Mechanistic and data-driven perspectives on plant uptake of organic pollutants.

Establishing reliable predictive models for plant uptake of organic pollutants is crucial for environmental risk assessment and guiding phytoremediation efforts. This study compiled an expanded dataset of plant cuticle-water partition coefficients (Kcw), a useful indicator for plant uptake, for 371 data points of 148 unique compounds and various plant species. Quantum/computational chemistry software and tools were utilized to compute various molecular descriptors, aiming to comprehensively characterize the properties and structures of each compound. Three types of models were developed to predict Kcw: a mechanism-driven pp-LFER model, a data-driven machine learning model, and an integrated mechanism-data-driven model. The mechanism-data-driven GBRT-ppLFER model exhibited superior performance, achieving RMSEtrain = 0.133 and RMSEtest = 0.301 while maintaining interpretability. The Shapley Additive Explanation analysis indicated that pp-LFER parameters, ESPI, FwRadicalmax, ExtFP607, and RDF70s are the key factors influencing plant uptake in the GBRT-ppLFER model. Overall, pp-LFER parameter, ESPI, and ExtFP607 show positive effects, while the remaining factors exhibit negative effects. Partial dependency analysis further indicated that plant uptake is not solely determined by individual factors but rather by the combined interactions of multiple factors. Specifically, compounds with ppLFER parameter >4, ESPI > -25.5, 0.098 < FwRadicalmax <0.132, and 2 < RFD70s < 3, are generally more readily taken up by plants. Besides, the predicted Kcw values from the GBRT-ppLFER model were effectively employed to estimate the plant-water partition coefficients and bioconcentration factors across different plant species and growth media (water, sand, and soil), achieving an outstanding performance with an RMSE of 0.497. This study provides effective tools for assessing plant uptake of organic pollutants and deepens our understanding of plant-environment-compound interactions.

Microbial mechanisms in nitrogen fertilization: Modulating the re-mobilization of clay mineral-bound cadmium in agricultural soils.

Soil cadmium (Cd) can affect crop growth and food safety, and through the enrichment in the food chain, it ultimately poses a risk to human health. Reducing the re-mobilization of Cd caused by the release of protons and acids by crops and microorganisms after stabilization is one of the significant technical challenges in agricultural activities. This study aimed to investigate the re-mobilization of stabilized Cd within the clay mineral-bound fraction of soil and its subsequent accumulation in crops utilizing nitrogen ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N), at 60 and 120 mg kg-1. Furthermore, the study harvested root exudates at various growth stages to assess their direct influence on the re-mobilization of stabilized Cd and to evaluate the indirect effects mediated by soil microorganisms. The results revealed that, in contrast to the NO3--N treatment, the NH4+-N treatment significantly enhanced the conversion of clay mineral-bound Cd in the soil to NH4NO3-extractable Cd. It also amplified the accumulation of Cd in edible amaranth, with concentrations in roots and shoots rising from 1.7-6.0 mg kg-1 to 4.3-9.8 mg kg-1. The introduction of NH4+-N caused a decrease in the pH value of the rhizosphere soil and stimulated the production and secretion organic and amino acids, such as oxalic acid, lactic acid, stearic acid, succinic acid, and l-serine, from the crop roots. Furthermore, compared to NO3--N, the combined interaction of root exudates with NH4+-N has a more pronounced impact on the abundance of microbial genes associated with glycolysis pathway and tricarboxylic acid cycle, such as pkfA, pfkB, sucB, sucC, and sucD. The effects of NH4+-N on crops and microorganisms ultimately result in a significant increase in the re-mobilization of stabilized Cd. However, the simulated experiments showed that microorganisms only contribute to 3.8-6.6 % of the re-mobilization of clay mineral-bound Cd in soil. Therefore, the fundamental strategy to inhibit the re-mobilization of stabilized Cd in vegetable cultivation involves the regulation of proton and organic acid secretion by crops.

Disordered regions in proteusin peptides guide post-translational modification by a flavin-dependent RiPP brominase.

