Contact lens care and early diagnosis of Acanthamoeba keratitis (AK) are very important to prevent progression to blindness due to AK, which develops when Acanthamoeba attaches to contact lens-damaged corneas. Therefore, we propose a novel, non-invasive, immuno-surface-enhanced Raman scattering (SERS) sensing platform for rapid and accurate detection of Acanthamoeba infection in the tears and contact lens solutions of humans. This optic analysis method was based on the proven biological performance of chorismate mutase (CM)-specific monoclonal and polyclonal antibodies on trophozoite and cyst forms of Acanthamoeba castellanii, and its conditioned media. SERS-based, ultra-low concentration detection was achieved by the anisotropic fanblade-shaped core-shell nanoassembly (Ag@AuFNP) embedded with 4-fluorobenzenethiol Raman reporter. The immuno-SERS platform combining Ag@AuFNP and CM-specific antibody complexes was evaluated in vitro and in vivo. The non-invasive SERS-activated biosensing platform indicates strong feasibility for AK detection in human tears and contact lens solutions.
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease primarily driven by inappropriate infiltration and activation of immune cells and pro-inflammatory cytokines. Among them, neutrophils with high plasticity play a pathogenic role in RA by abnormal neutrophil immune activities. As anti-IL-17A therapies failed to achieve long-term ideal therapeutic outcomes in clinical trials, we speculated that the underlying cause may be associated with the abnormal activity of neutrophils that have a direct link to IL-17A. Herein, we created a cationic hydrogel loaded with anti-IL-17A nanobodies (Nbs) capable of synergistically weakening the inflammatory activities of neutrophils and relieving inflammation in RA. Based on the host-guest interaction, the hydrogel was comprised of β-cyclodextrin-modified hyperbranched polylysine (HBPL-CD) and adamantane-modified hyaluronic acid (HA-Ad). The physical properties were adjusted to match the mechanical environment of joints and enable injection. The hydrogel with Nbs could adsorb cell-free DNA (cfDNA) persistently and slowly release anti-IL-17A Nbs, which synergistically alleviated the inflammatory activities of neutrophils via inhibiting the IL-17A stimulated neutrophil extracellular traps (NETs) of neutrophils from RA patients and mice with collagen-induced arthritis (CIA), reducing the level of pro-inflammatory cytokines, and suppressing the inflammatory phenotype of neutrophils in vitro. The ankle injection of the hydrogel with Nbs into a mouse model of CIA could alleviate the RA symptoms in vivo. This novel platform is believed to provide a guideline for treating IL-17A-related diseases by combining Nbs with the immunoregulation of neutrophils.
Although immune checkpoint blockade (ICB) therapy enhances the tumour recognition of cytotoxic T lymphocytes (CTLs), the limited infiltration of CTLs into the centre of solid tumours significantly restricts the effect of ICB therapy. Herein, we showed that increased tumour interstitial fluid pressure (TIFP) is a critical factor in the tumour “marginalization” of CTLs. Additionally, we utilized a spatiotemporally controllable thermoelectric catalytic nanodrug (BF@M) to decompose water from the tumour interstitial fluid into oxygen, effectively reducing the TIFP and leading to enhanced infiltration of CTLs from the periphery to the interior of the solid tumour. The results revealed that BF@M significantly increased the intratumor infiltration of CTLs in three different tumour-bearing mouse models, with a maximum increase of 18.1 times. Overall, this study highlighted the intrinsic relationship between TIFP and CTLs infiltration and the mechanism underlying the effect of the TIFP, successfully addressing the tumour “marginalization” of CTLs to enhance ICB therapy.
The family of nanomagnetic arrays termed artificial spin ice (ASI) possess a vast range of metastable microstates. These states exhibit both exotic fundamental physics and more recently applied functionality, garnering attention as reconfigurable magnonic circuits and neuromorphic computing platforms. However, open questions remain on the role of microstate imperfections or angular disorder – particularly in the GHz response of the system. We report a study on the GHz dynamics of a series of five carefully prepared microstates in the same ASI sample, with both coexistence of vortex and uniformly magnetized macrospins, and disorder in the orientation of the macrospins at different vertices. We observe microstate-specific mode frequency shifting, mode creation and mode crossing. This versatility of characteristic spin-wave (SW) peaks for specific magnetic microstates in ASI enables identification of microstate configurations via SW spectral characterization. The wide reconfigurability of microstate-specific SW dynamics also opens avenues for developing rich magnonic devices operating in the GHz frequency regime and advances the understanding of ASI physics.
