Iron-Catalyzed Cross-Dehydrogenative Coupling of para-Quinone Methides with Formamides: In Situ Activation of C(sp2)-H Bonds.

A novel and straightforward method for the iron-catalyzed regioselective cross-dehydrogenative coupling of para-quinone methides (p-QMs) with formamides has been developed, facilitated by the in situ activation of the C(sp2)-H bonds of the formyl and alkenyl substituents via a radical strategy. This method does not require the preactivation of the substrates, and it can accommodate a wide range of p-QMs and formamides under the optimized reaction conditions, resulting in the formation of the expected C-7 acetamides-functionalized para-quinone methides with moderate to good yields. The control experiments revealed that the reaction follows the fundamental equation of second-order kinetics. Additionally, an exploration of the Hammett effect was undertaken to elucidate the impact of the substituents for the reaction. In combination with the DFT calculation, a plausible reaction mechanism was proposed through meticulously controlled experiments.

Prediction of survival and analysis of prognostic factors for patients with AFP negative hepatocellular carcinoma: a population-based study.

PURPOSE: Hepatocellular carcinoma (HCC) has a poor prognosis, and alpha-fetoprotein (AFP) is widely used to evaluate HCC. However, the proportion of AFP-negative individuals cannot be disregarded. This study aimed to establish a nomogram of risk factors affecting the prognosis of patients with AFP-negative HCC and to evaluate its diagnostic efficiency. PATIENTS AND METHODS: Data from patients with AFP-negative initial diagnosis of HCC (ANHC) between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results database for model establishment and validation. We randomly divided overall cohort into the training or validation cohort (7:3). Univariate and multivariate Cox regression analysis were used to identify the risk factors. We constructed nomograms with overall survival (OS) and cancer-specific survival (CSS) as clinical endpoint events and constructed survival analysis by using Kaplan-Meier curve. Also, we conducted internal validation with Receiver Operating Characteristic (ROC) analysis and Decision curve analysis (DCA) to validate the clinical value of the model. RESULTS: This study included 1811 patients (1409 men; 64.7% were Caucasian; the average age was 64 years; 60.7% were married). In the multivariate analysis, the independent risk factors affecting prognosis were age, ethnicity, year of diagnosis, tumor size, tumor grade, surgery, chemotherapy, and radiotherapy. The nomogram-based model related C-indexes were 0.762 (95% confidence interval (CI): 0.752-0.772) and 0.752 (95% CI: 0.740-0.769) for predicting OS, and 0.785 (95% CI: 0.774-0.795) and 0.779 (95% CI: 0.762-0.795) for predicting CSS. The nomogram model showed that the predicted death was consistent with the actual value. The ROC analysis and DCA showed that the nomogram had good clinical value compared with TNM staging. CONCLUSION: The age(HR:1.012, 95% CI: 1.006-1.018, P-value < 0.001), ethnicity(African-American: HR:0.946, 95% CI: 0.783-1.212, P-value: 0.66; Others: HR:0.737, 95% CI: 0.613-0.887, P-value: 0.001), tumor diameter(HR:1.006, 95% CI: 1.004-1.008, P-value < 0.001), year of diagnosis (HR:0.852, 95% CI: 0.729-0.997, P-value: 0.046), tumor grade(Grade 2: HR:1.124, 95% CI: 0.953-1.326, P-value: 0.164; Grade 3: HR:1.984, 95% CI: 1.574-2.501, P-value < 0.001; Grade 4: HR:2.119, 95% CI: 1.115-4.027, P-value: 0.022), surgery(Liver Resection: HR:0.193, 95% CI: 0.160-0.234, P-value < 0.001; Liver Transplant: HR:0.102, 95% CI: 0.072-0.145, P-value < 0.001), chemotherapy(HR:0.561, 95% CI: 0.471-0.668, P-value < 0.001), and radiotherapy(HR:0.641, 95% CI: 0.463-0.887, P-value:0.007) were independent prognostic factors for patients with ANHC. We developed a nomogram model for predicting the OS and CSS of patients with ANHC, with a good predictive performance.

[Research Photon Energy Spectrum of Medical Linear Accelerator by Monte Carlo Method].

