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Cultured meat is emerging as a new type of food that can provide animal protein in a sustainable way. Many previous studies employed various types of scaffolds to develop cultured meat with similar properties to slaughtered meat. However, important properties such as flavor were not discussed, even though they determine the quality of food. Flavor characteristics vary dramatically depending on the amount and types of amino acids and sugars that produce volatile compounds through the Maillard reaction upon cooking. In this study, a flavor-switchable scaffold is developed to release meaty flavor compounds only upon cooking temperature mimicking the Maillard reaction of slaughtered meat. By introducing a switchable flavor compound (SFC) into a gelatin-based hydrogel, we fabricate a functional scaffold that can enhance the aromatic properties of cultured meat. The temperature-responsive SFC stably remains in the scaffold during the cell culture period and can be released at the cooking temperature. Surprisingly, cultured meat fabricated with this flavor-switchable scaffold exhibits a flavor pattern similar to that of beef. This research suggests a strategy to develop cultured meat with enhanced sensorial characteristics by developing a functional scaffold which can mimic the natural cooking flavors of conventional meat.
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Culinaria , Aromatizantes , Reacción de Maillard , Carne , Animales , Carne/análisis , Aromatizantes/química , Gusto , Bovinos , Hidrogeles/química , Humanos , Andamios del Tejido/química , Temperatura , Gelatina/química , Carne in VitroRESUMEN
The Liesegang pattern is a beautiful natural anisotropic patterning phenomenon observed in rocks and sandstones. This study reveals that the Liesegang pattern can induce nonlinear elasticity. Here, a Liesegang-patterned complex with biomineral-hydrogel repetitive layers is prepared. This Liesegang-patterned complex is obtained only when the biomineralization is performed under the supersaturated conditions. The Liesegang-patterned complex features a nonlinear elastic response, whereas a complex with a single biomineral shell shows a linear behavior, thus demonstrating that the Liesegang pattern is essential in achieving nonlinear elasticity. The stiff biomineral layers have buffered the concentrated energy on behalf of soft hydrogels, thereby exposing the hydrogel components to reduced stress and, in turn, enabling them to perform the elasticity continuously. Moreover, the nonlinear elastic Liesegang-patterned complex exhibits excellent stress relaxation to the external loading, which is the biomechanical characteristic of cartilage. This stress relaxation allows the bundle of fiber-type Liesegang-patterned complex to endure greater deformation.
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Research on cultured meat has primarily focused on the mass proliferation or differentiation of muscle cells; thus, the food characteristics of cultured meat remain relatively underexplored. As the quality of meat is determined by its organoleptic properties, cultured meat with similar sensory characteristics to animal-derived meat is highly desirable. In this study, we control the organoleptic and nutritional properties of cultured meat by tailoring the 2D differentiation of primary bovine myoblasts and primary bovine adipose-derived mesenchymal stem cells on gelatin/alginate scaffolds with varying stiffness. We assess the effect of muscle and adipose differentiation quality on the sensory properties of cultured meat. Thereafter, we fabricate cultured meat with similar sensory profiles to that of conventional beef by assembling the muscle and adipose constructs composed of highly differentiated cells. We introduce a strategy to produce cultured meat with enriched food characteristics by regulating cell differentiation with scaffold engineering.
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Células Madre Mesenquimatosas , Andamios del Tejido , Animales , Bovinos , Células Cultivadas , Carne in Vitro , Diferenciación CelularRESUMEN
Guided bone regeneration aided by the application of occlusive membranes is a promising therapy for diverse inflammatory periodontal diseases. Symbiosis, homeostasis between the host microbiome and cells, occurs in the oral environment under normal, but not pathologic, conditions. Here, we develop a symbiotically integrating occlusive membrane by mimicking the tooth enamel growth or multiple nucleation biomineralization processes. We perform human saliva and in vivo canine experiments to confirm that the symbiotically integrating occlusive membrane induces a symbiotic healing environment. Moreover, we show that the membrane exhibits tractability and enzymatic stability, maintaining the healing space during the entire guided bone regeneration therapy period. We apply the symbiotically integrating occlusive membrane to treat inflammatory-challenged cases in vivo, namely, the open and closed healing of canine premolars with severe periodontitis. We find that the membrane promotes symbiosis, prevents negative inflammatory responses, and improves cellular integration. Finally, we show that guided bone regeneration therapy with the symbiotically integrating occlusive membrane achieves fast healing of gingival soft tissue and alveolar bone.
