Interleukin-17A Promotes Airway Remodeling in Chronic Obstructive Pulmonary Disease by Activating C-X-C Motif Chemokine Ligand 12 Secreted by Lung Fibroblasts.

Background: The interactions between fibroblasts and bronchial epithelial cells play important roles in the development of chronic obstructive pulmonary disease (COPD). Interleukin (IL)-17A triggers the activation of fibroblasts and the secretion of inflammatory mediators, which promotes epithelial-mesenchymal transition (EMT) in bronchial epithelial cells. Fibroblasts secrete C-X-C motif chemokine ligand 12 (CXCL12), which specifically binds to its receptor, C-X-C motif chemokine receptor 4 (CXCR4) to mediate inflammatory responses. This study aims to investigate IL-17A- and CXCL12-induced airway remodeling. Methods: Primary lung fibroblasts were isolated from human and murine lung tissue for the in vitro experiments, and a mouse model of cigarette smoke (CS)-induced COPD was established for the in vivo experiments. The results were analyzed using a one-way analysis of variance and Tukey's test or Bonferroni's test for the post-hoc test. A p-value < 0.05 was considered statistically significant. Results: Through in vitro experiments, we found that IL-17A-activated primary lung fibroblasts secreted CXCL12 and stimulated EMT in bronchial epithelial cells. However, these effects could be blocked by neutralizing IL-17A or CXCL12. In vivo, an anti-IL-17A antibody or a CXCR4 antagonist could reverse the degree of EMT in the lungs of the COPD mouse model. The IL-17A-induced EMT and increased CXCL12 expression occurred via extracellular signal-regulated kinase (ERK)/phosphorylated-ERK pathways. Conclusion: This study showed that exposure of mice to CS and IL-17A stimulation upregulated CXCL12 expression and induced EMT by activating the ERK signaling pathway. These data offer a novel perspective regarding the molecular mechanism of CXCL12/CXCR4 signaling in IL-17A-induced EMT related to airway remodeling.

Characterization of the structural and molecular interactions of Ferulic acid ethyl ester with human serum albumin and Lysozyme through multi-methods.

Ferulic acid ethyl ester (FAEE) is an essential raw material for the formulation of drugs for cardiovascular and cerebrovascular diseases and leukopenia. It is also used as a fixed aroma agent for food production due to its high pharmacological activity. In this study, the interaction of FAEE with Human serum albumin (HSA) and Lysozyme (LZM) was characterized by multi-spectrum and molecular dynamics simulations at four different temperatures. Additionally, the quenching mechanism of FAEE-HSA and FAEE-LZM were explored. Meanwhile, the binding constants, binding sites, thermodynamic parameters, molecular dynamics, molecular docking binding energy, and the influence of metal ions in the system were evaluated. The results of Synchronous fluorescence spectroscopy, UV-vis spectroscopy, CD, three-dimensional fluorescence spectrum, and resonance light scattering showed that the microenvironment of HSA and LZM and the protein conformation changed in the presence of FAEE. Furthermore, the effects of some common metal ions on the binding constants of FAEE-HSA and FAEE-LZM were investigated. Overall, the experimental results provide a theoretical basis for promoting the application of FAEE in the cosmetics, food, and pharmaceutical industries and significant guidance for food safety, drug design, and development.

Multifunctional photon conversion materials for enhancing silicon solar cells.

A type of multifunctional erbium (Er3+) and ytterbium (Yb3+) codoped NaY(WO4)2 phosphors, with simultaneous photon upconversion, photon quantum cutting, and luminescence ratiometric temperature sensing abilities, have been developed, opening up new possibilities for high-performance silicon solar cells.

All-Inorganic Perovskite Solar Cells: Defect Regulation and Emerging Applications in Extreme Environments.