To biosynthesize ribosomally synthesized and post-translationally modified peptides (RiPPs), enzymes recognize and bind to the N-terminal leader region of substrate peptides which enables catalytic modification of the C-terminal core. Our current understanding of RiPP leaders is that they are short and largely unstructured. Proteusins are RiPP precursor peptides that defy this characterization as they possess unusually long leaders. Proteusin peptides have not been structurally characterized, and we possess scant understanding of how these atypical leaders engage with modifying enzymes. Here, we determine the structure of a proteusin peptide which shows that unlike other RiPP leaders, proteusin leaders are preorganized into a rigidly structured region and a smaller intrinsically disordered region. With residue level resolution gained from NMR titration experiments, the intermolecular peptide-protein interactions between proteusin leaders and a flavin-dependent brominase are mapped onto the disordered region, leaving the rigidly structured region of the proteusin leader to be functionally dispensable. Spectroscopic observations are biochemically validated to identify a binding motif in proteusin peptides that is conserved among other RiPP leaders as well. This study provides a structural characterization of the proteusin peptides and extends the paradigm of RiPP modification enzymes using not only unstructured peptides, but also structured proteins as substrates.

Aluminum phytotoxicity in acidic environments: A comprehensive review of plant tolerance and adaptation strategies.

Aluminum (Al), a non-essential metal for plant growth, exerts significant phytotoxic effects, particularly on root growth. Anthropogenic activities would intensify Al's toxic effects by releasing Al3+ into the soil solution, especially in acidic soils with a pH lower than 5.5 and rich mineral content. The severity of Al-induced phytotoxicity varies based on factors such as Al concentration, ionic form, plant species, and growth stages. Al toxicity leads to inhibited root and shoot growth, reduced plant biomass, disrupted water uptake causing nutritional imbalance, and adverse alterations in physiological, biochemical, and molecular processes. These effects collectively lead to diminished plant yield and quality, along with reduced soil fertility. Plants employ various mechanisms to counter Al toxicity under stress conditions, including sequestering Al in vacuoles, exuding organic acids (OAs) like citrate, oxalate, and malate from root tip cells to form Al-complexes, activating antioxidative enzymes, and overexpressing Al-stress regulatory genes. Recent advancements focus on enhancing the exudation of OAs to prevent Al from entering the plant, and developing Al-tolerant varieties. Gene transporter families, such as ATP-Binding Cassette (ABC), Aluminum-activated Malate Transporter (ALMT), Natural resistance-associated macrophage protein (Nramp), Multidrug and Toxic compounds Extrusion (MATE), and aquaporin, play a crucial role in regulating Al toxicity. This comprehensive review examined recent progress in understanding the cytotoxic impact of Al on plants at the cellular and molecular levels. Diverse strategies developed by both plants and scientists to mitigate Al-induced phytotoxicity were discussed. Furthermore, the review explored recent genomic developments, identifying candidate genes responsible for OAs exudation, and delved into genome-mediated breeding initiatives, isolating transgenic and advanced breeding lines to cultivate Al-tolerant plants.

Identification of novel flavin-dependent monooxygenase from Strobilanthes Cusia reveals molecular basis of indoles' biosynthetic logic.

BACKGROUND: Strobilanthes cusia (Nees) Kuntze is a traditional medical plant distributed widely in south China. The indole compounds that originated from the plant are responsible for its pharmacological activities. However, the reason why indole ingredients are accumulated in this herb and how it is biosynthesized has remained largely unknown. RESULTS: In this study, metabolic and transcriptional profiling measurement experiments of different S. cusia organs were carried out to understand the underlying molecular basis of indoles' biosynthetic logic. A metabolic investigation demonstrated that the indoles are primarily accumulated mainly in aerial parts, particularly in leaves. RNA-seq was employed to reveal the organ specific accumulation of indoles in different S. cusia organs. Meanwhile, a flavin-dependent monooxygenase gene (ScFMO1) was found in S. cusia, and it has capacity to produce indoxyl from indole by the fermentation assay. Finally, we assessed the outcomes of transient expression experiment in tobacco and confirmed that ScFMO1 localizes in cytoplasm. CONCLUSIONS: Our results suggest that ScFMO1 plays a key role in biosynthesis of indoles (Indigo, indirubin, indican, etc.), it will be useful for illuminating the molecular basis of the medicinal indoles' biosynthesis and developing strategies for improving their yields.

