Toxic Form Research Articles

Communicating with Stakeholders to Identify High-Impact Research Directions for Non-Targeted Analysis.

Non-targeted analysis (NTA) using high-resolution mass spectrometry without defined chemical targets has the potential to expand and improve chemical monitoring in many fields. Despite rapid advancements within the research community, NTA methods and data remain underutilized by many potential beneficiaries. To better understand barriers toward widespread adoption, the Best Practices for Non-Targeted Analysis (BP4NTA) working group conducted focus group meetings and follow-up surveys with scientists (n = 61) from various sectors (e.g., drinking water utilities, epidemiologists, n = 9) where NTA is expected to provide future value. Meeting participants included producers and end-users of NTA data with a wide range of familiarity with NTA methods and outputs. Discussions focused on identifying specific barriers that limit adoption and on setting NTA product development priorities. Stated priorities fell into four major categories: 1) education and training materials; 2) QA/QC frameworks and study design guidance; 3) accessible compound databases and libraries; and 4) NTA data linkages with chemical fate and toxicity information. Based on participant feedback, this manuscript proposes research directions, such as standardization of training materials, that BP4NTA and other institutions can pursue to expand NTA use in various application scenarios and decision contexts.

Microbe-assisted phytoremediation for sustainable management of heavy metal in wastewater - A green approach to escalate the remediation of heavy metals.

Water pollution from Heavy metal (HM) contamination poses a critical threat to environmental sustainability and public health. Industrial activities have increased the presence of HMs in wastewater, necessitating effective remediation strategies. Conventional methods like chemical precipitation, ion exchange, adsorption, and membrane filtration are widely used but possess various limitations. These include high costs, environmental impacts, and the potential for generating secondary pollutants, highlighting the need for sustainable alternatives. Phytoremediation, enhanced by microbial interactions, offers an eco-friendly solution to this issue. The unique physiological and biochemical traits of plants, combined with microbial metabolic capabilities, enable efficient uptake and detoxification of HMs. Microbial enzymes play a crucial role in these processes by breaking down complex compounds, enhancing HM bioavailability, and facilitating their conversion into less toxic forms. Synergistic interactions between root-associated microbes and plants further improves metal absorption and stabilization, boosting phytoremediation efficiency. However, challenges remain, including the limited bioavailability of contaminants and plant resilience in highly polluted environments. Recent advancements focus on improving microbial-assisted phytoremediation through mechanisms like bioavailability facilitation, phytoextraction, and phytostabilization. Genetic engineering facilitates the altering of genes that control plant immune responses and growth which improves the ability of plants to interact beneficially with microbes to thrive in HM rich environments while efficiently cleaning contaminated wastewater. This review examines these strategies and highlights future research directions to enhance wastewater remediation using phytoremediation technologies.

Solar-based technologies for removing potentially toxic metals from water sources: a review.

Technological advances have led to a proportional increase in the deposition of contaminants across various environmental compartments, including water sources. Heavy metals, also known as potentially toxic metals, are of particular concern due to their significant harmful impacts on environmental and human health. Among the available methods for mitigating the threat of these metals in water, solar radiation-based technologies stand out for their cleanliness, cost-effectiveness, and efficiency in removing or reducing the toxicity of heavy metals. The performance and productivity of these methods in removing heavy metals such as arsenic (As), chromium (Cr), mercury (Hg), and uranium (U) from water still need to be comprehensively synthesized. Thus, this work aims to address that gap. The performance, potential, and challenges of real-world applications of conventional solar stills (CSS), membrane-based solar stills, and solar heterogeneous photocatalysis are concisely summarized and critically reviewed. CSS and membrane-based stills are highly effective (efficacy > 98%) in removing and capturing heavy metals from water. However, structural and functional improvements are needed to enhance productivity (especially for CSS) and usability in real-world environmental remediation and drinking water supply scenarios. Solar heterogeneous photocatalysis is highly effective in removing and/or converting As, Cr, Hg, and U into their non-toxic or less toxic forms, which subsequent processes can easily remove. Further research is necessary to evaluate the safety of photocatalytic materials, their integration into scalable solar reactors, and their usability in real-world environmental remediation applications.

