Stretchable and recyclable gelatin Ionogel based ionic skin with extensive temperature tolerant, self-healing, UV-shielding, and sensing capabilities.

Fabricating sustainable ionic skin with multi-functional outstanding performances using biocompatible natural polymer-based ionogel is highly desired but remains a great challenge up to now. Herein, a green and recyclable ionogel has been fabricated by in-situ cross-linking of gelatin with a green bio-based multifunctional cross-linker of Triglycidyl Naringenin in ionic liquid. Benefiting from the unique multifunctional chemical crosslinking networks along with multiple reversible non-covalent interactions, the as-prepared ionogels exhibit high stretchability (>1000 %), excellent elasticity, fast room-temperature self-healability (>98 % healing efficiency at 6 min), and good recyclability. These ionogels are also highly conductive (up to 30.7 mS/cm at 150 °C), and exhibit extensive temperature tolerance (-23 to 252 °C) and outstanding UV-shielding ability. As a result, the as-prepared ionogel can easily be applied as stretchable ionic skin for wearable sensors, which exhibits high sensitivity, fast response time (102 ms), excellent temperature tolerance, and stability over 5000 stretching-relaxing cycles. More importantly, the gelatin-based sensor can be used in signal monitor system for various human motion real-time detection. This sustainable and multifunctional ionogel provides a new idea for easy and green preparation of advanced ionic skins.

Safety and efficacy of Yupingfeng granules in children with recurrent respiratory tract infection: A randomized clinical trial.

Importance: Recurrent respiratory tract infection (RRTI) is common in children. Inappropriate RRTI treatment will lead to asthma and other diseases, thereby seriously affecting the growth and physical health of children. Immune function modulation can prevent and alleviate childhood RRTI. Yupingfeng (YPF), a patented traditional Chinese medicine (TCM), has immunomodulatory effects and is widely used in China to treat children with RRTI. Objective: To evaluate the safety and efficacy of YPF monotherapy in treating children with RRTI. Methods: This multicenter, randomized, double-blind, double-simulation, noninferiority clinical trial was conducted from January 2015 to August 2017, with an 8-week treatment period and 52-week follow-up after the drug withdrawal. Children aged 2-6 years with RRTI meeting the inclusion and exclusion criteria were enrolled in 13 hospitals in China and divided randomly into three groups (2:2:1 ratio) to receive YPF, pidotimod, or placebo. The primary outcome was the proportion of RRTI returning to normal standard level during the follow-up. The secondary outcomes were reduction in the number of RRTI recurrences, effect on clinical symptoms (in accord with TCM practice), effect per symptom, and safety. The trial was registered at the Chinese Clinical Trials Registry (www.chictr.org.cn) under the unique identifier ChiCTR-IPR-15006847. Results: Three hundred and fifty-one children were enrolled and randomly assigned to 3 groups; 124, 125, and 61 children in the YPF, pidotimod, and placebo groups, respectively, had completed the trial. During the follow-up, the proportion of RRTI returning to normal standard level was 73.13%, 67.15%, and 38.81% with YPF, pidotimod, and placebo, respectively (P < 0.0001). The proportion of cases who returned to normal standard level in the YPF group was 34.32% higher than that in the placebo group. The safety profile did not significantly differ among the groups. Interpretation: YPF granules were noninferior to the active control drug pidotimod oral solution for the treatment of RRTI in children, and were superior to placebo, with a high safety profile.

An Easily Fabricated High Performance Fabry-Perot Optical Fiber Humidity Sensor Filled with Graphene Quantum Dots.

