Proteolytic Shedding of Human Colony-Stimulating Factor 1 Receptor and its implication.

Both Colony-stimulating factor 1 receptor (CSF1R) and triggering receptor expressed on myeloid cells-2 (TREM2) are trans-membrane receptors and are expressed in the brain primarily by microglia. Mutations in these two microglia-expressed genes associated with neurodegenerative disease have recently been grouped under the term "microgliopathy". Several literatures have indicated that CSF1R and TREM2 encounters a stepwise shedding and TREM2 variants impair or accelerate the processing. However, whether CSF1R variant affects the shedding of CSF1R remains elusive. Here, plasmids containing human CSF1R or TREM2 were transiently transfected into the human embryonic kidney (HEK) 293T cells. Using Western Blot and/or ELISA assay, we demonstrated that, similar to those of TREM2, an N-terminal fragment (NTF) shedding of CSF1R ectodomain and a subsequent C-terminal fragment (CTF) of CSF1R intra-membrane were generated by a disintegrin and metalloprotease (ADAM) family member and by γ-secretase, respectively. And the shedding was inhibited by treatment with Batimastat, an ADAM inhibitor, or DAPT or compound E, a γ-secretase inhibitor. Importantly, we show that the cleaved fragments, both extracellular domain and intracellular domain of a common disease associated I794T variant, were decreased significantly. Together, our studies demonstrate a stepwise approach of human CSF1R cleavage and contribute to understand the pathogenicity of CSF1R I794T variant in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). These studies also suggest that the cleaved ectodomain fragment released from CSF1R may be proposed as a diagnostic biomarker for ALSP.

Innovation Strategy Selection Facilitates High-Performance Flexible Piezoelectric Sensors.

Piezoelectric sensors with high performance and low-to-zero power consumption meet the growing demand in the flexible microelectronic system with small size and low power consumption, which are promising in robotics and prosthetics, wearable devices and electronic skin. In this review, the development process, application scenarios and typical cases are discussed. In addition, several strategies to improve the performance of piezoelectric sensors are summed up: (1) material innovation: from piezoelectric semiconductor materials, inorganic piezoceramic materials, organic piezoelectric polymer, nanocomposite materials, to emerging and promising molecular ferroelectric materials. (2) designing microstructures on the surface of the piezoelectric materials to enlarge the contact area of piezoelectric materials under the applied force. (3) addition of dopants such as chemical elements and graphene in conventional piezoelectric materials. (4) developing piezoelectric transistors based on piezotronic effect. In addition, the principle, advantages, disadvantages and challenges of every strategy are discussed. Apart from that, the prospects and directions of piezoelectric sensors are predicted. In the future, the electronic sensors need to be embedded in the microelectronic systems to play the full part. Therefore, a strategy based on peripheral circuits to improve the performance of piezoelectric sensors is proposed in the final part of this review.

Insights into Materials, Physics, and Applications in Flexible and Wearable Acoustic Sensing Technology.

Sound plays a crucial role in the perception of the world. It allows to communicate, learn, and detect potential dangers, diagnose diseases, and much more. However, traditional acoustic sensors are limited in their form factors, being rigid and cumbersome, which restricts their potential applications. Recently, acoustic sensors have made significant advancements, transitioning from rudimentary forms to wearable devices and smart everyday clothing that can conform to soft, curved, and deformable surfaces or surroundings. In this review, the latest scientific and technological breakthroughs with insightful analysis in materials, physics, design principles, fabrication strategies, functions, and applications of flexible and wearable acoustic sensing technology are comprehensively explored. The new generation of acoustic sensors that can recognize voice, interact with machines, control robots, enable marine positioning and localization, monitor structural health, diagnose human vital signs in deep tissues, and perform organ imaging is highlighted. These innovations offer unique solutions to significant challenges in fields such as healthcare, biomedicine, wearables, robotics, and metaverse. Finally, the existing challenges and future opportunities in the field are addressed, providing strategies to advance acoustic sensing technologies for intriguing real-world applications and inspire new research directions.