Enhanced mercury deposition in Arctic Alaskan lake sediments coincides with early Holocene hydroclimate shift.

Substantial amounts of mercury (Hg) are projected to be released into Arctic watersheds as permafrost thaws amid warmer and wetter conditions. This may have far-reaching consequences because the highly toxic methylated form of Hg biomagnifies rapidly in ecosystems. However, understanding how climate change affects Hg dynamics in permafrost regions is limited due to the lack of long-term Arctic Hg records. Using a 27-ka Hg sediment record from Burial Lake, northwestern Alaska, we examine how well-characterized temperature, precipitation, and vegetation shifts affected Hg mobilization in a catchment underlain by permafrost. During the Last Glacial Maximum (29.6-19.6ka), Hg concentrations (63±5μg/kg) and Hg flux (8.6±2.2μgm-2yr-1) remain relatively stable. Abrupt warming trends, starting at 17.6ka, do not coincide with Hg levels. After 15ka, the ecosystem transitions to shrub tundra, Hg concentrations (101.2μg/kg) peak at 14.2ka, while flux (5.3±1.3μgm-2yr-1) declines and stabilizes. At ~11ka, increased precipitation coincides with a 72% rise in Hg concentrations and a 32% increase in Hg flux compared to average Hg levels since 15ka. These results suggest that summer rainfall was the primary driver of Hg mobilization from the catchment, while the vegetation shift influenced lake sediment Hg concentrations. At 1990CE, peak Hg levels represent an 88% increase in Hg concentrations (196.3μg/kg) and a sixfold rise in Hg flux (38.1μgm-2yr-1) above background levels, underscoring the need for further research to understand Hg dynamics driven by anthropogenic Hg emissions and climate change.

Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statins.

Statins are widely used for treating lipid disorders and cardiovascular diseases. However, the therapeutic efficiency and adverse effects of statins vary among different patients, which numerous clinical and epidemiological studies have attributed to genetic polymorphisms in statin-metabolizing enzymes and transport proteins. The metabolic processes of statins are relatively complex, involving spontaneous or enzyme-catalyzed interconversion between more toxic lactone metabolites and active acid forms in the liver and bloodstream, influenced by multiple factors, including the expression levels of many metabolic enzymes and transporters. Addressing the variable statin therapeutic outcomes is a pressing clinical challenge. Transcription factors and epigenetic modifications regulate the metabolic enzymes and transporters involved in statin metabolism and disposition and, therefore, hold promise as 'personalized' targets for achieving optimized statin therapy. In this review, we explore the potential for customizing therapy by targeting the metabolism of statin medications. The biochemical bases of adverse reactions to statin drugs and their correlation with polymorphisms in metabolic enzymes and transporters are summarized. Next, we mainly focus on the regulatory roles of transcription factors and epigenetic modifications in regulating the gene expression of statin biochemical machinery. The recommendations for future therapies are finally proposed by targeting the central regulatory factors of statin metabolism.

Unknown roles of tau pathology in neurological disorders. Challenges and new perspectives.

Aging presents progressive changes that increase the susceptibility of the central nervous system (CNS) to suffer neurological disorders (NDs). Several studies have reported that an aged brain suffering from NDs shows the presence of pathological forms of tau protein, a microtubule accessory protein (MAP) critical for neuronal function. In this context, accumulative evidence has shown a pivotal contribution of pathological forms of tau to Alzheimer's disease (AD) and tauopathies. However, current investigations have implicated tau toxicity in other NDs that affect the central nervous system (CNS), including Parkinson's disease (PD), Huntington's disease (HD), Traumatic brain injury (TBI), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). These diseases are long-term acquired, affecting essential functions such as motor movement, cognition, hearing, and vision. Previous evidence indicated that toxic forms of tau do not have a critical contribution to the genesis or progression of these diseases. However, recent studies have shown that these tau forms contribute to neuronal dysfunction, inflammation, oxidative damage, and mitochondrial impairment events that contribute to the pathogenesis of these NDs. Recent studies have suggested that these neuropathologies could be associated with a prion-like behavior of tau, which induces a pathological dissemination of these toxic protein forms to different brain areas. Moreover, it has been suggested that this toxic propagation of tau from neurons into neighboring cells impairs the function of glial cells, oligodendrocytes, and endothelial cells by affecting metabolic function and mitochondrial health and inducing oxidative damage by tau pathology. Therefore, in this review, we will discuss current evidence demonstrating the critical role of toxic tau forms on NDs not related to AD and how its propagation and induced-bioenergetics failure may contribute to the pathogenic mechanism present in these NDs.

