HADH suppresses clear cell renal cell carcinoma progression through reduced NRF2-dependent glutathione synthesis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a serious threat to human life. It is very important to clarify the pathogenesis of ccRCC. In this study we evaluated the clinical value of HADH and explored its role and mechanism in the malignant progression of ccRCC. METHODS: HADH expression and its relationship with prognosis were analyzed using bioinformatics database. RT-PCR, Western blot and immunohistochemistry were used to examine the expression of HADH in ccRCC tissues and tissue microarrays. To examine the cell proliferation, apoptosis, migration and invasion ability, ccRCC cells with HADH overexpressed were constructed. Xenograft experiments were performed to determine the role of HADH. Non-target metabolomics was applied to explore the potential metabolic pathway by which HADH inhibited ccRCC progression. Plasmid pcDNA3.1-NRF2 was used to confirm whether HADH inhibited the process of ccRCC cells through NRF2-related glutathione (GSH) synthesis. RESULTS: Bioinformatics database analysis showed that HADH expression was significantly decreased in ccRCC tissues, and its low expression predicted a poor prognosis. Both ccRCC tissues and tissue microarrays exhibited a significantly decreased HADH level compared with adjacent normal renal tissues. HADH overexpression inhibited the malignant behaviors of ccRCC cells. Furthermore, HADH overexpression attenuated GSH synthesis and induced oxidative stress damage. Exogenously increased NRF2 effectively attenuated the inhibitive effect of HADH overexpression on ccRCC cells. CONCLUSION: Our data revealed that HADH suppressed the malignant behaviors of ccRCC cells by attenuating GSH synthesis through inhibition of NRF2 nuclear translocation, and HADH might be a novel therapeutic target for ccRCC treatment.

Cocrystal engineering for sustained release of dicamba: Mitigating secondary drift and reducing leaching.

The off-target effects of herbicides present significant challenges in agricultural practices, posing serious threats to both ecological systems and human health. Dicamba, one of the most widely used herbicides, is particularly problematic due to its high volatility and water solubility, which can lead to rapid environmental dispersal, non-target toxicity, and groundwater contamination. To mitigate these issues, we synthesized a novel cocrystal of dicamba and phenazine (DCB-PHE cocrystal) through a combination of theoretical prediction and mechanochemical screening. The DCB-PHE cocrystal was characterized using single-crystal and powder X-ray diffraction, Fourier-transform infrared spectroscopy (FT-IR), and thermal analysis. Compared to pure dicamba, the DCB-PHE cocrystal exhibited a substantial reduction in volatility by 59 % and a decrease in equilibrium solubility by up to 5.4 times across various temperatures (15 °C, 25 °C, 35 °C). Additionally, the dissolution rates were significantly lowered by over 94 %. Leaching experiments demonstrated that the DCB-PHE cocrystal reduced total leachate by 4.9 % and delayed percolation. In greenhouse trials, the DCB-PHE cocrystal caused less damage to exposed soy plants and enhanced herbicidal activity against target weeds, with fresh weight reduction of chicory and ryegrass by 32 % and 28 %, respectively, at the highest dosage. Furthermore, safety assays confirmed that the DCB-PHE cocrystal's safety profile was comparable to that of dicamba in terms of its impact on wheat, and it did not exhibit increased genotoxicity to broad beans. These findings suggest that the DCB-PHE cocrystal is a promising candidate for reducing the environmental impacts of dicamba while maintaining its herbicidal efficacy.

Diagnostic screening of private well water using gas chromatography with high resolution mass spectrometry to support well water management.

