Latest ArticlesBackground: Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide, and its progression is closely associated with redox imbalance. The biological role and upstream regulation of the antioxidant enzyme glutathione peroxidase 3 (GPx3) remain poorly understood in CRC. Methods: This study integrated analyses from clinical CRC tissues, in vitro functional experiments, molecular biology assays, and public The Cancer Genome Atlas datasets. Techniques included gene expression profiling, N6-methyladenosine methylation analysis, mitochondrial reactive oxygen species detection, lipophagy assays, lipid droplet staining, transcriptomic and proteomic analyses, ferroptosis sensitivity testing, and in vivo xenograft and metastasis models to investigate the role and underlying mechanisms of GPx3 in CRC. In addition, lung metastatic burden was assessed using in vivo bioluminescence imaging and high-resolution micro-computed-tomography scanning. Results: GPx3 was substantially down-regulated in CRC tissues and cells, primarily due to N6-methyladenosine modification catalyzed by methyltransferase-like protein 3 (METTL3) and METTL14. Down-regulation of GPx3 expression elevated mitochondrial reactive oxygen species, impaired lipophagy flux, and caused excessive lipid droplet accumulation. Multiomics analyses identified Dickkopf-1 (DKK1) as a downstream target negatively regulated by GPx3 through reactive-oxygen-species-dependent β-catenin signaling. The GPx3–DKK1–solute carrier family 7 member 11 (SLC7A11) axis modulated lipid peroxidation and influenced ferroptosis sensitivity. In vivo xenograft and metastatic models showed that GPx3 suppressed tumor growth and metastasis, and these effects were partially reversed by DKK1. Conclusion: This study demonstrates that METTL3/14-mediated N6-methyladenosine modification is a key upstream mechanism leading to GPx3 down-regulation in CRC. Down-regulation of GPx3 expression promotes malignant progression by increasing mitochondrial oxidative stress, disrupting lipophagy, and cooperating with the DKK1–SLC7A11 pathway to reduce ferroptosis sensitivity. Targeting this regulatory axis may provide promising molecular strategies for CRC diagnosis and therapy.
Due to the importance of vision in human lives, 3-dimensional (3D) display has become a key and hot topic in the field of information research. With the advancement of computer science technology, holographic 3D display, capable of fully recording and reconstructing the complete wavefront information of 3D scenes, is considered as one of the most ideal 3D display technologies and has long been pursued by researchers. In recent years, substantial breakthroughs have been achieved in holographic 3D display; however, some bottlenecks continue to constrain its applications, such as slow hologram generation speed and limited space–bandwidth product. Here, the technical bottlenecks restricting the further development of holographic display are comprehensively analyzed. The latest development and progress of the key technologies of holographic 3D display are summarized. First, different fast generation methods for computer-generated holograms are analyzed. Then, the latest progress of holographic 3D display with high space–bandwidth product and low speckle noise is summarized. Finally, various application fields of holographic 3D display technology and its future development trends are discussed. This is aimed to summarize and analyze the key issues and progress in holographic 3D display technology and gain a deeper understanding of the cutting-edge developments in this rapidly developing field, providing assistance for its future applications in holographic near-eye display, virtual reality, augmented reality, optical encryption, and other fields.
Locomotion in animals such as fish, snakes, inchworms, and octopuses exhibits a remarkable diversity, with each species utilizing distinct body morphologies and movement strategies. Currently, no existing kinematic model is capable of describing the full range of locomotion exhibited by these animals. Addressing this challenge holds important implications for both the study of biomechanics of animals and the development of bioinspired robots. In this work, we propose a general kinematic model that integrates the curvature equation with a nonlinear oscillator. Through parameter adjustments, its morphology can transition between the motions of various animals. It is the most versatile kinematic model to date for describing multimodal locomotion of animals so far as we know. By translating the general kinematic model into a motion control algorithm and combining it with virtual simulation, we create a motion optimization framework that substantially simplifies the complexity of multimodal control for bionic robots with diverse actuation mechanisms, thereby enhancing their maneuverability. Using fish locomotion as an example, we validate the methodology on an untethered multijoint robotic fish, successfully enabling the robotic fish to perform cruising and various fast turn motions, thereby demonstrating its effectiveness in guiding motion control. This work is believed to have laid the foundation for the study of bionic motion and bioinspired robots.
