Selective lignin arylation for biomass fractionation and benign bisphenols.

Lignocellulose is mainly composed of hydrophobic lignin and hydrophilic polysaccharide polymers, contributing to an indispensable carbon resource for green biorefineries1,2. When chemically treated, lignin is compromised owing to detrimental intra- and intermolecular crosslinking that hampers downstream process3,4. The current valorization paradigms aim to avoid the formation of new C-C bonds, referred to as condensation, by blocking or stabilizing the vulnerable moieties of lignin5-7. Although there have been efforts to enhance biomass utilization through the incorporation of phenolic additives8,9, exploiting lignin's proclivity towards condensation remains unproven for valorizing both lignin and carbohydrates to high-value products. Here we leverage the proclivity by directing the C-C bond formation in a catalytic arylation pathway using lignin-derived phenols with high nucleophilicity. The selectively condensed lignin, isolated in near-quantitative yields while preserving its prominent cleavable ß-ether units, can be unlocked in a tandem catalytic process involving aryl migration and transfer hydrogenation. Lignin in wood is thereby converted to benign bisphenols (34-48 wt%) that represent performance-advantaged replacements for their fossil-based counterparts. Delignified pulp from cellulose and xylose from xylan are co-produced for textile fibres and renewable chemicals. This condensation-driven strategy represents a key advancement complementary to other promising monophenol-oriented approaches targeting valuable platform chemicals and materials, thereby contributing to holistic biomass valorization.

Aberrant DNA N6 -methyladenine incorporation via adenylate kinase 1 is suppressed by ADAL deaminase-dependent 2'-deoxynucleotide pool sanitation.

Intracellular decay of N6 -methyladenine (m6A)-containing RNA potentially induces aberrant N6 -methyl-2'-adenine (6mdA) misincorporation into DNA. Biophysically, misincorporated 6mdA may destabilize the DNA duplex in a manner similar to bona fide methylated 6mdA DNA, thereby affecting DNA replication and transcription. Utilizing heavy stable isotope labeling and ultrasensitive UHPLC-MS/MS assay, we demonstrate that intracellular m6A-RNA decay does not generate free 6mdA species, nor lead to any misincorporated DNA 6mdA in most mammalian cell lines tested, unveiling the existence of a sanitation mechanism that prevents 6mdA misincorporation. Depletion of deaminase ADAL increases the levels of free 6mdA species, concomitant with the presence of DNA-misincorporated 6mdA resulting from intracellular RNA m6A decay, suggesting that ADAL catabolizes 6mdAMP in vivo. Furthermore, we show that the overexpression of adenylate kinase 1 (AK1) promotes 6mdA misincorporation, while AK1 knockdown diminishes 6mdA incorporation, in ADAL-deficient cells. We conclude that ADAL together with other factors (such as MTH1) contributes to 2'-deoxynucleotide pool sanitation in most cells but compromised sanitation (e.g., in NIH3T3 cells) and increased AK1 expression may facilitate aberrant 6mdA incorporation. This sanitation mechanism may provide a framework for the maintenance of the epigenetic 6mdA landscape.

Triggering photocatalytic performance of La2CoxMn2-xO6 via heat activation.

The La-based perovskite (LaBO3) exhibits excellent optical properties. However, its valence band (VB) potential is not sufficiently positive to reach the oxidation potential required for the cleavage of chemical bonds (such as benzylic C-H), limiting its application in photocatalysis. Herein, we report the unconventional effects of heat activation on the reduction of the dissociation energy of benzylic C-H and aqueous H-O, thereby triggering the photocatalytic activity of La2CoxMn2-xO6 perovskites. Additionally, we demonstrate that photocatalysis is the main contributor to substrate conversion in the selective oxidation of toluene and reduction of CO2. Particularly, La2Co1.5Mn0.5O6 shows excellent performance with a product yield of 550.00 mmol gcat-1 and a toluene conversion of 22,866.67 µmol gcat-1 h-1. To the best of our knowledge, this is the highest reported product yield for the selective oxidation of benzylic C-H bond of toluene. Our findings provide insight into the specific role of heat activation in photocatalysis, which is crucial for breaking and overcoming the VB barrier to realize challenging reactions.

