Glycitein is an isoflavone that reportedly inhibits the proliferation of human breast cancer and prostate cancer cells. However, its anti‐cancer molecular mechanisms in human gastric cancer remain to ...be defined. This study evaluated the antitumor effects of glycitein on human gastric cancer cells and investigated the underlying mechanisms. We used MTT assay, flow cytometry and western blotting to investigate its molecular mechanisms with focus on reactive oxygen species (ROS) production. Our results showed that glycitein had significant cytotoxic effects on human gastric cancer cells. Glycitein markedly decreased mitochondrial transmembrane potential (ΔΨm) and increased AGS cells mitochondrial‐related apoptosis, and caused G0/G1 cell cycle arrest by regulating cycle‐related protein. Mechanistically, accompanying ROS, glycitein can activate mitogen‐activated protein kinase (MAPK) and inhibited the signal transducer and activator of transcription 3 (STAT3) and nuclear factor‐kappaB (NF‐κB) signaling pathways. Furthermore, the MAPK signaling pathway regulated the expression levels of STAT3 and NF‐κB upon treatment with MAPK inhibitor and N‐acetyl‐L‐cysteine (NAC). These findings suggested that glycitein induced AGS cell apoptosis and G0/G1 phase cell cycle arrest via ROS‐related MAPK/STAT3/NF‐κB signaling pathways. Thus, glycitein has the potential to a novel targeted therapeutic agent for human gastric cancer.
Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury, but preclinical studies in large animal models are required to determine optimal cell preparation ...and delivery strategies to maximize functional benefits and to evaluate safety. Here, we utilized a porcine model of acute myocardial infarction (MI) to investigate the functional impact of intramyocardial transplantation of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells, in combination with a 3D fibrin patch loaded with insulin growth factor (IGF)-encapsulated microspheres. hiPSC-derived cardiomyocytes integrated into host myocardium and generated organized sarcomeric structures, and endothelial and smooth muscle cells contributed to host vasculature. Trilineage cell transplantation significantly improved left ventricular function, myocardial metabolism, and arteriole density, while reducing infarct size, ventricular wall stress, and apoptosis without inducing ventricular arrhythmias. These findings in a large animal MI model highlight the potential of utilizing hiPSC-derived cells for cardiac repair.
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•Human iPSCs (hiPSCs) were differentiated into three cardiac lineages•hiPSC-derived cells were transplanted into a porcine model of myocardial infarction•Engraftment in combination with IGF-1-fibrin patch improves cardiac function•Intramyocardial delivery of hiPSC-cardiomyocytes did not cause arrhythmias
Large animal studies are required to assess the potential of human pluripotent stem cell (hPSC)-derived cells for cardiac repair. Ye et al. show that engraftment of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells into a porcine model of myocardial infarction improves heart function and metabolism without inducing ventricular arrhythmias.
With the rapid globalization of markets, integrating supply chain technology has become increasingly complex. That is, most supply chains are no longer limited to a particular region. Because the ...numbers of branch nodes of supply chains have increased, products and raw materials vary and resource constraints differ. Thus, integrating planning mechanisms should include the capacity to respond to change. In the past, mathematical programming and a general heuristics algorithm were used to solve globalized supply chain network design problems. When mathematical programming is used to solve a problem and the number of decision variables is too high or constraint conditions are too complex, computation time is long, resulting in low efficiency, and can easily become trapped in partial optimum solution. When a general heuristics algorithm is used and the number of variables and constraints is too high, the degree of complexity increases. This usually results in an inability of people to think about resource constraints of enterprises and obtain an optimum solution.
Therefore, this study uses genetic algorithms with optimum search features. This work combines the co-evolutionary mode, which is in accordance with various criteria and evolves dynamically, and constraint-satisfaction mode capacity to narrow the search space, which helps in finding rapidly a solution that, solves supply chain integration network design problems. Additionally, via mathematical programming, a simple genetic algorithm, co-evolutionary genetic algorithm, constraint-satisfaction genetic algorithm and co-evolutionary constraint genetic algorithm are used to compare the experiments result and processing time to confirm the performance of the proposed method.
