UPLC-MS/MS method for the determination of the herb composition of Tangshen formula and the in vivo pharmacokinetics of its metabolites in rat plasma.

INTRODUCTION: Tangshen formula (TSF) is a traditional Chinese medicine composed of seven medicinal herbs including Astragalus membranaceus, Rehmannia glutinosa Libosch, Citrus aurantium L., etc. which is used to treat diabetic nephropathy III, IV qi and yin deficiency and stasis syndrome. Most of the studies on TSF are pharmacological and pharmacodynamic experiments. There are few basic studies on its chemical substances, and the effective constituents are not clear. OBJECTIVE: To analyse the main chemical components of TSF and the absorbed components in rat plasma following oral administration based on liquid chromatography tandem mass spectrometry (LC-MS/MS). Moreover, providing a rapid and valid analytical strategy for simultaneous determination of six components in rat plasma and use it in pharmacokinetic studies. RESULTS: A total of 132 components were identified in TSF, and 44 components were identified in rat plasma after oral TSF, 35 of which were prototype components and nine were metabolic components. A sensitive and reliable LC-MS/MS method was developed for simultaneous determination of six components in rat plasma. The intra-day and inter-day precision relative standard deviation (RSD) was lower than 15%; the accuracy of low, medium and high concentrations ranged from 80% to 120%. The recovery met the requirements and the RSD of the recoveries was less than 15%. CONCLUSION: A total of 132 components were identified in TSF. The LC-MS/MS quantitative method for the simultaneous determination of morroniside, loganin, notoginsenoside R1 , ginsenoside Re, ginsenoside Rb1 and astragaloside IV in rat plasma was established for the first time. The pharmacokinetic parameters are clarified, which can guide the clinical medication of TSF.

A Novel Gel-Forming Solution Based on PEG-DSPE/Solutol HS 15 Mixed Micelles and Gellan Gum for Ophthalmic Delivery of Curcumin.

Curcumin (Cur) is a naturally hydrophobic polyphenol with potential pharmacological properties. However, the poor aqueous solubility and low bioavailability of curcumin limits its ocular administration. Thus, the aim of this study was to prepare a mixed micelle in situ gelling system of curcumin (Cur-MM-ISG) for ophthalmic drug delivery. The curcumin mixed micelles (Cur-MMs) were prepared via the solvent evaporation method, after which they were incorporated into gellan gum gels. Characterization tests showed that Cur-MMs were small in size and spherical in shape, with a low critical micelle concentration. Compared with free curcumin, Cur-MMs improved the solubility and stability of curcumin significantly. The ex vivo penetration study revealed that Cur-MMs could penetrate the rabbit cornea more efficiently than the free curcumin. After dispersing the micelles in the gellan gum solution at a ratio of 1:1 (v/v), a transparent Cur-MM-ISG with the characteristics of a pseudoplastic fluid was formed. No obvious irritations were observed in the rabbit eyes after ocular instillation of Cur-MM-ISG. Moreover, Cur-MM-ISG showed a longer retention time on the corneal surface when compared to Cur-MMs using the fluorescein sodium labeling method. These findings indicate that biocompatible Cur-MM-ISG has great potential in ophthalmic drug therapy.

Identification of some factors influencing soil transfer on shoes.

In criminal activities, soil can be transferred from a crime scene to items linked with a perpetrator; for example, shoes, cars or tools. Several parameters will influence the quantity of soil transferred in a given scenario. The knowledge of the most influential factors can help the expert to assess the evidence using a logical approach at the activity level or to predict the amount of soil that can be expected in a given scenario. The influence of five chosen parameters, namely the shoe profile, shoe size, walker's weight, soil type and soil humidity were assessed using Design of Experiment (DOE) in order to understand their influence on soil quantity transferred on shoes. The Faced Central Composite Design (FCCD) using a quadratic model was found to be highly significant, thus they could be adequately used to model and to interpret the amount of soil recovered from one shoe. These designs demonstrate that the characteristics of the donor (soil type and soil humidity), as well as a combination of these two factors have a very significant impact on the soil transfer. The characteristics of the receptor (shoe profile, shoe size and walker's weight) also have an impact on the transfer but to a lesser extent. Globally, this research provides valuable information for the forensic scientist both in investigative mode: evaluation of the soil quantity possibly transferred on shoes, and in the evaluative steps: is the quantity of soil found on the suspect shoes in accordance to the proposition/scenario given by the prosecution and the defence?

Ultrahigh Rate Performance of a Robust Lithium Nickel Manganese Cobalt Oxide Cathode with Preferentially Orientated Li-Diffusing Channels.

