High‐security nanoplatform with enhanced therapy compliance is extremely promising for tumor. Herein, using a simple and high‐efficient self‐assembly method, a novel active‐targeting nanocluster ...probe, namely, Ag2S/chlorin e6 (Ce6)/DOX@DSPE‐mPEG2000‐folate (ACD‐FA) is synthesized. Experiments indicate that ACD‐FA is capable of specifically labeling tumor and guiding targeting ablation of the tumor via precise positioning from fluorescence and photoacoustic imaging. Importantly, the probe is endowed with a photodynamic “on‐off” effect, that is, Ag2S could effectively quench the fluorescence of chlorin e6 (89.5%) and inhibit release of 1O2 (92.7%), which is conducive to avoid unwanted phototoxicity during transhipment in the body, and only after nanocluster endocytosed by tumor cells could release Ce6 to produce 1O2. Moreover, ACD‐FA also achieves excellent acid‐responsive drug release, and exhibits eminent chemo‐photothermal and photodynamic effects upon laser irradiation. Compared with single or two treatment combining modalities, ACD‐FA could provide the best cancer therapeutic effect with a relatively low dose, because it made the most of combined effect from chemo‐photothermal and controlled photodynamic therapy, and significantly improves the drug compliance. Besides, the active‐targeting nanocluster notably reduces nonspecific toxicity of both doxorubicin and chlorin e6. Together, this study demonstrates the potency of a newly designed nanocluster for nonradioactive concomitant therapy with precise tumor‐targeting capability.
A multifunctional nanoprobe Ag2S/Ce6/DOX@DSPE‐mPEG2000‐folate can specifically label tumor via precise positioning from fluorescence and photoacoustic imaging, which guide targeting ablation of tumor combined effect of chemo‐photothermal and controlled photodynamic therapy. In the process, the probe minimizes the administration dose as much as possible while achieving effective therapeutic effect, reducing nonspecific toxicity, and improving drug compliance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Non-invasive sonodynamic therapy (SDT) was developed because of its advantages of high penetration depth and low side effects; however, tumor hypoxia greatly restricts its therapeutic effect. In this ...study, we aimed to develop ideal O2 self-supplementing nanoparticles for imaging-guided enhanced sonodynamic therapy of tumors with the adept coalescence of biology with nanotechnology. Methods: Based on the natural enzyme system of red blood cells (RBC), biomimetic nanoparticles (QD@P)Rs were fabricated by encapsulating Ag2S quantum dots (QD) in RBC vesicle membranes. The anti-tumor drug PEITC was employed to increase the intracellular H2O2 concentration in tumor cells. Results: In vitro and in vivo experiments demonstrated excellent biocompatibility and prolonged blood circulation of (QD@P)Rs. Following oral administration of PEITC in mice to improve the H2O2 concentration, the enzyme in the nanoprobe catalyzed endogenous H2O2 to increase O2 content and effectively alleviate tumor hypoxia. Triggered by ultrasound under the guidance of fluorescence imaging, (QD@P)Rs generated reactive oxygen species (ROS) to induce tumor cell death, and the increased content of O2 significantly enhanced the effect of SDT. Conclusion: Ag2S QDs were used, for the first time, as a sonosensitizer in the SDT field. In this study, we integrated the advantages of the natural enzyme system and SDT to develop a novel approach for effective non-invasive treatment of cancer.
For doubly fed induction generator (DFIG)-based wind energy conversion systems (WECSs), large electromotive force will be induced in the rotor circuit during grid faults. Without proper protection ...scheme, the rotor side of DFIG will suffer from overcurrents, which may even destroy the rotor-side converter (RSC). To mitigate this problem, a new flux-linkage-tracking-based low-voltage ride-through (LVRT) control strategy is proposed to suppress the short-circuit rotor current. Under the proposed control strategy, the rotor flux linkage is controlled to track a reduced fraction of the changing stator flux linkage by switching the control algorithm of RSC during grid faults. To validate the proposed control strategy, a case study of a typical 1.5-MW DFIG-based WECS is carried out by simulation using the full-order model in SIMULINK/SimPowerSystems. In the case study, a comparison with a typical LVRT method based on RSC control is given, and the effect of the control parameter on the control performance is also investigated. Finally, the validity of the proposed method is further verified by means of laboratory experiments with a scaled-size DFIG system.
Intestinal-type gastric cancer is preceded by premalignant lesions, including chronic atrophic gastritis and intestinal metaplasia. In this study, we constructed a single-cell atlas for 32,332 ...high-quality cells from gastric antral mucosa biopsies of patients spanning a cascade of gastric premalignant lesions and early gastric cancer (EGC) using single-cell RNA sequencing. We then constructed a single-cell network underlying cellular and molecular characteristics of gastric epithelial cells across different lesions. We found that gland mucous cells tended to acquire an intestinal-like stem cell phenotype during metaplasia, and we identified OR51E1 as a marker for unique endocrine cells in the early-malignant lesion. We also found that HES6 might mark the pre-goblet cell cluster, potentially aiding identification of metaplasia at the early stage. Finally, we identified a panel of EGC-specific signatures, with clinical implications for the precise diagnosis of EGC. Our study offers unparalleled insights into the human gastric cellulome in premalignant and early-malignant lesions.