All-inorganic perovskite solar cells (PSCs), such as CsPbX3, have garnered considerable attention recently, as they exhibit superior thermodynamic and optoelectronic stabilities compared to the organic-inorganic hybrid PSCs. However, the power conversion efficiency (PCE) of CsPbX3 PSCs is generally lower than that of organic-inorganic hybrid PSCs, as they contain higher defect densities at the interface and within the perovskite light-absorbing layers, resulting in higher non-radiative recombination and voltage loss. Consequently, defect regulation has been adopted as an important strategy to improve device performance and stability. This review aims to comprehensively summarize recent progresses on the defect regulation in CsPbX3 PSCs, as well as their cutting-edge applications in extreme scenarios. The underlying fundamental mechanisms leading to the defect formation in the crystal structure of CsPbX3 PSCs are firstly discussed, and an overview of literature-adopted defect regulation strategies in the context of interface, internal, and surface engineering is provided. Cutting-edge applications of CsPbX3 PSCs in extreme environments such as outer space and underwater situations are highlighted. Finally, a summary and outlook are presented on future directions for achieving higher efficiencies and superior stability in CsPbX3 PSCs.

Molecular near-infrared triplet-triplet annihilation upconversion with eigen oxygen immunity.

Molecular triplet-triplet annihilation upconversion often experiences drastic luminescence quenching in the presence of oxygen molecules, posing a significant constraint on practical use in aerated conditions. We present an oxygen-immune near-infrared triplet-triplet annihilation upconversion system utilizing non-organometallic cyanine sensitizers (λex = 808 nm) and chemically synthesized benzo[4,5]thieno[2,3-b][1,2,5]thiadiazolo[3,4-g]quinoxaline dyes with a defined dimer structure as annihilators (λem = 650 nm). This system exhibits ultrastable upconversion under continuous laser irradiance (>480 mins) or extended storage (>7 days) in aerated solutions. Mechanistic investigations reveal rapid triplet-triplet energy transfer from sensitizer to annihilators, accompanied by remarkably low triplet oxygen quenching efficiencies ( η O 2 < 13% for the sensitizer, <3.7% for the annihilator), endowing the bicomponent triplet-triplet annihilation system with inherent oxygen immunity. Our findings unlock the direct and potent utilization of triplet-triplet annihilation upconversion systems in real-world applications, demonstrated by the extended and sensitive nanosensing of peroxynitrite radicals in the liver under in vivo nitrosative stress.

SEM Electron-Beam-Induced Ultrathin Carbon Deposition Layer on Cu Substrate: Improved Dry Oxidation Protection Performance than CVD Single Layer Graphene.

An amorphous carbon deposition layer (CDL) with nanoscale thickness induced by scanning electron microscope (SEM) electron beam is studied as a carbon-based protective layer on copper (Cu). CDL is prepared by inducing the deposition of pollutants or hydrocarbons in the cavity of SEM through electron beam irradiation (EBI). Wrinkles and cracks will not form and the interfacial spacing of CDL/Cu is smaller than Graphene/Cu (Gr/Cu). The thickness and coverage of the interfacial oxide layer of CDL/Cu are all smaller than that of the Gr/Cu after the same oxidation conditions. Characterization of Raman mapping also demonstrates that CDL shows better oxidation inhibition effects than graphene. The structure of CDL is determined to be C = C and C = O, CH3- and C-O can be loaded vertically on CDL. Density functional theory (DFT) is employed for demonstrating the smaller interfacial gap of CDL/Cu, less wrinkles and cracks and larger adsorbing energy of water/oxygen compared with Gr/Cu. Molecular dynamic (MD) simulation also indicates that the diffusion of water or oxygen into CDL/Cu is more difficult and the oxidation of Cu covered by CDL is well suppressed. This work provides a new approach for the study of carbon-based antioxidant materials on Cu.

Ultrasensitive NIR-II Ratiometric Nanothermometers for 3D In Vivo Thermal Imaging.

