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Osmanthus fragrans is widely grown for the purpose of urban greening and the pleasant aroma emitted from its flowers. The floral scent is determined by several monoterpenoid volatiles, such as linalool and its oxides, which are a few of the most common volatiles and the main components of the essential oils in most sweet osmanthus cultivars. In addition, the relative contents of cis - and trans -linalool oxide (furan) may affect the aromas and quality of the essential oils. MYB proteins represent the largest family of transcription factors in plants and participate in regulating secondary metabolites. Several cis -elements, especially AC-rich regions, are known to be bound by 2R-MYBs and could be found in the promoter of the enzyme genes in the terpenoid metabolic pathway. However, there has to date been no investigation into the 2R-MYB family genes involved in regulating terpenoid biosynthesis in O. fragrans . Here, 243 non-redundant 2R-MYB proteins were grouped into 33 clusters based on the phylogeny and exon-intron distribution. These genes were unevenly distributed on 23 chromosomes. Ka/Ks analysis showed that the major mode of 2R-MYB gene evolution was purifying selection. Expression analysis indicated that 2R-MYB genes in O. fragrans exhibited varied expression patterns. A total of 35 OfMYBs representing the highest per kilobase per million mapped reads in the flower were selected for quantitative real-time PCR analysis. The correlation analysis between the expression level and the contents of fragrant compounds at different flowering stages suggested that OfMYB19 / 20 exhibited remarkably positive correlation with the accumulation of cis -linalool oxides. OfMYB51 / 65 / 88 / 121 / 137 / 144 showed significantly negative correlations with one or more linalool oxides. Characterization of these proteins revealed that OfMYB19 and OfMYB137 were localized in the nuclei, but did not show transcriptional activation in the yeast system, which suggested that they may be bound to other transcription factors to exert regulatory functions. These findings provide useful information for further functional investigation of the 2R-MYBs and offer a foundation for clarifying the 2R-MYB transcription factors involved in the molecular mechanism of the regulation of monoterpenoid biosynthesis in Osmanthus fragrans .

Background and Objective: A previous study reported alterations in the intestinal microbiota in patients with Graves' orbitopathy (GO). Thyrotropin receptor autoantibody (TRAb) stimulates orbital and periorbital tissues and plays a pivotal role in the development of GO. However, the association between gut microbiota and TRAb in GO patients has still remained elusive. In this study, we explored the relationships between gut microbiota and GO-related traits, in which we applied a metabolic-network-driven analysis to identify GO trait-related modules and extracted significant operational taxonomic units (OTUs)., Methods: In the present study, we profiled gut microbiota using 16S rRNA gene sequencing in 31 GO patients. We performed metabolic-network-driven analysis to investigate the association between gut microbiota and GO-related traits (e.g., TRAb, TGAb, and TPOAb) in the combination of microbial effects., Results: Applying microbiome network analysis of cooccurrence patterns and analysis of topological properties, we found that s_Prevotella_copri and f_Prevotellaceae showed a significant correlation with TRAb. In particular, we applied the latent class model to explore the association between gut microbiota and GO-related traits in the combination of microbial effects. It was revealed that the subjects involved in the latent class model with the higher abundance of s_Prevotella_copri and g_Bacteroides had a higher TRAb level., Conclusions: Our results revealed the potential relationships between gut microbiota and GO-related traits in the combination of microbial effects. This study may provide a new insight into the interaction between the intestinal microbiota and TRAb-associated immune responses in GO patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019 Ting-Ting Shi et al.)

Traditional Chinese medicine is planted in mountainous areas with suitable natural conditions. The planting area is complex in terrain,and the planting plots are mostly irregularly shaped. It is difficult to accurately calculate the planting area by traditional survey methods. The method of extracting Chinese herbal medicine planting area combined with remote sensing and GIS technology is of great significance for the rational development and utilization of traditional Chinese medicine resources. Taking Bletilla striata planting in Ningshan county of Shaanxi province as an example,the extraction method of planting area of traditional Chinese medicine in county was studied. High-resolution ZY-3 and GF-1 multi-spectral multi-temporal remote sensing images were used as data sources. Through field sampling,samples such as B. striata,cultivated land,forest land,water body,artificial surface,alpine meadow,etc. are collected. The spectral features,texture features and shape features of remotely identifiable objects in different planting areas and cultivated land,vegetable sheds were analyzed,confusing ground objects were eliminated and interpretation marks were establish. The method of visual interpretation is used to realize the extraction of B. striata planting areas,and the B. striata planting area are calculated by combining GIS technology. The results showed that the method of visual interpretation,using high-resolution ZY-3 and GF-1 multi-spectral multi-temporal remote sensing image data extracted the planting area of 403.05 mu. It can effectively extract the B. striata planting area in research region.

In order to solve the problem of manual area measurement,the traditional methods of medicinal planting area statistics are difficult to meet the needs of rapid area survey application. This paper uses the UAV remote sensing method with the advantages of unmanned,automatic,high efficiency,high score and short production cycle to monitor the shape of Callicarpa nudiflora. A solution for aerial photography,image data acquisition and data processing of drones were designed for characteristics and planting conditions. After data processing and statistical analysis,detailed information on the location and area of the C. nudiflora in the target area was obtained. Then the accuracy comparison analysis was carried out with the measured results of the C. nudiflora. The results show that the UAV is feasible for the monitoring of C. nudiflora,and has a good application prospect in the monitoring of Chinese herbal medicine planting.

Due to the large amount of Codonopsis pilosula planted in Weiyuan county,and the arable land area,the local medicinal materials office uses a large amount of manpower,financial resources and material resources to estimate its area every year. In order to extract the information of local Chinese medicinal materials more quickly and simply,we try to apply remote sensing technology to the extraction of Chinese medicinal materials. This paper will use Weiyuan county of Gansu province as the research area,and use the domestic ZY-3 Satellite multi-spectral remote sensing image as the data source to find out the spectral characteristics of the party's participation in other remote sensing images. The visual interpretation method was used to extract the planting area of the C. pilosula in Weiyuan county. The estimated value of the planting area of C. pilosula using satellite remote sensing technology was 75 965 mu( 1 mu≈667 m 2 ),which was basically consistent with the field survey data of the local medicinal materials office. After the accuracy verification,it was found that the precision of C. pilosula planted by visual interpretation was more than 70%. It is concluded that the satellite remote sensing technology can be used to extract the information of C. pilosula and it can provide the relevant information of the planting area of Chinese medicinal materials quickly and accurately.

The study is aimed to effectively obtain the planting area of traditional Chinese medicine resources. The herbs used as the material for traditional Chinese medicine are mostly planted in natural environment suitable mountainous areas. The UAV low altitude remote sensing data were used as the samples and the GF-2 remote sensing images were applied for the data source to extract the planting area of Salvia miltiorrhiza and Artemisia argyi in Luoning county combined with field investigation. Remote sensing satellite data of standard processing obtain specific remote sensing data coverage. The UAV data were pre-processed to visually interpret the species and distribution of traditional Chinese medicine resources in the sample quadrat. Support vector machine( SVM) was used to classify and estimate the area of traditional Chinese medicine resources in Luoning county,confusion matrix was used to determine the accuracy of spatial distribution of traditional Chinese medicine resources. The result showed that the application of UAV of low altitude remote sensing technology and remote sensing image of satellite in the extraction of S. miltiorrhiza and other varieties planting area was feasible,it also provides a scientific reference for poverty alleviation policies of the traditional Chinese medicine Industry in local areas.Meanwhile,research on remote sensing classification of Chinese medicinal materials based on multi-source and multi-phase high-resolution remote sensing images is actively carried out to explore more effective methods for information extraction of Chinese medicinal materials.

