Quantitative Chemoproteomic Profiling of Targets of Au(I) Complexes by Competitive Activity-Based Protein Profiling.

Owing to the encouraging pharmacological action and acceptable toxicity profile, Au(I) complexes have attracted growing interest in the application of disease treatment. In order to investigate their potential target proteins and related bioinformation, herein, we screened four Au(I) complexes and explored the binding proteins utilizing a competitive activity-based protein profiling (ABPP) strategy, including identification experiments and reactivity classification experiments, which offers a simple and robust method to identify the target proteins of Au(I) complexes. We quantified the target proteins of the four Au(I) complexes and found that most of proteins were associated with cancer. In addition, the newly Au(I)-binding proteins and biological gold-protein interaction pathways were exhibited. Furthermore, we estimated the correlation between target proteins of Au(I) complexes and various cancers, which will promote the development of the gold anticancer drugs.

One-Pot Synthesis of Multifunctional Carbon-Based Nanoparticle-Supported Dispersed Cu2+ Disrupts Redox Homeostasis to Enhance CDT.

In chemodynamic therapy (CDT), the levels of reactive oxygen species (ROS) production plays an important role for evaluating the therapeutic efficacy. However, the high levels of glutathione (GSH) in tumor cells consume the ROS, directly reducing the therapeutic efficiency. Herein, we synthesized carbon-based nanoparticle (Cu-cys CBNPs) using one-pot strategy, which consume GSH via redox reactions to produce Cu+ that catalyze H2 O2 to produce . OH, thus the ROS level was observably increased through this synergistic effect. In vivo experiments further revealed that Cu-cys CBNPs could effectively inhibit tumor growth. Additionally, Cu-cys CBNPs can affect the activity of some protein sulfhydryl groups in cells, which was assessed by rdTOP-ABPP assay. In general, this study not only provides a potential CDT drug, but also provides a strategy for one-pot synthesis of multifunctional nanomaterials.

Phosphorene Nanoribbon-Augmented Optoelectronics for Enhanced Hole Extraction.

Phosphorene nanoribbons (PNRs) have been widely predicted to exhibit a range of superlative functional properties; however, because they have only recently been isolated, these properties are yet to be shown to translate to improved performance in any application. PNRs show particular promise for optoelectronics, given their predicted high exciton binding energies, tunable bandgaps, and ultrahigh hole mobilities. Here, we verify the theorized enhanced hole mobility in both solar cells and space-charge-limited-current devices, demonstrating the potential for PNRs improving hole extraction in universal optoelectronic applications. Specifically, PNRs are demonstrated to act as an effective charge-selective interlayer by enhancing hole extraction from polycrystalline methylammonium lead iodide (MAPbI3) perovskite to the poly(triarylamine) semiconductor. Introducing PNRs at the hole-transport/MAPbI3 interface achieves fill factors above 0.83 and efficiencies exceeding 21% for planar p-i-n (inverted) perovskite solar cells (PSCs). Such efficiencies are typically only reported for single-crystalline MAPbI3-based inverted PSCs. Methylammonium-free PSCs also benefit from a PNR interlayer, verifying applicability to architectures incorporating mixed perovskite absorber layers. Device photoluminescence and transient absorption spectroscopy are used to demonstrate that the presence of the PNRs drives more effective carrier extraction. Isolation of the PNRs in space-charge-limited-current hole-only devices improves both hole mobility and conductivity, demonstrating applicability beyond PSCs. This work provides primary experimental evidence that the predicted superlative functional properties of PNRs indeed translate to improved optoelectronic performance.

Fabrication of a "Selenium Signature" Chemical Probe-Modified Paper Substrate for Simultaneous and Efficient Determination of Biothiols by Paper Spray Mass Spectrometry.

