Research on the flexible hybrid epidermal electronic system (FHEES) has attracted considerable attention due to its potential applications in human–machine interaction and healthcare. Through material and structural innovations, FHEES combines the advantages of traditional stiff electronic devices and flexible electronic technology, enabling it to be worn conformally on the skin while retaining complex system functionality. FHEESs use multimodal sensing to enhance the identification accuracy of the wearer's motion modes, intentions, or health status, thus realizing more comprehensive physiological signal acquisition. However, the heterogeneous integration of soft and stiff components makes balancing comfort and performance in designing and implementing multimodal FHEESs challenging. Herein, multimodal FHEESs are first introduced in 2 types based on their different system structure: all-in-one and assembled, reflecting totally different heterogeneous integration strategies. Characteristics and the key design issues (such as interconnect design, interface strategy, substrate selection, etc.) of the 2 multimodal FHEESs are emphasized. Besides, the applications and advantages of the 2 multimodal FHEESs in recent research have been presented, with a focus on the control and medical fields. Finally, the prospects and challenges of the multimodal FHEES are discussed.

Flexible epidermal electrodes hold substantial promise in realizing human electrophysiological information collections. Conventional electrodes exhibit certain limitations, including the requirement of skin pretreatment, reliance on external object-assisted fixation, and a propensity of dehydration, which severely hinder their applications in medical diagnosis. To tackle those issues, we developed a hydrogel electrode with both transcutaneous stimulation and neural signal acquisition functions. The electrode consists of a composite conductive layer (CCL) and adhesive conductive hydrogel (ACH). The CCL is designed as a laminated structure with high conductivity and charge storage capacity (CSC). Based on the optimization of Hoffmeister effect, the ACH demonstrates excellent electrical (resistivity of 3.56 Ω·m), mechanical (tensile limit of 1,650%), and adhesion properties (peeling energy of 0.28 J). The utilization of ACH as electrode/skin interface can reduce skin contact impedance and noise interference and enhance the CSC and charge injection capacity of electrodes. As a proof of concept, peripheral nerve conduction studies were performed on human volunteers to evaluate the as-fabricated hydrogel electrodes. Compared with the commercial electrodes, our hydrogel electrodes achieved better signal continuity and lower distortion, higher signal-to-noise ratio (~35 dB), and lower stimulation voltages (up to 27% lower), which can improve the safety and comfort of nerve conduction studies.

Mitophagy maintains tissue homeostasis by self-eliminating defective mitochondria through autophagy. How mitophagy regulates stem cell activity during hair regeneration remains unclear. Here, we found that mitophagy promotes the proliferation of hair germ (HG) cells by regulating glutathione (GSH) metabolism. First, single-cell RNA sequencing, mitochondrial probe, transmission electron microscopy, and immunofluorescence staining showed stronger mitochondrial activity and increased mitophagy-related gene especially Prohibitin 2 (Phb2) expression at early-anagen HG compared to the telogen HG. Mitochondrial inner membrane receptor protein PHB2 binds to LC3 to initiate mitophagy. Second, molecular docking and functional studies revealed that PHB2-LC3 activates mitophagy to eliminate the damaged mitochondria in HG. RNA-seq, single-cell metabolism, immunofluorescence staining, and functional validation discovered that LC3 promotes GSH metabolism to supply energy for promoting HG proliferation. Third, transcriptomics analysis and immunofluorescence staining indicated that mitophagy was down-regulated in the aged compared to young-mouse HG. Activating mitophagy and GSH pathways through small-molecule administration can reactivate HG cell proliferation followed by hair regeneration in aged hair follicles. Our findings open up a new avenue for exploring autophagy that promotes hair regeneration and emphasizes the role of the self-elimination effect of mitophagy in controlling the proliferation of HG cells by regulating GSH metabolism.

