Background: No robust biomarkers have been identified to predict the efficacy of programmed cell death protein 1 (PD-1) inhibitors in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). We aimed to develop radiomic models using pre-immunotherapy MRI to predict the response to PD-1 inhibitors and the patient prognosis. Methods: This study included 246 LANPC patients (training cohort, n = 117; external test cohort, n = 129) from 10 centers. The best-performing machine learning classifier was employed to create the radiomic models. A combined model was constructed by integrating clinical and radiomic data. A radiomic interpretability study was performed with whole slide images (WSIs) stained with hematoxylin and eosin (H&E) and immunohistochemistry (IHC). A total of 150 patient-level nuclear morphological features (NMFs) and 12 cell spatial distribution features (CSDFs) were extracted from WSIs. The correlation between the radiomic and pathological features was assessed using Spearman correlation analysis. Results: The radiomic model outperformed the clinical and combined models in predicting treatment response (area under the curve: 0.760 vs. 0.559 vs. 0.652). For overall survival estimation, the combined model performed comparably to the radiomic model but outperformed the clinical model (concordance index: 0.858 vs. 0.812 vs. 0.664). Six treatment response-related radiomic features correlated with 50 H&E-derived (146 pairs, |r|= 0.31 to 0.46) and 2 to 26 IHC-derived NMF, particularly for CD45RO (69 pairs, |r|= 0.31 to 0.48), CD8 (84, |r|= 0.30 to 0.59), PD-L1 (73, |r|= 0.32 to 0.48), and CD163 (53, |r| = 0.32 to 0.59). Eight prognostic radiomic features correlated with 11 H&E-derived (16 pairs, |r|= 0.48 to 0.61) and 2 to 31 IHC-derived NMF, particularly for PD-L1 (80 pairs, |r|= 0.44 to 0.64), CD45RO (65, |r|= 0.42 to 0.67), CD19 (35, |r|= 0.44 to 0.58), CD66b (61, |r| = 0.42 to 0.67), and FOXP3 (21, |r| = 0.41 to 0.71). In contrast, fewer CSDFs exhibited correlations with specific radiomic features. Conclusion: The radiomic model and combined model are feasible in predicting immunotherapy response and outcomes in LANPC patients. The radiology–pathology correlation suggests a potential biological basis for the predictive models.

Enzyme–photosensitizer (PS) conjugates hold great promise for clinical treatment of cancer and infectious diseases via catalysis-augmented photodynamic therapy (PDT). Compared to covalent coupling, physical binding utilizing noncovalent interactions provides a simple and nondestructive strategy to combine PS with enzymes. However, the mechanism of enzyme–PS physical combination remains largely unknown, and physically bonded enzyme–PS conjugates are rarely reported. Here, we systematically investigate the interacting behaviors of representative enzymes with one of the most popular PS of chlorin e6 (Ce6) and elucidate their binding dynamics and crucial determinants. Our results reveal that the positively charged and hydrophobic residues on the surface of enzymes are crucial determinants of Ce6 binding. In addition, we demonstrate that the positively charged surface area of enzymes can be employed as a reliable criterion for assessing and predicting the enzyme–Ce6 binding affinity. Guided by this criterion, we further construct catalase–Ce6 nanoconjugates (CAT–Ce6 NCs) with superior stability and robust photodynamic antimicrobial capability via physical binding. In a showcase treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected mouse model of subcutaneous abscess, CAT–Ce6 NCs enable hypoxia pathological microenvironment remodeling and bacteria elimination, realizing effective catalysis-augmented PDT. This study deciphers the physical binding mechanism of enzyme–PS and establishes a theoretical framework to facilitate the design and construction of outstanding enzyme–PS NCs for catalysis-augmented PDT.

Micro-electro-mechanical systems (MEMS) light detection and ranging (LiDAR) systems are widely employed in diverse applications for their precise ranging and high-resolution imaging capabilities. However, conventional Lissajous scanning patterns, despite their design flexibility, are increasingly limited in meeting the growing demands for image quality. In this study, we propose a novel programmable scanning method that enhances angular resolution within defined regions of interest (ROIs). By applying parameter modulation techniques, we establish a direct, analytical link between the scanning trajectory and ROI placement, enabling precise resolution control. The proposed method increases point cloud density by 2 to 6 times across any ROI within a Lissajous scan, achieving localized improvements of up to 650%, independent of frequency constraints. Moreover, it reduces the design complexity of MEMS scanning mirrors by half, while maintaining comparable high-resolution performance. Incorporating a gaze-inspired trajectory modulation strategy and random modulation continuous wave ranging, we develop a MEMS LiDAR prototype that greatly enhances point cloud fidelity and enables accurate 3-dimensional imaging within ROIs—achieving a ranging accuracy of 2.4 cm (3σ). This approach not only improves angular resolution in targeted regions but also extends the practical applicability of MEMS LiDAR to multitarget tracking and recognition scenarios. Furthermore, the study establishes a robust theoretical framework for ROI-based trajectory control, contributing to the advancement of next-generation high-resolution imaging systems.

