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Doxorubicin (DOX) is an effective anti-tumor drug accompanied with many side effects, especially heart injury. To explore what effects of sophocarpine (SOP) on DOX-induced heart injury, this study conducted in vivo experiment and in vitro experiment, and the C57BL/6J mice and the H9C2 cells were used. The experimental methods used included echocardiography, enzyme-linked immunosorbent assay (ELISA), dihydroethidium (DHE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, western blotting and so on. Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements of left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), while SOP reduced these indices. The relevant stainings showed that SOP reversed the increases of total superoxide level induced by DOX. DOX also contribute to a higher level of MDA and lower levels of SOD and GSH, but these changes were suppressed by SOP. DOX increased the pro-oxidative protein level of NOX-4 while decreased the anti-oxidative protein level of SOD-2, but SOP reversed these effects. In addition, this study further discovered that SOP inhibited the decreases of Nrf2 and HO-1 levels induced by DOX. The TUNEL staining revealed that SOP reduced the high degree of apoptosis induced by DOX. Besides, pro-apoptosis proteins like Bax, cleaved-caspase-3 and cytochrome-c upregulated while anti-apoptosis protein like Bcl-2 downregulated when challenged by DOX, but them were suppressed by SOP. These findings suggested that SOP could alleviate DOX-induced heart injury by suppressing oxidative stress and apoptosis, with molecular mechanism activating of the Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Despite the remarkable success of immunotherapy in many types of cancer, pancreatic ductal adenocarcinoma has yet to benefit. Innate immune cells are critical to anti-tumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Here we demonstrate that yeast-derived particulate β-glucan, an inducer of trained immunity, traffics to the pancreas, which causes a CCR2-dependent influx of monocytes/macrophages to the pancreas that display features of trained immunity. These cells can be activated upon exposure to tumor cells and tumor-derived factors, and show enhanced cytotoxicity against pancreatic tumor cells. In orthotopic models of pancreatic ductal adenocarcinoma, β-glucan treated mice show significantly reduced tumor burden and prolonged survival, which is further enhanced when combined with immunotherapy. These findings characterize the dynamic mechanisms and localization of peripheral trained immunity and identify an application of trained immunity to cancer. The advent of immunotherapy has revolutionised cancer therapeutics, but its application in the context of pancreatic ductal adenocarcinoma has been limited. Here authors explore the effect of innate trained responses to fungal β-glucan and assess its effect in a murine model of pancreatic ductal adenocarcinoma where they observe reduced tumour burden and enhanced survival. [ABSTRACT FROM AUTHOR]

Glutinous rice flour (GRF) was prepared using three milling process (wet milling, low temperature impact milling (dry milling), and roller milling (dry milling)) to investigate their effects on the physicochemical properties of glutinous rice flour and sweet dumplings prepared with that flour. Results revealed that a method of grinding used in the milling process had a significant (P < 0.05) effect on the properties of GRF and the resulting sweet dumplings. Dry milling (low temperature impact milling and roller milling) resulted in higher damaged starch content and coarser particle size than wet milling. Dry-milled flour exhibited a significantly lower hunter whiter value, apparent viscosity, pasting temperature, enthalpy value, and degree of crystalline compared to the wet-milling method. Dry milling significantly decreased the smoothness of the surface, whiteness value, transmittance of soup, resilience of dumplings, as well as increased the cracking rate and water loss during the fast-freeze. The obtained results could be used as reference for improving sweet dumpling made from dry-milled GRF. [ABSTRACT FROM AUTHOR]

Silicon has been raised as an appealing anode candidate for high-energy lithium-ion batteries. However, the inevitable capacity fade, resulting from the dramatic volume changes over (de)alloying reactions, limits its practical application. Herein, we proposed a conductive polymer of PSSA@PANI as water-soluble binder component for silicon anode in lithium-ion batteries. By PVA hybridization, the as-fabricated nano-Si electrodes using these composite binders exhibit superior reversibility and cycling stability for lithium storage. The improved performance can be attributed to the unique interaction between Si surface and hydrophilic binder, as well as the conductive PSSA@PANI skeleton, which can buffer the Si volume expansion during the lithiation process and facilitate the charge transfer. These results demonstrate an easy and efficient approach to design water-soluble binders for high-performance Si electrodes. [ABSTRACT FROM AUTHOR]

