A rapid
and sensitive isothermal method is crucial for point-of-care
(POC) nucleic acid testing. Recently, RNA-guided CRISPR/Cas12a proteins
were discovered to exhibit target-triggered nonspecific single-stranded
deoxyribonuclease (ssDNase) activity. Herein, the ssDNase cleavage
capacity of the CRISPR/Cas12a system for interfacial hairpin DNA (hpDNA)
and linear DNA was investigated in detailed. A novel electrochemical
DNA biosensor was then developed via target-induced Cas12a cleaving
interfacial hpDNA. In this strategy, the RNA-guided target DNA binding
activates the robust Cas12a ssDNase activity. The immobilized hpDNA
electrochemical reporters with a low surface coverage and incompact
morphological structure present accessible substrates for highly efficient
Cas12a cleavage, leading to a highly sensitive electrochemical DNA
biosensor. Under the optimal conditions, as low as 30 pM target DNA
was detected in about 60 min with 3.5 orders of magnitude dynamic
range from 50 pM to 100 nM. Furthermore, the practical application
ability of the established sensing method for detecting the target
in complex matrices was also demonstrated. The proposed strategy enables
rapid and sensitive DNA determination, providing a potential tool
for POC molecular diagnostics.
Acute lung injury (ALI) and the more severe acute respiratory distress syndrome are common and complex inflammatory lung diseases. MicroRNAs (miRs) have emerged as novel gene regulatory molecules, serving a crucial role in a variety of complex diseases, including ALI. In the present study, the anti-inflammatory action of miR-223 on inflammation in ALI was demonstrated and the possible mechanism was further examined. In lipopoly-saccharide-induced ALI, the expression of miR-223 was reduced compared with that in the control normal group. An in vitro model was used to analyze the effect of miR-223 downregulation on an ALI model, which increased inflammation, and induced the activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome and Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway via rho-related GTP-binding protein RhoB (RHOB). In addition, the overexpression of miR-223 reduced inflammation and suppressed the NLRP3 inflammasome and TLR4/NF-κB signaling pathway via RHOB in the in vitro model. Furthermore, TLR4 inhibitor or NLRP3 inhibitor reduced the pro-inflammatory effect of miR-223 downregulation in ALI. In conclusion, the results of the present study indicated that miR-223 functioned as a biological indicator by regulating inflammation in ALI, and may represent a novel potential therapeutic target and prognostic marker of ALI.
Soliton explosions, as one of the most fascinating nonlinear phenomena in dissipative systems, have been investigated in different branches of physics, including the ultrafast laser community. Herein, we reported on the soliton dynamics of an ultrafast fiber laser from steady state to soliton explosions, and to huge explosions by simply adjusting the pump power level. In particular, the huge soliton explosions show that the exploding behavior could operate in a sustained, but periodic, mode from one explosion to another, which we term as "successive soliton explosions." The experimental results will prove to be fruitful to the various communities interested in soliton explosions.
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