An easily fabricated Fabry-Perot optical fiber humidity sensor with high performance was presented by filling Graphene Quantum Dots (GQDs) into the Fabry-Perot resonator, which consists of two common single mode optical fibers. The relative humidity sensing performance was experimentally investigated by an interference spectrum drift between 11 %RH to 85 %RH. 0.567 nm/%RH sensitivity and 0.99917 linear correlation were found in experiments that showed high sensitivity, good and wide-range linear responding. Meanwhile, its good responding repeatability was demonstrated by two circle tests with increasing and decreasing relative humidity. For investigating the measurement influence caused by a temperature jitter, the temperature responding was experimentally investigated, which showed its linear responding with 0.033 nm/°C sensitivity. The results demonstrate the humidity sensitivity is greatly higher than the temperature sensitivity. The wavelength shift influence is 0.0198 nm with 0.6 °C max temperature jitter in the experiment, which can be ignored in humidity experiments. The fast-dynamic responses at typical humidity were demonstrated in experiments, with 5.5 s responding time and 8.5 s recovering time. The sensors with different cavity lengths were also investigated for their humidity response. All sensors gave good linear responding and high sensitivity. In addition, the relation curve between cavity length and response sensitivity also had good linearity. The combination of GQDs and single mode optical fibers showed easy fabrication and good performance for an optical fiber relative humidity sensor.

Regulation Efficacy and Mechanism of the Toxicity of Microcystin-LR Targeting Protein Phosphatase 1 via the Biodegradation Pathway.

Biodegradation is important to regulate the toxicity and environmental risk of microcystins (MCs). To explore their regulation effectiveness and mechanism, typical biodegradation products originating from microcystin-LR (MCLR) were prepared and purified. The protein phosphatase 1 (PP1) inhibition experiment showed the biodegradation pathway was effective in regulating the toxicity of the biodegradation products by extending the biodegradation. With the assistance of molecular docking, the specific interaction between the toxins and PP1 was explored. The MCLR/MCLR biodegradation products combined with PP1 mainly by the aid of interactions related to the active sites Adda5, Glu6, Mdha7, and the ionic bonds/hydrogen bonds between the integral toxin and PP1. As a consequence, the interactions between Mn22+ and Asp64/Asp92 in the catalytic center were inhibited to varying degrees, resulting in the reduced toxicity of the biodegradation products. During the biodegradation process, the relevant key interactions might be weakened or even disappear, and thus the toxicity was regulated. It is worth noting that the secondary pollution of the partial products (especially for Adda5-Glu6-Mdha7-Ala1 and the linearized MCLR), which still possessed the major active sites, is of deep concern.

Research on the Impact and Mechanism for the Inhibition of Micrococcus Catalase Activity by Typical Tetracyclines.

As potential inhibitors target to biological enzymes, antibiotics may have certain impacts on the biochemical treatment process. With micrococcus catalase (CAT) served as the target molecule, the impact and inhibition mechanism for typical tetracyclines (TCs) were evaluated. Toxicity experiments showed that TCs had significant inhibition on CAT in the sequence of tetracycline>chlortetracycline>oxytetracycline>doxycycline. To clarify the inhibition mechanism between TCs and CAT which was explored with the assistance of fluorescence spectroscopy and MOE molecule simulation. According to fluorescence analysis, TCs quenched the fluorescence signal of CAT by the mode of static quenching. Combined with toxicity data, it could be presumed that TCs combined with the catalytic active center and thus inhibited CAT. Above presumption was further verified by the molecular simulation data. When TCs combined with the catalytic center of CAT, the compounds have increased combination areas and prominent energy change (compared with the compounds formed by TCs and noncatalytic center recommend by MOE software). IBM SPSS statistics showed that TC toxicity positively correlated with the hydrogen bonds such as O13→Glu252, O1←Arg195, and O6→Asp249, but negatively correlated with the hydrogen bonds such as O10→Pro363, O10→Lys455, and O12 â†’ Asn127. TC toxicity also positively correlated with the ion bonds ofN4-Glu252, but negatively correlated with the ion bonds of N4-Asp379. Hydrogen bonds and ion bonds for above key sites were closely related to the inhibition effect of TCs on CAT.

Dimethylolurea as a Novel Slow-Release Nitrogen Source for Nitrogen Leaching Mitigation and Crop Production.