In the US, private well users are responsible for their own water quality testing, but local health officials are often uncertain what tests to recommend, particularly for regulated organic chemical contaminants. This study evaluated the utility of suspect and non-target screening (NTS) high resolution mass spectrometry (HRMS) as a tool to identify a wide range of organic chemicals of emerging concern in private well water and to inform well water management decisions. Qualitative NTS, which detects chemicals without providing concentrations, was used to analyze 25 private well water samples from Wake County, North Carolina. Using the NIST 20 mass spectral database (M1), NTS tentatively identified 106 unique organic chemicals across the 25 samples and an average of 11 organic chemicals per sample. At least one USEPA ToxCast chemical was identified in each private well water sample. Private well water users were interviewed prior to and after their sample's NTS results were reported back; four county groundwater managers were interviewed after aggregated results for all 25 water samples were reported back. All but one well user participant chose to participate in the reporting-back post-interview. The 24 private well users found NTS results useful and valued the contextualization of their results using NTS results for other well users and a local municipal water sample. Most private well users (67 %) were surprised by their well water results, especially regarding the number of tentatively identified organic chemicals detected. All the groundwater managers believed the NTS results were useful and could help improve their testing recommendations to private well users. Even with qualitative limitations, NTS results can be an effective and valuable tool to inform the public and governance stakeholders in decisions around groundwater quality management.

Overlooked Trace Molecules in Organic Aerosol Revealed by Gas Chromatography-Orbitrap Mass Spectrometry.

Molecular characterization of organic aerosol (OA) is crucial for understanding its sources and atmospheric processes. However, the chemical components of OA remain not well constrained. This study used gas chromatography-Orbitrap mass spectrometry (GC-Orbitrap MS) and GC-Quadrupole MS (GC-qMS) to investigate the organic composition in PM2.5 from Xi'an, Northwest China. GC-Orbitrap MS identified 335 organic tracers, including overlooked isomers and low-concentration molecules, approximately 1.6 times more than GC-qMS. The "molecular corridor" assessment shows the superior capability of GC-Orbitrap MS in identifying an expansive range of compounds with higher volatility and oxidation states, such as furanoses/pyranoses, di/hydroxy/ketonic acids, di/poly alcohols, aldehydes/ketones, and amines/amides. Seasonal variations in OA composition reflect diverse sources: increased di/poly alcohols in winter are derived from indoor emissions, furanoses/pyranoses and heterocyclics in spring and summer might be from biogenic emissions and secondary formation, and amides in autumn are probably from biomass burning. Integrating partial least squares discriminant analysis (PLS-DA) and potential source contribution function (PSCF) models, the source similarities and differences are further elucidated, highlighting the role of local emissions and transport from southern cities. This study offers new insights into the OA composition aided by the high mass resolution and sensitivity of GC-Orbitrap MS.

Widespread exposure to anticoagulant rodenticides among common urban mesopredators in Chicago.

Anticoagulant rodenticides (ARs) are currently the most common method to control rats in cities, but these compounds also cause morbidity and mortality in non-target wildlife. Little attention has been focused on AR exposure among mesopredators despite their ecological role as scavengers and prey for larger carnivores, thus serving as an important bridge in the biomagnification of rodenticides in food webs. In this study, we sampled liver tissue from raccoons (Procyon lotor; n = 37), skunks (Mephitis mephitis; n = 15), and Virginia opossums (Didelphis virginiana; n = 45) euthanized by pest professionals and brown rats (Rattus norvegicus; n = 101) trapped in alleys in Chicago, USA to evaluate how often these species are exposed to ARs. We tested whether mesopredators had a higher prevalence of ARs and to more AR compounds compared to rats and calculated biomagnification factors (mean concentration in mesopredators/rats) as indicators of biomagnification. Of 93 sampled mesopredators, 100 % were exposed to at least one AR compound, mainly brodifacoum (≥80 %), and 79 % were exposed to multiple AR compounds. We also documented teal stomach contents consistent with the consumption of rat bait and altricial young tested positive to the same AR as their mother, suggesting mammary transfer. Of the 101 rats, 74 % tested positive to at least one AR compound and 32 % were exposed to multiple AR compounds. All mesopredator species had biomagnification factors exceeding 1.00 for brodifacoum (6.57-29.07) and bromadiolone (1.08-4.31). Our results suggest widespread exposure to ARs among urban mesopredators and biomagnification of ARs in mesopredators compared to rats. Policies that limit AR availability to non-target species, such as restricting the sale and use of ARs to licensed professionals in indoor settings, education on alternatives, and more emphasis on waste management may reduce health risks for urban wildlife and people in cities around the world.

