Fasudil promotes polyploidization of megakaryoblasts in an acute megakaryocyte leukemia model.

Acute megakaryocytic leukemia (AMKL) is a rare neoplasm caused by abnormal megakaryoblasts. Megakaryoblasts keep dividing and avoid undergoing polyploidization to escape maturation. Small-molecule probes inducing polyploidization of megakaryocytic leukemia cells accelerate the differentiation of megakaryocytes. This study aims to determine that Rho kinase (ROCK) inhibition on megakaryoblasts enhances polyploidization and the inhibition of ROCK1 by fasudil benefits AMKL mice. The study investigated fasudil on the megakaryoblast cells in vitro and in vivo. With the differentiation and apoptosis induction, fasudil was used to treat 6133/MPLW515L mice, and the differentiation level was evaluated. Fasudil could reduce proliferation and promote the polyploidization of megakaryoblasts. Meanwhile, fasudil reduced the disease burden of 6133/MPLW515L AMKL mice at a dose that is safe for healthy mice. Combination therapy of ROCK1 inhibitor fasudil and reported clinical AURKA inhibitor MLN8237 achieved a better antileukemia effect in vivo, which alleviated hepatosplenomegaly and promoted the differentiation of megakaryoblast cells. ROCK1 inhibitor fasudil is a good proliferation inhibitor and polyploidization inducer of megakaryoblast cells and might be a novel rationale for clinical AMKL treatment.

Realizing Holistic Charging-Discharging for Dendrite-Free Lithium Metal Anodes via Constructing Three-Dimensional Li+ Conductive Networks.

Lithium (Li) metal is a promising candidate for next-generation anode materials with high energy densities. However, Li dissolution/deposition processes are limited at the upper surface in contact with the electrolyte, which brings a locally high current density and then results in dendritic Li growth. This restraint of the local surface reaction during cycling has not been solved by commonly used modification strategies. In this study, a three-dimensional (3D) Li+ conductive skeleton is activated from atomic layer deposition (ALD) coating Li3PO4 (LPO) on the surface of the Ni foam (LPNF). Then, the skeleton is efficiently constructed in the Li metal anode by the lower-temperature Li infusion. Ionic conductor LPO layers and electronic conductor Ni fibers supply charge transport channels between the electrolyte and the internal Li. The mixed conductive network realizes holistic charge transfer, which is proved by in situ scanning electron microscopy experiments. In virtue of dispersive dissolution/deposition and optimized electrochemical kinetics brought by a Li+ conductive network, the composited Li electrode presents an excellent symmetric battery cycling stability (over 1200 h) and enhanced rate performances (stable cycling even at 10.0 mA cm-2). When matching with a LiCoO2 (LCO) cathode, LCO||Li@LPNF full batteries exhibit a capacity retention of 80.8% over 250 cycles. During cycling, there was no evidence of dendrite growth and the remaining Li in the composited anode showed a smooth, compact, and well-combined condition with LPNF. Through constructing a 3D Li+ conductive network, the composited Li metal anode breaks through the limit of the local surface reaction; this work proposes a novel insight of realizing holistic charging/discharging for the dendrite-free Li metal anode.

Combined metabolomics and machine learning algorithms to explore metabolic biomarkers for diagnosis of acute myocardial ischemia.

Acute myocardial ischemia (AMI) remains the leading cause of death worldwide, and the post-mortem diagnosis of AMI represents a current challenge for both clinical and forensic pathologists. In the present study, the untargeted metabolomics based on ultra-performance liquid chromatography combined with high-resolution mass spectrometry was applied to analyze serum metabolic signatures from AMI in a rat model (n = 10 per group). A total of 28 endogenous metabolites in serum were significantly altered in AMI group relative to control and sham groups. A set of machine learning algorithms, namely gradient tree boosting (GTB), support vector machine (SVM), random forest (RF), logistic regression (LR), and multilayer perceptron (MLP) models, was used to screen the more valuable metabolites from 28 metabolites to optimize the biomarker panel. The results showed that classification accuracy and performance of MLP model were better than other algorithms when the metabolites consisting of L-threonic acid, N-acetyl-L-cysteine, CMPF, glycocholic acid, L-tyrosine, cholic acid, and glycoursodeoxycholic acid. Finally, 17 blood samples from autopsy cases were applied to validate the classification model's value in human samples. The MLP model constructed based on rat dataset achieved accuracy of 88.23%, and ROC of 0.89 for predicting AMI type II in autopsy cases of sudden cardiac death. The results demonstrated that MLP model based on 7 molecular biomarkers had a good diagnostic performance for both AMI rats and autopsy-based blood samples. Thus, the combination of metabolomics and machine learning algorithms provides a novel strategy for AMI diagnosis.