Rapid hydrolysis of urea results in further fertilization frequency and excessive nitrogen (N) input. A modified urea, dimethylolurea (DMU), was synthesized in this study. The structure of the sample was characterized by Fourier transform infrared and nuclear magnetic resonance analysis, manifesting the formation of DMU. N release investigation confirmed that DMU enabling provided a gradual N supply. The N leaching experiment indicated that increasing the applied DMU significantly reduced the NH4+-N, NO3--N, and total N leaching, compared with urea application alone. The application effect on maize and wheat was evaluated. The results revealed that singly applied DMU with 100% or 80% N input, irrespective of the amount, promoted crop yield and agronomic characteristic and N use efficiency (NUE) of maize and wheat, beyond urea with two split applications at the recommended rate. Thus, the potential availability of DMU was proven; this could be widely used in agricultural fields as a slow-release fertilizer.

Regulation on the toxicity of microcystin-LR target to protein phosphatase 1 by biotransformation pathway: effectiveness and mechanism.

Biotransformation was an important pathway to regulate the toxicity of microcystins (MCs) targeted to protein phosphatases (PPs). To explore the regulation effectiveness and mechanism, several typical biothiol transformation products originated from MCLR were prepared by nucleophilic addition reaction. The reduced inhibition effect of MCLR transformation products on PP1 was evaluated and compared with their original toxin. Though molecular simulation showed the introduced biothiols enhanced the total combination areas and energies for target complexes, the steric hindrance of introduced biothiols inhibited the combination between the key action sites (Mdha7 and Adda5 residues) and PP1. Furthermore, the introduced biothiols also weakened the hydrogen bonds for some key interaction sites and altered the ion bonds between PP1 and the two Mn2+ ions in the catalytic center. The discrepant regulation effect for biothiols on the toxicity of MCLR was closely related to above indexes and influenced by molecular sides.

Evaluation of the Direct and Indirect Regulation Pathways of Glutathione Target to the Hepatotoxicity of Microcystin-LR.

Glutathione (GSH) plays crucial roles in regulating the hepatotoxicity of Microcystin-LR (MCLR) by inhibiting oxidative stress or by toxin conjugation. Based on MCLR conjugation product preparation and purification, the direct and indirect regulation pathways for GSH were fully evaluated. Protein phosphatase inhibition analysis verified that GSH conjugation was an effective pathway to regulate the inhibition effect of MCLR, while GSH had slight influence on the toxicity of MCLR. Research on oxidative stress showed that both regulation pathways could reduce the formation of reactive oxygen species (stimulated by MCLR and regulated by NADH oxidase) and regulate the adverse effects on antioxidant enzymes. By evaluating the contributions for both pathways, it could be found that the indirect pathway had significant contribution to eliminating cellular reactive oxygen species and regulating protein phosphatases inhibition, while the direct regulation pathway had moderate influence. As glutathione transferases facilitated the transformation of MCLR, the hepatotoxicity of MCLR could be effectively regulated by GSH conjugation pathway, especially with abundant exogenous GSH.

[Emissions Inventory of Smoldering Chinese Kangs and Their Contribution to PM2.5 Pollution in Lanzhou City].

Considering regional differences in economic development, the activity level of smoldering Chinese kangs was confirmed by surveys in typical areas in Lanzhou City. An emissions inventory of smoldering Chinese kangs in Lanzhou City in 2016 was established using the emissions factor approach. The emissions amounts of SO2, NOx, NH3, CO, volatile organic compounds (VOCs), PM10, PM2.5, organic carbon (OC) and elemental carbon (EC) were 340.8, 201.8, 106.0, 36628.2, 4997.2, 6070.3, 5645.1, 1089.3, and 1233.1 t·a-1, respectively. Emissions amounts were allocated by spatial and temporal characteristics. The emissions were concentrated from November to mid-April of the following year. Spatially, there were significant differences in emissions at different economic levels. The high value areas of emissions were mainly concentrated in the southern part of Yuzhong, central Yongdeng, and south of Qilihe. The weather research and forecasting with chemistry (WRF-Chem) model was used to determine the average contribution of smoldering Chinese kangs to PM2.5 concentration in Lanzhou City during the heating season. The simulation results were improved after applying the emissions inventory. The average PM2.5 concentration at Lanyuan Hotel (in the city) and Yuzhong Station (in the countryside) increased 32 µg·m-3 and 34 µg·m-3 in the simulation, respectively, and the corresponding rates of pollution contribution were 37.6% and 49.2%. Thus, researching and enacting scientific control measures for smoldering Chinese kang pollutants is significant to improving regional air quality.

