The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multi-protein complex that can be activated by a variety of pathogen-associated molecular patterns or ...damage-associated molecular patterns. Inappropriate NLRP3 inflammasome activation can induce autoinflammatory, autoimmune, or metabolic disorders. Therefore, NLRP3 is an attractive target against NLRP3 inflammasome activation, and specific targeting of NLRP3 might be an intriguing approach to the development of drugs for the treatment of NLRP3 inflammasome-related diseases. Although many studies with varied mechanistic approaches were reported in inhibition of NLRP3 inflammasome activation, mechanisms related to regulation of posttranslational modification (PTM) of NLRP3, as a focal point has not been thoroughly addressed. Recently, extensive investigations of PTMs of NLRP3 have led to partial understanding of the mechanisms involved in NLRP3 inflammasome activation. In this review, we focused on the role of PTMs regulating NLRP3 inflammasome activation.
The aim of this study is to investigate less conservative conditions for a parameterized linear matrix inequality (PLMI) expressed in the form of a double convex sum. This type of PLMI frequently ...appears in Takagi-Sugeno (T-S) fuzzy control system analysis and design problems. In this letter, we derive new less conservative linear matrix inequalities (LMIs) for the PLMI by employing the proposed sum relaxation method based on Young's inequality. The derived LMIs are proven to be less conservative than the existing conditions related to this topic in the literature. The proposed technique is applicable to various stability analysis and control design problems for T-S fuzzy systems, which are formulated as solving the PLMIs in the form of a double convex sum. Furthermore, examples are provided to illustrate the reduced conservatism of the derived LMIs.
Neuromorphic circuits that can function under extreme deformations are important for various data‐driven wearable and robotic applications. Herein, biphasic liquid metal particle (BMP) with ...unprecedented stretchability and strain‐insensitivity (ΔR/R0 = 1.4@ 1200% strain) is developed to realize a stretchable neuromorphic circuit that mimics a spike‐based biologic sensory system. The BMP consists of liquid metal particles (LMPs) and rigid liquid metal particles (RLMPs), which are homogeneously mixed via spontaneous solutal‐Marangoni mixing flow during coating. This permits facile single step patterning directly on various substrates at room temperature. BMP is highly conductive (2.3 × 106 S/m) without any post activation steps. BMP interconnects are utilized for a sensory system, which is capable of distinguishing variations of biaxial strains with a spiking neural network, thus demonstrating their potential for various sensing and signal processing applications.
Biphasic liquid metal particle (BMP) with two uniformly mixed particles is realized with the Marangoni mixing during the evaporation of co‐solvents. The mixed morphology enables high conductivity and strain‐insensitivity of the film. With BMP as stretchable interconnects, a stretchable multilayer neuromorphic circuit that can distinguish different signals with spike‐based neuromorphic signal processing is demonstrated.
Papaver plants can produce diverse bioactive alkaloids. Papaver rhoeas Linnaeus (common poppy or corn poppy) is an annual flowering medicinal plant used for treating cough, sleep disorder, and as a ...sedative, pain reliever, and food. It contains various powerful alkaloids like rhoeadine, benzylisoquinoline, and proaporphine. To investigate and identify alkaloids in the aerial parts of P. rhoeas, samples were collected at different growth stages and analyzed using liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry. A liquid chromatography with mass spectrometry method was developed for the identification and metabolite profiling of alkaloids for P. rhoeas by comparing with Papaver somniferum. Eighteen alkaloids involved in benzylisoquinoline alkaloid biosynthesis were used to optimize the liquid chromatography gradient and mass spectrometry conditions. Fifty‐five alkaloids, including protoberberine, benzylisoquinoline, aporphine, benzophenanthridine, and rhoeadine‐type alkaloids, were identified authentically or tentatively by liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry in samples taken during various growth stages. Rhoeadine alkaloids were observed only in P. rhoeas samples, and codeine and morphine were tentatively identified in P. somniferum. The liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry method can be a powerful tool for the identification of diverse metabolites in the genus Papaver. These results may help understand the biosynthesis of alkaloids in P. rhoeas and evaluate the quality of this plant for possible medicinal applications.
