Isoniazide modified Ag nanoparticles triggered photothermal immunoassay for carcinoembryonic antigen detection.

As the most well-known analytical tool, the thermometer has been extended to the field of biological analysis based on the photothermal effect. Herein, isoniazide modified Ag nanoparticles were prepared as nanolabels to build an immunoassay. The nanoparticles were characterized by transmission electron microscope (TEM), dynamic laser scattering (DLS), X-ray powder diffraction (XRD), and Fourier transform infrared (FT-IR). When the target protein was present, the sandwich immunoassay was developed and the photothermal reaction was triggered by isoniazide modified Ag nanoparticles. As a reducing agent, isoniazide is used to transform phosphomolybdic acid hydrate into molybdenum blue solution. And molybdenum blue had good photothermal stability and high photothermal conversion efficiency. The temperature variation of molybdenum blue solution showed a positive correlation with the concentration of carcinoembryonic antigen (CEA). Thus, the target protein of CEA was quantitative detection by thermometer. The linear response range is 0.1 ng mL-1 to 40 ng mL-1, and the detection limit is 0.08 ng mL-1. Moreover, the proposed protocol had satisfactory selectivity, accuracy, and reproducibility.

Three-Component Synthesis of Di-Keto Aziridines and Highly Functionalized Alkenes from Sulfoxonium Ylides, Nitrosoarenes, and Alkynes.

A catalyst-free one-pot three-component method of sulfoxonium ylides, nitrosoarenes, and alkynes for the synthesis of highly functionalized di-keto aziridines and alkenes is described. This strategy features the catalyst-free and additive-free approach, the employment of safe, more stable, and readily accessible sulfoxonium ylides, which bear a much wider substrate scope as starting materials. In terms of terminal alkynes, a cascade reaction of nitrone formation/1,3-diploar cycloaddition/Baldwin rearrangement is involved to afford a wide variety of di-keto aziridines. However, highly functionalized alkenes could be obtained instead of di-keto aziridines through the same nitrone formation/1,3-diploar cycloaddition and another different rearrangement reaction when internal alkynes are employed as starting materials.

Construction of 1,2-dihydro-1,3,5-triazines via reactions involving amidines.

1,2-Dihydro-1,3,5-triazine compounds were synthesized through three sets of reactions of amidines with, respectively, paraformaldehyde, aldehydes and N-arylnitrones under different conditions. The catalysts used in these three reactions were Cu(OAc)2, ZnI2 and CuCl2·2H2O, respectively. Most of the substrates tested for these reactions provided the target products in moderate to good yields. In the reactions involving paraformaldehyde, Cu(OAc)2 also accelerated the release of formaldehyde from paraformaldehyde during the catalytic reaction process. In the case of the reactions involving nitrones, CuCl2·2H2O not only catalyzed the normal progress of the main reaction, but also promoted the reaction of nitrones to produce nitroso compounds and aldehydes.

Cycloaddition of N-arylnitrones with donor-acceptor oxiranes via C-C bond cleavage to construct 1,5,2-dioxazinanes.

Highly functionalized 1,5,2-dioxazinanes could be smoothly produced via a Sc(OTf)3-catalyzed chemoselective [3 + 3] cycloaddition of various N-arylnitrones with a series of donor-acceptor oxiranes. This reaction involves in situ generation of 1,3-dipoles through Sc(OTf)3-catalyzed C-C bond cleavage of oxiranes and moderate to high yields were obtained for most substrates. This transformation features C-C bond cleavage of donor-acceptor oxiranes, accessible starting materials and mild reaction conditions.

Sulfone-Embedded Heterocyclic Narrowband Emitters with Strengthened Molecular Rigidity and Suppressed High-Frequency Vibronic Coupling.