Surface Effect on Oil Transportation in Nanochannel: a Molecular Dynamics Study.

In this work, we investigate the dynamics mechanism of oil transportation in nanochannel using molecular dynamics simulations. It is demonstrated that the interaction between oil molecules and nanochannel has a great effect on the transportation properties of oil in nanochannel. Because of different interactions between oil molecules and channel, the center of mass (COM) displacement of oil in a 6-nm channel is over 30 times larger than that in a 2-nm channel, and the diffusion coefficient of oil molecules at the center of a 6-nm channel is almost two times more than that near the channel surface. Besides, it is found that polarity of oil molecules has the effect on impeding oil transportation, because the electrostatic interaction between polar oil molecules and channel is far larger than that between nonpolar oil molecules and channel. In addition, channel component is found to play an important role in oil transportation in nanochannel, for example, the COM displacement of oil in gold channel is very few due to great interaction between oil and gold substrate. It is also found that nano-sized roughness of channel surface greatly influences the speed and flow pattern of oil. Our findings would contribute to revealing the mechanism of oil transportation in nanochannels and therefore are very important for design of oil extraction in nanochannels.

Molecular Mechanism for the Regulation of Microcystin Toxicity to Protein Phosphatase 1 by Glutathione Conjugation Pathway.

Glutathione (GSH) conjugation was an important pathway to regulate the toxicity of microcystins (MCs) targeted to protein phosphatases. To explore the specific molecular mechanism for GSH detoxification, two typical MC-GSHs (derived from MCLR and MCRR) were synthesized, prepared, and purified according to previous research. Then, the reduced inhibition effect for MC-GSHs on protein phosphatase 1 was verified by comparing with their original toxins. To further clarify the molecular mechanism for MC-GSHs detoxification, we evaluated the interactions between MCs/MC-GSHs and PP1 with the assistance of MOE molecule simulation. When GSH was introduced to MCs, the covalent binding (Mdha7 to Cys273), the hydrophobic interaction (Adda5 with PP1), the hydrogen bonds (especially for Lys2-Arg96 and Glu6-Tyr272), the covalent combination (between Mdha7 and Cys273), and the ion bonds (between Mn2+ and Asn124/His248/Asp64/His66) of MCLR/MCRR-PP1 complexes weakened to a certain extent, while the ion bonds between Mn2+ and His173/Asp92 residues increased. It was not difficult to find that the toxicity of MCs was closely related to the above sites/interactions and the above key information for MCs-PP1; MC-GSHs-PP1 complexes were important for clarifying the detoxification mechanism of MC-GSHs pathway. This study offers a comprehensive cognition on MCs toxicity regulation and provides valid theoretical support to control their potential risk.

Novel biomarker pipeline to probe the oxidation sites and oxidation degrees of hemoglobin in bovine erythrocytes exposed to oxidative stress.

Research on biomarkers for protein oxidation might give insight into the mechanistic mode of oxidative stress. In the work present here, a novel pipeline was established to probe the oxidation mechanism of bovine hemoglobin (Hb) with its oxidation products serving as the biomarkers. Reactive oxygen species generated by irradiation were used to mimic oxidative stress conditions to oxidize Hb in bovine erythrocytes. After Hb extraction and digestion, oxidized peptides in the tryptic fragments were assigned by comparison with the extracted ion chromatography spectra of native peptide from the control sample. Subsequent tandem mass spectrometry analysis of these peptides proved that oxidation was limited to partially exposed amino acid residues (α-Phe36 , ß-Met1 , ß-Trp14 , for instance) in Hb. Quantitation analysis on these oxidized peptides showed that oxidation degrees of target sites had positive correlations with the extended oxidation dose and the oxidation processes were also controlled by residues types. Compared with the conventional protein carbonyl assay, the identified oxidized products were feasibility biomarkers for Hb oxidation, indicating that the proposed biomarker pipeline was suitable to provide specific and valid information for protein oxidation. Copyright © 2015 John Wiley & Sons, Ltd.

