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Chemodynamic therapy (CDT), which suppresses tumors via the conversion of endogenous hydrogen peroxide (H

A novel 5-exo-dig/6-endo-trig bicyclization of 1,6-enynes with sulfonyl hydrazides in the aqueous phase using the cheap and available tetrabutylammonium iodide (TBAI)–tert-butyl hydroperoxide (TBHP) combined system is reported.

With the increasing prevalence of illicit drugs, social security and human health are at serious risk. However, traditional detection techniques require a lengthy pretreatment process to eliminate matrix interference and do not allow rapid, in situ analysis. Ambient ionization is a powerful tool for the rapid determination of illicit drugs in different matrices because it usually eliminates the need for sample pretreatment, and the portable mass spectrometer brings convenience to in situ detection. This study employed a thermal desorption-electrospray ionization (TD-ESI) source combined with a portable mass spectrometer to rapidly characterize illicit drugs in drinks, instant powders, and solid food surfaces. Air was utilized instead of nitrogen as the carrier gas for TD-ESI/MS in order to save space and cost together with rapid on-site analysis. A full-scan waveform combined with a qualitative pre-scan waveform (QPSW) was employed to form a two-step scanning mode to accurately identify the drugs. The results showed that the limits of detection (LODs) for the analytes were 100–200 ppb in drinks, 700–1000 ppb in instant powders, and 1 ng/cm2 on solid food surfaces. The complete TD-ESI/MS analysis time was less than 1 min.

A novel visible-light-catalyzed tandem radical addition/1,5-hydrogen atom transfer/cyclization cascade of 2-alkynylarylethers with sulfonyl chlorides in 2-methyltetrahydrofuran was developed under photocatalyst- and additive-free conditions. This reaction relies on unique energy transfer and solvent-radical relay strategies to generate sulfonyl radicals for the preparation of a series of sulfonyl-functionalized dihydrobenzofurans in moderate to high yields catalyzed by visible light or solar radiation.

A novel hydrophilic porous biocomposite was fabricated by incorporating graphene oxide (GO) @chitosan (CS) foam substrate (GO@CS@ZIF-8 foam) with ZIF-8 crystals in situ via a facile stirring method for simultaneous enrichment of glycopeptides and phosphopeptides from complex biological samples. The experimental results demonstrated that GO@CS@ZIF-8 foam exhibited favorable specificity for simultaneous enrichment of N-glycopeptides and phosphopeptides under the same condition for HRP and β-casein tryptic digest mixtures. The novel material was further applied to enriching both glycopeptides and phosphopeptides simultaneously from 4 μL complex human serum, and 423 N-glycopeptides and 40 phosphopeptides corresponding to 133 glycoproteins and 29 phosphoproteins were identified, respectively.

A selective C3–H nitration of bioactive 2-sulfanilamidopyridine derivatives, including corticosteroid 11-β-dehydrogenase isozyme, secretory phospholipase A2 inhibitor and human neutrophil elastase inhibitor, has been reported.

A novel super-hydrophilic hydrogel (ZIF-8/SAP) was first proposed and facilely fabricated to capture N-glycopeptides from complex biological samples with excellent selectivity and sensitivity.

The existing particle swarm optimization (PSO) algorithms are only effective in deconvoluting the overlapping peaks in ion mobility spectrum with less than four component peaks, which limits the applicability of these algorithms.A high-performance two-step particle swarm optimization (TSPSO) algorithm was developed. As compared to the existing PSO algorithms, TSPSO can narrow the search ranges of all coefficients for the overlapping peaks through Gaussian model calculation, and thus, can deconvolute various overlapping peaks with high accuracy, even for 30 component overlapping peaks. In addition, the TSPSO could be further applied to enhance the resolution of the spectra by narrowing the peak widths after the peak deconvolution.Simulated overlapping peaks were first used to evaluate the performance of TSPSO as compared to the dynamic inertia weight particle swarm optimization (DIWPSO) algorithm. The results showed that the profiles of the peaks deconvoluted by using TSPSO were more consistent with the original ones. The fitness values and the standard deviations of the fitness values from TSPSO were also at least an order of magnitude less than those from DIWPSO. By applying TSPSO, the overlapping peaks from both MS and FAIMS spectra can also be well-deconvoluted. In addition, the resolutions of the MS and FAIMS spectra can be effectively enhanced after the peak deconvolution. The enhanced spectra matched excellently with the experimental ones acquired at high resolution modes.The experiment results convincingly demonstrated that TSPSO algorithm is capable of both deconvoluting complex overlapping peaks and enhancing the spectrum resolution with high accuracy.

