Neutrophils activated during acute lung injury (ALI) form neutrophil extracellular traps (NETs) to capture pathogens. However, excessive NETs can cause severe inflammatory reactions. Macrophages are ...classified as M1 macrophages with proinflammatory effects or M2 macrophages with anti-inflammatory effects. During ALI, alveolar macrophages (AMs) polarize to the M1 phenotype. This study tested the hypothesis that NETs may aggravate ALI or acute respiratory distress syndrome (ARDS) inflammation by promoting alveolar macrophage polarization to the M1 type. Our research was carried out in three aspects: clinical research, animal experiments and in vitro experiments. We determined that NET levels in ARDS patients were positively correlated with M1-like macrophage polarization. NET formation was detected in murine ALI tissue and associated with increased M1 markers and decreased M2 markers in BALF and lung tissue. Treatment with NET inhibitors significantly inhibitor NETs generation, downregulated M1 markers and upregulated M2 markers. Regardless of LPS pre-stimulation, significant secretion of proinflammatory cytokines and upregulated M1 markers were detected from bone marrow-derived macrophages (M0 and M2) cocultured with high concentrations of NETs; conversely, M2 markers were downregulated. In conclusion, NETs promote ARDS inflammation during the acute phase by promoting macrophage polarization to the M1 phenotype. We propose that NETs play an important role in the interaction between neutrophils and macrophages during the early acute phase of ALI.
Current mainstream cancer treatment methods have their limitations. New approaches are thus desired to assist our battle against cancer. Herein, multifunctional ultrasmall FeS2 nanodots with the size ...of 7 nm are synthesized by biomineralization and used for imaging-guided combined tumor therapy. Bovine serum albumin (BSA), which acts as the reaction template to induce the mineralization of FeS2 nanomaterials under alkaline conditions, could also be used as a drug delivery system for coupling photosensitive molecule such as Chlorin e6 (Ce6). Taking advantage of the near-infrared (NIR) absorbance and the high r 2 relaxivity of the synthesized ultrasmall FeS2 nanodots, as well as the Ce6 fluorescence, in vivo trimodal imaging of optical/magnetic resonance/photoacoustics was carried out, showing efficient tumor accumulation of FeS2@BSA-Ce6 after intravenous injection. In vitro and in vivo photothermal and photodynamic therapy were then conducted for synergistic tumor therapy and did not cause any apparent toxicity to the treated animals. Our work thus provides a new kind of ultrasmall FeS2 multifunctional nanodot modified by albumin via a simple method, promising for combination phototherapy as well as cancer theranostics.
Echinacoside (ECH), a natural phenylethanoid glycoside, was first isolated from
DC. (Compositae) sixty years ago. It was found to possess numerous pharmacologically beneficial activities for human ...health, especially the neuroprotective and cardiovascular effects. Although ECH showed promising potential for treatment of Parkinson's and Alzheimer's diseases, some important issues arose. These included the identification of active metabolites as having poor bioavailability in prototype form, the definite molecular signal pathways or targets of ECH with the above effects, and limited reliable clinical trials. Thus, it remains unresolved as to whether scientific research can reasonably make use of this natural compound. A systematic summary and knowledge of future prospects are necessary to facilitate further studies for this natural product. The present review generalizes and analyzes the current knowledge on ECH, including its broad distribution, different preparation technologies, poor pharmacokinetics and kinds of therapeutic uses, and the future perspectives of its potential application.
Graphene networks (GNs) with ultralow density of 5.6–8.6 mg/cm3 were prepared with polyurethane/graphene (PUG) composite foams as templates and ethanol flame as a mild carbonizing condition. After ...the pyrolysis of the PU matrix in dozens of seconds, the structural integrity of the foams was well preserved by the embedded graphene sheets at a sufficient content (≥12 wt%), forming interconnected GNs with pore size in nano- and micron-scale. When encapsulated with epoxy resin, the CNs composites showed excellent electrical conductivity of 340–830 S/m at the filler content of 2.5–4.2 wt% and exceptional electromagnetic interference (EMI) shielding effectiveness (SE) of 30–61 dB in sample thickness of 0.9–1.5 mm. The excellent EMI shielding property of GN composites, as well as the mild, high-efficient flame-carbonizing process, make our self-templating method very promising in the facile fabrication of high-performance EMI shielding materials.
