Search

BackgroundThe current 2019 novel coronavirus disease (COVID-19) pandemic is a major threat to global health. It is currently uncertain whether and how liver injury affects the severity of COVID-19. Therefore, we conducted a meta-analysis to determine the association between liver injury and the severity of COVID-19.MethodsA systematic search of the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2022, was performed to analyse the reported liver chemistry data for patients diagnosed with COVID-19. The pooled odds ratio (OR), weighted mean difference (WMD) and 95% confidence interval (95% CI) were assessed using a random-effects model. Furthermore, publication bias and sensitivity were analyzed.ResultsForty-six studies with 28,663 patients were included. The pooled WMDs of alanine aminotransferase (WMD = 12.87 U/L, 95% CI: 10.52–15.23, I2 = 99.2%), aspartate aminotransferase (WMD = 13.98 U/L, 95% CI: 12.13–15.83, I2 = 98.2%), gamma-glutamyl transpeptidase (WMD = 20.67 U/L, 95% CI: 14.24–27.10, I2 = 98.8%), total bilirubin (WMD = 2.98 μmol/L, 95% CI: 1.98–3.99, I2 = 99.4%), and prothrombin time (WMD = 0.84 s, 95% CI: 0.46–1.23, I2 = 99.4%) were significantly higher and that of albumin was lower (WMD = −4.52 g/L, 95% CI: −6.28 to −2.75, I2 = 99.9%) in severe cases. Moreover, the pooled OR of mortality was higher in patients with liver injury (OR = 2.72, 95% CI: 1.18–6.27, I2 = 71.6%).ConclusionsHepatocellular injury, liver metabolic, and synthetic function abnormality were observed in severe COVID-19. From a clinical perspective, liver injury has potential as a prognostic biomarker for screening severely affected patients at early disease stages.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, Identifier: CRD42022325206.

This paper employed a physiologically based pharmacokinetic model (PBPK) to investigate the transformations of folic acid and its metabolites in vivo. Additionally, an ultra-performance liquid chromatography (UPLC) method was developed to accurately measure the body's retention rate and conversion rate of folic acid, tetrahydrofolate, and 5-methyltetrahydrofolate. Furthermore, the bioavailability of folic acid in the body was assessed by combining this method with an evaluation technique for animal models. The study found that the gastric metabolism time was 2 h, while the small intestinal metabolism duration was 4 h. The maximum conversion rate was observed in plasma and liver after 6 h, and in the brain after 8 h. This serves as a framework for creating a model to assess the bioavailability of folic acid in living organisms, to enhance the safety and efficacy of folic acid intake., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Covalent protein adducts formed by drugs or their reactive metabolites are risk factors for adverse reactions, and inactivation of cytochrome P450 (CYP) enzymes. Characterization of drug-protein adducts is limited due to lack of methods identifying and quantifying covalent adducts in complex matrices. This study presents a workflow that combines data-dependent and data-independent acquisition (DDA and DIA) based liquid chromatography with tandem mass spectrometry (LC-MS/MS) to detect very low abundance adducts resulting from CYP mediated drug metabolism in human liver microsomes (HLMs). HLMs were incubated with raloxifene as a model compound and adducts were detected in 78 proteins, including CYP3A and CYP2C family enzymes. Experiments with recombinant CYP3A and CYP2C enzymes confirmed adduct formation in all CYPs tested, including CYPs not subject to time-dependent inhibition by raloxifene. These data suggest adducts can be benign. DIA analysis showed variable adduct abundance in many peptides between livers, but no concomitant decrease of unadducted peptides. This study sets a new standard for adduct detection in complex samples, offering insights into the human adductome resulting from reactive metabolite exposure. The methodology presented will aid mechanistic studies to identify, quantify and differentiate between adducts that result in adverse drug reactions and those that are benign.

