Site-specific variations in surface structure and Young's modulus of human hair surfaces at the nanometer scale as induced through bleach treatment.

The effect of bleach treatments on the morphology and mechanical properties of hair surfaces was measured at the nanometer scale using atomic force microscopy. We used an ultrahigh-precision relocation technique to observe the variations in these properties at precise locations on hair surfaces in their virgin state and then after each of the two bleach treatments, to rule out position-dependent fluctuations. We demonstrate that statistically significant variations in roughness and Young's modulus are observed as a result of exposure to bleach, which is known to disrupt the disulfide linkage network throughout the fiber. The rate at which surface roughness changes increased with the number of treatments, with very little effect seen after 10 min, and an increase of up to 65% was observed after a further 10 min. The Young's modulus decreased by up to 40% after each treatment. We also investigate micropores and show that they are subsurface, but revealed through bleaching, and oriented along the direction of the hair shaft with a characteristic aspect ratio. This work demonstrates the profound effect bleaching has on the molecular structure of hair, which manifests as changes in morphology and stiffness, and this should be taken into account in the formulation of future hair-care products.

Photooxidation crosslinking to recover residual stress in decellularized blood vessel.

Decellularization method based on trypsin-digestion is widely used to construct small diameter vascular grafts. However, this method will reduce the opening angle of the blood vessel and result in the reduction of residual stress. Residual stress reduced has an adverse effect on the compliance and permeability of small diameter vascular grafts. To improve the situation, acellular blood vessels were treated with glutaraldehyde and photooxidation crosslinking respectively, and the changes of opening angle, circumferential residual strain of native blood vessels, decellularized arteries and crosslinked blood vessels were measured by means of histological examination, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in this study. The opening angle of decellularized arteries significantly restored after photooxidation crosslinking (P = 0.0216), while that of glutaraldehyde crosslinking blood vessels reduced. The elastic fibers inside the blood vessels became densely rearranged after photooxidation crosslinking. The results of finite element simulation showed that the residual stress increased with the increase of opening angle. In this study, we found at the first time that photooxidation crosslinking method could significantly increase the residual stress of decellularized vessels, which provides biomechanical support for the development of new biomaterials of vascular grafts.

Cadmium-induced dysfunction of the blood-brain barrier depends on ROS-mediated inhibition of PTPase activity in zebrafish.

Increasing evidence has demonstrated that cadmium accumulation in the blood increases the risk of neurological diseases. However, how cadmium breaks through the blood-brain barrier (BBB) and is transferred from the blood circulation into the central nervous system is still unclear. In this study, we examined the toxic effect of cadmium chloride (CdCl2) on the development and function of BBB in zebrafish. CdCl2 exposure induced cerebral hemorrhage, increased BBB permeability and promoted abnormal vascular formation by promoting VEGF production in zebrafish brain. Furthermore, in vivo and in vitro experiments showed that CdCl2 altered cell-cell junctional morphology by disrupting the proper localization of VE-cadherin and ZO-1. The potential mechanism involved in the inhibition of protein tyrosine phosphatase (PTPase) mediated by cadmium-induced ROS was confirmed with diphenylene iodonium (DPI), a ROS production inhibitor. Together, these data indicate that BBB is a critical target of cadmium toxicity and provide in vivo etiological evidence of cadmium-induced neurovascular disease in a zebrafish BBB model.

Recent advances of electrochemical sensors for detecting and monitoring ROS/RNS.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are prominent metabolic products which show well-established significance. At relatively low concentrations, they play multifaceted roles in regulating a number of physiological processes. Overproduction of ROS/RNS contributes to the pathogenesis of a plethora of physiological disorders, including but not limited to cardiovascular diseases, neurodegenerative diseases, cancer. Electrochemistry have been extensively used for detecting and monitoring ROS/RNS, benefiting from their inherent advantages including fast response, low costs, real-time detection, high sensitivity and selectivity. This review focuses on three types of ROS/RNS (H2O2, O2-, NO) with emphasis on their electrochemical detection/monitoring respectively. We demonstrate the application of electrochemical strategies for ROS/RNS detection in body fluids, in vitro, and in vivo, outlining the hardware architecture and comparing analytical performance of these sensors. This review aims for a holistic view of limitations in existing ROS/RNS detection by comprehensively explaining the shortcomings of the current works in the hope of drawing attentions to the challenges of ROS/RNS electrochemical technologies. We pay particular attention to in vitro and in vivo sensors and extend our evaluation to suggest possible solutions. Specifically, this review focuses on the development of currently nanotechnologies, biomimetic engineering, 3D-culture methods and implanted sensors to provide a guideline for future works.