Objective: The distribution of the photon energy spectrum in isocenter plane of the medical linear accelerator and the influence of secondary collimator on the photon energy spectrum are studied. Methods Use the BEAMnrc program to simulate the transmission of the 6 MeV electrons and photons in 5 cm×5 cm,10 cm×10 cm,15 cm×15 cm and 20 cm×20 cm fields in treatment head of the medical linear accelerator, where a phase space file was set up at the isocenter plane to record the particle information passing through this plane. The BEAMdp program is used to analyze the phase space file, in order to obtain the distribution of the photon energy spectrum in isocenter plane and the influence of secondary collimator on the photon energy spectrum. Results: By analyzing the photon energy spectrum of a medical linear accelerator with a nominal energy of 6 MV, it is found that the secondary collimator has little effect on the photon energy spectrum; different fields have different photon energy spectrum distributions; the photon energy spectrum in different central regions of the same field have the same normalized distribution. Conclusion: In the dose calculation of radiation therapy, the influence of photon energy spectrum should be carefully considered.

Ruthenium-Catalyzed 1,6-Hydroalkylation of para-Quinone Methides with Ketones via the in Situ Activation of C(sp3)-H Bonds.

A simple and efficient method for the ruthenium-catalyzed 1,6-hydroalkylation of para-quinone methides (p-QMs) with ketones via the in situ activation of C(sp3)-H bonds has been disclosed. Without the need for preactivation of the substrates and oxidant, a broad range of p-QMs and ketones are well tolerated, producing the expected 1,6-hydroalkylation products with moderate to good yields. Step-by-step control experiments and DFT calculation were conducted systematically to gain insights for the plausible reaction mechanism. This finding may have potential application in the selective diarylmethylation of ketones at the α-C position in organic synthesis.

Metal-containing organic compounds for memory and data storage applications.

With the upcoming trend of Big Data era, some new types of memory technologies have emerged as substitutes for the traditional Si-based semiconductor memory devices, which are encountering severe scaling down technical obstacles. In particular, the resistance random access memory (RRAM) and magnetic random access memory (MRAM) hold great promise for the in-memory computing, which are regarded as the optimal strategy and pathway to solve the von Neumann bottleneck by high-throughput in situ data processing. As far as the active materials in RRAM and MRAM are concerned, organic semiconducting materials have shown increasing application perspectives in memory devices due to their rich structural diversity and solution processability. With the introduction of metal elements into the backbone of molecules, some new properties and phenomena will emerge accordingly. Consequently, the RRAM and MRAM devices based on metal-containing organic compounds (including the small molecular metal complexes, metallopolymers, metal-organic frameworks (MOFs) and organic-inorganic-hybrid perovskites (OIHPs)) have been widely explored and attracted intense attention. In this review, we highlight the fundamentals of RRAM and MRAM, as well as the research progress of the applications of metal-containing organic compounds in both RRAM and MRAM. Finally, we discuss the challenges and future directions for the research of organic RRAM and MRAM.

Dispersibility Characterization of Cellulose Nanocrystals in Polymeric-Based Composites.

Cellulose nanocrystals (CNCs) are hydrophilic nanoparticles extracted from biomass with properties and functions different from cellulose and are being developed for property-oriented applications such as high stiffness, abundant active groups, and biocompatibility. It has broad application prospects in the field of composite materials, while the dispersibility of the CNC in polymers is the key to its application performance. Many reviews have discussed in-depth the modification strategies to improve the dispersibility of the CNC and summarized all characterization for the CNC, but there are no reviews on the in-depth exploration of dispersion characterization. This review is a comprehensive summary of the characterization of CNC dispersion in the matrix in terms of direct observation, indirect evaluation, and quantified evaluation, summarizing how and why different characterization tools reveal dispersibility. In addition, "decision tree" flowcharts are presented to provide the reader with a reference for selecting the appropriate characterization method for a specific composite.

Toxicity of Tetrabromobisphenol A and Its Derivative in the Mouse Liver Following Oral Exposure at Environmentally Relevant Levels.

As typical brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA) and its derivative TBBPA-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) are ubiquitous in various environmental compartments. However, the potential health risk posed by these compounds, especially at environmentally relevant levels, remains unclear. In this study, using adult male mice, we investigated the toxicity of orally administered TBBPA and TBBPA-BDBPE at an environmentally relevant dose (57 nmol/kg body weight). After a single exposure and daily exposure, we assessed lipid metabolism homeostasis, the transcriptome, and immune cell components in the liver. We found that the single exposure to TBBPA or TBBPA-BDBPE alone increased the number of hepatic macrophages, induced alterations in the levels of lipids, including triacylglycerol and free fatty acids, and caused transcriptome perturbation. The results from the daily administration groups showed that TBBPA and TBBPA-BDBPE both significantly increased the triacylglycerol content; however, the elevation of hepatic macrophages was observed only in the TBBPA-BDBPE treatment group. This study confirmed that environmentally relevant levels of TBBPA and TBBPA-BDBPE are toxic to the liver. Our findings revealed that dysfunction of the liver is a health concern, following exposure to BFRs, even at very low concentrations. The chronic effects induced by TBBPA and its derivatives should be further investigated.

