Research最新文献

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a ^-/-, Angptl4 ^-/-, and Il17a ^-/- Angptl4 ^-/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4⁺ T cells (T_regs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced T_reg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

Golgi protein 73 (GP73), a resident protein of the Golgi apparatus, is notably elevated in hepatocellular carcinoma (HCC). While its critical role in remodeling the tumor microenvironment (TME) is recognized, the intricate mechanisms are not fully understood. This study reveals that GP73 in HCC cells interacts with prolyl hydroxylase-2 (PHD-2) in a competitive manner, thereby impeding the hydroxylation of hypoxia-induced factor-1α (HIF-1α). The effect above promotes the production and secretion of vascular endothelial growth factor A (VEGFA). Moreover, exosomal GP73 derived from HCC cells can be internalized by human umbilical vein endothelial cells (HUVECs) and competitively interact with HECTD1, an E3 ubiquitin ligase targeting growth factor receptor-bound protein 2 (GRB2). This interaction stabilizes GRB2, thereby activating the Ras-mitogen-activated protein kinase (MAPK) signaling pathway. Consequently, escalated levels of GP73 intensify VEGF production in HCC cells and potentiate mitogenic signaling in vascular endothelial cells, fostering angiogenesis in the TME. Our findings propose that GP73 might serve as a novel target for anti-angiogenic therapy in HCC.

Ulcerative colitis (UC) is often accompanied by intestinal inflammation and disruption of intestinal epithelial structures, which are closely associated with changes in the intestinal microbiota. We previously revealed that Min pigs, a native Chinese breed, are more resistant to dextran sulfate sodium (DSS)-induced colitis than commercial Yorkshire pigs. Characterizing the microbiota in Min pigs would allow identification of the core microbes that confer colitis resistance. By analyzing the microbiota linked to the disease course in Min and Yorkshire pigs, we observed that Bacillus spp. were enriched in Min pigs and positively correlated with pathogen resistance. Using targeted screening, we identified and validated Bacillus siamensis MZ16 from Min pigs as a bacterial species with biofilm formation ability, superior salt and pH tolerance, and antimicrobial characteristics. Subsequently, we administered B. siamensis MZ16 to conventional or microbiota-deficient BALB/c mice with DSS-induced colitis to assess its efficacy in alleviating colitis. B. siamensis MZ16 partially counteracted DSS-induced colitis in conventional mice, but it did not mitigate DSS-induced colitis in microbiota-deficient mice. Further analysis revealed that B. siamensis MZ16 administration improved intestinal ecology and integrity and immunological barrier function in mice. Compared to the DSS-treated mice, mice preadministered B. siamensis MZ16 exhibited improved relative abundance of potentially beneficial microbes (Lactobacillus, Bacillus, Christensenellaceae R7, Ruminococcus, Clostridium, and Eubacterium), reduced relative abundance of pathogenic microbes (Escherichia-Shigella), and maintained colonic OCLN and ZO-1 levels and IgA and SIgA levels. Furthermore, B. siamensis MZ16 reduced proinflammatory cytokine levels by reversing NF-κB and MAPK pathway activation in the DSS group. Overall, B. siamensis MZ16 from Min pigs had beneficial effects on a colitis mouse model by enhancing intestinal barrier functions and reducing inflammation in a gut microbiota-dependent manner.

With the development of artificial intelligence and breakthroughs in deep learning, large-scale foundation models (FMs), such as generative pre-trained transformer (GPT), Sora, etc., have achieved remarkable results in many fields including natural language processing and computer vision. The application of FMs in autonomous driving holds considerable promise. For example, they can contribute to enhancing scene understanding and reasoning. By pre-training on rich linguistic and visual data, FMs can understand and interpret various elements in a driving scene, and provide cognitive reasoning to give linguistic and action instructions for driving decisions and planning. Furthermore, FMs can augment data based on the understanding of driving scenarios to provide feasible scenes of those rare occurrences in the long tail distribution that are unlikely to be encountered during routine driving and data collection. The enhancement can subsequently lead to improvement in the accuracy and reliability of autonomous driving systems. Another testament to the potential of FMs' applications lies in world models, exemplified by the DREAMER series, which showcases the ability to comprehend physical laws and dynamics. Learning from massive data under the paradigm of self-supervised learning, world models can generate unseen yet plausible driving environments, facilitating the enhancement in the prediction of road users' behaviors and the off-line training of driving strategies. In this paper, we synthesize the applications and future trends of FMs in autonomous driving. By utilizing the powerful capabilities of FMs, we strive to tackle the potential issues stemming from the long-tail distribution in autonomous driving, consequently advancing overall safety in this domain.

