Advanced Science最新文献

Fine particulate matter (PM_2.5) is suggested to pose a severe risk to the kidneys by inducing functional degradation and chronic kidney diseases (CKD). This study aims to explore the nephrotoxicity of PM_2.5 exposure and the underlying mechanism. Herein, based on the UK Biobank, it is found that per interquartile range (IQR) increase in PM_2.5 is associated with a 6% (95% CI: 1%-11%), 7% (95% CI: 3%-11%), 9% (95% CI: 4%-13%), 11% (95% CI: 9%-13%), and 10% (95% CI: 8%-12%) increase in the risk of nephritis, hydronephrosis, kidney stone, acute renal failure, and CKD, respectively. In experimental study, noticeable kidney injury, which is the initiation of kidney diseases, is observed with PM_2.5 exposure in C57BL/6N mice (n = 8), accompanied with oxidative stress, autophagy and pyroptosis. In vitro, HK-2 cells with PM_2.5-stimulation exhibit tubulopathy, increased reactive oxygen species (ROS) generation and activated pyroptosis and autophagy. All changes are abolished by ROS scavenger of N-acetyl-L-cysteine (NAC) both in vivo and in vitro. In conclusion, the study provides evidence showing that PM_2.5 exposure is associated with 5 kinds of kidney diseases by directly inducing nephrotoxicity, in which ROS may be the potential target by triggering autophagy and pyroptosis.

Current induced spin-orbit torque (SOT) manipulation of magnetization is pivotal in spintronic devices. However, its application for perpendicular magnetic anisotropy magnets, crucial for high-density storage and memory devices, remains nondeterministic and inefficient. Here, a highly efficient approach is demonstrated to generate collinear spin currents by artificial modulation of interfacial symmetry, achieving 100% current-induced field-free SOT switching in CoFeB multilayers with perpendicular magnetization on stepped Al₂O₃ substrates. This field-free switching is primarily driven by the out-of-plane anti-damping SOT generated by the planar spin Hall effect (PSHE), resulting from reduced interface symmetry due to orientation-determined steps. Microscopic theoretical analysis confirms the presence and significance of PSHE in this process. Notably, this method for generating out-of-plane spin polarization along the collinear direction of the spin-current with artificial modulation of interfacial symmetry, overcomes inherent material symmetry constraints. These findings provide a promising avenue for universal control of spin-orbit torque, addressing challenges associated with low crystal symmetry and highlighting its great potential to advance the development of energy-efficient spintronic devices technology.

Accurately predicting the power conversion efficiency (PCE) in dye-sensitized solar cells (DSSCs) represents a crucial challenge, one that is pivotal for the high throughput rational design and screening of promising dye sensitizers. This study presents precise, predictive, and interpretable machine learning (ML) models specifically designed for Zn-porphyrin-sensitized solar cells. The model leverages theoretically computable, effective, and reusable molecular descriptors (MDs) to address this challenge. The models achieve excellent performance on a "blind test" of 17 newly designed cells, with a mean absolute error (MAE) of 1.02%. Notably, 10 dyes are predicted within a 1% error margin. These results validate the ML models and their importance in exploring uncharted chemical spaces of Zn-porphyrins. SHAP analysis identifies crucial MDs that align well with experimental observations, providing valuable chemical guidelines for the rational design of dyes in DSSCs. These predictive ML models enable efficient in silico screening, significantly reducing analysis time for photovoltaic cells. Promising Zn-porphyrin-based dyes with exceptional PCE are identified, facilitating high-throughput virtual screening. The prediction tool is publicly accessible at https://ai-meta.chem.ncu.edu.tw/dsc-meta.