Trace elements in Alaska's ice seals in the 2000s and 2010s.

Ringed (Pusa hispida), bearded (Erignathus barbatus), spotted (Phoca largha), and ribbon (Histriophoca fasciata) seals are ice-associated seals that are important subsistence resources for coastal Alaska Native people. These seals are also mid- to upper trophic level Arctic predators and primary prey of polar bears (Ursus maritimus). We analyzed concentrations of 19 trace elements in seal liver, kidney, muscle, and blubber, including arsenic, cadmium, lead, mercury, and vanadium due to their potential toxicity. We also measured monomethyl mercury, the more biologically available and toxic form of mercury, in a subsample of seals. We tested for differences in elemental concentrations by seal sex, age, and two periods, 2003-2007 and 2011-2016, to detect environmental trends, assess seal health, and explore trace elements in seal tissues as indicators of seal diet. Trace element concentrations were within ranges that were similar or below that previously measured for these species throughout their range in the Arctic and subarctic. We found relationships between concentration and seal sex or age, as well as differences between periods, with a notable decline over time in magnesium for bearded seal liver and kidney, and ringed and spotted seal liver. Relative concentrations of methyl mercury and total mercury among the four seal species matched known patterns of piscivory and pelagic feeding. Cadmium concentrations were highest in bearded and ribbon seals, possibly due to greater benthic feeding and consumption of squid, respectively. Tissue trace element concentrations from sick seals collected during the 2011-2016 Northern Alaska Pinnipeds Unusual Mortality Event did not differ from those of healthy subsistence harvested seals. Our analysis of trace elements in four Alaskan ice seal species can inform toxicological risk assessments regarding non-essential elements of concern and assessments of nutritional benefits regarding essential elements for seals and for the people and polar bears that eat them.

Optimizing Feeding and Pupation Bioassays to Assess the Effects of Insecticidal and Repellent Treatments on Aethina tumida Larval Development and Pupation Success.

European honey bee (Apis mellifera) colonies are an ideal host to the invasive beetle Aethina tumida, providing a nutrient rich environment that is protected from the elements and facilitates beetle reproduction. Although various management techniques and chemical treatments for A. tumida have been developed, understanding the efficacy of these treatments and techniques is limited. Throughout this study, several methods for impairing A. tumida development and delivering insecticidal, repellent, or antifungal treatments were examined. A series of A. tumida larval feeding bioassays developed and optimized feeding gel pellet for delivery of insecticidal treatments, revealing that A. tumida larvae are sensitive to the two common in-hive varroa mite (Varroa destructor) treatments: coumaphos (EC50 = 25.6 ppm) and tau-fluvalinate (EC50 = 21.2 ppm). Feeding bioassays also demonstrated that A. tumida were more sensitive to the pyrethroid compounds permethrin (EC50 = 3.37 ppm), deltamethrin (EC50 = 2.69 ppm), and bifenthrin (EC50 = 0.365 ppm), which have been previously used to control this beetle. Feeding bioassays also revealed that the antifungal drug Amphotericin B was palatable to A. tumida larvae via feeding, but was also injected into A. tumida larvae and adults. Two types of pupation bioassays were also developed to test the effects of several insecticidal and repellent treatments on pupation burrowing and pupation success. Overall, this work details specific toxicity information regarding common insecticidal treatments found in the apiary setting study and provides groundwork and methods for testing insecticidal compounds on A. tumida larvae in in the future.

