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Nitric oxide (NO) has been implicated in a variety of physiological and pathological processes. Monitoring cellular levels of NO requires a sensor to feature adequate sensitivity, transient recording ability and biocompatibility. Herein we report a single-atom catalysts (SACs)-based electrochemical sensor for the detection of NO in live cellular environment. The system employs nickel single atoms anchored on N-doped hollow carbon spheres (Ni SACs/N-C) that act as an excellent catalyst for electrochemical oxidation of NO. Notably, Ni SACs/N-C shows superior electrocatalytic performance to the commonly used Ni based nanomaterials, attributing from the greatly reduced Gibbs free energy that are required for Ni SACs/N-C in activating NO oxidation. Moreover, Ni SACs-based flexible and stretchable sensor shows high biocompatibility and low nanomolar sensitivity, enabling the real-time monitoring of NO release from cells upon drug and stretch stimulation. Our results demonstrate a promising means of using SACs for electrochemical sensing applications. The monitoring of nitric oxide is important to a number of disease states and biomedical applications. Here, the authors report on a single nickel atom catalyst based sensor for detecting nitric oxide production from cells.

Electrochemical methods with tissue-implantable microelectrodes provide an excellent platform for real-time monitoring the neurochemical dynamics in vivo due to their superior spatiotemporal resolution and high selectivity and sensitivity. Nevertheless, electrode implantation inevitably damages the brain tissue, upregulates reactive oxygen species level, and triggers neuroinflammatory response, resulting in unreliable quantification of neurochemical events. Herein, we report a multifunctional sensing platform for inflammation-free in vivo analysis with atomic-level engineered Fe single-atom catalyst that functions as both single-atom nanozyme with antioxidative activity and electrode material for dopamine oxidation. Through high-temperature pyrolysis and catalytic performance screening, we fabricate a series of Fe single-atom nanozymes with different coordination configurations and find that the Fe single-atom nanozyme with FeN 4 exhibits the highest activity toward mimicking catalase and superoxide dismutase as well as eliminating hydroxyl radical, while also featuring high electrode reactivity toward dopamine oxidation. These dual functions endow the single-atom nanozyme-based sensor with anti-inflammatory capabilities, enabling accurate dopamine sensing in living male rat brain. This study provides an avenue for designing inflammation-free electrochemical sensing platforms with atomic-precision engineered single-atom catalysts. Electrochemical methods are promising for monitoring neurochemical dynamics, but are limited by inflammation effects from electrode implantation. Here, the authors report the development of a single-atom catalyst that acts both as an antioxidative nanozyme and an electrode material for the inflammation-free sensing of dopamine in the brain.

Background Achieving precise cancer subtype classification is imperative for effective prognosis and treatment. Multi-omics studies, encompassing diverse data modalities, have emerged as powerful tools for unraveling the complexities of cancer. However, owing to the intricacies of biological data, multi-omics datasets generally show variations in data types, scales, and distributions. These intractable problems lead to challenges in exploring intact representations from heterogeneous data, which often result in inaccuracies in multi-omics information analysis. Results To address the challenges of multi-omics research, our approach DeepMoIC presents a novel framework derived from deep Graph Convolutional Network (GCN). Leveraging autoencoder modules, DeepMoIC extracts compact representations from omics data and incorporates a patient similarity network through the similarity network fusion algorithm. To handle non-Euclidean data and explore high-order omics information effectively, we design a Deep GCN module with two strategies: residual connection and identity mapping. With extracted higher-order representations, our approach consistently outperforms state-of-the-art models on a pan-cancer dataset and 3 cancer subtype datasets. Conclusion The introduction of Deep GCN shows encouraging performance in terms of supervised multi-omics feature learning, offering promising insights for precision medicine in cancer research. DeepMoIC can potentially be an important tool in the field of cancer subtype classification because of its capacity to handle complex multi-omics data and produce reliable classification findings.

[This corrects the article DOI: 10.1371/journal.pone.0250750.].

