Rational Molecular Design of a Fluorescent Probe for Selectively Sensing Human Cytochrome P450 2D6.

Cytochrome P450 2D6 (CYP2D6) is a key enzyme that mediates the metabolism of various drugs and endogenous substances in humans. However, its biological role in drug-drug interactions especially mechanism-based inactivation (MBI), and various diseases remains poorly understood, owing to the lack of molecular tools suitable for selectively monitoring CYP2D6 in complex biological systems. Herein, using a tailored molecular strategy, we developed a fluorescent probe BDPM for CYP2D6. BDPM exhibits excellent specificity and imaging capability for CYP2D6, making it suitable for the real-time monitoring of endogenous CYP2D6 activity in living bio-samples. Therefore, our tailored strategy proved useful for constructing the highly selective and enzyme-activated fluorescent probes. BDPM as a molecular tool to explore the critical roles of CYP2D6 in the pathogenesis of diseases, high-throughput screening of inhibitors and intensive investigation of CYP2D6-induced MBI in natural systems.

Real-Space Visualization of Charged Polymer Network of Hydrogel by Double Network Strategy and Mineral Staining.

Hydrogels consist of three-dimensional (3D) and complicated polymer networks that determine their physical properties. Among the methods for structural analyses of hydrogels, the real-space imaging of a polymer network of hydrogels on a nanometer scale is one of the optimal methods; however, it is highly challenging. In this study, we propose a direct observation method for cationic polymer networks using transmission electron microscopy (TEM). By combining the double network strategy and the mineral staining technique, we overcame the challenges of polymer aggregation and the low electron density of the polymer. An objective cationic network was incorporated into a neutral skeleton network to suppress shrinkage during subsequent staining. Titania mineralization along the cationic polymer strands provided sufficient electron density for the objective polymer network for TEM observation. This observation method enables the visualization of local structures in real space and plays a complementary role to scattering methods for soft matter structure analysis.

A new class of contaminants of concern? A comprehensive review of liquid crystal monomers.

Liquid crystal monomers (LCMs) are a class of emerging contaminants of concern predicted to be persistent, bioaccumulative and toxic (PBT). Being one of the key components in liquid crystal displays (LCDs), the disposal of LCD containing devices is closely related to the emission of LCMs into the environment. LCMs have been detected in a wide range of environmental matrices including dust, sediment, soil, sewage leachate, and air, with concentration ranges between 17 and 2121 ng/g found in indoor residential dust. Furthermore, they have been detected on human skin at concentrations up to 2,071,000 ng/m2 and in the serum of e-waste dismantling workers, at concentrations ranging from 3.9 to 276 ng/mL. Despite the far-reaching contamination of these compounds, there is limited knowledge of their environmental behaviour, fate, and toxicity. Model predictions show that 297 of 330 LCMs are persistent and bioaccumulative compounds, with many more indicated as being toxic. However, current knowledge of their physicochemical and PBT properties is largely restricted to theoretical predictions and limited to a small number of experimental toxicity studies. As an emerging class of contaminants of concern, a lack of standardisation between studies was identified as a key challenge to advancing the state of knowledge of these compounds. Not only are harmonised analytical methods for their determination and quantification in environmental media yet to be established, but there is also a need for a universal abbreviation system. To further harmonise the reporting of data on LCMs we propose reporting the sum concentration of ten priority LCMs, selected on the basis detection frequency, toxicity and potential for human exposure. Of the ten priority LCMs five are fluorinated biphenyls and analogues, four are biphenyls/bicyclohexyls and analogues and one is a cyanobiphenyl.

A systematic review of the botany, traditional use, phytochemistry, analytical methods, pharmacological effects and pharmacokinetics of NOTOPTERYGII RHIZOMA ET RADIX.

