MyTrack+: Human-centered design of an mHealth app to support long-term weight loss maintenance.

A growing body of research has focused on the utility of adaptive intervention models for promoting long-term weight loss maintenance; however, evaluation of these interventions often requires customized smartphone applications. Building such an app from scratch can be resource-intensive. To support a novel clinical trial of an adaptive intervention for weight loss maintenance, we developed a companion app, MyTrack+, to pair with a main commercial app, FatSecret (FS), leveraging a user-centered design process for rapid prototyping and reducing software engineering efforts. MyTrack+ seamlessly integrates data from FS and the BodyTrace smart scale, enabling participants to log and self-monitor their health data, while also incorporating customized questionnaires and timestamps to enhance data collection for the trial. We iteratively refined the app by first developing initial mockups and incorporating feedback from a usability study with 17 university students. We further improved the app based on an in-the-wild pilot study with 33 participants in the target population, emphasizing acceptance, simplicity, customization options, and dual app usage. Our work highlights the potential of using an iterative human-centered design process to build a companion app that complements a commercial app for rapid prototyping, reducing costs, and enabling efficient research progress.

Nogo-B mediates endothelial oxidative stress and inflammation to promote coronary atherosclerosis in pressure-overloaded mouse hearts.

AIMS: Endothelial dysfunction plays a pivotal role in atherosclerosis, but the detailed mechanism remains incomplete understood. Nogo-B is an endoplasmic reticulum (ER)-localized protein mediating ER-mitochondrial morphology. We previously showed endothelial Nogo-B as a key regulator of endothelial function in the setting of hypertension. Here, we aim to further assess the role of Nogo-B in coronary atherosclerosis in ApoE-/- mice with pressure overload. METHODS AND RESULTS: We generated double knockout (DKO) mouse models of systemically or endothelium-specifically excising Nogo-A/B gene on an ApoE-/- background. After 7 weeks of transverse aortic constriction (TAC) surgery, compared to ApoE-/- mice DKO mice were resistant to the development of coronary atherosclerotic lesions and plaque rapture. Sustained elevation of Nogo-B and adhesion molecules (VCAM-1/ICAM-1), early markers of atherosclerosis, was identified in heart tissues and endothelial cells (ECs) isolated from TAC ApoE-/- mice, changes that were significantly repressed by Nogo-B deficiency. In cultured human umbilical vein endothelial cells (HUVECs) exposure to inflammatory cytokines (TNF-α, IL-1ß), Nogo-B was upregulated and activated reactive oxide species (ROS)-p38-p65 signaling axis. Mitofusin 2 (Mfn2) is a key protein tethering ER to mitochondria in ECs, and we showed that Nogo-B expression positively correlated with Mfn2 protein level. And Nogo-B deletion in ECs or in ApoE-/- mice reduced Mfn2 protein content and increased ER-mitochondria distance, reduced ER-mitochondrial Ca2+ transport and mitochondrial ROS generation, and prevented VCAM-1/ICAM-1 upregulation and EC dysfunction, eventually restrained atherosclerotic lesions development. CONCLUSION: Our study revealed that Nogo-B is a critical modulator in promoting endothelial dysfunction and consequent pathogenesis of coronary atherosclerosis in pressure overloaded hearts of ApoE-/- mice. Nogo-B may hold the promise to be a common therapeutic target in the setting of hypertension.

Decoding the underlying mechanisms of Di-Tan-Decoction in treating intracerebral hemorrhage based on network pharmacology.

