EVA1A reverses lenvatinib resistance in hepatocellular carcinoma through regulating PI3K/AKT/p53 signaling axis.

Lenvatinib is a commonly used first-line drug for the treatment of advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is limited due to the drug resistance. EVA1A was a newly identified tumor suppressor, nevertheless, the impact of EVA1A on resistance to lenvatinib treatment in HCC and the potential molecular mechanisms remain unknown. In this study, the expression of EVA1A in HCC lenvatinib-resistant cells is decreased and its low expression was associated with a poor prognosis of HCC. Overexpression of EVA1A reversed lenvatinib resistance in vitro and in vivo, as demonstrated by its ability to promote cell apoptosis and inhibit cell proliferation, invasion, migration, EMT, and tumor growth. Silencing EVA1A in lenvatinib-sensitive parental HCC cells exerted the opposite effect and induced resistance to lenvatinib. Mechanistically, upregulated EVA1A inhibited the PI3K/AKT/MDM2 signaling pathway, resulting in a reduced interaction between MDM2 and p53, thereby stabilizing p53 and enhancing its antitumor activity. In addition, upregulated EVA1A suppressed the PI3K/AKT/mTOR signaling pathway and promoted autophagy, leading to the degradation of mutant p53 and attenuating its oncogenic impact. On the contrary, loss of EVA1A activated the PI3K/AKT/MDM2 signaling pathway and inhibited autophagy, promoting p53 proteasomal degradation and mutant p53 accumulation respectively. These findings establish a crucial role of EVA1A loss in driving lenvatinib resistance involving a mechanism of modulating PI3K/AKT/p53 signaling axis and suggest that upregulating EVA1A is a promising therapeutic strategy for alleviating resistance to lenvatinib, thereby improving the efficacy of HCC treatment.

All-Nanofiber-Based Janus Epidermal Electrode with Directional Sweat Permeability for Artifact-Free Biopotential Monitoring.

Epidermal electronics have been developed with gas/sweat permeability for long-term wearable electrophysiological monitoring. However, the state-of-the-art breathable epidermal electronics ignore the sweat accumulation and immersion at the skin/device interface, resulting in serious degradation of the interfacial conformality and adhesion, leading to signal artifacts with unstable and inaccurate biopotential measurements. Here, the authors present an all-nanofiber-based Janus epidermal electrode endowed with directional sweat transport properties for artifact-free biopotential monitoring. The designed Janus multilayered membrane (≈15 µm) of superhydrophilic-hydrolyzed-polyacrylonitrile (HPAN)/polyurethane (PU)/Ag nanowire (AgNW) can quickly (less than 5 s) drive sweat away from the skin/electrode interface while resisting its penetration in the reverse direction. Along with the medical adhesive (MA)-reinforced junction-nodes, the adhesion strength among the heterogeneous interfaces can be greatly enhanced for robust mechanical-electrical stability. Therefore, their measured on-body electromyography (EMG) and electrocardiography (ECG) signals are free of sweat artifacts with negligible degradation and baseline drift compared to commercial Ag/AgCl gel electrodes and hydrophilic textile electrodes. This work paves a way to design novel directional-sweat-permeable epidermal electronics that can be conformally attached under sweaty conditions for long-term biopotential monitoring and shows the potential to apply epidermal electronics to many challenging conditions.

Stretchable multifunctional hydrogels for sensing electronics with effective EMI shielding properties.

Hydrogel-based soft and stretchable materials with skin/tissue-like mechanical properties provide new avenues for the design and fabrication of wearable sensors. However, synthesizing multifunctional hydrogels that simultaneously possess excellent mechanical, electrical and electromagnetic interference (EMI) shielding effectiveness is still a great challenge. In this work, the freeze-casting method is employed to fabricate a multifunctional hydrogel by filling Fe3O4 clusters into poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid) (PEDOT:PSS) and polyvinyl alcohol (PVA) composite aqueous solution. The hydrogel possesses superior electrical and mechanical properties as well as great electromagnetic wave shielding properties. Benefiting from the high stretchability (∼904.5%) and fast sensing performance (response time ∼9 ms and self-recovery time ∼12 ms within the strain range ∼100%), the monitoring of human activities and manipulation of a remote-controlled toy car using the hydrogel-based stretchable strain sensors are successfully demonstrated. In addition, a great EMI shielding effectiveness with more than 46 dB in the frequencies of 8-12.5 GHz can be obtained, which provides an alternative strategy for designing next-generation EMI shielding materials. These results indicate that the multifunctional hydrogels can be used as flexible and stretchable sensing electronics requiring effective EMI shielding.

