RESUMO
Single atom catalysts (SACs) are highly favored in Li-S batteries due to their excellent performance in promoting the conversion of lithium polysulfides (LiPSs) and inhibiting their shuttling. However, the intricate and interrelated microstructures pose a challenge in deciphering the correlation between the chemical environment surrounding the active site and its catalytic activity. Here, a novel SAC featuring a distinctive Mn-N3-Cl moiety anchored on B, N co-doped carbon nanotubes (MnN3Cl@BNC) is synthesized. Subsequently, the selective removal of the Cl ligands while inheriting other microstructures is performed to elucidate the effect of Cl coordination on catalytic activity. The Cl coordination effectively enhances the electron cloud density of the Mn-N3-Cl moiety, reducing the band gap and increasing the adsorption capacity and redox kinetics of LiPSs. As a modified separator for Li-S batteries, MnN3Cl@BNC exhibits high capacities of 1384.1 and 743 mAh g-1 at 0.1 and 3C, with a decay rate of only 0.06% per cycle over 700 cycles at 1 C, which is much better than that of MnN3OH@BNC. This study reveals that Cl coordination positively contributes to improving the catalytic activity of the Mn-N3-Cl moiety, providing a fresh perspective for the design of high-performance SACs.
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Hard carbon is the most promising anode for potassium-ion batteries (PIBs) due to its low cost and abundance, but its limited storage capacity remains a major challenge. Herein, edge coordination of metal single atoms is proved to be an effective strategy for promoting potassium storage in hard carbon for the first time, taking B, N co-doped hard carbon nanotubes anchored by edge Ni-N4 -B atomic sites (Ni@BNHC) as an example. It is revealed that edge Ni-N4 -B can provide active sites for interlayer adsorption of K+ and that Ni atoms can facilitate the reversibility of K+ storage on N and B atoms. Furthermore, an unprecedentedly reversible K+ storage capacity of 694 mAh g-1 at 0.05 A g-1 is realized by introducing commercial carbon nanotubes. This work provides a new perspective for the application of single-atom engineering and the design of high-performance carbon anodes for PIBs.
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1q gain (+1q) is the most common high-risk cytogenetic abnormality (HRCA) in patients with multiple myeloma (MM). However, its prognostic value remains unclear in the era of novel agents. Here, we retrospectively analyzed the impact of +1q on the outcomes of 934 patients newly diagnosed with MM. +1q was identified in 53.1% of patients and verified as an independent variate for inferior overall survival (OS) (hazard ratio, 1.400; 95% confidence interval, 1.097-1.787; p = .007). Concurrence of other HRCAs (particularly t(14;16) and del(17p)) further exacerbated the outcomes of patients with +1q, suggesting prognostic heterogeneity. Thus, a risk-scoring algorithm based on four risk variates (t(14;16), hypercalcemia, ISS III, and high LDH) was developed to estimate the outcomes of patients with +1q. Of the patients, 376 evaluable patients with +1q were re-stratified into low (31.6%), intermediate (61.7%), and high risk (6.7%) groups, with significantly different progression-free survival and OS (p < .0001), in association with early relapse of the disease. The prognostic value of this model was validated in the CoMMpass cohort. While attaining undetectable MRD largely circumvented the adverse impact of +1q, it scarcely ameliorated the outcome of the patients with high risk, who likely represent a subset of patients with extremely poor survival. Hence, patients with +1q are a heterogeneous group of high-risk patients, therefore underlining the necessity for their re-stratification. The proposed simple risk-scoring model can estimate the outcomes of patients with +1q, which may help guide risk-adapted treatment for such patients.