Navigating the intricate and narrow vascular pathways of the body remains a formidable challenge in vascular embolization, often limiting the maneuverability and steerability of traditional catheters. This study, by T.T. Xu and co-workers, introduces dual-responsive reconfigurable miniature fiberbots, which are capable of catheter-assisted deployment, navigation, and embolization in vascular systems. Through meticulous design and magnetic control, this work successfully validates a multistage vascular embolization approach in the renal artery of rabbits in vivo. The experiments not only overcome the existing limitations of conventional catheterization techniques but also open new avenues for minimally invasive treatments.

Organic polymer materials, as the most abundantly produced materials, possess a flammable nature, making them potential hazards to human casualties and property losses. Target polymer design is still hindered due to the lack of a scientific foundation. Herein, we present a robust, generalizable, yet intelligent polymer discovery framework, which synergizes diverse capabilities, including the in situ burning analyzer, virtual reaction generator, and material genomic model, to achieve results that surpass the sum of individual parts. Notably, the high-throughput analyzer created for the first time, grounded in multiple spectroscopic principles, enables in situ capturing of massive combustion intermediates; then, the created realistic apparatus transforming to the virtual reaction generator acquires exponentially more intermediate information; further, the proposed feature engineering tool, which embedded both polymer hierarchical structures and massive intermediate data, develops the generalizable genomic model with excellent universality (adapting over 20 kinds of polymers) and high accuracy (88.8%), succeeding discovering series of novel polymers. This emerging approach addresses the target polymer design for flame-retardant application and underscores a pivotal role in accelerating polymeric materials discovery.

Colon cancer is increasing worldwide and is commonly regarded as hormone independent, yet recent reports have implicated sex hormones in its development. Nevertheless, the role of hormones from the hypothalamus-hypophysis axis in colitis-associated colorectal cancer (CAC) remains uncertain. In this study, we observed a significant reduction in the expression of the oxytocin receptor (OXTR) in colon samples from both patient with colitis and patient with CAC. To investigate further, we generated mice with an intestinal-epithelium-cell-specific knockout of OXTR. These mice exhibited markedly increased susceptibility to dextran-sulfate-sodium-induced colitis and dextran sulfate sodium/azoxymethane-induced CAC compared to wild-type mice. Our findings indicate that OXTR depletion impaired the inner mucus of the colon epithelium. Mechanistically, oxytocin was found to regulate Mucin 2 maturation through β₁-3-N-acetylglucosaminyltransferase 7 (B3GNT7)-mediated fucosylation. Interestingly, we observed a positive correlation between B3GNT7 expression and OXTR expression in human colitis and CAC colon samples. Moreover, the simultaneous activations of OXTR and fucosylation by l-fucose significantly alleviated tumor burden. Hence, our study unveils oxytocin's promising potential as an affordable and effective therapeutic intervention for individuals affected by colitis and CAC.

The combination of all-inorganic perovskites (PVSKs) and polymers allows for free-standing flexible optoelectronic devices. However, solubility difference of the PVSK precursors and concerns over the compatibility between polymer carriers and PVSKs imply a great challenge to incorporate different kinds of PVSKs into polymer matrices by the same manufacturing process. In this work, PVSK precursors are introduced into poly(2-hydroxyethyl acrylate) (PHEA) hydrogels in sequence, in which the PVSK-gel composites are achieved with full-color emissions by simply varying the precursor species. Moreover, it is found that CsBr has a higher interaction energy with the (111) plane of CsPbBr₃ than the (110) plane; thus, the CsPbBr₃ crystals with a shape of truncated cube and tetragon are observed during the CsPbBr₃-Cs₄PbBr₆ phase transition over time. The PVSK-gel composites feature excellent bendability, elasticity, and stretchable deformation (tensile strain > 500%), which allows for 3D printing emissive customized stereoscopic architectures with shape-memory features.