Quality control and analytic best practices for testing genetic models of sex differences in large populations.

Phenotypic sex-based differences exist for many complex traits. In other cases, phenotypes may be similar, but underlying biology may vary. Thus, sex-aware genetic analyses are becoming increasingly important for understanding the mechanisms driving these differences. To this end, we provide a guide outlining the current best practices for testing various models of sex-dependent genetic effects in complex traits and disease conditions, noting that this is an evolving field. Insights from sex-aware analyses will not only teach us about the biology of complex traits but also aid in achieving the goals of precision medicine and health equity for all.

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.

Unrevealing the connection between real sample analysis and analytical method. The case of cytokines.

Cytokines are compounds that belong to a special class of signaling biomolecules that are responsible for several functions in the human body, being involved in cell growth, inflammatory, and neoplastic processes. Thus, they represent valuable biomarkers for diagnosing and drug therapy monitoring certain medical conditions. Because cytokines are secreted in the human body, they can be detected in both conventional samples, such as blood or urine, but also in samples less used in medical practice such as sweat or saliva. As the importance of cytokines was identified, various analytical methods for their determination in biological fluids were reported. The gold standard in cytokine detection is considered the enzyme-linked immunosorbent assay method and the most recent ones have been considered and compared in this study. It is known that the conventional methods are accompanied by a few disadvantages that new methods of analysis, especially electrochemical sensors, are trying to overcome. Electrochemical sensors proved to be suited for the elaboration of integrated, portable, and wearable sensing devices, which could also facilitate cytokines determination in medical practice.

Bacterial Glycolipid Acting on Protein Transport Across Membranes.

The process of protein transport across membranes involves a variety of factors and has been extensively investigated. Traditionally, proteinaceous translocons and chaperones have been recognized as crucial factors in this process. However, recent studies have highlighted the significant roles played by lipids and a glycolipid present in biological membranes in membrane protein transport. Membrane lipids can influence transport efficiency by altering the physicochemical properties of membranes. Notably, our studies have revealed that diacylglycerol (DAG) attenuates mobility in the membrane core region, leading to a dramatic suppression of membrane protein integration. Conversely, a glycolipid in Escherichia coli inner membranes, named membrane protein integrase (MPIase), enhances integration not only through the alteration of membrane properties but also via direct interactions with membrane proteins. This review explores the mechanisms of membrane protein integration mediated by membrane lipids, specifically DAG, and MPIase. Our results, along with the employed physicochemical analysis methods such as fluorescence measurements, nuclear magnetic resonance, surface plasmon resonance, and docking simulation, are presented to elucidate these mechanisms.

Solid-State Glass Nanopipettes: Functionalization and Applications.

Solid-state glass nanopipettes provide a promising confined space that offers several advantages such as controllable size, simple preparation, low cost, good mechanical stability, and good thermal stability. These advantages make them an ideal choice for various applications such as biosensors, DNA sequencing, and drug delivery. In this review, we first delve into the functionalized nanopipettes for sensing various analytes and the methods used to develop detection means with them. Next, we provide an in-depth overview of the advanced functionalization methodologies of nanopipettes based on diversified chemical kinetics. After that, we present the latest state-of-the-art achievements and potential applications in detecting a wide range of targets, including ions, molecules, biological macromolecules, and single cells. We examine the various challenges that arise when working with these targets, as well as the innovative solutions developed to overcome them. The final section offers an in-depth overview of the current development status, newest trends, and application prospects of sensors. Overall, this review provides a comprehensive and detailed analysis of the current state-of-the-art functionalized nanopipette perception sensing and development of detection means and offers valuable insights into the prospects for this exciting field.

N-Aryl-DABCO Salts as an Unprecedented Sensing Platform for the Detection of Thiols and Selenols.

Quaternary N-aryl-DABCO salts were introduced for the first time as a highly selective sensing platform for thiols and selenols. By employing this platform, a highly sensitive coumarin based "off-on" fluorescent probe was designed and synthesized. The probe possesses a good solubility in water, low background fluorescence, and, most importantly, demonstrates high selectivity to aryl thiols and selenols over their aliphatic counterparts and other common nucleophiles. A dramatic increase in fluorescence intensity is achieved through the selective cleavage of the quaternized DABCO-ring, yielding a piperazine derivatives with a high fluorescence quantum yield (~72 %). Moreover, stability of the probe to the most used reducing agents DTT and TCEP was demonstrated. The limits of detection for p-thiocresol and phenyl selenide were evaluated to be 22 nM and 6 nM, respectively.