Efficient Synthesis of Phosphonamidates through One-Pot Sequential Reactions of Phosphonites with Iodine and Amines.

A one-pot sequential strategy to construct phosphonamidates has been developed by generating phosphonites in situ from arylmagnesium bromides and triethyl phosphite followed by treatment with iodine and amines. A variety of phosphonamidates were obtained with good to excellent yields at room temperature from easily available materials.

[Review of the research of spiking neuron network based on memristor].

The rapid development of artificial intelligence put forward higher requirements for the computational speed, resource consumption and the biological interpretation of computational neuroscience. Spiking neuron networks can carry a large amount of information, and realize the imitation of brain information processing. However, its hardware is an important way to realize its powerful computing ability, and it is also a challenging technical problem. The memristor currently is the electronic devices that functions closest to the neuron synapse, and able to respond to spike voltage in a highly similar spike timing dependent plasticity (STDP) mechanism with a biological brain, and has become a research hotspot to construct spiking neuron networks hardware circuit in recent years. Through consulting the relevant literature at home and abroad, this paper has made a thorough understanding and introduction to the research work of the spiking neuron networks based on the memristor in recent years.

Synergistic Effects of 125I Seed Implantation Brachytherapy and Gemcitabine in Pancreatic Tumors.

BACKGROUND: Monotherapy consisting of radiotherapy or chemotherapy has limited efficacy in pancreatic tumors. This study aims to investigate whether the combination of 125I brachytherapy and gemcitabine (GEM) chemotherapy has a synergistic effect on pancreatic cancer (PC). METHODS: In vitro, PANC-1 cells in the exponential phase were treated with 125I radioactive seeds (6 Gy) and GEM (30 nM). Cell proliferation, apoptosis, and mitochondrial membrane potential were measured using the Cell Counting Kit-8 (CCK-8) assay, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and flow cytometry, respectively. In vivo, we examined the inhibitory effect of three different treatment regimens on tumor growth in mice when combined with 125I brachytherapy and GEM. Next, we investigated the effects of the optimal scheme among the three on the tumor microenvironment, tumor tissue morphology, tumor cell apoptosis, systemic inflammatory response, and levels of apoptosis-related proteins in the tumor. Changes in the tumor microenvironment and levels of apoptosis-related proteins were measured by Western blot. The extent of damage to tumor tissue morphology was assessed by Hematoxylin and Eosin (HE) staining. Tumor cell apoptosis was measured by TUNEL staining. Changes in inflammation-related factors were determined by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: The results of in vitro cell experiments demonstrated that the combination of 125I radioactive seeds (6 Gy) and GEM (30 nM) had a stronger inhibitory effect on PANC-1 cells than either alone (p < 0.05). In vivo, data showed that the GEM (after 3 d) + 125I treatment group had the strongest tumor inhibition effect on PC (p < 0.05). Western blot analysis showed that the combined treatment of 125I brachytherapy and GEM caused changes in the expression of collagen and connexin in the tumor microenvironment, promoted tumor cell apoptosis, upregulated the expression of pro-apoptotic proteins, and helped to restore pancreatic function (p < 0.01). CONCLUSION: Our research results suggest that the strategy of 125I seed implantation surgery in mice after 3 days of GEM treatment has a more pronounced synergistic effect on the treatment of PC.

Dried bear bile exerts its antidepressant effect by modulating adrenal FXR to reduce peripheral glucocorticoid levels.

