Throughout billions of years, biological systems have evolved sophisticated, multiscale hierarchical structures to adapt to changing environments. Biomaterials are synthesized under mild conditions through a bottom-up self-assembly process, utilizing substances from the surrounding environment, and meanwhile are regulated by genes and proteins. Additive manufacturing, which mimics this natural process, provides a promising approach to developing new materials with advantageous properties similar to natural biological materials. This review presents an overview of natural biomaterials, emphasizing their chemical and structural compositions at various scales, from the nanoscale to the macroscale, and the key mechanisms underlying their properties. Additionally, this review describes the designs, preparations, and applications of bioinspired multifunctional materials produced through additive manufacturing at different scales, including nano, micro, micro-macro, and macro levels. The review highlights the potential of bioinspired additive manufacturing to develop new functional materials and insights into future directions and prospects in this field. By summarizing the characteristics of natural biomaterials and their synthetic counterparts, this review inspires the development of new materials that can be utilized in various applications.

Ventricular arrhythmogenesis is a key cause of sudden cardiac death following myocardial infarction (MI). Accumulating data show that ischemia, sympathetic activation, and inflammation contribute to arrhythmogenesis. However, the role and mechanisms of abnormal mechanical stress in ventricular arrhythmia following MI remain undefined. We aimed to examine the impact of increased mechanical stress and identify the role of the key sensor Piezo1 in ventricular arrhythmogenesis in MI. Concomitant with increased ventricular pressure, Piezo1, as a newly recognized mechano-sensitive cation channel, was the most up-regulated mechanosensor in the myocardium of patients with advanced heart failure. Piezo1 was mainly located at the intercalated discs and T-tubules of cardiomyocytes, which are responsible for intracellular calcium homeostasis and intercellular communication. Cardiomyocyte-conditional Piezo1 knockout mice (Piezo1^Cko) exhibited preserved cardiac function after MI. Piezo1^Cko mice also displayed a dramatically decreased mortality in response to the programmed electrical stimulation after MI with a markedly reduced incidence of ventricular tachycardia. In contrast, activation of Piezo1 in mouse myocardium increased the electrical instability as indicated by prolonged QT interval and sagging ST segment. Mechanistically, Piezo1 impaired intracellular calcium cycling dynamics by mediating the intracellular Ca²⁺ overload and increasing the activation of Ca²⁺-modulated signaling, CaMKII, and calpain, which led to the enhancement of phosphorylation of RyR2 and further increment of Ca²⁺ leaking, finally provoking cardiac arrhythmias. Furthermore, in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), Piezo1 activation remarkably triggered cellular arrhythmogenic remodeling by significantly shortening the duration of the action potential, inducing early afterdepolarization, and enhancing triggered activity.This study uncovered a proarrhythmic role of Piezo1 during cardiac remodeling, which is achieved by regulating Ca²⁺ handling, implying a promising therapeutic target in sudden cardiac death and heart failure.

Modern scleractinian corals are classified into robust, complex, and basal clades through comparative molecular studies. However, only few morphological or biological criteria can systematically determine the evolutionary trajectories of these major scleractinian coral clades. Here, we obtained the structural information of 21 scleractinian coral species representing robust and complex clades: High-resolution micro-computed tomography was used to reconstruct the polyp-canal systems in their colonies and to visualize the dynamic polyp growth processes. We found that the emergence of mesh-like canals may distinguish representatives of complex and robust clades. The differences in polyp-canal connections suggest distinct evolutionary trajectories among coral species: The formation of the canal network promoted the development of more complex coral structures, and coral polyps within this network formed calices of very similar volume, following precise axial growth directions. The influence of individual polyps on the coral colony becomes less significant as coral structures become more complex, and coral species with more complicated polyp-canal systems occupied niches more efficiently. This work supplements current evolutionary studies on reef-building corals, providing insight for further studies on coral growth patterns.

