Zebularine potentiates anti-tumor immunity by inducing tumor immunogenicity and improving antigen processing through cGAS-STING pathway.

DNA methylation is an important epigenetic mechanism involved in the anti-tumor immune response, and DNA methyltransferase inhibitors (DNMTi) have achieved impressive therapeutic outcomes in patients with certain cancer types. However, it is unclear how inhibition of DNA methylation bridges the innate and adaptive immune responses to inhibit tumor growth. Here, we report that DNMTi zebularine reconstructs tumor immunogenicity, in turn promote dendritic cell maturation, antigen-presenting cell activity, tumor cell phagocytosis by APCs, and efficient T cell priming. Further in vivo and in vitro analyses reveal that zebularine stimulates cGAS-STING-NF-κB/IFNß signaling to enhance tumor cell immunogenicity and upregulate antigen processing and presentation machinery (AgPPM), which promotes effective CD4+ and CD8+ T cell-mediated killing of tumor cells. These findings support the use of combination regimens that include DNMTi and immunotherapy for cancer treatment.

Hierarchical Piezoelectric Composites for Noninvasive Continuous Cardiovascular Monitoring.

Continuous monitoring of blood pressure (BP) and multiparametric analysis of cardiac functions are crucial for the early diagnosis and therapy of cardiovascular diseases. However, existing monitoring approaches often suffer from bulky and intrusive apparatus, cumbersome testing procedures, and challenging data processing, hampering their applications in continuous monitoring. Here, a heterogeneously hierarchical piezoelectric composite is introduced for wearable continuous BP and cardiac function monitoring, overcoming the rigidity of ceramic and the insensitivity of polymer. By optimizing the hierarchical structure and components of the composite, the developed piezoelectric sensor delivers impressive performances, ensuring continuous and accurate monitoring of BP at Grade A level. Furthermore, the hemodynamic parameters are extracted from the detected signals, such as local pulse wave velocity, cardiac output, and stroke volume, all of which are in alignment with clinical results. Finally, the all-day tracking of cardiac function parameters validates the reliability and stability of the developed sensor, highlighting its potential for personalized healthcare systems, particularly in early diagnosis and timely intervention of cardiovascular disease.

Mass-Produced Skin-Inspired Piezoresistive Sensing Array with Interlocking Interface for Object Recognition.

E-skins, capable of responding to mechanical stimuli, hold significant potential in the field of robot haptics. However, it is a challenge to obtain e-skins with both high sensitivity and mechanical stability. Here, we present a bioinspired piezoresistive sensor with hierarchical structures based on polyaniline/polystyrene core-shell nanoparticles polymerized on air-laid paper. The combination of laser-etched reusable templates and sensitive materials that can be rapidly synthesized enables large-scale production. Benefiting from the substantially enlarged deformation of the hierarchical structure, the developed piezoresistive electronics exhibit a decent sensitivity of 21.67 kPa-1 and a subtle detection limit of 3.4 Pa. Moreover, an isolation layer is introduced to enhance the interface stability of the e-skin, with a fracture limit of 66.34 N/m. Furthermore, the e-skin can be seamlessly integrated onto gloves without any detachment issues. With the assistance of deep learning, it achieves a 98% accuracy rate in object recognition. We anticipate that this strategy will render e-skin with more robust interfaces and heightened sensing capabilities, offering a favorable pathway for large-scale production.

Glycolysis inhibition for synergistic phototherapy of triple-negative breast cancer.