Depression is a psychological disorder associated with prolonged stress, which involves abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated levels of glucocorticoids (GC). Excessive GC can cause damage to the structure and function of the hippocampus, thereby triggering depressive symptoms. Studies suggest that the bile acid receptor farnesoid X receptor (FXR) may play a role in adrenal GC synthesis. This study aimed to explore the potential therapeutic effects of dried bear bile (DBB) on depression and its mechanism. We used the chronic unpredictable mild stress (CUMS) mouse model and FXR agonist GW4064 stimulated mice, as well as H295R human adrenal cortical carcinoma cells, employing behavioral tests, biochemical analysis, and gene expression analysis to assess the effects of DBB treatment on depressive behavior, serum corticosterone (CORT) levels, and adrenal FXR and steroid biosynthesis-related gene expression. The results showed that in both CUMS and GW4064-stimulated mice, DBB treatment significantly improved depressive-like behaviors and reversed serum CORT levels. Additionally, DBB suppressed the expression of steroidogenic regulatory genes in the adrenal glands of CUMS mice. In H295R cells, DBB treatment effectively reduced cortisol secretion induced by Forskolin, inhibited the expression of steroid biosynthesis-related genes, and suppressed cortisol production and HSD3B2 expression under conditions of FXR overexpression and FXR activation. Our findings suggest that DBB regulates adrenal FXR to modulate glucocorticoid synthesis and exerts antidepressant effects. DBB may serve as a potential therapeutic agent for depression by regulating GC levels and steroidogenesis pathway. Further research is underway to test the antidepressant effects of each DBB component to understand their specific contribution.

Sex differences in a corticosterone-induced depression model in mice: Behavioral, neurochemical, and molecular insights.

Depression is characterized by a significant sex disparity, with higher rates observed in women compared to men. This study aimed to investigate the impact of sex on depressive behaviors and explore the underlying mechanisms using a corticosterone (CORT)-induced depression model in mice. Behavioral tests, Nissl staining, UPLC-MS/MS, and Western blot analysis were performed to assess behavioral changes, as well as neuronal alterations, neurotransmitter levels, and protein expressions in the hippocampus. The mice in the model group exhibited sex-specific anxiety- and depression-like behaviors. Nissl staining revealed structural abnormalities in the CA3 region of the hippocampus in females. Neurotransmitter analysis indicated decreased serotonin and norepinephrine levels in both sexes, while glutamate levels were elevated in females. Furthermore, female mice demonstrated elevated serum CORT levels. Western blot analysis revealed sex-specific alterations in specific protein expression. Female mice exhibited downregulated glucocorticoid receptor and brain-derived neurotrophic factor expression, whereas male mice showed minimal changes. Additionally, female mice displayed reduced phosphorylated AKT, phosphorylated PI3K, and phosphorylated mTOR levels. These findings enhance our understanding of sex-specific differences in the CORT-induced depression model and provide insights into the underlying mechanisms of depression. This research emphasizes sex in depression studies and supports tailored interventions.

Antidepressant potential of total flavonoids from Astragalus in a chronic stress mouse model: Implications for myelination and Wnt/ß-catenin/Olig2/Sox10 signaling axis modulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Astragali, a versatile traditional Chinese medicinal herb, has a rich history dating back to "Sheng Nong's herbal classic". It has been employed in clinical practice to address various ailments, including depression. One of its primary active components, total flavonoids from Astragalus (TFA), remains unexplored in terms of its potential antidepressant properties. This study delves into the antidepressant effects of TFA using a mouse model subjected to chronic unpredictable mild stress (CUMS). AIMS OF THE STUDY: The study aimed to scrutinize how TFA influenced depressive behaviors, corticosterone and glutamate levels in the hippocampus, as well as myelin-related protein expression in CUMS mice. Additionally, it sought to explore the involvement of the Wnt/ß-catenin/Olig2/Sox10 signaling axis as a potential antidepressant mechanism of TFA. MATERIALS AND METHODS: Male C57BL/6 mice were subjected to CUMS to induce depressive behaviors. TFA were orally administered at two different doses (50 mg/kg and 100 mg/kg). A battery of behavioral tests, biochemical analyses, immunohistochemistry, UPLC-MS/MS, real-time PCR, and Western blotting were employed to evaluate the antidepressant potential of TFA. The role of the Wnt/ß-catenin/Olig2/Sox10 signaling axis in the antidepressant mechanism of TFA was validated through MO3.13 cells. RESULTS: TFA administration significantly alleviated depressive behaviors in CUMS mice, as evidenced by improved sucrose preference, reduced immobility in tail suspension and forced swimming tests, and increased locomotor activity in the open field test. Moreover, TFA effectively reduced hippocampal corticosterone and glutamate levels and promoted myelin formation in the hippocampus of CUMS mice. Then, TFA increased Olig2 and Sox10 expression while inhibiting the Wnt/ß-catenin pathway in the hippocampus of CUMS mice. Finally, we further confirmed the role of TFA in promoting myelin regeneration through the Wnt/ß-catenin/Olig2/Sox10 signaling axis in MO3.13 cells. CONCLUSIONS: TFA exhibited promising antidepressant effects in the CUMS mouse model, facilitated by the restoration of myelin sheaths and regulation of corticosterone, glutamate, Olig2, Sox10, and the Wnt/ß-catenin pathway. This research provides valuable insights into the potential therapeutic application of TFA in treating depression, although further investigations are required to fully elucidate the underlying molecular mechanisms and clinical relevance.

