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The “shuttle effect” and several issues related to it are seen as “obstacles” to the study and development of lithium–sulfur batteries (LSBs). This work aims at finding how to fully expose bimetallic sites and quicken the battery reaction kinetics. Here, a bimetallic NiCo-MOF and its derivative NiCo@C with a hollow sea urchin structure are produced. The obtained NiCo@C possesses a micromesoporous structure and fully disclosed bimetallic active sites because of its distinctive structure. The experimental findings demonstrate that fully exposed bimetallic active sites take on chemical adsorbents and collaborate with micromesopores as physical constraints to effectively suppress the “shuttle effect”. Furthermore, the hollow sea urchin structure of NiCo@C enables a highly conductive grid, which provides channels to facilitate the movement of solvated Li+. Thanks to these advantages, the NiCo@C-based sulfur cathode offers a high initial discharge specific capacity of 924.41 mAh g–1at 0.1 C and sustains 390.35 mAh g–1discharge specific capacity after 100 cycles. The quick transfer of solvated lithium ions (DLi+= 1.81 × 10–8cm2s–1) enables the battery to still contribute a discharge specific capacity of 367.54 mAh g–1at 1 C. This work provides a new understanding for the structural design of positive electrodes in LSBs.

DNAzyme is emerging for gene therapy. The administration of the in vivocatalytic activity of DNAzyme has proven important but challenging for clinical applications. Herein, we report a synergistic DNA-polydopamine-MnO2nanocomplex, which enables near-infrared (NIR)-light-powered catalytic activity of DNAzyme in vivo. The nanocomplex has a hierarchical structure: a DNA nanoframework as the scaffold and polydopamine-MnO2(PM) as the coating layer. The DNA nanoframework contains repeated DNAzyme sequences. PM assembles on the surface of the DNA nanoframework. When the nanocomplex accumulates at tumor sites, upon NIR-light radiation, polydopamine induces a temperature elevation at tumor sites via photothermal conversion; meanwhile, glutathione triggers decomposition of PM to release Mn2+to activate DNAzyme in the cytoplasm for gene regulation. In vitroand in vivoexperiments show that the PM-induced temperature elevation enhances the Egr-1 mRNA cleavage activity of DNAzyme, promoting downregulation of the Egr-1 protein in tumor cells. In addition, the temperature elevation induces heat stress, achieving a synergistic tumor ablation effect.

Herein, we report a catalytic radical-Smiles rearrangement system of arene migration from ether to carboxylic acid with riboflavin tetraacetate (RFT), a readily available ester of natural vitamin B2, as the photocatalyst and water as a green solvent, being free of external oxidant, base, metal, inert gas protection, and lengthy reaction time. Not only the known substituted 2-phenyloxybenzoic acids substrates but also a group of naphthalene- and heterocycle-based analogues was converted to the corresponding aryl salicylates for the first time. Mechanistic studies, especially a couple of kinetic isotope effect (KIE) experiments, suggested a sequential electron transfer-proton transfer processes enabled by the bifunctional flavin photocatalyst.

Visual tracking is a popular research area in computer vision, which is very difficult to actualize because of challenges such as changes in scale and illumination, rotation, fast motion, and occlusion. Consequently, the focus in this research area is to make tracking algorithms adapt to these changes, so as to implement stable and accurate visual tracking. This paper proposes a visual tracking algorithm that integrates the scale invariance of SURF feature with deep learning to enhance the tracking robustness when the size of the object to be tracked changes significantly. Particle filter is used for motion estimation. The confidence of each particle is computed via a deep neural network, and the result of particle filter is verified and corrected by mean shift because of its computational efficiency and insensitivity to external interference. Both qualitative and quantitative evaluations on challenging benchmark sequences demonstrate that the proposed tracking algorithm performs favorably against several state-of-the-art methods throughout the challenging factors in visual tracking, especially for scale variation.

The employment of readily available photocatalysts and green oxygen atom sources is recognized as a promising strategy to develop sustainable catalysis for oxidation reactions. We herein reported a sacrificial reagent-free system consisting of riboflavin tetraacetate (RFT), an ester of natural vitamin B2 as the photocatalyst, and Sc(OTf)3and NaCl as the cocatalysts for alkyne oxidation under blue light or even sunlight irradiation to produce 1,2-diketone in which the oxygen atoms were from both water and molecular oxygen, respectively. A major Cl–/Cl• cycle was proposed to be involved and achieved by the excited [RFT-2Sc3+]* complex via single electron transfer for the first time, distinguished from the OCl–active species by a two-electron process in previous flavin–halide photo-oxidation systems.