Plasmon-Induced Trap State Emission from Single Quantum Dots.

Charge carriers trapped at localized surface defects play a crucial role in quantum dot (QD) photophysics. Surface traps offer longer lifetimes than band-edge emission, expanding the potential of QDs as nanoscale light-emitting excitons and qubits. Here, we demonstrate that a nonradiative plasmon mode drives the transfer from two-photon-excited excitons to trap states. In plasmonic cavities, trap emission dominates while the band-edge recombination is completely suppressed. The induced pathways for excitonic recombination not only shed light on the fundamental interactions of excitonic spins, but also open new avenues in manipulating QD emission, for optoelectronics and nanophotonics applications.

Theoretical estimation of size effects on the electronic transport in tailored graphene nanoribbons.

Focusing on the potential applications of tailored graphene nanoribbons (t-GNRs), in this work, we systematically study size effects on the electronic transport in t-GNR-based molecular junctions. As a result of the manufacturing error generated during the processing or synthesis of t-GNRs using techniques such as ion beam lithography, the final dimensions of the as-fabricated devices often deviate from the design values, giving rise to a size distribution around the mean value which could considerably affect the device performance. To simulate the effects of the manufacturing error, a series of t-GNR-based junctions with various dimensions have been modelled and systematically investigated using density functional theory (DFT) coupled with the non-equilibrium Green's function (NEGF). For junctions that consist of an acene chain connected with two graphene nanosheets, it is found that the chain length has little influence on the electronic transport and that, on the other hand, the junction conductivity is significantly altered by its width due to the different number and nature of the electron transfer pathways. Furthermore, increasing the width of the junction leads to a clear odd-even variation of decreasing amplitude in its transport behavior. These findings underpin further fundamental and device-based studies of t-GNRs.

Nanoparticles retard immune cells recruitment in vivo by inhibiting chemokine expression.

The large-scale utilization of nanotechnology depends on public and consumer confidence in the safety of this new technology. Studying the interaction of nanoparticles with immune cells plays a vital role in the safety assessment of nanomedicine. Although some researches have indicated that the immune cells undergo severe interfere after phagocytosis of nanoparticles, the impact on immune system of the whole body are still unclear. Here, we use immune cells labeled transgenic zebrafish to study the mechanisms of nanoparticles on zebrafish immune cells. We demonstrate that gold nanoparticles (Au NPs) phagocytized by immune cells can reduce and retard the sensitivity of immune response, resulting nanoparticle-induced bluntness in immune cell (NIBIC). RNA-seq and functional analysis reveal that NIBIC is mainly induced by the inhibiting expression of chemokine receptor 5 (CCR5). Furthermore, PVP-modified Au NPs can eliminate NIBIC by inhibiting the cell phagocytosis. Our results highlight the potential risk for Au NPs in vivo and further the understanding of the mechanism of the interaction between Au NPs and the immune response. We should consider this factor in future material design and pay more attention to the process of using nanomedicines on immune diseases.

High-Fidelity Determination and Tracing of Small Extracellular Vesicle Cargoes.

Direct tracing of small extracellular vesicle (sEV) cargoes holds unprecedented importance for elucidating the mechanisms involved in intercellular communication. However, high-fidelity determination of sEVs' molecular cargoes in situ has yet to be achieved due to the difficulty in transporting molecular probes into intact sEVs. Herein, a fLuorescent Intracellular-Guided Hairpin-Tetrahedron (fLIGHT) nanoprobe is described for direct visualization of sEV microRNAs in situ. Integrating the advantages of nondestructive sEV penetration via DNA origami and single-nucleotide discrimination as well as wash-free fluorescence readout using a hairpin probe, the proposed approach enables high-fidelity fluorescence visualization of sEVs' microRNA without RNA extraction or leakage, demonstrating the potential of on-site tracing of sEV cargoes. This strategy opens an avenue to establishing universal molecular detection and labeling platforms that can facilitate both sEV-derived fundamental biological studies and molecular diagnostics.

M2 macrophage-derived exosomes promote the c-KIT phenotype of vascular smooth muscle cells during vascular tissue repair after intravascular stent implantation.