Psoriasis is a chronic inflammatory skin disease featuring rapid proliferation of epidermal cells. Although elevated glycolysis flux has been reported in psoriasis, the molecular mechanisms underlying its pathogenesis remain unclear. We investigated the role of the integral membrane protein CD147 in psoriasis pathogenesis, observing its high expression in psoriatic skin lesions of humans and imiquimod (IMQ)-induced mouse models. In mouse models, genomic deletion of epidermal CD147 markedly attenuated IMQ-induced psoriatic inflammation. We found that CD147 interacted with glucose transporter 1 (Glut1). Depletion of CD147 in the epidermis blocked glucose uptake and glycolysis in vitro and in vivo. In CD147-knockout mice and keratinocytes, oxidative phosphorylation was increased in the epidermis, indicating CD147's pivotal role in glycolysis reprogramming during pathogenesis of psoriasis. Using non-targeted and targeted metabolic techniques, we found that epidermal deletion of CD147 significantly increased the production of carnitine and α-ketoglutaric acid (α-KG). Depletion of CD147 also increased transcriptional expression and activity of γ-butyrobetaine hydroxylase (γ-BBD/BBOX1), a crucial molecule for carnitine metabolism, by inhibiting histone trimethylations of H3K9. Our findings demonstrate that CD147 is critical in metabolic reprogramming through the α-KG–H3K9me3–BBOX1 axis in the pathogenesis of psoriasis, indicating that epidermal CD147 is a promising target for psoriasis treatment.

The hybrid electromagnetic-triboelectric generator (HETG) is a prevalent device for mechanical energy harvesting. However, the energy utilization efficiency of the electromagnetic generator (EMG) is inferior to that of the triboelectric nanogenerator (TENG) at low driving frequencies, which limits the overall efficacy of the HETG. To tackle this issue, a layered hybrid generator consisting of a rotating disk TENG, a magnetic multiplier, and a coil panel is proposed. The magnetic multiplier not only forms the EMG part with its high-speed rotor and the coil panel but also facilitates the EMG to operate at a higher frequency than the TENG through frequency division operation. The systematic parameter optimization of the hybrid generator reveals that the energy utilization efficiency of EMG can be elevated to that of rotating disk TENG. Incorporating a power management circuit, the HETG assumes the responsibility for monitoring the water quality and fishing conditions by collecting low-frequency mechanical energy. The magnetic- multiplier-enabled hybrid generator demonstrated in this work offers a universal frequency division approach to improve the overall outputs of any hybrid generator that collects rotational energy, expanding its practical applications in diverse multifunctional self-powered systems.

Small-molecule photothermal agents (PTAs) with intense second near-infrared (NIR-II, 1,000 to 1,700 nm) absorption and high photothermal conversion efficiencies (PCEs) are promising candidates for treating deep-seated tumors such as osteosarcoma. To date, the development of small-molecule NIR-II PTAs has largely relied on fabricating donor–acceptor–donor (D–A–D/D′) structures and limited success has been achieved. Herein, through acceptor engineering, a donor–acceptor–acceptor (D–A–A′)-structured NIR-II aza-boron-dipyrromethene (aza-BODIPY) PTA (SW8) was readily developed for the 1,064-nm laser-mediated phototheranostic treatment of osteosarcoma. Changing the donor groups to acceptor groups produced remarkable red-shifts of absorption maximums from first near-infrared (NIR-I) regions (~808 nm) to NIR-II ones (~1,064 nm) for aza-BODIPYs (SW1 to SW8). Furthermore, SW8 self-assembled into nanoparticles (SW8@NPs) with intense NIR-II absorption and an ultrahigh PCE (75%, 1,064 nm). This ultrahigh PCE primarily originated from an additional nonradiative decay pathway, which showed a 100-fold enhanced decay rate compared to that shown by conventional pathways such as internal conversion and vibrational relaxation. Eventually, SW8@NPs performed highly efficient 1,064-nm laser-mediated NIR-II photothermal therapy of osteosarcoma via concurrent apoptosis and pyroptosis. This work not only illustrates a remote approach for treating deep-seated tumors with high spatiotemporal control but also provides a new strategy for building high-performance small-molecule NIR-II PTAs.

Anaplastic lymphoma kinase (ALK), a tyrosine receptor kinase, has been proven to be associated with the occurrence of numerous malignancies. Although there have been already at least 3 generations of ALK inhibitors approved by FDA or in clinical trials, the occurrence of various mutations seriously attenuates the effectiveness of the drugs. Unfortunately, most of the drug resistance mechanisms still remain obscure. Therefore, it is necessary to reveal the bottom reasons of the drug resistance mechanisms caused by the mutations. In this work, on the basis of verifying the accuracy of 2 main kinds of binding free energy calculation methodologies [end-point method of Molecular Mechanics with Poisson-Boltzmann/Generalized Born and Surface Area (MM/PB(GB)SA) and alchemical method of Thermodynamic Integration (TI)], we performed a systematic analysis on the ALK systems to explore the underlying shared and specific drug resistance mechanisms, covering the one-drug-multiple-mutation and multiple-drug-one-mutation cases. Through conventional molecular dynamics (cMD) simulation in conjunction with MM/PB(GB)SA and umbrella sampling (US) in conjunction with contact network analysis (CNA), the resistance mechanisms of the in-pocket, out-pocket, and multiple-site mutations were revealed. Especially for the out-pocket mutation, a possible transfer chain of the mutation effect was revealed, and the reason why different drugs exhibited various sensitivities to the same mutation was also uncovered. The proposed mechanisms may be prevalent in various drug resistance cases.

