Multi-spectroscopic characterization of organic salt components in medicinal plant.

The characterization of structure of organic salts in complex mixtures has been a difficult problem in analytical chemistry. In the analysis of Scutellariae Radix (SR), the pharmacopoeia of many countries stipulates that the quality control component is baicalin (≥9% by high performance liquid chromatography (HPLC)). The component with highest response in SR was also baicalin detected by liquid chromatography-mass spectrometry (LC-MS). However, in the attenuated total reflection Fourier transform infrared spectroscopy, the carbonyl peak of glucuronic acid of baicalin did not appear in SR. The results of element analysis, time of flight secondary ion mass spectrometry, matrix assisted laser desorption ionization mass spectrometry and solid-state nuclear magnetic resonance all supported the existence of baicalin magnesium salt. Based on this, this study proposes an analysis strategy guided by infrared spectroscopy and combined with multi-spectroscopy techniques to analyze the structure of organic salt components in medicinal plant. It is meaningful for the research of mechanisms, development of new drugs, and quality control.

TOF-SIMS study of latent fingerprints on challenging substrates with the aid of transfer films.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been applied in forensic science for fingerprint detection. However, due to limitations of the instrument, it is not always possible to directly sample fingerprints on certain substrates. In this report, we indirectly sampled fingerprints using transfer films. First, we optimized the experimental conditions and identified transfer films with better results. We then explored the feasibility of revealing fingerprints after transfer and successfully transferred and revealed the detailed features of fingerprints on several common objects that could not be directly sampled. Fingerprints transferred from smooth surfaces yield clearer feature details in ion images. Additionally, we analyzed the substances in the transferred fingerprints and detected components of morphine and MDMA(3,4-methylenedioxy-n-methylamphetamine). By combining feature details with identified chemical components, the identity of a person can be determined, linking suspects to the crime scene. This work provides a new approach for sample introduction in instrumental analysis, enabling TOF-SIMS to be applied in more scenarios.

Engineered exosome-mediated messenger RNA and single-chain variable fragment delivery for human chimeric antigen receptor T-cell engineering.

BACKGROUND AIMS: Most current chimeric antigen receptor (CAR) T cells are generated by viral transduction, which induces persistent expression of CARs and may cause serious undesirable effects. Messenger RNA (mRNA)-based approaches in manufacturing CAR T cells are being developed to overcome these challenges. However, the most common method of delivering mRNA to T cells is electroporation, which can be toxic to cells. METHODS: The authors designed and engineered an exosome delivery platform using the bacteriophage MS2 system in combination with the highly expressed protein lysosome-associated membrane protein 2 isoform B on exosomes. RESULTS: The authors' delivery platform achieved specific loading and delivery of mRNA into target cells and achieved expression of specific proteins, and anti-CD3/CD28 single-chain variable fragments (scFvs) expressed outside the exosomal membrane effectively activated primary T cells in a similar way to commercial magnetic beads. CONCLUSIONS: The delivery of CAR mRNA and anti-CD3/CD28 scFvs via designed exosomes can be used for ex vivo production of CAR T cells with cancer cell killing capacity. The authors' results indicate the potential applications of the engineered exosome delivery platform for direct conversion of primary T cells to CAR T cells while providing a novel strategy for producing CAR T cells in vivo.

Contamination and health risks of heavy metals in the soil of a historical landfill in northern China.

Landfill-induced heavy metal (HM) contamination of soils is a widespread and complex problem. The levels and potential hazards of HM contamination in landfills must be evaluated before they can be reused for any purpose. In order to reuse a historical landfill in northern China, 376 sampling sites were selected in 2019 using the checkerboard layout method, and the levels of arsenic (As), mercury (Hg), antimony (Sb), copper (Cu), lead (Pb), cadmium (Cd), nickel (Ni), zinc (Zn), and thallium (Tl) in the soil were measured. Multiple evaluation methods established the HM pollution levels, agricultural suitability, and health risks associated with the sampling sites. In most parts of the study area, the concentrations of all nine HMs exceeded the screening levels and maximum allowable concentrations for agricultural soils. Only the soils in Zones 5 and 6 can be used for agricultural activity. Moreover, the deep soils were heavily contaminated with HMs in certain areas, possibly because of leaching and infiltration in the surface soil and the rise and diffusion of polluted groundwater. The soil HMs in the study area posed a higher carcinogenic risks to both adults and children. The average carcinogenic risk associated with As was 6.12 × 10-4, which was the major contributor to carcinogenic risk at all HM-contaminated sites. The results of this work empirically demonstrated that soil HM pollution is severe and problematic in the study area and remedial measures are urgently required.

