Multiple studies demonstrated that early growth response factor 1 (EGR1) induces myocardial damage after acute myocardial infarction (AMI). Recent evidence indicates that microRNAs (miRNA) play an ...important role in exosome‐mediated cardioprotection after AMI. Bioinformatics analysis has shown that miR‐146a can regulate the expression of EGR1, so the aim of this study was to determine if miR‐146a plays a role in exosome‐mediated cardioprotection by regulation of EGR1 after AMI. Exosomes were isolated from wild‐ or miR‐146a‐modified adipose‐derived stem cells (ADSCs), and the therapeutic effect of exosomes was assessed in an AMI model in rats and hypoxic‐induced H9c2 model cells. The results showed that miR‐146a containing exosomes had more effect than the exosome treatment group on the suppression of AMI‐induced apoptosis, inflammatory response, and fibrosis in an AMI rat model. Both in vivo and in vitro experiments found that miR‐146a interacted with the 3′‐untranslated region of EGR1 and suppressed posttranscriptional EGR1 expression, which was confirmed by the luciferase reporter assay. We also found that suppressed EGR1 expression reversed AMI or hypoxia‐induced TLR4/NFκB signal activation, which played an important role in the promotion of myocardial cell apoptosis, inflammatory response, and fibrosis. Taken together, these findings suggested that exosomes derived from miR‐146a‐modified ADSCs attenuated AMI‐induced myocardial damage via downregulation of EGR1.
This study findings suggest that exosomes derived from miR‐146a‐modified adipose‐derived stem cells attenuated acute myocardial infarction‐induced myocardial damage via downregulation of an early growth response factor 1.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Non‐small cell lung cancer (NSCLC) is a primary threat to human health. Cisplatin is always in first‐line treatment of NSCLC; however, cisplatin resistance restricts the application in the clinic. ...Herein, an innovative 2D platinum delivery platform based on manganese dioxide nanosheet is presented to overcome cisplatin‐resistance and enhance theranostic efficacy in NSCLC. The photo‐induced hyperthermia of nanosheets can inhibit Pt drug efflux from the multidrug resistance‐associated protein (MRP1) repression. Then the intracellular l‐Glutathione (GSH) consumed by MnO2 nanosheets can reduce the generation of GSH‐Pt complex. Working along both lines accelerates access to the nucleus for cisplatin. Moreover, chemo‐photothermal synergistic therapy of Pt nanosheets significantly enhances therapeutic efficacy in vitro and in vivo. In addition, nanosheets can exert an on‐demand activable magnetic resonance imaging contrast effect to monitor Pt drug release. For the first time, a promising photoactivated 2D vector is provided to overcome cisplatin resistance in NSCLC therapy.
A simple 2D manganese dioxide nanosheet is presented as a cisplatin prodrug‐delivery platform to overcome cisplatin‐resistance and to enhance diagnosis and therapy efficacy in non‐small cell lung cancer therapy. This biocompatible multifunctional 2D nanosheet is a promising vector to augment the sensitivity and treatment effect of platinum drugs in the clinic.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A deep-seated flexural toppling failure of rock masses is located on the right bank upstream of the Lancang River, Southwest China. The rock masses unloaded intensely in two directions and formed ...intense toppled rock masses with lengths and widths of 1200 m and 950 m, respectively, and volumes over 1.5 × 108 m3. The toppled rock masses could be classified into three grades from surface to deep rock masses: strongly, moderately and weakly toppled rock masses. The strong unloading of rock masses during the rapid downcutting process of rivers was one of the main external factors that induced deep-seated toppling failure. The mechanism could be summarized as follows: intense unloading destroyed the structure of rock masses and weakened the mechanical properties of rock masses by forming many unloading cracks in rock masses; additionally, the stress field of the slope was further redistributed and a stress relaxation zone formed in the strong unloading zone. Then, the stresses of rock masses in the relaxation zone were dominated by gravity, and the deep-seated toppling failure formed in the strongly unloaded rock masses under the action of gravity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Beyond hemostasis, thrombosis and wound healing, it is becoming increasingly clear that platelets play an integral role in inflammatory response and immune regulation. Platelets recognize pathogenic ...microorganisms and secrete various immunoregulatory cytokines and chemokines, thus facilitating a variety of immune effects and regulatory functions. In this review, we discuss recent advances in signaling of platelet activation-related biomarkers in inflammatory settings and application prospects to apply for disease diagnosis and treatment.
