45 research outputs found

    Equivariant Energy-Guided SDE for Inverse Molecular Design

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    Inverse molecular design is critical in material science and drug discovery, where the generated molecules should satisfy certain desirable properties. In this paper, we propose equivariant energy-guided stochastic differential equations (EEGSDE), a flexible framework for controllable 3D molecule generation under the guidance of an energy function in diffusion models. Formally, we show that EEGSDE naturally exploits the geometric symmetry in 3D molecular conformation, as long as the energy function is invariant to orthogonal transformations. Empirically, under the guidance of designed energy functions, EEGSDE significantly improves the baseline on QM9, in inverse molecular design targeted to quantum properties and molecular structures. Furthermore, EEGSDE is able to generate molecules with multiple target properties by combining the corresponding energy functions linearly

    Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment.

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    Ectopic epigenetic mechanisms play important roles in facilitating tumorigenesis. Here, we first demonstrated that ANKDD1A is a functional tumor suppressor gene, especially in the hypoxia microenvironment. ANKDD1A directly interacts with FIH1 and inhibits the transcriptional activity of HIF1α by upregulating FIH1. In addition, ANKDD1A decreases the half-life of HIF1α by upregulating FIH1, decreases glucose uptake and lactate production, inhibits glioblastoma multiforme (GBM) autophagy, and induces apoptosis in GBM cells under hypoxia. Moreover, ANKDD1A is highly frequently methylated in GBM. The tumor-specific methylation of ANKDD1A indicates that it could be used as a potential epigenetic biomarker as well as a possible therapeutic target

    Robust estimation of bacterial cell count from optical density

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    Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

    The Potential Role of circRNA in Tumor Immunity Regulation and Immunotherapy

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    Non-coding RNAs (ncRNAs) can be divided into circular non-coding RNAs (circRNAs) and linear ncRNAs. ncRNAs exist in different cell types, including normal cells, tumor cells and immunocytes. Linear ncRNAs, such as long ncRNAs and microRNAs, have been found to play important roles in the regulation of tumor immunity and immunotherapy; however, the functions of circRNAs in tumor immunity and immunotherapy are less known. Here, we review the current status of ncRNAs in the regulation of tumor immunity and immunotherapy and emphatically discuss the potential roles of circRNAs as tumor antigens in the regulation of tumor immunity and immunotherapy

    The nuclear transportation routes of membrane-bound transcription factors

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    Abstract Membrane-bound transcription factors (MTFs) are transcription factors (TFs) that are anchored in membranes in a dormant state. Activated by external or internal stimuli, MTFs are released from parent membranes and are transported to the nucleus. Existing research indicates that some plasma membrane (PM)-bound proteins and some endoplasmic reticulum (ER) membrane-bound proteins have the ability to enter the nucleus. Upon specific signal recognition cues, some PM-bound TFs undergo proteolytic cleavage to liberate the intracellular fragments that enter the nucleus to control gene transcription. However, lipid-anchored PM-bound proteins enter the nucleus in their full length for depalmitoylation. In addition, some PM-bound TFs exist as full-length proteins in cell nucleus via trafficking to the Golgi and the ER, where membrane-releasing mechanisms rely on endocytosis. In contrast, the ER membrane-bound TFs relocate to the nucleus directly or by trafficking to the Golgi. In both of these pathways, only the fragments of the ER membrane-bound TFs transit to the nucleus. Several different nuclear trafficking modes of MTFs are summarized in this review, providing an effective supplement to the mechanisms of signal transduction and gene regulation. Moreover, targeting intracellular movement pathways of disease-associated MTFs may significantly improve the survival of patients

    The Potential Role of circRNA in Tumor Immunity Regulation and Immunotherapy

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    Non-coding RNAs (ncRNAs) can be divided into circular non-coding RNAs (circRNAs) and linear ncRNAs. ncRNAs exist in different cell types, including normal cells, tumor cells and immunocytes. Linear ncRNAs, such as long ncRNAs and microRNAs, have been found to play important roles in the regulation of tumor immunity and immunotherapy; however, the functions of circRNAs in tumor immunity and immunotherapy are less known. Here, we review the current status of ncRNAs in the regulation of tumor immunity and immunotherapy and emphatically discuss the potential roles of circRNAs as tumor antigens in the regulation of tumor immunity and immunotherapy
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