A Novel Multi-Functional Fluorescence Probe for the Detection of Al3+/Zn2+/Cd2+ and its Practical Applications.

A novel multi-functional fluorescence probe HMIC based on hydrazide Schiff base has been successfully synthesized and characterized. It can distinguish Al3+/Zn2+/Cd2+ in ethanol, in which fluorescence emission with different colors (blue for Al3+, orange for Zn2+, and green for Cd2+) were presented. The limits of detection of HMIC towards three ions were calculated from the titration curve as 7.70 × 10- 9 M, 4.64 × 10- 9 M, and 1.35 × 10- 8 M, respectively. The structures of HMIC and its complexes were investigated using UV-Vis spectra, Job's plot, infrared spectra, mass spectrometry, 1H-NMR and DFT calculations. Practical application studies have also demonstrated that HMIC can be applied to real samples with a low impact of potential interferents. Cytotoxicity and cellular imaging assays have shown that HMIC has good cellular permeability and potential antitumor effects. Interestingly, HMIC can image Al3+, Zn2+ and Cd2+ in the cells with different fluorescence signals.

Abnormalities of the Halogen Bonds in the Complexes between Y2CTe (Y = H, F, CH3) and XF (X = F, Cl, Br, I).

In this work, the hydrogen bonds and halogen bonds in the complexes between Y2CTe (Y = H, F, CH3) and XF (X = F, Cl, Br, I) have been studied by quantum chemical calculations. We found three interesting abnormalities regarding the interactions. Firstly, the strength of halogen bonds increases in the order of IF < BrF < ClF < F2. Secondly, the halogen bonds formed by F2 are very strong, with an interaction energy in the range between −199.8 and −233.1 kJ/mol. Thirdly, all the halogen bonds are stronger than the hydrogen bonds in the systems we examined. All these results are against the general understanding of halogen bonds. These apparent abnormal properties are reconciled with the high polarizability of the Te atom and the strong inducing effect of F on the Te atom of Y2CTe. These findings provide a new perspective on halogen bonds. Additionally, we also proposed bonding distance-based methods to compare the strength of halogen/hydrogen bonds formed between different donor atoms and the same acceptor atom.

A novel double target fluorescence probe for Al3+/Mg2+ detection with distinctively different responses and its applications in cell imaging.

The metal cations, Al3+ and Mg2+, could affect human health and cell biological processes. Their fast and selective detection using one probe remains a challenge. A novel fluorescence probe, N'-((1-hydroxynaphthalen-2-yl)methylene)isoquinoline-3-carbohydrazide (NHMI), was developed for selectively monitoring Al3+ and Mg2+. The probe NHMI showed a distinctive "turn-on" fluorescence signal towards Al3+ and Mg2+ (cyan for Al3+ with 2556-folds enhancement and yellow for Mg2+ with 88-folds enhancement), which is quite distinct from other metal cations and allows for naked-eye detection. This interesting response was attributed to the influence of PET, ESIPT process and CHEF effect, when Al3+ or Mg2+ chelated with NHMI. Furthermore, the fluorescence titration experiments manifested that the detection limit of probe NHMI for Al3+/Mg2+ was as low as 1.20 × 10-8 M and 7.69 × 10-8 M, respectively. The formed complexes NHMI-Al3+ and NHMI-Mg2+ were analyzed by Job's plot, ESI-MS, 1H NMR and FT-IR. The coordination pockets and fluorescence mechanisms of two metal complexes were explored by density functional theory calculation. Moreover, NHMI showed low cytotoxicity and good cell permeability. Fluorescence bioimaging of Al3+/Mg2+ in MCF-7 cells with NHMI indicated its potential application in biological diagnostic analysis.

Clinical characteristics of otogenic lateral sinus thrombosis in patients under 18 years old compared with that in adult patients.