Direct determination of the binding sites of cisplatin on insulin-like growth factor-1 by top-down mass spectrometry.

Cisplatin has been widely used in the chemotherapy of a variety of tumors, and the interactions of cisplatin with proteins play very important roles in its side effects and drug resistance, as well as its pharmacokinetics and the biodistribution. Insulin-like growth factor-1 (IGF-1) was found to be associated with the drug resistance of cisplatin. Here, the interaction between cisplatin and IGF-1 was investigated using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. IGF-1-Pt(NH3)Cl was the main mono-adduct and the trans labilization was important to the reaction between IGF-1 and cisplatin, while another special mono-adduct IGF-1-Pt(NH3)Cl2 was observed. The rapid and sensitive top-down mass spectrometry-based approach in linear ion trap mass spectrometer has been developed to identify the binding sites of cisplatin in IGF-1 directly without tedious enzyme digestion. Three binding sites (Met59, Arg56 and Cys6) of cisplatin in IGF-1 were determined. The results not only provide a rapid and efficient way to identify the platinum binding sites in proteins, but also indicate that the binding of cisplatin could promote the fragmentation of IGF-1 and the rupture of disulfide bond.

Comprehensive identification of the binding sites of cisplatin in hen egg white lysozyme.

Platinum drugs have become one of the most important kinds of chemotherapy agents, and the interactions of these drugs with proteins play very important roles in their side effects and drug resistance. However, it is still a challenge to determine the binding sites of platinum drugs in proteins with multiple disulfide bonds and stable three-dimensional structures using mass spectrometry. Here, the interaction between cisplatin and hen egg white lysozyme (HEWL), a multi-disulfide-bond-containing protein with a stable three-dimensional structure, was investigated using Fourier transform ion cyclotron resonance mass spectrometry. Typical disulfide bond reduction with dithiothreitol/tris(2-carboxyethyl)phosphine before trypsin digestion destroyed the binding of cisplatin to HEWL, and no platination sites were found. Efficient trypsin digestion methods for HEWL-cisplatin adducts were developed to avoid the loss of platinum binding to protein. At 55 °C, platinated HEWL was digested directly by trypsin in 6 h, and multiple platinated peptides were observed. In 60% acetonitrile, the digestion time of platinated HEWL was shortened to 2 h, and most of the platinated peptides were observed. In addition, the reduction of the disulfide bonds of HEWL greatly accelerated the reaction between HEWL and cisplatin, and the potential binding sites of cisplatin in reduced HEWL could be easily recognized. On the basis of the above-mentioned methods, multiple binding sites of cisplatin in HEWL were first identified by mass spectrometry.

Self-assembly of C4H-type hydrogenated graphene.

We demonstrate by molecular dynamic (MD) simulations that patterned partially hydrogenated graphene (C4H) can self-assemble at room temperature. The main driving force of the self-assembly of C4H is due to the one-sided distribution of hydrogen and the corresponding asymmetric orientation of sp(3) bonding, there exists strong electrostatic repulsion between the relatively close H atoms. The simulations show that C4H can self-assemble into various carbon nanoscroll (CNS) structures, this is mainly controlled by its geometry (size and aspect ratio). And the carbon nanotube (CNT) is a good candidate to activate and guide C4H to form CNS, whose core size can be controlled. Meanwhile, a novel CNT/C4H core/shell composite nanostructure is also formed. The theoretical results shed important light on a feasible approach to fabricate high-quality CNS and other novel nanostructures including core/shell structures, which hold great potential applications in optics, optoelectronic devices, hydrogen storage, sensors, and energy storage in supercapacitors or batteries.

Probing the interaction of cisplatin with cytochrome C by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.

