Puddle formation and persistent gaps across the non-mean-field breakdown of superconductivity in overdoped (Pb,Bi)2Sr2CuO6+δ.

The cuprate high-temperature superconductors exhibit many unexplained electronic phases, but the superconductivity at high doping is often believed to be governed by conventional mean-field Bardeen-Cooper-Schrieffer theory1. However, it was shown that the superfluid density vanishes when the transition temperature goes to zero2,3, in contradiction to expectations from Bardeen-Cooper-Schrieffer theory. Our scanning tunnelling spectroscopy measurements in the overdoped regime of the (Pb,Bi)2Sr2CuO6+δ high-temperature superconductor show that this is due to the emergence of nanoscale superconducting puddles in a metallic matrix4,5. Our measurements further reveal that this puddling is driven by gap filling instead of gap closing. The important implication is that it is not a diminishing pairing interaction that causes the breakdown of superconductivity. Unexpectedly, the measured gap-to-filling correlation also reveals that pair breaking by disorder does not play a dominant role and that the mechanism of superconductivity in overdoped cuprate superconductors is qualitatively different from conventional mean-field theory.

Why Shot Noise Does Not Generally Detect Pairing in Mesoscopic Superconducting Tunnel Junctions.

The shot noise in tunneling experiments reflects the Poissonian nature of the tunneling process. The shot-noise power is proportional to both the magnitude of the current and the effective charge of the carrier. Shot-noise spectroscopy thus enables us, in principle, to determine the effective charge q of the charge carriers of that tunnel. This can be used to detect electron pairing in superconductors: In the normal state, the noise corresponds to single electron tunneling (q=1e), while in the paired state, the noise corresponds to q=2e. Here, we use a newly developed amplifier to reveal that in typical mesoscopic superconducting junctions, the shot noise does not reflect the signatures of pairing and instead stays at a level corresponding to q=1e. We show that transparency can control the shot noise, and this q=1e is due to the large number of tunneling channels with each having very low transparency. Our results indicate that in typical mesoscopic superconducting junctions, one should expect q=1e noise and lead to design guidelines for junctions that allow the detection of electron pairing.

Fluorescence Enhancement of Adamantane-Modified Dyes in Aqueous Solution via Supramolecular Interaction with Methyl-ß-cyclodextrin and Their Application in Cell Imaging.

The fluorescence of functional dyes was generally quenched in aqueous solution, which hindered their application in water-bearing detections. In this work, a novel strategy based on host-guest interaction was provided for the purpose of fluorescence enhancement in aqueous solution and cell imaging. Three adamantane-modified fluorescent dyes (Coum-Ad, NP-Ad, NR-Ad) with coumarin, 1,8-naphthalimide and Nile Red as fluorophores were initially designed and prepared. The ((adamantan-1-yl)methyl)amino group, as the auxochrome of those dyes, complexed with methylated ß-cyclodextrin (M-ß-CD) via supramolecular interaction, and then fluorescent supramolecular nanoparticles (FSNPs) were formed by self-assembly in water. The inclusion equilibrium constant (K) could be as high as 3.94×104  M-1 . With the addition of M-ß-CD, fluorescence quantum yields of these dyes were separately improved to 69.8 %, 32.9 % and 41.3 %. Inspired by the above satisfactory results, six adamantane-modified probes organelle-NPAds with organelle-targeting capability were further obtained. As the formation of hydrogen bonds between organelle-NPAd2 and M-ß-CD verified by theoretical calculation, K of organelle-NPAd2 (5.13×104  M-1 ~4.53×105  M-1 ) with M-ß-CD was higher than that of organelle-NPAd1 (1.15×104  M-1 ~3.66×104  M-1 ) and their fluorescence quantum yields increased to 32.8 %~83.6 % in aqueous solution. In addition, fluorescence enhancement was realized in cell imaging with the addition of M-ß-CD.

Viscosity probes towards different organelles with red emission based on an identical hemicyanine structure.

A series of viscosity probes targeting different organelles were obtained using a single hemicyanine dye as the matrix structure. Specifically, probes 1a-d were obtained by introducing four amines (6-amino-2H-chromen-2-one, N-(2-aminoethyl)-4-methylbenzenesulfonamide, dodecan-1-amine and N,N diphenylbenzene-1,4-diamine) into the indole hemicyanine dye of the carboxylic acid with a D-π-A structure. Their maximum absorption wavelengths were in the range 570-586 nm and they had relatively large molar absorption coefficients, while their maximum emission wavelengths in the red light region were in the range 596-611 nm. Moreover, their fluorescence intensity in glycerol was 35-184 times higher than that in phosphate buffer solution (PBS). The lg(Fl) and lg η of probes 1a-d showed good linearity with high correlation coefficients according to the Förster-Hoffman equation. In addition, cell staining experiments demonstrated that 1a-c could target lysosomes, endoplasmic reticulum and mitochondria, respectively. They could also undergo viscosity-detectable changes in the corresponding organelles under the action of the corresponding ion carriers.