Nanomaterial-based drug delivery systems are susceptible to premature drug leakage and systemic toxicity due to lack of specific targeting, and live-cell drug delivery is also prone to be restricted by drug carrier–cell interactions. Here, a method is established to adsorb drug-loaded nanomaterials externally to the live cells, which reduces cytotoxicity caused by drug uptake and improves the bioactivity of the carrier cells and drug release at the lesion site. It was found that polyphenols act like “double-sided tape” to bridge metal–organic framework (MOF) nanoparticles with live macrophages (Mφ), attaching MOFs to the Mφ surface and minimizing intracellular uptake, with no negative effect on cell proliferation. On this basis, a “macrophage missile” with peroxymonosulfate (PMS)-loaded MOF nanoparticles on the cell surface was constructed. As a “propellant”, the Mφ, in which bioactivity is preserved, can selectively identify and target tumor cells, precisely bringing nanomedicines to the lesion. MOF nanoparticles are used to load and catalyze PMS, which acts as an exogenous source of reactive oxygen species, showing higher efficacy and lower toxicity in an oxygen-independent manner. The primary study results demonstrate that this innovative combination of biology and nanomaterials remarkably enhances tumor targeting and therapeutic efficacy while reducing systemic side effects. This approach is expected to provide a more effective and safer treatment for lung cancer and holds promise for broader applications in other cancer therapies.

Candida albicans is an opportunistic fungal pathogen of humans. It causes a variety of infections ranging from superficial mucocutaneous conditions to severe systemic diseases that result in substantial morbidity and mortality. This pathogen frequently forms biofilms resistant to antifungal drugs and the host immune system, leading to treatment failures. Recent research has demonstrated the potential of nanorobots to penetrate biological barriers and disrupt fungal biofilms. In this perspective paper, we provide a brief overview of recent breakthroughs in nanorobots for candidiasis treatment and discuss current challenges and prospects.

Direct current triboelectric nanogenerators (DC-TENGs) are a groundbreaking technology to capture micromechanical energy from the natural environment, which is crucial for directly powering sensor networks. However, the research bottleneck in enhancing the triboelectric electrification capability and charge storage capability of dielectrics has hindered the overall performance breakthroughs of the DC-TENG. Here, a field emission model-based DC-TENG (FEM-TENG) is proposed, inspired by lightning rods. The enhanced local electric field between dielectric materials and electrodes induces strong electron tunneling, which improves charge neutralization on the surface of materials and their internal charge storage space, thereby utilizing the dielectric volume effect effectively and strengthening triboelectricity. Guided by the field emission model, the FEM-TENG with a historic crest factor of 1.00375 achieves a groundbreaking record of an average power density of 16.061 W m⁻² Hz⁻¹ (1,591 W m⁻³ Hz⁻¹), which is 5.36-fold of the latest DC-TENG. In particular, the FEM-TENG with high durability (100%) truly realizes the collection of breeze energy and continuously drives 50 thermohygrometers. Four additional applications exemplify the FEM-TENG, enabling comprehensive sensing of land, water, and air. This work proposes a paradigm strategy for the in-depth utilization of dielectric films, aiming to enhance the output power of DC-TENGs.

Super strength and toughness, excellent deformation resistance, and high-temperature service performance are the key factors to determine the practical application of new thermal barrier coatings (TBCs). The limited mobility of dislocations and the internal inherent defects in ceramics will inevitably lead to the decline of strength–plasticity and the reduction of service performance. Introducing preexisting twin boundaries and stacking faults (SFs) or preparing ceramic materials with high configuration entropy has demonstrated to be an effective strategy for enhancing the mechanical properties of ceramics. However, due to the positive thermal expansion coefficient of most ceramics and the remarkable increase of structural disorder at elevated temperature, the problem of elastic softening has become a bottleneck restricting the high-temperature service life of new TBCs. In this paper, the deformation behavior of high configuration entropy Zr₆Ta₂O₁₇ ceramics at 25 to 1,200 °C was in situ monitored via digital image correlation technique and three-point bending test platform in high-temperature environment. A remarkable Elinvar-like effect appears in the Zr₆Ta₂O₁₇ ceramic. More interestingly, mechanical deformation dominates the severe lattice distortion (deformation twins, SFs) and the disorder–order transition of chemical order at the atomic scale, while temperature can further enhance the degree of lattice distortion and ordering of Zr₆Ta₂O₁₇ ceramics. Furthermore, the atomic fluctuations at high temperature promotes the comprehensive improvement of mechanical properties in the Zr₆Ta₂O₁₇ ceramics.

