (SNPs) (rs2854116, rs2854117, rs4520 and rs5128) on the risk of ischemic stroke in a northern Chinese Han population. The SNaPshot Multiplex sequencing assay was used for SNP genotyping, and the potential association of genotype distributions and allele frequencies with ischemic stroke was analyzed statistically. Compared with the GG genotype, the CC+GC genotype of rs5128 was significantly associated with an increased risk in females (adjusted OR = 3.38, 95% CI = 1.82–6.28, P <0.01) after all of the risk factors were adjusted for with logistic regression analyses. A similar relationship was found between the rs4520 polymorphism and ischemic stroke risk in Han Chinese women. Under a recessive genetic model, the TT+TC genotypes of this variant increased ischemic stroke risk (adjusted OR = 2.05; 95% CI = 1.28–3.29; P <0.01). Haplotype analysis revealed that in males, the T-C-T-C haplotype of rs2854116-rs2854117-rs4520-rs5128 was significantly more frequent in the ischemic stroke group than in the control group (OR = 1.49, 95% CI = 1.18–1.87, P<0.01). The results of our study indicate that the APOC3 polymorphisms contribute to ischemic stroke susceptibility in females in the northern Chinese Han population. [ABSTRACT FROM AUTHOR]

Background: Stroke is the second most common cause of death and major cause of disability worldwide. The SNP 83 in PDE4D gene has been suggested as a risk factor in ischemic stroke, but direct evidence from genetic association studies remains inconclusive even in Chinese population. Methods: Meta-analysis of case-control studies on the relationship between SNP 83 in PDE4D gene and susceptibility to ischemic stroke in Chinese population published domestically and abroad from January 2003 to September 2012. Results: 9 case-control studies were selected. Meta-analysis results showed that the significant association between SNP 83 and ischemic stroke was found under the dominant model (OR = 1.34, 95% CI: 1.20–1.49) and recessive model (OR = 1.45, 95% CI: 1.19–1.76) in Chinese population. In subgroup meta-analysis, SNP 83 and atherothrombotic stroke, rather than lacunar stroke, showed the significant association under the dominant model (OR = 1.69, 95% CI: 1.41–2.01) and recessive model (OR = 1.47, 95% CI: 1.04–2.06). Conclusions: The results suggest that SNP 83 in PDE4D gene is significantly associated with susceptibility to ischemic stroke in Chinese population. [ABSTRACT FROM AUTHOR]

Data stream learning has been largely studied for extracting knowledge structures from continuous and rapid data records. As data is evolving on a temporal basis, its underlying knowledge is subject to many challenges. Concept drift, 1 1 This work is addressing the challenge concept drift in machine learning as opposed to concept drift in the Semantic Web community where "concept" (class) meaning in ontology TBox shifts from versioning, iterations or modifications. Note that changes in ABox alone can also lead to concept drift in learning from ontology streams.. as one of core challenge from the stream learning community, is described as changes of statistical properties of the data over time, causing most of machine learning models to be less accurate as changes over time are in unforeseen ways. This is particularly problematic as the evolution of data could derive to dramatic change in knowledge. We address this problem by studying the semantic representation of data streams in the Semantic Web, i.e., ontology streams. Such streams are ordered sequences of data annotated with ontological vocabulary. In particular we exploit three levels of knowledge encoded in ontology streams to deal with concept drifts: i) existence of novel knowledge gained from stream dynamics, ii) significance of knowledge change and evolution, and iii) (in)consistency of knowledge evolution. Such knowledge is encoded as knowledge graph embeddings through a combination of novel representations: entailment vectors, entailment weights, and a consistency vector. We illustrate our approach on classification tasks of supervised learning. Key contributions of the study include: (i) an effective knowledge graph embedding approach for stream ontologies, and (ii) a generic consistent prediction framework with integrated knowledge graph embeddings for dealing with concept drifts. The experiments have shown that our approach provides accurate predictions towards air quality in Beijing and bus delay in Dublin with real world ontology streams. [ABSTRACT FROM AUTHOR]

