Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs.

T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-I) remains uncharacterized. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two cell lines at different times post infection using mass spectrometry. We found HLA-I peptides derived not only from canonical open reading frames (ORFs) but also from internal out-of-frame ORFs in spike and nucleocapsid not captured by current vaccines. Some peptides from out-of-frame ORFs elicited T cell responses in a humanized mouse model and individuals with COVID-19 that exceeded responses to canonical peptides, including some of the strongest epitopes reported to date. Whole-proteome analysis of infected cells revealed that early expressed viral proteins contribute more to HLA-I presentation and immunogenicity. These biological insights, as well as the discovery of out-of-frame ORF epitopes, will facilitate selection of peptides for immune monitoring and vaccine development.

Spike and nsp6 are key determinants of SARS-CoV-2 Omicron BA.1 attenuation.

The SARS-CoV-2 Omicron variant is more immune evasive and less virulent than other major viral variants that have so far been recognized1-12. The Omicron spike (S) protein, which has an unusually large number of mutations, is considered to be the main driver of these phenotypes. Here we generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron (BA.1 lineage) in the backbone of an ancestral SARS-CoV-2 isolate, and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escaped vaccine-induced humoral immunity, mainly owing to mutations in the receptor-binding motif; however, unlike naturally occurring Omicron, it efficiently replicated in cell lines and primary-like distal lung cells. Similarly, in K18-hACE2 mice, although virus bearing Omicron S caused less severe disease than the ancestral virus, its virulence was not attenuated to the level of Omicron. Further investigation showed that mutating non-structural protein 6 (nsp6) in addition to the S protein was sufficient to recapitulate the attenuated phenotype of Omicron. This indicates that although the vaccine escape of Omicron is driven by mutations in S, the pathogenicity of Omicron is determined by mutations both in and outside of the S protein.

Solid-state high harmonic spectroscopy for all-optical band structure probing of high-pressure quantum states.

High pressure has triggered various novel states/properties in condensed matter, as the most representative and dramatic example being near-room-temperature superconductivity in highly pressured hydrides (~200 GPa). However, the mechanism of superconductivity is not confirmed, due to the lacking of effective approach to probe the electronic band structure under such high pressures. Here, we theoretically propose that the band structure and electron-phonon coupling (EPC) of high-pressure quantum states can be probed by solid-state high harmonic generation (sHHG). This strategy is investigated in high-pressure Im-3m H3S by the state-of-the-art first-principles time-dependent density-functional theory simulations, where the sHHG is revealed to be strongly dependent on the electronic structures and EPC. The dispersion of multiple bands near the Fermi level is effectively retrieved along different momentum directions. Our study provides unique insights into the potential all-optical route for band structure and EPC probing of high-pressure quantum states, which is expected to be helpful for the experimental exploration of high-pressure superconductivity in the future.

Computing geodesic paths encoding a curvature prior for curvilinear structure tracking.

In this paper, we introduce an efficient method for computing curves minimizing a variant of the Euler-Mumford elastica energy, with fixed endpoints and tangents at these endpoints, where the bending energy is enhanced with a user-defined and data-driven scalar-valued term referred to as the curvature prior. In order to guarantee that the globally optimal curve is extracted, the proposed method involves the numerical computation of the viscosity solution to a specific static Hamilton-Jacobi-Bellman (HJB) partial differential equation (PDE). For that purpose, we derive the explicit Hamiltonian associated with this variant model equipped with a curvature prior, discretize the resulting HJB PDE using an adaptive finite difference scheme, and solve it in a single pass using a generalized fast-marching method. In addition, we also present a practical method for estimating the curvature prior values from image data, designed for the task of accurately tracking curvilinear structure centerlines. Numerical experiments on synthetic and real-image data illustrate the advantages of the considered variant of the elastica model with a prior curvature enhancement in complex scenarios where challenging geometric structures appear.

The utility of P-I-R classification in predicting the on-treatment histological and clinical outcomes of patients with hepatitis B and advanced liver fibrosis.

