Receptor Tyrosine Kinase Interaction with the Tumor Microenvironment in Malignant Progression of Human Glioblastoma

Glioblastoma (GBM) is the most malignant brain tumor, characterized with a rapid progression and poor prognosis despite modern therapies. Receptor tyrosine kinase (RTK) is a membrane tyrosine kinase that could be activated by binding ligands with the extracellular domain, and communicating signals according to the tyrosine kinase activity of the intracellular domain. Recent studies revealed that RTKs such as EGFR, PDGFR and MET play key roles in cancer progression through regulation of abundant cellular processes. As transmembrane proteins, RTKs work as a mediator between the extracellular environment and intracellular compartments, translating the tumor microenvironment (TME) signals into the tumor cells. TME is also a critical regulator for the malignant process, lately receiving considerable attention. It is composed of extracellular matrix (ECM), the stromal cells (i.e., endothelial cells, microglia and fibroblasts), secreted factors, and hypoxia environment, etc. Among these, the strong invasion and sustained angiogenesis of GBM are closely related to ECM-receptor interaction and -associated signaling events. In this chapter, we consider the interaction and mechanisms of RTKs and TME in GBM progression, especially the role of ECM-receptor mediated signaling in tumor invasion, hypoxia and angiogenesis, glioma stem cells and tumor metabolism. We then summarize and discuss recent improvements on the approaches of targeting RTK and TME as the therapy in the primary GBM

GLP-1RAs caused gastrointestinal adverse reactions of drug withdrawal: a system review and network meta-analysis

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduce postprandial blood glucose, inhibit appetite, and delay gastrointestinal emptying. However, it is controversial that some patients are intolerant to GLP-1RAs.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials (RCTs) using GLP-1RAs with documented withdrawal due to gastrointestinal adverse reactions (GI AEs) from their inception to September 28, 2022. After extracting the information incorporated into the studies, a random-effects network meta-analysis was performed within a frequentist framework.Results64 RCTs were finally enrolled, which included six major categories of the GLP-1RA. The sample size of the GLP-1RAs treatment group was 16,783 cases. The risk of intolerable gastrointestinal adverse reactions of Liraglutide and Semaglutide was higher than that of Dulaglutide. Meanwhile, the higher the dose of the same GLP-1RA preparation, the more likely to cause these adverse reactions. These intolerable GI AEs were not significantly related to drug homology or formulations and may be related to the degree of suppression of the appetite center.ConclusionDulaglutide caused the lowest intolerable GI AEs, while Liraglutide and Semaglutide were the highest. For Semaglutide, the higher the dose, the more likely it is to drive GI AEs. Meanwhile, the risk of these GI AEs is independent of the different formulations of the drug. All these findings can effectively guide individualized treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359346, identifier CRD42022359346

Meta-analysis of cortical thickness abnormalities in medication-free patients with major depressive disorder

Alterations in cortical thickness have been identified in major depressive disorder (MDD), but findings have been variable and inconsistent. To date, no reliable tools have been available for the meta-analysis of surface-based morphometric (SBM) studies to effectively characterize what has been learned in previous studies, and drug treatments may have differentially impacted findings. We conducted a comprehensive meta-analysis of magnetic resonance imaging (MRI) studies that explored cortical thickness in medication-free patients with MDD, using a newly developed meta-analytic mask compatible with seed-based d mapping (SDM) meta-analytic software. We performed the meta-regression to explore the effects of demographics and clinical characteristics on variation in cortical thickness in MDD. Fifteen studies describing 529 patients and 586 healthy controls (HCs) were included. Medication-free patients with MDD, relative to HCs, showed a complex pattern of increased cortical thickness in some areas (posterior cingulate cortex, ventromedial prefrontal cortex, and anterior cingulate cortex) and decreased cortical thickness in others (gyrus rectus, orbital segment of the superior frontal gyrus, and middle temporal gyrus). Most findings in the whole sample analysis were confirmed in a meta-analysis of studies recruiting medication-naive patients. Using the new mask specifically developed for SBM studies, this SDM meta-analysis provides evidence for regional cortical thickness alterations in MDD, mainly involving increased cortical thickness in the default mode network and decreased cortical thickness in the orbitofrontal and temporal cortex