Background: Discussion of the benefits of moderate alcohol consumption is ongoing. Broadly, research focusing on ethanol consumption tends to report no benefits. However, studies that distinguish between different types of alcoholic beverages, particularly beers, often reveal positive effects. The present study evaluated the genotoxic and mutagenic effects of moderate chronic consumption of India Pale Ale (IPA) craft beer. Sixty-four adult male Swiss mice were used and divided into control and treatment groups receiving water, IPA beer with 55.23 g of ethanol per liter of beer, aqueous solution with 55.23 g of ethanol per liter, and hop infusion ad libitum for 30 days. After this period, the animals were genetically evaluated with a comet assay. For the ex vivo comet assay, blood was collected and exposed to hydrogen peroxide (H 2 O 2 ). For the in vivo assay, the alkylating agent cyclophosphamide (CP) was administered to the groups after blood collection and sacrificed after 24 h. Brain, liver, and heart tissues were analyzed. Bone marrow was collected and submitted to the micronucleus test., Results: The groups treated with IPA beer, ethanol, and hops did not show genotoxic and mutagenic action in the blood, brain, heart, or liver. The antigenotoxic action of IPA beer and hops was observed in both in vivo and ex vivo models, showing a similar reduction in DNA damage caused by CP. There was no significant difference between the groups with regard to the formation of micronuclei by CP., Conclusion: Moderate chronic consumption of IPA beer and hops infusion showed antigenotoxic effects in mice but no antimutagenic action. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Cysteine (Cys) not only plays an indispensable role in maintaining the redox balance in organisms, but is also an important nutrient in the food industry. Fluorescence-based detection systems have emerged as an effective method to track the locations and concentrations of different species. To achieve efficient monitoring of Cys in both food samples and biological systems, a novel lipid droplet (LD) targeted fluorescent probe (namely NIT-Cys) was constructed for the turn-on detection of Cys, characterized by a large Stokes shift (142 nm), a short response time (<8 min), and a low Cys detection limit (39 nM). Furthermore, the NIT-Cys probe has been successfully used not only to quantify the amounts of Cys in selected food samples, but also to enable the visualization of endogenous Cys in acetaminophen (APAP)-induced drug-induced liver injury cells, zebrafish larvae and mice models. Consequently, the work presented here provides an efficient tool for monitoring Cys., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Liquid chromatography-triple quadrupole mass spectrometry (LC-MS-MS) assays are frequently utilized for screening and confirmatory purposes in the forensic toxicology laboratory. While these techniques are excellent for the targeted identification and quantitation of a wide variety of drug classes, validation and determining fit-for-purpose is a significant requirement for each method. In the USA, the American National Standards Institute and Academy Standards Board first edition of Standard 036 currently serves as a primary resource in forensic toxicology method validation and mandates that laboratories evaluate critical performance characteristics to help ensure the production of forensically defensible results. Due to the variability of specimen quality frequently encountered in the discipline of postmortem toxicology, the State of Maryland Office of the Chief Medical Examiner Forensic Toxicology Laboratory routinely analyzes solid tissue specimens as part of the medicolegal death investigation process and evaluates liver as a representative solid tissue matrix during method validation. Authentic postmortem specimens (e.g. liver, kidney, skeletal muscle, and spleen) were used to investigate the effects of analyzing solid tissue homogenate versus solid tissue supernatant on bias, precision, and ionization suppression/enhancement of Δ9-THC and Δ9-THCCOOH. Bias was <20% for Δ9-THC and Δ9-THCCOOH in liver homogenate and supernatant with a single exception of the low QC concentration for Δ9-THC in liver homogenate (-29%). Within-run and between-run CV was <20% for Δ9-THC and Δ9-THCCOOH in liver homogenate and supernatant. Δ9-THC and Δ9-THC-d3 exhibited significant ion suppression in both liver homogenate and supernatant, while Δ9-THCCOOH and Δ9-THCCOOH-d3 showed both ion suppression and enhancement in these matrices. Noticeable quantitative differences were observed in authentic postmortem solid tissue homogenate and supernatant specimens despite evaluating identical tissue samplings. A brief discussion of the results is presented using a validated LC-MS-MS method for the confirmation and quantitation of Δ9-THC and Δ9-THCCOOH in postmortem casework., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and albumin are well-established liver biomarkers with significant physiological functions. Alterations in these liver function tests can be indicative of the presence and progression of acute and chronic liver conditions such as liver cirrhosis, non-alcoholic fatty liver disease, biliary disease, and liver failure. Therefore, accurate and quantitative detection of these biomarkers is crucial for diagnosing and monitoring liver disease. There are several commercially available chemistry analyzers capable of simultaneously detecting all these biomarkers, as well as numerous biosensors designed for individual detection. Various techniques have been employed, including colorimetry, surface-enhanced Raman spectroscopy (SERS), electrochemiluminescence (ECL), fluorescence-based techniques, and electrochemical methods. Among these, electrochemical detection stands out due to its simplicity, cost-effectiveness, low sample volume requirement, label-free detection, high sensitivity, fast response times, miniaturization, and portability. Information on recently developed electrochemical biosensors is summarized through detailed tables and is intended to guide future research and development efforts in this area.