Contact between water vapor and silicate surface causes abiotic formation of reactive oxygen species in an anoxic atmosphere.

Spontaneous generation of reactive oxygen species (ROS) in aqueous microdroplets or at a water vapor-silicate interface is a new source of redox chemistry. However, such generation occurs with difficulty in liquid water having a large ionic strength. We report that ROS is spontaneously produced when water vapor contacts hydrogen-bonded hydroxyl groups on a silicate surface. The evolution of hydrogen-bonded species such as hydroxyl groups was investigated by using two-dimensional, time-resolved FT-IR spectroscopy. The participation of water vapor in ROS generation is confirmed by investigating the reaction of D2O vapor and hydroxyl groups on a silicate surface. We propose a reaction pathway for ROS generation based on the change of the hydrogen-bonding network and corresponding electron transfer onto the silicate surface in the water vapor-solid contact process. Our observations suggest that ROS production from water vapor-silicate contact electrification could have contributed to oxidation during the Archean Eon before the Great Oxidation Event.

Identification and Prioritization of Environmental Organic Pollutants: From an Analytical and Toxicological Perspective.

Exposure to environmental organic pollutants has triggered significant ecological impacts and adverse health outcomes, which have been received substantial and increasing attention. The contribution of unidentified chemical components is considered as the most significant knowledge gap in understanding the combined effects of pollutant mixtures. To address this issue, remarkable analytical breakthroughs have recently been made. In this review, the basic principles on recognition of environmental organic pollutants are overviewed. Complementary analytical methodologies (i.e., quantitative structure-activity relationship prediction, mass spectrometric nontarget screening, and effect-directed analysis) and experimental platforms are briefly described. The stages of technique development and/or essential parts of the analytical workflow for each of the methodologies are then reviewed. Finally, plausible technique paths and applications of the future nontarget screening methods, interdisciplinary techniques for achieving toxicant identification, and burgeoning strategies on risk assessment of chemical cocktails are discussed.

Converting Nanotoxicity Data to Information Using Artificial Intelligence and Simulation.

Decades of nanotoxicology research have generated extensive and diverse data sets. However, data is not equal to information. The question is how to extract critical information buried in vast data streams. Here we show that artificial intelligence (AI) and molecular simulation play key roles in transforming nanotoxicity data into critical information, i.e., constructing the quantitative nanostructure (physicochemical properties)-toxicity relationships, and elucidating the toxicity-related molecular mechanisms. For AI and molecular simulation to realize their full impacts in this mission, several obstacles must be overcome. These include the paucity of high-quality nanomaterials (NMs) and standardized nanotoxicity data, the lack of model-friendly databases, the scarcity of specific and universal nanodescriptors, and the inability to simulate NMs at realistic spatial and temporal scales. This review provides a comprehensive and representative, but not exhaustive, summary of the current capability gaps and tools required to fill these formidable gaps. Specifically, we discuss the applications of AI and molecular simulation, which can address the large-scale data challenge for nanotoxicology research. The need for model-friendly nanotoxicity databases, powerful nanodescriptors, new modeling approaches, molecular mechanism analysis, and design of the next-generation NMs are also critically discussed. Finally, we provide a perspective on future trends and challenges.

Flanking strand separation activity of RecA nucleoprotein filaments in DNA strand exchange reactions.

The recombinase RecA/Rad51 ATPase family proteins catalyze paramount DNA strand exchange reactions that are critically involved in maintaining genome integrity. However, it remains unclear how DNA strand exchange proceeds when encountering RecA-free defects in recombinase nucleoprotein filaments. Herein, by designing a series of unique substrates (e.g. truncated or conjugated incoming single-stranded DNA, and extended donor double-stranded DNA) and developing a two-color alternating excitation-modified single-molecule real-time fluorescence imaging assay, we resolve the two key steps (donor strand separation and new base-pair formation) that are usually inseparable during the reaction, revealing a novel long-range flanking strand separation activity of synaptic RecA nucleoprotein filaments. We further evaluate the kinetics and free energetics of strand exchange reactions mediated by various substrates, and elucidate the mechanism of flanking strand separation. Based on these findings, we propose a potential fundamental molecular model involved in flanking strand separation, which provides new insights into strand exchange mechanism and homologous recombination.

