Pulmonary fibrosis, a serious complication of systemic lupus erythematosus (SLE) and coronavirus disease 2019 (COVID-19), leads to irreversible lung damage. However, the underlying mechanism of this ...condition remains unclear. In this study, we revealed the landscape of transcriptional changes in lung biopsies from individuals with SLE, COVID-19-induced pulmonary fibrosis, and idiopathic pulmonary fibrosis (IPF) using histopathology and RNA sequencing, respectively. Despite the diverse etiologies of these diseases, lung expression of matrix metalloproteinase genes in these diseases showed similar patterns. Particularly, the differentially expressed genes were significantly enriched in the pathway of neutrophil extracellular trap formation, showing similar enrichment signature between SLE and COVID-19. The abundance of Neutrophil extracellular traps (NETs) was much higher in the lungs of individuals with SLE and COVID-19 compared to those with IPF. In-depth transcriptome analyses revealed that NETs formation pathway promotes epithelial-mesenchymal transition (EMT). Furthermore, stimulation with NETs significantly up-regulated α-SMA, Twist, Snail protein expression, while decreasing the expression of E-cadherin protein in vitro. This indicates that NETosis promotes EMT in lung epithelial cells. Given drugs that are efficacious in degrading damaged NETs or inhibiting NETs production, we identified a few drug targets that were aberrantly expressed in both SLE and COVID-19. Among these targets, the JAK2 inhibitor Tofacitinib could effectively disrupted the process of NETs and reversed NET-induced EMT in lung epithelial cells. These findings support that the NETs/EMT axis, activated by SLE and COVID-19, contributes to the progression of pulmonary fibrosis. Our study also highlights that JAK2 as a potential target for the treatment of fibrosis in these diseases.
•SLE and COVID-19 patients exhibit a common transcriptomics pattern.•DEGs in both SLE and COVID-19 patients are enriched in the NETs formation pathway.•Activation of the NETs contributes to promoting EMT in lung epithelial cells.•Tofacitinib is predicted as a potential therapy for fibrosis associated with SLE and COVID-19.
A polyaniline composite doped with etched multi-walled carbon nanotubes and UiO-66-NH
2
was prepared by electropolymerization. It was used as a sorbent to extract the polycyclic aromatic hydrocarbons ...(PAHs) phenanthrene, fluoranthene and pyrene. Its surface morphology, crystal structure and capability of adsorbing PAHs were characterized by scanning electron microscopy, X-ray photoelectron spectrometry, Fourier transform infrared spectrometry and zeta potentiometry. The π stacking and anion-π interactions are shown to play dominant roles in the sorption mechanism. Coupled with high performance liquid chromatography, the composite-modified fiber was applied to detect PAHs in lake water samples by direct immersion extraction. The method excels by (a) wide linear range (0.05–20 ng mL
−1
), (b) low limits of detection (10 pg mL
−1
), (c) satisfactory recovery from spiked samples (84.7–113.8%), and (d) good reproducibility (relative standard deviations of <6.5%). The method is superior in terms of costs and reproducibility compared to some pretreatment methods with mass spectrometric detection.
Graphical abstract
Schematic representation for interaction between PANI-etched MWCNT/UiO-66-NH
2
and polycyclic aromatic hydrocarbons (phenanthrene, fluoranthene, pyrene).
The brightness and color of lemon fruit directly determine its commodity value. Ethylene (ETH) and gibberellic acid (GA3) treatment are widely adopted to achieve postharvest uniform peel color, which ...may affect fruit surface brightness. Fruit brightness is closely associated with cuticular wax. However, little is known about how ETH and GA3 treatment affect cuticular wax metabolism in lemon fruit. Here, we treated green lemon fruit with ethephon and GA3 solution, and analyzed the changes in wax crystal morphology, chemical composition and expression levels of wax-related genes during storage. ETH increased the density and size of platelet-like wax crystals. Moreover, ETH accelerated cuticular wax accumulation, particularly alkanes and aldehydes, while GA3 inhibited these processes. ETH treatment increased the total wax content by 56% after four-day storage, particularly very-long-chain (VLC) alkanes (by 83%), while GA3 decreased the total wax content by 53% after fourteen-day storage, particularly VLC alkanes (by 56%). The main differentially expressed genes, including those involved in total wax accumulation (KCS19–1 and KCS19–2) and transformation of VLC aldehydes to VLC alkanes (CER1–1 and CER3), were up-regulated by ETH treatment while down-regulated by GA3 treatment. In summary, ETH accelerates and GA3 inhibits the accumulation of total wax, VLC aldehydes and VLC alkanes. I In addition, ETH and GA3 treatment have little effect on the intrinsic quality, but can alter the membrane lipid property and oxidase activity of fruit.