Sulfone-embedded heterocyclics are of great interest in organic light-emitting diodes (OLEDs), however, exploring highly efficient narrowband emitters based on sulfone-embedded heterocyclics remains challenging. Herein, five emitters with different sulfur valence state and molecular rigidity, namely tP, tCPD, 2tCPD, tPD and tPT, are thoroughly analysed. With restricted twisting of flexible peripheral phenyl by strengthening molecular rigidity, molecular emission spectra can be enormously narrowed. Further, introducing the sulfone group with bending vibration in low-frequency region that suppresses high-frequency vibration, sharp narrow full-widths at half-maximum of 28 and 25 nm are achieved for 2tCPD and tPD, respectively. Maximum external quantum efficiencies of 22.0 % and 27.1 % are successfully realized for 2tCPD- and tPD-based OLED devices. These results offer a novel design strategy for constructing narrowband emitters by introducing sulfone group into a rigid molecular framework.

Hydrazones as Substrates in the Synthesis of Isoxazolidines via a KOH-Promoted One-Pot Three-Component Cycloaddition with Nitroso Compounds and Olefins.

Hydrazones have been employed as the starting materials in a KOH-mediated one-pot three-component cycloaddition with readily accessible nitroso compounds and olefins to construct various isoxazolidines. Compared with diazo compounds as starting materials, this methodology could afford a wider range of products in good to excellent yields and diastereoselectivities for most substrates, and hydrazones are cheaper, more accessible, and safer substrates. The experimental study shows that the choice of suitable hydrazones is crucial.

Access to highly functionalized imidazolones bearing α-amino acid esters via KOH-promoted annulation of amidines, nitrosoarenes and malonic esters.

An efficient approach to obtain highly functionalized imidazolones bearing α-amino acid esters through KOH-mediated one-pot three-component annulation of amidines, nitrosoarenes and malonic esters is reported. This reaction features broad substrate scope, a cheap and readily available promoter, good to high yields for most substrates and mild reaction conditions. The mechanism study shows that the KOH-mediated formation of the imine intermediate via the reaction of nitrosoarenes with malonic esters is a key step.

Modification of a magnetic carbon composite for ciprofloxacin adsorption.

A magnetic carbon composite, Fe3O4/C composite, was fabricated by one-step hydrothermal synthesis, modified by heat treatment under an inert atmosphere (N2), and then used as an adsorbent for ciprofloxacin (CIP) removal. Conditions for the modification were optimized according to the rate of CIP removal. The adsorbent was characterized by Fourier transform infrared spectroscopy, X-ray diffraction measurements, vibrating-sample magnetometry, scanning electron microscopy, transmission electron microscopy, and N2 adsorption/desorption isotherm measurements. The results indicate that the modified adsorbent has substantial magnetism and has a large specific area, which favor CIP adsorption. The effects of solution pH, adsorbent dose, contact time, initial CIP concentration, ion strength, humic acid and solution temperature on CIP removal were also studied. Our results show that all of the above factors influence CIP removal. The Langmuir adsorption isotherm fits the adsorption process well, with the pseudo second-order model describing the adsorption kinetics accurately. The thermodynamic parameters indicate that adsorption is mainly physical adsorption. Recycling experiments revealed that the behavior of adsorbent is maintained after recycling for five times. Overall, the modified magnetic carbon composite is an efficient adsorbent for wastewater treatment.

Interaction between eye movements and adhesion of extraocular muscles.

The contact and pull-off tests and finite element simulations were used to study the extraocular muscle-sclera adhesion and its variation with eye movement in this research. The effect of the adhesion on the eye movements was also determined using equilibrium equations of eye motion. The contact and pull-off tests were performed using quasi-static and non-quasi-static unloading velocities. Finite element models were developed to simulate these tests in cases with high unloading velocity which could not be achieved experimentally. These velocities range from the eye's fixation to saccade movement. The tests confirmed that the pull-off force is related to the unloading velocity. As the unloading velocity increases, the pull-off force increases, with an insignificant increase at the high ocular saccade velocities. The adhesion moment between the extraocular muscles and the sclera exhibited the same trend, increasing with higher eye movement velocities and higher separation angles between the two interfaces. The adhesion moment ratio to the total moment was calculated by the traditional model and the active pulley model of eye movements to assess the effect of adhesion behavior on eye movements. At the high ocular saccade velocities (about 461 deg/s), the adhesion moment was found to be 0.53% and 0.50% of the total moment based on the traditional and active pulley models, respectively. The results suggest that the adhesion behavior between the extraocular muscles and the sclera has a negligible effect on eye movements. At the same time, this adhesion behavior can be ignored in eye modeling, which simplifies the model reasonably well. STATEMENT OF SIGNIFICANCE: 1. Adhesion behavior between the extraocular muscles and the sclera at different indenter unloading velocities determined by contact and pull-off tests. 2. A finite element model was developed to simulate the adhesive contact between the extraocular muscles and the sclera at different indenter unloading velocities. The bilinear cohesive zone model was used for adhesive interactions. 3. The elastic modulus and viscoelastic parameters of the extraocular muscle along the thickness direction were obtained by using compressive stress-relaxation tests. 4. The influence of the adhesion moment between the extraocular muscles and the sclera on eye movement was obtained according to the equation of oculomotor balance. The adhesion moment between the extraocular muscles and the sclera was found to increase with increased eye movement velocity and increased separation angle between the two interfaces.

