Flexible DNA Nanoclaws Offer Multivalent and Powerful Spatial Pattern-Recognition for Tumor Cells.

Multivalent receptor-ligand interactions (RLIs) exhibit excellent affinity for binding when targeting cell membrane receptors with low expression. However, existing strategies only allow for limited control of the valency and spacing of ligands for a certain receptor, lacking recognition patterns for multiple interested receptors with complex spatial distributions. Here, we developed flexible DNA nanoclaws with multivalent aptamers to achieve powerful cell recognition by controlling the spacing of aptamers to match the spatial patterns of receptors. The DNA nanoclaw with spacing-controllable binding sites was constructed via hybrid chain reaction (HCR), enabling dual targeting of HER2 and EpCAM molecules. The results demonstrate that the binding affinity of multivalent DNA nanoclaws to tumor cells is enhanced. We speculate that the flexible structure may conform better to irregularly shaped membrane surfaces, increasing the probability of intermolecular contact. The capture efficiency of circulating tumor cells successfully verified the high affinity and selectivity of this spatial pattern. This strategy will further promote the potential application of DNA frameworks in future disease diagnosis and treatment.

Application of microfluidic technologies on COVID-19 diagnosis and drug discovery.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has boosted the development of antiviral research. Microfluidic technologies offer powerful platforms for diagnosis and drug discovery for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis and drug discovery. In this review, we introduce the structure of SARS-CoV-2 and the basic knowledge of microfluidic design. We discuss the application of microfluidic devices in SARS-CoV-2 diagnosis based on detecting viral nucleic acid, antibodies, and antigens. We highlight the contribution of lab-on-a-chip to manufacturing point-of-care equipment of accurate, sensitive, low-cost, and user-friendly virus-detection devices. We then investigate the efforts in organ-on-a-chip and lipid nanoparticles (LNPs) synthesizing chips in antiviral drug screening and mRNA vaccine preparation. Microfluidic technologies contribute to the ongoing SARS-CoV-2 research efforts and provide tools for future viral outbreaks.

Multiplex immunoassays reveal increased serum cytokines and chemokines associated with the subtypes of achalasia.

BACKGROUND: Achalasia is an esophageal motility disorder with unknown etiology. Previous findings indicate that immune-mediated inflammatory process causes inhibitory neuronal degeneration. This study was designed to evaluate levels of serological cytokines and chemokines in patients with achalasia. METHODS: We collected information from forty-seven patients with achalasia who underwent peroral endoscopic myotomy. Control samples were collected from forty-seven age- and sex-matched healthy people. The concentrations of serological cytokines and chemokines were analyzed by Luminex xMAP immunoassay. Serological and clinical data were compared between groups. KEY RESULTS: Compared with healthy controls, achalasia patients had significantly increased concentrations of eleven cytokines and chemokines, namely, TGF-ß1 (P < .001), TGF-ß2 (P < .001), TGF-ß3 (P < .001), IL-1ra (P < .001), IL-17 (P = .005), IL-18 (P < .001), IFN-γ (P < .001), MIG (P < .001), PDGF-BB (P < .001), IP-10 (P = .003), and SCGF-B (P < .001). Gene ontology (GO) and network functional enrichment analysis revealed regulation of signaling receptor activity and receptor-ligand activity were the most related pathways of these cytokines and chemokines. Levels of twelve cytokines and chemokines were significantly increased in type III compared with I/II achalasia, namely, TGF-ß2, IL-1ra, IL-2Ra, IL-18, MIG, IFN-γ, SDF-1a, Eotaxin, PDGF-BB, IP-10, MCP-1, and TRAIL. CONCLUSIONS AND INFERENCES: Patients with achalasia exhibited increased levels of serological cytokines and chemokines. Levels of cytokines and chemokines were significantly increased in type III than in type I/II achalasia. Cytokines and chemokines might contribute to the inflammatory development of achalasia.

Expression and correlation analysis of RegIV and vascular endothelial growth factors (VEGF-A and VEGF-C) in metastatic spinal tumors.

The expression and correlation analysis of the regenerating gene family member 4 (RegIV) and vascular endothelial growth factors (VEGF-A and VEGF-C) in metastatic spinal tumors were studied. Fifteen patients with metastatic spinal tumors who underwent operation in our hospital from January 2011 to January 2013 were selected into this study. The expression level of tumor tissues in patients with spinal metastasis and RegIV, VEGF-A and VEGF-C of the corresponding paracancer normal tissue samples were evaluated by immunohistochemical staining method and the correlation between the expression of RegIV, VEGF-A and VEGF-C was analyzed. qRT-PCR results showed that the expression of RegIV was increased (P<0.05) in paracancer normal tissues and spinal metastatic tumor tissues. Compared with normal tissues, expression of RegIV, VEGF-A and VEGF-C was higher in metastatic spinal tumor tissues and the difference had statistical difference (P<0.05). Spearman's correlation analysis showed that the expression of RegIV was positively correlated with VEGF-A (r=0.683, P<0.05); the expression of RegIV positively correlated with VEGF-C (r=0.717, P<0.05). Cox regression analysis showed that RegIV, VEGF-A, VEGF-C expression and microvessel density counts are prognostic factors affecting spine metastasis (P<0.05), RegIV expression affected the survival of patients with relative risk. The high expression of RegIV in spinal metastatic tumors may promote the expression of VEGF-A and VEGF-C to increase the microvascular density, promote angiogenesis, and accelerate the occurrence and progression of spinal metastatic tumors.

Reversed Z-plasty and its variations to release wide-scar contraction.

BACKGROUND AND AIM: Z-plasty is one of the most widely used techniques in plastic and reconstructive surgery. It is useful especially to release linear-scar contractures, yet difficult to use for wide scars. The aim of this study was to report on a new technique for the effective release of contractures for wide scars using reversed Z-plasty and its variations. METHODS: This report describes a novel technique to release contractures effectively for wide scars using reversed Z-plasty and its variation. The design is a reverse style of conventional Z-plasty. In our case series, the reversed three-flap, four-flap Z-plasty or its variation was chosen depending on the width of the contracted scar. RESULTS: We performed this technique on 28 patients. All wounds healed well and the scar contracture was satisfactorily released. CONCLUSION: This procedure is useful and practical for wide-scar contractures.