The dried roots of Panax ginseng are used as medicines. In this paper,multi-time satellite sensing image data are used for image registration by radiometric correction,atmospheric pressure correction,the data of different years were compared. The multiscale segmentation of the sensing image was successively carried out by using object-oriented method. Combining with the characteristics of the sensing image participated in the field survey,the objective was to understand the speckles of the environmental parameters distribution map of Changbai county in 2017 and 2018. The parameter area of Changbai county was calculated by using GIS spatial analysis tools. The union,erase and intersect tools of " analysis to OLS" overlay in " Arc Toolbox" were used to analyze the parametric area of Changbai county from 2017 to 2018. The results showed that the parameter area of Changbai county in 2017 was 27 400 mu( 1 mu≈667 m 2 ),and the parameter area in 2018 was 13 900 mu. The parameter area of the new park in Changbai County in 2018 was 12 500 mu,and the harvested area in 2017 was 27 000 mu. Through the analysis and study of the regional change of the park participating in the training area,it has significance for guiding the park participating in the actual production planning and layout in Changbai county in the next step.

With digital satellite remote sensing image data of GF-1,in 2018 the object-oriented classification method was used to extract Zizyphus jujuba planting area in Jia county of Shaanxi province. The results showed that the remote sensing classification method based on rule set could extract and reckon Z. jujube planting area in the study area effectively. The planting area of Z. jujube in Jia county was about 5. 34×104 hm2 and the area of consistent accuracy was 97. 92%. The method used in this study could provide a technical reference for the area extraction of the same type of medicinal materials. And it is of great significance to provide decision support for the protection and utilization of Z. jujube resources.

The planting area of Chinese medicinal materials is an important basis for formulating policies such as production and poverty alleviation of Chinese medicinal materials and is determining the quantity of medicinal materials trade. Accurately mastering the information of the distribution,area and yield of Chinese medicinal materials cultivation is the basis of the adjustment of the planting structure of traditional Chinese medicine. It is now the largest planting place of Mongolian traditional Chinese medicinal materials in Naiman banner that is belonging to Tongliao city,Inner Mongolia. It is of great significance to obtain the planting area of Mongolian Chinese medicinal materials in Naiman banner in time and effectively for the development of subsequent industries. In this study,Saposhnikovia divaricata,a medicinal plant planted in Naiman banner,was selected as an example,and the fusion 2 m resolution ZY-3 remote sensing image was used as the data source. Based on the ground survey data,the sample data of each typical ground object were selected,and the spectral characteristic curves of different ground objects were obtained,and the S. divaricata spectral information was obtained. Using the filtering texture analysis method based on probability statistics,five kinds of texture image display results under different texture filtering were compared and analyzed,and finally the S. divaricata texture features based on information entropy are determined. The distribution range and planting area of S. divaricata in Naiman banner were extracted and interpreted by using the texture and spectral information of remote sensing images. The results showed that: S. divaricata was mainly distributed in the northeast and central south of Naiman banner,and the planting area was 5 336 mu( 1 mu≈667 m 2 ). The field verification data were in good agreement with the remote sensing interpretation results,and the difference was small. It shows that the combination of spectral information and texture information can realize the discrimination of S. divaricata,and the interpretation results can provide a reference for the county to formulate the poverty alleviation action of Chinese medicinal material industry and the economic development plan of agricultural producing areas.

Due to the large amount of nutrients required during the cultivation of Angelica sinensis and in order to prevent the occurrence of pests and diseases,and the annual reduction of the planting area of Angelica and the balance of supply and demand of A. sinensis,the A. sinensis plantation adopts the rotation mode. This paper takes Wuyuan county of Gansu province as the research scope and use GF-1 Satellite data as the data source,using remote sensing technology combined with field survey results,to explore the effective method of visual interpretation for the extraction of A. sinensis planting area. A sample was selected to generate a spectrum according to different feature types. The different characteristics of A. sinensis and other features were analyzed and distinguished in remote sensing images,so that the A. sinensis planting plots were extracted and verified in remote sensing images. The results showed that the accuracy verification value of the visual interpretation method was 95. 85%. It is determined that the visual interpretation method can effectively extract the A. sinensis planting plots within the research scope and realize the comprehensive grasp of the spatial distribution information of A. sinensis.

In order to comprehensively monitor the dynamic change of Paeonia lactiflora planting area,the investigation of P. lactiflora planting area in Dangshan was carried out. It can provide reference for the planting detection of P. lactiflora in Huaibei Plain.Based on remote sensing technology,this paper extracts the planting area of P. lactiflora in Dangshan in 2018 by using the minimum distance method,maximum likelihood method,parallel hexahedron method and Mahalanobis distance method,using the remote sensing image of ZY-3 Satellite as the data source,and makes a comparative analysis with the results. The results show that the maximum likelihood method is better than the other three methods. This method can provide reference for remote sensing monitoring of P. lactiflora planting area in China.

Taking the Xiushui township of Baisha county in Hainan province as the research area,the random forest algorithm with obvious advantages in feature selection and classification extraction was used to extract the information of the Callicarpa nudiflora planting in the study area. Firstly,four kinds of different characteristic variables were generated based on World View-3 data,including spectral features,principal component features,vegetation index and texture features. Secondly,the spatial distribution of the C. nudiflora in the study area was extracted by remote sensing by random forest classification algorithm. Finally,the feature space of the random forest classification algorithm was optimized based on the feature importance to obtain the best random forest classification results,and this result is compared with the classification result of the random forest algorithm of the unoptimized feature space. The results showed that:①The overall accuracy of the C. nudiflora extracted by World View-3 image was 89. 97%,and the Kappa coefficient was 0. 84,which indicates that the random forest algorithm had higher classification accuracy and better applicability in Hainan C. nudiflora recognition.② The overall accuracy of extracting C. nudiflora with the dimension reduction feature was 90. 4,and the Kappa coefficient was 0. 85,which indicates that the random forest algorithm can effectively select features. At the same time as the feature variable data mining,the precision of the information extraction of the C. nudiflora was still guaranteed,and the operation efficiency was improved. This study provides a new idea,method and technical means for information extraction of cultivated medicinal plant resources in terms of feature selection and method selection.