Phototherapy is a local and precise therapeutic technique for tumor treatment. However, the therapeutic effects of photothermal and photodynamic therapies are inevitably encountered by hypoxia of the tumor microenvironment and heat shock protein induced by hyperthermia, respectively. Herein, we found that mannose, a glucose analog, could reverse tumor hypoxia by inhibiting glycolysis of cancer cells and suppressing the expression of heat shock protein through inhibiting cellular adenosine triphosphate (ATP) generation. Next, we used lipid nanoparticles simultaneously loaded with indocyanine green (ICG) and mannose molecules, named imLipo, for tumor therapy. Both in vitro and in vivo experiments evidenced that the imLipo nanoplatform has significant therapeutic efficacy through synergistic phototherapy under single near-infrared laser irradiation. This work shows that glycolysis inhibition can overcome the challenges of phototherapy. In addition, all three parts (mannose, ICG, and lipid) of imLipo are clinically approved and our designed nanoplatforms have great potential for future tumor treatment.

Modulating piezoelectricity and mechanical strength via three-dimensional gradient structure for piezoelectric composites.

Advanced flexible electronic devices make urgent demand for wearing comfort and data accuracy. Piezoelectric composites exhibit great potential, but mutually constrained mechanical strength and electrical output limit their further applications. Here, we design a gradient PMN-PT/PVDF nanocomposite via a non-equilibrium process integrated with a modified electrospinning and hot-pressing process to modulate the piezoelectric output and mechanical strength. The enhanced piezoelectric output together with the mechanical strength of the gradient structure are verified from both the experimental and simulation results. Ascribed to a unique three-dimensional gradient distribution, the prepared PMN-PT/PVDF nanocomposite exhibits an excellent mechanical strength (830 MPa) and piezoelectric performance (1.08 V), which are substantially higher than those of a randomly dispersed nanocomposite. The enhancement mechanism is revealed in terms of polarization, stress and crystallinity. These results of the gradient structure offer new opportunities to understand the structure-related mechanical and electrical behaviors of a nanocomposite, and support the design of a nanocomposite with overall performance.

DWL-4-140: A allene small molecule targeting STING that alleviates lupus-like phenotype in Trex1-/- mice.

The innate immune system plays a critical role in the host response against pathogenic microbial infection. However, aberrant activation of the innate immune pathways is a characteristic feature of various diseases. Thus, targeted drugs must be developed based on the understanding of the innate immune signaling pathways. This study demonstrated that an allene small molecule (DWL-4-140) can efficiently and selectively exert regulatory effects on the stimulator of interferon genes (STING), resulting in the downregulation of DNA-induced interferon responses. Mechanistically, DWL-4-140 targeted the cyclized nucleotide-binding domain (CBD) of STING, inhibiting the assembly of the STING multimeric complex and the recruitment of downstream signaling mediators. In addition to downregulating the 10-carboxymethyl-9-acridanone-induced production of inflammatory factors, DWL-4-140 alleviated the pathological features of Trex1 deletion-induced lupus in mice. Thus, this study demonstrated that DWL-4-140 pharmacologically inhibits STING with potential therapeutic applications in auto-inflammatory diseases.

Binding of ankaflavin with bovine serum albumin (BSA) in the presence of carrageenan and protective effects of Monascus yellow pigments against oxidative damage to BSA after forming a complex with carrageenan.

Ankaflavin (AK) is a typical yellow pigment extracted from Monascus-fermented rice with several biological effects; however, its solubility is poor. Thus, research studies of the delivery systems of AK, especially those constructed from protein-polysaccharide complexes, have attracted considerable attention. However, the interactions that exist in the system have rarely been investigated. This work focused on the interactions between AK and bovine serum albumin (BSA) as well as the influence of carrageenan (Car) on the binding of AK to BSA. Results revealed that the quenching of BSA by AK involved the static quenching mechanism. The formed BSA-AK complexes were mainly maintained by hydrophobic forces and AK was located within the hydrophobic cavity of BSA. Compared to free AK or AK only complexed with BSA, a higher absorption intensity of AK was observed for the formed BSA-AK-Car complexes, indicating changes in the microenvironment of AK. This was confirmed by the increase in the α-helix content of BSA after the formation of BSA-AK-Car complexes. Hydrogen bond, van der Waals, and electrostatic interactions were verified to be the primary forces preserving the BSA-AK-Car complexes. Moreover, the antioxidant potential of Monascus-fermented products rich in AK (denoted as Mps), namely BSA-Mps and BSA-Mps-Car was evaluated. The antioxidant activity of Mps was negatively impacted by BSA, while the addition of Car could enhance the antioxidant capacity of BSA-Mps-Car complexes. Meanwhile, Mps showed a protective effect against free radical-induced oxidation damage to BSA, and Car could further improve this effect.