Micro/Nano Energy Storage Devices Based on Composite Electrode Materials.

It is vital to improve the electrochemical performance of negative materials for energy storage devices. The synergistic effect between the composites can improve the total performance. In this work, we prepare α-Fe2O3@MnO2 on carbon cloth through hydrothermal strategies and subsequent electrochemical deposition. The α-Fe2O3@MnO2 hybrid structure benefits electron transfer efficiency and avoids the rapid decay of capacitance caused by volume expansion. The specific capacitance of the as-obtained product is 615 mF cm-2 at 2 mA cm-2. Moreover, a flexible supercapacitor presents an energy density of 0.102 mWh cm-3 at 4.2 W cm-2. Bending tests of the device at different angles show excellent mechanical flexibility.

Impacts of Dissolved Ni2+ on the Solid Electrolyte Interphase on a Graphite Anode.

Transition metal (e.g. Ni) ions dissolved from layered-structured Ni-rich cathodes can migrate to the anode side and accelerate the failure of lithium-ion batteries. The investigations of the impact and distribution of Ni species on the solid electrolyte interphase (SEI) on the anode are crucial to understand the failure mechanism. Herein, we used time-of-flight secondary ion mass spectroscopy (TOF-SIMS) coupled with multivariate curve resolution (MCR) analysis to intuitively characterize the distribution of Ni species in the SEI. We find that the SEI on the graphite electrode using an EC-based electrolyte exhibits a multi-stratum structure. During accelerated aging of the LiNi0.88 Co0.08 Mn0.04 O2 /graphite full cell, the dissolution of Ni aggravates significantly upon cycling. A strong correlation between the dissolved-Ni and organic species in the SEI on graphite is illustrated. The ion-exchange reaction between Ni2+ and Li+ ions in the SEI is demonstrated to be the main reason for the increase of SEI resistivity.

A rapid and label-free platform for virus enrichment based on electrostatic microfluidics.

Virus surveillance and discovery are crucial for virus prediction and outbreak preparedness. Virus samples are frequently bulky and complicated so that effective virus detection remain challenging. Herein, we develop an 3D electrostatic microfluidic platform to rapidly and label-free enrich viruses from bulky samples at low concentrations. The platform consists of double microchannels for streamlining large volume processing and electrodes for enriching viruses by electrostatic interaction. The trajectories of simulation show that particle is successfully enriched under different forces of electrostatic field and different sample flow rates. We demonstrate that the electrostatic microfluidic platform can increase the limit of detection in 100-fold higher based on real-time PCR quantified analysis. Our design thus provides a simple, rapid, label-free and high-throughput viruses concentration platform and would thus have significant utility for various viral detection.

In Situ Identification and Spatial Mapping of Microplastic Standards in Paramecia by Secondary-Ion Mass Spectrometry Imaging.

Microplastics (MPs) are universally present in the ecosystem and pose great threats to the environment and living organisms. Research studies have shown that small MPs (<50 µm in diameter) are especially toxic and account for more than half of all MPs collected in the Atlantic Ocean. Nevertheless, current methods for the detection and analysis of MPs are incapable of achieving rapid and in situ analysis of small MPs in the biota to ultimately enable the study of their biological effects. In this work, we report a method that allows rapid in situ identification and spatial mapping of small MPs directly from paramecia with high accuracy by acquiring chemical composition information using secondary-ion mass spectrometry (SIMS) imaging. Specifically, six types of common MPs (polymethyl methacrylate, polyvinyl chloride, polypropylene, polyethylene terephthalate, polyglycidyl methacrylate, and polyamide 6) with a diameter of 1-50 µm were simultaneously imaged with high chemical specificity at a spatial resolution of 700 nm. In situ spatial mapping of a group of MPs ingested by paramecia was performed using SIMS fragments specific to the plastic composition with no sample pretreatment, revealing the aggregation of MPs in paramecia after ingestion. Compared with existing methods, one additional advantage of the developed method is that the MPs and the organism can be analyzed in the same experimental workflow to record their fingerprint spectra, acquiring biochemical information to evaluate MP fate, toxicity, and the MP-biota interaction.

Evaluation of Time-of-Flight Secondary Ion Mass Spectrometry Spectra of Peptides by Random Forest with Amino Acid Labels: Results from a Versailles Project on Advanced Materials and Standards Interlaboratory Study.