Background: Mitochondrial dysfunction is an important mechanism of non-alcoholic fatty liver disease (NAFLD). Developing mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for NAFLD therapy. In China, Polygonatum kingianum (PK) has been used as a herb and food nutrient for centuries. So far, studies in which the effects of PK on NAFLD are evaluated are lacking. Our study aims at identifying the effects and mechanism of action of PK on NAFLD based on mitochondrial regulation., Methods: A NAFLD rat model was induced by a high-fat diet (HFD) and rats were intragastrically given PK (1, 2 and 4 g/kg) for 14 weeks. Changes in body weight, food intake, histological parameters, organ indexes, biochemical parameters and mitochondrial indicators involved in oxidative stress, energy metabolism, fatty acid metabolism, and apoptosis were investigated., Results: PK significantly inhibited the HFD-induced increase of alanine transaminase, aspartate transaminase, total cholesterol (TC), and low density lipoprotein cholesterol in serum, and TC and triglyceride in the liver. In addition, PK reduced high density lipoprotein cholesterol and liver enlargement without affecting food intake. PK also remarkably inhibited the HFD-induced increase of malondialdehyde and the reduction of superoxide dismutase, glutathione peroxidase, ATP synthase, and complex I and II, in mitochondria. Moreover, mRNA expression of carnitine palmitoyl transferase-1 and uncoupling protein-2 was significantly up-regulated and down-regulated after PK treatment, respectively. Finally, PK notably inhibited the HFD-induced increase of caspase 9, caspase 3 and Bax expression in hepatocytes, and the decrease of expression of Bcl-2 in hepatocytes and cytchrome c in mitochondria., Conclusion: PK alleviated HFD-induced NAFLD by promoting mitochondrial functions. Thus, PK may be useful mitochondrial regulators/nutrients to remedy mitochondrial dysfunction and alleviate NAFLD., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: The intestinal microbiota was linked to autoimmune diseases. Graves' orbitopathy (GO) is an autoimmune disease that is usually associated with Graves' disease. However, information on the microbiome of GO patients is yet lacking., Objectives: To investigate whether GO patients differ from healthy controls in the fecal microbiota., Design: A cross-sectional study., Setting: 33 patients with severe and active GO and 32 healthy controls of Han nationality were enrolled between March 2017 and March 2018., Methods: The Gut microbial communities of the fecal samples of GO patients and healthy controls were analyzed and compared by 16S rRNA gene sequencing., Results: Community diversity (Simpson and Shannon) was significantly reduced in fecal samples from patients with GO as compared to controls (p < 0.05). The similarity observed while assessing the community diversity (PCoA) proposed that the microbiota of patients with GO differ significantly from those of controls (p < 0.05). At the phyla levels, the proportion of Bacteroidetes increased significantly in patients with GO (p < 0.05), while at the genus and species levels, significant differences were observed in the bacterial profiles between the two groups (p < 0.05)., Limitations: Single-centered study design and limited fecal samples., Conclusions: The present study indicated distinctive features of the gut microbiota in GO patients. The study provided evidence for further exploration in the field of intestinal microbiota with respect to the diagnosis and treatment of GO patients by modifying the microbiota profile.

A series of novel 3-(thiophen-2-ylthio)pyridine derivatives as insulin-like growth factor 1 receptor (IGF-1R) inhibitors was designed and synthesized. IGF-1R kinase inhibitory activities and cytotoxicities against HepG2 and WSU-DLCL2 cell lines were tested. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through the inhibition of IGR-1R. Selected compounds were further screened against various kinases. Typical compound 22 (50% inhibitory concentration [IC 50 ] values, HepG2: 2.98 ± 1.11 μM and WSU-DLCL2: 4.34 ± 0.84 μM) exhibited good inhibitory activities against fibroblast growth factor receptor-2 (FGFR2), FGFR3, epidermal growth factor receptor, Janus kinase, and RON (receptor originated from Nantes), with IC 50 values ranging from 2.14 to 12.20 μM. Additionally, the cell-cycle analysis showed that compound 22 could arrest HepG2 cells in the G1/G0 phase. Taken together, all the experiments confirmed that the compounds in this series were multitarget anticancer agents worth further optimizing., (© 2019 Deutsche Pharmazeutische Gesellschaft.)

Recently published studies on the association between depression and hip fracture (HF) are inconsistent. Therefore, we performed this meta-analysis with the main aim to clarify the association between depression and HF, and also to identify possible susceptible groups. Relevant literature published until February 2019 was obtained and screened according to established inclusion criteria. Two researchers independently processed quality assessment and data extraction prior to the meta-analysis. Pooled hazard ratios (HRs) with 95%CI (confidence intervals) were calculated. To explore the sources of heterogeneity, subgroup analyses were performed based on study design, study region, NOS scores, follow-up duration, diagnostic criteria, sex, national income level, and adjustments (bone mineral density (BMD), antidepressant, calcium intake, and smoking). Ten studies with 13 estimates, involving 375,438 participants and 4576 HFs, were included. It was found that patients with depression had a higher risk of HF than non-depressed patients (HR = 1.21; 95%CI 1.11-1.31). Sensitivity analysis results show that the association is relatively stable. The studies that were not adjusted for confounders (e.g., antidepressant, BMD, calcium intake, and smoking) had higher overall HR compared to the studies that adjusted for the corresponding confounding factors. HFs are more likely to occur in European and male depression patients. This meta-analysis provided evidence of a modest positive association between depression and the risk of HFs, and the association is stronger in European and male patients. Implementation of practical measures to prevent and treat depression is of great public health significance.

Background: Previous works indicated that the stress on the endoplasmic reticulum (ER) affected nonalcoholic fatty liver disease (NAFLD). However, there is no clear evident on the effect of the regulation of ER stress by angiotensin-converting enzyme 2 (ACE2) on the prevention of NAFLD., Methods: HepG2 cells were treated with thapsigargin (Tg) or palmitic acid (PA). We analysed ACE2 expression using Western-blotting analyses. ER stress-related proteins were detected in ACE2 knockout mice and Ad-ACE2-treated db/db mice by immunofluorescence or Western-blotting analyses. In ACE2-overexpression HepG2 cells, the triglyceride (TG), total cholesterol (TC), and glycogen content were detected by assay kits. Meanwhile, the expression of hepatic lipogenic proteins (ACCα, SREBP-1c, FAS, and LXRα), enzymes for gluconeogenesis (PEPCK, G6Pase, and IRS2), and IKKβ/NFκB/IRS1/Akt pathway were analysed by Western-blotting analyses., Results: ACE2 was significantly increased in Tg/PA-induced cultured hepatocytes. Additionally, ACE2 knockout mice displayed elevated levels of ER stress, while Ad-ACE2-treated db/db mice showed reduced ER stress in liver. Furthermore, activation of ACE2 can ameliorate ER stress, accompanied by decreased TG content, increased intracellular glycogen, and downregulated expression of hepatic lipogenic proteins and enzymes for gluconeogenesis in Tg/PA-induced hepatocytes. As a consequence of anti-ER stress, the activation of ACE2 led to improved glucose and lipid metabolism through the IKKβ/NFκB/IRS1/Akt pathway., Conclusions: This is the first time documented that ACE2 had a notable alleviating role in ER stress-induced hepatic steatosis and glucose metabolism via the IKKβ/NFκB/IRS1/Akt-mediated pathway. This study may further provide insight into a novel underlying mechanism and a strategy for treating NAFLD., (© 2019 John Wiley & Sons, Ltd.)

Aim: This study investigated the association of DNA methylation with Graves' orbitopathy (GO) incidence through a combined analysis in the context of biological network to identify and validate potential genes for Chinese patients with GO., Methods: A genome-scale screening of DNA methylation was performed on the peripheral blood sample of six patients with GO and six controls. After extracting differentially methylated regions (DMRs), the study focused on two classes of genes with obviously different methylation levels: low methylated genes (LMGs) and high methylated genes (HMGs). Mutual information was applied to construct LMG- and HMG-regulated networks, and the top 10 LMGs and HMGs were extracted based on the topological properties. Then, 9 candidate genes were extracted to validate their association with GO in an expanded population (48 patients with GO vs. 24 normal controls) using single-cell methylation sequencing., Results: In the LMG-regulated network, some LMGs displayed a higher degree, such as HIST1H2AL, EFCAB1, and BOLL. Similarly, in the HMG-regulated network, some HMGs, such as MBP, ANGEL1, and LYAR, also showed a higher degree. For validation using an enlarged population, BOLL still displayed the lower methylation level whereas CDK5 and MBP still displayed the higher methylation level in patients with GO in the multivariable logistic regression analysis adjusted by age and gender ( P < 0.01)., Conclusions: BOLL, CDK5, and MBP are potential genes associated with GO. This study was novel in clinically investigating the relation of these genomic loci with GO. The findings might provide new insights into understanding this disease.

