Simvastatin attenuates silica-induced pulmonary inflammation and fibrosis in rats via the AMPK-NOX pathway.

BACKGROUND: Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms. METHODS: The rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway. RESULTS: Sim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and transforming growth factor-ß1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions. CONCLUSIONS: Sim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.

Effect of an automated flexible endoscope channel brushing system on improving reprocessing quality: a randomized controlled study.

BACKGROUND: Qualified reprocessing, of which meticulous channel brushing is the most crucial step, is essential for prevention and control of endoscopy-associated infections. However, channel brushing is often omitted in practice. This study aimed to evaluate the effect of an automated flexible endoscope channel brushing system (AECBS) on improving the quality of endoscope reprocessing. METHODS: This prospective, randomized controlled study was conducted between 24 November 2021 and 22 January 2022 at Renmin Hospital of Wuhan University, China. Eligible endoscopes were randomly allocated to the auto group (channels brushed by AECBS) or the manual group (channels brushed manually), with sampling and culturing after high-level disinfection and drying. The primary end point was the proportion of endoscopes with positive cultures. RESULTS: 204 endoscopes in the auto group and 205 in the manual group were analyzed. The proportion of endoscopes with positive cultures was significantly lower in the auto group (15.2 % [95 %CI 10.7 %-21.0 %]) than in the manual group (23.4 % [95 %CI 17.9 %-29.9 %]). CONCLUSIONS: AECBS could effectively reduce bioburden and improve reprocessing quality of gastroscopes and colonoscopes. AECBS has the potential to replace manual brushing and lower the risk of endoscopy-associated infections, providing a new option for the optimization of reprocessing.

IL-27 alleviates airway remodeling in a mouse model of asthma via PI3K/Akt pathway.

Purpose: Airway remodeling is one of the features of severe asthma. Previous study shows that IL-27 inhibits airway inflammation in asthmatic mice. However, the role of IL-27 on airway remodeling in OVA-induced asthmatic mice and its possible mechanism remain unclear. Methods: We established an ovalbumin (OVA)-induced asthmatic mice model. IL-27 were preventative administered to OVA-induced asthmatic mice. The total cells in Bronchoalveolar lavage fluid (BALF) and Airway hyperresponsiveness (AHR) were measured. The lung tissues were performed by Hematoxylin and eosin (HE) staining to estimate the pathological changes. Masson staining was used to observe the collagen deposition area. The expression of α-smooth muscle actin (α-SMA) and Type I collagen was measured by immunohistochemistry, western blot, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Additionally, western blot was also used to measure the expression of phosphorylated-Akt (p-Akt) in each group. Results: IL-27 group showed significant inhibitory effect on the α-SMA and Type I collagen. The expression of p-Akt in the tissues of asthma model was increased and inhibited by IL-27. Conclusions: IL-27 can alleviate airway remodeling in OVA-induced asthmatic mice, and the mechanism may relate to PI3K/Akt pathway.

Dihydroartemisinin up-regulates VE-cadherin expression in human renal glomerular endothelial cells.

The antimalarial agent dihydroartemisinin (DHA) has been shown to be anti-inflammatory. In this study, we found that DHA increased the expression of the junctional protein vascular endothelial (VE)-cadherin in human renal glomerular endothelial cells. In addition, DHA inhibited TGF-ß RI-Smad2/3 signalling and its downstream effectors SNAIL and SLUG, which repress VE-cadherin gene transcription. Correspondingly, DHA decreased the binding of SNAIL and SLUG to the VE-cadherin promoter. Together, our results suggest an effect of DHA in regulating glomerular permeability by elevation of VE-cadherin expression.

In Silico Discovery of a Small Molecule Suppressing Lung Carcinoma A549 Cells Proliferation and Inducing Autophagy via mTOR Pathway Inhibition.

Mammalian target of rapamycin (mTOR) kinase is vital to the regulation of cell growth and proliferation, and it has been taken as a promising target to develop cancer therapies. By reference to the crystal structure of mTOR-PP242, we explored to discover potential ATP-competitive inhibitors of mTOR. Through the integrated use of multiple in silico screenings, the tremendous amount of compounds from the SPECS database were finally reduced to 30. After several rounds of convincing biological tests in A549 cells, the newfound C-4 was identified as a potential ATP-competitive inhibitor of mTOR. Besides A549 cell proliferation suppression caused by C-4, autophagy was also determined through autophagosome observation and autophagy flux detection in C-4 treated A549 cells. We demonstrated that C-4 could inhibit cell growth and proliferation, and this inhibition may be associated with autophagy.

The miR-599 promotes non-small cell lung cancer cell invasion via SATB2.

MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. Here, we identified that miR-599 is up-regulated in non-small cell lung cancer (NSCLC) patients. It promoted NSCLC cell proliferation by negatively regulating SATB2. In NSCLC cell lines, CCK-8 proliferation assay indicated that the cell proliferation is promoted by miR-599 mimics. Transwell assay showed that miR-599 mimics promoted the invasion and migration of NSCLC cells. Luciferase assays confirmed that miR-599 directly binds to the 3'untranslated region of SATB2, and western blotting showed that miR-599 suppresses the expression of SATB2 at the protein level. This study indicates that miR-599 promotes proliferation and invasion of NSCLC cell lines via SATB2. The miR-599 may represent a potential therapeutic target for NSCLC treatment.

A promising approach of overcoming the intrinsic resistance of Candida krusei to fluconazole (FLC)--combining tacrolimus with FLC.

Candida krusei is intrinsically resistant to fluconazole (FLC). This study aimed to investigate whether tacrolimus (FK506) could enhance the susceptibility of FLC against C. krusei. The tested strains included the following: five isolates with minimal inhibitory concentration (MIC) of 32 µg mL(-1), two with MIC of 256 µg mL(-1), and one with MIC of 512 µg mL(-1). MICs of FK506 and FLC alone and in combination were determined by checkerboard assay, with data analyzed by fractional inhibitory concentration index model. The time-kill curves were plotted to investigate the antifungal activity at 0, 6, 12, 24, and 48 h after drug exposure. The results revealed that FK506 reduced the resistance of all isolates obviously and degree of reduction in MICs varied with susceptibilities of strains. Addition of FK506 resulted in a fourfold and 16-fold downward shift in MICs of the isolates with MICs of 32 µg mL(-1) and of ≥ 256 µg mL(-1), respectively. The synergy was further confirmed by the time-kill assay. When they were in combination against CK4/CK9 with MIC of 32/256 µg mL(-1), there was a 2.25/2.03 log10 CFU mL(-1) decrease at 24 h compared with FLC alone, respectively. In conclusion, combination of FK506 and FLC may represent a promising approach of overcoming the intrinsic resistance of C. krusei to FLC.

Synergistic effect of doxycycline and fluconazole against Candida albicans biofilms and the impact of calcium channel blockers.

Candida albicans is a clinically important fungus and is capable of forming biofilms, which contributes to the emergence of fluconazole resistance. Here, sessile minimum inhibitory concentrations (SMICs) of fluconazole combined with doxycycline against biofilms of C. albicans were determined, and the results of SMICs were compared with minimum inhibitory concentrations (MICs) of planktonic cells. SMICs and MICs were determined by microdilution checkerboard method, and the interactions between two drugs were interpreted by two models of fractional inhibitory concentration index and the percentage of growth difference (ΔE). For the biofilms formed over 4, 8, and 12 h, synergism was displayed by the combination of doxycycline(1-64 mg L(-1)) and fluconazole, and the fluconazole SMIC reduced from 64-512 mg L(-1) to 1-16 mg L(-1) against all the tested isolates. Calcium homeostasis is an important factor in growth of C. albicans. In this study, the impact of calcium channel blocker on the drug combination was observed by plate streaking and determined by liquid methods quantitatively. Obvious enhancement of antifungal effect appeared by combination of three drugs. These results show us that fluconazole combined with doxycycline could be effective against C. albicans biofilm, and the combined antifungal mechanism is associated with calcium.

Analysis of spatiotemporal difference and driving factors of green total factor energy efficiency in RCEP members: insights from SBM-GML and Tobit models.

It is vital to determine the changing spatiotemporal patterns and driving factors of green total factor energy efficiency (GTFEE) in order to design scientific policies to promote energy efficiency in the Regional Comprehensive Economic Partnership (RCEP) region. From 2010 to 2019, the super-efficient SBM model and the global Malmquist-Luenberger index provide an appropriate framework for measuring the spatiotemporal evolution of GTFEE and the dynamics of energy productivity in RCEP countries. With the coefficient of variation and the Thiel index, an extensive view of the spatiotemporal variance in GTFEE is offered, taking regional heterogeneity into account. Furthermore, the Tobit model is introduced to investigate the factors influencing the GTFEE of RCEP members, which may address the restricted values of the dependent variable when compared to the least squares regression model. Findings suggest that (1) The GTFEE of RCEP members tends to be low and unevenly distributed spatially and temporally, with much room for improvement. (2) The energy productivity index fluctuates strongly, and the improvement primarily comes from technological progress. (3) The Non-ASEAN region possesses higher GTFEE than the ASEAN region, albeit regional variations are diminishing. (4) In terms of the major factors influencing the regional GTFEE, the non-ASEAN region looks to be distinct from the ASEAN region. The findings shed light on the trends and influencing factors of GTFEE in RCEP and serve as a resource for international energy cooperation and sustainable development.

