Nanoplasmonic biosensors for multicolor visual analysis of acetylcholinesterase activity and drug inhibitor screening in point-of-care testing.

The monitoring of acetylcholinesterase (AChE) activity and the screening of its inhibitors are significance of the diagnosis and drug therapy of nervous diseases. A metal ions-mediated signal amplification strategy was developed for the highly sensitive and multicolor assay of AChE activity and visually screening its drug inhibitors. After the specific reaction between AChE and acetylthiocholine (ATCh), the hydrolysis product thiocholine (TCh) can directly and decompose the α-FeOOH nanorods (NRs) to release amounts of Fe2+, which was regarded as Fenton reagent to efficiently catalyze H2O2 to produce ·OH. Then, the as-formed ·OH can further largely shorten the gold nanobipyramids (Au NBPs), generating a series of palpable color variations. The linear range for AChE activity was 0.01-500.0 U/L with the limit of detection as low as 0.0074 U/L. The vivid visual effects could be easily distinguished for the multicolor assay of AChE activity by naked eye in visible light. To achieve the point-of-care testing, Au NBPs were further assembled on polymeric electrospun nanofibrous films (ENFs) surface as test strips for the easy-to-use test of AChE activity by RGB values with a smartphone. Fascinatingly, this proposed strategy can be used for the visual screening AChE inhibitors or non-inhibitors. Comparing with the clinical drugs (rivastigmine tartrate, and donepezil), some natural alkaloids such as evodiamine, caffeine, camptothecin, and berberine hydrochloride were selected as inhibitor modes to confirm the drug screening capability of this method. This proposed strategy may have great potential in the other disease-related enzymatic biomarkers assay and the rapid screening of drug therapy.

An electrochemical aptasensor based on intelligent walking DNA nanomachine with cascade signal amplification powered by nuclease for Mucin 1 assay.

Intelligently walking DNA nanomachines have sprung up an upsurge in various nucleic acid testing, but the rapid and sensitive test methods toward disease biomarker proteins based on the signal amplification strategy of DNA nanomachines were still ongoing development. In this work, an electrochemical aptasensor coupling the magnetic separation technique with the nuclease-powered walking DNA nanomachine was established for Mucin 1 (MUC1) detection. The magnetic beads (MBs) were modified by MUC1 aptamer hybridized with blocker DNA probe (BDP). After reacting with MUC1 proteins, the BDP was released from MBs to trigger the opening of capture hairpin DNA on Au nanoparticle (Au NPs)/MXene-modified electrode surface. In the presence of exonuclease III (Exo III), the BDP as a DNA walker is activated to autonomously move on the electrode. Then, lots of residual DNA fragments can still stay on electrode, further hybridizing with hairpin DNA, which can capture more UiO-66-NH2 metal-organic frameworks (MOFs). The amounts of ligands in MOFs can generate enhanced differential pulse voltammetry (DPV) signal probes. Furthermore, the concentrations of MUC1 can convert into the amplified DPV signals by introducing the signal amplification between the BDP as DNA walkers and Exo III as driven forces. This proposed electrochemical aptasensor achieved MUC1 detection ranging from 5 pg/mL to 50 ng/mL with detection limit of 0.72 pg/mL. Consequently, the designed and nuclease-powered walking DNA nanomachine provided an efficient strategy for the quantitative analysis of proteins by the interconversion between protein and BDP as a walker, which exhibited practical applicability of MUC1 detection in human serum.

A visual peroxidase mimicking aptasensor based on Pt nanoparticles-loaded on iron metal organic gel for fumonisin B1 analysis in corn meal.

A visual colorimetric aptasensor combining platinum nanoparticles (Pt NPs) loaded on Fe-based metal organic gel (Fe-MOG) as peroxidase mimics with magnetic separation technique was designed for the detection of fumonisin B1 (FB1). Interestingly, based on the inherent properties of Fe-MOG such as porous nanostructures, abundant Fe2+/Fe3+ active metal centers and synergetic effect between Pt NPs and Fe-MOG, Pt NPs/Fe-MOG composites can be employed as excellent peroxidase mimetic enzyme to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2. This process was accompanied by a color variation of the solution from colorless to blue. Kinetic analysis showed that the Pt NPs/Fe-MOG composites make an effective peroxidase mimic with low Michaelis constant (Km), high substrate binding affinity and rapid catalytic velocity (Vm). Furthermore, the Pt NPs/Fe-MOG based colorimetric aptasensor was used to detect FB1. The prepared Pt NPs/Fe-MOG achieved lower detection limit (2.7 pg/mL, 3σ/k) with a wide linear range of 0.01-2000.0 ng/mL. Finally, as a proof of concept of the rapidity and the simplicity of this colorimetric aptasensor, Pt NPs/Fe-MOG was used for the detection of FB1 in real corn samples.

WSTF acetylation by MOF promotes WSTF activities and oncogenic functions.

