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Abstract Liver cancer arises from the evolutionary selection of the dynamic tumor microenvironment (TME), in which the tumor cell generally becomes more heterogeneous; however, the mechanisms of TME-mediated transcriptional diversity of liver cancer remain unclear. Here, we assess transcriptional diversity in 15 liver cancer patients by single-cell transcriptome analysis and observe transcriptional diversity of tumor cells is associated with stemness in liver cancer patients. Tumor-associated fibroblast (TAF), as a potential driving force behind the heterogeneity in tumor cells within and between tumors, was predicted to interact with high heterogeneous tumor cells via COL1A1-ITGA2. Moreover, COL1A1-mediated YAP-signaling activation might be the mechanistic link between TAF and tumor cells with increased transcriptional diversity. Strikingly, the levels of COL1A1, ITGA2, and YAP are associated with morphological heterogeneity and poor overall survival of liver cancer patients. Beyond providing a potential mechanistic link between the TME and heterogeneous tumor cells, this study establishes that collagen-stimulated YAP activation is associates with transcriptional diversity in tumor cells by upregulating stemness, providing a theoretical basis for individualized treatment targets.

Background: To observe the relationship between Tumor Necrosis Factor-alpha (TNF-α) and Neuropeptide Y (NPY) expression and neurological function score in epileptic children. Methods: Fifty-four epileptic children diagnosed and treated in Xuzhou Children's Hospital, China from Feb 2017 to Mar 2018 were collected and included in a research group (RG), while 30 healthy children who underwent physical examination at the same time were included in the control group (CG). ELISA was used to detect the expression of TNF-α and NPY in the serum of children in the two groups, and those before treatment were compared. The National Institute of Health stroke scale (NIHSS) and Hamilton Anxiety (HAMA) scores before and after treatment were observed, and Pearson correlation was used to analyze the relationship between the expression levels of TNF-α and NPY in the serum as well as NIHSS and HAMA scores. Results: The expression levels of TNF-α and NPY in the serum of children in the RG were significantly higher than those in the CG (P

Background. Infant colic is a common benign disease during early infancy. Migraine and tension-type headache (TTH) are the most common primary headache forms among pediatric population. Several studies have investigated the incidence of infant colic in patients with migraine and TTH. The meta-analysis was to assess the relationship between infant colic and migraine as well as TTH. Methods. PubMed, Web of Science, and Cochrane Library were searched until August 16, 2018, for potential studies. Data were extracted by two independent authors and analyzed using RevMan 5.2 software. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the association between infant colic and migraine as well as TTH, respectively. Results. A total of 148 studies were found, and 7 studies were finally included. A higher incidence of colic during infancy was revealed in migraine patients than controls (P=0.05, OR: 2.51, 95% CI: 1.32–4.77) and TTH subjects (P=0.02, OR: 0.33, 95% CI: 0.13–0.86), respectively. And no significances were found between TTHs with controls (P=0.51, OR: 1.17, 95% CI: 0.73–1.89). Conclusion. This meta-analysis indicated that migraine was associated with increased incidence of infantile colic history, but TTH incidence was not relevant with the incidence of infantile colic history.

Abstract This paper addresses a multi-objective energy-efficient scheduling problem of the distributed permutation flowshop with sequence-dependent setup time and no-wait constraints (EEDNWFSP), which have important practical applications. Two objectives minimization of both makespan and total energy consumption (TEC) are considered simultaneously. To address this problem, a new mixed-integer linear programming (MILP) model is formulated. Considering the issues faced in solving large-scale instances, an improved non-dominated sorting genetic algorithm (INSGA-II) is further proposed that uses two variants of the Nawaz-Enscore-Ham heuristic (NEH) to generate high-quality initial population. Moreover, two problem-specific speed adjustment heuristics are presented, which can enhance the qualities of the obtained non-dominated solutions. In addition, four local and two global search operators are designed to improve the exploration and exploitation abilities of the proposed algorithm. The effectiveness of the proposed algorithm was verified using extensive computational tests and comparisons. The experimental results show that the proposed INSGA-II is more effective compared to other efficient multi-objective algorithms.

Various physiological and pathological changes are related to the occurrence and development of neurodegenerative diseases. Neuroinflammation is a major trigger and exacerbation of neurodegenerative diseases. One of the main symptoms of neuritis is the activation of microglia. Thus, to alleviate the occurrence of neuroinflammatory diseases, an important method is to inhibit the abnormal activation of microglia. This research evaluated the inhibitory effect of trans-ferulic acid (TJZ-1) and methyl ferulate (TJZ-2), isolated from Zanthoxylum armatum, on neuroinflammation, by establishing the human HMC3 microglial cell neuroinflammation model induced by lipopolysaccharide (LPS). The results showed both compounds significantly inhibited the production and expression of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) contents, and increased the level of anti-inflammatory factor β-endorphin (β-EP). Furthermore, TJZ-1 and TJZ-2 can inhibit LPS-induced activation of nuclear factor kappa B (NF-κB). It was found that of two ferulic acid derivatives, both had anti-neuroinflammatory effects by inhibiting the NF-κB signaling pathway and regulating the release of inflammatory mediators, such as NO, TNF-α, IL-1β, and β-EP. This is the first report that demonstrates that TJZ-1 and TJZ-2 had inhibitory effects on LPS-induced neuroinflammation in human HMC3 microglial cells, which indicates that two ferulic acid derivates from Z. armatum could be used as potential anti-neuroinflammatory agents.