Venus Flytrap-Inspired Data-Center-Free Fast-Responsive Soft Robots Enabled by 2D Ni3(HITP)2 MOF and Graphite.

The rapid and responsive capabilities of soft robots in perceiving, assessing, and reacting to environmental stimuli are highly valuable. However, many existing soft robots, designed to mimic humans and other higher animals, often rely on data centers for the modulation of mechanoelectrical transduction and electromechanical actuation. This reliance significantly increases system complexity and time delays. Herein, drawing inspiration from Venus flytraps, a soft robot employing a power modulation strategy is presented for active stimulus reaction, eliminating the need for a data center. This robot achieves mechanoelectrical transduction through Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2 (Ni3(HITP)2) metal-organic framework (MOF) with an ultralow time delay (256 ns) and electromechanical actuation via graphite. The Joule heating effect in graphite is effectively modulated by Ni3(HITP)2 before and after the presence of pressure, thus enabling the stimulus reaction of soft robots. As demonstrated, three soft robots are created: low-level edge tongue robots, Venus flytrap robots, and high-level nerve-center-controlled dragonfly robots. This power modulation strategy inspires designs of edge soft robots and high-level robots with a human-like effective fusion of conditioned and unconditioned reflexes.

A double-crack structure for bionic wearable strain sensors with ultra-high sensitivity and a wide sensing range.

Flexible strain sensors are crucial in fully monitoring human motion, and they should have a wide sensing range and ultra-high sensitivity. Herein, inspired by lyriform organs, a flexible strain sensor based on the double-crack structure is designed. An MXene layer and an Au layer with cracks are constructed on both sides of the insulated polydimethylsiloxane (PDMS) film, forming an equivalent parallel circuit that guarantees the integrity of the conductive path under a large strain. The rapid disconnection of the crack junctions causes a significant change in the resistance value. Due to the effect of cracks on the conductive path, the sensitivity of the sensor is largely improved. Benefiting from the double-crack structure, the as-obtained sensor shows ultra-high sensitivity (maximum gauge factor of up to 14 373.6), a wide working range (up to 21%), a fast response time (183 ms) and excellent dynamical stability (almost no performance loss after 1000 stretching cycles and different frequency cycles). In practical applications, the sensor is applied to different parts of the human body to sense the deformation of the skin, demonstrating its great potential application value in human physiological detection and the human-machine interaction. This study can provide new ideas for preparing high-performance flexible strain sensors.

Enhancement of phase transition temperature through hydrogen bond modification in molecular ferroelectrics.

Molecular ferroelectrics are attracting great interest due to their light weight, mechanical flexibility, low cost, ease of processing and environmental friendliness. These advantages make molecular ferroelectrics viable alternatives or supplements to inorganic ceramics and polymer ferroelectrics. It is expected that molecular ferroelectrics with good performance can be fabricated, which in turns calls for effective chemical design strategies in crystal engineering. To achieve so, we propose a hydrogen bond modification method by introducing the hydroxyl group, and successfully boost the phase transition temperature (Tc) by at least 336 K. As a result, the molecular ferroelectric 1-hydroxy-3-adamantanammonium tetrafluoroborate [(HaaOH)BF4] can maintain ferroelectricity until 528 K, a Tc value much larger than that of BTO (390 K). Meanwhile, micro-domain patterns, in stable state for 2 years, can be directly written on the film of (HaaOH)BF4. In this respect, hydrogen bond modification is a feasible and effective strategy for designing molecular ferroelectrics with high Tc and stable ferroelectric domains. Such an organic molecule with varied modification sites and the precise crystal engineering can provide an efficient route to enrich high-Tc ferroelectrics with various physical properties.

Bioinspired Young's Modulus-Hierarchical E-Skin with Decoupling Multimodality and Neuromorphic Encoding Outputs to Biosystems.

