Multiple factors have been shown to promote the progression of diabetic cardiomyopathy. A link has previously been found between Mir30 and autophagy in cancer cells and in the heart, but the role of ...Mir30 in diabetic heart has not been studied. Using in vitro and in vivo approaches, we found that the depletion of Mir30c and induction of BECN1 enhanced autophagy in diabetic (db/db) hearts and in cardiomyocytes treated with the fatty acid palmitate. We verified that Mir30c repressed BECN1 expression by direct binding to the BECN1 3′ UTRs. Mir30c overexpression inhibited the induction of BECN1 and subsequent autophagy in diabetic hearts and improved cardiac function and structure in diabetic mice. However, these effects were abrogated by BECN1 overexpression. Similarly, Mir30c knockdown resulted in increased BECN1 levels and autophagic flux, aggravating cardiac abnormalities. We also show that SP1, an important transcriptional factor in energy metabolism regulation, is a key upstream activator of Mir30c that binds the promoter region of Mir30c. Our findings indicate that downregulation of Mir30c and subsequent activation of BECN1 promotes autophagy, contributing to the pathogenesis of diabetic cardiomyopathy. This observation suggests a theoretical ground for developing microRNA-based therapeutics against diabetic cardiomyopathy by inhibiting autophagy.
Neem leaves have long been used in traditional medicine for promoting longevity. However, the precise mechanisms underlying their anti-aging effects remain elusive. In this study, we investigated the ...impact of neem leaf extract (NLE) extracted from a 50% ethanol solution on the chronological lifespan of Saccharomyces cerevisiae, revealing an extension in lifespan, heightened oxidative stress resistance, and a reduction in reactive oxygen species. To discern the active compounds in NLE, LC/MS and the GNPS platform were employed. The majority of identified active compounds were found to be flavonoids. Subsequently, compound-target pharmacological networks were constructed using the STP and STITCH platforms for both S. cerevisiae and Homo sapiens. GOMF and KEGG enrichment analyses of the predicted targets revealed that "oxidoreductase activity" was among the top enriched terms in both yeast and human cells. These suggested a potential regulation of oxidative stress response (OSR) by NLE. RNA-seq analysis of NLE-treated yeast corroborated the anti-oxidative effect, with "oxidoreductase activity" and "oxidation-reduction process" ranking high in enriched GO terms. Notably, CTT1, encoding catalase, emerged as the most significantly up-regulated gene within the "oxidoreductase activity" cluster. In a
null mutant, the enhanced oxidative stress resistance and extended lifespan induced by NLE were nullified. For human cells, NLE pretreatment demonstrated a decrease in reactive oxygen species levels and senescence-associated β-galactosidase activity in HeLa cells, indicative of anti-aging and anti-oxidative effects. This study unveils the anti-aging and anti-oxidative properties of NLE while delving into their mechanisms, providing novel insights for pharmacological interventions in aging using phytochemicals.
It is a difficult undertaking to reliably estimate global terrestrial evapotranspiration (ET) using the Visible Infrared Imaging Radiometer Suite (VIIRS) at high spatial and temporal scales. We ...employ deep neural networks (DNN) to enhance the estimation of terrestrial ET on a global scale using satellite data. We accomplish this by merging five algorithms that are process-based and that make use of VIIRS data. These include the Shuttleworth–Wallace dual-source ET method (SW), the Priestley–Taylor-based ET algorithm (PT-JPL), the MOD16 ET product algorithm (MOD16), the modified satellite-based Priestley–Taylor ET algorithm (MS-PT), and the simple hybrid ET algorithm (SIM). We used 278 eddy covariance (EC) tower sites from 2012 to 2022 to validate the DNN approach, comparing it to Bayesian model averaging (BMA), gradient boosting regression tree (GBRT) and random forest (RF). The validation results demonstrate that the DNN significantly improves the accuracy of daily ET estimates when compared to three other merging methods, resulting in the highest average determination coefficients (R2, 0.71), RMSE (21.9 W/m2) and Kling–Gupta efficiency (KGE, 0.83). Utilizing the DNN, we generated a VIIRS ET product with a 500 m spatial resolution for the years 2012–2020. The DNN method serves as a foundational approach in the development of a sustained and comprehensive global terrestrial ET dataset. The basis for characterizing and analyzing global hydrological dynamics and carbon cycling is provided by this dataset.