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Pérdida de Hueso Alveolar , Periodontitis , Humanos , Regeneración Tisular Guiada Periodontal , Cicatrización de Heridas/fisiología , Encía , Membranas Artificiales , Regeneración Ósea/fisiologíaRESUMEN
Myriad lung diseases are life threatening and macrophages play a key role in both physiological and pathological processes. Macrophages have each pro-/anti-inflammatory phenotype, and each lung disease can be aggravated by over-polarized macrophage. Therefore, development of a method capable of mediating the macrophage phenotype is one of the solutions for lung disease treatment. For mediating the phenotype of macrophages, the pulmonary delivery system (PDS) is widely used due to its advantages, such as high efficiency and accessibility of the lungs. However, it has a low drug delivery efficiency ironically because of the perfect lung defense system consisting of the mucus layer and airway macrophages. In this study, zwitterion-functionalized poly(lactide-co-glycolide) (PLGA) inhalable microparticles (ZwPG) are synthesized to increase the efficiency of the PDS. The thin layer of zwitterions formed on PLGA surface has high nebulizing stability and show high anti-mucus adhesion and evasion of macrophages. As a reprogramming agent for macrophages, ZwPG containing dexamethasone (Dex) and pirfenidone (Pir) are treated to over-polarized M2 macrophages. As a result, a synergistic effect of Dex/Pir induces reprogramming of M2 macrophage to pro-inflammatory phenotypes.
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Enfermedades Pulmonares , Macrófagos , Humanos , Fenotipo , Pulmón , Nebulizadores y VaporizadoresRESUMEN
Background: Cholangiocarcinoma (CCA) is a molecularly heterogenous disease that is often fatal. Whole genome sequencing (WGS) can provide additional knowledge of mutational spectra compared with panel sequencing. We describe the molecular landscape of CCA using whole-genome sequencing and compare the mutational landscape between short-term and long-term survivors. Methods: We explored molecular differences between short-term and long-term survivors by performing WGS on 20 patient samples from our biliary tract cancer database. Short-term survivors were enriched for cases with underlying primary sclerosing cholangitis (PSC) and patients with cirrhosis. All samples underwent tumour epithelial enrichment using laser capture microdissection (LCM). Results: Dominant single base substitution (SBS) signatures across the cohort included SBS1 and SBS5, with the latter more prevalent in long-term survivors. SBS17 was evident in 3 cases, all of whom had underlying ulcerative colitis (UC) with PSC. Additional rare signatures included SBS3 in a patient treated for prior mantle cell lymphoma and SBS26/SBS6 in a patient with a tumor mutational burden of 33 mutations/Mb and a pathogenic MLH1 germline mutation. Somatic TP53 inactivating mutations were present in 8/10 (80%) short-term survivors and in none of the long-term survivors. Additional mutations occurred in KRAS, SMAD4, CDKN2A, and chromatin remodelling genes. The long-term survivor group harboured predicted fusions in FGFR (n=2) and pathogenic mutations in BRAF and IDH1 (n=2). Conclusions: TP53 alterations are associated with poor outcomes in patients with CCA. Patients with underlying inflammatory/autoimmune conditions may be enriched for unique tumour mutational signatures.
