Materials Characterization at High Speed by Dynamic Tensile Tests

Abstract In this paper, the dynamic deformation behaviors of 2 aluminum alloys (AA6016, AA5182) and 2 steels (v 1158, FeP04

Susceptibility of acute myeloid leukemia cells to ferroptosis and evasion strategies

Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with a 5-year survival rate of less than 30%. Continuous updating of diagnostic and therapeutic strategies has not been effective in improving the clinical benefit of AML. AML cells are prone to iron metabolism imbalance due to their unique pathological characteristics, and ferroptosis is a novel cell death mode that is dominated by three cellular biological processes: iron metabolism, oxidative stress and lipid metabolism. An in-depth exploration of the unique ferroptosis mechanism in AML can provide new insights for the diagnosis and treatment of this disease. This study summarizes recent studies on ferroptosis in AML cells and suggests that the metabolic characteristics, gene mutation patterns, and dependence on mitochondria of AML cells greatly increase their susceptibility to ferroptosis. In addition, this study suggests that AML cells can establish a variety of strategies to evade ferroptosis to maintain their survival during the process of occurrence and development, and summarizes the related drugs targeting ferroptosis pathway in AML treatment, which provides development directions for the subsequent mechanism research and clinical treatment of AML

Remodeling the Epigenetic Landscape of Cancer—Application Potential of Flavonoids in the Prevention and Treatment of Cancer

Epigenetics, including DNA methylation, histone modification, and noncoding RNA regulation, are physiological regulatory changes that affect gene expression without modifying the DNA sequence. Although epigenetic disorders are considered a sign of cell carcinogenesis and malignant events that affect tumor progression and drug resistance, in view of the reversible nature of epigenetic modifications, clinicians believe that associated mechanisms can be a key target for cancer prevention and treatment. In contrast, epidemiological and preclinical studies indicated that the epigenome is constantly reprogrammed by intake of natural organic compounds and the environment, suggesting the possibility of utilizing natural compounds to influence epigenetics in cancer therapy. Flavonoids, although not synthesized in the human body, can be consumed daily and are common in medicinal plants, vegetables, fruits, and tea. Recently, numerous reports provided evidence for the regulation of cancer epigenetics by flavonoids. Considering their origin in natural and food sources, few side effects, and remarkable biological activity, the epigenetic antitumor effects of flavonoids warrant further investigation. In this article, we summarized and analyzed the multi-dimensional epigenetic effects of all 6 subtypes of flavonoids (including flavonols, flavones, isoflavones, flavanones, flavanols, and anthocyanidin) in different cancer types. Additionally, our report also provides new insights and a promising direction for future research and development of flavonoids in tumor prevention and treatment via epigenetic modification, in order to realize their potential as cancer therapeutic agents

Static equivalent of distribution network with distributed PV considering correlation between fluctuation of PV and load

With the grid connection of a large number of distributed photovoltaics (PVs), the structure and operation mode of the distribution network are changed. Detailed modeling of the distribution network can accurately analyze the impact of these changes on the power system but leads to high model complexity and large amounts of calculation. Equivalent of the distribution network effectively reduces the model scale, where the static equivalent is the basis for the other equivalents. Most of the existing static equivalent methods target a few typical operation modes. However, they are unsuitable for multiple variable scenarios caused by PV power fluctuation. This paper proposes a static equivalent method of the distribution network with distributed PVs to adapt to complex and changeable operation modes. Firstly, a scenario generation method of PV and load power based on kernel density estimation and a copula function is proposed considering fluctuation and correlation of PV and load. Secondly, a parameter optimization method based on particle swarm optimization (PSO) is proposed to optimize the parameters in the static equivalent model of the distribution network under a single operation mode. Thirdly, an equivalent parameter estimation model based on convolutional neural network (CNN) is proposed to improve the efficiency of model parameter calculation under multiple operation modes. The effectiveness of the proposed method is verified under an example of an actual distribution network in Shandong, China. This method has efficiency and is suitable for multiple operating modes