Graphene networks (GNs) with exceptional electromagnetic interference shielding performance were fabricated by flame-carbonizing polyurethane/graphene (PUG) composite foams for dozens of seconds. Display omitted
Mesoporous silica nanoparticles （MSNs） have attracted tremendous attention in recent years as drug delivery carriers due to their large surface areas, tunable sizes, facile modification and ...considerable biocompatibility. In this work, we fabricate an interesting type of MSNs which are intrinsically doped with photosensitizing molecules, chlorin e6 （Ce6）. By increasing the amount of Ce6 doped inside the silica matrix, it is found that the morphology of MSNs changes from spheres to rod-like shapes. The obtained Ce6-doped mesoporous silica nanorods （CMSNRs） are not only able to produce singlet oxygen for photodynamic therapy, but can also serve as a drug delivery platform with high drug loading capacity by utilizing their mesoporous structure. Compared to spherical nano- particles, it is found that CMSNRs with a larger aspect ratio show much faster uptake by cancer cells. With doxorubicin （DOX） employed as a model drug, the combined photodynamic and chemotherapy is carried out, achieving synergistic anti-tumor effects both in vitro and in vivo. Our study presents a new design of an MSN-based drug delivery platform, which intrinsically is fluorescent and able to serve as a photodynamic agent, promising for future imaging-guided combination therapy of cancer.
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•Pathogenesis and characteristics of idiopathic pulmonary fibrosis (IPF) are presented.•The history and current situation of traditional Chinese medicine (TCM) in treating lung ...diseases are introduced.•Therapeutic mechanisms of different TCM to treat IPF are summarized.•Advantages and types of pulmonary drug delivery systems (PDDS) are emphasized.•Combining TCM with PDDS is a potential strategy to treat IPF.
Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary interstitial inflammatory disease of unknown etiology, and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Nintedanib and pirfenidone are the only two known drugs which are conditionally recommended for the treatment of IPF by the FDA. However, these drugs pose some adverse side effects such as nausea and diarrhoea during clinical applications. Therefore, it is of great value and significance to identify effective and safe therapeutic drugs to solve the clinical problems associated with intake of western medicine. As a unique medical treatment, Traditional Chinese Medicine (TCM) has gradually exerted its advantages in the treatment of IPF worldwide through a multi-level and multi-target approach. Further, to overcome the current clinical problems of oral and injectable intakes of TCM, pulmonary drug delivery system (PDDS) could be designed to reduce the systemic metabolism and adverse reactions of the drug and to improve the bioavailability of drugs. Through PubMed, Google Scholar, Web of Science, and CNKI, we retrieved articles published in related fields in recent years, and this paper has summarized twenty-seven Chinese compound prescriptions, ten single TCM, and ten active ingredients for effective prevention and treatment of IPF. We also introduce three kinds of inhaling PDDS, which supports further research of TCM combined with PDDS to treat IPF.
•Titania-decorated graphene-based sensor was fabricated by layer-by-layer (LbL) self-assembly route.•Sensing properties of titania/graphene composite toward SO2 gas were investigated.•The sensor ...exhibited ppb-level detection, good reversibility, selectivity and repeatability for SO2 gas sensing.
This paper demonstrates layer-by-layer (LbL) self-assembled titania (TiO2)/graphene film device towards ultralow sulfur dioxide (SO2) gas sensing at room temperature. The as-prepared film was realized through the layer-by-layer alternative deposition of TiO2 nanospheres and graphene oxide (GO) to form a nanostructure, and followed by thermally reducing GO into reduced graphene oxide (rGO). The nanostructural, morphological and compositional properties of TiO2/rGO sample was examined by SEM, TEM, XRD, EDS and Raman spectroscopy. The gas-sensing properties of TiO2/rGO hybrid were investigated at room temperature against low concentration SO2 gas. The sensor in our work exhibited ppb-level detection, rapid response and recovery, good reversibility, selectivity and repeatability for SO2 gas sensing. The possible sensing mechanism for the presented sensor was attributed to the synergistic effect of TiO2 and rGO, as well as special interaction at TiO2/rGO interfaces. This work shows that the fabricated TiO2/rGO film sensor possesses potential applications for SO2 detection with advantages of cost-effective, low power consumption and distinguished sensing abilities.