Biodegradation of trace sulfonamide antibiotics accelerated by substrates across oxic to anoxic conditions during column infiltration experiments.

Frequent occurrence of trace organic contaminants in aquatic environments, such as sulfonamide antibiotics in rivers receiving reclaimed water, is concerning. Natural attenuation by soil and sediment is increasingly relied upon. In the case of riverbank filtration for water purification, the reliability of antibiotic attenuation has been called into question due to incomplete understanding of their degradation processes. This study investigated influence of substrates and redox evolution along infiltration path on biotransformation of sulfonamides. Eight sand columns (length: 28 cm) with a riverbed sediment layer at 3-8 cm were fed by groundwater-sourced tap water spiked with 1 µg/L of sulfadiazine (SDZ), sulfamethazine (SMZ), and sulfamethoxazole (SMX) each, with or without amendments of dissolved organic carbon (5 mg-C/L of 1:1 yeast and humics) or ammonium (5 mg-N/L). Two flow rates were tested over 120 days (0.5 mL/min and 0.1 mL/min). Iron-reducing conditions persisted in all columns for 27 days during the initial high flow period due to respiration of sediment organics, evolving to less reducing conditions until the subsequent low flow period to resume more reducing conditions. With surplus substrates, the spatial and temporal patterns of redox conditions differentiated among columns. The removal of SDZ and SMZ in effluents was usually low (15 ± 11%) even with carbon addition (14 ± 9%), increasing to 33 ± 23% with ammonium addition. By contrast, SMX removal was higher and more consistent among columns (46 ± 21%), with the maximum of 64 ± 9% under iron-reducing conditions. When sulfonamide removal was compared between columns for the same redox zones during infiltration, their enhancements were always associated with the availability of dissolved or particulate substrates, suggesting co-metabolism. Manipulation of the exposure time to optimal redox conditions with substrate amendments, rather than to simply prolong the overall residence time, is recommended for nature-based solutions to tackle target antibiotics.

Mechanism of polycyclic aromatic hydrocarbons degradation in the rhizosphere of Phragmites australis: Organic acid co-metabolism, iron-driven, and microbial response.

Microbial co-metabolism is crucial for the efficient biodegradation of polycyclic aromatic hydrocarbons (PAHs); however, their intrinsic mechanisms remain unclear. To explore the co-metabolic degradation of PAHs, root organic acids (ROAs) (phenolic ROAs: caffeic acid [CA] and ferulic acid [FA]; non-phenolic ROAs: oxalic acid [OA]) were exogenously added as co-metabolic substrates under high (HFe) and low (LFe) iron levels in this study. The results demonstrated that more than 90% of PAHs were eliminated from the rhizosphere of Phragmites australis. OA can promote the enrichment of unrelated degrading bacteria and non-specific dioxygenases. FA with a monohydroxy structure can activate hydroxylase; however, it relies on phytosiderophores released by plants (such as OA) to adapt to stress. Therefore, non-specific co-metabolism occurred in these units. The best performance for PAH removal was observed in the HFe-CA unit because: (a) HFe concentrations enriched the Fe-reducing and denitrifying bacteria and promoted the rate-limiting degradation for PAHs as the enzyme cofactor; (b) CA with a dihydroxyl structure enriched the related degrading bacteria, stimulated specific dioxygenase, and activated Fe to concentrate around the rhizosphere simultaneously to perform the specific co-metabolism. Understanding the co-metabolic degradation of PAHs will help improve the efficacy of rhizosphere-mediated remediation.