Water-solid contact electrification causes hydrogen peroxide production from hydroxyl radical recombination in sprayed microdroplets.

Contact electrification between water and a solid surface is crucial for physicochemical processes at water-solid interfaces. However, the nature of the involved processes remains poorly understood, especially in the initial stage of the interface formation. Here we report that H2O2 is spontaneously produced from the hydroxyl groups on the solid surface when contact occurred. The density of hydroxyl groups affects the H2O2 yield. The participation of hydroxyl groups in H2O2 generation is confirmed by mass spectrometric detection of 18O in the product of the reaction between 4-carboxyphenylboronic acid and 18O-labeled H2O2 resulting from 18O2 plasma treatment of the surface. We propose a model for H2O2 generation based on recombination of the hydroxyl radicals produced from the surface hydroxyl groups in the water-solid contact process. Our observations show that the spontaneous generation of H2O2 is universal on the surfaces of soil and atmospheric fine particles in a humid environment.

Cu Nanowires Trigger Efficient Cuproptosis via Special Intracellular Distribution and Excessive Cu Ion Release.

Cuproptosis, dependent on Cu overload, presents novel opportunities for cancer therapy. Cu-based nanomaterials have shown excellent advantages for the intracellular delivery of Cu. However, the biological process of Cu nanomaterials transporting Cu ions into cancer cells remains unclear. In this study, we tracked the Cu ion release process of copper nanowires (CuNWs) and copper nanoparticles (CuNPs) at the single-cell level. CuNWs with 5-µm length and CuNPs were found to be completely internalized by cancer cells. Interestingly, CuNWs escaped from the endolysosomal system, whereas CuNPs were mainly trapped in the lysosomes. This specific intracellular distribution of CuNWs led to cytoplasmic Cu ion overload, directly damaging mitochondria and inducing dihydrolipoamide S-acetyltransferase (DLAT) protein aggregation. Through these excessive Cu ions, CuNWs triggered more efficient cuproptosis than CuNPs to further increase cell death. Thus, CuNWs are more effective in delivering Cu ions than CuNPs, providing a novel perspective for designing cuproptosis-based functional nanomaterials for cancer therapy.

In Vivo Exposure Pathways of Ambient Magnetite Nanoparticles Revealed by Machine Learning-Aided Single-Particle Mass Spectrometry.

Nanosized ultrafine particles (UFPs) from natural and anthropogenic sources are widespread and pose serious health risks when inhaled by humans. However, tracing the inhaled UFPs in vivo is extremely difficult, and the distribution, translocation, and metabolism of UFPs remain unclear. Here, we report a label-free, machine learning-aided single-particle inductively coupled plasma mass spectrometry (spICP-MS) approach for tracing the exposure pathways of airborne magnetite nanoparticles (MNPs), including external emission sources, and distribution and translocation in vivo using a mouse model. Our results provide quantitative analysis of different metabolic pathways in mice exposed to MNPs, revealing that the spleen serves as the primary site for MNP metabolism (84.4%), followed by the liver (11.4%). The translocation of inhaled UFPs across different organs alters their particle size. This work provides novel insights into the in vivo fate of UFPs as well as a versatile and powerful platform for nanotoxicology and risk assessment.

Efficient Photoreduction of CO2 to CO with 100% Selectivity by Slowing Down Electron Transport.

It remains challenging to obtain a single product in the gas-solid photocatalytic reduction of CO2 because CO and CH4 are usually produced simultaneously. This study presents the design of the I-type nested heterojunction TiO2/BiVO4 with controllable electron transport by modulating the TiO2 component. This study demonstrates that slowing electron transport could enable TiO2/BiVO4-4 to generate CO with 100% selectivity. In addition, modifying TiO2/BiVO4-4 by loading a Cu single atom further increased the CO product yield by 3.83 times (17.33 µmol·gcat-1·h-1), while maintaining 100% selectivity for CO. Characterization and density functional theory (DFT) calculations revealed that the selectivity was mainly determined by the electron transport of the support, whereas CO2 was efficiently adsorbed and activated by the Cu single atom. Such a two-step regulation strategy of combining heterojunction with single atom enhances the possibility of simultaneously obtaining high selectivity and high yield in the photocatalytic reduction of CO2.

