5 research outputs found

    PU.1-CD23 signaling mediates pulmonary innate immunity against Aspergillus fumigatus infection by driving inflammatory response

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    Abstract Background Aspergillosis is a common cause of morbidity and mortality in immunocompromised populations. PU.1 is critical for innate immunity against Aspergillus fumigatus (AF) in macrophages. However, the molecular mechanism underlying PU.1 mediating immunity against AF infection in human alveolar macrophages (AMs) is still unclear. Methods In this study, we detected the expressions of PU.1, CD23, p-ERK, CCL20 and IL-8 and key inflammatory markers IL-1β, IL-6, TNF-α and IL-12 in human THP-1-derived macrophages (HTMs) or PU.1/CD23-overexpressed immunodeficient mice with AF infection. Moreover, we examined these expressions in PU.1-overexpressed/interfered HTMs. Additionally, we detected the phagocytosis of macrophages against AF infection with altered PU.1 expression. Dual luciferase, ChIP and EMSAs were performed to detect the interaction of PU.1 and CD23. And we invested the histological changes in mouse lung tissues transfected with PU.1/CD23-expressing adenoviruses in AF infection. Results The results showed that the expressions of PU.1, CD23, p-ERK, CCL20, IL-8, IL-1β, IL-6, TNF-α and IL-12 increased significantly with AF infection, and PU.1 regulated the later 8 gene expressions in HTMs. Moreover, CD23 was directly activated by PU.1, and overexpression of CD23 in PU.1-interfered HTMs upregulated IL-1β, IL-6, TNF-α and IL-12 levels which were downregulated by PU.1 interference. PU.1 overexpression strengthened the phagocytosis of the HTMs against AF. And injection of PU.1/CD23-expressing adenoviruses attenuated pathological defects in immunodeficient mouse lung tissues with AF infection. Adenovirus (Ad)-PU.1 increased the CD23, p-ERK, CCL20, IL-8 levels. Conclusions Our study concluded that PU.1-CD23 signaling mediates innate immunity against AF in lungs through regulating inflammatory response. Therefore, PU.1-CD23 may be a new anti-aspergillosis therapeutic for the treatment of invasive aspergillosis with the deepening of gene therapy and its wide application in the clinic

    An Innovative Signal Processing Scheme for Spaceborne Integrated GNSS Remote Sensors

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    The vigorous development of the global navigation satellite system (GNSS) has led to a boom in GNSS radio occultation (GNSS RO) and GNSS reflectometry (GNSS-R) techniques. Consequently, we have proposed an innovative signal processing scheme for spaceborne integrated GNSS remote sensors (SIGRS), combining a GNSS RO and a GNSS-R module. In the SIGRS, the GNSS-R module shares one precise orbit determination (POD) module with the GNSS RO module, and the GNSS-R module first achieves compatibility with GPS, BDS, and Galileo. Moreover, the programmable non-uniform delay resolution was introduced and first used by the SIGRS to generate the output DDM, which achieves a high delay resolution in the DDM central region around the specular point to improve the accuracy of basic observables but requires fewer delay bins than the conventional DDM with uniform delay resolution. The SIGRS has been successfully used to design the GNOS II onboard the Chinese FY-3E satellite, and the results of in-orbit operation validate the performance of the SIGRS, which means the SIGRS is an economically and technically efficient design and has become the first successful signal processing scheme for spaceborne integrated GNSS remote sensors around the world