Luminescent nanothermometry, particularly the one based on ratiometric, has sparked intense research for non-invasive in vivo or intracellular temperature mapping, empowering their uses as diagnosis tools in biomedicine. However, ratiometric detection still suffers from biased sensing induced by wavelength-dependent tissue absorption and scattering, low thermal sensitivity (Sr ), and lack of imaging depth information. Herein, this work constructs an ultrasensitive NIR-II ratiometric nanothermometer with self-calibrating ability for 3D in vivo thermographic imaging, in which temperature-insensitive lanthanide nanocrystals and strongly temperature-quenched Ag2 S quantum dots are co-assembled to form a hybrid nanocomposite material. Precise control over the amount ratio between two sub-materials enables the manipulation of heat-activated back energy transfer from Ag2 S to Yb3+ in lanthanide nanoparticles, thereby rendering Sr up to 7.8% °C-1 at 43.5 °C, and higher than 6.5% °C-1 over the entire physiological temperature range. Moreover, the luminescence intensity ratio between two separated spectral regions within the narrow Yb3+ emission peak is used to determine the depth information of nanothermometers in living mice and correct the effect of tissue depth on 2D thermographic imaging, and therefore allows a proof-of-concept demonstration of accurate 3D in vivo thermographic imaging, constituting a solid step toward the development of advanced ratiometric nanothermometry for biological applications.

Polyoxometalate-Organic Hybrid "Calixarenes" as Supramolecular Hosts.

Calixarenes are among the most useful and versatile macrocycles in supramolecular chemistry. The one thing that has not changed in the 80 years since their discovery, despite numerous derivatizations, is their fully organic, covalent scaffolds. Here, we report a new type of organic-inorganic hybrid "calixarenes" constructed by means of coordination-driven assembly. Replacing acetate ligands on the {SiW10 Cr2 (OAc)2 } clusters with 5-hydroxyisophthalates allows these 95° inorganic building blocks to be linked into bowl-shaped, hybrid "calix[n]arenes" (n=3, 4). With a large concave cavity, the metal-organic calix[4]arene can accommodate nanometer-sized polyoxoanions in an entropically driven process. The development of hybrid variants of calixarenes is expected to expand the scope of their physicochemical properties, guest/substrate binding, and applications on multiple fronts.

Triplet-Induced Singlet Oxygen Photobleaches Near-Infrared Dye-Sensitized Upconversion Nanosystems.

The rapid photobleaching of near-infrared (NIR) dye-sensitized upconversion nanosystems is one of the crucial problems that has blocked their technological applications. Uncovering the photophysical and photochemical pathways of NIR dyes would help to elucidate the photobleaching mechanism and thereby improve the photostability of the system. Here we investigate the triplet dynamics of NIR dyes and their interaction with triplet oxygen in the typically investigated IR806-sensitized upconversion nanoparticle (UCNP) nanosystem. Low-temperature fluorescence at 77 K provides direct proof of the generation of singlet oxygen (1O2) under 808 nm laser irradiation. Mass spectrometry indicates that all three double bonds in the structure of IR806 can be broken in the photochemical process. Coupling IR806 to the surface of UCNPs can accelerate its triplet dynamics, thus producing more 1O2 to photocleave IR806. Importantly, we find that the addition of ß-carotene can scavenge the generated 1O2, thereby providing a simple method to effectively inhibit photobleaching.

Wafer-Level Highly Dense Metallic Nanopillar-Enabled High-Performance SERS Substrates for Molecular Detection.

Seeking sensitive, large-scale, and low-cost substrates is highly important for practical applications of surface-enhanced Raman scattering (SERS) technology. Noble metallic plasmonic nanostructures with dense hot spots are considered an effective construction to enable sensitive, uniform, and stable SERS performance and thus have attracted wide attention in recent years. In this work, we reported a simple fabrication method to achieve wafer-scale ultradense tilted and staggered plasmonic metallic nanopillars filled with numerous nanogaps (hot spots). By adjusting the etching time of the PMMA (polymethyl methacrylate) layer, the optimal SERS substrate with the densest metallic nanopillars was obtained, which possessed a detection limit down to 10-13 M by using crystal violet as the detected molecules and exhibited excellent reproducibility and long-term stability. Furthermore, the proposed fabrication approach was further used to prepare flexible substrates; for example, a SERS flexible substrate was proven to be an ideal platform for analyzing low-concentration pesticide residues on curved fruit surfaces with significantly enhanced sensitivity. This type of SERS substrate possesses potential in real-life applications as low-cost and high-performance sensors.