BACKGROUND AND AIMS: The predominantly progressive, indeterminate, and predominantly regressive (P-I-R) classification extends beyond staging and provides information on dynamic changes of liver fibrosis. However, the prognostic implication of P-I-R classification is not elucidated. Therefore, in the present research, we investigated the utility of P-I-R classification in predicting the on-treatment clinical outcomes. APPROACH AND RESULTS: In an extension study on a randomized controlled trial, we originally enrolled 1000 patients with chronic hepatitis B and biopsy-proven histological significant fibrosis, and treated them for more than 7 years with entecavir-based therapy. Among the 727 patients with a second biopsy at treatment week 72, we compared P-I-R classification and Ishak score changes in 646 patients with adequate liver sections for the histological evaluation. Progressive, indeterminate, and regressive cases were observed in 70%, 17%, and 13% of patients before treatments and 20%, 14%, and 64% after 72-week treatment, respectively, which could further differentiate the histological outcomes of patients with stable Ishak scores. The 7-year cumulative incidence of HCC was 1.5% for the regressive cases, 4.3% for the indeterminate cases, and 22.8% for the progressive cases ( p <0.001). After adjusting for age, treatment regimen, platelet counts, cirrhosis, Ishak fibrosis score changes, and Laennec staging, the posttreatment progressive had a HR of 17.77 (vs. posttreatment regressive; 95% CI: 5.55-56.88) for the incidence of liver-related events (decompensation, HCC, and death/liver transplantation). CONCLUSIONS: The P-I-R classification can be a meaningful complement to the Ishak fibrosis score not only in evaluating the histological changes but also in predicting the clinical outcomes.

Inhibition of RhoGEF/RhoA alleviates regorafenib resistance and cancer stemness via Hippo signaling pathway in hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) are vulnerable to drug resistance. Although drug resistance has been taken much attention to HCC therapy, little is known of regorafenib and regorafenib resistance (RR). This study aimed to determine the drug resistance pattern and the role of RhoA in RR. Two regorafenib-resistant cell lines were constructed based on Huh7 and Hep3B cell lines. In vitro and in vivo assays were conducted to study RhoA expression, the activity of Hippo signaling pathway and cancer stem cell (CSC) traits. The data showed that RhoA was highly expressed, Hippo signaling was hypoactivated and CSC traits were more prominent in RR cells. Inhibiting RhoA could reverse RR, and the alliance of RhoA inhibition and regorafenib synergistically attenuated CSC phenotype. Furthermore, inhibiting LARG/RhoA increased Kibra/NF2 complex formation, prevented YAP from shuttling into the nucleus and repressed CD44 mRNA expression. Clinically, the high expression of RhoA correlated with poor prognosis. LARG, RhoA, YAP1 and CD44 show positive correlation with each other. Thus, inhibition of RhoGEF/RhoA has the potential to reverse RR and repress CSC phenotype in HCC.

Promising role of protein arginine methyltransferases in overcoming anti-cancer drug resistance.

Drug resistance remains a major challenge in cancer treatment, necessitating the development of novel strategies to overcome it. Protein arginine methyltransferases (PRMTs) are enzymes responsible for epigenetic arginine methylation, which regulates various biological and pathological processes, as a result, they are attractive therapeutic targets for overcoming anti-cancer drug resistance. The ongoing development of small molecules targeting PRMTs has resulted in the generation of chemical probes for modulating most PRMTs and facilitated clinical treatment for the most advanced oncology targets, including PRMT1 and PRMT5. In this review, we summarize various mechanisms underlying protein arginine methylation and the roles of specific PRMTs in driving cancer drug resistance. Furthermore, we highlight the potential clinical implications of PRMT inhibitors in decreasing cancer drug resistance. PRMTs promote the formation and maintenance of drug-tolerant cells via several mechanisms, including altered drug efflux transporters, autophagy, DNA damage repair, cancer stem cell-related function, epithelial-mesenchymal transition, and disordered tumor microenvironment. Multiple preclinical and ongoing clinical trials have demonstrated that PRMT inhibitors, particularly PRMT5 inhibitors, can sensitize cancer cells to various anti-cancer drugs, including chemotherapeutic, targeted therapeutic, and immunotherapeutic agents. Combining PRMT inhibitors with existing anti-cancer strategies will be a promising approach for overcoming anti-cancer drug resistance. Furthermore, enhanced knowledge of the complex functions of arginine methylation and PRMTs in drug resistance will guide the future development of PRMT inhibitors and may help identify new clinical indications.

