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.

Developing low-cost plastic recycling technologies is crucial for ecological sustainability and the circular economy. The recent publication in Science by Conk et al. introduces an innovative method employing base-metal catalysts, specifically WO₃/SiO₂ and Na/γ-Al₂O₃, to efficiently convert polyethylene, polypropylene, or their mixtures into valuable products, representing a marked advancement in the field of base-metal catalysis and plastic recycling.

Ocean acidification is becoming more prevalent and may contribute to coral reef degradation, yet our understanding of its role in global reef decline remains limited. Therefore, there is an urgent need to study the impact of reduced pH levels on the growth patterns of major reef-building corals. Here, we studied the skeleton-forming strategies of 4 widely distributed coral species in a simulated acidified habitat with a pH of 7.6 to 7.8. We reconstructed and visualized the skeleton-forming process, quantified elemental calcium loss, and determined gene expression changes. The results suggest that different reef-building corals have diverse growing strategies in lower pH conditions. A unique “cavity-like” forming process starts from the inside of the skeletons of Acropora muricata, which sacrifices skeletal density to protect its polyp–canal system. The forming patterns in Pocillopora damicornis, Montipora capricornis, and Montipora foliosa were characterized by “osteoporosis”, exhibiting disordered skeletal structures, insufficient synthesis of adhesion proteins, and low bone mass, correspondingly. In addition, we found that damage from acidification particularly affects pre-existing skeletal structures in the colony. These results enhance our understanding of skeleton-forming strategies in major coral species under lower pH conditions, providing a foundation for coral reef protection and restoration amidst increasing ocean acidification.

The explosive growth of data has intensified challenges to information security, spurring a critical need for advanced encryption technologies, and relying solely on digital encryption still leaves information vulnerable to interception and leakage during transmission. Therefore, encryption technologies that combine digital algorithms with physical keys to further enhance information security are widely studied. In this work, we present an angle- and polarization-selective dual-wavelength long-wavelength infrared narrowband thermal emitter for infrared encryption–decryption applications. The thermal emitter is composed of an epsilon-near-zero material upon a metallic layer, designed to enable the excitation of the Berreman mode and asymmetric Fabry–Pérot resonance simultaneously. Numerical simulations combined with the transfer matrix method are employed to analytically investigate the optical responses, demonstrating good agreement with experimental results. Moreover, a robust multilevel cryptographic communication system is developed, utilizing the thermal emitter's imaging results as the physical-layer key to enable highly efficient information encryption and decryption. We anticipate that the proposed thermal emitters will pave the way for realizing relevant applications in various information encryption devices.

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.

Tryptophan (Trp), an essential amino acid, performs as a precursor for synthesizing various bioactive molecules primarily metabolized through the kynurenine (Kyn), serotonin, and indole pathways. The diverse metabolites were deeply implicated in multiple physiological processes. Emerging research has revealed the multifaceted contribution of Trp in skeletal health and pathophysiology of bone-related disease with the involvement of specific receptors including aryl hydrocarbon receptor (AhR), which modulated the downstream signaling pathways to manage the expression of pivotal genes and thereby altered cellular biological processes, such as proliferation and differentiation. Accompanied by distinct alterations in immune function, inflammatory responses, endocrine balance, and other physiological aspects, their impact and efficacy in osteochondrogenic disorders have also been well documented. Nevertheless, a thorough understanding of Trp metabolism within bone biology is currently lacking. In this review, we elucidate the complexities of Trp metabolic pathway and several metabolites, delineating their versatile modulatory roles in the physiology and pathology of osteoblasts (OBs), osteoclasts (OCs), chondrocytes, and intercellular coupling effects, as well as in the progression of osteochondral disorder. Moreover, we comprehensively delineate the regulatory mechanisms by which gut microbiota-generated indole derivatives mediate bidirectional crosstalk along the gut–bone axis. The establishment of an elaborate governing network about bone homeostasis provides a novel insight on therapeutic interventions.

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.

Mechanical metamaterials, by introducing porous structures into the materials, can achieve complex nonlinear responses through the large deformation of structures, which support a new generation of impact energy absorption and vibration damping systems, wearable electronics, and tactile simulation devices. However, arbitrarily customizable stress–strain curves have yet to be achieved by existing mechanical metamaterials, which are inherently multi-degree-of-freedom (multi-DOF) deformable systems, and their deformation sequence is influenced by the minimum energy gradient principle. Multi-DOF metamaterials behave like underactuated systems, where the number of degrees of freedom exceeds the number of actuators. As a result, their deformation is controlled by the material's elastic forces, inertial forces, and boundary constraints. Here, we propose a novel composition of elastic components integrated with one-degree-of-freedom (1-DOF) kinematic bases, forming a fully actuated system in which the number of actuators equals the number of degrees of freedom. The deformation of each elastic component is governed by its designed 1-DOF kinematic path. Consequently, the stress–strain profile can be arbitrarily prescribed, for instance, controlled multistage strain softening curve is achievable, as the principle of minimum energy gradient does not affect the deformation sequence dictated by the 1-DOF kinematic base. Furthermore, a class of shape memory alloys (SMAs) is introduced as active components to enable rapid in situ property change, providing versatility in switching between different target responses. The analytical inverse design method, numerical analysis, parametric study of different target responses, and experimental validation are carried out. Lastly, preliminary demonstrations of designable anisotropic nonlinear responses are presented.

Protein kinases are key mediators of cellular signaling and control cell functions through the phosphorylation of target proteins. They have become major targets for therapeutic agents aimed at treating human diseases, particularly cancer. Protein kinase inhibitors (PKIs) have emerged at the forefront of drug development, and their investigations continue to be intense, with several candidates undergoing clinical trials and persistent endeavors to identify new chemical scaffolds. The main focus is still on developing isoform-selective compounds, which are inhibitors designed to target certain protein kinases, specifically isoforms, for more precise treatment. The identification and advancement of versatile inhibitor scaffolds that more effectively target individual kinases is essential for minimizing off-target effects and resistance. This review highlights important progress in PKI therapy, emphasizing the expansion of treatments for cancer, inflammatory diseases, and neurodegenerative diseases. Future efforts should focus on improving the specificity of inhibitors via mechanistic insights, developing combination therapies, establishing novel strategies, such as CRISPR-Cas9 integration with artificial intelligence-driven drug design, and overcoming resistance to enhance clinical treatment outcomes. Clinical case stories show the challenges and possible opportunities in this quickly evolving area.

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.