Innovative and versatile surface-enhanced Raman spectroscopy-inspired approaches for viral detection leading to clinical applications: A review.

The evolution of analytical techniques has opened the possibilities of accurate analyte detection through a straightforward method and short acquisition time, leading towards their applicability to identify medical conditions. Surface-enhanced Raman spectroscopy (SERS) has long been proven effective for rapid detection and relies on SERS spectra that are unique to each specific analyte. However, the complexity of viruses poses challenges to SERS and hinders further progress in its practical applications. The principle of SERS revolves around the interaction among substrate, analyte, and Raman laser, but most studies only emphasize the substrate, especially label-free methods, and the synergy among these factors is often ignored. Therefore, issues related to reproducibility and consistency of results, which are crucial for medical diagnosis and are the main highlights of this review, can be understood and largely addressed when considering these interactions. Viruses are composed of multiple surface components and can be detected by label-free SERS, but the presence of non-target molecules in clinical samples interferes with the detection process. Appropriate spectral data processing workflow also plays an important role in the interpretation of results. Furthermore, integrating machine learning into data processing can account for changes brought about by the presence of non-target molecules when analyzing spectral features to accurately group the data, for example, whether the sample corresponds to a positive or negative patient, and whether a virus variant or multiple viruses are present in the sample. Subsequently, advances in interdisciplinary fields can bring SERS closer to practical applications.

Acute cor pulmonale following uterine artery embolization.

Uterine artery embolization (UAE) is a common procedure for controlling gynecological and obstetric bleeding. We report a case of a 38-year-old female with placenta increta who underwent UAE following a cesarean section and subsequently developed pulmonary embolism from nontarget embolization. Excellent CTPA images demonstrate embolization agents used in the procedure in the pulmonary vasculature. The patient developed acute cor pulmonale, an infrequent complication from the procedure. This case presents a rare and clear demonstration of a complication of uterine artery embolization with clear imaging evidence.

Non-Target Screening of Chemicals in Selected Cotton Products by GC/MS and Their Safety Assessment.

Cotton is used for the production of textiles, hygiene and cosmetic materials. During cultivation and technological processes, various types of substances (surfactants, softeners, lubricants, etc.) penetrate cotton, which can have a harmful effect on both the human body and the environment. The aim of this study was to analyze selected cotton products in order to identify the substances contained and to describe the potential possibilities of inducing textile contact dermatitis (CD). The impact of the identified compounds on the aquatic environment was also taken into account. Nine samples of cotton clothing and seven samples of cotton pads from various manufacturers were tested. Samples after extraction using the FUSLE (Focused Ultrasonic Liquid Extraction) technique were analyzed with GC/MS. Qualitative analysis was based on comparing mass spectra with library spectra using the following mass spectra deconvolution programs: MassHunter (Agilent), AMDIS (NIST), and PARADISE (University of Copenhagen). The parameter confirming the identification of the substance was the retention index. Through the non-target screening process, a total of 36 substances were identified, with an average AMDIS match factor of approximately 900 ("excellent match"). Analyzing the properties of the identified compounds, it can be concluded that most of them have potential properties that can cause CD, also due to the relatively high content in samples. This applies primarily to long-chain alkanes (C25-C31), saturated fatty acids, fatty alcohols (e.g., oleyl alcohol), and fatty acid amides (e.g., oleamide). However, there are not many reports describing cases of cotton CD. Information on the identified groups of compounds may be helpful in the case of unexplained sources of sensitization when the skin comes into contact with cotton materials. Some of the identified compounds are also classified as dangerous for aquatic organisms, especially if they can be released during laundering.

Integration of Nontarget Screening and QSPR Models to Identify Novel Organophosphate Esters of High Priority in Aquatic Environment.

