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Granular cell tumor (GCT) is a benign neuroectodermal tumor typically in the dermis or subcutis, although deep soft tissues and organs are occasionally involved. Multifocal GCTs are estimated to occur as many as 10% of patients. A 40-year-old female presented with multiple GCTs asynchronously involving various body sites including gastrointestinal, gynecologic, breast, urinary, and soft tissue systems. Pathologic examinations suggested benign GCTs. TruSight Tumor 170 next-generation sequencing (NGS) analysis performed on four resected tumors revealed subclonal mutation of PIK3CA p.H1047R identified in the esophageal GCT but not in the right vulva or the two cecal GCTs, suggesting that each is a primary tumor with a distinct genetic profile, rather than metastasis. PIK3CA p.H1047R is a common mutation in many cancers. Our benign GCT case demonstrates PIK3CA mutation with a low mutant allele frequency of 7%, which may represent an evolving subclone and might confer a more aggressive behavior.

Application of nanotechnology to detection can effectively increase the biocompatibility of detection sensors. However, since the traditional signal output element has a high background value, the ...

Isothermal amplification, such as hybridization chain reaction (HCR), is a simple and reliable method for detecting signal amplification. However, the hairpin in HCR will not fully participate in the reaction. And after the hairpin is opened, the distance between the fluorophore and the quencher does not change much. Therefore, the signal magnification is limited. Here, we designed a new isothermal amplification method named hybridization assemble nicked displacement amplification (HANDA), combining HCR and strand displacement amplification (SDA) ingeniously. HANDA first triggers HCR through the target sequence to form long double-strand DNA (dsDNA) with gaps. Then SDA is performed from the gap to obtain a large amount of single-stranded DNA (ssDNA), so as to achieve the purpose of double signal amplification. The base sequence of DNA hairpin had also been optimized. The best sequence design rule was found and had universal applicability. We have demonstrated that HANDA combined with DNA barcodes can be used for trace detection of ricin. This new isothermal amplification method provides an effective and universal platform for the trace detection of various toxic substances.

BACKGROUND: Transbronchial forceps biopsy is the widely accepted modality for obtaining tissue specimens for the evaluation of unexplained lung parenchymal abnormalities. However, cryoprobe biopsy provides large specimen sizes and higher yield performance. Utilization of cryoprobe biopsy remains limited by its need to be performed under rigid bronchoscopy and subsequent required operator expertise. We evaluated whether a larger, 2.8 mm forceps could be utilized for parenchymal biopsies. A larger size would surrogate the cryoprobe’s large sample size and forceps mechanism to obviate the need for rigid bronchoscopy and its requirement for removing the sample en bloc. METHODS: This prospective, randomized controlled, single-blinded porcine study compared a 1.9 mm cryoprobe, a 2.4 mm cryoprobe, and a 2.8 mm forceps. Assessment of histopathologic quality, sample quality and surface area, attempts to retrieve specimen samples, fluoroscopy activation time, overall procedural time, and complications were compared. RESULTS: Although cryoprobe yielded larger specimens, there was no statistical difference amongst all tools with respect to alveolar tissue surface area. There was bleeding on all cryoprobe biopsies. No bleeding was observed with forceps. Out of 32 potential combinations of interventions for bleeding control, 18 (56.3%) were made. There was no significant difference in sample quality between all three modalities. There was one pneumothorax in the forceps arm. CONCLUSIONS: Large forceps (LF) biopsy is a feasible technique while providing high diagnostic yield without the need for advanced therapeutic tools. Human studies are needed to further corroborate this technique.

Bisphenol A (BPA) is a typical environmental endocrine disruptor that can migrate into organisms through skin contact, breathing, diet and various other approaches. The reproductive toxicity and neurotoxicity of BPA has been confirmed by several toxicological studies. However, the neurotoxicity of BPA is still controversial. In the present study, we used PC12 cells as a model to investigate the mechanism of BPA-induced neuronal apoptosis. BPA exposure reduced cell viability, altered cell morphology and aggravated intracellular Lactate dehydrogenase (LDH) release, intracellular Ca2+ concentration, Reactive oxygen species (ROS) levels, apoptosis and the reduction in the mitochondrial transmembrane potential (ΔΨm). Moreover, the results of the Western blot (WB) and Real-time quantitative polymerase chain reaction (RT-qPCR) assays indicated that the expression levels of Nur77 in the BPA group were down-regulated and accompanied by the downregulation of the NF-κb/Bcl-2 proteins and the upregulation of cleaved-caspase 3, which is a marker of apoptosis. However, these changes were significantly reversed with the upregulation of the Nur77 protein by introducing plasmids carrying the nur77 gene. These results indicated that BPA-induced apoptosis was closely related to Nur77-mediated inhibition of the NF-κb/Bcl-2 pathway.