Globally, perfluoroalkyl acids (PFAA) are ubiquitous due to their almost unlimited applications in industry and households and are detected in a wide variety of matrices.Aquatic ecosystems are of particular importance due to the spread of PFAA via water fluxes. The majority of published studies describe PFAA concentrations in fish or aquatic mammals, but not the dependence of PFAA concentrations in tissues and organs in fish of different ages. Since this is very important for understanding the accumulation behavior of these substances our study systematically investigates the influence of age on the PFAA concentration in the tissues of 74 perches (Perca fluviatilis), a very popular edible fish. Fish are particularly suitable as indicators of PFAA contamination of water because of their uptake via water (gills and skin) and food (predominantly piscivorous diet). The mean total PFAA concentrations (as the sum of the individual concentrations of 11 compounds) were: 114 μg/kg (kidney), 112 μg/kg (heart), 79.9 μg/kg (liver), 78.4 μg/kg (spleen), 64.6 μg/kg (gills) and 21.7 μg/kg (muscle), with longer-chain compounds accounting for 90% of the substances. Perfluorooctanesulfoic acid (PFOS) accounted for the largest percentage of the total PFAA concentration in all tissues at 43-63%. With the exception of the heart and spleen, a significant increase in total concentrations was observed with increasing age of the perch. The strongest correlation was observed for the kidney, followed by the liver and gills. With regard to their consumption as human nutrition the tolerable weekly PFAA intake of 4.4 ng/kg bodyweight and week for the sum of the 4 EFSA PFAA in adults and children was exceeded many times over (860% and 1600% respectively) with an average fish consumption per week. The maximum PFAA levels set in the E.U. since January 2023 were exceeded five times., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Heavy metals and metalloids in the environment are recognised as a threat to the health of organism. Terrestrial birds are ideal subjects for the examination of these pollutants because of their high mobility and high intra- and interspecific variation in trophic levels. We examined the contents of 6 trace metals (Cd, Pb, Cr, Sb and V) and metalloids (As) in the liver, kidney, muscle, and feathers of woodcocks (Scolopax rusticola) from Southern Italy by a validated ICP-MS method. Significant differences in trace elements were found in all the tissues examined (p < 0.05). The highest Sb and Cr levels were found in feathers samples with mean values of 0.019 mg/Kg and 0.085 mg/Kg, respectively. High Pb levels were found in muscle, with 23 % of the samples exceeding the limits set by the European Union. Cd was predominantly found in the kidney samples (0.76 mg/Kg). Vanadium was the less abundant trace metal, showing the highest concentrations in the liver (0.028 ± 0.011 mg/Kg). Higher As levels were found in muscle (0.02 ± 0.015 mg/Kg). No significant differences between sex and age classes (juveniles vs. adults) were found, nor were there correlations between morphometric parameters and trace metal/metalloid contents. Principal Component Analysis determined differences in metal accumulation between tissues. Feathers were confirmed as useful indicators of metal contamination. The results of this work confirmed that the accumulation of toxic elements in the tissues of woodcocks is primarily influenced by ecological traits such as feeding habits and migration status. Statistical analysis of the tissues would seem to exclude important accumulation phenomena of Pb. The high levels found in the muscle could be due to lead ammunition. This work provides the first data on the accumulation of As, Cr, Sb, and V in woodcocks tissue, providing a more comprehensive insight into the potential impact of these pollutants on birds., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To date, the presence of pharmaceuticals has been extensively documented across a wide range of aquatic systems and biota. Further, substantial progress has been made in transitioning from laboratory assessments of pharmaceutical fate and effects in fish to in situ assessments of exposure and effects; however, certain research areas remain understudied. Among these is investigation of differential accumulation across multiple internal tissues in wild marine fish beyond the species commonly sampled in laboratory and freshwater field settings. This study examined the presence of pharmaceuticals across four tissues (plasma, muscle, brain, and liver) in a wild marine fish, bonefish (Albula vulpes), throughout coastal South Florida, USA. Differential accumulation across tissues was assessed for the number and concentration, identity, and composition of accumulated pharmaceuticals by sampling 25 bonefish and analyzing them for 91 pharmaceuticals. The concentration of pharmaceuticals was highest in plasma > liver > brain > muscle, while the number of pharmaceuticals was highest in liver > brain > plasma > muscle. The identity of detected pharmaceuticals was tissue specific, and there was an inverse relationship between the number of detections for each pharmaceutical and its log K ow . The composition of pharmaceuticals was tissue specific for both pharmaceutical presence/absence and concentration. Across all tissues, the greatest similarity was between brain and liver, which were more similar to plasma than to muscle, and muscle was the most distinct tissue. For tissue compositional variability, muscle was the most diverse in accumulated pharmaceuticals, while plasma, brain, and liver were similarly variable. With the highest concentrations in plasma and highest number in liver, and documented variability in accumulated pharmaceuticals across tissues, our results highlight the importance of tissue selection when surveying exposure in wild fish, suggesting that multi-tissue analysis would allow for a more comprehensive assessment of exposure diversity and risk of adverse effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Gangliosides play an imperative role in cell signaling, neuronal recovery, apoptosis, and other physiological processes. For example, GM 3 can regulate hypothalamic leptin resistance and control energy homeostasis, GD 3 can mediate cell proliferation and differentiation and induce apoptosis, and GQ1b can stimulate neurogenesis. Therefore, the present study sought to establish and optimize the targeted analysis method for ganglioside subclasses and their molecular species using hydrophilic interaction liquid chromatography-triple quadrupole-MS/MS (HILIC-QQQ-MS/MS). Additionally, the fragmentation pattern of different ganglioside subclasses and their retention time patterns were analyzed, providing more accurate qualitative results. The limit of quantitation (LOQ) was as low as 10 -4  ng. Moreover, the molecular species of gangliosides in the liver, cortex, and hypothalamus of C57BL/6 mice were analyzed using the established method. A total of 23 ganglioside subclasses with 164 molecular species, including 40 O-acetylated ganglioside molecular species and 28 NeuGc ganglioside molecular species, were identified using the semi-quantitative analysis method of an external standard curve corrected by an internal standard. In addition to NeuGc gangliosides, the contents of ganglioside subclasses were more abundant in the mouse brain than those in the mouse liver; especially, the contents of unsaturated gangliosides in the hypothalamus were much higher than those in the liver. Among them, O-acetylated gangliosides were detected only in the cortex and hypothalamus at a concentration of up to 100 μg/mg protein (40 molecular species). Overall, the proposed method expanded the detectable number of ganglioside subclasses and molecular species in biological samples and provided more opportunities for further study of the biological functions of gangliosides., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Relatively little information exists on the effects of mercury on terrestrial wildlife populations. We analyzed 38 free-living small rodent females (Myodes glareolus, Microtus agrestris, and Apodemus flavicolis), of which 11 were pregnant, for total mercury concentrations in combined liver and kidney samples. Using a single-purpose atomic absorption spectrometer for mercury determination, the measured mercury values ranged from 0.006 to 0.079 mg/kg. Pregnant females had significantly (P<0.041) higher mercury levels in liver and kidney than did nonpregnant females. Our results suggest that during mercury biomonitoring studies it is necessary to consider the pregnancy of the analyzed animals., (© Wildlife Disease Association 2024.)

