A sensitive and stable acetylcholinesterase biosensor with TiO2 nanoparticles anchored on graphitic carbon nanofibers for determination of organophosphate pesticides.

Electrode materials play a central role in assembling biosensors. In this work, a titanium dioxide nanoparticle loaded graphitized carbon nanofiber (TiO2/GNF) composite is prepared for the sensitive detection of organophosphorus pesticide residues (OPs). The TiO2/GNF composite with superior conductivity, catalytic activity and biocompatibility offers an extremely hydrophilic surface for the effective immobilization of acetylcholinesterase (AChE). Furthermore, the Ti atoms of TiO2/GNFs could coordinate with AChE to improve its stability, and TiO2 has a strong adsorption on OPs. The developed AChE/TiO2/GNFs/GCE biosensor showed a high affinity to acetylthiocholine chloride (ATCh) and could catalyze the hydrolysis of ATCh with an apparent Michaelis-Menten constant (Km) of 50 µM. The constructed AChE/TiO2/GNFs/GCE biosensor exhibits a wide detection linear range (1.0 × 10-13 M to 1.0 × 10-8 M) with a low detection limit (3.3 fM) for paraoxon determination (a model of OPs). In addition, the developed biosensor possesses remarkable anti-interference, acceptable reproducibility and good long-term stability, and is successfully used for the determination of OPs in lake water, providing a new strategy for the analysis of OPs in ecological environments.

IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin.

Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1.

Principal component regression-based contrast-enhanced ultrasound evaluation system for the management of BI-RADS US 4A breast masses: objective assistance for radiologists.

A portion of detected breast masses might be overrated by using the Breast Imaging-Reporting and Data System ultrasonography (BI-RADS US) lexicon. A principal component regression-based contrast-enhanced ultrasound (PCR-CEUS) evaluation system was built to quantitatively illustrate whether CEUS could help radiologists to differentiate 4A masses. The PCR-CEUS evaluation system, based on principal component analysis (PCA) and logistic regression, was verified by random assignment into training and test sets and shown to reduce the data dimension and avoid collinearity in CEUS variables. This prospective study consecutively collected 238 patients with 238 4A masses confirmed pathologically. All enrolled patients accepted CEUS examination. The diagnostic performance of senior and junior radiologists, PCR-CEUS and combined methods was compared. The PCR-CEUS system had consistent diagnostic performance in both the training and test sets, with an area under the curve (AUC) of 0.831 (0.765-0.897), 0.798 (0.7034-0.892) and 0.854 (0.765-0.943) (all P > 0.05). The AUC of the combined diagnostic model (PCR-CEUS + Senior radiologists) was higher than that of senior radiologists, and the combined model had higher sensitivity (0.875 (0.781-0.969) vs. 0.729 (0.603-0.855)) without compromising specificity. Furthermore, the AUC and specificity of the combined model (PCR-CEUS + Junior radiologists) (0.852 (0.787-0.916)) was higher than that of junior radiologists (0.665 (0.592-0.737) (P < 0.00001)). PCR-CEUS demonstrated good ability in differentiating malignant BI-RADS-US 4A masses and was helpful for both senior and junior radiologists.

A retrospective study of reducing unnecessary thyroid biopsy for American College of Radiology Thyroid Imaging Reporting and Data Systems 4 assessment through applying shear wave elastography

ABSTRACT Objective The purpose of the study is to quantitatively assess shear-wave elastography (SWE) value in American College of Radiology Thyroid Imaging Reporting and Data Systems (ACR TI-RADS) 4. Materials and methods One hundred and fifty-two ACR TI-RADS 4 thyroid nodules undergoing SWE were included in the study. The mean (EMean), minimum (EMin) and maximum (EMax) of SWE elasticity were measured. Results The areas under the receiver operating characteristic (ROC) curves for SWE EMean, EMin and EMax in detecting benign and malignant nodules were 0.95, 0.83 and 0.84, respectively. Cut-off value of EMean ≤ 23.30 kPa is able to downgrade the lesion category to ACR TI-RADS 3 and cut-off value of EMean ≥ 52.14 kPa is able to upgrade the lesion category to ACR TI-RADS 5. Conclusions The EMean of SWE will probably identify nodules that have a high potential for benignity in ACR TI-RADS 4. It may help identify and select benign nodules while reducing unnecessary biopsy of benign thyroid nodules.

A retrospective study of reducing unnecessary thyroid biopsy for American College of Radiology Thyroid Imaging Reporting and Data Systems 4 assessment through applying shear wave elastography.