Urban computing at present often relies on a large number of manually extracted features. This may require a considerable amount of feature engineering, and the procedure may miss certain hidden features and relationships among data items. In this paper, we propose a method to use structured prior knowledge in the form of knowledge graphs to improve the precision and interpretability in applications such as optimal store placement and traffic accident inference. Specifically, we integrate sub-graph feature extraction, sub-knowledge graph gated neural networks, and kernel-based knowledge graph convolutional neural networks as ways of incorporating large urban knowledge graphs into a fully end-to-end learning system. Experiments using data from several large cities showed that our method outperforms the baseline methods. [ABSTRACT FROM AUTHOR]

Abstract: Background: The single-nucleotide polymorphisms (SNPs) of the phosphodiesterase 4D (PDE4D) and interleukin-1 (IL-1) genes are associated with increased risk for the development of ischemic stroke (IS) in whites. However, little is known about whether this association could also occur in Han Chinese. Method: A total of 371 patients with IS and unrelated healthy controls were recruited and the SNPs of the PDE4D (83T/C), (87T/C), IL-1 (−889C/T) and IL-1 (−511C/T) were characterized, respectively, by polymerase chain reactions-restriction fragment length polymorphism (PCR-RFLP). The genotype and allele frequencies of these SNPs in this population were statistically analyzed. Results: The genotype and allele frequencies of the PDE4D (87T/C) and IL-1 (−511C/T) were similar between IS patients and controls. In contrast, the frequencies of CC genotype and C allele of the PDE4D (83T/C) and the T allele frequency of IL-1 (−889C/T) in IS patients were significantly higher than that in healthy controls (p =0.001, p =0.003 and p =0.02, respectively), independent of the conventional risk factors. The values of odds ratio (OR) reached at OR=1.603; 95%CI=1.032–2.489; p =0.036 for the CC genotype of the PDE4D (83T/C) and OR=1.913; 95%CI=1.621–2.375; p =0.034 for the TT genotype of the IL-1 (−889C/T), respectively. Conclusions: the SNPs of the PDE4D (83T/C) and IL-1 (−889C/T) were associated with increased risk for the development of IS in Northern Han Chinese. [Copyright &y& Elsevier]

Objectives: Ischemic stroke has long been a global health threat. Genetic factors, a looming risk for ischemic stroke, remain unexplored. The high-mobility group box 1 (HMGB1) protein showed a connection with the occurrence and development of ischemic stroke. This study was conducted to find whether frequent HMGB1 polymorphisms (rs1045411, rs1412125, and rs2249825) play a role in ischemic stroke susceptibility and recurrence risk., Methods: Our study was carried out in a Chinese Han population with a sample size of 871 patients and 858 age-matched healthy controls. Tag single nucleotide polymorphisms (tagSNPs) were selected by conventional protocols and DNA was extracted for genotype analysis after the participants had signed an informed consent. Comprehensive statistical analyses were conducted., Results: It was found that the C allele of the HMGB1 rs1412125 (OR = 1.263, 95% CI = 1.075-1.483, P = 0.004) and HMGB1 rs2249825 (adjusted OR = 2.464, 95% CI = 1.215-4.996, P = 0.012) variants was associated with a high risk of ischemic stroke, with the male subgroup carrying the TT allele of the HMGB1 rs1045411 variant tended to suffer more from the disease (adjusted OR = 3.600, 95% CI = 1.272-10.193, P = 0.016). A haplotype study also showed significant results (OR = 1.554, 95% CI = 1.246-1.938, P = 0.001). The rs1412125 polymorphism was highly associated with the chance of recurrence but not with the onset age (TC vs. TT: P = 0.034; CC vs. TT: P < 0.001). Cox regression analysis and stratified analysis were carried out with notable conclusions., Conclusions: Our study provided evidence for the association between HMGB1 polymorphisms and ischemic stroke susceptibility and recurrence, indicating that HMGB1 gene variants may be potential markers for first and secondary stroke prevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (AJTR Copyright © 2023.)

