Biomass-derived magnetic nanocomposites modified by choline chloride/citric acid based natural deep eutectic solvents for the magnetic solid phase extraction of trypsin.

A novel biomass-derived magnetic nanocomposite of Fe3O4-Chitin@NADES-CC composed of a natural deep eutectic solvent (NADES), biological polysaccharide (Chitin) and magnetic Fe3O4 was synthesized. After being systematically characterized by Fourier transform infrared spectrometry, thermogravimetry, vibrating sample magnetometry, X-ray diffraction, transmission electron microscopy and dynamic light scattering, Fe3O4-Chitin@NADES-CC was used as an extractant to separate trypsin (Tryp) on the basis of magnetic solid phase extraction. Simultaneously, the extraction conditions of Fe3O4-Chitin@NADES-CC for Tryp were investigated in turn by single-factor experiments, including screening the types of extractants, the initial concentration of Tryp, the pH value of the solution, the influence of ionic strength, extraction time and temperature, etc. Under the optimal conditions, the extraction capacity of Fe3O4-Chitin@NADES-CC for Tryp could reach up to 1082.67 mg g-1. Adsorption isotherm tests certified that the Langmuir adsorption equilibrium fitted well with the extraction model in this study, which showed that the extraction of Fe3O4-Chitin@NADES-CC for Tryp was monolayer adsorption. In addition, in the sections on the regeneration-reuse, selectivity and methodological studies, all the results exhibited the superiority of the Fe3O4-Chitin@NADES-CC and Tryp separation strategy which has been established in this work. Finally, Fe3O4-Chitin@NADES-CC was ultimately applied to the separation of Tryp from a real bovine pancreas crude extract by the analysis of SDS-PAGE. All the above results highlight that the proposed Fe3O4-Chitin@NADES-CC biomass-derived magnetic nanocomposite can be applied in the field of protein purification.

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.

Specific recognition of protein by deep eutectic solvent-based magnetic ß-cyclodextrin molecularly imprinted polymer.

A magnetic ß-cyclodextrin (MCD) surface molecularly imprinted polymer (MIP) based on deep eutectic solvents (DESs) as cross-linker and functional monomer (MCD@DES-MIP) was successfully synthesized for the specific recognition of bovine hemoglobin (BHb). The adsorption behavior of MCD@DES-MIP for BHb was investigated by adsorption thermodynamics, adsorption kinetics, and pH control experiments. The maximum adsorption capacity of MCD@DES-MIP for BHb under the optimized conditions was 195.94 mg g-1 and the imprinting factor was 4.68. In addition, the competitive adsorption experiments demonstrated that MCD@DES-MIP showed excellent selective extraction ability for BHb in the binary mixture of BHb and bovine serum albumin (BSA). The actual sample analysis manifested that MCD@DES-MIP effectively separated BHb from complex samples. The results of circular dichroism spectra proved that the secondary structure of BHb did not change during elution. The result indicated that MCD@DES-MIP can be used as a new imprinting material for the separation and purification of BHb.Graphical abstract Magnetic imprinted microspheres (MCD@DES-MIP) were prepared by free radical polymerization using magnetic ß-cyclodextrin (MCD) as carrier, deep eutectic solvents (DESs) as functional monomer and cross-linker. MCD@DES-MIP show high adsorption capacity and excellent selectivity for BHb.

A green deep eutectic solvent modified magnetic titanium dioxide nanoparticles for the solid-phase extraction of chymotrypsin.