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Thermoelectric (TE) performance of a specific semicrystalline polymer is studied experimentally only in a limited range of doping levels with molecular doping methods. The doping level is finely controlled via in situ electrochemical doping in a wide range of carrier concentrations with an electrolyte ([PMIM]+ [TFSI]- )-gated organic electrochemical transistor system. Then, the charge generation/transport and TE properties of four p-type semicrystalline polymers are analyzed and their dynamic changes of crystalline morphologies and local density of states (DOS) during electrochemical doping are compared. These polymers are synthesized based on poly[(2,5-bis(2-alkyloxy)phenylene)-alt-(5,6-difluoro-4,7-di(thiophene-2-yl)benzo[c][1,2,5]thiadiazole)] by varying side chains: With oligoethylene glycol (OEG) substituents, facile p-doping is achieved because of easy penetration of TFSI- ions into the polymer matrix. However, the charge transport is hindered with longer OEG chains length because of the enhanced insulation. Therefore, with the shortest OEG substituents the electrical conductivity (30.1 S cm-1 ) and power factor (2.88 µW m-1 K-2 ) are optimized. It is observed that all polymers exhibit p- to n-type transition in Seebeck coefficients in heavily doped states, which can be achieved by electrochemical doping. These TE behaviors are interpreted based on the relation between the localized DOS band structure and molecular packing structure during electrochemical doping.
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Ruddlesden-Popper oxides (A2 BO4 ) have attracted significant attention regarding their potential application in novel electronic and energy devices. However, practical uses of A2 BO4 thin films have been limited by extended defects such as out-of-phase boundaries (OPBs). OPBs disrupt the layered structure of A2 BO4 , which restricts functionality. OPBs are ubiquitous in A2 BO4 thin films but inhomogeneous interfaces make them difficult to suppress. Here, OPBs in A2 BO4 thin films are suppressed using a novel method to control the substrate surface termination. To demonstrate the technique, epitaxial thin films of cuprate superconductor La2- x Srx CuO4 (x = 0.15) are grown on surface-reconstructed LaSrAlO4 substrates, which are terminated with self-limited perovskite double layers. To date, La2- x Srx CuO4 thin films are grown on LaSrAlO4 substrates with mixed-termination and exhibit multiple interfacial structures resulting in many OPBs. In contrast, La2- x Srx CuO4 thin films grown on surface-reconstructed LaSrAlO4 substrates energetically favor only one interfacial structure, thus inhibiting OPB formation. OPB-suppressed La2- x Srx CuO4 thin films exhibit significantly enhanced superconducting properties compared with OPB-containing La2- x Srx CuO4 thin films. Defect engineering in A2 BO4 thin films will allow for the elimination of various types of defects in other complex oxides and facilitate next-generation quantum device applications.
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In nature, water is vital for maintaining homeostasis. Particularly, organisms (e.g., plant leaf, bird feather) exploit water fluidics for motions. Hydration-adaptive crystallization is the representative water-responsive actuation of biopolymers. This crystallization has inspired the development of intelligent human-robot interfaces. At the same time, it hinders the consistent adhesion of tissue adhesive. As hydration-adaptive crystallization is inevitable, the on-demand control of crystallization is desirable in the innovative biopolymeric biomedical systems. To this end, this study developed an amino acid-based technology to artificially up- or down-regulate the inevitable crystallization of silk fibroin. A case II diffusion model was constructed, and it revealed that the activity of polar amino acid is related to crystallization kinetics. Furthermore, the water dynamics study suggested that active amino acid stabilizes crystallization-triggering water molecules. As a proof-of-concept, we verified that a 30% increase in the activity of serine resulted in a 50% decrease in the crystallization rate. Furthermore, the active amino acid-based suppression of hydration-adaptive crystallization enabled the silk fibroin to keep its robust adhesion (approximately 160 kJ m-3) by reducing the water-induced loss of adhesive force. The proposed silk fibroin was demonstrated as a stable tissue adhesive applied on ex vivo porcine mandible tissue. This amino acid-based regulation of hydration-adaptive crystallization will pioneer next-generation biopolymer-based healthcare.
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Bombyx , Fibroínas , Adhesivos Tisulares , Humanos , Animales , Porcinos , Fibroínas/química , Agua/química , Bombyx/química , Aminoácidos , Serina , Seda/químicaRESUMEN
Edible scaffolds are needed in cultured meat to mimic meat's three-dimensional structure by organizing cells and replenishing the insufficient meat mass of cells alone. However, there is still a large gap between slaughtered meat and cells developed into tissues using scaffolds. This is mainly due to the difference in size, texture, flavor, and taste. In this study, we develop a coating matrix to modify the surface of textured vegetable protein (TVP), a vegetable cell support, to produce cultured meat having slaughtered meat's essential characteristics. We optimized the fish gelatin/agar matrix's microstructure by controlling the ratio of the two biopolymers, stably introducing a cell adhesive environment on the TVP. By coating the optimized gelatin/agar matrix on the TVP's surface using an easy and fast dipping method, hybrid cultured meat composed of animal cells and plant protein was produced. As the cells proliferated, their synergistic effect permitted the cultured meat's texture, flavor, and taste to reach a level comparable to that of slaughtered meat. The TVP-based cultured meat prepared with the present technology has been recreated as high-quality cultured meat by satisfying five challenging factors: cells, texture, cost, mass, and flavor.