With the development of large numbers of novel organophosphate esters (OPEs) alternatives, it is imperative to screen and identify those with high priority. In this study, surface water, biofilms, and freshwater snails were collected from the flow-in rivers of Taihu Lake Basin, China. Screened by target, suspect, and nontarget analysis, 11 traditional and 14 novel OPEs were identified, of which 5 OPEs were first discovered in Taihu Lake Basin. The OPE concentrations in surface water ranged from 196 to 2568 ng/L, with the primary homologue tris(2,4-ditert-butylphenyl) phosphate (TDtBPP) being newly identified, which was likely derived from the transformation of tris(2,4-ditert-butylphenyl) phosphite. The majority of the newly identified OPEs displayed substantially higher bioaccumulation and biomagnification potentials in the biofilm-snail food chain than the traditional ones. Quantitative structure-property relationship models revealed both hydrophobicity and polarity influenced the bioaccumulation and biomagnification of the OPEs, while electrostatic attraction also had a contribution to the bioaccumulation in the biofilm. TDtBPP was determined as the utmost priority by toxicological priority index scheme, which integrated concentration, bioaccumulation, biomagnification, acute toxicity, and endocrine disrupting potential of the identified OPEs. These findings provide novel insights into the behaviors of OPEs and scientific bases for better management of high-risk pollutants in aquatic ecosystem.

Deciphering fungicide resistance in Phytophthora: mechanisms, prevalence, and sustainable management approaches.

The genus Phytophthora contains more than 100 plant pathogenic species that parasitize a wide range of plants, including economically important fruits, vegetables, cereals, and forest trees, causing significant losses. Global agriculture is seriously threatened by fungicide resistance in Phytophthora species, which makes it imperative to fully comprehend the mechanisms, frequency, and non-chemical management techniques related to resistance mutations. The mechanisms behind fungicide resistance, such as target-site mutations, efflux pump overexpression, overexpression of target genes and metabolic detoxification routes for fungicides routinely used against Phytophthora species, are thoroughly examined in this review. Additionally, it assesses the frequency of resistance mutations in various Phytophthora species and geographical areas, emphasizing the rise of strains that are resistant to multiple drugs. The effectiveness of non-chemical management techniques, including biological control, host resistance, integrated pest management plans, and cultural practices, in reducing fungicide resistance is also thoroughly evaluated. The study provides important insights for future research and the development of sustainable disease management strategies to counter fungicide resistance in Phytophthora species by synthesizing current information and identifying knowledge gaps.

Electrophysiological Responses of Trissolcus japonicus, T. basalis, and T. oenone (Hymenoptera: Scelionidae) to Volatile Compounds Associated with New Zealand Stink Bugs (Hemiptera: Pentatomidae).

Parasitoid biological control agents rely heavily on olfaction to locate their hosts. Chemical cues associated with hosts and non-hosts are known to influence the expression of host preferences and host-specificity. A better understanding of how and why parasitoids attack some species and not others, based on volatile organic compounds associated with potential hosts, can provide key information on the parasitoid's host preferences, which could be applied to pre-release risk assessments for classical biological control agents. Electrophysiological techniques such as electroantennography (EAG) and GC-EAD (gas chromatography coupled with electroantennographic detection) are widely used to identify bioactive semiochemicals. But the application of these techniques to understanding how chemical ecological cues mediate parasitoid host specificity has not been as thoroughly explored. We conducted GC-EAD and EAG studies to identify olfactory-active compounds associated with adult females of nine stink bug species from Aotearoa/New Zealand on the antennae of three closely related parasitoid species: Trissolcus japonicus Ashmead, a pre-emptively (= proactively) approved biocontrol agent against brown marmorated stink bug; T. basalis (Wollaston), a biocontrol agent introduced against Nezara viridula L. in 1949; and T. oenone Johnson, a native Australasian pentatomid parasitoid. Eight compounds associated with stink bugs elicited antennal responses from all three parasitoids, and we were able to identify seven of these. (E)-2-hexenal, (E)-4-oxo-2-hexenal, (E)-2-octenal and (E)-2-decenal generally elicited stronger responses in the three parasitoids, while n-tridecane, n-dodecane, and (E)-2-decenyl acetate elicited weaker responses. We discuss how and why the results from electrophysiological experiments can be applied to non-target risk assessments within biological control programmes.

Discovery of perfluoroalkyl sulfonyl quaternary ammonium substances in the environment and their environmental behaviors.

