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Abstract Background The causes of migraine remain unclear. Evidence suggests that the MAPK and PI3K/Akt signaling pathways play a role in migraine pathogenesis. However, studies on genetic polymorphisms in the two pathways associated with migraine are still limited. Methods This study included 226 migraineurs and 452 age‐ and sex‐matched nonmigraine control individuals. Genotyping of 31 Single Nucleotide Polymorphisms (SNPs) in 21 genes was performed. The relationship between migraine and gene polymorphisms was analyzed by using logistic regression. SNP–SNP interactions were examined by a generalized multifactor dimension reduction (GMDR) approach. The possible role of SNPs was evaluated with gene expression data from the GTEx database. Results The RASGRP2‐rs2230414 GT genotype was associated with decreased migraine risk compared with the wild‐type GG genotype [ORadj (95% CI): 0.674(0.458–0.989)]. PIK3R1‐rs3730089 was associated with migraine in the recessive model [ORadj (95% CI): 1.446(1.004–2.083)]. The CACNA1H‐rs61734410 CT genotype was associated with migraine risk [ORadj (95% CI): 1.561(1.068–2.281)]. One significant two‐way SNP–SNP interaction was found (PRKCA rs2228945‐BDNF rs6265) (p = 0.0107). Significant eQTL and sQTL signals were observed for the SNP rs2230414. Conclusions This is the first study to systematically reveal significant associations between MAPK and PI3K/Akt signaling pathway‐related gene polymorphisms and migraine risk.

Background: Genetic and environmental factors contribute to migraine and the comorbidities of anxiety and depression. However, the association between genetic polymorphisms in the transient receptor potential (TRP) channels and glutamatergic synapse genes with the risk of migraine and the comorbidities of anxiety and depression remain unclear.Methods: 251 migraine patients containing 49 comorbidities with anxiety and 112 with depression and 600 controls were recruited. A customized 48-plex SNPscan kit was used for genotyping 13 SNPs of nine target genes. Logistic regression was conducted to analyze these SNPs’ association with the susceptibility of migraine and comorbidities. The generalized multifactor dimension reduction (GMDR) was applied to analyze the SNP-SNP and gene-environment interactions. The GTEx database was used to examine the effects of the significant SNPs on gene expressions.Results: The TRPV1 rs8065080 and TRPV3 rs7217270 were associated with an increased risk of migraine in the dominant model [ORadj (95% CI): 1.75 (1.09–2.90), p = 0.025; 1.63 (1.02–2.58), p = 0.039, respectively]. GRIK2 rs2227283 was associated with migraine in the edge of significance [ORadj (95% CI) = 1.36 (0.99–1.89), p = 0.062]. In migraine patients, TRPV1 rs222741 was associated with both anxiety risk and depression risk in the recessive model [ORadj (95% CI): 2.64 (1.24–5.73), p = 0.012; 1.97 (1.02–3.85), p = 0.046, respectively]. TRPM8 rs7577262 was associated with anxiety (ORadj = 0.27, 95% CI = 0.10–0.76, p = 0.011). TRPV4 rs3742037, TRPM8 rs17862920 and SLC17A8 rs11110359 were associated with depression in dominant model [ORadj (95% CI): 2.03 (1.06–3.96), p = 0.035; 0.48 (0.23–0.96), p = 0.042; 0.42 (0.20–0.84), p = 0.016, respectively]. Significant eQTL and sQTL signals were observed for SNP rs8065080. Individuals with GRS (Genetic risk scores) of Q4 (14–17) had a higher risk of migraine and a lower risk of comorbidity anxiety than those with Genetic risk scores scores of Q1 (0–9) groups [ORadj (95% CI): 2.31 (1.39–3.86), p = 0.001; 0.28 (0.08–0.88), p = 0.034, respectively].Conclusion: This study suggests that TRPV1 rs8065080, TRPV3 rs7217270, and GRIK2 rs2227283 polymorphism may associate with migraine risk. TRPV1 rs222741 and TRPM8 rs7577262 may associate with migraine comorbidity anxiety risk. rs222741, rs3742037, rs17862920, and rs11110359 may associate with migraine comorbidity depression risk. Higher GRS scores may increase migraine risk and decrease comorbidity anxiety risk.