Background and aims
Seed dormancy-break via cold stratification is of fundamental importance for plant adaptation to environmental conditions and response to climate change through timing ...germination, seedling emergence and consequently community dynamics. Although cold stratification requirements for dormancy break vary among species, it is not known if this variation is determined by the environmental conditions experienced by seeds or by differences among species.
Methods
We determined the soil moisture content and duration of cold stratification required for seed dormancy-break of species from alpine and desert habitats (soil moisture content: 20 and 18 species from alpine and desert habitats, respectively; duration: 16 and 16 species from the alpine and desert, respectively), and examined the correlation between environmental conditions (soil moisture content and duration of cold stratification) required for dormancy-break and seed traits.
Results
Seed germination increased and then decreased as soil moisture content or duration of cold stratification increased. The optimal and critical soil moisture content for seed dormancy-break were higher for alpine species than desert species. A positive correlation between optimal soil moisture content and seed shape was found. However, the duration of cold stratification required for dormancy-break was not related to habitat, seed mass or seed shape.
Conclusions
Our results suggest that soil moisture content rather than duration of cold stratification resulting from climate change could affect seed germination and consequently seedling emergence and establishment, especially for desert species.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aims: Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide and one of the greatest threats to public health. Tenascin C (TNC) is an extracellular matrix ...glycoprotein that is found in low concentrations in normal tissues and is enhanced by a range of cardiovascular pathologies. This study aimed to evaluate the value of TNC in assessing the severity of atherosclerosis measured by the Gensini score.Methods: A total of 157 patients with chest pains who underwent selective coronary angiography for suspected coronary atherosclerosis were enrolled. The patients were divided into the CAD group and non-CAD group according to symptoms and angiography. Demographic data and laboratory analyses were collected.Results: The mean TNC level was significantly higher in the CAD group than in the non-CAD group (p＜0.001). A significant positive correlation between TNC levels and Gensini score (p＜0.01, r=0.672) was found. ROC curve analysis demonstrated that the cutoff value for TNC at 89.48 ng/mL was well differentiated in the CAD and non-CAD groups. Furthermore, TNC was also a good predictor for a higher Gensini score (the third tertile) in the ROC curve analysis. When the cutoff was accepted as 100.91 ng/mL, the sensitivity and specificity were 82.7% and 79%, respectively.Conclusion: A significant relationship was found between the Gensini score and serum TNC level. TNC levels can be considered in risk assessments for CAD before angiography.
An old large-scale landslide with a volume of 4.6 × 10
6
m
3
located on the right bank of the Lancang River, Southwest China, was formed by the deep-seated toppling failure of a rock mass. The rock ...mass located downstream of the landslide toppled intensely with a maximum toppling depth exceeding 200 m and a volume over 1.5 × 10
8
m
3
. We studied the formation mechanism of the landslide and determined the most likely future instability range of the toppled rock mass. The results show that the toppled rock mass located downstream of the landslide could be classified into four zones, namely, highly toppled, moderately toppled, weakly toppled and normal rock mass, from the surface to the deep-seated rock mass along the slope according to three factors: the unloading intensity, variation in the occurrence of the rock layer, and toppling fracture zone. The bottom boundary of the highly toppled rock mass was limited by the depth of strong unloading of the rock mass. The landslide deposits mainly originated from the highly toppled rock mass, and the slip zone was formed based on the toppling fracture zones. The highly toppled rock mass in the rock slope located downstream of the landslide will be the most likely area of instability in the future.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Stem rot caused by Sclerotinia sclerotiorum in many important dicotyledonous crops, including oilseed rape (Brassica napus), is one of the most devastating fungal diseases and imposes huge yield loss ...each year worldwide. Currently, breeding for Sclerotinia resistance in B. napus, as in other crops, can only rely on germplasms with quantitative resistance genes. Thus, the identification of quantitative trait locus (QTL) for S. sclerotiorum resistance/tolerance in this crop holds immediate promise for the genetic improvement of the disease resistance. In this study, ten QTLs for stem resistance (SR) at the mature plant stage and three QTLs for leaf resistance (LR) at the seedling stage in multiple environments were mapped on nine linkage groups (LGs) of a whole genome map for B. napus constructed with SSR markers. Two major QTLs, LRA9 on LG A9 and SRC6 on LG C6, were repeatedly detected across all environments and explained 8.54-15.86% and 29.01%-32.61% of the phenotypic variations, respectively. Genotypes containing resistant SRC6 or LRA9 allele showed a significant reduction in disease lesion after pathogen infection. Comparative mapping with Arabidopsis and data mining from previous gene profiling experiments identified that the Arabidopsis homologous gene of IGMT5 (At1g76790) was related to the SRC6 locus. Four copies of the IGMT5 gene in B. napus were isolated through homologous cloning, among which, only BnaC.IGMT5.a showed a polymorphism between parental lines and can be associated with the SRC6. Furthermore, two parental lines exhibited a differential expression pattern of the BnaC.IGMT5.a gene in responding to pathogen inoculation. Thus, our data suggested that BnaC.IGMT5.a was very likely a candidate gene of this major resistance QTL.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diabetes is well recognized to increase the risk of heart failure, which is associated with higher mortality and morbidity. It is important for the development of novel therapeutic methods targeting ...heart failure in diabetic patients. Ferroptosis, an iron-dependent regulated cell death, has been implicated in the progression of diabetes-induced heart failure (DIHF). This study was designed to investigate the contribution of Nr2f2 to the activation of ferroptosis and mitochondrial dysfunction in DIHF. We established a diabetic model by a high-fat feeding diet combined with an intraperitoneal injection of streptozotocin. After 16 weeks, Nr2f2 expression was increased in heart tissue of DIHF mice. In vivo, DIHF mice overexpressing Nr2f2 (AAV9-cTNT-Nr2f2) exhibited severe heart failure and enhanced cardiac ferroptosis compared with DIHF control mice (AAV9-cTNT-ctrl), accompanied by mitochondrial dysfunction and aggravated oxidative stress reaction. In vitro, Nr2f2 knockdown ameliorated ferroptosis and mitochondrial dysfunction by negatively regulating PGC-1α, a crucial metabolic regulator. PGC-1α knockdown counteracted the protective effect of Nr2f2 knockdown. These data suggest that Nr2f2 promotes heart failure and ferroptosis in DIHF by modulating the PGC-1α signaling. Our study provides a new idea for the treatment of diabetes-induced heart failure.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Plant-specific TIFY proteins are widely found in terrestrial plants and play important roles in plant adversity responses. Although the genome of loquat at the chromosome level has been published, ...studies on the TIFY family in loquat are lacking. Therefore, the EjTIFY gene family was bioinformatically analyzed by constructing a phylogenetic tree, chromosomal localization, gene structure, and adversity expression profiling in this study.
Twenty-six EjTIFY genes were identified and categorized into four subfamilies (ZML, JAZ, PPD, and TIFY) based on their structural domains. Twenty-four EjTIFY genes were irregularly distributed on 11 of the 17 chromosomes, and the remaining two genes were distributed in fragments. We identified 15 covariate TIFY gene pairs in the loquat genome, 13 of which were involved in large-scale interchromosomal segmental duplication events, and two of which were involved in tandem duplication events. Many abiotic stress cis-elements were widely present in the promoter region. Analysis of the Ka/Ks ratio showed that the paralogous homologs of the EjTIFY family were mainly subjected to purifying selection. Analysis of the RNA-seq data revealed that a total of five differentially expressed genes (DEGs) were expressed in the shoots under gibberellin treatment, whereas only one gene was significantly differentially expressed in the leaves; under both low-temperature and high-temperature stresses, there were significantly differentially expressed genes, and the EjJAZ15 gene was significantly upregulated under both low- and high-temperature stress. RNA-seq and qRT-PCR expression analysis under salt stress conditions revealed that EjJAZ2, EjJAZ4, and EjJAZ9 responded to salt stress in loquat plants, which promoted resistance to salt stress through the JA pathway. The response model of the TIFY genes in the jasmonic acid pathway under salt stress in loquat was systematically summarized.
These results provide a theoretical basis for exploring the characteristics and functions of additional EjTIFY genes in the future. This study also provides a theoretical basis for further research on breeding for salt stress resistance in loquat. RT-qPCR analysis revealed that the expression of one of the three EjTIFY genes increased and the expression of two decreased under salt stress conditions, suggesting that EjTIFY exhibited different expression patterns under salt stress conditions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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