GBP2 inhibits pathological angiogenesis in the retina via the AKT/mTOR/VEGFA axis.

Pathological retinal angiogenesis is not only the hallmark of retinopathies, but also a major cause of blindness. Guanylate binding protein 2 (GBP2) has been reported to be associated with retinal diseases such as diabetic retinopathy and hypoxic retinopathy. However, GBP2-mediated pathological retinal angiogenesis remains largely unknown. The present study aimed to investigate the role of GBP2 in pathological retinal angiogenesis and its underlying molecular mechanism. In this study, we established oxygen-induced retinopathy (OIR) mice model for in vivo study and hypoxia-induced angiogenesis in ARPE-19 cells for in vitro study. We demonstrated that GBP2 expression was markedly downregulated in the retina of mice with OIR and ARPE-19 cells treated with hypoxia, which was associated with pathological retinal angiogenesis. The regulatory mechanism of GBP2 in ARPE-19 cells was studied by GBP2 silencing and overexpression. The regulatory mechanism of GBP2 in the retina was investigated by overexpressing GBP2 in the retina of OIR mice. Mechanistically, GBP2 downregulated the expression and secretion of vascular endothelial growth factor (VEGFA) in ARPE-19 cells and retina of OIR mice. Interestingly, overexpression of GBP2 significantly inhibited neovascularization in OIR mice, conditioned medium of GBP2 overexpressing ARPE-19 cells inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, we confirmed that GBP2 downregulated VEGFA expression and angiogenesis by inhibiting the AKT/mTOR signaling pathway. Taken together, we concluded that GBP2 inhibited pathological retinal angiogenesis via the AKT/mTOR/VEGFA axis, thereby suggesting that GBP2 may be a therapeutic target for pathological retinal angiogenesis.

ZnSnO3 based gas sensors for pyridine volatile marker detection in rice aging during storage.

This study reports the development of ZnSnO3 based gas sensors for pyridine detection in rice aging. Pyridine is one of heterocyclic markers formed via Maillard reaction and lipid oxidation. Herein, graphitic carbon nitride (g-C3N4) decorated ZnSnO3 microstructures were obtained through a template-free approach. And the sensing results reveal that 5 wt%g-C3N4 decorated ZnSnO3 exhibited a high sensitivity (47.9), a short response/recovery time (14/120 s) and a low detection limit (0.45 ppm), which is due to the catalysis of g-C3N4 nanosheets, the decorated microstructure and the formation of heterojunctions. Meanwhile, the practical experiment demonstrates that the sensitivity towards volatiles generated from Japonica rice aging is 48.7, which is around 4 and 2.5 times higher than those of Indica rice and Polished Glutinous rice, indicating that the sensor has anticipated application in the development of a high-performance E-nose for the quality inspection of rice and other products.

DDX1 is a prognostic biomarker and correlates with immune infiltrations in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading lethal malignant tumors worldwide. DEAD-box (DDX) family helicases are implicated in numerous human cancers. However, the role of DDX1 in HCC has not yet been fully elucidated. We downloaded gene expression data and clinical information data of HCC from The Cancer Genome Atlas and International Cancer Genome Consortium (ICGC) database and conducted subsequent analyses using the R package and online portal. The results revealed that HCC tissues had higher DDX1 expression compared with either paired or unpaired normal tissues. The increased DDX1 expression was closely related to the advanced pathological grade and histologic grade of HCC. Further analysis suggested that patients with high DDX1 expression contributed to poor prognosis The Cox regression analysis revealed that the expression level of DDX1 was an independent prognostic factor for HCC. In addition, an ICGC cohort was used for external validation. The cBio-Portal, MethSurv, and UALCAN database were used for evaluating the genomic mechanism. Moreover, the Tumor Immune Estimation Resource dataset and QUANTISEQ algorithm revealed that DDX1 expression positively correlates with immune infiltrating cells. We also identified the DDX1-related differentially expressed genes (DEGs) and explored their biological functions by GO, KEGG, and GSEA analyses, which indicated that DDX1 may regulate the progression of HCC. In general, increased DDX1 expression predicts a poor prognosis and drives the progression of HCC.

Research advance in gas detection of volatile organic compounds released in rice quality deterioration process.