Background: As one of the speculated bisphenols to replace bisphenol A (BPA), bisphenol F (BPF), naturally present in mustard, is structurally similar to BPA and may have similar estrogenic activity, but information on its toxicity is very limited compared to BPA., Objective: In order to support the toxicology study of BPF at Heath Canada, a GC-MS method based on solid-phase extraction (SPE) and derivatization was developed for analysis of BPF in liver samples., Methods: Samples were treated with β-glucuronidase to convert BPF glucuronide to free BPF for analysis of total BPF., Results: The method was validated for free BPF at different spiking levels, and recoveries ranged from 90-97.5% with RSDs from 0.11-5.54%. The method was also validated for glucuronide-conjugated BPF at different spiking levels of BPF mono-β-D-glucuronide: recoveries ranged from 72.3-93.3% with RSDs from 1.7-8.94%. The method was used to analyze 60 liver tissue samples from rats dosed with BPF at different levels in a toxicology study. Free and glucuronide-conjugated BPF were not detected in any of the control samples, which were not dosed with BPF (average method detection limit: 0.31 ng/g) but detected in all the other liver tissue samples with levels increasing at higher doses. The percentage of glucuronide-conjugated BPF in total BPF varied among the liver samples, from as low as 9.8% to as high as 77.9%, indicating the importance of analyzing biological samples for BPF in both free and conjugated forms for total exposure., Conclusion: A GC-MS method based on solid-phase extraction (SPE) and derivatization was developed for analysis of both free and glucuronide-conjugated BPF in liver samples. This method was validated not only for free BPF, but also for mono-β-D-glucuronide-conjugated BPF for the first time to confirm the efficiency of the deconjugation procedure with enzyme., Highlights: This method can be adapted and applied for analysis of free and glucuronide-conjugated BPF in other biological samples with appropriate validation in target sample matrixes., (© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pesticide residues may enter the human body through the food chain when livestock and poultry consume pesticide-contaminated feed. Therefore, monitoring and limiting pesticide residues in animal feed and animal-origin foods is necessary. Carbendazim is one of the most frequently detected pesticides in food and feed and has various toxic effects on non-target animals. This study investigated the effects of varying concentrations of carbendazim contamination in feed on broiler chicken growth performance, serum biochemical indicators, histopathology, and carbendazim residues in broiler muscles and livers. The results demonstrated that contamination of 5-100 mg/kg carbendazim in feed did not affect broiler growth performance or health. Carbendazim contamination in feed at 200-800 mg/kg slightly reduced growth performance. Broiler kidneys showed minor histopathological alterations after 400 mg/kg carbendazim exposure. Furthermore, when the carbendazim content in feed was less than 25 mg/kg, the residual carbendazim in the muscles and livers of broilers did not exceed the maximum residue level set by the European Union and China. Based on the above findings, carbendazim residues in the feed of less than 25 mg/kg can be considered safe for chicken products., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

This study aimed to present a selective and effective method for analyzing quinolones (QNs) in food matrix. Herein, a NiFe 2 O 4 -based magnetic sodium disulfonate covalent organic framework (NiFe 2 O 4 /COF) was prepared using a simple solvent-free grinding method, and was adopted as a selective adsorbent for magnetic solid phase extraction of QNs. Coupled with UHPLC-Q-Orbitrap HRMS, an efficient method for simultaneous detection of 18 kinds of QNs was established. The method exhibited good linearity (0.01-100 ng g -1 ), high sensitivity (LODs ranging from 0.0011 to 0.0652 ng g -1 ) and precision (RSDs below 9.5%). Successful extraction of QNs from liver and kidney samples was achieved with satisfactory recoveries ranging from 82.2% to 108.4%. The abundant sulfonate functional groups on NiFe 2 O 4 /COF facilitated strong affinity to QNs through electrostatic and hydrogen bonding interactions. The proposed method provides a new idea for the extraction of contaminants with target selectivity., Competing Interests: Declaration of competing interest The authors declare that none of the work presented in this study may have been impacted by any known competing financial interests or personal ties., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bile acids (BA) play a crucial role not only in lipid digestion but also in the regulation of overall energy homeostasis, including glucose and lipid metabolism. The aim of this study was to investigate BA profiles and mRNA expression of BA-related genes in the liver of high versus normal body condition in dairy cows. We hypothesized that