Tumor-secreted LCN2 impairs gastric cancer progression via autocrine inhibition of the 24p3R/JNK/c-Jun/SPARC axis.

Gastric cancer (GC) is one of the most lethal malignancies worldwide. Despite extensive efforts to develop novel therapeutic targets, effective drugs for GC remain limited. Recent studies have indicated that Lipocalin (LCN)2 abnormalities significantly impact GC progression; however, its regulatory network remains unclear. Our study investigates the functional role and regulatory mechanism of action of LCN2 in GC progression. We observed a positive correlation between LCN2 expression, lower GC grade, and better prognosis in patients with GC. LCN2 overexpression suppressed GC proliferation and metastasis both in vitro and in vivo. Transcriptome sequencing identified secreted protein acidic and rich in cysteine (SPARC) as a pivotal downstream target of LCN2. Mechanistically, c-Jun acted as a transcription factor inducing SPARC expression, and LCN2 downregulated SPARC by inhibiting the JNK/c-Jun pathway. Moreover, LCN2 bound to its receptor, 24p3R, via autocrine signaling, which directly inhibited JNK phosphorylation and then inhibited the JNK/c-Jun pathway. Finally, analysis of clinical data demonstrated that SPARC expression correlated negatively with lower GC grade and better prognosis, and that LCN2 expression correlated negatively with p-JNK, c-Jun, and SPARC expression in GC. These findings suggest that the LCN2/24p3R/JNK/c-Jun/SPARC axis is crucial in the malignant progression of GC, offering novel prognostic markers and therapeutic targets.

Determining toxicity of europium oxide nanoparticles in immune cell components and hematopoiesis in dominant organs in mice: Role of lysosomal fluid interaction.

Extensive application of rare earth element oxide nanoparticles (REE NPs) has raised a concern over the possible toxic health effects after human exposure. Once entering the body, REE NPs are primarily processed by phagocytes in particular macrophages and undergo biotic phosphate complexation in lysosomal compartment. Such biotransformation affects the target organs and in vivo fate of REE NPs after escaping the lysosomes. However, the immunomodulatory effects of intraphagolysosomal dissolved REE NPs remains insufficient. Here, europium oxide (Eu2O3) NPs were pre-incubated with phagolysosomal simulant fluid (PSF) to mimic the biotransformation of europium oxide (p-Eu2O3) NPs under acid phagolysosome conditions. We investigated the alteration in immune cell components and the hematopoiesis disturbance on adult mice after intravenous administration of Eu2O3 NPs and p-Eu2O3 NPs. Our results indicated that the liver and spleen were the main target organs for Eu2O3 NPs and p-Eu2O3 NPs. Eu2O3 NPs had a much higher accumulative potential in organs than p-Eu2O3 NPs. Eu2O3 NPs induced more alterations in immune cells in the spleen, while p-Eu2O3 NPs caused stronger response in the liver. Regarding hematopoietic disruption, Eu2O3 NPs reduced platelets (PLTs) in peripheral blood, which might be related to the inhibited erythrocyte differentiation in the spleen. By contrast, p-Eu2O3 NPs did not cause significant disturbance in peripheral PLTs. Our study demonstrated that the preincubation with PSF led to a distinct response in the immune system compared to the pristine REE NPs, suggesting that the potentially toxic effects induced by the release of NPs after phagocytosis should not be neglected, especially when evaluating the safety of NPs application in vivo.

Catalyst- and Additive-free, Regioselective 1,6-Hydroarylation of para-Quinone Methides with Anilines in HFIP.

A simple and efficient method for the synthesis of diarylmethyl-functionalized anilines through the hexafluoroisopropanol (HFIP)-mediated regioselective 1,6-hydroarylation reaction of para-quinone methides (p-QMs) with anilines under catalyst- and additive-free conditions is reported. Various kinds of p-QMs and amines (e. g. primary, secondary and tertiary amines) are well tolerated in this transformation without the pre-protection of amino group, and the corresponding products could be generated with good to excellent yields and satisfactory regioselectivity under the optimized reaction conditions. In addition to adaptable amine compounds, indoles and their derivatives are also compatible with this reaction system. This transformation can be easily extended to a gram scale-synthesis level to synthesize the target product. Furthermore, it is worth noting that some complex small aniline molecules with biological activity can be selectively modified using this method. The possible reaction mechanism is proposed through the step-by-step control experiments and DFT calculations, showing that the key process for achieving the regioselective 1,6-hydroarylation of p-QMs is the hydrogen bonding effect of HFIP to substrates.