Farm biogas project considering carbon trading indicates promising economic results-a case study.

The application of the farm biogas project is a perfect measure to deal with the increasingly nervous global climate problem and energy crisis and can support the accomplishment of urgently needed carbon peaking and carbon neutrality effectively. But the poor economic benefits hinder its better development. Thus, this paper aims to enhance the economics of farm biogas projects and explore a win-win model for economic and environmental benefits by studying the economic impact of participation in carbon trading on three types of farm biogas projects. First, economic analysis of farm biogas projects based on life cycle cost is carried out using case analysis. Second, the greenhouse gas emission reductions are calculated and benefits from carbon trading are considered. Then, the economic robustness was tested. Specifically, the economics of all three types of farm biogas projects is improved after carbon trading. The ecological farm biogas project has the best economic performance, with a net present value of $551,689.11, internal rate of return of 49%, and payback period of 2.39 years. In addition, the emission reductions of 5045.79 t CO2e, 7420.28 t CO2e, and 148.41 t CO2e are very significant. Based on these, suggestions for developing farm biogas projects and introducing biogas projects to carbon trading are put forward for the reference of governments and investors when making investments and reforms. According to the result, participation of farm biogas projects in carbon trading can effectively enhance economic benefits and accelerate the achievement of the greenhouse gas emission reduction target which is of great significance to the urgent goal of global green and low-carbon transformation.

Application, planning, and techno-economic analysis of the multi-renewable energy complementary system in rural economic development zones: an empirical study in China.

The multi-renewable energy complementary system (MRECS) is a good plan that can effectively support the accomplishment of carbon peaking and carbon neutrality on schedule and take full advantage of renewable resources in rural areas. This research investigates the techno-economic feasibility of MRECS in rural areas to promote its large-scale implementation. A MRECS with integrated solar, wind, and biomass energy is proposed for a rural economic development zone. First, a scientific evaluation of the potential for renewable resources in rural areas is done. Second, a case study of the Jize Economic Development Zone is applied to examine the optimal MRECS configuration. Finally, an economic evaluation model that takes environmental benefits into account was created based on life cycle costs (LCCs). For the techno-economic analysis, the net present value (NPV), dynamic investment payback period, and internal rate of return (IRR) are also employed. Findings reveal that (1) the Jize Economic Development Zone has considerable development potential due to its abundance of renewable energy resources and ability to plan for 168.42 MW of renewable energy units; (2) to meet the demand for continuous power generation and realize the sensible use of renewable energy, a combination of 10 MW photovoltaic power generation (PV), 25 MW wind power generation (WT), 2 MW biogas power generation (BG), and 1 MW straw direct combustion power generation (SDC) is able to be implemented; (3) the provided renewable energy system can save indirect expenses up to 10.60 million RMB/year, with significant environmental advantages, when compared to grid extension; and (4) the NPV of the dynamic investment reaches RMB 322.44 million after accounting for the environmental advantages in the income of MRECS. The dynamic investment payback period is 6.42 years, and the IRR is 21.44%. According to the findings, the MRECS is economically viable, and capitalizing on the environmental advantages can increase those advantages even more.

Spatio-temporal variations, spatial spillover, and driving factors of carbon emission efficiency in RCEP members under the background of carbon neutrality.

Improving carbon emission efficiency (CEE) has emerged as a critical way for Regional Comprehensive Economic Partnership (RCEP) members to promote carbon reduction in the context of climate change mitigation and carbon neutrality. The super-efficiency slacks-based measure (SBM) model, which considers non-desired outputs, is adopted to comprehensively assess the current state and trend of CEE in 15 RCEP countries from a spatio-temporal dynamic perspective, and the global Malmquist-Luenberger (GML) index is coupled to quantify the spatial and temporal differences and dynamic changes. Following that, taking into account the spatial characteristics of CEE, the extended STIRPAT model and the spatial Durbin model are combined to further investigate the primary influencing factors of CEE. It is found that (1) the CEE of RCEP members is generally poor and unevenly distributed in temporal and spatial dimensions, with significant room for improvement and an overall positive spatial autocorrelation; (2) CEE varies considerably among RCEP members, with developed countries far outstripping developing countries in terms of both the current status and trend of CEE; (3) on a dynamic level, the GML index exhibits W-shaped fluctuations, with technological progress acting as the dominant force; and (4) in terms of spillover effects, affluence and economic agglomeration inhibit CEE enhancement, whereas technology level and investment capacity facilitate it. The findings will be useful in developing carbon-neutral plans for various countries as well as coordinated sustainable development for RCEP regions.