body condition and the transition from gestation to lactation affect hepatic BA concentrations as well as the mRNA abundance of BA-related receptors, regulatory enzymes, and transporters. Therefore, we analyzed BA in the liver as well as the mRNA abundance of BA-related synthesizing enzymes, transporters, and receptors in the liver during the transition period in cows with different body conditions around calving. In a previously established animal model, 38 German Holstein cows were divided into groups with high body condition score (HBCS; n = 19) or normal body condition score (NBCS; n = 19) based on BCS and backfat thickness (BFT). Cows were fed diets aimed at achieving the targeted differences in BCS and BFT (NBCS: BCS <3.5, BFT <1.2 cm; HBCS: BCS >3.75, BFT >1.4 cm) until they were dried off at wk 7 before parturition. Both groups were fed identical diets during the dry period and subsequent lactation. Liver biopsies were taken at wk -7, 1, 3, and 12 relative to parturition. For BA measurement, a targeted metabolomics approach with liquid chromatography electrospray ionization MS/MS was used to analyze BA in the liver. The mRNA abundance of targeted genes related to BA synthesizing enzymes, transporters, and receptors in the liver was analyzed using microfluidic quantitative PCR. In total, we could detect 14 BA in the liver: 6 primary and 8 secondary BA, with glycocholic acid (GCA) being the most abundant one. The increase of glycine-conjugated BA after parturition, in parallel to increasing serum glycine concentrations may originate from an enhanced mobilization of muscle protein to meet the high nutritional requirements in early lactating cows. Higher DMI in NBCS cows compared with HBCS cows was associated with higher liver BA concentrations such as GCA, deoxycholic acid, and cholic acid. The mRNA abundance of BA-related enzymes measured herein suggests the dominance of the alternative signaling pathway in the liver of HBCS cows. Overall, BA profiles and BA metabolism in the liver depend on both, the body condition and lactation-induced effects in periparturient dairy cows., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Lack of n-3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short-term supplementation with DHA-enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n-3-deficient mice., Results: Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA-enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA-PS and DHA-PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether-linked PC (ePC) and liver lyso-phosphatidylcholine molecular species. DHA-PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA-PS., Conclusion: The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Human activities have changed the natural rates at which metals are moved and accumulated in both land and water environments, resulting in negative impacts on local wildlife. In this study, concentrations of Cr, Ni, Cd, Pb, Cu, Mn, Co, and Zn were evaluated in water and riverbed sediment samples collected from the Verde River basin (VR), as well as in tissue samples from five native Loricariidae species. Sediment samples collected from the central section of the VR riverbed indicated the presence of metal concentrations, which were primarily attributed to scattered pollution sources linked to rural activities in the surrounding areas. The bioconcentration factor in the Loricariids liver presented the highest average values for Zn (1.27-58.21), Co (0.48-14.91) and Cu (1.15-11.14). The same pattern was observed in the muscle, but in a lower proportion. Regarding the bioaccumulation factor, Co (1.54-34.84), Cu (5.85-25.22) and Zn (0.64-18.08) attained the highest average values in the liver. The co-inertia analysis examined the spatial distribution of metal concentrations in riverbed sediments and in tissues of Loricariids from the upper, middle, and lower stretches of the river, including the river mouth. The analysis revealed varying patterns, with samples from some regions showing higher bioaccumulation levels. This suggests that riverbed sediments are a primary source of metal contamination in Loricariids from these areas. The pollution has had a significant impact on the bioaccumulation of metals in the VR' Loricariids, which are good indicators of sediment-associated metal bioaccumulation. The metal concentrations recorded in both the riverbed sediments and Loricariids surpassed international and Brazilian limits set for aquatic health and safe human consumption. Given the importance of the Verde River in terms of its ecological, social, cultural, and economic roles, it is essential to implement biomonitoring and control measures to safeguard both terrestrial and aquatic resources., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Estevan Luiz da Silveira reports a relationship with Araucaria Foundation (State of Paraná Research Foundation) and Boticário Group Foundation for Nature Protection. That includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Accurate interpretation