Amino acid-based compounds have attracted attention as environmentally friendly bio-based materials. Our group has recently developed a novel family of N α -acylation lysine based derivatives. We introduced long chain acyl groups at the N α position selectively by a new synthetic route that avoided the process of amino protection and deprotection. Sodium N α -octanamide lysine (C8), sodium N α -capramide lysine (C10) and sodium N α -lauramide lysine (C12) can self-assemble into vesicles spontaneously. As a result, not only do they have potential in drug delivery system but also they may be used as bio-based surfactants applied in cosmetics and other industries., Competing Interests: The authors declared that they have no conflicts of interest to this work., (This journal is © The Royal Society of Chemistry.)

Remote sensing change detection based on fractional vegetation cover (FVC) has become an important way in the research of vegetation and related ecosystems. It is difficult to meet the requirement for optical remote sensing in subtropical areas because of cloudy/rainy weather conditions. Using images from different seasons in the vegetation change detection will inevitably lead to errors in the change detection results due to the seasonal difference. To overcome this problem, we proposed a method for correcting vegetation seasonal variations by taking advantage of high temporal resolution advantage of MODIS remote sensing data and the high spatial resolution of remote sensing data. Based on the relationship between MODIS vegetation data in different seasons via regression analysis, we transformed the vegetation information of the high resolution images of corresponding years to the required season of the years. The method was applied in the Aojiang basin area of Lianjiang County in Fujian Province, China, with good results of vegetation information transformation. The results showed that after transforming vegetation information of the 2007 winter scene and 2013 spring scene of high resolution images to those of summer season, the FVC was enhanced from 66.5% to 79.7% for 2007, and from 58.6% to 77.9% for 2013. Our method effectively removed the seasonal difference of FVC and improved the accuracy of the FVC-based change detection results.

Background: The pathogenesis Graves' Orbitopathy (GO) is not yet fully understood. Here, we conducted a pathway analysis based on genome-wide DNA methylation data of Chinese GO patients to explore GO-related pathways and potential feature genes., Methods: Six GO patients and 6 age-matched control individuals were recruited, and a genome-scale screen of DNA methylation was measured using their peripheral blood sample. After extracting the differentially methylated regions (DMRs), we classified DMRs into three clusters with respect to median absolute deviation (MAD) for GO and control group, respectively. Then the extract tests were performed to identify significant pathways by comparing the counts of genes in each cluster between GO and control group in a pathway. For each significant pathway, we calculated the Methylation-based Inference of Regulatory Activity (MIRA) score to infer the regulatory activity of genes involved in the pathway. Furthermore, we took the significant pathways as the subsets and applied Random forests (RF) method to extract GO-related feature genes., Results: We identified four potential significant pathways associated with the occurrence and development of GO disease. There were Toxoplasmosis, Axon guidance, Focal adhesion, and Proteoglycans in cancer (p<0.001 or p=0.007). The identified genes involved in the significant pathways, such as LDLR (p=0.019), CDK5 (p=0.036), and PIK3CB (p=0.020), were found to be correlated with GO phenotype., Conclusion: Our study suggested pathway analyses can help understand the potential relationships between the DNA methylation level of some certain genes and their regulation in Chinese GO patients.

Glucose-stimulated insulin secretion from islet β cells is mediated by K ATP channels. However, the role of non-K ATP K + channels in insulin secretion is largely unknown. Here, we show that a non-K ATP K + channel, KCNH6, plays a key role in insulin secretion and glucose hemostasis in humans and mice. KCNH6 p.P235L heterozygous mutation co-separated with diabetes in a four-generation pedigree. Kcnh6 knockout (KO) or Kcnh6 p.P235L knockin (KI) mice had a phenotype characterized by changing from hypoglycemia with hyperinsulinemia to hyperglycemia with insulin deficiency. Islets from the young KO mice had increased intracellular calcium concentration and increased insulin secretion. However, islets from the adult KO mice not only had increased intracellular calcium levels but also had remarkable ER stress and apoptosis, associated with loss of β cell mass and decreased insulin secretion. Therefore, dysfunction of KCNH6 causes overstimulation of insulin secretion in the short term and β cell failure in the long term., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Serum alanine aminotransferase (ALT) is a biomarker of hepatocyte damage. However, the relationship between normal range of serum ALT level and metabolic syndrome (MetS) has not been completely understood. This study aimed to investigate the correlation between normal range of serum ALT level and MetS.A total of 2453 participants from the Beijing Community Pre-Diabetes study were enrolled. Multiple linear regression analysis was performed to calculate the regression coefficient. Normal serum ALT levels were divided into quartiles. Logistic regression model was used to compare the relative risk of MetS, and the receiver operating characteristic (ROC) curve to calculate the optimal ALT boundary value for predicting MetS.The frequency of MetS increased with the ALT level within the normal range. Compared with the first group, the risk of MetS was greater in the other quartiles of ALT level in males, the difference was significant for the fourth group. For females, the risk of MetS increased with ALT level within the normal range as well, with all differences showing statistical significance. The optimal ALT boundary value of the ROC curve for males and females was 24.5 and 14.5 U/L, respectively.ALT was related to metabolic factors and used as one of the indicators to assess the morbidity risk of metabolic diseases.

Chemotherapy represents an important treatment option for colorectal cancer (CRC), but only half of the patients benefit from these regimens. We explored the potential predicting value and mechanism of PIK3CA mutation in CRC chemotherapy. CRC specimens from 440 patients were retrospectively collected and examined with a fluorescence PCR-based method. The correlation of first-line chemotherapy response and PIK3CA mutation was evaluated according to follow-up and medical records. The underlying mechanism of PIK3CA mutation in chemotherapy resistance was assessed with CRC tumors and primary cells. The mutation frequency of the PIK3CA gene in CRC patients was 9.55%, which was correlated with late TNM staging and lower histological grade. The CRC patients with PIK3A mutation showed worse response to first-line chemotherapy than those without PIK3CA mutation. PIK3A mutation tumor cells showed poor sensitivity to first-line chemotherapy in vitro and in vivo. PIK3CA mutation induced PI3K/Akt signaling activation to increase LGR5 + CRC stem cells survival and proliferation, from which lead to chemotherapy resistance. Furthermore, PIK3CA mutation /LGR5 + expression was an independent detrimental factor for CRC patients. Our findings indicated that PIK3CA mutation induced PI3K/Akt activation contributed to CRC stem cells survival and proliferation, from which cells further resistance to chemotherapy. PIK3CA mutation /LGR5 + expression was a potential biomarker for monitoring chemotherapy resistance in CRC.