The relationship between fungi and cancer is gradually receiving attention. Among them, some clinical evidence has shown that Candida may be a contributor to gastrointestinal cancers, especially oral cancer. The association between Candida albicans ( C. albicans ) and oral cancer (OC) has been noticed for a long time, but the mechanisms for C. albicans promoting OC are rarely explored. In this study, we determined that C. albicans infection promoted OC incidence in a 4-nitroquinoline 1-oxide (4NQO)-induced mouse tongue carcinogenesis model as well as promoted OC progression in a tongue tumor-bearing mouse model (C3H/HeN-SCC VII). We then demonstrated that tumor-associated macrophage (TAMs) infiltration was elevated during C. albicans infection. Meanwhile, the attracted TAMs polarized into M2-like macrophages with high expression of programmed death ligand 1 (PD-L1) and galectin-9 (GAL-9). Further analysis suggested that the interleukin (IL)-17A/IL-17RA pathway activated in OC cells was a contributor to the excessive TAMs infiltration in C. albicans -infected mice. Thus, we constructed IL-17A neutralization and macrophage depletion experiments in C3H/HeN-SCC VII mice to explore the role of IL-17A/IL-17RA and TAMs in OC development caused by C. albicans infection. The results showed that both IL-17A neutralization and macrophage depletion tended to reduce the TAMs number and tumor size in mice with C. albicans infection. Collectively, our finding revealed that C. albicans promoted OC development via the IL-17A/IL-17RA-macrophage axis, opening perspectives for revealing C. albicans -tumor immune microenvironment links. IMPORTANCE The relationship between fungi and cancer is gradually receiving attention. Among them, some clinical evidence has shown that Candida may be a contributor to gastrointestinal cancers, especially oral cancer. However, the underlying mechanisms for Candida promoting oral cancer need to be explored. For this reason, this study demonstrated the role of C. albicans in oral cancer development. Moreover, this study revealed the underlying mechanisms for C. albicans promoting oral cancer from the perspective of the tumor immune microenvironment.

Nuclear receptors (NRs) are important transcriptional modulators in metazoans. Typical NRs possess a conserved DNA binding domain (DBD) and a ligand binding domain (LBD). Since we discovered a type of novel NRs each of them has two DBDs and single LBD (2DBD-NRs) more than decade ago, there has been very few studies about 2DBD-NRs. Recently, 2DBD-NRs have been only reported in Platyhelminths and Mollusca and are thought to be specific NRs to lophotrochozoan. In this study, we searched different databases and identified 2DBD-NRs in different animals from both protostomes and deuterostomes. Phylogenetic analysis shows that at least two ancient 2DBD-NR genes were present in the urbilaterian, a common ancestor of protostomes and deuterostomes. 2DBD-NRs underwent gene duplication and loss after the split of different animal phyla, most of them in a certain animal phylum are paralogues, rather than orthologues, like in other animal phyla. Amino acid sequence analysis shows that the conserved motifs in typical NRs are also present in 2DBD-NRs and they are gene specific. From our phylogenetic analysis of 2DBD-NRs and following the rule of Nomenclature System for the Nuclear Receptors, a nomenclature for 2DBD-NRs is proposed.

Newcastle disease virus (NDV) is a representative paramyxovirus that usually causes severe infections and substantial economic losses to the global poultry industry. Over the years, NDV has attracted widespread attention as a promising oncolytic virotherapy agent and vector vaccine against many pathogens and an important prototype for elucidating the replication and pathogenesis of other paramyxoviruses. The F and HN glycoproteins are two kinds of glycosylated transmembrane proteins located on the virion envelope that play multiple roles in the virulence, infection, replication, and pathogenicity of NDV. In view of the ability to induce neutralizing and protective antibodies and the similarity in the structural features of the F and HN glycoproteins of NDV and other paramyxoviruses, investigating their structures and functions is beneficial for understanding the viral lifecycle and pathogenesis and developing more effective broad-spectrum antibodies or antiviral drugs against viral infection. This systematic review aims to summarize the structural features and membrane fusion mechanism of the F and HN glycoproteins and their relationships with viral virulence, pathogenic phenotype and thermostability, coupled with the crucial roles of F/HN-host protein/compound interactions in the infection, replication, and pathogenicity of NDV. Additionally, this review also highlights the importance of technologies such as protein‒protein interactome analysis, single-particle cryo-electron microscopy, genome-wide CRISPR/Cas9 library screening, and computational structural biology for providing novel viewpoints on the lifecycle and pathogenesis of NDV and related paramyxoviruses and valuable reference information for the future development of efficient treatment strategies targeting viral glycoproteins.