Rationale: For intravascular stent implantation to be successful, the processes of vascular tissue repair and therapy are considered to be critical. However, the mechanisms underlying the eventual fate of vascular smooth muscle cells (VSMCs) during vascular tissue repair remains elusive. In this study, we hypothesized that M2 macrophage-derived exosomes to mediate cell-to-cell crosstalk and induce dedifferentiation phenotypes in VSMCs. Methods:In vivo, 316L bare metal stents (BMS) were implanted from the left iliac artery into the abdominal aorta of 12-week-old male Sprague-Dawley (SD) rats for 7 and 28 days. Hematoxylin and eosin (HE) were used to stain the neointimal lesions. En-face immunofluorescence staining of smooth muscle 22 alpha (SM22α) and CD68 showed the rat aorta smooth muscle cells (RASMCs) and macrophages. Immunohistochemical staining of total galactose-specific lectin 3 (MAC-2) and total chitinase 3-like 3 (YM-1) showed the total macrophages and M2 macrophages. In vitro, exosomes derived from IL-4+IL-13-treated macrophages (M2Es) were isolated by ultracentrifugation and characterized based on their specific morphology. Ki-67 staining was conducted to assess the effects of the M2Es on the proliferation of RASMCs. An atomic force microscope (AFM) was used to detect the stiffness of the VSMCs. GW4869 was used to inhibit exosome release. RNA-seq was performed to determine the mRNA profiles of the RASMCs and M2Es-treated RASMCs. Quantitative real-time PCR (qRT-PCR) analysis was conducted to detect the expression levels of the mRNAs. Western blotting was used to detect the candidate protein expression levels. T-5224 was used to inhibit the DNA binding activity of AP-1 in RASMCs. Results: M2Es promote c-KIT expression and softening of nearby VSMCs, hence accelerating the vascular tissue repair process. VSMCs co-cultured in vitro with M2 macrophages presented an increased capacity for de-differentiation and softening, which was exosome dependent. In addition, the isolated M2Es helped to promote VSMC dedifferentiation and softening. Furthermore, the M2Es enhanced vascular tissue repair potency by upregulation of VSMCs c-KIT expression via activation of the c-Jun/activator protein 1 (AP-1) signaling pathway.Conclusions: The findings of this study emphasize the prominent role of M2Es during VSMC dedifferentiation and vascular tissue repair via activation of the c-Jun/AP-1 signaling pathway, which has a profound impact on the therapeutic strategies of coronary stenting techniques.

SRGN, a new identified shear-stress-responsive gene in endothelial cells.

Endothelial cells (ECs) play an important role in the pathogenesis of cardiovascular disease, especially atherosclerosis (AS). The abnormal wall shear stress (WSS) which directly contacts with ECs is the key stimulating factor leading to AS. However, the underlying mechanism of ECs responding to WSS is still incompletely understood. This study aims to explore the novel mechano-sensitive genes and its potential mechanism in response to WSS in ECs by employing bioinformatics methods based on previously available high-throughput data from zebrafish embryos, both before and after blood flow formation. Six common differentially expressed genes (DEGs) (SRGN, SLC12A3, SLC25A4, PVALB1, ITGAE.2, zgc:198419) were selected out from two high-throughput datasets (GSE126617 and GSE20707) in the GEO database. Among them, SRGN was chosen for further verification through the in vitro shear stress loading experiments with human umbilical vein endothelial cells (HUVECs) and the in vivo partial ligation of carotid artery in mice. Our data indicated that low shear stress (LSS) could enhance the expression of SRGN via the PKA/CREB-dependent signaling pathway. The proportion of Ki67+ cells and the concentration of nitric oxide (NO) were high in SRGN high expression cells, suggesting that SRGN may be involved in the proliferation of HUVECs. Furthermore, in the partial ligation of the carotid artery mice model, we observed that the expression of SRGN was significantly increased in atherosclerotic plaques induced by abnormal shear stress. Taken together, this study demonstrated that SRGN is a key gene in the response of ECs to WSS and could be involved in AS.

Mussel adhesive protein fused with VE-cadherin extracellular domain promotes endothelial-cell tight junctions and in vivo endothelization recovery of vascular stent.

Improving the surface properties of vascular stents to accelerate endothelialization in vivo could play an important role in minimizing the risk of late thrombosis. We previously showed that mussel adhesive protein fused with VE-cadherin extracellular domain (VE-M) specifically triggered endothelial cell adhesion in vitro. In this study, using stent implants coated with VE-M, we evaluated the clinical applicability of VE-M in endothelialization recovery in vivo. First, we explored the effect of VE-M on hemocompatibility and tight junctions between endothelial cells (ECs) in vitro. VE-M significantly inhibited platelet adhesion and promoted EC proliferation. Furthermore, VE-M drastically increased the centralization of F-actin in human umbilical vein endothelial cells (HUVECs) along the cell contacts, reduced fluorescein isothiocyanate (FITC)-dextran transport across the HUVECs, and elevated expression levels of tight junction proteins (TJPs) in ECs. We then evaluated the effect of VE-M on endothelialization recovery in vivo through implantation of vascular stents. At 1 day after implantation, stents coated with VE-M recruited more endothelial progenitor cells (EPCs) than bare stents. At 7 days after implantation, VE-M stents had a greater coverage of ECs than bare stents. At 1 month after implantation, ECs on VE-M stents were appropriately elliptical in morphology and closely resembled physiological morphology. Hematoxylin-eosin (HE) staining revealed little in-stent neointima formation on VE-M stents, and SEM images revealed that smooth endothelium had formed on VE-M stents without adherent platelets. Taken together, these findings indicate that VE-M accelerates in vivo endothelialization of vascular stents via recruitment of EPCs and promotes endothelium formation and could be explored as a potential bioactive coating for vascular implant. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:94-103, 2020.