RNA-Activated CRISPR/Cas12a Nanorobots Operating in Living Cells.

Active clustered regularly interspaced short palindromic repeats (CRISPR/Cas12a) systems possess both cis-cleavage (targeted) and trans-cleavage (collateral) activities, which are useful for genome engineering and diagnostic applications. Both single- and double-stranded DNA can activate crRNA-Cas12a ribonucleoprotein (RNP) to achieve cis- and trans-cleavage enzymatic activities. However, it is not clear whether RNA can activate the CRISPR/Cas12a system and what is critical to the trans-cleavage activity. We report here that RNA can activate the CRISPR/Cas12a system and trigger its trans-cleavage activity. We reveal that the activated crRNA-Cas12a RNP favors the trans-cleavage of longer sequences than commonly used. These new findings of the RNA-activated trans-cleavage capability of Cas12a provided the foundation for the design and construction of CRISPR nanorobots that operate in living cells. We assembled the crRNA-Cas12a RNP and nucleic acid substrates on gold nanoparticles to form CRISPR nanorobots, which dramatically increased the local effective concentration of the substrate in relation to the RNP and the trans-cleavage kinetics. Binding of the target microRNA to the crRNA-Cas12a RNP activated the nanorobots and their trans-cleavage function. The repeated (multiple-turnover) trans-cleavage of the fluorophore-labeled substrates generated amplified fluorescence signals. Sensitive and real-time imaging of specific microRNA in live cells demonstrated the promising potential of the CRISPR nanorobot system for future applications in monitoring and modulating biological functions within living cells.

Self-Assembly of Super-Uniform Covalent Organic Framework Colloidal Particles into Multi-Dimensional Ordered Superstructures.

Precise self-assembly of colloidal particles is crucial for understanding their aggregation properties and preparing macroscopic functional devices. It is currently very challenging to synthesize and self-assemble super-uniform covalent organic framework (COF) colloidal particles into well-organized multidimensional superstructures. Here, simple and versatile strategies are proposed for synthesis of super-uniform COF colloidal particles and self-assembly of them into 1D supraparticles, 2D ordered mono/multilayers, and 3D COF films. For this purpose, several self-assembly techniques are developed, including emulsion solvent evaporation, air-liquid interfacial self-assembly, and drop-casting. These strategies enable the superstructural self-assembly of particles of varying sizes and species without any additional surfactants or chemical modifications. The assembled superstructures maintain the porosity and high specific surface area of their building blocks. The feasibility of the strategies is examined with different types of COFs. This research provides a new approach for the controllable synthesis of super-uniform COF colloidal particles capable of self-assembling into multidimensional superstructures with long-range order. These discoveries hold great promise for the design of emerging multifunctional COF superstructures.

High-Efficiency Degradation of PET Plastics by Glutathione S-Transferase under Mild Conditions.

Plastic pollution is a significant environmental concern globally. Plastics are normally considered chemically inert and resistant to biodegradation. Although many papers have reported enzyme-induced biodegradation of plastics, these studies are primarily limited to enzymes of microbial origin or engineered enzymes. This study reveals that poly(ethylene terephthalate) (PET, ∼6000 Da and 100 kDa) particles and plastic bottle debris (PBD, 24.9 kDa) can be efficiently degraded by a mammal-origin natural phase II metabolic isozyme, glutathione S-transferase (GST), under mild conditions. The degradation efficiency of PET plastics reached 98.9%, with a degradation rate of 2.6 g·L-1·h-1 under ambient or physiological conditions at 1 atm. PET plastics can be degraded by GST with varying environmental or biological factors (i.e., temperature, light irradiation, pH, and presence of humic acid or protein). We suggest a novel mechanism for PET degradation other than hydrolysis, i.e., the mechanism of cleavage and release of PET plastic monomers via nitridation and oxidation. This finding also reveals a novel function of GST, previously thought to only degrade small molecules (<1000 Da). This method has been successfully applied in real human serum samples. Additionally, we have tested and confirmed the ability to degrade PET of a mammal-origin natural digestive enzyme (trypsin) and a human-derived natural metabolic enzyme (CYP450). Overall, our findings provide a potential new route to plastic pollution control and contribute to our understanding of the metabolism and fate of plastics in organisms.