BACKGROUND: Otogenic lateral sinus thrombosis (OLST) is a rare complication of otitis media. We do not know whether the disease progress between the pediatric and adult OLST patients is consistent. However, pediatric surgical methods always refer to the adults'. AIMS/OBJECTIVES: This study aimed to seek evidence for suitable surgical methods in pediatric patients. MATERIALS AND METHODS: The clinical manifestation, laboratory findings, and findings in operation between children and adult groups were compared. RESULTS: Ten children and 17 adults OLST patients were included. Most pediatric patients had no history of chronic otitis media or cholesteatoma (p<.001). The ratios of otorrhea, tympanic perforation and sclerotic type mastoid in CT scan were significantly lower in the children group (p<.05). The mean air conduction hearing threshold in the children and adolescent group (31.25 ± 21.27 dB) was significantly lower than that of the adult group (77.6 ± 23.66 dB) (p<.001). The diseases in attics (66.7%) and the ossicular chain destruction (33.3%) were not as severe as those in the adult group (p<.05). The eustachian tube closure was found similar in two groups. CONCLUSIONS AND SIGNIFICANCE: Conservative surgery is recommended to pediatric OLST to obliterate the diseases and improve middle ear and mastoid drainage, preserving hearing function.

A novel hydrazide Schiff base self-assembled nanoprobe for selective detection of human serum albumin and its applications in renal disease surveillance.

Human serum albumin (HSA) is considered as a biomarker for the early diagnosis of renal disease, therefore identifying and detecting HSA in biological fluids (especially urine) with an easy method is of great importance. Herein, we report a novel hydrazide Schiff base fluorescent probe N'-((7-(diethylamino)-2-oxo-2H-chromen-3-yl)methylene)pyrazine-2-carbohydrazide (NPC), which self-assembled into nanoparticles in aqueous solution. Based on disassembly-induced emission and the site-specific recognition mechanism, the binding of NPC with HSA resulted in a fluorescence "turn-on" response. Probe NPC exhibited superior selectivity and sensitivity toward HSA with a detection limit of 0.59 mg L-1 in PBS and 0.56 mg L-1 in the urine sample. The site-binding mechanism of NPC with HSA was explored by fluorescence quenching study, Job's plot analysis, HSA destruction, site marker displacement and molecular docking. Fluorescence imaging of HSA in MCF-7 cells was achieved by using a non-toxic NPC probe, suggesting that NPC could be applied to visualize the level of HSA in vivo. More importantly, further practical applications of probe NPC in human urine samples were achieved with satisfactory results by using a fluorometer or test paper, which could provide extensive application in clinical diagnosis.

A dual-functional fluorescent probe for sequential determination of Cu2+/S2- and its applications in biological systems.

A new acylhydrazine-derived Schiff base fluorescence probe DMI based on "ON-OFF-ON" fluorescence strategy was presented in this paper. Probe DMI could detect Cu2+ selectively and sensitively with dramatic fluorescence quenching in CH3OH-PBS (v/v = 3:7) mixed solution. Once the complex DMI-Cu2+ interacted with S2-, 10.67-folds fluorescence increase was induced via a displacement mechanism under the same experimental conditions. The corresponding detection limits for Cu2+ and S2- were calculated to be 1.52 × 10-8 M and 1.79 × 10-8 M, respectively. The structures of DMI and DMI-Cu2+ were systematically characterized by Job's plot analysis, ESI-MS, IR, X-ray diffraction and density functional theory calculations. Furthermore, fluorescence imaging in MCF-7 cells and zebrafish demonstrated the probe DMI could act as a useful tool to monitor and track intracellular Cu2+ and S2-, which was encouraged by remarkable fluorescence performance and low cytotoxicity. Importantly, the complex DMI-Cu2+ could be applied to detect corrupt blood samples, which could estimate the time of death.

Highly selective and sensitive chemosensor for Al(III) based on isoquinoline Schiff base.

As a colorimetric and fluorescent turn-on sensor to Al3+, N'-(2-hydroxybenzylidene)isoquinoline-3-carbohydrazide (HL) has been easily synthesized. The fluorescence intensity increases by 273 times in the presence of Al3+ at 458 nm. Meanwhile, the experiment data indicate that the limit of detection for Al3+ is 1.11 × 10-9 M. Remarkably, the blue fluorescence signal of HL-Al3+ could be specially observed by the naked eye under UV light and is significantly different from those of other metal ions. Fluorescence switch based on the control of Al3+ and EDTA proved HL could act as a reversible chemosensor. According to ESI-MS result and the Job's plots, the 2:1 coordination complex formed by HL and Al3+ could be produced. Density functional theory calculations were performed to illustrate the structures of HL and complex. The cell imaging experiment indicates that HL can be applied for monitoring intracellular Al3+ levels in cells.