Different expression profiles of circulating miR-31 and miR-181a in CD4+ T cells and plasma of patients with oral lichen planus.

Oral lichen planus (OLP) is a T cell-mediated inflammatory-immune disease in which CD4+ T cells may be significantly involved in the dysregulated immune response. MicroRNAs (miRNAs) critically control gene expression post-transcriptionally and regulate the immune response and inflammation. Here, we explored the expression profiles of circulating miRs (miR-19b, miR-31, and miR-181a), which can modulate CD4+ T cell activation, differentiation, and immune function. Quantitative real-time PCR showed that miR-31 and miR-181a dramatically decreased in peripheral CD4+ T cells, whereas they markedly increased in the plasma of OLP patients, especially in the erosive form. However, no significant differences were observed in the expression of miR-19b in CD4+ T cells and plasma between OLP patients and healthy controls or between different forms of OLP. Moreover, miR-31 expression positively correlated with the miR-181a expression in the CD4+ T cells and plasma of OLP patients. Furthermore, receiver operating characteristic (ROC) curve analyses indicated that miR-31 and miR-181a, rather than miR-19b, in CD4+ T cells and plasma could discriminate OLP, especially erosive OLP, from healthy controls. In conclusion, there were different expression profiles of circulating miR-31 and miR-181a in CD4+ T cells and plasma of patients with OLP, which could synergistically serve as potential biomarkers for OLP.

Deep Face Video Inpainting via UV Mapping.

This paper addresses the problem of face video inpainting. Existing video inpainting methods target primarily at natural scenes with repetitive patterns. They do not make use of any prior knowledge of the face to help retrieve correspondences for the corrupted face. They therefore only achieve sub-optimal results, particularly for faces under large pose and expression variations where face components appear very differently across frames. In this paper, we propose a two-stage deep learning method for face video inpainting. We employ 3DMM as our 3D face prior to transform a face between the image space and the UV (texture) space. In Stage I, we perform face inpainting in the UV space. This helps to largely remove the influence of face poses and expressions and makes the learning task much easier with well aligned face features. We introduce a frame-wise attention module to fully exploit correspondences in neighboring frames to assist the inpainting task. In Stage II, we transform the inpainted face regions back to the image space and perform face video refinement that inpaints any background regions not covered in Stage I and also refines the inpainted face regions. Extensive experiments have been carried out which show our method can significantly outperform methods based merely on 2D information, especially for faces under large pose and expression variations. Project page: https://ywq.github.io/FVIP.

Ex vivo near-infrared targeted imaging of human bladder carcinoma by ICG-anti-CD47.

Objective: The low detection rate of early-stage and small tumors remains a clinical challenge. A solution to this unmet need is urgently warranted for the accurate diagnosis and treatment of bladder cancer (BC). This study aimed to evaluate the feasibility of CD47 as a target for optical molecular imaging of human BC and conduct preliminary ex vivo imaging experiments. Method: Using indocyanine green (ICG) and a CD47 antibody (anti-CD47), we synthesized a new targeted fluorescent probe ICG-anti-CD47. A total of 25 patients undergoing radical cystectomy were prospectively included in ex vivo imaging experiments. Following surgery, the freshly isolated bladder specimens were incubated with ICG-anti-CD47, and images were captured under white light and near-infrared (NIR) light. Standard histopathologic evaluation was performed, and findings were correlated with those of CD47-targeted NIR molecular imaging. Results: Based on the ex vivo imaging experiments, 23 and 2 patients were pathologically diagnosed with bladder urothelial carcinoma and bladder squamous cell carcinoma, respectively. There were no adverse effects of ICG-anti-CD47 on the histological structure of the tumor and normal uroepithelium. In the NIR grayscale images, the mean fluorescence intensity of the tumor tissue was significantly higher than that of the adjacent normal background tissue, which markedly improved tumor visualization. Conclusion: Anti-CD47-targeted NIR molecular imaging may be a feasible and powerful strategy for the accurate diagnosis of BC. Nevertheless, larger-scale randomized trials are warranted to verify the present findings.

