Bone morphogenetic protein-6 suppresses TGF-ß2-induced epithelial-mesenchymal transition in retinal pigment epithelium.

AIM: To evaluate the effect of bone morphogenetic protein-6 (BMP-6) on transforming growth factor (TGF)-ß2-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE). METHODS: Adult retinal pigment epithelial cell line (ARPE-19) were randomly divided into control, TGF-ß2 (5 µg/L), and BMP-6 small interfering RNA (siRNA) group. The cell morphology was observed by microscopy, and the cell migration ability were detected by Transwell chamber. The EMT-related indexes and BMP-6 protein levels were detected by Western blotting. Furthermore, a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group, TGF-ß2+empty plasmid group, BMP-6 overexpression group, and TGF-ß2+BMP-6 overexpression group. The EMT-related indexes and extracellular regulated protein kinases (ERK) protein levels were detected. RESULTS: Compared with the control group, the migration of RPE cells in the TGF-ß2 group was significantly enhanced. TGF-ß2 increased the protein expression levels of α-smooth muscle actin (α-SMA), fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6 (P<0.05) in RPE. Similarly, the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced. BMP-6 siRNA increased the protein expression levels of α-SMA, fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin (P<0.05). Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-ß2 and prevented TGF-ß2 from affecting EMT-related biomarkers (P<0.05). CONCLUSION: BMP-6 prevents the EMT in RPE cells induced by TGF-ß2, which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.

Engineering Covalent Organic Frameworks Toward Advanced Zinc-Based Batteries.

Zinc-based batteries (ZBBs) have demonstrated considerable potential among secondary batteries, attributing to their advantages including good safety, environmental friendliness, and high energy density. However, ZBBs still suffer from issues such as the formation of zinc dendrites, occurrence of side reactions, retardation of reaction kinetics, and shuttle effects, posing a great challenge for practical applications. As promising porous materials, covalent organic frameworks (COFs) and their derivatives have rigid skeletons, ordered structures, and permanent porosity, which endow them with great potential for application in ZBBs. This review, therefore, provides a systematic overview detailing on COFs structure pertaining to electrochemical performance of ZBBs, following an in depth discussion of the challenges faced by ZBBs, which includes dendrites and side reactions at the anode, as well as dissolution, structural change, slow kinetics, and shuttle effect at the cathode. Then, the structural advantages of COF-correlated materials and their roles in various ZBBs are highlighted. Finally, the challenges of COF-correlated materials in ZBBs are outlined and an outlook on the future development of COF-correlated materials for ZBBs is provided. The review would serve as a valuable reference for further research into the utilization of COF-correlated materials in ZBBs.

Exosomal MALAT1 promotes the proliferation of esophageal squamous cell carcinoma through glyoxalase 1-dependent methylglyoxal removal.

In previous study we characterized the oncogenic role of long non-coding RNA MALAT1 in esophageal squamous cell carcinoma (ESCC), but the detailed mechanism remains obscure. Here we identified glyoxalase 1 (GLO1) as the most possible executor of MALAT1 by microarray screening. GLO1 is responsible for degradation of cytotoxic methylglyoxal (MGO), which is by-product of tumor glycolysis. Accumulated MGO may lead to glycation of DNA and protein, resulting in elevated advanced glycation end products (AGEs), while glyoxalase 1 detoxify MGO to alleviate its cytotoxic effect to tumor cells. GLO1 interfering led to accumulation of AGEs and following activation of DNA injury biomarkers, which lead to cell cycle arrest and growth inhibition. In silico analysis based on online database revealed abundant enrichment of histone acetylation marker H3K27ac in GLO1 promotor, and acetyltransferase inhibitor C646 declined GLO1 expression. Acetyltransferase KAT2B, which was also identified as a target of MALAT, mediated histone lysine acetylation of GLO1 promotor, which was confirmed by ChIP-qPCR experiment. Shared binding sites of miR-206 were found on MALAT1 and KAT2B mRNA. Dual-luciferase reporter assays confirmed interaction within MALAT1-miR-206-GLO1. Finally, we identified MALAT1 encapsuled by exosome from donor cells, and transferred malignant behaviors to recipient cells. The secreted exosomes may enter circulation, and serum MALAT1 level combined with traditional tumor markers showed potential power for ESCC diagnosis.