A variety of per- and polyfluoroalkyl substances (PFASs) have been released into the environment via wastewater treatment plant (WWTP) effluent, with current target and nontarget analytical methods typically focusing on negatively ionized PFASs while largely overlooking positively ionized ones. In this study, five cationic PFASs, perfluoroalkyl sulfonyl quaternary ammonium substances (PFAQASs), were first identified in surface water impacted by the WWTP effluent, applying a metabolomics-based nontarget analysis method. Environmental behaviors of identified novel PFAQASs were further investigated. In surface water, sediment, and fish (Coilia mystus) samples collected from the Yangtze River, 8:3 PFAQA was consistently the predominant PFAQASs, with the mean concentrations of 90 ng/L (< LOD-558 ng/L), 92 ng/g dw (< LOD-421 ng/g dw), and 2.3 ng/g ww (< LOD-4.6 ng/g ww), respectively. This study highlights the necessity to discover other cationic PFASs in the environment. Among PFAQASs, 8:4 PFAQA (4.2, range 3.4 - 4.6) had the highest mean sediment-water partitioning coefficient (log Koc), followed by 8:3 PFAQA (3.9, 2.8 - 4.5) and 6:3 PFAQA (3.7, 3.3 - 4.1). The log Koc of PFAQASs showed a general increase trend with the increasing carbon chain length. Mean bioaccumulation factor (BAF) values of PFAQASs calculated in the collected fish from the Yangtze River ranged from 1.9 ± 0.32 (4:3 PFAQA) to 2.9 ± 0.34 (8:4 PFAQA). The mean BAF values of PFAQASs generally increased with the carbon chain length. Further studies are warranted to elucidate the environmental fate, potential toxicity, and human exposure implications for these identified novel PFASs.

Respiratory system: Highly exposed yet under-reported organ in pyrethrin and pyrethroid toxicity.

Pyrethrin and pyrethroid are a relatively new class of pesticides with potent insecticidal properties. Pyrethrins are naturally occurring pesticides obtained from the Chrysanthemum cinerariaefolium flower, while pyrethroids are their synthetic derivatives. They are widely used as the insecticides of choice in agriculture, veterinary medicine, public health programs, and household activities. Pyrethrin, being a broad-spectrum insecticide kills a wide range of pests, while pyrethroids last longer in the environment owing to low susceptibility to sunlight, and greater stability and efficacy than parent molecules. Humans can be exposed through inhalation, ingestion, and dermal routes. Indoor usage of an insecticide poses a serious risk to human health, especially to women, children, and stay-at-home people. Although pyrethrin and pyrethroid are generally considered safe, sustained skin or inhalation exposure or direct contact with open wounds results in higher toxicity to mammals. There is a paucity of data on the impact of pyrethrin and pyrethroid on overall pulmonary health. The respiratory system, from the nose, nasal passages, airways, and bronchi to the pulmonary alveoli, is vulnerable to environmental contaminants such as pesticides because of its anatomical location as well as being a highly blood profused organ. Under and over-functioning of the respiratory system triggers diverse pathologies such as serious infections, allergies, asthma, metastatic malignancies, and auto-immune conditions. While the association between workplace-related pesticide exposures and respiratory diseases and symptoms is well documented, it is important to understand the adverse health impact of pyrethrin and pyrethroid on the general population for awareness and also for better regulation and implementation of the law.

What can laboratory studies tell us about potential effects of pesticides on nontarget arthropods populations and communities in the field?