Purpose This study aims to explore the potential mechanism of Achyranthoside D (AD) in improving intervertebral disc (IVD) degeneration (IDD).Methods The IDD model of SD rats and nucleus pulposus cells (NPCs) was established by lumbar cone annulus puncture and tert-butyl peroxide, respectively. Cell proliferation was detected by CCK8 assay. Apoptosis was detected by flow cytometry and TUNEL staining. IVD tissue injury was observed by HE staining. Alcian blue staining observed the glycoprotein secretion in IVD. Monodansylcadaverin (MDC) staining was used to detect the formation of autophagosomes. The LC3 expression was tested by immunofluorescence. The type II collagen, aggrecan and MMP3 expression were detected by ELISA. RT-qPCR was used to detect the Casp 3, Bax, Bcl2, Acan, Col2a1 and Mmp3 expression. The LC3, P62, type II collagen, aggrecan, Beclin1, Akt, MMP3, p-mTOR, PI3K, mTOR, p-PI3K and p-Akt expression were analyzed by western blot.Results The IVD tissue damage and apoptosis occurred in the Model group, and the glycoprotein secretion decreased. Compared with Model group, AD-H group alleviated the injury of IVD tissue, inhibited the apoptosis of cells, and increased the secretion of glycoprotein. 40 μg/mL AD restored the proliferation activity of NPCs. Compared to the Normal group, the NPCs apoptosis increased, the Collagen II, aggrecan and Bcl2 expressions were significantly decreased, the MMP3, Bax and Casp 3 expression were significantly increased, and the LC-3 II/I expression in IVD tissues were increased significantly in Model group, all of which was reversed in AD group. AD promoted the p-Akt, p-PI3K, p-mTOR, LC-3 II/I and Beclin1 expression, inhibited the P62 expression to alleviate the damage of nucleus pulporeus cells and the degeneration of IVD.Conclusion AD improved IDD by affecting the PI3K/Akt/mTOR pathway and autophagy.

Qualitative urinalysis can verify abstinence of drug misuse but cannot detect changes in drug intake. For drugs with slow elimination, such as methamphetamine (MA), a single episode of abuse can result in up to 5 days of positive urine drug screens. Thus, interventions that produce substantial decreases in drug use but do not achieve almost complete abstinence are classified as ineffective. Using nonpharmacologic doses of deuterium-labeled l-methamphetamine (l-MA-d(3)) we have developed a simple, robust method that reliably estimates changes in MA intake. Twelve subjects were dosed with 5 mg of l-MA-d(3) daily and challenged with 15, 30, and 45 mg of nonlabeled d-MA (d-MA-d(0)) after reaching plasma steady status of l-MA-d(3). Urinary concentration ratios of d-MA-d(0) to l-MA-d(3) provided clear separation of the administered doses with as little as 15-mg dose increments. Administered doses could not be resolved using d-MA-d(0) concentrations alone. In conclusion, the urinary [d-MA-d(0)]:[l-MA-d(3)] provides a quantitative, continuous measure of illicit MA exposure. The method reliably detects small, clinically relevant changes in illicit MA intake from random urine specimens, is amenable to deployment in clinical trials, and can be used to quantify patterns of MA abuse.

Interstitial deletion of 16q has emerged into a recognizable pattern of congenital malformation. We report on a 9yearold boy with short stature, psychomotor retardation, high forehead, broad flat nasal bridge, hypertelorism, cupshaped ears, short neck, and a normal karyotype. Using highdensity oligonucleotide array chip Affymetrix 6.0 to perform parental and proband samples concurrently on three chips and interpreted as a trio set, a de novo 3.2 Mb deletion from bands q12.2 to q13 on chromosome 16 from 52.08 to 55.3 Mb of paternal origin was identified. The deletion was confirmed by quantitative genomic PCR and the break points were defined by junction PCR. Our study demonstrated the power of highdensity oligonucleotide array chip in identifying novel submicroscopic deletions that were not detectable using Gbanding cytogenetic technology. Furthermore, our result narrowed down the critical region for craniofacial features in interstitial 16q11.2q13 deletion syndrome. In patients who have high forehead, broad flat nasal bridge, hypertelorism, cupshaped ears, short neck and short stature, highdensity array should be included in initial work up. © 2010 WileyLiss, Inc.

