Infection-associated inflammation and coagulation are critical pathologies in sepsis-induced acute lung injury (ALI). This study aimed to investigate the effects of microRNA-363-3p (miR-363-3p) on sepsis-induced ALI and explore the underlying mechanisms. A cecal ligation and puncture-induced septic mouse model was established. The results of this study suggested that miR-363-3p was highly expressed in lung tissues of septic mice. Knockdown of miR-363-3p attenuated sepsis-induced histopathological damage, the inflammation response and oxidative stress in lung tissues. Furthermore, knockdown of miR-363-3p reduced the formation of platelet-derived microparticles and thrombin generation in blood samples of septic mice. Downregulation of miR-363-3p suppressed sphingosine-1-phosphate receptor 1 (S1PR1) expression in lung tissues and subsequently inactivated the nuclear factor kappa-B ligand (NF-κB) signaling. A luciferase reporter assay confirmed that miR-363-3p directly targeted the 3’-untranslated region of the mouse S1pr1 mRNA. Collectively, our study suggests that inactivation of NF-κB signaling is involved in the miR-363-3p/S1PR1 axis-mediated protective effect on septic ALI. 相似文献
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) damages lung epithelial stem/progenitor cells. Ideal anti-SARS-CoV-2 drug candidates should be screened to prevent secondary injury to the lungs. Here, we propose that in vitro three-dimensional organoid and lung injury repair mouse models are powerful models for the screening antiviral drugs. Lung epithelial progenitor cells, including airway club cells and alveolar type 2 (AT2) cells, were co-cultured with supportive fibroblast cells in transwell inserts. The organoid model was used to evaluate the possible effects of hydroxychloroquine, which is administered as a symptomatic therapy to the coronavirus disease 2019 (COVID-19) patients, on the function of mouse lung stem/progenitor cells. Hydroxychloroquine was observed to promote the self-renewal of club cells and differentiation of ciliated and goblet cells in vitro. Additionally, it inhibited the self-renewal ability of AT2 cells in vitro. Naphthalene- or bleomycin-induced lung injury repair mouse models were used to investigate the in vivo effects of hydroxychloroquine on the regeneration of club and AT2 cells, respectively. The naphthalene model indicated that the proliferative ability and differentiation potential of club cells were unaffected in the presence of hydroxychloroquine. The bleomycin model suggested that hydroxychloroquine had a limited effect on the proliferation and differentiation abilities of AT2 cells. These findings suggest that hydroxychloroquine has limited effects on the regenerative ability of epithelial stem/progenitor cells. Thus, stem/progenitor cell-derived organoid technology and lung epithelial injury repair mouse models provide a powerful platform for drug screening, which could possibly help end the pandemic. 相似文献
运用空间热点分析定量分析了生态系统服务在不同尺度上的空间分异特征,基于四象限模型对生态质量进行评价,并采用地理探测器探讨影响其空间分异的主要驱动因素。结果表明:(1)生态系统服务价值(Ecosystem Service Value,ESV)存在显著的空间异质性,分布格局呈现空间自相关性,冷热点分布具有明显尺度效应。(2)示范区人类活动强度与ESV耦合程度基本协调一致,生态质量总体状况较好。人类活动强度与ESV耦合程度因研究尺度不同而存在一定差异。(3)各探测因子的解释力在县域和乡镇尺度上存在显著差异,社会经济驱动因素在县域尺度上解释力大于乡镇尺度。各驱动因子之间存在明显的协同增强效应,双因子交互作用增强了对ESV空间分异的解释力。 相似文献
Gastroesophageal reflux disease (GERD) is associated with sleep disturbances. However, mechanisms underlying these interactions remain unclear. Male acute and chronic sleep deprivation (SD) mice were used for this study. Mice in the chronic SD group exhibited anxiety- and depression-like behaviors. We further performed high-throughput genome sequencing and bioinformatics analysis to screen for featured differentially expressed genes (DEGs) in the esophageal tissue. The acute SD group, comprised 25 DEGs including 14 downregulated and 11 upregulated genes. Compared with the acute SD group, more DEGs were present in the chronic SD group, with a total of 169 DEGs, including 88 downregulated and 81 upregulated genes. Some DEGs that were closely related to GERD and associated esophageal diseases were significantly different in the chronic SD group. Quantitative real-time polymerase chain reaction verified the downregulation of Krt4, Krt13, Krt15 and Calml3 and upregulation of Baxl1 and Per3. Notably, these DEGs are involved in biological processes, which might be the pathways of the neuroregulatory mechanisms of DEGs expression. 相似文献