Abstract
Artificially performing chemical reactions in living biosystems to attain various physiological aims remains an intriguing but very challenging task. In this study, the Schiff base reaction ...was conducted in cells using Sc(OTf)
3
as a catalyst, enabling the in situ synthesis of a hollow covalent organic polymer (HCOP) without external stimuli. The reversible Schiff base reaction mediated intracellular Oswald ripening endows the HCOP with a spherical, hollow porous structure and a large specific surface area. The intracellularly generated HCOP reduced cellular motility by restraining actin polymerization, which consequently induced mitochondrial deactivation, apoptosis, and necroptosis. The presented intracellular synthesis system inspired by the Schiff base reaction has strong potential to regulate cell fate and biological functions, opening up a new strategic possibility for intervening in cellular behavior.
Plant-derived exosome-like nanoparticles (ELNs) have been proposed as a novel therapeutic tool for preventing human diseases. However, the number of well-verified plant ELNs remains limited. In this ...study, the microRNAs in ELNs derived from fresh Rehmanniae Radix, a well-known traditional Chinese herb for treating inflammatory and metabolic diseases, were determined by using microRNA sequencing to investigate the active components in the ELNs and the protection against lipopolysaccharide (LPS)-induced acute lung inflammation in vivo and in vitro. The results showed that rgl-miR-7972 (miR-7972) was the main ingredient in ELNs. It exerted stronger protective activities against LPS-induced acute lung inflammation than catalpol and acteoside, which are two well-known chemical markers in this herb. Moreover, miR-7972 decreased the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), reactive oxygen species (ROS) and nitric oxide (NO) in LPS-exposed RAW264.7 cells, thereby facilitating M2 macrophage polarization. Mechanically, miR-7972 downregulated the expression of G protein-coupled receptor 161 (GPR161), activating the Hedgehog pathway, and inhibited the biofilm form of Escherichia coli via targeting virulence gene sxt2. Therefore, miR-7972 derived from fresh R. Radix alleviated LPS-induced lung inflammation by targeting the GPR161-mediated Hedgehog pathway, recovering gut microbiota dysbiosis. It also provided a new direction for gaining novel bioactivity nucleic acid drugs and broadening the knowledge on cross-kingdom physiological regulation through miRNAs.
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•Rgl-miR-7972 was the main ingredient in ELNs derived from fresh Rehmanniae Radix.•Rgl-miR-7972 improved LPS-induced inflammation via inhibiting GPR161.•Rgl-miR-7972 inhibited the biofilm form of Escherichia coli via inhibiting sxt2.•ELNs act as novel drug deliver for cross-kingdom physiological regulation.
This paper reports a polydimethylsiloxane-polycarbonate (PDMS-PC) hybrid microfluidic device capable of performing cell culture under combinations of chemical and oxygen gradients. The microfluidic ...device is constructed of two PDMS layers with microfluidic channel patterns separated by a thin PDMS membrane. The top layer contains an embedded PC film and a serpentine channel for a spatially confined oxygen scavenging chemical reaction to generate an oxygen gradient in the bottom layer for cell culture. Using the chemical reaction method, the device can be operated with a small amount of chemicals, without bulky gas cylinders and sophisticated flow control schemes. Furthermore, it can be directly used in conventional incubators with syringe pumps to simplify the system setup. The bottom layer contains arrangements of serpentine channels for chemical gradient generation and a cell culture chamber in the downstream. The generated chemical and oxygen gradients are experimentally characterized using a fluorescein solution and an oxygen-sensitive fluorescent dye, respectively. For demonstration, a 48 hour cell-based drug test and a cell migration assay using human lung adenocarcinoma epithelial cells (A549) are conducted under various combinations of the chemical and oxygen gradients in the experiments. The drug testing results show an increase in A549 cell apoptosis due to the hypoxia-activated cytotoxicity of tirapazamine (TPZ) and also suggest great cell compatibility and gradient controllability of the device. In addition, the A549 cell migration assay results demonstrate an aerotactic behavior of the A549 cells and suggest that the oxygen gradient plays an essential role in guiding cell migration. The migration results, under combinations of chemokine and oxygen gradients, cannot be simply superposed with single gradient results. The device is promising to advance the control of in vitro microenvironments, to better study cellular responses under various physiological conditions for biomedical applications.