ETHNOPHARMACOLOGICAL RELEVANCE: NOTOPTERYGII RHIZOMA ET RADIX (NRR), a traditional Chinese medicine (TCM), has been utilized in China for millennia. Thriving in high-altitude regions with cold climates, wild NRR has been heavily exploited for its significant economic worth, particularly in the medical sector. THE AIM OF THE REVIEW: This paper presents a comprehensive review of the botany, traditional uses, phytochemistry, analytical methods, quality control, processing methods, pharmacological effects, and pharmacokinetics of NRR. These findings offer valuable insights for future research endeavors and establish a solid groundwork for the judicious clinical utilization of NRR. MATERIALS AND METHOD: The related information for NRR comes from scientific databases (such as Baidu Scholar, CNKI, Google Scholar, PubMed, Science Direct, Web of Science, SciFinder Scholar, Chinese Herb Classics, Chinese Pharmacopeia, PhD and MSC Dissertations, etc.). RESULTS: Currently, components isolated from NRR are identified as coumarins, volatile oils, organic acids, flavonoids, glycosides, polyacetylenes, and trace elements. Most compounds are analyzed using HPLC and GC techniques. NRR exhibits a broad spectrum of pharmacological effects, such as anti-inflammatory, analgesic, antipyretic, antitumor, antiviral, antibacterial, immunosuppressive activities, as well as promoting blood circulation, removing blood stasis, providing neuroprotection, and liver protection. CONCLUSION: The research on NRR in phytochemistry and pharmacology has made great progress, and some traditional uses have been proven by modern pharmacology. However, because the complex chemical composition of NRR has not been effectively related to its pharmacological action, its mechanism of action has not been clearly expounded. In this review, the processing methods of NRR are summarized, and the exploration of further strengthening the processing mechanism of NRR is put forward, which provides some theoretical help for the clinical application of NRR. Furthermore, the complex chemical composition of NRR makes quality control difficult, so we must study its quality control thoroughly. In order to better develop and utilize NRR, we should establish a reasonable, reliable, and accurate quality control standard, and focus on the relationship between its active components and pharmacodynamic indicators and the study of its mechanism of pharmacological effects.

Directional Bias in Molecular Photogearing Evidenced by LED-Coupled Chiral Cryo-HPLC.

Molecular gearing systems are technomimetic nanoscale analogues to complex geared machinery in the macroscopic world and are likewise defined as systems incorporating intermeshed elements which perform correlated rotational motions by mechanical engagement. Only recently, new methods to actively drive molecular gearing motions instead of relying on passive thermal activation have been developed. Further progress in this endeavor will pave the way for unidirectional molecular gearing devices with a distinct type of molecular machine awaiting its realization. Within this work an essential step towards this goal is achieved by evidencing directional biases for the light-induced rotations in molecular photogear system 1. Using a custom-designed LED-coupled chiral cryo-HPLC setup for the in-situ irradiation of enantiomeric analytes, an intrinsic selectivity for clockwise or counterclockwise rotations was elucidated experimentally. Significant directional biases in the photogearing processes and light-induced single bond rotations (SBRs) are observed for photogear 1 with directional preferences of up to 4.8:1. Harnessing these effects will allow to rationally design and construct a fully directional molecular gearing motor in the future.

Volatilomics of Fruit Wines.

Volatilomics is a scientific field concerned with the evaluation of volatile compounds in the food matrix and methods for their identification. This review discusses the main groups of compounds that shape the aroma of wines, their origin, precursors, and selected metabolic pathways. The paper classifies fruit wines into several categories, including ciders and apple wines, cherry wines, plum wines, berry wines, citrus wines, and exotic wines. The following article discusses the characteristics of volatiles that shape the aroma of each group of wine and the concentrations at which they occur. It also discusses how the strain and species of yeast and lactic acid bacteria can influence the aroma of fruit wines. The article also covers techniques for evaluating the volatile compound profile of fruit wines, including modern analytical techniques.

Nitrophenols in the environment: An update on pretreatment and analysis techniques since 2017.

Nitrophenols, a versatile intermediate, have been widely used in leather, medicine, chemical synthesis, and other fields. Because these components are widely applied, they can enter the environment through various routes, leading to many hazards and toxicities. There has been a recent surge in the development of simple, rapid, environmentally friendly, and effective techniques for determining these environmental pollutants. This review provides a comprehensive overview of the latest research progress on the pretreatment and analysis methods of nitrophenols since 2017, with a focus on environmental samples. Pretreatment methods include liquid-liquid extraction, solid-phase extraction, dispersive extraction, and microextraction methods. Analysis methods mainly include liquid chromatography-based methods, gas chromatography-based methods, supercritical fluid chromatography. In addition, this review also discusses and compares the advantages/disadvantages and development prospects of different pretreatment and analysis methods to provide a reference for further research.