Multichannel Gradient Piezoelectric Transducer Assisted with Deep Learning for Broadband Acoustic Sensing.

As an important part of human-machine interfaces, piezoelectric voice recognition has received extensive attention due to its unique self-powered nature. However, conventional voice recognition devices exhibit a limited response frequency band due to the intrinsic hardness and brittleness of piezoelectric ceramics or the flexibility of piezoelectric fibers. Here, we propose a cochlear-inspired multichannel piezoelectric acoustic sensor (MAS) based on gradient PVDF piezoelectric nanofibers for broadband voice recognition by a programmable electrospinning technique. Compared with the common electrospun PVDF membrane-based acoustic sensor, the developed MAS demonstrates the greatly 300%-broadened frequency band and the substantially 334.6%-enhanced piezoelectric output. More importantly, this MAS can serve as a high-fidelity auditory platform for music recording and human voice recognition, in which the classification accuracy rate can reach up to 100% in coordination with deep learning. The programmable bionic gradient piezoelectric nanofiber may provide a universal strategy for the development of intelligent bioelectronics.

Insight into Interfacial Polarization for Enhancing Piezoelectricity in Ferroelectric Nanocomposites.

The interfacial effect is widely used to optimize the properties of ferroelectric nanocomposites, however, there is still a lack of direct evidence to understand its underlying mechanisms limited by the nano size and complex structures. Here, taking piezoelectricity, for example, the mechanism of interfacial polarization in barium titanate/poly(vinylidene fluoride-ran-trifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite is revealed at multiple scales by combining Kelvin probe force microscope (KPFM) with theoretical stimulation. The results prove that the mismatch of permittivity between matrix and filler leads to the accumulation of charges, which in turn induces local polarization in the interfacial region, and thus can promote piezoelectricity independently. Furthermore, the strategy of interfacial polarization to enhance piezoelectricity is extended and validated in other two similar nanocomposites. This work uncovers the mechanism of interfacial polarization and paves newfangled insights to boost performances in ferroelectric nanocomposites.

Flexible Lead-Free Piezoelectric Ba0.94Sr0.06Sn0.09Ti0.91O3/PDMS Composite for Self-Powered Human Motion Monitoring.

Piezoelectric wearable electronics, which can sense external pressure, have attracted widespread attention. However, the enhancement of electromechanical coupling performance remains a great challenge. Here, a new solid solution of Ba1-xSrxSn0.09Ti0.91O3 (x = 0.00~0.08) is prepared to explore potential high-performance, lead-free piezoelectric ceramics. The coexistence of the rhombohedral phase, orthorhombic phase and tetragonal phase is determined in a ceramic with x = 0.06, showing enhanced electrical performance with a piezoelectric coefficient of d33~650 pC/N. Furthermore, Ba0.94Sr0.06Sn0.09Ti0.91O3 (BSST) is co-blended with PDMS to prepare flexible piezoelectric nanogenerators (PENGs) and their performance is explored. The effects of inorganic particle concentration and distribution on the piezoelectric output of the composite are systematically analyzed by experimental tests and computational simulations. As a result, the optimal VOC and ISC of the PENG (40 wt%) can reach 3.05 V and 44.5 nA, respectively, at 138.89 kPa, and the optimal sensitivity of the device is up to 21.09 mV/kPa. Due to the flexibility of the device, the prepared PENG can be attached to the surface of human skin as a sensor to monitor vital movements of the neck, fingers, elbows, spine, knees and feet of people, thus warning of dangerous behavior or incorrect posture and providing support for sports rehabilitation.