Lipopolysaccharides are important components of the gram-negative bacterial cell envelope that are involved in immune evasion and act as a protective barrier. Employing cryo-electron microscopy, we resolved the structure and dynamics of FepE, the copolymerase component of the Wzy-dependent pathway, responsible for the length modulation of very long O-antigen molecules. Comparison of the interior volumes of related copolymerases’ periplasmic domains with the volume of hydrated sugars suggests that the size of the periplasmic domain controls the length of the O-antigen, implying that polysaccharide chain polymerization occurs inside the copolymerase periplasmic domain. Moreover, we show the opening of the FepE complex as well as other large mechanistically relevant movements. The opening of the complex presents an attractive corridor for the release of completed polysaccharide chains.
Droplet manipulation technology plays a crucial role in academic research and engineering applications. However, current manipulation technology requires integrated circuits and electrode configurations, which introduce the risk of short circuits and droplet cross-contamination during operation. Herein, we developed an omnidirectional wireless electro-droplet manipulation system (WEDMS) without using electrode/circuit control that obviates droplet cross-contamination to precisely manipulate droplet movement in separated or isolated space. This system innovatively generates localized electric fields through the synergistic effects of dielectric polarization and air discharge, achieving a noncontact, electrode-free droplet charging and driving strategy. It achieves synchronous movement of the slider and droplets via hand movement, enhancing droplet operation flexibility and human–droplet interaction on triboelectric nanogenerators. Moreover, WEDMS is capable of manipulation droplets with high speed across a wide range of volumes (10 to 2,000 μl) and effective control of droplets in both gas and oil phases, achieving a series of manipulations such as droplet positioning, chemical reactions, flexible steering, and droplet climbing, showcasing an innovative, efficient, portable, and comprehensive droplet manipulation strategy. Based on the prominent advantages of WEDMS in structural simplicity and high-efficiency control, its adaptability in multidisciplinary microfluidic applications can be further enhanced, demonstrating tremendous potential in drug delivery, green chemical synthesis, and environmental monitoring.
Tumor-infiltrating neutrophils are increasingly recognized as key drivers of cancer progression, but the mechanisms that govern their protumoral reprogramming remain elusive. Here, we demonstrated that lung cancer-derived exosomes (LDEs) deliver free fatty acids into neutrophils, triggering lipid accumulation, fatty acid β-oxidation, and mitochondrial reactive oxygen species production. This metabolic reprogramming culminates in enhanced neutrophil extracellular traps (NETs) formation, which accelerates lung cancer growth. Mechanistically, Ras-related protein Rab-34 (Rab34), a small guanosine triphosphatase, regulates neutrophil uptake of LDEs. Knockdown of Rab34 in neutrophils dramatically attenuated LDEs-induced lipid accumulation, fatty acid β-oxidation activation, and NETs formation, thereby mitigating neutrophil-involved lung cancer progression in vivo. Deoxyribonuclease I-mediated NETs degradation further confirmed the dependency of lung cancer growth on NETs. These findings uncovered a Rab34-dependent way by which LDEs reprogram neutrophils via exosomal free fatty acids, offering Rab34 and NET-associated pathways as potential therapeutic targets in lung cancer.
Organelle-targeted photodynamic therapy (PDT) shows substantial promise for precision tumor treatment. However, the clinical translation of oxygen-independent photosensitizers (PSs) designed for mitochondrial localization remains challenging. Herein, we propose a “dual-boosting” strategy to enhance the type-I PDT efficacy of mitochondria-targeted PSs. The first boost leverages multi-branched donor/π-bridge engineering to develop a series of mitochondria-targeted pyrido cyanines. Among them, McL3 displays broad visible-light absorption and a reduced singlet–triplet energy gap (ΔES1-T3 = 0.24 eV), which collectively lead to a 4.2-fold increase in superoxide anion radical (•O2−) generation compared to McL1. The second boost is achieved through the self-assembly of McL3 with human serum albumin (HSA) into McL3@HSA nanoparticles (~40 nm). This confinement further narrows ΔES1-T2 to 0.08 eV, amplifying •O2− production by 20.3-fold. Mechanistic studies indicate that HSA confinement modulates molecular conformation and promotes ISC efficiency from 33% to 52%, enabling efficient •O2− generation. Upon white-light irradiation, McL3@HSA selectively accumulates in mitochondria, inducing apoptosis and effectively inhibiting tumor growth even under hypoxic conditions. This work establishes a “dual-boosting” paradigm for the rational design of mitochondria-targeted, hypoxia-tolerant PSs, offering a promising avenue for clinical phototheranostics.
