Detection of 11 carbamate pesticide residues in raw and pasteurized camel milk samples using liquid chromatography tandem mass spectrometry: Method development, method validation, and health risk assessment.

This study aimed to use ultra-high-performance liquid chromatography coupled to a triple-quadrupole mass spectrometer to detect 11 carbamate pesticide residues in raw and pasteurized camel milk samples collected from the United Arab Emirates. A method was developed and validated by evaluating limits of detection, limits of quantitation, linearity, extraction recovery, repeatability, intermediate precision, and matrix effect. Due to the high protein and fat content in camel milk, a sample preparation step was necessary to avoid potential interference during analysis. For this purpose, 5 different liquid-liquid extraction techniques were evaluated to determine their efficiency in extracting carbamate pesticides from camel milk. The established method demonstrated high accuracy and precision. The matrix effect for all carbamate pesticides was observed to fall within the soft range, indicating its negligible effect. Remarkably, detection limits for all carbamates were as low as 0.01 µg/kg. Additionally, the coefficients of determination were >0.998, demonstrating excellent linearity. A total of 17 camel milk samples were analyzed, and only one sample was found to be free from any carbamate residues. The remaining 16 samples contained at least one carbamate residue, yet all detected concentrations were below the recommended maximum residue limits set by Codex Alimentarius and the European Union pesticide databases. Nonetheless, it is worth noting that the detected levels of ethiofencarb in 3 samples were close to the borderline of the maximum residue limit. To assess the health risk for consumers of camel milk, the hazard index values of carbofuran, carbaryl, and propoxur were calculated. The hazard index values for these 3 carbamate pesticides were all below 1, indicating that camel milk consumers are not at risk from these residues.

Uncovering the Dominant Role of an Extended Asymmetric Four-Coordinated Water Network in the Hydrogen Evolution Reaction.

In situ and accurate measurement of the structure and dynamics of interfacial water in the hydrogen evolution reaction (HER) is a well-known challenge because of the coupling of water among varied structures and its dual role as reactants and solvents. Further, the interference of bulk water and intricate interfacial interactions always hinders the probing of interfacial water. Surface-enhanced infrared absorption spectroscopy is extremely sensitive for the measurement of interfacial water; herein, we develop a nanoconfinement strategy by introducing nonaqueous ionic liquids to decouple and tailor the water structure in the electric double layer and further combined with molecular dynamics simulations, successfully gaining the correlation between isolated water, water clusters, and the water network with HER activity. Our results clearly disclosed that the potential-dependent asymmetric four-coordinated water network, whose connectivity could be regulated by hydrophilic and hydrophobic cations, was positively correlated with HER activity, which provided a pioneering guidance framework for revealing the function of water in catalysis, energy, and surface science.

Glutathione-Induced In Situ Michael Addition between Nanoparticles for Pyroptosis and Immunotherapy.

Most tumor treatments will fail when ignoring competition and cooperation between each cancer cell and its microenvironment. Inspired by game theory, therapeutic agents can be introduced to compete for intracellular molecules to disrupt the cooperation between molecules and cells. Biomineralized oxidized (-)-epigallocatechin-3-o-gallate (EGCG)-molybdenum ion coordination nanoparticles were prepared for disrupting redox equilibria and simultaneously reacting with intracellular GSH in a Michael addition to form large aggregates that can mechanically disrupt endosomal and plasma membranes, stimulating pyroptosis and anti-tumor immunological responses for versatile inhibition of different types of tumors. This design disrupts the cooperation between molecules and between cancer and immune cells, achieving an optimal payoff in competition and cooperation in cancer therapy.

Enhancing Peroxidase Activity of Cytochrome c by Modulating Interfacial Interaction Forces with Graphene Oxide.