Highly Horizontal Oriented Tricomponent Exciplex Host with Multiple Reverse Intersystem Crossing Channels for High-Performance Narrowband Electroluminescence and Eye-Protection White Organic Light-Emitting Diodes.

Despite multiple-resonance thermally activated delayed fluorescence (MR-TADF) emitters with small full-width at half maximum are attractive for wide color-gamut display and eye-protection lighting applications, their inefficient reverse intersystem crossing (RISC) process and long exciton lifetime induce serious efficiency roll-off, which significantly limits their development. Herein, a novel device concept of building highly efficient tricomponent exciplex with multiple RISC channels is proposed to realize reduced exciton quenching and enhanced upconversion of nonradiative triplet excitons, and subsequently used as a host for high-performance MR-TADF organic light-emitting diodes (OLEDs). Compared with traditional binary exciplex, the tricomponent exciplex exhibits obviously improved photoluminescence quantum yield, emitting dipole orientation and RISC rate constant, and a record-breaking external quantum efficiency (EQE) of 30.4% is achieved for tricomponent exciplex p-PhBCzPh: PO-T2T: DspiroAc-TRZ (50: 20: 30) based OLED. Remarkably, maximum EQEs of 36.2% and 40.3% and ultralow efficiency roll-off with EQEs of 26.1% and 30.0% at 1000 cd m-2 are respectively achieved for its sky-blue and pure-green MR-TADF doped OLEDs. Additionally, the blue emission unit hosted by tricomponent exciplex is combined with an orange-red TADF emission unit to achieve a double-emission-layer blue-hazard-free warm white OLED with an EQEmax of 30.3% and stable electroluminescence spectra over a wide brightness range.

Three-dimensionally ordered macroporous iron oxide for removal of H2S at medium temperatures.

A series of iron oxide sorbents with novel structures of three-dimensionally ordered macropores (3DOM), ranging in size from 60 to 550 nm, were fabricated and creatively used as sorbents for the removal of H2S at medium temperatures of 300-350 °C. Evaluation tests using thermogravimetric analysis (TGA) and a fixed-bed reactor showed that, in comparison to the iron oxide sorbent prepared by a conventional mixing method, the fabricated iron oxide sorbent with a 3DOM structure exhibited much higher reactivity and efficiency, as well as high sorbent utilization with low regeneration temperature. The excellent performance of 3DOM iron oxide as a sulfur sorbent is attributed to its special texture, i.e., the open and interconnected macroporous, large surface area, and nanoparticles of iron oxide, which are revealed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and nitrogen adsorption techniques. The investigation results of the pore effect on the performance of the sorbent show that sorbents with pores size around 150 nm in diameter revealed the best performance. The reason is that pores of this size are large enough to allow gas to pass through even if the channel is partially blocked during the reaction process while remaining a large surface area that can provide more active sites for the reaction.

Bifurcations to transient and oscillatory excitations in inhomogeneous excitable media: Insights into arrhythmogenesis in long QT syndrome.