Williams syndrome transcription factor (WSTF) is a transcription factor and tyrosine kinase. WSTF overexpression promotes migration and proliferation of various cancers, and Ser158 (WSTFS158) phosphorylation plays an important role in this process. However, the role of the other posttranslational modifications of WSTF is unknown. Here, we report that lysine (K) 426 on WSTF is acetylated by MOF and deacetylated by SIRT1. Mechanistically, male-specific lethal (MSL) 1v1 interaction with WSTF facilitates its interaction with MOF for WSTF acetylation, which in turn promotes WSTFS158 phosphorylation. The kinase and transcriptional regulatory activity of WSTF were enhanced by acetylation. WSTFK426ac levels positively and significantly correlated with tumor size, histological grade, and age. Moreover, we demonstrated that acetylated WSTF promotes cancer cell proliferation, migration, invasion, and tumor formation. In conclusion, we identified the enzymes regulating WSTF K426 acetylation, and demonstrated an acetylation-dependent mechanism that modulates the activities of WSTF and contributes to tumorigenesis. Our findings provide new clues to study WSTF-mediated normal development and disease.

JMJD6 regulates histone H2A.X phosphorylation and promotes autophagy in triple-negative breast cancer cells via a novel tyrosine kinase activity.

Overexpression of Jumonji domain-containing 6 (JMJD6) has been reported to be associated with more aggressive breast cancer characteristics. However, the precise role of JMJD6 in breast cancer development remains unclear. Here, we demonstrate that JMJD6 has intrinsic tyrosine kinase activity and can utilize ATP and GTP as phosphate donors to phosphorylate Y39 of histone H2A.X (H2A.XY39ph). High JMJD6 levels promoted autophagy in triple negative breast cancer (TNBC) cells by regulating the expression of autophagy-related genes. The JMJD6-H2A.XY39ph axis promoted TNBC cell growth via the autophagy pathway. We show that combined inhibition of JMJD6 kinase activity and autophagy efficiently decreases TNBC growth. Together, these findings suggest an effective strategy for TNBC treatment.

[Short-term therapeutic effect of posterior pedicle screw fixation for treatment of degenerative lumbar scoliosis].

OBJECTIVE: To evaluate the short-term outcomes of patients receiving orthopedic surgery with posterior pedicle screw fixation for degenerative lumbar scoliosis. METHODS: Between March, 2006 and August, 2009, 36 patients with degenerative lumbar scoliosis (19 males and 17 females) underwent procedures of decompression, bone implantation and pedicle screw fixation. Fifteen patients were also treated by PLIF and 21 cases received posterior-lateral fusion. The JOA scores, Oswestry disability index (ODI), and Cobb angle were recorded before and after the operation, and the surgical complications were also observed. RESULTS: The JOA scores increased significantly by 83.3% after the operation (P<0.05). The procedures resulted in significantly lowered ODI from (67.1∓11.4)% before the operation to (32.1∓10.8)% after the operation (P<0.01). A significant improvement of the coronal Cobb's angle was achieved after the operation (26.7° preoperatively vs 12.3° postoperatively, P<0.01), and the lordosis angle was improved from 10.7° to 36.6° after the operation (P<0.01). All the patients were followed up for 12 to 50 months (mean 38 months), and no implant loosening, displacement or fragmentation, or pseudarthrosis was found at the final follow-up. CONCLUSION: Posterior pedicle screw fixation shows good short-term therapeutic effect in treatment of degenerative lumbar scoliosis. Individualized surgical plans and adequate preoperative evaluation are keys to successful operations.

[Observation on lower back myofascitis treated with penetration needling on yang meridians of the back and electroacupuncture as compared with Western medication].

OBJECTIVE: To compare the difference in the therapeutic effect on lower back myofascitis between the combined therapy of penetration needling on yang meridian of the back and electroacupuncture and the western medication of Ibuprofen capsules, and probe into a better method of treatment for lower back myofascitis. METHODS: Sixty cases of lower back myofascitis were randomly divided into two groups. 30 cases in observation group were treated with penetration needling combined with electroacupuncture on the back shu points on the first line of the Bladder Meridian and the points of the corresponding levels on the Governor Vessel. 30 cases in control group were treated with Ibuprofen capsules. The treatment session was 30 days. The therapeutic effects were compared and the Visual Analog Scales (VAS) and Oswestry disability index were detected before and after treatment in two groups separately. RESULTS: The total effective rate in observation group was 96.7% (29/30), which was superior to that (73.3%, 22/30) in control group. VAS and Oswestry disability index decreased in either group (P < 0.01, P < 0.05). The improvement extent in observation group was superior to that in control group (P < 0.05). CONCLUSION: The therapy of penetration needling on yang meridian of the back combined with electroacupuncture has the advantageous therapeutic effect on lower back myofascitis as compared with the medication of Ibuprofen capsules, which can release pain and improve the functional disturbance effectively.