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.

An automated parallel multi-channel chromatographic system for isotopic analysis - Demonstration considering Sr.

A fully automated, closed-column chromatographic system with parallel multi-channel has been developed. This system is established with seven reagent reservoirs, one multi-channel syringe pump, eight 10-port valves, forty sample tubes, 40 columns, and a fraction collection tray. Four samples can be purified simultaneously at a time, and 40 samples can be purified in one batch. Each sample can be purified by an independent channel, avoiding cross-contamination. The sample tubes can be flipped upside down for automatic cleaning, which eliminates the residue of samples. Moreover, the fraction collection tray can collect up to 104 different target components. The key performance of the system has been investigated. The results show that the sample tubes are well-cleaned, the bubble does not affect the chemical behavior of columns, the consistency of the parallel channels is excellent and the blank of the system is negligible. The system was demonstrated by the purification of Sr from reference materials (BCR-2, JB-2, JB-3, and NIST SRM 987). The recoveries of Sr are better than 89.4% and the blank of the whole procedure is less than 200 pg. The Sr isotope values agree well with the reference values.

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.

Odor-mediated contextual learning induced memory consolidation and hippocampus development in neonate rat.

The hippocampus in neonatal rats is not fully developed after birth, and the effect of odor-aversion learning on memory consolidation in the immature hippocampus is not well understood. Therefore, the aim of the present study was to explore the effects of odor-aversion learning in neonatal rats on memory consolidation and neurodevelopment in the immature hippocampus. The effect of hippocampal-induced learning was measured at two different developmental stages using the Y-maze and c-Fos protein levels. Furthermore, hippocampal cell proliferation and growth-associated protein 43 (GAP-43) expression were evaluated at different developmental stages, namely, postnatal day 7 (PN7) and PN24, after odor-aversion learning. Both PN7 and PN24 rats avoided conditioned odor stimuli after odor-aversion learning. PN7 and PN24 rats in the odor-averse learning groups exhibited high c-Fos protein levels. PN7 rats exhibited high cell proliferation rates and GAP-43 protein levels after odor-aversion learning. These results showed that the immature hippocampus can participated in odor-aversion learning, which may induce cell proliferation and axonal development.

Correction to: The Association Between Phosphorylated Neurofilament Heavy Chain (pNF-H) and Small Fiber Neuropathy (SFN) in Patients with Impaired Glucose Tolerance.

In the original article, there was some error in Table 2. The correct table is given below.

The Association Between Phosphorylated Neurofilament Heavy Chain (pNF-H) and Small Fiber Neuropathy (SFN) in Patients with Impaired Glucose Tolerance.

INTRODUCTION: Small fiber neuropathy (SFN)-the early stage of diabetic peripheral neuropathy (DPN)-progresses gradually and is difficult to diagnose using neurophysiological tests. To facilitate the early diagnosis of SFN, biomarkers for SFN must be identified. The purpose of this study was to investigate the characteristics of SFN in prediabetic patients and the relationship between pNF-H and SFN. METHODS: 44 IGT patients (inpatients and outpatients) were selected at random. 33 healthy subjects served as controls. Data on clinical characteristics and laboratory parameters were collected. Quantitative sensory testing (QST), electromyography (EMG), and Sudoscan were performed, and pNF-H was measured by ELISA. RESULTS: 24 of the 44 patients with impaired glucose tolerance (IGT) were diagnosed with SFN according to the modified Toronto Diabetic Neuropathy Expert Group consensus criteria. The thermal sensory thresholds of the IGT-SFN group were significantly different from those of the CTRL group (p < 0.05), except for the heat pain threshold. The sensory nerve action potential (SNAP) of the sural nerve was 12.39 in the IGT-SFN group, which was significantly lower than those in the other groups. No significant difference in nerve conduction velocity (NCV) was observed among the three groups. The electrochemical skin conductance (ESC) in the IGT-SFN group was 69.78 ± 14.03uS, which was significantly lower than that in the CTRL group. The pNF-H in the IGT-SFN group was 170.6 (140.0, 223.6) pg/ml, which was significantly higher than those in the CTRL and IGT-non-SFN groups (76.55 and 64.7 pg/ml, respectively). Multivariate regression analysis demonstrated that pNF-H and 2h plasma glucose were independently correlated with SFN; the ORs (95% CI) were 1.429 (1.315, 1.924) and 2.375 (1.157, 4.837), respectively. CONCLUSIONS: Serum pNF-H may be associated with SFN in IGT patients, and serum pNF-H could therefore serve as a sensitive biomarker for the detection of SFN.

Chinese cropland losses due to urban expansion in the past four decades.

