De Novo Design of a Highly Stable Ratiometric Probe for Long-Term Continuous Imaging of Endogenous HClO Burst.

Long-term continuous imaging of endogenous HClO burst is of great importance for the elucidation of various physiological or pathological processes. However, most of the currently reported HClO probes have failed to achieve this goal due to their insufficient photobleaching resistance under a laser source. Herein, a highly stable ratiometric probe, HFTC-HClO 1, which is capable of continuously monitoring endogenous HClO burst over a long period of time, has been judiciously developed. Briefly, the de novo development of HFTC-HClO 1 mainly involved three main steps: (1) novel coumarins (HFTC 1-5) were designed and synthesized; (2) the most stable scaffold, HFTC 3, was selected through dye screening and cell imaging validation; and (3) based on HFTC 3, three candidate HClO probes were constructed, and HFTC-HClO 1 was finally selected due to its superior sensing properties toward HClO. Furthermore, HFTC-HClO 1 can quantitatively measure HClO levels in various real samples with excellent recovery (>90.4%), and the use of HFTC-HClO 1-coated test strips for qualitative analysis of HClO in real samples was also achieved. In addition, the application of HFTC-HClO 1 for long-term continuous monitoring of intracellular HClO burst was successfully demonstrated. Significantly, HFTC-HClO 1 was able to visualize HClO generated in the rheumatoid arthritis mouse model.

Organophosphate esters in rural wastewater along the Yangtze river Basin: Occurrence, removal efficiency and environmental implications.

Organophosphate esters (OPEs) discharged from rural domestic wastewater were one of the important sources of OPEs in receiving water bodies, which has posed a potential threat to the ecological environment. However, very little information on the characteristics of OPEs in the rural domestic wastewater is available. Herein, the occurrence, removal efficiency and environmental implication of OPEs in rural domestic wastewater treatment facilities (RD-WWTFs) along the Yangtze River Basin were investigated. Results indicated that the median concentrations of ΣAlkyl-OPEs, ΣHalogenated-OPEs, ΣAryl-OPEs and the total OPE (ΣOPEs) in influents were 28.28, 99.25, 10.22 and 136.84 ng/L, while the median concentrations of them in effluents were 25.80, 141.86, 7.98 and 173.31 ng/L, respectively. Undoubtedly, halogenated OPEs were the most abundant in both influent and effluent, followed by alkyl and aryl OPEs, and they accounted for average proportions of 69.50%, 19.96%and 10.54% for influents, and 78.16%, 16.14%and 5.71% for effluents, respectively. Specifically, tris(2-chloroisopropyl) phosphate (TCPP, median: 55.17 ng/L in influents and 85.75 ng/L in effluents) was the dominant contributor to the ΣOPEs concentrations with average proportions of 37.75% and 47.33% for influents and effluents, respectively. Moreover, the concentration ranks for most OPEs except for aryl OPEs from high to low were upper reaches > lower reaches > middle reaches. However, negative values of tris(2-chloroethyl)phosphate (TCEP, -32.4%), TCPP (-55.4%) and tris(1,3-dichloroisopropyl) phosphate (TDCPP, -26.3%) were observed. The removal rates of alkyl OPEs (10-20%) and aryl OPEs (20-30%) were also not sufficient. Ecological risk values of ΣOPEs showed that there were 2.44% of high risk, 31.7% of moderate risk and 41.5% of low risk for effluents; while 0.00%, 48.8% and 46.3% were exhibited in high, moderate and low risk for influents, indicating that very slight reduction in risk was achieved by the RD-WWTFs.

Autotaxin: A Potential biomarker for primary biliary cholangitis.

