Latest ArticlesNavigating 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.
Engineered microstructures that mimic in vivo tissues have demonstrated great potential for applications in regenerative medicine, drug screening, and cell behavior exploration. However, current methods for engineering microstructures that mimic the multi-extracellular matrix and multicellular features of natural tissues to realize tissue-mimicking microstructures in vitro remain insufficient. Here, we propose a versatile method for constructing tissue-mimicking heterogeneous microstructures by orderly integration of macroscopic hydrogel exchange, microscopic cell manipulation, and encapsulation modulation. First, various cell-laden hydrogel droplets are manipulated at the millimeter scale using electrowetting on dielectric to achieve efficient hydrogel exchange. Second, the cells are manipulated at the micrometer scale using dielectrophoresis to adjust their density and arrangement within the hydrogel droplets. Third, the photopolymerization of these hydrogel droplets is triggered in designated regions by dynamically modulating the shape and position of the excitation ultraviolet beam. Thus, heterogeneous microstructures with different extracellular matrix geometries and components were constructed, including specific cell densities and patterns. The resulting heterogeneous microstructure supported long-term culture of hepatocytes and fibroblasts with high cell viability (over 90%). Moreover, the density and distribution of the 2 cell types had significant effects on the cell proliferation and urea secretion. We propose that our method can lead to the construction of additional biomimetic heterogeneous microstructures with unprecedented potential for use in future tissue engineering applications.
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.
The menace of drought has persistently loomed over global crop production, posing a serious threat to agricultural sustainability. Research on drought stress highlights the important role of the phytohormone abscisic acid (ABA) in orchestrating plant responses to drought conditions. ABA regulates various drought/dehydration-responsive genes, initiates stomatal closure, and influences cellular responses to drought stress. Additionally, plants employ a phosphate starvation response (PSR) mechanism to manage phosphate (Pi) deficiency, with ABA playing a role in its regulation. However, despite intensive research in these fields, the precise connection among PSRs, drought stress, and ABA signaling still needs to be determined. Recently, PSR-related gene induction has been reported to occur before the induction of ABA-responsive genes under progressive mild drought. Mild drought decreases Pi uptake and contents in plants, triggering PSRs, which play an important role in plant growth during mild drought. Both ABA-responsive and PSR-related gene expression could indicate plant perception of external moisture conditions. Thus, integrating the information regarding their associated gene expression with soil moisture contents and thermographic data can enable timely irrigation optimization to mitigate the effect of drought on crop productivity.
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.
Protein loop modeling is a challenging yet highly nontrivial task in protein structure prediction. Despite recent progress, existing methods including knowledge-based, ab initio, hybrid, and deep learning (DL) methods fall substantially short of either atomic accuracy or computational efficiency. To overcome these limitations, we present KarmaLoop, a novel paradigm that distinguishes itself as the first DL method centered on full-atom (encompassing both backbone and side-chain heavy atoms) protein loop modeling. Our results demonstrate that KarmaLoop considerably outperforms conventional and DL-based methods of loop modeling in terms of both accuracy and efficiency, with the average RMSDs of 1.77 and 1.95 Å for the CASP13+14 and CASP15 benchmark datasets, respectively, and manifests at least 2 orders of magnitude speedup in general compared with other methods. Consequently, our comprehensive evaluations indicate that KarmaLoop provides a state-of-the-art DL solution for protein loop modeling, with the potential to hasten the advancement of protein engineering, antibody–antigen recognition, and drug design.
Extracellular vesicles (EVs) are lipid bilayer-enclosed vesicles released by cells. EVs encapsulate proteins and nucleic acids of their parental cell and efficiently deliver the cargo to recipient cells. These vesicles act as mediators of intercellular communication and thus play a crucial role in various physiological and pathological processes. Moreover, EVs hold promise for clinical use. They have been explored as drug delivery vehicles, therapeutic agents, and targets for disease diagnosis. In the landscape of cancer research, while strides have been made in EV-focused cancer physiopathology, liquid biopsy, and drug delivery, the exploration of EVs as immunotherapeutic agents may not have seen substantial progress to date. Despite promising findings reported in cell and animal studies, the clinical translation of EV-based cancer immunotherapeutics encounters challenges. Here, we review the existing strategies used in EV-based cancer immunotherapy, aiming to propel the development of this emerging yet crucial field.