Comparative investigation of the structural characteristics of tobacco stalk lignin during the DES and alkaline deconstruction toward sustainable materials.

Lignin polymer as a natural aromatic macromolecule presents significant prospects in producing functional and sustainable materials, and achieving a comprehensive characterization will facilitate their target valorization. In the present study, deep eutectic solvent (DES) and alkaline delignification were adopted to deconstruct tobacco stalk before and after hydrothermal pretreatment, obtaining diverse lignin fractions with fascinating characteristics. DES lignin exhibited a higher yield and homogenous molecular structure than MWL. A severe cleavage of the inter-unit linkages in lignin was also observed. This result mostly originated from the efficient delignification of the DES deconstruction system adopted. Moreover, all the recovered lignin fractions exhibited good micro-nanoparticle size that can enhance the valorization of lignin in nanomaterial production, in which the hydrothermal-assisted DES deconstruction promoted the formation of the smaller lignin nanoparticle size. Next, all the recovered lignin presented an excellent UV absorption and structure-related absorption performance or thermal properties. Overall, this work provides an important foundation for further exploiting DES/alkaline delignification lignin that can be applied as an ideal feedstock for producing sustainable functional or micro/nanomaterials.

UCHL1 acts as a potential oncogene and affects sensitivity of common anti-tumor drugs in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is the leading cause of cancer death worldwide. Recently, ubiquitin C-terminal hydrolase L1 (UCHL1) has been demonstrated to be highly expressed in many tumors and plays the role of an oncogene. However, the functional mechanism of UCHL1 is unclear in lung adenocarcinoma progression. METHODS: We analyzed the differential expression of the UCHL1 gene in lung adenocarcinoma and normal lung tissues, and the correlation between the UCHL1 gene and prognosis was also analyzed by the bioinformatics database TCGA. Meanwhile, we detected and analyzed the expression of UCHL1 and Ki-67 protein in a tissue microarray (TMA) containing 150 patients with lung adenocarcinoma by immunohistochemistry (IHC) and clinicopathological characteristics by TCGA database. In vitro experiments, we knocked down the UCHL1 gene of A549 cells and detected the changes in cell migration, invasion, and apoptosis. At the same time, we analyzed the effect of UCHL1 on anti-tumor drug sensitivity of lung adenocarcinoma by a bioinformatics database. In terms of the detection rate of lung adenocarcinoma indicators, we analyzed the impact of UCHL1 combined with common clinical indicators on the detection rate of lung adenocarcinoma through a bioinformatics database. RESULTS: In this study, the analysis of UCHL1 protein expression in lung adenocarcinoma proved that obviously higher UCHL1 protein level was discovered in lung adenocarcinoma tissues. The expression of UCHL1 was closely related to poor clinical outcomes. Interestingly, a significantly positive correlation between the expression of UCHL1 and Ki-67-indicated UCHL1 was associated with tumor migration and invasion. Through executing loss of function tests, we affirmed that silencing of UCHL1 expression significantly inhibited migration and invasion of lung adenocarcinoma cells in vitro. Furthermore, lung adenocarcinoma cells with silenced UCHL1 showed a higher probability of apoptosis. In terms of the detection rate of lung adenocarcinoma indicators, we discovered UCHL1 could improve the detection rate of clinical lung adenocarcinoma and affect drug sensitivity. CONCLUSION: In lung adenocarcinoma, UCHL1 promotes tumor migration, invasion, and metastasis by inhibiting apoptosis and has an important impact on the clinical drug treatment of lung adenocarcinoma. In addition, UCHL1 can improve the detection rate of clinical lung adenocarcinoma. Above all, UCHL1 may be a new marker for the diagnosis of lung adenocarcinoma and provide a new target for the treatment of clinical diseases.

Establishment of prognostic risk model and drug sensitivity based on prognostic related genes of esophageal cancer.

