Response of "Glacier-Runoff" system in a typical monsoonal temperate glacier region, Hailuogou Basin in Mt. Gongga of China, to global warming

International audienceThe method of correlation analysis and trend analysis were used in this research in order to confirm the response of "glacier-runoff" system to global warming. Hailuogou glacier had retreated by 1871.8 m over the past 76 years, Hailuogou No. 2 glacier had also retreated by 1100 m. Glaciers retreats are contrary to the climatic warming trend in China and the Northern Hemisphere. Glaciers in Hailuogou basin were in the loss with a fluctuating manner since 1950s, and accumulative value of mass balance is ?10 825.5 mm water equivalent with an annual mean value of ?240.6 mm. The inverse correlation is highly significant between mass balance variation and climatic fluctuation of China and the Northern Hemisphere after 1950s. Glacier ablation is intensive with a ratio of 7.86 m yr?1. A steady rise tendency toward glaciers runoff has been observed since 1980s, and the runoff rise is mainly responsible for melt water in Hailuogou basin. It is noticeable that climatic warming not only strengthened ablation extent and enlarged ablation area, but also prolonged ablation period. Global warming is the main cause of glacier retreat, mass loss and runoff rise in Hailuogou basin

Microvascular Endothelial Cells-Derived Microvesicles Imply in Ischemic Stroke by Modulating Astrocyte and Blood Brain Barrier Function and Cerebral Blood Flow

Background Endothelial cell (EC) released microvesicles (EMVs) can affect various target cells by transferring carried genetic information. Astrocytes are the main components of the blood brain barrier (BBB) structure in the brain and participate in regulating BBB integrity and blood flow. The interactions between ECs and astrocytes are essential for BBB integrity in homeostasis and pathological conditions. Here, we studied the effects of human brain microvascular ECs released EMVs on astrocyte functions. Additionally, we investigated the effects of EMVs treated astrocytes on regulating BBB function and cerebral ischemic damage. Results EMVs prepared from ECs cultured in normal condition (n-EMVs) or oxygen and glucose deprivation (OGD-EMVs) condition had diverse effects on astrocytes. The n-EMVs promoted, while the OGD-EMVs inhibited the proliferation of astrocytes via regulating PI3K/Akt pathway. Glial fibrillary acidic protein (GFAP) expression (marker of astrocyte activation) was up-regulated by n-EMVs, while down-regulated by OGD-EMVs. Meanwhile, n-EMVs inhibited but OGD-EMVs promoted the apoptosis of astrocytes accompanied by up/down-regulating the expression of Caspase-9 and Bcl-2. In the BBB model of ECs-astrocytes co-culture, the n-EMVs, conversely to OGD-EMVs, decreased the permeability of BBB accompanied with up-regulation of zonula occudens-1(ZO-1) and Claudin-5. In a transient cerebral ischemia mouse model, n-EMVs ameliorated, while OGD-EMVs aggravated, BBB disruption, local cerebral blood flow (CBF) reduction, infarct volume and neurological deficit score. Conclusions Our data suggest that EMVs diversely modulate astrocyte functions, BBB integrity and CBF, and could serve as a novel therapeutic target for ischemic stroke

miR-205-5p Mediated Downregulation of PTEN Contributes to Cisplatin Resistance in C13K Human Ovarian Cancer Cells

Cisplatin resistance is a major cause of treatment failure in advanced ovarian cancer. The limited evidence shows the paradoxical regulation of miR-205 on chemotherapy resistance in cancer. Herein, we found that miR-205-5p was enormously increased in cisplatin-resistant C13K ovarian cancer cells compared with its cisplatin-sensitive OV2008 parental cells using miRNA microarrays, which was further verified by quantitative PCR. Furthermore, we confirmed that inhibition of miR-205-5p upregulated PTEN and subsequently attenuated its downstream target p-AKT, which inversed C13K cells from cisplatin resistance to sensitivity. Our data suggest that miR-205-5p contributes to cisplatin resistance in C13K ovarian cancer cells may via targeting PTEN/AKT pathway

