is a traditional Chinese herbal medicine that is widely used to regulate immunity, and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. However, the ...application of CPhGs is negatively affected by their poor absorption and low oral utilization. Targeted drug delivery is an important development direction for pharmaceutics. Previous studies have indicated that CPhGs could block the conduction of the signaling pathways in TGF-β1/smad and inhibit the activation of hepatic stellate cells (HSCs). The aim of this study was to evaluate the anti-hepatic fibrosis effect of CPhG liposomes by inhibiting HSC activation, promoting apoptosis, blocking the cell cycle, suppressing the conduction of signaling pathways in focal adhesion kinase(FAK)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), and determining their in vitro hepatoprotective activity. In vitro release studies demonstrated that CPhG liposomes have a sustained release effect compared to drug CPhGs. HSC proliferation was inhibited after treatment with the CPhG liposomes (29.45, 14.72, 7.36 µg/mL), with IC
values of 42.54 µg/mL in the MTT assay. Different concentrations of the CPhG liposomes could inhibit HSC proliferation, promote apoptosis, and block the cell cycle. The MTT method showed an obvious inhibition of HSC proliferation after CPhG liposome and Recombinant Rat Platelet-derived growth factor-BB(rrPDGF-BB) treatment. The levels of collagen-1, metallopeptidase inhibitor 1 (TIMP-1), α smooth muscle actin (α-SMA), and phosphorylated PI3K/Akt were downregulated, and matrix metalloproteinase-1 (MMP-1) was upregulated, by pretreatment with different concentrations of CPhG liposomes. Moreover, 29.45 μg/mL of CPhG liposomes could decrease the expression of the FAK protein and the phosphorylated PI3K and Akt protein downstream of FAK by overexpression of the FAK gene. This experiment suggests that CPhG liposomes may inhibit the activation of HSCs by inhibiting FAK and then reducing the expression of phosphorylated Akt/PI3K, thereby providing new insights into the application of CPhGs for liver fibrosis.
Plants form a mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi, which facilitates the acquisition of scarce minerals from the soil. In return, the host plants provide sugars and lipids to ...its fungal partner. However, the mechanism by which the AM fungi obtain sugars from the plant has remained elusive.
In this study we investigated the role of potential SWEET family sugar exporters in AM symbiosis in Medicago truncatula.
We show that M. truncatula SWEET1b transporter is strongly upregulated in arbuscule-containing cells compared to roots and localizes to the peri-arbuscular membrane, across which nutrient exchange takes place. Heterologous expression of MtSWEET1b in a yeast hexose transport mutant showed that it mainly transports glucose. Overexpression of MtSWEET1b in M. truncatula roots promoted the growth of intraradical mycelium during AM symbiosis. Surprisingly, two independent Mtsweet1b mutants, which are predicted to produce truncated protein variants impaired in glucose transport, exhibited no significant defects in AM symbiosis. However, arbuscule-specific overexpression of MtSWEET1bY57A/G58D, which are considered to act in a dominant-negative manner, resulted in enhanced collapse of arbuscules.
Taken together, our results reveal a (redundant) role for MtSWEET1b in the transport of glucose across the peri-arbuscular membrane to maintain arbuscules for a healthy mutually beneficial symbiosis.
Radical‐initiated difunctionalization of alkenes is one of the most important methods in organic synthesis and medicinal chemistry, which can be applied to synthesize value complex compounds as well ...as structural motifs that found in bioactive natural products and pharmaceuticals. In recent years, impressive progress have been made in this area with ideal silver catalysis. Here, we summarize recent advances in silver‐mediated radical difunctionalization of alkenes for the formation of diverse bonds, including 1) two‐component radical difunctionalization reactions enabled by an intramolecular cyclization process toward various cyclic compounds and 2) three‐component radical difunctionalization reactions leading to complex linear compounds. These silver‐mediated radical alkene difunctionalization transformations are general initiated by different radicals, such as carbon‐, oxygen‐, sulfur‐, phosphinyl‐, and halogen‐center radicals, followed by terminated with nucleophiles to form two new bonds in a single reaction.