Conjugated structures based on quinazolinones and their application in fluorescent labeling.

As an alkaloid, quinazolinone exhibits excellent biological properties; structurally, it also has the potential to construct fluorescent probes with conjugated structures. In this work, probes 5a-c and 6b were obtained by introducing quinazolone into aldehydes with different numbers of double bonds. Their absorption maxima were located at 420-540 nm and their emission maxima were at 500-600 nm in solvents of different polarities. In particular, probe 5c showed significant fluorescence enhancement with the increase in viscosity due to the limited intramolecular rotation, and its fluorescence intensity in glycerol was 37.8 times higher than that in water. Moreover, probes 5a-c and 6b containing the NH structure showed sensitive response to pH, and their fluorescence intensity in alkaline solution (pH 9-11) was suddenly enhanced, which was elucidated with the help of theoretical calculation. In addition, the cell experiments showed that probes 5a and 5b had the ability to target mitochondria and probes 5c and 6b targeted lysosomes in HeLa cells. Furthermore, the viscosity-sensitive probe 5c could be used for monitoring changes in lysosomal viscosity in HeLa cells, which had important guiding significance for designing multi-response fluorogenic probes and promoting the advancement of cancer diagnosis.

Improved emission performance of benzo[a]phenoxazine in aqueous solution through host-guest interaction.

To evaluate the contribution of host-guest chemistry in fluorescence enhancement under aqueous conditions, two benzo[a]phenoxazine derivatives with the adamantyl group were prepared. After they formed stable complexes with methyl-ß-cyclodextrin, their emissions at 625-825 nm were greatly increased and fluorescence quantum yields reached 11.5-12.6% in aqueous solution. Furthermore, they were successfully applied in fluorescence labeling of organelles in HeLa cells.

Methylated Chromenoquinoline as a Novel Nucleus Fluorescent Probe for Nucleic Acid Imaging.

Two chromenoquinoline-based fluorescent probes 1a-b have been synthesized and investigated. Photofading behaviors of compounds 1a-b showed that at least 89% absorption remained after 6 h irradiating, meanwhile, many of ions and amino acids had negligible impacts on their fluorescence intensity, which meant they had excellent photostability and selectivity. Probes 1a-b exhibited strong absorption and emission in organic solvents with large fluorescence quantum yields, even in water probe 1a still had a relatively large fluorescence quantum yield (20%). Combined with DFT calculation, the influence of alkylation on optical properties of 1b was elucidated. In addition, the fluorescence intensity of probe 1b with red emission enhanced by 5.4-fold and 5.3-fold after DNA and RNA added, and the fluorescence quantum yield increased from 3% to 17% and 14%, respectively, but the neutral molecule 1a had no response to nucleic acid. Furthermore, confocal microscopy imaging of probes 1a-b showed that 1a targeted lipid droplets while the methylated probe 1b to nucleus in living HeLa cells. The results indicated that the subcellular targeting zone could be changed by alkylation of nitrogen atom on chromenoquinoline-based conveniently, which provided a new idea for designing and synthesizing new subcellular labeled probes.

Preparation of Chromeno[b]quinoline Derivatives and Their Application for Lipid Droplets Markers.

Functional dyes with a chromeno[b]quinoline skeleton (3a-d) were synthesized by one-step cyclization between coumarin derivatives and aromatic amines under the promotion of anhydrous aluminum chloride in 41.2-45.8% yields. Their maximum absorption and emission wavelengths locate at 358-396 and 420-603 nm with large Stokes shifts (168-231 nm), and their intramolecular charge transfer has been corroborated by density functional theory calculations. Cell experiments have proved that the probes 3a-c possess the ability to target lipid droplets.

Fluorescent probes based on acridine derivatives and their application in dynamic monitoring of cell polarity variation.