The ATPase activity of NLRP3 has pivotal role in inflammasome activation and is recognized as a good target for the development of the NLRP3 inflammasome-specific inhibitor. However, signals in the ...vicinity of the ATPase activity of NLRP3 have not been fully elucidated. Here, we demonstrate NLRP3 inflammasome-specific action of a benzoxathiole derivative, BOT-4-one. BOT-4-one exhibited an inhibition of NLRP3 inflammasome activation, which was attributable to its alkylating capability to NLRP3. In particular, the NLRP3 alkylation by BOT-4-one led to an impaired ATPase activity of NLRP3, thereby obstructing the assembly of the NLRP3 inflammasome. Additionally, we found that NLRP3 alkylators, including BOT-4-one, enhance the ubiquitination level of NLRP3, which might also contribute to the inhibition of NLRP3 inflammasome activation. Finally, BOT-4-one appeared to be superior to other known NLRP3 alkylators in inhibiting the functionality of the NLRP3 inflammasome and its resulting anti-inflammatory activity was confirmed in vivo using a monosodium urate-induced peritonitis mouse model. Collectively, the results suggest that NLRP3 alkylators function by inhibiting ATPase activity and increasing the ubiquitination level of NLRP3, and BOT-4-one could be the type of NLRP3 inhibitor that may be potentially useful for the novel development of a therapeutic agent in controlling NLRP3 inflammasome-related diseases.
CROP reactivity of organic coatings composed of three structurally different monomers with epoxy or oxetane derivatives was investigated, focusing on rheological and surface mechanical properties. ...Real‐time crosslinking behavior of CROP monomers was monitored using a rotational rheometer. Results of differential scanning calorimetry with in situ UV irradiation revealed that the ring opening reactivity of CROP monomers protonated by a photoacid generator (PAG) was correlated with the heat released during the exothermic polymerization reaction. In addition, reaction conversions of monomers with epoxy and oxetane groups were compared using Fourier transform infrared spectroscopy (FT‐IR) under dark curing conditions. Surface and internal mechanical properties of coating films, including adhesion with polycarbonate substrate, were comprehensively evaluated by nano‐indentation, nano‐scratch, and surface and interfacial cutting analysis system (SAICAS) tests. By understanding the unique crosslinking characteristics of each CROP monomer, the ternary CROP monomer system, optimally containing with ECC of 53.6 wt%, DOX of 22.9 wt%, and DEO of 15.3 wt%, exhibited improved crosslinking density (G′ from 104 to 107 Pa) and exceptional mechanical (with scratch resistance increasing from 7.11 to 16.17 mN for Lc1), adhesion (with crosscut resistance increasing from 0 to 5B), and transparency properties, surpassing the performance of unitary ECC coating system.
UV‐induced CROP reaction for light‐weight automotive plastic coating.
Mesenchymal stem cells (MSCs) are an attractive candidate for the treatment of inflammatory bowel disease (IBD), but their poor delivery rate to an inflamed colon is a major factor hampering the ...clinical potential of stem cell therapies. Moreover, there remains a formidable hurdle to overcome with regard to survival and homing in to injured sites. Here, we develop a strategy utilizing monodisperse hydrogel microcapsules with a thin intermediate oil layer prepared by a triple-emulsion drop-based microfluidic approach as an in-situ oral delivering carrier. The oral delivery of stem-cell-loaded hydrogel microcapsules (SC-HM) enhances MSC survival and retention in the hostile stomach environment due to the intermediate oil layer and low value of the overall stiffness, facilitating programmable cell release during gastrointestinal peristalsis. SC-HM is shown to induce tissue repair, reduce the colonic macrophage infiltration responsible for the secretion of the pro-inflammatory factors, and significantly mitigate the severity of IBD in a mouse model, where MSCs released by SC-HM successfully accumulate at the colonic crypt. Moreover, a metagenomics analysis reveals that SC-HM ameliorates the dysbiosis of specific bacterial genera, including Bacteroides acidifaciens, Lactobacillus (L.) gasseri, Lactobacillus reuteri, and L. intestinalis, implying optimization of the microorganism's composition and abundance. These findings demonstrate that SC-HM is a potential IBD treatment candidate.