Aims
Long non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis ...(FM), remain unclear.
Methods
FM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.
Results
First, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.
Conclusion
Expression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.
Sustainable urban renewal is an important approach to achieving high-quality urban development. The elements of megacities are diverse, and their structures are complex. It is critical to carry out ...the scientific classification of grassroots governance units based on the concept and needs of urban renewal to promote targeted sustainability evaluation and achieve the precise application of renewal design and planning. This study takes the jurisdiction of Chengdu City as an example and constructs a hierarchical dimension composite classification. For this classification, 128 grassroots governance units are divided into nine types, according to their obvious spatial differences. Based on the properties of these types, suggestions for evaluating and implementing urban renewal are proposed: (1) high-density central areas generally face the dilemma of complex and rigid needs and administrative weaknesses, so the development of public participatory governance is an urgent issue; (2) in transitional suburban zones, areas on and between the development axes are significantly different, indicating that extra attention should be paid to the fairness of the renewal of semi-urbanized areas; (3) outer areas are generally marginalized in urban renewal processes and destructive redevelopment behaviors should be avoided.
Diabetes could directly induce cardiac injury, leading to cardiomyopathy. However, treatment strategies for diabetic cardiomyopathy remain limited. ZNF593-AS knockout and cardiomyocyte-specific ...transgenic mice were constructed. In addition, high-fat diet (HFD)-induced diabetic mouse model and db/db mice, another classic diabetic mouse model, were employed. ZNF593-AS was silenced using GapmeR, a modified antisense oligonucleotide, while overexpressed using a recombinant adeno-associated virus serotype 9-mediated gene delivery system. Transcriptome sequencing, RNA pull-down assays, and RNA immunoprecipitation assays were also performed to investigate the underlying mechanisms. ZNF593-AS expression was decreased in diabetic hearts. ZNF593-AS attenuated the palmitic acid-induced apoptosis of cardiomyocytes in vitro. In HFD-induced diabetic mice, ZNF593-AS deletion aggravated cardiac dysfunction and enhanced cardiac apoptosis and inflammation. In contrast, HFD-induced cardiac dysfunction was improved in ZNF593-AS transgenic mice. Consistently, ZNF593-AS exerted the same cardioprotective effects in db/db mice. Mechanistically, ZNF593-AS directly interacted with the functional domain of interferon regulatory factor 3 (IRF3), and suppressed fatty acid-induced phosphorylation and activation of IRF3, contributing to the amelioration of cardiac cell death and inflammation. In conclusion, our results identified the protective role of ZNF593-AS in diabetic cardiomyopathy, suggesting a novel potential therapeutic target.
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Wang and colleagues demonstrate that a conserved lncRNA, ZNF593-AS, protects against diabetes-induced cardiac injury via suppressing IRF3 phosphorylation, providing a new target for the treatment of diabetic cardiomyopathy.
Objectives
Pericardial effusion is a rare clinical manifestation in idiopathic inflammatory myopathies (IIMs). It has been described in a small number of literature studies worldwide. We describe the ...clinical and laboratory characteristics of 19 IIM patients combined with pericardial effusion, and compare them with previously reported cases. The single-center observational-study-inspired collected of 156 IIM patients with complete data from January 1, 2016 to January 1, 2021 in the First Affiliated Hospital of Xinjiang Medical University, of which 19 patients had pericardial effusion.
Methods
The clinical characteristics of 19 IIM patients complicated with pericardial effusion were investigated by descriptive analysis and compared with previously reported cases.