Lithium nickel manganese cobalt oxide (NMC) materials, with low cost and high energy density, are considered to be among the most promising cathode materials for Li-ion batteries (LIBs). However, several issues have hindered their further deployment, particularly for high-powered applications, including limited rate capability, capacity loss during cycling (especially at high temperatures and high voltages), and difficulty in reproducibly preparing the desired particle morphology. In this work, we have developed a robust LiNi0.33Mn0.33Co0.33O2 cathode material (NMC-111) capable of high-rate performance for LIBs. Our high power NMC-111 (HP-NMC) cathode materials showed significantly enhanced electrochemical performance, relative to a commercial NMC-111 (c-NMC), with discharge capacities of 138 and 131 mAh/g at high current rates of 20 and 30 C, respectively. The material also exhibited enhanced cycling stability under both room temperature and at 50 °C. We ascribe the high performance of our material to a unique crystalline microstructure observed by electron microscopy characterization, which showed preferential orientation of the Li-diffusing channels radially outward. This HP-NMC material achieved one of the highest performance metrics among NMC materials reported to date, especially for high-powered electric vehicles.

Investigation of Metal-Organic Framework-5 (MOF-5) as an Antitumor Drug Oridonin Sustained Release Carrier.

Oridonin (ORI) is a natural active ingredient with strong anticancer activity. But its clinical use is restricted due to its poor water solubility, short half-life, and low bioavailability. The aim of this study is to utilize the metal organic framework material MOF-5 to load ORI in order to improve its release characteristics and bioavailability. Herein, MOF-5 was synthesized by the solvothermal method and direct addition method, and characterized by Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetric Analysis (TG), Brunauer-Emmett-Teller (BET), and Dynamic Light Scattering (DLS), respectively. MOF-5 prepared by the optimal synthesis method was selected for drug-loading and in vitro release experiments. HepG2 cells were model cells. MTT assay, 4',6-diamidino-2-phenylindole (DAPI) staining and Annexin V/PI assay were used to detect the biological safety of blank carriers and the anticancer activity of drug-loaded materials. The results showed that nano-MOF-5 prepared by the direct addition method had complete structure, uniform size and good biocompatibility, and was suitable as an ORI carrier. The drug loading of ORI@MOF-5 was 52.86% ± 0.59%. The sustained release effect was reliable, and the cumulative release rate was about 87% in 60 h. ORI@MOF-5 had significant cytotoxicity (IC50:22.99 µg/mL) and apoptosis effect on HepG2 cells. ORI@MOF-5 is hopeful to become a new anticancer sustained release preparation. MOF-5 has significant potential as a drug carrier material.

The mitochondrial tRNAAla 5587T>C and tRNALeu(CUN) 12280A>G mutations may be associated with hypertension in a Chinese family.

Hypertension is a very common cardiovascular disorder, however, the molecular mechanism underlying this disease remains poorly understood. Recently, an increasing number of studies have demonstrated that mitochondrial (mt)DNA mutations serve important roles in the pathogenesis of hypertension. The current study reported the clinical and molecular characterization of a Chinese family with maternally inherited hypertension (the penetrance of hypertension was 71.4%). In addition, the entire mitochondrial transfer (mt-t)RNA genomes was amplified using a polymerase chain reaction (PCR) and identified through direct Sanger sequencing. Additionally, the mtDNA copy number in matrilineal relatives in this family was evaluated using quantitative PCR. The sequence analysis of the 22 mt-tRNA genes led to the identification of tRNAAla 5587T>C (thymine to cytosine) and tRNALeu(CUN) 12280A>G (adenine to guanine) mutations. Notably, the heteroplasmic 5587T>C mutation was located at the 3' end of tRNAAla (position 73), which is highly conserved from bacteria to human mitochondria. In addition, the 12280A>G mutation was revealed to occurs at the dihydrouridine loop of tRNALeu(CUN) (position 15) and may decrease the steady-state level of mt-tRNA. As a result, 5587T>C and 12280A>G mutations may lead to the failure of tRNAs metabolism and subsequently cause mitochondrial protein synthesis defects. Molecular analysis revealed that patients carrying the 5587T>C and 12280A>G mutations had a lower copy number of mtDNA compared with a control with hypertension, but without the mutations, suggesting that these mutations may cause mitochondrial dysfunctions that are responsible for hypertension. Therefore, mt-tRNAAla 5587T>C and tRNALeu(CUN) 12280A>G mutations may be involved in the pathogenesis of hypertension in this family.