Emerging pollutant in surface water bodies: a review on monitoring, analysis, mitigation measures and removal technologies of micro-plastics.

Water bodies play a crucial role in supporting life, maintaining the environment, and preserving the ecology for the people of India. However, in recent decades, human activities have led to various alterations in aquatic environments, resulting in environmental degradation through pollution. The safety of utilizing surface water sources for drinking and other purposes has come under intense scrutiny due to rapid population growth and industrial expansion. Surface water pollution due to micro-plastics (MPs) (plastics < 5 mm in size) is one of the emerging pollutants in metropolitan cities of developing countries because of its utmost resilience and synthetic nature. Recent studies on the surface water bodies (river, pond, Lake etc.) portrait the correlation between the MPs level with different parameters of pollution such as specific conductivity, total phosphate, and biological oxygen demand. Fibers represent the predominant form of MPs discovered in surface water bodies, exhibiting fluctuations across seasons. Consequently, present study prioritizes understanding the adaptation, prevalence, attributes, fluctuations, and spatial dispersion of MPs in both sediment and surface water environments. Furthermore, the study aims to identify existing gaps in the current understanding and underscore opportunities for future investigation. From the present study, it has been reported that, the concentration of MPs in the range of 0.2-45.2 items/L at the Xisha Islands in the south China sea, whereas in India it was found in the range of 96 items/L in water samples and 259 items/kg in sediment samples. This would certainly assist the urban planners in achieving sustainable development goals to mitigate the increasing amount of emergent pollutant load.

Microplastic-mediated environmental behavior of metal contaminants: mechanism and implication.

Microplastics (MPs) and metals are currently two of the most concerning environmental pollutants due to their persistent nature and potential threats to ecosystems and human health. This review examines the intricate interactions between MPs and metals in diverse environmental compartments, including aquatic, terrestrial, and atmospheric environments by focusing on the complex processes of adsorption and desorption and the mechanisms that govern these interactions. MPs act as carriers and concentrators of metals in aquatic and terrestrial environments, affecting the bioavailability and toxicity of these contaminants to aquatic and terrestrial organisms. This review highlights the existing challenges and constraints associated with current analytical methods, including microscopy, spectroscopy, and isotherm models in studying microplastic-heavy metal interactions. Moreover, we identified the knowledge gaps and future research directions that can enhance our understanding of the dynamic interplay between MPs and metals in various environmental settings.

Analytical methods for quantifying PS and PVC Nanoplastic attachment to activated sludge Bacteria and their impact on community structure.

Nanoplastics are anticipated to be ubiquitous in various environmental compartments. However, challenges in analytical methods hinder our understanding of risks related to specific nanplastics characteristics such as size and chemical compositions, and interactions between nanoplastics and microorganisms. In this study, we applied fit-for-purpose analytical methods and techniques to understand how nanoplastic chemical composition influences their interaction with bacteria collected from activated sludge. When exposed to polystyrene (PS) and polyvinyl chloride (PVC) nanoplastics for 5 days, the nanoplastics attached to the bacteria. Specifically, on day 1, there was a significant predominance of PS nanoplastics over PVC ones of similar size and shape, possibly due to differences in their chemical composition. After 5 days, there is a substantial decrease in nanoplastics attached to bacteria, suggesting bacterial defence mechanisms may reduce particles attachment over time. The overall bacterial community structure demonstrated a high degree of resilience. This resilience highlights the ability of microbial communities to maintain their structure despite nanoplastic stressors, as evidenced by consistent alpha diversity, PCoA, and PERMANOVA results. Understanding these mechanisms is crucial for assessing nanoplastic fate and thus environmental impacts.

Diagnostic Aspects of Paraquat in the Forensic Toxicology: A Systematic Review.