Aluminum and Fluoride Stresses Altered Organic Acid and Secondary Metabolism in Tea (Camellia sinensis) Plants: Influences on Plant Tolerance, Tea Quality and Safety.

Tea plants have adapted to grow in tropical acidic soils containing high concentrations of aluminum (Al) and fluoride (F) (as Al/F hyperaccumulators) and use secret organic acids (OAs) to acidify the rhizosphere for acquiring phosphorous and element nutrients. The self-enhanced rhizosphere acidification under Al/F stress and acid rain also render tea plants prone to accumulate more heavy metals and F, which raises significant food safety and health concerns. However, the mechanism behind this is not fully understood. Here, we report that tea plants responded to Al and F stresses by synthesizing and secreting OAs and altering profiles of amino acids, catechins, and caffeine in their roots. These organic compounds could form tea-plant mechanisms to tolerate lower pH and higher Al and F concentrations. Furthermore, high concentrations of Al and F stresses negatively affected the accumulation of tea secondary metabolites in young leaves, and thereby tea nutrient value. The young leaves of tea seedlings under Al and F stresses also tended to increase Al and F accumulation in young leaves but lower essential tea secondary metabolites, which challenged tea quality and safety. Comparisons of transcriptome data combined with metabolite profiling revealed that the corresponding metabolic gene expression supported and explained the metabolism changes in tea roots and young leaves via stresses from high concentrations of Al and F. The study provides new insight into Al- and F-stressed tea plants with regard to responsive metabolism changes and tolerance strategy establishment in tea plants and the impacts of Al/F stresses on metabolite compositions in young leaves used for making teas, which could influence tea nutritional value and food safety.

You Exude What You Eat: How Carbon-, Nitrogen-, and Sulfur-Rich Organic Substrates Shape Microbial Community Composition and the Dissolved Organic Matter Pool.

Phytoplankton is the major source of labile organic matter in the sunlit ocean, and they are therefore key players in most biogeochemical cycles. However, studies examining the heterotrophic bacterial cycling of specific phytoplankton-derived nitrogen (N)- and sulfur (S)-containing organic compounds are currently lacking at the molecular level. Therefore, the present study investigated how the addition of N-containing (glycine betaine [GBT]) and S-containing (dimethylsulfoniopropionate [DMSP]) organic compounds, as well as glucose, influenced the microbial production of new organic molecules and the microbial community composition. The chemical composition of microbial-produced dissolved organic matter (DOM) was analyzed by ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) demonstrating that CHO-, CHON-, and CHOS-containing molecules were enriched in the glucose, GBT, and DMSP experiments, respectively. High-throughput sequencing showed that Alteromonadales was the dominant group in the glucose, while Rhodobacterales was the most abundant group in both the GBT and DMSP experiments. Cooccurrence network analysis furthermore indicated more complex linkages between the microbial community and organic molecules in the GBT compared with the other two experiments. Our results shed light on how different microbial communities respond to distinct organic compounds and mediate the cycling of ecologically relevant compounds. IMPORTANCE Nitrogen (N)- and sulfur (S)-containing compounds are normally considered part of the labile organic matter pool that fuels heterotrophic bacterial activity in the ocean. Both glycine betaine (GBT) and dimethylsulfoniopropionate (DMSP) are representative N- and S-containing organic compounds, respectively, that are important phytoplankton cellular compounds. The present study therefore examined how the microbial community and the organic matter they produce are influenced by the addition of carbohydrate-containing (glucose), N-containing (GBT), and S-containing (DMSP) organic compounds. The results demonstrate that when these carbon-, N-, and S-rich compounds are added separately, the organic molecules produced by the bacteria growing on them are enriched in the same elements. Similarly, the microbial community composition was also distinct when different compounds were added as the substrate. Overall, this study demonstrates how the microbial communities metabolize and transform different substrates thereby, expanding our understanding of the complexity of links between microbes and substrates in the ocean.

microRNAs transcriptional profiling of mammary stem cells isolated by PKH26 staining and FACS sorting.