Rice quality deterioration will cause grievous waste of stored grain and various food safety problems. Gas detection of volatile organic compounds (VOCs) produced by deterioration is a nondestructive detection method to judge rice quality and alleviate rice spoilage. This review discussed the research advance of VOCs detection in terms of nondestructive detection methods of rice quality deterioration, applications of VOCs in grain detection, inspection of characteristic gas produced during rice spoilage, rice deterioration prevention and control, and detection of VOCs released by rice mildew and insect attack. According to the main causes of rice quality deterioration and major sources of VOCs with off-odor generated during rice storage, deterioration can be divided into mold and insect infection. The results of literature manifested that researches mainly focused on the infection of Aspergillus in the mildew process and the attack of certain pests in recent years, thus the research scope was limited. In this paper, the gas detection methods combined with the chemometrics to qualitatively analyze the VOCs, as well as the correlation with the number of colonies and insects were further studied based on the common dominant strains during rice mildew, that is, Aspergillus and Penicillium fungi, and the common pests during storage, that is, Sitophilus oryzae and Rhyzopertha dominica. Furthermore, this paper pointed out that the quantitative determination of characteristic VOCs, the numeration relationship between VOCs and the degree of mildew and insect infestation, the further expansion of detection range, and the application of degraded rice should be the spotlight of future research.

Alkaline Phosphatase-Instructed Self-Assembly of Gadolinium Nanofibers for Enhanced T2-Weighted Magnetic Resonance Imaging of Tumor.

Alkaline phosphatase (ALP) is an important enzyme but using ALP-instructed self-assembly of gadolinium nanofibers for enhanced T2-weighted magnetic resonance imaging (MRI) of tumor has not been reported. In this work, we rationally designed a hydrogelator Nap-FFFYp-EDA-DOTA(Gd) (1P) which, under the catalysis of ALP, was able to self-assemble into gadolinium nanofibers to form hydrogel Gel I for enhanced T2-weighted MR imaging of ALP activity in vitro and in tumor. T2 phantom MR imaging indicated that the transverse relaxivity (r2) value of Gel I was 33.9% higher than that of 1P and both of them were 1 order of magnitude higher than that of Gd-DTPA. In vivo T2-weighted MR imaging showed that, at 9.4 T, ALP-overexpressing HeLa tumors of 1P-injected mice showed obviously enhanced T2 contrast. We anticipate that, by replacing ALP with other enzymes, our approach could be applied for MR diagnosis of other diseases in the future.

Casp3/7-Instructed Intracellular Aggregation of Fe3O4 Nanoparticles Enhances T2 MR Imaging of Tumor Apoptosis.

Large magnetic nanoparticles or aggregates are advantageous in their magnetic resonance properties over ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs), but the former are cleared faster from the blood pool. Therefore, the "smart" strategy of intracellular aggregation of USPIO NPs is required for enhanced T2-weighted MR imaging. Herein, employing an enzyme-instructed condensation reaction, we rationally designed a small molecule Ac-Asp-Glu-Val-Asp-Cys(StBu)-Lys-CBT (1) to covalently modify USPIO NPs to prepare monodispersive Fe3O4@1 NPs. In vitro results showed that Fe3O4@1 NPs could be subjected to caspase 3 (Casp3)-instructed aggregation. T2 phantom MR imaging showed that the transverse molar relaxivity (r2) of Fe3O4@1 NPs with Casp3 or apoptotic HepG2 cells was significantly larger than those of control groups. In vivo tumor MR imaging results indicated that Fe3O4@1 NPs could be specifically applied for enhanced T2 MR imaging of tumor apoptosis. We propose that the enzyme-instructed intracellular aggregation of Fe3O4 NPs could be a novel strategy for the design of "smart" probes for efficient T2 MR imaging of in vivo biomarkers.

[Study on the differentiation of human mesenchymal stem cells into vascular endothelial-like cells].

To explore the feasibility of mesenchymal stem cells (MSCs) acting as seed cells in tissue engineering, we isolated human bone marrow MSCs and differentiated them into vascular endothelial-like cells (ELCs) in vitro. Bone marrow mononuclear cells (BMSCs) were isolated by the method of percoll density centrifugation, and seeded in Dulbecco Modified Eagle Medium supplemented with 10% fetal bovine serum. MSCs were purified through multiple adherent cultures, and differentiated into ELCs induced by endothelial cell growth medium-2 (EBM-2) medium containing vascular endothelial growth factor (VEGF), human fibroblast growth factor (hFGF), insulin like growth factors 1 (IGF-1), and human epidermal growth factor (hEGF). The relative biologic characteristics of ELCs including cell morphology and phenotype were studied by inverted microscope and flow cytometry. The induced cells were identified by immunofluorescence with CD31 and Von Willebrand factor (vWF). The results showed that the morphology of MSCs was long-spindle and vortex-like growth. After induction of differentiation, the cells were round, and similar to vascular endothelial cells (ECs). Flow cytometric analysis revealed that ELCs expressed ECs specific surface markers of CD31 and vascular endothelial cadherin (VE-cadherin), but not CD133. Immunofluorescence results also confirmed that ELCs expressed CD31 and vWF. The results suggested that ELCs possed similar cell biological characteristics with ECs. In one word, human MSCs derived from bone marrow have the potential to differentiate into ECs in vitro, and show clinical feasibility acting as ideal donor cells of vascular tissue engineering.