Near-Infrared Photoluminescence from Ytterbium- and Erbium-Codoped CsPbCl3 Perovskite Quantum Dots with Negative Thermal Quenching.

Near-infrared (NIR) luminescent phosphors hold promise for a wide range of applications, from bioimaging to light-emitting diodes (LEDs), but are typically confined to wavelengths <1300 nm and manifest substantial thermal quenching pervasive in luminescent materials. Here we observed the thermally enhanced NIR luminescence of Er3+ (1540 nm), a 2.5-fold enhancement with increasing temperature from 298 to 356 K, from Yb3+- and Er3+-codoped CsPbCl3 perovskite quantum dots (PQDs) (photoexcited at ∼365 nm). Mechanistic investigations revealed that thermally enhanced phenomena originated from combined effects of thermally stable cascade energy transfer (from a photoexcited exciton to a pair of Yb3+ and then to surrounding Er3+) and minimized quenching of surface-adsorbed water molecules on the 4I13/2 state of Er3+ induced by the temperature increase. Importantly, these PQDs enable producing phosphor-converted LEDs emitting at 1540 nm with inherited thermally enhanced properties, having implications for a wide range of photonic applications.

Shell Engineering on Thermal Sensitivity of Lifetime-Based NIR Nanothermometers for Accurate Temperature Measurement in Murine Internal Liver Organ.

Lifetime-based NIR luminescent nanothermometry is ideally suited for temperature detection in living cells and in vivo, but the thermal sensitivity (Sr) modulation remains elusive. Herein, a thorough investigation is performed to unveil the shell effect on lifetime-based Sr by finely controlling the shell thickness of lanthanide-doped core-shell-shell nanoparticles. Owing to the space-dependent energy transfer and back energy transfer between Nd3+ and Yb3+ as well as the energy migration to surface quenchers, both active and inert shells can regulate the thermal-dependent nonradiative decays and NIR luminescence lifetime of Yb3+, which in turn modulates the Sr from 0.56% to 1.54% °C-1. After poly(acrylic acid) modification of the optimal architecture, the tiny nanoprobes possess robust stability to fluctuations in the microenvironment, which enables accurate temperature mapping of inflammation in the internal liver organ of living mouse. This work will provide new insights for optimizing Sr and guidance for precise temperature measurements in vivo.

Specific and Long-Term Luminescent Monitoring of Hydrogen Peroxide in Tumor Metastasis.

Luminescent monitoring of endogenous hydrogen peroxide (H2 O2 ) in tumors is conducive to understanding metastasis and developing novel therapeutics. The clinical transformation is obstructed by the limited light penetration depth, toxicity of nano-probes, and lack of long-term monitoring modes of up to days or months. New monitoring modes are introduced via specific probes and implantable devices, which can achieve real-time monitoring with a readout frequency of 0.01 s or long-term monitoring for months to years. Near-infrared dye-sensitized upconversion nanoparticles (UCNPs) are fabricated as the luminescent probes, and the specificity to reactive oxygen species is subtly regulated by the self-assembled monolayers on the surfaces of UCNPs. Combined with the passive implanted system, a 20-day monitoring of H2 O2 in the rat model of ovarian cancer with peritoneal metastasis is achieved, in which the limited light penetration depth and toxicity of nano-probes are circumvented. The developed monitoring modes show great potential in accelerating the clinical transformation of nano-probes and biochemical detection methods.

Responsive Accumulation of Nanohybrids to Boost NIR-Phototheranostics for Specific Tumor Imaging and Glutathione Depletion-Enhanced Synergistic Therapy.