Osmanthus fragrans , or "RiXiangGui", is an ornamental, woody, evergreen plant that is cultivated widely because it blooms recurrently and emits a strong fragrance. Recently, the germplasm resources, classification, and aroma compositions of O . fragrans have been investigated. However, the molecular mechanisms of the floral scent formation and regulation have remained largely unknown. To obtain a global perspective on the molecular mechanism of the aroma formation during blooming, nine RNA Sequencing (RNA-Seq) libraries were constructed from three flowering stages: The initial, full, and final flowering stage. In short, a total of 523,961,310 high-quality clean reads were assembled into 136,611unigenes, with an average sequence length of 792 bp. About 47.43% of the unigenes (64,795) could be annotated in the NCBI non-redundant protein database. A number of candidate genes were identified in the terpenoid metabolic pathways and 1327 transcription factors (TFs), which showed differential expression patterns among the floral scent formation stages, were also identified, especially OfMYB1 , OfMYB6 , OfWRKY1 , and OfWRKY3 , which could play critical roles in the floral scent formation. These results indicated that the floral scent formation of O . fragrans was a very complex process which involved a large number of TFs. This study provides reliable resources for further studies of the O.fragrans floral scent formation.

Objective: Graves' orbitopathy (GO) is an inflammatory orbital disease of autoimmune origin with the potential to cause severe functional and psychosocial effects. The pathogenesis has not been fully elucidated. We investigated whether DNA methylation was associated with GO incidence in Chinese patients., Materials and Methods: Six GO patients and six age-matched controls were recruited, and genome-wide DNA methylation patterns were analyzed in their peripheral blood. t tests were performed to determine differential methylated sites in genomic regions and the univariable logistic regression analyses was performed to evaluate their risk with GO incidence. Cluster analysis and principal component analysis (PCA) were performed to determine the effects of the extracted differentially methylated sites., Results: One hundred and forty-eight differentially methylated sites were identified, including CD14 (fold change = 4.31, p = 0.005), IL17RE (fold change = 2.128, p = 0.005), and DRD4 (fold change = 0.25, p = 0.004), and were supported by cluster and PCA analyses. Univariable logistic regression analyses showed that the methylation patterns at 12 loci were associated with GO incidence. The relative risk per 1% decrease in methylation at ZCCHC6 and GLI3 was 0.15 (95% CI 0.03-0.91; p = 0.039) and 0.65 (95% CI 0.42-0.98; p = 0.042), respectively. Pearson correlation analyses demonstrated that methylation levels at IL17RE were positively associated with Clinical Activity Score (CAS) (r = 0.967, p < 0.05)., Conclusions: Our results demonstrate that differential methylation levels at analyzed sites (genes) may be risk markers of GO. DNA methylation analysis could provide new insights into understanding the disease and provide new treatment strategies for GO in Chinese patients.

Mitochondrial metabolism plays an essential role in the regulation of insulin release and glucose homeostasis. Evidence demonstrated that the angiotensin-converting enzyme 2 (ACE2) participates in the regulation of glucose metabolism, however, its role in mitochondrial metabolism remains unclear. The purpose of our study was to determine if ACE2 can regulate mitochondrial function in pancreatic β-cells. We found that ACE2 over-expression restored glucose-stimulated insulin secretion (GSIS) and mitochondrial membrane potential (MMP) in the presence of H 2 O 2 in INS-1 cells. PCR array demonstrated that ACE2 over-expression up-regulated 67 mitochondria-related genes in INS-1 cells. In pancreatic islets, ACE2 ablation attenuated intracellular calcium influx with a decrease in GSIS. Ace2 -/y mice islets exhibited impaired mitochondrial respiration and lower production of ATP, along with decreased expression of genes involved in mitochondrial oxidation. In islets from db/db mice, ACE2 over-expression increased intracellular calcium influx and restored impaired mitochondrial oxidation, potentially causing an increase in GSIS. These results shed light on the potential roles of ACE2 in mitochondrial metabolism, moreover, may improve our understanding of diabetes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The herbs used as the material for traditional Chinese medicine are always planted in the mountainous area where the natural environment is suitable. As the mountain terrain is complex and the distribution of planting plots is scattered, the traditional survey method is difficult to obtain accurate planting area. It is of great significance to provide decision support for the conservation and utilization of traditional Chinese medicine resources by studying the method of extraction of Chinese herbal medicine planting area based on remote sensing and realizing the dynamic monitoring and reserve estimation of Chinese herbal medicines. In this paper, taking the Peucedanum praeruptorum planted area in Ningguo prefecture of Anhui province as an example, the multispectral remote sensing images that include Landsat-8 with a 30 m resolution and China-made GF-1 with a 16 m resolution were used as data source. Since the spectral characteristics of P. praeruptorum in the two periods are different from those of other crops, the changes of the images at two stages in the same year could be used to extract the P. praeruptorum planted area intercropped in cultivated land. Then the texture and spectral characteristics of young pecan trees were used to extract the P. praeruptorum planted area intercropped in woodland. The results showed that the extracted area of planted P. praeruptorum with the original imagery of 30 m spatial resolution and 16 m spatial resolution was 25 635.43,24 585.43 mu, respectively., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The herbs used as the material for traditional Chinese medicine are always planted in the mountainous area where the natural environment is suitable. As the mountain terrain is complex and the distribution of planting plots is scattered, the traditional survey method is difficult to obtain accurate planting area. It is of great significance to provide decision support for the conservation and utilization of traditional Chinese medicine resources by studying the method of extraction of Chinese herbal medicine planting area based on remote sensing and realizing the dynamic monitoring and reserve estimation of Chinese herbal medicines. In this paper, taking the Panax notoginseng plots in Wenshan prefecture of Yunnan province as an example, the China-made GF-1multispectral remote sensing images with a 16 m×16 m resolution were obtained. Then, the time series that can reflect the difference of spectrum of P. notoginseng shed and the background objects were selected to the maximum extent, and the decision tree model of extraction the of P. notoginseng plots was constructed according to the spectral characteristics of the surface features. The results showed that the remote sensing classification method based on the decision tree model could extract P. notoginseng plots in the study area effectively. The method can provide technical support for extraction of P. notoginseng plots at county level., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Dao-di herbs are preferred by long-term clinical application of Chinese medicine, they are produced in a specific area and affected by the specific production and processing methods. Dao-di herbs have a high reputation, compared with other regions produced by the same kind of herbs with good quality, good efficacy and stable quality characteristics. Geo-herbal is a unique concept that has been formed by the history of Chinese civilization for thousands of years and the history of Chinese medicine. According to the definition of geo-herbal, it can be seen that there are some differences in the quality and efficacy of the same kind of medicinal herbs in different regions, and there is some similarity in the specific area. In this study, based on the content of artemisinic acid in sampling points and its potential environmental factors, the effects of geographical environment factors on the spatial distribution of artemisinic acid content in Artemisia annua were studied by using the geophysical model. The results show that the spatial distribution of artemisinic acid content is the result of a combination of multiple factors. The effects of environmental factors on the spatial distribution of artemisinic acid were in the order of soil type (0.233)> radiation (0.208)> vegetation type (0.192)> elevation (0.171)> sunshine (0.170)> annual mean temperature (0.153) >annual precipitation (0.111)> slope (0.110)> relative humidity. Among them, the soil type and the amount of radiation are the main influencing factors, and the main influencing area is in the soil type as the initial soil and the average annual radiation of 1 200-1 400 kWh•m⁻². The main influencing factors selected in this study can be used to monitor the spatial distribution of artemisinic acid by remote sensing technology, so as to provide the theoretical basis for the cultivation of A. annua., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