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Mieloma Múltiplo , Humanos , Prognóstico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Estudos Retrospectivos , Aberrações Cromossômicas , Modelos de Riscos ProporcionaisRESUMO
G-quadruplex (G4)/hemin DNAzyme is promising horseradish peroxidase (HRP)-mimic candidate in the biological field. However, its relatively unsatisfactory catalytic capacity limits the potential applications. Inspired by nature protease, we conducted a proximity-enhanced cofactor assembly strategy (PECA) to form an exceptional HRP mimic, namely zippered G4/hemin DNAzyme (Z-G4/H). The hybridization of short oligonucleotides induced proximity assembly of the DNA-grafted hemin (DGH) with the complementary G4 sequences (cG4s), mimicking the tight configuration of protease cofactor and apoenzyme. The detailed investigations of catalytic efficiency and mechanism verified the higher activity, more rapid catalytic rate and high environmental tolerance of the Z-G4/H than the classical G4/hemin DNAzymes (C-G4/H). Furthermore, a proximity recognition transducer has been developed based on the PECA for sensitive detection of gene rearrangement and imaging human epidermal growth factor receptor 2 protein (HER2) dimerization on cell surfaces. Our studies demonstrate the high efficiency of Z-G4/H and its universal application potential in clinical diagnostics and biomolecule interaction research. It also may offer significant opportunities and inspiration for the engineering of the protease-free mimic enzyme.
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DNA Catalítico/metabolismo , Ensaios Enzimáticos/métodos , Quadruplex G , Hemina/metabolismo , Biocatálise , Linhagem Celular Tumoral , Dicroísmo Circular/métodos , DNA Catalítico/genética , Estabilidade Enzimática , Hemina/química , Humanos , Concentração de Íons de Hidrogênio , Cinética , Células MCF-7 , Estrutura Molecular , Mutação , Espectrofotometria/métodos , TemperaturaRESUMO
Metallic Bi, as an alloying-type anode material, has demonstrated tremendous potential for practical application of potassium-ion batteries. However, the giant volume expansion, severe structure pulverization, and sluggish dynamics of Bi-based materials result in unsatisfied rate performance and unstable cycling stability. Here, 2D bismuth@N-doped carbon sheets with BiOC bond and internal void space (2D Bi@NOC) are successfully fabricated via a self-template strategy to address these issues, which own ultrafast electrochemical kinetics and impressive long-term cycling stability for delivering an admirable capacity of 341.7 mAh g-1 after 1000 cycles at 10 A g-1 and impressive rate capability of 220.6 mAh g-1 at 50 A g-1 . Particularly, the in situ transmission electron microscopy observations visualize the real-time alloying/dealloying process and reveal that plastic carbon shell and void space can availably relieve dramatic volume stress and powerfully maintain structural integrity. Density functional theory calculation and ultraviolet photoelectron spectroscopy test certify that the robust BiOC bond is thermodynamically and kinetically beneficial for adsorption/diffusion of K+ . This work will light on designing advanced high-performance energy materials and provide important evidence for understanding the energy storage mechanism of alloy-based materials.
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Bismuth-antimony alloy is considered as a promising potassium ion battery anode because of its combination of the high theoretical capacity of antimony and the excellent rate capacity of bismuth. However, the large volume change and sluggish reaction kinetic upon cycling have triggered severe capacity fading and poor rate performance. Herein, a nanoconfined BiSb in tremella-like carbon microspheres (BiSb@TCS) are delicately designed to address these issues. As-prepared BiSb@TCS renders an outstanding potassium-storage performance with a reversible capacity of 181 mAh g-1 after ultralong 5700 cycles at a current density of 2 A g-1 , and an excellent rate capacity of 119.3 mAh g-1 at 6 A g-1 . Such a superior performance can be ascribed to the delicate microstructure. The self-assembled carbon microspheres can strengthen integral structure and effectively accommodate the volume expansion of BiSb nanoparticles, and 2D carbon nanowalls in carbon microspheres can provide fast ion/electron diffusion dynamic. Theoretical calculation also suggests a thermodynamic feasibility of alloyed BiSb nanoparticles for storing potassium ion. Such a work shows that BiSb@TCS possesses a great potential to be a high-performance anode of potassium ion batteries. The rational designing of multiscaled structure would be instructive to the exploitation of other energy-storage materials.
