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Strong coupling between a single quantum emitter and an optical cavity (at rate Ω) accesses fundamental quantum optics and provides an essential building block for photonic quantum technologies. However, the minimum mode volume of conventional dielectric cavities restricts their operation to cryogenic temperature for strong coupling. Here we harness surface self-assembly to make deterministic strong coupling at room temperature using CdSe/CdS quantum dots (QDs) in nanoparticle-on-mirror (NPoM) plasmonic nanocavities. We achieve a fabrication yield of ~70% for single QD strong coupling by optimizing their size and nano-assembly. A clear and reliable Rabi splitting is observed both in the scattering of each nanocavity and their photoluminescence, which are however not equal. Integrating these quantum elements with electrical pumping allows demonstration of strong coupling in their electroluminescence. This advance provides a straightforward way to achieve practical quantum devices at room temperature, and opens up exploration of their nonlinear, electrical, and quantum correlation properties.
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Optical nanocavities have revolutionized the manipulation of radiative properties of molecular and semiconductor emitters. Here, we investigate the amplified photoluminescence arising from exciting a dark transition of ß-carotene molecules embedded within plasmonic nanocavities. Integrating a molecular monolayer into nanoparticle-on-mirror nanostructures unveils enhancements surpassing 4 orders of magnitude in the initially light-forbidden excitation. Such pronounced enhancements transcend conventional dipolar mechanisms, underscoring the presence of alternative enhancement pathways. Notably, Fourier-plane scattering spectroscopy shows that the photoluminescence excitation resonance aligns with a higher-order plasmonic cavity mode, which supports strong field gradients. Combining quantum chemistry calculations with electromagnetic simulations reveals an important interplay between the Franck-Condon quadrupole and Herzberg-Teller dipole contributions in governing the absorption characteristics of this dark transition. In contrast to free space, the quadrupole moment plays a significant role in photoluminescence enhancement within nanoparticle-on-mirror cavities. These findings provide an approach to access optically inactive transitions, promising advancements in spectroscopy and sensing applications.
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The rational modification of siRNA molecules is crucial for ensuring their drug-like properties. Machine learning-based prediction of chemically modified siRNA (cm-siRNA) efficiency can significantly optimize the design process of siRNA chemical modifications, saving time and cost in siRNA drug development. However, existing in-silico methods suffer from limitations such as small datasets, inadequate data representation capabilities, and lack of interpretability. Therefore, in this study, we developed the Cm-siRPred algorithm based on a multi-view learning strategy. The algorithm employs a multi-view strategy to represent the double-strand sequences, chemical modifications, and physicochemical properties of cm-siRNA. It incorporates a cross-attention model to globally correlate different representation vectors and a two-layer CNN module to learn local correlation features. The algorithm demonstrates exceptional performance in cross-validation experiments, independent dataset, and case studies on approved siRNA drugs, and showcasing its robustness and generalization ability. In addition, we developed a user-friendly webserver that enables efficient prediction of cm-siRNA efficiency and assists in the design of siRNA drug chemical modifications. In summary, Cm-siRPred is a practical tool that offers valuable technical support for siRNA chemical modification and drug efficiency research, while effectively assisting in the development of novel small nucleic acid drugs. Cm-siRPred is freely available at https://cellknowledge.com.cn/sirnapredictor/.
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Algoritmos , Aprendizado de Máquina , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/químicaRESUMO
Integrating cavity-enhanced colloidal quantum dots (QDs) into photonic chip devices would be transformative for advancing room-temperature optoelectronic and quantum photonic technologies. However, issues with efficiency, stability, and cost remain formidable challenges to reach the single antenna limit. Here, we present a bottom-up approach that delivers single QD-plasmonic nanoantennas with electrical addressability. These QD nanojunctions exhibit robust photoresponse characteristics, with plasmonically enhanced photocurrent spectra matching the QD solution absorption. We demonstrate electroluminescence from individual plasmonic nanoantennas, extending the device lifetime beyond 40 min by utilizing a 3 nm electron-blocking polymer layer. In addition, we reveal a giant voltage-dependent redshift of up to 62 meV due to the quantum-confined Stark effect and determine the exciton polarizability of the CdSe QD monolayer to be 4 × 10-5 meV/(kV/cm)2. These developments provide a foundation for accessing scalable quantum light sources and high-speed, tunable optoelectronic systems operating under ambient conditions.
