Exosomes are implicated in cancer cell development, migration and invasion. Pigment epithelium-derived factor (PEDF) is a secreted anticancer protein that can regulate lung cancer progression; ...however, the role of PEDF in non-small cell lung cancer (NSCLC), including metastasis and cancer cell-derived exosome secretion, is unclear. In this study, we analyzed the effects of PEDF on exosome-mediated migration, invasion, and tumorigenicity of cultured NSCLC cells. The results showed that PEDF overexpression significantly reduced NSCLC invasion and migration, while inducing cell aggregation, whereas PEDF knockdown had the opposite effects. Exosomes from NSCLC cells treated with recombinant PEDF had a significantly reduced ability to promote cancer cell motility, migration, and invasion compared to exosomes from untreated cells. Exosomes from PEDF-treated cells contained thrombospondin 1 (THBS1), which inhibited cytoskeletal remodeling and exosome-induced lung cancer cell motility, migration, and invasion. Furthermore, PEDF-overexpressing NSCLC cells formed smaller xenograft tumors with higher THBS1 expression compared to control tumors. Our findings indicate that PEDF decreases the metastatic potential of NSCLC cells through regulation of THBS1 release in cancer cell-derived exosomes, thus uncovering a new mechanism of lung cancer progression.
•PEDF induces aggregation and reduces invasion and migration of lung cancer cells.•Exosomes from PEDF-treated cancer cells inhibit metastatic behavior of NSCLC cells.•PEDF-expressing NSCLC cells have reduced tumorigenicity in vivo.•PEDF increases thrombospondin 1 content in lung cancer cell-derived exosomes.•Thrombospondin 1 inhibits exosome-induced lung cancer cell migration and invasion.
Oxygen evolution reaction (OER) is a pivotal reaction in many technologies for renewable energy, such as water splitting, metal–air batteries, and regenerative fuel cells. However, this reaction is ...known to be kinetically sluggish and proceeds at rather high overpotential due to the universal scaling relationship, namely, the adsorption energies of intermediates are linearly correlated and cannot be optimized simultaneously. Several approaches have been proposed to break the scaling relationship by introducing additional active sites; however, positive experimental results are still absent. Herein, a different solution is suggested on the basis of dynamic tridimensional adsorption of the OER intermediates at NiO/NiFe layered double hydroxide intersection, by which the adsorption energy of each intermediate can be adjusted independently, so as to bypass the scaling relationship and achieve high catalytic performance. Experimentally, the OER overpotential is reduced to ≈205 mV at current density of 30 mA cm−2, which represents the best performance achieved by state‐of‐the‐art OER catalysts.
The oxygen evolution reaction (OER), a key reaction for energy conversion and storage, is kinetically sluggish due to the limits of the scaling relationship. A strategy to bypass the scaling relationship through dynamic tridimensional adsorption of OER intermediates is reported, and OER overpotential is reduced to 205 mV at current density of 30 mA cm−2.
Hepatocellular carcinoma (HCC) is the third leading cause of the cancer‐related death in the world. Human amniotic mesenchymal stem cells (hAMSCs) have been characterized with a pluripotency, low ...immunogenicity and no tumorigenicity. Especially, the immunosuppressive and anti‐inflammatory effects of hAMSCs make them suitable for treating HCC. Here, we reported that hAMSCs administrated by intravenous injection significantly inhibited HCC through suppressing cell proliferation and inducing cell apoptosis in tumour‐bearing mice with Hepg2 cells. Cell tracking experiments with GFP‐labelled hAMSCs showed that the stem cells possessed the ability of migrating to the tumorigenic sites for suppressing tumour growth. Importantly, both hAMSCs and the conditional media (hAMSC‐CM) have the similar antitumour effects in vitro, suggesting that hAMSCs‐derived cytokines might be involved in their antitumour effects. Antibody array assay showed that hAMSCs highly expressed dickkopf‐3 (DKK‐3), dickkopf‐1 (DKK‐1) and insulin‐like growth factor‐binding protein 3 (IGFBP‐3). Furthermore, the antitumour effects of hAMSCs were further confirmed by applications of the antibodies or the specific siRNAs of DKK‐3, DKK‐1 and IGFBP‐3 in vitro. Mechanically, hAMSCs‐derived DKK‐3, DKK‐1 and IGFBP‐3 markedly inhibited cell proliferation and promoted apoptosis of Hepg2 cells through suppressing the Wnt/β‐catenin signalling pathway and IGF‐1R‐mediated PI3K/AKT signalling pathway, respectively. Taken together, our study demonstrated that hAMSCs possess significant antitumour effects in vivo and in vitro and might provide a novel strategy for HCC treatment clinically.
