Circulating Angiopoietin-2 as a Biomarker in ANCA-Associated Vasculitis

The endothelial-specific Angiopoietin-Tie2 ligand-receptor system is an important regulator of endothelial activation. Binding of angiopoietin-2 (Ang-2) to Tie2 receptor renders the endothelial barrier responsive to pro-inflammatory cytokines. We previously showed that circulating Ang-2 correlated with disease severity in a small cohort of critically ill patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. The current study reassessed Ang-2 as a biomarker of disease activity and relapse in AAV. Circulating Ang-2 was measured in 162 patients with severe AAV (BVAS/WG≥3, with or without glomerulonephritis) in a clinical trial. Ang-2 levels during active AAV were compared to levels in the same patients during remission (BVAS/WG = 0). Levels in clinical subsets of AAV were compared, and association with future disease course was assessed. Ang-2 levels were elevated in severe disease (median 3.0 ng/ml, interquartile range 1.9–4.4) compared to healthy controls (1.2, 0.9–1.5). However, they did not reliably decline with successful treatment (median 2.6 ng/ml, interquartile range 1.9–3.8, median change −0.1). Ang-2 correlated weakly with BVAS/WG score (r = 0.17), moderately with markers of systemic inflammation (r = 0.25–0.41), and inversely with renal function (r = −0.36). Levels were higher in patients with glomerulonephritis, but levels adjusted for renal dysfunction were no different in patients with or without glomerulonephritis. Levels were higher in patients with newly diagnosed AAV and lower in patients in whom treatment had recently been started. Ang-2 levels during active disease did not predict response to treatment, and Ang-2 levels in remission did not predict time to flare. Thus, Ang-2 appears to have limited practical value in AAV as a biomarker of disease activity at time of measurement or for predicting future activity

Antibiotics and antibiotic resistance genes in global lakes:A review and meta-analysis

Lakes are an important source of freshwater, containing nearly 90% of the liquid surface fresh water worldwide. Long retention times in lakes mean pollutants from discharges slowly circulate around the lakes and may lead to high ecological risk for ecosystem and human health. In recent decades, antibiotics and antibiotic resistance genes (ARGs) have been regarded as emerging pollutants. The occurrence and distribution of antibiotics and ARGs in global freshwater lakes are summarized to show the pollution level of antibiotics and ARGs and to identify some of the potential risks to ecosystem and human health. Fifty-seven antibiotics were reported at least once in the studied lakes. Our meta-analysis shows that sulfamethoxazole, sulfamerazine, sulfameter, tetracycline, oxytetracycline, erythromycin, and roxithromycin were found at high concentrations in both lake water and lake sediment. There is no significant difference in the concentration of sulfonamides in lake water from China and that from other countries worldwide; however, there was a significant difference in quinolones. Erythromycin had the lowest predicted hazardous concentration for 5% of the species (HC5) and the highest ecological risk in lakes. There was no significant difference in the concentration of sulfonamide resistance genes (sul1 and sul2) in lake water and river water. There is surprisingly limited research on the role of aquatic biota in propagation of ARGs in freshwater lakes. As an environment that is susceptible to cumulative build-up of pollutants, lakes provide an important environment to study the fate of antibiotics and transport of ARGs with a broad range of niches including bacterial community, aquatic plants and animals

Sequence of a complete chicken BG haplotype shows dynamic expansion and contraction of two gene lineages with particular expression patterns.

Many genes important in immunity are found as multigene families. The butyrophilin genes are members of the B7 family, playing diverse roles in co-regulation and perhaps in antigen presentation. In humans, a fixed number of butyrophilin genes are found in and around the major histocompatibility complex (MHC), and show striking association with particular autoimmune diseases. In chickens, BG genes encode homologues with somewhat different domain organisation. Only a few BG genes have been characterised, one involved in actin-myosin interaction in the intestinal brush border, and another implicated in resistance to viral diseases. We characterise all BG genes in B12 chickens, finding a multigene family organised as tandem repeats in the BG region outside the MHC, a single gene in the MHC (the BF-BL region), and another single gene on a different chromosome. There is a precise cell and tissue expression for each gene, but overall there are two kinds, those expressed by haemopoietic cells and those expressed in tissues (presumably non-haemopoietic cells), correlating with two different kinds of promoters and 5' untranslated regions (5'UTR). However, the multigene family in the BG region contains many hybrid genes, suggesting recombination and/or deletion as major evolutionary forces. We identify BG genes in the chicken whole genome shotgun sequence, as well as by comparison to other haplotypes by fibre fluorescence in situ hybridisation, confirming dynamic expansion and contraction within the BG region. Thus, the BG genes in chickens are undergoing much more rapid evolution compared to their homologues in mammals, for reasons yet to be understood.This is the final published version. It was originally published by PLOS in PLOS Genetics here: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1004417

