Sucrose synthase gene SUS3 could enhance cold tolerance in tomato.

Tomatoes are susceptible to damage from cold temperatures in all stages of growth. Therefore, it is important to identify genetic resources and genes that can enhance tomato's ability to tolerate cold. In this study, a population of 223 tomato accessions was used to identify the sensitivity or tolerance of plants to cold stress. Transcriptome analysis of these accessions revealed that SUS3, a member of the sucrose synthase gene family, was induced by cold stress. We further investigated the role of SUS3 in cold stress by overexpression (OE) and RNA interference (RNAi). Compared with the wild type, SUS3-OE lines accumulated less MDA and electrolyte leakage and more proline and soluble sugar, maintained higher activities of SOD and CAT, reduced superoxide radicals, and suffered less membrane damage under cold. Thus, our findings indicate that SUS3 plays a crucial role in the response to cold stress. This study indicates that SUS3 may serve as a direct target for genetic engineering and improvement projects, which aim to augment the cold tolerance of tomato crops.

Clinical application of whole exome sequencing technology in small-for-gestational-age children.

AIM: To apply whole exome sequencing (WES) for molecular diagnosis of small-for-gestational-age (SGA) children. METHODS: We retrospectively analyzed the data of 60 SGA children in our hospital, and performed developmental assessment, laboratory tests, imaging tests, and whole exome sequencing (WES), which were combined with clinical phenotypes to clarify the pathogenicity of the variant genes in the children. RESULTS: Sixty SGA children were tested, and pathogenic SGA was detected at relatively high frequencies on chromosomes 7, 8, and 22. Of these, karyotype analysis clearly suggested developmental disorders in 4 patients. Also, a case of Wiedemann-Steiner syndrome due to a de novo nonsense variant in the KMT2A gene was detected. CONCLUSIONS: The use of WES testing technology to increase the diagnosis rate of children with special SGA is conducive to the correct diagnosis and treatment of such children.

The associations among athlete gratitude, athlete engagement, athlete burnout: A cross-lagged study in China.

The purpose of this study is to explore the causal relationship among athlete gratitude, athlete engagement, athlete burnout by cross-lag analysis of longitudinal associations. Two questionnaire surveys were conducted on 352 Chinese athletes with an interval of 1 year using gratitude questionnaire, athlete engagement questionnaire and athlete burnout questionnaire. The analysis yielded four main findings. (1) The overall level of athlete gratitude and athlete engagement was high in China. Chinese athletes at master level had higher levels of gratitude and athlete engagement than athletes at I and II grades. (2) Athlete gratitude is a significant negative predictor of athlete burnout, and also a significant positive predictor of athlete engagement. (3) Athlete engagement and athlete burnout are mutually causal and can be mutually predicted. (4) Athlete gratitude indirectly affects athlete burnout through athlete engagement, and also indirectly affects athlete engagement through athlete burnout. The results of the current study demonstrated the important value of gratitude in the growth process of athletes, and clarified the mechanism of gratitude affecting athlete engagement and athlete burnout. These findings have important implications for athlete development by raising athlete gratitude, motivating athlete engagement levels and relieve athlete burnout.

Association between Urban Built Environments and Moderate-to-Vigorous Physical Activity of Adolescents: A Cross-Lagged Study in Shanghai, China.

The aim of this study was to determine the relationship between the built environment and moderate-to-vigorous physical activity (MVPA) among adolescents aged 14−16 years. This study used a cross-lagged panel analysis to investigate the relationship between the urban built environment and adolescents' MVPA in Shanghai, China. A total of 517 adolescents (275 boys and 242 girls) aged 14−17 years were recruited in Shanghai, China. Geographic information system technology was used to collect data on the built environment variables of the residential areas assessed. ActiGraphGT3X+ was used to monitor the physical activity of the adolescents at two time points (T1 and T2) spanning 2 years. The correlations between the T1 and T2 built environment variables were significant (r = 0.54−0.65, p < 0.05), and the T2 built environment was significantly better than the T1 built environment. The correlation between the T1 and T2 MVPA was significant (r = 0.28−0.56, p < 0.05), and the T2 weekend MVPA was higher than the T1 weekend MVPA. The T1 built environment could not predict the T2 weekday MVPA (ß = 0.17, p > 0.05), but it positively predicted the T2 weekend MVPA (ß = 0.24, p < 0.05). In conclusion, the urban built environment significantly affected weekend MVPA among adolescents.