Graphene oxide (GO) has drawn worldwide attention in various biomedical fields because of its unique properties, and great progress has been made in the past years. Probing the interaction between GO and proteins, understanding and evaluating potential impact of GO on the protein structure and function, is of significant importance for design and optimization of functional interfaces and revealing the bioeffect of GO materials. Cytochrome c (cyt c), one of the key components of respiratory chain, has played important roles in energy generation/consumption and many cellular processes including growth, proliferation, differentiation, and apoptosis. In this study, by combination of solution chemistry and spectroscopy, we systematically studied the interfacial interaction between GO and cyt c. Results suggest that GO could slightly perturb the active site of cyt c, enhancing its peroxidase activity. Structure of the active site is obviously changed with elapsed time, which in turn reduces peroxidase activity. Further study suggests that adsorption of cyt c on GO and the resulted structure change is a complex process resulting from the cooperation of various interaction forces. Hydrophobic interaction and π-π stacking, as well as electrostatic attraction, only slightly perturb the microenvironment of the active site of cyt c while hydrogen-bonding interaction is the main driving force for the structural change of the active site. Furthermore, long range electrostatic attraction between GO and cyt c may facilitate the short range hydrogen-bonding interaction, which intensifies the hydrogen-bonding-induced structural change. In addition, cyt c is partially reduced by GO in an alkaline environment. Based on the understanding of interfacial interaction mechanism between GO and cyt c, stable nanocomposites with enhanced peroxidase activity are successfully constructed by modulating the interfacial interaction forces. This work not only deepens the understanding of interaction between GO and functional protein, but also is of great importance for designing and applying of GO-based biomaterials.

The Structure of Water Bonded to Phosphate Groups at the Electrified Zwitterionic Phospholipid Membranes/Aqueous Interface.

Gaining insight into the water structure at the electrified phospholipid membranes/aqueous interface is vital and essential for elucidating the mechanism of many biochemical reactions, but still remains a formidable challenge. Herein, based on the superiority of surface enhanced infrared absorption (SEIRA) spectroscopy combined with electrochemistry in interfacial analysis, the evolution of local water structure at the zwitterionic phospholipid membranes/aqueous interface with an external electric field is revealed by means of ion perturbation. The strongly hydrogen-bonded water directly bonded to the phosphate groups (PO2- ) has a strong mechanical strength to resist potential perturbations, and that portion of water greatly affects the electrostatic properties of the phospholipid membranes. This study innovates the basic understanding of electric double layer (EDL) at the membranes/aqueous interface.

Specific "Unlocking" of a Nanozyme-Based Butterfly Effect To Break the Evolutionary Fitness of Chaotic Tumors.

Chaos and the natural evolution of tumor systems can lead to the failure of tumor therapies. Herein, we demonstrate that iridium oxide nanoparticles (IrOx ) possess acid-activated oxidase and peroxidase-like functions and wide pH-dependent catalase-like properties. The integration of glucose oxidase (GOD) unlocked the oxidase and peroxidase activities of IrOx by the production of gluconic acid from glucose by GOD catalysis in cancer cells, and the produced H2 O2 was converted into O2 to compensate its consumption in GOD catalysis owing to the catalase-like function of the nanozyme, thus resulting in the continual consumption of glucose and the self-supply of substrates to generate superoxide anion and hydroxyl radical. Moreover, IrOx can constantly consume glutathione (GSH) by self-cyclic valence alternation of IrIV and IrIII . These cascade reactions lead to a "butterfly effect" of initial starvation therapy and the subsequent pressure of multiple reactive oxygen species (ROS) to completely break the self-adaption of cancer cells.

Understanding the Synergic Mechanism of Weak Interactions between Graphene Oxide and Lipid Membrane Leading to the Extraction of Lipids.

Revealing how weak forces interact synergistically to induce differences in nanobio effects is critical to understanding the nature of the nanobio interface. Herein, graphene oxide (GO) and a lipid membrane are selected as a nanobio model, and interaction forces at the GO-biomembrane interface are modulated by varying the amounts and species of oxygenated functional groups on the surface of GO. A synergic mechanism of interfacial interaction forces is investigated by a combination of surface-enhanced infrared absorption (SEIRA) spectroscopy, confocal laser scanning microscopy (CLSM), and electrochemical impedance spectroscopy (EIS). The results reveal that after balancing with electrostatic repulsion, the moderate attraction between GO and lipid headgroups (such as electrostatic and/or hydrophobic interactions) is most favorable for lipid extraction, whereas lipid extraction is inhibited under an attraction that is too strong or too weak. Under moderate attraction between GO and the headgroups of lipids, the appropriate degree of rotation freedom is maintained for GO, which is beneficial to the hydrogen-bonding interaction between the C═O group in the phosphatide hydrophobic region and GO, thus triggering the insertion of GO into the lipid alkyl chain region, resulting in the rapid and significant extraction of lipids. Our results have important guiding significance for how to reveal the synergistic mechanism of weak interactions at the nanobio interface.