of mercury (Hg) isotopic data requires the consideration of several biotic factors such as age, diet, geographical range, and tissue metabolic turnover. A priori knowledge of prey-predator isotopic incorporation rates and Hg biomagnification is essential. This study aims to assess Hg stable isotopes incorporation in an Arctic species of Phocidae, the hooded seal Cystophora cristata, kept in human care for 24 months (2012-2014) and fed on a constant diet of Norwegian Spring Spawning herring Clupea harengus. We measured THg, MMHg and iHg levels, as well as Hg stable isotope composition with both mass dependent (MDF) and mass independent (MIF) fractionation (e.g. δ 202 Hg and Δ 199,200,201,204 Hg) in hooded seal kidney, liver, hair and muscle, in addition to herring muscle. We then calculated Hg MDF and MIF isotopic fractionation between hooded seals and their prey. We found a significant shift in δ 202 Hg between hooded seal hair (+0.80‰) and kidney (-0.78‰), and herring muscle. In hooded seals tissues δ 202 Hg correlated positively with MMHg percentage. These findings suggest that tissue-specific Hg speciation is the major driver of changes in Hg isotopic fractionation rates in this Arctic predator. Δ 199 Hg, Δ 200 Hg, Δ 201 Hg and Δ 204 Hg values did not vary between herring and hooded seal tissues, confirming their utility as tracers of Hg marine and atmospheric sources in top predators. To our knowledge, this represents the first attempt to assess complex Hg isotope dynamics in the internal system of Arctic Phocidae, controlling the effects of age, diet, and distribution. Our results confirm the validity of Hg stable isotopes as tracers of environmental Hg sources even in top predators, but emphasize the importance of animal age and tissue selection for inter-study and inter-species comparisons., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Tilapia is a model fish species used as a pollution biomonitor due to its tolerance and availability in many contaminated sites. Blue tilapia Oreochromis aureus specimens (n = 320) were collected in eleven dams influenced by mining in the SE Gulf of California region (dams 1, 2 and, 3 comprise 55 mining sites; dam 4 comprises 8; dams 6, 8, 10, and 11, ≤ 6; and dams 5, 7, and 9 include 19, 20, and 16 mining sites, respectively). Cadmium, Cu, Pb, and Zn concentrations were analyzed in the muscle, liver, gills, and guts to identify metal pollution and evaluate risks and seasonal changes. The distinct tissues exhibited different metal accumulation capacities, therefore allowed develop a diagnosis comparative between the eleven dams. In general, metal concentrations were higher in dams 1, 2, 5, and 9, which are associated with more mining sites in their sub-basins. The four metals exhibited the highest levels in the tilapia liver in dams 1 and 2, which can be related to the present and past mining activity in the lower watershed (55 sites) and the geothermal activity in these dams. In general, Zn exhibited the highest level in the tilapia livers from dams 1, 2, 3, 4, 5, and 10 compared to the maximum mean (220 µg/g) concentrations previously recorded. The non-carcinogenic risks indicated that the Pb risk was enhanced when the intake was ≥ 231.5 g week -1 of tilapia muscle, indicating a potential risk of adverse health effects for the entire population., (© 2024. The Author(s).)

Highly abundant proteins present in biological fluids and tissues significantly interfere with low-abundance protein identification by mass spectrometry (MS), limiting proteomic depth and hindering protein biomarker discovery. Herein, to enhance the coverage of tissue proteomics, we developed a nanoparticle-protein corona (NP-PC)-based method for the aging mouse proteome atlas. Based on this method, we investigated the complexity of life process of 5 major organs, including the heart, liver, spleen, lungs, and kidneys, from 4 groups of mice at different ages. Compared with the conventional strategy, NP-PC-based proteomics significantly increased the number of identified protein groups in the heart (from 3007 to 3927; increase of 30.6%), liver (from 2982 to 4610; increase of 54.6%), spleen (from 5047 to 7351; increase of 45.7%), lungs (from 4984 to 6903; increase of 38.5%), and kidneys (from 3550 to 5739; increase of 61.7%), and we identified a total of 10 104 protein groups. The overall data indicated that 3-week-old mice showed more differences compared with the other three age groups. The proteins of amino acid-related metabolism were increased in aged mice compared with those in the 3-week-old mice. Protein-related infections were increased in the spleen of the aged mice. Interestingly, the spliceosome-related pathway significantly changed from youth to elders in the liver, spleen, and lungs, indicating the vital role of the spliceosome during the aging process. Our established aging mouse organ proteome atlas provides comprehensive insights into understanding the aging process, and it may help in prevention and treatment of age-related diseases.