Magnetic titanium dioxide nanoparticles modified with green deep eutectic solvent (DES) composed of choline chloride (ChCl) and xylitol (Xyl) (Fe3O4@TiO2@[ChCl][Xyl]) were synthesized and applied to the solid-phase extraction(MSPE) of chymotrypsin (Chy). The physicochemical properties and morphology of Fe3O4@TiO2@[ChCl][Xyl] was characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), Zeta potential, X-ray diffraction (XRD), vibrating sample magnetometer (VSM) and transmission electron microscope (TEM). The experiment parameters such as initial concentration of Chy, extraction time, pH value, ionic strength, extraction temperature and sample matrix were effectively optimized. Under the optimal experimental conditions, the extraction capacity of Fe3O4@TiO2@[ChCl][Xyl] obtained a significantly improvement after the modification of Fe3O4@TiO2 nanoparticles by [ChCl][Xyl], and reached up to 347.8 mg g-1. In the elution experiment, 10% sodium dodecyl sulfate-acetic acid (SDS-HAc) was used as eluent, achieving an elution rate of 85.9% for the Chy on Fe3O4@TiO2@[ChCl][Xyl]. And the Fe3O4@TiO2@[ChCl][Xyl] still maintained a good extraction capacity for Chy after six times of reuse. The application result in the extraction of Chy from porcine pancreas crude extract showed a good practical application ability for Chy extraction. All the results indicated that the synthesized Fe3O4@TiO2@[ChCl][Xyl] has good application potential in the extraction of biomolecular molecules such as protein.

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.

Preparation of a double-network hydrogel based on wastepaper and its application in the treatment of wastewater containing copper(ii) and methylene blue.

To reclaim and utilize wastepaper (WP), a WP/acrylamide double-network hydrogel (WP/PAM) was prepared to transform WP into efficient adsorbent for heavy metals and dye wastewater treatment. The structure and properties of the WP/PAM were characterized systematically by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), swelling performance (SR), Fourier transform infrared spectrum (FTIR), and X-ray photoelectron spectroscopy (XPS). Batch experiments showed that the adsorption process of Cu(ii) and MB followed the pseudo-second-order kinetic model and the Langmuir model. The maximum adsorption capacities of the WP/PAM for Cu(ii) and MB were 142.2 mg g-1 and 1714.5 mg g-1, respectively. The adsorption mechanism of Cu(ii) on the WP/PAM was related to ion exchange and complexation, while MB adsorption was driven by hydrogen bonding and electrostatic interaction. Besides, the WP/PAM performed well in treating simulated wastewater. The regeneration test indicated that the WP/PAM could be successfully reused after 6 cycles. This work provided an alternative choice for the recycling of WP and produced a potential adsorbent for the dye and heavy metals wastewater treatment.

Hydroxyapatite modified sludge-based biochar for the adsorption of Cu2+ and Cd2+: Adsorption behavior and mechanisms.

This study prepared sewage sludge, a municipal solid waste, into a biochar modified by hydroxyapatite (HAP) as a new and efficient absorbent (HAP-SSBC) for removal of Cu2+ and Cd2+ from aqueous solution. Adsorption experiment revealed that HAP-SSBC exhibited significantly higher adsorption performance than raw sludge-based biochar (SSBC). At 298.15 K, the maximum adsorption capacity of Cu2+ and Cd2+ via Langmuir model were 89.98 and 114.68 mg/g, respectively. Adsorption kinetic experiment revealed that chemisorption was the main reaction. Analysis of X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectrum (XPS) further confirmed that the main mechanisms were ion exchange with Ca2+, complexion by -OH and -COOH, and forming Cu-π or Cd-π binding with aromatic CC on HAP-SSBC surface. Overall, combing HAP and SSBC to be a new adsorbent is beneficial to the resource utilization of sludge and shows a good prospect for heavy metal removal in aqueous solution.

A novel"turn-off"fluorescence assay based on acid-copper nanoclusters in deep eutectic solvent micelles for co-aggregation inducing fluorescence enhancement and its application.