Over the past decades, concern has been increasing over reported declines in aboveground biodiversity on farmland. In many regions, data on the toxicity of pesticides to honeybees (Apis mellifera), but not wider nontarget arthropod (NTA) data, are required for pesticide registration. In Europe, the effects of pesticides on NTAs and honeybees have been the subject of regulatory risk assessment for more than 30 years, resulting in a large database. Although insecticides may be expected to affect NTA populations, solely identifying insecticidal modes of action for further NTA testing would result in redundancy among low-risk testing products and may also exclude other modes of action with potential effects in the field. This study assessed whether the honeybee acute risk assessment could provide any indication of the potential impact and recovery time of NTAs in cropped areas at the field scale and, if so, how it might be used in a tiered testing approach. The hazard quotients (HQs; foliar application rate/LR50) were derived for 151 active substances (32% insecticides, 28% fungicides, 38% herbicides, 2% plant growth regulators) for which toxicity data for established EU Tier 1 NTA indicator species (Typhlodromus pyri, Aphidius rhopalosiphi) and application rate data were available. These HQs were compared with published NTA HQ thresholds indicating the time to recovery of NTA populations and communities in field studies (>1 to >12 months). Using the same application rate data, honeybee acute risk quotient (RQ) and HQ were also determined and compared with NTA HQs and honeybee regulatory thresholds. These comparisons demonstrated that, where required, the current regulatory honeybee acute RQ of 0.4 or honeybee HQ of 50 can provide an efficient screening tier to target NTA testing at those products and uses with potential effects in the field where recovery may exceed 12 months. Integr Environ Assess Manag 2024;00:1-8. © 2024 SETAC.

The effects of long-term application of fomesafen on weed seedbank and resistance levels of Amaranthus retroflexus L.

Amaranthus retroflexus L. is one of the invasive malignant weeds in soybean fields. Diphenyl ether herbicides are commonly used to control weeds in soybean fields currently, among which fomesafen is the most widely used. With the long-term use of fomesafen, the weed species in soybean fields in multiple areas declined, and the control effect of fomesafen against Amaranthus retroflexus decreased significantly. This study aims to confirm the effects of long-term use of fomesafen on weed community richness and the current resistance level of Amaranthus retroflexus. In this paper, the result of seed germination indicated that the weed community richness decreased significantly due to the long-term application of fomesafen, and the primary dominant weed was Amaranthus retroflexus. The result of the whole-plant bioassay showed that Amaranthus retroflexus has developed resistance to fomesafen, and the resistance index was 50~59 g a.i. ha-1. The resistance level and mechanism of Amaranthus retroflexus were clarified by target gene detection, enzyme activity determination, and gene expression analysis. The results showed that there were both target resistance with Arg128Gly mutation in the PPX2 gene and non-target resistance (NTSR), with increased activity of metabolic enzymes (cytochromes P450 (P450s) and glutathione S-transferase (GSTs)) and protective enzymes (peroxidase (POD) and catalase (CAT)) in Amaranthus retroflexus.

Identification of Key Toxic Substances Considering Metabolic Activation: A Combination of Transcriptome and Nontarget Analysis.

There have been numerous studies using effect-directed analysis (EDA) to identify key toxic substances present in source and drinking water, but none of these studies have considered the effects of metabolic activation. This study developed a comprehensive method including a pretreatment process based on an in vitro metabolic activation system, a comprehensive biological effect evaluation based on concentration-dependent transcriptome (CDT), and a chemical feature identification based on nontarget chemical analysis (NTA), to evaluate the changes in the toxic effects and differences in the chemical composition after metabolism. Models for matching metabolites and precursors as well as data-driven identification methods were further constructed to identify toxic metabolites and key toxic precursor substances in drinking water samples from the Yangtze River. After metabolism, the metabolic samples showed a general trend of reduced toxicity in terms of overall biological potency (mean: 3.2-fold). However, metabolic activation led to an increase in some types of toxic effects, including pathways such as excision repair, mismatch repair, protein processing in endoplasmic reticulum, nucleotide excision repair, and DNA replication. Meanwhile, metabolic samples showed a decrease (17.8%) in the number of peaks and average peak area after metabolism, while overall polarity, hydrophilicity, and average molecular weight increased slightly (10.3%). Based on the models for matching of metabolites and precursors and the data-driven identification methods, 32 chemicals were efficiently identified as key toxic substances as main contributors to explain the different transcriptome biological effects such as cellular component, development, and DNA damage related, including 15 industrial compounds, 7 PPCPs, 6 pesticides, and 4 natural products. This study avoids the process of structure elucidation of toxic metabolites and can trace them directly to the precursors based on MS spectra, providing a new idea for the identification of key toxic pollutants of metabolites.