Abstract: The industry faces a trend of fabricating a product with high-variety and short life cycles since the change of consumer behaviors. The quality control becomes critical. In milling process, surface roughness is key quality characteristic measured by an off-line method. The off-line measurement is time consuming. Therefore, online surface roughness monitoring systems, which can eliminate the measurement time and enhance the productivity, have gained popularity for machining. However, to accurately construct the system, a large amount of data and time for off-line training and modeling are required, which make the system not suitable for a high-variety job shop production. It is necessary to develop a method without large data and off-line training and modeling. Therefore, a Grey online modeling surface roughness monitoring (GOMSRM) system is proposed in this study by utilizing the Grey theory GM(1, N) with bilateral best-fit method, which requires less data and no training time to perform the online modeling surface roughness monitoring system. The ability of an online modeling makes the system flexible to monitor different types of products. The model could be built during each changeover process of the milling, which can significantly eliminate the time of training in advance used by other off-line modeling methods. The results show the GOMSRM system can accurately predict the surface roughness. The comparison between the GOMSRM system and the system developed by a neural network shows the GOMSRM system has better accuracy and fewer samples for modeling.Graphical Abstract: [ABSTRACT FROM AUTHOR]

We developed a new scheme to suppress the electric-field-screening effect in high growth density of a carbon nanotube (CNT) film during its intense pulsed emission. We synthesize the CNT film on a tridimensional surface (t-CNT film). The tridimensional surface includes wet etched silicon pyramids, and the Ni layer is electroless plated thereon. The intense pulsed emission characteristics of the t-CNT and planar-grown CNT (p-CNT) films were measured using a diode structure in single-pulse mode. The even turn-on field decreased from 5.5 V/μm for p-CNTs to 2.8 V/μm for t-CNTs, and the peak emission current increased from 232 A for p-CNTs to 324 A for t-CNTs at a peak field intensity ∼12.2 V/μm. The peak current of the t-CNT film increased by ∼39.7% over the p-CNT film. It is clear that the micro-pyramid array can effectively suppress the field screening effect to improve the electron-emission of CNT films. [ABSTRACT FROM AUTHOR]

Carbon nanotube (CNT) films were grown on silicon wafers with and without a nickel layer (Si-CNT and Ni-CNT) via the pyrolysis of iron phthalocyanine. The nickel layer was prepared using the electroless plating method. To study the emission stability of Si-CNT and Ni-CNT cathodes during intense pulsed emission, emission characteristics were measured repeatedly with a diode structure using a Marx generator as a voltage source. For the peak values of the pulsed voltage, which were in the range between 1.62-1.66 MV (corresponding to electric field intensities between 11.57-11.85 V/μm), the first cycle emission current was 109.4 A for Si-CNT and 180.5 A for Ni-CNT. By comparing the normalized emission currents of the Si-CNT and Ni-CNT cathodes, the improvement in the emission stability can be easily quantified. The number of emission cycles necessary for the peak current to decay from 100% to 50% increased from ∼3 for Si-CNT to ∼11 for a Ni-CNT film. [ABSTRACT FROM AUTHOR]

The initial layer phenomena for a class of singular perturbed nonlinear system with slow variables are studied. By introducing stretchy variables with different quantity levels and constructing the correction term of initial layer with different “thickness”, the N-order approximate expansion of perturbed solution concerning small parameter is obtained, and the “multiple layer” phenomena of perturbed solutions are revealed. Using the fixed point theorem, the existence of perturbed solution is proved, and the uniformly valid asymptotic expansion of the solutions is given as well. [ABSTRACT FROM AUTHOR]

Theoretical equations for computing sensitivity coefficients of wellbore pressures to estimate the reservoir parameters in low-permeability reservoirs conditioning to non-Darcy flow data at low velocity were obtained. It is shown by a lot of numerical calculations that the wellbore pressures are much more sensitive to permeability very near the well than to permeability a few gridblocks away from the well. When an initial pressure gradient existent sensitivity coefficients in the region are closer to the active well than to the observation well. Sensitivity coefficients of observation well at the line between the active well and the observation well are influenced greatly by the initial pressure gradient. [ABSTRACT FROM AUTHOR]

A major problem associated with adenovirus gene therapy is the T cell-mediated immune response, which is elicited by inoculation of the adenovirus vector and leads to rapid clearance of the virus and loss of transgene expression. In this study, the immune response to adenovirus was prevented by induction of specific T-cell tolerance by pretreatment with adenovirus-infected antigen-presenting cells (APC) that express Fas ligand. Compared with control-treated mice, the tolerized mice showed prolonged expression of lacZ upon administration of AdCMVlacZ 1 week after tolerance induction. In contrast to the control mice, the tolerized mice did not display proliferation of CD[SUP3+] T cells in the spleen in response to AdCMVlacZ. Tolerance induction also was indicated by the lower production of interferon-γ and inter-leukin-2 by peripheral T cells isolated from AdCMVlacZ-challenged tolerized mice than by AdCMVlacZ-challenged control-treated mice. The T-cell tolerance was specific for the adenovirus as the T-cell responses to irrelative murine cytomegalovirus remained unimpaired. Our results indicate that adenovirus-specific T-cell tolerance can be induced by APCs that coexpress Fas ligand and adenovirus antigens. We propose that this new strategy can be used to induce tolerance to adenovirus vector gene therapy with resultant prolonged expression of the transgene. [ABSTRACT FROM AUTHOR]