Moisture-Driven Power Generation for Multifunctional Flexible Sensing Systems.

Flexible self-powered multifunctional sensing systems provide a promising direction for the development of wearable electronics. Although increased efforts have been devoted to developing self-powered integrated devices, the development of flexible and adaptable sensing systems with miniaturized stable power supplies is highly desirable yet greatly challenging. Herein, an ambient moisture-induced self-powered wearable sensing system was fabricated by integrating a porous polydopamine layer with a hydroxy group gradient (called g-PDA) based moisture-enabled power generator and a flexible pressure sensor. Due to the large amount of gradient-distributed free cations (H+) and locally confined anions produced in wide electrode spaces during hydration of the thin porous g-PDA film, the moisture-induced potential and effective output power density of the g-PDA-based power generator rapidly reaches up to 0.52 V and 0.246 mW cm-2, respectively. Importantly, the voltage output within 120 s only has 6% change, and a continuously open-circuit voltage can be maintained after 1900 s of attenuation, which is a breakthrough for the duration of humidity generation. Finally, a self-powered wearable multifunctional sensing system has been demonstrated to be able to provide real-time monitoring of human physiological signals, without an external power supply, which opens new opportunities for future self-powered multifunctional sensing systems.

Anisotropic Boron-Carbon Hetero-Nanosheets for Ultrahigh Energy Density Supercapacitors.

A 2D boron nanosheet that exhibits high theoretical capacitance, around four times that of graphene, is a significant supercapacitor electrode. However, its bulk structure with low interlaminar conduction and porosity restricts the charge transfer, ion diffusion, and energy density. Herein, we develop a new 2D hetero-nanosheet made of anisotropic boron-carbon nanosheets (ABCNs) by B-C chemical bonds via gas-phase exfoliation and condensation bottom-up strategy. The ABCNs are constructed into high flexible supercapacitor electrode by microfluidic electrospinning. The ABCN electrode greatly promotes smooth migration and excessive storage of electrolyte ions due to large interlayer conductivity, ionic pathways, and accessible surfaces. The flexible supercapacitor delivers ultrahigh volumetric energy density of 167.05 mWh cm-3 and capacitance of 534.5 F cm-3 . A wearable energy-sensor system is designed to stably monitor physiological signals.

Bioinspired Flexible Volatile Organic Compounds Sensor Based on Dynamic Surface Wrinkling with Dual-Signal Response.

Living systems can respond to external stimuli by dynamic interface changes. Moreover, natural wrinkle structures allow the surface to switch dynamically and reversibly from flat to rough in response to specific stimuli. Artificial wrinkle structures have been developed for applications such as optical devices, mechanical sensors, and microfluidic devices. However, chemical molecule-triggered flexible sensors based on dynamic surface wrinkling have not been demonstrated. Inspired by human skin wrinkling, herein, a volatile organic compound (VOC)-responsive flexible sensor with a switchable dual-signal response (transparency and resistance) is achieved based on a multilayered Ag nanowire (AgNW)/SiOx /polydimethylsiloxane (PDMS) film. Wrinkle structures can form dynamically in response to VOC vapors (such as ethanol, toluene, acetone, formaldehyde, and methanol) due to the instability of the multilayer induced by their different swelling capabilities. By controlling the modulus of PDMS and the thickness of the SiOx layer, tunable sensitivities in resistance and transparency of the device are achieved. Additionally, the proximity mechanism of the solubility parameter is proposed, which explains the high selectivity of the device toward ethanol vapor compared with that of other VOCs well. This stimuli-responsive sensor exhibits the dynamic visual feedback and the quantitative electrical signal, which provide a novel approach for developing smart flexible electronics.

Highly Sensitive Microstructure-Based Flexible Pressure Sensor for Quantitative Evaluation of Motor Function Recovery after Spinal Cord Injury.