The role of ABCC10/MRP7 in anti-cancer drug resistance and beyond.

Multidrug resistance protein 7 (MRP7), also known as ATP-binding cassette (ABC) transporter subfamily C10 (ABCC10), is an ABC transporter that was first identified in 2001. ABCC10/MRP7 is a 171 kDa protein located on the basolateral membrane of cells. ABCC10/MRP7 consists of three transmembrane domains and two nucleotide binding domains. It mediates multidrug resistance of tumor cells to a variety of anticancer drugs by increasing drug efflux and results in reducing intracellular drug accumulation. The transport substrates of ABCC10/MRP7 include antineoplastic drugs such as taxanes, vinca alkaloids, and epothilone B, as well as endobiotics such as leukotriene C4 (LTC4) and estradiol 17 ß-D-glucuronide. A variety of ABCC10/MRP7 inhibitors, including cepharanthine, imatinib, erlotinib, tariquidar, and sildenafil, can reverse ABCC10/MRP7-mediated MDR. Additionally, the presence or absence of ABCC10/MRP7 is also closely related to renal tubular dysfunction, obesity, and other diseases. In this review, we discuss: 1) Structure and functions of ABCC10/MRP7; 2) Known substrates and inhibitors of ABCC10/MRP7 and their potential therapeutic applications in cancer; and 3) Role of ABCC10/MRP7 in non-cancerous diseases.

Photon blockade with high photon occupation via cavity electromagnetically induced transparency.

Photon blockade (PB) is one of the effective methods to generate single-photon sources. In general, both the PB effect with the significant sub-Poissonian statistics and a large mean photon number are desired to guarantee the brightness and the purity of single-photon sources. Here, we propose to obtain the PB effect at the cavity dark-state polariton (DSP) using a cavity Λ-type electromagnetically induced transparency (EIT) system with and without the two-photon dissipation (TPD). In the Raman resonance case, the PB effect at the DSP could by realized by using the TPD process in the weak or intermediate coupling regime, which accompanies with near unity transmission, i.e., very high photon occupation. In the slightly detuned Raman resonance case, the excited state is induced into the components of the DSP, and the atomic dissipation path is added into the two-photon excitation paths. Thus, the PB effect at the DSP can be obtained due to the quantum destructive interference (QDI) in the strong coupling regime, which can be further enhanced using the TPD process. Due to the slight detuning, the PB effect still remains high photon occupation and has highly tunability. This work provides an alternative way to manipulate the photon statistics by the PB effect and has potential applications in generating single-photon sources with high brightness and purity.

Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes.

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) threatens global public health and economy unprecedentedly, requiring accelerating development of prophylactic and therapeutic interventions. Molecular understanding of neutralizing antibodies (NAbs) would greatly help advance the development of monoclonal antibody (mAb) therapy, as well as the design of next generation recombinant vaccines. Here, we applied H2L2 transgenic mice encoding the human immunoglobulin variable regions, together with a state-of-the-art antibody discovery platform to immunize and isolate NAbs. From a large panel of isolated antibodies, 25 antibodies showed potent neutralizing activities at sub-nanomolar levels by engaging the spike receptor-binding domain (RBD). Importantly, one human NAb, termed PR1077, from the H2L2 platform and 2 humanized NAb, including PR953 and PR961, were further characterized and subjected for subsequent structural analysis. High-resolution X-ray crystallography structures unveiled novel epitopes on the receptor-binding motif (RBM) for PR1077 and PR953, which directly compete with human angiotensin-converting enzyme 2 (hACE2) for binding, and a novel non-blocking epitope on the neighboring site near RBM for PR961. Moreover, we further tested the antiviral efficiency of PR1077 in the Ad5-hACE2 transduction mouse model of COVID-19. A single injection provided potent protection against SARS-CoV-2 infection in either prophylactic or treatment groups. Taken together, these results shed light on the development of mAb-related therapeutic interventions for COVID-19.