Iron plays vital roles in important biological processes in fish, but can be toxic in high concentrations. The information on metalloproteins that participate in maintenance of Fe homeostasis in an esocid fish, the northern pike, as an important freshwater bioindicator species, are rather scarce. The aim of this study was to identify main cytosolic constituents that sequester Fe in the northern pike liver. The method applied consisted of two-dimensional HPLC separation of Fe-binding biomolecules, based on anion-exchange followed by size-exclusion fractionation. Apparent molecular masses of two main Fe-metalloproteins isolated by this procedure were ~360 kDa and ~50 kDa, with the former having more acidic pI, and indicated presence of ferritin and hemoglobin, respectively. MALDI-TOF-MS provided confirmation of ferritin subunit with a m/z peak at 20.65 kDa, and hemoglobin with spectra containing main m/z peak at 16.1 kDa, and smaller peaks at 32.1, 48.2, and 7.95 kDa (single-charged Hb-monomer, dimer, and trimer, and double-charged monomer, respectively). LC-MS/MS with subsequent MASCOT database search confirmed the presence of Hb-β subunits and pointed to close relation between esocid and salmonid fishes. Further efforts should be directed towards optimization of the conditions for metalloprotein analysis by mass spectrometry, to extend the knowledge on intracellular metal-handling mechanisms., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

This study reports OCP and PAH concentrations in the tissues of stranded sea snakes from Sharjah, UAE. Samples from 10 Hydrophis lapemoides, 2 Hydrophis ornatus and 1 Hydrophis curtus were analyzed. Muscle, liver and fat tissues were extracted using micro-QuEChERs, followed by d-SPE and analyzed using GC/MS. Higher concentrations of OCPs were detected, while PAHs were more frequently detected. Significant correlations suggest that OCPs and PAHs do bioaccumulate in the tissues of sea snakes. Additionally, OCPs with lower log Kow (octanol-water partition coefficient) values were mainly detected in the muscle samples of H. lapemoides, whereas OCPs with higher log Kow values were more commonly present in the liver and fat samples. The concentrations of OCPs reported in this study were higher than those previously documented in other marine reptiles in the UAE or sea snakes from different geographical regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Understanding the mechanism by which non-native fish species integrate into native communities is crucial for evaluating the possibility of their establishment success. The genus Pangasianodon, comprising Pangasianodon gigas and Pangasianodon hypophthalmus, has been introduced into reservoirs, which are non-native habitats, for fishery stock enhancement. P. gigas and P. hypophthalmus often successfully establish and co-occur in several Thai reservoirs, but there is little information on differences in food resource use between the two species. To investigate the trophic niche width of P. gigas and P. hypophthalmus in a Thai reservoir, we conducted stable carbon and nitrogen ratio (δ 13 C and δ 15 N) analyses. We examined the degree of individual specialization in both species using the δ 13 C and δ 15 N values of muscle and liver tissues, which provides long- and short-term diet information. The isotopic niches did not overlap between P. gigas and P. hypophthalmus. The δ 15 N value of P. gigas was significantly higher than that of P. hypophthalmus, whereas the δ 13 C value did not significantly differ between the two species. The isotopic niche sizes were larger in P. hypophthalmus than in P. gigas. Individual specialization was observed in P. hypophthalmus but not in P. gigas, indicating that intraspecific variation in food resource use was larger in P. hypophthalmus compared to P. gigas. These findings suggest that trophic niche partitioning was one of the factors facilitating the establishment success of P. gigas and P. hypophthalmus in a reservoir, but the establishment process may differ between the two species., (© 2024 Fisheries Society of the British Isles.)

Bats constitute about 22% of known mammal species; they have various ecological roles and provide many ecosystem services. Bats suffer from several threats caused by anthropization, including exposure to toxic metals and metalloids. We analyzed 75 papers in a systematic literature review to investigate how species, diet, and tissue type impact bioaccumulation. Most studies documented element accumulation in fur, liver, and kidney; at least 36 metals and metalloids have been measured in bat tissues, among the most studied were mercury and zinc. Comparisons with known toxicological thresholds for other mammals showed concerning values for mercury and zinc in bat hair, lead and some essential metals in liver, and iron and calcium in kidneys. Moreover, accumulation patterns in tissues differed depending on bat diet: insectivorous bats showed higher metal concentrations in fur than in liver and kidney while frugivorous species showed higher values in liver and kidney than in fur. Finally, among the bat species that have been studied in more than two papers, the big brown bat (Eptesicus fuscus) show values of mercury in hair and copper in liver that exceed the known thresholds; as does copper in the liver of the little brown bat (Myotis lucifugus). Most studies have been conducted in temperate North America and Eurasia, areas with the lowest bat species diversity; there is a paucity of data on tropical bat species. This review points out several information gaps in the understanding of metal contamination in bats, including a lack of measured toxicity thresholds specific for bat tissues. Data on trace element bioaccumulation and its associated health effects on bats is important for conservation of bat species, many of which are threatened., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Spent hemp biomass (SHB) contains trace amounts of cannabinoids, including Δ 9 -tetrahydrocannabinol (Δ 9 -THC), that may accumulate in the tissues of animals consuming SHB. We measured cannabinoid residues in the liver, adipose tissue, and muscle of finishing lambs fed either 10% or 20% SHB for 8 weeks, or 4 weeks followed by 4 weeks SHB withdrawal. We detected multiple cannabinoids in the liver at a similar proportion to the SHB. However, CBD and Δ 9 -THC were enriched >20-fold in the adipose and muscle, compared to their proportion in SHB. The highest concentration of Δ 9 -THC was detected in adipose tissue and was 7.4-times higher than in muscle. Most cannabinoids were undetectable in tissues after 4 weeks of clearance. The consumers' exposure assessment on Δ 9 -THC revealed tissue levels of total THC (THCA+Δ 9 -THC) that exceed the acute reference dose of 1 μg/kg BW across population groups. When consuming meat from the lambs fed 10% and 20% SHB, the maximum total THC exposure was 2.03 and 7.32 μg/kg BW, respectively, equal to or below the Lowest Observed Adverse Effect Level of 36 μg/kg BW, the No Observed Adverse Effect