Multi-omics provide insights into the regulation of DNA methylation in pear fruit metabolism.

BACKGROUND: Extensive research has been conducted on fruit development in crops, but the metabolic regulatory networks underlying perennial fruit trees remain poorly understood. To address this knowledge gap, we conduct a comprehensive analysis of the metabolome, proteome, transcriptome, DNA methylome, and small RNAome profiles of pear fruit flesh at 11 developing stages, spanning from fruitlet to ripening. Here, we systematically investigate the metabolic landscape and regulatory network involved. RESULTS: We generate an association database consisting of 439 metabolites and 14,399 genes to elucidate the gene regulatory network of pear flesh metabolism. Interestingly, we detect increased DNA methylation in the promoters of most genes within the database during pear flesh development. Application of a DNA methylation inhibitor to the developing fruit represses chlorophyll degradation in the pericarp and promotes xanthophyll, ß-carotene, and abscisic acid (ABA) accumulation in the flesh. We find the gradual increase in ABA production during pear flesh development is correlated with the expression of several carotenoid pathway genes and multiple transcription factors. Of these transcription factors, the zinc finger protein PbZFP1 is identified as a positive mediator of ABA biosynthesis in pear flesh. Most ABA pathway genes and transcription factors are modified by DNA methylation in the promoters, although some are induced by the DNA methylation inhibitor. These results suggest that DNA methylation inhibits ABA accumulation, which may delay fruit ripening. CONCLUSION: Our findings provide insights into epigenetic regulation of metabolic regulatory networks during pear flesh development, particularly with regard to DNA methylation.

[Efficacy and mechanism of Xuefu Zhuyu Decoction on model rats of coronary heart disease with heart blood stasis syndrome based on metabolomics].

This study investigated the effects of Xuefu Zhuyu Decoction on myocardial metabolites in a rat model of coronary heart disease with heart blood stasis syndrome and explored the therapeutic mechanism of blood circulation-promoting and blood stasis-removing therapy. SD rats were randomly divided into a sham operation group, a model group, a Xuefu Zhuyu Decoction group(14.04 g·kg~(-1)), and a trimetazidine group(5.4 mg·kg~(-1)). The sham operation group underwent thread insertion without ligation, while the other groups underwent coronary artery left anterior descending branch ligation to induce a model of coronary heart disease with heart blood stasis syndrome. Three days after modeling, drug intervention was performed, and samples were taken after 14 days of intervention. General conditions were observed, and electrocardiogram and cardiac ultrasound indices were measured. Hematoxylin-eosin(HE) staining and Masson staining were used to observe tissue pathological morphology. The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of triglyceride(TG) and total cholesterol(TC) in the serum. Ultra high performance liquid chromatography-quantitative exactive-mass spectrometry(UHPLC-QE-MS) technology was used to screen differential metabolites in myocardial tissue and conduct metabolic pathway enrichment analysis. The results showed that Xuefu Zhuyu Decoction significantly improved the general condition of the model rats, reduced heart rate and ST segment elevation in the electrocardiogram, increased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), and decreased left ventricular internal diameter in diastole(LVIDd) and left ventricular internal diameter in systole(LVIDs). HE staining and Masson staining showed that Xuefu Zhuyu Decoction effectively alleviated myocardial tissue structural disorders, inflammatory cell infiltration, and collagen fiber deposition in the model rats. ELISA results showed that Xuefu Zhuyu Decoction effectively regulated serum TG and TC levels in the model rats. There were significant differences in the metabolic phenotypes of myocardial samples in each group. Fourteen differential metabolites were identified in the Xuefu Zhuyu Decoction group, involving five metabolic pathways, including arginine and proline metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, ether lipid metabolism, and alanine, aspartate, and glutamate metabolism. Xuefu Zhuyu Decoction improved cardiac function and myocardial structural damage in the rat model of coronary heart disease with heart blood stasis syndrome, and its biological mechanism involved the regulation of lipid metabolism, choline metabolism, amino acid metabolism, energy metabolism, and protein synthesis pathways.

