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BackgroundApigenin is a non-toxic natural flavonoid that is abundantly present in common fruits and vegetables. It has been reported that apigenin has various beneficial health effects such as anti-inflammation and chemoprevention. Multiple studies have shown that inflammation is an important risk factor for atherosclerosis, diabetes, sepsis, various liver diseases, and other metabolic diseases. Although it has been long realized that apigenin has anti-inflammatory activities, the underlying functional mechanisms are still not fully understood.Methodology and Principal FindingsIn the present study, we examined the effect of apigenin on LPS-induced inflammatory response and further elucidated the potential underlying mechanisms in human THP-1-induced macrophages and mouse J774A.1 macrophages. By using the PrimePCR array, we were able to identify the major target genes regulated by apigenin in LPS-mediated immune response. The results indicated that apigenin significantly inhibited LPS-induced production of pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF-α through modulating multiple intracellular signaling pathways in macrophages. Apigenin inhibited LPS-induced IL-1β production by inhibiting caspase-1 activation through the disruption of the NLRP3 inflammasome assembly. Apigenin also prevented LPS-induced IL-6 and IL-1β production by reducing the mRNA stability via inhibiting ERK1/2 activation. In addition, apigenin significantly inhibited TNF-α and IL-1β-induced activation of NF-κB.Conclusion and SignificanceApigenin Inhibits LPS-induced Inflammatory Response through multiple mechanisms in macrophages. These results provided important scientific evidences for the potential application of apigenin as a therapeutic agent for inflammatory diseases.

The rapid progress in flexible electronic devices has attracted immense interest in many applications, such as health monitoring devices, sensory skins, and implantable apparatus. Here, inspired by the adhesion features of mussels and the color shift mechanism of chameleons, a novel stretchable, adhesive, and conductive structural color film is presented for visually flexible electronics. The film is generated by adding a conductive carbon nanotubes polydopamine (PDA) filler into an elastic polyurethane (PU) inverse opal scaffold. Owing to the brilliant flexibility and inverse opal structure of the PU layer, the film shows stable stretchability and brilliant structural color. Besides, the catechol groups on PDA impart the film with high tissue adhesiveness and self‐healing capability. Notably, because of its responsiveness, the resultant film is endowed with color‐changing ability that responds to motions, which can function as dual‐signal soft human‐motion sensors for real‐time color‐sensing and electrical signal monitoring. These features make the bio‐inspired hydrogel‐based electronics highly potential in the flexible electronics field.

Cholangiocarcinoma (CCA) is an often fatal primary malignancy of the intra- and extrahepatic biliary tract that is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids (CBAs), which are correlated with bile duct obstruction (BDO). BDO has also recently been shown to promote CCA progression. However, whereas there is increasing evidence linking chronic cholestasis and abnormal bile acid profiles to CCA development and progression, the specific mechanisms by which bile acids may be acting to promote cholangiocarcinogenesis and invasive biliary tumor growth have not been fully established. Recent studies have shown that CBAs, but not free bile acids, stimulate CCA cell growth, and that an imbalance in the ratio of free to CBAs may play an important role in the tumorigenesis of CCA. Also, CBAs are able to activate extracellular signal-regulated kinase (ERK)1/2- and phosphatidylinositol-3-kinase/protein kinase B (AKT)-signaling pathways through sphingosine 1-phosphate receptor 2 (S1PR2) in rodent hepatocytes. In the current study, we demonstrate S1PR2 to be highly expressed in rat and human CCA cells, as well as in human CCA tissues. We further show that CBAs activate the ERK1/2- and AKT-signaling pathways and significantly stimulate CCA cell growth and invasion in vitro. Taurocholate (TCA)-mediated CCA cell proliferation, migration, and invasion were significantly inhibited by JTE-013, a chemical antagonist of S1PR2, or by lentiviral short hairpin RNA silencing of S1PR2. In a novel organotypic rat CCA coculture model, TCA was further found to significantly increase the growth of CCA cell spheroidal/“duct-like” structures, which was blocked by treatment with JTE-013. Conclusion: Our collective data support the hypothesis that CBAs promote CCA cell-invasive growth through S1PR2.

Wound dressing with the capacities of antioxidation, antiinflammation, and efficient angiogenesis induction is expected for effectively promoting wound healing. Herein, a novel core‐shell hyaluronic acid (HA) microneedle (MN) patch with ferrum‐mesenchymal stem cell‐derived artificial nanovesicles (Fe‐MSC‐NVs) and polydopamine nanoparticles (PDA NPs) encapsulated in the needle tips is presented for wound healing. Fe‐MSC‐NVs containing multifunctional therapeutic cytokines are encapsulated in the inner HA core of the MN tips for accelerating angiogenesis. The PDA NPs are encapsulated in the outer methacrylated hyaluronic acid (HAMA) shell of the MN tips to overcome the adverse impacts from reactive oxygen species (ROS)‐derived oxidative stress. With the gradual degradation of HAMA patch tips in the skin, the PDA NPs are sustainably released at the lesion to suppress the ROS‐induced inflammation reaction, while the Fe‐MSC‐NVs significantly increase the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVEC). More attractively, the combination of PDA NPs and Fe‐MSC‐NVs further promotes M2 macrophage polarization, thereby suppressing wound inflammation. Through in vivo experiment, the Fe‐MSC‐NVs/PDA MN patch shows an excellent effect for diabetic wound healing. These features of antioxidation, antiinflammation, and pro‐angiogenesis indicate the proposed composite core‐shell MN patch is valuable for clinical wound healing applications.

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Purpose COVID-19 has severely affected urban and rural tourism in China, which has been extensively reported in the newspapers. This paper aims to discuss the impact of COVID-19 on urban and rural tourism at each critical juncture of the COVID-19 pandemic, as well as the studies, measures and attitudes of various stakeholders toward urban and rural tourism and their future development. Design/methodology/approach This paper collects Chinese news reports as the research object and uses ROST Content Mining 6.0 and Gephi software to analyze and visualize the data for high-frequency words and analyzed the discourse of stakeholders within the newspaper text. Findings This study found that prior to February 20, 2020, the Chinese Government mainly focused on pandemic prevention. From February 21 to April 3 (before The Qingming Festival), resumption of work and production became the theme. From April 4 to May 1 (before May Day), a time-sharing reservation system was widely implemented and the differentiation between urban and rural tourism became more prominent. After May 1, rural tourism attracted greater attention. Originality/value This paper uses discourse analysis to understand the impact of COVID-19 on urban and rural tourism from the perspective of time nodes and the relationship between various stakeholders and predicts the development trends within urban and rural tourism. This paper enriches and expands tourism management knowledge in the face of major crises, providing valuable advice for managers and investors and makes suggestions for the development of urban and rural tourism.