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.

The hidden treasures in endophytic fungi: a comprehensive review on the diversity of fungal bioactive metabolites, usual analytical methodologies, and applications.

This review provides a comprehensive overview of the key aspects of the natural metabolite production by endophytic fungi, which has attracted significant attention due to its diverse biological activities and wide range of applications. Synthesized by various fungal species, these metabolites encompass compounds with therapeutic, agricultural, and commercial significance. We delved into strategies and advancements aimed at optimizing fungal metabolite production. Fungal cultivation, especially by Aspergillus, Penicillium, and Fusarium, plays a pivotal role in metabolite biosynthesis, and researchers have explored both submerged and solid-state cultivation processes to harness the full potential of fungal species. Nutrient optimization, pH, and temperature control are critical factors in ensuring high yields of the targeted bioactive metabolites especially for scaling up processes. Analytical methods that includes High-Performance Liquid Chromatography (HPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), Gas Chromatography-Mass Spectrometry (GC-MS), Nuclear Magnetic Resonance (NMR), and Mass Spectrometry (MS), are indispensable for the identification and quantification of the compounds. Moreover, genetic engineering and metabolic pathway manipulation have emerged as powerful tools to enhance metabolite production and develop novel fungal strains with increased yields. Regulation and control mechanisms at the genetic, epigenetic, and metabolic levels are explored to fine-tune the biosynthesis of fungal metabolites. Ongoing research aims to overcome the complexity of the steps involved to ensure the efficient production and utilization of fungal metabolites.

PFAS ghosts: how to identify, evaluate, and exorcise new and existing analytical interference.

With increasing public awareness of PFAS, and their presence in biological and environmental media across the globe, comes a matching increase in the number of PFAS monitoring studies. As more matrices and sample cohorts are examined, there are more opportunities for matrix interferents to appear as PFAS where there are none (i.e., "seeing ghosts"), impacting subsequent reports. Addressing these ghosts is vital for the research community, as proper analytical measurements are necessary for decision-makers to understand the presence, levels, and potential risks associated with PFAS and protect human and environmental health. To date, PFAS interference has been identified in several matrices (e.g., food, shellfish, blood, tissue); however, additional unidentified interferents are likely to be observed as PFAS research continues to expand. Therefore, the aim of this commentary is several fold: (1) to create and support a publicly available dataset of all currently known PFAS analytical interferents, (2) to allow for the expansion of that dataset as more sources of interference are identified, and (3) to advise the wider scientific community on how to both identify and eliminate current or new analytical interference in PFAS analyses.

A state-of-the-science review of analytical methods for urinary dialkylphosphate metabolites in the assessment of exposure to organophosphate pesticides: From 2000 to 2022.

The general population and workers are exposed to organophosphate insecticides, one of the leading chemical classes of pesticides used in rural and urban areas. This paper aims to conduct an integrative review of the most used analytical methods for identifying and quantifying dialkylphosphate-which are metabolites of organophosphate insecticides-in the urine of exposed workers, discussing their advantages, limitations and applicability. Searches utilized the PubMed, the Scientific Electronic Library Online and the Brazilian Digital Library of Theses and Dissertations databases between 2000 and 2021. Twenty-five studies were selected. The extraction methods most used were liquid-liquid extraction (LLE) (36%) and solid-phase extraction (SPE) (36%), with the SPE being more economical in terms of time and amount of solvents needed, and presenting the best percentage of recovery of analytes, when compared with LLE. Nineteen studies (76%) used the gas chromatography method of separation, and among these, 12 records (63%) indicated mass spectrometry used as a detection technology (analyzer). Studies demonstrate that dialkylphosphates are sensitive and representative exposure biomarkers for environmental and occupational organophosphate exposure.

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.

An insight into recent updates on analytical techniques for bioactive alkaloids.