The Chinese medicine Xin-tong-tai granule protects atherosclerosis by regulating oxidative stress through NOX/ROS/NF-κB signal pathway.

BACKGROUND: Xin-tong-tai Granule (XTTG), a traditional Chinese medicine, has been used to treat atherosclerosis (AS), but its mechanism is poorly understood. Intriguingly, oxidative stress has been recognized as vital factors in the treatment of atherosclerosis. PURPOSE: This study aims to explore the potential mechanism of XTTG for treating AS. METHODS: An in-vivo model of AS was established by feeding ApoE-/- mice with a high-fat diet (HFD), and the Human Aortic Vascular Smooth Muscle Cells (HAVSMCs) were induced by oxidized low-density lipoprotein (ox-LDL) in vitro. After treatment, the blood lipid levels and pathological aortic changes of each group were observed, and the cell proliferation and lipid droplet aggregation in each group were evaluated. The oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) levels and related NOX/ROS/NF-κB signaling pathway indicators were observed. RESULTS: XTTG improved blood lipid levels and pathological aortic changes of ApoE-/- mice with HFD feeding, inhibited HAVSMCs proliferation and lipid droplet aggregation induced by ox-LDL, reduced MDA content, increased SOD content, inhibited NOX4 and p22phox protein expression, downregulated ROS content, inhibited IKK-α, IKK-ß, NF-κB protein and mRNA expression and the phosphorylation of NF-κB. CONCLUSION: XTTG can inhibit NOX/ROS/NF-κB signaling pathway, reduce damages caused by oxidative stress, and exert anti-AS effects.

Intelligent Chinese Medicine: A New Direction Approach for Integrative Medicine in Diagnosis and Treatment of Cardiovascular Diseases.

High mortality rates from cardiovascular diseases (CVDs) persist worldwide. Older people are at a higher risk of developing these diseases. Given the current high treatment cost for CVDs, there is a need to prevent CVDs and or develop treatment alternatives. Western and Chinese medicines have been used to treat CVDs. However, several factors, such as inaccurate diagnoses, non-standard prescriptions, and poor adherence behavior, lower the benefits of the treatments by Chinese medicine (CM). Artificial intelligence (AI) is increasingly used in clinical diagnosis and treatment, especially in assessing efficacy of CM in clinical decision support systems, health management, new drug research and development, and drug efficacy evaluation. In this study, we explored the role of AI in CM in the diagnosis and treatment of CVDs, and discussed application of AI in assessing the effect of CM on CVDs.

The NAM/ATAF1/2/CUC2 transcription factor PpNAC.A59 enhances PpERF.A16 expression to promote ethylene biosynthesis during peach fruit ripening.

Peach is a typical climacteric fruit that releases ethylene during fruit ripening. Several studies have been conducted on the transcriptional regulation of ethylene biosynthesis in peach fruit. Herein, an ethylene response factor, PpERF.A16, which was induced by exogenous ethylene, could enhance ethylene biosynthesis by directly inducing the expression of 1-aminocyclopropane-1-carboxylic acid synthase (PpACS1) and 1-aminocyclopropane-1-carboxylic acid oxidase (PpACO1) genes. Moreover, the NAM/ATAF1/2/CUC2 (NAC) transcription factor (TF) PpNAC.A59 was coexpressed with PpERF.A16 in all tested peach cultivars. Interestingly, PpNAC.A59 can directly interact with the promoter of PpERF.A16 to induce its expression but not enhance LUC activity driven by any promoter of PpACS1 or PpACO1. Thus, PpNAC.A59 can indirectly mediate ethylene biosynthesis via the NAC-ERF signaling cascade to induce the expression of both PpACS1 and PpACO1. These results enrich the genetic network of fruit ripening in peach and provide new insight into the ripening mechanism of other perennial fruits.

