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Autophagy, a process of degradation that occurs via the lysosomal pathway, has an essential role in multiple aspects of immunity, including immune system development, regulation of innate and adaptive immune and inflammatory responses, selective degradation of intracellular microorganisms, and host protection against infectious diseases1,2. Autophagy is known to be induced by stimuli such as nutrient deprivation and suppression of mTOR, but little is known about how autophagosomal biogenesis is initiated in mammalian cells in response to viral infection. Here, using genome-wide short interfering RNA screens, we find that the endosomal protein sorting nexin 5 (SNX5)3,4 is essential for virus-induced, but not for basal, stress- or endosome-induced, autophagy. We show that SNX5 deletion increases cellular susceptibility to viral infection in vitro, and that Snx5 knockout in mice enhances lethality after infection with several human viruses. Mechanistically, SNX5 interacts with beclin 1 and ATG14-containing class III phosphatidylinositol-3-kinase (PI3KC3) complex 1 (PI3KC3-C1), increases the lipid kinase activity of purified PI3KC3-C1, and is required for endosomal generation of phosphatidylinositol-3-phosphate (PtdIns(3)P) and recruitment of the PtdIns(3)P-binding protein WIPI2 to virion-containing endosomes. These findings identify a context- and organelle-specific mechanism-SNX5-dependent PI3KC3-C1 activation at endosomes-for initiation of autophagy during viral infection.
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Autofagia/imunologia , Nexinas de Classificação/metabolismo , Vírus/imunologia , Animais , Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Proteína Beclina-1/metabolismo , Linhagem Celular , Classe III de Fosfatidilinositol 3-Quinases/metabolismo , Endossomos/metabolismo , Feminino , Humanos , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/genética , Nexinas de Classificação/deficiência , Nexinas de Classificação/genética , Proteínas de Transporte Vesicular/metabolismoRESUMO
Extensive efforts have been made to harvest energy from water in the form of raindrops1-6, river and ocean waves7,8, tides9 and others10-17. However, achieving a high density of electrical power generation is challenging. Traditional hydraulic power generation mainly uses electromagnetic generators that are heavy, bulky, and become inefficient with low water supply. An alternative, the water-droplet/solid-based triboelectric nanogenerator, has so far generated peak power densities of less than one watt per square metre, owing to the limitations imposed by interfacial effects-as seen in characterizations of the charge generation and transfer that occur at solid-liquid1-4 or liquid-liquid5,18 interfaces. Here we develop a device to harvest energy from impinging water droplets by using an architecture that comprises a polytetrafluoroethylene film on an indium tin oxide substrate plus an aluminium electrode. We show that spreading of an impinged water droplet on the device bridges the originally disconnected components into a closed-loop electrical system, transforming the conventional interfacial effect into a bulk effect, and so enhancing the instantaneous power density by several orders of magnitude over equivalent devices that are limited by interfacial effects.
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Contact electrification (CE) in water has attracted much attention, owing to its potential impacts on the chemical reactions, such as the recent discovery of spontaneous generation of hydrogen peroxide (H2O2) in water microdroplets. However, current studies focus on the CE of bulk water, the measurement of CE between micrometer-size water droplets is a challenge and its mechanism still remains ambiguous. Here, a method for quantifying the amount of charge carried by the water microdroplets produced by ultrasonic atomization is proposed. In the method, the motions of water microdroplets in a uniform electric field are observed and the electrostatic forces on the microdroplets are calculated based on the moving speed of the microdroplets. It is revealed that the charge transfer between water microdroplets is size-dependent. The large microdroplets tend to be positively charged while the small microdroplets tend to receive negative charges, implying that the negative charges transfer from large microdroplets to the small microdroplets during ultrasonic atomization. Further, a theoretical model for microdroplets charging is proposed, in which the curvature-induced surface potential/energy difference is suggested to be responsible for the charge transfer between microdroplets. The findings show that the electric field strength between two microdroplets with opposite charges during separation is strong enough to convert OHâ to OH*, providing evidence for the CE-induced spontaneous generation of H2O2 in water microdroplets.