Carrier concentration-dependent interface engineering for high-performance zinc oxide piezoelectric device.

Piezoelectric semiconductor zinc oxide (ZnO) shows promising applications in many fields, however, its excellent piezoelectric performance is limited by the intrinsic screening effect. Forming p-n junction through interface engineering is an effective strategy to enhance its piezoelectric output, but the unclear regulation mechanism is a bottleneck in developing high-performance devices. In this work, the enhancement mechanism of interface engineering on the piezoelectric performance of ZnO nanorods (NRs) based devices is revealed from the perspective of carrier concentration. Both the theoretical and experimental results show that the piezoelectric output is significantly correlated with the carrier concentration, which is mainly attributed to the suppression of screening effect and the modulation of the device capacitance. After a reasonable matching design of carrier concentration, the piezoelectric potential of the ZnO NRs-based device is greatly enhanced by about 12 times. Apparently, these findings provide a fresh insight to further understand the enhancement mechanism of interface engineering on the electrical output of piezoelectric semiconductor devices, and provide effective support for the design of p-n junction piezoelectric devices.

Understanding the Enhancement Mechanism of ZnO Nanorod-based Piezoelectric Devices through Surface Engineering.

ZnO is a typical piezoelectric semiconductor, and enhancing the piezoelectric output of ZnO-based devices is essential for their efficient applications. Surface engineering is an effective strategy to improve the piezoelectric output of ZnO-based devices, but its unclear regulation mechanism leads to a lack of reasonable guidance for device design. In this work, the regulation effect of the barrier layer in ZnO-based piezoelectric devices is systematically investigated from the carrier perspective through surface engineering, resulting in a significant improvement (nearly 10-fold) in the output performance of piezoelectric devices. The regulation mechanism of the ZnO-Cu2O p-n heterojunction devices on piezoelectric output is revealed in terms of built-in electric field, depletion layer width, and junction capacitance. These findings facilitate further insight into the enhancement mechanism of the piezoelectric output of ZnO-based devices and provide reasonable ideas for efficient device design.

Piezoelectric nanogenerators for personalized healthcare.

The development of flexible piezoelectric nanogenerators has experienced rapid progress in the past decade and is serving as the technological foundation of future state-of-the-art personalized healthcare. Due to their highly efficient mechanical-to-electrical energy conversion, easy implementation, and self-powering nature, these devices permit a plethora of innovative healthcare applications in the space of active sensing, electrical stimulation therapy, as well as passive human biomechanical energy harvesting to third party power on-body devices. This article gives a comprehensive review of the piezoelectric nanogenerators for personalized healthcare. After a brief introduction to the fundamental physical science of the piezoelectric effect, material engineering strategies, device structural designs, and human-body centered energy harvesting, sensing, and therapeutics applications are also systematically discussed. In addition, the challenges and opportunities of utilizing piezoelectric nanogenerators for self-powered bioelectronics and personalized healthcare are outlined in detail.

Ambulatory Cardiovascular Monitoring Via a Machine-Learning-Assisted Textile Triboelectric Sensor.

Wearable bioelectronics for continuous and reliable pulse wave monitoring against body motion and perspiration remains a great challenge and highly desired. Here, a low-cost, lightweight, and mechanically durable textile triboelectric sensor that can convert subtle skin deformation caused by arterial pulsatility into electricity for high-fidelity and continuous pulse waveform monitoring in an ambulatory and sweaty setting is developed. The sensor holds a signal-to-noise ratio of 23.3 dB, a response time of 40 ms, and a sensitivity of 0.21 µA kPa-1 . With the assistance of machine learning algorithms, the textile triboelectric sensor can continuously and precisely measure systolic and diastolic pressure, and the accuracy is validated via a commercial blood pressure cuff at the hospital. Additionally, a customized cellphone application (APP) based on built-in algorithm is developed for one-click health data sharing and data-driven cardiovascular diagnosis. The textile triboelectric sensor enabled wireless biomonitoring system is expected to offer a practical paradigm for continuous and personalized cardiovascular system characterization in the era of the Internet of Things.