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A series of 6-substituted carbazole-based retinoic acid-related orphan receptor gamma-t (RORγt) modulators were discovered through 6-position modification guided by insights from the crystallographic profiles of the "short" inverse agonist 6. With the increase in the size of the 6-position substituents, the "short" inverse agonist 6 first reversed its function to agonists and then to "long" inverse agonists. The cocrystal structures of RORγt complexed with the representative "short" inverse agonist 6 (PDB: 6LOB), the agonist 7d (PDB: 6LOA) and the "long" inverse agonist 7h (PDB: 6LO9) were revealed by X-ray analysis. However, minor differences were found in the binding modes of "short" inverse agonist 6 and "long" inverse agonist 7h. To further reveal the molecular mechanisms of different RORγt inverse agonists, we performed molecular dynamics simulations and found that "short" or "long" inverse agonists led to different behaviors of helixes H11, H11', and H12 of RORγt. The "short" inverse agonist 6 destabilizes H11' and dislocates H12, while the "long" inverse agonist 7h separates H11 and unwinds H12. The results indicate that the two types of inverse agonists may behave differently in downstream signaling, which may help identify novel inverse agonists with different regulatory mechanisms.
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Carbazóis/farmacologia , Cristalografia , Agonismo Inverso de Drogas , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/agonistas , Receptores do Ácido Retinoico/agonistas , Carbazóis/síntese química , Simulação de Dinâmica Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Receptor gama de Ácido RetinoicoRESUMO
In this study, a novel electrochemical biosensor was constructed for ultrasensitive and locus-specific detection of N6-Methyladenine (m6A) in DNA using double-hindered replication and nucleic acid-coated methylene blue (MB)@Zr-MOF. Based on the combination of m6A-impeded replication and AgI-mediated mismatch replication, this mode could effectively stop the extension of the strand once DNA polymerase encountered m6A site, which specifically distinguish the m6A site from natural A site in DNA. Also, Zr-MOF with high porosity and negative surface potential features was carefully chose to load cationic MB, resulting a stable and robust MB@Zr-MOF electrochemical tag. As a result, the developed biosensor exhibited a wide linear range from 1 fM to 1 nM with detection limit down to 0.89 fM. Profiting from the high sensitivity and selectivity, the biosensing strategy revealed good applicability, which had been demonstrated by quantitating m6A DNA at specific site in biological matrix. Thus, the biosensor provides a promising platform for locus-specific m6A DNA analysis.
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Adenina/análogos & derivados , Técnicas Biossensoriais/métodos , DNA/química , Estruturas Metalorgânicas/química , Azul de Metileno/química , Adenina/análise , Adenina/química , Limite de Detecção , Nanotecnologia , Análise de Sequência de DNA , Zircônio/químicaRESUMO
A novel cytosensor was constructed for the ultrasensitive detection and nondestructive release of circulating tumor cells (CTCs) by combining Au nanoparticles-loaded two-dimensional bimetallic PdMo (2D Au@PdMo) nanozymes and electrochemical reductive desorption. The 2D Au@PdMo nanozymes possessed high-efficiency peroxidase-like activity and were assembled with an aptamer composed of a thiol-modified epithelial specific cell adhesion molecule (EpCAM) to strengthen CTCs adhesion. Moreover, the electrode surface was decorated with highly fractal Au nanostructures (HFAuNSs) composites due to the similarity in fractal nanostructure with the CTCs membrane to enhance the CTCs anchoring efficiency and release capability. The captured CTCs could be further efficiently dissociated and nondestructively released from the modified electrodes upon electrochemical reductive desorption. The designed cytosensor showed an excellent analytical performance, with a wide linear range from 2 to 1 × 105 cells mL-1 and low limit of detection (LOD) of 2 cells mL-1 (S/N = 3) at the working potential in the range -0.6 to 0.2 V. A satisfactory CTCs release reaching a range of 93.7-97.4% with acceptable RSD from 3.55 to 6.41% and good cell viability was obtained. Thus, the developed cytosensor might provide a potential alternative to perform CTC-based liquid biopsies, with promising applications in early diagnosis of tumors. Preparation and mechanism of desorption of the cytosensor based on 2D Au@PdMo nanozymes and electrochemical reductive desorption for the detection and release of CTCs. A Preparation procedure of the Apt/Au@PbMo bioconjugates. B Fabrication process of the sandwich-type cytosensor. C Electrochemical signal produced by the Au@PdMo nanozymes. D Mechanism of electrochemical reductive desorption for CTCs release.