Eco-Environmental Effects of Changes in Territorial Spatial Pattern and Their Driving Forces in Qinghai, China (1980–2020)

As urbanization and industrialization have advanced in leaps and bounds, the territorial spatial pattern of Qinghai has experienced profound transformation and reconstruction, which has been directly reflected in land-use changes and affected the eco-environment. In this context, we constructed a functional classification system of “production-living-ecological” (PLE), used remote sensing data for six periods from 1980 to 2020, and employed the land transfer matrix, eco-environmental quality index, ecological contribution rate of land-use transformation and geographical detectors to analyze the changes in the territorial spatial patterns, eco-environmental effects and driving forces of eco-environmental quality. The results revealed that (1) the spatial distribution of the province was characterized by the relative agglomeration of the production and living spaces and the absolute dominance of ecological spaces; (2) The eco-environmental quality of the region portrayed a steady improvement, with a significant reduction in the medium–low and low-quality areas; and (3) the annual average precipitation, proportion of non-agricultural area, and socio-economic factors had a significant impact on the eco-environmental quality of the region, meanwhile, national economy and ecological policies are important indirect driving forces of eco-environmental quality. Our findings will provide guidelines for territorial spatial management and serve as a reference for eco-environmental protection in Qinghai

Eco-Environmental Effects of Changes in Territorial Spatial Pattern and Their Driving Forces in Qinghai, China (1980–2020)

As urbanization and industrialization have advanced in leaps and bounds, the territorial spatial pattern of Qinghai has experienced profound transformation and reconstruction, which has been directly reflected in land-use changes and affected the eco-environment. In this context, we constructed a functional classification system of “production-living-ecological” (PLE), used remote sensing data for six periods from 1980 to 2020, and employed the land transfer matrix, eco-environmental quality index, ecological contribution rate of land-use transformation and geographical detectors to analyze the changes in the territorial spatial patterns, eco-environmental effects and driving forces of eco-environmental quality. The results revealed that (1) the spatial distribution of the province was characterized by the relative agglomeration of the production and living spaces and the absolute dominance of ecological spaces; (2) The eco-environmental quality of the region portrayed a steady improvement, with a significant reduction in the medium–low and low-quality areas; and (3) the annual average precipitation, proportion of non-agricultural area, and socio-economic factors had a significant impact on the eco-environmental quality of the region, meanwhile, national economy and ecological policies are important indirect driving forces of eco-environmental quality. Our findings will provide guidelines for territorial spatial management and serve as a reference for eco-environmental protection in Qinghai

Prediction on import volume of Central Asian gas for stable supply in winter

The Trans-Asia Gas Pipeline is an important onshore energy corridor for China. In the recent winters requiring stable supply, the supply and download volumes of the imported Central Asian gas in the gas source and transit countries fluctuate greatly due to the influence of temperature change, which often leads to the unplanned and unexpected reduction of gas transferred to China. In this case, no measure can be taken in advance, thus affecting China's capacity to ensure the stable supply of gas in winter. In order to solve this problem, the historical data of the factors affecting the supply and download volumes of gas in winters requiring stable supply were analyzed and evaluated, the correlation between the factors was quantified, and a mathematical prediction model with the temperature of the gas source and transit countries of imported Central Asian gas as the independent variable was established to predict the change trend of Central Asian gas transferred to China. In addition, the model is verified to be accurate by comparing the model prediction results with the actual gas volume, and the prediction results could provide support for timely raising of emergency resources in China, which is conductive to effectively controlling the operation and adjusting optimal window period, so as to avoid the loss of energy consumption caused by delayed adjustment of working conditions

Correlation of hypogammaglobulinaemia with proteinuria, and the relationship between hypogammaglobulinaemia and infection in active lupus nephritis.