In the present work, a novel n-UV convertible colour-tunable emitting phosphor was obtained based on the efficient Ce3+-Tb3+ energy transfer in the Y10Al2Si3O18N4 host. By properly controlling the ratio of Ce3+/Tb3+, the colour hue of the obtained powder covered the blue and green regions, under excitation of 365 nm. The steady-state and dynamic-state luminescence measurement was performed to shed light on the related mechanism, which was justified by the electronic dipole–quadrupole dominating the related energy transfer process. Preliminary studies showed that Y10Al2Si3O18N4:Ce3+,Tb3+ can be promising as an inorganic phosphor for white LED applications. 相似文献
Defects within perovskite have been known to act as the nonradiative recombination centers, negatively impacting the carrier transport, which degrades the photovoltaic performance of perovskite solar cells (PSCs). Therefore, preparing a high-quality perovskite film is of vital significance. To this end, a room-temperature molten salt, dimethylamine formate (DMAFa), is introduced into perovskite precursor solution to regulate the crystallization process of CsPbI3 films. DMAFa can coordinate with Pb2+ as HCOO−-Pb2+ in the early stages, then HCOO−-Pb2+ is gradually displaced by I−-Pb2+ due to its decomposition during the subsequent annealing, thus delaying the crystallization rate, meanwhile, the DMA+ can interact with the uncoordinated Pb2+ to passivate defects of perovskite films, thereby, forming a high-quality CsPbI3 film with large grain size and low-defect density. As a result of this strategy, the power conversion efficiency is increased to 20.40%, and the open-circuit voltage is up to 1.21 V. These findings indicate that the introduction of DMAFa offers a fundamental way to achieve high-performance CsPbI3 PSCs. 相似文献
Low-bandgap mixed tin (Sn)-lead (Pb) perovskite solar cells promise efficiency beyond the pure-Pb ones. However, the difference in the interaction rate of SnI2 and PbI2 with organic salts causes spatial distribution heterogeneity of Sn2+ and Pb2+ in mixed Sn─Pb perovskite layers. This causes a Sn-rich surface, which can trigger more severe Sn2+ oxidation and nonradiative recombination. A strategy, of introducing indium ion (In3+) into the perovskite precursor solution to compete with Sn2+ when reacting with organic salts is developed. Therefore, the nucleation and crystallization of perovskite films are well-controlled, leading to improved film quality with a more balanced Sn/Pb ratio on the film surface. Additionally, In3+ has a lower reduction potential compared to Sn2+ which can generate an extra energy barrier for Sn2+ oxidation. The improved film quality and reduced surface oxidation result in accelerated electron transfer and reduced carrier recombination rate. The modified devices achieve a power conversion efficiency (PCE) of 23.34%, representing one of the highest PCEs in mixed Sn─Pb solar cells made with PCBM. 相似文献
Polyploidy and the subsequent ploidy reduction and genome shuffling are the major driving forces of genome evolution. Here, we revealed short-term allopolyploid genome evolution by sequencing a synthetic intergeneric hybrid (Raphanobrassica, RRCC). In this allotetraploid, the genome deletion was quick, while rearrangement was slow. The core and high-frequency genes tended to be retained while the specific and low-frequency genes tended to be deleted in the hybrid. The large-fragment deletions were enriched in the heterochromatin region and probably derived from chromosome breaks. The intergeneric translocations were primarily of short fragments dependent on homoeology, indicating a gene conversion origin. To accelerate genome shuffling, we developed an efficient genome editing platform for Raphanobrassica. By editing Fanconi Anemia Complementation Group M (FANCM) genes, homoeologous recombination, chromosome deletion and secondary meiosis with additional ploidy reduction were accelerated. FANCM was shown to be a checkpoint of meiosis and controller of ploidy stability. By simultaneously editing FLIP genes, gene conversion was precisely introduced, and mosaic genes were produced around the target site. This intergeneric hybrid and genome editing platform not only provides models that facilitate experimental evolution research by speeding up genome shuffling and conversion but also accelerates plant breeding by enhancing intergeneric genetic exchange and creating new genes. 相似文献