Proliferative Activity and Neuroprotective Effect of Ligustrazene Derivative by Irritation of Vascular Endothelial Growth Factor Expression in Middle Cerebral Artery Occlusion Rats

Purpose: To investigate the proliferative activity and neuroprotective effect of a newly identified ligustrazine derivative (4-((3,5,6-trimethylpyrazine-2 yl)methoxyl)-3-methox-ybenzoic acid-3,5,6- trimethylpyrazin- 2-methyl ester, T VA) and the possible mechanism related to vascular endothelial growth factor (VEGF) in cerebral ischemic injury.Methods: The pharmacological activity of T-VA was evaluated using MTT ((3 (4,5-dimethylthiazolyl2- yl)-2,5-diphenyltetrazolium bromide)) assay, while cellular morphology was observed with hematoxylin and eosin (HE) staining. Chick chorioallantoic membrane (CAM) model, immuno-histochemical analysis, and enzyme-linked immunosorbent assay (ELISA) were used to determine the expression of VEGF. Middle cerebral artery occlusion (MCAO) model was used to investigate both VEGF expression and the survival rate after treatment with T-VA.Results: T-VA promoted neuron activity, and the doses of 15 and 30 μM showed more significant effect (p < 0.05). The viability of PC12 cells increased significantly in T-VA (30 and 60 μM) groups (p < 0.05) and increased in a dose dependent manner. Immunohistochemical analysis showed stimulated VEGF expression, and CAM model results showed that T-VA (20 mg/egg) significantly promoted microangiogenesis (p < 0.01). Moreover, in MCAO model, the survival rate of T-VA (60 mg/kg) group reached 86.7 % while for the ischemia group it was 60.0 %. In addition, ELISA results showed that T-VA promoted the expression of VEGF (p < 0.05).Conclusion: These findings indicate that T-VA helps to prevent ischemic injury by increasing VEGF expression.Keywords: Ligustrazine, Neuron, PC12 cell, Chick Chorioallantoic Membrane, Middle Cerebral Artery Occlusion, Vascular Endothelial Growth Facto

The Calcineurin-TFEB-p62 Pathway Mediates the Activation of Cardiac Macroautophagy by Proteasomal Malfunction

Rationale: The ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway (ALP) are pivotal to proteostasis. Targeting these pathways is emerging as an attractive strategy for treating cancer. However, a significant proportion of patients who receive a proteasome inhibitor-containing regime show cardiotoxicity. Moreover, UPS and ALP defects are implicated in cardiac pathogenesis. Hence, a better understanding of the cross-talk between the two catabolic pathways will help advance cardiac pathophysiology and medicine.Objective: Systemic proteasome inhibition (PSMI) was shown to increase p62/SQSTM1 expression and induce myocardial macroautophagy. Here we investigate how proteasome malfunction activates cardiac ALP.Methods and Results: Myocardial macroautophagy, transcription factor EB (TFEB) expression and activity, and p62 expression were markedly increased in mice with either cardiomyocyte-restricted ablation of Psmc1 (an essential proteasome subunit gene) or pharmacological PSMI. In cultured cardiomyocytes, PSMI-induced increases in TFEB activation and p62 expression were blunted by pharmacological and genetic calcineurin inhibition and by siRNA-mediated Molcn1 silencing. PSMI induced remarkable increases in myocardial autophagic flux in wild type (WT) mice but not p62 null (p62-KO) mice. Bortezomib-induced left ventricular wall thickening and diastolic malfunction was exacerbated by p62 deficiency. In cultured cardiomyocytes from WT mice but not p62-KO mice, PSMI induced increases in LC3-II flux and the lysosomal removal of ubiquitinated proteins. Myocardial TFEB activation by PSMI as reflected by TFEB nuclear localization and target gene expression was strikingly less in p62-KO mice compared with WT mice.Conclusions: (1) The activation of cardiac macroautophagy by proteasomal malfunction is mediated by the Mocln1-calcineurin-TFEB-p62 pathway; (2) p62 unexpectedly exerts a feed-forward effect on TFEB activation by proteasome malfunction; and (3) targeting the Mcoln1-calcineurin-TFEB-p62 pathway may provide new means to intervene cardiac ALP activation during proteasome malfunction

Generation of synthetic fingerprints

Bibliography: p. 79-85Some pages are in colour

Genome-Wide Identification of the SAMS Gene Family in Upland Cotton (Gossypium hirsutum L.) and Expression Analysis in Drought Stress Treatments

Cotton is an important commercial crop whose growth and yield are severely affected by drought. S-adenosylmethionine (SAM) is widely involved in the plant stress response and growth regulation; however, the role of the S-adenosylmethionine synthase (SAMS) gene family in this process is poorly understood. Here, we systematically analyzed the expression of SAMS genes in Upland Cotton (Gossypium hirsutum L.). A total of 16 SAMS genes were identified, each with a similar predicted structure. A large number of cis-acting elements involved in the response to abiotic stress were predicted based on promoter analysis, indicating a likely important role in abiotic stress responses. The results of qRT-PCR validation showed that GhSAMS genes had different expression patterns after drought stress and in response to drought stress. Analysis of a selected subset of GhSAMS genes showed increased expression in cultivar Xinluzhong 39 (drought resistant) when compared to cultivar Xinluzao 26 (drought-sensitive) upland cotton. This study provides important relevant information for further study of SAMS genes in drought resistance research of upland cotton, which is helpful for drought-resistance improvement of upland cotton

