Controversial role of ILC3s in intestinal diseases: A novelty perspective on immunotherapy

ILC3s have been identified as crucial immune regulators that play a role in maintaining host homeostasis and modulating the antitumor response. Emerging evidence supports the idea that LTi cells play an important role in initiating lymphoid tissue development, while other ILC3s can promote host defense and orchestrate adaptive immunity, mainly through the secretion of specific cytokines and crosstalk with other immune cells or tissues. Additionally, dysregulation of ILC3-mediated overexpression of cytokines, changes in subset abundance, and conversion toward other ILC subsets are closely linked with the occurrence of tumors and inflammatory diseases. Regulation of ILC3 cytokines, ILC conversion and LTi-induced TLSs may be a novel strategy for treating tumors and intestinal or extraintestinal inflammatory diseases. Herein, we discuss the development of ILCs, the biology of ILC3s, ILC plasticity, the correlation of ILC3s and adaptive immunity, crosstalk with the intestinal microenvironment, controversial roles of ILC3s in intestinal diseases and potential applications for treatment

Immune-related potential biomarkers and therapeutic targets in coronary artery disease

BackgroundCoronary artery disease (CAD) is a complex illness with unknown pathophysiology. Peripheral biomarkers are a non-invasive method required to track the onset and progression of CAD and have unbeatable benefits in terms of early identification, prognostic assessment, and categorization of the diagnosis. This study aimed to identify and validate the diagnostic and therapeutic potential of differentially expressed immune-related genes (DE-IRGs) in CAD, which will aid in improving our knowledge on the etiology of CAD and in forming genetic predictions.MethodsFirst, we searched coronary heart disease in the Gene Expression Omnibus (GEO) database and identified GSE20680 (CAD = 87, Normal = 52) as the trial set and GSE20681 (CAD = 99, Normal = 99) as the validation set. Functional enrichment analysis using protein-protein interactions (PPIs), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) was carried out on the identified differentially expressed genes. Optimal feature genes (OFGs) were generated using the support vector machine recursive feature elimination algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm. Furthermore, immune infiltration in CAD patients and healthy controls was compared using CIBERSORT, and the relationship between immune cells and OFGs was examined. In addition, we constructed potential targeted drugs for this model through the Drug-Gene Interaction database (DGIdb) database. Finally, we verify the expression of S100A8-dominated OFGs in the GSE20681 dataset to confirm the universality of our study.ResultsWe identified the ten best OFGs for CAD from the DE-IRGs. Functional enrichment analysis showed that these marker genes are crucial for receptor-ligand activity, signaling receptor activator activity, and positive control of the response to stimuli from the outside world. Additionally, CIBERSORT revealed that S100A8 could be connected to alterations in the immune microenvironment in CAD patients. Furthermore, with the help of DGIdb and Cytoscape, a total of 64 medicines that target five marker genes were subsequently discovered. Finally, we verified the expression of the OFGs genes in the GSE20681 dataset between CAD patients and normal patients and found that there was also a significant difference in the expression of S100A8.ConclusionWe created a 10-gene immune-related prognostic model for CAD and confirmed its validity. The model can identify potential biomarkers for CAD prediction and more accurately gauge the progression of the disease

Sorting nexin 12 interacts with BACE1 and regulates BACE1-mediated APP processing

Background: beta-site APP cleaving enzyme 1 (BACE1) cleaves beta-amyloid precursor protein (APP) to initiate the production of beta-amyloid (A beta), the prime culprit in Alzheimer's disease (AD). Dysregulation of the intracellular trafficking of BACE1 may affect A beta generation, contributing to AD pathology. In this study, we investigated whether BACE1 trafficking and BACE1-mediated APP processing/A beta generation are affected by sorting nexin 12 (SNX12), a member of the sorting nexin (SNX) family that is involved in protein trafficking regulation. Results: Herein, we find that SNX12 is widely expressed in brain tissues and is mainly localized in the early endosomes. Overexpression of SNX12 does not affect the steady-state levels of APP, BACE1 or gamma-secretase components, but dramatically reduces the levels of A beta, soluble APP beta and APP beta-carboxyl terminal fragments. Downregulation of SNX12 has the opposite effects. Modulation of SNX12 levels does not affect gamma-secretase activity or in vitro beta-secretase activity. Further studies reveal that SNX12 interacts with BACE1 and downregulation of SNX12 accelerates BACE1 endocytosis and decreases steady-state level of cell surface BACE1. Finally, we find that the SNX12 protein level is dramatically decreased in the brain of AD patients as compared to that of controls. Conclusion: This study demonstrates that SNX12 can regulate the endocytosis of BACE1 through their interaction, thereby affecting beta-processing of APP for A beta production. The reduced level of SNX12 in AD brains suggests that an alteration of SNX12 may contribute to AD pathology. Therefore, inhibition of BACE1-mediated beta-processing of APP by regulating SNX12 might serve as an alternative strategy in developing an AD intervention.Alzheimer's Association; National Natural Science Foundation of China [30973150, 81161120496, 81000540]; 973 Prophase Project [2010CB535004]; Natural Science Foundation of Fujian Province of China [2009J06022, 2010J01235]; Program for New Century Excellent Talents in Universities (NCET); Fundamental Research Funds for the Central Universities; Fok Ying Tung Education Foundatio