Systematic Optimization of Battery Materials: Key Parameter Optimization for the Scalable Synthesis of Uniform, High-Energy, and High Stability LiNi0.6Mn0.2Co0.2O2 Cathode Material for Lithium-Ion Batteries.

Ni-rich LiNixMnyCo1-x-yO2 (x > 0.5) (NMC) materials have attracted a great deal of interest as promising cathode candidates for Li-ion batteries due to their low cost and high energy density. However, several issues, including sensitivity to moisture, difficulty in reproducibly preparing well-controlled morphology particles and, poor cyclability, have hindered their large scale deployment; especially for electric vehicle (EV) applications. In this work, we have developed a uniform, highly stable, high-energy density, Ni-rich LiNi0.6Mn0.2Co0.2O2 cathode material by systematically optimizing synthesis parameters, including pH, stirring rate, and calcination temperature. The particles exhibit a spherical morphology and uniform size distribution, with a well-defined structure and homogeneous transition-metal distribution, owing to the well-controlled synthesis parameters. The material exhibited superior electrochemical properties, when compared to a commercial sample, with an initial discharge capacity of 205 mAh/g at 0.1 C. It also exhibited a remarkable rate capability with discharge capacities of 157 mAh/g and 137 mAh/g at 10 and 20 C, respectively, as well as high tolerance to air and moisture. In order to demonstrate incorporation into a commercial scale EV, a large-scale 4.7 Ah LiNi0.6Mn0.2Co0.2O2 Al-full pouch cell with a high cathode loading of 21.6 mg/cm2, paired with a graphite anode, was fabricated. It exhibited exceptional cyclability with a capacity retention of 96% after 500 cycles at room temperature. This material, which was obtained by a fully optimized scalable synthesis, delivered combined performance metrics that are among the best for NMC materials reported to date.

Development of a colloidal gold immunochromatographic strip based on HSP70 for the rapid detection of Echinococcus granulosus in sheep.

Echinococcus granulosus is the causative pathogen of cystic echinococcosis, a serious disease endangering human and animal health. In this study, an immunochromatographic strip was developed based on the recombinant protein Heat shock protein 70 (HSP70) for the serological detection of E. granulosus. The protocol completes within 20min requiring no specialized equipment or chemical reagents, while specificity tests confirmed no cross-reactivity with positive serum of Fasciola hepatica, Haemonchus contortus, Peste des petits ruminants virus (PPRV) and Foot-and-mouth disease virus (FMDV). The strips remained stable after storage at 4°C for up to 8 months. Both immunochromatographic strip and ELISA tests were applied to detect E. granulosus antibody in a total of 728 serum samples obtained from slaughter houses in Zhejiang Province. Our data revealed positive rates of 2.61 and 1.65% by immunochromatographic strip and ELISA methods, respectively. The immunochromatographic strip test developed in this study provides a simple, specific and rapid method of E. granulosus antibody detection and infected sheep monitoring.

Nanomaterial datasets to advance tomography in scanning transmission electron microscopy.

Electron tomography in materials science has flourished with the demand to characterize nanoscale materials in three dimensions (3D). Access to experimental data is vital for developing and validating reconstruction methods that improve resolution and reduce radiation dose requirements. This work presents five high-quality scanning transmission electron microscope (STEM) tomography datasets in order to address the critical need for open access data in this field. The datasets represent the current limits of experimental technique, are of high quality, and contain materials with structural complexity. Included are tomographic series of a hyperbranched Co2P nanocrystal, platinum nanoparticles on a carbon nanofibre imaged over the complete 180° tilt range, a platinum nanoparticle and a tungsten needle both imaged at atomic resolution by equal slope tomography, and a through-focal tilt series of PtCu nanoparticles. A volumetric reconstruction from every dataset is provided for comparison and development of post-processing and visualization techniques. Researchers interested in creating novel data processing and reconstruction algorithms will now have access to state of the art experimental test data.

Identical Location Transmission Electron Microscopy Imaging of Site-Selective Pt Nanocatalysts: Electrochemical Activation and Surface Disordering.

We have employed identical location transmission electron microscopy (IL-TEM) to study changes in the shape and morphology of faceted Pt nanoparticles as a result of electrochemical cycling; a procedure typically employed for activating platinum surfaces. We find that the shape and morphology of the as-prepared hexagonal nanoparticles are rapidly degraded as a result of potential cycling up to +1.3 V. As few as 25 potential cycles are sufficient to cause significant degradation, and after about 500-1000 cycles the particles are dramatically degraded. We also see clear evidence of particle migration during potential cycling. These finding suggest that great care must be exercised in the use and study of shaped Pt nanoparticles (and related systems) as electrocatlysts, especially for the oxygen reduction reaction where high positive potentials are typically employed.