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In recent years, cardiovascular health problems are becoming more and more serious. At the same time, mechanical stimulation closely relates to cardiovascular health. In this context, Piezo1, which is very sensitive to mechanical stimulation, has attracted our attention. Here, we review the critical significance of Piezo1 in mechanical stimulation of endothelial cells, NO production, lipid metabolism, DNA damage protection, the development of new blood vessels and maturation, narrowing of blood vessels, blood pressure regulation, vascular permeability, insulin sensitivity, and maintenance of red blood cell function. Besides, Piezo1 may participate in the occurrence and development of atherosclerosis, diabetes, hypertension, and other cardiovascular diseases. It is worth noting that Piezo1 has dual effects on maintaining cardiovascular health. On the one hand, the function of Piezo1 is necessary to maintain cardiovascular health; on the other hand, under some extreme mechanical stimulation, the overexpression of Piezo1 may bring adverse factors such as inflammation. Therefore, this review discusses the Janus-faced role of Piezo1 in maintaining cardiovascular health and puts forward new ideas to provide references for gene therapy or nanoagents targeting Piezo1.
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Cerebral ischemia/reperfusion (I/R) injury can result in different levels of cerebral impairment, and in severe cases, death. Curcumin, an essential bioactive component of turmeric, has a rich history as a traditional medicine for various ailments in numerous countries. Experimental and clinical research has established that curcumin offers a protective effect against cerebral I/R injury. Curcumin exerts its protective effects by acting on specific mechanisms such as antioxidant, anti-inflammatory, inhibition of ferroptosis and pyroptosis, protection of mitochondrial function and structure, reduction of excessive autophagy, and improvement of endoplasmic reticulum (ER) stress, which ultimately help to preserve the blood-brain barrier (BBB) and reducing apoptosis. There is currently a shortage of drugs undergoing clinical trials for the treatment of cerebral I/R injury, highlighting the pressing need for research and development of novel treatments to address this injury. The primary objective of this study is to establish a theoretical basis for future clinical applications of curcumin by delineating the mechanisms and protective effects of curcumin against cerebral I/R injury. Adapted with permission from [1].
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Isquemia Encefálica , Curcumina , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Humanos , Curcumina/farmacologia , Curcumina/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Apoptose , Traumatismo por Reperfusão/prevenção & controle , Isquemia Encefálica/tratamento farmacológicoRESUMO
Atherosclerotic cardiovascular disease is a typical age-related disease accompanied by stiffening arteries. We aimed to elucidate the influence of aged arteries on in-stent restenosis (ISR) after the implantation of bioresorbable scaffolds (BRS). Histology and optical coherence tomography showed increased lumen loss and ISR in the aged abdominal aorta of Sprague-Dawley rats, with apparent scaffold degradation and deformation, which induce lower wall shear stress (WSS). This was also the case at the distal end of BRS, where the scaffolds degraded faster, and significant lumen loss was followed by a lower WSS. In addition, early thrombosis, inflammation, and delayed re-endothelialization were presented in the aged arteries. Degradation of BRS causes more senescent cells in the aged vasculature, increasing endothelial cell dysfunction and the risk of ISR. Thus, profoundly understanding the mechanism between BRS and senescent cells may give a meaningful guide for the age-related scaffold design. STATEMENT OF SIGNIFICANCE: The degradation of bioresorbable scaffolds aggravates senescent endothelial cells and a much lower wall shear stress areas in the aged vasculature, lead to intimal dysfunction and increasing in-stent restenosis risk. Early thrombosis and inflammation, as well as delayed re-endothelialization, are presented in the aged vasculature after bioresorbable scaffolds implantation. Age stratification during the clinical evaluation and senolytics in the design of new bioresorbable scaffolds should be considered, especially for old patients.
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Reestenose Coronária , Intervenção Coronária Percutânea , Animais , Ratos , Implantes Absorvíveis , Reestenose Coronária/etiologia , Desenho de Prótese , Células Endoteliais , Angiografia Coronária/efeitos adversos , Ratos Sprague-Dawley , Constrição Patológica , Inflamação , Tomografia de Coerência Óptica/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Vasos CoronáriosRESUMO
A liquid-based surface-enhanced Raman spectroscopy assay termed PSALM is developed for the selective sensing of neurotransmitters (NTs) with a limit of detection below the physiological range of NT concentrations in urine. This assay is formed by quick and simple nanoparticle (NP) "mix-and-measure" protocols, in which FeIII bridges NTs and gold NPs inside the sensing hotspots. Detection limits of NTs from PreNP PSALM are significantly lower than those of PostNP PSALM, when urine is pretreated by affinity separation. Optimized PSALM enables the long-term monitoring of NT variation in urine in conventional settings for the first time, allowing the development of NTs as predictive or correlative biomarkers for clinical diagnosis.