BACKGROUND: Chinese medicine usually acts as "multi-ingredients, multi-targets and multi-pathways" on complex diseases, and these action modes reflect the coordination and integrity of the treatment process with traditional Chinese medicine (TCM). System pharmacology is developed based on the cross-disciplines of directional pharmacology, system biology, and mathematics, has the characteristics of integrity and synergy in the treatment process of TCM. Therefore, it is suitable for analyzing the key ingredients and mechanisms of TCM in treating complex diseases. Intracerebral Hemorrhage (ICH) is one of the leading causes of death in China, with the characteristics of high mortality and disability rate. Bring a significant burden on people and society. An increasing number of studies have shown that Chinese medicine prescriptions have good advantages in the treatment of ICH, and Ditan Decoction (DTT) is one of the commonly used prescriptions in the treatment of ICH. Modern pharmacological studies have shown that DTT may play a therapeutic role in treating ICH by inhibiting brain inflammation, abnormal oxidative stress reaction and reducing neurological damage, but the specific key ingredients and mechanism are still unclear. METHODS: To solve this problem, we established PPI network based on the latest pathogenic gene data of ICH, and CT network based on ingredient and target data of DTT. Subsequently, we established optimization space based on PPI network and CT network, and constructed a new model for node importance calculation, and proposed a calculation method for PES score, thus calculating the functional core ingredients group (FCIG). These core functional groups may represent DTT therapy for ICH. RESULTS: Based on the strategy, 44 ingredients were predicted as FCIG, results showed that 80.44% of the FCIG targets enriched pathways were coincided with the enriched pathways of pathogenic genes. Both the literature and molecular docking results confirm the therapeutic effect of FCIG on ICH via targeting MAPK signaling pathway and PI3K-Akt signaling pathway. CONCLUSIONS: The FCIG obtained by our network pharmacology method can represent the effect of DTT in treating ICH. These results confirmed that our strategy of active ingredient group optimization and the mechanism inference could provide methodological reference for optimization and secondary development of TCM.

Decoding the Key Functional Combined Components Group and Uncovering the Molecular Mechanism of Longdan Xiegan Decoction in Treating Uveitis.

Objective: Longdan Xiegan Decoction (LXD) is a famous herbal formula in China. It has been proved that LXD has been shown to have a significant inhibitory effect on suppresses the inflammatory cells associated with uveitis. However, the key functional combination of component groups and their possible mechanisms remain unclear. Methods: The community detecting model of the network, the functional response space, and reverse prediction model were utilized to decode the key components group (KCG) and possible mechanism of LXD in treating uveitis. Finally, MTT assay, NO assay and ELISA assay were applied to verify the effectiveness of KCG and the accuracy of our strategy. Results: In the components-targets-pathogenic genes-disease (CTP) network, a combination of Huffman coding and random walk algorithm was used and eight foundational acting communities (FACs) were discovered with important functional significance. Verification has shown that FACs can represent the corresponding C-T network for treating uveitis. A novel node importance calculation method was designed to construct the functional response space and pick out 349 effective proteins. A total of 54 components were screened and defined as KCG. The pathway enrichment results showed that KCG and their targets enriched signal pathways of IL-17, Toll-like receptor, and T cell receptor played an important role in the pathogenesis of uveitis. Furthermore, experimental verification results showed that important KCG quercetin and sitosterol markedly inhibited the production of nitric oxide and significantly regulated the level of TNF-α and IFN-γ in Lipopolysaccharide-induced RAW264.7 cells. Discussion: In this research, we decoded the potential mechanism of the multi-components-genes-pathways of LXD's pharmacological action mode against uveitis based on an integrated pharmacology approach. The results provided a new perspective for the future studies of the anti-uveitis mechanism of traditional Chinese medicine.

Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke.

Stroke is a cerebrovascular event with cerebral blood flow interruption which is caused by occlusion or bursting of cerebral vessels. At present, the main methods in treating stroke are surgical treatment, statins, and recombinant tissue-type plasminogen activator (rt-PA). Relatively, traditional Chinese medicine (TCM) has widely been used at clinical level in China and some countries in Asia. Xiao-Xu-Ming decoction (XXMD) is a classical and widely used prescription in treating stroke in China. However, the material basis of effect and the action principle of XXMD are still not clear. To solve this issue, we designed a new system pharmacology strategy that combined targets of XXMD and the pathogenetic genes of stroke to construct a functional response space (FRS). The effective proteins from this space were determined by using a novel node importance calculation method, and then the key functional components group (KFCG) that could mediate the effective proteins was selected based on the dynamic programming strategy. The results showed that enriched pathways of effective proteins selected from FRS could cover 99.10% of enriched pathways of reference targets, which were defined by overlapping of component targets and pathogenetic genes. Targets of optimized KFCG with 56 components can be enriched into 166 pathways that covered 80.43% of 138 pathways of 1,012 pathogenetic genes. A component potential effect score (PES) calculation model was constructed to calculate the comprehensive effective score of components in the components-targets-pathways (C-T-P) network of KFCGs, and showed that ferulic acid, zingerone, and vanillic acid had the highest PESs. Prediction and docking simulations show that these components can affect stroke synergistically through genes such as MEK, NFκB, and PI3K in PI3K-Akt, cAMP, and MAPK cascade signals. Finally, ferulic acid, zingerone, and vanillic acid were tested to be protective for PC12 cells and HT22 cells in increasing cell viabilities after oxygen and glucose deprivation (OGD). Our proposed strategy could improve the accuracy on decoding KFCGs of XXMD and provide a methodologic reference for the optimization, mechanism analysis, and secondary development of the formula in TCM.