DNMT3L inhibits hepatocellular carcinoma progression through DNA methylation of CDO1: insights from big data to basic research.

BACKGROUND: DNMT3L is a crucial DNA methylation regulatory factor, yet its function and mechanism in hepatocellular carcinoma (HCC) remain poorly understood. Bioinformatics-based big data analysis has increasingly gained significance in cancer research. Therefore, this study aims to elucidate the role of DNMT3L in HCC by integrating big data analysis with experimental validation. METHODS: Dozens of HCC datasets were collected to analyze the expression of DNMT3L and its relationship with prognostic indicators, and were used for molecular regulatory relationship evaluation. The effects of DNMT3L on the malignant phenotypes of hepatoma cells were confirmed in vitro and in vivo. The regulatory mechanisms of DNMT3L were explored through MSP, western blot, and dual-luciferase assays. RESULTS: DNMT3L was found to be downregulated in HCC tissues and associated with better prognosis. Overexpression of DNMT3L inhibits cell proliferation and metastasis. Additionally, CDO1 was identified as a target gene of DNMT3L and also exhibits anti-cancer effects. DNMT3L upregulates CDO1 expression by competitively inhibiting DNMT3A-mediated methylation of CDO1 promoter. CONCLUSIONS: Our study revealed the role and epi-transcriptomic regulatory mechanism of DNMT3L in HCC, and underscored the essential role and applicability of big data analysis in elucidating complex biological processes.

Zinc-Bismuth Binary Alloy Enabling High-Performance Aqueous Zinc Ion Batteries.

Reconfiguration of zinc anodes efficiently mitigates dendrite formation and undesirable side reactions, thus favoring the long-term cycling performance of aqueous zinc ion batteries (AZIBs). This study synthesizes a Zn@Bi alloy anode (Zn@Bi) using the fusion method, and find that the anode surfaces synthesized using this method have an extremely high percentage of Zn(002) crystalline surfaces. Experimental results indicate that the addition of bismuth inhibits the hydrogen evolution reaction and corrosion of zinc anodes. The finite-element simulation results indicate that Zn@Bi can effectively achieve a uniform anodic electric field, thereby regulating the homogeneous depositions of zinc ions and reducing the production of Zn dendrite. Theoretical calculations reveal that the incorporation of Bi favors the anode structure stabilization and higher adsorption energy of Zn@Bi corresponds to better Zn deposition kinetics. The Zn@Bi//Zn@Bi symmetric cell demonstrates an extended cycle life of 1000 h. Furthermore, when pairing Zn@Bi with an α-MnO2 cathode to construct a Zn@Bi//MnO2 cell, a specific capacity of 119.3 mAh g-1 is maintained even after 1700 cycles at 1.2 A g-1 . This study sheds light on the development of dendrite-free anodes for advanced AZIBs.

Analysis of the mechanism of enhanced heat transfer by nanofluids.

CONTEXT: Industrial production and humans cannot exist without energy, but the low efficiency of the heat transfer in the excessive use of energy is the most significant aspect of energy saving and emission reduction. Molecular dynamics simulation methods are devoted to simulate the heat transfer efficiency of a nanofluid system with different particle sizes, and the heat transfer enhancement mechanism of the nanofluid is simulated and studied from a microscopic perspective. The analysis showed that as nanoparticle size increases, the thermal conductivity of the Al-Ar nanofluid tends to decrease, but all of them are still higher than the thermal conductivity of the liquid argon system. According to the findings of the density and radial distribution function analyses, it can be seen that the microstructure of the system changes after putting solid nanoparticles to the original fluid. This alteration in the system's microstructure is the primary component responsible for the increased heat transfer efficiency of nanofluids. METHODS: In this paper, based on the theory of molecular dynamics, the simulation calculations were mainly performed using LAMMPS software, which is a commonly used open source computational program in the field of MD simulation research. VMD is used for visualization and analysis. The Lennard-Jones potential function was used in the simulation to accurately describe the forces acting between the atoms.

Synergistic Effect of Treatment with Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Lipopolysaccharide on the Inflammatory Response of Porcine Pulmonary Microvascular Endothelial Cells.