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Gelatina , Carne , Agar , Animales , Carne/análisis , Glycine max , Gusto , VerdurasRESUMEN
Polyalkenoate cement (PAC) is a promising material for regenerative hard tissue therapy. The ionically rich glass component of PAC encourages bioactive interaction via. the release of essential ions. However, PAC bioactivity is restricted owing to (i) structurally inherent cationic network formers and (ii) surface bacterial biofilm formation. These two factors cause a deficiency in ion release, further complicated by secondary infections and premature therapeutic failure. Here, a multivalent zwitterionic network modifier (mZM) is presented for upregulation of ionic exchange and bioactivity enhancement. By introducing a non-zero charged mZM into PACs, an increase in the proportion of non-bridging oxygen occurs. The network modification promotes ion channel formation, causing a multiple-fold increase in ion release and surface deposition of hydroxy-carbonate apatite (ca. 74%). Experiments ex vivo and animal models also demonstrate the efficient remineralization ability of the mZM. Furthermore, divalent cationic interaction results in bacterial biofilm reduction (ca. 68%) while also influencing a shift in the biofilm species composition, which favors commensal growth. Therefore, PAC modification with mZM offers a promising solution for upregulation of bioactivity, even aiding in customization by targeting site-specific regenerative therapy in future applications.
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The kinetic body motions have guided the core-shell fabrics of wearable bioelectronics to be elastoplastic. However, the polymeric electrodes follow the trade-off relationship between toughness and stretchability. To this end, the stress dissipation encoded silk fibroin electrode is proposed as the core electrode of wearable bioelectronics. Significantly, the high degree of intrinsic stress dissipation is realized via an amino acid crosslink. The canonical phenolic amino acid (i.e., tyrosine) of silk fibroin is engineered to bridge the secondary structures. A sufficient crosslink network is constructed when tyrosine is exposed near the amorphous strand. The stress dissipative tyrosine crosslink affords 12.5-fold increments of toughness (4.72 to 58.9 MJ m-3 ) and implements the elastoplastic silk fibroin. The harmony of elastoplastic core electrodes with shell fabrics enables the wearable bioelectronics to employ mechanical performance (elastoplasticity of 750 MJ m-3 ) and stable electrical response. The proposed wearable is capable of assisting the effective workouts via triboelectricity. In principle, active mobility with suggested wearables potentially relieves muscular fatigues and severe injuries during daily fitness.
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Fibroínas , Atletas , Electrodos , Fibroínas/química , Humanos , Polímeros , SedaRESUMEN
Despite the widespread use of polymers for antifouling coatings, the effect of the polymeric topology on the antifouling property has been largely underexplored. Unlike conventional brush polymers, a loop conformation often leads to strong steric stabilization of surfaces and antifouling and lubricating behavior owing to the large excluded volume and reduced chain ends. Herein, we present highly antifouling multiloop polyethers functionalized with a mussel-inspired catechol moiety with varying loop dimensions. Specifically, a series of polyethers with varying catechol contents were synthesized via anionic ring-opening polymerization by using triethylene glycol glycidyl ether (TEG) and catechol-acetonide glycidyl ether (CAG) to afford poly(TEG-co-CAG)n. The versatile adsorption and antifouling effects of multiloop polyethers were evaluated using atomic force microscopy and a quartz crystal microbalance with dissipation. Furthermore, the crucial role of the loop dimension in the antifouling properties was analyzed via a surface force apparatus and a cell attachment assay. This study provides a new platform for the development of versatile antifouling polymers with varying topologies.