Study on Fatigue Performance of Pulsed Tungsten Inert Gas Welding Joint of Duplex Stainless Steel Thin Tube.

To solve the shortage of austenite phase precipitation caused by nitrogen loss in the welding process of UNS S2205 duplex stainless steel (DSS), shielding gas nitriding was investigated by adding different N2 contents in Ar shielding gas during the welding process. A good thin-walled pipe butt joint was formed using the pulsed tungsten inert gas (P-TIG) welding method with Ar-N2 shielding gas. High cycle fatigue tests of the weld joints were conducted to study the effect of shielding gas nitriding on the fatigue properties. Fatigue tests at three stress levels of 225 MPa, 270 MPa, and 360 MPa were carried out on the weld joints with different N2 contents, and the fatigue samples were all fractured in the high temperature heat-affected zone (H-HAZ). Within the current process parameters, the fatigue life of the 4 vol.% N2 welded joints was optimal. Fatigue striations appeared in the fatigue crack propagation zone, and the transient fracture zone was similar to the tensile fracture. Under the low-stress level, the area of the crack propagation zone under 4 vol.% N2 was the highest, the tear ridges all expanded around the crack source area, and the fatigue crack propagation zone presented a radial distribution. The proliferation and expansion of dislocations were mainly carried out in the austenite grains, and the dislocation density of the fatigue specimens under 4 vol.% N2 was smaller than that of the Ar specimens. Shielding gas nitriding effectively improved the balance of the two-phase ratio and the hardness of austenite phase, optimized the internal slip system, inhibited the proliferation of dislocations in the austenite phase, and improved the fatigue life of weld joints.

Analysis of sensitivity and specificity: precise recognition of neutrophils during regeneration of contused skeletal muscle in rats.

In this report, we applied the TissueFAXS 200 digital pathological analysis system to rapidly and accurately identify neutrophils during regeneration of contused skeletal muscle, and to provide information for follow-up studies on neutrophils to estimate wound age. Rat injury model was established, and skeletal muscle samples were obtained from the control group and contusion groups at 1, 1.5, 2, 3, 4, and 6 h, as well as at 1, 3, 5, and 15 d post-injury (n = 5 per group). The expression of nuclei and neutrophils was detected by hematoxylin and eosin (HE) staining and immunohistochemical (IHC) staining. A total of 20 injury site areas of 0.25 mm2 (0.5 mm × 0.5 mm) were then randomly selected at all time points. A TissueFAXS 200 digital pathological analysis system was used to identify the positive and negative numbers. Knowledge of five professional medical workers were considered the gold standard to measure the false positive rate (FPR), false negative rate (FNR), sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic (ROC) curves. As a result, with a staining area of neutrophils from 8 µm2 to 15 µm2, the FPR was 4.28%-12.14%, the FNR was 12.42%-64.08%, the sensitivity was 35.92%-87.58%, the specificity was 87.86%-95.72%, the Youden index was 0.316-0.754, the accuracy was 82.80%-88.30%, and the AUC was 0.771-0.826. The AUC was largest when the cut-off value of the staining area was 12 µm2. Our results show that this software-based method is more accurate than the human eye in evaluating neutrophil infiltration. Based on the sensitivity and specificity, neutrophils can be accurately identified during regeneration of contused skeletal muscle. The TissueFAXS 200 digital pathological analysis system can also be used to optimize conditions for different cell types under various injury conditions to determine the optimal cut-off value of the staining area and provide optimal conditions for further study. Furthermore, it will provide evidence for forensic pathology cases.

Estimating the time of skeletal muscle contusion based on the spatial distribution of neutrophils: a practical approach to forensic problems.

The study aimed to explore the neutrophil's spatial distributions used to estimate the histological age of contused skeletal muscle, and assessed the accuracy of various indicators, such as the proportion of neutrophils, "neutrophil mean distance," and distribution of neutrophils in areas of "contiguous contour lines." Fifty-five Sprague-Dawley rats were divided randomly into a control group and contusion groups at 1, 1.5, 2, 3, 4, and 6 h, as well as 1, 3, 5, and 15 days, post-injury (n = 5 per group). Nuclei and neutrophils were detected by hematoxylin and eosin (HE) staining and immunohistochemical (IHC) staining. At 0-24 h after injury, the distribution of neutrophils at distances of 100, 200, 300, 400, 500, and 600 µm from adjacent blood vessels was determined, and the best samples were screened to estimate wound age. To estimate wound age as accurately as possible, Fisher discriminant analysis (FDA) of the proportion of neutrophils, neutrophil mean distance, and distribution of neutrophils was performed, and 100.0% and 95.0% of the original and cross-validated cases were correctly classified, respectively. The spatial distribution of neutrophils at different distances from adjacent blood vessels showed a strong correlation with the histological age of contusion skeletal muscle, and the combination of the proportion of neutrophils, neutrophil mean distance, and distribution of neutrophils could be used to accurately estimate wound age.