Angiopoietin-2: A Therapeutic Target for Vascular Protection in Hutchinson-Gilford Progeria Syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a pediatric condition characterized by clinical features that resemble accelerated aging. The abnormal accumulation of a toxic form of the lamin A protein known as progerin disrupts cellular functions, leading to various complications, including growth retardation, loss of subcutaneous fat, abnormal skin, alopecia, osteoporosis, and progressive joint contractures. Death primarily occurs as the result of complications from progressive atherosclerosis, especially from cardiac disease, such as myocardial infarction or heart failure, or cerebrovascular disease like stroke. Despite the availability of lonafarnib, the only US Food and Drug Administration-approved treatment for HGPS, cardiovascular complications remain the leading cause of morbidity and mortality in affected patients. Defective angiogenesis-the process of forming new blood vessels from existing ones-plays a crucial role in the development of cardiovascular disease. A recent study suggests that Angiopoietin-2 (Ang2), a pro-angiogenic growth factor that regulates angiogenesis and vascular stability, may offer therapeutic potential for the treatment of HGPS. In this review, we describe the clinical features and key cellular processes impacted by progerin and discuss the therapeutic potential of Ang2 in addressing these challenges.

Respiratory quaternary ammonium and volatile organic compound exposures experienced by home care aides during residential bathroom cleaning using conventional and green products.

US home care (HC) aide visits to clients' homes typically involve cleaning and disinfecting (C&D) environmental surfaces, particularly in bathrooms. Some ingredients in C&D products are associated with respiratory illness: sodium hypochlorite (bleach), quaternary ammonium compounds (QACs), and volatile organic compounds (VOCs). This study assessed and compared aides' respiratory exposures to specific VOCs and QACs while using 2 conventional and 1 "green" household C&D spray products during bathroom cleaning. Measured exposures were compared to ingredients listed on publicly available sources. Three C&D products were selected with principal active disinfecting ingredients: 1% to 5% sodium hypochlorite by weight ("bleach-based"); 0.1% to 1% QACs ("QACs-based"); and 0.05% thymol ("green"). Twenty-two aides were recruited to perform C&D tasks in a simulated residential bathroom constructed in an environmental monitoring laboratory. A balanced experimental study design involved each aide visiting the lab 4 times to perform typical cleaning tasks with the 3 products and distilled water (as a control), randomly assigned across the 4 visits. Aides wore air sampling equipment for breathing zone samples: canisters to collect whole air for VOC analyses and filter cassettes for QACs analyses. Aides performed 84 cleaning visits contributing approximately 20 air samples each for VOCs and QACs, for each of the 3 products and distilled water. In total, 38 unique VOCs were identified in the canister whole air samples: 20 in the QACs-based product samples, 15 in the bleach-based, and 10 in the green. Most VOCs were not listed in publicly available sources of cleaning product ingredients. Toxicity information was limited. Few VOCs had occupational exposure limits. The QACs-based product generated QACs aerosol: benzalkonium chloride (BAC)12 (geometric mean (GM) = 6.98 µg/m3), BAC14 (GM=2.97 µg/m3), BAC16 (GM=0.78 µg/m3); and the 3 QACs summed (GM=10.86 µg/m3). The use of C&D spray products for residential cleaning can generate respiratory exposures to complex mixtures of volatile and nonvolatile compounds. Notably, we measured aerosols containing QACs during the use of the QACs-based product. Dermal is usually considered the main route of exposure because QACs are nonvolatile salts. This study provides evidence that QACs inhalation exposure should be recognized and minimized in addition to the well-accepted dermal exposure routes. The green product generated the fewest VOCs. However, more toxicity information is needed on the health impacts of green C&D products. Spraying of C&D products, conventional and green, should be avoided. Aides' respiratory health should be protected from chemical exposures while performing C&D in home care.