As an essential part of urban public space, the basic framework of urban pattern, and the human landscape of the city and street space is of great significance to urban development. From the perspective of urban living safety, the demand for urban space for health has been considered in depth again. Therefore, with emerging new issues in the post-urbanization period such as the development of public health and slow traffic transportation, street space becomes disordered, and the health of street space has drawn great attention. This paper takes the old urban area of Daoli District of Harbin City as an example. The degree of spatial disorder of different streets in the old urban area of Daoli District of Harbin City is derived by using the off-site built environment audit method and mean square weight analysis and other technical methods with multi-source data such as Baidu map API. In this paper, the spatial health measurement of streets with different properties of land usage in the old urban area of Daoli District of Harbin City is classified, and the classification strategies are proposed based on the calculation results. Based on the theory of spatial disorder, a large-scale measurement of street space health provides insights and references for practical urban management in the future. In terms of theoretical research, this paper attempts to fill the gap in urban geospatial disorder research in China.

Despite the tremendous clinical potential of nucleic acid-based vaccines, their efficacy to induce therapeutic immune response has been limited by the lack of efficient local gene delivery techniques in the human body. In this study, we develop a hydrogel-based organic electronic device (pEPO) for both transdermal delivery of nucleic acids and in vivo microarrayed cell electroporation, which is specifically oriented toward one-step transfection of DNAs in subcutaneous antigen-presenting cells (APCs) for cancer immunotherapy. The pEPO device contains an array of microneedle-shaped electrodes with pre-encapsulated dry DNAs. Upon a pressurized contact with skin tissue, the electrodes are rehydrated, electrically triggered to release DNAs, and then electroporate nearby cells, which can achieve in vivo transfection of more than 50% of the cells in the epidermal and upper dermal layer. As a proof-of-concept, the pEPO technique is employed to facilitate transdermal delivery of neoantigen genes to activate antigen-specific immune response for enhanced cancer immunotherapy based on a DNA vaccination strategy. In an ovalbumin (OVA) cancer vaccine model, we show that high-efficiency transdermal transfection of APCs with OVA-DNAs induces robust cellular and humoral immune responses, including antigen presentation and generation of IFN-Y+ cytotoxic T lymphocytes with a more than 10-fold dose sparing over existing intramuscular injection (IM) approach, and effectively inhibits tumor growth in rodent animals. [ABSTRACT FROM AUTHOR]

With emerging Network Functions Virtualization (NFV) and Software Defined Networking (SDN) paradigms in Network Management (NM), new network devices and features can immediately become available. Available network resources and services can be altered and optimized in real time to gain the maximum benefit. However, this requires real time analytics information sent to SDN controllers rather than traditional manual offine or batch analytic outputs which are delivered on hourly or monthly basis in NM Systems. As a result, real time stream analytics is becoming a critical element for NM. In this paper, we describe a anomaly detection analytic engine for NM system development. We describe the design principles, innovative algorithm design, architecture and implementation of the engine in relation to streaming data and mobile NM. Finally, we present use cases and evaluation results. [ABSTRACT FROM AUTHOR]

Background Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that is characterized by dementia, cognitive impairment, and memory loss. Diverse factors are related to the development of AD, such as increased level of β-amyloid (Aβ), acetylcholine, metal ion deregulation, hyperphosphorylated tau protein, and oxidative stress. Methods The following methods were used: organic syntheses of 1H-phenanthro[9,10-d]imidazole derivatives, inhibition of self-mediated and metal-induced Aβ1-42 aggregation, inhibition studies for acetylcholinesterase and butyrylcholinesterase, anti-oxidation activity studies, CD, MTT assay, transmission electron microscopy, dot plot assay, gel electrophoresis, Western blot, and molecular docking studies. Results We synthesized and characterized a new type of 1H-phenanthro[9,10-d]imidazole derivatives as multifunctional agents for AD treatment. Our results showed that most of these derivatives exhibited strong Aβ aggregation inhibitory activity. Compound 9g had 74% Aβ1-42 aggregation inhibitory effect at 10 μM concentration with its IC50 value of 6.5 μM for self-induced Aβ1-42 aggregation. This compound also showed good inhibition of metal-mediated (Cu2 + and Fe2 +) and acetylcholinesterase-induced Aβ1-42 aggregation, as indicated by using thioflavin T assay, transmission electron microscopy, gel electrophoresis, and Western blot. Besides, compound 9g exhibited cholinesterase inhibitory activity, with its IC50 values of 0.86 μM and 0.51 μM for acetylcholinesterase and butyrylcholinesterase, respectively. In addition, compound 9g showed good anti-oxidation effect with oxygen radical absorbance capacity (ORAC) value of 2.29. Conclusions Compound 9g was found to be a potent multi-target-directed agent for Alzheimer's disease. [ABSTRACT FROM AUTHOR]