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Investigating coherent acoustic vibrations in nanostructured materials provides fundamental insights into optomechanical responses and microscopic energy flow. Extensive measurements of vibrational dynamics have been performed for a wide variety of nanoparticles and nanoparticle assemblies. However, virtually all of them show that only the dilation modes are launched after laser excitations, and the acoustic bending and torsional motions, which are commonly observed in photoexcited chemical bonds, are absent. Unambiguous identification and refined characterization of these "missing" modes have been a long-standing issue. In this report, we investigated the acoustic vibrational dynamics of individual Au nanoprisms on free-standing graphene substrates using an ultrafast high-sensitivity dark-field imaging approach in four-dimensional transmission electron microscopy. Following optical excitations, we observed low-frequency multiple-mode oscillations and higher superposition amplitudes at nanoprism corners and edges on the subnanoparticle level. In combination with finite-element simulations, we determined that these vibrational modes correspond to out-of-plane bending and torsional motions, superimposed by an overall tilting effect of the nanoprisms. The launch and relaxation processes of these modes are highly pertinent to substrate effects and nanoparticle geometries. These findings contribute to the fundamental understanding about acoustic dynamics of individual nanostructures and their interaction with substrates.
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With the advancements in materials science and micro/nanoengineering, the field of wearable electronics has experienced a rapid growth and significantly impacted and transformed various aspects of daily human life. These devices enable individuals to conveniently access health assessments without visiting hospitals and provide continuous, detailed monitoring to create comprehensive health data sets for physicians to analyze and diagnose. Nonetheless, several challenges continue to hinder the practical application of wearable electronics, such as skin compliance, biocompatibility, stability, and power supply. In this review, we address the power supply issue and examine recent innovative self-powered technologies for wearable electronics. Specifically, we explore self-powered sensors and self-powered systems, the two primary strategies employed in this field. The former emphasizes the integration of nanogenerator devices as sensing units, thereby reducing overall system power consumption, while the latter focuses on utilizing nanogenerator devices as power sources to drive the entire sensing system. Finally, we present the future challenges and perspectives for self-powered wearable electronics.
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Dispositivos Eletrônicos Vestíveis , Humanos , Fontes de Energia Elétrica , Eletrônica , TecnologiaRESUMO
Patients with hepatocellular carcinoma (HCC) are vulnerable to drug resistance. Although drug resistance has been taken much attention to HCC therapy, little is known of regorafenib and regorafenib resistance (RR). This study aimed to determine the drug resistance pattern and the role of RhoA in RR. Two regorafenib-resistant cell lines were constructed based on Huh7 and Hep3B cell lines. In vitro and in vivo assays were conducted to study RhoA expression, the activity of Hippo signaling pathway and cancer stem cell (CSC) traits. The data showed that RhoA was highly expressed, Hippo signaling was hypoactivated and CSC traits were more prominent in RR cells. Inhibiting RhoA could reverse RR, and the alliance of RhoA inhibition and regorafenib synergistically attenuated CSC phenotype. Furthermore, inhibiting LARG/RhoA increased Kibra/NF2 complex formation, prevented YAP from shuttling into the nucleus and repressed CD44 mRNA expression. Clinically, the high expression of RhoA correlated with poor prognosis. LARG, RhoA, YAP1 and CD44 show positive correlation with each other. Thus, inhibition of RhoGEF/RhoA has the potential to reverse RR and repress CSC phenotype in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Piridinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Via de Sinalização Hippo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Compostos de Fenilureia/farmacologiaRESUMO
Contact-electro-catalysis (CEC) is an emerging field that utilizes electron transfer occurring at the liquid-solid and even liquid-liquid interfaces because of the contact-electrification effect to stimulate redox reactions. The energy source of CEC is external mechanical stimuli, and solids to be used are generally organic as well as in-organic materials even though they are chemically inert. CEC has rapidly garnered extensive attention and demonstrated its potential for both mechanistic research and practical applications of mechanocatalysis. This review aims to elucidate the fundamental principle, prominent features, and applications of CEC by compiling and analyzing the recent developments. In detail, the theoretical foundation for CEC, the methods for improving CEC, and the unique advantages of CEC have been discussed. Furthermore, we outline a roadmap for future research and development of CEC. We hope that this review will stimulate extensive studies in the chemistry community for investigating the CEC, a catalytic process in nature.