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Aptâmeros de Nucleotídeos/metabolismo , Separação Celular/métodos , Nanopartículas Metálicas/química , Células Neoplásicas Circulantes/química , Aptâmeros de Nucleotídeos/química , Catálise , Linhagem Celular Tumoral , Técnicas Eletroquímicas/métodos , Molécula de Adesão da Célula Epitelial/metabolismo , Ouro/química , Humanos , Limite de Detecção , Molibdênio/química , Paládio/químicaRESUMO
Micronutrient metals, such as Mn, Cu, Fe, and Zn, are essential heavy metals for plant growth and development, while Cd is a nonessential heavy metal that is highly toxic to both plants and humans. Our understanding of the molecular mechanisms underlying Cd and micronutrient metal accumulation in plants remains incomplete. Here, we show that OsFWL7, an FW2.2-like (FWL) family gene in Oryza sativa, is preferentially expressed in the root and encodes a protein localized to the cell membrane. The osfwl7 mutation reduces both the uptake and the root-to-shoot translocation of Cd in rice plants. Additionally, the accumulation of micronutrient metals, including Mn, Cu, and Fe, was lower in osfwl7 mutants than in the wildtype plants under normal growth conditions. Moreover, the osfwl7 mutation affects the expression of several heavy metal transporter genes. Protein interaction analyses reveal that rice FWL proteins interact with themselves and one another, and with several membrane microdomain marker proteins. Our results suggest that OsFWL7 is involved in Cd and micronutrient metal accumulation in rice. Additionally, rice FWL proteins may form oligomers and some of them may be located in membrane microdomains.
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Metais/metabolismo , Micronutrientes/metabolismo , Oryza/genética , Proteínas de Plantas/genética , Oligoelementos/metabolismo , Cádmio/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/genética , Cobre/metabolismo , Ferro/metabolismo , Manganês/metabolismo , Metais Pesados/metabolismo , Metais Pesados/toxicidade , Micronutrientes/química , Mutação/genética , Oryza/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Zinco/metabolismoRESUMO
A novel non-enzyme electrochemical biosensor for the rapid detection of Gram-positive bacteria has been constructed that relys on a stable and efficient combination between the peptidoglycan layer and platinum-nickel-copper nanocubes (Pt-Ni-Cu NCs). Briefly, bacteria were first captured by a specific antibody. Then, the electrochemical signal materials (Pt-Ni-Cu NCs) were bound to the bacteria peptidoglycan layer using specific structural and surface features. The rapid and sensitive bacterial detection was then achieved using intrinsic electrochemical characteristics and superoxidase-like activity of the Pt-Ni-Cu NCs. Moreover, the nature of peptidoglycan covering the whole bacteria provided the premise for signal amplification. Under optimal conditions, the electrochemical signal variation was proportional to the concentration of bacteria ranging from 1.5 × 102 to 1.5 × 108 CFU/mL with a detection limit of 42 CFU/mL using a working potential of - 0.4 V. This electrochemical biosensor has been successfully applied to detect bacteria concentrations in urine samples, and the recoveries range from 90.4 to 107%. The proposed biosensor could be applied for broad-spectrum detection of Gram-positive bacteria since most Gram-positive bacteria possess a thick peptidoglycan layer. The developed electrochemical biosensing strategy might be used as a potential tool for clinical pathogenic bacteria detection and point-of-care testing (POCT).
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Carga Bacteriana/métodos , Bactérias Gram-Positivas/química , Nanopartículas Metálicas/química , Peptidoglicano/metabolismo , Anticorpos Imobilizados/imunologia , Técnicas Biossensoriais/métodos , Catálise , Cobre/química , Técnicas Eletroquímicas/métodos , Bactérias Gram-Positivas/imunologia , Peróxido de Hidrogênio/química , Limite de Detecção , Níquel/química , Oxirredução , Platina/químicaRESUMO
OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory immune disease, recognized as an oral potentially malignant disorder by the World Health Organization. There is considerable controversy over the standardized treatment of OLP, with great diversities in the outcome measures in clinical trials. This methodological study aimed to estimate the degree of consensus on outcome measures in randomized controlled trials (RCTs) for OLP treatment. METHODS: PubMed, Embase, and Cochrane databases were searched to identify RCTs published from 2004 to 2018 about OLP treatment. All the outcome measures and measurement methods mentioned in the trials were extracted and analyzed. RESULTS: After identification of 1087 articles, 88 RCTs were included. A total of 193 single-outcome measures and 119 composite outcome measures were classified into 11 different domains, the chief of which consisted of clinical symptom (78 trials; 88.6%) and clinical score (58 trials; 65.9%). Visual analog scale (65 trials; 73.9%) and Thongprasom scoring system (38 trials; 43.2%) were the predominant measurement methods. Oral health-related quality of life (except for clinical symptoms) accounted for 4.8% of all the outcome measures. CONCLUSIONS: There was high heterogeneity in outcome measures of RCTs for OLP treatment, making it difficult to make valid comparisons between different clinical trials. A core outcome set should be developed and adopted in future trials for OLP treatment.