INTRODUCTION: Alkaloids represent a wide class of naturally existing nitrogen-containing organic compounds having diverse biological activities. They are primary bioactive substances extracted from diverse plant parts. Due to their diverse biological activities, they are frequently used as medicines. The alkaloids have diverse pharmacological impacts on the human body; alkaloids are used for prevention, treatment, and reduction of discomfort associated with chronic illnesses. As most alkaloids exist in plants in complex form, combined with numerous other natural plant components, it is essential to recognize and characterize these molecules using different analytical techniques. OBJECTIVES: We aimed to review the literature on the methods and protocols for the analysis of naturally occurring alkaloids. METHODS: We carried out a literature survey using the PubMed, Scopus, and Google Scholar databases and other relevant published materials. The keywords used in the searches were "alkaloids," "analytical methods," "HPLC method," "GC method," "electrochemical methods," and "bioanalytical methods," in various combinations. RESULTS: In this article, several classes of alkaloids are presented, along with their biological activities. Moreover, it includes a thorough explanation of chromatographic techniques, hyphenated techniques, electrochemical techniques, and current trending analytical methods utilized for the isolation, identification, and comprehensive characterization of alkaloids. CONCLUSIONS: The various analytical techniques play an important role in the identification as well as the characterization of various alkaloids from plants, plasma samples, and urine samples. The hyphenation of various chromatographic techniques with mass spectrometry and NMR spectroscopy plays a crucial role in the characterization of unknown compounds.

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.

Definition, detection, and tracking of nanowaste in foods: Challenges and perspectives.

Commercial applications of nanotechnology in the food industry are rapidly increasing. Accordingly, there is a simultaneous increase in the amount and diversity of nanowaste, which arise as byproducts in the production, use, disposal, or recycling processes of nanomaterials utilized in the food industry. The potential risks of this nanowaste to human health and the environment are alarming. It is of crucial significance to establish analytical methods and monitoring systems for nanowaste to ensure food safety. This review provides comprehensive information on nanowaste in foods as well as comparative material on existing and new analytical methods for the detection of nanowaste. The article is specifically focused on nanowaste in food systems. Moreover, the current techniques, challenges as well as potential use of new and progressive methods are underlined, further highlighting advances in technology, collaborative efforts, as well as future perspectives for effective nanowaste detection and tracking. Such detection and tracking of nanowaste are required in order to effectively manage this type ofwasted in foods. Although there are devices that utilize spectroscopy, spectrometry, microscopy/imaging, chromatography, separation/fractionation, light scattering, diffraction, optical, adsorption, diffusion, and centrifugation methods for this purpose, there are challenges to be overcome in relation to nanowaste as well as food matrix and method characteristics. New technologies such as radio-frequency identification, Internet of things, blockchain, data analytics, and machine learning are promising. However, the cooperation of international organizations, food sector, research, and political organizations is needed for effectively managing nanowaste. Future research efforts should be focused on addressing knowledge gaps and potential strategies for optimizing nanowaste detection and tracking processes.

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.

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.

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.

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.

Illuminating Sub-Cellular Organelles by Small Molecule AIEgens.

Sub-cellular organelles play a critical role in a myriad biological phenomena. Consequently, organelle structures and functions are invariably highjacked in diverse diseases including metabolic disorders, aging, and cancer. Hence, illuminating organelle dynamics is crucial in understanding the diseased states as well as developing organelle-targeted next generation therapeutics. In this review, we outline the novel small molecules which show remarkable aggregation-induced emission (AIE) properties due to restriction in intramolecular motion (RIM). We outline the examples of small molecules developed to image organelles like mitochondria, endoplasmic reticulum (ER), Golgi, lysosomes, nucleus, cell membrane and lipid droplets. These AIEgens have tremendous potential for next-generation phototherapy.

Recent Advances in Strategies for Imaging Detection and Intervention of Cellular Senescence.

Cellular senescence is a stable cell cycle arrest state that can be triggered by a wide range of intrinsic or extrinsic stresses. Increased burden of senescent cells in various tissues is thought to contribute to aging and age-related diseases. Thus, the detection and interventions of senescent cells are critical for longevity and treatment of disease. However, the highly heterogeneous feature of senescence makes it challenging for precise detection and selective clearance of senescent cells in different age-related diseases. To address this issue, considerable efforts have been devoted to developing senescence-targeting molecular theranostic strategies, based on the potential biomarkers of cellular senescence. Herein, we review recent advances in the field of anti-senescence research and highlight the specific visualization and elimination of senescent cells. Additionally, the challenges in this emerging field are outlined.