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As tactile force sensing has become increasingly significant in the field of machine haptics, achieving multidimensional force sensing remains a challenge. We propose a 3D flexible force sensor that consists of an axisymmetric hemispherical protrusion and four equally sized quarter-circle electrodes. By simulating the device using a force and electrical field model, it has been found that the magnitude and direction of the force can be expressed through the voltage relationship of the four electrodes when the magnitude of the shear force remains constant and its direction varies within 0-360°. The experimental results show that a resolution of 15° can be achieved in the range 0-90°. Additionally, we installed the sensor on a robotic hand, enabling it to perceive the magnitude and direction of touch and grasp actions. Based on this, the designed 3D flexible tactile force sensor provides valuable insights for multidimensional force detection and applications.
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Chemical analysis of ions and small organic molecules in liquid samples is crucial for applications in chemistry, biology, environmental sciences, and health monitoring. Mainstream electrochemical and chromatographic techniques often suffer from complex and lengthy sample preparation and testing procedures and require either bulky or expensive instrumentation. Here, we combine triboelectrification and charge transfer on the surface of electrical insulators to demonstrate the concept of triboelectric spectroscopy (TES) for chemical analysis. As a drop of the liquid sample slides along an insulating reclined plane, the local triboelectrification of the surface is recorded, and the charge pattern along the sample trajectory is used to build a fingerprinting of the charge transfer spectroscopy. Chemical information extracted from the charge transfer pattern enables a new nondestructive and ultrafast (<1 s) tool for chemical analysis. TES profiles are unique, and through an automated identification, it is possible to match against standard and hence detect over 30 types of common salts, acids, bases and organic molecules. The qualitative and quantitative accuracies of the TES methodology is close to 93%, and the detection limit is as low as ppb levels. Instruments for TES chemical analysis are portable and can be further miniaturized, opening a path to in situ and rapid chemical detection relying on inexpensive, portable low-tech instrumentation.
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Electron transfer during solid-liquid contact electrification has been demonstrated to produce reactive oxygen species (ROS) such as hydroxyl radicals (â¢OH) and superoxide anion radicals (â¢O2-). Here, we show that such a process also occurs in liquid-liquid contact electrification. By preparing perfluorocarbon nanoemulsions to construct a perfluorocarbon-water "liquid-liquid" interface, we confirmed that electrons were transferred from water to perfluorocarbon in ultrasonication-induced high-frequency liquid-liquid contact to produce â¢OH and â¢O2-. The produced ROS could be applied to ablate tumors by triggering large-scale immunogenic cell death in tumor cells, promoting dendritic cell maturation and macrophage polarization, ultimately activating T cell-mediated antitumor immune response. Importantly, the raw material for producing â¢OH is water, so the tumor therapy is not limited by the endogenous substances (O2, H2O2, etc.) in the tumor microenvironment. This work provides new perspectives for elucidating the mechanism of generation of free radicals in liquid-liquid contact and provides an excellent tumor therapeutic modality.