Polarity and viscosity, as important microenvironment parameters, play an essential role in cell metabolism. Therefore, 9-acridine carboxaldehyde reacted with cyano compounds to obtain polarity-sensitive probes 1a-b and viscosity-sensitive probes 1c-d. Among them, with the increase in solvent polarity, the maximum emission wavelength of acridine-dicyanoisophorone-based probe 1a red-shifted from 553 nm to 594 nm, the fluorescence quantum yield increased from 0.5% to 35.6%, and the fluorescence intensity enhanced 38 fold. The acridine-cyanofuranone based probe 1b also has a polarity response similar to 1a. Nevertheless, when the solution viscosity increased from 0.89 cP (100% water) to 856 cP (1% water), the fluorescence intensity of the acridine-tricyanodihydrofuran based probe 1c at 430 nm enhanced 5.6 times. The acridine-cyanobenzothiazole based probe 1d also had a viscosity response similar to 1c. In addition, probes 1a-b were used for further HeLa cell imaging experiments due to their good photostability and the results suggested that probe 1a could locate lipid droplets and probes 1b-c could stain lysosomes. Moreover, probes 1a-b could dynamically monitor the changes in intracellular polarity.

Near-infrared fluorescent probes based on a quinoxaline skeleton for imaging nucleic acids in mitochondria.

In this paper, two cationic probes 1a and 1b and a neutral dye 1c were successfully designed and synthesized according to the Knoevenagel condensation reaction, which combines the good optical properties of hemocyanine and the biocompatibility of nitrogen-containing heterocyclic rings based on a quinoxaline skeleton. Probes 1a and 1b showed an OFF-ON fluorescence response to nucleic acids with excellent selectivity. Specifically, the fluorescence intensity of probe 1a was enhanced by 18 and 133 times, respectively, along with the increase of DNA or RNA concentrations (0-600 µg mL-1). Furthermore, a good linear correlation between the fluorescence intensity of probes 1a and 1b and the concentrations of DNA or RNA (0-350 µg mL-1) was obtained. In particular, the maximum emission wavelengths of probes 1a and 1b reached the near-infrared region (660-664 nm) when DNA or RNA was detected, which might reduce the light damage to cells and facilitate cell experiments. Fluorescence imaging revealed that all three dyes could be localized in the mitochondria of HeLa cells. The difference was that probes 1a and 1b could stain the nucleic acid in the mitochondria, while dye 1c was only a neutral mitochondrial biomarker. The results indicated that probes 1a and 1b are promising in the development of low toxicity mitochondrial nucleic acid probes and are expected to be used in monitoring the normal state of mitochondrial nucleic acids for living cells, which will help improve the situation in that currently reported studies of fluorescent probes are mainly focused on the nucleic acids in the nucleus, but less so on DNA in the mitochondria.

Design and synthesis of a series of OFF-ON near infrared fluorescent probes for nucleic acid in aqueous solution.

Five cyanine dyes (6a-e) with aza units were prepared by the reaction of pyridinum or quinolinium with suitable aldehydes. They present several remarkable features including large Stokes shift (235-282 nm), long emission wavelength (640-698 nm) and excellent selectivity. Moreover, probes 6a-b display obvious and sensitive fluorescent response to DNA and RNA in aqueous solution, and the quantum yield of probe 6a response to RNA increases from 0 to 8.9%. More importantly, probes 6c and 6e can effectively avoid DNA interference and only respond to RNA in aqueous solution. In addition, laser confocal cell experiment has showed that probe 6b can image the nucleolus of nucleic acids in HeLa cells.

Series of Mitochondria/Lysosomes Self-Targetable Near-Infrared Hemicyanine Dyes for Viscosity Detection.

Six mitochondria/lysosomes self-targetable and viscosity-sensitive dyes (1a-1f) were developed via simple structure modification on cyanine-derived dyes. They all showed remarkable OFF-ON fluorescent response to viscosity in the near-infrared region (652-690 nm) and exhibited good linear relationship with solution viscosity. The transient absorption spectra were used to evaluate the excited-state lifetime of dye 1a in different viscosity environments. Furthermore, cellular imaging assays indicated that different derivatives (1a-1f) with the same chromophore core exhibited different organelle-targeting abilities. Among them, dyes 1a-1c could sense lysosomal viscosity fluctuations while dyes 1d-1f could be applied in mitochondrial viscosity detections.

The fluorescent markers based on oxazolopyridine unit for imaging organelles.