Since 1970s, China has experienced the large-scale losses of croplands during urban expansion process, which has drawn great attentions to Chinese government. Although in-depth studies about cropland losses have been executed widely, relatively little attention has been paid to describe long term and high frequency influences of urban expansion on it and reveal its differences systematically. Based on remote sensing and GIS technology, we quantified, analyzed, and mapped cropland losses in China due to urban expansion from the national, administrative-level, population-size, and city scales. Results indicated that (1) Since the 1970s, croplands were the primary contributor to urban expansion in China, and their losses due to urban expansion underwent five obvious stages. The consciousness of cropland protection is being strengthened continuously and has developed from the initial to the deep execution stages. (2) Cropland losses were unbalanced in China, with the loss magnitude, rate, and influences on urban expansion positively related to the administrative-level and large population-size. That is, obvious losses always emerged in cities with high administrative-level and large population-size. (3) Seven basic trends of cropland losses were quantitatively recognized, which was conducive to the formulation of different policies or strategies for cropland protection for different cities.

17ß-Estradiol Promotes Islet Cell Proliferation in a Partial Pancreatectomy Mouse Model.

17ß-Estradiol (E2) is a multifunctional steroid hormone in modulating metabolism in vivo. Previous studies have reported that E2 could promote insulin secretion and protect ß cells from apoptosis. In this study, the partial pancreatectomy (PPx) model was used to study the role of E2 in islet cell proliferation. The animals were divided into four groups, including sham control, PPx model, E2, and E2 plus estrogen antagonist (E2 plus ICI) groups. In the E2 group, 5-bromo-2'-deoxyuridine- and Ki67-positive cells significantly increased after PPx, and the protein expression of forkhead transcription factor M1, cyclin A2, cyclin B1, and cyclin E2 also significantly increased in the isolated islets. The messenger RNA expression of cyclin A2 and cyclin B2 increased in E2 treatment group. Additionally, the effects of E2 on the PPx mice were partially blocked by estrogen antagonist ICI182,780. The results indicated that E2 significantly promoted islet cell proliferation in PPx model mice, and it upregulated the expression of cell cycle genes. In conclusion, E2 treatment is beneficial for islet cell proliferation in adult mice after PPx. A partial pancreatectomy in mice may be an attractive model for the study of islet cell proliferation.

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.

Ziziphi spinosae lily powder suspension in the treatment of depression-like behaviors in rats.

BACKGROUND: Depression is a chronic, recurring and potentially life-threatening illness. Current treatments for depression are characterized by a low success rate and associated with a wide variety of side effects. The aim of the present study was to evaluate the behavioral anti-depressant effect of a novel herbal compounds named ziziphi spinosae lily powder suspension, as well as to investigate its potential mechanisms. METHODS: Except for body weight, depressive-like behaviors were also evaluated using forced swimming test, sucrose consumption test and open field test. In order to investigate the underlying potential mechanisms, serum 5-HT and brain 5-HIAA were measured using ultrahigh-performance liquid chromatography and high-performance liquid chromatography, respectively. RESULTS: Results showed that the herbal compounds ziziphi spinosae lily suspension could alleviate depressive symptoms in rat model of chronic depression. Biochemical analysis revealed that the herbal compounds elevated serum 5-HT and brain 5-HIAA. CONCLUSION: Ziziphi spinosae lily powder suspension could alleviate depressive behaviors in depression model animals. The underlying mechanisms may be related to the increase of serum 5-HT in peripheral blood and 5-HIAA in brain. The study provides important mechanistic insights into the protective effect of the herbal compounds against chronic depressive disorder and suggests that the herbal compounds may be a potential pharmacological agent for treatment of major depressive disorder.

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.

Vanillin-induced amelioration of depression-like behaviors in rats by modulating monoamine neurotransmitters in the brain.

Olfaction plays an important role in emotions in our daily life. Pleasant odors are known to evoke positive emotions, inducing relaxation and calmness. The beneficial effects of vanillin on depressive model rats were investigated using a combination of behavioral assessments and neurotransmitter measurements. Before and after chronic stress condition (or olfactory bulbectomy), and at the end of vanillin or fluoxetine treatment, body weight, immobility time on the forced swimming test and sucrose consumption in the sucrose consumption test were measured. Changes in these assessments revealed the characteristic phenotypes of depression in rats. Neurotransmitters were measured using ultrahigh-performance liquid chromatography. Our results indicated that vanillin could alleviate depressive symptoms in the rat model of chronic depression via the olfactory pathway. Preliminary analysis of the monoamine neurotransmitters revealed that vanillin elevated both serotonin and dopamine levels in brain tissue. These results provide important mechanistic insights into the protective effect of vanillin against chronic depressive disorder via olfactory pathway. This suggests that vanillin may be a potential pharmacological agent for the treatment of major depressive disorder.

[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.