Fut2-mediated α1,2-fucosylation is important for gut homeostasis, including the intestinal stem cell (ISC). The stemness of ISC declines with age, and aging-associated ISC dysfunction is closely related to many age-related intestinal diseases. We previously found intestinal epithelial dysfunction in some aged Fut2 knockout mice. However, how Fut2-mediated α1,2-fucosylation affects ISC aging is still unknown. On this basis, the herein study aims to investigate the role of Fut2-mediated α1,2-fucosylation in ISC aging. Aging models in ISC-specific Fut2 knockout mice were established. ISCs were isolated for proteomics and N-glycoproteomics analysis. ISC functions and mitochondrial functions were examined in mice and organoids. Ulex europaeus agglutinin I chromatography and site-directed mutagenesis were used to validate the key target fucosylated proteins of Fut2. As a result, Fut2 knockout impaired ISC stemness and promoted aging marker expression in aged mice. Proteomics analysis indicated mitochondrial dysfunction in Fut2 knockout ISC. More injured mitochondria, elevated levels of reactive oxygen species, and decreased levels of adenosine 5′-triphosphate (ATP) in Fut2 knockout ISC were found. Moreover, respiratory chain complex impairment and mitophagy dysfunction in Fut2 knockout ISC were further noted. Finally, Fut2 was demonstrated to regulate mitochondrial functions mainly by regulating the α1,2-fucosylation of N-acyl sphingosine amidohydrolase 2 (Asah2) and Niemann–Pick type C intracellular cholesterol transporter 1 (Npc1). In conclusion, this study demonstrated the substantial role of Fut2 in regulating ISC functions during aging by affecting mitochondrial function. These findings provide novel insights into the molecular mechanisms of ISC aging and therapeutic strategies for age-related intestinal diseases.

Intelligent metasurfaces have garnered widespread attention owing to their properties of sensing electromagnetic (EM) environments and multifunctional adaptive EM wave manipulation. However, intelligent metasurfaces with broadband high optical transparency have not been studied to date, and most of the previous intelligent metasurfaces lack an integrated design for their actuators and sensors, resulting in lower integration levels. This study proposes a novel intelligent metasurface with adaptive EM wave manipulation ability and high optical transparency from visible to infrared bands. This metasurface consists of a transparent and current-controlled reconfigurable metasurface as an actuator by integrating patterned vanadium dioxide (VO₂) into metal-meshed resonant units, transparent broadband microstrip antenna as a sensor, recognition-and-feedback module, and actuator- and sensor-integrated design on the same substrate. The EM-regulating capability of the designed transparent intelligent metasurface is theoretically analyzed using the coupled mode theory, and a prototype metasurface device is fabricated for experimental verification. Simulation and experimental results demonstrate that the metasurface exhibits over 80% normalized transmittance from 380 to 5,000 nm and adaptive EM wave manipulation (reflective strong shielding function with a shielding efficiency of over 24 dB, high transmittance function with a transmission loss of 1.24 dB, and strong absorption function with an absorption of 97%) according to the EM wave power parameters without manual intervention. This study provides an avenue for transparent intelligent metasurfaces with extensive application prospects in areas such as intelligent optical windows, radar enclosures, and communication.

Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.

Circular RNAs (circRNAs) play a critical regulatory role in degenerative diseases; however, their functions and therapeutic applications in intervertebral disc degeneration (IVDD) have not been explored. Here, we identified that a novel circATXN1 highly accumulates in aging nucleus pulposus cells (NPCs) accountable for IVDD. CircATXN1 accelerates cellular senescence, disrupts extracellular matrix organization, and inhibits mitochondrial respiration. Mechanistically, circATXN1, regulated by heterogeneous nuclear ribonucleoprotein A2B1-mediated splicing circularization, promotes progerin translocation from the cell nucleus to the cytoplasm and inhibits the expression of insulin-like growth factor 1 receptor (IGF-1R). To demonstrate the therapeutic potential of circATXN1, siRNA targeting the backsplice junction of circATNX1 was screened and delivered by tetrahedral framework nucleic acids (tFNAs) due to their unique compositional and tetrahedral structural features. Our siRNA delivery system demonstrates superior abilities to transfect aging cells, clear intracellular ROS, and enhanced biological safety. Using siRNA–tFNAs to silence circATXN1, aging NPCs exhibit reduced mislocalization of progerin in the cytoplasm and up-regulation of IGF-1R, thereby demonstrating a rejuvenated cellular phenotype and improved mitochondrial function. In vivo, administering an aging cell-adapted siRNA nucleic acid framework delivery system to progerin pathologically expressed premature aging mice (zmpste24^−/−) can ameliorate the cellular matrix in the nucleus pulposus tissue, effectively delaying IVDD. This study not only identified circATXN1 functioning as a cell senescence promoter in IVDD for the first time, but also successfully demonstrated its therapeutic potential via a tFNA-based siRNA delivery strategy.

Catheters navigating through complex vessels, such as sharp turns or multiple U-turns, remain challenging for vascular embolization. Here, we propose a novel multistage vascular embolization strategy for hard-to-reach vessels that releases untethered swimming shape-memory magnetic microrobots (SMMs) from the prior catheter to the vessel bifurcation. SMMs, made of organo-gel with magnetic particles, ensure biocompatibility, radiopacity, thrombosis, and fast thermal and magnetic responses. An SMM is initially a linear shape with a 0.5-mm diameter at 20 °C inserted in a catheter. It transforms into a predetermined helix within 2 s at 38 °C blood temperature after being pushed out of the catheter into the blood. SMMs enable agile swimming in confined and tortuous vessels and can swim upstream using helical propulsion with rotating magnetic fields. Moreover, we validated this multistage vascular embolization in living rabbits, completing 100-cm travel and renal artery embolization in 2 min. After 4 weeks, the SMMs maintained the embolic position, and the kidney volume decreased by 36%.