As mixtures, deep eutectic solvent (DES) is designability. By adjusting the long alkyl chain hydrogen bond acceptors (HBAs) or hydrogen bond donors (HBDs), the DES displays surfactant characteristics and can form micelles. Hence, a novel, simple, facile and green natural organic acids capped copper nanoclusters (Aci-CuNCs) was synthesized and the spectrum behavior of Aci-CuNCs in DES micelles was researched. It was found that the surfactant-like DES can form micellar co-aggregation with Aci-CuNCs, resulting in the fluorescence (FL) intensive of Aci-CuNCs increase. Corresponding performance of spectral properties of Aci-CuNCs in DES medium were systematically studied by fourier transform infrared spectrometer, 3D FL spectroscopy, FL emission/excitation spectra, ultraviolet absorption spectroscopy. In the mechanism exploration part, on the one hand, the existence of micellar co-aggregation was confirmed by the conductivity, the mass effect of DES, dynamic light scattering and transmission electron microscopy. On the other hand, the influence of different kinds of DESs (types of HBAs/HBDs, molar ratio) and some possible factors (ionic strength and temperature) were discussed in detail to investigate the main driving forces for the formation of micellar co-aggregates. The results of mechanism exploration prove that the long alkyl chain of DES is amphiphilic which can form micellar co-aggregation with Aci-CuNCs through hydrogen bonding. The DES micelle provides Aci-CuNCs with a relatively stable and closed micro-environment which can effectively prevent collisions with water molecules and weakening of fluorescence intensity. On the basic of the above research, a "turn-off" fluorimetric method based on Aci-CuNCs in DES medium was applied for the determination of Fe3+. Under the optimum conditions, the assay worked in the Fe3+ concentration ranges from 1 to -20 µM and had a detection limit of 0.0374 µM. Method validation study illustrates the proposed system can provide a good accuracy, repeatability and stability conditions. Furthermore, the real sample analysis result demonstrates that no obvious matrix effect is found. As a consequence, the FL assays (Aci-CuNCs-based DES) composed of natural organic acid capped CuNCs and green solvent DES provides a simple, gentle and environmentally friendly method for the detection of iron ions.

A deep eutectic solvent modified magnetic ß-cyclodextrin particle for solid-phase extraction of trypsin.

An environmentally friendly deep eutectic solvent (DES) composed of trifluoroacetamide and benzyltrimethylammonium chloride modified ß-cyclodextrin (CD) grafted magnetic beads (MB-NH2@CD@DES) were synthesized for the first time and applied to the solid-phase extraction of trypsin. Among the five trypsin extractants prepared in this work (MB, MB-NH2, MB-NH2@CD, MB-NH2@DES, MB-NH2@CD@DES), the extractant MB-NH2@CD@DES with higher extraction capacity for trypsin was selected as final extractant. The extraction capacity of MB-NH2@CD@DES for trypsin can reach up to 549.87 mg⋅g-1 under the optimized conditions. The Langmuir adsorption equilibrium was found fitted better with equilibrium relation between MB-NH2@CD@DES and trypsin than Freundlich adsorption equilibrium. And a superior extraction for trypsin was verified by comparing the extraction capacity of MB-NH2@CD@DES for trypsin and four other common proteins. Compared with some reported trypsin extractants, the MB-NH2@CD@DES had a shorter extraction process, higher extraction capacity, more convenient operation of separation, a safer and more environmentally friendly synthesis process. With the optimized eluent, a great elution rate (74.32%) of trypsin was achieved. The absolute recovery of trypsin in trypsin standard solution was calculated to be 16.8%. And the extraction capacity of MB-NH2@CD@DES toward trypsin still maintained well after ten times recycling and reuse. The detection limit (LOD) and quantitative limit (LOQ) were 0.072 mg⋅mL-1 and 0.240 mg⋅mL-1 respectively. By sodium dodecyl sulfate polyacrylamide gel electrophoresis experiment, the extraction ability of MB-NH2@CD@DES to trypsin from real sample was fully demonstrated. All above results showed the potential of fabricated MB-NH2@CD@DES as a superior extractant for trypsin from real complex samples.

A new magnetic molecularly imprinted polymer based on deep eutectic solvents as functional monomer and cross-linker for specific recognition of bovine hemoglobin.