Significant efforts have been made to develop robust and reliable methods for simultaneous biothiols determination in different matrices, but there still exist the problems such as easy oxidation, tedious derivatization, and difficulty in discrimination, which brings unsatisfactory results in their accuracy and fast quantification in biological samples. To overcome these problems, a simultaneous biothiols detection method combining a "selenium signature" chemical probe and paper spray mass spectrometry (PS-MS) was proposed. In the strategy, the modified-paper substrate is used to enhance the analytical performance. Chemical probe Ebselen-NH2 that has a specific response to biothiols was designed and covalently fixed on the surface of an oxidized paper substrate. By the identification of derivatized product with distinctive selenium isotope distribution and employment of the optimized PS-MS method, qualitative and quantitative analysis of five biothiols including glutathione (GSH), cysteine (Cys), cysteinylglycine (CysGly), N-acetylcysteine (Nac), and homocysteine (Hcy) were realized. Biothiols in plasma and cell lysates were measured with satisfactory results. The established method not only provides a novel protocol for simultaneous determination of biothiols, but also is helpful for understanding the biological and clinical roles played by these bioactive small molecules.

Covalent organic frameworks-based paper solid phase microextraction combined with paper spray mass spectrometry for highly enhanced analysis of tetrabromobisphenol A.

How to further improve the sensitivity of paper spray mass spectrometry (PS-MS) is very important for its application in low content substance detection. Covalent organic frameworks (COFs) are a kind of novel crystalline materials that exhibit tremendous potential for multifarious applications. Nevertheless, the applications of COFs in PS-MS are still unexplored. Herein, for the first time, a method that used COFs nanoparticles as a coated matrix of PS-MS coupled with solid phase microextraction (SPME) was developed, and as a proof of concept, it was applied for highly sensitive analysis of pollutant tetrabromobisphenol A (TBBPA) in environmental samples. In order to prepare the COFs-coated papers, a variety of factors, such as starch type and amount, loaded COFs amount and spray solvent, have been explored in detail. Compared with the naked paper substrates, a lower limit of quantitation of 1 nmol L-1 with 50-fold enhancement was achieved using COFs-based paper composites, which indicated that papers decorated with COFs might be a promising candidate for paper spray with high sensitivity in the analysis of environmental samples.

Mixed carbon source improves deep denitrification performance in up-flow anaerobic sludge bed reactor.

To investigate the advantages of mixed carbon source over a single one in deep denitrification, sodium acetate, glucose and their mixture were used as carbon sources in present study. Denitrification performance, effluent pH, microbial community and carbon source cost were taken into account. With the same influent NO3 --N concentration of 50 mg/L and the same C/N ratio of 1.5, the NO3 --N removal rate with the mixed carbon source (96.53%) was slightly lower than that with sodium acetate (98.15%), but significantly higher than that with glucose (74.69%). The specific denitrification rates of the sodium acetate, glucose and sodium acetate/glucose reactor were 47.7, 29.7 and 45.4 mg N/g VSS d, respectively. The effluent pH with sodium acetate varied in the range of 9.13-9.60, exceeding the discharge standard limit of 9.0, whereas the sodium acetate/glucose reactor could keep pH in the range of 7.80-8.23. The 16S rRNA gene-based high-throughput sequencing revealed that carbon sources determined the microbial community structure and the sludge Shannon index with the mixed carbon source was the highest. Furthermore, cost estimation indicated that the mixed carbon source was the cheapest. This study is significant as it tests reasonable selection of carbon sources for deep denitrification in practice.

A Simple 3D-Printed Enzyme Reactor Paper Spray Mass Spectrometry Platform for Detecting BuChE Activity in Human Serum.

To achieve personalized healthcare, a quick, accurate, and high-throughput method to detect disease biomarkers is essential. In the traditional practice, mass spectrometry is one of the most powerful tools and is widely studied. However, the test of human serum usually requires complicated sample pretreatment, tedious operations, and precise condition control, especially for the detection of enzymes as biomarkers. As butyrylcholinesterase (BuChE) has an indicative significance in detecting degenerative disease, liver injury, and organophosphate poisoning, the quick quantification of BuChE is of vital importance to the clinic. In this paper, we report the design and fabrication of a portable 3D-printed enzyme reactor paper spray cartridge (3D ER-PS) with integrated functions: temperature control, enzyme reaction, analyte transfer, and paper spray ionization. Coupled with mass spectrometry, quantitative testing of BuChE activity in human serum was realized conveniently and accurately. While it only requires very simple sample preparation, the results from current 3D ER-PS approach are well consistent with those obtained using Ellman's method. This 3D ER-PS platform not only provides a novel solution for the liquid biopsy of BuChE in clinics but also contributes to the development of quick and targeted medical approaches for analyzing other types of serum biomarker molecules in the field of disease diagnosis.