Ventricular arrhythmias are the leading cause of sudden cardiac death. Understanding the mechanisms of arrhythmia initiation is important for developing effective therapeutics for prevention. Arrhythmias can be induced via premature external stimuli or occur spontaneously via dynamical instabilities. Computer simulations have shown that a large repolarization gradient due to regional prolongation of the action potential duration can result in instabilities leading to premature excitations and arrhythmias, but the bifurcation remains to be elucidated. In this study we carry out numerical simulations and linear stability analyses using a one-dimensional heterogeneous cable consisting of the FitzHugh-Nagumo model. We show that a Hopf bifurcation leads to local oscillations, which, once their amplitudes are large enough, lead to spontaneous propagating excitations. Depending on the degree of heterogeneities, these excitations can range from one to many and to be sustained oscillations, manifesting as premature ventricular contractions (PVCs) and sustained arrhythmias. The dynamics depends on the repolarization gradient and the length of the cable. Complex dynamics is also induced by the repolarization gradient. The mechanistic insights from the simple model may help in the understanding of the genesis of PVCs and arrhythmias in long QT syndrome.

Molybdenum blue mediated photothermal immunoassay for CEA detection based on Ag4P2O7@Ag nanocomposites.

A photothermal immunoassay was built for tumor marker detection based on Ag4P2O7@Ag nanocomposites. Ag4P2O7@Ag nanomaterials were synthesized by precipitation-photoreduction reaction, and characterized by transmission electron microscope (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectra (XPS) and X-ray powder diffraction (XRD). Come about PO43- derived from Ag4P2O7@Ag under acidic conditions react with ammonium molybdate in the action of reductant generating molybdenum blue. The photothermal change is due to molybdenum blue solution depending on the concentration of carcinoembryonic antigen (CEA) in immunoassay. Under optimal conditions, there is a linear relation between ΔT and CEA concentration in the range of 1 pg mL-1-40 ng mL-1 with the detection limit of 0.33 pg mL-1. Meanwhile, the developed photothermal immunoassay displays preferable selectivity, repeatability, and stability.

Engineering Bio-MOF/polydopamine as a biocompatible targeted theranostic system for synergistic multi-drug chemo-photothermal therapy.

In this study, a biodegradable multifunctional photothermal drug delivery nanoparticles (MPH NPs) using curcumin (Cur) as the ligand coated with hyaluronic acid (HA) was successfully prepared, which could simultaneously deliver Cur and doxorubicin hydrochloride (DOX·HCl) to overcome the common drug resistance in cancer cells. Polydopamine (PDA) as a protective shell prevents premature degradation of Cur in physiological environment and enables it to play effective medicinal value. MPH NPs can specifically recognize CD44 receptors on the surface of cancer cells for tumor targeting, with the damage of the partially released DOX to the superficial tumor cells, and then the positively charged Cur released may gradually penetrate into the cells through electron interaction to improve the problem of low permeability. In vitro cell experiments showed that hydrophobic/hydrophilic drugs co-loaded MPDH (MPH loaded with DOX·HCl) could enter the cancer cells through the endocytosis mediated by clathrin / caveolin, and the inhibition rate of MPDH on HeLa cells reached 79.28 % irradiation under 808 nm laser. MPH were composed of safe materials that have been proven to be biodegradable in human body, which avoided the disadvantages that NPs were difficult to discharge and caused damage to normal organs during long-term use.

Preliminary Exploration on the Value of Shear Wave Elastography in Evaluating the Effectiveness of Microwave Ablation on Hepatic Malignancies.

ABSTRACT: Shear wave elastography (SWE) is a new type of ultrasonic elastography that can quantitatively assess the elasticity and stiffness of tissues. This study aimed to investigate the value of SWE in evaluating the effectiveness of microwave ablation in hepatic malignancies. A total of 24 patients (including 30 lesions) with liver malignancies receiving microwave ablation treatment at the Cancer Hospital of Guangzhou Medical University from April 2018 to January 2019 were enrolled. The elastography was performed within 1 week before and after ablation. The SWE values in the central zone, the marginal zone of the lesion, and peripheral liver parenchyma were collected and analyzed. Before ablation, the mean of SWE value was 65.80 ± 13.37 kPa for the central zone of the tumor and 39.93 ± 7.87 kPa for the marginal zone, both of which were significantly greater than that for the perinatal liver parenchyma (12.85 ± 2.67 kPa, both P < 0.05). In the central and marginal zone of the lesions, the SWE value was significantly elevated after ablation (both P < 0.001) but not in the peripheral liver parenchyma (P = 0.444). Receiver operating characteristic curve analysis showed that the cutoff value for ablation in the marginal zone was 53.87 kPa, suggesting that an SWE exceeding 53.87 kPa is an index guaranteeing the ablation effectiveness. These results suggested that SWE has the potential to be used in evaluating the effectiveness of microwave ablation in liver cancers.