Tumor hypoxia and high levels of intracellular glutathione (GSH) significantly limit the efficacy of photodynamic therapy (PDT). In addition, a single PDT treatment strategy is relatively insufficient to eliminate tumor, further limiting its application in biomedicine. Therefore, we demonstrated an omnipotent nanoplatform based on 2,2'-azobis [2-(2 imidazolin-2-yl)propane] dihydrochloride (AIPH) loaded manganese dioxide (MnO

Gas chromatography-mass spectrometry (GC-MS) is an analytical technique widely used in materials science, biomedicine, and other fields. The target compound in the experiment is identified by searching for its mass spectrum in a large mass spectrum database using some algorithms. This work introduces the use of deep learning ranking for the identification of small molecules using low-resolution electron ionization MS. Because different spectra are often very similar, the algorithm produces wrong search results, and the search accuracy needs improvement. Due to the library's large amount of data, the algorithm sometimes requires a large amount of calculation and is very time consuming.Given these two problems, this work aims to develop a model for ranking based on mass-to-charge ratio (m/z) pre-retrieval method combined with deep learning to improve search accuracy and reduce the algorithm's computational time. The master spectral library maintained by the National Institute of Standards and Technology is used as the reference library for all the experiments, and the replicate library is used as the query library to evaluate the method's performance.Compared with non-machine learning algorithms, the combination of m/z matching pre-retrieval and deep learning significantly improves library retrieval accuracy by about 4%. Moreover, compared with the deep learning sorting algorithm that does not use the pre-retrieval process, it improves the accuracy of spectral library retrieval by about 0.1% and reduces the computational time of the algorithm by more than 2 h.This method identifies compounds more efficiently and accurately than non-machine learning and deep learning algorithms without a pre-retrieval process.

Because of its powerful analytical ability, ion mobility spectrometry (IMS) plays an important role in the field of mass spectrometry. However, one of the main defects of IMS is its low structural resolution, which leads to the phenomenon of peak overlap in the analysis of compounds with similar mass charge ratio.A multiobjective dynamic teaching-learning-based optimization (MDTLBO) method was proposed to separate IMS overlapping peaks. This method prevents local optimization and identifies peak model coefficients efficiently. In addition, the position information of particles largely reflects the half-peak width of IMS, which makes single peaks difficult to appear and coefficient identification easier.The performance comparison of MDTLBO with other deconvolution methods (genetic algorithm, improved particle swarm optimization algorithm, and dynamic inertia weight particle swarm optimization algorithm) shows that the maximum deconvolution error of MDTLBO is only 0.7%, which is much lower than that for the other three methods. In addition, robustness is a performance index that reflects the advantages and disadvantages of the algorithm.MBTLBO is more robust than other algorithms for separating overlapping peaks. The algorithm can separate the heavily overlapped mobility peaks, produce better analysis results, and improve the resolution of IMS.

Mass spectrometry (MS) data is susceptible to random noises and alternating baseline, posing great challenges to spectral peak detection, especially for weak peaks and overlapping peaks. Herein, an efficient peak detection algorithm combining continuous wavelet transform (CWT) and genetic algorithm-based threshold segmentation (denoted as WSTGA) for mass spectrometry was proposed. Firstly, Mexican Hat wavelet was selected as the mother wavelet by comparing the matching degree between the difference of Gaussian (DOG) and different wavelets. Subsequently, the ridges and valleys were identified from 2D wavelet coefficient matrix. Afterward, an improved threshold segmentation method, Otsu method based on genetic algorithm, was introduced to find optimal segmentation threshold and achieve better image segmentation, overcoming the deficiency of traditional Otsu method that cannot handle long-tailed unimodal histograms. Finally, the characteristic peaks were successfully identified by utilizing the ridge-valley lines in wavelet space and original spectrum. Receiver operating characteristic (ROC) curve, area under curve (AUC) and F₁ measure are used as criterions to evaluate performance of peak detection algorithms. Compared with multi-scale peak detection (MSPD) and CWT and image segmentation (CWT-IS) methods, all the results showed that WSTGA can achieve better peak detection. More importantly, the experimental results from MALDI-TOF spectra demonstrated that WSTGA can effectively detect more weak peaks and overlapping peaks while maintaining a lower false peak detection rate than MSPD and CWT-IS methods, indicating its great advantages in characteristic peak identification.