As one of the most important platinum drugs, the interactions of cisplatin with proteins play very important roles in its anticancer action and side effects. Here, the interaction of cisplatin with cytochrome c was investigated using Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS). On the basis of the high-resolution data, cytochrome c-Pt(NH(3))Cl was found to be the primary monoadduct. The platinated monoadducts were related to molar ratios of cytochrome c and cisplatin, and corresponding reaction pathways were proposed. Multiple binding sites of cisplatin on cytochrome c were directly determined by FTICR MS combined with trypsin digestion without liquid chromatography (LC) separation. Four binding sites (Met65, Met80, His18, and His33) for cisplatin on cytochrome c were identified. Moreover, hydrogen/deuterium exchange (H/DX) combined with FTICR MS provides the sensitive method to insight the small conformation change of cytochrome c induced by cisplatin. This strategy can be applied to comprehensive investigation of metallodrug/protein complexes.

Studies of interaction between insulin and glutathione using electrospray ionization mass spectrometry.

RATIONALE: The interaction of glutathione (GSH) with insulin plays an important role in the degradation or regulation of insulin. The characterization of the reaction products of GSH and insulin is very important for a proper understanding of the mechanism of insulin regulation of GSH. METHODS: Solutions of insulin and glutathione were incubated under different experimental conditions in vitro. The reaction products were determined by electrospray ionization (ESI) ion trap mass spectrometry combined with Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. RESULTS: The multi-reaction products were identified, including insulin A chain with two intrachain disulfides, insulin B chain with one intrachain disulfides, GSH-modified insulin, GSH-modified A chain, GSH-modified B chain, aggregates of A chain and B chain, and reduced A chain and B chain. The binding site of the B chain with insulin was determined directly by tandem mass spectrometry (MS/MS) without enzyme digestion. It was found that the reaction between GSH and insulin was pH-, O(2)- and temperature-dependent. CONCLUSIONS: The results provide insight into the interaction between GSH and insulin. It has also been demonstrated that ESI-MS combined with high-resolution FTICRMS and MS/MS provides a powerful tool for screening the reactions of proteins and small molecules.

[Study of effects of drugs on myocardial hypertrophy due to overload].

OBJECTIVE: To study the relation of expression change of tumor necrosis factor-alpha (TNF-alpha), angiotensin II (Ang II), and endothelin-1 (ET-1), and the effect of imidapril on myocardial hypertrophy due to overload. METHODS: Sixty-three rats were randomly divided into four groups: sham operation (n=15), overload group (n=16), imidapril group (n=16), and Caweidiluo group (n=16). Hypertrophic myocardium was reproduced in rats by constricting abdominal aorta. Blood samples and heart were harvested 12 weeks after aorta constriction, and myocardial hypertrophy index, the contents of Ang II, ET-1 in the myocardium and plasma were determined by radioimmunoassay and TNF-alpha in the myocardium and plasma were determined by enzyme linked immunoadsorbent assay. RESULTS: Left ventricle showed obvious hypertrophy 12 weeks after operation. The contents of TNF-alpha, Ang II and ET-1 in the myocardium, and the content of TNF-alpha in serum, Ang II and ET-1 in plasma were increased compared with those of controls (all P<0.01). The treatment of imidapril and Caweidiluo could restrain the development of left ventricle hypertrophy after operation, and imidapril decreased the contents of TNF-alpha, Ang II and ET-1 in myocardium compared with overload group (all P<0.01). Imidapril lowered the contents of TNF-alpha in serum, Ang II and ET-1 in plasma, compared with overload group (all P<0.01), but not ET-1. Caweidiluo lowered the contents of TNF-alpha, Ang II and ET-1 in myocardium, the contents of TNF-alpha in serum, Ang II and ET-1 in plasma (all P<0.01) compared with overload group (both P<0.01). CONCLUSION: The activation of rennin-angiotensin system (RAS) by over load results to an elevation of TNF-alpha contents in plasma and myocardium, and it is probably one of the major regulatory pathways of myocardial hypertrophy.