A chimeric Adenovirus-Simian Virus 40 (AdSV40) containing the large T antigen was used to transform rheumatoid synovial fibroblasts. A rheumatoid synovial fibroblast cell line was established by infection of primary rheumatoid arthritis (RA) synovial fibroblasts at Passage 10 with AdSV40 recombinants followed by selection in semisoft agarose cultures. The transformed cells grew anchor independent, exhibited continuous proliferation (>65 passages) in monolayer culture, and formed multiple visible foci. The transformed synovial fibroblasts showed expression of the simian virus 40 large T antigen in the nucleus as determined by immunofluorescence staining. In addition, indirect immunofluorescence staining demonstrated that the transformed cells stained specifically with a fibroblast-specific antibody 1B10. Studies involving expression of metalloproteinases showed that collagenase and stromelysin were induced by phorbol 12-myristate 13-acetate (PMA), and such an induction was repressed by dexamethasone typical of primary RA fibroblasts. Levels of mRNAs for IL-1β, TNF-α, and c- jun were increased by PMA, and the mRNA transcripts of these genes were also repressed by addition of dexamethasone to the culture media. Our results indicate that transformed RA synovial fibroblasts display a similar gene expression pattern in response to PMA and dexamethasone as observed for untransformed primary RA synovial fibroblasts. These transformed rheumatoid arthritis synovial fibroblast cells provide an ideal cell culture model in which to test the efficacy of novel arthritis gene therapy reagents. [ABSTRACT FROM AUTHOR]

The importance of gut microbiota in human health and pathophysiology is undisputable. Despite the abundance of metagenomics data, the functional dynamics of gut microbiota in human health and disease remain elusive. Urolithin A (UroA), a major microbial metabolite derived from polyphenolics of berries and pomegranate fruits displays anti-inflammatory, anti-oxidative, and anti-ageing activities. Here, we show that UroA and its potent synthetic analogue (UAS03) significantly enhance gut barrier function and inhibit unwarranted inflammation. We demonstrate that UroA and UAS03 exert their barrier functions through activation of aryl hydrocarbon receptor (AhR)- nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent pathways to upregulate epithelial tight junction proteins. Importantly, treatment with these compounds attenuated colitis in pre-clinical models by remedying barrier dysfunction in addition to anti-inflammatory activities. Cumulatively, the results highlight how microbial metabolites provide two-pronged beneficial activities at gut epithelium by enhancing barrier functions and reducing inflammation to protect from colonic diseases. Urolithins are microbial metabolites derived from food polyphenols. Here, Singh et al. show that urolithin A and a synthetic analogue enhance gut barrier function via Nrf2-dependent pathways and mitigate inflammation and colitis in mice, highlighting a potential application for inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

Exosomes have shown increasing potential as delivery vesicles for therapy, but challenges like cost/yield, drug payload, and targeting specificity still exist. Plant derived exosome-like nanoparticles have been reported as a promising substitution and exhibit biocompatibility through oral, intranasal administration; however, systemic delivery of siRNA by exosome-like nanoparticles directly isolated from plants has not been reported. Recently, we reported the control of RNA orientation to decorate human derived exosome with cell targeting ligands for specific delivery of siRNA to tumors. Here, we expand to the application of arrowtail RNA nanoparticles for displaying ligands on ginger derived exosome-like nanovesicles (GDENs) for siRNA delivery and tumor inhibition through IV administration. Cushion ultracentrifugation coupled with equilibrium density gradient ultracentrifugation were used for purifying GDENs that displayed size, density, and morphology similar to human derived exosomes. Folic acid (FA), as a ligand, was displayed on the surface of GDENs for targeted delivery of survivin siRNA to KB cancer models. In vitro gene knockdown efficacy by FA-3WJ/GDENs/siRNA complex was comparable to transfection. We observed inhibition of tumor growth on a xenograft model by intravenous administration, which reveals the potential of GDENs as an economic delivery system for siRNA. [ABSTRACT FROM AUTHOR]

Although the use of nanotechnology for the delivery of a wide range of medical treatments has potential to reduce adverse effects associated with drug therapy, tissue-specific delivery remains challenging. Here we show that nanoparticles made of grapefruit-derived lipids, which we call grapefruit-derived nanovectors, can deliver chemotherapeutic agents, short interfering RNA, DNA expression vectors and proteins to different types of cells. We demonstrate the in vivo targeting specificity of grapefruit-derived nanovectors by co-delivering therapeutic agents with folic acid, which in turn leads to significantly increasing targeting efficiency to cells expressing folate receptors. The therapeutic potential of grapefruit-derived nanovectors was further demonstrated by enhancing the chemotherapeutic inhibition of tumour growth in two tumour animal models. Grapefruit-derived nanovectors are less toxic than nanoparticles made of synthetic lipids and, when injected intravenously into pregnant mice, do not pass the placental barrier, suggesting that they may be a useful tool for drug delivery. [ABSTRACT FROM AUTHOR]