Embryo implantation and decidualization are crucial for a successful pregnancy. How the inflammatory response is regulated during these processes is undefined. Pyroptosis is an inflammatory form of cell death mediated by gasdermin D (GSDMD). Through in vivo, cultured epithelial cells and organoids, it is shown that pyroptosis occurs in epithelial cells at the implantation site. Compared with those on day 4 of pseudopregnancy and delayed implantation, pyroptosis-related protein levels are significantly increased on day 4 of pregnancy and activated implantation, suggesting that blastocysts are involved in regulating pyroptosis. Blastocyst-derived cathepsin B (CTSB) is stimulated by preimplantation estradiol-17β and induces pyroptosis in epithelial cells. Pyroptosis-induced IL-18 secretion from epithelial cells activates a disintegrin and metalloprotease 12 (ADAM12) to process the epiregulin precursor into mature epiregulin. Epiregulin (EREG) enhances in vitro decidualization in mice. Pyroptosis-related proteins are detected in the mid-secretory human endometrium and are elevated in the recurrent implantation failure endometrium. Lipopolysaccharide treatment in pregnant mice causes implantation failure and increases pyroptosis-related protein levels. Therefore, the data suggest that modest pyroptosis is beneficial for embryo implantation and decidualization. Excessive pyroptosis can be harmful and lead to pregnancy failure.

The SARS-CoV-2 pandemic has challenged more scientists to detect viruses and to visualize virus-containing spots for diagnosis and infection control; however, detection principles of commercially available technologies are not optimal for visualization. Here, a convenient and universal homogeneous detection platform named proximity-unlocked luminescence by sequential enzymatic reactions from antibody and antibody/aptamer (PULSERAA) is developed. This is designed so that the signal appears only when the donor and acceptor are in proximity on the viral surface. PULSERAA specifically detected in the range of 25-500 digital copies/mL of inactivated SARS-CoV-2 after simply mixing reagents; it is elucidated that the accumulation of chemical species in a limited space of the viral surface contributed to such high sensitivity. PULSERAA was quickly adapated to detect another virus variant, inactivated influenza A virus, and infectious SARS-CoV-2 in a clinical sample. Furthermore, on-site (direct, rapid, and portable) visualization of the inactivated SARS-CoV-2-containing spots by a conventional smartphone camera was achieved, demonstrating that PULSERAA can be a practical tool for preventing the next pandemic in the future.

The development of environmentally adaptive solutions for magnetically actuated microrobots to enable targeted delivery in complex and confined fluid environments presents a significant challenge. Inspired by the natural locomotion of crucian carp, a barbell-shaped soft microrobot (MBS²M) is proposed. A mechano-electromagnetic hybrid actuation system is developed to generate oscillating magnetic fields to manipulate the microrobot. The MBS²M can seamlessly transition between three fundamental locomotion modes: fast navigation (FN), high-precision navigation (HPN), and fixed-point rotation (FPR). Moreover, the MBS²M can move in reverse without turning. The multimodal locomotion endows the MBS²M's adaptability in diverse environments. It can smoothly pass through confined channels, climb over obstacles, overcome gravity for vertical motion, track complex pathways, traverse viscous environments, overcome low fluid resistance, and navigate complex spaces mimicking in vivo environments. Additionally, the MBS²M is capable of drug loading and release in response to ultrasound excitation. In an ex vivo porcine liver vein, the microrobot demonstrated targeted navigation under ultrasound guidance, showcasing its potential for specialized in vivo tasks.

Detection and anti-detection with multispectral camouflage are of pivotal importance, while suffer from significant challenges due to the inherent contradiction between detection and anti-detection and conflict microwave and infrared (IR) stealth mechanisms. Here, a strategy is proposed to asymmetrically control transmitted microwave wavefront under radar-IR bi-stealth scheme using composite metasurface. It is engineered composed of infrared stealth layer (IRSL), microwave absorbing layer (MAL), and asymmetric microwave transmissive structure (AMTS) with polarization conversion from top to bottom. Therein, IR emissivity, microwave reflectivity, and transmissivity are simultaneously modulated by elaborately designing the filling ratio of ITO square patches on IRSL, which ensures both efficient microwave transmission and IR camouflage. Furthermore, full-polarized backward microwave stealth is achieved on MAL by transmitting and absorbing microwaves under x- and y- polarization, respectively, while forward wavefront is controlled by precise curvature phase compensation on AMTS according to ray-tracing technology. For verification, a proof-of-concept metadevice is numerically and experimentally characterized. Both results coincide well, demonstrating spiral detective wavefront manipulation under y-polarized forward wave excitation while effective reduction of radar cross section within 8-18 GHz and low IR emissivity (<0.3) for backward detection. This strategy provides a new paradigm for integration of detection and anti-detection with multispectral camouflage.