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) often causes secondary bacterial infection in piglets, resulting in inflammatory lung injury and leading to high mortality rates and significant economic losses in the pig industry. Microvascular endothelial cells (MVECs) play a crucial role in the inflammatory response. Previous studies have shown that HP-PRRSV can infect porcine pulmonary MVECs and damage the endothelial glycocalyx. To further understand the role of pulmonary MVECs in the pathogenesis of HP-PRRSV and its secondary bacterial infection, in this study, cultured porcine pulmonary MVECs were stimulated with a HP-PRRSV HN strain and lipopolysaccharide (LPS). The changes in gene expression profiles were analyzed through transcriptome sequencing, and the differentially expressed genes were verified using qRT-PCR, Western blot, and ELISA. Furthermore, the effects on endothelial barrier function and regulation of neutrophil trans-endothelial migration were detected using the Transwell model. HP-PRRSV primarily induced differential expression of numerous genes associated with immune response, including IFIT2, IFIT3, VCAM1, ITGB4, and CCL5, whereas LPS triggered an inflammatory response involving IL6, IL16, CXCL8, CXCL14, and ITGA7. Compared to the individual effect of LPS, when given after HN-induced stimulation, it caused a greater number of changes in inflammatory molecules, such as VCAM1, IL1A, IL6, IL16, IL17D, CCL5, ITGAV, IGTB8, and TNFAIP3A, a more significant reduction in transendothelial electrical resistance, and higher increase in neutrophil transendothelial migration. In summary, these results suggest a synergistic effect of HP-PRRSV and LPS on the inflammatory response of porcine pulmonary MVECs. This study provides insights into the mechanism of severe lung injury caused by secondary bacterial infection following HP-PRRSV infection from the perspective of MVECs, emphasizing the vital role of pulmonary MVECs in HP-PRRSV infection.

Evaluation of Citizen Epidemic Prevention Information Literacy in the Post-Epidemic Era in Mainland China.

Improving citizen epidemic prevention information literacy is one of the most cost-efficient and important measures to improve people's epidemic prevention abilities to effectively deal with future public health crises. Epidemic prevention information literacy is beneficial to improve individuals' ability to deal with public health crises in the future. By summarizing related domestic and international research, and utilizing an empirical methodology, we constructed an epidemic prevention information literacy assessment model with good reliability, validity, and model fit. The model is composed of four indicators: (1) "epidemic prevention information awareness"; (2) "epidemic prevention information knowledge"; (3) "epidemic prevention information ability"; (4) "epidemic prevention information morality". We used the model to assess the epidemic prevention information literacy of Chinese citizens. The results showed the following: (1) the overall level of the epidemic prevention information literacy of Chinese citizens was comparatively high, however, its development was unbalanced, and the capability and moral levels of the epidemic prevention information were comparatively low; (2) the four dimensions of the epidemic prevention information literacy were different in terms of the citizens' education levels and locations. We analyzed the probable causes of these problems, and we propose specific corresponding countermeasures. The research provides a set of methods and norms for the evaluation of citizen epidemic prevention information literacy in the post-epidemic era.

Modal Decomposition of Acoustic Emissions from Pencil-Lead Breaks in an Isotropic Thin Plate.

Acoustic emission (AE) testing and Lamb wave inspection techniques have been widely used in non-destructive testing and structural health monitoring. For thin plates, the AEs arising from structural defect development (e.g., fatigue crack propagation) propagate as Lamb waves, and Lamb wave modes can be used to provide important information about the growth and localisation of defects. However, few sensors can be used to achieve the in situ wavenumber-frequency modal decomposition of AEs. This study explores the ability of a new multi-element piezoelectric sensor array to decompose AEs excited by pencil lead breaks (PLBs) on a thin isotropic plate. In this study, AEs were generated by out-of-plane (transverse) and in-plane (longitudinal) PLBs applied at the edge of the plate, and waveforms were recorded by both the new sensor array and a commercial AE sensor. Finite element analysis (FEA) simulations of PLBs were also conducted and the results were compared with the experimental results. To identify the wave modes present, the longitudinal and transverse PLB test results recorded by the new sensor array at five different plate locations were compared with FEA simulations using the same arrangement. Two-dimensional fast Fourier Transforms were then applied to the AE wavefields. It was found that the AE modal composition was dependent on the orientation of the PLB direction. The results suggest that this new sensor array can be used to identify the AE wave modes excited by PLBs in both in-plane and out-of-plane directions.