For many regenerative electrochemical energy‐conversion systems, hybrid electrocatalysts comprising transition metal (TM) oxides and heteroatom‐doped (e.g., nitrogen‐doped) carbonaceous materials are ...promising bifunctional oxygen reduction reaction/oxygen evolution reaction electrocatalysts, whose enhanced electrocatalytic activities are attributed to the synergistic effect originated from the TM–N–C active sites. However, it is still ambiguous which configuration of nitrogen dopants, either pyridinic or pyrrolic N, when bonded to the TM in oxides, predominately contributes to the synergistic effect. Herein, an innovative strategy based on laser irradiation is described to controllably tune the relative concentrations of pyridinic and pyrrolic nitrogen dopants in the hybrid catalyst, i.e., NiCo2O4 NPs/N‐doped mesoporous graphene. Comparative studies reveal the dominant role of pyridinic‐NCo bonding, instead of pyrrolic‐N bonding, in synergistically promoting reversible oxygen electrocatalysis. Moreover, density functional theory calculations provide deep insights into the corresponding synergistic mechanism. The optimized hybrid, NiCo/NLG‐270, manifests outstanding reversible oxygen electrocatalytic activities, leading to an overpotential different ΔE among the lowest value for highly efficient bifunctional catalysts. In a practical reversible Zn–air battery, NiCo/NLG‐270 exhibits superior charge/discharge performance and long‐term durability compared to the noble metal electrocatalysts.
An innovative strategy based on laser irradiation is developed to selectively regulate relative contents of pyridinic and pyrrolic nitrogen in NiCo2O4/N‐graphene hybrids. Strong chemical bonding forms between nitrogen and cobalt, and pyridinic‐NCo bonds, instead of pyrrolic‐NCo bonds, are identified to predominantly contribute to synergistic catalysis, leading to substantially enhanced oxygen electrocatalytic activities, outperforming a combination of benchmark noble metal catalysts.
A novel four-dimensional Einstein-Gauss-Bonnet gravity was formulated by Glavan and Lin (Phys. Rev. Lett. 124:081301, 2020), which is intended to bypass the Lovelock’s theorem and to yield a ...non-trivial contribution to the four-dimensional gravitational dynamics. However, the validity and consistency of this theory has been called into question recently. We study a static and spherically symmetric black hole charged by a Born–Infeld electric field in the novel four-dimensional Einstein–Gauss–Bonnet gravity. It is found that the black hole solution still suffers the singularity problem, since particles incident from infinity can reach the singularity. It is also demonstrated that the Born-Infeld charged black hole may be superior to the Maxwell charged black hole to be a charged extension of the Schwarzschild-AdS-like black hole in this new gravitational theory. Some basic thermodynamics of the black hole solution is also analyzed. Besides, we regain the black hole solution in the regularized four-dimensional Einstein–Gauss–Bonnet gravity proposed by Lü and Pang (
arXiv:2003.11552
).
Apical lesions, the general term for chronic infectious diseases, are very common dental diseases in modern life, and are caused by various factors. The current prevailing endodontic treatment makes ...use of X-ray photography taken from patients where the lesion area is marked manually, which is therefore time consuming. Additionally, for some images the significant details might not be recognizable due to the different shooting angles or doses. To make the diagnosis process shorter and efficient, repetitive tasks should be performed automatically to allow the dentists to focus more on the technical and medical diagnosis, such as treatment, tooth cleaning, or medical communication. To realize the automatic diagnosis, this article proposes and establishes a lesion area analysis model based on convolutional neural networks (CNN). For establishing a standardized database for clinical application, the Institutional Review Board (IRB) with application number 202002030B0 has been approved with the database established by dentists who provided the practical clinical data. In this study, the image data is preprocessed by a Gaussian high-pass filter. Then, an iterative thresholding is applied to slice the X-ray image into several individual tooth sample images. The collection of individual tooth images that comprises the image database are used as input into the CNN migration learning model for training. Seventy percent (70%) of the image database is used for training and validating the model while the remaining 30% is used for testing and estimating the accuracy of the model. The practical diagnosis accuracy of the proposed CNN model is 92.5%. The proposed model successfully facilitated the automatic diagnosis of the apical lesion.