At present, the treatment of esophageal cancer (EC) is mainly surgical and drug treatment. However, due to drug resistance, these therapies can not effectively improve the prognosis of patients with the EC. Therefore, a multigene prognostic risk scoring system was constructed by bioinformatics analysis method to provide a theoretical basis for the prognosis and treatment decision of EC. The gene expression profiles and clinical data of esophageal cancer patients were gathered from the Cancer Genome Atlas TCGA database, and the differentially expressed genes (DEGs) were screened by R software. Genes with prognostic value were screened by Kaplan Meier analysis, followed by functional enrichment analysis. A cox regression model was used to construct the prognostic risk score model of DEGs. ROC curve and survival curve were utilized to evaluate the performance of the model. Univariate and multivariate Cox regression analysis was used to evaluate whether the model has an independent prognostic value. Network tool mirdip was used to find miRNAs that may regulate risk genes, and Cytoscape software was used to construct gene miRNA regulatory network. GSCA platform is used to analyze the relationship between gene expression and drug sensitivity. 41 DEGs related to prognosis were pre-liminarily screened by survival analysis. A prognostic risk scoring model composed of 8 DEGs (APOA2, COX6A2, CLCNKB, BHLHA15, HIST1H1E, FABP3, UBE2C and ERO1B) was built by Cox regression analysis. In this model, the prognosis of the high-risk score group was poor (P < 0.001). The ROC curve showed that (AUC = 0.862) the model had a good performance in predicting prognosis. In Cox regression analysis, the comprehensive risk score can be employed as an independent prognostic factor of the EC. HIST1H1E, UBE2C and ERO1B interacted with differentially expressed miRNAs. High expression of HIST1H1E was resistant to trametinib, selumetinib, RDEA119, docetaxel and 17-AAG, High expression of UBE2C was resistant to masitinib, and Low expression of ERO1B made the EC more sensitive to FK866. We constructed an EC risk score model composed of 8 DEGs and gene resistance analysis, which can provide reference for prognosis prediction, diagnosis and treatment of the EC patients.

CAV1 is a prognostic predictor for patients with idiopathic pulmonary fibrosis and lung cancer.

The extremely high mortality of both lung cancer and Idiopathic pulmonary fibrosis (IPF) is a global threat. Early detection and diagnosis can reduce their mortality. Since fibrosis is a necessary process of cancer, identifying the common potential prognostic genes involved in these two diseases will significantly contribute to disease prevention and targeted therapy. Microarray datasets of IPF and lung cancer were extracted from the GEO database. GEO2R was exploited to retrieve the differentially expressed genes (DEGs). The intersecting DEGs were obtained by the Venn tool. DAVID tools were used to perform GO and KEGG pathway enrichment analysis of DEGs. Then, the Kaplan-Meier plotter was employed to determine the prognostic value and verify the expression, pathological stage, and phosphorylation level of the hub gene in the TCGA and GTEx database. Finally, the extent of immune cell infiltration in lung cancer was estimated by the TIMER2 tool. The Venn diagram revealed 1 upregulated gene and 15 downregulated genes from GSE32863, GSE43458, GSE118370, and GSE75037 of lung cancer, as well as GSE2052 and GSE53845 of IPF. CytoHubba identified the top three genes [TEK receptor tyrosine kinase (TEK), caveolin 1 (CAV1), and endomucin (EMCN)] as hub genes following the connectivity degree. Survival analysis claimed the association of only TEK and CAV1 expression to both overall survival (OS) and first progression (FP). Pathological stage analyses revealed the relationship of only CAV1 expression to the pathological stage and the significant correlation of only CAV1 phosphorylation expression level for lung cancer. Furthermore, a statistically positive correlation was observed between the immune infiltration of cancer-associated fibroblasts, endothelial, and neutrophils with the CAV1 expression in lung cancer, whereas the contradictory result was noted for the immune infiltration of T cell follicular helper. Early detection and diagnostic potential of lung cancer are ameliorated by the combined selection of key genes among IPF and lung cancer.

Vitamin D reduces autophagy by regulating NF-κB resistance to Aspergillus fumigatus infection.