A HD-ZIP II HOMEBOX transcription factor, PpHB.G7, mediates ethylene biosynthesis during fruit ripening in peach.

Homeobox transcription factors belong to a superfamily that has been widely studied in plant growth and development, but little is known regarding their role in fruit development and ripening. Using a genome-wide expression analysis of homeobox (HB) genes and quantitative real-time PCR, a HD-ZIP II member, PpHB.G7, which presented higher levels of expression in ripening fruits than in developing fruits in all of the tested cultivars, was isolated from peach. Transient transformations showed that PpHB.G7 affects ethylene production and the expression of ethylene biosynthesis genes (PpACS1 and PpACO1). Both dual-luciferase and yeast one-hybrid assays confirmed that PpHB.G7 interacts with the promoters of PpACS1 and PpACO1. Thus, PpHB.G7 mediates ethylene biosynthesis by stimulating PpACS1 and PpACO1 activities. Furthermore, we also found that the other eight HB genes were differentially expressed in the developing fruits, with seven of these genes belonging to the HD-ZIP family. These results suggest that the HB genes in the HD-ZIP family play important roles in fruit development and ripening.

Multiple regulatory roles of AP2/ERF transcription factor in angiosperm.

APETALA2/ethylene response factor (AP2/ERF) transcription factor (TF) is a superfamily in plant kingdom, which has been reported to be involved in regulation of plant growth and development, fruit ripening, defense response, and metabolism. As the final response gene in ethylene signaling pathway, AP2/ERF TF could feedback modulate phytohormone biosynthesis, including ethylene, cytokinin, gibberellin, and abscisic acid. Moreover, AP2/ERF TF also participates in response to the signals of auxin, cytokinin, abscisic acid, and jasmonate. Thus, this superfamily is key regulator for connecting the phytohormonal signals. In this review, based on the evidence of structural and functional studies, we discussed the multiple regulator roles of AP2/ERF TF in angiosperm, and then constructed the network model of AP2/ERF TF in response to various phytohormonal signals and regulatory mechanism of the cross-talk.

Brief cognitive-behavioural therapy for patients in the community with schizophrenia: randomised controlled trial in Beijing, China.

BackgroundBrief cognitive-behavioural therapy (CBT) is an emerging treatment for schizophrenia in community settings; however, further trials are needed, especially in non-Western countries.AimsTo test the effects of brief CBT for Chinese patients with schizophrenia in the community (trial registration: ChiCTR-TRC-13003709).MethodA total of 220 patients with schizophrenia from four districts of Beijing were randomly assigned to either brief CBT plus treatment as usual (TAU) or TAU alone. Patients were assessed at baseline, post-treatment and at 6- and 12-month follow-ups by raters masked to group allocation.ResultsAt the post-treatment assessment and the 12-month follow-up, patients who received brief CBT showed greater improvement in overall symptoms, general psychopathology, insight and social functioning. In total, 37.3% of those in the brief CBT plus TAU group experienced a clinically significant response, compared with only 19.1% of those in the TAU alone group (P = 0.003).ConclusionsBrief CBT has a positive effect on Chinese patients with schizophrenia in the community.

[GIS platform for real-time monitoring and early warning of forestry schistosomiasis-control project: a case study in Renshou County, Sichuan Province].

OBJECTIVE: To real-timely monitor the environment in the forestry schistosomiasis control project (CFSCP) area and to early warn the status of Oncomelania hupensis snails in the schistosomiasis endemic area. METHODS: Based on ArcGIS Engine 10.1 software, the Geographic Information System (GIS) platform of the forestry schistosomiasis project of real-time monitoring, early warning and emergency management in Renshou County, Sichuan Province, was designed and established. RESULTS: The functions of the platform mainly included real-time monitoring of the environment in CFSCP area, and early warning of the crisis status of 0. hupensis snails, as well as editing the map of snail distribution, query, spatial analysis and other GIS functions. CONCLUSION: This platform could provide the scientific support to the forestry administrative department of the CFSCP area.