A porous aromatic framework as a versatile fiber coating for solid-phase microextraction of polar and nonpolar aromatic organic compounds.

A porous aromatic framework (PAF) derived from triphenylamine (type PAF-41) was prepared and is shown to be a viable coating for fibrous solid-phase microextraction (SPME). PAF-41 can be easily synthesized and has a high surface area, a rich π-electron structure, and electron-rich nitrogen atoms in its framework. The PAF-41-coated fibrous SPME extractor was combined with a gas chromatographic separation and flame ionization detection. The method was applied to the quantitation of some aromatic organic compounds (AOCs), including polar amphetamine and methamphetamine and nonpolar ethylbenzene, o-, m- and p-xylenes, and styrene. The method was optimized after which a linear response is found for the 10-500 ng·mL-1 amphetamine and methamphetamine concentration ranges. The limits of detection are 1.0 and 0.5 ng·mL-1; and relative standard deviations for six repeated extractions with a single fiber are 5.3 and 6.7%. The method was applied for the determination of amphetamine and methamphetamine in spiked urine samples without any pretreatment except for dilution with water. The PAF-41 modified fiber also was applied to the extraction of styrene, xylenes and ethylbenzene. The enrichment capacities of the extractor for these AOCs were superior to those of commercial SPME extractors. Graphical abstract (a) Schemetic of the PAF-41-coated solid-phase microextraction (SPME) fiber. (b) Scanning electron microscope images of the PAF-41 fiber.

Preharvest zinc sulfate spray improves the storability of longan (Dimocarpus longan Lour.) fruits by protecting the cell wall components and antioxidants of pericarp.

BACKGROUND: Zinc (Zn) fertilization has been reported to improve the quality and storability of many fruits, but the mechanism had not been systematically studied. In this study, the effect of preharvest 0.2% zinc sulfate (ZnSO4 ) spray on the storability of longan fruits was investigated. RESULTS: The preharvest ZnSO4 spray did not significantly influence the quality but increased the Zn content in longan pericarp by 12.5-fold. More importantly, the treatment significantly reduced the rotting rate, pericarp browning, and aril breakdown of longan fruits stored at room temperature and low temperature. Physiological and biochemical results indicated that the treatment resulted in higher water retention capacity and inhibited the degradation of cellulose, pectin, flavonoid, and phenolics of longan pericarp at the late stages of storage. Consistent with these results, the activity of cellulase, polygalacturonase, polyphenol oxidase, and lipoxygenase was significantly inhibited in the ZnSO4 -treated longan pericarp at the late stages of storage. CONCLUSION: Higher Zn content in the ZnSO4 -treated longan pericarp might help to enhance the resistance against microbial infection, inhibit the hydrolysis of cell wall components, and thus effectively protected the cell wall components, maintained the cellular compartmentation, and prevented the phenolics and flavonoid from degradation by browning-related enzymes. © 2018 Society of Chemical Industry.

Determination of aromatic amines in the urine of smokers using a porous organic framework (JUC-Z2)-coated solid-phase microextraction fiber.

A solid-phase microextraction (SPME) fiber coated with a two-dimensional porous organic framework (POF), JUC-Z2, was synthesized by a sol-gel process. The JUC-Z2-coated SPME fiber was combined with gas chromatography-mass spectrometry/mass spectrometry (GC-MS/MS), and a direct analysis method without any derivatization step was developed for the determination of two major harmful aromatic amines (1-naphthylamine, 1-NA; 2-naphthylamine, 2-NA) in the urine of amokers. The new method exhibited satisfactory linearity in the wide range of 0.05-100 µg L-1 with correlation coefficients (R) of 0.9999. The limits of detection are 0.010 and 0.012 ng L-1. The relative standard deviations for repeated extraction (n = 6) with one fiber are less than 7.7%. The JUC-Z2-coated fiber demonstrates obviously superior extraction efficiencies for the two aromatic amines over the commercial fibers (CW/PEG, PA, PDMS/DVB, PDMS, CAR/PDMS, DVB/CAR PDMS). The structure-activity relationship was deeply investigated by the extraction comparison experiment with another similar POF material (PAF-48) and theoretical simulations. The extraction efficiencies of JUC-Z2 for 1-NA and 2-NA are 9.6 and 16.2 times higher than those of PAF-48, and JUC-Z2 has higher binding energies with the aromatic amines than PAF-48. The results indicate that the N atom on the JUZ-Z2 framework played a crucial role for adsorbing aromatic amines. Finally, the novel fiber has been successfully used to detect 1-NA and 2-NA in the urine of smokers.