Evaluation of Agricultural Water Resources Carrying Capacity and Its Influencing Factors: A Case Study of Townships in the Arid Region of Northwest China

The water resources carrying capacity (WRCC) strongly determines the agricultural development in arid areas. Evaluation of WRCC is important in balancing the availability of water resources with society’s economic and environmental demands. Given the demand for sustainable utilization of agricultural water resources, we combine the water stress index and comprehensive index of WRCC and use multi-source data to evaluate agricultural WRCC and its influencing factors at the township scale. It makes up for the deficiencies of current research, such as the existence of single-index evaluation systems, limited calibration data, and a lack of a sub-watershed (i.e., township) scale. By applying multi-source data, this study expands the spatial scale of WRCC assessment and establishes a multidimensional evaluation framework for the water resources in dryland agriculture. The results indicate water stress index ranges from 0.52 to 1.67, and the comprehensive index of WRCC ranges from 0.25 to 0.70, which are significantly different in different types of irrigation areas and townships. Water quantity and water management are key factors influencing WRCC, the water ecosystem is an area requiring improvement, and the water environment is not a current constraint. Different irrigation areas and different types of townships should implement targeted measures to improve WRCC

Evaluation of Agricultural Water Resources Carrying Capacity and Its Influencing Factors: A Case Study of Townships in the Arid Region of Northwest China

The water resources carrying capacity (WRCC) strongly determines the agricultural development in arid areas. Evaluation of WRCC is important in balancing the availability of water resources with society’s economic and environmental demands. Given the demand for sustainable utilization of agricultural water resources, we combine the water stress index and comprehensive index of WRCC and use multi-source data to evaluate agricultural WRCC and its influencing factors at the township scale. It makes up for the deficiencies of current research, such as the existence of single-index evaluation systems, limited calibration data, and a lack of a sub-watershed (i.e., township) scale. By applying multi-source data, this study expands the spatial scale of WRCC assessment and establishes a multidimensional evaluation framework for the water resources in dryland agriculture. The results indicate water stress index ranges from 0.52 to 1.67, and the comprehensive index of WRCC ranges from 0.25 to 0.70, which are significantly different in different types of irrigation areas and townships. Water quantity and water management are key factors influencing WRCC, the water ecosystem is an area requiring improvement, and the water environment is not a current constraint. Different irrigation areas and different types of townships should implement targeted measures to improve WRCC

Regional Differences and Influential Factors of Open Public Space in Chinese Cities Based on Big Earth Data

Urban open public spaces that provide multiple services for residents are essential for improving life quality and urban ecosystem function and promoting healthy development, the safety of human settlements and the sustainable development of urban cities. Based on Sustainable Development Goal 11.7 of the United Nations (UN) 2030 Agenda, this study combines the big earth data with the Theil index, a coefficient of variation and Exploratory Spatial Data Analysis (ESDA) to analyze the regional differences and spatial distribution of urban open public space in 2015 for China, and uses the geographical detector to identify key factors that affect the distribution of open public spaces. The results show that (1) open public space scales in provincial-level cities have an ‘East–Central–West’ low-lying land pattern in spatial distribution, where the eastern region has a relatively larger open public space scale. (2) In the prefecture-level cities, the open public space scale increases with an increase in city size and economic development level, and the differences in urban open public space reduce with an increase in city size and increase with a decrease in the economic development level. (3) Factors including economic development level, residents’ living standards, the urbanization level and the population size have sound explanatory powers in varying degrees on the scale of open public spaces; interactions between these factors have improved the explanatory power of the scale of urban open public space

Identification of a uranium-rhodium triple bond in a heterometallic cluster

International audienceThe chemistry of d-block metal-metal multiple bonds has been extensively investigated in the past 5 decades. However, the synthesis and characterization of species with f-block metal-metal multiple bonds are significantly more challenging and such species remain extremely rare. Here, we report the identification of a uranium-rhodium triple bond in a heterometallic cluster, which was synthesized under routine conditions. The uranium-rhodium triple-bond length of 2.31 angstrom in this cluster is only 3% longer than the sum of the covalent triple-bond radii of uranium and rhodium (2.24 angstrom). Computational studies reveal that the nature of this uranium-rhodium triple bond is 1 covalent bond with 2 rhodium-to-uranium dative bonds. This heterometallic cluster represents a species with f-block metal-metal triple bond structurally authenticated by X-ray diffraction. These studies not only demonstrate the authenticity of the uranium-metal triple bond, but also provide a possibility for the synthesis of other f-block metal-metal multiple bonds. We expect that this work may further our understanding of the bonding between uranium and transition metals, which may help to design new d-f heterometallic catalysts with uranium-metal bonds for small-molecule activation and to promote the utilization of abundant depleted uranium resources