AZD9291, a third‐generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI), is highly selective against EGFR T790M‐mutant non–small cell lung cancer (NSCLC). On investigating ...the growth inhibitory effects of AZD9291 on NSCLC and the underlying mechanism, we found that AZD9291 can trigger autophagy‐mediated cell death in both A549 and H1975 cells by increasing the expression of phosphatidylethanolamine‐modified microtubule‐associated protein light‐chain 3 (LC3) and decreasing the expression of p62. In the presence of the autophagy inhibitor chloroquine, the AZD9291‐induced increase in LC3 level was further augmented. AZD9291 decreased the levels of phosphoinositide‐3 kinase (PI3K), protein kinase B (Akt), and phosphorylated Akt. AZD9291‐induced cell death was enhanced by Akt knockdown, and the levels of both EGFR and phosphorylated EGFR were decreased by AZD9291. AZD9291 was also found to significantly suppress the tumor growth in H1975 xenograft nude mice. Thus, AZD9291 was found to induce autophagy, decrease in EGFR levels, and show a strong inhibitory effect on NSCLC both in vitro and in vivo. Furthermore, the PI3K/Akt signaling pathway was found to play a critical role in AZD9291‐induced cell death.
1.
AZD9291 induces autophagy in A549 and H1975 non–small cell lung cancer (NSCLC) cell lines.
2.
AZD9291 inhibits the PI3K/Akt pathway in NSCLC cancer cells.
3.
AZD9291 suppresses H1975 tumor growth in nude mice.
In this paper, we first establish a locally converged bioinformatics dataset based on gradient sampling and design an optimal data mining control model to improve the accuracy of bioinformatics big ...data feature mining. The performance of the Compressive Tracking algorithm and Online Bosting algorithm is compared with the mining error as a test index. At the same time, we propose a social media information dissemination algorithm applicable to large-scale social network datasets, taking the degree value of each node as the node’s full influence and comparing and analyzing the dissemination influence of BP-IM, RAND and MC-CELF algorithms. Finally, taking public health big data as the research object, the least squares regression method was used to analyze the influence of the amount of public attention to bioinformatics scientific knowledge on their scientific literacy in different media. The results showed that there was a significant positive correlation between scientific literacy and willingness to engage in science participation behavior on social media when the amount of public attention to scientific information was
=0225,
<0.01. When more people are interested in scientific knowledge of bioinformatics on social media, their scientific literacy will improve.
Cutaneous melanoma is an aggressive cancer, which is the most common type of melanoma. In our previous studies, gambogenic acid (GNA) inhibited the proliferation and migration of melanoma cells. ...Maternally expressed gene 3 (MEG3) is a long noncoding RNA (lncRNA) that has been shown to have inhibitory effects in a variety of cancers. However, the mechanisms in melanoma progression need to be further investigated. In the current study, we investigated the inhibitory effect of GNA on melanoma and its molecular mechanism through a series of cell and animal experiments. We found that GNA could improve epithelial mesenchymal transition by up-regulating the expression of the lncRNA MEG3 gene, thereby inhibiting melanoma metastasis in vitro and in vivo.
A chemical modification of cotton fabrics by 2-diethylaminoethyl chloride (DEAE-Cl) was achieved, and the resulted cotton fabrics demonstrated salt-free dyeing properties with anionic dyes. ...Nucleophilic property of hydroxyl groups in cotton cellulose was enhanced under alkaline conditions and could react with DEAE-Cl, a chemical possessing both nucleophilic and electrophilic sites. The monolayered DEAE-grafted cotton cellulose could further react with DEAE-Cl to form multiple cationic quaternary ammonium salts (denoted as DEAE@Cotton), which are highly interactive with anionic dye molecules. The strong electrostatic interactions between the DEAE@Cotton and the dyes eliminated the use of inorganic salts in cotton dyeing process. The chemical structure and property of DEAE@Cotton were characterized and compared with untreated cotton. The DEAE@Cotton can be dyed in a salt-free system, and the dye exhaustion was faster than the conventional dyeing method due to the robust electrostatic interactions of the fabrics with anionic dyes. The dyed fabrics demonstrated outstanding color fastness under repeated washing, light exposure, and crocking. The dye adsorption process on DEAE@Cotton follows Langmuir isotherm model (R
2
= 0.9667). The mechanism of enhanced dyeability was experimentally proved by treating the fabric with other anionic dyes in a salt-free system, proving the process to be environmentally friendly and cost-effective.