Human cognition is usually underpinned by intrinsic structure and functional neural co-activation in spatially distributed brain regions. Owing to lacking an effective approach to quantifying the covarying of structure and functional responses, how the structural–functional circuits interact and how genes encode the relationships, to deepen our knowledge of human cognition and disease, are still unclear. Here, we propose a multimodal covariance network (MCN) construction approach to capture interregional covarying of the structural skeleton and transient functional activities for a single individual. We further explored the potential association between brain-wide gene expression patterns and structural–functional covarying in individuals involved in a gambling task and individuals with major depression disorder (MDD), adopting multimodal data from a publicly available human brain transcriptomic atlas and 2 independent cohorts. MCN analysis showed a replicable cortical structural–functional fine map in healthy individuals, and the expression of cognition- and disease phenotype-related genes was found to be spatially correlated with the corresponding MCN differences. Further analysis of cell type-specific signature genes suggests that the excitatory and inhibitory neuron transcriptomic changes could account for most of the observed correlation with task-evoked MCN differences. In contrast, changes in MCN of MDD patients were enriched for biological processes related to synapse function and neuroinflammation in astrocytes, microglia, and neurons, suggesting its promising application in developing targeted therapies for MDD patients. Collectively, these findings confirmed the correlations of MCN-related differences with brain-wide gene expression patterns, which captured genetically validated structural–functional differences at the cellular level in specific cognitive processes and psychiatric patients.

Natural tactile sensation is complex, which involves not only contact force intensity detection but also the perception of the force direction, the surface texture, and other mechanical parameters. Nevertheless, the vast majority of the developed tactile sensors can only detect the normal force, but usually cannot resolve shear force or even distinguish the directions of the force. Here, we present a new paradigm of bioinspired tactile sensors for resolving both the intensity and the directions of mechanical stimulations via synergistic microcrack-bristle structure design and cross-shaped configuration engineering. The microcrack sensing structure gives high mechanical sensitivity to the tactile sensors, and the synergistic bristle structure further amplifies the sensitivity of the sensors. The cross-shaped configuration engineering of the synergistic microcrack-bristle structure further endows the tactile sensors with good capability to detect and distinguish the directions of the applied mechanical forces. The as-fabricated tactile sensors exhibit a high sensitivity (25.76 N⁻¹), low detection limit (5.4 mN), desirable stability (over 2,500 cycles), and good capability to resolve both mechanical intensity and directional features. As promising application scenarios, surface texture recognition and biomimetic path explorations are successfully demonstrated with these tactile sensors. This newly proposed tactile sensation strategy and technology have great potential applications in ingenious tactile sensation and construction of various robotic and bionic prostheses with high operational dexterity.

Capacitive mixing is a promising blue energy technology due to its membrane-free electricity generation and long electrode life cycle. However, because of limited performance, existing systems do not lend themselves to practical implementation. Although it is a crucial factor directly influencing electrode behavior, surface chemistry has largely been overlooked in capacitive mixing. Here, we show that manipulating surface functionalization alone can tune the responses of electrodes to produce a high voltage rise without altering the pore structure of the electrodes. Our findings reveal that the spontaneous electrode potential of a surface-modified carbon electrode shifts negatively proportional to the surface charge due to the surface groups, which explains why and how manipulating the surface chemistry can improve the power generation capacity. Using electrodes fabricated with identical activated carbon material but with different surface treatments, we have achieved a remarkably high power density of 166 mW/m² delivered to an electrical load under a 0.6 M to 0.01 M salinity gradient, with the total power generated of 225 mW/m². The corresponding volumetric power densities were 0.88 kW/m³ net and 1.17 kW/m³ total. The volumetric power density of our prototype is comparable to or better than those of prevailing membrane technologies, such as pressure retarded osmosis and reverse electrolysis, whose volumetric power density values are 1.1 kW/m³ and 0.16 kW/m³, respectively. In the seawater stage, the net power density reached 432 mW/m² or 2.3 kW/m³. Such performance far exceeds existing membrane-free systems, with the highest reported power density of 65 mW/m² under a 0.5 M to 0.02 M salinity gradient (121 mW/m² in this work). The device demonstrated unparalleled durability, maintaining 90% of the maximum energy capacity after 54,000 charge–discharge cycles.