A novel magnetic molecularly imprinted polymer only based on deep eutectic solvents (DESs-MMIP) was successfully synthesized. The DESs-MMIP was constructed by using 2-hydroxyethyl methacrylate/tetrabutylammonium chloride deep eutectic solvent (DES1) as functional monomer, arylamide/(3-acrylamidopropyl) trimethylammonium chloride deep eutectic solvent (DES2) as cross-linker and bovine hemoglobin (BHb) as template through surface imprinting technology. The obtained DESs-MMIP was characterized by transmission electron microscope, X-ray diffraction, fourier transform infrared spectrometry, thermal gravimetric analysis and vibrating sample magnetometer. Under the optimized conditions, the maximum adsorption capacity of DESs-MMIP on BHb was 229.54 mg g-1 and the imprinting factor reached up to 21.89. The selective adsorption experiments indicated that compared with seven references, DESs-MMIP showed significant selectivity for BHb. The new-type DESs-MMIP exhibited higher adsorption capacity and imprinting factor on BHb than molecularly imprinted polymers constructed with traditional functional monomer and cross-linker in reported methods. The recognition of BHb by DESs-MMIP in calf blood samples demonstrated the practicality of the particles. The DESs-MMIP only based on deep eutectic solvents with excellent selectivity is expected to become an ideal candidate for selective recognition of BHb in complicated samples.

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.

Functional wastepaper-montmorillonite composite aerogel for Cd2+ adsorption.

In this study, a composite aerogel (WP-MMT) composed of wastepaper (WP) and montmorillonite (MMT) was prepared by ambient pressure drying technology to adsorb Cd2+. The study of compression performance indicated that the composite aerogel had ideal mechanical strength when the mass ratio of WP to MMT was 1:1. The specific surface areas of the aerogels modified by hydrogen peroxide (WP-MMT-H2O2) and sodium hydroxide (WP-MMT-NaOH) were increased greatly. The sorption isotherms and kinetics of Cd2+ sorption on WP-MMT-H2O2 and WP-MMT-NaOH were investigated. The Cd2+ sorption data could be well described by a simple Langmuir model, and the pseudo-second-order kinetic model best fitted the kinetic data. The maximum sorption capacity obtained from the Langmuir model was 232.50 mg/g for WP-MMT-NaOH. The adsorption mechanism of WP-MMT was chemical adsorption of a single-molecule layer. In general, it was proved that the composite aerogel with high adsorption capacity of Cd2+ could be synthesized from modified WP and MMT by ambient pressure drying. The composite aerogel fabricated by wastepaper and montmorillonite showed bright application prospect in the aqueous heavy metal pollution control.

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.

Magnetic carbon nanotube modified with polymeric deep eutectic solvent for the solid phase extraction of bovine serum albumin.

This article described the fabrication of novel magnetic carbon nanotube modified with polymeric deep eutectic solvent (M-CNT@PDES) and its application as extractant for the magnetic solid phase extraction (MSPE) of bovine serum albumin (BSA). The physicochemical properties and morphology of M-CNT@PDES were characterized by X-ray diffraction (XRD), vibrating sample magnetometer (VSM), thermo-gravimetric analysis (TGA), zeta potentials, fourier transform infrared spectrometry (FT-IR) and transmission electron microscope (TEM). Afterwards, several parameters such as pH value, initial concentration of BSA, extraction time, ionic strength and extraction temperature were optimized. The results indicated that the modification of PDES significantly improved the extraction performance for BSA, and the maximum extraction capacity was 225.15 mg/g under the optimized conditions. In addition, 0.20 mol/L NaCl-PBS solution was chosen as the appropriate eluent, and favourable elution rate (81.22%) was obtained. Circular dichroism spectroscopy (CD) indicated that the secondary structure of BSA has not changed during extraction and elution. The regenerative experiment and application in real calf serum confirmed the outstanding durability and practical application ability of M-CNT@PDES. All of above verified that the proposed M-CNT@PDES coupled with MSPE method has great application potential for the pre-concentration of biomolecules.

A composite consisting of a deep eutectic solvent and dispersed magnetic metal-organic framework (type UiO-66-NH2) for solid-phase extraction of RNA.