Uncovering the potential mechanism of Xue Fu Zhu Yu Decoction in the treatment of intracerebral hemorrhage.

BACKGROUND: Chinese herbal medicine (CHM) is characterized by "multi- compounds, multi-targets and multi-pathway", which has advanced benefits for preventing and treating complex diseases, but there still exists unsolved issues, mainly include unclear material basis and underlying mechanism of prescription. Integrated pharmacology is a hot cross research area based on system biology, mathematics and poly-pharmacology. It can systematically and comprehensively investigate the therapeutic reaction of compounds or drugs on pathogenic genes network, and is especially suitable for the study of complex CHM systems. Intracerebral Hemorrhage (ICH) is one of the main causes of death among Chinese residents, which is characterized with high mortality and high disability rate. In recent years, the treatment of ICH by CHM has been deeply researched. Xue Fu Zhu Yu Decoction (XFZYD), one of the commonly used prescriptions in treating ICH at clinic level, has not been clear about its mechanism. METHODS: Here, we established a strategy, which based on compounds-targets, pathogenetic genes, network analysis and node importance calculation. Using this strategy, the core compounds group (CCG) of XFZYD was predicted and validated by in vitro experiments. The molecular mechanism of XFZYD in treating ICH was deduced based on CCG and their targets. RESULTS: The results show that the CCG with 43 compounds predicted by this model is highly consistent with the corresponding Compound-Target (C-T) network in terms of gene coverage, enriched pathway coverage and accumulated contribution of key nodes at 89.49%, 88.72% and 90.11%, respectively, which confirmed the reliability and accuracy of the effective compound group optimization and mechanism speculation strategy proposed by us. CONCLUSIONS: Our strategy of optimizing the effective compound groups and inferring the mechanism provides a strategic reference for explaining the optimization and inferring the molecular mechanism of prescriptions in treating complex diseases of CHM.

Elucidating the Synergistic Effect of Multiple Chinese Herbal Prescriptions in the Treatment of Post-stroke Neurological Damage.

Background: Traditional Chinese medicine (TCM) has been widely used in the treatment of human diseases. However, the synergistic effects of multiple TCM prescriptions in the treatment of stroke have not been thoroughly studied. Objective of the study: This study aimed to reveal the mechanisms underlying the synergistic effects of these TCM prescriptions in stroke treatment and identify the active compounds. Methods: Herbs and compounds in the Di-Tan Decoction (DTD), Xue-Fu Zhu-Yu Decoction (XFZYD), and Xiao-Xu-Ming Decoction (XXMD) were acquired from the TCMSP database. SEA, HitPick, and TargetNet web servers were used for target prediction. The compound-target (C-T) networks of three prescriptions were constructed and then filtered using the collaborative filtering algorithm. We combined KEGG enrichment analysis, molecular docking, and network analysis approaches to identify active compounds, followed by verification of these compounds with an oxygen-glucose deprivation and reoxygenation (OGD/R) model. Results: The filtered DTD network contained 39 compounds and 534 targets, the filtered XFZYD network contained 40 compounds and 508 targets, and the filtered XXMD network contained 55 compounds and 599 targets. The filtered C-T networks retained approximately 80% of the biological functions of the original networks. Based on the enriched pathways, molecular docking, and network analysis results, we constructed a complex network containing 3 prescriptions, 14 botanical drugs, 26 compounds, 13 targets, and 5 pathways. By calculating the synergy score, we identified the top 5 candidate compounds. The experimental results showed that quercetin, baicalin, and ginsenoside Rg1 independently and synergistically increased cell viability. Conclusion: By integrating pharmacological and chemoinformatic approaches, our study provides a new method for identifying the effective synergistic compounds of TCM prescriptions. The filtered compounds and their synergistic effects on stroke require further research.