Porous Aromatic Framework 48/Gel Hybrid Material Coated Solid-Phase Microextraction Fiber for the Determination of the Migration of Styrene from Polystyrene Food Contact Materials.

A novel solid-phase microextraction (SPME) fiber was fabricated by a porous aromatic framework 48 (PAF-48)/gel hybrid material through a sol-gel process. PAF-48 is a porous organic framework (POF) material that was polymerized from 1,3,5-triphenylbenzene. The uniform pore structure, high surface area, continuous conjugate network, and hydrophobicity make PAF-48 expected to have special abilities to absorb and extract styrene as well as some other harmful volatile aromatic compounds (VACs). The PAF-48/gel-coated fiber was explored for the extraction of styrene and six VACs (benzene, toluene, ethylbenzene, and xylenes) from aqueous food simulants followed by gas chromatography (GC) separation. The fiber was found to be very sensitive for the determination of the target molecules with wide linear ranges (0.1-200 or 500 µg·kg-1), low limits of detection (LODs, 0.003-0.060 µg·kg-1), acceptable precisions (intraday relative standard deviation, RSD < 5.9%, interday RSD < 7.3%), and long lifetime (>200 times). Particularly for styrene, the PAF-48/gel-coated fiber exhibited a much lower LOD (0.006 µg·kg-1) compared with most of the reported fibers. Moreover, the PAF-48/gel-coated fiber had a high extraction selectivity for styrene and VACs over alcohols, phenols, aromatic amines, and alkanes and show a molecular sieving effect for the different molecule sizes. Finally, the PAF-48/gel-coated SPME fiber was successfully applied in GC for the determination of the specific migrations of styrene and VACs from polystyrene (PS) plastic food contact materials (FCMs).

A water resistant solid-phase microextraction fiber with high selectivity prepared by a metal organic framework with perfluorinated pores.

A novel solid-phase microextraction (SPME) fiber was fabricated by the construction of fluorous metal organic frameworks (FMOF) and a polyimide (PI) composite strategy. As an auxiliary material, PI was expected to help FMOF particles form well-knit film on the surface of stainless steel wire and reinforce the coating, and FMOF was expected to afford a special structure to absorb, extract and enrich. Furthermore, it was explored for the headspace SPME (HS-SPME) of six volatile aromatic compounds (VACs) from water samples followed by gas chromatographic (GC) separation with flame ionization detection. Under the optimized conditions, the fiber afforded wide linear ranges (1-1000 µgL(-1)), low detection limits (0.15-0.9 µgL(-1)) and acceptable repeatability (<4.6%) and reproducibility (<7.3%). The FMOF@PI coated fiber not only offered large enhancement factors for benzene (1227) but also exhibited high extraction selectivity for benzene to other benzene homologues, hydrocarbons and phenols; for example, the extraction ratio of benzene to toluene, n-hexane and phenol could be as high as 10.2, 64.1 and 32.3, respectively. Moreover, the FMOF@PI-coated fiber afforded good thermal, water and organic solvent stabilities, and a long lifetime (over 200 times). The developed method was successfully applied to the determination of VACs in wastewater samples.

Copper(I)-catalyzed aryl bromides to form intermolecular and intramolecular carbon-oxygen bonds.

A highly efficient Cu-catalyzed C-O bond-forming reaction of alcohol and aryl bromides has been developed. This transformation was realized through the use of copper(I) iodide as a catalyst, 8-hydroxyquinoline as a ligand, and K(3)PO(4) as a base. A variety of functionalized substrates were found to react under these reaction conditions to provide products in good to excellent yields.

N-Acetyl-N-{2-[(Z)-2-chloro-3,3,3-tri-fluoro-prop-1-en-yl]phen-yl}acetamide.

The title compound, C(13)H(11)ClF(3)NO(2), adopts a Z conformation. Halogen⋯oxygen inter-actions [Cl⋯O = 2.967 (3) Å] in the crystal packing lead to the formation of a dimer joined by two Cl⋯O bonds.

An efficient Ullmann-type C-O bond formation catalyzed by an air-stable copper(I)-bipyridyl complex.

An efficient O-arylation of phenols and aliphatic alcohols with aryl halides was developed that uses an air-stable copper(I) complex as the catalyst. This arylation reaction can be performed in good yield in the absence of Cs2CO3. A variety of functional groups are compatible with these reaction conditions with low catalyst loading levels.