The impact of different turbulence on beams can be seen as optical distortions caused by refractive index fluctuations around vortices in turbulence. Therefore, from the perspective of transmission effects, the transmission outcomes of beam in different turbulences can be mutually equivalent. Since the mechanisms of beam propagation in compressible turbulence are not yet fully understood and the relevant theories are not well-established, a preliminary analysis of beam transmission in compressible turbulence is necessary. This analysis will help understand the medium characteristics of compressible turbulence, particularly its similarities and differences with atmospheric turbulence, before the optical effects of compressible turbulence are fully resolved. This paper establishes a connection between anisotropic atmospheric turbulence and compressible turbulence parameters by utilizing the mature solutions of beam in anisotropic atmospheric turbulence. We then employ the optical parameters of anisotropic atmospheric turbulence to represent those in compressible turbulence, leveraging existing solutions to assess beam transmission in compressible turbulence. Building upon the original equivalent method, we extend the dimension of transmission distance, ensuring that beams equivalence is maintained across different turbulence regimes. The results indicate that the equivalent method can effectively adapt to compressible turbulence. By using the equivalent structure function, it is possible to represent compressible turbulence parameters with the atmospheric refractive index structure constant. This method also works across different transmission distances. The method facilitates finding various solutions for beam in compressible turbulence.

Lower-grade gliomas (LGGs) exhibit diverse clinical behaviors and varying immune infiltration levels. Mitochondria have been implicated in numerous cancer pathogenesis and development, including LGGs. However, the precise biological functions of mitochondrial genes in shaping the immune landscape and the prognostic significance of LGGs remain elusive. Utilizing the Mito-Carta3.0 database, we curated a total of 1136 genes implicated in mitochondrial functions. By leveraging the expression profiles of 1136 genes related to mitochondria, we successfully categorized LGGs into four distinctive mitochondria-related transcriptome (MRT) subtypes. Our thorough analysis conclusively demonstrated that these subtypes exhibited marked disparities. To enable a personalized and integrated evaluation of LGG patients, we developed a prognostic signature known as MRT-related prognostic signature (MTRS). MTRS demonstrated correlation with mitochondria-related transcriptome (MRT) subtypes, allowing the assessment of patients’ prognosis and immune microenvironment. We conducted a detailed exploration of the single-cell distribution of MTRS in lower-grade gliomas and verified the core genes of MTRS within the spatial transcriptome of these tumors. Furthermore, our study pinpointed MGME1 as the pivotal gene in the model, functioning as an oncogene that exerts influence on cell proliferation and migration capabilities. Our research highlights the importance of mitochondrial transcriptomic features in LGGs, offering paths for tailored therapies.

Since the first complete set of Platyhelminth nuclear receptors (NRs) from Schistosoma mansoni were identified a decade ago, more flatworm genome data is available to identify their NR complement and to analyze the evolutionary relationship of Platyhelminth NRs. NRs are important transcriptional modulators that regulate development, differentiation and reproduction of animals. In this study, NRs are identified in genome databases of thirty-three species including in all Platyhelminth classes (Rhabditophora, Monogenea, Cestoda and Trematoda). Phylogenetic analysis shows that NRs in Platyhelminths follow two different evolutionary lineages: 1) NRs in a free-living freshwater flatworm ( Schmidtea mediterranea ) and all parasitic flatworms share the same evolutionary lineage with extensive gene loss. 2) NRs in a free-living intertidal zone flatworm ( Macrostomum lignano ) follow a different evolutionary lineage with a feature of multiple gene duplication and gene divergence. The DNA binding domain (DBD) is the most conserved region in NRs which contains two C4-type zinc finger motifs. A novel zinc finger motif is identified in parasitic flatworm NRs: the second zinc finger of parasitic Platyhelminth HR96b possesses a CHC2 motif which is not found in NRs of all other animals studied to date. In this study, novel NRs (members of NR subfamily 3 and 6) are identified in flatworms, this result demonstrates that members of all six classical NR subfamilies are present in the Platyhelminth phylum. NR gene duplication, loss and divergence in Platyhelminths are analyzed along with the evolutionary relationship of Platyhelminth NRs.