ObjectiveTo evaluate hypogammaglobulinaemia and risk of serious infectious adverse events in active lupus nephritis.MethodsThe Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS) compared abatacept with placebo in participants with lupus nephritis undergoing treatment with Euro-Lupus Nephritis low-dose cyclophosphamide. Serum IgG levels were assessed prior to initiation of treatment and throughout the trial. Hypogammaglobulinaemia was defined as IgG <450 mg/dL.ResultsHypogammaglobulinaemia was observed in 16/102 (15.7%) participants prior to initiation of induction therapy for active lupus nephritis. Participants with nephrotic range proteinuria were more likely to have hypogammaglobulinaemia, and serum IgG levels were inversely correlated with urine protein to creatinine ratio (r=-0.42, p<0.0001). Following initiation of treatment for active lupus nephritis, additional participants developed hypogammaglobulinaemia by weeks 2-4. Serum IgG levels then increased, and all but one participant had serum IgG ≥450 mg/dL at 24 weeks. Hypogammaglobulinaemia was not associated with an increased risk of serious infectious adverse events.ConclusionsIn active lupus nephritis in ACCESS, hypogammaglobulinaemia was common and inversely correlated with proteinuria. Serum IgG levels were lowest in the weeks immediately following initiation of induction therapy, and subsequently improved by 24 weeks. Hypogammaglobulinaemia was not associated with serious infectious adverse events.Trial registratio

Inhibition of LSD1 induces ferroptosis through the ATF4-xCT pathway and shows enhanced anti-tumor effects with ferroptosis inducers in NSCLC.

Lysine-specific demethylase 1 (LSD1) has been identified as an important epigenetic target, and recent advances in lung cancer therapy have highlighted the importance of targeting ferroptosis. However, the precise mechanisms by which LSD1 regulates ferroptosis remain elusive. In this study, we report that the inhibition of LSD1 induces ferroptosis by enhancing lipid peroxidation and reactive oxygen species (ROS) accumulation. Mechanistically, LSD1 inhibition downregulates the expression of activating transcription factor 4 (ATF4) through epigenetic modification of histone H3 lysine 9 dimethyl (H3K9me2), which sequentially inhibits the expression of the cystine-glutamate antiporter (xCT) and decreases glutathione (GSH) production. Furthermore, LSD1 inhibition transcriptionally upregulates the expression of transferrin receptor (TFRC) and acyl-CoA synthetase long chain family member 4 (ACSL4) by enhancing the binding of histone H3 lysine 4 dimethyl (H3K4me2) to their promoter sequences. Importantly, the combination of an LSD1 inhibitor and a ferroptosis inducer demonstrates an enhanced anti-tumor effect in a xenograft model of non-small cell lung cancer (NSCLC), surpassing the efficacy of either agent alone. These findings reveal new insights into the mechanisms by which LSD1 inhibition induces ferroptosis, offering potential guidance for the development of new strategies in the treatment of NSCLC

Inhibition of LSD1 induces ferroptosis through the ATF4-xCT pathway and shows enhanced anti-tumor effects with ferroptosis inducers in NSCLC

Abstract Lysine-specific demethylase 1 (LSD1) has been identified as an important epigenetic target, and recent advances in lung cancer therapy have highlighted the importance of targeting ferroptosis. However, the precise mechanisms by which LSD1 regulates ferroptosis remain elusive. In this study, we report that the inhibition of LSD1 induces ferroptosis by enhancing lipid peroxidation and reactive oxygen species (ROS) accumulation. Mechanistically, LSD1 inhibition downregulates the expression of activating transcription factor 4 (ATF4) through epigenetic modification of histone H3 lysine 9 dimethyl (H3K9me2), which sequentially inhibits the expression of the cystine–glutamate antiporter (xCT) and decreases glutathione (GSH) production. Furthermore, LSD1 inhibition transcriptionally upregulates the expression of transferrin receptor (TFRC) and acyl-CoA synthetase long chain family member 4 (ACSL4) by enhancing the binding of histone H3 lysine 4 dimethyl (H3K4me2) to their promoter sequences. Importantly, the combination of an LSD1 inhibitor and a ferroptosis inducer demonstrates an enhanced anti-tumor effect in a xenograft model of non-small cell lung cancer (NSCLC), surpassing the efficacy of either agent alone. These findings reveal new insights into the mechanisms by which LSD1 inhibition induces ferroptosis, offering potential guidance for the development of new strategies in the treatment of NSCLC