Identification and verification of a prognostic signature based on a miRNA–mRNA interaction pattern in colon adenocarcinoma

The expression characteristics of non-coding RNA (ncRNA) in colon adenocarcinoma (COAD) are involved in regulating various biological processes. To achieve these functions, ncRNA and a member of the Argonaute protein family form an RNA-induced silencing complex (RISC). The RISC is directed by ncRNA, especially microRNA (miRNA), to bind the target complementary mRNAs and regulate their expression by interfering with mRNA cleavage, degradation, or translation. However, how to identify potential miRNA biomarkers and therapeutic targets remains unclear. Here, we performed differential gene screening based on The Cancer Genome Atlas dataset and annotated meaningful differential genes to enrich related biological processes and regulatory cancer pathways. According to the overlap between the screened differential mRNAs and differential miRNAs, a prognosis model based on a least absolute shrinkage and selection operator-based Cox proportional hazards regression analysis can be established to obtain better prognosis characteristics. To further explore the therapeutic potential of miRNA as a target of mRNA intervention, we conducted an immunohistochemical analysis and evaluated the expression level in the tissue microarray of 100 colorectal cancer patients. The results demonstrated that the expression level of POU4F1, DNASE1L2, and WDR72 in the signature was significantly upregulated in COAD and correlated with poor prognosis. Establishing a prognostic signature based on miRNA target genes will help elucidate the molecular pathogenesis of COAD and provide novel potential targets for RNA therapy

NaTi2(PO4)3/N‐Doped Hard Carbon Nanocomposites with Sandwich Structure for High‐Performance Na‐Ion Full Batteries

The well‐matched technology of cathode and anode in Na‐ion full batteries is highly challenging yet critically important in practical applications. Here, the high‐performance Na‐ion full batteries are developed by using NaTi2(PO4)3/N‐doped mesoporous hard carbon hybrid anode and porous Na3V2(PO4)3 cathode. The different anodes are designed for well‐matched Na‐ion full batteries. The unique sandwich and mesoporous structural features endow the hybrid anode with a high reversible capacity (240 mAh g−1 at 1 C), high rate performance (109.7 mAh g−1 at 100 C), ultrahigh energy/power densities (76.56 Wh kg−1/5104 W kg−1) and a long cycle‐life (capacity retention of 92.1 % after 1000 cycles at 100 C) in a half cell. In a full battery this hybrid anode can also deliver a higher capacitive contribution (79.5–87.7 %) and high energy/power densities (104 Wh kg−1/5256 W kg−1). This design provides a promising pathway for developing high performance and low‐cost Na‐ion full batteries

The Modulatory Properties of Astragalus membranaceus Treatment on Triple-Negative Breast Cancer: An Integrated Pharmacological Method.

Background: Studies have shown that the natural products of Astragalus membranaceus (AM) can effectively interfere with a variety of cancers, but their mechanism of action on breast cancer remains unclear. Triple-negative breast cancer (TNBC) is associated with a severely poor prognosis due to its invasive phenotype and lack of biomarker-driven-targeted therapies. In this study, the potential mechanism of the target composition acting on TNBC was explored by integrated pharmacological models and in vitro experiments. Materials and Methods: Based on the Gene Expression Omnibus (GEO) database and the relational database of Traditional Chinese Medicines (TCMs), the drug and target components were initially screened to construct a common network module, and multiattribute analysis was then used to characterize the network and obtain key drug-target information. Furthermore, network topology analysis was used to characterize the betweenness and closeness of key hubs in the network. Molecular docking was used to evaluate the affinity between compounds and targets and obtain accurate combination models. Finally, in vitro experiments verified the key component targets. The cell counting kit-8 (CCK-8) assay, invasion assay, and flow cytometric analysis were used to assess cell viability, invasiveness, and apoptosis, respectively, after Astragalus polysaccharides (APS) intervention. We also performed western blot analysis of key proteins to probe the mechanisms of correlated signaling pathways. Results: We constructed "compound-target" (339 nodes and 695 edges) and "compound-disease" (414 nodes and 6458 edges) networks using interaction data. Topology analysis and molecular docking were used as secondary screens to identify key hubs of the network. Finally, the key component APS and biomarkers PIK3CG, AKT, and BCL2 were identified. The in vitro experimental results confirmed that APS can effectively inhibit TNBC cell activity, reduce invasion, promote apoptosis, and then counteract TNBC symptoms in a dose-dependent manner, most likely by inhibiting the PIK3CG/AKT/BCL2 pathway. Conclusion: This study provides a rational approach to discovering compounds with a polypharmacology-based therapeutic value. Our data established that APS intervenes with TNBC cell invasion, proliferation, and apoptosis via the PIK3CG/AKT/BCL2 pathway and could thus offer a promising therapeutic strategy for TNBC