Nationwide Investigation on Organophosphate Flame Retardants in Tea from China: Migration from Packaging Materials and Implications for Global Risk Assessment.

In this study, we measured 15 common organophosphate flame retardants (OPFRs) in six categories of tea samples across China. OPFRs were found in all the tea samples, with the total concentrations of OPFRs (∑OPFRs) at 3.44-432 ng/g [geometric mean (GM): 17.6 ng/g]. Triphenyl phosphate (TPhP) was the dominant OPFR, accounting for 39.0-76.2% of ∑OPFRs across all tea categories. The potential factors influencing the residual OPFRs in tea were thoroughly examined, including the agricultural environment, fermentation, and packaging of teas. Tea packaging materials (TPMs) were then identified as the primary sources of OPFRs in teas. The migration test revealed that OPFRs with lower molecular weights and log Kow values exhibited a higher propensity for facilitating the migration of OPFRs from TPMs to teas. The estimated daily intakes of OPFRs from teas were relatively higher for the general populations in Mauritania, Gambia, Togo, Morocco, and Senegal (3.18-9.79 ng/kg bw/day) than China (3.12 ng/kg bw/day). The health risks arising from OPFRs in Chinese teas were minor. This study established a baseline concentration and demonstrated the contamination sources of OPFRs in Chinese tea for the first time, with an emphasis on enhancing the hygiene standards for TPMs.

Comprehensive Toxicological Assessment of Halobenzoquinones in Drinking Water at Environmentally Relevant Concentration.

Halobenzoquinones (HBQs), an emerging unregulated category of disinfection byproduct (DBP) in drinking water, have aroused an increasing concern over their potential health risks. However, the chronic toxicity of HBQs at environmentally relevant concentrations remains largely unknown. Here, the occurrence and concentrations of 13 HBQs in drinking water from a northern megacity in China were examined using ultrahigh performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UHPLC-MS/MS). Four HBQs, including 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), 2,6-dibromo-1,4-benzoquinone (2,6-DBBQ), 2,3,6-trichloro-1,4-benzoquinone (TriCBQ), and 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ), were detected beyond 50% occurrence frequency and at median concentrations from 4 to 50 ng/L. The chronic toxicity of these four HBQs to normal human colon and liver cells (FHC and THLE-2) was investigated at these concentrations. After 90 days of exposure, 2,5-DBBQ and 2,6-DCBQ induced the highest levels of oxidative stress and deoxyribonucleic acid (DNA) damage in colon and liver cells, respectively. Moreover, 2,5-DBBQ and 2,6-DCBQ were also found to induce epithelial-mesenchymal transition (EMT) in normal human liver cells via the extracellular signal regulated kinase (ERK) signaling pathway. Importantly, heating to 100 °C (boiling) was found to efficiently reduce the levels of these four HBQs in drinking water. These results suggested that environmentally relevant concentrations of HBQs could induce cytotoxicity and genotoxicity in normal human cells, and boiling is a highly efficient way of detoxification for HBQs.

Environmentally Relevant Concentrations of Microplastic Exposure Cause Cholestasis and Bile Acid Metabolism Dysregulation through a Gut-Liver Loop in Mice.

The massive production of plastics causes the ubiquitous existence of microplastics (MPs) in the biota, therefore, posing exposure risks and potential health concerns to human beings. However, the exact mechanisms of MPs-induced toxicities and abnormalities are largely unknown. In this study, we developed a mouse model of gavage polystyrene microplastics (PS MPs) for 30 days. We found that PS MPs can damage the intestinal barrier, accumulate in the liver tissue, and cause injury. The liver and intestine are both highly associated with bile acid (BA) metabolism. Indeed, we found that PS MPs dysregulate BA synthesis and efflux-related gene expression in the liver, causing cholestasis. Tandemly, PS MPs alter the ratio of primary to secondary BA in the feces by affecting the composition of the intestinal flora. At last, PS MPs alter mice's fecal BA profile, which affects normal BA metabolism. Taken together, the present study provides robust data on the mechanism of toxicity of MPs causing the disturbance of BA metabolism via a 4-step gut-liver loop.

Structure-Related Thyroid Disrupting Effect of Perfluorooctanesulfonate-like Substances in Zebrafish Larvae.