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Líquen Plano Bucal , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Líquen Plano Bucal/tratamento farmacológico , Qualidade de VidaRESUMO
Antimony is a competitive and promising anode material for sodium-ion batteries (SIBs) due to its high theoretical capacity. However, the poor rate capability and fast capacity fading greatly restrict its practical application. To address the above issues, a facile and eco-friendly sacrificial template method is developed to synthesize hollow Sb nanoparticles impregnated in open carbon boxes (Sb HPs@OCB). The as-obtained Sb HPs@OCB composite exhibits excellent sodium storage properties even when operated at an elevated temperature of 50 °C, delivering a robust rate capability of 345 mAh g-1 at 16 A g-1 and rendering an outstanding reversible capacity of 187 mAh g-1 at a high rate of 10 A g-1 after 300 cycles. Such superior electrochemical performance of the Sb HPs@OCB can be attributed to the comprehensive characteristics of improved kinetics derived from hollow Sb nanoparticles impregnated into 2D carbon nanowalls, the existence of robust SbOC bond, and enhanced pseudocapacitive behavior. All those factors enable Sb HPs@OCB great potential and distinct merit for large-scale energy storage of SIBs.
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Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Plasmócitos , Prognóstico , Biomarcadores TumoraisRESUMO
The homomeric α7 nicotinic receptor (α7 nAChR) is widely expressed in the human brain that could be activated to suppress neuroinflammation, oxidative stress and neuropathic pain. Consequently, a number of α7 nAChR agonists have entered clinical trials as anti-Alzheimer's or anti-psychotic therapies. However, high-resolution crystal structure of the full-length α7 receptor is thus far unavailable. Since acetylcholine-binding protein (AChBP) from Lymnaea stagnalis is most closely related to the α-subunit of nAChRs, it has been used as a template for the N-terminal domain of α-subunit of nAChR to study the molecular recognition process of nAChR-ligand interactions, and to identify ligands with potential nAChR-like activities.Here we report the discovery and optimization of novel acetylcholine-binding protein ligands through screening, structure-activity relationships and structure-based design. We manually screened in-house CNS-biased compound library in vitro and identified compound 1, a piperidine derivative, as an initial hit with moderate binding affinity against AChBP (17.2% inhibition at 100 nmol/L). During the 1st round of optimization, with compound 2 (21.5% inhibition at 100 nmol/L) as the starting point, 13 piperidine derivatives with different aryl substitutions were synthesized and assayed in vitro. No apparent correlation was demonstrated between the binding affinities and the steric or electrostatic effects of aryl substitutions for most compounds, but compound 14 showed a higher affinity (Ki=105.6 nmol/L) than nicotine (Ki=777 nmol/L). During the 2nd round of optimization, we performed molecular modeling of the putative complex of compound 14 with AChBP, and compared it with the epibatidine-AChBP complex. The results suggested that a different piperidinyl substitution might confer a better fit for epibatidine as the reference compound. Thus, compound 15 was designed and identified as a highly affinitive acetylcholine-binding protein ligand. In this study, through two rounds of optimization, compound 15 (Ki=2.8 nmol/L) has been identified as a novel, piperidine-based acetylcholine-binding protein ligand with a high affinity.