Hierarchically Microstructure-Bioinspired Flexible Piezoresistive Bioelectronics.

The naturally microstructure-bioinspired piezoresistive sensor for human-machine interaction and human health monitoring represents an attractive opportunity for wearable bioelectronics. However, due to the trade-off between sensitivity and linear detection range, obtaining piezoresistive sensors with both a wide pressure monitoring range and a high sensitivity is still a great challenge. Herein, we design a hierarchically microstructure-bioinspired flexible piezoresistive sensor consisting of a hierarchical polyaniline/polyvinylidene fluoride nanofiber (HPPNF) film sandwiched between two interlocking electrodes with microdome structure. Ascribed to the substantially enlarged 3D deformation rates, these bioelectronics exhibit an ultrahigh sensitivity of 53 kPa-1, a pressure detection range from 58.4 to 960 Pa, a fast response time of 38 ms, and excellent cycle stability over 50 000 cycles. Furthermore, this conformally skin-adhered sensor successfully demonstrates the monitoring of human physiological signals and movement states, such as wrist pulse, throat activity, spinal posture, and gait recognition. Evidently, this hierarchically microstructure-bioinspired and amplified sensitivity piezoresistive sensor provides a promising strategy for the rapid development of next-generation wearable bioelectronics.

Ternary Electrification Layered Architecture for High-Performance Triboelectric Nanogenerators.

The triboelectric nanogenerator (TENG) has been proved to be a green and efficient energy harnessing technology for electricity generation from ambient mechanical motions based on its ability to leverage the triboelectrification process. Enhancing TENG output performance through rational structural design still triggers increasing research interest. Here, we report a ternary electrification layered architecture beyond the current binary TENG systems, with improved performance for mechanical energy harvesting. Introducing a ternary Kapton layer into the traditional binary electrification layered architecture of TENGs consisting of copper and fluorinated ethylene propylene, yields a 2.5 times enhancement of peak power output, representing a 6.29-fold increase compared to the TENG composed of copper and Kapton. A wide-range of material configurations were systematically tested using this ternary electrification layered architecture to prove its practical effectiveness. The ternary electrification layered architecture invented in this work provides an alternative strategy to enhance TENG output performance, which represents a solid step for TENGs application in high-performance mechanical energy harvesting.

Manipulating Relative Permittivity for High-Performance Wearable Triboelectric Nanogenerators.

As the world marches into the era of the Internet of Things (IoT), the practice of human health care is on the cusp of a revolution, driven by an unprecedented level of personalization enabled by a variety of wearable bioelectronics. A sustainable and wearable energy solution is highly desired , but challenges still remain in its development. Here, we report a high-performance wearable electricity generation approach by manipulating the relative permittivity of a triboelectric nanogenerator (TENG). A compatible active carbon (AC)-doped polyvinylidene fluoride (AC@PVDF) composite film was invented with high relative permittivity and a specific surface area for wearable biomechanical energy harvesting. Compared with the pure PVDF, the 0.8% AC@PVDF film-based TENG obtained an enhancement in voltage, current, and power by 2.5, 3.5, and 9.8 times, respectively. This work reports a stable, cost-effective, and scalable approach to improve the performance of the triboelectric nanogenerator for wearable biomechanical energy harvesting, thus rendering a sustainable and pervasive energy solution for on-body electronics.

Understanding the Potential Screening Effect through the Discretely Structured ZnO Nanorods Piezo Array.