Specific Generation of Singlet Oxygen through the Russell Mechanism in Hypoxic Tumors and GSH Depletion by Cu-TCPP Nanosheets for Cancer Therapy.

The generation of singlet oxygen (1 O2 ) during photodynamic therapy is limited by the precise cooperation of light, photosensitizer, and oxygen, and the therapeutic efficiency is restricted by the elevated glutathione (GSH) levels in cancer cells. Herein, we report that an ultrathin two-dimensional metal-organic framework of Cu-TCPP nanosheets (TCPP=tetrakis(4-carboxyphenyl)porphyrin) can selectively generate 1 O2 in a tumor microenvironment. This process is based on the peroxidation of the TCPP ligand by acidic H2 O2 followed by reduction to peroxyl radicals under the action of the peroxidase-like nanosheets and Cu2+ , and their spontaneous recombination reaction by the Russell mechanism. In addition, the nanosheets can also deplete GSH. Consequently, the Cu-TCPP nanosheets can selectively destroy tumor cells with high efficiency, constituting an attractive way to overcome current limitations of photodynamic therapy.

A Facile Ion-Doping Strategy To Regulate Tumor Microenvironments for Enhanced Multimodal Tumor Theranostics.

Integration of multiple therapeutic/diagnostic modalities into a single system holds great promise to improve theranostic efficiency for tumors, but still remains a technical challenge. Herein, we report a new multimodal theranostic nanoconstruct based on Fe-doped polydiaminopyridine nanofusiforms, built easily and on a large scale, which can dual-regulate intracellular oxygen and glutathione levels, transport iron ions, and simultaneously be used for thermal imaging and magnetic resonance imaging. Co-loading of dihydroartemisinin and methylene blue generates a superior multifunctional theranostic agent with enhanced photochemotherapy efficiency and biodegradability, leading to almost complete destruction of tumors with near-infrared light irradiation. This represents an attractive route to develop multimodal anticancer theranostics.

Proton Transfer at the Interaction Interface of Graphene Oxide.

Proton transfer plays a crucial role in a variety of biological phenomena. The transformation of nanomaterials in the environment and biology makes probing the potential proton transfer between nanomaterials and biomolecules a crucial issue, but it still remains a significant challenge. Here, we report proton transfer at the interface of graphene oxide (GO) by studying the GO-induced vibrational changes of interfacial water and carboxyl-terminated self-assembled monolayer (SAM) with surface-enhanced infrared absorption spectroscopy. In addition to simply acting as a macromolecular buffer in solution, the GO sheet behaves as a two-dimensional hydrogen-bonded exchangeable proton pool to dissociate and transfer protons at the interface with a suitable Brønsted base pair, which may bear a significant potential toxic origin for biological systems with proton-coupled reactions.

In Situ Surface-Enhanced Infrared Absorption Spectroscopy of Aqueous Molecules with Facile-Prepared Large-Area Reduced Graphene Oxide Island Film.

Midinfrared plasmons in patterned graphene could advance the development of surface-enhanced infrared absorption spectroscopy (SEIRAS). However, limitation in measuring the extinction spectra with transmission and external reflection configurations greatly restricts the analyses of aqueous samples. In addition, complicated, time- and cost-consuming preparation of patterned graphene also limits its progress. Here we demonstrate a facile-prepared large-scale reduced graphene oxide island film on a total internal reflection silicon prism, which not only shows a prominent enhancement effect in mid-infrared region but also effectively eliminates the contribution of bulk solution by optical near-field effect. As a result, the entire vibrational fingerprints of methylene blue monolayer in aqueous solution can be acquired with high sensitivity in real time. Our work extends the application of graphene-based SEIRAS to aqueous environment, breaking through previously unattainable technology.

Photosensitizer-Conjugated Bi2Te3 Nanosheets as Theranostic Agent for Synergistic Photothermal and Photodynamic Therapy.

Phototherapy, including photothermal therapy (PTT)/photodynamic therapy (PDT), is usually considered as a promising strategy for cancer treatment due to its noninvasive and selective therapeutic effect by laser irradiation. A light-activatable nanoplatform based on bovine serum albumin (BSA)-coated Bi2Te3 nanosheets conjugated with methylene blue (MB) was successfully designed and constructed for bimodal PTT/PDT combination therapy. The resultant nanoconstruct (BSA-Bi2Te3/MB) exhibited high stability in various physiological solutions and excellent biocompatibility. Especially, the nanoconstruct not only possessed strong near-infrared absorption and high photothermal conversion as a photothermal agent for efficient tumor ablation but also could successfully load photosensitizer for PDT of tumor. When exposed to laser irradiation, tumors in mice with BSA-Bi2Te3/MB injection were completely eliminated without recurrence within 15 d, demonstrating the potential of the nanoconstruct as a bimodal PTT/PDT therapeutic platform for cancer treatment.