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Fluorocarbonos , Água , Fluorocarbonos/química , Água/química , Camundongos , Animais , Neoplasias/tratamento farmacológico , Radicais Livres/química , Humanos , Radical Hidroxila/química , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance is the bottleneck in ovarian cancer treatment. The increasing use of novel drugs in clinical practice poses challenges for the treatment of drug-resistant ovarian cancer. Continuing to classify drug resistance according to drug type without understanding the underlying mechanisms is unsuitable for current clinical practice. We reviewed the literature regarding various drug resistance mechanisms in ovarian cancer and found that the main resistance mechanisms are as follows: abnormalities in transmembrane transport, alterations in DNA damage repair, dysregulation of cancer-associated signaling pathways, and epigenetic modifications. DNA methylation, histone modifications and noncoding RNA activity, three key classes of epigenetic modifications, constitute pivotal mechanisms of drug resistance. One drug can have multiple resistance mechanisms. Moreover, common chemotherapies and targeted drugs may have cross (overlapping) resistance mechanisms. MicroRNAs (miRNAs) can interfere with and thus regulate the abovementioned pathways. A subclass of miRNAs, "epi-miRNAs", can modulate epigenetic regulators to impact therapeutic responses. Thus, we also reviewed the regulatory influence of miRNAs on resistance mechanisms. Moreover, we summarized recent phase I/II clinical trials of novel drugs for ovarian cancer based on the abovementioned resistance mechanisms. A multitude of new therapies are under evaluation, and the preliminary results are encouraging. This review provides new insight into the classification of drug resistance mechanisms in ovarian cancer and may facilitate in the successful treatment of resistant ovarian cancer.
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MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Metilação de DNA , Epigênese Genética , Resistencia a Medicamentos Antineoplásicos/genéticaRESUMO
Triboelectric nanogenerators (TENGs) as an avant-garde technology that transforms mechanical energy into electrical energy, offering a new direction for green energy and sustainable development. By means of high-efficiency TENGs, conventional materials as new triboelectric materials have exhibited multi-attribute characteristics, achieving innovative applications in the field of micro-nano energy harvesting and self-powered sensing. The progress of TENGs technology with the triboelectric materials is complementary and mutually promoting. On the one hand, one of the cruxes of TENGs lies in the triboelectric materials, which have a decisive impact on their performance. On the other hand, as the research and application of TENGs continue to deepen, higher demands are placed on triboelectric materials, which in turn promotes the advancement of the entire material system as well as the fields of materials science and physics. This work aims to delve into the characteristics, types, preferred choices, and modification treatments of triboelectric materials on the performances of TENGs, hoping to provide guidance and insights for future research and applications.
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Photothermal therapy (PTT) is a new treatment modality for tumors. However, the efficient delivery of photothermal agents into tumors remains difficult, especially in hypoxic tumor regions. In this study, an approach to deliver melanin, a natural photothermal agent, into tumors using genetically engineered bacteria for image-guided photothermal and immune therapy is developed. An Escherichia coli MG1655 is transformed with a recombinant plasmid harboring a tyrosinase gene to produce melanin nanoparticles. Melanin-producing genetically engineered bacteria (MG1655-M) are systemically administered to 4T1 tumor-bearing mice. The tumor-targeting properties of MG1655-M in the hypoxic environment integrate the properties of hypoxia targeting, photoacoustic imaging, and photothermal therapeutic agents in an "all-in-one" manner. This eliminates the need for post-modification to achieve image-guided hypoxia-targeted cancer photothermal therapy. Tumor growth is significantly suppressed by irradiating the tumor with an 808 nm laser. Furthermore, strong antitumor immunity is triggered by PTT, thereby producing long-term immune memory effects that effectively inhibit tumor metastasis and recurrence. This work proposes a new photothermal and immune therapy guided by an "all-in-one" melanin-producing genetically engineered bacteria, which can offer broad potential applications in cancer treatment.