Identification of sulfhydryl-containing proteins and further evaluation of the selenium-tagged redox homeostasis-regulating proteins.

Chemoproteomic profiling of sulfhydryl-containing proteins has consistently been an attractive research hotspot. However, there remains a dearth of probes that are specifically designed for sulfhydryl-containing proteins, possessing sufficient reactivity, specificity, distinctive isotopic signature, as well as efficient labeling and evaluation capabilities for proteins implicated in the regulation of redox homeostasis. Here, the specific selenium-containing probes (Se-probes) in this work displayed high specificity and reactivity toward cysteine thiols on small molecules, peptides and purified proteins and showed very good competitive effect of proteins labeling in gel-ABPP. We identified more than 6000 candidate proteins. In TOP-ABPP, we investigated the peptide labeled by Se-probes, which revealed a distinct isotopic envelope pattern of selenium in both the primary and secondary mass spectra. This unique pattern can provide compelling evidence for identifying redox regulatory proteins and other target peptides. Furthermore, our examiation of post-translational modification (PTMs) of the cysteine site residues showed that oxidation PTMs was predominantly observed. We anticipate that Se-probes will enable broader and deeper proteome-wide profiling of sulfhydryl-containing proteins, provide an ideal tool for focusing on proteins that regulate redox homeostasis and advance the development of innovative selenium-based pharmaceuticals.

Detection of Cysteine Sulfenic Acid on E. coli Proteins with a Biotin-Benzoboroxole Probe.

S-sulfenylation of cysteine residues on proteins can effectively change protein structures and accordingly regulate their functions in vivo. Investigation of S-sulfenylation in different biological environments is thus vital for a systematic understanding of cellular redox regulation. In this work, a functional probe, biotin-benzoboroxole (Bio-ben), was designed for the detection of cysteine sulfenic acid (Cys-SOH). The performance of Bio-ben was characterized by small-molecule sulfenic acid, protein models, and proteome tests via mass spectra and western blotting. The results showed that Bio-ben was validated for cysteine sulfenic acid on proteins with good capture efficiency even at low concentrations. Compared with commonly used probes such as dimedone, the current probe has significantly shortened labeling time and exhibited comparable sensitivity. The proposed method provides a new approach for exploring S-sulfenylation in the oxidative modification of proteins and is helpful for related biological and clinical applications.

Understanding drug nanocarrier and blood-brain barrier interaction based on a microfluidic microphysiological model.

As many nanoparticles (NPs) have been exploited as drug carriers to overcome the resistance of the blood-brain barrier (BBB), reliable in vitro BBB models are urgently needed to help researchers to comprehensively understand drug nanocarrier-BBB interaction during penetration, which can prompt pre-clinical nanodrug exploitation. Herein, we developed a microfluidic microphysiological model, allowing the analysis of BBB homeostasis and NP penetration. We found that the BBB penetrability of gold nanoparticles (AuNPs) was size- and modification-dependent, which might be caused by a distinct transendocytosis pathway. Notably, transferrin-modified 13 nm AuNPs held the strongest BBB penetrability and induced the slightest BBB dysfunction, while bare 80 nm and 120 nm AuNPs showed opposite results. Moreover, further analysis of the protein corona showed that PEGylation reduced the protein absorption, and some proteins facilitated the BBB penetration of NPs. The developed microphysiological model provides a powerful tool for understanding the drug nanocarrier-BBB interaction, which is vital for exploiting high-efficiency and biocompatible nanodrugs.

Additive-Free, Low-Temperature Crystallization of Stable α-FAPbI3 Perovskite.