Design, synthesis and molecular docking of salicylic acid derivatives containing metronidazole as a new class of antimicrobial agents.

A series of novel salicylic acid derivatives containing metronidazole as Staphylococcus aureus Tyrosyl-tRNA synthetase (TyrRS) inhibitors have been synthesized and evaluated their biology activities as potential antibacterial agents. Among these compounds, compound 5r exhibited the most potent antibacterial activity against Gram-positive (S. aureus ATCC 6538 and Bacillus subtilis ATCC 6633) and Gram-negative (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 13525) with MICs of 0.39-1.57 µg/mL and showed the most potent S. aureus Tyrosyl-tRNA synthetase inhibitory with 2.3 µM. Docking simulation was performed to insert compound 5r into the crystal structure of S. aureus Tyrosyl-tRNA synthetase active site to determine the probable binding model. These results suggested that compound 5r may be a promising antibacterial agent.

[Effect of Yixintai Granule on mRNA and protein expression levels of AQP, in renal medulla of chronic heart failure rabbits].

OBJECTIVE: To explore the effect of Yixintai Granule (YG) on mRNA and protein expression levels of AQP2 in renal medulla of chronic heart failure (CHF) rabbits. METHODS: CHF rat model was established by ear marginal vein injection of adriamycin. Successfully modeled rabbits were divided into the model group, the high (8.4 g/kg), middle (4.2 g/kg), and low dose (2.1 g/kg) YG group, and the Furosemide group (2 mg/kg). Besides, a normal control group was set up. Equal volume of physiological saline was administered to rabbits of the model group and the normal control group by gastrogavage. YG at different doses was administered to rabbits of the 3 YG groups by gastrogavage. The intervention lasted for 4 weeks, once per day. After treatment the urine volume and pathomorphological changes of renal medulla tissue were observed. mRNA and its protein expression levels of AQP2 were detected. RESULTS: Compared with the normal control group, the urine volume decreased significantly, mRNA and protein expression levels of renal medulla AQP2 increased significantly in the model group (all P < 0.01). Compared with the model group, the urine volume increased significantly, and mRNA and protein expression levels of renal medulla AQP2 decreased significantly in all medicated groups (all P < 0.01). Compared with the low dose YG group, the urine volume significantly increased and the mRNA expression level of renal medulla AQP2 significantly decreased in the middle and high dose YG groups (all P < 0.01). The expression level of AQP2 protein significantly decreased in the high dose YG group (P < 0.01). Pathological changes of the renal medulla was the most obviously seen in the model group. But they were alleviated to various degrees in all medicated groups. They were more obviously attenuated in the middle and high dose YG groups. CONCLUSION: YG could improve CHF possibly through down-regulating mRNA and protein expression levels of AQP2 in renal medulla, and elevating the urine volume.

Therapeutic effects of Chinese herbal medicine against neuroendocrinological diseases especially related to hypothalamus-pituitary-adrenal and hypothalamus-pituitary-gonadal axis.

This is a systemic review of plants used traditionally for neuroendocrinological diseases related to hypothalamus-pitutary-adrenal (HPA) and hypothalamus-pitutary-gland (HPG) axis. By searching from PubMed literature search system (1950-2013), Medline (1950-2013) and CNKI (China Journals of Full-text database; 1989-2013), 105 papers met the inclusion criteria were displayed in this review. 96 herbal drugs were classified into two parts which include hormones mainly related to HPA and HPG axis. The full scientific name of each herbal medicine, dose ranges and routes, models or diseases, affect on hormones and pertinent references are presented via synoptic tables. Herbal remedies that have demonstrable the activities of hormones have provided a potential to various diseases related to neunoendocrine and deserve increased attention in future studies. This review provides a basis for herbs use in neuroendocrinological diseases. The data collected here will benefit to further research associated to herbal medicines and hormones.

