Peroxidase from foxtail millet bran exerts anticolorectal cancer activity via targeting cellsurface GRP78 to inactivate STAT3 pathway

Molecular targeted therapy has become an emerging promising strategy in cancer treatment,and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment.Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran(FMBP)exhibited excellent targeting anti-colorectal cancer(CRC)activity in vivo and in vitro,whereas its underlying target remains unclear.The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78(cs GRP78)abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP,indicating it serves as a potential target of FMBP against CRC.Further,we demonstrated that the combination of FMBP with the nucleotide binding domain(NBD)of cs GRP78interfered with the downstream activation of signal transducer and activator of transcription 3(STAT3)in CRC cells,thus promoting the intracellular accumulation of reactive oxygen species(ROS)and cell grown inhibition.These phenomena were further confirmed in nude mice tumor model.Collectively,our study highlights cs GRP78 acts as an underlying target of FMBP against CRC,uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.

Volatile organic compounds in wintertime North China Plain:Insights from measurements of proton transfer reaction time-of-flight mass spectrometer(PTR-ToF-MS)

The characteristics of wintertime volatile organic compounds(VOCs)in the North China Plain(NCP)region are complicated and remain obscure.VOC measurements were conducted by a proton transfer reaction time-of-flight mass spectrometer(PTR-ToF-MS)at a rural site in the NCP from November to December 2018.Uncalibrated ions measured by PTRToF-MS were quantified and the overall VOC compositions were investigated by combining the measurements of PTR-ToF-MS and gas chromatography-mass spectrometer/flame ionization detector(GC-MS/FID).The measurement showed that although atmospheric VOCs concentrations are often dominated by primary emissions,the secondary formation of oxygenated VOCs(OVOCs)is non-negligible in the wintertime,i.e.,OVOCs accounts for 42%±7%in the total VOCs(151.3±75.6 ppbV).We demonstrated that PTR-MS measurements for isoprene are substantially overestimated due to the interferences of cycloalkanes.The chemical changes of organic carbon in a pollution accumulation period were investigated,which suggests an essential role of fragmentation reactions for large,chemically reduced compounds during the heavy-polluted stage in wintertime pollution.The changes of emission ratios of VOCs between winter 2011 and winter 2018 in the NCP support the positive effect of“coal to gas”strategies in curbing air pollutants.The high abundances of some key species(e.g.oxygenated aromatics)indicate the strong emissions of coal combustion in wintertime of NCP.The ratio of naphthalene to C8 aromatics was proposed as a potential indicator of the influence of coal combustion on VOCs.

Inter-comparisons of VOC oxidation mechanisms based on box model:A focus on OH reactivity

Volatile organic compounds(VOCs)oxidation processes play a very important role in atmospheric chemistry,and the chemical reactions are expressed in various manners in chemical mechanisms.To gain an improved understanding of VOCs evolution during oxidation processes and evaluate the discrepancies of VOCs oxidation schemes among different mechanisms,we used the total VOC reactivity as a diagnostic and evaluated tool to explore the differences for six widely used chemical mechanisms.We compared the total VOC reactivity evolution under high-NO_(x)xconditions for several sets of precursors,including n-pentane,toluene,ethene,isoprene and a mixture of 57 Photochemical Assessment Monitoring Stations(PAMS)species in a 0-D photochemical box model.Inter-comparison of total VOC reactivity of individual precursor simulations showed discrepancies to different extent of the oxidation schemes among the studied mechanisms,which are mainly attributed to the different lumping approaches for organic species.The PAMS simulation showed smaller discrepancy than individual precursor cases in terms of total VOC reactivity.SAPRC07 and RACM2 performances are found to better match the MCM for simulation of total VOC reactivity.Evidences suggest that the performance in simulating secondary organic products,OH concentrations and NO_(x)concentrations are related to the OH reactivity discrepancies among various chemical mechanisms.Information in this study can be used in selection of chemical mechanisms to better model OH reactivity in different environments.The results in this study also provide directions to further improve the ability in modelling total VOC reactivity with the chemical mechanisms.

Human endothelial senescence can be induced by TNF-α

TNF-α is one of the most important proin-flammatory cytokines in mediating multiple physio-patho-logical functions during immunological responses. Vascular endothelial cells, when stimulated by TNF-α, can increase the expression of multiple cytokines and cellular adhesion molecules and, in turn, actively promote the inflammatory responses by recruiting and activating of leukocytes to the inflammatory site. In addition to endothelial death induced by TNF-α, we found for the first time that TNF-α can also induce the human endothelial cells senescence. The induced senescent endothelial cells will display SA-B-Gal staining and they were arrested in G0-G1 phase. We found that △(?)m would always be up-regulated in response to TNF-α stimula-tion at early time but when the cells become senescent, △(?)m shows a tendency to decrease. It may reflect the sthenic func-tion of mitochondria at early time in response to TNF-α stimulation and decay when the endothelial cells were in-duced senescent. ROS