Ras plays a pivotal role in many cellular activities, and its subcellular compartmentalization provides spatial and temporal selectivity. Here we report a mode of spatial regulation of Ras signaling ...in the Golgi apparatus by two highly homologous proteins PAQR10 and PAQRll of the progestin and AdipoQ receptors family. PAQRI0 and PAQRll are exclusively localized in the Golgi apparatus. Overexpression of PAQR10/PAQRll stimulates basal and EGF-induced ERK phosphorylation and increases the expression of ERK target genes in a dose-dependent man- ner. Overexpression of PAQR10/PAQRll markedly elevates Golgi localization of HRas, NRas and KRas4A, but not KRas4B. PAQR10 and PAQRll can also interact with HRas, NRas and KRas4A, but not KRas4B. The increased Ras protein at the Golgi apparatus by overexpression of PAQR10/PAQRll is in an active state. Consistently, knockdown of PAQR10 and PAQRll reduces EGF-stimulated ERK phosphorylation and Ras activation at the Golgi apparatus. Intriguingly, PAQR10 and PAQRll are able to interact with RasGRP1, a guanine nucleotide exchange protein of Ras, and increase Golgi localization of RasGRP1. The C1 domain of RasGRP1 is both necessary and sufficient for the interaction of RasGRP1 with PAQR10/PAQRll. The simulation of ERK phosphorylation by overexpressed PAQR10/ PAQRll is abrogated by downregulation of RasGRP1. Furthermore, differentiation of PC12 cells is significantly enhanced by overexpression of PAQR10/PAQRll. Collectively, this study uncovers a new paradigm of spatial regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQRll.
Facial mask is a kind of skin care cosmetics, in which fluorescent whitening agents（FWAs） were added to make face skin look whiter and brighter. In this work, pig skin was used instead of human skin ...to test the methods. Three methods, including pig skin migration fluorescent spectrophotometry（FS）, fiber paper migration FS, and fiber paper migration visual colourimetry（VC）, were developed for determining the migration amount of FWAs from facial mask to pig skin. In the methods, a self-assembly light source and fluorescence collecting unit was used. The unit can be easily moved and the measurement was very convenient. Some experimental conditions were optimized. The fiber paper migration VC can give semi-quantitative results and was the simplest one in the three methods because collec- tion, separation and detection of the fluorescence were not needed. Both the pig skin migration FS and fiber paper migration FS can give quantitative results and compared with fiber paper migration FS, the pig skin migration FS could give more practical results by simulating the real way of using facial mask. The limits of detection for disodium 4,4＇-bis（4-anilino-6-hydroxyethylamion-1,3,5-triazin-2-yl）amionstilbene-2,2＇-disulphonate（VBL） obtained by pig skin migration FS and fiber paper migration FS were 0.03 and 0.05 mg/m2, respectively. 96 kinds of samples were analyzed and the migration amounts of FWAs in 21 kinds of samples were detectable. Correlations between migration amounts obtained by the three methods were very good. Experimental results indicate that the present methods can be applied to the determination of migration amount of FWAs in facial masks.
The metal-organic framework (MOF) functionalized magnetic graphene oxide/mesoporous silica composites (Fe3O4@SiO2-GO/MIL-101(Cr)) were synthesized and utilized as magnetic solid-phase extraction ...(MSPE) adsorbent for the extraction of seven triazine herbicides (terbuthylazine, secbumeton, terbumeton, atraton, atrazine, prometon and trietazine) in rice samples. Several experimental parameters, including type and volume of extraction solvent, amount of MIL-101(Cr), extraction time, volume of desorption solvent and desorption time were investigated and optimized. The limits of detection (LODs) of seven triazine herbicides obtained by using the proposed MSPE method combined with high performance liquid chromatography (HPLC) were in the range of 0.010–0.080µgkg−1. The recoveries of the triazine herbicides in spiked rice samples ranged from of 83.9–103.5% with the relative standard deviations lower than 8.7%. The intra and inter-day (n = 6) precisions for all triazine herbicides at the spiked level of 100.0µgkg−1 were 1.4–5.9% and 2.6–7.8%, respectively.
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•Fe3O4@SiO2-GO/MIL-101(Cr) is prepared for the first time.•A rapid and efficient magnetic solid-phase extraction method was established.•Seven triazine herbicides in rice samples were determined by this method.•The proposed method demonstrates great potential in real applications.