We report the results of a VAMAS (Versailles Project on Advanced Materials and Standards) interlaboratory study on the identification of peptide sample TOF-SIMS spectra by machine learning. More than 1000 time-of-flight secondary ion mass spectrometry (TOF-SIMS) spectra of six peptide model samples (one of them was a test sample) were collected using 27 TOF-SIMS instruments from 25 institutes of six countries, the U. S., the U. K., Germany, China, South Korea, and Japan. Because peptides have systematic and simple chemical structures, they were selected as model samples. The intensity of peaks in every TOF-SIMS spectrum was extracted using the same peak list and normalized to the total ion count. The spectra of the test peptide sample were predicted by Random Forest with 20 amino acid labels. The accuracy of the prediction for the test spectra was 0.88. Although the prediction of an unknown peptide was not perfect, it was shown that all of the amino acids in an unknown peptide can be determined by Random Forest prediction and the TOF-SIMS spectra. Moreover, the prediction of peptides, which are included in the training spectra, was almost perfect. Random Forest also suggests specific fragment ions from an amino acid residue Q, whose fragment ions detected by TOF-SIMS have not been reported, in the important features. This study indicated that the analysis using Random Forest, which enables translation of the mathematical relationships to chemical relationships, and the multi labels representing monomer chemical structures, is useful to predict the TOF-SIMS spectra of an unknown peptide.

Metabolic fingerprinting of cell types in mouse skeletal muscle by combining TOF-SIMS with immunofluorescence staining.

Skeletal muscle tissue is composed of various muscle cell types which differ in physiological functions. Changes in cell type composition of skeletal muscle are associated with the development of metabolic diseases. Skeletal muscle cell types are currently distinguished by immunofluorescence (IF) staining based on myosin heavy chain (MHC) isoform difference. However, it remains a challenge to provide metabolic fingerprints of different muscle cell types by IF staining. Therefore, in this study, we proposed a method to examine metabolite distribution within different cell types by time-of-flight secondary ion mass spectrometry (TOF-SIMS) with high spatial resolution. Skeletal muscle samples from C57/BL6 mice were obtained by slicing. Cell types in TOF-SIMS images were labelled corresponding to IF images from the same region of serially cut sections. Mass spectra corresponding to individual muscle cells were extracted to compare metabolic fingerprints among cell types. Skeletal muscle cells were classified into two clusters based on the mass spectra of individual cells. Unsaturated diacylglycerol (DG) and fatty acid (FA) species were found to be distributed in a cell-type dependent manner. Moreover, relative quantification showed that the content of unsaturated DGs, oleic acid and linoleic acid was higher in type I and type IIA cells than in type IIB cells. TOF-SIMS in combination with IF enables us to directly visualize metabolite distribution in different cell types, to find potential biomarkers for cell type classification. TOF-SIMS imaging coupled with IF staining has been proved to be a promising tool for metabolic fingerprinting of different skeletal muscle cell types.

Pollution Characteristics of Microplastics in Soils in Southeastern Suburbs of Baoding City, China.

Microplastics (MPs) are emerging pollutants that exist in different environmental media. Because of their wide range and large potential environmental hazards, they have attracted widespread attention in recent years. At present, the research on MP is mostly concentrated on the water ecosystems, and the impact on soil ecosystems is less studied. In this study, 12 typical soil samples from southeastern suburbs of Baoding city were investigated and characterized by time-of-flight secondary ion mass spectrometry (TOF-SIMS) combined with mass high resolution mode and positive and negative ion imaging mode. Four types of MPs, poly (propylene) (PP), poly (vinyl chloride) (PVC), poly (ethylene terephthalate) (PET), and poly (amide 6) (PA6), were quickly identified, of which PET and PA6 accounted for the largest proportion of both up to 30.2%; the particle size of the obtained MPs ranged from 0 to 35 µm, of which the proportion of <10 µm MPs was more than 26.3%, while that of 20-25 µm and 25-35 µm MPs was relatively small (17.83% and 9.3%, respectively). Risk assessment results of the MP in the soil showed that the risk level of MPs in the non-ferrous metal industrial parks and in concentrated with small workshops areas is relatively high, and attention should be paid to such areas. In addition, the study provides a reference method for the investigation and risk assessment of MPs in terrestrial soils, coastal beaches, and sediments.

Bottom-Up Construction of Active Sites in a Cu-N4-C Catalyst for Highly Efficient Oxygen Reduction Reaction.