Study of oxygen-deficient W18O49-based drug delivery system readily absorbed through cellular internalization pathways in tumor-targeted chemo-/photothermal therapy.

W18O49-mediated photothermal therapy (PTT) is affected by the easily oxidized property and its direct exposure to physiological environment can cause biological events, which limit its development in the biomedical field. Herein, a composite nanoparticle PVP-W18O49@C (PW@C), with significant antioxidant and excellent biocompatibility, was constructed to overcome the limitations of W18O49 in the medical field. Oxygen-deficient W18O49, with irregular defect structure, was combined with hollow carbon nanospheres treated by reflux to obtain W18O49@C (W@C) similar to sea urchins. Compared with W18O49, W@C shows stronger antioxidant properties, and it still has the ability to convert light energy to heat energy after 6 months. In addition, polyvinyl pyrrolidone is coated on the surface of W@C to construct PW@C, which significantly improves biocompatibility of W@C. The photothermal conversion efficiency of PW@C was 42.9 ± 1.3. PWD (PW@C loaded with DOX·HCl) showed controllable drug release behavior under pH and NIR stimulation, and the drug release rate reached 69.1 ± 1.6% at pH = 5.0. Notably, PWD was readily absorbed by cells through clathrin/caveolae-mediated internalization channels, and the viability of HeLa cells treated with PWD + NIR was only 21.5 ± 1.0%. Through photothermal, drug delivery/release and cytotoxicity evaluation, PWD was proved to be an effective platform for chemo-/photothermal combinational tumor therapy.

Development of purification process for dual-function recombinant human heavy-chain ferritin by the investigation of genetic modification impact on conformation.

Ferritin is a promising drug delivery platform and has been functionalized through genetic modifications. This work has designed and expressed a dual-functional engineered human heavy-chain ferritin (HFn) with the inserted functional peptide PAS and RGDK to extend half-life and improve tumor targeted drug delivery. A facile and cost-effective two-step purification pathway for recombinant HFn was developed. The genetic modification was found to affect HFn conformation, and therefore varied the purification performance. Heat-acid precipitation followed by butyl fast flow hydrophobic interaction chromatography (HIC) has been developed to purify HFn and modified HFns. Nucleic acid removal reached above 99.8% for HFn and modified HFns. However, HFn purity reached above 95% and recovery yield (overall) above 90%, compared with modified HFns purity above 82% and recovery yield (overall) above 58%. It is interesting to find that the inserted functional peptides significantly changed the molecule conformation, where a putative turnover of the E-helix with the inserted functional peptides formed a "flop" conformation, in contrast with the "flip" conformation of HFn. It could be the cause of fragile stability of modified HFns, and therefore less tolerant to heat and acid condition, observed by the lower recovery yield in heat-acid precipitation.

Evaluation of Microwave Ablation Efficacy by Strain Elastography and Shear Wave Elastography in ex Vivo Porcine Liver.

The aim of this study was to evaluate the efficacy of microwave ablation by ultrasound (US), strain elastography (SE) and shear-wave elastography (SWE). An ex vivo model of porcine liver was adopted. According to ablation power and duration, 30 samples were divided into three groups: group 1 (45 W, 30 s), group 2 (45 W, 15 s) and group 3 (30 W, 30 s). US was used to measure the largest transverse diameter (D1), vertical diameter (D2) and anteroposterior diameter (D3) of the ablated area. SE was used to measure the largest transverse diameter (SEL1), vertical diameter (SEL2) and anteroposterior diameter (SEL3). The actual size of the ablated area was measured as the largest transverse diameter (L1), vertical diameter (L2) and anteroposterior diameter (L3). SWE values and temperatures were measured in the central lesion (region a), marginal area (region b) and unablated area (region c). At 1 h post-ablation, the values measured by US (D1, D2, D3) were all significantly smaller than the ablated area (L1, L2, L3) in all three groups. Except for SEL2 in group 1, there was no significant difference in the results between SEL and L among the three groups. All SWE results were significantly higher post-ablation than pre-ablation in the central lesion (region a) and marginal area (region b, all p values <0.05). In regions a, b and c, the temperatures measured immediately and 5 min post-ablation were all higher than that measured pre-ablation. These results suggest that SE and SWE can be used to evaluate the ablation efficacy of liver tissue.