Background: Paraquat (N, N-dimethyl-4,4-bipyridinium dichloride) is a nonselective, fast-acting, and contact chemical herbicide used extensively for weed control. It has high acute oral toxicity, the ability to accumulate in the lungs, and a high potential for pulmonary fibrosis after its intoxication. The present systematic review focuses on evaluating diagnostic aspects of paraquat (PQ) in forensic toxicology. Methods: Evaluation of the literature according to the following criteria: only human studies published from February 1971 to March 2022 which are in English on the following databases: 1) Medline/PubMed/MeSH search words: ((Methyl viologen [Title/Abstract]) OR (paraquat [MeSH Terms])) AND (forensic [Title/Abstract]); 2) Scopus Keywords related to the study aim included forensic toxicology, paraquat, Methyl viologen; 3) Web of Science. Keywords related to the study aim included forensic toxicology, paraquat, and Methyl viologen. Results: Thirty full-text articles were included. The results of our review indicate plasma and urine are more used for identifying PQ, and liver, lung, and gastric fluid are important in postmortem cases. Preparation methods, including liquid-liquid extraction (LLE), solid-phase extraction, and acetonitrile-precipitated protein, are often required for removing interfering substances. Chromatographic methods, among other analytical techniques, are more sensitive, specific, and applicable. Conclusion: Our review suggests that plasma, urine, and lungs should be prioritized in sampling. Solid-phase extraction has better recovery than LLE in many samples. Colorimetric methods are not used much today, and radioimmunoassay (RIA) has limited application despite its high sensitivity. Gas and liquid chromatography methods appear to offer the best approach for the analysis of PQ.

Curcuma Longa: Nutraceutical Use and Association With Nanotechnology.

Curcumin is a natural product found in the rhizome of Curcuma longa (L.) and other Curcuma spp. As a lipophilic molecule, it has greater affinity for polar, non-polar, alkaline, or extremely acidic organic solvents. Several studies indicate that curcumin has several benefits for human health, for example, against degenerative diseases, cancer, and infectious diseases. To obtain a quality product with nutraceutical properties, it is necessary to know its physicochemical characteristics and preserve it from cultivation until ingestion by the human. However, its low solubility leads to low absorption; in this context, nanotechnological systems can contribute to increase curcumin bioavailability. This review aims to highlight important issues in all stages that curcumin goes through: from aspects related to its extraction to its association with nanotechnology. Although curcumin extraction process is already well established, it is possible to observe more and more research focused on increasing yield and being more environmentally friendly. Further, curcumin's low absorption is notable due to its physicochemical characteristics, mainly due to its low aqueous solubility. However, its association with nanotechnology shows to be promising and an increasingly growing trend because the use of this "Indian solid gold" is the hope of many patients.

The application of PTR-MS and non-targeted analysis to characterize VOCs emitted from a plastic recycling facility fire.

BACKGROUND: On April 11th, 2023, the My Way Trading (MWT) recycling facility in Richmond, Indiana caught fire, mandating the evacuation of local residents and necessitating the U.S. Environmental Protection Agency (EPA) to conduct air monitoring. The EPA detected elevated levels of plastic combustion-related air pollutants, including hydrogen cyanide and benzene. OBJECTIVE: We aimed to identify these and other volatile organic compounds (VOCs) present as well as to identify the potential hazard of each compound for various human health effects. METHODS: To identify the VOCs, we conducted air monitoring at sites within and bordering the evacuation zone using proton transfer reaction mass spectrometry (PTR-MS) and non-targeted analysis (NTA). To facilitate risk assessment of the emitted VOCs, we used the EPA Hazard Comparison Dashboard. RESULTS: We identified 46 VOCs, within and outside the evacuation zone, with average detection levels above local background levels measured in Middletown, OH. Levels of hydrogen cyanide and 4 other VOCs were at least 1.8-fold higher near the incidence site in comparison to background levels and displayed unique temporal and spatial patterns. The 46 VOCs identified had the highest hazardous potential for eye and skin irritation, with approximately 45% and 39%, respectively, of the VOCs classified as high and very high hazards for these endpoints. Notably, all detected VOC levels were below the hazard thresholds set for single VOC exposures; however, hazard thresholds for exposure to VOC mixtures are currently unclear. IMPACT: This study serves as a proof-of-concept that PTR-MS coupled with NTA can facilitate rapid identification and hazard assessment of VOCs emitted following anthropogenic disasters. Furthermore, it demonstrates that this approach may augment future disaster responses to quantify additional VOCs present in complex combustion mixtures.

Comprehensive overview of analytical and bioanalytical methodologies for the opioid analgesics - Tramadol and combinations.