Exposure of Peregrine Falcons to Halogenated Flame Retardants: A 30 Year Retrospective Biomonitoring Study across North America.

Compared to aquatic ecosystem, terrestrial systems have been subjected to fewer investigations on the exposure to halogenated flame retardants (HFRs). Our study utilized peregrine falcon eggs collected from multiple habitats across North America to retrospectively explore both spatial distribution and temporal changes in legacy (e.g., polybrominated diphenyl ethers) and alternative HFRs over a 30 year period (1984-2016). The results reveal intensive HFR exposure in terrestrial ecosystems and chemical-specific spatiotemporal distribution patterns. The correlations between egg levels of the selected HFRs and human population density clearly illustrated a significant urban influence on the exposure of this wildlife species to these HFRs and subsequent maternal transfer to their eggs. Temporal analyses suggest that, unlike aquatic systems, terrestrial ecosystems may undergo continual exposure to consistently high levels of legacy HFRs for a long period of time. Our findings collectively highlight the effectiveness of using peregrine eggs to monitor terrestrial exposure to HFRs and other bioaccumulative chemicals and the need for continuous monitoring of HFRs in terrestrial ecosystems.

Lactate-to-albumin ratio and cholesterol levels predict neurological outcome in cardiac arrest survivors.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) increases lactate levels and reduces albumin levels on admission and tends to lead to a poor neurological prognosis. In our experience, reduced cholesterol levels predict poor neurological prognosis. However, the relationship between cholesterol levels and neurological prognosis in OHCA survivors remains unclear. METHODS: This retrospective observational study included data from January 2015 to June 2023 on 219 OHCA survivors at our intensive care unit. Patients were categorized into two groups based on cerebral functional classification (CPC) scores: Group A (CPC score of 1 or 2), including patients with a favorable neurological outcome, and Group B (CPC scores of 3 to 5), comprising those with a poor neurological outcome. We analyzed their lactate, albumin levels, and lipid profiles measured at 6 h after resuscitation. A model to predict the neurological prognosis of admission of OHCA survivors was developed. RESULTS: Approximately 40% of the patients had favorable neurological outcomes at the 30-day follow-up. The lactate-to-albumin ratio (LAR) was significantly lower in Group A than in Group B (3.1 vs. 5.0 mmol/dag, p < 0.001). However, the albumin, total cholesterol, and high-density lipoprotein (HDL) cholesterol levels were significantly higher in Group A than in Group B (3.6 vs. 2.9 g/dL, 166.1 vs. 131.4 mg/dL, and 38.8 vs. 29.7 mg/dL, respectively, p < 0.001). Favorable neurological outcome was indicated at the following thresholds: LAR < 3.7 mmol/dag, albumin level > 3.1 g/dL, total cholesterol level > 146.4 mg/dL, and HDL-cholesterol level > 31.9 mg/dL. These findings underscore the high sensitivity and negative predictive value of the biomarkers. Furthermore, the area under the curve values for LAR, albumin, total cholesterol, and HDL-cholesterol levels were 0.70, 0.75, 0.71, and 0.71, respectively. The corresponding odds ratios were 3.37, 7.08, 3.67, and 3.94, respectively. CONCLUSIONS: The LAR, albumin, total cholesterol, and HDL-cholesterol levels measured on admission may predict neurological prognosis in OHCA survivors. Thus, routine practice should include the measurement of these biomarkers at 6 h after resuscitation, especially in patients with a lactate level of > 5 mmol/L. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02633358.

Transcriptomic and physiological analyses of Symphytum officinale L. in response to multiple heavy metal stress.