Evaluated expression of CELSR3 in oral squamous cell carcinoma is associated with perineural invasion and poor prognosis.

OBJECTIVE: The objective of this study was to evaluate CELSR3 expression and explore its potential mechanism in oral squamous cell carcinoma. STUDY DESIGN: CELSR3 mRNA expression was analyzed using The Cancer Genome Atlas (TCGA) database. CELSR3 protein expression in 135 surgical oral squamous cell carcinoma specimens was observed by immunohistochemical staining. Staining results were used to investigate the association between CELSR3 expression and clinicopathologic characteristics and prognosis. Bioinformatics analyses were used to explore the potential mechanism of CELSR3 in head and neck squamous cell carcinoma. RESULTS: CELSR3 mRNA expression was upregulated in patients with head and neck squamous cell carcinoma in the TCGA head and neck squamous cell carcinoma data set. Increased CELSR3 protein expression was associated with perineural invasion and poor clinical outcomes in patients with oral squamous cell carcinoma. Bioinformatics analyses revealed that CELSR3 is involvement in axonogenesis, neuron migration, and cell-cell adhesion, all of which are involved in the process of perineural invasion. CONCLUSION: CELSR3 may play a pro-oncogenic role in oral squamous cell carcinoma and can predict perineural invasion and poor survival. CELSR3 may be involved in oral squamous cell carcinoma progression by modulating perineural invasion.

Corrigendum: Detecting key functional components group and speculating the potential mechanism of Xiao-Xu-Ming decoction in treating stroke.

[This corrects the article DOI: 10.3389/fcell.2022.753425.].

Detecting Critical Functional Ingredients Group and Mechanism of Xuebijing Injection in Treating Sepsis.

Sepsis is a systemic inflammatory reaction caused by various infectious or noninfectious factors, which can lead to shock, multiple organ dysfunction syndrome, and death. It is one of the common complications and a main cause of death in critically ill patients. At present, the treatments of sepsis are mainly focused on the controlling of inflammatory response and reduction of various organ function damage, including anti-infection, hormones, mechanical ventilation, nutritional support, and traditional Chinese medicine (TCM). Among them, Xuebijing injection (XBJI) is an important derivative of TCM, which is widely used in clinical research. However, the molecular mechanism of XBJI on sepsis is still not clear. The mechanism of treatment of "bacteria, poison and inflammation" and the effects of multi-ingredient, multi-target, and multi-pathway have still not been clarified. For solving this issue, we designed a new systems pharmacology strategy which combines target genes of XBJI and the pathogenetic genes of sepsis to construct functional response space (FRS). The key response proteins in the FRS were determined by using a novel node importance calculation method and were condensed by a dynamic programming strategy to conduct the critical functional ingredients group (CFIG). The results showed that enriched pathways of key response proteins selected from FRS could cover 95.83% of the enriched pathways of reference targets, which were defined as the intersections of ingredient targets and pathogenetic genes. The targets of the optimized CFIG with 60 ingredients could be enriched into 182 pathways which covered 81.58% of 152 pathways of 1,606 pathogenetic genes. The prediction of CFIG targets showed that the CFIG of XBJI could affect sepsis synergistically through genes such as TAK1, TNF-α, IL-1ß, and MEK1 in the pathways of MAPK, NF-κB, PI3K-AKT, Toll-like receptor, and tumor necrosis factor signaling. Finally, the effects of apigenin, baicalein, and luteolin were evaluated by in vitro experiments and were proved to be effective in reducing the production of intracellular reactive oxygen species in lipopolysaccharide-stimulated RAW264.7 cells, significantly. These results indicate that the novel integrative model can promote reliability and accuracy on depicting the CFIGs in XBJI and figure out a methodological coordinate for simplicity, mechanism analysis, and secondary development of formulas in TCM.