As key interfaces for the disabled, optimal prosthetics should elicit natural sensations of skin touch or proprioception, by unambiguously delivering the multimodal signals acquired by the prosthetics to the nervous system, which still remains challenging. Here, a bioinspired temperature-pressure electronic skin with decoupling capability (TPD e-skin), inspired by the high-low modulus hierarchical structure of human skin, is developed to restore such functionality. Due to the bionic dual-state amplifying microstructure and contact resistance modulation, the MXene TPD e-skin exhibits high sensitivity over a wide pressure range and excellent temperature insensitivity (91.2% reduction). Additionally, the high-low modulus structural configuration enables the pressure insensitivity of the thermistor. Furthermore, a neural model is proposed to neutrally code the temperature-pressure signals into three types of nerve-acceptable frequency signals, corresponding to thermoreceptors, slow-adapting receptors, and fast-adapting receptors. Four operational states in the time domain are also distinguished after the neural coding in the frequency domain. Besides, a brain-like machine learning-based fusion process for frequency signals is also constructed to analyze the frequency pattern and achieve object recognition with a high accuracy of 98.7%. The TPD neural system offers promising potential to enable advanced prosthetic devices with the capability of multimodality-decoupling sensing and deep neural integration.

Water-Modulated Biomimetic Hyper-Attribute-Gel Electronic Skin for Robotics and Skin-Attachable Wearables.

Electronic skin (e-skin), mimicking the physical-chemical and sensory properties of human skin, is promising to be applied as robotic skins and skin-attachable wearables with multisensory functionalities. To date, most e-skins are dedicated to sensory function development to mimic human skins in one or several aspects, yet advanced e-skin covering all the hyper-attributes (including both the sensory and physical-chemical properties) of human skins is seldom reported. Herein, a water-modulated biomimetic hyper-attribute-gel (Hygel) e-skin with reversible gel-solid transition is proposed, which exhibits all the desired skin-like physical-chemical properties (stretchability, self-healing, biocompatibility, biodegradability, weak acidity, antibacterial activities, flame retardance, and temperature adaptivity), sensory properties (pressure, temperature, humidity, strain, and contact), function reconfigurability, and evolvability. Then the Hygel e-skin is applied as an on-robot e-skin and skin-attached wearable to demonstrate its highly skin-like attributes in capturing multiple sensory information, reconfiguring desired functions, and excellent skin compatibility for real-time gesture recognition via deep learning. This Hygel e-skin may find more applications in advanced robotics and even skin-replaceable artificial skin.

Bioinspired Stretchable MXene Deformation-Insensitive Hydrogel Temperature Sensors for Plant and Skin Electronics.

Temperature sensing is of high value in the wearable healthcare, robotics/prosthesis, and noncontact physiological monitoring. However, the common mechanic deformation, including pressing, bending, and stretching, usually causes undesirable feature size changes to the inner conductive network distribution of temperature sensors, which seriously influences the accuracy. Here, inspired by the transient receptor potential mechanism of biological thermoreceptors that could work precisely under various skin contortions, we propose an MXene/Clay/poly(N-isopropylacrylamide) (PNIPAM) (MCP) hydrogel with high stretchability, spike response, and deformation insensitivity. The dynamic spike response is triggered by the inner conductive network transformation from the 3-dimensional structure to the 2-dimensional surface after water being discharged at the threshold temperature. The water discharge is solely determined by the thermosensitivity of PNIPAM, which is free from mechanical deformation, so the MCP hydrogels can perform precise threshold temperature (32 °C) sensing under various deformation conditions, i.e., pressing and 15% stretching. As a proof of concept, we demonstrated the applications in plant electronics for the real-time surface temperature monitoring and skin electronics for communicating between human and machines. Our research opens venues for the accurate temperature-threshold sensation on the complicated surface and mechanical conditions.