Background: In some patients especially those AMA negative, the diagnosis may be a challenge requiring liver biopsy. This study determined whether autotaxin, a secreted lysophospholipase D encoded by the exonucleotide pyrophosphatase phosphodiesterase 2 gene, can be used as a serum biomarker for primary biliary cholangitis. Methods: Plasma samples were collected from 103 patients with PBC and 74 healthy controls. autotaxin levels were determined by Enzyme-linked immunosorbent assay, and its predictive value for diagnosing primary biliary cholangitis was analysed. The relationship between autotaxin and the clinical data was also evaluated. Results: Autotaxin levels in patients with primary biliary cholangitis were significantly higher than those in healthy control (median: 60.7 ng/ml vs. 32.6 ng/ml, P < 0.001). The cut-off value of autotaxin in patients with primary biliary cholangitis was 38.5 ng/ml, and the positivity rate was 33.9 %, calculated twice. The sensitivity, specificity, positive predictive value, and negative predictive value were 54.3 %, 93.1 %, 84.4 %, and 74.8 %, respectively, and the area under the curve was 0.73. Autotaxin level positively correlated with immunoglobulin M level (r = -0.22, P < 0.05) and Ludwig's classification (r = 0.76, P < 0.01) in patients with primary biliary cholangitis. The positivity rate of autotaxin (50.0 %) was higher than that of anti-sp100 (16.7 %) and anti-gp210 (11.1 %) antibodies in anti-mitochondrial antibody -negative patients with primary biliary cholangitis. Conclusions: Autotaxin may be an effective noninvasive biomarker used in diagnosis, prognosis of primary biliary cholangitis, particularly in anti-mitochondrial antibody -negative patients.

Improved slime mould algorithm based on hybrid strategy optimization of Cauchy mutation and simulated annealing.

In this article, an improved slime mould algorithm (SMA-CSA) is proposed for solving global optimization and the capacitated vehicle routing problem (CVRP). This improvement is based on the mixed-strategy optimization of Cauchy mutation and simulated annealing to alleviate the lack of global optimization capability of the SMA. By introducing the Cauchy mutation strategy, the optimal solution is perturbed to increase the probability of escaping from the local extreme value; in addition, the annealing strategy is introduced, and the Metropolis sampling criterion is used as the acceptance criterion to expand the global search space to enhance the exploration phase to achieve optimal solutions. The performance of the proposed SMA-CSA algorithm is evaluated using the CEC 2013 benchmark functions and the capacitated vehicle routing problem. In all experiments, SMA-CSA is compared with ten other state-of-the-art metaheuristics. The results are also analyzed by Friedman and the Wilcoxon rank-sum test. The experimental results and statistical tests demonstrate that the SMA-CSA algorithm is very competitive and often superior compared to the algorithms used in the experiments. The results of the proposed algorithm on the capacitated vehicle routing problem demonstrate its efficiency and discrete solving ability.

Discovery of Pyrazole-5-yl-amide Derivatives Containing Cinnamamide Structural Fragments as Potential Succinate Dehydrogenase Inhibitors.

To promote the development of novel agricultural succinate dehydrogenase inhibitor (SDHI) fungicides, we introduced cinnamamide and nicotinamide structural fragments into the structure of pyrazol-5-yl-amide by carbon chain extension and scaffold hopping, respectively, and synthesized a series of derivatives. The results of the biological activity assays indicated that most of the target compounds exhibited varying degrees of inhibitory activity against the tested fungi. Notably, compounds G22, G28, G34, G38, and G39 exhibited excellent in vitro antifungal activities against Valsa mali with EC50 values of 0.48, 0.86, 0.57, 0.73, and 0.87 mg/L, respectively, and this result was significantly more potent than boscalid (EC50 = 2.80 mg/L) and closer to the specialty control drug tebuconazole (EC50 = 0.30 mg/L). Compounds G22 and G34 also exhibited excellent in vivo protective and curative effects against V. mali at 40 mg/L. The SEM and TEM observations indicated that compounds G22 and G34 may affect normal V. mali mycelial morphology as well as the cellular ultrastructure. Molecular docking analysis results indicated that G22 and boscalid possessed a similar binding mode to that of SDH, and detailed SDH inhibition assays validated the feasibility of the designed compounds as potential SDH inhibitors. Compounds G22 and G3 were selected for theoretical calculations, and the terminal carboxylic acid group of this series of compounds may be a key region influencing the antifungal activity. Furthermore, toxicity tests on Apis mellifera l. revealed that compounds G22 and G34 exhibited low toxicity to A. mellifera l. populations. The above results demonstrated that these series of pyrazole-5-yl-amide derivatives are promising for development as potential low-risk drug-resistance agricultural SDHI fungicides.