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Biodegradable polymers are expected to be an alternative to plastics. Because of its high biocompatibility, poly (lactic-co-glycolic acid) (PLGA) is widely used in medicine. It has been reported that micro-nano plastics can be accumulated in the circulatory system and cause tissue injury. With the increasing environmental exposure of degradable polymer nanoparticles (NPs), the impact of this risk factor on cardiovascular disease deserves attention. Thus, we aim to study the harmful effect of PLGA NPs on the process of vascular stenosis which is a typical pathological feature of cardiovascular diseases. We establish a mouse vascular stenosis model with intravenously injecting of PLGA NPs for 2 weeks. This model leads to a significant narrowing of the left common carotid artery which is characterized by the increasing intima area and focal stenosis. We observe that PLGA NPs accelerate stenosis progression by inducing inflammation and impairing vascular function. It promotes the proliferation of smooth muscle cells and causes abnormal collagen distribution. The combination of wall shear stress and PLGA NPs uptake speed up endothelial cell damage, decrease endothelial permeability and cell migration capacity. Our results suggest that PLGA NPs may pose a risk in cardiovascular stenosis which inspire us to concern the biodegradable polymeric materials in our living especially the clinic applications.
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Doenças Cardiovasculares , Nanopartículas , Animais , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ácido Poliglicólico , Ácido Láctico , Constrição Patológica , Inflamação , Endotélio , Portadores de FármacosRESUMO
Plasmonic nanoantennas can focus light at nanometer length scales providing intense field enhancements. For the tightest optical confinements (0.5-5 nm) achieved in plasmonic gaps, the gap spacing, refractive index, and facet width play a dominant role in determining the optical properties making tuning through antenna shape challenging. We show here that controlling the surrounding refractive index instead allows both efficient frequency tuning and enhanced in-/output coupling through retardation matching as this allows dark modes to become optically active, improving widespread functionalities.
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Bottom-up assembly of nanoparticle-on-mirror (NPoM) nanocavities enables precise inter-metal gap control down to ≈ 0.4 nm for confining light to sub-nanometer scales, thereby opening opportunities for developing innovative nanophotonic devices. However limited understanding, prediction, and optimization of light coupling and the difficulty of controlling nanoparticle facet shapes restricts the use of such building blocks. Here, an ultraprecise symmetry-breaking plasmonic nanocavity based on gold nanodecahedra is presented, to form the nanodecahedron-on-mirror (NDoM) which shows highly consistent cavity modes and fields. By characterizing > 20 000 individual NDoMs, the variability of light in/output coupling is thoroughly explored and a set of robust higher-order plasmonic whispering gallery modes uniquely localized at the edges of the triangular facet in contact with the metallic substrate is found. Assisted by quasinormal mode simulations, systematic elaboration of NDoMs is proposed to give nanocavities with near hundred-fold enhanced radiative efficiencies. Such systematically designed and precisely-assembled metallic nanocavities will find broad application in nanophotonic devices, optomechanics, and surface science.
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As one of the main functions of vascular endothelial cells, Vascular permeability is determined by four tight junction proteins (TJPs): Zonula Occludens-1 (ZO-1), Claudin-5, Occludin and Tricellulin. The barrier function of blood vessels will be reconstructed after they are damaged by endothelial mechanical injuries caused by vascular interventions. In this study, the effects of balloon expansion (transient mechanical injury) on four TJPs and vascular permeability were compared with those of poly-l-lactic acid bioresorbable scaffolds (BRSs) implantation (continuous mechanical stimulation). We found that BRSs do not affect vascular permeability, while the recovery of vascular barrier function was found to be only related to the mechanical injuries and repair of endothelium. Mechanical stimulation affects and accelerates the recovery process of vascular permeability with the heterogeneous expression levels of TJPs induced after BRSs implantation. Different TJPs have different sensitivity to different loyal mechanical stimuli. ZO-1 is more sensitive to shear stress and tension than to static pressure. Occludin is sensitive to static pressure and shear stress. Tricellulin is more sensitive to tension stretching. Compared with the other three TJPs, Claudin-5 can respond to mechanical stimulation, with relatively low sensitivity, though. This difference in sensitivity determines the heterogeneous expression of TJPs. Mechanical stimulation of different kinds and strengths can also cause different cell morphological changes and inflammatory reactions. As an important element affecting endothelial function, the mechanical factors emerging after BRSs implantation are worthy of more attention.