Proteomic profiling of extracellular vesicles (EVs) represents a promising approach for early detection and therapeutic monitoring of diseases such as cancer. The focus of this study was to apply ...robust EV isolation and subsequent data-independent acquisition mass spectrometry (DIA-MS) for urinary EV proteomics of prostate cancer and prostate inflammation patients. Urinary EVs were isolated by functionalized magnetic beads through chemical affinity on an automatic station, and EV proteins were analyzed by integrating three library-base analyses (Direct-DIA, GPF-DIA, and Fractionated DDA-base DIA) to improve the coverage and quantitation. We assessed the levels of urinary EV-associated proteins based on 40 samples consisting of 20 cases and 20 controls, where 18 EV proteins were identified to be differentiated in prostate cancer outcome, of which three (i.e., SERPINA3, LRG1, and SCGB3A1) were shown to be consistently upregulated. We also observed 6 out of the 18 (33%) EV proteins that had been developed as drug targets, while some of them showed protein-protein interactions. Moreover, the potential mechanistic pathways of 18 significantly different EV proteins were enriched in metabolic, immune, and inflammatory activities. These results showed consistency in an independent cohort with 20 participants. Using a random forest algorithm for classification assessment, including the identified EV proteins, we found that SERPINA3, LRG1, or SCGB3A1 add predictable value in addition to age, prostate size, body mass index (BMI), and prostate-specific antigen (PSA). In summary, the current study demonstrates a translational workflow to identify EV proteins as molecular markers to improve the clinical diagnosis of prostate cancer.
Cu‐based metal–organic frameworks have attracted much attention for electrocatalytic CO2 reduction, but they are generally instable and difficult to control the product selectivity. We report ...flexible Cu(I) triazolate frameworks as efficient, stable, and tunable electrocatalysts for CO2 reduction to C2H4/CH4. By changing the size of ligand side groups, the C2H4/CH4 selectivity ratio can be gradually tuned and inversed from 11.8 : 1 to 1 : 2.6, giving C2H4, CH4, and hydrocarbon selectivities up to 51 %, 56 %, and 77 %, respectively. After long‐term electrocatalysis, they can retain the structures/morphologies without formation of Cu‐based inorganic species. Computational simulations showed that the coordination geometry of Cu(I) changed from triangular to tetrahedral to bind the reaction intermediates, and two adjacent Cu(I) cooperated for C−C coupling to form C2H4. Importantly, the ligand side groups controlled the catalyst flexibility by the steric hindrance mechanism, and the C2H4 pathway is more sensitive than the CH4 one.
Flexible Cu(I) triazolate frameworks functionalized with dinuclear copper sites can serve as highly stable and efficient electrocatalysts for CO2 reduction to C2H4/CH4, and the selectivity is tunable by the size of uncoordinated ligand side groups.
The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS‐CoV) calls for the development of novel vaccine technology that offers ...safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus‐like fashion. STING agonists are first encapsulated into capsid‐like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH‐responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen‐specific T cell responses in mice immunized with a MERS‐CoV nanoparticle vaccine candidate. Using a MERS‐CoV‐permissive transgenic mouse model, it is shown that mice immunized with this nanoparticle‐based MERS‐CoV vaccine are protected against a lethal challenge of MERS‐CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.
To improve vaccination efforts against Middle East respiratory syndrome coronavirus (MERS‐CoV), a virus‐mimicking vaccine is herein prepared with a capsid‐like hollow polymeric nanoparticle loaded with STING agonists and coated in MERS‐CoV antigens. The viromimetic nanoparticle facilitates safe and effective vaccination against the lethal virus and offers a versatile platform for combatting emerging infectious threats.
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