Integrative bioinformatics approaches to establish potential prognostic immune-related genes signature and drugs in the non-small cell lung cancer microenvironment

Introduction: Research has revealed that the tumor microenvironment (TME) is associated with the progression of malignancy. The combination of meaningful prognostic biomarkers related to the TME is expected to be a reliable direction for improving the diagnosis and treatment of non-small cell lung cancer (NSCLC).Method and Result: Therefore, to better understand the connection between the TME and survival outcomes of NSCLC, we used the “DESeq2” R package to mine the differentially expressed genes (DEGs) of two groups of NSCLC samples according to the optimal cutoff value of the immune score through the ESTIMATE algorithm. A total of 978 up-DEGs and 828 down-DEGs were eventually identified. A fifteen-gene prognostic signature was established via LASSO and Cox regression analysis and further divided the patients into two risk sets. The survival outcome of high-risk patients was significantly worse than that of low-risk patients in both the TCGA and two external validation sets (p-value < 0.05). The gene signature showed high predictive accuracy in TCGA (1-year area under the time-dependent ROC curve (AUC) = 0.722, 2-year AUC = 0.708, 3-year AUC = 0.686). The nomogram comprised of the risk score and related clinicopathological information was constructed, and calibration plots and ROC curves were applied, KEGG and GSEA analyses showed that the epithelial-mesenchymal transition (EMT) pathway, E2F target pathway and immune-associated pathway were mainly involved in the high-risk group. Further somatic mutation and immune analyses were conducted to compare the differences between the two groups. Drug sensitivity provides a potential treatment basis for clinical treatment. Finally, EREG and ADH1C were selected as the key prognostic genes of the two overlapping results from PPI and multiple Cox analyses. They were verified by comparing the mRNA expression in cell lines and protein expression in the HPA database, and clinical validation further confirmed the effectiveness of key genes.Conclusion: In conclusion, we obtained an immune-related fifteen-gene prognostic signature and potential mechanism and sensitive drugs underling the prognosis model, which may provide accurate prognosis prediction and available strategies for NSCLC

Gut mycobiome dysbiosis contributes to the development of hypertension and its response to immunoglobulin light chains

ObjectivesHuman gut microbiome has gained great attention for its proposed roles in the development of hypertension. The fungal microbiome in the human gut (i.e. the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. However, the existing knowledge of human mycobiome has never revealed the association between gut mycobiome and hypertension. It is known that inflammation and immunity contribute to human hypertension. Here, we sought to investigate whether gut mycobiome could predict the development of hypertension and its association with immunoglobulin light chains.Methods and materialsParticipants were classified into three cohorts: prehypertension (pre-HTN), hypertension (HTN), and normal-tension (NT) based on their blood pressure. Fresh samples were collected, and the ITS transcribed spacer ribosomal RNA gene sequence was performed. An immunoturbidimetric test was used to examine the serum levels of immunological light chains.ResultsSubjects in both of the states of pre-HTN and HTN had different fungal microbiome community compared to the NT group (FDR<0.05). Slightly higher levels of fungal richness and diversity were observed in the groups of pre-HTN and HTN. The relative abundance of Malassezia increased in the HTN group compared to that in the NT group, and the relative abundance of Mortierella enriched in the NT group. For the pre-HTN group, the relative abundance of Malassezia was positively associated with serum the concentration of light chain (LC) κ (r=0.510, P=0.044); for the HTN group, the relative abundance of Mortierella was positively associated with the serum concentration of LC κ (P<0.05), the relative abundance of Malassezia was positively associated with both the serum concentrations of LC κ and LC λ (r>0.30, P<0.05).ConclusionsOur present study demonstrated that gut fungal dysbiosis occurred in the state of prehypertension, and fungal dysbiosis can predict the dysregulation of serum light chains in hypertension patients. Further study on modulating gut fungal community should be focused on balancing the immunological features in hypertension

The role of Th17 cells and regulatory T cells in Coxsackievirus B3-induced myocarditis

