First-Line Contact Aspiration vs Stent Retriever for Proximal Occlusion in Acute Ischemic Stroke: A Systemic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to compare the performance of first-line contact aspiration (ASP) and stent retriever (SR) in acute ischemic stroke caused by proximal large vessel occlusion. METHODS: Cochrane databases, MEDLINE and EMBASE were systematically searched for literatures reporting outcomes on thrombectomy with both first-line aspiration and first-line stent retriever in proximal occlusion. RESULTS: Thirteen studies with a total of 1614 patients were included. No differences were identified between the SR and ASP groups in terms of final reperfusion rate (modified thrombolysis in cerebral infarction 2b/3) (OR: 1.54, 95% CI: 0.88-2.70), complete recanalization rate (modified thrombolysis in cerebral infarction 3) (OR: 1.78, 95% CI: 0.58-5.44), and favorable outcomes (modified Rankin scale ≤2) (OR: 1.02, 95% CI: 0.79-1.32). With regard to adverse events, emboli to new territories (OR: 0.81, 95% CI: 0.31-2.14), intracranial hemorrhage (OR: 0.71, 95% CI: 0.40-1.28), 90-days mortality (OR: 1.02, 95% CI: 0.71-1.47) were similar between groups, while symptomatic intracerebral hemorrhage (OR: 0.43 95% CI: 0.21-0.86) was less seen in ASP. Subgroup analysis indicated that ASP was comparable to stent retriever with local aspiration (SRLA) (OR: 1.25 95% CI: 0.25-6.22) and superior to stent retriever alone (OR: 1.85 95% CI: 1.22-2.81). Moreover, in posterior circulation, contact aspiration achieved a significantly higher reperfusion (OR: 1.97 95% CI: 1.03-3.76) compared to stent retriever, and needed relatively less rescue therapies (21.5% vs 29.6%, p < 0.05). CONCLUSION: Our study suggested that contact aspiration might be advantageous over stent retriever alone and more suitable in posterior circulation. While ASP and SRLA thrombectomy were equally effective in achieving good clinical outcomes. However, further studies are needed to confirm these results.

Programmable Mg(2+)-dependent DNAzyme switch by the catalytic hairpin DNA assembly for dual-signal amplification toward homogeneous analysis of protein and DNA.

The catalytic hairpin DNA assembly-programmed active Mg(2+)-dependent DNAzyme was proposed for dual-signal amplified detection toward protein and DNA. The protein detection was implemented with the further combination of an additional terminal protection strategy. The detection limit toward avidin and target DNA could be achieved as 2 pM and 0.5 pM, respectively, with a high selectivity.

Highly sensitive fluorescence detection of target DNA by coupling exonuclease-assisted cascade target recycling and DNAzyme amplification.

Because of the intrinsic importance of nucleic acid as bio-targets, the simple and sensitive detection of nucleic acid is very essential for biological studies and medical diagnostics. Herein, a simple, isothermal and highly sensitive fluorescence detection of target DNA was developed with the combination of exonuclease III (Exo III)-assisted cascade target recycling and DNAzyme amplification. A hairpin DNA probe was designed, which contained the 3'-protruding DNA fragment as target recognition unit, the caged DNA fragment in the stem region as target analogue, and the caged 8-17 DNAzyme sequence in the loop region as signal response unit. Upon sensing of target DNA, the 3'-strand of hairpin DNA probe could be stepwise removed by Exo III, accompanied by the releasing of target DNA and autonomous generation of new target analogues for the successive hybridization and cleavage process. Simultaneously, the 8-17 DNAzyme unit could be exponentially released from this hairpin DNA probe and activated for the cyclic cleavage toward the ribonucleotide-containing molecular beacon substrate, inducing a remarkable fluorescence signal amplification for target detection. A low detection limit of 20 fM with an excellent selectivity toward target DNA could be achieved. The developed cascade amplification strategy may be further extended for the detection of a wide spectrum of analytes including protein and biological small molecules by combining DNA aptamer technology.

Exonuclease III-aided autocatalytic DNA biosensing platform for immobilization-free and ultrasensitive electrochemical detection of nucleic acid and protein.