Microglia, which are the primary inflammatory cells of the brain, can undergo phenotypic switching between M1 and M2 polarization, which have opposing effects on inflammation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor family of ligand-inducible transcription factors, and PPARγ is known to regulate M2 macrophage polarization. Previous studies have shown that the natural pentacyclic triterpenoid ursolic acid (3β-hydroxy-urs-12-en-28-oic acid; UA) influences microglial activation. Additionally, UA increases tissue inhibitor matrix metalloproteinase 1 (TIMP1), while greatly reducing the release of matrix metalloproteinase 2 (MMP2) and MMP9 in a PPARγ-dependent manner. Here, we examined the anti-inflammatory properties of UA by observing how well it promotes the phenotypic transition of lipopolysaccharide (LPS) and interferon gamma (IFNγ)-activated BV2 microglia from M1 to M2 polarization. To determine if PPARγ is involved in the underlying molecular pathway, we treated rats with UA and the PPARγ inhibitor BADGE. We also investigated the mechanisms by which PPARγ controls transcription from the MMP2 promoter. The in-vitro experiments showed that UA shifted LPS/IFNγ-activated BV2 microglia from the M1 to the M2 phenotype, which was associated with a reduction in the neurotoxic factors MMP2 and MMP9, and an increase in the anti-inflammatory factor TIMP1. Co-treatment with increased MMP2 and MMP9 synthesis while decreasing TIMP1 release, indicating that UA has anti-inflammatory effects on LPS/IFNγ-activated BV2 cells via activation of PPARγ. Next, we found that PPARγ directly influences MMP2 transcriptional activity by identifying the crucial peroxisome proliferator response element (PPRE) among five potential PPREs in the MMP2 promoter. These results suggest that UA has a protective anti-inflammatory effect against neuroinflammatory toxicity, which is exerted by direct activation of PPARγ and selectively modulates microglial polarization and suppresses MMP2 formation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Neuroinflammation contributes to secondary brain injury following intracerebral hemorrhage (ICH). Triggering receptor expressed on myeloid cells 2 (TREM2) confers strong neuroprotective effect by suppressing neuroinflammatory response in experimental ischemic stroke. This study aimed to clarify the neuroprotective role of TREM2 and potential underlying mechanism in a mouse model of ICH and in vitro . Adeno-associated virus (AAV) and green fluorescent protein-lentivirus (GFP-LV) strategies were employed to enhance TREM2 expression in the C57/BL6 mice and BV2 cells, respectively. The adult male C57/BL6 mice were subjected to ICH by administration of collagenase-IV in 1 month after the AAV particles injection. An in vitro ICH model was performed with oxygen hemoglobin in BV2 cells. Toll-like receptor 4 (TLR4) antagonist TAK242 was applied at 6 h following ICH. Neurological function, TREM2, pro-inflammatory cytokines, brain water content and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were evaluated at 24 h following ICH. TLR4, NF-κB and mitogen-activated protein kinases (MAPK) signaling pathways were also determined by Western blot analysis at the same time point. The levels of TREM2 were increased at 12 h, peaked at 24 h and recovered on 7d following ICH. TREM2 overexpression ameliorated ICH induced neurological dysfunction, inhibited neuroinflammation, and attenuated apoptosis and brain edema. Further mechanistic study revealed that TREM2 overexpression inhibited TLR4 activation and NF-κB and MAPK signaling pathways. ICH increased the percentage of TUNEL-positive cells, which was markedly decreased by TREM2 overexpression. A similar improvement was also observed by the administration of TAK242 following ICH. TREM2 improves neurological dysfunction and attenuates neuroinflammation and neuronal apoptosis in the acute phase of ICH, which is, at least in part, mediated by negatively regulating TLR4 signaling pathway. These findings highlight TREM2 as a potential target for early brain injury following ICH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Cao, Wu, Deng, Fu, Wang and Liu.)

Toll-like receptors (TLRs) play key roles in cerebral ischemia and reperfusion injury by inducing the production of inflammatory mediators, such as interleukins (ILs) and tumor necrosis factor-alpha (TNF-α). According to recent studies, ursolic acid (UA) regulates TLR signaling and exhibits notable anti-inflammatory properties. In the present study, we explored the mechanism by which UA regulates inflammation in the rat middle cerebral artery occlusion and reperfusion (MCAO/R) model. The MCAO/R model was induced in male Sprague-Dawley rats (MCAO for 2 h, followed by reperfusion for 48 h). UA was administered intragastrically at 0.5, 24, and 47 h after reperfusion. The direct high mobility group box 1 (HMGB1) inhibitor glycyrrhizin (GL) was injected intravenously after 0.5 h of ischemia as a positive control. The degree of brain damage was estimated using the neurological deficit score, infarct volume, histopathological changes, and neuronal apoptosis. We assessed IL-1β, TNF-α, and IL-6 levels to evaluate post-ischemic inflammation. HMGB1 and TLR4 expression and phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) were also examined to explore the underlying mechanism. UA (10 and 20 mg/kg) treatment significantly decreased the neurological deficit scores, infarct volume, apoptotic cells, and IL-1β, TNF-α, and IL-6 concentrations. The infarct area ratio was reduced by (33.07 ± 1.74), (27.05 ± 1.13), (27.49 ± 1.87), and (39.74 ± 2.14)% in the 10 and 20 mg/kg UA, GL, and control groups, respectively. Furthermore, UA (10 and 20 mg/kg) treatment significantly decreased HMGB1 release and the TLR4 level and inactivated NFκB signaling. Thus, the effects of intragastric administration of 20 mg/kg of UA and 10 mg/kg of GL were similar. We provide novel evidence that UA reduces inflammatory cytokine production to protect the brain from cerebral ischemia and reperfusion injury possibly through the HMGB1/TLR4/NFκB signaling pathway.