Ultrasensitive and Selective Detection of Chromium(VI) Using Biowaste Derived Fluorescent Nanoprobes of Hydrothermally Synthesized Carbon‐Dots

AbstractThe Selective detection of hexavalent chromium Cr(VI), a highly toxic and carcinogenic form of chromium, at nanomolar concentration is critical due to its widespread industrial use and severe environmental and health impacts. This study presents the synthesis and application of carbon dots (CDs) derived from banana peel biowaste as a fluorescent nanosensor for the ultrasensitive and selective detection of Cr(VI). The CDs were synthesized through hydrothermal carbonization, yielding an average size of 1.9 nm, a quantum yield of 5%, and maximum fluorescence emission at 440 nm. The CDs displayed strong fluorescence quenching in Cr(VI), with minimal interference from other metal ions, highlighting their higher selectivity. CDs detection limit for Cr(VI) was determined as 52 nM or 2.7 ppb, significantly lower than those reported in recent studies, demonstrating the superior sensitivity. The quenching mechanism was further explored using X‐ray photoelectron spectroscopy (XPS), indicating that Cr(VI) undergoes reduction to Cr(III) upon interaction with the nitrogen‐containing surface functional groups of the CDs, suggesting a chemisorption process. This approach aligns with circular economy principles and supports achieving sustainable development goals (SDGs). Utilizing biowaste for synthesizing nanomaterials offers a promising pathway for creating environment friendly and cost‐effective sensors for detecting toxic metals.

Detecting and Tracking β-Amyloid Oligomeric Forms and Dynamics In Vitro by a High-Sensitivity Fluorescent-Based Assay.

Aggregation of β-amyloid protein is a hallmark pathology of the neurodegenerative disorder Alzheimer's disease and proceeds from monomers to insoluble misfolded fibril forms via soluble and highly toxic oligomeric intermediates. Given the dual feature of being the most toxic form of the Aβ aggregate proteome and an early marker of pathogenesis, there is a need for sensitive methods that can be used to detect Aβ oligomers and investigate the dynamics of aggregation. Herein, we describe a method based on the application of an oligomer-sensitive fluorescent chemical probe pTP-TFE combined with the use of a QIAD (Quantitative determination of Interference with Aβ Aggregate Size Distribution) assay to correctly identify Aβ oligomers in high sensitivity. pTP-TFE was evaluated and compared to thioflavin T and pFTAA, the two most widely used amyloid fibril dyes, and shown to be the only probe capable of detecting significant differences across all oligomeric species of β-amyloid. Furthermore, by observing changes in pTP-TFE fluorescence emission over time, we could track the dynamics of oligomer populations and thereby obtain kinetic information on the Aβ42 dynamic aggregation model. Therefore, we have established a highly sensitive, readily available, and simple method for studying β-amyloid protein aggregation dynamics.

Enhancing mitochondrial one-carbon metabolism is neuroprotective in Alzheimer’s disease models

Alzheimer’s disease (AD) is the most common form of age-related dementia. In AD, the death of neurons in the central nervous system is associated with the accumulation of toxic amyloid β peptide (Aβ) and mitochondrial dysfunction. Mitochondria are signal transducers of metabolic and biochemical information, and their impairment can compromise cellular function. Mitochondria compartmentalise several pathways, including folate-dependent one-carbon (1C) metabolism and electron transport by respiratory complexes. Mitochondrial 1C metabolism is linked to electron transport through complex I of the respiratory chain. Here, we analysed the proteomic changes in a fly model of AD by overexpressing a toxic form of Aβ (Aβ-Arc). We found that expressing Aβ-Arc caused alterations in components of both complex I and mitochondrial 1C metabolism. Genetically enhancing mitochondrial 1C metabolism through Nmdmc improved mitochondrial function and was neuroprotective in fly models of AD. We also found that exogenous supplementation with the 1C donor folinic acid improved mitochondrial health in both mammalian cells and fly models of AD. We found that genetic variations in MTHFD2L, the human orthologue of Nmdmc, were linked to AD risk. Additionally, Mendelian randomisation showed that increased folate intake decreased the risk of developing AD. Overall, our data suggest enhancement of folate-dependent 1C metabolism as a viable strategy to delay the progression and attenuate the severity of AD.

Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cells

Amyloid β42 (Aβ42) plays a decisive role in the pathology of Alzheimer’s disease. The Aβ42 peptide can aggregate into various supramolecular structures, with oligomers being the most toxic form. However, different Aβ species that cause different effects have been described. Many cell death pathways can be activated in connection with Aβ action, including apoptosis, necroptosis, pyroptosis, oxidative stress, ferroptosis, alterations in mitophagy, autophagy, and endo/lysosomal functions. In this study, we used a model of differentiated SH-SY5Y cells and applied two different Aβ42 preparations for 2 and 4 days. Although we found no difference in the shape and size of Aβ species prepared by two different methods (NaOH or NH4OH for Aβ solubilization), we observed strong differences in their effects. Treatment of cells with NaOH-Aβ42 mainly resulted in damage of mitochondrial function and increased production of reactive oxygen species, whereas application of NH4OH-Aβ42 induced necroptosis and first steps of apoptosis, but also caused an increase in protective Hsp27. Moreover, the two Aβ42 preparations differed in the mechanism of interaction with the cells, with the effect of NaOH-Aβ42 being dependent on monosialotetrahexosylganglioside (GM1) content, whereas the effect of NH4OH-Aβ42 was independent of GM1. This suggests that, although both preparations were similar in size, minor differences in secondary/tertiary structure are likely to strongly influence the resulting processes. Our work reveals, at least in part, one of the possible causes of the inconsistency in the data observed in different studies on Aβ-toxicity pathways.Graphical

Interstitial HDR brachytherapy for anal cancer-results and quality of life.

While anal cancer is avery rare oncological diagnosis representing less than 2% of lower gastrointestinal tract cancers, the incidence has doubled in the past 20years. Radical radiochemotherapy with sequential or simultaneous boost is now the standard treatment modality. Interstitial HDR brachytherapy is one of the boost application options. Implementation of new radiotherapy techniques has resulted in improved therapeutic outcomes; however, it is still associated with acute and especially late toxicity. Gastrointestinal disorders and sexual dysfunction are the most frequent factors affecting the long-term quality of cured patients' lives. Atotal of 96patients consecutively treated between 2000 and 2022 with external beam radio-/chemotherapy and an interstitial brachytherapy boost for histologically verified nonmetastatic anal squamous cell carcinoma were evaluated. The median follow-up time was 15.4 years (range 13.4-17.3 years). The primary objective of the study was to assess local control (LC) and quality of life (QoL). The Czech versions of internationally validated EORTC questionnaires were used to evaluate life quality-the basic EORTC QOL-C30v.3 and the specific QOL-ANL27 questionnaire. Local control was 85.5% at 5years, 83.4% at 10years, 83.4% at 15years, and 83.4% at 20years, and there was no dependence on clinical stage. The most common forms of acute toxicity were cutaneous and hematological but were gastrointestinal for late toxicities. In the evaluation of quality of life, 80.5% of patients alive at the time participated. In the EORTC quality of life questionnaire C30v.3, patients rated the functional scale score as 86.2 points (standard deviation [SD] = 12.6) and the symptom score as 15.5 points (SD = 12.5). The global health score achieved 68.4 points (SD = 23.6). The most common symptoms were fatigue with 25.6 points (SD = 20.2) and diarrhea with 19.0 points (SD = 27.8). In the QOL-ANL27 questionnaire, symptom scales assessing bowel symptoms were scored 27.5 points (SD = 19) in non-stoma patients and 11.9 points (SD = 17.2) in stoma patients. In the single-item symptom scales, the highest scores were rated for frequency of urination with 26.4 points (SD = 30.8), need to be close to atoilet with 22.4 points (SD = 27.3), and self-cleaning more often with 25.3 points (SD = 31.8). In the functional scales assessing sex life and interest, men and women reported scores of 45.2 (SD = 23) and 45.5 points (SD = 19), respectively. Boost with interstitial HDR brachytherapy is an established safe method of anal cancer treatment, with excellent results and limited late toxicity. Functioning scales were rated relatively highly in QoL questionnaires, and the overall global health score was comparable to published data. Gastrointestinal difficulties, fatigue, and sexual dysfunction dominated the symptom scales in our cohort.