La–Mg–Ni-based hydrogen storage alloys are a promising candidate for the negative electrode materials of nickel metal hydride batteries. However, their fast capacity degradation hinders them from ...more extensive application. In this study, the electrochemical performance and capacity degradation mechanism of single-phase La2MgNi9, La3MgNi14 and La4MgNi19 alloys are studied from the perspective of their constituent subunits. It is found that the rate capability and cycling stability of the alloy electrodes increase with higher LaNi5/LaMgNi4 subunit ratio, while the discharge capacity shows a reverse trend. Degradation study shows that the inter-molecular strains in the alloys are the main reason that leads to the fast capacity degradation of La–Mg–Ni-based alloys. The strains are caused by the difference in the expansion/contraction properties between LaNi5 and LaMgNi4 subunits during charge/discharge which is mainly observed in the H-dissolved solid solution instead of hydride. It is also found that the strains can be relieved by adjusting LaNi5/LaMgNi4 subunit ratio of the alloys, thus achieving less pulverization and oxidation, and better cycling stability. We expect our findings can inspire new thoughts on improving the electrochemical performance of La–Mg–Ni-based alloys by tuning their superlattice structures.
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•Single-phase AB3-, A2B7- and A5B19-type La–Mg–Ni-based alloys are obtained.•Relationship between subunit structure and electrochemical properties is studied.•Behavior of LaNi5 and LaMgNi4 subunits during charge/discharge is observed.•Mismatch between LaNi5 and LaMgNi4 is a basic cause for capacity degradation.
Not all breast cancer (BC) patients who receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR), but the reasons for this are unknown. Previous studies have shown that exosomes ...produced in the tumor microenvironment in response to chemotherapy promote a chemotherapy-resistant phenotype in tumors. However, the role of BC chemotherapy-elicited exosomes in regulating chemoresistance is poorly understood.
Using commercial kits, serum exosomes were extracted from patients before neoadjuvant chemotherapy, after one cycle of chemotherapy and after four cycles of chemotherapy consisting of doxorubicin (DOX) and paclitaxel (PTX). Their miRNAs were sequenced, and the correlation between the sequencing results and chemotherapy effects was further verified by RT-qPCR using patient serum exosomes. Cell Counting Kit-8 (CCK-8) was used to detect chemosensitivity. Stemness was assessed by CD44+/CD24- population analysis and mammosphere formation assays. Chromatin immunoprecipitation (ChIP) experiments were performed to verify the binding of signal transducer and activator of transcription 3 (STAT3) to the promoter of miRNAs.
Here, we provide clinical evidence that chemotherapy-elicited exosomal miR-378a-3p and miR-378d are closely related to the chemotherapy response and that exosomes produced by BC cells after stimulation with DOX or PTX deliver miR-378a-3p and miR-378d to neighboring cells to activate WNT and NOTCH stemness pathways and induce drug resistance by targeting Dickkopf 3 (DKK3) and NUMB. In addition, STAT3, which is enhanced by zeste homolog 2 (EZH2), bound to the promoter regions of miR-378a-3p and miR-378d, thereby increasing their expression in exosomes. More importantly, chemotherapeutic agents combined with the EZH2 inhibitor tazemetostat reversed chemotherapy-elicited exosome-induced drug resistance in a nude mouse tumor xenograft model.
This study revealed a novel mechanism of acquired chemoresistance whereby chemotherapy activates the EZH2/STAT3 axis in BC cells, which then secrete chemotherapy-elicited exosomes enriched in miR-378a-3p and miR-378d. These exosomes are absorbed by chemotherapy-surviving BC cells, leading to activation of the WNT and NOTCH stem cell pathways via the targeting of DKK3 and NUMB and subsequently resulting in drug resistance. Therefore, blocking this adaptive mechanism during chemotherapy may reduce the development of chemotherapy resistance and maximize the therapeutic effect.
Many studies have attempted to estimate forest aboveground biomass (AGB) from satellite data accurately. Temporal information may be beneficial to AGB estimation but remains underexplored. Thus, this ...paper aims to investigate whether and how temporal features extracted from multiple satellite-derived data products can improve prediction accuracy. To this end, we develop four methods to exploit the temporal features of moderate resolution imaging spectroradiometer (MODIS) data products: the method that uses all annual features (AAF), the method that selects essential features based on the Spearman correlation coefficient (SCC) criterion, the method that employs the seasonal average and principal component analysis (PCA) components (SAP), and the method that includes phenological characteristic parameters (PCP) as the predictors of forest AGB. Lidar-derived forest AGB in California serves as the reference AGB data, and the XGBoost ensemble algorithm is utilized to model forest AGB with temporal features of MODIS data products. The results demonstrate that the AAF-based features lead to the most accurate AGB prediction, whereas using information extracted by SAP and PCP gives rise to less accurate results. Annual MODIS surface reflectance data combined with forest canopy height can provide the AGB estimates, with an average R-squared (R
2
) of 0.58 and root-mean-squared error (RMSE) of 147.58 Mg/ha. The results of this study highlight the necessity of utilizing annual time-series data, particularly the annual surface reflectance data, for AGB prediction.
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