DNA methylation changes in the hippocampus of learning and memory disorder offspring rats of lead exposure during pregnant and lactation period.

BACKGROUND: Pregnant female rats exposed to lead may give birth to offspring with learning and memory disorders. Many studies have shown that there are many mechanisms that cause learning and memory impairment. Epigenetic mechanisms may play an important function in the learning and memory impairment. METHODS: We examined DNA methylation changes in the hippocampus of rats with learning and memory disorder that were the offsprings of rats exposed to lead during pregnant and lactation period. The Morris Water Maze was applied as a learning and memory test, and a Roche NimbleGen's rat DNA methylation 385K Promoter Plus CpG Island Array was used for array hybridization. RESULTS: The results of the integrated navigation and spacial exploration test showed that until 21 days after birth and the lactation period, the learning and memory abilities of offsprings with lead exposure during pregnant and lactation period were significantly lower than those of the control group. The hippocampus DNA methylation levels of the three types of promoters increased compared with those of the control group. According to the Gene Ontology (GO) terms, metal ion transport, cell connections, the lamellar body, the axon bulge, and methylation of various metal transporters were found to be significantly enriched. Pathway analysis showed that the hedgehog signaling pathway, neuroactive receptor-ligand interaction with the ligase pathway, and interaction between cytokines had high methylation. CONCLUSIONS: DNA methylation of the whole genome in the hippocampus of the rats with learning and memory impairment induced by perinatal lead contact showed a lot of changes compared with that in the group of control.

Study on the Role of Paclitaxel Nano-Drug Delivery System in Inhibiting Intimal Hyperplasia and Improving Vascular Remodeling in Abdominal Aortic Injury Model.

The surface-modified paclitaxel nanoparticles were prepared to observe its inhibitory effect on the intimal and mediator proliferation and the improvement of vascular remodeling after rabbit abdominal aortic injury. First, paclitaxel nanoparticles were prepared by ultrasonic emulsification solvent evaporation method. The surface of paclitaxel nanoparticles was modified by physical adsorption, the nanoparticles were characterized and the encapsulation efficiency was evaluated. Secondly, the endometrial thickness was measured by hematoxylin and eosin staining, and a spheroid with a smooth surface was observed under a scanning electron microscope. Finally, compared with the control group, local infusion of paclitaxel nanoparticles could effectively inhibit the proliferation of vascular endothelium in a dose-dependent manner. Local intravascular infusion of paclitaxel nanoparticle suspension can effectively inhibit the proliferation of vascular endothelial cells, and its inhibitory effect increases with the increase of the concentration of nanoparticle suspension. The paclitaxel nanoparticle suspension at a concentration of 30 mg/ml can play a good inhibitory role.

Downregulating long non-coding RNA PVT1 expression inhibited the viability, migration and phenotypic switch of PDGF-BB-treated human aortic smooth muscle cells via targeting miR-27b-3p.

Long non-coding RNA Plasmacytoma Variant Translocation 1 (LncRNA PVT1) was involved in various human diseases, but its role in aortic dissection (AD) remained to be fully examined. In this study, the viability and migration of human aortic smooth muscle cells (HASMCs) were respectively measured by MTT assay and wound-healing assay. Relative phenotypic switch-related protein expressions were measured with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. An AD model was established in animals and hematoxylin-eosin (H&E) staining was used for pathological examination. We found that, in HASMCs, microRNA (miR)-27b-3p could competitively bind with PVT1. In AD, PVT1 expression was upregulated, yet that of miR-27b-3p was downregulated. Downregulating PVT1 reversed the effects of growth factor-BB (PDGF-BB) treatment on PVT1, miR-27b-3p and expressions of phenotypic switch-related markers, and cell viability and migration, while downregulating miR-27b-3p reversed the effects of downregulating PVT1. Moreover, downregulating PVT1 suppressed the effects of upregulated PVT1 and downregulated miR-27b-3p induced by AD as well as media degeneration in vivo. In conclusion, downregulating PVT1 expression suppressed the proliferation, migration and phenotypic switch of HASMCs treated by PDGF-BB via targeting miR-27b-3p.