[Carbon storage and carbon sink of mangrove wetland: research progress].

Mangrove forest is a special wetland forest growing in the inter-tidal zone of tropical and subtropical regions, playing important roles in windbreak, promoting silt sedimentation, resisting extreme events such as cyclones and tsunamis, and protecting coastline, etc. The total area of global mangrove forests is about 152000 km2, only accounting for 0. 4% of all forest area. There are about 230 km2 mangrove forests in China. The mangrove forests in the tropics have an average carbon storage as high as 1023 Mg hm-2, and the global mangrove forests can sequestrate about 0. 18-0. 228 Pg C a-1. In addition to plant species composition, a variety of factors such as air temperature, seawater temperature and salinity, soil physical and chemical properties, atmospheric CO2 concentration, and human activities have significant effects on the carbon storage and sink ability of mangrove forests. Many approaches based onfield measurements, including allometric equations, remote sensing, and model simulation, are applied to quantify the carbon storage and sink ability of mangrove forest wetland. To study the carbon storage and sink ability of mangrove wetland can promote the further understanding of the carbon cycle of mangrove wetland and related controlling mechanisms, being of significance for the protection and rational utilization of mangrove wetland.

Associations of self-esteem, dysfunctional beliefs and coping style with depression in patients with schizophrenia: a preliminary survey.

Psychological models of depression in schizophrenia have proposed that cognitive structures (e.g., self-esteem, dysfunctional beliefs) may have a role in the development and maintenance of depression. However, it has not been clear what the characteristics of these cognitive structures were in people with schizophrenia and whether they have an independent association with depression, especially in those from a Chinese cultural background. The present investigation examined 133 people with schizophrenia and 50 healthy controls and indicated that compared to the controls people with schizophrenia showed lower self-esteem, higher levels of dysfunctional beliefs and negative coping styles. Multiple linear regression analysis revealed that only low frustration tolerance, problem solving and self-blame were found to be the independent correlates of depression in schizophrenia. Results are discussed with the view of clinical implications of cognitive formulation and therapy for schizophrenia in China.

Complete video-assisted thoracoscopic surgery for pulmonary sequestration.

OBJECTIVE: To analyze the characteristics and technical difficulties of complete video-assisted thoracoscopic surgery (c-VATS) for treatment of pulmonary sequestration operation. METHODS: 25 cases of c-VATS lobectomy for intrapulmonary sequestration performed between January 2009 and May 2012 were reviewed. The 25 patients included 13 (52%) males and 12 (48%) females, with a mean age of 34.7 years (range, 16-62 years). Preoperative imaging by CT scan and three-dimensional reconstruction of abnormal blood vessels diagnosed 19 cases as pulmonary sequestration, misdiagnosed 1 case as pulmonary cyst syndrome, 4 cases as bronchiectasis and 1 case as benign tumor. RESULTS: All the patients underwent c-VATS excision, 16 in the left lower lobe, 7 in the right lower lobe, 1 in right middle lobe and 1 extralobar pulmonary sequestration. Vascular abnormality was observed intraoperative including the thoracic aorta in 20 cases, abdominal aorta in 2 cases, phrenic arteries and intercostal artery in 1 cases and thoracic aorta combined with abdominal aorta in 1 case. No conversion to open was achieved in all cases. The mean operating time was 114.2 mins (range, 78-156 mins), the mean blood loss was 228 mL (range, 50-3,000 mL), the mean duration of chest drainage was 3.2 days (range, 2-7 days) and the mean length of post-operative hospital stay was 6.6 days (range, 3-13 days). There was no mortality, without significant postoperative complications, were cured and discharged. Patients were followed up for 2-32 months, mean 21.4 months, with no recurrence. CONCLUSIONS: c-VATS is feasible, effective, and safe in treatment of pulmonary sequestration. It is worthy of clinical application.