Homogenous electrochemical biosensor has attracted substantial attention owing to its simplicity, rapid response, and improved recognition efficiency compared with heterogeneous biosensor, but the relatively low detection sensitivity and the limited detection analytes prohibit its potential applications. To address these issues, herein, a simple, rapid, isothermal, and ultrasensitive homogeneous electrochemical DNA biosensing platform for target DNA and protein detection has been developed on the basis of an exonuclease III (Exo III)-aided autocatalytic target recycling strategy. A ferrocene-labeled hairpin probe (HP1) is ingeniously designed, which contains a protruding DNA fragment at 3'-termini as the recognition unit for target DNA. Also, the DNA fragment that could be used as secondary target analogue was introduced, but it was caged in the stem region of HP1. In the presence of target DNA, its recognition with the protruding fragment of HP1 triggered the Exo III cleavage process, accompanied with the target recycling and autonomous generation of secondary target analogues. This accordingly resulted into the autonomous accumulation of ferrocene-labeled mononucleotide, inducing a distinct increase in the electrochemical signal owing to its elevated diffusivity toward indium tin oxide (ITO) electrode surface. The autocatalytic biosensing system was further extended for protein detection by advising an aptamer hairpin switch with the use of thrombin as a model analyte. The current developed autocatalytic and homogeneous strategy provided an ultrasensitive electrochemical detection of DNA and thrombin down to the 0.1 and 5 pM level, respectively, with a high selectivity. It should be further used as a general autocatalytic and homogeneous strategy toward the detection of a wide spectrum of analytes and may be associated with more analytical techniques. Thus, it holds great potential for the development of ultrasensitive biosensing platform for the applications in bioanalysis, disease diagnostics, and clinical biomedicine.

Enzyme-free and label-free ultrasensitive electrochemical detection of DNA and adenosine triphosphate by dendritic DNA concatamer-based signal amplification.

Hybridization chain reaction (HCR) strategy has been well developed for the fabrication of various biosensing platforms for signal amplification. Herein, a novel enzyme-free and label-free ultrasensitive electrochemical DNA biosensing platform for the detection of target DNA and adenosine triphosphate (ATP) was firstly proposed, in which three auxiliary DNA probes were ingeniously designed to construct the dendritic DNA concatamer via HCR strategy and used as hexaammineruthenium(III) chloride (RuHex) carrier for signal amplification. With the developed dendritic DNA concatamer-based signal amplification strategy, the DNA biosensor could achieve an ultrasensitive electrochemical detection of DNA and ATP with a superior detection limit as low as 5 aM and 20 fM, respectively, and also demonstrate a high selectivity for DNA and ATP detection. The currently proposed dendritic DNA concatamer opens a promising direction to construct ultrasensitive DNA biosensing platform for biomolecular detection in bioanalysis and clinical biomedicine, which offers the distinct advantages of simplicity and cost efficiency owing to no need of any kind of enzyme, chemical modification or labeling.

Highly sensitive detection of T4 polynucleotide kinase activity by coupling split DNAzyme and ligation-triggered DNAzyme cascade amplification.

In current study, a dual strategy for sensitive detection of T4 polynucleotide kinase (T4 PNK) activity was proposed, which combined split DNAzyme-based background reduction with ligation-triggered DNAzyme cascade for signal amplification. The 8-17 DNAzyme is split into two separate oligonucleotide fragments, which can be separately hybridized to the template DNA to form a ligatable nick after one of the fragments is phosphorylated at the 5at the yl by T4 PNK. With the further addition of Escherichia coli DNA ligase, the two oligonucleotides can be ligated to produce the activated 8-17 DNAzyme, the amount of which is positively related to the activity of T4 PNK. The signal amplification can be achieved through the cyclic cleavage of 8-17 DNAzyme toward the molecular beacon substrate, resulting in an evident fluorescence signal enhancement. The current dual strategy can significantly improve the detection sensitivity of the sensing systems, resulting in a detection limit of 0.001 U mL(-1) for T4 PNK activity, which is superior or comparable to the reported methods. Furthermore, the inhibition effects of adenosine diphosphate and sodium hydrogen phosphate on T4 PNK activity have also been demonstrated with satisfactory results. The current method may be further developed as a universal protocol for monitoring activity and inhibition of nucleotide kinase, and may show the huge potentials in biological process researches, drug discovery, and clinic diagnostics.

Enzyme-free and ultrasensitive electrochemical detection of nucleic acids by target catalyzed hairpin assembly followed with hybridization chain reaction.

An isothermal, enzyme-free and ultrasensitive protocol for electrochemical detection of DNA is proposed based on the ingenious combination of target catalyzed hairpin assembly and hybridization chain reaction (HCR) strategies for two-step signal amplification. The DNA hairpin assembly on the electrode is triggered by target DNA, accompanied by the release of target DNA for the successive hybridization and assembly process. The newly emerging DNA fragment on the electrode after hairpin assembly is further used to propagate the HCR between methylene blue-labeled signal probe and auxiliary probe, inducing a remarkably amplified electrochemical signal. The current dual signal amplification strategy is relatively simple and inexpensive owing to avoid the use of any kind of enzyme or sophisticated equipment. It can achieve a sensitivity of 0.1 fM with a wide linear dynamic range from 1 × 10(-15) to 1 × 10(-10)M and discriminate mismatched DNA from perfect matched target DNA with a high selectivity. The high sensitivity and selectivity make this method a great potential for early diagnosis in gene-related diseases.