•Ethylene increases the density and size of platelet-like wax crystals.•Ethylene and GA3 change the cuticular wax metabolism of lemon.•Ethylene accelerates and GA3 inhibits cuticular wax accumulation.•Ethylene upregulated and GA3 downregulated genes related to wax accumulation.•ETH and GA3 treatment change lemon peel membrane lipid property and oxidase activity.
Abstract
This study combines the Defense Meteorological Satellite Program's Operational Linescan System (DMSP/OLS) nighttime light data with the Suomi National Polar-Orbiting Partnership satellite ...visible infrared imaging radiometer suite (NPP/VIIRS) nighttime light data, to research 21 urban agglomerations in China from 1995 to 2015. The expansion is described by analyzing the changes in the area, expansion intensity, and relative development speed of different urban agglomerations. First, nighttime light image from different sensors are mutually corrected according to eight partitions. Then, the built-up areas are extracted. Lastly, the brightness is calculated to analyze the distribution and characteristics of urban agglomeration. This paper reveals the following results: (1) Urban expansion in the northern and western regions is lagging that of the eastern and southern regions. The eastern region shows the most obvious change for all regions; (2) The Yangtze River Delta, the Pearl River Delta, and Beijing–Tianjin–Hebei have changed the most. Central Guizhou, Chengyu, and Poyang Lake Ring are growing the fastest. Jinzhong, Harbin-Daqing-Changchun, and the Pearl River Delta have the slowest growth intensity; (3) The internal characteristics of urban agglomerations are measured by internal development differences and relative development rates. Moreover, they can be divided into “single-core,” “dual-core,” “group,” or “striped” development modes.
Communication between adipocytes and endothelial cells (EC) is suggested to play an important role in the metabolic function of white adipose tissue. In order to generate tools to investigate in ...detail the physiology and communication of EC and adipocytes, a method for isolation of adipose microvascular EC from visceral adipose tissue (VAT) biopsies of subjects with obesity was developed. Moreover, mature white adipocytes were isolated from the VAT biopsies by a method adapted from a previously published Membrane aggregate adipocytes culture (MAAC) protocol. The identity and functionality of the cultivated and isolated adipose microvascular EC (AMvEC) was validated by imaging their morphology, analyses of mRNA expression, fluorescence activated cell sorting (FACS), immunostaining, low-density lipoprotein (LDL) uptake, and in vitro angiogenesis assays. Finally, we established a new trans filter co-culture system (membrane aggregate adipocyte and endothelial co-culture, MAAECC) for the analysis of communication between the two cell types. EC-adipocyte communication in this system was validated by omics analyses, revealing several altered proteins belonging to pathways such as metabolism, intracellular transport and signal transduction in adipocytes co-cultured with AMvEC. In reverse experiments, induction of several pathways including endothelial development and functions was found in AMvEC co-cultured with adipocytes. In conclusion, we developed a robust method to isolate EC from small quantities of human VAT. Furthermore, the MAAECC system established during the study enables one to study the communication between primary white adipocytes and EC or vice-versa and could also be employed for drug screening.
【Objective】The study aims to explore the change law of fruit quality of the main citrus varieties in Ruili area of Yunnan Province during maturity, offering a theoretical foundation for identifying ...the appropriate time for fruit harvesting.【Method】Four citrus varieties including Orah, Bingtang, Murcott, and W·Murcott were used as tested materials. Fruits were harvested 150-330 d after flowering (August 12, 2020 to February 8, 2021) and 240-405 d after flowering (November 8, 2021 to April 28, 2022). Samples were taken every fifteen days routinely, and the quality of the fruits was determined.【Result】The single fruit quality and the fruit horizontal and longitudinal diameters of the four citrus varieties exhibited a trend of growing first and then flattening as the maturity of fruits. Orah, Bingtang, Murcott and W·Murcott fruits terminated their rapid growth and expansion period before 270, 255, 300 and 285 days after flowering, respectively. In a span of two years, except for Murcott (with transition period being consistent in the first and the second year), the color transition period of W·Murcott peel was earlier in the first year, and the color transition period of Orah and Bingtang was later than the first year. Bingtang, Orah, Murcott and W·Murcott all showed stable mass fractions of total soluble solids content (TSS) after 240, 315, 300 and 270 days of flowering, respectively; while the mass fractions of titratable acid content (TA) showed no significant change at 180, 210, 240 and 240 d of flowering, respectively.【Conclusion】Combining the indicators such as single fruit weight, horizontal and longitudinal diameter, peel colour, and mass fraction of internal substance content, the fruits of Orah, Bingtang, Murcott, and W·Murcott reach harvest maturity at 315, 255, 300, and 285 d after flowering, which are suitable for harvesting.