Genotype and environment factors driven licorice growth and rhizospheric soil fungal community changes

IntroductionLicorice (Glycyrrhiza uralensis Fisch.) is a widely recognized significant form of medicine in China, with a long-standing history and extensive usage. It is considered the oldest and most prevalent herbal medicine in China. Currently, the licorice market is confronted with the primary challenges of mixed genotypes, inconsistent quality, and inadequate glycyrrhizic acid content.MethodsWe conducted field experiments to investigate the impact of various cultivation locations on the growth characteristics, active ingredients, rhizospheric soil physicochemical properties and fungal communities of licorice that ten different genotypes.ResultsThe findings indicated significant variations in these parameters across ten different genotypes of licorice originating from two distinct production regions. The growth characteristics of licorice were primarily influenced by genotype, whereas the active ingredients of licorice were mainly influenced by environmental factors and soil physicochemical properties. Furthermore, the rhizospheric soil physicochemical properties of licorice plants were more influenced by environmental factors than genotypes. Additionally, the distribution of rhizospheric soil fungi in licorice plants of the same genotype exhibited significant variations across different cultivation areas. The utilization of structural equation model synthesis reveals variations in the quantity and strength of pathways that influence the growth characteristics, active ingredients, and rhizospheric soil microbial community of licorice across different cultivation regions.DiscussionBased on the main results, according to its growth characteristics and active ingredients, Z009 proved to be the most suitable genotype for cultivation in Jingtai. From a perspective centered on the active ingredient, Z010 proved to be the most optimal genotype for licorice cultivation in both production areas. Our study aims to enhance the understanding of the ecological adaptability of various genotypes of licorice resources and to identify appropriate licorice genotypes for specific cultivation regions. This research holds significant practical implications for enhancing the yield and quality of licorice, thereby improving its overall development

Angiotensin (1–7) reverses glucose-induced islet β cell dedifferentiation by Wnt/β-catenin/FoxO1 signalling pathway

Introduction: Recent studies have shown that a decline in islet β cells quality is due to β-cell dedifferentiation, not only β-cell apoptosis. Angiotensin (1–7) [Ang(1-7)] could attenuate high glucose-induced apoptosis and dedifferentiation of pancreatic β cells by combining with MAS receptors. However, the mechanism of such action has not been elucidated. Recent studies have revealed that Wnt/β-catenin and forkhead box transcription factor O1 (FoxO1) are associated with β-cell dedifferentiation. Our study aims to explore whether the effects of Ang(1-7)on islet b cell dedifferentiation are mediated through the Wnt/β-catenin/FoxO1 pathway. Material and methods: Islet β cells were divided into 6 groups: a control group, a high-glucose group, high glucose with Ang(1-7) group, high-glucose with Ang(1-7) and A779 group, high-glucose with angiotensin(1-7) and CHIR99021 group, and high-glucose with CHIR99021 group. A779 is a kind of MAS receptor antagonist that blocks the action of Ang(1-7), and CHIR99021 is a Wnt pathway activator. The morphology of pancreatic β cells was observed in each group after 48 hours of intervention. β-cell insulin secretory function and expressions of relevant factors were measured. Results: Compared with the control group, the cell morphology became degraded in the high-glucose group and the capability of insulin secretion was reduced. Meanwhile, the expressions of mature β cells markers [pancreatic and duodenal homeobox 1 (Pdx1) and MAF BZIP transcription factor A (MafA)] were reduced, while the expressions of endocrine progenitor cells makers [octamer-binding transcription factor 4 (Oct4) and Nanog] were increased. The addition of CHIR99021 resulted in profound deep destruction of β cells compared with the high-glucose group. However, such changes were dramatically reversed following the treatment of Ang(1-7). The addition of A779 significantly inhibited the improvement caused by Ang(1-7). Conclusion: Ang(1-7) can effectively reverse β cell dedifferentiation through Wnt/β-catenin/FoxO1 pathway. It might be a new strategy for preventing and treating diabetes

