Search

Abstract Nucleotide-binding oligomerization domain 2 (NOD2) is an immune sensor crucial for eliciting the innate immune responses. Nevertheless, discrepancies exist regarding the effect of NOD2 on different types of cancer. This study aimed to investigate these function of NOD2 in melanoma and its underlying mechanisms. We have validated the tumor suppressor effect of NOD2 in melanoma. NOD2 inhibited the proliferation of melanoma cells, hindering their migration and invasion while promoting the onset of apoptosis. Our study showed that NOD2 expression is closely related to pyrimidine and folate metabolism. NOD2 inhibits thymidylate synthase (TYMS) expression by promoting K48-type ubiquitination modification of TYMS, thereby decreasing the resistance of melanoma cells to 5-fluorouracil (5-FU) and capecitabine (CAP). TYMS was identified to form a complex with Polo-like Kinase 1 (PLK1) and activate the PLK1 signaling pathway. Furthermore, we revealed that the combination of the PLK1 inhibitor volasertib (BI6727) with 5-FU or CAP had a synergistic effect repressing the proliferation, migration, and autophagy of melanoma cells. Overall, our research highlights the protective role of NOD2 in melanoma and suggests that targeting NOD2 and the TYMS/PLK1 signaling axis is a high-profile therapy that could be a prospect for melanoma treatment.

In order to achieve an optical signal memory device with read–write functions, a topological Su–Schrieffer–Heeger lattice is proposed. It is found that a transformation between a topological corner state and an edge state occurs under the magneto-optical effect. Without an external magnetic field, the electromagnetic (EM) signal is confined and stored at the corner, which realizes the writing process of a signal. When an external magnetic field is applied, the EM signal is released from the corner to the edge, which realizes the reading process of the signal. The result is expected to provide guidance for the design of high-performance reading–writing EM memories. [ABSTRACT FROM AUTHOR]

AIM: This study explores how the combination of rapamycin (Rapa) and flagellin (FliC) affects the inhibition of 4T1 breast cancer cells. The approach involves using mRNA high-throughput sequencing to examine the underlying mechanisms of this combination therapy in vitro. METHODS: 4T1 breast cancer cells were divided into four groups: control group, Rapa group, FliC group, and Rapa+FliC group. The changes in cell viability and apoptosis were detected by the CCK-8 method and flow cytometry. Concurrently, the KEGG pathway of differentially expressed genes (DEGs) was analyzed by high-throughput mRNA sequencing. Furthermore, the DEGs between the Rapa+FliC group and Rapa groups were analyzed using STRING. The PPI network of DEGs was then constructed, and the Hub genes were subsequently screened. The protein expression of the Hub gene was verified based on the HPA database. RESULTS: CCK-8 assays and flow cytometry analysis revealed that the combination of Rapa and FliC significantly increased both the inhibition and apoptosis rates in 4T1 breast cancer cells compared to the rates observed with Rapa or FliC alone (P<0. 05). Transcriptome sequencing indicated 579 DEGs between the Rapa group and the control group, predominantly in the PI3K/ Akt signaling pathway. In contrast, DEGs between the FliC group and control were mainly concentrated in signaling pathways like NOD-like receptor signaling. Additionally, 150 DEGs were identified between the Rapa+FliC group and the Rapa group, focusing primarily on pathways such as mTOR. From the protein-protein interaction (PPI) network, ten hub genes, including Atm and Itga2, were identified. CONCLUSION: The combination of Rapa+FliC could inhibit the viability of 4T1 breast cancer cells in vitro and promote apoptosis, potentially through the PI3K/Akt/mTOR signaling pathway. The genes Atm and Itga2 could be pivotal in mediating the joint effect of this combination therapy. [ABSTRACT FROM AUTHOR]

Jiangxi Province is one oi the first ecological civilization demonstration provinces in China. Understanding the impacts oi meteorological conditions on ecosystem regulatory services is beneficial for conducting ecological protection and restoration work. Based on MODIS data, net primary productivity data, and monthly meteorological data from 2000 to 2022, we used models such as water balance equation and soil loss equation to measure the four regulatory service functions oi ecosystem in Jiangxi Province, including carbon sequestration, oxygen release, water conservation and soil conservation. We used trend analysis and partial correlation analysis methods to analyze the spatio-temporal patterns and meteorological influencing factors oi those four regulation service functions. The results showed that from 2000 to 2022, the annual average values of carbon sequestration and oxygen release in Jiangxi Province were 178.8 and 130.0 g •m 2, respectively, with annual increases of 0.4 and 0.3 g^m 2. The spatial distribution of both services was consistent, and the average annual carbon sequestration and oxygen release showed an upward trend in 77.3% regions of Jiangxi Province. The average water conservation and soil retention in Jiangxi Province were 591.8 mm and 723.8 t • hm 2, respectively, with similar spatial distributions. The annual increases were 5.6 mm and 3.7 t • hm 2. The soil conservation and water conservation functions of 73.3% and 69.3% regions [ABSTRACT FROM AUTHOR]