Relationship Between Subclinical Cardiovascular Diseases and Cardiac Morpho-Functional Parameters in Preclinical Stage A/B Heart Failure Adults with Type 2 Diabetes.

Purpose: Type 2 diabetes mellitus (T2DM) is a common risk factor for cardiovascular disease which increases the risk of heart failure. This study aimed to determine whether clinical characteristics and subclinical cardiovascular disease (CVD) features are correlated with echocardiographic morpho-functional parameters of T2DM patients. Patients and Methods: Two hundred and fifty-five T2DM patients without a history of coronary heart disease were enrolled in this cross-sectional study. The demographic characteristics, glucose and lipid levels were assessed for each patient. Carotid ultrasonography and peripheral artery examination were performed to measure carotid intima-media thickness (cIMT), carotid plaque, ankle-brachial index (ABI), brachial artery pulse wave velocity (baPWV), and carotid-femoral pulse wave velocity (cfPWV). Furthermore, echocardiography was conducted to evaluate cardiac morphology and systolic and diastolic function. The relationship between clinical characteristics, subclinical cardiovascular diseases, and cardiac morpho-functional parameters was explored with the Pearson and stepwise multivariable linear regression analyses. Results: A total of 255 subjects aged 18-80 years were enrolled in the study. Multiple regression analysis revealed that left ventricular mass index (LVMI) was correlated with age (ß=0.463, p = 0.000) and systolic blood pressure (SBP) (ß=0.179, p = 0.003). Relative wall thickness (RWT) was related to cfPWV (ß=0.006, p = 0.007) and homeostasis model assessment of insulin resistance (HOMA-IR) (ß=0.000, p = 0.036). In contrast, left ventricular ejection fraction (LVEF) was inversely related to cIMT (ß=-0.925, p = 0.019). The ratio of the peak flow velocity of early diastole to atrial contraction (peak E/A) was correlated with age (ß=-0.014, p = 0.000), diastolic blood pressure (DBP) (ß=-0.006, p = 0.001) and cfPWV (ß=-0.025, p = 0.044). Conclusion: In preclinical stage A/B heart failure adults with T2DM, age, BP, HOMA-IR, cfPWV and cIMT are correlated with cardiac morpho-functional parameters.

Acoustic Emission Source Characterisation during Fatigue Crack Growth in Al 2024-T3 Specimens.

While acoustic emission (AE) testing can be used as a valuable technique in structural health monitoring and non-destructive testing, little research has been conducted to establish its sources, particularly in 2024-T3 aluminium alloys. The major contribution of this work is that it provides a method to obtain a better linear relationship of count rate with crack growth rate based on waveform. This paper aims to characterise AE sources by synchronising the AE waveforms with load levels and then to propose possible dominant frequency ranges. The AE waveforms during fatigue crack growth in edge-notched 2024-T3 aluminium specimens, from an initial crack length of 10 mm to 70 mm, were collected at two different load ratios R = 0.125 and 0.5. At the same time, the crack growth rate was determined using thermal imaging and associated control software. The AE waveforms obtained were processed using the fast Fourier transform. It was shown that a significantly higher AE count rate was recorded at R = 0.125 compared to R = 0.5 when the maximum load was kept the same. This means that the R-ratio would affect the total amount of AE activities collected. It was also found that the dominant frequency range of the AE waveforms directly related to crack growth was 152-487 kHz, and the ranges due to crack closure were likely to be 310 kHz-316 kHz and 500-700 kHz. Based on the proposed frequency ranges, waveform selection was conducted and a better linear relationship between count rate and crack growth rate was observed. This study provides a better understanding of the AE sources and waveforms for future structural health monitoring applications.

A RASSF8-AS1 based exosomal lncRNAs panel used for diagnostic and prognostic biomarkers for esophageal squamous cell carcinoma.

