Preparation of bimetal-polydopamine organic frameworks with core-shell structure and their application in HER2 detection.

Human epidermal growth factor receptor 2 (HER2) is one of the specific markers of breast cancer, which is of great significance to the early diagnosis and prognosis of breast cancer. Here, a fluorescence biosensor was established to detect HER2 based on the fluorescence resonance energy transfer (FRET) and photoinduced electron transfer (PET) occurring between the bimetal-polydopamine organic framework with core-shell structure Au@PDA@UiO-66 and the Cy5 fluorophore in HER2-Cy5-Apt. Au@PDA@UiO-66 owns high-efficiency fluorescence quenching ability due to its large specific surface area and strong adsorption of single-stranded DNA. When the target appears, the fluorescence recovery space mediated by the target is large, so the proposed biosensor has better sensitivity in theory. Under optimized conditions, the proposed fluorescent biosensor can detect HER2 in a range of 0.005 ng mL-1 to 15 ng mL-1, with an actual detection limit as low as 0.005 ng mL-1. Corresponding selective experiments, reproducible experiments, and spiked experiments performed well, showing its great potential in HER2 detection.

Ultra-fast supercritically solvothermal polymerization for large single-crystalline covalent organic frameworks.

Crystalline polymer materials, e.g., hyper-crosslinked polystyrene, conjugate microporous polymers and covalent organic frameworks, are used as catalyst carriers, organic electronic devices and molecular sieves. Their properties and applications are highly dependent on their crystallinity. An efficient polymerization strategy for the rapid preparation of highly or single-crystalline materials is beneficial not only to structure-property studies but also to practical applications. However, polymerization usually leads to the formation of amorphous or poorly crystalline products with small grain sizes. It has been a challenging task to efficiently and precisely assemble organic molecules into a single crystal through polymerization. To address this issue, we developed a supercritically solvothermal method that uses supercritical carbon dioxide (sc-CO2) as the reaction medium for polymerization. Sc-CO2 accelerates crystal growth due to its high diffusivity and low viscosity compared with traditional organic solvents. Six covalent organic frameworks with different topologies, linkages and crystal structures are synthesized by this method. The as-synthesized products feature polarized photoluminescence and second-harmonic generation, indicating their high-quality single-crystal nature. This method holds advantages such as rapid growth rate, high productivity, easy accessibility, industrial compatibility and environmental friendliness. In this protocol, we provide a step-by-step procedure including preparation of monomer dispersion, polymerization in sc-CO2, purification and characterization of the single crystals. By following this protocol, it takes 1-5 min to grow sub-mm-sized single crystals by polymerization. The procedure takes ~4 h from preparation of monomer dispersion and polymerization in sc-CO2 to purification and drying of the product.

The interplay of Cxcl10+/Mmp14+ monocytes and Ccl3+ neutrophils proactively mediates silica-induced pulmonary fibrosis.

As a fatal occupational disease with limited therapeutic options, molecular mechanisms underpinning silicosis are still undefined. Herein, single-cell RNA sequencing of the lung tissue of silicosis mice identified two monocyte subsets, which were characterized by Cxcl10 and Mmp14 and enriched in fibrotic mouse lungs. Both Cxcl10+ and Mmp14+ monocyte subsets exhibited activation of inflammatory marker genes and positive regulation of cytokine production. Another fibrosis-unique neutrophil population characterized by Ccl3 appeared to be related to the pro-fibrotic process, specifically the "inflammatory response". Meanwhile, the proportion of monocytes and neutrophils was significantly higher in the serum of silicosis patients and slices of lung tissue from patients with silicosis further validated the over-expression of Cxcl10 and Mmp14 in monocytes, also Ccl3 in neutrophils, respectively. Mechanically, receptor-ligand interaction analysis identified the crosstalk of Cxcl10+/Mmp14+ monocytes with Ccl3+ neutrophils promoting fibrogenesis via coupling of HBEGF-CD44 and CSF1-CSF1R. In vivo, administration of clodronate liposomes, Cxcl10 or Mmp14 siRNA-loaded liposomes, Ccl3 receptor antagonist BX471, CD44 or CSF1R neutralizing antibodies significantly alleviated silica-induced lung fibrosis. Collectively, these results demonstrate that the newly defined Cxcl10+/Mmp14+ monocytes and Ccl3+ neutrophils participate in the silicosis process and highlight anti-receptor-ligand pair treatment as a potentially effective therapeutic strategy in managing silicosis.

Surface Plasmon-Enhanced NIR-II Fluorescence in a Multilayer Nanoprobe for Through-Skull Mouse Brain Imaging.

Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds great potential for the accurate visualization of deeply located biological structures in vivo. However, the weak fluorescence of current NIR-II fluorophores remains a long-standing challenge for the ever-growing imaging demand. Here, we describe a surface plasmon-enhanced NIR-II fluorescence strategy by incorporating silica-coated gold nanorods (GNRs) and polymer dots (Pdots) into a multilayer nanostructure. Precise manipulation of the silica spacing layer thickness signifies an optimum distance of 8.6 nm, where an enhancement factor of up to 6.4 is achieved in the NIR-II imaging window. The surface plasmon enhancement approach is successfully extended to several types of Pdots fluorophores with NIR-II emission. We finally perform outer-layer encapsulation and PEGylation for the multilayer probes and demonstrate surface plasmon-enhanced NIR-II fluorescence for mouse brain imaging through the skull, which exhibits a refined signal-to-background ratio and penetration depth as compared to the clinically approved ICG dye.

[Efficacy observation of dysphagia after acute stroke treated with acupuncture and functional electric stimulation].

OBJECTIVE: To observe the impacts on the recovery of swallowing function in patients of dysphagia after acute stroke treated with acupuncture and functional electric stimulation. METHODS: Seventy-four patients were randomized into an acupuncture plus electric stimulation group (38 cases) and an electric stimulation group (36 cases). The functional electric stimulator was used in the two groups. The electric pads were placed on the hyoid bone, the upper part of thyroid cartilage, the masseter muscle and the mandibular joint. The treatment lasted for 30 mm each time. In the acupuncture plus electric stimulation group, acupuncture was supplemented at motor area of Jiao's scalp acupuncture, lower 2/5 of sensory area, Baihui (CV 20), Lianquan (CV 23), Jinjin (EX-HN 12) and Yuye (EX-HN 13), 30 mm each time. The treatment was given once a day, 6 treatments for one session and there was 1 day at interval between the sessions, 4 sessions were required totally in the two groups. The dysphagia scale was adopted for efficacy evaluation before treatment and after 4 sessions of treatment in the two groups. The removal rate of nasal feeding tube was observed after treatment. RESULTS: The dysphagia score was increased apparently after treatment compared with that before treatment in the two groups (both P < 0.05). After treatment, in the acupuncture plus electric stimulation group, the dysphagia score was increased much more apparently than that in the electric stimulation group (8.01 +/- 1.25 vs 6.73 +/- 1.36, P < 0.05). The remarkably effective rate was 84.2% (32/38) in the acupuncture plus electric stimulation group, better than 58.3% (21/36) in the electric stimulation group (P < 0.05). The removal rate of nasal feeding tube was 89.5% (34/38) in the acupuncture plus electric stimulation group, which was higher than 50. 0% (18/36) in the electric stimulation group (P < 0.05). CONCLUSION: Acupuncture combined with electric stimulation achieves the much better efficacy on dysphagia after acute stroke and promotes the early removal of nasal feeding tube. The efficacy is better than that of the simple electric stimulation therapy.