Ag catalysis: Recent advances in the silver‐mediated intermolecular radical 1,2‐difunctionalization of alkenes are summarized. These reaction are classified by the substrate type and radical regents. Two new C−C/C−C bonds, C−C/C−X bonds (X=F, O, S…) and C−X/C−X bonds (X=O, Br, I…) could be constructed in a single reaction.
Three-dimensional measurement of shiny or reflective surface is a challenging issue for optical-based instrumentations. In this paper, we present a novel structured light approach for direct ...measurement of shiny target so as to skip the coating preprocedure. In comparison with traditional image-intensity-based structured light coding strategies like sinusoidal and line patterns, strip edges not raw image intensities are encoded in the illuminated patterns. With strip edges generally better preserved than individual image intensity in the image data in the presence of surface reflections, such a coding strategy is more robust. To remove the periodic ambiguity within strip patterns, traditional Gray code patterns are adopted. To localize the strip edges more precisely, both positive and negative strip patterns are used. An improved zero-crossing feature detector that has subpixel accuracy is proposed for strip-edge localization. The experimental setup is configured with merely an off-the-shelf pico-projector and a camera. Extensive experiments including accuracy evaluation, comparison with previous structured light algorithms, and the reconstruction of some real shiny objects are shown to demonstrate the system's accuracy and endurance against reflective nature of surfaces.
A variety of chiral nine‐membered N‐heterocycles were prepared in moderate to good yields with high diastereoselectivity through a silver(I)‐catalyzed 3+2 cycloaddition and 3,3‐rearrangement of ...N‐vinyl‐α, β‐unsaturated nitrones and chiral 3‐propioloyloxazolidin‐2‐ones. Experimental studies showed that silver catalyst promoted the cycloaddition and rearrangement process, and the stereochemistry of the nine‐membered N‐heterocycles was controlled via 3,3‐rearrangement by chiral oxazolidinone‐auxiliary through a boat‐like transition state. Moreover, the obtained nine‐membered N‐heterocycle diastereomers were converted to chiral pyrrolizines with high diastereoselectivity and pyrrolizine carboxylate was obtained in 54% yield with 90% ee by the removal of chiral auxiliary.
The beneficial effects of tea consumption on cancer prevention have been generally reported, while (-)-Epigallocatechin-3-gallate (EGCG) is the major active component from green tea. Cancer stem ...cells (CSCs) play a crucial role in the process of cancer development. Targeting CSCs may be an effective way for cancer intervention. However, the effects of EGCG on colorectal CSCs and the underlying mechanisms remain unclear. Spheroid formation assay was used to enrich colorectal CSCs from colorectal cancer cell lines. Immunoblotting analysis and quantitative real-time polymerase chain reaction were used to measure the alterations of critical molecules expression. Immunofluorescence staining analysis was also used to determine the expression of CD133. We revealed that EGCG inhibited the spheroid formation capability of colorectal cancer cells as well as the expression of colorectal CSC markers, along with suppression of cell proliferation and induction of apoptosis. Moreover, we illustrated that EGCG downregulated the activation of Wnt/β-catenin pathway, while upregulation of Wnt/β-catenin diminished the inhibitory effects of EGCG on colorectal CSCs. Taken together, this study suggested that EGCG could be an effective natural compound targeting colorectal CSCs through suppression of Wnt/β-catenin pathway, and thus may be a promising agent for colorectal cancer intervention.
Messenger RNA (mRNA) vaccination has proven to be highly successful in combating Coronavirus disease 2019 (COVID-19) and has recently sparked tremendous interest. This technology has been a popular ...topic of research over the past decade and is viewed as a promising treatment strategy for cancer immunotherapy. However, despite being the most prevalent malignant disease for women worldwide, breast cancer patients have limited access to immunotherapy benefits. mRNA vaccination has the potential to convert cold breast cancer into hot and expand the responders. Effective mRNA vaccine design for in vivo function requires consideration of vaccine targets, mRNA structures, transport vectors, and injection routes. This review provides an overview of pre-clinical and clinical data on various mRNA vaccination platforms used for breast cancer treatment and discusses potential approaches to combine appropriate vaccination platforms or other immunotherapies to improve mRNA vaccine therapy efficacy for breast cancer.