Using Smartwatches to Detect Face Touching.

Frequent spontaneous facial self-touches, predominantly during outbreaks, have the theoretical potential to be a mechanism of contracting and transmitting diseases. Despite the recent advent of vaccines, behavioral approaches remain an integral part of reducing the spread of COVID-19 and other respiratory illnesses. The aim of this study was to utilize the functionality and the spread of smartwatches to develop a smartwatch application to identify motion signatures that are mapped accurately to face touching. Participants (n = 10, five women, aged 20-83) performed 10 physical activities classified into face touching (FT) and non-face touching (NFT) categories in a standardized laboratory setting. We developed a smartwatch application on Samsung Galaxy Watch to collect raw accelerometer data from participants. Data features were extracted from consecutive non-overlapping windows varying from 2 to 16 s. We examined the performance of state-of-the-art machine learning methods on face-touching movement recognition (FT vs. NFT) and individual activity recognition (IAR): logistic regression, support vector machine, decision trees, and random forest. While all machine learning models were accurate in recognizing FT categories, logistic regression achieved the best performance across all metrics (accuracy: 0.93 ± 0.08, recall: 0.89 ± 0.16, precision: 0.93 ± 0.08, F1-score: 0.90 ± 0.11, AUC: 0.95 ± 0.07) at the window size of 5 s. IAR models resulted in lower performance, where the random forest classifier achieved the best performance across all metrics (accuracy: 0.70 ± 0.14, recall: 0.70 ± 0.14, precision: 0.70 ± 0.16, F1-score: 0.67 ± 0.15) at the window size of 9 s. In conclusion, wearable devices, powered by machine learning, are effective in detecting facial touches. This is highly significant during respiratory infection outbreaks as it has the potential to limit face touching as a transmission vector.

A metabolic data-driven systems pharmacology strategy for decoding and validating the mechanism of Compound Kushen Injection against HCC.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Kushen Injection (CKI) is a widely used TCM formula for treatment of carcinomatous pain and tumors of digestive system including hepatocellular carcinoma (HCC). However, the potential mechanisms of CKI for treatment of HCC have not been systematically and deeply studied. AIM OF STUDY: A metabolic data-driven systems pharmacology approach was utilized to investigate the potential mechanisms of CKI for treatment of HCC. MATERIALS AND METHODS: Based on phenotypic data generated by metabolomics and genotypic data of drug targets, a propagation model based on Dijkstra program was proposed to decode the effective network of key genotype-phenotype of CKI in treating HCC. The pivotal pathway was predicted by target propagation mode of our proposed model, and was validated in SMMC-7721 cells and diethylnitrosamine-induced rats. RESULTS: Metabolomics results indicated that 12 differential metabolites, and 5 metabolic pathways might be involved in the anti-HCC effect of CKI. A total of 86 metabolic related genes that affected by CKI were obtained. The results calculated by propagation model showed that 6475 shortest distance chains might be involved in the anti-HCC effect of CKI. According to the results of propagation mode, EGFR was identified as the core target of CKI for the anti-HCC effect. Finally, EGFR and its related pathway EGFR-STAT3 signaling pathway were validated in vivo and in vitro. CONCLUSION: The proposed method provides a methodological reference for explaining the underlying mechanism of TCM in treating HCC.

Comparative genomic and transcriptomic analyses of chemosensory genes in the citrus fruit fly Bactrocera (Tetradacus) minax.

The citrus fruit fly Bactrocera (Tetradacus) minax is a major and devastating agricultural pest in Asian subtropical countries. Previous studies have shown that B. minax interacts with plant hosts via the efficient chemosensory system. However, the molecular components of the B. minax chemosensory system have not been well characterized. Herein, we identified a total of 25 putative odorant-binding receptors (OBPs), 4 single-copy chemosensory proteins (CSPs) and 53 candidate odorant receptors (ORs) using a newly generated whole-genome dataset for B. minax. This study significantly extended the chemosensation-related gene profiles (particularly, OBPs and ORs) in six other tephritid species. Comparative transcriptome analysis of adult B. minax and Bactrocera dorsalis showed that there were 14 highly expressed OBPs (FPKM > 100) in B. dorsalis and 7 highly expressed ones in B. minax. The expression level of CSP3 gene and CSP4 gene was higher in B. dorsalis than that in B. minax. Comparative genomic and transcriptomic analyses of chemosensory genes in the citrus fruit fly B. minax provided new insights for preventive control of this agriculture important pest and closely related species.