Group 2 innate lymphoid cells (ILC2s) play a critical role in asthma pathogenesis. Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is associated with reduced ...signaling via EP2, a receptor for prostaglandin E
(PGE
). However, the respective roles for the PGE
receptors EP2 and EP4 (both share same downstream signaling) in the regulation of lung ILC2 responses has yet been deciphered.
The roles of PGE
receptors EP2 and EP4 on ILC2-mediated lung inflammation were investigated using genetically modified mouse lines and pharmacological approaches in IL-33-induced lung allergy model. The effects of PGE
receptors and downstream signals on ILC2 metabolic activation and effector function were examined using in vitro cell cultures.
Deficiency of EP2 rather than EP4 augments IL-33-induced mouse lung ILC2 responses and eosinophilic inflammation in vivo. In contrast, exogenous agonism of EP4 and EP2 or inhibition of phosphodiesterase markedly restricts IL-33-induced lung ILC2 responses. Mechanistically, PGE
directly suppresses IL-33-dependent ILC2 activation through the EP2/EP4-cAMP pathway, which downregulates STAT5 and MYC pathway gene expression and ILC2 energy metabolism. Blocking glycolysis diminishes IL-33-dependent ILC2 responses in mice where endogenous PG synthesis or EP2 signaling is blocked but not in mice with intact PGE
-EP2 signaling.
We have defined a mechanism for optimal suppression of mouse lung ILC2 responses by endogenous PGE
-EP2 signaling which underpins the clinical findings of defective EP2 signaling in patients with NERD. Our findings also indicate that exogenously targeting the PGE
-EP4-cAMP and energy metabolic pathways may provide novel opportunities for treating the ILC2-initiated lung inflammation in asthma and NERD.
Background
Group 2 innate lymphoid cells (ILC2s) play a critical role in asthma pathogenesis. Non‐steroidal anti‐inflammatory drug (NSAID)‐exacerbated respiratory disease (NERD) is associated with ...reduced signaling via EP2, a receptor for prostaglandin E2 (PGE2). However, the respective roles for the PGE2 receptors EP2 and EP4 (both share same downstream signaling) in the regulation of lung ILC2 responses has yet been deciphered.
Methods
The roles of PGE2 receptors EP2 and EP4 on ILC2‐mediated lung inflammation were investigated using genetically modified mouse lines and pharmacological approaches in IL‐33‐induced lung allergy model. The effects of PGE2 receptors and downstream signals on ILC2 metabolic activation and effector function were examined using in vitro cell cultures.
Results
Deficiency of EP2 rather than EP4 augments IL‐33‐induced mouse lung ILC2 responses and eosinophilic inflammation in vivo. In contrast, exogenous agonism of EP4 and EP2 or inhibition of phosphodiesterase markedly restricts IL‐33‐induced lung ILC2 responses. Mechanistically, PGE2 directly suppresses IL‐33‐dependent ILC2 activation through the EP2/EP4‐cAMP pathway, which downregulates STAT5 and MYC pathway gene expression and ILC2 energy metabolism. Blocking glycolysis diminishes IL‐33‐dependent ILC2 responses in mice where endogenous PG synthesis or EP2 signaling is blocked but not in mice with intact PGE2‐EP2 signaling.
Conclusion
We have defined a mechanism for optimal suppression of mouse lung ILC2 responses by endogenous PGE2‐EP2 signaling which underpins the clinical findings of defective EP2 signaling in patients with NERD. Our findings also indicate that exogenously targeting the PGE2‐EP4‐cAMP and energy metabolic pathways may provide novel opportunities for treating the ILC2‐initiated lung inflammation in asthma and NERD.
Deficiency of EP2 rather than EP4 enhances IL‐33‐induced lung ILC2 responses and eosinophilic inflammation. Both EP2 and EP4 agonism represses IL‐33‐induced mouse lung ILC2 responses. PGE2‐EP2/EP4‐cAMP signaling inhibits ILC2 survival, proliferation and effector function through disturbing the IL‐2/IL‐7/IL‐33‐activated metabolic program in ILC2s.Abbreviations: AMP, adenosine monophosphate; cAMP, cyclic adenosine monophosphate; EP2, E prostanoid receptor 2; EP4, E prostanoid receptor 4; ILC2, group 2 innate lymphoid cell; NF‐κB, nuclear factor kappa B; PDE, phosphodiesterase; PGE2, prostaglandin E2; STAT5: signal transducer and activator of transcription 5.