Efficient coordination and planning is essential for large-scale multi-agent systems that collaborate in a shared dynamic environment. Heuristic search methods or learning-based approaches often lack the guarantee on correctness and performance. Moreover, when the collaborative tasks contain both spatial and temporal requirements, e.g., as linear temporal logic (LTL) formulas, formal methods provide a verifiable framework for task planning. However, since the planning complexity grows exponentially with the number of agents and the length of the task formula, existing studies are mostly limited to small artificial cases. To address this issue, a new planning paradigm is proposed in this work for system-wide temporal task formulas that are released online and continually. It avoids two common bottlenecks in the traditional methods, i.e., (a) the direct translation of the complete task formula to the associated Büchi automaton and (b) the synchronized product between the Büchi automaton and the transition models of all agents. Instead, an adaptive planning algorithm is proposed, which computes the product of relaxed partially ordered sets (R-posets) on-the-fly and assigns these subtasks to the agents subject to the ordering constraints. It is shown that the first valid plan can be derived with a polynomial time and memory complexity with respect to the system size and the formula length. Our method can take into account task formulas with a length of more than 400 and a fleet with more than 400 agents, while most existing methods fail at the formula length of 25 within a reasonable duration. The proposed method is validated on large fleets of service robots in both simulation and hardware experiments.

Haptic interactions between human and machines are essential for information acquisition and object manipulation. In virtual reality (VR) system, the haptic sensing device can gather information to construct virtual elements, while the haptic feedback part can transfer feedbacks to human with virtual tactile sensation. Therefore, exploring high-performance haptic sensing and feedback interface imparts closed-loop haptic interaction to VR system. This review summarizes state-of-the-art VR-related haptic sensing and feedback techniques based on the hardware parts. For the haptic sensor, we focus on mechanism scope (piezoresistive, capacitive, piezoelectric, and triboelectric) and introduce force sensor, gesture translation, and touch identification in the functional view. In terms of the haptic feedbacks, methodologies including mechanical, electrical, and elastic actuators are surveyed. In addition, the interactive application of virtual control, immersive entertainment, and medical rehabilitation is also summarized. The challenges of virtual haptic interactions are given including the accuracy, durability, and technical conflicts of the sensing devices, bottlenecks of various feedbacks, as well as the closed-loop interaction system. Besides, the prospects are outlined in artificial intelligence of things, wise information technology of medicine, and multimedia VR areas.

Miniaturization of health care, biomedical, and chemical systems is highly desirable for developing point-of-care testing (POCT) technologies. In system miniaturization, micropumps represent one of the major bottlenecks due to their undesirable pumping performance at such small sizes. Here, we developed a microelectromechanical system fabricated acoustic micropump based on an ultrahigh-frequency bulk acoustic wave resonator. The concept of an inner-boundary-confined acoustic jet was introduced to facilitate unidirectional flow. Benefitting from the high resonant frequency and confined acoustic streaming, the micropump reaches 32.620 kPa/cm³ (pressure/size) and 11.800 ml/min∙cm³ (flow rate/size), showing a 2-order-of-magnitude improvement in the energy transduction efficiency compared with the existing acoustic micropumps. As a proof of concept, the micropump was constructed as a wearable and wirelessly powered integrated drug delivery system with a size of only 9×9×9 mm³ and a weight of 1.16 g. It was demonstrated for ocular disease treatment through animal experimentation and a human pilot test. With superior pumping performance, miniaturized pump size, ultralow power consumption, and complementary metal–oxide–semiconductor compatibility, we expect it to be readily applied to various POCT applications including clinical diagnosis, prognosis, and drug delivery systems.

Triple-negative breast cancer (TNBC) is the most aggressive and lethal malignancy in women, with a lack of effective targeted drugs and treatment techniques. Gradient rotating magnetic field (RMF) is a new technology used in oncology physiotherapy, showing promising clinical applications due to its satisfactory biosafety and the abundant mechanical force stimuli it provides. However, its antitumor effects and underlying molecular mechanisms are not yet clear. We designed two sets of gradient RMF devices for cell culture and animal handling. Gradient RMF exposure had a notable impact on the F-actin arrangement of MDA-MB-231, BT-549, and MDA-MB-468 cells, inhibiting cell migration and invasion. A potential cytoskeleton F-actin-associated gene, CCDC150, was found to be enriched in clinical TNBC tumors and cells. CCDC150 negatively correlated with the overall survival rate of TNBC patients. CCDC150 promoted TNBC migration and invasion via activation of the transforming growth factor β1 (TGF-β1)/SMAD3 signaling pathway in vitro and in vivo. CCDC150 was also identified as a magnetic field response gene, and it was marked down-regulated after gradient RMF exposure. CCDC150 silencing and gradient RMF exposure both suppressed TNBC tumor growth and liver metastasis. Therefore, gradient RMF exposure may be an effective TNBC treatment, and CCDC150 may emerge as a potential target for TNBC therapy.