Full-color based on bismuth core-shell nanoparticles in one-step fabrication.

Plasmonic resonances in metallic nanostructures are promising for the structure-dependent color-rendering effect. In this study, bismuth is selected as an alternative plasmonic material due to its large tunable range from near-ultraviolet to near-infrared. Various sizes of core-shell bismuth nanoparticles are fabricated on a large-area silicon substrate using a one-step thermal evaporation deposition process. Particle diameters, cross-sections, and arrangement are characterized at 12 featured sections, which reveal spectral shifts and full visible colors in a hue order with a color gamut that is close to sRGB. Color palettes on the chromaticity coordinates rendered from both measured and simulation reflection spectra are in very good accordance with the microscopic image colors of all sections.

An Enhanced Region Proposal Network for object detection using deep learning method.

Faster Region-based Convolutional Network (Faster R-CNN) is a state-of-the-art object detection method. However, the object detection effect of Faster R-CNN is not good based on the Region Proposal Network (RPN). Inspired by RPN of Faster R-CNN, we propose a novel proposal generation method called Enhanced Region Proposal Network (ERPN). Four improvements are presented in ERPN. Firstly, our proposed deconvolutional feature pyramid network (DFPN) is introduced to improve the quality of region proposals. Secondly, novel anchor boxes are designed with interspersed scales and adaptive aspect ratios. Thereafter, the capability of object localization is increased. Thirdly, a particle swarm optimization (PSO) based support vector machine (SVM), termed PSO-SVM, is developed to distinguish the positive and negative anchor boxes. Fourthly, the classification part of multi-task loss function in RPN is improved. Consequently, the effect of classification loss is strengthened. In this study, our proposed ERPN is compared with five object detection methods on both PASCAL VOC and COCO data sets. For the VGG-16 model, our ERPN obtains 78.6% mAP on VOC 2007 data set, 74.4% mAP on VOC 2012 data set and 31.7% on COCO data set. The performance of ERPN is the best among the comparison object detection methods. Furthermore, the detection speed of ERPN is 5.8 fps. Additionally, ERPN obtains good effect on small object detection.

3-Acetyl-oleanolic acid ameliorates non-alcoholic fatty liver disease in high fat diet-treated rats by activating AMPK-related pathways.

3-Acetyl-oleanolic acid (3Ac-OA) is a derivative of oleanolic acid (OA), which has shown therapeutic beneficial effects on diabetes and metabolic syndrome. In this study we investigated whether 3Ac-OA exerted beneficial effect on non-alcoholic fatty liver disease (NAFLD) in rats and its potential underlying mechanisms. Treatment with 3Ac-OA (1-100 µmol/L) dose-dependently decreased the intracellular levels of total cholesterol (TC) and triglyceride (TG) in FFA-treated primary rat hepatocytes and human HepG2 cell lines in vitro. Furthermore, oil red staining studies showed that 3Ac-OA caused dose-dependent decrease in the number of lipid droplets in FFA-treated primary rat hepatocytes. SD rats were fed a high fat diet (HFD) for 6 weeks and subsequently treated with 3Ac-OA (60, 30, 15 mg·kg-1·d-1) for 4 weeks. 3Ac-OA administration significantly decreased the body weight, liver weight and serum TC, TG, LDL-C levels in HFD rats. Furthermore, 3AcOA administration ameliorated lipid accumulation and cell apoptosis in the liver of HFD rats. Using adipokine array analyses, we found that the levels of 11 adipokines (HGF, ICAM, IGF-1, IGFBP-3, IGFBP-5, IGFBP-6, lipocalin-2, MCP-1, M-CSF, Pref-1 and RAGE) were increased by more than twofold in the serum of 3Ac-OA-treated rats, whereas ICAM, IGF-1 and lipocalin-2 had levels increased by more than 20-fold. Moreover, 3Ac-OA administration significantly increased the expression of glucose transporter type 2 (GLUT-2) and low-density lipoprotein receptor (LDLR), as well as the phosphorylation of AMP-activated protein kinase (AMPK), protein kinase B (AKT) and glycogen synthase kinase 3ß (GSK-3ß) in the liver tissues of HFD rats. In conclusion, this study demonstrates that 3Ac-OA exerts a protective effect against hyperlipidemia in NAFLD rats through AMPK-related pathways.

