Although intestinal flora are crucial in maintaining immune homeostasis of the intestine, the role of intestinal flora in immune responses at other mucosal surfaces remains less clear. Here, we show that intestinal flora composition critically regulates the toll-like receptor 7 (TLR7) signaling pathway following respiratory influenza virus infection. TLR7 ligands rescued the immune impairment in antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for TLR7, MyD88, IRAK4, TRAF6, and NF-κB at steady state. Significant changes in the composition of culturable commensal bacteria reduced the expression levels of components of the TLR7 signaling pathway. Our results reveal the importance of intestinal flora in regulating immunity in the respiratory mucosa through the upregulation of the TLR7 signaling pathway for the proper activation of inflammasomes.
A reliable surface-enhanced Raman scattering (SERS) substrate composed of two-dimensional (2D) MXene (Ti 3 C 2 T x ) nanosheets and gold nanorods (AuNRs) is designed and fabricated for sensitive detection of organic pollutants. The AuNRs are uniformly distributed on the surface of the 2D MXene nanosheets because of the strong electrostatic interactions, forming abundant SERS hot spots. The MXene/ AuNR SERS substrate exhibits high sensitivity and excellent reproducibility in the determination of common organic dyes such as rhodamine 6G, crystal violet, and malachite green. The detection limits are 1 × 10 −12 , 1 × 10 −12 , and 1 × 10 −10 M, and relative standard deviations determined from 13 areas on each sample are 18.1, 10.1, and 15.6%, respectively. In the determination of more complex organic pesticides and pollutants, the substrate also shows excellent sensitivity and quantitative detection, and the detection limits for thiram and diquat of 1 × 10 −10 and 1 × 10 −8 M, respectively, are much lower than the contaminant levels stipulated by the US Environmental Protection Agency. The MXene/AuNR composite constitutes an efficient SERS platform for reliable and high-sensitivity environmental analysis and food safety monitoring.
Hepatic injury is often accompanied by pulmonary inflammation and tissue damage, but the underlying mechanism is not fully elucidated. Here we identify hepatic miR-122 as a mediator of pulmonary inflammation induced by various liver injuries. Analyses of acute and chronic liver injury mouse models confirm that liver dysfunction can cause pulmonary inflammation and tissue damage. Injured livers release large amounts of miR-122 in an exosome-independent manner into the circulation compared with normal livers. Circulating miR-122 is then preferentially transported to mouse lungs and taken up by alveolar macrophages, in which it binds Toll-like receptor 7 (TLR7) and activates inflammatory responses. Depleting miR-122 in mouse liver or plasma largely abolishes liver injury-induced pulmonary inflammation and tissue damage. Furthermore, alveolar macrophage activation by miR-122 is blocked by mutating the TLR7-binding GU-rich sequence on miR-122 or knocking out macrophage TLR7. Our findings reveal a causative role of hepatic miR-122 in liver injury-induced pulmonary dysfunction.
As new 2D layered nanomaterials, Bi2O2Se nanoplates have unique semiconducting properties that can benefit biomedical applications. Herein, a facile top‐down approach for the synthesis of Bi2O2Se quantum dots (QDs) in a solution is described. The Bi2O2Se QDs with a size of 3.8 nm and thickness of 1.9 nm exhibit a high photothermal conversion coefficient of 35.7% and good photothermal stability. In vitro and in vivo assessments demonstrate that the Bi2O2Se QDs possess excellent photoacoustic (PA) performance and photothermal therapy (PTT) efficiency. After systemic administration, the Bi2O2Se QDs accumulate passively in tumors enabling efficient PA imaging of the entire tumors to facilitate imaging‐guided PTT without obvious toxicity. Furthermore, the Bi2O2Se QDs which exhibit degradability in aqueous media not only have sufficient stability during in vivo circulation to perform the designed therapeutic functions, but also can be discharged harmlessly from the body afterward. The results reveal the great potential of Bi2O2Se QDs as a biodegradable multifunctional agent in medical applications.
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