“Boundarics in Biomedicine” is a cutting-edge interdisciplinary discipline, which is of great significance for understanding the origin of life, the interaction between internal and external environments, and the mechanism of disease occurrence and evolution. Here, the definition of Boundarics in Biomedicine is first described, including its connotation, research object, research method, challenges, and future perspectives.

“Boundarics in Biomedicine” is a cutting-edge interdisciplinary discipline involving multiple fields (e.g., bioscience, medicine, chemistry, materials science, and information science) dedicated to investigating and solving key scientific questions in the formation, identification, and evolution of living organism boundaries. Specifically, it encompasses 3 levels: (a) the boundary between the living organism and the external environment, (b) internal boundary within living organism, and (c) the boundary related to disease in living organism. The advancement of research in Boundarics in Biomedicine is of great scientific significance for understanding the origin of life, the interaction between internal and external environments, and the mechanism of disease occurrence and evolution, thus providing novel principles, technologies, and methods for early diagnosis and prevention of major diseases, personalized drug development, and prognosis assessment (Fig. 1).

Although microgravity has been implicated in osteoporosis, the precise molecular mechanism remains elusive. Here, we found that microgravity might induce mitochondrial protein buildup in skeletal muscle, alongside reduced levels of LONP1 protein. We revealed that disruptions in mitochondrial proteolysis, induced by the targeted skeletal muscle-specific deletion of the essential mitochondrial protease LONP1 or by the acute inducible deletion of muscle LONP1 in adult mice, cause reduced bone mass and compromised mechanical function. Moreover, the bone loss and weakness phenotypes were recapitulated in skeletal muscle-specific overexpressing ΔOTC mice, a known protein degraded by LONP1. Mechanistically, mitochondrial proteostasis imbalance triggered the mitochondrial unfolded protein response (UPR^mt) in muscle, leading to an up-regulation of multiple myokines, including FGF21, which acts as a pro-osteoclastogenic factor. Surprisingly, this mitochondrial proteostasis stress influenced muscle–bone crosstalk independently of ATF4 in skeletal muscle. Furthermore, we established a marked association between serum FGF21 levels and bone health in humans. These findings emphasize the pivotal role of skeletal muscle mitochondrial proteostasis in responding to alterations in loading conditions and in coordinating UPR^mt to modulate bone metabolism.

Stereoscopic imaging of single molecules at the plasma membrane of single cell requires spatial resolutions in 3 dimensions (x-y-z) at 10-nm level, which is rarely achieved using most optical super-resolution microscopies. Here, electrochemical stereoscopic microscopy with a detection limit down to a single molecule is achieved using a photoreduction-assisted cycle inside a 20-nm gel electrolyte nanoball at the tip of a nanopipette. On the basis of the electrochemical oxidation of Ru(bpy)₃²⁺ into Ru(bpy)₃³⁺ followed by the reduction of Ru(bpy)₃³⁺ into Ru(bpy)₃²⁺ by photogenerated isopropanol radicals, a charge of 1.5 fC is obtained from the cycling electron transfers involving one Ru(bpy)₃^2+/3+ molecule. By using the nanopipette to scan the cellular membrane modified with Ru(bpy)₃²⁺-tagged antibody, the morphology of the cell membrane and the distribution of carcinoembryonic antigen (CEA) on the membrane are electrochemically visualized with a spatial resolution of 14 nm. The resultant stereoscopic image reveals more CEA on membrane protrusions, providing direct evidence to support easy access of membrane CEA to intravenous antibodies. The breakthrough in single-molecule electrochemistry at the cellular level leads to the establishment of high-resolution 3-dimensional single-cell electrochemical microscopy, offering an alternative strategy to remedy the imperfection of stereoscopic visualization in optical microscopes.