Morphology and activity tuning of Cu3Pt/C ordered intermetallic nanoparticles by selective electrochemical dealloying.

Improving the catalytic activity of Pt-based bimetallic nanoparticles is a key challenge in the application of proton-exchange membrane fuel cells. Electrochemical dealloying represents a powerful approach for tuning the surface structure and morphology of these catalyst nanoparticles. We present a comprehensive study of using electrochemical dealloying methods to control the morphology of ordered Cu3Pt/C intermetallic nanoparticles, which could dramatically affect their electrocatalytic activity for the oxygen reduction reaction (ORR). Depending on the electrochemical dealloying conditions, the nanoparticles with Pt-rich core-shell or porous structures were formed. We further demonstrate that the core-shell and porous morphologies can be combined to achieve the highest ORR activity. This strategy provides new guidelines for optimizing nanoparticles synthesis and improving electrocatalytic activity.

Template-free synthesis of hollow-structured Co3O4 nanoparticles as high-performance anodes for lithium-ion batteries.

We have developed a template-free procedure to synthesize Co3O4 hollow-structured nanoparticles on a Vulcan XC-72 carbon support. The material was synthesized via an impregnation-reduction method followed by air oxidation. In contrast to spherical particles, the hollow-structured Co3O4 nanoparticles exhibited excellent lithium storage capacity, rate capability, and cycling stability when used as the anode material in lithium-ion batteries. Electrochemical testing showed that the hollow-structured Co3O4 particles delivered a stable reversible capacity of about 880 mAh/g (near the theoretical capacity of 890 mAh/g) at a current density of 50 mA/g after 50 cycles. The superior electrochemical performance is attributed to its unique hollow structure, which combines nano- and microscale properties that facilitate electron transfer and enhance structural robustness.

Cryptosporidiosis in broiler chickens in Zhejiang Province, China: molecular characterization of oocysts detected in fecal samples.

Cryptosporidium is one of the most important parasites in poultry, and this pathogen can infect more than 30 avian species. The present study investigated the infection rate of Cryptosporidium among broiler chicken flocks. A total of 385 fecal samples from broiler chickens in 7 regions of Zhejiang Province collected from November 2010 to January 2012 were examined by microscopy. Thirty-eight (10%) samples were positive for Cryptosporidium infection, and 3 genotypes (Cryptosporidium baileyi, Cryptosporidium meleagridis, and avian genotype II) were identified by PCR and sequencing. A phylogenetic tree of the isolates was analyzed. These results suggest that cryptosporidiosis is widespread in poultry in Zhejiang Province, and is a potential threat to public health as well as the economy. This is the first report about the infection rate and molecular characterization of Cryptosporidium in broiler chickens in Zhejiang.

Synthesis of structurally ordered Pt3Ti and Pt3V nanoparticles as methanol oxidation catalysts.

Structurally ordered Pt3Ti or Pt3V intermetallic nanoparticle catalysts with ultrasmall particle sizes have never been successfully synthesized. Herein, we present a KCl-nanoparticle method to successfully provide such compounds. These two catalysts show enhanced catalytic activity and stability for methanol oxidation compared to pure Pt.

Nanoparticle metamorphosis: an in situ high-temperature transmission electron microscopy study of the structural evolution of heterogeneous Au:Fe2O3 nanoparticles.

High-temperature in situ electron microscopy and X-ray diffraction have revealed that Au and Fe2O3 particles fuse in a fluid fashion at temperatures far below their size-reduced melting points. With increasing temperature, the fused particles undergo a sequence of complex structural transformations from surface alloy to phase segregated and ultimately core-shell structures. The combination of in situ electron microscopy and spectroscopy provides insights into fundamental thermodynamic and kinetic aspects governing the formation of heterogeneous nanostructures. The observed structural transformations present an interesting analogy to thin film growth on the curved surface of a nanoparticle. Using single-particle observations, we constructed a phase diagram illustrating the complex relationships among composition, morphology, temperature, and particle size.

Breaking the Crowther limit: combining depth-sectioning and tilt tomography for high-resolution, wide-field 3D reconstructions.

To date, high-resolution (<1 nm) imaging of extended objects in three-dimensions (3D) has not been possible. A restriction known as the Crowther criterion forces a tradeoff between object size and resolution for 3D reconstructions by tomography. Further, the sub-Angstrom resolution of aberration-corrected electron microscopes is accompanied by a greatly diminished depth of field, causing regions of larger specimens (>6 nm) to appear blurred or missing. Here we demonstrate a three-dimensional imaging method that overcomes both these limits by combining through-focal depth sectioning and traditional tilt-series tomography to reconstruct extended objects, with high-resolution, in all three dimensions. The large convergence angle in aberration corrected instruments now becomes a benefit and not a hindrance to higher quality reconstructions. A through-focal reconstruction over a 390 nm 3D carbon support containing over 100 dealloyed and nanoporous PtCu catalyst particles revealed with sub-nanometer detail the extensive and connected interior pore structure that is created by the dealloying instability.