With the development of computer and image processing technology, image recognition technology has been applied to the national medicine resources census work at all stages.Among them: ①In the preparatory work, in order to establish a unified library of traditional Chinese medicine resources, using text recognition technology based on paper materials, be the assistant in the digitalization of various categories related to Chinese medicine resources; to determine the representative area and plots of the survey from each census team, based on the satellite remote sensing image and vegetation map and other basic data, using remote sensing image classification and other technical methods to assist in determining the key investigation area. ②In the process of field investigation, to obtain the planting area of Chinese herbal medicine was accurately, we use the decision tree model, spectral feature and object-oriented method were used to assist the regional identification and area estimation of Chinese medicinal materials.③In the process of finishing in the industry, in order to be able to relatively accurately determine the type of Chinese medicine resources in the region, based on the individual photos of the plant, the specimens and the name of the use of image recognition techniques, to assist the statistical summary of the types of traditional Chinese medicine resources. ④In the application of the results of transformation, based on the pharmaceutical resources and individual samples of medicinal herbs, the development of Chinese medicine resources to identify APP and authentic herbs 3D display system, assisted the identification of Chinese medicine resources and herbs identification characteristics. The introduction of image recognition technology in the census of Chinese medicine resources, assisting census personnel to carry out related work, not only can reduce the workload of the artificial, improve work efficiency, but also improve the census results of information technology and sharing application ability. With the deepening of the work of Chinese medicine resources census, image recognition technology in the relevant work will also play its unique role., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Due to the particularity of ginseng cultivation, the soil fertility of cultivated ginseng is seriously depleted, so that the cultivated ginseng land can not be reused in the short term, and the land area available for cultivating ginseng becomes less and less with the growth of ginseng cultivation time. Therefore, in order to effectively manage ginseng cultivation, and achieve the sustainable use of ginseng land, it is necessary to obtain accurate information on the distribution of ginseng planting space. In this study, the object-oriented classification method based on rule set was used to extract ginseng planting area based on the ZY-3 satellite data in Fusong county, Jilin province. Firstly, multi-scale segmentation of ZY-3 remote sensing image in the study area was made, and the optimal segmentation scale was determined on the basis of multi-scale segmentation results. Secondly, a spectral curve according to the different feature type samples was generated. The similarities and differences between ginseng plot and other types of surface features were analyzed, and a rule set based on the results of spectral analysis was established to achieve the final extraction. The results show that the object-oriented classification method based on rule set can effectively extract the ginseng planting plots in the study area, and solve the problem that the extraction result is broken compared with the traditional pixel-based classification method., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Yin Yang 1 (YY1) is a multifunctional DNA-binding transcription factor shown to be critical in a variety of biological processes, and its activity and function have been shown to be regulated by multitude of mechanisms, which include but are not limited to post-translational modifications (PTMs), its associated proteins and cellular localization. YY2, the paralog of YY1 in mouse and human, has been proposed to function redundantly or oppositely in a context-specific manner compared with YY1. Despite its functional importance, how YY2's DNA-binding activity and function are regulated, particularly by PTMs, remains completely unknown. Here we report the first PTM with functional characterization on YY2, namely lysine 247 monomethylation (K247me1), which was found to be dynamically regulated by SET7/9 and LSD1 both in vitro and in cultured cells. Functional study revealed that SET7/9-mediated YY2 methylation regulated its DNA-binding activity in vitro and in association with chromatin examined by chromatin immunoprecipitation coupled with sequencing (ChIP-seq) in cultured cells. Knockout of YY2, SET7/9 or LSD1 by CRISPR (clustered, regularly interspaced, short palindromic repeats)/Cas9-mediated gene editing followed by RNA sequencing (RNA-seq) revealed that a subset of genes was positively regulated by YY2 and SET7/9, but negatively regulated by LSD1, which were enriched with genes involved in cell proliferation regulation. Importantly, YY2-regulated gene transcription, cell proliferation and tumor growth were dependent, at least partially, on YY2 K247 methylation. Finally, somatic mutations on YY2 found in cancer, which are in close proximity to K247, altered its methylation, DNA-binding activity and gene transcription it controls. Our findings revealed the first PTM with functional implications imposed on YY2 protein, and linked YY2 methylation with its biological functions., Competing Interests: The authors declare no conflict of interest.

Through the collection and collation of the industrial sales output values of Chinese patent medicines in 31 provinces of China from 2005 to 2014,the regional distribution characteristics and changing trend of Chinese patent medicine industry in the past ten years were analyzed by using the descriptive statistical analysis method in statistics.The results showed that the industrial sales output values of Chinese patent medicines in Jilin, Shandong, Jiangxi, Sichuan and Guangdong accounted for the largest proportion of the country, while Ningxia accounted for only 0.04% of the whole country. Anhui Province had the largest fluctuations in data, and its coefficient of variation was as high as 102.03%.The average annual growth rate of the industrial sales output value of Chinese patent medicines was lowest in Ningxia, only －1.09%.Based on the statistical analysis of the industrial sales output value of Chinese patent medicines in four major economic regions, the data concentration trend was as follows： east> west> central> northeast; the data fluctuation trend was northeast> central> west> east, and the average annual growth rate from large to small was northeast> central> west> east.This study was conducive to understand the differencesin the industrial sales output value of Chinese patent medicines among various provinces and economic regions,and to lay the foundation for the correct understanding and in-depth exploration of the factors that may affect the industrial sales output value of Chinese patent medicines.This study has reference value for the management and economic research of traditional Chinese medicine resources., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objectives: To explore the criminal characteristics of forensic psychiatry expertise in depression patients and schizophrenics with homicide behavior., Methods: A total of 40 depression （depressive episode） patients and 50 schizophrenics with homicide behavior were randomly assigned into the study group and control group, respectively. Data of demographic and criminal characteristic of the two groups were collected by a self-designed questionnaire, and then were compared., Results: There were no statistical differences in age, education level and career between study and control groups （ P >0.05）. Compared with the control group, the victims in the study group were mainly the patient's children and parents, and most offenders had suicidal behavior after homicide （70%）. In study group, the motives of crime were mainly extended suicide and indirect suicide, and most offenders had attempted suicide （85%） and diminished capacity of criminal responsibility （70%）, which in control group had no capacity of criminal responsibility （56%）. Except for criminal site, there were statistical differences in other criminal characteristics between two groups （ P <0.05）., Conclusions: There are different criminal characteristics between depression patients and schizophrenics with homicide behavior in forensic psychiatry, and these characteristics should be considered when these two diagnoses are distinguished in forensic psychiatry expertise., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine)

This study was aimed to evaluate the relationship between normal serum uric acid (SUA) level and metabolic syndrome (MetS) risk. This cross-sectional study involved 1914 subjects with MetS and 3 659 healthy controls aged 18-79 years. All participants filled out questionnaires and underwent physical examination and blood sample collection for biochemical examination. Demographic and clinical characteristics data were analyzed by t-test or chi-squared test. Normal SUA levels were divided into quartiles. Associations between quartiles of normal SUA level and the risk of MetS were explored using logistic regression analysis and receiver operating characteristic (ROC) curve analysis. Values of age, waist circumference, blood lipid, blood pressure, fasting plasma glucose, SUA, and body mass index were all higher in subjects with MetS than that of healthy controls significantly. The frequency of MetS increased with SUA level within the normal range. Compared with Q1, the risk of MetS was greater in the other quartiles of SUA level in men (OR, 1.495-2.288); this difference was significant for Q3 and Q4 (p<0.05), but not for Q2. Among women, the risk of MetS also increased with SUA level within the normal range, with all differences showing statistical significance (p<0.05). The area under the ROC curve of normal SUA level for MetS presence was larger for women than for men. In conclusion, the results provide support for the use of normal SUA level as a contributing clinical predictor of MetS, especially in women., (© Georg Thieme Verlag KG Stuttgart · New York.)