Bistable structures, which leverage mechanical instability, have emerged as a promising paradigm in the development of robotic grippers, providing advantages including rapid response and low energy consumption. A critical limitation of existing bistable grippers, however, lies in their invariable energy barriers, which hinder the balance between compliant triggering and powerful grasping. In this study, we propose a bistable robotic gripper capable of in situ energy barrier modulation, inspired by the adaptive seed dispersal behavior of Impatiens pods. This robotic gripper features an elastic curved beam-based architecture integrated with a motor-driven mechanism, enabling dynamic regulation of its energy landscape. This approach allows the energy barrier to be tuned over an order of magnitude during manipulation. In the low-barrier state, the robotic gripper initiates object interaction with a triggering force as low as 0.66 N, allowing for delicate manipulation. Upon state transition, instant energy barrier modulation (~300 ms) enhances grasping stability, achieving failure forces up to 12.08 N. This adaptive modulation strategy enables our robotic gripper to implement rapid, compliant, and powerful interaction. When incorporated into an unmanned aerial vehicle, the robotic gripper showcases reliable perching across diverse scenarios, highlighting the potential of energy barrier modulation to advance the adaptability and functionality of robotic systems.

Ferroptosis plays a role in wound healing during the maturation of senescent endothelial cells. This study explores the modulation of ferroptosis in senescent human umbilical vein endothelial cells (HUVECs) and wound-healing processes by Piezo1 activation at the molecular, cellular, and tissue levels. Elevated Piezo1 expression was observed in HUVECs treated with the senescence inducer doxorubicin (Doxo) and the ferroptosis inducer erastin and in aged wound tissue. Pharmacological inhibition or knockdown of Piezo1 protected senescent HUVECs and aged wound tissue from ferroptosis. Additionally, Piezo1 channel activity was found to promote ferroptosis in senescent HUVECs by increasing intracellular Ca²⁺ levels. The calmodulin-dependent kinase II (CaMKII)/activating transcription factor 3 (ATF3)/SLC7A11 signaling axis was activated upon stimulation with erastin and Doxo, driving Piezo1-induced ferroptosis. CaMKII directly interacted with ATF3, which could be modulated through Piezo1 channel regulation. Notably, Piezo1 knockout mice or adeno-associated virus 9-mediated silencing of ATF3 attenuated ferroptosis in senescent cells and accelerated wound repair. Mechanistically, both genetic and pharmacological inhibition of Piezo1 promoted wound healing in aged tissues and regulated ferroptosis in senescent HUVECs through the CaMKII/ATF3/SLC7A11 pathway. In conclusion, these findings suggest that targeting Piezo1-mediated ferroptosis in senescent HUVECs offers a promising therapeutic approach for improving wound healing in the elderly.

Limited research has investigated the connection between long COVID (LC) and the respiratory microbiome, particularly in older adults. This study aimed to characterize the respiratory microbiome of older LC patients (with an average age of 65 years old), through meta-transcriptomic sequencing of 201 individual samples. Marked differences in microbial diversity were observed between LC and non-LC patients, including disruptions in both pathogenic bacteria and fungi. Importantly, viral taxa, such as Herpes simplex virus type 1 and Human coronavirus 229E, were more frequently detected in LC patients, indicating the vulnerability of LC patients to viral infections. Functional annotation at the expression level revealed notable differences in microbial metabolism with alterations observed in pathways related to tryptophan–serotonin metabolism in LC patients. These findings underscore the altered microbial landscape, especially in older adults who developed LC, and fill the gap for the potentially clinical roles played by the respiratory microbiome.