Formamidinium lead triiodide (FAPbI3 ) is attractive for photovoltaic devices due to its optimal bandgap at around 1.45 eV and improved thermal stability compared with methylammonium-based perovskites. Crystallization of phase-pure α-FAPbI3 conventionally requires high-temperature thermal annealing at 150 °C whilst the obtained α-FAPbI3 is metastable at room temperature. Here, aerosol-assisted crystallization (AAC) is reported, which converts yellow δ-FAPbI3 into black α-FAPbI3 at only 100 °C using precursor solutions containing only lead iodide and formamidinium iodide with no chemical additives. The obtained α-FAPbI3 exhibits remarkably enhanced stability compared to the 150 °C annealed counterparts, in combination with improvements in film crystallinity and photoluminescence yield. Using X-ray diffraction, X-ray scattering, and density functional theory simulation, it is identified that relaxation of residual tensile strains, achieved through the lower annealing temperature and post-crystallization crystal growth during AAC, is the key factor that facilitates the formation of phase-stable α-FAPbI3 . This overcomes the strain-induced lattice expansion that is known to cause the metastability of α-FAPbI3 . Accordingly, pure FAPbI3 p-i-n solar cells are reported, facilitated by the low-temperature (≤100 °C) AAC processing, which demonstrates increases of both power conversion efficiency and operational stability compared to devices fabricated using 150 °C annealed films.

In Situ Construction of COF-Based Paper Serving as a Plasmonic Substrate for Enhanced PSI-MS Detection of Polycyclic Aromatic Hydrocarbons.

Accurate detection, quantitation, and differentiation of polycyclic aromatic hydrocarbons (PAHs) and their isomers in diverse samples is elusive for paper spray ionization mass spectrometry (PSI-MS). To address these issues, herein, for the first time, we propose to fabricate a novel, flexible, and stable paper substrate based on covalent organic frameworks (COFs) via an in situ method under room temperature in air. After embedding gold nanoparticles (AuNPs), this paper substrate (COFs-paper) could further serve as a multifunctional plasmonic matrix (AuNPs-COFs-paper) for dual-wavelength laser-assisted PSI-MS detection of PAHs and feasible paper surface-enhanced Raman scattering (pSERS)-aided isomer discrimination. Taking advantage of the synergistic effect between the AuNPs and COFs present on the novel AuNP-embedded COFs-paper substrate, a satisfied LOD of 0.50 ng/µL for phenanthrene was realized, which improved almost 300 times compared with the naked-paper matrix, and the regression coefficient R2 was up to 0.999. Real sample corn oil-containing PAHs can be efficiently detected and identified using this technique. The established platform has promising potential for on-site chemical analysis with portable PSI-MS and pSERS instruments.

Target discovery of ebselen with a biotinylated probe.

Despite numerous studies on ebselen over the past decade, its cellular targets remain obscure. Here we synthesized a biotinylated ebselen probe (biotin-ebselen) and characterized ebselen-binding proteins via an efficient activity-based protein profiling (ABPP) method, which allowed for the robust identification of 462 targeted proteins in HeLa cells. This first work of global target profiling of ebselen will be helpful to re-design ebselen-based therapy appropriately in clinical trials.

Fluorescent sensing of pyrophosphate anion in synovial fluid based on DNA-attached magnetic nanoparticles.

In this work, a new fluorescent method for sensitive detection of pyrophosphate anion (P2O7(4-), PPi) in the synovial fluid was developed using fluorophore labeled single-stranded DNA-attached Fe3O4 NPs. The sensing approach is based on the strong affinity of PPi to Fe3O4 NPs and highly efficient fluorescent quenching ability of Fe3O4 NPs for fluorophore labeled single-stranded DNA. In the presence of PPi, the fluorescence would enhance dramatically due to desorption of fluorophore labeled single-stranded DNA from the surface of Fe3O4 NPs, which allowed the analysis of PPi in a very simple manner. The proposed sensing system allows for the sensitive determination of PPi in the range of 2.0 × 10(-7)-4 × 10(-6)M with a detection limit of 76 nM. Importantly, the protocol exhibits excellent selectivity for the determination of PPi over other phosphate-containing compounds. The method was successfully applied to the determination of PPi in the synovial fluid, which suggests our proposed method has great potential for diagnostic purposes.