Dynamic regulation of nanoparticles in a controllable manner has great potential in various areas. Compared to the individual nanoparticles, the assembled nanoparticles exhibit superior properties and functions, which can be applied to achieve desirable performances. Here, a pH-responsive i-motif DNA-mediated strategy to tailor the programmable behaviors of erbium-based rare-earth nanoparticles (ErNPs) decorated copper doped metal-organic framework (CPM) nanohybrids (ECPM) under physiological conditions is reported. Within the acidic tumor microenvironment, the i-motif DNA strands are able to form quadruplex structures, resulting in the assembly of nanohybrids and selective tumor accumulation, which further amplify the ErNPs downconversion emission (1550 nm) signal for imaging. Meanwhile, the ECPM matrix acts as a near-infrared (NIR) photon-activated reactive oxygen species (ROS) amplifier through the singlet oxygen generation of the matrix in combination with its ability of intracellular glutathione depletion upon irradiation. In short, this work displays a classical example of engineering of nanoparticles, which will manifest the importance of developing nanohybrids with structural programmability in biomedical applications.

Vitamin B12 deficiency may play an etiological role in atrophic glossitis and its grading: A clinical case-control study.

BACKGROUND: Existing studies have reported the significant association between atrophic glossitis (AG) and hematinic deficiencies, including iron, folate and vitamin B12 deficiency. However, these findings were inconsistent. AG can be graded as partial or complete atrophy. It is still unclear whether hematinic deficiencies are associated with the grading of AG. METHODS: 236 AG patients and 208 sex- and age-matched healthy controls were enrolled in this study. Hematological tests including complete blood count, and serum levels of folate, ferritin and vitamin B12 were performed. The AG group was divided into those with partial AG and those with complete AG according to the extent of papillary atrophy. Statistical analysis was performed to assess whether hematinic deficiencies are risk factors for AG and its grading. RESULTS: Compared with the healthy controls, AG patients had significantly higher frequencies of vitamin B12 deficiency (68.22%), ferritin deficiency (13.98%) and anemia (21.61%). The differences in hematinic deficiencies and anemia between AG patients and healthy controls changed according to gender and age. The frequencies of serum vitamin B12 deficiency and anemia in the complete AG subgroup were significantly higher than those in the partial AG subgroup. Logistic regression analysis revealed that vitamin B12 deficiency and anemia were significantly correlated with AG and its grading. The AG patients with vitamin B12 deficiency responded well to supplement therapy. CONCLUSION: AG could be an important clinical indicator for potential vitamin B12 deficiency, especially when the degree of tongue atrophy more than 50% and complete atrophy. Vitamin B12 deficiency might play an etiological role in the development of AG.

A bimodal type of AgPd Plasmonic Blackbody Nanozyme with boosted catalytic efficacy and synergized photothermal therapy for efficacious tumor treatment in the second biological window.

Nanozymes are promising for precise cancer treatment, but are typically limited in terms of the low catalytic efficiency and the complexity in tumor microenvironment (TME). Herein, we describe a bimodal type of AgPd plasmonic blackbody (AgPd PB) nanozyme of compact sizes (< 30 nm), which presents not only boosted enzyme efficacy but also efficient photothermal therapy (PTT) for synergized therapy through tissue-penetrating light in the second biological window (1000-1700 nm). The synthesized hyperbranched AgPd PB nanozymes possess intense and broadband localized surface plasmonic resonance absorption of 400-1300 nm, entailing prominent photothermal efficiency (η = 45.1% at 1064 nm) for PTT. Importantly, PTT was found to significantly boost the nanozyme efficacy of both catalase (CAT) and peroxidase (POD) processes, which correspondingly decompose H2O2 to into O2 to relieve tumor hypoxia, and activate H2O2 to generate oxidative •OH radical. While the generated •OH was found to be able to minimize heat shock proteins (HSPs), which plays a vital role to counterbalance PTT effect both in vitro and in vivo. As compared to control ground without treatment, the synergized nanozyme and PTT activities resulted in about 7-fold reduction of tumor volume, thus elevating the survival rate from 0 to 80% at 30 days posttreatment. Besides the synergistic therapy, the AgPd PB nanozyme were shown to own fluorescence, computed tomography (CT), and photoacoustic (PA) imaging abilities, thus having implications for uses in imaging-guided precise cancer therapy. This study provides a paradigm of TME responsive theranostics under NIR-II light irradiation.