Biotransformation pathways of pharmaceuticals and personal care products (PPCPs) during acidogenesis and methanogenesis of anaerobic digestion.

Pharmaceuticals and personal care products (PPCPs) exhibit varying biodegradability during the acidogenic and methanogenic phases of anaerobic digestion. However, there is limited information regarding the end products generated during these processes. This work investigates the biotransformation products (BTPs) generated in a two-phase (TP) acidogenic-methanogenic (Ac-Mt) bioreactor using advanced suspect and nontarget strategies. Fourteen BTPs were confidently identified from ten parent PPCPs including carbamazepine (CBZ), naproxen (NPX), diclofenac (DCF), ibuprofen (IBU), acetaminophen (ACT), metoprolol (MTP), sulfamethoxazole (SMX), ciprofloxacin (CIP), methylparaben (MPB) and propylparaben (PPB). These BTPs were linked with oxidation reactions such as hydroxylation, demethylation and epoxidation. Their generation was related to organic acid production, since all metabolites were detected during acidogenesis, with some being subsequently consumed during methanogenesis, e.g., aminothiophenol and kynurenic acid. Another group of BTPs showed increased concentrations under methanogenic conditions, e.g., hydroxy-diclofenac and epoxy-carbamazepine. The most PPCPs showed high removal efficiencies (> 90 %) - SMX, CIP, NPX, MTP, ACT, MPB, PPB, while DCF, CBZ and IBU demonstrated higher persistence - DCF (42 %); CBZ (40 %), IBU (47 %). The phase separation of anaerobic digestion provided a deeper understanding of the biotransformation pathways of PPCPs, in addition to enhancing the biodegradability of the most persistent compounds, i.e., DCF, CBZ and IBU.

Fingerprinting of emerging contaminants in L'Albufera natural park (Valencia, Spain): Implications for wetland ecosystem health.

Wetlands are crucial ecosystems that are increasingly threatened by anthropogenic activities. L'Albufera Natural Park, the second-largest coastal wetland in Spain, faces significant pressures from surrounding agricultural lands, industrial activities, human settlements, and associated infrastructures, including treated wastewater inputs. This study aimed at (i) establishing pathways of emerging pollutants entering the natural wetland using both target and non-target screening (NTS) for management purposes, (ii) distinguishing specific contamination hotspots through Geographic Information System (GIS) and (iii) performing basic ecological risk assessment to evaluate ecosystem health. Two sampling campaigns were conducted in the spring and summer of 2019, coinciding with the start and end of the rice cultivation season, the region's primary agricultural activity. Each campaign involved the collection of 51 samples. High-resolution mass spectrometry (HRMS) was employed, using a simultaneous NTS approach with optimized gradients for pesticides and moderately polar compounds, along with complementary NTS methods for polar compounds, to identify additional contaminants of emerging concern (CECs). Quantitative analysis revealed that fungicides comprised a substantial portion of detected CECs, constituting approximately 50% of the total quantified pesticides. Tebuconazole emerged as the predominant fungicide, with the highest mean concentration (>16.9 µg L-1), followed by azoxystrobin and tricyclazole. NTS tentatively identified 16 pesticides, 43 pharmaceuticals and personal care products (PPCPs), 24 industrial compounds, and 12 other CECs with high confidence levels. Spatial distribution analysis demonstrated significant contamination predominantly in the southwestern region of the park, gradually diminishing towards the north-eastern outlet. The composition of contaminants varied between water and sediment samples, with pharmaceuticals predominating in water and industrial compounds in sediments. Risk assessment, evaluated through risk quotient calculations based on parent compound concentrations, revealed a decreasing trend towards the outlet, suggesting wetland degradation capacity. However, significant risk levels persist throughout much of the Natural Park, highlighting the urgent need for mitigation measures to safeguard the integrity of this vital ecosystem.

Non-target lesion progression: Unveiling critical predictors and outcomes in patients with in-stent restenosis.