Manipulating terahertz (THz) polarization in an efficient and broadband manner is of great significance to facilitating THz applications, including communications, imaging, defense, and homeland ...security. In this work, a dispersion compensation scheme is proposed for high‐efficiency and ultra‐broadband THz polarization manipulation using an anisotropic dielectric‐metal hybrid metadevice. The operating bandwidth is broadened by dispersion compensation, where the dielectric grating provides an artificial birefringence with a phase dispersion of positive slope and the metallic grating provides a phase dispersion of negative slope. Experimental results show that the device achieves two ultra‐broadband dispersion compensation, corresponding to the achromatic quarter‐wave plate in the lower frequency band (QWP: 0.5–2.0 THz, PCR >0.95) and the achromatic half‐wave plate in the higher frequency band (HWP: 1.0–2.1 THz, PCR >0.9), respectively. Theoretically, the bandwidth of QWP can be further improved to 2.6 THz by optimizing the grating dispersion, which brings huge application space to cover most of the THz radiation. This hybrid metadevice configuration offers a versatile platform for engineering electromagnetic waves, and the strategy of phase compensation can be generalized to extend the bandwidth of the metadevice in imaging and communications.
A dispersion compensation scheme is proposed for high‐efficiency and ultra‐broadband THz polarization manipulation using a dielectric‐metal hybrid metadevice. Based on the superposition of positive and negative phase retardations, broadband and dispersion‐free phase retardations of ≈π/2 and π can be achieved in composite devices. As a result, two working modes of QWP and HWP are achieved in this work.
L-carnitine (LC) is well known for its antioxidant activity. In this study, we explored the potential mechanistic effects of LC supplementation on aged bovine oocytes in vitro. We showed that ...in-vitro maturation could enhance the subsequent developmental capacity of aging oocytes, when supplemented with LC. After in vitro fertilization, the blastocyst formation rate in the aged oocytes post-LC treatment significantly increased compared to that in untreated aged oocytes (29.23 ± 2.20% vs. 20.90 ± 3.05%). Furthermore, after LC treatment, the level of intracellular reactive oxygen species in aged oocytes significantly decreased, and glutathione levels significantly increased, compared to those in untreated aged oocytes. Mitochondrial membrane potential, the percentage of early apoptotic oocytes, and caspase-3 activity were significantly reduced in LC-treated aged oocytes compared to those in untreated aged oocytes. Furthermore, during in vitro aging, the mRNA levels of the anti-apoptotic genes, Bcl-xl and survivin in LC-treated aged oocytes were significantly higher than those in untreated aged oocytes. Overall, these results indicate that at least in in vitro conditions, LC can prevent the aging of bovine oocytes and improve the developmental capacity of bovine embryo.
B cells use B‐cell receptors (BCRs) to sense antigens that are usually presented on substrates with different stiffness. However, it is not known how substrate stiffness affects B‐cell proliferation, ...class switch, and in vivo antibody responses. We addressed these questions using polydimethylsiloxane (PDMS) substrates with different stiffness (20 or 1100 kPa). Live cell imaging experiments suggested that antigens on stiffer substrates more efficiently trigger the synaptic accumulation of BCR and phospho‐Syk molecules compared with antigens on softer substrates. In vitro expansion of mouse primary B cells shows different preferences for substrate stiffness when stimulated by different expansion stimuli. LPS equally drives B‐cell proliferation on stiffer or softer substrates. Anti‐CD40 antibodies enhance B‐cell proliferation on stiffer substrates, while antigens enhance B‐cell proliferation on softer substrates through a mechanism involving the enhanced phosphorylation of PI3K, Akt, and FoxO1. In vitro class switch differentiation of B cells prefers softer substrates. Lastly, NP67‐Ficoll on softer substrates accounted for an enhanced antibody response in vivo. Thus, substrate stiffness regulates B‐cell activation, proliferation, class switch, and T cell independent antibody responses in vivo, suggesting its broad application in manipulating the fate of B cells in vitro and in vivo.
The pathophysiology of heart failure (HF) is diverse, owing to multiple etiologies and aberrations in a number of cellular processes. Therefore, it is essential to understand how defects in the ...molecular pathways that mediate cellular responses to internal and external stressors function as a system to drive the HF phenotype. Mass spectrometry (MS)-based proteomics strategies have great potential for advancing our understanding of disease mechanisms at the systems level because proteins are the effector molecules for all cell functions and, thus, are directly responsible for determining cell phenotype. Two MS-based proteomics strategies exist: peptide-based bottom-up and protein-based top-down proteomics—each with its own unique strengths and weaknesses for interrogating the proteome. In this review, we will discuss the advantages and disadvantages of bottom-up and top-down MS for protein identification, quantification, and analysis of post-translational modifications, as well as highlight how both of these strategies have contributed to our understanding of the molecular and cellular mechanisms underlying HF. Additionally, the challenges associated with both proteomics approaches will be discussed and insights will be offered regarding the future of MS-based proteomics in HF research.
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