Synthetic opioids like Tramadol are used to treat mild to moderate pain. Its ability to relieve pain is about a tenth that of morphine. Furthermore, Tramadol shares similar effects on serotonin and norepinephrine to several antidepressants known as serotonin-norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine and duloxetine. The present review paper discusses the recent developments in analytical methods for identifying drugs in pharmaceutical preparations and toxicological materials, such as blood, saliva, urine, and hair. In recent years, a wide variety of analytical instruments, including capillary electrophoresis, NMR, UV-visible spectroscopy, HPTLC, HPLC, LC-MS, GC, GC-MS, and electrochemical sensors, have been used for drug identification in pharmaceutical preparations and toxicological samples. The primary quantification techniques currently employed for its quantification in various matrices are highlighted in this research.

Paper-in-Tip Bipolar Electrospray Mass Spectrometry for Real-Time Chemical Reaction Monitoring.

Capturing short-lived intermediates at the molecular level is key to understanding the mechanism and dynamics of chemical reactions. Here, we have developed a paper-in-tip bipolar electrolytic electrospray mass spectrometry platform, in which a piece of triangular conductive paper incorporated into a plastic pipette tip serves not only as an electrospray emitter but also as a bipolar electrode (BPE), thus triggering both electrospray and electrolysis simultaneously upon application of a high voltage. The bipolar electrolysis induces a pair of redox reactions on both sides of BPE, enabling both electro-oxidation and electro-reduction processes regardless of the positive or negative ion mode, thus facilitating access to complementary structural information for mechanism elucidation. Our method enables real-time monitoring of transient intermediates (such as N,N-dimethylaniline radical cation, dopamine o-quinone (DAQ) and sulfenic acid with half-lives ranging from microseconds to minutes) and transient processes (such as DAQ cyclization with a rate constant of 0.15 s-1). This platform also provides key insights into electrocatalytic reactions such as Fe (III)-catalyzed dopamine oxidation to quinone species at physiological pH for neuromelanin formation.

Contamination of ultraviolet absorbers in food: toxicity, analytical methods, occurrence and risk assessments.

Ultraviolet (UV) absorbers are chemical substances that are widely used as defenses against the damaging effects of solar radiations. UV absorbers, despite their benefits, are categorized as emerging pollutants because they have been demonstrated to be mutagenic, toxic, pseudo-persistent, bio-accumulative, and to have strong estrogenic effects. Because of their common use in personal care products, they continue to enter the environment. Several food samples, particularly those derived from aquatic sources, have been found to be contaminated with these compounds. Toxic effects on aquatic life, such as metabolic imbalance and developmental toxicity, result from the continued presence of UV absorbers in aquatic bodies. In addition, the degree of exposure to these pollutants in foods should be examined because there are certain risks associated with their consumption by humans. Therefore, this review focuses on the toxicity, analytical techniques, occurrence, and risk assessments of UV absorbers found in food.

Chromatographic Methods for the Determination of Glyphosate in Cereals Together with a Discussion of Its Occurrence, Accumulation, Fate, Degradation, and Regulatory Status.

The European Union's recent decision to renew the authorization for the use of glyphosate until 15 December 2033 has stimulated scientific discussion all around the world regarding its toxicity or otherwise for humans. Glyphosate is a chemical of which millions of tons have been used in the last 50 years worldwide to dry out weeds in cultivated fields and greenhouses and on roadsides. Concern has been raised in many areas about its possible presence in the food chain and its consequent adverse effects on health. Both aspects that argue in favor of toxicity and those that instead may indicate limited toxicity of glyphosate are discussed here. The widespread debate that has been generated requires further investigations and field measurements to understand glyphosate's fate once dispersed in the environment and its concentration in the food chain. Hence, there is a need for validated analytical methods that are available to analysts in the field. In the present review, methods for the analytical determination of glyphosate and its main metabolite, AMPA, are discussed, with a specific focus on chromatographic techniques applied to cereal products. The experimental procedures are explained in detail, including the cleanup, derivatization, and instrumental conditions, to give the laboratories involved enough information to proceed with the implementation of this line of analysis. The prevalent chromatographic methods used are LC-MS/MS, GC-MS/SIM, and GC-MS/MS, but sufficient indications are also given to those laboratories that wish to use the better performing high-resolution MS or the simpler HPLC-FLD, HPLC-UV, GC-NPD, and GC-FPD techniques for screening purposes. The concentrations of glyphosate from the literature measured in wheat, corn, barley, rye, oats, soybean, and cereal-based foods are reported, together with its regulatory status in various parts of the world and its accumulation mechanism. As for its accumulation in cereals, the available data show that glyphosate tends to accumulate more in wholemeal flours than in refined ones, that its concentration in the product strictly depends on the treatment period (the closer it is to the time of harvesting, the higher the concentration), and that in cold climates, the herbicide tends to persist in the soil for a long time.