Results
19 cases of IIM patients had pericardial effusion (12.2%), patients without a large amount of pericardial effusion or pericardial tamponade. There was a predominance of women in the patients with 78.9% pericardial effusion . In the clinical examination, 10 cases showed chest tightness (52.6%), pulmonary fibrosis (47.4%), and the frequency of muscle nuclear magnetic, which suggested that muscle lymphocyte infiltration rate was 63.2%. Anti-Ro-52 antibody and anti-Jo-1 antibody were positive (26.3%, 42.1%). IIM patients with pericardial effusion were accompanied by decreased serum albumin levels and elevated ESR. In the literature review, the most common clinical characteristics of IIM patients with pericardial effusion were female, pulmonary fibrosis, shortness of breath, positive anti-Ro-52 pulmonary fibrosis, and anti-Jo-1 antibody.
Conclusion
In the study, 19 patients of IIMs with pericardial effusion present with chest tightness, and are accompanied by pulmonary fibrosis, positive anti-Jo-1 antibody, and anti-Ro-52 antibody. It is suggested that pericardial effusion in IIM patients may be related to anti-synthetase antibody.
Background:
We determined the competitive endogenous in serum exosomes of ovarian cancer patients
via
sequencing technology and raw signal analysis. We performed an in-depth study of the potential ...mechanisms of ovarian cancer, predicted potential therapeutic targets and performed survival analysis of the potential targets.
Methods:
Serum exosomes from three ovarian cancer patients were used as the experimental group, serum exosomes from three patients with uterine fibroids were used as the control group, and whole transcriptome analysis of serum exosomes was performed to identify differentially expressed long noncoding RNAs (lncRNAs) and mRNAs in ovarian cancer. The miRcode database and miRNA target gene prediction website were used to predict the target genes. Cytoscape software was used to generate a competing endogenous RNA (ceRNA) network of competitive endogenous mechanism of serum exosomes in ovarian cancer, and the R language was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the target genes. Finally, the TCGA website was used to download clinical and expression data related to ovarian cancer, and the common potential target genes obtained previously were analyzed for survival.
Results:
A total of 117 differentially expressed lncRNAs as well as 513 differentially expressed mRNAs (
p
< 0.05, |log2 fold change (FC)|≥ 1.0) were obtained by combining sequencing data and raw signal analysis, and 841 predicted target genes were reciprocally mapped by combining the data from the miRcode database and miRNA target gene prediction website, resulting in 11 potential target genes related to ovarian cancer (FGFR3, BMPR1B, TRIM29, FBN2, PAPPA, CCDC58, IGSF3, FBXO10, GPAM, HOXA10, and LHFPL4). Survival analysis of the above 11 target genes revealed that the survival curve was statistically significant (
p
< 0.05) for HOXA10 but not for the other genes. Through enrichment analysis, we found that the above target genes were mainly involved in biological processes such as regulation of transmembrane receptor protein kinase activity, structural molecule activity with elasticity, transforming growth factor-activated receptor activity, and GABA receptor binding and were mainly enriched in signaling pathways regulating stem cell pluripotency, bladder cancer, glycerolipid metabolism, central carbon metabolism of cancer, and tyrosine stimulation to EGFR in signaling pathways such as resistance to enzyme inhibitors.
Conclusions:
The serum exosomal DIO3OS-hsa-miR-27a-3p-HOXA10 competitive endogenous signaling axis affects ovarian cancer development and disease survival by targeting dysregulated transcriptional pathways in cancer.
At present, designing museum art derivatives attracts more and more attention. Experts in the field often use hand painting or image editing software to process images. This is time-consuming work ...and requires professional knowledge for design. In order to address this problem, by exploiting the advanced computer simulation and image processing techniques, we develop a novel museum art derivative design system, named NK-CDS. This system consists of element operation and element application modules. Given a cultural relic image, the user extracts the interest region in the image, then processes the appearance of the element by denoising, sharpening, etc. Finally, with the application interface, the user can flexibly map the processed elements to any location of a lifestyle model. This system is intuitive and easy to operate, which can improve the design efficiency of museum derivatives and inspire ideas for creative culture product design.
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