Adsorption of 4-n-Nonylphenol, Carvacrol, and Ethanol onto Iron Oxide from Nonaqueous Hydrocarbon Solvents.

The adsorption of 4-n-nonylphenol (4NP), carvacrol, and ethanol onto the surface of iron oxide from nonaqueous solutions is presented. It is found that adsorption of 4NP from alkanes is strong and proceeds to monolayer formation, where the molecules are essentially "upright". However, at high relative concentrations, ethanol successfully out-competes 4NP for the iron oxide surface. Estimates of the enthalpy and entropy of binding of 4NP were found to be exothermic and entropically disfavored. Sum frequency generation vibrational spectroscopy data indicate some evidence of binding through a phenolate anion, despite the nonpolar, nonaqueous solvent. Carvacrol is also found to adsorb as a monolayer where the molecules are lying "flat". The adsorption of ethanol onto iron oxide from dodecane was investigated through the use of quantitative NMR, which is a convenient analytical technique for measuring adsorption isotherms. It was concluded that ethanol does not form adsorbed monolayers on the surface. Instead, it partitions onto the surface as a surface-enhanced local phase separation related to its poor solubility in alkane solvents.

Atherosclerosis Treatment with Stimuli-Responsive Nanoagents: Recent Advances and Future Perspectives.

Atherosclerosis is the root of approximately one-third of global mortalities. Nanotechnology exhibits splendid prospects to combat atherosclerosis at the molecular level by engineering smart nanoagents with versatile functionalizations. Significant advances in nanoengineering enable nanoagents to autonomously navigate in the bloodstream, escape from biological barriers, and assemble with their nanocohort at the targeted lesion. The assembly of nanoagents with endogenous and exogenous stimuli breaks down their shells, facilitates intracellular delivery, releases their cargo to kill the corrupt cells, and gives imaging reports. All these improvements pave the way toward personalized medicine for atherosclerosis. This review systematically summarizes the recent advances in stimuli-responsive nanoagents for atherosclerosis management and its progress in clinical trials.

Anomalously Large Spectral Shifts near the Quantum Tunnelling Limit in Plasmonic Rulers with Subatomic Resolution.

The resonance wavelength of a coupled plasmonic system is extremely sensitive to the distance between its metallic surfaces, resulting in "plasmon rulers". We explore this behavior in the subnanometer regime using self-assembled monolayers of bis-phthalocyanine molecules in a nanoparticle-on-mirror (NPoM) construct. These allow unprecedented subangstrom control over spacer thickness via choice of metal center, in a gap-size regime at the quantum-mechanical limit of plasmonic enhancement. A dramatic shift in the coupled plasmon resonance is observed as the gap size is varied from 0.39 to 0.41 nm. Existing theoretical models are unable to account for the observed spectral tuning, which requires inclusion of the quantum-classical interface, emphasizing the need for new treatments of light at the subnanoscale.

Overview of Crosstalk Between Multiple Factor of Transcytosis in Blood Brain Barrier.

Blood brain barrier (BBB) conserves unique regulatory system to maintain barrier tightness while allowing adequate transport between neurovascular units. This mechanism possess a challenge for drug delivery, while abnormality may result in pathogenesis. Communication between vascular and neural system is mediated through paracellular and transcellular (transcytosis) pathway. Transcytosis itself showed dependency with various components, focusing on caveolae-mediated. Among several factors, intense communication between endothelial cells, pericytes, and astrocytes is the key for a normal development. Regulatory signaling pathway such as VEGF, Notch, S1P, PDGFß, Ang/Tie, and TGF-ß showed interaction with the transcytosis steps. Recent discoveries showed exploration of various factors which has been proven to interact with one of the process of transcytosis, either endocytosis, endosomal rearrangement, or exocytosis. As well as providing a hypothetical regulatory pathway between each factors, specifically miRNA, mechanical stress, various cytokines, physicochemical, basement membrane and junctions remodeling, and crosstalk between developmental regulatory pathways. Finally, various hypotheses and probable crosstalk between each factors will be expressed, to point out relevant research application (Drug therapy design and BBB-on-a-chip) and unexplored terrain.