Exogenous sodium nitroprusside exhibits multiple positive roles in alleviating cadmium toxicity in tobacco (Nicotiana tabacum L.)

As a donor of the gaseous signaling molecule nitric oxide (NO), sodium nitroprusside (SNP) has been shown to play a positive role in enhancing plant resistance to abiotic stress. However, its role in alleviating cadmium (Cd) toxicity in tobacco (Nicotiana tabacum L.) is not fully understood. This study found that Cd stress significantly inhibited tobacco growth. At the same time, 150 μM SNP was the most effective concentration in alleviating Cd toxicity in seedlings, restoring three stress tolerance indicators—MDA, H2O2, and proline—to control levels. Exogenous SNP mitigated Cd-induced oxidative stress by promoting the accumulation of non-enzymatic antioxidants (total phenolics and flavonoids) and activating key antioxidant enzymes (SOD, CAT, POD, APX, and GR) along with their gene expression. SNP also facilitated Cd accumulation in the root cell wall and prevented Cd translocation from roots to shoots. Additionally, SNP altered Cd's subcellular distribution, promoting its sequestration in vacuoles and cell walls, which may be related to the NO-mediated upregulation of the metallothionein gene NtMT2F and the phytochelatin gene NtPCS2. The addition of SNP significantly increased the proportion of Cd in less toxic chemical forms, with the residual Cd fraction in the Cd + SNP group reaching 7.30 %, higher than the 4.86 % in the Cd-only group. Furthermore, exogenous SNP counteracted Cd's inhibition of nitrate reductase (NR) activity, promoting endogenous NO production. This study systematically reveals the positive roles of exogenous SNP in mitigating Cd toxicity in tobacco, offering valuable insights for producing low-Cd tobacco.

Computational insights into mercuric reductase from Pseudomonas fluorescens: a bioinformatic and molecular dynamics approach for mercury detoxification

Mercury (Hg) pollution poses significant threats to human health and ecosystems worldwide due to its persistence, bioaccumulation, and toxic effects. This study focuses on mercuric reductase from Pseudomonas fluorescens (UniProt ID Q51772), a key enzyme involved in detoxifying mercury through reduction to its less toxic elemental form, Hg(0). This study aims to explore the potential of this enzyme for bioremediation applications, focusing on structural insights, functional mechanisms, and biotechnological enhancements to facilitate mercury detoxification. The protein sequence of Q51772 was analyzed using bioinformatics tools to determine its structural and functional attributes. Physiochemical properties, including molecular weight, isoelectric point, and secondary structure predictions, were assessed. Virulence prediction tools confirmed the protein’s nontoxic and nonpathogenic nature. Homology modeling and docking studies provided insights into its three-dimensional structure and binding interactions with mercury substrates. Q51772 consists of 548 amino acids and belongs to the Pyridine nucleotide-disulphide oxidoreductase family, class I. It features specific domains crucial for mercury reduction, identified through Pfam and InterPro analyses. Physiochemical analysis indicated a stable protein with hydrophilic tendencies conducive to enzymatic function. Structural modeling validated by ProQ and PROCHECK confirmed the reliability of the predicted structure. Molecular docking of organic mercury compound with wild-type and mutant mercuric reductase revealed strong binding affinities, with key hydrogen bonds involving residues Gly95, Thr122, and Asp390. Mercuric reductase Q51772 from Pseudomonas fluorescens emerges as a promising candidate for bioremediation of mercury-contaminated environments. Future research should focus on optimizing its performance under diverse environmental conditions to advance sustainable solutions for mercury pollution control.