AbstractIL-17-producing (Th17) and regulatory T (Treg) cells have been well established in the pathogenesis of many inflammatory diseases. To assess whether Th17 and Treg were altered in acute virus-induced myocarditis (AVMC) mice, we assessed Th17/Treg functions on different levels in AVMC. It was shown that the expression of splenic Th17 cells and Th17-related cytokines (IL-17A, IL-21) markedly increased. Interestingly, the expression of splenic Treg cells and Treg-related cytokines (TGF-β, IL-10) also significantly increased. Using neutralization of IL-17 in the AVMC, we found that Treg cells roughly decreased compared with isotype control mice. However, T cells and perforin dramatically increased, followed by a marked reduction in CVB3 replication. The results suggested that Th17 cells possibly contributed to viral replication through the action of Treg cells in mediating T cells and perforin response in AVMC

Photoluminescence mechanism and applications of Zn-doped carbon dots

Heteroatom-doped carbon dots (CDs) with excellent optical characteristics and negligible toxicity have emerged in many applications including bioimaging, biosensing, photocatalysis, and photothermal therapy. The metal-doping of CDs using various heteroatoms results in an enhancement of the photophysics but also imparts them with multifunctionality. However, unlike nonmetal doping, typical metal doping results in low fluorescence quantum yields (QYs), and an unclear photoluminescence mechanism. In this contribution, we detail results concerning zinc doped CDs (Zn-CDs) with QYs of up to 35%. The zinc ion charges serve as a surface passivating agent and prevent the aggregation of graphene p–p stacking, leading to an increase in the QY of the Zn-CDs. Structural and chemical investigations using spectroscopic and first principle simulations further revealed the effects of zinc doping on the CDs. The robust Zn-CDs were used for the ultra-trace detection of Hg2+ with a detection limit of 0.1 mM, and a quench mechanism was proposed. The unique optical properties of the Zn-CDs have promise for use in applications such as in vivo sensing and future phototherapy applications

Study on Relationship between Environmental Regulation and Green Total Factor Productivity from the Perspective of FDI—Evidence from China

The existing literature has paid less attention to the key role of FDI in the realization of Porter’s hypothesis. Based on China’s provincial panel data from 2007 to 2020, this paper uses the SBM function and the Luenberger productivity index to measure the green total factor productivity (GTFP) of China’s provinces while considering energy consumption and undesired output. Using FDI as the mediating variable and threshold variable, this paper studies the relationship between environmental regulation (ENV), FDI, and GTFP. The research results show that: (1) There is a U-shaped relationship between ENV and GTFP. China is currently on the left side of the U-shaped inflection point. Further improving the intensity of ENV can promote the growth of GTFP. (2) The mediating effect of FDI is significantly established. ENV and FDI show a significant U-shaped relationship. Further development of FDI can promote GTFP. (3) FDI has a threshold effect. When FDI is at a low level of development, ENV and GTFP are negatively correlated and insignificant; when FDI is at a high level of development, ENV can significantly promote the growth of GTFP. The marginal effect on green TFP increases with FDI growth. The results of this paper show that FDI is a necessary prerequisite for the Porter hypothesis to become a reality in China. The research of this paper has important reference value for realizing the sustainable development of environment, economy, and society

Has the Construction of National High-Tech Zones Promoted Regional Economic Growth?—Empirical Research from Prefecture-Level Cities in China

As a “special economic zone” and “policy test field” in the region, the national high-tech zone is an important strategy for the country to promote the development of high-tech industries and regional economy, but its effect needs to be verified. This paper uses panel data of 281 prefecture-level cities in China from 1994 to 2019, and uses the differences-in-differences method to study the impact of high-tech zones on regional economic development. On this basis, the heterogeneity effects of different types of high-tech zones on regional economic growth are explored. The empirical research results show that the national high-tech zone promotes regional economic growth, and this conclusion still holds after conducting multiple robustness tests. Further research found that the promotion of national high-tech zones to economic development showed the law of “diminishing marginal effect”: Compared with higher-level cities, lower-level cities gained faster development from the construction of national high-tech zones. Compared with the developed regions in the east, the underdeveloped regions in the west have achieved faster development from the construction of the national high-tech zone. In addition, this paper finds that growth-type high-tech zones have a greater marginal contribution to regional economic growth than mature high-tech zones; multi-zone high-tech zones have a greater marginal contribution to regional economic growth than single-zone high-tech zones. The research of this paper shows that the national high-tech zones as “policy test fields” and “special economic zones” can not only drive economic development, but also help narrow the economic development gap between regions through their rational distribution. This provides important inspiration for the future layout of the national high-tech zone and the establishment of other related policies