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The optical properties of nanogap plasmonic cavities formed by a NanoParticle-on-Mirror (NPoM, or patch antenna) are determined here, across a wide range of geometric parameters including the nanoparticle diameter, gap refractive index, gap thickness, facet size and shape. Full understanding of the confined optical modes allows these nanocavities to be utilized in a wide range of experiments across many fields. We show that the gap thickness t and refractive index n are spectroscopically indistinguishable, accounted for by a single gap parameter G = n/t 0.47. Simple tuning of mode resonant frequencies and strength is found for each quasi-normal mode, revealing a spectroscopic "fingerprint" for each facet shape, on both truncated spherical and rhombicuboctahedral nanoparticles. This is applied to determine the most likely nanoscale morphology of facets hidden below each NPoM in experiment, as well as to optimize the constructs for different applications. Simple scaling relations are demonstrated, and an online tool for general use is provided.
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Transient bonds between molecules and metal surfaces underpin catalysis, bio/molecular sensing, molecular electronics, and electrochemistry. Techniques aiming to characterize these bonds often yield conflicting conclusions, while single-molecule probes are scarce. A promising prospect confines light inside metal nanogaps to elicit in operando vibrational signatures through surface-enhanced Raman scattering. Here, we show through analysis of more than a million spectra that light irradiation of only a few microwatts on molecules at gold facets is sufficient to overcome the metallic bonds between individual gold atoms and pull them out to form coordination complexes. Depending on the molecule, these light-extracted adatoms persist for minutes under ambient conditions. Tracking their power-dependent formation and decay suggests that tightly trapped light transiently reduces energy barriers at the metal surface. This opens intriguing prospects for photocatalysis and controllable low-energy quantum devices such as single-atom optical switches.
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Depression is identified as one of the most common psychiatric symptoms in Alzheimer's disease (AD). The comorbidity of AD and depression increases the burden of clinical treatment and care in elderly patients. In order to find new treatment options, we first proposed the dual RAGE/SERT inhibitors by fusing the key pharmacophore of vilazodone and azeliragon for the potential treatment of AD with comorbid depression. After a series of structural modifications, 34 dual-target directed ligands were designed and synthesized, and their RAGE and SERT inhibitory activities were systematically evaluated. Among them, compound 12 showed good dual-target bioactivities against RAGE (IC50 = 8.26 ± 1.12 µM) and SERT (IC50 = 31.09 ± 5.15 nM) in vitro, better safety profile than azeliragon, good liver microsomal stability, weak CYP inhibition, and acceptable pharmacokinetic properties. Moreover, 12 ameliorated Aß25-35-induced neurotoxicity in SH-SY5Y cells and alleviated the depressive symptom in tail suspension test. In brief, these results indicated that 12 is a prospective prototype for the potential treatment of AD with comorbid depression.
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Doença de Alzheimer , Idoso , Doença de Alzheimer/tratamento farmacológico , Comorbidade , Depressão/tratamento farmacológico , Desenho de Fármacos , Humanos , Estudos Prospectivos , Receptor para Produtos Finais de Glicação Avançada/uso terapêuticoRESUMO
Bioresorbable scaffolds have emerged as a new generation of vascular implants for the treatment of atherosclerosis, and designed to provide a temporary scaffold that is subsequently absorbed by blood vessels over time. Presently, there is insufficient data on the biological and mechanical responses of blood vessels accompanied by bioresorbable scaffolds (BRS) degradation. Therefore, it is necessary to investigate the inflexion point of degradation, the response of blood vessels, and the pathophysiological process of vascular, as results of such studies will be of great value for the design of next generation of BRS. In this study, abdominal aortas of SD rats were received 3-D printed poly-l-actide vascular scaffolds (PLS) for various durations up to 12 months. The response of PLS implanted aorta went through two distinct processes: (1) the neointima with desirable barrier function was obtained in 1 month, accompanied with slow degradation, inflammation, and intimal hyperplasia; (2) significant degradation occurred from 6 months, accompanied with decreasing inflammation and intimal hyperplasia, while the extracellular matrix recovered to normal vessels which indicate the positive remodeling. These in vivo results indicate that 6 months is a key turning point. This "two-stage degradation and vascular characteristics" is proposed to elucidate the long-term effects of PLS on vascular repair and demonstrated the potential of PLS in promoting endothelium function and positive remodeling, which highlights the benefits of PLS and shed some light in the future researches, such as drug combination coatings design.