[Effects of Nitrogen Application on Selenium Uptake, Translocation and Distribution in Winter Wheat].

In order to better understand the effects of nitrogen application on accumulation, translocation and distribution of selenium in winter wheat and to provide theoretical reference for reasonable nitrogen application and increasing selenium content of grains. A pot experiment was carried out under greenhouse conditions with Se1 (0.74 mg·kg-1) or Se2 (2.60 mg·kg-1) levels of selenium, and each Se treatment was supplied with N1 (100 mg·kg-1) or N2 (200 mg·kg-1) levels of nitrogen, respectively. Selenium concentrations and biomass amounts of different parts of wheat were determined at jointing and maturity stage. The results showed that grain yield increased with increasing nitrogen levels by 13.2% and 24.0% in Se1 and Se2 treatment, respectively. Regardless of N rate, Se concentration of wheat increased with raising Se amended rate (P<0.01). Increasing nitrogen application could promote Se uptake of root and thus increase the selenium concentration of wheat grains and leaves, which was greater in Se1 treatment than in Se2 treatments. Se concentrations in wheat grain increased by 22.6% and 12.1% with the increasing N application rate in low and high Se treatment, respectively. The distribution ratios of Se in each organ ranked the same as BCFs, following the order of leaf > grain > glume > root. Increasing N fertilization increased the distribution ratio of Se in grains by 11.1% and 25.9% in low and high selenate treatments, respectively. High nitrogen fertilization could promote uptake and translocation of Se in wheat under low Se conditions, and improve Se use efficiency as well in the agricultural production.

Asiatic acid mitigates hyperglycemia and reduces islet fibrosis in Goto-Kakizaki rat, a spontaneous type 2 diabetic animal model.

The Goto-Kakizaki (GK) rat is a spontaneous type 2 diabetic animal model, which is characterized by a progressive loss of beta islet cells with fibrosis. In the present study, the hypoglycemic effect of asiatic acid (AA) in GK rats was examined. GK rats receiving AA at a daily dose of 25 mg·kg(-1) for four weeks showed a significant reduction in blood glucose levels. Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose (CMC-Na) solution for the same periods and used as control. Compared to the normal Wistar rats, GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level (P < 0.01) and insulin level (P < 0.05). Furthermore, the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats. Fibronectin, a key protein related to islet fibrosis, was over-expressed in GK rats, which was reversed significantly by AA treatment (P < 0.05). These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes, which may play a role in the prevention of islets dysfunction.

Correlation of high delta-like ligand 4 expression with peritumoral brain edema and its prediction of poor prognosis in patients with primary high-grade gliomas.

OBJECT: Peritumoral brain edema (PTBE) is a common phenomenon associated with high-grade gliomas (HGGs). In this study, the authors investigated the expression of Notch delta-like ligand 4 (DLL4) and its correlation with PTBE and prognosis in patients with an HGG. METHODS: Tumors from 99 patients with HGG were analyzed for DLL4 expression using immunohistochemistry. PTBE on preoperative MR images and the relationship between PTBE and DLL4 expression were evaluated. The effect of DLL4 on patient prognosis was assessed by using Kaplan-Meier survival and Cox proportional hazard models. RESULTS: Immunohistochemistry results revealed that the expression of DLL4 was distributed primarily within the cytoplasm of tumor vascular endothelial cells and seldom detected in tumor cells. DLL4 expression was correlated positively with the degree of edema (r = 0.845 and p < 0.001, Spearman's test). In addition, DLL4 was an independent predictor of prognosis in patients with HGGs (p = 0.001). CONCLUSIONS: DLL4 expression was correlated positively with the degree of PTBE and was an independent unfavorable prognostic indicator in patients with HGG.