Since China's reform and opening-up, the rapid growth of China's economy has greatly accelerated the expansion of built-up land, which has affected regional ecological environment to a great extent. Taking Jinjiang County of Fujian Province, one of the fastest economic-developing counties in the coastal areas of southeastern China, as a case study area, this paper focused on analyzing the rapid built-up land expansion process of the county and its impact on county's ecological quality using remote sensing techniques. Based on two Landsat images of 1996 and 2015 of Jinjiang, the built-up land of the county was extracted using the index-based built-up index (IBI) and its change was analyzed. In the meantime, the ecological status of Jinjiang was evaluated with a recently-proposed remote sensing based ecological index (RSEI) and the relationship between the built-up land dynamics and the ecological status changes of the county was quantitatively examined. The results showed that during the period from 1996 to 2015, the area of built-up land of Jinjiang had a net increase of 68.54 km 2 , a growth of 45%, and the expansion intensity was 0.55. The expansion of the built-up lands has caused overall degradation of the county's ecological quality. The mean value of RSEI of the county had declined from 0.532 in 1996 to 0.460 in 2015, a drop of13.5%. The area proportion of high ecological-quality grades also significantly fell from 39% in 1996 to 21% in 2015. The built-up land expansion intensity was negatively correlated with the ecological quality change.

Diacetyl causes an unwanted buttery off-flavor in lager beer. The production of diacetyl is reduced by modifying the metabolic pathway of yeast in the beer fermentation process. In this study, BDH2 and ILV5 genes, coding diacetyl reductase and acetohydroxy acid reductoisomerase, respectively, were expressed using a PGK1 promoter in Saccharomyces cerevisiae, which deleted one ILV2 allelic gene. Diacetyl contents and fermentation performances were examined and compared. Results showed that the diacetyl content in beer was remarkably reduced by 16.52% in QI2-KP (one ILV2 allelic gene deleted), 55.65% in QI2-B2Y (overexpressed BDH2 gene and one ILV2 allelic gene deleted), and 69.13% in QI2-I5Y (overexpressed ILV5 gene and one ILV2 allelic gene deleted) compared with the host strain S2. The fermentation ability of mutant strains was similar to that of S2. Results of the present study can lead to further advances in this technology and its broad application in scientific investigations and industrial beer production.

Purpose: Hydroxychloroquine (HCQ), the analog of chloroquine, augments the effect of chemotherapies and radiotherapy on various tumors identified in the current clinical trials. Meanwhile, the toxicity of HCQ retinopathy raises concern worldwide. Thus, the potent autophagy inhibitors are urgently needed., Methods: A systematic review was related to 'hydroxychloroquine' or 'chloroquine' with 'clinical trials,' 'retinopathy' and 'new autophagy inhibitors.' This led to many cross-references involving HCQ, and these data have been incorporated into the following study., Results: Many preclinical studies indicate that the combination of HCQ with chemotherapies or radiotherapies may enhance the effect of anticancer, providing base for launching cancer clinical trials involving HCQ. The new and more sensitive diagnostic techniques report a prevalence of HCQ retinopathy up to 7.5%. Lys05, SAR405, verteporfin, VATG-027, mefloquine and spautin-1 may be potent autophagy inhibitors., Conclusion: Additional mechanistic studies of HCQ in preclinical models are still required in order to answer these questions whether HCQ actually inhibits autophagy in non-selective tumors and whether the extent of inhibition would be sufficient to alter chemotherapy or radiotherapy sensitivity.

Objectives: To explore the characteristics of schizophrenia patients' homicide behaviors and the influences of the assessments of criminal capacity., Methods: Indicators such as demographic and clinical data, characteristics of criminal behaviors and criminal capacity from the suspects whom were diagnosed by forensic psychiatry as schizophrenia （ n =110） and normal mental （ n =70） with homicide behavior, were collected by self-made investigation form and compared. The influences of the assessments of criminal capacity on the suspects diagnosed as schizophrenia were also analyzed using logistic regression analysis., Results: There were no significant statistical differences between the schizophrenic group and the normal mental group concerning age, gender, education and marital status （ P >0.05）. There were significant statistical differences between the two groups concerning thought disorder, emotion state and social function before crime （ P <0.05） and there were significant statistical differences in some characteristics of the case such as aggressive history （ P <0.05）, cue, trigger, plan, criminal incentives, object of crime, circumstance cognition and self-protection （ P <0.05）. Multivariate logistic regression analysis suggested that thought disorder, emotion state, social function, criminal incentives, plan and self-protection before crime of the schizophrenic group were positively correlated with the criminal capacity （ P <0.05）., Conclusions: The relevant influences of psychopathology and crime characteristics should be considered comprehensively for improving the accuracy of the criminal capacity evaluation on the suspects diagnosed as schizophrenia with homicide behavior., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine)

Objective: The predictive value of microalbuminuria (MAU) for kidney damage is limited in type 2 diabetes (T2D). We studied whether a urine proteome specific for sight-threatening proliferative diabetic retinopathy (PDR) is an indicator to predict chronic renal insufficiency (CRI) in patients with T2D., Research Design and Methods: A shotgun urine proteomic analysis was performed in patients with MAU and PDR (case subjects) and in patients with MAU and a duration of T2D for >10 years but without any degree of retinopathy (control subjects). In the cohort study, 210 patients with T2D with an estimated glomerular filtration rate (eGFR) ≥80 mL/min/1.73 m 2 were followed for a median of 5.3 years. Urine proteins specific for PDR were used for predicting CRI (eGFR <60 mL/min/1.73 m 2 )., Results: The top two urine proteins with the highest difference in ratio of case subjects to control subjects were haptoglobin (8.7 times; P < 0.0001) and α-2-macroglobulin (5.7 times; P < 0.0001). In the cohort study, patients with baseline urinary haptoglobin ≥20 ng/min (haptoglobinuria) had a higher incidence of CRI than those without (hazard ratio [95% CI] 3.27 [1.41-7.58]; P = 0.006). The overall CRI rate was 3.2% for patients without haptoglobinuria or MAU, 9.5% for those with MAU, and 13.3% for those with haptoglobinuria. The highest rate for CRI (22.4%) was in patients with both MAU and haptoglobinuria (P < 0.001)., Conclusions: Urine haptoglobin, which is specific for PDR, is a novel biomarker and complement to urine albumin for predicting kidney damage in patients with T2D., (© 2017 by the American Diabetes Association.)

Objective: The aim of this study was to determine whether prenatal diagnosis of pyriform sinus cyst can improve the prognosis of this disorder., Methods: A retrospective review was performed in 15 neonates with a pyriform sinus cyst seen at a single center between 2010 and 2014. Among the 15 cases, the diagnosis was made prenatally in eight cases (PreD), while the diagnosis was made postnatally in seven cases (PostD). Neonatal outcome was compared in the two subgroups., Results: The mean gestational age at diagnosis of PreD was 27 ± 6.8 weeks, while the mean age at admission of PostD was 10.1 ± 8.8 days. Cervical mass, fever, respiratory distress, and hoarseness were common symptoms. The mean duration of postoperative mechanical ventilation was 11.5 ± 13.9 and 100.71 ± 80.0 h, respectively, in PreD and PostD (p < 0.01). The average postoperative length of stay and the length of hospital stay were 11.3 ± 3.34 and 19.6 ± 4.41 days in PreD, and 15.14 ± 8.28 and 24.14 ± 8.51 days in PostD, respectively., Conclusion: Prenatal diagnosis and timely postnatal sequential intervention were associated with less complications and shortened duration of postoperative mechanical ventilation. © 2016 John Wiley & Sons, Ltd., (© 2016 John Wiley & Sons, Ltd.)

