VANGL2 is a component of the planar cell polarity (PCP) pathway, which regulates tissue polarity and patterning. The Vangl2 Lp mutation causes lung branching defects due to dysfunctional actomyosin-driven morphogenesis. Since the actomyosin network regulates cell mechanics, we speculated that mechanosignaling could be impaired when VANGL2 is disrupted. Here, we used live-imaging of precision-cut lung slices (PCLS) from Vangl2 Lp/+ mice to determine that alveologenesis is attenuated as a result of impaired epithelial cell migration. Vangl2 Lp/+ tracheal epithelial cells (TECs) and alveolar epithelial cells (AECs) exhibited highly disrupted actomyosin networks and focal adhesions (FAs). Functional assessment of cellular forces confirmed impaired traction force generation in Vangl2 Lp/+ TECs. YAP signaling in Vangl2 Lp airway epithelium was reduced, consistent with a role for VANGL2 in mechanotransduction. Furthermore, activation of RhoA signaling restored actomyosin organization in Vangl2 Lp/+ , confirming RhoA as an effector of VANGL2. This study identifies a pivotal role for VANGL2 in mechanosignaling, which underlies the key role of the PCP pathway in tissue morphogenesis.The outbreak of novel coronavirus disease 2019 (COVID-19) has become the largest health threat worldwide, with more than 34.40 million positive cases and over 1.02 million deaths confirmed. In this study, we confirmed that significantly differentially expressed genes in COVID-19 patients were mainly involved in the regulation of immune and inflammation-related signaling pathways. It is worth noting that many infected COVID-19 patients have malignant tumors, and their prognosis is poor. To explore the susceptibility factors of cancer patients, we assessed the expression of ACE2, TMPRSS2, and the endocytic regulator AAK1 in lung adenocarcinoma (LUAD) patients and explored their effects on immune infiltration. We found that the expression of ACE2 and TMPRSS2 in LUAD patients was significantly increased, which may explain why LUAD patients are susceptible to SARS-CoV-2, and the patients with high-expression genes presented increased infiltration of immune cells such as B cells and CD4 T cells. In addition, we also identified miR-432-5p as a potential targeted molecule and bexarotene as a potential targeted drug of the three genes through bioinformatic analysis and further verified the anti-inflammatory effect of bexarotene, providing new ideas for the treatment of COVID-19.The existence during mouse lung development of an embryonic stage temporally and functionally distinct from the subsequent pseudoglandular stage has been proposed but never demonstrated; while studies in human embryonic lung tissue fail to recapitulate the molecular control of branching found in mice. Lung development in mice starts officially at embryonic day (E) 9.5 when on the ventral side of the primary foregut tube, both the trachea and the two primary lung buds emerge and elongate to form a completely separate structure from the foregut by E10. In the subsequent 6 days, the primary lung buds undergo an intense process of branching to form a ramified tree by E16.5. We used transgenic mice allowing to transiently inhibit endogenous fibroblast growth factor 10 (Fgf10) activity in mutant embryos at E9, E9.5, and E11 upon intraperitoneal exposure to doxycycline and examined the resulting lung phenotype at later developmental stages. We also determined using gene arrays the transcriptomic response of flow cytometry-isolated human alveolar epithelial progenitor cells derived from hESC or hiPSC, grown in vitro for 12 or 24 h, in the presence or absence of recombinant FGF10. Following injection at E9, the corresponding mutant lungs at E18.5 appear almost normal in size and shape but close up examination indicate failure of the right lung to undergo lobar septation. At E9.5, the lungs are slightly hypoplastic but display normal differentiation and functionality. However, at E11, the lungs show impaired branching and are no longer functional. Using gene array data, we report only a partial overlap between human and mouse in the genes previously shown to be regulated by Fgf10 at E12.5. This study supports the existence of an embryonic stage of lung development where Fgf10 signaling does not play a function in the branching process but rather in lobar septation. It also posits that functional comparisons between mouse and human organogenesis must account for these distinct stages.
  White matter injury (WMI) exists in the early stage of subarachnoid hemorrhage (SAH) and has not been well addressed so far.
 
  We utilized short hairpin RNA (shRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) to verify the role of peroxisomes in WMI following SAH. We evaluated short- and long-term neurobehavior after SAH. Western blotting, immunofluorescence, and Golgi staining techniques were performed to assess the changes in protein levels.
 
  Catalase (CAT) CRISPR treatment significantly attenuated neurological deficits and reduced long-term spatial learning and memory impairments after SAH by increasing the level of myelin basic protein (MBP) while decreasing the levels of amyloid precursor protein (APP), interleukin 6 (IL-6), and tumor necrosis factor (TNF)-α. The use of thioredoxin-interacting protein (TXNIP) shRNA significantly offset the effects of CAT shRNA, and the use of glycerone phosphate acyl transferase (GNPAT) shRNA significantly reversed the effects of CAT CRISPR by decreasing the levels of plasmalogens and reactive oxidative species (ROS).
 
  Peroxisomal dysfunction induced by SAH reversely exacerbated cerebral WMI following SAH, which was at least partly mediated by TXNIP and GNPAT pathways.
 Peroxisomal dysfunction induced by SAH reversely exacerbated cerebral WMI following SAH, which was at least partly mediated by TXNIP and GNPAT pathways.The maintenance of a fluid lipid bilayer is key for organelle function and cell viability. Given the critical role of lipid compositions in determining membrane properties and organelle identity, it is clear that cells must have elaborate mechanism for membrane maintenance during adaptive responses to environmental conditions. Emphasis of the presented study is on peroxisomes, oleic acid-inducible organelles that are essential for the growth of yeast under conditions of oleic acid as single carbon source.  https://www.selleckchem.com/products/incb28060.html  Here, we isolated peroxisomes, mitochondria and ER from oleic acid-induced Saccharomyces cerevisiae and determined the lipid composition of their membranes using shotgun lipidomics and compared it to lipid ordering using fluorescence microscopy. In comparison to mitochondrial and ER membranes, the peroxisomal membranes were slightly more disordered and characterized by a distinct enrichment of phosphaditylinositol, indicating an important role of this phospholipid in peroxisomal membrane associated processes.