Chemodynamic therapy (CDT), which employs Fenton/Fenton-like agents to decompose hydrogen peroxide (H

A high-performance field asymmetric waveform ion mobility spectrometry (FAIMS)-IMS-MS platform was developed and applied to explore the conformational diversity of the singly and doubly charged bradykinin (BK + H

Alzheimer's disease (AD) is a common neurodegenerative disease. Abnormal glycosylation and phosphorylation modification in AD may be closely related to its pathology. It is of substantial practical significance to simultaneously investigate the roles of phosphorylation and glycosylation in AD. In this work, a bifunctional super-hydrophilic mesoporous nanocomposite (denoted mTiO

RATIONALE FAIMS has a great potential to become a portable technology for rapid detection of chemical and biological agents. However the ion current signals, measured at the exit of the planar FAIMS directly, may contain different types of noises. The peak information in the FAIMS spectrum, such as the compensation voltage value at the maximum peak intensity (CVP ) and the peak width at half maximum (Wh ), could not be accurately determined under the weak signal condition which significantly limits the achievable instrument sensitivity, and there are no existing solutions to the problem. METHODS This study analyzed the noise type of FAIMS signal in detail, and three different signal processing algorithms, including median filtering (MF), discrete wavelet transform (DWT) and zero-phase digital filtering (ZDF), were evaluated for their performance in denoising the FAIMS signal. RESULTS The results show that the standard deviation of CVp obtained from the signal denoised by using ZDF algorithm is at least 31.82% smaller as compared to using MF and DWT algorithms. The standard deviation of Wh is at least 45.45% smaller by using ZDF algorithm. Moreover, only ZDF algorithm can keep the percentage error for the CV value of the denoised signal to be within 0.50±0.47% of the true CV value, implying the effectiveness of ZDF algorithm in denoising while retaining the integrity of the signal. CONCLUSIONS The ZDF algorithm greatly reduces the analyte peak extraction error and improves the limit of detection in FAIMS measurements.

A novel ultra-hydrophilic zwitterionic-HILIC (ZIC-HILIC) nanosphere (Fe

In this study, a novel type of covalent organic framework (COF) material rich in boronic acid sites was prepared through post-synthesis modification (TbBD@PEI@Au@4-MPBA). The surface of COF material had abundant carboxylic acid groups, which could bind a large amount of polyethyleneimine (PEI) through electrostatic interaction. At the same time, the amino groups on the PEI can be grafted with Au nanoparticles (Au NPs) in situ, and then 4-mercaptophenylboronic acid (4-MPBA) was modified by the reaction of Au and sulfhydryl groups. The massive grafting of boronic acid groups made the material's enrichment effect on glycopeptides expected. The results of experiments indicated that the composite material has high sensitivity (5 amol μL−1) and selectivity (1:1000). In addition, the material has outstanding stability and reusability, with a load capacity of about 100 mg g−1 and a recovery of 99.3 ± 2.2%. What's more, after enriched by TbBD@PEI@Au@4-MPBA, 56 endogenous glycopeptides from fresh human saliva were detected by MALDI-TOF MS, 56 unique glycopeptides corresponding to 31 glycoproteins from human saliva and 513 unique glycopeptides corresponding to 208 glycoproteins from serum of throat cancer patient were detected by nano-LC-MS/MS, respectively, which was expected to be applied to glycoproteomics research.