Behavioral assessment, such as systematic scoring or biomechanical measurement, is often used to evaluate the extent of the damage and the degree of recovery after spinal cord injury. However, the use of these methods in standardized evaluation is limited because they are subjective and require complex test systems to implement. Here, we report a novel, flexible, microstructure-based pressure sensor and demonstrate its superior sensitivity (235.12 kPa-1 for 5.5~135 Pa and 2.24 kPa-1 for 0.6~25 kPa), good waterproofness, fast response and recovery times (response time: 8 ms, recovery time: 12 ms), stable response over 8000 loading/unloading cycles, and wide sensing range. These features readily allow the sensor to be comfortably attached to the hindlimbs of mice for full-range, real-time detection of their behavior, such as crawling and swimming, helping to realize quantitative evaluation of animal motor function recovery after spinal cord injury.

Rapid Synthesis of Sub-5 nm Sized Cubic Boron Nitride Nanocrystals with High-Piezoelectric Behavior via Electrochemical Shock.

A key challenge in current superhard materials research is the design of novel superhard nanocrystals (NCs) whereby new and unexpected properties may be predicted. Cubic boron nitride (c-BN) is a superhard material which ranks next to diamond; however, downsizing c-BN material below the 10 nm scale is rather challenging, and the interesting new properties of c-BN NCs remain unexplored and wide open. Herein we report an electrochemical shock method to prepare uniform c-BN NCs with a lateral size of only 3.4 ± 0.6 nm and a thickness of only 0.74 ± 0.3 nm at ambient temperature and pressure. The fabrication process is simple and fast, with c-BN NCs produced in just a few minutes. Most interestingly, the NCs exhibit excellent piezoelectric performance with a large recordable piezoelectric coefficient of 25.7 pC/N, which is almost 6 times larger than that from bulk c-BN and even competitive to conventional piezoelectric materials. The phenomenon of enhancement in the piezoelectric properties of BN NCs might arise from the nanoscale surface effect and nanoscale shape effect of BN NCs. This work paves an interesting route for exploring new properties of superhard NCs.

Wearable Sweatband Sensor Platform Based on Gold Nanodendrite Array as Efficient Solid Contact of Ion-Selective Electrode.

As chemical sensors are in great demand for portable and wearable analytical applications, it is highly desirable to develop an all-solid-state ion-selective electrode (ISE) and reference electrode (RE) platform with simplicity and stability. Here we propose a wearable sensor platform with a new type of all-solid-state ISE based on a gold nanodendrite (AuND) array electrode as the solid contact and a poly(vinyl acetate)/inorganic salt (PVA/KCl) membrane-coated all-solid-state RE. A simple and controllable method was developed to fabricate the AuNDs on a microwell array patterned chip by one-step electrodeposition without additional processing. For the first time, the AuND electrodes with different real surface area and double layer capacitance were developed as solid contact of the Na+-ISE to investigate the relationship between performance of the ISE and surface area. As-prepared AuND-ISE with larger surface area (∼7.23 cm2) exhibited enhanced potential stability compared to those with smaller surface area (∼1.85 cm2) and to bare Au ISE. Important as the ISE, the PVA/KCl membrane-coated Ag/AgCl RE exhibited highly stable potential even after 3 months' storage. Finally, a wearable sweatband sensor platform was developed for efficient sweat collection and real-time analysis of sweat sodium during indoor exercise. This all-solid-state ISE and RE integrated sensor platform provided a very simple and reliable way to construct diverse portable and wearable devices for healthcare, sports, clinical diagnosis, and environmental analysis applications.

Rational design of a laminate-structured flexible sensor for human dynamic plantar pressure monitoring.

Flexible sensors are essential components in emerging fields such as epidermal electronics, biomedicine, and human-computer interactions, and creating high-performance sensors through simple structural design for practical applications is increasingly needed. Presently, challenges still exist in establishing efficient models of flexible piezoresistive pressure sensors to predict the design required for achieving target performance. This work establishes a theoretical model of a flexible pressure sensor with a simple laminated and enclosed structure. In the modeling, the electrical constriction effect is innovatively introduced to explain the sensitization mechanism of the laminated structure to a broad range of pressures and to predict the sensor performance. The experimental results confirmed the effectiveness of the theoretical model. The sensor exhibited excellent stability for up to three million cycles and superior durability when exposed to salt solution owing to its simple laminated and enclosed structural design. Finally, a wearable sensing system for real-time collection and analysis of plantar pressure is constructed for exercise and rehabilitation monitoring applications. This work aims to provide theoretical guidance for the rapid design and construction of flexible pressure sensors with target performance for practical applications.