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Imunoterapia , Melaninas , Animais , Imunoterapia/métodos , Camundongos , Escherichia coli/genética , Escherichia coli/metabolismo , Linhagem Celular Tumoral , Engenharia Genética , Terapia Fototérmica/métodos , Camundongos Endogâmicos BALB C , Fototerapia/métodos , Neoplasias/terapia , Feminino , Nanopartículas/químicaRESUMO
Shelter forests (or shelter-belts), while crucial for climate regulation, lack monitoring systems, e.g., Internet of Things (IoT) devices, but their abundant wind energy can potentially power these devices using the trees as mounting points. To harness wind energy, an omnidirectional fluid-induced vibration triboelectric nanogenerator (OFIV-TENG) has been developed. The device is installed on shelter forest trees to harvest wind energy from all directions, employing a fluid-induced vibration (FIV) mechanism (fluid-responding structure) that can capture and use wind energy, ranging from low wind speeds (vortex vibration) to high wind speeds (galloping). The rolling-bead triboelectric nanogenerator (TENG) can efficiently harvest energy while minimizing wear and tear. Additionally, the usage of double electrodes results in an effective surface charge density of 21.4 µC m-2 , which is the highest among all reported rolling-bead TENGs. The collected energy is utilized for temperature and humidity monitoring, providing feedback on the effect of climate regulation in shelter forests, alarming forest fires, and wireless wind speed warning. In general, this work provides a promising and rational strategy, using natural resources like trees as the supporting structures, and shows broad application prospects in efficient energy collection, wind speed warning, and environmentally friendliness.
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With the continuous rise of environmental pollution and energy crisis, the global energy revolution is risen. Development of renewable blue energy based on the emerging promising triboelectric nanogenerators (TENG) has become an important direction of future energy development. The solid-liquid contact triboelectric nanogenerator (TENG) has the advantages of flexible structure, easy manufacture, and long-term stability, which makes it easier to integrate and achieve large-scale conversion of wave mechanical energy. However, the electric power output is still not large enough, which limits its practical applications. In this work, a nanocomposite electret layer enhanced solid-liquid contact triboelectric nanogenerator (E-TENG) is proposed for water wave energy harvesting, which can effectively improve the electric output and achieve real-time power supply of wireless sensing. Through introducing a nanocomposite electret layer into flexible multilayer solid-liquid contact TENG, higher power output is achieved. The E-TENG (active size of 50 mm × 49 mm) shows desired output performance, a power density of 521 mW m-2. The generated electric energy can drive wireless temperature sensing by transmitting wireless signals carrying detection information at the period of Ë5.5 min. This research greatly improves the electric output and provides a solid basis for the industrialization of TENG in blue energy.
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Ocean energy is a kind of clean and renewable energy source, but it cannot be efficiently harvested by traditional electromagnetic generators, due to its low-frequency characteristic. The emergence of triboelectric nanogenerators provides a more promising technology for collecting ocean energy. In this work, a durable roller-based swing-structured triboelectric nanogenerator (RS-TENG) is designed and fabricated for low-frequency water wave energy harvesting. The rolling structure reduces the wear between triboelectric materials and improves the device's durability. After a continuous operation of 1 260 000 cycles, the attenuation of the electrical outputs of the RS-TENG is below 1.6%, exhibiting excellent durability. At the same time, the output current can arrive at 53.2 µA. Under the triggering of water waves, the RS-TENG can generate an output power of 4.27 mW, corresponding to a power density of 1.16 W m-3. After the arraying, the output performance can be doubled, so that the TENG can successfully power an environmental monitoring sensor and ensure long-term stable operation of the sensor. This work provides an effective strategy for improving the device durability, which benefits the practical applications of the TENGs in large-scale blue energy harvesting.
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Tribovoltaic nanogenerators (TVNG) represent a fantastic opportunity for developing low-frequency energy harvesting and self-powered sensing, by exploiting their real-time direct-current (DC) output. Here, a thorough study of the effect of relative humidity (RH) on a TVNG consisting of 4H-SiC (n-type) and metallic copper foil (SM-TVNG) is presented. The SM-TVNG shows a remarkable sensitivity to RH and an abnormal RH dependence. When RH increases from ambient humidity up to 80%, an increasing electrical output is observed. However, when RH rises from 80% to 98%, the signal output not only decreases, but its direction reverses as it crosses 90% RH. This behavior differs greatly from that of a Si-based TVNG, whose output constantly increases with RH. The behavior of the SM-TVNG might result from the competition between the built-in electric field induced by metal-semiconductor contact and a strong triboelectric electric field induced by solid-liquid triboelectrification under high RH. The authors also demonstrated that both SM-TVNG and Si-based TVNG can work effectively as-is even fully submerged in deionized water. This mechanism can affect other devices and be applied to design self-powered sensors working under high RH or underwater.