Direct growth of large-area vertically stacked two-dimensional (2D) van der Waal (vdW) materials is a prerequisite for their high-end applications in integrated electronics, optoelectronics and photovoltaics. Currently, centimetre- to even metre-scale monolayers of single-crystal graphene (MLG) and hexagonal boron nitride (h-BN) have been achieved by epitaxial growth on various single-crystalline substrates. However, in principle, this success in monolayer epitaxy seems extremely difficult to be replicated to bi- or few-layer growth, as the full coverage of the first layer was believed to terminate the reactivity of those adopting catalytic metal surfaces. Here, we report an exceptional layer-by-layer chemical vapour deposition (CVD) growth of large size bi-layer graphene single-crystals, enabled by proximity catalytic activity from platinum (Pt) surfaces to the outermost graphene layers. In-situ growth and real-time surveillance experiments, under well-controlled environments, unambiguously verify that the growth does follow the layer-by-layer mode on open surfaces of MLG/Pt(111). First-principles calculations indicate that the transmittal of catalytic activity is allowed by an appreciable electronic hybridisation between graphene overlayers and Pt surfaces, enabling catalytic dissociation of hydrocarbons and subsequently direct graphitisation of their radicals on the outermost sp2 carbon surface. This proximity catalytic activity is also proven to be robust for tube-furnace CVD in fabricating single-crystalline graphene bi-, tri- and tetra-layers, as well as h-BN few-layers. Our findings offer an exceptional strategy for potential controllable, layer-by-layer and wafer-scale growth of vertically stacked few-layered 2D single crystals.
Technological advances constantly set new challenges for materials development. The miniaturisation of electronic devices demands the migration of metallurgy from macro/micro to the nanoscale, thus requiring a re-definition of existing and classical concepts in this field. The present study reports on the behaviour of pure Cu nanowires with diameters ranging from 40 to 140 nm heated in a low-pressure environment within a transmission electron microscope. The response of Cu nanowires was investigated at different temperatures up to 1123 K and analysed using electron-microscopy techniques, revealing both volumetric and shape changes over time. Sublimation, with a steady-state length reduction of the nanowires, was identified as the dominant effect of such heating. Additionally, it was detected that sublimation occurred not only at temperatures above ≈ 1023 K, where Cu has a higher vapour pressure than the column pressure of the electron-microscope, but also at temperatures as low as 923 K. This behaviour is explained by the presence of active regions at sharply curved regions at the nanowire tip and the imbalance of evaporation and redeposition rates of Cu atoms due to the experimentally-induced loss of vapor atoms. The study of Cu nanowires at the nanoscale with the electron microscope facilitates the elucidation of some fundamental aspects of the emerging science of nanometallurgy.
Chemotherapy remains the core anticancer treatment for castration-resistant prostate cancer (CRPC). However, drug resistance still poses a major obstacle, leading to shorter survival times. Given the biosafety of porous Se@SiO2 nanospheres in normal tissues, their combination with chemotherapeutic drugs has emerged as an effective treatment for cancer. It is unknown whether porous Se@SiO2 nanospheres can protect CRPC cells from drug resistance. In our study, we synthesized porous Se@SiO2 nanospheres and confirmed their characteristics in line with previous studies. We discovered that porous Se@SiO2 nanospheres sensitize CRPC to docetaxel (DTX) treatment, both in vitro and in vivo. Mechanistically, the nanospheres induce dephosphorylation of autophagy-related 14 (ATG14) at Y357 by upregulating the expression of the cellular form of prostatic acid phosphatase (cPAP) protein, which prevents the induction of autophagy and the survival of prostate cancer cells after DTX treatment. Furthermore, there is a negative correlation between cPAP and autophagy in CRPC. Our results suggest that the combination of porous Se@SiO2 nanospheres with DTX could be a potentially effective treatment for CRPC.
We present cryo-responsive dynamic fractal ice nano-nucleators (DF-INNs) for cryo-cancer therapy applications. Our development of DF-INNs leverages their structural advantages, which inherently maximizes the number of active sites for heterogeneous ice nucleation. Owing to their radially attached nanocrystalline structure, DF-INNs expose an extensive array of grain boundaries. The rapid precipitation and subsequent radial attachments of nanocrystallites promote the exposure of facets with high Miller indices, intrinsically strained, five-fold twinned nanocrystals, and increasing point defects due to kinetically-limited precipitation. This unique fractal structure culminates in the elevating of freezing temperature compared to Euclidean-shaped ice nucleators. Additionally, the branched fractal structure of DF-INNs facilitates heterogenic ice formation within its nanoconfined region, leading to the production of numerous self-similar small fractal fragments. This fragmentation is primarily driven by nanoconfinement-induced delayed ice nucleation, similar to frost heaving. The shear stress can be easily relieved through grain boundary sliding within the radially stacked DF-INN, making itself prone to cryo-responsive fragmentation. Such dynamic attributes significantly enhance ice nucleating activity, presenting a powerful strategy to increase the efficacy of cryotherapy by enhancing cellular ice formation and in vivo tumor coverage.
Horizontally aligned carbon nanotube (HACNT) arrays hold significant potential for various applications in nanoelectronics and material science. However, their high-throughput characterization remains challenging due to the lack of methods with both high efficiency and high accuracy. Here, we present a novel technique, Calibrated Absolute Optical Contrast (CAOC), achieved through the implementation of differential principles to filter out stray signals and high-resolution calibration to endow optical contrast with physical significance. CAOC offers major advantages over previous characterization techniques, providing consistent and reliable measurements of HACNT array density with high throughput and non-destructive assessment. To validate its utility, we demonstrate wafer-scale uniformity assessment by rapid density mapping. This technique not only facilitates the practical evaluation of HACNT arrays but also provides insights into balancing high throughput and high resolution in nanomaterial characterization.