The potential screening effect of one-dimensional ZnO nanorods from carriers has been theoretically proved to severely limit its piezoelectricity, but its exact mechanism needs to be further revealed in experiments to guide the design of piezoelectric semiconductors. Here, a discretely structured design was proposed to prevent the free carriers from tunneling among adjacent ZnO nanorods for suppressing the screening effect. Piezoresponse force microscope and finite element analysis were employed in combination to uncover the underlying mechanism in experiment. Further, the output voltage of this discretely structured device was 1.62 times higher than that of the nondesigned device, which clearly authenticates this suppression behavior. Besides, this design prompts an unexpected improvement in flexibility, where the flexural modulus of this piezo-film was reduced by 35.74%. Notably, this work opens a new way to understand the potential screening effect, as expected, and to advance the development of piezo-electronics toward better piezoelectricity and more excellent flexibility.

Degradations of aroma characteristics and changes of aroma related compounds, PPO activity, and antioxidant capacity in sugarcane juice during thermal process.

Alterations of aroma properties and aroma-related attributes of sugarcane juice during thermal processing under different temperatures (90, 100, and 110 ℃) and treating time (10 s, 20 s, and 30 s) were assessed in this study. Changes in the volatility of aroma compounds were extremely complicated and respected to thermal processing conditions. Fructose, serine, and glutanic acid of sugarcane juice were increased at first and decreased at the end of treatment at high temperature. Phenolic compounds and PPO activity presented the decrease trends throughout the thermal treatment. The thermal processing of sugarcane juice could be roughly divided into three stages based on the cluster analysis of all the data in this study. Sugars, amino acids, and phenolic compounds might be important potential precursors of aroma deteriorating reactions. The comprehensive analysis of aroma relevant compounds and enzyme activities was beneficial for the investigation of degradation mechanism of aroma for sugarcane juice, and providing a theoretical basis for optimization of juice processing. PRACTICAL APPLICATION: This study demonstrated the changing process of aroma quality and associated compounds in sugarcane juice during thermal processing. This could help to find out the reasons of aroma degradations in sugarcane juice and other thermal sensitive juice. Our manuscript created a paradigm for future studies on the aroma quality control and parameter optimization during the processing of fruit and vegetable juice.

Strong Lewis Acid-Base and Weak Hydrogen Bond Synergistically Enhancing Ionic Conductivity of Poly(ethylene oxide)@SiO2 Electrolytes for a High Rate Capability Li-Metal Battery.

Solid-state composite polymer electrolytes (CPEs) usually suffer from intrinsic low ionic conductivity and a solid-solid interface, badly inhibiting their widespread commercial application in all-solid-state Li-metal battery (ASSLMB) energy storage. Herein, a synergetic strategy using strong Lewis acid-base and weak hydrogen bonds was employed for self-assembly in situ construction of three-dimensional (3D) network-structured poly(ethylene oxide) (PEO) and SiO2 CPEs (PEO@SiO2). Ascribed to this synergistically rigid-flexible coupling dynamic strategy, a harmonious incorporation of monodispersed SiO2 nanoparticles into PEO could remarkably reduce crystallinity of PEO, significantly enhancing the ionic conductivity (∼1.1 × 10-4 S cm-1 at 30 °C) and dramatically facilitating solid electrolyte interface stabilization (electrochemical stability window > 4.8 V at 90 °C). Moreover, the PEO@SiO2-based ASSLMBs possess excellent rate capability over a wide temperature range (∼105 mA h g-1 under 2 C at 90 °C), high temperature cycling capacity (retaining 90 mA h g-1 after 100 cycles at 90 °C), and high specific capacity (146 mA h g-1 under 0.3 C at 90 °C). Unambiguously, these high ionic conductivity CPEs along with excellent flexibility and safety can be one of the most promising candidates for high-performance ASSLMBs, evidently revealing that this synergistically rigid-flexible coupling dynamic strategy will open up a way to exploit the novel high ionic conductivity solid-state electrolytes.