Acid ceramidase (murine gene code Asah1) (50 kDa) belongs to N-terminal nucleophile hydrolase family. This enzyme is located in the lysosome, which mediates conversion of ceramide (CER) into sphingosine and free fatty acids at acidic pH. CER plays an important role in intracellular sphingolipid metabolism and its increase causes inflammation. The mammalian target of rapamycin complex 1 (mTORC1) signaling on late endosomes (LEs)/lysosomes may control cargo selection, membrane biogenesis, and exosome secretion, which may be fine controlled by lysosomal sphingolipids such as CER. This lysosomal-CER-mTOR signaling may be a crucial molecular mechanism responsible for development of arterial medial calcification (AMC). Torin-1 (5 mg/kg/day), an mTOR inhibitor, significantly decreased aortic medial calcification accompanied with decreased expression of osteogenic markers like osteopontin (OSP) and runt-related transcription factor 2 (RUNX2) and upregulation of smooth muscle 22α (SM22-α) in mice receiving high dose op-1 co-localization in Pi -stimulated CASMCs, associated with decreased exosome release. Functionally, Torin-1 significantly reduces arterial stiffening as shown by restoration from increased pulse wave velocity and decreased elastin breaks.  https://www.selleckchem.com/products/bay-1217389.html  These results suggest that lysosomal CER-mTOR signaling may play a critical role for the control of lysosome-MVB interaction, exosome secretion and arterial stiffening during AMC.
  The contribution of bacteria to fermented tea is not clear and the associated research is relatively limited. To reveal the role of microorganisms in fermented tea processing, the microbial community and metabolites of Fuzhuan brick tea (FBT), a Chinese traditional fermented tea, were revealed via high-throughput sequencing and liquid chromatography-mass spectrometry (LC-MS).
 
  In FBT, bacterial communities had a higher abundance and diversity, Lactococcus and Bacillus were the main bacteria, and Eurotium was the predominant fungus. The predictive metabolic function indicated the pathways of cellular growth, environmental information, genetics and material metabolism of bacterial communities were abundant, whereas the fungal community predictive metabolic function was almost saprotroph. Using LC-MS, 1143 and 536 metabolites were defined in positive and negative ion mode, respectively. There were essential correlations between bacterial populations and metabolites, such that Bacillus was correlated significantly with 44 metabolites (P < 0.05) and Enterococcus was significantly associated with 15 metabolites (P < 0.05). Some of the main active components were significantly correlated with the bacteria, such as Enterococcus, Lactococcus and Carnobacterium.
 
  Not only Eurotium, but also the bacteria were involved in the changes of metabolomics profile in fermented FBT. The present study assists in providing new insights into metabolomics profile generation in fermented tea. The present research lays a foundation for controlling the FBT fermentation by artificial inoculation to improve quality. © 2021 Society of Chemical Industry.
 Not only Eurotium, but also the bacteria were involved in the changes of metabolomics profile in fermented FBT. The present study assists in providing new insights into metabolomics profile generation in fermented tea. The present research lays a foundation for controlling the FBT fermentation by artificial inoculation to improve quality. © 2021 Society of Chemical Industry.Defective phagocytosis has been shown in chronic obstructive pulmonary disease (COPD) bronchoalveolar lavage and blood monocyte-derived macrophages. Phagocytic capabilities of sputum macrophages and neutrophils in COPD are unknown. We investigated phagocytosis in these cells from COPD patients and controls. Phagocytosis of Streptococcus pneumoniae or fluorescently labelled non-typeable Haemophilus influenzae (NTHi) by sputum macrophages and neutrophils was determined by gentamycin protection assay (COPD; n = 5) or flow cytometry in 14 COPD patients, 8 healthy smokers (HS) and 9 healthy never-smokers (HNS). Sputum macrophages and neutrophils were differentiated by adherence for the gentamycin protection assay or receptor expression (CD206 and CD66b, respectively), by flow cytometry. The effects of NTHi on macrophage expression of CD206 and CD14 and neutrophil expression of CD16 were determined by flow cytometry. There was greater uptake of S. pneumoniae [~10-fold more colony-forming units (CFU)/ml] by sputum neutrophils compared to macrophages in COPD patients. Flow cytometry showed greater NTHi uptake by neutrophils compared to macrophages in COPD (67 versus 38%, respectively) and HS (61 versus 31%, respectively). NTHi uptake by macrophages was lower in HS (31%, p = 0.019) and COPD patients (38%, p = 0.069) compared to HNS (57%). NTHi uptake by neutrophils was similar between groups. NTHi exposure reduced CD206 and CD14 expression on macrophages and CD16 expression on neutrophils. Sputum neutrophils showed more phagocytic activity than macrophages. There was some evidence that bacterial phagocytosis was impaired in HS sputum macrophages, but no impairment of neutrophils was observed in HS or COPD patients. These results highlight the relative contributions of neutrophils and macrophages to bacterial clearance in COPD.
  Sowing date, seeding rate, and nitrogen (N) topdressing ratio have strong effects on grain yield (GY) and bread-making quality (BQ) in bread wheat. Simultaneous improvement in GY and BQ in bread wheat has long been a challenge due to the inverse relationship between GY and grain protein concentration (GPC). In this study, we investigated whether the GY and BQ of bread wheat sown on different dates could be improved simultaneously by optimizing the seeding rate and the N topdressing ratio.
 
  Delaying sowing beyond a certain period led to decreases in both GY and BQ. Optimizing the seeding rate and N topdressing ratio enhanced the N uptake during pre- and post-anthesis, as well as N remobilization during grain filling for all wheat plants sown on different dates, thereby increasing the GPC and the total N per grain (N
  ). Consequently, grain protein composition was improved, resulting in an increased glutenin/gliadin ratio, sodium dodecyl sulfate-insoluble glutenin/total glutenin (i.e., glutenin polymerization index), and high-molecular-weight glutenin subunit/ low-molecular-weight glutenin subunit (HMW-GS/LMW-GS) ratio.