Electron transport behavior of quinoidal heteroacene-based junctions: effective electron-transport pathways and quantum interference.

The electron transport behavior through a series of molecular junctions composed of tetracene (TC) and S/O substituted-TC (S/O-TC) has been studied using density functional theory (DFT) combined with the non-equilibrium Green's function (NEGF) method. The unique transport behavior has been interpreted using correlated quantum interference and electron transport pathway models. In the TC system, two dominant electron transfer channels exist as demonstrated by a detailed transmission pathway analysis. In the substituted S/O-TC systems, the electron transport behavior is regulated through either constructive or destructive quantum interference due to the existence of additional p-electrons, leading to a significant diversity of current-voltage curves. Compared to the TC molecule in the bias region from 0 to 1.0 V, an α-connected molecular junction exhibits a greater current, whereas a ß-connected molecular junction shows a smaller current. The substitution with O and S atoms shows a minor effect on the conductance of the molecular junctions. In order to clarify the role of heteroatoms, a series of artificial models designed by removing specific sulfur and carbon atoms in α-S-TC have been investigated in detail. The results have demonstrated that only the S heteroatom on one side of the molecule contributes to the junction conductivity through constructive quantum interference. It has also been observed that current exchange occurs between the two electron transfer channels.

Recent advancements in the use of exosomes as drug delivery systems.

Extracellular vesicles (EVs) are the substances that are released by most types of cells and have an important role in cell to cell communication. Among the most highly researched EVs are exosome. Recent studies show that exosomes derived from cells have different roles and targets. Many studies show that exosome can efficiently deliver many different kinds of cargo to the target cell. Therefore, they are often used to deliver therapeutic cargo for treatment. The exosomes that have been used include both natural ones and those that have been modified with other substances to increase the delivery ability. This article provides a review of both exosomes derived from various cells and modified exosome and their ability in delivering the many kinds of cargo to the target cell.

Periodic ripples on thermally-annealed graphene on Cu (110)-reconstruction or moiré pattern?

We have used ultrahigh vacuum scanning tunneling microscopy (STM) to investigate the effect of thermal annealing of graphene grown by chemical vapor deposition on a Cu(110) foil. We show that the annealing appears to induce a reconstruction of the Cu surface along the [210] direction, with a period of 1.43 nm. Such reconstructions have been ascribed to the tensile strain induced in the Cu surface by its differential thermal expansion relative to the graphene over-layer, but we show that it is in fact a moiré pattern due to interference between the graphene and the underlying atomic lattice as evidenced by the appearance of an odd-even transition only observed due to misorientation of the top layer of a layered crystal. This highlights that the analysis of STM measurements of graphene on metal surfaces should take such interference effects into account and that the graphene-Cu interface is more complex than previously thought.

Endogenous pH-responsive nanoparticles with programmable size changes for targeted tumor therapy and imaging applications.

Nanotechnology-based antitumor drug delivery systems, known as nanocarriers, have demonstrated their efficacy in recent years. Typically, the size of the nanocarriers is around 100 nm. It is imperative to achieve an optimum size of these nanocarriers which must be designed uniquely for each type of delivery process. For pH-responsive nanocarriers with programmable size, changes in pH (~6.5 for tumor tissue, ~5.5 for endosomes, and ~5.0 for lysosomes) may serve as an endogenous stimulus improving the safety and therapeutic efficacy of antitumor drugs. This review focuses on current advanced pH-responsive nanocarriers with programmable size changes for anticancer drug delivery. In particular, pH-responsive mechanisms for nanocarrier retention at tumor sites, size reduction for penetrating into tumor parenchyma, escaping from endo/lysosomes, and swelling or disassembly for drug release will be highlighted. Additional trends and challenges of employing these nanocarriers in future clinical applications are also addressed.

Effect of Surface Treatments on the Nanomechanical Properties of Human Hair.

The structural properties of hair are largely determined by the state of the surface. Advanced imaging modes of atomic force microscopy, where the surface mechanics can be correlated with surface topography, have been used to spatially map variations in hair surfaces following chemical and mechanical treatments. Through analysis of multilayered data obtained in this way, we show that the processes of bleaching and combing of hair not only alter the surface roughness, but also alter the mechanical stiffness, adhesion properties, and surface potential of hair, in terms of the mean values and their distributions. These treatments are shown to have a significant effect on the nanoscale surface properties, consistent with what has previously been observed at the macroscopic fiber-level scale.