EGFR activates phosphatidylinositide 3-kinase (PI3K), but the mechanism underlying this activation is not completely understood. We demonstrated here that EGFR activation resulted in lysine ...acetyltransferase 5 (KAT5)-mediated K395 acetylation of the platelet isoform of phosphofructokinase 1 (PFKP) and subsequent translocation of PFKP to the plasma membrane, where the PFKP was phosphorylated at Y64 by EGFR. Phosphorylated PFKP binds to the N-terminal SH2 domain of p85α, which is distinct from binding of Gab1 to the C-terminal SH2 domain of p85α, and recruited p85α to the plasma membrane resulting in PI3K activation. PI3K-dependent AKT activation results in enhanced phosphofructokinase 2 (PFK2) phosphorylation and production of fructose-2,6-bisphosphate, which in turn promotes PFK1 activation. PFKP Y64 phosphorylation–enhanced PI3K/AKT-dependent PFK1 activation and GLUT1 expression promoted the Warburg effect, tumor cell proliferation, and brain tumorigenesis. These findings underscore the instrumental role of PFKP in PI3K activation and enhanced glycolysis through PI3K/AKT-dependent positive-feedback regulation.
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•KAT5 acetylates PFKP at K395 and promotes the binding of PFKP to EGFR•EGFR-phosphorylated PFKP Y64 binds to p85α SH2 domain and activates PI3K•PFKP-activated AKT enhances GLUT1 expression and PFK2-mediated PFK1 activity•PFKP Y64 phosphorylation enhances the Warburg effect and tumorigenesis
Lee et al. demonstrate that KAT5-mediated PFKP acetylation and subsequent EGFR-phosphorylated PFKP bind to the N-terminal SH2 domain of p85α to activate PI3K, leading to enhanced AKT-dependent PFK2 activation, F-2,6-BP-production-dependent PFK1 activation, and GLUT1 expression. Non-metabolic function of PFKP promotes the Warburg effect through PI3K/AKT-dependent positive-feedback regulation.
Radiographic periodontal bone loss is one of the most important basis for periodontitis staging, with problems such as limited accuracy, inconsistency, and low efficiency in imaging diagnosis. Deep ...learning network may be a solution to improve the accuracy and efficiency of periodontitis imaging staging diagnosis. This study aims to establish a comprehensive and accurate radiological staging model of periodontal alveolar bone loss based on panoramic images.
A total of 640 panoramic images were included, and 3 experienced periodontal physicians marked the key points needed to calculate the degree of periodontal alveolar bone loss and the specific location and shape of the alveolar bone loss. A two-stage deep learning architecture based on UNet and YOLO-v4 was proposed to localize the tooth and key points, so that the percentage of periodontal alveolar bone loss was accurately calculated and periodontitis was staged. The ability of the model to recognize these features was evaluated and compared with that of general dental practitioners.
The overall classification accuracy of the model was 0.77, and the performance of the model varied for different tooth positions and categories; model classification was generally more accurate than that of general practitioners.
It is feasible to establish deep learning model for assessment and staging radiographic periodontal alveolar bone loss using two-stage architecture based on UNet and YOLO-v4.
Mid-infrared photodetector based on submonolayer (SML) quantum dot quantum cascade structure monolithically grown on silicon substrate has been demonstrated in this paper. Both the optical and ...electrical characteristics of the SML quantum dot quantum cascade photodetectors (QD-QCD) were analyzed quantitatively. The performances of these devices were compared with that on native GaAs substrate. A large resistance-area (R0A ) product of 1.13 × 10 7 Ω.cm 2 is achieved at 77 K for the silicon-based devices, which is only roughly one order less than that on GaAs substrate. The device shows a normal-incident peak responsivity of 0.59 mA/W under zero bias at the wavelength of 6.2 μm at 77 K, indicating a photovoltaic operation mode. Johnson noise limited specific detectivity is 3 × 10 10 cm·Hz 1/2 /W at 77 K, with photoresponse up to 100 K. These results suggest that the silicon-based QD-QCD in this paper is a very promising candidate for large format mid-infrared focal plane array and mid-infrared silicon photonics applications.