Graphic abstract
Abstract
N6-methyladenosine (m
6
A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m
6
A writers, erasers, and readers, m
6
A ...modulation is involved in myriad physiological and pathological processes. Extensive studies have demonstrated m
6
A modulation in diverse tumours, with effects on tumorigenesis, metastasis, and resistance. Recent evidence has revealed an emerging role of m
6
A modulation in tumour immunoregulation, and divergent m
6
A methylation patterns have been revealed in the tumour microenvironment. To depict the regulatory role of m
6
A methylation in the tumour immune microenvironment (TIME) and its effect on immune evasion, this review focuses on the TIME, which is characterized by hypoxia, metabolic reprogramming, acidity, and immunosuppression, and outlines the m
6
A-regulated TIME and immune evasion under divergent stimuli. Furthermore, m
6
A modulation patterns in anti-tumour immune cells are summarized.
A Cu-2.35Ni-0.69Si alloy with low La content was designed in order to study the role of La addition on microstructure evolution and comprehensive properties. The results indicate that the La element ...demonstrates a superior ability to combine with Ni and Si elements, via the formation of La-rich primary phases. Owing to existing La-rich primary phases, restricted grain growth was observed, due to the pinning effect during solid solution treatment. It was found that the activation energy of the Ni
Si phase precipitation decreased with the addition of La. Interestingly, the aggregation and distribution of the Ni
Si phase, around the La-rich phase, was observed during the aging process, owing to the attraction of Ni and Si atoms by the La-rich phase during the solid solution. Moreover, the mechanical and conductivity properties of aged alloy sheets suggest that the addition of the La element showed a slight reducing effect on the hardness and electrical conductivity. The decrease in hardness was due to the weakened dispersion and strengthening effect of the Ni
Si phase, while the decrease in electrical conductivity was due to the enhanced scattering of electrons by grain boundaries, caused by grain refinement. More notably, excellent thermal stabilities, including better softening resistance ability and microstructural stability, were detected for the low-La-alloyed Cu-Ni-Si sheet, owing to the delayed recrystallization and restricted grain growth caused by the La-rich phases.
Rheumatoid arthritis (RA) is a chronic autoimmune disease (AD) characterized by persistent synovial inflammation, bone erosion and progressive joint destruction. This research aimed to elucidate the ...potential roles and molecular mechanisms of N6-methyladenosine (m6A) methylation regulators in RA.
An array of tissues from 233 RA and 126 control samples was profiled and integrated for mRNA expression analysis. Following quality control and normalization, the cohort was split into training and validation sets. Five distinct machine learning feature selection methods were applied to the training set and validated in validation sets.
Among the six models, the LASSO_λ-1se model not only performed better in the validation sets but also exhibited more stringent performance. Two m6A methylation regulators were identified as significant biomarkers by consensus feature selection from all four methods. IGF2BP3 and YTHDC2, which are differentially expressed in patients with RA and controls, were used to predict RA diagnosis with high accuracy. In addition, IGF2BP3 showed higher importance, which can regulate the G2/M transition to promote RA-FLS proliferation and affect M1 macrophage polarization.
This consensus of multiple machine learning approaches identified two m6A methylation regulators that could distinguish patients with RA from controls. These m6A methylation regulators and their target genes may provide insight into RA pathogenesis and reveal novel disease regulators and putative drug targets.
Rheumatoid arthritis (RA), the most common autoimmune disease, is characterized by symmetrical synovial inflammation of multiple joints with the infiltration of pro-inflammatory immune cells and ...increased cytokines (CKs) levels. In the past few years, numerous studies have indicated that several factors could affect RA, such as mutations in susceptibility genes, epigenetic modifications, age, and race. Recently, environmental factors, particularly polycyclic aromatic hydrocarbons (PAHs), have attracted increasing attention in RA pathogenesis. Therefore, exploring the specific mechanisms of PAHs in RA is vitally critical. In this review, we summarize the recent progress in understanding the mechanisms of PAHs and aryl hydrocarbon receptors (AHRs) in RA. Additionally, the development of therapeutic drugs that target AHR is also reviewed. Finally, we discuss the challenges and perspectives on AHR application in the future.
Prolonged exposure to polycyclic aromatic hydrocarbons (PAHs) may result in autoimmune diseases, such as rheumatoid arthritis (RA) and osteoporosis (OP), which are based on an imbalance in bone ...homeostasis. These diseases are characterized by bone erosion and even a disruption in homeostasis, including in osteoblasts and osteoclasts. Current evidence indicates that multiple factors affect the progression of bone homeostasis, such as genetic susceptibility and epigenetic modifications. However, environmental factors, especially PAHs from various sources, have been shown to play an increasingly prominent role in the progression of bone homeostasis. Hence, it is essential to investigate the effects and pathogenesis of PAHs in bone homeostasis. In this review, recent progress is summarized concerning the effects and mechanisms of PAHs and their ligands and receptors in bone homeostasis. Moreover, strategies based on the effects and mechanisms of PAHs in the regulation of the bone balance and alleviation of bone destruction are also reviewed. We further discuss the future challenges and perspectives regarding the roles of PAHs in autoimmune diseases based on bone homeostasis.
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