Effect of LncRNA XIST on Immune Cells of Primary Biliary Cholangitis.

Objective: Primary biliary cholangitis (PBC) is an autoimmune disease with significant gender difference. X chromosome inactivation (XCI) plays important roles in susceptibility to diseases between genders. This work focuses on the differences of LncRNA XIST in several defined immune cells populations as well as its effects on naive CD4+ T cells proliferation and differentiation in patients with PBC. Methods: NKs, B cells, CD4+ T, and CD8+ T cells were separated by MicroBeads from peripheral blood mononuclear cells (PBMCs) of PBC patients and healthy control (HC). The expression levels of LncRNA XIST in these immune cells were quantified by qRT-PCR and their subcellular localized analyzed by FISH. Lentivirus were used to interfere the expression of LncRNA XIST, and CCK8 was used to detect the proliferation of naive CD4+ T cells in PBC patients. Finally, naive CD4+ T cells were co-cultured with the bile duct epithelial cells (BECs), and the effects of LncRNA XIST on the typing of naive CD4+ T cells and related cytokines were determined by qRT-PCR and ELISA. Results: The expression levels of LncRNA XIST in NKs and CD4+ T cells in PBC patients were significantly higher than those in HC, and were primarily located at the nucleus. LncRNA XIST could promote the proliferation of naive CD4+ T cells. When naive CD4+ T cells were co-cultured with BECs, the expressions of IFN-γ, IL-17, T-bet and RORγt in naive CD4+ T cells were decreased. Conclusion: LncRNA XIST was associated with lymphocyte abnormalities in patients with PBC. The high expression of LncRNA XIST could stimulate proliferation and differentiation of naive CD4+ T cells, which might account for the high occurrence of PBC in female.

Low-Cost and High-Productivity Three-Dimensional Nanocapacitors Based on Stand-Up ZnO Nanowires for Energy Storage.

Highly powered electrostatic capacitors based on nanostructures with a high aspect ratio are becoming critical for advanced energy storage technology because of their high burst power and energy storage capability. We report the fabrication process and the electrical characteristics of high capacitance density capacitors with three-dimensional solid-state nanocapacitors based on a ZnO nanowire template. Stand-up ZnO nanowires are grown face down on p-type Si substrates coated with a ZnO seed layer using a hydrothermal method. Stacks of AlZnO/Al2O3/AlZnO are then deposited sequentially on the ZnO nanowires using atomic layer deposition. The fabricated capacitor has a high capacitance density up to 92 fF/µm(2) at 1 kHz (around ten times that of the planar capacitor without nanowires) and an extremely low leakage current density of 3.4 × 10(-8) A/cm(2) at 2 V for a 5-nm Al2O3 dielectric. Additionally, the charge-discharge characteristics of the capacitor were investigated, indicating that the resistance-capacitance time constants were 550 ns for both the charging and discharging processes and the time constant was not dependent on the voltage. This reflects good power characteristics of the fabricated capacitors. Therefore, the current work provides an exciting strategy to fabricate low-cost and easily processable, high capacitance density capacitors for energy storage.

Synthesis and characterization of a novel dialdehyde and cyclic anhydride.

The acid treatment of a ruthenabenzene yielded an unusual dialdehyde. Interestingly, this dialdehyde has notable anti-oxidative properties and resists even nitric acid. This stability is confirmed by chemical and electrochemical experiments. In addition, a stable cyclic anhydride is synthesized from the dialdehyde via an environmentally friendly electrochemical method.