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Depression is one of the most frequent comorbid psychiatric symptoms of Alzheimer's disease (AD), and no efficacious drugs have been approved specifically for this purpose thus far. Herein, we proposed a novel therapeutic strategy that merged the key pharmacophores of the antidepressant vilazodone (5-HT1A receptor partial agonist and serotonin transporter inhibitor) and the anti-AD drug donepezil (acetylcholinesterase inhibitor) together to develop a series of multi-target-directed ligands for potential therapy of the comorbidity of AD and depression. Accordingly, 55 vilazodone-donepezil chimeric derivatives were designed and synthesized, and their triple-target activities against acetylcholinesterase, 5-HT1A receptor, and serotonin transporter were systematically evaluated. Among them, compound 5 displayed strong triple-target bioactivities in vitro, low hERG potassium channel inhibition and acceptable brain distribution. Importantly, oral intake of 5 mg/kg of the compound 5 dihydrochloride significantly alleviated the depressive symptoms and ameliorated cognitive dysfunction in mouse models. In brief, these results highlight vilazodone-donepezil chimeras as a prospective therapeutic approach for the treatment of the comorbidity of AD and depression.
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Doença de Alzheimer/tratamento farmacológico , Depressão/tratamento farmacológico , Donepezila/química , Cloridrato de Vilazodona/química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Doença de Alzheimer/complicações , Animais , Antidepressivos/química , Antidepressivos/metabolismo , Antidepressivos/uso terapêutico , Sítios de Ligação , Encéfalo/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/uso terapêutico , Depressão/complicações , Desenho de Fármacos , Meia-Vida , Humanos , Ligantes , Camundongos , Simulação de Acoplamento Molecular , Ratos , Ratos Sprague-Dawley , Proteínas da Membrana Plasmática de Transporte de Serotonina/química , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Relação Estrutura-AtividadeRESUMO
Surface-enhanced Raman spectroscopy (SERS) is considered an attractive candidate for quantitative and multiplexed molecular sensing of analytes whose chemical composition is not fully known. In principle, molecules can be identified through their fingerprint spectrum when binding inside plasmonic hotspots. However, competitive binding experiments between methyl viologen (MV2+) and its deuterated isomer (d8-MV2+) here show that determining individual concentrations by extracting peak intensities from spectra is not possible. This is because analytes bind to different binding sites inside and outside of hotspots with different affinities. Only by knowing all binding constants and geometry-related factors, can a model revealing accurate concentrations be constructed. To collect sufficiently reproducible data for such a sensitive experiment, we fully automate measurements using a high-throughput SERS optical system integrated with a liquid handling robot (the SERSbot). This now allows us to accurately deconvolute analyte mixtures through independent component analysis (ICA) and to quantitatively map out the competitive binding of analytes in nanogaps. Its success demonstrates the feasibility of automated SERS in a wide variety of experiments and applications.
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Análise Espectral Raman , AutomaçãoRESUMO
Nature controls the assembly of complex architectures through self-limiting processes; however, few artificial strategies to mimic these processes have been reported to date. Here we demonstrate a system comprising two types of nanocrystal (NC), where the self-limiting assembly of one NC component controls the aggregation of the other. Our strategy uses semiconducting InP/ZnS core-shell NCs (3 nm) as effective assembly modulators and functional nanoparticle surfactants in cucurbit[n]uril-triggered aggregation of AuNCs (5-60 nm), allowing the rapid formation (within seconds) of colloidally stable hybrid aggregates. The resultant assemblies efficiently harvest light within the semiconductor substructures, inducing out-of-equilibrium electron transfer processes, which can now be simultaneously monitored through the incorporated surface-enhanced Raman spectroscopy-active plasmonic compartments. Spatial confinement of electron mediators (for example, methyl viologen (MV2+)) within the hybrids enables the direct observation of photogenerated radical species as well as molecular recognition in real time, providing experimental evidence for the formation of elusive σ-(MV+)2 dimeric species. This approach paves the way for widespread use of analogous hybrids for the long-term real-time tracking of interfacial charge transfer processes, such as the light-driven generation of radicals and catalysis with operando spectroscopies under irreversible conditions.