Summary of studies on hot corrosion of iron-based alloys by sodium sulfate in O2/SO2/SO3 environment

Iron base heat-resistant alloys are widely used in high temperature environments, especially in civil and industrial boilers and other combustors. This type of alloys was found to undergo hot corrosion when covered with a sulfate deposit. Recent studies of sulfate-deposit-induced hot corrosion of iron-base alloys are selectively reviewed in this paper. Emphasis is placed on studies of the hot corrosion occurring at relatively low temperatures, concerning the thermodynamics of the formation of liquid sulfate eutectics, the corrosion behavior of various iron-base alloys, and an electrochemical mechanism proposed by the present authors. In addition, electrochemical measurements for the evaluation of hot corrosion resistance of iron-base alloys are briefly reported. Some coatings were prepared and their performance in hot corrosion environments is included in this paper

Habitat orientation alters the outcome of interspecific competition: A microcosm study with zooplankton grazers

Habitat orientation has recently been demonstrated to affect the foraging behavior, growth, and production of plankton grazers. Because the orientation effect may vary with species, we hypothesize that habitat orientation may alter interspecific interactions between animal species. We experimentally investigated how habitat orientation (placing cuboid chambers in three orientations with long, medium, and small side as the chamber height) affected the interaction between two common cladoceran species, Daphnia magna and Moina micrura, which competitively exploited green algae of Chlorella pyrenoidosa at two volume scales (64 and 512ml). Results show that chamber orientation and volume additively affected the behavior and species performance of the grazers. Specifically, both grazer species generally decreased their average swimming velocity, grazing rate (on algal cells), body size, and survival and reproduction rates with increasing chamber height for both chamber volumes and with decreasing chamber volume regardless of chamber orientation. Nevertheless, the decrease magnitude was greater for M.micrura with increasing chamber height but was greater for D.magna with decreasing chamber volume. Correspondingly, when cocultured, the density ratio of D.magna to M.micrura increased with increasing chamber height but decreased with decreasing chamber volume. At the end of the experiment, none of D.magna individuals survived in the small and short (large-based) chambers, and few M.micrura individuals survived in large and tall (small-based) chambers. These results indicate that both habitat orientation and size affect the outcome of interspecific competition between grazer species. We suggest that variation in habitat orientation may improve community coexistence and species diversity in nature

Association between cognitive impairment and apolipoprotein A1 or apolipoprotein B levels is regulated by apolipoprotein E variant rs429358 in patients with chronic schizophrenia

ApoE gene polymorphism may be involved in the change in blood lipid profile and cognitive impairment of the general population. However, few studies explored the effects of ApoE gene polymorphism on blood lipid levels and cognition in schizophrenia. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was employed to evaluate the cognition and the SNPStats was used to investigate the association of ApoE rs429358 with schizophrenia. The models of analysis of covariance and multivariate analysis were conducted to investigate the effect of ApoE rs429358 on cognition in schizophrenia. Altogether, 637 patients with schizophrenia and 467 healthy controls were recruited in this study. The findings in the case group found that both the ApoA1 and ApoB levels were predictors for RBANS total score (p < 0.001 vs. p = 0.011), immediate memory (p < 0.001 vs. p = 0.019), language (p < 0.001 vs. p = 0.013), attention (p < 0.001 vs. p < 0.001), except ApoA1 level only was a predictor for visuospatial/constructional (p = 0.014) and delayed memory (p < 0.001). When the association was examined in different ApoE rs429358 genotype subgroups, the association between ApoA1 level and RBANS scores (except for the language score) or between ApoB level and RBANS scores (except for the attention score) was regulated by ApoE rs429358. Our results suggest that patients with schizophrenia have broad cognitive impairment compared with healthy controls. For patients with schizophrenia, both ApoA1 and ApoB levels were positively associated with cognition. There was a significant association between ApoA1 or ApoB levels and cognition in schizophrenia, which was regulated by the ApoE rs429358