Yin Yang 1 (YY1) is a multifunctional transcription factor shown to be critical in a variety of biological processes. Although it is regulated by multiple types of post-translational modifications (PTMs), whether YY1 is methylated, which enzyme methylates YY1, and hence the functional significance of YY1 methylation remains completely unknown. Here we reported the first methyltransferase, SET7/9 (KMT7), capable of methylating YY1 at two highly conserved lysine (K) residues, K173 and K411, located in two distinct domains, one in the central glycine-rich region and the other in the very carboxyl-terminus. Functional studies revealed that SET7/9-mediated YY1 methylation regulated YY1 DNA-binding activity both in vitro and at specific genomic loci in cultured cells. Consistently, SET7/9-mediated YY1 methylation was shown to involve in YY1-regulated gene transcription and cell proliferation. Our findings revealed a novel regulatory strategy, methylation by lysine methyltransferase, imposed on YY1 protein, and linked YY1 methylation with its biological functions.

The purpose of this study was to investigate the effect of moxifloxacin on HERG channel protein and glucose metabolism. HERG expression was investigated using immunohistochemistry. The whole-cell patch clamp method was used to examine the effect of moxifloxacin on HERG channel currents. A glucose tolerance test was used to analyze the effects of moxifloxacin on blood glucose and insulin concentrations in mice. Results show that HERG protein was expressed in human pancreatic β-cells. Moxifloxacin inhibited HERG time-dependent and tail currents in HEK293 cells in a concentration-dependent manner. The IC50 of moxifloxacin inhibition was 36.65 μmol/L. Moxifloxacin (200 mg/kg) reduced blood glucose levels and increased insulin secretion in wild-type mice at 60 min after the start of the glucose tolerance test. In contrast, moxifloxacin did not significantly alter blood glucose and insulin levels in HERG knockout mice. Serum glucose levels increased and insulin concentrations decreased in HERG knockout mice when compared to wild-type mice. The moxifloxacin-induced decrease in blood glucose and increase in insulin secretion occurred via the HERG protein; thus, HERG protein plays a role in insulin secretion.

Background. RhoJ, an endothelially expressed member of Cdc42 (cell division cycle 42) subfamily of Rho GTPase, plays an important role in endocytic pathway, adipocyte differentiation, endothelial motility, tube formation, and focal adhesion. RhoJ is a selective and effective therapeutic target in tumor tissues or retinopathy. Methods. A systematic review was related to "small Rho GTPase" or "RhoJ" with "endothelial motility, tube formation and focal adhesion" and "tumor therapy". This led to many cross-references involving RhoJ and these data have been incorporated into the following study. Results. We have grouped the role of RhoJ according to three main effects: RhoJ regulates endocytic pathway and adipocyte differentiation in early studies, and RhoJ shows an important role in endothelial cell biology; furthermore, RhoJ blockade serves as a target in tumor vasculature and enhances the effects of anticancer drug. Conclusions. More research is necessary to understand the role of RhoJ in many aspects, on the basis of current knowledge of the role of RhoJ blockade in tumor vessels, there are opportunities for the therapy of tumor, and RhoJ is expressed outside tumour vasculature and is involved in wound healing. Taking advantage of the opportunities could result in a development in tumor therapy.

The dispersal of many plants depends on transportation by birds as seed dispersers. The birds play an important role in long distance seed dispersal and may also affect seed germination. However, for plants who have many bird dispersers, the influence of dominant and non-dominant dispersers on retention time (dispersal distance) and germination remains poorly understood. In this study, we performed experiments with captive frugivorous birds and fruiting plant species to study the effects of dominant and non-dominant dispersers on seed retention time (SRT) and germination (seed germination percentage and germination speed). Our study showed a great interspecific variation in the effects of frugivorous birds on both SRT and germination. Some birds enhance the germination of a given plant species, but others do not. Generally, the dominant visitors improved the seed germination and performed longer seed retention time.

Although "histone" methyltransferases and demethylases are well established to regulate transcriptional programs and to use nonhistone proteins as substrates, their possible roles in regulation of heat-shock proteins in the nucleus have not been investigated. Here, we report that a highly conserved arginine residue, R469, in HSP70 (heat-shock protein of 70 kDa) proteins, an evolutionarily conserved protein family of ATP-dependent molecular chaperone, was monomethylated (me1), at least partially, by coactivator-associated arginine methyltransferase 1/protein arginine methyltransferase 4 (CARM1/PRMT4) and demethylated by jumonji-domain-containing 6 (JMJD6), both in vitro and in cultured cells. Functional studies revealed that HSP70 could directly regulate retinoid acid (RA)-induced retinoid acid receptor β2 (RARβ2) gene transcription through its binding to chromatin, with R469me1 being essential in this process. HSP70's function in gene transcriptional regulation appears to be distinct from its protein chaperon activity. R469me1 was shown to mediate the interaction between HSP70 and TFIIH, which involves in RNA polymerase II phosphorylation and thus transcriptional initiation. Our findings expand the repertoire of nonhistone substrates targeted by PRMT4 and JMJD6, and reveal a new function of HSP70 proteins in gene transcription at the chromatin level aside from its classic role in protein folding and quality control.

The nuclear factor κB (NF-κΒ) subunits RelA, RelB, cRel, p50, and p52 are each critical for B cell development and function. To systematically characterize their responses to canonical and noncanonical NF-κB pathway activity, we performed chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-seq) analysis in lymphoblastoid B cell lines (LCLs). We found a complex NF-κB-binding landscape, which did not readily reflect the two NF-κB pathway paradigms. Instead, 10 subunit-binding patterns were observed at promoters and 11 at enhancers. Nearly one-third of NF-κB-binding sites lacked κB motifs and were instead enriched for alternative motifs. The oncogenic forkhead box protein FOXM1 co-occupied nearly half of NF-κB-binding sites and was identified in protein complexes with NF-κB on DNA. FOXM1 knockdown decreased NF-κB target gene expression and ultimately induced apoptosis, highlighting FOXM1 as a synthetic lethal target in B cell malignancy. These studies provide a resource for understanding mechanisms that underlie NF-κB nuclear activity and highlight opportunities for selective NF-κB blockade., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Since HJ-1B was launched, 7 sets of blackbody data have been used to calculate onboard calibration coefficients, but the research work on the validation of coefficients is rare. According to the onboard calibration principle, calibration coefficients of HJ-1B thermal infrared channel on Sep 14th, 2009 were calculated with the half-width, moments and look-up table methods. MODIS was selected for the reference sensor, and algorithms of spectral match were improved between the HJ-1B thermal infrared channel and MODIS 31, 32 channels based on the spectral response divergence. The relationship of top of atmosphere (TOA) radiance between the remote sensors was calculated, based on which the surface leaving brightness temperature was calculated by Planck function to validate the brightness temperature calculated through the onboard calibration coefficients. The equivalent brightness temperature calculated by spectral response divergence method is 285.97 K, and the inversion brightness temperature calculated by half-width, moments and look-up table methods is 288.77, 274.52 and 285.97 K respectively. The difference between the inversion brightness temperature and the equivalent brightness temperature is 2.8, -11.46 and 0.02 K, respectively, which demonstrate that onboard calibration coefficients calculated by the look-up table method has better precision and feasibility.