A study of multinucleated giant cells in esophageal cancer

Objectives: To evaluate the occurrence, abundance, distribution, nature and clinical significance of multi-nucleated giant cell (MGC) in esophageal cancer. Materials and methods: MGCs were examined with conventional pathology, immunohistochemistry and immunofluorescence in 107 esophageal cancer tissues. The findings were correlated to pathological diagnosis and clinical behavior of the cancers. Results: MGCs were identified in 31.7% (34/107) of the cases. MGCs were positive for CD11c, CD11b, CD32, CD16, HLA-DR and MMP9, and negative for CD163, CD206 and CD64 giving a molecular profile of proinflammatory M1 but not immunosuppressive M2. MGCs were significantly related to decreased lymph node metastasis (p = 0.011), low pTNM stage (p = 0.044), favorable survival (p = 0.04), squamous cell cancer type rather than other histopathological subtypes (p = 0.020) and associated to better differentiation (p = 0.063). Conclusions: MGCs belong to M1 macrophage and perform phagocytosis and scavenging of cancer cells that would benefit patients' survival and could serve as a prognostic marker

Tailoring the interfaces of silicon/carbon nanotube for high rate lithium-ion battery anodes

Abstract(#br)Micrometer-sized silicon powders, due to its high specific capacity, easy accessibility, and low cost, have been regarded as an attractive anode material for lithium-ion batteries. The severer mechanical instability and high inter-particle resistance during cycling, however, hinder its further application. In this work, a novel potholed micrometer-sized silicon powders (PMSi)/carbon nanotubes (CNT)/C electrode is proposed. The resulting three-dimensional (3D) conductive framework and multi-point contact network exhibit ideal structural stability and high-rate cycling property. Hence, the volume resistivity of PMSi/CNT/C (157 Ω m) is reduced significantly relative to traditional PMSi/commercial carbon nanotubes (CCT)/C composite (400 Ω m). By testing the fabricated half-cell LIB with the PMSi/CNT/C composite anode, high reversible specific capacity of 2533 mAh g −1 with a remarkable high initial coulombic efficiency of 89.07% and over 840 mA h g −1 for 1000 cycles at 2 A g −1 is measured. Even at the rate of 20 A g −1 , the PMSi/CNT/C electrode shows a capacity of 463 mAh g −1 . A full cell contained the PMSi/CNT/C anode and a LiFePO 4 /LiMn 2 O 4 cathode successfully ignites an LED array (∼1.5W), further demonstrating its outstanding electrical driving property

Non-stationary non-Gaussian random vibration analysis of Duffing systems based on explicit time-domain method

Non-stationary non-Gaussian random vibration problems of structures are challenging and drawing increasing attention. In the present study, firstly, an explicit time-domain method (ETDM) is proposed to determine the higher-order response statistics of linear systems subjected to non-stationary non-Gaussian random excitations, in which the first four orders of cumulants of dynamic responses are directly formulated through the cumulant operation rule based on the explicit expressions of responses. Secondly, an equivalent linearization – explicit time-domain method (EL-ETDM) is further developed to solve the non-stationary non-Gaussian random vibration problems of Duffing systems, in which the equivalent linear system is derived discarding the assumption of Gaussian response, and the corresponding higher-order cumulant analyses of the linearized system are accomplished by the efficient ETDM. The present approach can account for non-Gaussian random excitations with arbitrary forms, and two specific applications to the Poisson white noise and the square form of Gaussian random process are investigated. Four numerical examples are presented to demonstrate the effectiveness of the proposed methods

Analysing trends in the spatio-temporal behaviour patterns of mainland Chinese tourists and residents in Hong Kong based on Weibo data

Visiting tourists and residents of a city interact at various locations at various times. Previous studies paid little attention to comparing the spatio-temporal behaviours of tourists and residents from a long-term perspective. The aim of the present study was to identify and compare the spatio-temporal behaviours of mainland Chinese tourists and residents in Hong Kong over a period of five years. Their behaviours were compared by means of kernel density analysis and temporal statistical analysis, using Weibo geotagged check-in data and geographic information systems (GIS). The results show that the spatial behaviours of mainland Chinese tourists (MCT) are more concentrated than those of residents, especially in central urban areas, whereas residents also visit suburban and exurban areas. Simultaneously, MCTs’ temporal behaviours varied significantly, whereas those of residents were relatively stable. From a long-term perspective, we found that in the central urban area, MCTs’ preferences for locations tended to be relatively fixed, but their activity in local neighbourhoods and residential quarters decreased. However, residents’ interest in typical tourism highlights decreased reflecting potential strategies of avoidance in those areas whereas their activities in other tourism hotspots were more stable. These findings can be applied in urban planning, destination management and sustainable development