BSA-IrO2 : Catalase-like Nanoparticles with High Photothermal Conversion Efficiency and a High X-ray Absorption Coefficient for Anti-inflammation and Antitumor Theranostics.

Intrinsically integrating precise diagnosis, effective therapy, and self-anti-inflammatory action into a single nanoparticle is attractive for tumor treatment and future clinical application, but still remains a great challenge. In this study, bovine serum albumin-iridium oxide nanoparticles (BSA-IrO2 NPs) with extraordinary photothermal conversion efficiency, good photocatalytic activity, and a high X-ray absorption coefficient were prepared through one-step biomineralization. The nanoparticles allow tumor phototherapy and simultaneous photoacoustic/thermal imaging and computed tomography. More importantly, BSA-IrO2 NPs can also act as a catalase to protect normal cells against H2 O2 -induced reactive oxygen pressure and inflammation while significantly enhancing photoacoustic imaging through microbubble-based inertial cavitation. These remarkable features may open up the exploration iridium-based nanomaterials in theranostics.

Revealing the Effect of Protein Weak Adsorption to Nanoparticles on the Interaction between the Desorbed Protein and its Binding Partner by Surface-Enhanced Infrared Spectroelectrochemistry.

In recent years, the properties of protein corona have attracted intense interest in the field of nanobio interface, but a long-ignored research issue is how the desorbed proteins suffering from conformational change upon weak association with nanoparticles affect their functional properties when further interacting with their downstream protein partners. In this Article, surface-enhanced infrared absorption spectroscopy (SEIRAS) and electrochemical cyclic voltammetry were used to study the adsorption and redox properties of the soluble cytochrome c (cyt c) on 11-mercaptoundecanoic acid (MUA) self-assembled monolayer (SAM) after weakly binding to and then desorbed from nano-TiO2. For the first time, our study reveals that the weak interaction between cyt c and nano-TiO2 induces the protein to undergo a heterogeneous conformational change. More importantly, the cyt c with a largely unfolded conformation exhibits a weaker interaction with its binding partner mimics than the native-like cyt c but a faster adsorption rate even at a concentration that is much lower than that of native-like cyt c. Correspondingly, the cyt c with a large unfolding shows a greatly positive-shifted formal potential (Ef) relative to the native-like protein possibly due to the disruption of the pocket structure of heme in the vicinity of Met80. These properties could enable the largely unfolded cyt c to undergo a favorable binding but an unavailable electron transfer to cytochrome c oxidase even in the presence of high-concentration native cyt c, probably causing the disruption of electron flow.

The Role of Water Distribution Controlled by Transmembrane Potentials in the Cytochrome†c-Cardiolipin Interaction: Revealing from Surface-Enhanced Infrared Absorption Spectroscopy.

The interaction of cytochrome c (cyt c) with cardiolipin (CL) plays a crucial role in apoptotic functions, however, the changes of the transmembrane potential in governing the protein behavior at the membrane-water interface have not been studied due to the difficulties in simultaneously monitoring the interaction and regulating the electric field. Herein, surface-enhanced infrared absorption (SEIRA) spectroelectrochemistry is employed to study the mechanism of how the transmembrane potentials control the interaction of cyt c with CL membranes by regulating the electrode potentials of an Au film. When the transmembrane potential decreases, the water content at the interface of the membranes can be increased to slow down protein adsorption through decreasing the hydrogen-bond and hydrophobic interactions, but regulates the redox behavior of CL-bound cyt c through a possible water-facilitated proton-coupled electron transfer process. Our results suggest that the potential drop-induced restructure of the CL conformation and the hydration state could modify the structure and function of CL-bound cyt c on the lipid membrane.

Ternary FexCo1-xP Nanowire Array as a Robust Hydrogen Evolution Reaction Electrocatalyst with Pt-like Activity: Experimental and Theoretical Insight.