Mesangial proliferative glomerulonephritis (MsPGN) is the most common glomerulonephritis pathological type, including IgA nephropathy (IgAN), in which regional immune injury leads to disease progression without targeted treatment approaches. The mechanism of regional immune injury in MsPGN is unclear. We previously performed single-cell RNA sequencing (scRNA-seq) of IgAN and identified that the CX3CR1 gene increased in kidney. In this study, further scRNA-seq analysis and cellchat analysis revealed that CX3CL1 and CX3CR1 expression was increased in mesangial cells and monocytes/macrophages, respectively, in IgAN, mediating stronger crosstalk. This result and its association with regional immune injury were validated in clinical specimens and MsPGN animal model. Deficiency of CX3CR1⁺ monocytes/macrophages in the MsPGN animal model attenuated proteinuria, cell proliferation, and inflammation in glomerulus. Mechanistically, CX3CL1 in activated mesangial cells induced CX3CR1⁺ monocyte/macrophage migration and activation, and RNA-seq, Luminex multiplex immunoassay, and molecular analysis revealed that CX3CR1⁺ monocytes/macrophages induced mesangial cell injury via the MIF–CD74 interaction and activated the phosphatidylinositol 3-kinase (PI3K)/proteinserine-threonine kinase (AKT) pathway. Lastly, the therapeutic effect of the CX3CL1 monoclonal antibody quetmolimab was validated for inhibiting the progression of MsPGN. These findings demonstrate that activated mesangial cells interact with CX3CR1⁺ monocytes/macrophages promoting glomerulus regional immune injury in MsPGN, providing evidence into the CX3CL1–CX3CR1 axis as a novel target of treatment for MsPGN.

Acute kidney injury (AKI) is a clinical syndrome with high mortality, and its pathogenesis involves complex inflammatory regulatory mechanisms. As core components of the cytokine network, interleukins (ILs) exert pleiotropic effects in the development of AKI, participating in processes such as inflammation, fibrosis, tissue damage repair, and remote organ injury. Moreover, ILs influence the progression of AKI by mediating the crosstalk among renal resident cells, immune cells, and fibroblasts. Pro-inflammatory ILs primarily accelerate the progression of AKI by recruiting neutrophils and inducing renal cell apoptosis, whereas anti-inflammatory ILs alleviate AKI by inhibiting the release of inflammatory cytokines and enhancing regulatory T cell function. Dual-function ILs may either promote disease progression or facilitate tissue repair depending on their cellular origin or the specific pathological stage. In terms of therapeutic strategies, monoclonal antibodies targeting ILs and their receptors, as well as advancements in extracellular vesicle technology, have shown promising potential. Future research should focus on elucidating the specific signaling networks of ILs and their intercellular interactions in order to promote precision medicine approaches for AKI and to block the transition from AKI to chronic kidney disease (CKD).

Natural killer (NK) cells, serving as pivotal mediators of innate immunity, play an important role in antitumor immunity. Immune checkpoint can be expressed on the surface of NK cells and meticulously regulates their activation states and effector functions through complex signaling networks. In recent years, tumor immunotherapy strategies focusing on NK cell immune checkpoints have demonstrated remarkable advancements. This review systematically elucidates the expression profiles, signaling pathways, and the immune checkpoint molecule regulatory mechanisms localized on the NK cell membrane (e.g., NKG2A, KIRs, and TIGIT) or intracellularly (e.g., BIM, Cbl-b, and EZH2) during tumor immune evasion. Particular attention is devoted to dissecting the regulatory mechanisms through which these immune checkpoint molecules influence NK cell-mediated cytotoxicity, cytokine secretion, proliferative capacity, and tunable modulation of NK cell immune checkpoint expression by diverse factors within the tumor microenvironment. Furthermore, this review comprehensively summarizes preclinical advancements in NK cell immune checkpoint blockade strategies, including single checkpoint blockade, combinatorial checkpoint approaches, and their integration with conventional therapeutic modalities. Additionally, emerging therapeutic advancements, such as gene-editing technologies and chimeric antigen receptor-NK (CAR-NK) cell therapy, are evaluated for their prospective applications in immunotherapy based on NK cells. By thoroughly elucidating the molecular regulatory networks underlying NK cell immune checkpoints and their mechanisms of action within the complex tumor microenvironment, this review aims to provide critical theoretical insights and translational foundations to foster the development of innovative tumor immunotherapy strategies, improvement of combination therapies, and realization of personalized precision medicine.

The first challenge in building a living robotic system inspired by life evolution is how to replicate the original form of life—the cell. However, current microrobots mimic cell motion control but fail to replicate the functional biological activities of cellular systems. Here, we propose a strategy that programs microparticle swarms encapsulated in droplets at an air/liquid interface to create cell-mimetic droplet microrobots with vitality by employing alternating magnetic fields. Through the design of algorithms and spontaneous interface waves, our collective system embodies reversible transitions between gas, chain, array, and disk-like collective modes, and emulates various complex activities of living cells in nature, including division and exocytosis. Based on these 2 capabilities learned from living cells, the cell-mimetic microrobots navigate the bile duct to the gallbladder under the guidance and control of magnetic fields, completing the drug release task. This cell-mimetic microrobots may provide a fundamental understanding of cellular life and pave the way for the construction of artificial living systems. Furthermore, they hold substantial potential for medical and environmental applications.