Accurate prediction of potential druggable proteins based on genetic algorithm and Bagging-SVM ensemble classifier.

Discovering and accurately locating drug targets is of great significance for the research and development of new drugs. As a different approach to traditional drug development, the machine learning algorithm is used to predict the drug target by mining the data. Because of its advantages of short time and low cost, it has received more and more attention in recent years. In this paper, we propose a novel method for predicting druggable proteins. Firstly, the features of the protein sequence are extracted by combining Chou's pseudo amino acid composition (PseAAC), dipeptide composition (DPC) and reduced sequence (RS), getting the 591 dimension of drug target dataset. Then, the feature information of druggable proteins dataset is selected by genetic algorithm (GA). Finally, we use Bagging ensemble learning to improve SVM classifier to get the final prediction model. The predictive accuracy rate reaches 93.78% by using 5-fold cross-validation and compared with other state-of-the-art predictive methods. The results indicate that the method proposed in this paper has a high reference value for the prediction of potential drug targets, which will successfully play a key role in the drug research and development. The source code and all datasets are available at https://github.com/QUST-AIBBDRC/GA-Bagging-SVM.

[Application of deep circumflex iliac artery based iliac-internal oblique musculofascial chimeric flaps in reconstruction of complex oromandibular defects].

Objective: To evaluate the reliability and effectiveness of a deep circumflex iliac artery based iliac-internal oblique musculofascial chimeric flap (DCIA-IIOF) in reconstruction of complex oromandibular defect. Methods: Between January 2010 and December 2015, DCIA-IIOFs were used to repair complex oromandibular defects in 11 patients. There were 8 males and 3 females, with an age of 27-75 years (median, 56 years). Original disease was lower gingival squamous cell carcinoma in 7 cases (T 3N 1M 0 in 2 cases, T 3N 2M 0 in 1 case, T 4N 0M 0 in 2 cases, and T 4N 2M 0 in 2 cases), osteoradionecrosis after radiotherapy for nasopharyngeal carcinoma in 2 cases, central mandibular squamous cell carcinoma in 1 case (T 4N 0M 0), and mandibular malignant fibrous histiocytoma in 1 case. The length of mandibular bone defects ranged from 7 to 10 cm (mean, 8 cm), and the area of the mucosal defects ranged from 5 cm×3 cm to 7 cm×4 cm. Preoperative ultrasonic identification of the DCIA and its ascending branch was routinely performed. The DCIA-IIOF was harvested by using an anterograde dissection technique, of which the iliac island was used for segmental mandibular defect repair and the musculofascial island for soft tissue and mucosal defect repair. Results: All 11 cases were followed up 15-75 months (median, 37 months). All flaps survived after operation, without necrosis of both iliac island and oblique internal musculofascial island. One patient had a mild submandibular infection which healed after wound drainage and intravenous antibiotics. At 1 month after operation, the color and texture of the musculofascial island were similar to oral mucosa without contracture, and the occluding relation was good for all patients. At 6 months after operation, the mouth opening hardly improved in 2 patients who had osteoradionecrosis; 1 patient who underwent postoperative radiotherapy had restriction of mouth opening; the remaining 8 patients had normal month opening and normal diet. Three patients died of cancer recurrence, 2 patients died of other diseases (encephalorrhagia in 1 case and myocardial infarction in 1 case), and the others survived without recurrence during follow-up. No patient developed abdominal hernia during follow-up. Conclusion: DCIA-IIOF is a reliable flap in reconstruction of complex oromandibular defects. The occluding relation after operation is good and the mucosal lining is soft. This technique provides an effective option for moderate complex oromandibular defects repair.