Unveiling the spatial-temporal variation of urban land use efficiency of Yangtze River Economic Belt in China under carbon emission constraints

Under the constraint of carbon emission, measuring and analyzing the spatial-temporal evolution characteristics of urban land use efficiency in the Yangtze River Economic Belt is the inherent requirement of its ecological protection and sustainable development. In this paper, we calculated the urban land use efficiency of 107 cities in the Yangtze River Economic Belt from 2006 to 2020 by using the SBM-Undesirable model with unexpected output, and analyzed its temporal evolution trend and spatial correlation relationship by using kernel density and spatial autocorrelation method. The results showed that: except in 2020, the urban land use efficiency was generally low due to the COVID-19 epidemic, and the urban land use efficiency in other years was mostly concentrated in the middle levels, and showed a trend of slow fluctuation and rise year by year. The difference of urban land use efficiency level between regions increased, and the dispersion degree in upstream, midstream and downstream increased with each passing year. Urban land use efficiency spatial imbalance was significant, and the urban land use efficiency level of large and medium-sized cities was generally lower than that of cities with low economic development level. The spatial correlation was weak, and the global spatial autocorrelation was basically insignificant, while the local spatial agglomeration areas were mainly distributed in the upstream and downstream regions, with a small distribution range and weak spatial interaction. The distribution areas of the standard deviation ellipse were gradually flattened, and the center of gravity as a whole shift significantly to the southwest. The research results are helpful to understand the development history and future trend of urban land use efficiency in various regions, and propose that cities should consider the impact of public crisis events in advance, reasonably control the scale of land expansion, and lead coordinated development and other reasonable suggestions when formulating land use policies

FaGAPC2/FaPKc2.2 and FaPEPCK reveal differential citric acid metabolism regulation in late development of strawberry fruit

Citric acid is the primary organic acid that affects the taste of strawberry fruit. Glycolysis supplies key substrates for the tricarboxylic acid cycle (TCA cycle). However, little is known about the regulatory mechanisms of glycolytic genes on citric acid metabolism in strawberry fruits. In this study, the citric acid content of strawberry fruit displayed a trend of rising and decreasing from the initial red stage to the full red stage and then dark red stage. Thus, a difference in citric acid metabolic regulation was suspected during strawberry fruit development. In addition, overexpression of either cytoplasm glyceraldehyde-3-phosphate dehydrogenase (FxaC_14g13400, namely FaGAPC2) or pyruvate kinase (FxaC_15g00080, namely FaPKc2.2) inhibited strawberry fruit ripening and the accumulation of citric acid, leading to a range of maturity stages from partial red to full red stage. The combined transcriptome and metabolome analysis revealed that overexpression of FaGAPC2 and FaPKc2.2 significantly suppressed the expression of phosphoenolpyruvate carboxykinase (FxaC_1g21491, namely FaPEPCK) but enhanced the content of glutamine and aspartic acid. Meanwhile, the activities of PEPCK and glutamate decarboxylase (GAD) were inhibited, but the activities of glutamine synthase (GS) were increased in FaGAPC2/FaPKc2.2-overexpressed fruit. Further, functional verification demonstrated that overexpression of FaPEPCK can promote strawberry fruit ripening, resulting in a range of maturity stage from full red to dark red stage, while the citric acid synthase (CS) activities and citric acid content were significantly decreased. Overall, this study revealed that FaGAPC2/FaPKc2.2 and FaPEPCK perform an important role in reducing citric acid content in strawberry fruit, and FaGAPC2/FaPKc2.2 mainly by promoting the GS degradation pathway and FaPEPCK mainly by inhibiting the CS synthesis pathway

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets