Research最新文献

Momentum conservation in the nucleon is examined in terms of continuous flow of the momentum current density (or, in short, momentum flow), which receives contributions from both kinetic motion and interacting forces involving quarks and gluons. While quarks conduct momentum flow through their kinetic motion and the gluon scalar (anomaly) contributes via pure interactions, the gluon stress tensor has both effects. The quarks momentum flow encodes the information of the color-Lorentz force density on them, and the momentum conservation allows to trace its origin to the gluon tensor and anomaly (a "negative pressure" potential). From the state-of-the-art lattice calculations and experimental fits on the form factors of the quantum chromodynamics energy-momentum tensor, we exhibit pictures of the momentum flow and the color-Lorentz forces on the quarks in the nucleon. In particular, the anomaly contributes a critical attractive force with a strength similar to that of a heavy-quark confinement potential.

Major psychiatric disorders are characterized by substantial clinical heterogeneity and high comorbidity, yet their underlying biological mechanisms are not fully uncovered. The microbiota-gut-brain axis (MGBA) offers a cross-system perspective for elucidating the pathophysiology of major psychiatric disorders. The Brain-Gut Health Initiative (BIGHI) was established as the first prospective longitudinal cohort in China dedicated to investigating major psychiatric disorders guided by the framework of MGBA, enabling large-scale, transdiagnostic, and longitudinal analyses of brain-gut interactions. To date, the BIGHI has enrolled over 1,200 participants with schizophrenia, major depressive disorder, bipolar disorder, and healthy controls, with multidimensional data collected including clinical symptomatology, neurocognitive performance, electroencephalography, magnetic resonance imaging, peripheral blood biomarkers, and gut microbiome profiles. The studies within the BIGHI reveal (a) brain-gut physiological alterations in psychiatric disorders; (b) systematic relationships among brain function, peripheral physiological markers, and gut microbiome; and (c) brain-gut network patterns with marked interindividual heterogeneity. In future studies, we will expand the BIGHI into a collaborative network and promote data harmonization and interdisciplinary collaboration to advance computational psychiatry as well as its clinical translation.

Liver fibrosis shows limited treatment efficacy, driven by metabolic reprogramming and epigenetics, while the role of lactate-mediated lactylation in hepatic microenvironment remains unclear. Here, through integrative analysis of public databases and human cirrhotic liver tissues, we identified a pathogenic FSP1⁺ (fibroblast specific protein 1) macrophage subset as a key therapeutic target. We uncovered a novel FSP1-glycolysis-lactylation axis that drives fibrotic progression through metabolic-immune crosstalk. Expanded FSP1⁺ macrophage infiltration was observed in human cirrhotic liver tissues and myeloid-specific Fsp1 knockout markedly attenuates inflammation and fibrosis. Mechanistic investigations reveal that FSP1 physically interacts with pyruvate kinase M2 (PKM2) in macrophages, inhibiting its ubiquitin-proteasome degradation to stabilize the enzyme. This FSP1-PKM2 interaction enhances glycolytic flux and lactate production, which in turn promotes KAT2B-dependent lactylation of phosphoglycerate kinase 1 (PGK1) at lysine 353 (K353). The posttranslational modification creates a positive feedback loop by concurrently activating PGK1 and pyruvate dehydrogenase kinase 1, which blocks mitochondrial pyruvate metabolism, thereby amplifying glycolysis and PGK1 lactylation. Notably, we developed a cell-penetrating peptide targeting PGK1-K353 lactylation that effectively attenuates the progression of liver fibrosis. Our findings establish lactate-mediated lactylation of PGK1 as a critical node in fibrotic metabolism and reveal a previously unrecognized FSP1-glycolysis axis that sustains the pro-fibrotic microenvironment. Targeting PGK1-K353 lactylation represents a promising therapeutic strategy for chronic liver diseases.

Large momentum effective theory (LaMET) provides a general framework for computing the multi-dimensional partonic structure of the proton from first principles using lattice quantum chromodynamics (QCD). In this effective field theory approach, LaMET predicts parton distributions through a power expansion and perturbative matching of a class of Euclidean observables-quasi-distributions-evaluated at large proton momenta. Recent advances in lattice renormalization, such as the hybrid scheme with leading renormalon resummation, together with improved matching kernel that incorporates higher-loop corrections and resummations, have enhanced both the perturbative and power accuracy of LaMET, enabling a reliable quantification of theoretical uncertainties. Moreover, the Coulomb-gauge correlator approach further simplifies lattice analyses and improves the precision of transverse-momentum-dependent structures, particularly in the non-perturbative region. State-of-the-art LaMET calculations have already yielded certain parton observables with important phenomenological impact. In addition, the recently proposed kinematically enhanced lattice interpolation operators promise access to unprecedented proton momenta with greatly improved signal-to-noise ratios, which will extend the range of LaMET prediction and further suppress the power corrections. The remaining challenges, such as controlling excited-state contamination in lattice matrix elements and extracting gluonic distributions, are expected to benefit from emerging lattice techniques for ground-state isolation and noise reduction. Thus, lattice QCD studies of parton physics have entered an exciting stage of precision control and systematic improvement, which will have a broader impact for nuclear and particle experiments.

[This corrects the article DOI: 10.34133/research.0895.].

Advances in 3-dimensional (3D) cardiac constructs have provided powerful preclinical models for investigating the pathological mechanisms underlying human cardiovascular diseases and facilitating drug discovery. In this review, we focused on recent advancements in 3D cardiac constructs technology and explored its potential applications in drug development. We summarized the main types of disease models built on 3D cardiac constructs, the key parameters used for assessing pathology and drug efficacy, and their role in drug discovery. We also discussed the application of novel biomaterials in 3D cardiac constructs, the latest research progress in 3D cardiac constructs-based drug screening, and the transformative potential of artificial intelligence-assisted research on 3D cardiac constructs. Finally, we addressed the existing technical limitations and outline future directions for the development of 3D cardiac constructs.

Solar-driven carbon dioxide (CO₂) reduction can sustainably produce chemicals and fuels but is often limited by rapid charge recombination and slow CO₂-to-product kinetics, typically necessitating homogeneous photosensitizers and cocatalysts. Here, we reported an integrated photocatalyst, TF-COF-CONH-Au₂₅-Co, constructed by immobilizing atomically precise Au₂₅ nanoclusters (NCs) on a covalent organic framework (COF) incorporating [Co(bpy)₃]²⁺ complex (Co-N₆ coordination). Under visible-light illumination, this hybrid catalyzes CO₂ conversion to syngas without external photosensitizers or cocatalysts, delivering a CO formation rate of 2,321.9 μmol·g^-1·h^-1 (turnover number of 171.9 and turnover frequency of 7.2 h^-1). The Au₂₅ NCs enhance light responsiveness and charge transfer efficiency, thereby enriching long-lived photogenerated electrons, while concurrently modulating the electronic state of Co sites to reduce the energy barrier for CO₂ reduction. This study illustrates a molecular-level strategy to synergistically integrate metal NCs, COFs, and [Co(bpy)₃]²⁺, showing a promising platform for high-performance photocatalytic CO₂ conversion.

Inflammatory arthritis, mainly including rheumatoid arthritis (RA) and ankylosing spondylitis (AS), is a group of chronic progressive autoimmune diseases that destroy joints. T helper 17 (Th17) cells are extensively involved in the joint inflammation as well as bone and cartilage destruction of these diseases. Previously, proviral integration site for Moloney-murine leukemia virus 1 (Pim1) was reported to be involved in various autoimmune diseases by mediating the proinflammatory effects of T cells. However, the pathological effect and the therapeutic potential of Pim1 in inflammatory arthritis remain elusive. The present study demonstrated that Pim1 expression was elevated in CD4⁺ T cells locally and systemically in patients with RA or AS and in 2 mice models of inflammatory arthritis. Conditional knockdown of Pim1 in CD4⁺ T cells (Pim1 cKO) or using the Pim1 inhibitor AZD1208 alleviated the development of inflammatory arthritis in association with decreasing the proportion of Th17 cells. In vitro experiments involving inhibition and overexpression confirmed the promoting effect of Pim1 on Th17 cell differentiation. Mechanistically, Pim1 phosphorylated mitochondrial calcium uptake protein 1 to increase mitochondrial calcium influx, which subsequently activated mitochondrial oxidative phosphorylation and promoted Th17 cell differentiation. Through molecular docking and dynamic simulation, nilotinib, a Food-and-Drug-Administration-approved drug, was identified as a selective substitute for the currently clinically nonapproved Pim1 inhibitors, which impeded Th17 cell differentiation and was well tolerated during the treatment of Pim1 cKO mice and 2 inflammatory arthritis mouse models. Our study contributes to a better understanding of the mechanism through which Pim1 promotes Th17 cell differentiation and advances the clinical application of Pim1 as an effective target for treating inflammatory arthritis.

In response to the disparity between the notable biological efficacy and systemic toxicity of celastrol (Cel), this study established a synergistic delivery system (Cel/Lipo+/BHMs) that integrates Bletilla striata polysaccharide (BSP) and hyaluronic acid biomimetic lubricating double-cross-linked microgels (BHMs) infused with Cel cationic liposomes (Cel/Lipo+). The objective is to collaboratively attain attenuation, sustained retention, and reconfiguration of the immunological milieu for the treatment of osteoarthritis. Cel/Lipo+ selectively targets chondrocytes via electrostatic interactions, hence improving Cel delivery and reducing off-target damage. Biolubrication by BHMs reduces friction and markedly extends the drug's retention duration within the joint cavity. In vitro studies have shown that Cel/Lipo+/BHMs possess excellent biocompatibility, enhance the proliferation and migration of chondrocytes, diminish oxidative stress, and work in conjunction with Cel/BSP to modulate macrophage reprogramming while suppressing the release of proinflammatory factors tumor necrosis factor-α and interleukin-1β. In a rat osteoarthritis model induced by monosodium iodoacetate, Cel/Lipo+/BHMs effectively mitigated cartilage degeneration by synergistically suppressing the inflammatory response, diminishing the expression of the cartilage degradation enzyme matrix metalloproteinase 13, enhancing the synthesis of type II collagen and aggrecan, and ameliorating subchondral bone microstructure. The therapeutic efficacy markedly exceeds that of either Cel/Lipo+ or BHMs individually, thereby emphasizing the primary benefits of the multitiered collaborative mechanism of the delivery system.

RNA has been established as an essential molecule in virtually all cellular processes. Besides its role in cellular modulation via extracellular vesicular release, it has long been thought to only exert its function intracellularly. Recent discoveries have shown evidence of extracellular RNA tethered to the cell surface of different cell types. These cell surface RNAs are predominantly modified with sialylated glycans, denominating them cell surface glycoRNAs. While the expression of cell surface glycoRNAs has been found on a wide array of immune cell and cancer cell types, research on its functional roles has only recently been explored due to challenges in detection, isolation, and sequencing of this new subclass of RNA. In this review, the history, biogenesis, detection and isolation techniques, and functional roles of cell surface RNA to date will be discussed, in addition to commenting on its translational capacity for studying immunomodulation and disease. Acknowledging the presence of cell surface RNAs and propelling our understanding on their function will provide a new avenue to study cellular modulation and cell-cell communication.