Influence of ORM1 polymorphisms on the maintenance stable warfarin dosage.

PURPOSE: ORM1 is a plasma drug binding protein. Its polymorphism rs17650 (S>F) has been reported to be an important factor affecting the binding ability and effect of antiretroviral protease inhibitors. The aim of this study was to determine whether the ORM1 rs17650 polymorphism also influences warfarin therapy. METHODS: A total of 191 Chinese patients with steady-dose warfarin therapy were enrolled in this study. The patients were studied for warfarin maintenance dose, the ORM1 rs17650 polymorphism, and two polymorphisms previously demonstrated to affect warfarin response [CYP2C9 rs1057910 (3) and VKORC1 rs7294 (-1639 G>A)]. RESULTS: Warfarin dose was partially correlated with the VKORC1 rs7294, CYP2C9 rs1057910 and ORM1 rs17650 polymorphisms. Patients carrying the wild-type of these three genes (n = 96) took a mean dose of 3.0 ± 1.1 mg warfarin, which was significantly higher than that taken by the 52 S patients (2.7 ± 0.7) and 11 S S patients (2.5 ± 0.6 mg) (p = 0.048). CONCLUSION: We identified ORM1 as another polymorphic gene affecting warfarin dose requirements. ORM1 S carriers require lower maintenance doses to achieve and maintain an optimal level of anticoagulation.

[Spatial characteristics of grain size of surface sediments in mangrove wetlands in Gaoqiao of Zhanjiang, Guangdong province of South China].

Mangrove wetland is an important type of coastal wetlands, and also, an important sediment trap. Sediment is an essential medium for mangrove recruitment and development, which records the environmental history of mangrove wetlands and can be used for the analysis of material sources and the inference of the materials depositing process, being essential to the ecological restoration and conservation of mangrove. In this paper, surface sediment samples were collected along a hydrodynamic gradient in Gaoqiao, Zhanjiang Mangrove National Nature Reserve in 2011. The characteristics of the surface sediments were analyzed based on grain size analysis, and the prediction surfaces were generated by the geo-statistical methods with ArcGIS 9.2 software. A correlation analysis was also conducted on the sediment organic matter content and the mangrove community structure. In the study area, clay and silt dominated the sediment texture, and the mean content of sand, silt, and clay was (27.8 +/- 15.4)%, (40.3 +/- 15.4)%, and (32.1 +/- 11.4)%, respectively. The spatial gradient of the sediment characteristics was expressed in apparent interpolation raster. With increasing distance from the seawall, the sediment sand content increased, clay content decreased, and silt content was relatively stable at a certain level. There was a positive correlation between the contents of sediment organic matter and silt, and a negative correlation between the contents of sediment organic matter and sand. Much more sediment organic matter was located at the high tide area with weak tide energy. There existed apparent discrepancies in the characteristics of the surface sediments in different biotopes. The sediment characteristics had definite correlations with the community structure of mangroves, reflecting the complicated correlations between the hydrodynamic conditions and the mangroves.

[The variability of vegetation beginning date of greenness period in spring in the north-south transect of eastern China based on NOAA NDVI].

NDVI based on NOAA/AVHRR from 1982 to 2003 are used to monitor variable rules for the growing season in spring of vegetation in the north-south transect of eastern China (NSTEC). The following, mainly, are included: (1) The changing speed of greenness period in spring of most regions in NSTEC is slow and correlation with the year is not distinct; (2) The regions in which greenness period in spring distinctly change mainly presented an advance; (3) The regions in which inter-annual fluctuation of greenness period in spring is over 10 days were found in 3 kinds of areas: the area covered with agricultural vegetation types; the areas covered with evergreen vegetation types; the areas covered with steppe vegetation types; (4) changes of vegetation greenness period in spring have spatio-temporal patterns.