Atrazine is the second mostly used herbicide in USA,but low utilization ratio causes severe environmental problem,so controlled release system is highly needed in order to minimize the negative ...impact on environment.In this paper,a herbicide delivery system,atrazine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were prepared by forming an oil-in-water emulsion using the emulsion-solvent evaporation method.By varying the preparation conditions of PLGA-NPs,such as sonication time,surfactant content,solvent fraction,and polymer content,the particle sizes of the PLGA-NPs were well controlled from 204 to 520 nm.The morphology and size distribution of PLGA-NPs were evaluated using dynamic light scattering (DLS) and scanning electron microscopy (SEM).Both the encapsulation efficiency and release profile of the herbicide from the PLGA-NPs were typically evaluated by using 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine (atrazine,ATZ) as the model.ATZ encapsulation efficiency within the PLGA-NPs was ranged from 31.6 to 50.5％.The release profiles of ATZ-loaded PLGA-NPs exhibited a much slower release rate in comparison with that of pure herbicide.The results demonstrated that the prepared PLGA-NPs had a high encapsulation efficiency and slow release rate,which could be used as a promising herbicide release system in agriculture to diminish the impact on the environment and minimize the potential harm to the farmers.
•We model piezoelectric actuators (PAs) by a generalized Bouc–Wen model.•The generalized Bouc–Wen model possesses the asymmetrical characteristics and the frequency-dependent behavior.•We establish a ...model-based control based on the proposed generalized Bouc–Wen model.
Piezoelectric actuators (PAs) are widely used in precision positioning control and active vibration control. However, positioning accuracy can be compromised by the hysteresis of PAs. We can put forward a model to accurately describe the hysteresis and then compensate the hysteretic effect to solve the above problem based on the proposed model. In order to model the hysteresis of a PA which possesses the asymmetrical characteristics and the frequency-dependent behavior, a generalized Bouc–Wen model is developed for the PA. A model-based control using the proposed generalized Bouc–Wen model is applied to force the output displacement of the PA to track the desired displacement accurately thereafter. Experiments are conducted to validate this new approach. The results highlight significantly improved accuracy in the displacement control of the PA.
Fibrosis in animal models and human diseases is associated with aberrant activation of the Wnt/β‐catenin pathway. Despite extensive research efforts, effective therapies are still not available. ...Myofibroblasts are major effectors, responsible for extracellular matrix deposition. Inhibiting the proliferation of the myofibroblast is crucial for treatment of fibrosis. Proliferation of myofibroblasts can have many triggering effects that result in fibrosis. In recent years, the Wnt pathway has been studied as an underlying factor as a primary contributor to fibrotic diseases. These efforts notwithstanding, the specific mechanisms by which Wnt‐mediated promotes fibrosis reaction remain obscure. The central role of the transforming growth factor‐β (TGF‐β) and myofibroblast activity in the pathogenesis of fibrosis has become generally accepted. The details of interaction between these two processes are not obvious. The present investigation was conducted to evaluate the level of sustained expression of fibrosis iconic proteins (vimentin, α‐SMA and collagen I) and the TGF‐β signalling pathway that include smad2/3 and its phosphorylated form p‐smad2/3. Detailed analysis of the possible molecular mechanisms mediated by β‐catenin revealed epithelial–mesenchymal transition and additionally demonstrated transitions of fibroblasts to myofibroblast cell forms, along with increased activity of β‐catenin in regulation of the signalling network, which acts to counteract autocrine TGF‐β/smad2/3 signalling. A major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFβ1‐smad2/3 signalling through Wnt/β‐catenin contribute to lung fibrosis.
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