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Pan-cancer analysis reveals netrin-1 receptors as potential tumor biomarkers and immune-related therapeutic targets
Abstract The signal pathways mediated by axon guiding molecule netrin-1 (NTN1) are transduced via its several membrane-bound receptors that include deleted in colorectal cancer (DCC), UNC5 (A–D), neogenin 1 (Neo1), melanoma cell adhesion molecule (MCAM), and Down syndrome cell adhesion molecule (DSCAM). Most of these genes play a role in the occurrence and progression of some solid tumors. Sufficient systematic studies have not been performed on the expression characteristics of the role of NTN1 and its receptors in the context of pan-cancer. Based on data from 10,437 subjects with 33 types of solid tumors in The Cancer Genome Atlas, we systematically analyzed the tumor molecular biological characteristics of NTN1 and its receptors through bioinformatics. Candidate small-molecule drugs were identified based on molecular docking analysis. Netrin-1 and its receptors exhibited stereotypical genetic alterations in tumor-suppressor genes or oncogenes. Promoter methylation and miRNA-mediated post-transcriptional inhibition likely represent the primary regulatory mechanisms, whereas the promotion of epithelial-mesenchymal transition (EMT) emerges as a conserved cellular function. we predicted potential small-molecule drugs that could bind to Netrin1 receptors. NTN1 and its receptors can be used as potential targets for tumor immunotherapy. Our results showed the important cancer biological functions of NTN1 and its receptors and their transformational value as candidate tumor biomarkers. This study also showed some critical potential immune-related therapeutic targets and provided a basis for future studies on their role in clinical immunotherapy.
Assessing sustainability effects of tobacco use and control in global supply chains
Fermentation and clone selection modulate the biochemical and nutritional profile of cocoa beans grown in the southwestern Amazon
Violet/ultraviolet light-induced depassivation in halide perovskite solar cells
Abstract Ammonium-terminated ligands, used directly or in the form of two-dimensional perovskites, are leading defect-passivating agents for halide perovskites and have significantly contributed to achieving the highest efficiencies across diverse perovskite solar cells. However, even these state-of-the-art perovskite solar cells suffer from rapid degradation during operation, raising concerns over the durability of the passivation. In this work, we unveil a mechanism of violet/ultraviolet light-induced depassivation that universally affects ammonium ligands. Exposure to violet/ultraviolet light triggers a charge-carrier transition from ammonium-terminated ligands to the halide perovskite framework, leading to the deprotonation of the ammonium group. This deprotonation disrupts the ammonium-perovskite interaction, resulting in depassivated perovskites susceptible to photodegradation, as validated in cells with 26.44% efficiency. This updated understanding surpasses existing ligand failure models limited to thermal intolerance and iodide oxidation, highlighting an essential perspective for enhancing the long-term efficacy of passivating agents.
Genetic determinism of fatty acid composition in liver, muscle, backfat and plasma and its link to immunocompetence and performance in pigs
Local clustering decoder as a fast and adaptive hardware decoder for the surface code
The binge scrolling scale measures excessive scrolling through a validated three-factor structure
Linked data storage using DNA origami nanostructures
A novel predictive model for abrasive waterjet deep hole drilling on AL7075 T6 using machine learning and evolutionary algorithmic approach
Wafer-Scale Synthesis of Aligned One-Dimensional Arsenene
Engineered antibodies that stabilize drug-modified KRASG12C neoantigens enable selective and potent cross-HLA immunotherapy
The differences of enamel hardness post application of silver diamine fluoride and fluoride varnish on demineralized tooth surface (in vitro)
Abstract This research aimed to determine the difference in enamel hardness after the application of silver diamine fluoride and fluoride varnish on the surface of demineralized tooth. An in vitro true experimental research was conducted by collecting 27 maxillary premolars, which were separated into crowns and roots and divided into three groups (control, silver diamine fluoride, fluoride varnish). Demineralization was performed on all groups. Silver diamine fluoride remineralizing agent and fluoride varnish were applied for 3 min to the tooth enamel surface before the specimens were immersed in artificial saliva and placed in an incubator at 37 °C for 7 days. Tooth enamel hardness was measured using the MicroVickers hardness tester before demineralization, after demineralization, and after remineralization. The data analysis used in this research was one-way ANOVA with post hoc Tukey test for analyzing the differences in enamel hardness between groups and paired t-tests for analyzing the differences in enamel hardness in each group. The level of significance α was set at ≤ 0.05. All groups showed a significant increase in enamel hardness after remineralization ( p < 0.05), with the highest mean value observed in the silver diamine fluoride group. Post hoc Tukey analysis revealed a significant difference between silver diamine fluoride and fluoride varnish groups ( p < 0.05). There was a significant difference in enamel hardness between silver diamine fluoride and fluoride varnish post-application on the demineralized tooth surface. Silver diamine fluoride may be more effective option in managing early enamel demineralization and preventing the progression of caries.