Stem-cell-loaded hydrogel microcapsules (SC-HM) with a thin oil layer has the potential to rupture and release the encapsulated stem cells by the segmenting during the moment and peristalsis in the gut. Stem cells released from SC-HM induce the tissue repair, reduce the colonic macrophage infiltration responsible for the secretion of the pro-inflammatory factors, and significantly mitigate the severity of IBD in a mouse model. Moreover, SC-HM can restore gut microbiome dysbiosis and reestablish the composition of the gut microbiota in acute colitis. Display omitted
•We develop the SC-HM prepared by a triple-emulsion drop-based microfluidic approach.•The delivery of SC-HM augments the local retention of the cell at colonic sites.•Stem cells released from the SC-HM ameliorate gut inflammation in a mouse IBD model.•SC-HM restores gut microbiome dysbiosis in active colitis.
Antimicrobial peptides (AMPs), also called host defense peptides, particularly those with amphipathic helical structures, are emerging as target molecules for therapeutic development due to their ...immunomodulatory properties. Although the antimicrobial activity of AMPs is known to be exerted primarily by permeation of the bacterial membrane, the mechanism underlying its anti-inflammatory activity remains to be elucidated. We report potent anti-inflammatory activity of WALK11.3, an antimicrobial model peptide with an amphipathic helical conformation, in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. This peptide inhibited the expression of inflammatory mediators, including nitric oxide, COX-2, IL-1β, IL-6, INF-β, and TNF-α. Although WALK11.3 did not exert a major effect on all downstream signaling in the MyD88-dependent pathway, toll-like receptor 4 (TLR4)- mediated pro-inflammatory signals were markedly attenuated in the TRIF-dependent pathway due to inhibition of the phosphorylation of STAT1 by attenuation of IRF3 phosphorylation. WALK11.3 specifically inhibited the endocytosis of TLR4, which is essential for triggering TRIF-mediated signaling in macrophage cells. Hence, we suggest that specific interference with TLR4 endocytosis could be one of the major modes of the anti-inflammatory action of AMPs. Our designed WALK11 peptides, which possess both antimicrobial and anti-inflammatory activities, may be promising molecules for the development of therapies for infectious inflammation.
Osteoporosis is a disease caused by impaired bone remodeling that is especially prevalent in elderly and postmenopausal women. Although numerous chemical agents have been developed to prevent ...osteoporosis, arguments remain regarding their side effects. Here, we demonstrated the effects of loganin, a single bioactive compound isolated from
, on osteoblast and osteoclast differentiation in vitro and on ovariectomy (OVX)-induced osteoporosis in mice in vivo. Loganin treatment increased the differentiation of mouse preosteoblast cells into osteoblasts and suppressed osteoclast differentiation in primary monocytes by regulating the mRNA expression levels of differentiation markers. Similar results were obtained in an osteoblast-osteoclast co-culture system, which showed that loganin enhanced alkaline phosphatase (ALP) activity and reduced TRAP activity. In in vivo experiments, the oral administration of loganin prevented the OVX-induced loss of bone mineral density (BMD) and microstructure in mice and improved bone parameters. In addition, loganin significantly increased the serum OPG/RANKL ratio and promoted osteogenic activity during bone remodeling. Our findings suggest that loganin could be used as an alternative treatment to protect against osteoporosis.
Summary
Flow calculations in an unbounded domain have limitations and challenges due to its infiniteness. A common approach is to impose a far‐field asymptotic condition to determine a unique flow. ...The leading behavior of the flow is identified at the far field, and then an unknown coefficient is assumed for the second behavior. This allows us to propose an efficient numerical method to solve two‐dimensional steady Stokes and potential flows in a truncated domain along with the coefficients. The second term provides crucial hydrodynamic information for the flow and is referred to as the informative boundary condition. The truncation creates artificial boundaries requiring boundary conditions for the approximate solution. The axial Green function method (AGM), combined with a specific one‐dimensional Green function over a semi‐infinite axis‐parallel line extended to infinity, allows us to implement the informative boundary condition in the truncated domain. AGMs, designed for complicated domains, are now applied to infinite domain cases because AGMs' versatility enables implementing the informative boundary condition by changing only the axial Green function. This approach's efficiency, accuracy, and consistency are investigated through several appealing Stokes flow problems including potential ones in infinite domains.
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