Estimation of biomass utilization potential in China and the impact on carbon peaking.

China has abundant agricultural and forestry waste resources that are crucial sources of energy for substituting fossil fuels and achieving the carbon peaking and carbon neutrality goals. These resources play an essential role in reducing carbon dioxide emissions and promoting sustainable development. This paper presents an estimation of the number of biomass resources that can be used for energy in 2020 by using parameters such as the grass-to-grain ratio coefficient and excretion coefficient. Moreover, the potential for conversion of biomass resources into biomass energy is evaluated by using parameters such as lower heating value and gas production coefficient. Finally, based on the whole life cycle theory, the potential of biomass energy utilization to reduce carbon dioxide emissions and its impact on carbon peaking is calculated. It was found that the total amount of fossil fuels that can be replaced by biomass energy is 256 million tons of standard coal. Utilizing biomass energy can reduce carbon dioxide emissions by approximately 520 million tons, with a peak impact of 4-6% on carbon peaking. The research results presented in this article can provide valuable data to support the promotion of green transformation in various regions. The findings can serve as a useful reference for formulating localized biomass utilization plans and designing effective emission reduction policies.

Interleukin-34 and immune checkpoint inhibitors: Unified weapons against cancer.

Interleukin-34 (IL-34) is a cytokine that is involved in the regulation of immune cells, including macrophages, in the tumor microenvironment (TME). Macrophages are a type of immune cell that can be found in large numbers within the TME and have been shown to have a role in the suppression of immune responses in cancer. This mmune suppression can contribute to cancer development and tumors' ability to evade the immune system. Immune checkpoint inhibitors (ICIs) are a type of cancer treatment that target proteins on immune cells that act as "checkpoints," regulating the activity of the immune system. Examples of these proteins include programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). ICIs work by blocking the activity of these proteins, allowing the immune system to mount a stronger response against cancer cells. The combination of IL-34 inhibition with ICIs has been proposed as a potential treatment option for cancer due to the role of IL-34 in the TME and its potential involvement in resistance to ICIs. Inhibiting the activity of IL-34 or targeting its signaling pathways may help to overcome resistance to ICIs and improve the effectiveness of these therapies. This review summarizes the current state of knowledge concerning the involvement of IL-34-mediated regulation of TME and the promotion of ICI resistance. Besides, this work may shed light on whether targeting IL-34 might be exploited as a potential treatment option for cancer patients in the future. However, further research is needed to fully understand the mechanisms underlying the role of IL-34 in TME and to determine the safety and efficacy of this approach in cancer patients.

Highly selective and sensitive determination of free and total amino acids in Apocynum venetum L. (Luobuma tea) by a developed HPLC-FLD method coupled with pre-column fluorescent labelling.

Amino acids (AA) are important chemical constituents of tea leaves remarkably influencing the quality of tea. In this study, free AA and total AA in Apocynum venetum L. (Luobuma tea) were estimated by HPLC equipped with fluorescent detector using 2-[2-(7H-dibenzo[a,g]carbazol-7-yl)-ethoxy] ethyl chloroformate (DBCEEC) as a fluorescent labelling reagent. Different parameters for derivatization and separation were optimized. AA were rapidly derivatized within 3 min at room temperature with DBCEEC. In conjunction with a gradient elution, a baseline resolution of 20 analytes was achieved on a reversed-phase Hypersil BDS C18 column. LC separation for the derivatized AA showed good reproducibility. Twenty AA were detected and showed significant linear responses with correlation coefficients (>0.9992). This developed method offered the low detection limit of 2.88-23.4 fmol.

Analysis of coordination between urban compactness and green total factor energy efficiency: a case study of 35 cities in China.

Rapid urban expansion and energy transformation are two major challenges facing China. Many researchers have explored urban compactness and energy efficiency, but there is little literature on the coordinated development of the two. Therefore, this paper takes 35 cities in China as research object: The urban compactness evaluation index system is established, and the score is calculated using the entropy weight method; considering the bad output, SBM is used to calculate the green total factor energy efficiency (GTFEE); and the coupling coordination degree model is used to calculate their coordinated degree. The following conclusions can be inferred: (1) Although China's urban compactness has increased, it has not maintained a steady upward trend. Some more developed cities have the phenomenon of compactness rising first and then falling; (2) The overall GTFEE shows a continuous upward trend, but there is still much room for improvement, and regional disparities are significant; (3) The degree of coordination between the two maintains a steady upward trend, and the city's compactness lags behind GTFEE. Based on the findings of the study, this paper proposes policy recommendations that can serve as a reference for key decision-makers and are critical in promoting China's urbanization and energy transformation.