MicroRNAs (miRNAs) are an evolutionarily conserved class of small (18-22 nucleotides) noncoding RNAs involved in the regulation of a variety of cellular and developmental processes. MiRNA expression is frequently altered in human cancers compared to normal tissues, potentially contributing to tumorigenesis. Generally, high-throughput profiles of miRNA expression levels are generated using bulk samples, from both normal and cancer tissues. However, cancer tissues are quite heterogeneous and might contain subpopulations critical for tumor development, i.e., cancer stem cells (CSCs) or tumor-initiating cells (TICs) with aberrant stem-like features, such as unlimited self-renewal potential. The isolation of these aberrant subpopulations from solid tumors is a relatively recent achievement, with breast cancer being one of the first solid human cancers in which CSCs have been identified and biologically characterized. Here, we describe a new methodology that can overcome the main challenge in dealing with rare cells such as SCs/CSCs, represented by the paucity of the starting material. Based on previously published protocols, used by both our and other research groups, we used the FACS-sorting approach to isolate mammary normal and cancer stem cells based on the amount of PKH26 fluorescent dye they retained. Depending on the number of SCs/CSCs isolated, we established two different protocols for the reliable and analytically sensitive detection of up to 384 miRNAs using the Taqman Low Density Array (TLDA) platform.

Confocal microscopy analysis reveals that only a small proportion of extracellular vesicles are successfully labelled with commonly utilised staining methods.

Assessing genuine extracellular vesicle (EV) uptake is crucial for understanding the functional roles of EVs. This study measured the bona fide labelling of EVs utilising two commonly used fluorescent dyes, PKH26 and C5-maleimide-Alexa633. MCF7 EVs tagged with mEmerald-CD81 were isolated from conditioned media by size exclusion chromatography (SEC) and characterised using Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), MACsPlex immunocapture assay and immunoblots. These fluorescently tagged EVs were subsequently stained with C5-maleimide-Alexa633 or PKH26, according to published protocols. Colocalisation of dual-labelled EVs was assessed by confocal microscopy and quantified using the Rank-Weighted Colocalisation (RWC) algorithm. We observed strikingly poor colocalisation between mEmerald-CD81-tagged EVs and C5-Maleimide-Alexa633 (5.4% ± 1.8) or PKH26 (4.6% ± 1.6), that remained low even when serum was removed from preparations. Our data confirms previous work showing that some dyes form contaminating aggregates. Furthermore, uptake studies showed that maleimide and mEmerald-CD81-tagged EVs can be often located into non-overlapping subcellular locations. By using common methods to isolate and stain EVs we observed that most EVs remained unstained and most dye signal does not appear to be EV associated. Our work shows that there is an urgent need for optimisation and standardisation in how EV researchers use these tools to assess genuine EV signals.

Cadmium, lead, and zinc immobilization in soil by rice husk biochar in the presence of low molecular weight organic acids.

Heavy metal immobilization using biochar (BC) is different from the usual soil incubation due to the low molecular weight organic acids (LMWOAs) in the rhizosphere and is an issue worth evaluating. Therefore, the impacts of rice husk BC (5%), tartaric acid, and oxalic acid, coupled with combinations of BC and tartaric acid/oxalic acid on the transformation of cadmium (Cd), lead (Pb), and zinc (Zn) among their geochemical forms, including their bioavailability in a metal-contaminated soil, were investigated in an incubation experiment. The application of BC, low concentration of tartaric acid (2 mmol kg-1 soil) (TA2), and the combined BC plus a low level of tartaric acid (BC-TA2) markedly reduced the acid-soluble and available (CaCl2-extractable) Cd, Pb, and Zn compared to control (CK) in which BC-TA2 was found to be the most effective treatment. The trends were reversed in the case of the high concentrations of tartaric acid (>5-20 mmol kg-1 soil), all levels of oxalic acid (2-20 mmol kg-1 soil), and the combined BC plus high levels of tartaric acid/oxalic acid treatments. The BC-TA2 transformed the highest amounts of acid-soluble and reducible Cd, Pb, and Zn to the oxidizable and residual fractions with incubation time. The results suggested that the low concentration of tartaric acid enhanced Cd, Pb, and Zn immobilization, while the higher level of tartaric acid and all concentrations of oxalic acid increased their mobilization. In conclusion, BC-TA2 could immobilize the most heavy metals and serve as an amendment for metals' immobilization/redistribution in contaminated soils.