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Incrustaciones Biológicas , Adsorción , Incrustaciones Biológicas/prevención & control , Microscopía de Fuerza Atómica , Polímeros/química , Propiedades de SuperficieRESUMEN
Zwitterions have been attracting emerging attention as an anti-fouling polymer. However, the relationship between structured solvation shells and controlled drug release induced by deceleration of water molecule's translational and vibrational motions of zwitterions is an uncharted territory. Herein, sulfobetaine zwitterion nanoparticles (ZWNPs) were designed as a stable nitric oxide (NO)-delivering carrier. The condensed water structure of the solvation shell at its isoelectric point (PI) and the loose structure of water under different pH conditions were investigated through rheological and thermodynamical analyses. The ZWNPs showed a sustained-release profile at the PI, which presented a structured solvation barrier. On the other hand, NO-loaded ZWNPs showed different release profiles with the burst release at pH 5.5. Notably, an increased cell proliferation rate and a decreased antibacterial effect were observed at the same concentration depending on solvation shell's characteristics.
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Antibacterianos/química , Betaína/análogos & derivados , Nanopartículas/química , Óxido Nítrico/química , Antibacterianos/farmacología , Betaína/química , Incrustaciones Biológicas/prevención & control , Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química , Liberación de Fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad Microbiana , Óxido Nítrico/farmacología , Solubilidad , Staphylococcus aureus/efectos de los fármacos , TermodinámicaRESUMEN
Automatic meter infrastructure (AMI) systems using remote metering are being widely used to utilize water resources efficiently and minimize non-revenue water. We propose a convolutional neural network-long short-term memory network (CNN-LSTM)-based solution that can predict faulty remote water meter reading (RWMR) devices by analyzing approximately 2,850,000 AMI data collected from 2762 customers over 360 days in a small-sized city in South Korea. The AMI data used in this study is a challenging, highly unbalanced real-world dataset with limited features. First, we perform extensive preprocessing steps and extract meaningful features for handling this challenging dataset with limited features. Next, we select important features that have a higher influence on the classifier using a recursive feature elimination method. Finally, we apply the CNN-LSTM model for predicting faulty RWMR devices. We also propose an efficient training method for ML models to learn the unbalanced real-world AMI dataset. A cost-effective threshold for evaluating the performance of ML models is proposed by considering the mispredictions of ML models as well as the cost. Our experimental results show that an F-measure of 0.82 and MCC of 0.83 are obtained when the CNN-LSTM model is used for prediction.
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Tecnología de Sensores Remotos , Agua , Análisis Costo-Beneficio , Memoria a Largo Plazo , Redes Neurales de la ComputaciónRESUMEN
For graphene-based 2D materials, charge transfer at the interface between graphene and ferromagnetic metal leads to many intriguing phenomena. However, because of the unidirectional spin orientation in ferromagnetic transition metals, interface interaction plays a detrimental role in diminishing the magnetic parameters on 2D surfaces. To overcome this issue, we have synthesized ultrathin 2D weak antiferromagneticß-NiOOH layers on a graphene surface. By exploiting the charge transfer effect and tuning the thickness of the thinß-NiOOH layers, conversion of ferromagnetism along with giant coercivity and the thermo-remnant magnetic memory effect were observed. As antiferromagnets have two spin orientations, transfer of charge at the interface breaks the nullifying effect of zero magnetization in antiferromagnets and the combined system behaves like a 2D ferrimagnet. Whenever, the sandwich structure ofß-NiOOH/graphene/ß-NiOOH is formed, it also shows interlayer exchange coupling those results in huge exchange bias and anomalous temperature dependence of coercivity. Due to the strong exchange interaction between the layers, the combined system also shows a robust temperature-based memory effect. Spin-polarized density functional theory was also calculated to confirm the interface interaction and its quantitative evaluation by means of Bader charge analysis and charge-density mapping.
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Precise controlled filling of point vacancies in hBN with carbon atoms is demonstrated using a focused electron beam method, which guides mobile C atoms into the desired defect site. Optimization of the technique enables the insertion of a single C atom into a selected monovacancy, and preferential defect filling with sub-2 nm accuracy. Increasing the C insertion process leads to thicker 3D C nanodots seeded at the hBN point vacancy site. Other light elements are also observed to bind to hBN vacancies, including O, opening up a wide range of complex defect structures that include B, C, N, and O atoms. The ability to selectively fill point vacancies in hBN with C atoms provides a pathway for creating non-hydrogenated covalently bonded C molecules embedded in the insulating hBN.