BACKGROUND: Exosomal long non-coding RNA (lncRNA) has been shown to be potential biomarker for cancer diagnosis and follow up. However, little is known about its application in esophageal squamous cell carcinoma (ESCC) detection. Here, we sought to develop a novel diagnostic model based on serum exosomal lncRNAs to improve ESCC screening efficiency. METHODS: A multiphase, case-control study was conducted among 140 ESCC patients and 140 healthy controls. Microarray screening was performed to acquire differentially expressed exosomal lncRNAs in the discovery phase. The diagnostic model Index I was constructed based on a panel of three lncRNAs using logistic regression in the training phase, and were confirmed in a subsequent validation phase. A receiver operating characteristic (ROC) curve was generated to calculate the diagnostic value. The effects of the selected lncRNAs level on ESCC mortality were evaluated using a Cox hazard regression model and Kaplan-Meier curve analysis, and the expression level with clinicopathological features was also calculated. Finally, we explored the oncogenic potential of candidate lncRNA RASSF8-AS1 in vitro and by target mRNA sequencing. RESULTS: Index I was able to discriminate ESCC patients from healthy controls, and showed superiority to classic tumor biomarkers. Moreover, serum levels of the exosomal lncRNAs correlated with clinicopathological features and prognosis. The in vitro assays showed that RASSF8-AS1 played an oncogenic role in ESCC. Target mRNA scanning results suggested involvement of RASSF8-AS1 in tumor immunity and metabolism. CONCLUSION: The newly identified serum exosomal lncRNAs could be used as new biomarkers for ESCC, and showed oncogenic potential in ESCC.

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177).

Prostate-specific membrane antigen (PSMA) is a promising target for the diagnosis and radionuclide therapy of prostate cancer. This study reports conversion of a previously reported 68Ga-imaging agent, [68Ga]Ga-P16-093, to a Lu-177 radionuclide therapeutic agent. Substitution of the HBED-CC metal chelating group with DOTA(GA)2 led to P17-087 (4) and P17-088 (7). Both agents showed excellent PSMA binding affinity (IC50 = 10-30 nM) comparable to that of recently FDA-approved [177Lu]Lu-PSMA-617 (Pluvicto). Biodistribution studies in PSMA expressing tumor bearing mice showed that [177Lu]Lu-4 exhibited very high tumor uptake and a fast blood clearance similar to those of [177Lu]Lu-PSMA-617. Conversely, [177Lu]Lu-7, containing an albumin binder, extended its blood half-life and exhibited significantly higher uptake and longer tumor residence time than [177Lu]Lu-4 and [177Lu]Lu-PSMA-617. The switch from chelator HBED-CC to DOTA(GA)2 and the switch from the imaging isotope gallium-68 to the therapeutic isotope lutetium-177 have successfully transformed a PSMA-targeting agent from diagnosis to promising radionuclide therapeutic agents.

Pyroptosis-Related Gene Model Predicts Prognosis and Immune Microenvironment for Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) has a high incidence and mortality worldwide. Moreover, it needs more accurate means for predicting prognosis and treatments. Pyroptosis is a novel form of cell death about inflammation which was highly related to the occurrence and development of tumors. Despite having some studies about pyroptosis-related genes (PRGs) and cancer, the correlation has not been explored enough between PRGs and immune in NSCLC. In this study, we constructed a PRG model by WGCNA to access the prognosis value PRGs have. The testing cohort (n = 464) with four datasets from the GEO database conducted a survival analysis to confirm the stability of the prognostic model. The risk score and age are examined as independent prognostic factors. Based on the PRGs, we found multiple pathways enriched in immune in NSCLC. Separating samples into three subtypes by consensus cluster analysis, Cluster 3 was identified as immune-inflamed phenotype with an optimistic prognostic outcome. A three-gene PRG signature (BNIP3, CASP9, and CAPN1) was identified, and BNIP3 was identified as the core gene. Knockdown of BNIP3 significantly inhibited the growth of H358 cells and induced pyroptosis. In conclusion, the model construction based on PRGs provides novel insights into the prediction of NSCLC prognosis, and BNIP3 can serve as a diagnostic biomarker for NSCLC.

Identification of ferroptosis-related genes for overall survival prediction in hepatocellular carcinoma.