2D PtSe2 Enabled Wireless Wearable Gas Monitoring Circuits with Distinctive Strain-Enhanced Performance.

The application of 2D materials-based flexible electronics in wearable scenarios is limited due to performance degradation under strain fields. In contrast to its negative role in existing transistors or sensors, herein, we discover a positive effect of strain to the ammonia detection in 2D PtSe2. Linear modulation of sensitivity is achieved in flexible 2D PtSe2 sensors via a customized probe station with an in situ strain loading apparatus. For trace ammonia absorption, a 300% enhancement in room-temperature sensitivity (31.67% ppm-1) and an ultralow limit of detection (50 ppb) are observed under 1/4 mm-1 curvature strain. We identify three types of strain-sensitive adsorption sites in layered PtSe2 and pinpoint that basal-plane lattice distortion contributes to better sensing performance resulting from reduced absorption energy and larger charge transfer density. Furthermore, we demonstrate state-of-the-art 2D PtSe2-based wireless wearable integrated circuits, which allow real-time gas sensing data acquisition, processing, and transmission through a Bluetooth module to user terminals. The circuits exhibit a wide detection range with a maximum sensitivity value of 0.026 V·ppm-1 and a low energy consumption below 2 mW.

Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders.

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer's disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Interacts With Colony-Stimulating Factor 1 Receptor (CSF1R) but Is Not Necessary for CSF1/CSF1R-Mediated Microglial Survival.

Triggering receptor expressed on myeloid cells-2 (TREM2) and colony-stimulating factor 1 receptor (CSF1R) are crucial molecules for microgliopathy, which is characterized by microglia dysfunction and has recently been proposed as the neuropathological hallmark of neurological disorders. TREM2 and CSF1R are receptors expressed primarily in microglia in the brain and modulate microglial activation and survival. They are thought to be in close physical proximity. However, whether there is a direct interaction between these receptors remains elusive. Moreover, the physiological role and mechanism of the interaction of TREM2 and CSF1R remain to be determined. Here, we found that TREM2 interacted with CSF1R based on a co-immunoprecipitation assay. Additionally, we found that CSF1R knockdown significantly reduced the survival of primary microglia and increased the Trem2 mRNA level. In contrast, CSF1R expression was increased in Trem2-deficient microglia. Interestingly, administration of CSF1, the ligand of CSF1R, partially restored the survival of Trem2-deficient microglia in vitro and in vivo. Furthermore, CSF1 ameliorated Aß plaques deposition in Trem2-/-; 5XFAD mouse brain. These findings provide solid evidence that TREM2 and CSF1R have intrinsic abilities to form complexes and mutually modulate their expression. These findings also indicate the potential role of CSF1 in therapeutic intervention in TREM2 variant-bearing patients with a high risk of Alzheimer's disease (AD).

Conductive Porous MXene for Bionic, Wearable, and Precise Gesture Motion Sensors.

Reliable, wide range, and highly sensitive joint movement monitoring is essential for training activities, human behavior analysis, and human-machine interfaces. Yet, most current motion sensors work on the nano/microcracks induced by the tensile deformation on the convex surface of joints during joint movements, which cannot satisfy requirements of ultrawide detectable angle range, high angle sensitivity, conformability, and consistence under cyclic movements. In nature, scorpions sense small vibrations by allowing for compression strain conversion from external mechanical vibrations through crack-shaped slit sensilla. Here, we demonstrated that ultraconformal sensors based on controlled slit structures, inspired by the geometry of a scorpion's slit sensilla, exhibit high sensitivity (0.45%deg-1), ultralow angle detection threshold (~15°), fast response/relaxation times (115/72 ms), wide range (15° ~120°), and durability (over 1000 cycles). Also, a user-friendly, hybrid sign language system has been developed to realize Chinese and American sign language recognition and feedback through video and speech broadcasts, making these conformal motion sensors promising candidates for joint movement monitoring in wearable electronics and robotics technology.