A detailed experimental characterization and theoretical analysis on the sensitivity, resolution and ion transmission efficiency of a planar FAIMS under different operating conditions including electrospray flow rate, solution concentration, curtain voltage and dispersion voltage are reported in the study based on the direct measurements of the ion current on the FAIMS detector. The sensitivity of FAIMS was shown to increase initially with the increase of electrospray flow rate. At a certain flow rate, which is typically compound dependent, an optimum FAIMS sensitivity was observed. Further increasing the electrospray flow rate would result in the decrease of the FAIMS sensitivity. Interestingly, the ion transmission efficiency of the FAIMS was shown experimentally to monotonically increase with the decrease of the electrospray flow rates. Both the ion transmission efficiency/sensitivity and the resolution of the FAIMS were significantly affected by the dispersion voltage. There is a strong tradeoff between the FAIMS ion transmission efficiency/sensitivity and separation resolution. As the FAIMS dispersion voltage increases, the separation resolution increases while the ion transmission efficiency/sensitivity decreases. The curtain voltage can also dramatically affect the performance of FAIMS, especially in the ion separation mode. The sensitivity of FAIMS at curtain voltage of 1.8 kV is about two-fold higher than the one at 1.0 kV. This study allows one to select the desirable FAIMS operating conditions based on the actual analysis needs.

Chemodynamic therapy (CDT) is an emerging tumour-specific therapeutic technology. However, the relatively insufficient catalytic activity of CDT agents in the tumour microenvironment (TME) limits their biomedical application. In addition, severe hypoxia and glutathione (GSH) overexpression in the TME greatly limit the antitumour efficiency of monotherapy. Herein, a cancer cell membrane-camouflaged and ultrasmall CeO2-decorated MnO2 (mMC) composite is developed for amplified CDT, photodynamic therapy (PDT) and photothermal therapy (PTT). Due to the homotypic targeting ability of cancer cell membranes, mMC nanoparticles preferentially accumulate in tumour tissue. In the TME, CeO2 acts as a highly efficient CDT agent to convert endogenous H2O2 to toxic reactive oxygen species (ROS) for killing cancer cells. Meanwhile, MnO2 irradiated with near-infrared (NIR) light displays prominent hyperthermia and ROS generation performance to perform PTT and PDT. Moreover, MnO2 can produce oxygen to ameliorate hypoxia and deplete GSH to relieve the antioxidant capability of tumours, which is beneficial to the simultaneous augmentation of PDT and CDT. Most importantly, the catalytic activity of CeO2 was greatly improved by hyperthermia. Consequently, a significantly enhanced therapeutic efficiency was obtained by the above multiple synergistic effects. This work provides a proof of concept for amplified tumour therapy by synchronously self-supplying oxygen, consuming GSH, and enhancing catalytic activity.

To solve the problem of low mass ion discrimination of conventional ion funnel and optimize ion transmission, a new ion funnel with a quadrupolar electrode configuration, was evaluated, based on the theoretical modeling, in this paper. The theoretical model was constructed by using the SIMION and the performance characteristics of the new ion funnel was simulated systematically by calculating the ion trajectory under different operating conditions. As the low mass ions lossed at the exit of ion funnel was mainly due to the opposite phase radio frequency (RF) voltage applied to the front and rear electrodes, the new ion funnel configuration rotated RF by 90 degrees and suppressed the axial potential wells near the ion funnel exit. The transmission efficiencies of the conventional and the new ion funnels for ions with low mass to charge ratio (m/z) were compared under the same operating conditions. The results showed that the new ion funnel configuration could improve the transmission efficiency by about 10% as compared to the conventional ion funnel in the m/z range below 70 while there was little differences in the transmission efficiency for high m/z ions.

Herein, a hydrophilic graphene composite functionalized with glutathione (GSH) and L(+)-Cysteine (Cys) was prepared via a simple and fast synthesis route, which was named G@S@Au@GC. The combination attack with two different zwitterionic polymers resulted in enhanced adsorption sites for glycopeptides. The obtained G@S@Au@GC exhibited excellent performance on a low limit of detection (0.2 fmol), a high selectivity (HRP: bovine serum albumin = 1:1500), a good load capacity (250 μg•mg−1) and recovery rate (93%), which was also evaluated with IgG. Subsequently, 60 glycopeptides from complex biological sample (human saliva) were identified by Nano-LC-MS/MS. The advantages of combination attack, low-cost, simple and fast synthesis, and superior enrichment performance make G@S@Au@GC composite a bright future on glycoproteomics analysis and related diseases.