Metal-organic frameworks (MOFs) present diverse building blocks for high-performance materials across industries, yet their crystallization mechanisms remain incompletely understood due to gaps in nucleation and growth knowledge. In this study, MOF structural evolution is probed using in situ liquid phase transmission electron microscopy (TEM) and cryo-TEM, unveiling a blend of classical and nonclassical pathways involving liquid-liquid phase separation, particle attachment-coalescence, and surface layer deposition. Additionally, ultrafast high-temperature sintering (UHS) is employed to dope ultrasmall Cobalt nanoparticles (Co NPs) uniformly within nitrogen-doped hard carbon nanocages confirmed by 3D electron tomography. Lithium-sulfur battery tests demonstrate the nanocage-Co NP structure's exceptional capacity and cycling stability, attributed to Co NP catalytic effects due to its small size, uniform dispersion, and nanocage confinement. The findings propose a holistic framework for MOF crystallization understanding and Co NP tunability through ultrafast sintering, promising advancements in materials science and informing future MOF synthesis strategies and applications.

Despite remarkable progress in understanding the fundamental bases of itching, its cortical mechanisms remain poorly understood. Herein, the causal contributions of defined anterior cingulate cortex (ACC) neuronal populations to acute itch modulation in mice are established. Using cell type-specific manipulations, the opposing functions of ACC glutamatergic and GABAergic neurons in regulating acute itching are demonstrated. Photometry studies indicated that ACC glutamatergic neurons are activated during scratching induced by both histamine and chloroquine, whereas the activation pattern of GABAergic neurons is complicated by GABAergic subpopulations and acute itch modalities. By combining cell type- and projection-specific techniques, a thalamocortical circuit is further identified from the mediodorsal thalamus driving the itch-scratching cycle related to histaminergic and non-histaminergic itching, which is contingent on the activation of postsynaptic parvalbumin-expressing neurons in the ACC. These findings reveal a cellular and circuit signature of ACC neurons orchestrating behavioral responses to itching and may provide insights into therapies for itch-related diseases.

Despite progress significant advances in immunotherapy for some solid tumors, pancreatic ductal adenocarcinoma (PDAC) remains unresponsive poorly responsive to such interventions, largely due to its highly immunosuppressive tumor microenvironment (TME) with limited CD8⁺ T cell infiltration. This study explores the role of the epigenetic factor Sin3B in the PDAC TME. Using murine PDAC models, we found that tumor cell-intrinsic Sin3B loss reshapes the TME, increasing CD8⁺ T cell infiltration and cytotoxicity, thus impeding tumor progression and enhancing sensitivity to anti-PD1 treatment. Sin3B-deficient tumor cells exhibited amplified CXCL9/10 secretion in response to Interferon-gamma (IFNγ), creating a positive feedback loop via the CXCL9/10-CXCR3 axis, thereby intensifying the anti-tumor immune response against PDAC. Mechanistically, extensive epigenetic regulation is uncovered by Sin3B loss, particularly enhanced H3K27Ac distribution on genes related to immune responses in PDAC cells. Consistent with the murine model findings, analysis of human PDAC samples revealed a significant inverse correlation between SIN3B levels and both CD8⁺ T cell infiltration and CXCL9/10 expression. Notebly, PDAC patients with lower SIN3B expression showed a more favorable response to anti-PD1 therapy. The findings suggest that targeting SIN3B can enhance cytotoxic T cell infiltration into the tumor site and improve immunotherapy efficacy in PDAC, offering potential avenues for therapeutic biomarker or target in this challenging disease.