Is the Fourier Transform Infrared Free-OH Band of t-Butanol Only from Free OHs? Case Studies on the Binary Systems of the Alcohol with CCl4 and CHCl3.

Attenuated total reflection-Fourier transform infrared spectroscopy and quantum chemical calculations were performed on tert-butyl alcohol (t-BuOH) and its binary solutions with CCl4 and CHCl3. The study was focused on the free-OH stretching bands. Two resolution-enhancing methods, excess spectroscopy and two-dimensional correlation spectroscopy, were employed to examine the structural heterogeneity and search for the detailed contributors to the free-OH bands. Unexpectedly, CCl4 was found not to be an inert solvent and, similar to CHCl3, formed hydrogen/halogen bonds (H-/X-bond) with t-BuOH. It was observed that the free-OH band in the t-BuOH-CHCl3 system is larger and more red-shifted than that in the t-BuOH-CCl4 system, indicating the stronger intermolecular interactions in the former system. Furthermore, in the t-BuOH-CHCl3 system, the H-bonds are stronger than the X-bonds, while in the t-BuOH-CCl4 system, both interactions are similar in strength. To assign the free-OH bands, it was found that they are not only from the free OH of the t-BuOH monomer, but they are also contributed by the quasi-free OH with the oxygen bonded to H or Cl and even the weakly H-bonded OH of t-BuOH molecules. Finally, all the identified species increased simultaneously via cosolvent addition, suggestive of the destabilization of the highly associated t-BuOH clusters.

Modulation engineering of in situ cathodic activation of FePx based on W-incorporation for the hydrogen evolution reaction.

In situ electrochemical activation as a new pretreating method to adjust electrocatalytic performance attracts extensive attention. However, the activation mechanisms of electrocatalysts are still ambiguous. Herein, we propose a facile modulation strategy of in situ cathodic activation of FePx based on W-incorporation (W-FePx/IF) for the hydrogen evolution reaction (HER). The activated W-FeOx with obvious surface reconstruction demonstrates the role of W-incorporation for driving the cathodic activation of FePx, which suggests the larger surface area and more active sites. In fact, W incorporation can not only accelerate the cathodic activation process but also act as the adsorption sites for Had to form the synergistic effect with FeOx for water dissociation. The obtained W-FeOx/IF exhibits greatly enhanced HER activity featuring decreased overpotential from 237.7 to 154.0 mV at 100 mA cm-2, which may be ascribed to W-FeOx with double catalytic active sites after cathodic activation. Additionally, the modulation effects of cathodic activation can be exactly achieved by changing electrochemical parameters such as CV cycles. W-FeOx/IF also shows excellent long-term stability for at least 100 h at 100 mA cm-2. This modulation engineering based on metal doping is expected to provide inspiration for the understanding of the cathodic activation process for efficient electrocatalysts.

A highly selective colorimetric and fluorescent probe for quantitative detection of Cu2+/Co2+: The unique ON-OFF-ON fluorimetric detection strategy and applications in living cells/zebrafish.

Identifying and detecting similar target cations through combining "turn on" and "turn off" fluorescence mechanism is effective and challenging. Now a new colorimetric and ON-OFF-ON fluorescent probe N'-((7-(diethylamino)-2-oxo-2H-chromen-3-yl)methylene)-3-hydroxy-2-naphthohydrazide (L) was reported, which could detect Cu2+ and Co2+ in phosphate buffered CH3CH2OH-H2O solvent system. With the assistance of glutathione and pH adjustment, a unique ON-OFF-ON fluorescence detection strategy could be achieved for distinguishing Cu2+ and Co2+. The emission of probe could recover from the L-Cu2+ and L-Co2+ system by addition of GSH or adjusting pH value to 4, respectively, which is due to the abolishment of paramagnetic Cu2+/Co2+. Based on fluorescence titration experiments, the limit of detection was determined as 3.84 × 10-9 M and 4.55 × 10-9 M for Cu2+ and Co2+, respectively. Meanwhile, the detection limit reached 6.21 × 10-8 M for Cu2+ and 6.96 × 10-8 M for Co2+ according to absorbance signal output. Fast recognition of Cu2+/Co2+ can be achieved by obvious color changes from green to colorless under UV light, as well as from yellow to orange-red in room light. The binding mode of L toward Cu2+ and Co2+ have been systematically studied by Job's plot analysis, ESI-MS, IR and density functional theory calculations. Most strikingly, further practical applications of the probe L in fluorescence imaging were investigated in MCF-7 cells and zebrafish due to its low cytotoxicity and good optical properties, suggesting that L could serve as a fluorescent sensor for tracking Cu2+ and Co2+in vivo.