Objective Given its effects on lipid metabolism, the apolipoprotein A1-C3-A5 ( APOA1-C3-A5) gene cluster is thought to play an important role in ischemic stroke pathogenesis. Here, we evaluated whether the APOA1-C3-A5 cluster is associated with ischemic stroke in the northern Chinese Han population. Methods This case-control study analyzed 812 patients with ischemic stroke and 844 healthy controls with regard to four APOA1-C3-A5 cluster promoter single nucleotide polymorphisms (SNPs), rs670, rs2854116, rs2854117, and rs662799, using the SNaPshot Multiplex sequencing assay. Potential associations among ischemic stroke, genotyping, and allele frequencies were assessed. Results APOA1 rs670 CT/TT genotypes, APOA5 rs662799 AG/GG genotypes, and the APOC3 rs2854116 CC genotype were associated with an increased risk of ischemic stroke according to multivariate logistic analysis after adjusting for confounding factors. A significantly increased risk for ischemic stroke was also identified among high-risk haplotypes (C-C-T-A and T-T-C-A) for rs670-rs2854116-rs2854117-rs662799. Conclusion This study showed that rs670, rs2854116, and rs662799 SNPs of the APOA1-C3-A5 cluster are associated with ischemic stroke in the northern Chinese Han population.

Background: Activators of PPARs, particularly PPARγ, may be effective neuroprotective drugs against inflammatory responses in cerebral ischemia and reperfusion injury. Ursolic acid (UA) may act as a PPARγ agonist and serve as an anti-inflammatory agent. In this study, we used a rat middle cerebral artery occlusion and reperfusion model to examine how UA acts as a neuroprotective agent to modulate the metalloprotease/anti-metalloprotease balance., Methods: The middle cerebral artery occlusion and reperfusion model (occlusion for 2 hours followed by reperfusion for 48 hours) was induced in male Sprague Dawley rats. UA was administered intragastrically 0.5, 24, and 47 hours after reperfusion. Bisphenol A diglycidyl ether (a PPARγ antagonist) was intraperitoneally administered 1, 24.5, and 47.5 hours after reperfusion. Forty-eight hours after reperfusion, neurological deficits and infarct volume were estimated. The PPARγ level and the metalloprotease/anti-metalloprotease balance were examined by Western blotting and immunohistochemistry. The activation of MAPK signaling pathways was also assessed., Results: UA-treated (5, 10, or 20 mg/kg) rats showed significant improvement in neurological deficit score, infarct volume, and the number of intact neurons compared with control rats (P<0.01). Both the PPARγ protein level and the percentage of PPARγ-positive cells were increased in the UA-treated groups (P<0.01). Compared with the control group, the UA-treated groups exhibited reduced protein levels of MMP2, MMP9, and activated MAPKs (P<0.01) but an increased level of TIMP1 (P<0.01). UA exerted its protective effects in a dose-dependent manner. Co-treatment with UA and bisphenol A diglycidyl ether completely abolished the UA-induced changes in PPARγ expression; however UA continued to exert a significant but partial neuroprotective effect., Conclusion: UA can act as a PPARγ agonist to improve the metalloprotease/anti-metalloprotease balance, possibly by inhibiting the activation of the MAPK signaling pathway, thereby attenuating cerebral ischemia and reperfusion injury. Therefore, UA may serve as a novel neuroprotective therapeutic agent.