CDKN2B-AS1 Aggravates the Pathogenesis of Human Thoracic Aortic Dissection by Sponge to miR-320d.

In the present study, the role and molecular mechanism of long noncoding RNA CDKN2B-AS1 in human thoracic aortic dissection (TAD), a highly lethal cardiovascular disease, was investigated. The expression of CDKN2B-AS1 in human TAD and normal aortic tissues of donors were examined by quantitative real-time polymerase chain reaction. RNA pull-down assay and a series of luciferase reporter assays were performed to predict the relationships between CDKN2B-AS1, miR-320d, and STAT3. Cell counting kit 8 (CCK-8), TUNEL, and western blot assays were applied to validate the biological functions of CDKN2B-AS1 in rat aortic vascular smooth muscle cells. Results showed that CDKN2B-AS1 was expressed at a higher level in human TAD than in normal aortic tissues. CDKN2B-AS1 overexpression significantly promoted apoptosis and suppressed the proliferation of vascular smooth muscle cells. CDKN2B-AS1 silence exhibited the opposite effects. Mechanistically, CDKN2B-AS1 was identified as a molecular sponge for miR-320d and positively modulated STAT3 expression via repressing miR-320d. In conclusion, our study revealed that CDKN2B-AS1 was dysregulated and displayed multiple potential functions in human TAD. These findings suggested that CDKN2B-AS1 was a novel potential therapeutic target for human TAD.

The Subchronic Toxic Effects of Mosla chinensis Maxim in Normal Rats.

BACKGROUND: The aim of this work was to study the toxic effects and target organs of Mosla chinensis Maxim (MCM) in rats and provide theoretical basis for clinical medication. METHODS: The subchronic toxicity study was conducted on 60 male and female SD rats using the fixed-dose method for the treatment groups and 20 male and female SD rats for the control. At the subchronic toxicity study, the water extract of MCM with fixed doses of 0.2 g/kg/day, 2 g/kg/day, and 20 g/kg/day was administered for 90 days intragastric, and the control group was given the same amount of distilled water. After 90 days, the general conditions of the rats were observed. Assessment on safety of the extract was conducted by a subchronic toxicity test which mainly examined alteration occurrence in gut flora and urine metabolism. RESULTS: There was no significant difference in physical signs, reactivity, and stool characteristics in the four groups. Compared with the control group, the number of red blood cells in the male 2 g/kg/day group and the female 0.2 g/kg/day group was significantly different (P < 0.05). The detection of serum biochemical indicators showed that MCM has an effect on liver and kidney function but has no physiological significance. The level of low-density lipoprotein in male rats was lower than that in the control group (P < 0.05). Compared with the control group, the blood glucose levels of female rats in the 0.2 g/kg/day, 2 g/kg/day, and 20 g/kg/day groups were significantly increased (P < 0.05). As far as the diversity of intestinal flora is concerned, feeding MCM for 90 days has an influence on the distribution of intestinal flora. The content of lactic acid bacteria increased, and the ratio of hard bacteria to Bacteroides (f/b) was also affected, but there was no significant difference. CONCLUSIONS: These findings showed that the long-term intragastric administration of the MCM is safe to use within its dose recommendation. But it could have a slight effect on the metabolism of uric acid by changing the composition of intestinal flora and affecting the metabolism of tryptophan.

Comparative study of the pyrolysis of lignocellulose and its major components: characterization and overall distribution of their biochars and volatiles.

In order to investigate the pyrolysis differences among lignocellulose and its major components, the biochars and volatiles of lignocellulose (bamboo), lignin, hemicellulose and holocellulose (from bamboo), and cellulose (from cotton linter) were studied using elemental analysis, FTIR, XRD, SEM, Py-GC/MS and TGA-FTIR. Result showed that the biochar yield of lignin (48.8%) was much higher than those of hemicellulose (21.1%), cellulose (8.3%), holocellulose (20.4%) and bamboo (15.1%), while no obvious elemental difference among these biochars was found. Results from Py-GC/MS indicated that carbonyl compounds, ethers and alcohols were the major volatiles of polysaccharide component pyrolysis, while aromatic compounds were the major volatiles of lignin pyrolysis. The pyrolysis of polysaccharide component mainly occurred at 200-400°C, while the pyrolysis of lignin happened at 300-700°C.