All addictive drugs produce tolerance and addicts compensate by increasing drug exposure. Thus, the quantity of illicit drug ingested is related to the severity of addiction. Unfortunately, there are no objective methods to estimate intake for most addictive drugs. Using experimenter-administered doses of deuterium-labeled R-methamphetamine (R-[-]-MA-d3), we have developed a method to estimate the amount of abused methamphetamine intake in addicts enrolled in clinical trials. This study assessed the pharmacokinetics, pharmacodynamics, and tolerability of single oral doses of R-MA in healthy adults to select a dose of R-MA-d3 to be used as a biomarker for estimation the amount of methamphetamine abuse. This was a five-session randomized, double-blind, placebo-controlled, balanced crossover study in eight subjects. Oral R-(-)-MA was dosed at 0 mg, 1 mg, 2.5 mg, 5 mg, or 10 mg; bioavailability was estimated by slow intravenous dosing (30 minutes) of 2.5 mg R-(-)-MA-d3 given with the 2.5 mg R-(-)-MA oral dose condition. Pharmacokinetic and pharmacodynamic measures were obtained. No serious adverse events occurred during the study and all doses of R-MA were well tolerated. Linear pharmacokinetics was observed within our oral dose range of 1 to 10 mg. Complete bioavailability and pharmacologic inactivity were found for all oral doses. These characteristics indicate the advantage of using a small oral R-(-)-MA-d3 dose as a biomarker to estimate exposure to abused methamphetamine. Based on these results, 5 mg R-(-)-MA-d3 has been selected as the biomarker dose in future studies. Preliminary findings from our study indicate that experimenter-administered oral R-(-)-MA-d3 may allow estimation of abused methamphetamine intake and exposure. Knowledge of the quantity of methamphetamine intake may allow better estimation of disease severity and treatment efficacy. Experience gained from this study also can be applied to the management of other drug dependence problems such as cocaine, cannabinoid, and opiate addiction.

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The human concentrative nucleoside transporter 2 (hCNT2) plays a major role in the intestinal absorption of naturally occurring nucleosides as well as some nucleoside analog drugs. To determine if single nucleotide polymorphisms (SNPs) in the promoter region of hCNT2 affect gene expression, we examined approximately 1 kb upstream the hCNT2 transcription start site. Ninety Chinese samples were screened and seven SNPs were identified:–115T>G, –146T>A, –264A>G, –564G>A, –861A>C, –880T>C and – 906C>T. Based on these seven variants and their relative positions, eight haplotypes were identified using PHASE v2.1.1. Three naturally occurring haplotypes were cloned into the pGL3-Basic vector and transfected into HEK293 cells. Dual luciferase assay revealed that haplotype 4 (GTAGACC) and 7 (GAGAACT) exhibited significantly lower expression levels compared to the published haplotype 1 (TTAGATC). Results from our in-vitro study showed that the hCNT2 promoter region haplotype may modulate gene expression and cause different drug responses.

The human concentrative nucleoside transporter (hCNT2), also known as SLC28A2, plays an important role in the cellular uptake across intestinal membrane of some naturally occurring nucleosides and nucleoside analogs. This study aims to determine the genetic variability of hCNT2 (SLC28A2) in three major Asian ethnic groups residing in Singapore Chinese, Malay and Indian, and functionally characterize the variants of hCNT2. Healthy participants (n96) from each group were screened for genetic variations in the exons of hCNT2 (SLC28A2) using denaturing high performance liquid chromatography and sequencing analyses. A total of 23 polymorphisms were identified in the exonic and flanking intronic regions, and ethnic differences in single nucleotide polymorphism frequencies were evident. Five novel nonsynonymous variants (L12R, R142H, E172D, E385K, M612T) were constructed by mutagenesis and functionally characterized in U-251 cells. Expression of these variants in U-251 cells revealed that all except E385K can uptake various substrates of hCNT2 inosine, ribavirin and uridine.

Extraordinary high degrees of polar order can be achieved by a rational design that involves the polar stacking of parallel beloamphiphile monolayers (PBAM). This strategy is exemplified by the acetophenone azines MCA (4-methoxy-4′-chloroacetophenone azine) and DCA (4-decoxy-4′-chloroacetophenone azine). The beloamphiphile design aims to achieve strong lateral interactions by way of arene–arene, azine–azine, arene–azine and halogen-bonding interactions. Dipole-induced interactions and halogen bonding dominate interlayer interactions and halogen bonding is shown to effect the layer stacking. Crystals of DCA contain PBAMs with perfect polar order andperfect polar layer stacking, while crystals of MCA features perfect polar order only in one of two layers and layer stacking is polar but not entirely perfect. We report the synthesis of the beloamphiphile DCA, its crystal structure, and we present a comparative discussion of the structures and intermolecular interactions of MCA and DCA. Absorbance and photoluminescence measurements have been carried out for solutions of DCA and for DCA crystals. DCA exhibits a broad emission centered at 2.5 eV when excited with UV radiation. The nonlinear optical response was studied by measuring second harmonic generation (SHG). Strong SHG signals have been observed due to the polar alignment and the DCA crystal's NLO response is 34 times larger than that of urea. Optimization of the beloamphiphile and systematic SAR studies of the polar organic crystals, which are now possible for the very first time, will further improve the performance of this new class of functional organic materials. The materials are organic semiconductors and show promise as blue emitters, as nonlinear optical materials and as OLED materials.