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Background and Objectives: Symptomatic adjacent segment degeneration (ASD) with lumbar spinal canal stenosis (LSCS) is a common complication after spinal intervention, particularly interbody fusion. Stand-alone posterior expandable cages enable interbody fusion with preservation of the previous operation site, and screw-related complications are avoided. Thus, the aim of this study was to investigate the clinicoradiologic outcomes of stand-alone posterior expandable cages for ASD with LSCS. Materials and Methods: Patients with persistent neurologic symptoms and radiologically confirmed ASD with LSCS were evaluated between January 2011 and December 2016. The five-year follow-up data were used to evaluate the long-term outcomes. The radiologic parameters for sagittal balance, pain control (visual analogue scale), disability (Oswestry Disability Index), and early (peri-operative) and late (implant) complications were evaluated. Results: The data of 19 patients with stand-alone posterior expandable cages were evaluated. Local factors, such as intervertebral and foraminal heights, were significantly corrected (p < 0.01 and p < 0.01, respectively), and revision was not reported. The pain level (p < 0.01) and disability rate (p < 0.01) significantly improved, and the early complication rate was low (n = 2, 10.52%). However, lumbar lordosis (p = 0.62) and sagittal balance (p = 0.80) did not significantly improve. Furthermore, the rates of subsidence (n = 4, 21.05%) and retropulsion (n = 3, 15.79%) were high. Conclusions: A stand-alone expandable cage technique should only be considered for older adults and patients with previous extensive fusion. Although this technique is less invasive, improves the local radiologic factors, and yields favorable clinical outcomes with low revision rates, it does not improve the sagittal balance. For more widespread application, the strength of the cage material and high subsidence rates should be improved.
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Fusión Vertebral , Anciano , Constricción Patológica , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Estudios Retrospectivos , Canal Medular , Fusión Vertebral/efectos adversos , Resultado del TratamientoRESUMEN
Piezoelectric nanogenerators (PENGs) and triboelectric nanogenerators (TENGs) are representative technologies that can harvest mechanical energy. In general, piezoelectric/triboelectric hybrid generators can harvest considerable energy with a limited input; however, PENGs and TENGs entail different requirements for harvesting energy. Specifically, PENGs produce a large output when a large mechanical strain is applied, and TENGs require a large surface area to produce a high power. Therefore, it is necessary to develop an innovative strategy in terms of the structural design to satisfy the requirements of both PENGs and TENGs. In this study, we developed a triangulated cylinder origami-based piezoelectric/triboelectric hybrid generator (TCO-HG) with an origami structure to enable effective energy harvesting. The proposed structure consists of a vertical contact-separation TENG on the surface of the triangulated cylinder, PENG on the inner hinge, and rotational TENG on the top substrate to harvest mechanical energy from each motion. Each generator could produce a separate electrical output with a single input. The TCO-HG could charge a 22 µF commercial capacitor and power 60 LEDs when operated.
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Zwitterionic polymers have extraordinary properties, that is, significant hydration and the so-called antipolyelectrolyte effect, which make them suitable for biomedical applications. The hydration induces an antifouling effect, and this has been investigated significantly. The antipolyelectrolyte effect refers to the extraordinary ion-responsive behavior of particular polymers that swell and hydrate considerably in physiological solutions. This actuation begins to attract attention to achieve in vivo antifouling that is challenging for general polyelectrolytes. In this study, we established the sophisticated cornerstone of the antipolyelectrolyte effect in detail, including (i) the essential parameters, (ii) experimental verifications, and (iii) effect of improving antifouling performance. First, we find that both osmotic force and charge screening are essential factors. Second, we identify the antipolyelectrolyte effect by visualizing the swelling and hydration dynamics. Finally, we verify that the antifouling performance can be enhanced by exploiting the antipolyelectrolyte effect and report reduction of 85% and 80% in ex and in vivo biofilm formation, respectively.