Ferroptosis is a novel type of cell death depending on iron and is strongly related to the development of tumors. Hepatocellular carcinoma (HCC) is a malignancy with high incidence. Despite some reports demonstrating the relation between ferroptosis-related genes and HCC, more details have not been excavated. In the present study, we collected and analyzed HCC patients' datasets from the TCGA-LIHC project and ICGC portal, respectively. Through the bioinformatic methods, we screened 126 differentially expressed genes. Then a prognostic model was established with four genes (GPX2, MT3, PRDX1, and SRXN1). PRDX1 is the hub gene of the prognosis model and has a high expression in hepatocellular carcinoma tumor tissue and cell lines. We further found that silencing PRDX1 increased the accumulation of ferrous ions and lipid peroxidation accumulation in HEPG2 cells and promoted ferroptosis in hepatocellular carcinoma. In conclusion, the study demonstrated the four-gene signature can be used to predict HCC prognosis. It also revealed the potential function of the ferroptosis-related gene PRDX1 in HCC, which can be a biomarker of the prediction for HCC outcome.

Regression-based heterogeneity analysis to identify overlapping subgroup structure in high-dimensional data.

Heterogeneity is a hallmark of complex diseases. Regression-based heterogeneity analysis, which is directly concerned with outcome-feature relationships, has led to a deeper understanding of disease biology. Such an analysis identifies the underlying subgroup structure and estimates the subgroup-specific regression coefficients. However, most of the existing regression-based heterogeneity analyses can only address disjoint subgroups; that is, each sample is assigned to only one subgroup. In reality, some samples have multiple labels, for example, many genes have several biological functions, and some cells of pure cell types transition into other types over time, which suggest that their outcome-feature relationships (regression coefficients) can be a mixture of relationships in more than one subgroups, and as a result, the disjoint subgrouping results can be unsatisfactory. To this end, we develop a novel approach to regression-based heterogeneity analysis, which takes into account possible overlaps between subgroups and high data dimensions. A subgroup membership vector is introduced for each sample, which is combined with a loss function. Considering the lack of information arising from small sample sizes, an l2$l_2$ norm penalty is developed for each membership vector to encourage similarity in its elements. A sparse penalization is also applied for regularized estimation and feature selection. Extensive simulations demonstrate its superiority over direct competitors. The analysis of Cancer Cell Line Encyclopedia data and lung cancer data from The Cancer Genome Atlas show that the proposed approach can identify an overlapping subgroup structure with favorable performance in prediction and stability.

Fermentation process optimization, chemical analysis, and storage stability evaluation of a probiotic barley malt kvass.

Kvass is a popular low-alcohol beverage produced by the natural fermentation of dark rye bread or malt with complex microbial flora. However, few pieces of research focus on the microflora of traditional bread kvass, and the industrial kvass based on malt concentrate has some disadvantages, including the lack of viable probiotics and containing multiple artificial additives. Therefore, in the present study, based on the different homemade traditional bread kvass, the predominant species including Lacticaseibacillus paracasei, Acetobacter pasteurianus, and Saccharomyces cerevisiae were screened and identified. In addition, barley malt was used instead of bread for kvass production, and the co-fermentation conditions with three different strains were optimized as wort concentration of 7.4°Brix, cell ratio of 2/2/1 (S. cerevisiae/L. paracasei/A. pasteurianus), inoculum amount of 8%, fermentation temperature of 29.5 °C and fermentation time of 24.6 h. Moreover, the physicochemical (pH, total soluble solids, color, and alcohol content) and probiotic (microorganisms counting and antioxidant activity) properties of the barley malt kvass prepared at optimal conditions were symmetrically evaluated. Besides, compared with the commercial kvass products, the produced barley malt kvass exhibited better taste and more desirable antioxidant activity, and also maintained around 6-7 log CFU/mL of viable probiotic microorganisms during a week of storage. The present study not only enriched the biological resource of the traditional kvass, but also promoted the development of the kvass as a live-bacteria beverage.

Research on the Paths and Effectiveness of Governance Tools Based on the Evolution of Environmental NIMBY Event.