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Traffic lights play vital roles in urban traffic management systems, providing clear directional guidance for vehicles and pedestrians while ensuring traffic safety. However, the vast quantity of traffic lights widely distributed in the transportation system aggravates energy consumption. Here, a self-powered traffic light system is proposed through wind energy harvesting based on a high-performance fur-brush dish triboelectric nanogenerator (FD-TENG). The FD-TENG harvests wind energy to power the traffic light system continuously without needing an external power supply. Natural rabbit furs are applied to dish structures, due to their outstanding characteristics of shallow wear, high performance, and resistance to humidity. Also, the grid pattern of the dish structure significantly impacts the TENG outputs. Additionally, the internal electric field and the influences of mechanical and structural parameters on the outputs are analyzed by finite element simulations. After optimization, the FD-TENG can achieve a peak power density of 3.275 W m-3. The portable and miniature features of FD-TENG make it suitable for other natural environment systems such as forests, oceans, and mountains, besides the traffic light systems. This study presents a viable strategy for self-powered traffic lights, establishing a basis for efficient environmental energy harvesting toward big data and Internet of Things applications.
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Tailoring nanoparticles' composition and morphology is of particular interest for improving their performance for catalysis. A challenge of this approach is that the nanoparticles' optimized initial structure often changes during use. Visualizing the three dimensional (3D) structural transformation in situ is therefore critical, but often prohibitively difficult experimentally. Although electron tomography provides opportunities for 3D imaging, restrictions in the tilt range of in situ holders together with electron dose considerations limit the possibilities for in situ electron tomography studies. Here, an in situ 3D imaging methodology is presented using single particle reconstruction (SPR) that allows 3D reconstruction of nanoparticles with controlled electron dose and without tilting the microscope stage. This in situ SPR methodology is employed to investigate the restructuring and elemental redistribution within a population of PtNi nanoparticles at elevated temperatures. The atomic structure of PtNi is further examined and a heat-induced transition is found from a disordered to an ordered phase. Changes in structure and elemental distribution are linked to a loss of catalytic activity in the oxygen reduction reaction. The in situ SPR methodology employed here can be extended to a wide range of in situ studies employing not only heating, but gaseous, aqueous, or electrochemical environments to reveal in-operando nanoparticle evolution in 3D.
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Triboelectric nanogenerator (TENG) is a promising solution to harvest the low-frequency, low-actuation-force, and high-entropy droplet energy. Conventional attempts mainly focus on maximizing electrostatic energy harvest on the liquid-solid surface, but enormous kinetic energy of droplet hitting the substrate is directly dissipated, limiting the output performance. Here, a dual-mode TENG (DM-TENG) is proposed to efficiently harvest both electrostatic energy at liquid-solid surface from a droplet TENG (D-TENG) and elastic potential energy of the vibrated cantilever from a contact-separation TENG (CS-TENG). Triggered by small droplets, the flexible cantilever beam, rather than conventional stiff ones, can easily vibrate multiple times with large amplitude, enabling frequency multiplication of CS-TENG and producing amplified output charges. Combining with the top electrode design to sufficiently utilize charges at liquid-solid interface, a record-high output charge of 158 nC is realized by single droplet. The energy conversion efficiency of DM-TENG is 2.66-fold of D-TENG. An array system with the specially designed power management circuit is also demonstrated for building self-powered system, offering promising applications for efficiently harvesting raindrop energy.