Recent progress in covalent warheads for in vivo targeting of endogenous proteins.

Covalent drugs exert potent and durable activity by chemical modification of the endogenous target protein in vivo. To maximize the pharmacological efficacy while alleviating the risk of toxicity due to nonspecific off-target reactions, current covalent drug discovery focuses on the development of targeted covalent inhibitors (TCIs), wherein a reactive group (warhead) is strategically incorporated onto a reversible ligand of the target protein to facilitate specific covalent engagement. Various aspects of warheads, such as intrinsic reactivity, chemoselectivity, mode of reaction, and reversibility of the covalent engagement, would affect the target selectivity of TCIs. Although TCIs clinically approved to date largely rely on Michael acceptor-type electrophiles for cysteine targeting, a wide array of novel warheads have been devised and tested in TCI development in recent years. In this short review, we provide an overview of recent progress in chemistry for selective covalent targeting of proteins and their applications in TCI designs.

Virus-associated organosulfur metabolism in human and environmental systems.

Viruses influence the fate of nutrients and human health by killing microorganisms and altering metabolic processes. Organosulfur metabolism and biologically derived hydrogen sulfide play dynamic roles in manifestation of diseases, infrastructure degradation, and essential biological processes. Although microbial organosulfur metabolism is well studied, the role of viruses in organosulfur metabolism is unknown. Here, we report the discovery of 39 gene families involved in organosulfur metabolism encoded by 3,749 viruses from diverse ecosystems, including human microbiomes. The viruses infect organisms from all three domains of life. Six gene families encode for enzymes that degrade organosulfur compounds into sulfide, whereas others manipulate organosulfur compounds and may influence sulfide production. We show that viral metabolic genes encode key enzymatic domains, are translated into protein, and are maintained after recombination, and sulfide provides a fitness advantage to viruses. Our results reveal viruses as drivers of organosulfur metabolism with important implications for human and environmental health.

Lipin-1, a Versatile Regulator of Lipid Homeostasis, Is a Potential Target for Fighting Cancer.

The rewiring of lipid metabolism is a major adaptation observed in cancer, and it is generally associated with the increased aggressiveness of cancer cells. Targeting lipid metabolism is therefore an appealing therapeutic strategy, but it requires a better understanding of the specific roles played by the main enzymes involved in lipid biosynthesis. Lipin-1 is a central regulator of lipid homeostasis, acting either as an enzyme or as a co-regulator of transcription. In spite of its important functions it is only recently that several groups have highlighted its role in cancer. Here, we will review the most recent research describing the role of lipin-1 in tumor progression when expressed by cancer cells or cells of the tumor microenvironment. The interest of its inhibition as an adjuvant therapy to amplify the effects of anti-cancer therapies will be also illustrated.

Decrypting bacterial polyphenol metabolism in an anoxic wetland soil.

Microorganisms play vital roles in modulating organic matter decomposition and nutrient cycling in soil ecosystems. The enzyme latch paradigm posits microbial degradation of polyphenols is hindered in anoxic peat leading to polyphenol accumulation, and consequently diminished microbial activity. This model assumes that polyphenols are microbially unavailable under anoxia, a supposition that has not been thoroughly investigated in any soil type. Here, we use anoxic soil reactors amended with and without a chemically defined polyphenol to test this hypothesis, employing metabolomics and genome-resolved metaproteomics to interrogate soil microbial polyphenol metabolism. Challenging the idea that polyphenols are not bioavailable under anoxia, we provide metabolite evidence that polyphenols are depolymerized, resulting in monomer accumulation, followed by the generation of small phenolic degradation products. Further, we show that soil microbiome function is maintained, and possibly enhanced, with polyphenol addition. In summary, this study provides chemical and enzymatic evidence that some soil microbiota can degrade polyphenols under anoxia and subvert the assumed polyphenol lock on soil microbial metabolism.