Structural duality enables a single protein to act as a toxin–antidote pair for meiotic drive

In sexual reproduction, selfish genetic elements known as killer meiotic drivers (KMDs) bias inheritance by eliminating gametes that do not carry them. The selective killing behavior of most KMDs can be explained by a toxin-antidote model, where a toxin harms all gametes while an antidote provides resistance to the toxin in carriers. This study investigates whether and how the KMD element tdk1 in the fission yeast Schizosaccharomyces pombe deploys this strategy. Intriguingly, tdk1 relies on a single protein product, Tdk1, for both killing and resistance. We show that Tdk1 exists in a nontoxic tetrameric form during vegetative growth and meiosis but transforms into a distinct toxic form in spores. This toxic form acquires the ability to interact with the histone reader Bdf1 and assembles into supramolecular foci that disrupt mitosis in noncarriers after spore germination. In contrast, Tdk1 synthesized during germination of carrier spores is nontoxic and acts as an antidote, dismantling the preformed toxic Tdk1 assemblies. Replacement of the N-terminal region of Tdk1 with a tetramer-forming peptide reveals its dual roles in imposing an autoinhibited tetrameric conformation and facilitating the assembly of supramolecular foci when autoinhibition is released. Moreover, we successfully reconstituted a functional KMD element by combining a construct that exclusively expresses Tdk1 during meiosis ("toxin-only") with another construct that expresses Tdk1 specifically during germination ("antidote-only"). This work uncovers a remarkable example of a single protein employing structural duality to form a toxin-antidote pair, expanding our understanding of the mechanisms underlying toxin-antidote systems.

Genomic Study in Opioid-Treated Cancer Patients Identifies Variants Associated With Nausea-Vomiting

ContextOpioids are the mainstay therapy for patients affected by cancer pain. However, about 10%–20% of patients do not benefit from the received analgesic treatment or experience side effects. Genetic variability might account for the variation in individual responses to opioids, both in terms of efficacy and toxicity. ObjectivesThe aim of this genome-wide association study (GWAS) was to identify genetic markers of opioid toxicity, in terms of nausea-vomiting. MethodsCancer patients receiving morphine, oxycodone, buprenorphine, and fentanyl were recruited from different European countries. Data about toxicity (nausea-vomiting score, NVS) and other relevant clinical information were collected, as well as genotyping data. Regression analysis between genotypes of 2052 patients and NVS was performed, using appropriate covariates, with REGENIE software. ResultsWe found 65 variants associated with NVS (P-value < 1.0×10−5). Of note, 14 intronic variants on chromosome 2 were in NPAS2 gene, encoding a circadian transcription factor reported to play a role in another opioid side effect, the alteration of sleep. Some of these variants were previously identified as splicing quantitative trait loci of the NPAS2 gene. ConclusionsThis is the first GWAS, performed in more than two thousand individually genotyped patients treated with opioids for cancer pain, that investigated the genetic bases of opioid-induced nausea-vomiting. Although further studies are needed to confirm our findings and to characterize the functional role of the identified variants, our results emphasize the importance of performing large pharmacogenomic studies to identify germline variants associated with opioid response, with the ultimate goal of tailoring cancer pain therapies.

Microbial remediation of heavy metal-polluted water

Heavy metal pollution in water has become a global environmental problem, threatening aquatic ecosystems and human health. Physical and chemical methods can effectively remove heavy metal pollutants, while their applications are limited due to the high costs, complex operation, and susceptibility to secondary pollution. Bioremediation is the most promising method for eliminating toxic pollutants. Microorganisms including bacteria, fungi, and algae can convert toxic heavy metals into less toxic forms, which has become an effective and environmentally friendly solution for the remediation of heavy metal pollution in water environments. This paper expounds the toxicity and mechanism of heavy metal pollution, microbial remediation mechanisms, and primary microbial remediation strategies, providing a reference for the removal or reduction of metal pollutants in water environments as well as the development of related technologies.