Multiomics insight into disease trajectories of cardiometabolic diseases and cancer
Stakeholder perceptions and planning implications for urban rewilding as a nature-based solution in Poland
S100B triggers neuroendocrine macrophage networks to drive airway regeneration in mice
A framework for reconfigurable production line changeover task planning based on large language model
AAK1 activation-mediated iron trafficking drives ferroptotic cell death
Abstract Ferrous iron is necessary for the occurrence of ferroptosis. The molecular mechanisms that maintain iron homeostasis within cells play a crucial role in the regulation of ferroptosis. However, how cells regulate iron uptake during ferroptosis remains unclear. Here, PKCβII is identified as a key kinase mediating transferrin receptor 1 (TFR1) endocytosis through phosphorylation and activation of AP2-associated protein kinase 1 (AAK1) during the ferroptotic process. Mechanistically, activated AAK1 phosphorylates AP2M1, which facilitates the recruitment of clathrin to mediate the endocytosis of TFR1, increasing the levels of both cellular total iron and ferrous iron and thereby promoting ferroptosis. The non-phosphorylatable mutation of AAK1 inhibits ferroptosis and consequently promotes breast tumor growth in vivo. In conclusion, we identify that the PKCβII-AAK1-AP2M1 pathway is a crucial mechanism for the regulation of cellular iron uptake during ferroptosis, which is correlated with the prognosis of breast cancer patients and presents a potential target for cancer therapy.
Negative permittivity and permeability of polyethylene-based composites with segregated filler network in microwave range
Time or distance encoding by hippocampal neurons via heterogeneous ramping rates
Abstract To navigate their environments effectively, animals frequently track time elapsed or distance traveled while seeking food and avoiding threats. The hippocampus is implicated in this process, but the neural mechanisms remain unclear. Using virtual reality tasks that require mice to integrate time or distance to collect a reward, we identified two previously unknown functional subpopulations of CA1 pyramidal neurons. Both subpopulations encode time or distance via distinct ramping dynamics. The first subpopulation exhibits a rapid, synchronous rise in activity upon movement-initiated integration. Subsequently, individual neurons ramp down at heterogeneous rates, creating progressively diverging firing rates that encode elapsed time or distance. Closed-loop optogenetic inactivation of somatostatin-positive (SST) interneurons counterintuitively reduced the ramping activity, leading mice to prematurely attempt reward collection, suggesting impaired time/distance estimation. Conversely, the second CA1 subpopulation shows opposite dynamics — an initial rapid suppression followed by a gradual ramp-up. Inactivating parvalbumin-positive (PV) interneurons diminished this initial suppression, resulting in transient attempts to collect reward near integration onset. These findings reveal parallel hippocampal circuits that initiate and maintain time or distance encoding, controlled by PV and SST interneurons, respectively, and provide insights into the neural computations supporting goal-directed navigation.