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•We construct a single-cell network of premalignant lesions and early gastric cancer•We examine transcriptional dynamics of various cell types across lesions•We characterize the early stage of goblet cells during intestinal metaplasia•We identify biomarkers of gastric early-malignant cells
Zhang et al. conduct a single-cell transcriptomic study on gastric antral biopsies from patients across premalignant lesions and early gastric cancer. They construct the single-cell network for epithelial cells across lesions and dissect the molecular characteristics for representative cell types in each lesion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide because of metastasis. Epithelial‐mesenchymal transition (EMT) is widely considered to be crucial to the invasion‐metastasis ...cascade during cancer progression. Actin‐like 6A (ACTL6A) is initially verified important for cell proliferation, differentiation, and migration. In this study, we find that ACTL6A plays an essential role in metastasis and EMT of HCC. ACTL6A expression is up‐regulated in HCC cells and tissues. A high level of ACTL6A in HCCs is correlated with aggressive clinicopathological features and is an independent poor prognostic factor for overall and disease‐free survival of HCC patients. Ectopic expression of ACTL6A markedly promotes HCC cells migration, invasion, as well as EMT in vitro and promotes tumor growth and metastasis in the mouse xenograft model. Opposite results are observed when ACTL6A is knocked down. Mechanistically, ACTL6A promotes metastasis and EMT through activating Notch signaling. ACTL6A knockdown has the equal blockage effect as the Notch signaling inhibitor, N‐N‐(3,5‐difluorophenacetyl)‐L‐alanyl‐S‐phenylglycine t‐butylester, in HCC cells. Further studies indicate that ACTL6A might manipulate SRY (sex determining region Y)‐box 2 (SOX2) expression and then activate Notch1 signaling. Conclusions: ACTL6A promotes metastasis and EMT by SOX2/Notch1 signaling, indicating a prognostic biomarker candidate and a potential therapeutic target for HCC. (Hepatology 2016;63:1256–1271)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Microbial biochemicals have been indicated as the primary stimulators of innate immunity, the first line of the body's defence against infections. However, the influence of topological features on a ...microbe's surface on immune responses remains largely unknown. Here we demonstrate the ability of TiO
microparticles decorated with nanospikes (spiky particles) to activate and amplify the immune response in vitro and in vivo. The nanospikes exert mechanical stress on the cells, which results in potassium efflux and inflammasome activation in macrophages and dendritic cells during phagocytosis. The spiky particles augment antigen-specific humoral and cellular immune responses in the presence of monophosphoryl lipid A and elicit protective immunity against tumour growth and influenza viral infection. The study offers insights into how surface physical cues can tune the activation of innate immunity and provides a basis for engineering particles with increased immunogenicity and adjuvanticity.
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IJS, NUK, SBMB, UL, UM, UPUK
Cancer stem cells promote tumorigenesis and progression of hepatocellular carcinoma (HCC). Recently, emerging evidence indicates tumor‐associated macrophages (TAMs) play an important role in tumor ...progression. However, TAMs often occurs with unknown mechanisms. As an important mediator in intercellular communications, exosomes secreted by host cells mediate the exchange of genetic materials and proteins, which involves tumor aggressiveness. The aim of the study was to investigate whether exosomes derived from TAMs mediate stem cell properties in HCC. TAMs were isolated from the tissues of HCC. microRNA (miRNA) expression profiles of TAMs were analyzed using miRNA microarray. In vitro cell coculture was further conducted to investigate the crosstalk between TAMs and tumor cells mediated by TAMs exosomes. In this study, we showed that TAMs exosomes promote HCC cell proliferation and stem cell properties. Using miRNA profiles assay, we identified significantly lower levels of miR‐125a and miR‐125b in exosomes and cell lysate isolated from TAMs. Functional studies revealed that the HCC cells were treated with TAM exosomes or transfected with miR‐125a/b suppressed cell proliferation and stem cell properties by targeting CD90, a stem cell marker of HCC stem cells. The study indicated that miR‐125a/b targeting CD90 played important roles in cancer stem cells of HCC.
The study demonstrated that the in vitro coculture of tumor‐associated macrophages ‐derived exosomes with low levels of miR‐125a and miR‐125b promoted hepatocellular carcinoma (HCC) cell proliferation, sphere cell formation and metastasis by downregulating CD90, a stem cell marker of HCC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Tree-shaped fins were introduced to improve the heat transfer of metal hydride reactor. A two-dimensional steady-state model was first applied to obtain the optimal geometric structures of ...tree-shaped fins using genetic algorithm with the constraint of fixed fin mass. Then, the hydrogen absorption performance of MH reactors with embedded radial fins and tree-shaped fins were numerically studied and compared using a multi-physical model. It was indicated that the hydrogen absorption time for 90% saturation for the reactor with optimized tree-shaped fins nearly decreases by 20.7% as compared with that for radial fins. The heat transfer and absorption performance of MH reactor were much sensitive to the length ratio of tree-shaped fins, which can be improved with increasing the length ratio. Besides, the performance of optimized tree-shaped fins reactor with variable angle ratio was only slightly better than that for fixing angle ratio at 1, indicating that the angle ratio of tree-shaped fins can be kept at 1 for simplifying the design. Moreover, the absorption performance of the reactor can be enhanced with increasing the maximum branch level of tree-shaped fins. Furthermore, it was shown that the optimized geometric structures of tree-shaped fins under different MHs thermal conductivities are nearly identical.
•Tree-shaped fins are introduced to improve the heat transfer of MH reactor.•Genetic algorithm is used to optimize the geometric structures of tree-shaped fins.•Optimized tree-shaped fins can decrease 20.7% of absorption time than radial fins.•The angle ratio of tree-shaped fins can be kept at 1 to simplify the design.•Increasing maximum branch level can enhance the absorption process.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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