[Suppression subtractive hybridization for the identification of differentially expressed genes in the hippocampus of the offsprings of lead exposed female rats].

OBJECTIVE: To screen and identify differentially expressed genes in the hippocampus of the offsprings of lead exposed female rats in order to provide a theoretical basis for identifying learning and memory deficits related genes. METHODS: RNA was extracted from the hippocampus of young rats with learning and memory deficits due to maternal lead exposure. Suppression subtractive hybridization was used to identify the differentially expressed genes in the hippocampus. RESULTS: An effective subtracted library was constructed which consisted of approximately 200 clones. Sequencing for the library identified 93 clones harboring insertion fragments which included 43 different genes and 4 unknown genes. These genes might be related to learning and memory deficits due to maternal lead exposure. CONCLUSIONS: The up-regulated genes in the hippocampus of young rats from pregnant rats under lead exposure include some housekeeping genes and some proteins involved in cellular protein folding, signal transduction, stress response and DNA methylation. These proteins might be directly related to a significant reduction in learning and memory abilities in the young rats.

Synthesis and evaluation of isosteres of N-methyl indolo[3,2-b]-quinoline (cryptolepine) as new antiinfective agents.

Isosteres of cryptolepine (1) were synthesized and evaluated for their antiinfective activities. Overall, the sulfur isostere, 5-methyl benzothieno[3,2-b]quinolinium salt (5b), was equipotent to 1 and has shown no cytotoxicity at 23.8 microg/mL. Compound 5b was also found to have a broad spectrum of activity. Both the carbon and oxygen isosteres were less potent than cryptolepine. A limited library of 2-substituted analogs of 5b has been synthesized and evaluated in antifungal screens but did not show increase in potency compared to the unsubstituted 5b. Similarly, evaluation of tricyclic benzothieno[3,2-b]pyridines while showing promise in individual screens did not produce an overall increase in potency. Overall, the evaluation of the activities of 5b compared with standard antifungal/anti-protozoal agents suggests that the benzothienoquinoline scaffold could serve as a lead for optimization.

Haloperidol: towards further understanding of the structural contributions of its pharmacophoric elements at D2-like receptors.

An attempt to understand the pharmacophore-relevant position of the alcoholic moiety in haloperidol and the contributions of other pharmacophoric elements led to the re-synthesis of its tropane analogue (compound 2). An analysis of the binding data suggests that haloperidol binds to the DA receptors with the OH group in the axial position and the OH group, while not essential for binding, enhances binding especially at the D2 receptor. It also became clear that shortening the butyrophenone chain not only reduces binding affinity at the DA receptors but eliminates subtype selectivity.

The acute EPS of haloperidol may be unrelated to its metabolic transformation to BCPP+.

We have previously proposed that haloperidol's debilitating extrapyramidal symptoms (EPS) may be associated with its quaternary BCPP+ (an MPP+ like species) metabolite formed in vivo. However, recent work on D2 knock out mice suggests that haloperidol's EPS may be related to its potent D2 binding (K(i)=0.9 nM). In this study, we explore this question by synthesizing and testing an analogue (DS-27) that binds to D2 receptors with higher affinity than haloperidol, but cannot form quaternary metabolites. This study suggests that D2 affinity may be the primary underlying mechanism for acute catalepsy induction by haloperidol.

Substituted indoloquinolines as new antifungal agents.

Cryptolepine (2) possesses desirable properties to serve as a lead in developing new antifungal agents. Using SAR techniques, several analogues of cryptolepine were designed to increase potency and to broaden the antifungal spectrum over several opportunistic microorganisms. A number of 2-substituted indoloquinolines have been synthesized and evaluated in antifungal screens and several have been shown to increase potency and expand the antifungal spectrum of cryptolepine. Comparison of MICs of a number of these analogues with standard antifungal agents, shows them to be comparable to Amphotericin B and Ketoconazole.