Related and unrelated donor transplantation for β-thalassemia major: results of an international survey.

We studied 1110 patients with β-thalassemia major aged ≤25 years who received transplants with grafts from HLA-matched related (n = 677; 61%), HLA-mismatched related (n = 78; 7%), HLA-matched unrelated (n = 252; 23%), and HLA-mismatched unrelated (n = 103; 9%) donors between 2000 and 2016. Ninety percent of transplants were performed in the last decade. Eight-five percent of patients received ≥20 transfusions and 88% were inadequately chelated. All patients received myeloablative-conditioning regimen. Overall and event-free survival were highest for patients aged ≤6 years and after HLA-matched related and HLA-matched unrelated donor transplantation. The 5-year probabilities of overall survival for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years, adjusted for donor type and conditioning regimen were 90%, 84%, and 63%, respectively (P < .001). The corresponding probabilities for event-free survival were 86%, 80%, and 63% (P < .001). Overall and event-free survival did not differ between HLA-matched related and HLA-matched unrelated donor transplantation (89% vs 87% and 86% vs 82%, respectively). Corresponding probabilities after mismatched related and mismatched unrelated donor transplantation were 73% vs 83% and 70% vs 78%. In conclusion, if transplantation is considered as a treatment option it should be offered early (age ≤6 years). An HLA-matched unrelated donor is a suitable alternative if an HLA-matched relative is not available

Identifying the Antiproliferative Effect of Astragalus Polysaccharides on Breast Cancer: Coupling Network Pharmacology With Targetable Screening From the Cancer Genome Atlas

Background:Astragalus polysaccharides (APS), natural plant compounds, have recently emerged as a promising strategy for cancer treatment, but little is known concerning their effects on breast cancer (BC) tumorigenesis.Methods: We obtained breast cancer genetic data from The Cancer Genome Atlas (TCGA) database, network pharmacology to further clarify its biological properties. Survival analysis and molecular docking techniques were implemented for the final screening to obtain key target information. Our experiments focused on the detection of intervention effects of APS on BC cells (MCF-7 and MDA-MB-231), and quantitative RT-PCR (qRT-PCR) was used to assess the expression of key targets.Results: A total of 1,439 differentially expressed genes (DEGs) were identified by TCGA and used to build disease networks. Module analysis, gene ontology and pathway analysis revealed characteristic of the DEGs network. Topological properties were used to identify key targets, survival analysis and molecular docking finally found that the targets of APS regulation of BC cells may be CCNB1, CDC6, and p53. Through cell viability, migration and invasion assays, we found that APS interferes with the development of breast cancer in MCF7 and MDA-MB-231 cells in a dose-dependent manner. Furthermore, qRT-PCR verification suggested that the expression of CCNB1 and CDC6 in breast cancer cells was significantly downregulated in response to APS, while expression of the tumor suppressor gene P53 was significantly increased.Conclusion: Results of this study suggest therapeutic potential for APS in BC treatment, possibly through interventions with CCNB1, CDC6, and P53. Furthermore, these findings illustrate the feasibility of using network pharmacology to connect large-scale target data as a way to discover the mechanism of natural products interfering with disease