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The suppression mechanism of Tregs remains an intensely investigated topic. As our focus has shifted toward a model centered on indirect inhibition of DCs, a universally applicable effector mechanism controlled by the transcription factor forkhead box P3 (Foxp3) expression has not been found. Here, we report that Foxp3 blocked the transcription of ER [Ca2.sup.+]-release channel ryanodine receptor 2 (RyR2). Reduced RyR2 shut down basal [Ca2.sup.+] oscillation in Tregs, which reduced m-calpain activities that are needed for T cells to disengage from DCs, suggesting a persistent blockage of DC antigen presentation. RyR2 deficiency rendered the [CD4.sup.+] T cell pool immune suppressive and caused it to behave in the same manner as [Foxp3.sup.+] Tregs in viral infection, asthma, hypersensitivity, colitis, and tumor development. In the absence of Foxp3, Ryr2-deficient [CD4.sup.+] T cells rescued the systemic autoimmunity associated with scurfy mice. Therefore, Foxp3- mediated [Ca2.sup.+] signaling inhibition may be a central effector mechanism of Treg immune suppression., Introduction The suppressive mechanism of Tregs remains a topic of continuing debate. Proposed mechanisms, including T cell cytolysis, surface protein extraction, local generation of adenosine, etc., all require Treg binding [...]

Motivation In the field of drug discovery, accurately and effectively predicting the binding affinity between proteins and ligands is crucial for drug screening and optimization. However, current research primarily utilizes representations based on sequence or structure to predict protein–ligand binding affinity, with relatively less study on protein surface information, which is crucial for protein–ligand interactions. Moreover, when dealing with multimodal information of proteins, traditional approaches typically concatenate features from different modalities in a straightforward manner without considering the heterogeneity among them, which results in an inability to effectively exploit the complementary between modalities. Results We introduce a novel multimodal feature extraction (MFE) framework that, for the first time, incorporates information from protein surfaces, 3D structures, and sequences, and uses cross-attention mechanism for feature alignment between different modalities. Experimental results show that our method achieves state-of-the-art performance in predicting protein–ligand binding affinity. Furthermore, we conduct ablation studies that demonstrate the effectiveness and necessity of protein surface information and multimodal feature alignment within the framework. Availability and implementation The source code and data are available at https://github.com/Sultans0fSwing/MFE. [ABSTRACT FROM AUTHOR]

Aim: There has been an increased focus on regulating cell function with Rho family GTPases, including proliferation, migration/invasion, polarity, and adhesion. Due to the challenges involved in targeting Rho family GTPases directly, it may be more effective to target their regulators, such as Rho GTPase‐activating protein 1 (ARHGAP1). This present research was performed to define the clinical significance of ARHGAP1 expression, as well as its regulatory mechanisms in hepatocellular carcinoma. Methods: ARHGAP1 and miR‐101‐3p expression of liver cancer patients, and their relevance with clinicopathological characteristics and prognosis were analyzed by the Cancer Genome Atlas sequencing data, and verified using samples of hepatocellular carcinoma patients. The interactions between miR‐101‐3p and ARHGAP1 or circPIP5K1A were validated by bioinformatic analyses, as well as confirmed by quantitative reverse transcription polymerase chain reaction, western blotting, and dual‐luciferase reporter analysis. Plate clonality assays, cell adhesion and migration experiments, and proliferation experiments were used for assessing the participation of the circPIP5K1A/miR‐101‐3p/ARHGAP1 pathway in cell proliferation and motility. Results: Elevated ARHGAP1 and reduced miR‐101‐3p expression are related to poorer survival. MiR‐101‐3p targets ARHGAP1 to suppress hepatocellular carcinoma cell colony formation and invasion, whereas miR‐101‐3p inhibitor reverses liver cancer proliferation and metastasis suppression caused by ARHGAP1 knockdown. In addition, circPIP5K1A, which is mainly distributed in the cytosol, showed carcinogenic effects by sponging miR‐101‐3p, thus regulating ARHGAP1 expression. Conclusions: ARHGAP1 serves as an oncogenic gene in liver cancer, and the expression thereof is regulated by circPIP5K1A through sponging miR‐101‐3p. [ABSTRACT FROM AUTHOR]