BACKGROUND: Percutaneous coronary intervention (PCI) has become the primary treatment for coronary artery disease. However, while PCI effectively addresses severe stenosis or occlusive lesions in target vessels, the progression of non-target vessel plaque remains a critical determinant of long-term patient prognosis. AIMS: The purpose of this study was to investigate the impact of non-target vascular plaque progression on prognosis after PCI for ISR. METHODS: This study included 195 patients diagnosed with ISR and multivessel disease who underwent successful PCI with drug-eluting stent (DES) placement, along with intraoperative optical coherence tomography (OCT) assessment of the culprit stent. Subsequent rechecked coronary angiography categorized eligible patients into non-target lesion progression (N-TLP) and no-N-TLP groups. We evaluated the baseline morphological characteristics of N-TLP by OCT and investigated the relationship between N-TLP, non-culprit vessel-related major adverse cardiovascular events (NCV-MACE), and pan-vascular disease-related clinical events (PVD-CE) incidence. RESULTS: Multivariate logistic regression analysis revealed that diabetes mellitus (OR 3.616, 95% CI: 1.735-7.537; P = 0.001), uric acid level (OR 1.005, 95% CI: 1.001-1.009; P = 0.006), in-stent neoatherosclerosis (ISNA) (OR 1.334, 95% CI: 1.114-1.985; P = 0.047) and heterogeneous neointima morphology (OR 2.48, 95% CI: 1.18-5.43; P = 0.019) were independent predictors for N-TLP. Furthermore, N-TLP was associated with a high incidence of NCV-MACE (19.4% vs 6.9%, P = 0.009) and PVD-CE (83.9% [95% CI: 79.7%-88.3%] vs 93.1% [95% CI: 88.4%-98.0%], P = 0.038) after PCI in ISR patients. CONCLUSION: Diabetes, uric acid levels, ISNA, and heterogeneous neointima are predictive factors for subsequent rapid plaque progression, with N-TLP exacerbating the incidence of NCV-MACE and PVD-CE after PCI.

Correlation between the Atherogenic Index of Plasma and Progression of Non-target Lesion Vascular Disease Following Percutaneous Coronary Intervention Using Drug-eluting Stents.

OBJECTIVE: To examine the correlation between Atherogenic Index of Plasma (AIP) levels and the progression of non-target lesion vascular disease following the deployment of drug-eluting stents (DES). METHODS: We retrospectively enrolled patients who had undergone successful treatment for CAD with DES and subsequently underwent a coronary angiography follow-up at the Cardiology Department of Tianjin Third Central Hospital from January 2017 to July 2022. The annual change in Gensini Score (GS) was calculated according to two angiographic evaluations in order to assess the progression of non-target lesion vascular disease; a change greater than 1 indicated progression, while a change of 1 or less indicated stability. AIP was calculated according to serum lipid parameters. Multivariate Logistic regression model was used to evaluate the relationship between AIP level and progression of non-target coronary artery lesions. The ROC curve analysis was performed to evaluate the diagnostic value of AIP for coronary artery non-target lesion vascular disease progression. RESULTS: Out of the 344 patients who were monitored over a median duration of 1.2 years, 113 exhibited progression of non-target lesion vascular disease. Initially, baseline AIP levels were notably higher in the progression group compared to the non-progression group (0.30 [0.14, 0.43] vs. 0.11 [-0.06, 0.31]), and this difference remained significant during the follow-up period (0.19 [0.06, 0.34] vs. 0.11 [-0.06, 0.22]). Multivariate logistic regression revealed that AIP is an independent predictor for the progression of non-target lesion vascular disease following DES treatment. Individuals in the highest tertile of AIP faced a considerably elevated risk compared to those in the lowest tertile (OR = 4.88, 95% CI: 2.12-11.21, P < 0.001). Moreover, utilizing receiver operating characteristic curve analysis, a 0.15 AIP level cut-off was determined for diagnosing disease progression, with a sensitivity of 73.5% and specificity of 56.7%, and an area under the curve of 0.672 (95% CI: 0.613-0.731, P < 0.01). CONCLUSION: AIP significantly correlates with the progression of non-target lesion vascular disease among patients with coronary artery disease who have undergone DES treatment, establishing itself as an independent risk factor in addition to conventional predictors.