Bioactive oxazolopyridine unit was used in the synthesis of fluorescent markers for specific organelles in this paper. The compounds 1a-c are linked with double bond between oxazolopyridine ring and photogenic precursors (3a-c). Compound 1a showed higher fluorescence yield (0.86 in THF), compounds 1b-c showed larger stokes shifts in DMSO. In lipid vesicles environment, they also showed good optical properties. In addition, the three compounds are biomarkers with lower cytotoxicity. Among them, compound 1a based on oxazolopyridine and coumarin unit is a dual targetable fluorescent marker for mitochondria and lipid droplets; while the other two compounds 1b-c are only biomarkers for lipid droplets.

Effectiveness of Virtual Reality in Nursing Education: Meta-Analysis.

BACKGROUND: Virtual reality (VR) is the use of computer technology to create an interactive three-dimensional (3D) world, which gives users a sense of spatial presence. In nursing education, VR has been used to help optimize teaching and learning processes. OBJECTIVE: The purpose of this study was to evaluate the effectiveness of VR in nursing education in the areas of knowledge, skills, satisfaction, confidence, and performance time. METHODS: We conducted a meta-analysis of the effectiveness of VR in nursing education based on the Cochrane methodology. An electronic literature search using the Cochrane Library, Web of Science, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature), up to December 2019 was conducted to identify studies that reported the effectiveness of VR on knowledge, skills, satisfaction, confidence, and performance time. The study selection and data extraction were carried out by two independent reviewers. The methodological quality of the selected studies was determined using the Cochrane criteria for risk-of-bias assessment. RESULTS: A total of 12 studies, including 821 participants, were selected for the final analysis. We found that VR was more effective than the control conditions in improving knowledge (standard mean difference [SMD]=0.58, 95% CI 0.41-0.75, P<.001, I2=47%). However, there was no difference between VR and the control conditions in skills (SMD=0.01, 95% CI -0.24 to 0.26, P=.93, I2=37%), satisfaction (SMD=0.01, 95% CI -0.79 to 0.80, P=.99, I2=86%), confidence (SMD=0.00, 95% CI -0.28 to 0.27, P=.99, I2=0%), and performance time (SMD=-0.55, 95% CI -2.04 to 0.94, P=.47, I2=97%). CONCLUSIONS: The results of this study suggest that VR can effectively improve knowledge in nursing education, but it was not more effective than other education methods in areas of skills, satisfaction, confidence, and performance time. Further rigorous studies with a larger sample size are warranted to confirm these results.

Tetradecanuclear and Octadecanuclear Gold(I) Sulfido Clusters: Synthesis, Structures, and Luminescent Selective Tracking of Lysosomes in Living Cells.

Reactions of the phosphanyl-gold(I) precursor [(AuCl)2(bdppmapy)] (1; bdppmapy = N,N-bis(diphenylphosphanylmethyl)-2-aminopyridine) with Na2S in a 1:1 or 1:2 molar ratio gave rise to one tetradecanuclear and one octanuclear Au(I) sulfido cluster, [Au14S6(bdppmapy)5]Cl2 (2) and [Au18S8(bdppmapy)6]Cl2 (3), respectively. The former displays a new structural framework in gold cluster chemistry. Compounds 2 and 3 showed strong green luminescence and were employed as excellent imaging probes to selectively light up the lysosomes of living cells. Their long-term tracking of lysosomes can be achieved for up to 36 h, while tracking with commercial Lyso-Tracker Red under the same conditions was limited to 3 h. Our work demonstrated the possibility of constructing novel gold(I) sulfido clusters supported by special P-N hybrid ligands and the potential application of these clusters as long-term selective trackers of lysosomes in bioimaging.

Rosamine with pyronine-pyridinium skeleton: unique mitochondrial targetable structure for fluorescent probes.

Two rosamine-based probes (1a-b) with pyronine-pyridinium skeleton were designed and prepared. Probe 1a bearing boron ester unit was oxidized and eliminated upon addition of hydrogen peroxide (H2O2), and the emission spectrum exhibited OFF-ON response accompanied by 33-fold fluorescent enhancement. In contrast, the fluorescence intensity of probe 1b enhanced 58 times after the dinitrophenyl ether part within the probe was removed by nucleophilic substitution with hydrosulfide (H2S). The design concept was based on the d-PET process in pyronine-pyridinium structures, and free 4-pyridinyl-substituted pyronine dye showing strong fluorescence was released followed by elimination. Furthermore, as biocompatible molecules, probes 1a-b have been successfully applied for imaging in live HeLa and Ges-1 cells, and all of them can serve as mitochondrial targetable probes in red channel for detecting independent species.

The improvement of lysosome targetability with oligoethyleneoxy chains linked benzo[a]phenoxazine.