The abuse of antibiotics leads to an increase in resistant strains, which in turn leads to the development of superbugs that pose great difficulties for the treatment of human diseases. A high-throughput and highly sensitive avidin biotin complex immunosorbent assay based on upconversion nanoparticles controllable assembly (ABC-ULISA) for the detection of antibiotics was developed, which enabled accurate quantitative detection in a shorter period of time. Streptavidin and biotin-labeled upconversion nanoparticles form avidin-biotin-upconversion complex, which was then combined with biotinylated antibody to achieve double amplification of the signal, further improving detection sensitivity. Upconversion nanoparticles with 808 nm excitation provide better penetration without the need for an external source. The 96-well enzyme-linked plate was used as a detection platform to meet the high-throughput needs. ABC-ULISA was used to simultaneously detect three antibiotics with a limit of detection of 0.15 ng/mL for sulfamethazine, 0.03 ng/mL for sarafloxacin, and 0.05 ng/mL for tetracycline. The detection limit of ABC-ULISA was much lower than the traditional ELISA and ordinary ULISA. Moreover, ABC-ULISA was also versatile, and the corresponding target can be detected by changing different antibodies. The results were stable and reliable, and the equipment could be miniaturized, which was expected to be commercialized and on-site.

Surface siloxane (3-aminopropyl triethoxysilane hydrolyzates)-modified silica materials were used as "initiators", which resulted in the release and desorption of intact molecules adsorbed on the surface of a matrix. A covalently cross-linked MIL-53(Al) material was used to enhance the ionization of analytes. Herein, we have provided an efficient matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) matrix strategy, which responded to both ion and laser irradiation with low background interference in the low-molecular-weight (MW) region. The matrixes MIL-53(Al), SBA-15@APTES, SiO2@APTES, SBA-15@APTES@MOF, and SiO2@APTES@MOF were synthetized and used for the analysis of a series of low-MW compounds to verify the effectiveness of the strategies. Compared to conventional matrixes, the surface-modified SBA-15@APTES@MOF and SiO2@APTES@MOF had low background, high sensitivity, extensive applicability, good stability, and ultrahigh tolerance of salt concentrations. The detection limits of standard analytes were determined to range from 0.1 to 1 × 10-5 mg/mL for 16 amino acids as well as citric acid, reserpine, tetraethylammonium chloride, melamine, bisphenol A, and malachite green. These results could help in designing more efficient nanostructure-initiator materials and further promote the application of MALDI-TOF MS.

A rapid and ultrasensitive method for colourimetric/photothermal dual-readout detection was developed using an 808 nm NIR laser and a thermal imaging app on mobile phone. Norfloxacin was used as a model contaminant to demonstrate this universal rapid detection method. It is innovatively, to use the advanced two-dimensional material black phosphorus as a colourimetric/photothermal reagent for the first time. The samples were added to the strip, and the analytes were selectively captured on the conjugate pad by monoclonal antibody-modified magnetic/upconversion nanocomposites. The samples flowed through the strips by capillary action until reaching the control line, where immune complex formation occurred due to the presence of secondary antibody. The added black phosphorus could be captured by the the antigens which were directly exposed to the test line and a brown band could be observed by naked eye. Upon illumination by NIR light for 1 min, the real-time temperature is obtained for quantitative analysis through the thermal imaging performed by mobile phone camera. This method can achieve the detection of norfloxacin in water samples within 20 min, and the detection limits of colorimetric and photothermal readout can reach 45 pg mL-1. Compared with conventional strips, this method provided an increased sensitivity by about two orders of magnitude, with a integrated portable laser and a mobile phone. It is a valuable method for rapid detection and can be applied to other environmental contaminants as well.

A highly selective and sensitive method for Cd(II) detection was developed based on aptamer and gold nanoparticles (AuNPs) combined with a colorimetric smartphone readout. The experimental conditions such as reaction time of polydiene dimethyl ammonium chloride (PDDA) and AuNPs, PDDA dose, time of aptamer and PDDA incubation, and aptamer concentration were optimized. Under the optimized conditions, the color and red(R) value of the solution was concentration-dependent on Cd(II). The proposed method exhibited a linear range of 1&ndash, 400 ng/mL (r2 = 0.9794) with a limit of detection (LOD) of 1 ng/mL. This method had been successfully applied to test and quantify Cd(II) in water and rice samples, and the results were in full agreement with those from the atomic absorption spectrometer. Therefore, low-cost colorimetry demonstrated its potential for practical application in visual or quantitative detection with a smartphone. This approach can be readily applied to other analytes.

D2-40 is a recently available mouse monoclonal antibody specific for human podoplanin and has been used in identifying lymphovascular invasion (LVI) of tumors. Although its expression has been evaluated in other tissues, its use as a marker for myoepithelial cells (MEC) of breast has not been studied. To explore its expression in the MEC of breast, paraffin-embedded tissue blocks from 48 patients with breast diseases were selected to include usual ductal hyperplasia (UDH, 41 cases), atypical ductal hyperplasia (ADH, 4 cases) and ductal carcinoma in situ (DCIS, 17 cases). Normal breast parenchyma and invasive carcinoma coexisting in the tissue sections were also included in the study. Immunohistochemistry for D2-40, calponin and p63 was performed and the staining patterns were reviewed and compared. D2-40 immunohistochemical staining is positive in the cytoplasm of MEC in UDH, ADH, and the majority of DCIS. The staining pattern of D2-40 is comparable with that of calponin, however D2-40 staining of MEC is weaker than that of calponin and with less background. In addition, myoepithelial cells and myofibroblasts at the edge of retraction spaces of DCIS are also stained by D2-40 that could be misinterpreted as tumor LVI. In conclusion, D2-40 immunohistochemistry reliably identifies the MEC of breast in a variety of lesions in a pattern similar to that of calponin and p63, and can be used as an additional MEC marker. Caution should be exercised when interpreting the staining of cells surrounding DCIS and carcinoma with retraction artifact.