Chlorinated polyfluorooctane ether sulfonate (6:2 Cl-PFESA), hydrogenated polyfluorooctane ether sulfonate (6:2 H-PFESA), and chlorinated polyfluorooctanesulfonate (Cl-PFOS) share structural similarities with the regulated perfluorooctanesulfonate (PFOS), but their toxic potential is rarely known. Here, the thyroid disrupting potential of these four compounds in zebrafish larvae has been comparably investigated. PFOS, Cl-PFOS, and 6:2 Cl-PFESA were accumulated in the larvae at similar levels, approximately 1.3-1.6 times higher than 6:2 H-PFESA. Additionally, PFOS, Cl-PFOS, and 6:2 Cl-PFESA exhibited stronger disruption than 6:2 H-PFESA on genetic regulation, particularly concerning thyroid hormone (TH) activation and action and on TH homeostasis in both free and total forms of thyroxine (T4) and 3,5,3'-triiodothyronine (T3). These results indicate that chlorination or oxygen insertion does not substantially alter the thyrotoxicity of PFOS, but hydrogenation mitigates it. Molecular docking analysis and the luciferase reporter gene assay provided mechanistic perspectives that the PFOS-like substances could competitively replace THs to bind with TH plasma and membrane transporters, thereby disrupting TH transport and action, respectively. Moreover, they are also potent to disrupt TH synthesis and activation through Na+/K+-dependent transport of I- or competitive binding to the sites of deiodinases.

Exposure to MEHP during Pregnancy and Lactation Impairs Offspring Growth and Development by Disrupting Thyroid Hormone Homeostasis.

Mono(2-ethylhexyl) phthalate (MEHP), as a highly toxic and biologically active phthalate metabolite, poses considerable risks to the environment and humans. Despite the existence of in vitro studies, there is a lack of in vivo experiments assessing its toxicity, particularly thyroid toxicity. Herein, we investigated the thyroid-disrupting effects of MEHP and the effects on growth and development of maternal exposure to MEHP during pregnancy and lactation on the offspring modeled by SD rats. We found that thyroid hormone (TH) homeostasis was disrupted in the offspring, showing a decrease in total TH levels, combined with an increase in free TH levels. Nonhomeostasis ultimately leads to weight loss in female offspring, longer anogenital distance in male offspring, prolonged eye-opening times, and fewer offspring. Our findings indicate that maternal exposure to MEHP during pregnancy and lactation indirectly influences the synthesis, transport, transformation, and metabolism of THs in the offspring. Meanwhile, MEHP disrupted the morphology and ultrastructure of the thyroid gland, leading to TH disruption. This hormonal disruption might ultimately affect the growth and development of the offspring. This study provides a novel perspective on the thyroid toxicity mechanisms of phthalate metabolites, emphasizing the health risks to newborns indirectly exposed to phthalates and their metabolites.

Associations of Bisphenols Exposure and Hyperuricemia Based on Human Investigation and Animal Experiments.

Hyperuricemia is characterized by elevated blood uric acid (UA) levels, which can lead to certain diseases. Epidemiological studies have explored the association between environmental contaminant exposure and hyperuricemia. However, few studies have investigated the role of chemical exposure in the development of hyperuricemia. Here, we sought to investigate the effects of bisphenol exposure on the occurrence of hyperuricemia. Fifteen bisphenol chemicals (BPs) were detected in human serum and urine samples collected from an area with a high incidence of hyperuricemia in China. Serum UA levels positively correlated with urinary bisphenol S (BPS), urinary bisphenol P (BPP), and serum bisphenol F (BPF). The effects of these three chemicals on UA levels in mice were explored at various exposure concentrations. An increase in serum UA levels was observed in BPS- and BPP-exposed mice. The results showed that BPS exposure increased serum UA levels by damaging the structure of the kidneys, whereas BPP exposure increased serum UA levels by disturbing purine metabolism in the liver. Moreover, BPF did not induce an increase in serum UA levels owing to the inhibition of guanine conversion to UA. In summary, we provide evidence of the mechanisms whereby exposure to three BPs disturbs UA homeostasis. These findings provide new insights into the risks of exposure to bisphenol chemicals.