Soil heavy metal contamination has become a global environmental issue, which threaten soil quality, food security and human health. Symphytum officinale L. have exhibited high tolerance and restoration capacity to heavy metals (HMs) stress. However, little is known about the mechanisms of HMs in S. officinale. In this study, transcriptomic and physiological changes of S. officinale response to different HMs (Pb, Cd and Zn) were analyzed and investigated the key genes and pathways involved in HMs uptake patterns. The results showed that phenotypic effects are not significant, and antioxidant enzyme activities were all upregulated. Transcriptome analysis indicated that 1247 differential genes were up-regulated, and 1963 differential genes were down-regulated under Cd stress, while 3752 differential genes were up-regulated, and 7197 differential genes were down-regulated under Pb stress; and 527 differential genes were up-regulated; and 722 differential genes were down-regulated under Zn stress. Based on their expression, we preliminarily speculate that different HMs resistance of S. officinale may be regulated by the differential expression of key genes. These results provide a theoretical basis for determining the exact expression of genes in plants under different heavy metal stress, the processes involved molecular pathways, and how they can be efficiently utilized to improve plant tolerance to toxic metals and improve phytoremediation efficiency.

Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

3D printing-based lateral flow visual assay utilizing the dual-excitation property of nitrogen-doped carbon dots for the ratiometric determination and chemometric discrimination of flavonoids.

A ratiometric fluorescence sensor has been established based on dual-excitation carbon dots (D-CDs) for the detection of flavonoids (morin is chosen as the typical detecting model for flavonoids). D-CDs were prepared using microwave radiation with o-phenylenediamine and melamine and exhibit controllable dual-excitation behavior through the regulation of their concentration. Remarkably, the short-wavelength excitation of D-CDs can be quenched by morin owing to the inner filter effect, while the long-wavelength excitation remains insensitive, serving as the reference signal. This contributes to the successful design of an excitation-based ratiometric sensor. Based on the distinct and differentiated variation of excitation intensity, morin can be determined from 0.156 to 110 µM with a low detection limit of 0.156 µM. In addition, an intelligent and visually lateral flow sensing device is developed for the determination  of morin content in real samples with satisfying recoveries, which indicates the potential application for human health monitoring.

Exploring the catalytic diversity of two short-chain dehydrogenases/reductases from Stachybotrys chartarum.

Short-chain dehydrogenase/reductases (SDRs) belong to the NAD(P)(H)-dependent oxidoreductase superfamily, which have various functions of catalyzing oxidation/reduction reactions and have been generally used as powerful biocatalysts in the production of pharmaceuticals. In this study, ScSDR1 and ScSDR2, two new SDRs have been identified and characterized from Stachybotrys chartarum 3.5365. Substrate scope investigation revealed that both of the enzymes possessed the ability to oxidize ß-OH to ketone specifically, and exhibited substrate promiscuity and high stereo-selectivity for efficiently catalyzing the structurally different prochiral ketones to chiral alcohols. These findings not only suggest that ScSDR1 and ScSDR2 might be potent synthetic tools in drug research and development, but also provide good examples for further engineered enzymes with higher efficiency and stereo-selectivity.

3D/3D Bamboo Charcoal/Bi2WO6 Bifunctional Photocatalyst for Degradation of Organic Pollutants and Efficient H2 Evolution Coupling with Furfuryl Alcohols Oxidation.

Photocatalysis is one of the most promising pathways to relieve the environmental contamination caused by the rapid development of modern technology. In this work, we demonstrate a green manufacturing process for the 3D/3D rod-shaped bamboo charcoal/Bi2WO6 photocatalyst (210BC-BWO) by controlled carbonization temperature. A series of morphology characterization and properties investigations (XRD, SEM, UV-vis DRS, transient photocurrent response, N2 absorption-desorption isotherms) indicate a 210BC-BWO photocatalyst with higher charge separation efficiency, larger surface area, and better adsorption capacity. The excellent photocatalytic performance was evaluated by degrading rhodamine B (RhB) (98.5%), tetracycline hydrochloride (TC-HCl) (77.1%), and H2 evolution (2833 µmol·g-1·h-1) coupled with furfuryl alcohol oxidation (3097 µmol·g-1·h-1) under visible light irradiation. In addition, the possible mechanisms for degradation of organic pollutants, H2 evolution, and furfuryl alcohol oxidation were schematically investigated, which make it possible to exert photocatalysis by increasing the active radical. This study shows that the combination of bamboo charcoal and bismuth tungstate can be a powerful photocatalyst that rationally combines H2 evolution coupled with furfuryl alcohol oxidation and degradation of pollutants.