Bottom-up construction of efficient active sites in transition metal-nitrogen-carbon (M-N-C) catalysts for oxygen reduction reaction (ORR) from single molecular building blocks remains one of the most difficult challenges. Herein, we report a bottom-up approach to produce a highly active Cu-N4-C catalyst with well-defined Cu-N4 coordination sites derived from a small molecular copper complex containing Cu-N4 moieties. The Cu-N4 moieties were found to be covalently integrated into graphene sheets to create the Cu-N4 active sites for ORR. Furthermore, the activity was boosted by tuning the structure of active sites. We find that the high ORR activity of the Cu-N4-C catalyst is related to the Cu-N4 center linked to edges of the graphene sheets, where the electronic structure of the Cu center has the right symmetry for the degenerate π* orbital of the O2 molecule. These findings point out the direction for the synthesis of the M-N-C catalysts at the molecular level.

Improving nutrient release of wall-disrupted bee pollen with a combination of ultrasonication and high shear technique.

BACKGROUND: Pollen collected by honey bees contains a substantial amount of nutrients and has a high nutritive value. However, it can be difficult to digest and absorb a high level of nutrients due to the complex wall of bee pollen. RESULTS: We observed that amino acids were mostly distributed inside the cell wall of lotus bee pollen, rape bee pollen, apricot bee pollen, wuweizi bee pollen, and camellia bee pollen, using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Thus, five species of bee pollen were wall disrupted with a combination of ultrasonication and high shear technique (US-HS). After the treatment, bee pollen walls were completely broken into fragments, and a large number of nutrients were released. The amino acid, fatty acid, protein, crude fat, reducing sugar, ß-carotene, calcium, iron, zinc, and selenium content increased after wall disruption. CONCLUSION: Overall, our study demonstrated that US-HS can disrupt bee pollen walls to release nutrients. Further studies are therefore being conducted to compare the digestibility and absorptivity of pollen nutrients before and after wall disruption. Time-of-flight secondary ion mass spectrometry seems to be a reliable mapping technique for determining the distribution of food ingredients. © 2018 Society of Chemical Industry.

A novel linear epitope crossing Group 1 and Group 2 influenza A viruses located in the helix A of HA2 derived from H7N9.

In this research, four monoclonal antibodies (mAbs) were first generated as an immunogen by using the GST fusion protein that carries the fusion peptide and helix A derived from H7N9 influenza A virus (IAV). These mAbs could react with HA of H7N9, H3N2, and H9N2 with neutralizing activity. A novel linear epitope recognized by these mAbs was identified by peptide-based ELISA, and this epitope was located in TAADYKSTQSAIDQITGKLN at the C terminus of the helix A of H7N9. 3 A11, which is one of the four mAbs, could efficiently recognize the corresponding epitopes derived from H9, H7, H5, H3, and H1. Analysis of sera against the corresponding epitope from different HAs revealed that the C terminus of helix A in H9, H7, and H3 possessed dominant B cell epitopes that cross both Group 1 and Group 2 IAV, whereas the C terminus of helix A in H5 possessed only dominant B cell epitopes that cross subtypes in Group 1 virus. All these results demonstrated that the linear epitope identified in the helix A of H7N9 could be a novel target for developing broad-spectrum influenza diagnostics or vaccine candidates.

Vacuum Ultraviolet Laser Desorption/Ionization Mass Spectrometry Imaging of Single Cells with Submicron Craters.

Mass spectrometry imaging (MSI) is a crucial label-free method to distinguish the localization patterns in single cells. MALDI-TOF MS and ToF-SIMS are now bearing the responsibility. However, MALDI-TOF MS is limited to micron spatial resolution and ToF-SIMS suffers from severe molecular fragmentation. Here, we proposed a new MSI methodology of vacuum ultraviolet laser desorption/ionization (VUVDI) with high spatial resolution, achieving higher ion yields and less fragmentation compared with ToF-SIMS at submicron level. The fluorescence image and mass spectrum of VUVDI were obtained simultaneously. In addition, the adjustable laser fluence acquired selective detection for different molecular and fragmental ions, thus realizing molecular identification. Furthermore, MSIs of single cells with submicron craters were presented. These results suggest VUVDI is a potential mass spectrometry method that provides a soft ionization source and submicron spatial resolution for molecular analysis in life science.

Ion Sputter Induced Interfacial Reaction in Prototypical Metal-GaN System.