A Universal Routing Algorithm Based on Intuitionistic Fuzzy Multi-Attribute Decision-Making in Opportunistic Social Networks

With the vigorous development of big data and the 5G era, in the process of communication, the number of information that needs to be forwarded is increasing. The traditional end-to-end communication mode has long been unable to meet the communication needs of modern people. Therefore, it is particularly important to improve the success rate of information forwarding under limited network resources. One method to improve the success rate of information forwarding in opportunistic social networks is to select appropriate relay nodes so as to reduce the number of hops and save network resources. However, the existing routing algorithms only consider how to select a more suitable relay node, but do not exclude untrusted nodes before choosing a suitable relay node. To select a more suitable relay node under the premise of saving network resources, a routing algorithm based on intuitionistic fuzzy decision-making model is proposed. By analyzing the real social scene, the algorithm innovatively proposes two universal measurement indexes of node attributes and quantifies the support degree and opposition degree of node social attributes to help node forward by constructing intuitionistic fuzzy decision-making matrix. The relay nodes are determined more accurately by using the multi-attribute decision-making method. Simulation results show that, in the best case, the forwarding success rate of IFMD algorithm is 0.93, and the average end-to-end delay, network load, and energy consumption are the lowest compared with Epidemic algorithm, Spray and Wait algorithm, NSFRE algorithm, and FCNS algorithm

A Comprehensive Multi-Scenario Routing Algorithm Based on Fuzzy Control Theory in Opportunistic Social Network

With the flourishing of big data and the 5G era, the amount of data to be transmitted in the communication process is increasing, and end-to-end communication in traditional social networks has been unable to meet the current communication needs. Therefore, in order to improve the success rate of data forwarding, social networks propose that the sender of the message should reasonably choose the next hop node. However, existing routing and forwarding algorithms do not take into account nodes that are live in different scenarios, and the applicable next hop node metrics are also different. These algorithms only consider the forwarding preferences of the nodes during working hours and do not consider the forwarding preferences of the nodes during non-working hours. We propose a routing algorithm based on fuzzy decision theory, which aims at a more accurate decision on selecting the next hop. A routing and forwarding algorithm based on fuzzy decision is proposed in this paper. This algorithm symmetrical divides scenes in opportunistic social networks into working time and non-working time according to real human activity. In addition, metrics are designed symmetrically for these two scenarios. Simulation results demonstrate that, in the best case, the proposed scheme presents an average delivery ratio of 0.95 and reduces the average end-to-end delay and average overhead compared with the epidemic routing algorithm, the EIMSTalgorithm, the ICMT algorithm, and the FCNSalgorithm

Effect of Dissipation on the Moonpool-Javelin Wave Energy Converter

In this work, the hydrodynamic performance of a novel wave energy converter (WEC) configuration which combines a moonpool platform and a javelin floating buoy, called the moonpool–javelin wave energy converter (MJWEC), was studied by semianalytical, computational fluid dynamics (CFD), and experimental methods. The viscous term is added to the potential flow solver to obtain the hydrodynamic coefficients. The wave force, the added mass, the radiation damping, the wave capture, and the energy efficiency of the configuration were assessed, in the frequency and time domains, by a semianalytical method. The CFD method results and the semianalytical results were compared for the time domain by introducing nonlinear power take-off (PTO) damping; additionally, the viscous dissipation coefficients under potential flow could be confirmed. Finally, a 1:10 scale model was physically tested to validate the numerical model and further prove the feasibility of the proposed system