Identifying the path and effectiveness of governance tools is the key to environmental NIMBY (not in my back yard) event governance. However, there are limited studies on the path between effective governance tools and environmental NIMBY events. Based on the theory of emotional catharsis, we establish an analytical framework for the evolution of the environmental NIMBY event and analyze the effectiveness of the current main governance tools. The results show that government solicitation of opinions (GSOs) governance tools are insignificant in the governance of resistance behavior. The effects of public demand communication (PDC) governance tools and compensation negotiation (CN)governance tools on resistance behaviors all show a significant negative correlation; negative emotions play an intermediary role in their governance tools. The overall performance is that the greater the compensation, the lower the willingness to engage in resistance behavior. The establishment of a reasonable compensation system can effectively reduce the public's willingness to engage in resistance behavior. Through the evaluation of the effectiveness of governance tools in environmental NIMBY events, this study helps to improve governance tools and has important practical significance for solving the environmental NIMBY dilemma.

FURIN correlated with immune infiltration serves as a potential biomarker in SARS-CoV-2 infection-related lung adenocarcinoma.

FURIN, as a proprotein convertase, has been found to be expressed in a variety of cancers and plays an important role in cancer. In addition, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires FURIN to enter human cells. However, the role of FURIN in lung adenocarcinoma remains unclear. And the expression of SARS-CoV-2 related gene in lung adenocarcinoma has not been clarified. Therefore, in order to explore the prognostic value and mechanism of FURIN in lung adenocarcinoma, we performed bioinformatics analysis with Oncomine, Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis, human protein atlas, UALCAN, PrognoScan, Kaplan-Meier plotter, cBioPortal and LinkedOmics databases. And then we used GSE44274 in the GEO (Gene Expression Omnibus) database to analyze the expression of FURIN in LUAD patients who infected with SARS-CoV. FURIN was highly expressed in lung adenocarcinoma and was significantly associated with poor overall survival. FURIN expression was found to be correlated with six major permeable immune cells and with macrophage immune marker in LUAD patients. In addition, SARS-CoV-2 infection might affect the expression of FURIN. FURIN can be used as a promising biomarker for determining prognosis and immune infiltration in LUAD patients.

The Ferroptosis-Related Noncoding RNA Signature as a Novel Prognostic Biomarker in the Tumor Microenvironment, Immunotherapy, and Drug Screening of Gastric Adenocarcinoma.

BACKGROUND: Ferroptosis is a new type of cell death different from apoptosis, necrosis, autophagy, and pyroptosis. This study aimed to explore the relationship between ferroptosis-related noncoding RNA (ncRNA) and gastric adenocarcinoma with regard to immunity and prognosis. METHODS: Ferroptosis-related ncRNA expression profiles and clinical pathology and overall survival information were collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database. The ferroptosis-related ncRNA signature was identified by Cox regression analysis and the least absolute shrinkage and selection operator analysis. The survival analysis, receiver operating characteristic (ROC) analysis, and decision curve analysis were adopted to evaluate the prognostic prediction performance of the signature. The correlation between risk and multiple clinical characteristics was analyzed using the chi-square test. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were used for mining functions and pathways. The CIBERSORT, ssGSEA, and ESTIMATE algorithms were used to assess immune infiltration and the tumor microenvironment. The response of immunotherapy was predicted using the Submap algorithm, and the Connectivity Map and the ridge regression model were used to screen and evaluate drugs. RESULTS: A carcinogenic risk signature was constructed using five ferroptosis-related ncRNAs. It showed an extraordinary ability to predict the prognoses of patients with gastric adenocarcinoma [area under the ROC curve (AUC) after 6 years = 0.689; GSE84426, AUC after 6 years = 0.747]. The lower ferroptosis potential level and lower tumor mutation burden were related to the poor prognoses of patients. The high-risk group had more immune cell recruitment, and the overall effect of the anti-immune checkpoint immunotherapy was not as good as that of the low-risk group. The high- and low-risk groups were enriched in tumor- and immune-related pathways, respectively. The screened antitumor drugs, such as genistein, guanabenz, and betulinic acid, improved the survival of the patients. CONCLUSIONS: The ferroptosis-related ncRNA signature is a potential carcinogenic prognostic biomarker of gastric adenocarcinoma.