ACE2 binding of spike proteins and concomitant viral uptake are the first and most decisive membrane-coupled events of SARS-CoV-2 infection, which rely on cholesterol-rich lipid raft microdomains of the host cell plasma membrane. Therefore, lowering membrane cholesterol levels may combat the infection, potentially complementing specific, resistance-prone antiviral approaches such as vaccines. High-throughput flow cytometry and quantitative 3-dimensional microscopy reveal that SH42, a novel, extremely potent, and highly selective 24-dehydrocholesterol reductase (DHCR24) blocker, markedly inhibits ACE2 binding of SARS-CoV-2 spike receptor-binding domains and entry of spike trimers of Wuhan-Hu-1 (WT), Delta, and Omicron BA.1 variants into living cells. These effects are related to SH42-induced reduction of plasma membrane cholesterol abundance and subsequent lipid raft disruption, which are accompanied by decreased cell surface ACE2 expression and its lowered raft partitioning. SH42 exhibits superior efficacy and potency in all aspects compared to the reference atorvastatin. Furthermore, inhibitory effects of SH42 are also corroborated by reduced SARS-CoV-2 RNA copy numbers of replication-competent complete virions of WT-resembling D614G, Delta, and Omicron-derived JN.1 strains. These results suggest that selective DHCR24 blockers such as SH42 may be promising novel candidates for inhibiting initial membrane-coupled events of SARS-CoV-2 infection and serve as potential alternative therapeutic option for COVID-19.
A3BX6 perovskites, a family of vacancy-ordered structures, exhibit diverse luminescence behaviors upon photon, electron, and high-energy excitation, primarily originating from intrinsic self-trapped excitons or dopant-induced electronic transitions. Upon B-site cation engineering, ns2 cations tune intrinsic luminescence, whereas transition-metal and rare-earth dopants activate characteristic d–d, d–f, and f–f transitions, enriching A3BX6 optical diversity. The tunable crystal structure and electronic configuration endow A3BX6 perovskites with exceptional versatility for photoluminescence, electroluminescence, and scintillation applications. This review systematically elucidates how B-site chemistry modulates the structure–property–application relationships in this material family. P-block B-site A3BX6 perovskites exhibit high photoluminescence efficiency, broadband emission, and strong ultraviolet absorption, enabling applications in high-sensitivity photodetectors (1.23 × 1012 Jones), information encryption, and white light-emitting diodes. In comparison, rare-earth-based A3BX6 perovskites enable high-efficiency electroluminescent devices, featuring deep-blue light-emitting diode with an external quantum efficiency of 7.9%. Moreover, they exhibit superior scintillation performance, including high x-ray light yield (88,800 ph/MeV), low x-ray detection limit (63 nGy/s), and notable γ-ray response under 137Cs excitation (47,000 ph/MeV; 4.0% energy resolution). These insights highlight the pivotal role of B-site cation engineering in tailoring luminescence mechanisms and enabling multifunctional A3BX6 perovskites for photonic and radiation applications.
Multifunctional polyurethanes face a fundamental design trade-off: enhanced cross-linking and rigidity improve mechanical robustness but inevitably restrict chain mobility, thereby compromising essential features such as self-healing and recyclability. This inherent compromise severely constrains their multifunctional application. Here, we report a supramolecular polyurethane (COPUSL) comprising a “dynamic switch” constructed from dynamic disulfide bonds and hydrogen bonds, together with a “rigid–flexible balanced network” composed of castor oil long fatty chains and polyphenol-functionalized lignin. This design endows COPUSL with excellent mechanical properties while also enabling rapid self-healing (self-healing efficiency: 87%) and efficient recyclability. Furthermore, COPUSL with introduced aromatic structures and extended conjugate systems exhibits 100% ultraviolet-blocking efficiency and a high photothermal conversion capability (surface temperature: 153 °C) due to the electron transition and energy release of the lignin structure after absorbing light energy. By systematically investigating the relaxation kinetics, dynamic behavior, and macroscopic properties, we elucidate the distinct roles of the “dynamic switch” and “rigid–flexible balanced network” in regulating the polymer architecture and connecting dynamic behavior with mechanical and functional performance. These findings provide molecular-level insights for the design of high-performance, bio-based polyurethane with tailored multifunctional responsiveness.