Environmental Stability and Transmissibility of Enveloped Viruses at Varied Animate and Inanimate Interfaces.

Enveloped viruses have been the leading causative agents of viral epidemics in the past decade, including the ongoing coronavirus disease 2019 outbreak. In epidemics caused by enveloped viruses, direct contact is a common route of infection, while indirect transmissions through the environment also contribute to the spread of the disease, although their significance remains controversial. Bridging the knowledge gap regarding the influence of interfacial interactions on the persistence of enveloped viruses in the environment reveals the transmission mechanisms when the virus undergoes mutations and prevents excessive disinfection during viral epidemics. Herein, from the perspective of the driving force, partition efficiency, and viral survivability at interfaces, we summarize the viral and environmental characteristics that affect the environmental transmission of viruses. We expect to provide insights for virus detection, environmental surveillance, and disinfection to limit the spread of severe acute respiratory syndrome coronavirus 2.

Hydrophobic and thermal-insulating aerogels based on rigid cellulose nanocrystal and elastic rubber.

Inspired from the ancient China philosophy of "coupling hardness with softness", we attempted the combination of rigid cellulose nanocrystals (CNC) and elastic rubbers to solve the limitations of structural brittleness and water sensitivity of CNC-based aerogels. Three rubber chains with the different chemical structures (silicon rubber, 1,2-polybutadiene, styreneic block copolymer) were covalently bonded on the CNC porous skeleton based on thiol-ene click chemistry, to fabricate the CNC/rubber composite aerogels. With the introduction of moderate loading levels of rubber, the composites aerogels exhibited low density and shrinkage, high porosity and specific surface area and improved mechanical performance. Furthermore, the presence of rubber components completely changed the hydrophilic nature of cellulose skeleton as the hydrophobic aerogels, contributing the superior solvents resistance and self-cleaning property. With their advantages on mechanical stability, heat insulation and hydrophobicity, the fabricated aerogels in this study exhibited the high added values in various potential applications.

Seeded-growth self-assembled polymerization of a ferrocene-bearing palladium(II)-terpyridyl bimetallic complex.

A new bimetallic complex containing a 4'-ferrocenyl-(2,2':6',2''-terpyridine)palladium core with polyethylene glycol-based pyridine is applied in seeded-growth self-assembled supramolecular polymerization, which affords nanoribbons with controllable lengths and the process follows a first-order reaction kinetics. This approach is successfully demonstrated for a bimetallic organic complex for the first time.

Effect-directed analysis for revealing aryl hydrocarbon receptor agonists in sediment samples from an electronic waste recycling town in China.

Exposure to electronic and electrical waste (e-waste) has been related to a few adverse health effects. In this study, sediment samples from an e-waste recycling town in China were collected, and aryl hydrocarbon receptor (AhR) agonists in the samples were identified using an effect-directed analysis (EDA) strategy. The CBG2.8D cell line reporter gene bioassay was used as a toxicity test, while suspect screening against chemical databases was performed for potential AhR agonist identification where both gas chromatography- and liquid chromatography-high resolution mass spectrometry analyses were run. When the original sample extract showed high AhR-mediated activity, sample fractionation was performed, and fractions exhibiting high bioactivity were chemically analyzed again to reveal the corresponding AhR agonists. In total, 23 AhR agonists were identified, including 14 commonly known ones and 9 new ones. Benzo [k]fluoranthene and 6-nitrochrysene were the dominant AhR agonists, covering 16-71% and 2.7-12%, respectively, of the AhR activation effects measured in the parent extracts. The newly identified AhR-active chemicals combined explained 0.13-0.20% of the parent extracts' effects, with 7,12-dimethylbenz [a]anthracene and 8,9,11-trimethylbenz [a]anthracene being the major contributors. A diagnostic isomer ratio analysis of polycyclic aromatic hydrocarbons suggested that the major source of AhR agonists identified in these e-waste related sediment samples were probably petroleum product combustion and biomass combustion. In the future, for a more comprehensive AhR agonist investigation, in-house chemical synthesis and purification, and, when necessary, a secondary sample fractionation, would be beneficial.