A cactus-shaped magnetic composite was prepared for solid-phase extraction of RNA. It is composed of the metal organic framework UiO-66-NH2 that was modified with Fe3O4 nanoparticles. The composite was then dispersed in a lactic acid-based deep eutectic solvent (DES, Fe3O4-COOH@UiO-66-NH2@DES). The structures of the sorbents were characterized by transmission electron microscopy, scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectrometry, vibrating sample magnetometry and thermogravimetric analysis. The extraction performance of sorbents was optimized and the maximum extraction capacity reached 246 mg·g-1. Extraction is shown to mainly rely on chelation interaction, electrostatic interaction, hydrophobic interaction and hydrogen bonding interaction. The sorbent can selectively extract RNA over DNA, bovine hemoglobin and amino acids. Regeneration studies indicated that the sorbent can be re-used (after regenreation with DES) several times without obvious change of the extraction capacity. The successful extraction of RNA from yeast testified the practical application of the sorbent. Graphical abstractSchematic representation of the fabrication Fe3O4-COOH@UiO-66-NH2@DES, and its application in the magnetic solid phase extraction of RNA.

A composite prepared from MnO2 nanosheets and a deep eutectic solvent as an oxidase mimic for the colorimetric determination of DNA.

A composite was fabricated from deep eutectic solvent and MnO2 nanosheets (DES/MnO2) and is shown to be a viable oxidase mimic. The property, morphology and composition of DES/MnO2 was characterized. DES/MnO2 displays oxidase-like activity and can oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to form a blue product (oxTMB) with an absorption maximum at 652 nm. Due to the presence of the DES, the polyanionic and negatively charged DNA is easily adsorbed on the surface of the composite by hydrogen bonding and electrostatic interactions. This leads to the inhibition of the oxidase-mimicking activity of DES/MnO2. This finding was used to design a colorimetric method for the determination of DNA. The assay work in the 10-100 µg mL-1 DNA concentration range and has a detection limit of 0.37 µg mL-1. The inhibiting mechanism was further studied by zeta potential measurements, dynamic light scattering and transmission electron microscopy. The selectivity study shows the DES/MnO2-TMB system to be highly selective for DNA when compared with many proteins, carbohydrates, salts and amino acid. RNA, on the other hand, interferes. The real sample analysis result illustrates that the new method can be used for the detection of DNA in bovine whole blood. Graphical abstractA novel oxidase mimic based on deep eutectic solvent-functionalized MnO2 nanosheets was synthesized, which can directly catalyze oxidation of 3,3',5,5'-tetramethylbenzidine (TMB, colorless) to oxTMB (blue). A sensitive and convenient colorimetric strategy for visual detection of DNA was established through DES/MnO2-TMB sensing system.

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.

SETD7 mediates spinal microgliosis and neuropathic pain in a rat model of peripheral nerve injury.

Gene transcription regulation is critical for the development of spinal microgliosis and neuropathic pain after peripheral nerve injury. Using a model of chronic constriction injury (CCI) of the sciatic nerve, this study characterized the role of SET domain containing lysine methyltransferase 7 (SETD7) which monomethylates histone H3 lysine 4 (H3K4me1), a marker for active gene transcription. SETD7 protein expression in the spinal dorsal horn ipsilateral to nerve lesion was increased from one day to 14 days after CCI, concomitantly with the expression of inflammatory genes, Ccl2, Il-6 and Il-1ß. The CCI-induced SETD7 expression was predominantly localized to microglia, as demonstrated by immunohistochemistry and western blot from magnetic activated cell sorted spinal microglia. SETD7 knockdown by intrathecal lentivirus shRNA delivery prior to CCI prevented spinal microgliosis and neuropathic pain, whereas lentiviral SETD7 transduction exacerbated these symptoms. In addition, SETD7 regulated H3K4me1 level and expression of inflammatory mediators both in CCI rats and in the HAPI rat microglia cell line. Accordingly, PFI-2, a specific inhibitor of SETD7 monomethylation activity, suppressed the lipopolysaccharides-induced amoeboid morphology of primary microglia and the expression of inflammatory genes, Ccl2, Il-6 and Il-1ß. Moreover, intrathecal administration of PFI-2 alleviated CCI-induced neuropathic pain. However, this effect was observed in male but not in female rats. These results demonstrate a critical role of SETD7 in the development of spinal microgliosis and neuropathic pain subsequently to peripheral nerve injury. The pharmacological approach further suggests that SETD7 is a new target for the treatment of neuropathic pain. The underlying mechanisms may involve H3K4me1-dependent regulation of inflammatory gene expression in microglia.

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.