Are Meniere's disease patients with otolith organ impairment more likely to have balance dysfunction?

Background: Patients with Meniere's disease (MD) may present with peripheral vestibular end organ dysfunction and balance dysfunction. Objective: This study aimed to compare the results of vestibular evoked myogenic potential (VEMP) tests with those of the sensory organization test (SOT) in patients with MD to determine whether they are correlated. Material and methods: In total, 132 patients with unilateral MD were evaluated using an audiometric test, the SOT, a caloric test and VEMP tests. Results: Cervical VEMP and ocular VEMP tests were conducted in 132 patients with MD, and the response rates of the affected side were lower than those of the unaffected side. The composite score, C5ES, and C6ES of the SOT were significantly decreased in patients with no VEMP responses compared to those with VEMP responses. Conclusions and significance: MD patients with no VEMP responses are more likely to develop balance impairment than those with VEMP responses. MD patients with otolith organ impairment may therefore have balance disorders, and should exercise caution to prevent falls and subsequent injuries.

A dual functional turn-on non-toxic chemosensor for highly selective and sensitive visual detection of Mg2+ and Zn2+: the solvent-controlled recognition effect and bio-imaging application.

A new dual functional turn-on chemosensor, 2,6-diformyl-4-methylphenol-di(isoquinolinyl-1-hydrazone) (HL), has been developed, which could highly selectively discriminate Mg2+ and Zn2+ in different solvent systems. The chemosensor HL exhibits rapid visual turn-on fluorescence enhancing recognition toward Mg2+/Zn2+, which is not interfered by other cations, especially for respective congeners Ca2+/Cd2+. The remarkable fluorescence enhancement (71-fold or 11-fold) was observed after adding Mg2+ in acetonitrile or Zn2+ in DMF-H2O solvent systems. Additionally such a solvent medium-controlled platform could achieve the quantitative determination of Mg2+ and Zn2+ quantitation with low detection limits of 2.97 × 10-8 M and 3.07 × 10-7 M, respectively. Furthermore, the turn-on fluorescence sensing mechanism is also investigated by 1H NMR, FT-IR and ESI-MS spectroscopy. Density functional theory (DFT) calculations derive optimized geometries of HL and its complexes. Notably, non-toxic HL also can be successfully applied as a visual probe for the practical determination of Mg2+/Zn2+ in MCF-7 cells, Zebrafish larvae, syrup and water samples, which might provide extensive application in biology and medicine fields.

A high performance 2-hydroxynaphthalene Schiff base fluorescent chemosensor for Al3+ and its applications in imaging of living cells and zebrafish in vivo.

Developing high performance fluorescent chemo-sensors for in vitro and in vivo Al3+ detection is highly desirable, because Al3+ accumulation has been involved to various diseases. Herein, we report a highly selective and sensitive Schiff base fluorescent probe, H3L, based on 2-hydroxynaphthalene, which can recognize aluminum ions and exhibit an "off-on" mode with high selectivity in methanol solutions. The detection limit of the probe for Al3+ is as low as 10-7 M which was determined by fluorescent titration. The high selectivity and high sensitivity of H3L for Al3+ are attributed to the inhibition of ESIPT. Additionally, the distribution of intracellular Al3+ ions could be observed under confocal fluorescence microscopy. Moreover, we also applied H3L for in vivo detection of Al3+ ions in living zebrafish larvae.

Tetrel Bond between 6-OTX3-Fulvene and NH3: Substituents and Aromaticity.