Objective The purpose of the study is to quantitatively assess shear-wave elastography (SWE) value in American College of Radiology Thyroid Imaging Reporting and Data Systems (ACR TI-RADS) 4. Materials and methods One hundred and fifty-two ACR TI-RADS 4 thyroid nodules undergoing SWE were included in the study. The mean (EMean), minimum (EMin) and maximum (EMax) of SWE elasticity were measured. Results The areas under the receiver operating characteristic (ROC) curves for SWE EMean, EMin and EMax in detecting benign and malignant nodules were 0.95, 0.83 and 0.84, respectively. Cut-off value of EMean ≤ 23.30 kPa is able to downgrade the lesion category to ACR TI-RADS 3 and cut-off value of EMean ≥ 52.14 kPa is able to upgrade the lesion category to ACR TI-RADS 5. Conclusions The EMean of SWE will probably identify nodules that have a high potential for benignity in ACR TI-RADS 4. It may help identify and select benign nodules while reducing unnecessary biopsy of benign thyroid nodules.

Comprehensive analysis of competing endogenous RNA networks associated with cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the second most common type of primary malignancy of the liver. Certain long non-coding RNAs (lncRNAs) have been demonstrated to have key roles in tumor pathogenesis by binding to microRNAs (miRNAs). However, the competing endogenous RNA (ceRNA) network of CCA remains to be fully determined. In the present study, the RNA expression profiles for CCA were downloaded from The Cancer Genome Atlas and further analyzed. A total of 318 differentially expressed (DE) lncRNAs, 87 DE miRNAs and 3,851 DE mRNAs were identified from 36 CCA samples and 9 adjacent non-tumor samples (for lncRNAs and miRNAs, fold change ≥2.5 and P<0.01; for mRNAs, fold change ≥2 and P<0.01). Further bioinformatics analyses were performed and the ceRNA network for CCA was constructed, which included 16 lncRNAs, 55 miRNAs and 373 mRNAs. Survival analysis of all genes in the network revealed that high expression of the mRNAs fucosyltransferase 4 (P<0.005) and huntingtin-interacting protein 1 related (P<0.001) has a positive impact on the overall survival of patients with CAA. Furthermore, the lncRNAs H19 and PVT1, and the miRNAs Homo sapiens (hsa)-miR-16-5p and hsa-miR-424-5p, together with peroxisome proliferator-activated receptors, may also have important roles in the pathogenesis of CCA. The present study provided data to further the understanding of and research into the molecular mechanisms implicated in CCA.

Is ultrasound combined with computed tomography useful for distinguishing between primary thyroid lymphoma and Hashimoto's thyroiditis?

INTRODUCTION: The aim of the study is to investigate the usefulness of ultrasound combined with computed tomography (CT) for distinguishing between primary thyroid lymphoma (PTL) and Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: The investigation was conducted retrospectively in 80 patients from January 2000 to July 2018. All patients underwent pathological tests to be classified into one of two groups: PTL group and HT group. The cut-off value of CT density was determined using receiver-operating characteristic (ROC) curve analysis. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of diagnosis for thyroid by CT alone, ultrasound alone, and the combination of CT plus ultrasound were calculated. RESULTS: Of the 80 study patients, 27 patients were PTL and 53 patients were HT. Mean CT density had a sensitivity of 90.6% and a specificity of 88.9% at a cut-off value of 53.5 HU, with area under the curve (AUC) 0.88. Ultrasound combined with CT had the highest specificity, accuracy, and PPV compared with CT alone and ultrasound alone (p value < 0.05). CONCLUSIONS: Features such as extremely hypoechogenicity, enhanced posterior echo, cervical lymphadenopathy in ultrasound image, and linear high-density strand signs, and very low density in CT imaging have high sensitivity and specificity in thyroid lymphoma. Therefore, ultrasound combined with CT may be useful for distinguishing between PTL and HT.

Development of different deep eutectic solvent aqueous biphasic systems for the separation of proteins.

In this work, aqueous biphasic systems (ABSs) formed by different deep eutectic solvents (DESs) were prepared and applied to extract proteins. The five kinds of DESs comprised amino acids and polyols ([amino acids][polyols]). They were combined with another DES resulting from tetrabutylammonium chloride and polypropylene glycol 400 ([TBAC][PPG400]) to form ABSs. The phase-forming abilities of [TBAC][PPG400]/[amino acids][polyols] were compared with those of [TBAC][PPG400]/amino acids and [TBAC][PPG400]/polyols. The results exhibited that the biphasic formation ability of [amino acids][polyols] lies between those of amino acids and polyols when [TBAC][PPG400] acts as the other phase in ABSs. The systems comprising [TBAC][PPG400] and [l-proline][xylitol] ([Pro][Xyl]) were further investigated to optimize the extraction performance. It was found that 97.30% chymotrypsin tended to distribute into the [Pro][Xyl]-rich phase under optimum conditions. The practical application of the system was demonstrated by the extraction of chymotrypsin from porcine pancreas. Besides, UV-Vis spectrophotometry (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), and circular dichroism (CD) spectroscopy proved that the conformation of proteins remained unchanged during the extraction process. The extraction mechanism of the formation of DES-protein aggregates was investigated via conductivity, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The overall results suggest that the DES/DES-based ABSs have outstanding potential in the green extraction of proteins.