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Proteínas de Transporte/química , Ligantes , Piperidinas/química , Piperidinas/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Proteínas de Transporte/metabolismo , Desenho de Fármacos , Modelos Moleculares , Simulação de Acoplamento Molecular , Nicotina/farmacologia , Piperidinas/síntese química , Piridinas/farmacologia , Ensaio Radioligante , Relação Estrutura-AtividadeRESUMO
Soliton explosions, as one of the most fascinating nonlinear phenomena in dissipative systems, have been investigated in different branches of physics, including the ultrafast laser community. Herein, we reported on the soliton dynamics of an ultrafast fiber laser from steady state to soliton explosions, and to huge explosions by simply adjusting the pump power level. In particular, the huge soliton explosions show that the exploding behavior could operate in a sustained, but periodic, mode from one explosion to another, which we term as "successive soliton explosions." The experimental results will prove to be fruitful to the various communities interested in soliton explosions.
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MicroRNAs are small regulatory molecules that can be used as potential biomarkers of clinical diagnosis, and efforts have been directed towards the development of a simple, rapid, and sequence-selective analysis of microRNAs. Here, we report a simple and versatile colorimetric strategy for ultrasensitive and specific determination of microRNAs based on molecular beacon initiated strand displacement amplification (SDA) and catalytic hairpin assembly (CHA) with DNAzyme formation. The presence of target microRNAs triggers strand displacement amplification to release nicking DNA triggers, which initiate CHA to produce large amounts of CHA products. Meanwhile, the numerous CHA products can combine with hemin to form G-quadruplex/hemin DNAzyme, a well-known horseradish peroxidase (HRP) mimic, catalyzing a colorimetric reaction. Moreover, the purification of the SDA mixture has been developed for eliminating matrix interference to decrease nonspecific CHA products. Under the optimal conditions and using the promising amplification strategy, the established colorimetric nanomachine (biosensor) shows high sensitivity and selectivity in a dynamic response range from 5 fM to 5 nM with a detection limit as low as 1.7 fM (S/N = 3). In addition, a versatile colorimetric biosensor has been developed for detection of different miRNAs by only changing the miRNA-recognition domain of molecular beacon. Thus, this colorimetric biosensor may become a potential alternative tool for biomedical research and clinical molecular diagnostics.
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Técnicas Biossensoriais , Quadruplex G , MicroRNAs/análise , Nanocompostos/química , Técnicas de Amplificação de Ácido Nucleico/métodos , Catálise , Colorimetria/métodos , DNA Catalítico/metabolismo , Hemina/química , Peroxidase do Rábano Silvestre/química , Humanos , Limite de Detecção , Células MCF-7 , MicroRNAs/genéticaRESUMO
Enhancing the sensitivity of capacitive pressure sensors through microstructure design may compromise the reliability of the device and rely on intricate manufacturing processes. It is an effective way to solve this issue by balancing the intrinsic properties (elastic modulus and dielectric constant) of the dielectric layer materials. Here, we introduce a liquid metal (LM) hybrid elastomer prepared by a chain-extension-free polyurethane (PU) and LM. The synergistic strategies of extender-free and LM doping effectively reduce the elastic modulus (7.6 ± 0.2-2.1 ± 0.3 MPa) and enhance the dielectric constant (5.12-8.17 @1 kHz) of LM hybrid elastomers. Interestingly, the LM hybrid elastomer combines reprocessability, recyclability, and photothermal conversion. The obtained flexible pressure sensor can be used for detecting hand and throat muscle movements, and high-precision speech recognition of seven words has been using a convolutional neural network (CNN) in deep learning. This work provides an idea for designing and manufacturing wearable, recyclable, and intelligent control pressure sensors.
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The CRISPR/Cas12a system is emerging as a promising candidate for next-generation diagnostic biosensing platforms, with the discovery of new activation modes greatly expanding its applications. Here, we have identified two novel CRISPR/Cas12a system activation modes: PAM- and toehold-free DNA hairpins, and DNA-RNA hybrid strands. Utilizing a well-established real-time fluorescence method, we have demonstrated a strong correlation between DNA hairpin structures and Cas12a activation. Compared with previously reported activation modes involving single-stranded DNA and PAM-contained double-stranded DNA, the DNA hairpin activation way exhibits similar specificity and generality. Moreover, our findings indicate that increasing the number of RNA bases in DNA-RNA hybrid strands can decelerate the kinetics of Cas12a-triggered trans-cleavage of reporter probes. These newly discovered CRISPR/Cas12a activation ways hold significant potential for the development of high-performance biosensing strategies.