NEDD4L mediates intestinal epithelial cell ferroptosis to restrict inflammatory bowel diseases and colorectal tumorigenesis.

Various factors play key roles in maintaining intestine homeostasis. Disruption of the balance may lead to intestinal inflammatory diseases (IBDs) and even colorectal cancer (CRC). Loss or gain of function of many key proteins can result in dysregulated intestinal homeostasis.

NDR2 is critical for osteoclastogenesis by regulating ULK1-mediated mitophagy.

Bone homeostasis primarily stems from the balance between osteoblasts and osteoclasts, wherein an augmented number or heightened activity of osteoclasts is a prevalent etiological factor in the development of bone loss. Nuclear Dbf2-related kinase (NDR2), also known as STK38L, is a member of the Hippo family with serine/threonine kinase activity. We unveiled an upregulation of NDR2 expression during osteoclast differentiation.

Embryonic 6:2 Fluorotelomer Alcohol Exposure Disrupts the Blood‒Brain Barrier by Causing Endothelial‒to‒Mesenchymal Transition in the Male Mice.

6:2 Fluorotelomer alcohol (6:2 FTOH) is a raw material used in the manufacture of short-chain poly- and perfluoroalkyl substances. Our previous study revealed that gestational exposure to 6:2 FTOH can impair blood‒brain barrier (BBB) function in offspring, accompanied by anxiety-like behavior and learning memory deficits. The aim of this study was to further investigate the specific mechanism by which maternal exposure to 6:2 FTOH resulted in impaired BBB function in offspring mice.

TBK1-Zyxin signaling controls tumor-associated macrophage recruitment to mitigate antitumor immunity.

Mechanical control is fundamental for cellular localization within a tissue, including for tumor-associated macrophages (TAMs). While the innate immune sensing pathways cGAS-STING and RLR-MAVS impact the pathogenesis and therapeutics of malignant diseases, their effects on cell residency and motility remain incompletely understood. Here, we uncovered that TBK1 kinase, activated by cGAS-STING or RLR-MAVS signaling in macrophages, directly phosphorylates and mobilizes Zyxin, a key regulator of actin dynamics.

Rapid elimination of scattering in three-dimensional fluorescence spectra via deep learning.

Three-dimensional fluorescence spectra are often affected by scattering effects, traditional scattering elimination methods rely excessively on parameter settings and cannot automatically eliminate scattering in batches, thereby limiting the application of fluorescence spectroscopy technology in rapid online monitoring and analysis of samples. In this study, we have developed a model based on a deep learning CycleGAN to rapidly eliminate scattering from three-dimensional fluorescence spectra. The proposed model efficiently eliminates scattering by simply inputting single or batches of contaminated fluorescent spectra.

Strategies and outcomes of endovascular treatment of posterior inferior cerebellar artery aneurysms: a single center experience.

To explore safe and reliable strategies and outcomes of endovascular procedures in the treatment of posterior inferior cerebellar artery (PICA) aneurysms. Retrospectively reviewed and analyzed the cases of PICA aneurysms that undergone endovascular therapy from July 2017 through January 2022 in our neurosurgical center, as well as outcomes of long-term follow-up. Total 24 cases were enrolled.

Unconventional posttranslational modification in innate immunity.

Pattern recognition receptors (PRRs) play a crucial role in innate immunity, and a complex network tightly controls their signaling cascades to maintain immune homeostasis. Within the modification network, posttranslational modifications (PTMs) are at the core of signaling cascades. Conventional PTMs, which include phosphorylation and ubiquitination, have been extensively studied.

Modeling and biological evaluation of pegmolesatide, a novel and potent erythropoiesis-stimulating agent.

Pegmolesatide, a synthetic, polyethylene-glycolylated, peptide-based erythropoiesis-stimulating agent (ESA), has been recently approved in China. Pegmolesatide is derived from the structure of endogenous erythropoietin (EPO), a natural product in mammals. This study compared the effects and selectivity of pegmolesatide to those of recombinant EPO and carbamylated EPO (CEPO) through computer-aided analyses and biological tests.

Lineage-specific splicing regulation of MAPT gene in the primate brain.

Divergence of precursor messenger RNA (pre-mRNA) alternative splicing (AS) is widespread in mammals, including primates, but the underlying mechanisms and functional impact are poorly understood. Here, we modeled cassette exon inclusion in primate brains as a quantitative trait and identified 1,170 (∼3%) exons with lineage-specific splicing shifts under stabilizing selection. Among them, microtubule-associated protein tau (MAPT) exons 2 and 10 underwent anticorrelated, two-step evolutionary shifts in the catarrhine and hominoid lineages, leading to their present inclusion levels in humans.

Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

Background: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China.

Methods: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time.

CRISPR-dCas13d-based deep screening of proximal and distal splicing-regulatory elements.

Pre-mRNA splicing, a key process in gene expression, can be therapeutically modulated using various drug modalities, including antisense oligonucleotides (ASOs). However, determining promising targets is hampered by the challenge of systematically mapping splicing-regulatory elements (SREs) in their native sequence context. Here, we use the catalytically inactive CRISPR-RfxCas13d RNA-targeting system (dCas13d/gRNA) as a programmable platform to bind SREs and modulate splicing by competing against endogenous splicing factors.

Result of a Pilot External Quality Assessment Scheme for Clinical Diagnosis of Inherited Metabolic Disorders in China.

Background: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice.

Methods: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys.

Solution-Processable Large-Area Black Phosphorus/Reduced Graphene Oxide Schottky Junction for High-Temperature Broadband Photodetectors.

2D materials-based broadband photodetectors have extensive applications in security monitoring and remote sensing fields, especially in supersonic aircraft that require reliable performance under extreme high-temperature conditions. However, the integration of large-area heterostructures with 2D materials often involves high-temperature deposition methods, and also limited options and size of substrates. Herein, a liquid-phase spin-coating method is presented based on the interface engineering to prepare larger-area Van der Waals heterojunctions of black phosphorus (BP)/reduced graphene oxide (RGO) films at room temperature on arbitrary substrates of any required size.

Cross-Modal Retrieval Between C NMR Spectra and Structures Based on Focused Libraries.

Library matching by comparing carbon-13 nuclear magnetic resonance (C NMR) spectra with spectral data in the library is a crucial method for compound identification. In our previous paper, we introduced a deep contrastive learning system called CReSS, which used a library that contained more structures. However, CReSS has two limitations: there were no unknown structures in the library, and a redundant library reduces the structure-elucidation accuracy.

Synergistic oxidation of toluene through bimetal/cordierite monolithic catalysts with ozone.

Toluene treatment has received extensive attention, and ozone synergistic catalytic oxidation was thought to be a potential method to degrade VOCs (violate organic compounds) due to its low reaction temperature and high catalytic efficiency. A series of bimetal/Cord monolithic catalysts were prepared by impregnation with cordierite, including MnCu/Cord, MnCo/Cord and CuCo/Cord (x = 1, 2, 3, 4). Analysis of textural properties, structures and morphology characteristics on the prepared catalysts were conducted to evaluate their performance on toluene conversion.

IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis.

Cytosolic double-stranded DNA surveillance by cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) signaling triggers cellular senescence, autophagy, biased mRNA translation, and interferon-mediated immune responses. However, detailed mechanisms and physiological relevance of STING-induced senescence are not fully understood. Here, we unexpectedly found that interferon regulatory factor 3 (IRF3), activated during innate DNA sensing, forms substantial endogenous complexes in the nucleus with retinoblastoma (RB), a key cell cycle regulator.

Protein Kinase STK24 Promotes Tumor Immune Evasion via the AKT-PD-L1 Axis.

Immunotherapy targeting PD-L1 is still ineffective for a wide variety of tumors with high unpredictability. Deploying combined immunotherapy with alternative targeting is practical to overcome this therapeutic resistance. Here, the deficiency of serine-threonine kinase STK24 is observed in tumor cells causing substantial attenuation of tumor growth in murine syngeneic models, a process relying on cytotoxic CD8 T and NK cells.

Prediction of F NMR chemical shifts for organic compounds with ORCA.

Accurate assignment of F NMR has long been a challenge, and quantum chemical methods are possible solutions. Herein we reported a scaling method for the prediction of F NMR chemical shift with freely available ORCA program package. Performance of 31 DFT functionals coupled with 11 basis sets were evaluated and influence of geometry optimization was also studied with five functionals coupled with three basis sets.

Biocompatibility and osteogenic potential of choline phosphate chitosan-coated biodegradable Zn1Mg.

Zinc alloys have demonstrated considerable potentials as implant materials for biodegradable vascular and orthopedic applications. However, the high initial release of Zn can trigger intense immune responses that impede tissue healing. To address this challenge and enhance the osteogenic capacity of zinc alloys, the surface of Zn1Mg was subjected to CO plasma modification (Zn1Mg-PP) followed by grafting with choline phosphate chitosan (Zn1Mg-PP-PCCs).