Epigenetic Target Fishing with Accurate Machine Learning Models.

Epigenetic targets are of significant importance in drug discovery research, as demonstrated by the eight approved epigenetic drugs for treatment of cancer and the increasing availability of chemogenomic data related to epigenetics. This data represents many structure-activity relationships that have not been exploited thus far to develop predictive models to support medicinal chemistry efforts. Herein, we report the first large-scale study of 26 318 compounds with a quantitative measure of biological activity for 55 protein targets with epigenetic activity. We built predictive models with high accuracy for small molecules' epigenetic target profiling through a systematic comparison of the machine learning models trained on different molecular fingerprints. The models were thoroughly validated, showing mean precisions of up to 0.952 for the epigenetic target prediction task. Our results indicate that the models reported herein have considerable potential to identify small molecules with epigenetic activity. Therefore, our results were implemented as a freely accessible web application.

A Protein-Binding Molecular Photothermal Agent for Tumor Ablation.

Photothermal therapy usually requires a high power density to activate photothermal agent for effective treatment, which inevitably leads to damage to normal tissues and inflammation in tumor tissues. Herein, we rationally design a protein-binding strategy to build a molecular photothermal agent for photothermal ablation of tumor. The synthesized photothermal agent can covalently bind to the thiol groups on the intracellular proteins. The heat generated by the photothermal agent directly destroyed the bioactive proteins in the cells, effectively reducing the heat loss and the molecular leakage. Under a low power density of 0.2 W cm-2 , the temperature produced by the photothermal agent was sufficient to induce apoptosis. In vitro and in vivo experiments showed that the therapeutic effect of photothermal therapy can be efficiently improved with the protein-binding strategy.

Targeting Bromodomain and Extraterminal Proteins for Drug Discovery: From Current Progress to Technological Development.

Bromodomain and extraterminal (BET) proteins bind acetylated lysine residues in histones and nonhistone proteins via tandem bromodomains and regulate chromatin dynamics, cellular processes, and disease procession. Thus targeting BET proteins is a promising strategy for treating various diseases, especially malignant tumors and chronic inflammation. Many pan-BET small-molecule inhibitors have been described, and some of them are in clinical evaluation. Nevertheless, the limited clinical efficacy of the current BET inhibitors is also evident and has inspired the development of new technologies to improve their clinical outcomes and minimize unwanted side effects. In this Review, we summarize the latest protein characteristics and biological functions of BRD4 as an example of BET proteins, analyze the clinical development status and preclinical resistance mechanisms, and discuss recent advances in BRD4-selective inhibitors, dual-target BET inhibitors, proteolysis targeting chimera degraders, and protein-protein interaction inhibitors.

The role of sample preparation in multidimensional gas chromatographic separations for non-targeted analysis with the focus on recent biomedical, food, and plant applications.

In this review, we consider and discuss the affinity and complementarity between a generic sample preparation technique and the comprehensive two-dimensional gas chromatography process. From the initial technical development focus (e.g., on the GC×GC and solid-phase microextraction techniques), the trend is inevitably shifting toward more applied challenges, and therefore, the preparation of the sample should be carefully considered in any GC×GC separation for an overreaching research. We highlight recent biomedical, food, and plant applications (2016-July 2020), and specifically those in which the combination of tailored sample preparation methods and GC×GC-MS has proven to be beneficial in the challenging aspects of non-targeted analysis. Specifically on the sample preparation, we report on gas-phase, solid-phase, and liquid-phase extractions, and derivatization procedures that have been used to extract and prepare volatile and semi-volatile metabolites for the successive GC×GC analysis. Moreover, we also present a milestone section reporting the early works that pioneered the combination of sample preparation techniques with GC×GC for non-targeted analysis.