Distribution of per- and polyfluoroalkyl substances in blood, serum, and urine of patients with liver cancer and associations with liver function biomarkers.

Studies have shown that per- and polyfluoroalkyl substances (PFASs) may be hepatotoxic in animals or humans. However, data on clinical epidemiology are very limited. In this study, 21 PFASs were determined in patients with liver diseases, with the highest median concentrations detected in the serum sample (26.7 ng/mL), followed by blood (10.7 ng/mL) and urine (5.02 ng/mL). Higher total PFAS concentrations were found in hepatocellular carcinoma (HCC) patients compared to non-HCC patients, with significant discrepancies in serum and blood samples. Besides, significant correlations were also found among PFAS concentrations and age, gender, body mass index (BMI), and liver function biomarkers levels. For example, PFAS concentrations are significantly higher in males than in females; Several serum PFASs concentrations increase with age and BMI, while the serum perfluorohexane sulfonic acid (PFHxS) concentrations are negatively correlated with age. In addition, multiple regression models adjusted for age, gender and BMI found that increased serum perfluorobutane sulfonic acid (PFBS), perfluoroheptane sulfonic acid (PFHpS) and perfluorohexylphosphonic acid (PFHxPA) conentrations are correlated with elevated alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alpha-fetoprotein (AFP) (p < 0.05). Our results provide epidemiological support for the future study on the potential clinical hepatotoxicity of PFAS.

Computational Design and Theoretical Properties of WC3N6, an H-Free Melaminate and Potential Multifunctional Material.

By means of first-principles theory, existence, synthetic conditions, and structural as well as physicochemical properties have been predicted for the first hydrogen-free melaminate salt of the composition WC3N6. We find at least two energetically favorable polymorphs adopting space groups P1 and P3, both of which are layer-like porous materials. In addition to sizable Madelung fields stabilizing saltlike WC3N6, the complex C3N66- anions are connected via perfectly optimized W-N bonds, forming WN5 in the P1 and WN6 coordination polyhedra in the P3 polymorphs. The band gaps of the P1 and P3 phases are HSE-predicted as 2.25 and 1.21 eV, respectively, significantly smaller than those of g-C3N4 and WO3. Moreover, both phases have suitable band-edge potentials that may provide sufficient driving force for photocatalytic water splitting; at least for the P1 phase, there is also a reasonable chance for reduced electron-hole recombination. In addition, the polymorphs's large optical absorption coefficients should greatly enhance the photocatalytic performance. WC3N6 defines a new class of compounds and has unique structural characteristics, mirrored from its electrical and optical properties, and it should provide another chemical path for preparing efficient photocatalysts and optoelectronic devices.

Screening for Bisphenol Chemicals: A Strategy Based on Dansyl Chloride Derivatizatio n Coupled with In-Source Fragmentation by High-Resolution Mass Spectrometry.

Bisphenol chemicals (BPs) represent a complexity of halogenated and nonhalogenated substances sharing a common structure of two phenol functionalities, some of which exhibit ubiquitous environmental distributions and endocrine-disrupting activities. However, environmental monitoring of complex BP-like chemicals has faced analytical challenges arising from the lack of commercially available reference standards and efficient screening strategies. In the present study, we developed a strategy based on dansyl chloride (DnsCl) derivatization in combination with in-source fragmentation (D-ISF) during high-resolution mass spectrometry analysis to screen for bisphenol chemicals in complex environmental samples. The strategy contains three steps, including DnsCl derivatization to enhance the detection sensitivity by one to more than four orders of magnitude, in-source fragmentation to produce characteristic loss of 234.0589, 63.9619, and 298.0208 Da for the identification of DnsCl-derivatized compounds, and data processing and annotation. The D-ISF strategy was further validated and then applied to identify BPs in six types of particular matters as representative environmental samples, including settled dust from an electronic waste dismantling site, homes, offices, and vehicles, and airborne particles from indoor and outdoor environments. A total of six halogenated and fourteen nonhalogenated BPs were identified in the particles, including several chemicals that had rarely or never been identified in environmental samples. Our strategy offers a powerful tool for the environmental monitoring of bisphenol chemicals and assessment of human exposure risks.