Chromium (Cr) is an internationally recognized carcinogenic hazard that causes serious pulmonary toxicity. However, Cr-induced pulmonary toxicity lacks effective treatment to date. Sulforaphane ...(SFN), a well-known organosulfur compound, has gained increasing attention because of its unique biological function. This study investigates if SFN could decrease K2Cr2O7-induced pulmonary toxicity and a potential mechanism involved using a rat 35-day Cr-induced pulmonary toxicity model and the mouse alveolar type II epithelial cell line (MLE-12). The results showed that SFN prevented Cr-induced oxidative stress, histopathological lesions, inflammation, apoptosis, and changes in protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK-3β) levels in vivo and in vitro. However, SFN can not play the protective effect against K2Cr2O7-induced cell injury after treating by an Akt-specific inhibitor (MK-2206 2HCl) in MLE-12 cells. Furthermore, SFN increased the expression of nuclear factor-E2-related factor-2 (Nrf2) phase II detoxification enzymes. Collectively, this study demonstrates that SFN prevents K2Cr2O7-induced lung toxicity in rats through enhancing Nrf2-mediated exogenous antioxidant defenses via activation of the Akt/GSK-3β/Fyn signaling pathway. SFN may be a novel natural substance to cure Cr-induced lung toxicity.
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•Chronic exposure of chromium (Cr) induces lung injury in rats.•Cr induces oxidative stress in the mouse alveolar type II epithelial cell line.•Oxidative stress is a key of Cr-induced lung toxicity.•Sulforaphane (SFN) relieves Cr-induced lung toxicity.•SFN prevents Cr-induced lung toxicity in rats via activation of the Akt/GSK-3β/Fyn signaling pathway.
Sulforaphane prevents chromium-induced lung toxicity in rats via activation of the Akt/GSK-3β/Fyn signaling pathway.
In this work, a rapid, convenient, sensitive, and cost-effective in-situ formed magnetic deep eutectic solvent based on a dispersive liquid-liquid extraction method was developed for the ...determination of triazine herbicides in rice. A novel tetrabutylammonium chloride (TBAC) based magnetic deep eutectic solvent (MDES), TBAC/ethylene glycolFeCl4 was generated by means of an simple in-situ reaction of the deep eutectic solvent (DES) with iron chloride in the sample solution. The solvent which has high affinity for target analytes and magnetic ability was successfully employed as an extraction solvent and simplified both the extraction and separation procedure. A series of parameters influencing the extraction efficiency were investigated. Under optimal conditions, calibration curves for the target triazine herbicides were obtained in the ranges of 5–1000 ng g−1, with correlation coefficients greater than 0.9910. The limits of detection (LOD) and quantification (LOQ) were in the range of 1.49–3.10 ng g−1 and 4.96–10.34 ng g−1, respectively. The precision of intra- and inter-day were under 6.2% and 9.6%, respectively, and the precision between laboratories were lower than 7.5%. The accuracy of the method varied from 84.9 to 117.5%. Furthermore, the method showed satisfactory matrix effect and robustness. These results indicate that the technique is suitable for rice sample analysis.
Schematic presentation of the extraction procedure. Display omitted
•A novel magnetic deep eutectic solvent was introduced.•Magnetic deep eutectic solvent was in-situ formed in sample solution.•The developed method had satisfactory accuracy, precision and sensitivity.
The PTEN tumor suppressor is frequently mutated or deleted in cancer and regulates glucose metabolism through the PI3K-AKT pathway. However, whether PTEN directly regulates glycolysis in tumor cells ...is unclear. We demonstrate here that PTEN directly interacts with phosphoglycerate kinase 1 (PGK1). PGK1 functions not only as a glycolytic enzyme but also as a protein kinase intermolecularly autophosphorylating itself at Y324 for activation. The protein phosphatase activity of PTEN dephosphorylates and inhibits autophosphorylated PGK1, thereby inhibiting glycolysis, ATP production, and brain tumor cell proliferation. In addition, knockin expression of a PGK1 Y324F mutant inhibits brain tumor formation. Analyses of human glioblastoma specimens reveals that PGK1 Y324 phosphorylation levels inversely correlate with PTEN expression status and are positively associated with poor prognosis in glioblastoma patients. This work highlights the instrumental role of PGK1 autophosphorylation in its activation and PTEN protein phosphatase activity in governing glycolysis and tumorigenesis.
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•PGK1, functioning as a protein kinase, autophosphorylates itself at Y324•PGK1 autophosphorylation enhances its glycolytic activity via promoting ATP release•PTEN, functioning as a protein phosphatase, dephosphorylates PGK1 pY324•PGK1 Y324 autophosphorylation promotes brain tumor formation
Qian et al. demonstrate that PGK1 functions as a protein kinase and autophosphorylates itself at Y324, leading to subsequent PGK1 activation. This phosphorylation is dephosphorylated by the protein phosphatase activity of PTEN. Loss of PTEN expression in tumors enhances PGK1 activity, thereby promoting glycolysis and brain tumor growth.
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