Vitamin D is one of the indispensable nutrients of human body. When vitamin D is deficient, it can cause a series of related diseases, such as respiratory tract infection. The regulatory role of vitamin D in inflammatory immune response and defense has attracted more and more attention. However, few studies have shown that vitamin D regulates inflammation and autophagy in Aspergillus fumigatus infected lungs. In this study, we will explain the mechanism of vitamin D regulating inflammation and autophagy in Aspergillus fumigatus infected lungs. METHODS: Different concentrations of Aspergillus fumigatus spores were injected into mice with deficien diets (VitD-) or sufficient vitamin D (VitD + ) , and the survival rates were recorded. Then, the weight changes of rats were measured every other time. At the same time, a gauze was used to filter the lapped lung tissue to get the pulmonary spores and measured the amount of the spores. The mice with the same concentration of Aspergillus fumigatus infected were cut off and the lung tissue for pathological examination in the deficien diets (VitD-) group or sufficient vitamin D (VitD + ) group. Moreover, the expression of inflammation related factors TNF-α, IL-1ß, IL-6 in lung was measured by immunohistochemical method. The expression of TNF-α, IL-1ß, IL-6 in the serum of vitamin D deficiency and sufficient mice were measured by ELISA. In vitro, we obtained macrophages from healthy mice and mixed cultures of Aspergillus fumigatus spores and lung macrophages in medium with or without vitamin D. After the cells were infected with Aspergillus fumigatus spores, the expressions of NF-κB and IL-8 were detected by RT-PCR and Western blot. The RAW264.7 cells transfected with GFP-LC3BII were mixed with Aspergillus fumigatus spores, and the expression of cell fluorescence was observed by the fluorescence microscope with or without chloroquine and rapamycin , and the autophagy flow of the cells was measured by Western blot. In the RAW264.7 cells, Lentivirus transfection and SiRNA technologies were used to enhance or reduce the expression of the NF-κB gene (siNF-κB) for investgating the influence of high or low expression of NF-κB in the autophagic flow of vitamin D + or vitamin D-treated RAW264.7 cells. RESULTS: The survival rate of vitamin D deficient mice infected Aspergillus fumigatus was significantly lower than that of vitamin D sufficient mice, while the number of spores, spore activity, pathological changes of lungs and inflammation in the lungs of vitamin D deficient mice were more severe than that of vitamin D sufficient mice. In vitro cell experiments, when cell was stimulated with vitamin D, the expressions of NF-κB and IL-8 in cells were lower. The autophagic flux and TNF-α, IL-1ß, IL-6 and LC3BII in vitamin D group were significantly lower than those in vitamin D deficiency group. CONCLUSIONS: Vitamin D deficiency can aggravate the inflammatory damage in the lungs of Aspergillus fumigatus. When the body is sufficient in vitamin D, if the lungs infect Aspergillus fumigatus spores, the body may resist the infection of Aspergillus fumigatus by reducing the expression of NF-κB, inflammatory factors and autophagy.

Exploration and Consideration of the Medical Alliance Modes.

BACKGROUND: The distribution of medical resources in China has long been in an unbalanced state. Since 2009, the government has initiated the planning and construction of a sound grass-roots medical and health service system, increased investment in grass-roots medical and health institutions, but it has not received the expected results. In order to solve the problem, the medical consortium-with a full-featured, hierarchical and resource-sharing structure has been proposed. METHODS: Overall, 1000 Electronic questionnaires about cognitive status of residents on medical alliance were randomly distributed in 50 community health service centers in 10 cities including Xuzhou, Nanjing, Hefei, Jinan, Zhengzhou, Changsha, Wuhan, Xi'an, Nanchang and Chengdu, China. RESULTS: 94.84% of the respondents responded they had heard about the construction of medical alliance, but they did not know the specific content. When asked about the preferred medical institution after illness, 93.50% participants preferred third-tier general hospital or specialist hospital. 62.58% of the respondents believe that the establishment of the medical alliance has not yet played a role and they are concerned that it cannot be effectively implemented. 62.27% of respondents were attracted by the convenience of medical alliance, 20.72% of respondents thought that they could easily get to famous doctors when they were in need, and 5.46% of respondents thought that there was no advantage in medical alliance. CONCLUSION: The establishment of the medical alliance is an effective means to promote the optimal allocation of medical and health resources. Government should perform its functions, and medical institutions and the whole society should all participate.

[NADPH oxidase-induced macrophage autophagy mediated by reactive oxygen species in Aspergillus fumigatus infection].

OBJECTIVE: To investigate whether or not NADPH oxidase (NOX) participates in Aspergillus fumigatus induced macrophage autophagy in RAW264.7 cells and explore the possible mechanism. METHODS: RAW264.7 cells in the exponential growth phase were randomized into three groups: Aspergillus fumigatus conidia (MOI 5:1) treated group, Aspergillus fumigatus conidia plus NOX inhibitor diphenyleneiodonium chloride (DPI) treated group; negative control group (untreated). The levels of intracellular reactive oxygen species (ROS) were measured with dichiorodihydrofluorescein diacetate (DCFH-DA) staining by fluorescence microscope. The expression of microtubule-associated protein light chain-3 (LC3) protein in RAW264.7 cells was detected by Western blotting. Then the expression and positioning of LC-3 were observed by immunofluorescence staining. RESULTS: After stimulated with conidia of Aspergillus fumigatus, RAW264.7 cells showed significant increases of ROS and LC3BII. Interestingly, LC3 was recruited to phagosomes which contained Aspergillus fumigatus conidia. After the NOX inhibitor DPI blocked the ROS production, the expressions of ROS and LC3BII had no significant increases as compared with the negative control group, and the distribution of LC3 was diffuse in cytoplasm. CONCLUSION: NOX induces macrophage autophagy by producing ROS in Aspergillus fumigatus infection.