Interplay of CD36, autophagy, and lipid metabolism: insights into cancer progression.

CD36, a scavenger receptor B2 that is dynamically distributed between cell membranes and organelle membranes, plays a crucial role in regulating lipid metabolism. Abnormal CD36 activity has been linked to a range of metabolic disorders, such as obesity, nonalcoholic fatty liver disease, insulin resistance and cardiovascular disease. CD36 undergoes various modifications, including palmitoylation, glycosylation, and ubiquitination, which greatly affect its binding affinity to various ligands, thereby triggering and influencing various biological effects. In the context of tumors, CD36 interacts with autophagy to jointly regulate tumorigenesis, mainly by influencing the tumor microenvironment. The central role of CD36 in cellular lipid homeostasis and recent molecular insights into CD36 in tumor development indicate the applicability of CD36 as a therapeutic target for cancer treatment. Here, we discuss the diverse posttranslational modifications of CD36 and their respective roles in lipid metabolism. Additionally, we delve into recent research findings on CD36 in tumors, outlining ongoing drug development efforts targeting CD36 and potential strategies for future development and highlighting the interplay between CD36 and autophagy in the context of cancer. Our aim is to provide a comprehensive understanding of the function of CD36 in both physiological and pathological processes, facilitating a more in-depth analysis of cancer progression and a better development and application of CD36-targeting drugs for tumor therapy in the near future.

Silk Fibroin-Regulated Nanochannels for Flexible Hydrovoltaic Ion Sensing.

The evaporation-induced hydrovoltaic effect based on ion-selective nanochannels can theoretically be employed for high-performance ion sensing; yet, the indeterminate ion-sensing properties and the acquisition of high sensing performance are rarely explored. Herein, a controllable nanochannel regulation strategy for flexible hydrovoltaic devices with highly sensitive ion-sensing abilities is presented across a wide concentration range. By multiple dip-coating of silk fibroin (SF) on an electrospinning nylon-66 nanofiber (NNF) film, the surface polarity enhancement, the fibers size regulation with a precision of ≈25 nm, and the nanostructure firm binding are achieved simultaneously. The resultant flexible freestanding hydrovoltaic device exhibits an open circuit voltage up to 4.82 V in deionized water, a wide ion sensing range of 10-7 to 100 m, and ultrahigh sensitivity as high as 1.37 V dec-1, which is significantly higher than the sensitivity of the traditional solid-contact ion-selective electrodes (SC-ISEs). The fabricated flexible ion-sensitive hydrovoltaic device is successfully applied for wearable human sweat electrolyte sensing and for environmental trace-ion monitoring, thereby confirming the potential application of the hydrovoltaic effect for ion sensing.

Adaptively resettable microfluidic patch for sweat rate and electrolytes detection.

Skin-interfaced microfluidic patch has become a reliable device for sweat collection and analysis. However, the intractable problems of emptying the microchannel for reuse, and the channel's volumetric capacity limited by the size of the patch, directly hinder the practical application of sweat sensors. Herein, we report an adaptively resettable microfluidic sweat patch (Art-Sweat patch) capable of continuously monitoring both sweat rate (0.2-4.0 µL min-1) and total ionic charge concentration (10-200 mmol L-1). We develop a platform with a vertical and horizontal microchannel combined strategy, enabling repeatedly filling sweat and emptying the microchannel for autonomously resetting and detecting. The variation in the emptied volume is designed to be adaptively identified by the sensor, resulting in enhanced stability and an enlarged volumetric capacity of over 300 µL. By integrating with self-designed wireless transmission modules, the proposed Art-Sweat patch shows product-level wearability and high performance in monitoring variations in regional sweat rate and concentration for hydration status assessment.

A Flexible Tough Hydrovoltaic Coating for Wearable Sensing Electronics.