Phthalate esters in clothing: A review.

Phthalate esters (PAEs) are widely used as plasticizers to enhance the flexibility and durability of different consumer products, including clothing. However, concerns have been raised about the potential adverse health effects associated with the presence of phthalates in textiles, such as endocrine disruption, reproductive toxicity and potential carcinogenicity. Based on examination of more than 120 published articles, this paper presents a comprehensive review of studies concerning the phthalate content in clothing and other textile products, with special emphasis on those conducted in the last decade (2014-2023). The types and role of PAEs as plasticizers, the relevant legislation in different countries (emphasizing the importance of monitoring PAE levels in clothing to protect consumer health) and the analytical methods used for PAE determination are critically evaluated. The review also discusses the models used to evaluate exposure to PAEs and the associated health risks. Finally, the study limitations and challenges related to determining the phthalate contents of textile products are considered.

Comparison of emissions across tobacco products: A slippery slope in tobacco control.

In this narrative review, we highlight the challenges of comparing emissions from different tobacco products under controlled laboratory settings (using smoking/vaping machines). We focus on tobacco products that generate inhalable smoke or aerosol, such as cigarettes, cigars, hookah, electronic cigarettes, and heated tobacco products. We discuss challenges associated with sample generation including variability of smoking/vaping machines, lack of standardized adaptors that connect smoking/vaping machines to different tobacco products, puffing protocols that are not representative of actual use, and sample generation session length (minutes or number of puffs) that depends on product characteristics. We also discuss the challenges of physically characterizing and trapping emissions from products with different aerosol characteristics. Challenges to analytical method development are also covered, highlighting matrix effects, order of magnitude differences in analyte levels, and the necessity of tailored quality control/quality assurance measures. The review highlights two approaches in selecting emissions to monitor across products, one focusing on toxicants that were detected and quantified with optimized methods for combustible cigarettes, and the other looking for product-specific toxicants using non-targeted analysis. The challenges of data reporting and statistical analysis that allow meaningful comparison across products are also discussed. We end the review by highlighting that even if the technical challenges are overcome, emission comparison may obscure the absolute exposure from novel products if we only focus on relative exposure compared to combustible products.

Current Analytical Methods for the Sensitive Assay of New-Generation Ovarian Cancer Drugs in Pharmaceutical and Biological Samples.

Ovarian cancer, which affects the female reproductive organs, is one of the most common types of cancer. Since this type of cancer has a high mortality rate from gynaecological cancers, the scientific community shows great interest in studies on its treatment. Chemotherapy, radiotherapy, and surgical treatment methods are used in its treatment. In the absence of targeted treatments in these treatment methods, side effects occur in patients, and patients show resistance to the drug. In addition, the underlying causes of ovarian cancer are still not fully known. The scientific world thinks that genetic factors, environmental conditions, and consumed foods may cause this cancer. The most important factor in the treatment of ovarian cancer is early diagnosis. Therefore, the drugs used in the treatment of ovarian cancer are platinum-based anticancer drugs. In addition to these drugs, the most preferred treatment method recently is targeted treatment approaches using poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors. In this review, studies on the sensitive analysis of the treatment methods of these new-generation drugs used in the treatment of ovarian cancer have been comprehensively examined. In addition, the basic features, structural aspects, and biological data of analytical methods used in treatments with new-generation drugs are explained. Analytical studies carried out in the literature in recent years aim to show future developments in how these new-generation drugs are used today and to guide future studies by comprehensively examining and explaining the structure-activity relationship, mechanism of action, toxicity, and pharmacokinetic studies. Finally, in this study, the methods used in the analysis of drugs used in the treatment of ovarian cancer and the studies conducted between 2015 and 2023 were discussed in detail.