Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing

RBM15, an RNA binding protein, determines cell-fate specification of many tissues including blood. We demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578 leading to its degradation via ubiquitylation by an E3 ligase (CNOT4). Overexpression of PRMT1 in acute megakaryocytic leukemia cell lines blocks megakaryocyte terminal differentiation by downregulation of RBM15 protein level. Restoring RBM15 protein level rescues megakaryocyte terminal differentiation blocked by PRMT1 overexpression. At the molecular level, RBM15 binds to pre-mRNA intronic regions of genes important for megakaryopoiesis such as GATA1, RUNX1, TAL1 and c-MPL. Furthermore, preferential binding of RBM15 to specific intronic regions recruits the splicing factor SF3B1 to the same sites for alternative splicing. Therefore, PRMT1 regulates alternative RNA splicing via reducing RBM15 protein concentration. Targeting PRMT1 may be a curative therapy to restore megakaryocyte differentiation for acute megakaryocytic leukemia

Estimation Strategy Utilization Is Modulated by Implicit Emotion Regulation: Evidence from Behavioral and Event-Related Potentials Studies

A large number of studies have studied the influence of emotional experience on an individual’s estimation performance, but the influence of implicit emotion regulation is still unknown. Participants were asked to complete the following tasks in order: idiom matching task, multiplication computational estimation task (MCE task), gender judgment task (GJ task), and emotional experience intensity assessment task. The words matching task was adopted to achieve the purpose of implicit emotion regulation (implicit reappraisal and implicit suppression). Behavioral results showed that implicit reappraisal and implicit suppression equally contributed to improving an individual’s estimation speed (but not ACC (accuracy)). The MCE task related ERP (event-related potential) results showed that the influence of implicit emotion regulation on estimation consisted of two phases. In the first phase (encoding phase), implicit reappraisal both enhanced (larger P1 amplitudes) and weakened (smaller N170 amplitudes) an individual’s encoding sensitivity, while implicit suppression enhanced an individual’s encoding sensitivity (larger P1 amplitudes). In the second phase (estimation strategies retrieval phase), implicit reappraisal (but not implicit suppression) cost more attention resources (larger LPC2 and LPC3 amplitudes). The present study suggested that both implicit reappraisal and implicit suppression contributed to improving an individual’s estimation performance, and the regulation effect of implicit suppression (vs. implicit reappraisal) was better

Combination of IDO inhibitors and platinum(IV) prodrugs reverses low immune responses to enhance cancer chemotherapy and immunotherapy for osteosarcoma

In recent years, immune checkpoint blockades (ICBs) have made great progress in the treatment of cancer. However, most ICBs have not yet been observed to be satisfactory in the treatment of osteosarcoma. Herein, we designed composite nanoparticles (NP–Pt-IDOi) from a reactive oxygen species (ROS) sensitive amphiphilic polymer (PHPM) with thiol-ketal bonds in the main chain to encapsulate a Pt(IV) prodrug (Pt(IV)–C12) and an indoleamine-(2/3)-dioxygenase (IDO) inhibitor (IDOi, NLG919). Once NP-Pt-IDOi enter the cancer cells, the polymeric nanoparticles could dissociate due to the intracellular ROS, and release Pt(IV)–C12 and NLG919. Pt(IV)–C12 induces DNA damage and activates the cGAS-STING pathway, increasing infiltration of CD8+ T cells in the tumor microenvironment. In addition, NLG919 inhibits tryptophan metabolism and enhances CD8+ T cell activity, ultimately activating anti-tumor immunity and enhancing the anti-tumor effects of platinum-based drugs. NP-Pt-IDOi were shown to have superior anti-cancer activity in vitro and in vivo in mouse models of osteosarcoma, providing a new clinical paradigm for combining chemotherapy with immunotherapy for osteosarcoma

Gold Enhanced Graphene-Based Photodetector on Optical Fiber with Ultrasensitivity over Near-Infrared Bands

Graphene has been widely used in photodetectors; however its photoresponsivity is limited due to the intrinsic low absorption of graphene. To enhance the graphene absorption, a waveguide structure with an extended interaction length and plasmonic resonance with light field enhancement are often employed. However, the operation bandwidth is narrowed when this happens. Here, a novel graphene-based all-fiber photodetector (AFPD) was demonstrated with ultrahigh responsivity over a full near-infrared band. The AFPD benefits from the gold-enhanced absorption when an interdigitated Au electrode is fabricated onto a Graphene-PMMA film covered over a side-polished fiber (SFP). Interestingly, the AFPD shows a photoresponsivity of >1 × 104 A/W and an external quantum efficiency of >4.6 × 106% over a broadband region of 980–1620 nm. The proposed device provides a simple, low-cost, efficient, and robust way to detect optical fiber signals with intriguing capabilities in terms of distributed photodetection and on-line power monitoring, which is highly desirable for a fiber-optic communication system

Supplementary Data from Chronic Stress Dampens <i>Lactobacillus Johnsonii</i>–Mediated Tumor Suppression to Enhance Colorectal Cancer Progression

Figure S6</p

Supplementary Data from Chronic Stress Dampens <i>Lactobacillus Johnsonii</i>–Mediated Tumor Suppression to Enhance Colorectal Cancer Progression

Figure S8</p