The lack of a strong binding mechanism between nanomaterials severely restricts the advantages of the evaporation-driven hydrovoltaic effect in wearable sensing electronics. It is a challenging task to observably improve the mechanical toughness and flexibility of hydrovoltaic devices to match the wearable demand without abandoning the nanostructures and surface function. Here, a flexible tough polyacrylonitrile/alumina (PAN/Al2 O3 ) hydrovoltaic coating with both good electricity generation (open-circuit voltage, Voc  ≈ 3.18 V) and sensitive ion sensing (2285 V M-1 for NaCl solutions in 10-4 to 10-3  m) capabilities is developed. The porous nanostructure composed of Al2 O3 nanoparticles is firmly locked by the strong binding effect of PAN, giving a critical binding force 4 times that of Al2 O3 film to easily deal with 9.92 m s-1 strong water-flow impact. Finally, skin-tight and non-contact device structures are proposed to achieve wearable multifunctional self-powered sensing directly using sweat. The flexible tough PAN/Al2 O3 hydrovoltaic coating breaks through the mechanical brittleness limitation and broadens the applications of the evaporation-induced hydrovoltaic effect in self-powered wearable sensing electronics.

Perspiration permeable, textile embeddable microfluidic sweat sensor.

Epidermal microfluidic devices are continuously being developed for efficient sweat collection and sweat rate detection. However, most microfluidic designs ignore the use of airtight/adhesive substrate will block the natural perspiration of the covered sweat pores, which will seriously affect normal sweat production and long-term wearable comfort. Herein, we present a Janus textile-embedded microfluidic sensor platform with high breathability and directional sweat permeability for synchronous sweat rate and total electrolyte concentration detection. The device consists of a hollowed-out serpentine microchannel with interdigital electrodes and Janus textile. The dual-mode signal of the sweat rate (0.2-4.0 µL min-1) and total ionic charge concentration (10-200 mmol L-1) can be obtained synchronously by decoupling conductance step signals generated when sweat flows through alternating interdigitated spokes at equal intervals in the microchannel. Meanwhile, the hollowed-out microchannel structure significantly reduces the coverage area of the sensor on the skin, and the Janus textile-embedded device ensures a comfortable skin/device interface (fewer sweat pores are blocked) and improves breathability (503.15 g m-2 d-1) and sweat permeability (directional liquid transportation) during long-term monitoring. This device is washable and reusable, which shows the potential to integrate with clothing and smart textile, and thus facilitate the practicality of wearable sweat sensors for personalized healthcare.

Biological Tissue-Inspired Ultrasoft, Ultrathin, and Mechanically Enhanced Microfiber Composite Hydrogel for Flexible Bioelectronics.

Hydrogels offer tissue-like softness, stretchability, fracture toughness, ionic conductivity, and compatibility with biological tissues, which make them promising candidates for fabricating flexible bioelectronics. A soft hydrogel film offers an ideal interface to directly bridge thin-film electronics with the soft tissues. However, it remains difficult to fabricate a soft hydrogel film with an ultrathin configuration and excellent mechanical strength. Here we report a biological tissue-inspired ultrasoft microfiber composite ultrathin (< 5 µm) hydrogel film, which is currently the thinnest hydrogel film as far as we know. The embedded microfibers endow the composite hydrogel with prominent mechanical strength (tensile stress ~ 6 MPa) and anti-tearing property. Moreover, our microfiber composite hydrogel offers the capability of tunable mechanical properties in a broad range, allowing for matching the modulus of most biological tissues and organs. The incorporation of glycerol and salt ions imparts the microfiber composite hydrogel with high ionic conductivity and prominent anti-dehydration behavior. Such microfiber composite hydrogels are promising for constructing attaching-type flexible bioelectronics to monitor biosignals.

An unconventional vertical fluidic-controlled wearable platform for synchronously detecting sweat rate and electrolyte concentration.

Epidermal microfluidic devices with long microchannels have been developed for continuous sweat analysis, which are crucial to assess personal hydration status and underlying health conditions. However, the flow resistance in long channels and the ionic concentration variation significantly affect the accuracy of both the sweat rate and electrolyte concentration measurements. Herein, we present a novel fluidic-controlled wearable platform for synchronously dropwise-detecting the sweat rate and total electrolyte concentration. The unconventional platform consisting of a vertically shortened channel, a pair of embedded electrodes and an absorption layer, is designed to minimize the flow resistance and transform sweat fluidics into uniform micro-droplets for chronological and dropwise detection. Real-time sweat conductance is decoupled from a square-wave-like curve, where the sweat rate and electrolyte concentration can be derived from the interval time and peak value, respectively. Flexible and wearable band devices are demonstrated to show their potential application for hydration status assessment during exercises.