Comprehensive Analyses of Ferroptosis-Related Alterations and Their Prognostic Significance in Glioblastoma.

Background: This study was designed to explore the implications of ferroptosis-related alterations in glioblastoma patients. Method: After obtaining the data sets CGGA325, CGGA623, TCGA-GBM, and GSE83300 online, extensive analysis and mutual verification were performed using R language-based analytic technology, followed by further immunohistochemistry staining verification utilizing clinical pathological tissues. Results: The analysis revealed a substantial difference in the expression of ferroptosis-related genes between malignant and paracancerous samples, which was compatible with immunohistochemistry staining results from clinicopathological samples. Three distinct clustering studies were run sequentially on these data. All of the findings were consistent and had a high prediction value for glioblastoma. Then, the risk score predicting model containing 23 genes (CP, EMP1, AKR1C1, FMOD, MYBPH, IFI30, SRPX2, PDLIM1, MMP19, SPOCD1, FCGBP, NAMPT, SLC11A1, S100A10, TNC, CSMD3, ATP1A2, CUX2, GALNT9, TNFAIP6, C15orf48, WSCD2, and CBLN1) on the basis of "Ferroptosis.gene.cluster" was constructed. In the subsequent correlation analysis of clinical characteristics, tumor mutation burden, HRD, neoantigen burden and chromosomal instability, mRNAsi, TIDE, and GDSC, all the results indicated that the risk score model might have a better predictive efficiency. Conclusion: In glioblastoma, there were a large number of abnormal ferroptosis-related alterations, which were significant for the prognosis of patients. The risk score-predicting model integrating 23 genes would have a higher predictive value.

A novel classification method for NSCLC based on the background interaction network and the edge-perturbation matrix.

The biological functional network of tumor tissues is relatively stable for a period of time and under different conditions, so the impact of tumor heterogeneity is effectively avoided. Based on edge perturbation, functional gene interaction networks were used to reveal the pathological environment of patients with non-small cell carcinoma at the individual level, and to identify cancer subtypes with the same or similar status, and then a multi-dimensional and multi-omics comprehensive analysis was put into practice. Two edge perturbation subtypes were identified through the construction of the background interaction network and the edge-perturbation matrix (EPM). Further analyses revealed clear differences between those two clusters in terms of prognostic survival, stemness indices, immune cell infiltration, immune checkpoint molecular expression, copy number alterations, mutation load, homologous recombination defects (HRD), neoantigen load, and chromosomal instability. Additionally, a risk prediction model based on TCGA for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) was successfully constructed and validated using the independent data set (GSE50081).

IL-27 attenuates airway inflammation and epithelial-mesenchymal transition in allergic asthmatic mice possibly via the RhoA/ROCK signalling pathway

Background: Asthma is an airway disease characterized by airflow limitation and various additional clinical manifestations. Repeated inflammatory stimulation of the airways leads to epithelial-mesenchymal transition (EMT) which aggravates subepithelial fibrosis during the process of airway remodelling and enhances resistance to corticosteroids and bronchodilators in refractory asthma. There is growing evidence that IL-27 modulates airway remodelling, however, the molecular mechanisms involving IL-27 and EMT are poorly understood. The objective of this study was to investigate the effects of IL-27 on ovalbumin (OVA)-challenged asthmatic mice in vivo and TGF-ß1-induced EMT in 16HBE cells in vitro. Methods: Airway inflammation, mucus secretion, and collagen deposition were analysed by conventional pathological techniques. The ratio of Th17 and Th9 cells in the spleen of mice was measured using flow cytometry, ELISA was performed for cytokine analysis to identify EMT-related molecules and signalling pathways, and other molecular and cellular techniques were used to explore the functional mechanism involving IL-27 and EMT. Results: Airway inflammation in asthmatic mice was significantly alleviated by IL-27, with downregulation of RhoA and ROCK, upregulation of E-cadherin, and a decrease of vimentin and α-SMA expression, compared to asthmatic mice. Moreover, the frequency of Th17 and Th9 cells in the spleen of asthmatic mice decreased following treatment with IL-27. In TGF-ß1-induced 16HBE cells, the addition of IL-27 was shown to inhibit EMT, based on the expression of E-cadherin, vimentin, and α-SMA. Conclusion: Intranasal administration of IL-27 attenuates airway inflammation and EMT in a murine model of allergic asthma possibly by downregulating the RhoA/ROCK signalling pathway.