Nanoscale imaging of lithium ion distribution during in situ operation of battery electrode and electrolyte.

A major challenge in the development of new battery materials is understanding their fundamental mechanisms of operation and degradation. Their microscopically inhomogeneous nature calls for characterization tools that provide operando and localized information from individual grains and particles. Here, we describe an approach that enables imaging the nanoscale distribution of ions during electrochemical charging of a battery in a transmission electron microscope liquid flow cell. We use valence energy-loss spectroscopy to track both solvated and intercalated ions, with electronic structure fingerprints of the solvated ions identified using an ab initio nonlinear response theory. Equipped with the new electrochemical cell holder, nanoscale spectroscopy and theory, we have been able to determine the lithiation state of a LiFePO4 electrode and surrounding aqueous electrolyte in real time with nanoscale resolution during electrochemical charge and discharge. We follow lithium transfer between electrode and electrolyte and image charging dynamics in the cathode. We observe competing delithiation mechanisms such as core-shell and anisotropic growth occurring in parallel for different particles under the same conditions. This technique represents a general approach for the operando nanoscale imaging of electrochemically active ions in the electrode and electrolyte in a wide range of electrical energy storage systems.

Yolk-shell structure of polyaniline-coated sulfur for lithium-sulfur batteries.

Lithium­sulfur batteries have attracted much attention in recent years due to their high theoretical capacity of 1672 mAh g(­1) and low cost. However, a rapid capacity fade is normally observed, attributed mainly to polysulfide dissolution and volume expansion. Although many strategies have been reported to prolong the cyclability, the high cost and complex preparation processes still hinder their practical application. Here, we report the synthesis of a polyaniline­sulfur yolk­shell nanocomposite through a heating vulcanization of a polyaniline­sulfur core­shell structure. We observed that this heating treatment was much more effective than chemical leaching to prepare uniform yolk­shell structures. Compared with its sulfur­polyaniline core­shell counterparts, the yolk­shell nanostructures delivered much improved cyclability owing to the presence of internal void space inside the polymer shell to accommodate the volume expansion of sulfur during lithiation. The yolk­shell material exhibited a stable capacity of 765 mAh g(­1) at 0.2 C after 200 cycles, representing a promising future for industrial scale Li­S batteries.

Amylopectin wrapped graphene oxide/sulfur for improved cyclability of lithium-sulfur battery.

An amylopectin wrapped graphene oxide-sulfur composite was prepared to construct a 3-dimensionally cross-linked structure through the interaction between amylopectin and graphene oxide, for stabilizing lithium sulfur batteries. With the help of this cross-linked structure, the sulfur particles could be confined much better among the layers of graphene oxide and exhibited significantly improved cyclability, compared with the unwrapped graphene oxide-sulfur composite. The effect of the electrode mass loading on electrochemical performance was investigated as well. In the lower sulfur mass loading cells, such as 2 mg cm(-2), both the capacity and the efficiency were obviously better than those of the higher sulfur mass loading cells, such as 6 mg cm(-2).

In situ electron energy-loss spectroscopy in liquids.

In situ scanning transmission electron microscopy (STEM) through liquids is a promising approach for exploring biological and materials processes. However, options for in situ chemical identification are limited: X-ray analysis is precluded because the liquid cell holder shadows the detector and electron energy-loss spectroscopy (EELS) is degraded by multiple scattering events in thick layers. Here, we explore the limits of EELS in the study of chemical reactions in their native environments in real time and on the nanometer scale. The determination of the local electron density, optical gap, and thickness of the liquid layer by valence EELS is demonstrated. By comparing theoretical and experimental plasmon energies, we find that liquids appear to follow the free-electron model that has been previously established for solids. Signals at energies below the optical gap and plasmon energy of the liquid provide a high signal-to-background ratio regime as demonstrated for LiFePO4 in an aqueous solution. The potential for the use of valence EELS to understand in situ STEM reactions is demonstrated for beam-induced deposition of metallic copper: as copper clusters grow, EELS develops low-loss peaks corresponding to metallic copper. From these techniques, in situ imaging and valence EELS offer insights into the local electronic structure of nanoparticles and chemical reactions.