Replacement of precious Pt with earth-abundant electrocatalysts for the hydrogen evolution reaction (HER) holds great promise for clean energy devices, but the development of low-cost and durable HER catalysts with Pt-like activity is still a huge challenge. In this communication, we report on the development of self-standing ternary FexCo1-xP nanowire array on carbon cloth (FexCo1-xP/CC) as a Pt-free HER catalyst with activities being strongly related to Fe substitution ratio. Electrochemical tests show that Fe0.5Co0.5P/CC not only possesses Pt-like activity with the need of overpotential of only 37 mV to drive 10 mA cm-2, outperforming all non-noble-metal HER catalysts reported to date, but demonstrates superior long-term durability in 0.5 M H2SO4. Density functional theory calculations further reveal that Fe substitution of Co in CoP leads to more optimal free energy of hydrogen adsorption to the catalyst surface. This study offers us a promising flexible monolithic catalyst for practical applications.

Analyzing Structural Properties of Heterogeneous Cardiolipin-Bound Cytochrome C and Their Regulation by Surface-Enhanced Infrared Absorption Spectroscopy.

Apoptotic mechanisms are not fully understood due to limitations in present analytical methods. Such understanding may be advanced by unravelling the structural properties of heterogeneous cardiolipin (CL)-bound cytochrome c (cyt c) and the factors or events that regulate them. In this study, surface-enhanced infrared absorption spectroscopy (SEIRAS) was employed to probe the adsorption of cyt c on CL membranes in biomimetic conditions. The results clearly show that pure electrostatic interactions result in the unfolding of partial α-helices, while the synergy between hydrogen bonding and electrostatic interactions governs orientation homogeneity of adsorbed protein, and conformational transition between α-helices and ß-sheet. Hydrogen bonding plays a dual role; along with hydrophobic interactions, it may disturb the microenvironment of some secondary structures such as the ß-turn type III, while it also triggers structural changes in lipid molecules likely resulting from the extension of CL acyl chains to the hydrophobic channels of cyt c. These findings provide the details of protein transitions in early apoptosis at the molecular level.

FeIII -Doped Two-Dimensional C3 N4 Nanofusiform: A New O2 -Evolving and Mitochondria-Targeting Photodynamic Agent for MRI and Enhanced Antitumor Therapy.

Local hypoxia in tumors, as well as the short lifetime and limited action region of 1 O2 , are undesirable impediments for photodynamic therapy (PDT), leading to a greatly reduced effectiveness. To overcome these adversities, a mitochondria-targeting, H2 O2 -activatable, and O2 -evolving PDT nanoplatform is developed based on FeIII -doped two-dimensional C3 N4 nanofusiform for highly selective and efficient cancer treatment. The ultrahigh surface area of 2D nanosheets enhances the photosensitizer (PS) loading capacity and the doping of FeIII leads to peroxidase mimetics with excellent catalytic performance towards H2 O2 in cancer cells to generate O2 . As such tumor hypoxia can be overcome and the PDT efficacy is improved, whilst at the same time endowing the PDT theranostic agent with an effective T 1 -weighted in vivo magnetic resonance imaging (MRI) ability. Conjugation with a mitochondria-targeting agent could further increase the sensitivity of cancer cells to 1 O2 by enhanced mitochondria dysfunction. In vitro and in vivo anticancer studies demonstrate an outstanding therapeutic effectiveness of the developed PDT agent, leading to almost complete destruction of mouse cervical tumor. This development offers an attractive theranostic agent for in vivo MRI and synergistic photodynamic therapy toward clinical applications.

Self-assembly of nitrogen-doped carbon nanoparticles: a new ratiometric UV-vis optical sensor for the highly sensitive and selective detection of Hg(2+) in aqueous solution.

Water-soluble nitrogen-doped carbon nanoparticles (N-CNPs) prepared by the one-step hydrothermal treatment of uric acid were found to show ratiometric changes in their UV-vis spectra due to Hg(2+)-mediated self-assembly. For the first time, such a property was developed into a UV-vis optical sensor for detecting Hg(2+) in aqueous solutions with high sensitively and selectively (detection limit = 1.4 nM). More importantly, this novel sensor exhibits a higher linear sensitivity over a wider concentration range compared with the fluorescence sensor based on the same N-CNPs. This work opens an exciting new avenue to explore the use of carbon nanoparticles in constructing UV-vis optical sensors for the detection of metal ions and the use of carbon nanoparticles as a new building block to self-assemble into superlattices.