Contact property is now becoming to be a key factor for achieving high performance and high reliability in GaN-based III-V semiconductor devices. Energetic ion sputter, as an effective interface probe, is widely used to profile the metal/GaN contacts for interfacial analysis and process optimization. However, the details of ion-induced interfacial reaction, as well as the formation of sputter by-products at the interfaces are still unclear. Here by combining state-of-the-art Ar+ ion sputter with in-situ X-ray photoelectron spectroscopy (XPS) and ex-situ high resolution transmission electron microscopy (HRTEM), we have observed clearly not only the ion-induced chemical state changes at interface, but also the by-products at the prototypical Ti/GaN system. For the first time, we identified the formation of a metallic Ga layer at the GaOx/GaN interface. At the Ti/GaOx interface, TiCx components were also detected due to the reaction between metal Ti and surface-adsorbed C species. Our study reveals that the corresponding core level binding energy and peak intensity obtained from ion sputter depth profile should be treated with much caution, since they will be changed due to ion-induced interface reactions and formation of by-products during ion bombardment.

Chemical Visualization of Sweat Pores in Fingerprints Using GO-Enhanced TOF-SIMS.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been used in imaging of small molecules (<500 Da) in fingerprints, such as gunshot residues and illicit drugs. However, identifying and mapping relatively high mass molecules are quite difficult owing to insufficient ion yield of their molecular ions. In this report, graphene oxide (GO)-enhanced TOF-SIMS was used to detect and image relatively high mass molecules such as poison, alkaloids (>600 Da) and controlled drugs, and antibiotics (>700 Da) in fingerprints. Detail features of fingerprints such as the number and distribution of sweat pores in a ridge and even the delicate morphology of one pore were clearly revealed in SIMS images of relatively high mass molecules. The detail features combining with identified chemical composition were sufficient to establish a human identity and link the suspect to a crime scene. The wide detectable mass range and high spatial resolution make GO-enhanced TOF-SIMS a promising tool in accurate and fast analysis of fingerprints, especially in fragmental fingerprint analysis.

Graphene Oxide as a Novel Evenly Continuous Phase Matrix for TOF-SIMS.

Using matrix to enhance the molecular ion signals for biomolecule identification without loss of spatial resolution caused by matrix crystallization is a great challenge for the application of TOF-SIMS in real-world biological research. In this report, graphene oxide (GO) was used as a matrix for TOF-SIMS to improve the secondary ion yields of intact molecular ions ([M + H]+). Identifying and distinguishing the molecular ions of lipids (m/z >700) therefore became straightforward. The spatial resolution of TOF-SIMS imaging could also be improved as GO can form a homogeneous layer of matrix instead of crystalline domain, which prevents high spatial resolution in TOF-SIMS imaging. Lipid mapping in presence of GO revealed the delicate morphology and distribution of single vesicles with a diameter of 800 nm. On GO matrix, the vesicles with similar shape but different chemical composition could be distinguished using molecular ions. This novel matrix holds potentials in such applications as the analysis and imaging of complex biological samples by TOF-SIMS. Graphical Abstract ᅟ.

Polyaniline/Carbon Nitride Nanosheets Composite Hydrogel: A Separation-Free and High-Efficient Photocatalyst with 3D Hierarchical Structure.

A polyaniline (PANI)/carbon nitride nanosheets (CNNS) composite hydrogel with 3D hierarchical nanostructure is synthesized via in situ polymerization. The 3D hierarchical structure is robust and stable, making the composite hydrogel separation-free and easy to recycling. It is highly excellent in removing organic pollutant for PANI/CNNS composite hydrogel on account of the cooperation of adsorptive preconcentration and the following photocatalytic oxidation. Pollutants are first adsorbed and concentrated into the 3D hierarchical nanostructure of the composite hydrogel. Then the pollutants are in situ oxidized via photocatalysis. The promoted photocatalytic performance can be mainly ascribed to the outstanding interfacial charge separation and photoelectrochemical performance. A new idea of the construction of 3D hierarchical photocatalysts is presented, which can be applied in the sustainability field.

[TOF-SIMS Study of Mannitol and Cordycepin in Cordyceps Sinensis].

Cordyceps sinensis is a well-known traditional Chinese medicine; it is also called DongChongXiaCao (winter worm summer grass) in Chinese. Mannitol and cordycepin, the most important two pharmacological active components of cordyceps sinensis, were studied with TOF-SIMS. This Study was focused on the chemical information including 251 amu mass peak. Based on high mass resolution of TOF-SIMS analysis, the fragment ions of 251 and 252 amu detected in Cordyceps sinensis may not be the molecular ion M+ and/or[M+H]+ of cordycepin, which ispossiblely the root cause of the argument in the study of cordycepin in published papers .It could be a basis for further study of cordycepin components of cordyceps sinensis in the future. The 181amu mass peak of minus ion in mannitol was also studied in detail and was certified to be a reliable evidence of mannitol. This research shows that TOF-SIMS has been proven as an effective method in the study of cordyceps sinensis.