In order to improve lysosome targetability of probes, fluorescent probes based on benzo[a]phenoxazine attaching different length oligoethyleneoxy chains were designed and prepared. Probes 2a-c containing N-pyridineium-3-yl exhibited almost ON-OFF near-infrared emission responses at 697-701 nm from pH 2.8 to 7.2, and the calculated pKa values of 2a-c were 4.90, 4.92 and 5.03 respectively. More importantly, fluorescent imaging experiments indicated that probes 2a-c were all lysosome biomarkers for Ges-1 and HeLa cells, which was because the introduction of oligoethyleneoxy groups improved the biocompatibility of probes, so that the probes 2a-c were better transported to lysosomes via the endocytosis pathway of the cells. Moreover, the probe 2a was selected as a representative, which not only showed good reversibility and selectivity, but used to successfully image lysosomal pH increases induced by chloroquine.

The fluorescent biomarkers for lipid droplets with quinolone-coumarin unit.

Two quinolone-coumarin skeleton derivatives (1a, 1b) have been prepared by Friedländer synthesis with 2-aminoaryl ketone and 3-acetyl-7-diethylaminocoumarin. The dyes showed excellent photo stability. Their optical properties in five organic solvents have been measured, and the wavelength range of the maximum fluorescence emission peaks was from 469 nm to 509 nm. Besides, both of them exhibited high fluorescence quantum yields (0.79-0.96) in these organic solvents. The pH influenced optical properties tests indicated dyes 1a-b have strong fluorescence in sub acid (pH = 6.0) to alkaline environment (pH = 9.0). Their fluorescence quantum yields in neutral aqueous solution (pH = 7.0) were 0.82 (1a) and 0.78 (1b) respectively. In addition, dyes 1a-b exhibited stable fluorescence intensity in the presence of some metal cations and biomolecules in neutral solution (pH = 7.0). Subsequently, confocal microscopy imaging indicated that dyes 1a-b could be used as biomarkers for lipid droplets in living and fixed cells (I929 and HeLa cells).

The pH-influenced PET processes between pyronine and different heterocycles.

The OFF-ON and ON-OFF type pH probes based on rosamine were designed by using the relative electron densities between pyronine and various linked heterocycles. Probe 1a with an indole-pyronine skeleton gave an OFF-ON pH response (pKa = 1.41) with decreasing pH, and the relative fluorescence intensity increased 15-fold, while probe 1b with an imidazole-pyronine skeleton did not give an ON-OFF response to different pH values. When pyronine was connected with a quinolinyl group, i.e., probes 1c-d, the red emission (around 575-800 nm) gave a monotonous ON-OFF pH response (pKa = 3.26 and 2.62, respectively) with decreasing pH. The relative fluorescence intensities decreased 263- and 46-fold, respectively. Changes in the electron donating abilities of the nitrogen containing heterocycles were used to explain variations in PET processes within the probes, and their pH-dependent PET mechanisms were verified using time-dependent density functional theory calculations. Confocal fluorescence imaging was also used to evaluate the potential biomedical application of probes 1a-d. Ultimately, probe 1d with an appropriate pKa value and good biocompatibility showed lysosome targeting ability.

Reversible Absorption and Emission Responses of Nile Blue and Azure A Derivatives in Extreme Acidic and Basic Conditions.

Oxazinium derivatives have recently played an important role in bioanalysis attributing to the distinguished properties, thus a detailed study of the structure-property relationship is especially significant. Herein, pH-sensitive optical properties of Nile Blue (1a), N-monoalkyl-Nile Blue (1b) and Azure A (1c) have been carried out in extreme acid and base conditions. Dyes 1a and 1c showed colorimetric changes by the protonation of nitrogen atom in strong acidic condition (pH < 2.0), and dyes 1a - c exhibited colorimetric changes by equilibrium between amino and imide groups in very strong basic case (pH > 7.6). Besides, their fluorescent properties were closed to ON - OFF and OFF - ON emissions at 640-820 nm under strong acidic and basic conditions. Moreover, the absorption and emission properties were reversible, and there were no remarkable optical intensity changes of dyes 1a - c under subacidic and neutral solutions (pH = 3.0-7.0). The (TD) DFT calculations were used to optimize the most stable structures of their corresponding protonated and deprotonated forms, and their absorption and emission properties were also explained. Their fluorescent properties nearly ON-OFF and OFF - ON in strong acidic and basic conditions at near-infrared region will give the possible application in pH detection for extreme conditions. Graphical abstract ᅟ.