Carbon bonding is a weak interaction, particularly when a neutral molecule acts as an electron donor. Thus, there is an interesting question of how to enhance carbon bonding. In this paper, we found that the ⁻OCH3 group at the exocyclic carbon of fulvene can form a moderate carbon bond with NH3 with an interaction energy of about -10 kJ/mol. The ⁻OSiH3 group engages in a stronger tetrel bond than does the ⁻OGeH3 group, while a reverse result is found for both ⁻OSiF3 and ⁻OGeF3 groups. The abnormal order in the former is mainly due to the stronger orbital interaction in the ⁻OSiH3 complex, which has a larger deformation energy. The cyano groups adjoined to the fulvene ring not only cause a change in the interaction type, from vdW interactions in the unsubstituted system of ⁻OCF3 to carbon bonding, but also greatly strengthen tetrel bonding. The formation of tetrel bonding has an enhancing effect on the aromaticity of the fulvene ring.

Carbon Excess C3N: A Potential Candidate as Li-Ion Battery Material.

Xu et al.'s recent experimental work ( Adv. Mater. 2017, 29, 1702007) suggested that C3N is a potential candidate as Li-ion battery with unusual electrochemical characteristics. However, the obvious capacity loss (from 787.3 to 383.3 mA h·g-1) occurs after several cycles, which restricts its high performance. To understand and further solve this issue, in the present study, we have studied the intercalation processes of Li ions into C3N via first-principle simulations. The results reveal that the Li-ion theoretical capacity in pure C3N is only 133.94 mA h·g-1, the value is obviously lower than experimental one. After examining the experimental results in detail, it is found that the chemical component of the as-generated C xN structure is actually C2.67N with N excess. In this case, the calculated theoretical capacity is 837.06 mA h·g-1, while part of Li ions are irreversibly trapped in C2.67N, resulting in the capacity loss. This phenomenon is consistent with the experimental results. Accordingly, we suggest that N excess C3N, but not pure C3N, is the proposed Li-ion battery material in Xu et al.'s experiment. To solve the capacity loss issue and maintain the excellent performance of C3N-based anode material, the C3N with slightly excess C (C3.33N), which has been successfully fabricated in the experiment, is considered in view of its relatively low chemical activity as compared with N excess C3N. Our results reveal that the C excess C3N is a potential Li-ion battery material, which exhibits the low open circle voltage (0.12 V), high reversible capacity (840.35 mA h·g-1), fast charging/discharging rate, and good electronic conductivity.

Nonlinear optical properties of aluminum nitride nanotubes doped by excess electron: a first principle study.

Aluminum nitride nanotubes (AlNNTs) doped by the excess electron, e@AlNNT and M@N-AlNNT (M = Li, Na, K), have been designed and their geometrical, electronic, and nonlinear optical (NLO) properties have been explored theoretically. The results showed that the excess electron narrows the energy gap between HOMO and LUMO values (EH-L) of the doped systems in the range of 3.42-5.37 eV, which is due to a new energy level HOMO formed for the doped excess electron, with higher energy than the original HOMO of AlNNT. Importantly, the doped excess electron considerably increases the first hyperpolarizability (ß0) from 130 a.u. of the undoped AlNNT to 646 a.u. for e@AlNNT, 2606 a.u. for Li@N-AlNNT, while 1.14 × 105 a.u. for Na@N-AlNNT, and 1.37 × 106 a.u. for K@N-AlNNT. The enormous ß0 values for Na@N-AlNNT and K@N-AlNNT are attributed to the low transition energy. These results demonstrate that AlNNTs are a promising material in high-performance NLO nanomaterials for electronic devices.

Effect of Magnesium Bond on the Competition Between Hydrogen and Halogen Bonds and the Induction of Proton and Halogen Transfer.

HOX (X=Cl, Br, I, and At) can engage in either a H-bond (HB) or halogen bond (XB) with a base-like HCN, NH3 , and imidazole. Although the former is energetically preferred for X=Cl and Br, it is the XB that is more stable for At, with I showing little preference. MgY2 forms a Mg-bond with the O atom of HOX, which grows stronger in the order X=Cl

Highly selective and sensitive turn-on fluorescent sensor for detection of Al3+ based on quinoline-base Schiff base.