Enhancing hydrovoltaic power generation through heat conduction effects.

Restricted ambient temperature and slow heat replenishment in the phase transition of water molecules severely limit the performance of the evaporation-induced hydrovoltaic generators. Here we demonstrate a heat conduction effect enhanced hydrovoltaic power generator by integrating a flexible ionic thermoelectric gelatin material with a porous dual-size Al2O3 hydrovoltaic generator. In the hybrid heat conduction effect enhanced hydrovoltaic power generator, the ionic thermoelectric gelatin material can effectively improve the heat conduction between hydrovoltaic generator and near environment, thus increasing the water evaporation rate to improve the output voltage. Synergistically, hydrovoltaic generator part with continuous water evaporation can induce a constant temperature difference for the thermoelectric generator. Moreover, the system can efficiently achieve solar-to-thermal conversion to raise the temperature difference, accompanied by a stable open circuit voltage of 6.4 V for the hydrovoltaic generator module, the highest value yet.

Tough Engineering Hydrogels Based on Swelling-Freeze-Thaw Method for Artificial Cartilage.

Articular cartilage, which exhibits toughness and ultralow friction even under high squeezing pressures, plays an important role in the daily movement of joints. However, joint soft tissue lesions or injuries caused by diseases, trauma, or human functional decline are inevitable. Poly(vinyl alcohol) (PVA) hydrogels, which have a water content and compressive strength similar to those of many tissues and organs, have the potential to replace tough connective tissues, including cartilage. However, currently, PVA hydrogels are not suitable for complex dynamic environments and lack rebound resilience, especially under long-term or multicycle mechanical loads. Inspired by biological tissues that exhibit increased mechanical strength after swelling, we report a tough engineered hydrogel (TEHy) fabricated by swelling and freeze-thaw methods with a high compressive strength (31 MPa), high toughness (1.17 MJ m-3), a low friction coefficient (0.01), and a low energy loss factor (0.22). Notably, the TEHy remained remarkably resilient after 100 000 cycles of contact extrusion and remains intact after being compressed by an automobile with a weight of approximately 1600 kg. The TEHy also exhibited excellent water swelling resistance (volume and weight changes less than 5%). Moreover, skeletal muscle cells were able to readily attach and proliferate on the surface of TEHy-6, suggesting its outstanding biocompatibility. Overall, this swelling and freeze-thaw strategy solves the antifatigue and stability problems of PVA hydrogels under large static loads (>10 000 N) and provides an avenue to fabricate engineering hydrogels with strong antifatigue and antiswelling properties and ultralow friction for potential use as biomaterials in tissue engineering.

"Top-down" and "bottom-up" strategies for wafer-scaled miniaturized gas sensors design and fabrication.

Manufacture of large-scale patterned nanomaterials via top-down techniques, such as printing and slurry coating, have been used for fabrication of miniaturized gas sensors. However, the reproducibility and uniformity of the sensors in wafer-scale fabrication are still a challenge. In this work, a "top-down" and "bottom-up" combined strategy was proposed to manufacture wafer-scaled miniaturized gas sensors with high-throughput by in-situ growth of Ni(OH)2 nanowalls at specific locations. First, the micro-hotplate based sensor chips were fabricated on a two-inch (2") silicon wafer by micro-electro-mechanical-system (MEMS) fabrication techniques ("top-down" strategy). Then a template-guided controllable de-wetting method was used to assemble a porous thermoplastic elastomer (TPE) thin film with uniform micro-sized holes (relative standard deviation (RSD) of the size of micro-holes <3.5 %, n > 300), which serves as the patterned mask for in-situ growing Ni(OH)2 nanowalls at the micro-hole areas ("bottom-up" strategy). The obtained gas microsensors based on this strategy showed great reproducibility of electric properties (RSD < 0.8%, n = 8) and sensing response toward real-time H2S detection (RSD < 3.5%, n = 8).