Supplemental O2 (hyperoxia) is a critical intervention for premature infants (<34 weeks) but consequently is associated with development of bronchial airway hyperreactivity (AHR) and asthma. Clinical practice shifted toward the use of moderate hyperoxia (<60% O2), but risk for subsequent airway disease remains. In mouse models of moderate hyperoxia, neonatal mice have increased AHR with effects on airway smooth muscle (ASM), a cell type involved in airway tone, bronchodilation, and remodeling. Understanding mechanisms by which moderate O2 during the perinatal period initiates sustained airway changes is critical to drive therapeutic advancements toward treating airway diseases. We propose that cellular clock factor BMAL1 is functionally important in developing mouse airways. In adult mice, cellular clocks target pathways highly relevant to asthma pathophysiology and Bmal1 deletion increases inflammatory response, worsens lung function, and impacts survival outcomes. Our understanding of BMAL1 in the developing lung is limited, but our previous findings show functional relevance of clocks in human fetal ASM exposed to O2. Here, we characterize Bmal1 in our established mouse neonatal hyperoxia model. Our data show that Bmal1 KO deleteriously impacts the developing lung in the context of O2 and these data highlight the importance of neonatal sex in understanding airway disease. [ABSTRACT FROM AUTHOR]

Light field (LF) cameras can capture the intensity and angle information of any scene in one single shot, and are widely used in virtual reality, refocusing, de-occlusion, depth estimation, etc. However, the fundamental limitation between angular and spatial resolution leads to low spatial resolution of LF images, which limits their development prospects in various fields. In this paper, we propose a new super-resolution network based on view interaction and hierarchical feature fusion to effectively improve LF image spatial resolution and preserve the consistency of the reconstructed LF structure. Initially, we provide novel view interaction blocks to represent the relationship between all views, and efficiently combine hierarchical features using a feature fusion block consisting of residual dense blocks (RDBs) to more effectively preserve the parallax structure. In addition, in the process of extracting features, we introduce residual channel-reconstruction blocks (RCBs) to minimize the duplication of channels in the features. An inter-view unit (InterU) and an intra-view unit (IntraU) are employed to minimize redundancy in the spatial domain as well. Our suggested method is tested using public LF datasets, which include large-disparity LF images. The experimental results demonstrate that our method exhibits the best performance in terms of both quantitative and qualitative results. [ABSTRACT FROM AUTHOR]

Olaquindox (OLA) and quinocetone (QCT) have been prohibited in aquatic products due to their significant toxicity and side effects. In this study, rapid and visual europium nanoparticle (EuNP)-based lateral flow strip biosensors (LFSBs) were developed for the simultaneous quantitative detection of OLA, QCT, and 3-methyl-quinoxaline-2-carboxylic acid (MQCA) in fish feed and tissue. The EuNP-LFSBs enabled sensitive detection for OLA, QCT, and MQCA with a limit of detection of 0.067, 0.017, and 0.099 ng/mL (R2 ≥ 0.9776) within 10 min. The average recovery of the EuNP-LFSBs was 95.13%, and relative standard deviations were below 9.38%. The method was verified by high-performance liquid chromatography (HPLC), and the test results were consistent. Therefore, the proposed LFSBs serve as a powerful tool to monitor quinoxalines in fish feeds and their residues in fish tissues. [ABSTRACT FROM AUTHOR]

Diosgenin, a natural steroidal sapogenin, has recently attracted a high amount of attention, as an effective anticancer agent in ovarian cancer. However, diosgenin mediated anticancer impacts are still not completely understood. Thus, the present study evaluated the effect of diosgenin on the proliferation, apoptosis, and metastasis of ovarian cancer cells. OVCAR‐3 and SKOV‐3 cells were treated with diosgenin, cellular viability was assessed by MTT assay and apoptosis was measured by ELISA and evaluated the protein expression levels of apoptotic markers through western blotting. Cell migration was examined by measuring the mRNA levels of genes involved in the cell invasion. The protein expression levels of main components of PI3K signaling were evaluated via western blotting. Diosgenin led to significant inhibition of cellular proliferation in a dose‐dependent manner. It also induced apoptosis through upregulating pro‐apoptotic markers and downregulating antiapoptotic mediators. In addition, OVCAR‐3 cells exposure to diosgenin decreased cell migration and invasion. More importantly, diosgenin downregulated the expression levels of main proteins in PI3K signaling including PI3K, Akt, mTOR, and GSK3. Diosgenin inhibited the proliferation and migration of OVCAR‐3 ovarian cancer cells and induced apoptosis, which may be mediated by targeting PI3K signaling. [ABSTRACT FROM AUTHOR]

Filamentous fungi produce numerous uncharacterized natural products (NPs) that are often challenging to characterize because of cryptic expression in laboratory conditions. Previously, we have successfully isolated novel NPs by expressing fungal artificial chromosomes (FACs) from a variety of fungal species into Aspergillus nidulans. Here, we demonstrate a twist to FAC utility wherein heterologous expression of a Pseudogymnoascus destructans FAC in A. nidulans altered endogenous terpene biosynthetic pathways. In contrast to wild type, the FAC transformant produced increased levels of squalene and aspernidine type compounds, including three new nidulenes (1- 2, and 5), and lost nearly all ability to synthesize the major A. nidulans characteristic terpene, austinol. Deletion of a squalene synthase gene in the FAC restored wild-type chemical profiles. The altered squalene to farnesyl pyrophosphate ratio leading to synthesis of nidulenes and aspernidines at the expense of farnesyl pyrophosphate- derived austinols provides unexpected insight into routes of terpene synthesis in fungi. [ABSTRACT FROM AUTHOR]