A new aluminum ion fluorescent probe (4-(diethylamino)-2-hydroxybenzylidene)isoquinoline-1-carbohydrazide (HL1) has been conveniently synthesized and characterized. HL1 exhibited a highly selective and pronounced enhancement for Al3+ in the fluorescence emission over other common cations by forming a 2:1 complex, with a recognition mechanism based on excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT). The strong fluorescent emission can be observed even at ppm level concentration of the probe in the presence of Al3+ with 41 fold intensity enhancement at 545 nm. HL1 displays good linear relationship with Al3+ in the low concentration and the limit of detection is 8.08 × 10-8 mol/L. Similar molecules with different substituents on salicylaldehyde phenyl ring were synthesized for studying the structure-activity relationship. Density-functional theory (DFT) calculations are in agreement with the proposed mechanism. It is confirmed that HL1 could be used to detect Al3+ ions in real sample by fluorescence spectrometry and Al3+ ions in cells by bioimaging.

Tanshinone IIA induces apoptosis via inhibition of Wnt/ß­catenin/MGMT signaling in AtT­20 cells.

A strategy to suppress the expression of the DNA repair enzyme O6­methylguanine­DNA methyltransferase (MGMT) by inhibition of Wnt/ß­catenin signaling may be useful as a novel treatment for pituitary adenoma. Previous studies have reported that Tanshinone IIA (TSA), a major quinone compound isolated from Salvia miltiorrhiza, had antitumor effects. However, whether TSA has antitumor effects against pituitary adenoma and whether the mechanisms are associated with the Wnt/ß­catenin/MGMT pathway remains to be clarified. In the present study, TSA treatment caused apoptosis in AtT­20 cells in a concentration­dependent manner, as demonstrated by cell viability reduction, phophatidylserine externalization detected by Annexin V staining and mitochondrial membrane potential disruption detected by JC­1 staining, which were associated with activation of caspase­3 and DNA fragmentation detected by TUNEL in AtT­20 cells. T­cell factor (TCF)­lymphoid­enhancing factor (LEF) reporter activity was determined by dual luciferase reporter assay and the interaction between ß­catenin and TCF­4 were detected using a co­immunoprecipitation kit. The results indicated TSA treatment increased ß­catenin phosphorylation, inhibited ß­catenin nuclear translocation, reduced ß­catenin/TCF­4 complex formation and TCF­LEF luciferase reporter activity, and subsequently reduced the expression of cyclin D1 and MGMT. Notably, overexpression of MGMT in ß­catenin knock down AtT­20 cells abrogated the TSA­mediated effects in AtT­20 cells. In conclusion, TSA induced apoptosis via inhibition of Wnt/ß­catenin­dependent MGMT expression, which may provide novel insights into the understanding of the mechanism of the antitumor effects of Salvia miltiorrhiza.

Radicol, a Novel Trinorguaiane-Type Sesquiterpene, Induces Temozolomide-Resistant Glioma Cell Apoptosis via ER Stress and Akt/mTOR Pathway Blockade.

Glioblastoma multiforme (GBM) is the most frequent, lethal and aggressive tumour of the central nervous system (CNS) in adults. Multidrug resistance (MDR) results in undesirable prognosis during GBM chemotherapy. In this study, we determined that Radicol (RAD), a novel trinorguaiane-type sesquiterpene originally isolated from the root of Dictamnus radicis Cortex, exhibited potently cytotoxic effect on temozolomide (TMZ)-resistant GBM cell lines in a dose-dependent manner. Radicol-induced apoptosis was confirmed with Hoechst 33342/propidium iodide and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labelling (TUNEL) staining. Studies investigating the mechanism revealed that RAD triggered an attenuation of protein disulphide isomerase (PDI) and induced the unmitigated unfolded protein response (UPR) and lethal endoplasmic reticulum (ER) stress. Simultaneously, we further demonstrated that RAD suppressed the activation of Akt/mTOR/p70S6K phosphorylation by up-regulating the induction of glycogen synthase kinase-3ß (GSK-3ß). These results established a link between RAD-induced ER stress and inhibition of the Akt/mTOR/p70S6K pathway, and the attenuation of PDI and activation of GSK-3ß might be the synergistic target of antineoplastic effects during RAD-induced apoptosis. These findings suggested that RAD, possessing multiple cytotoxicity targets, low molecular weight and high lipid solubility, could be a promising agent for the treatment of malignant gliomas. Copyright © 2017 John Wiley & Sons, Ltd.