Level of 12 μg/kg BW or a tolerable dose intake of 7 μg/kg BW., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Phosphatidylethanol (PEth) is an alcohol derivative that has been employed as a blood-based biomarker for regular alcohol use. This study investigates the utility of phosphatidylethanol (PEth) as a biomarker for assessing alcohol consumption in post-mortem brain tissue. Using samples from the New South Wales Brain Tissue Resource Centre, we analysed PEth(16:0/18:1) levels in the cerebellum and meninges of individuals with varying histories of alcohol use, including those diagnosed with alcohol use disorder (AUD) and controls. Our findings demonstrate a significant correlation between PEth levels and blood alcohol content (BAC) at the time of death, supporting the biomarker's sensitivity to recent alcohol intake. Furthermore, this study explores the potential of PEth levels in differentiating AUD cases from controls, taking into consideration the complexities of diagnosing AUD post-mortem. The study also examined the relationship between PEth levels and liver pathology, identifying a link with the severity of liver damage. These results underscore the value of PEth as a reliable indicator of alcohol consumption and its potential contributions to post-mortem diagnostics and consequently, research into alcohol-related brain damage., Competing Interests: Declaration of competing interest The Authors report no known competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The increasing recognition of the health impacts from human exposure to per- and polyfluorinated alkyl substances (PFAS) has surged the need for sophisticated analytical techniques and advanced data analyses, especially for assessing exposure by food of animal origin. Despite the existence of nearly 15,000 PFAS listed in the CompTox chemicals dashboard by the US Environmental Protection Agency, conventional monitoring and suspect screening methods often fall short, covering only a fraction of these substances. This study introduces an innovative automated data processing workflow, named PFlow, for identifying PFAS in environmental samples using direct infusion Fourier transform ion cyclotron resonance mass spectrometry (DI-FT-ICR MS). PFlow's validation on a bream liver sample, representative of low-concentration biota, involves data pre-processing, annotation of PFAS based on their precursor masses, and verification through isotopologues. Notably, PFlow annotated 17 PFAS absent in the comprehensive targeted approach and tentatively identified an additional 53 compounds, thereby demonstrating its efficiency in enhancing PFAS detection coverage. From an initial dataset of 30,332 distinct m/z values, PFlow thoroughly narrowed down the candidates to 84 potential PFAS compounds, utilizing precise mass measurements and chemical logic criteria, underscoring its potential in advancing our understanding of PFAS prevalence and of human exposure., (© 2024. The Author(s).)

Abstract: Titanium dioxide is a versatile compound that is found in a variety of consumer products, medical hardware, and pharmaceuticals. Although oral and topical ingestion of this compound is common, intravenous introduction is much less common. We present three cases where significant titanium dioxide deposits were identified in liver and splenic tissue of three decedents, all of whom died of illicit drug overdose in the same geographic area and had fentanyl and its metabolites in blood on postmortem toxicologic testing. At autopsy, liver sections had a granular texture with fine white stippling grossly, and histologic examination of hepatic and splenic tissues showed scattered patches of black granular material with pink birefringence. Energy-dispersive x-ray spectroscopy performed on these tissues revealed the presences of clusters of titanium dioxide. Immunohistochemical staining of both the liver and spleen with CD68 confirmed the titanium dioxide clusters were within macrophages. Intravenous titanium dioxide nanoparticle elimination studies in rats suggest a time sensitive period for this elimination, with a transient period of pigment deposition between 1-58 days following injection. If a time-dependent link between titanium dioxide pigment deposition within tissues and intravenous drug use can be shown, this could be a valuable tool for Pathologists., Competing Interests: GCP had no conflicts of interest to be declared. JEK had no conflicts of interest to be declared. RFC had no conflicts of interest to be declared. There are no sources of funding to be declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aconitum species are commonly used in traditional Chinese medicine, and they have a narrow therapy window due to the possibility of aconitine poisoning. Aconitine poisoning deaths appear infrequently in forensic practice. It is important to collect valuable body samples in time due to the rapid absorption and excretion of aconitine. However, it is unknown whether postmortem samples have value for toxicological analysis if the deceased has experienced long-term treatment before death. Herein, we present a case of a woman who died after 12 days of failed active treatment for aconitine poisoning. Aconitine was detected in the liver tissue. To our knowledge, this is the first case report describing the detection of aconitine in a decedent after long-term active treatment. The findings indicated that the aconitine concentration in liver tissue can be maintained after long-term treatment; this information may therefore serve as a reference in forensic practice., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The bioavailability of iron from a food depends on its concentration and chemical form but also on dietary factors and nutrient interactions, which are affected by storage conditions and time. Here we investigated the time-course profile of iron in a hybrid 3D-printed food composed of alternating layers of liver and lentils after 0, 5, 7, 14 and 21 days of storage at 4 °C under oxygen or nitrogen packaging. Synchrotron X-ray fluorescence highlighted major variations in iron distribution in both the animal and plant parts of the food as a function of storage conditions. FeP and FeS positive spatial correlations pointed to iron-associated compounds. X-ray absorption near-edge structure spectroscopy showed spectral signatures specific to the animal and plant mixtures, and then highlighted interactions between animal and plant parts during food storage, with a change in iron forms in the plant part., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Schiell reports financial support was provided by BPI (Public bank for investment France). Schiell reports financial support was provided by National Association of Technical Research. Portanguen reports equipment, drugs, or supplies was provided by SOLEIL. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cardiolipins (CL) are special lipids in many respects. First of all, CL are composed of four fatty acids linked by two phosphatidic acids, which provide CL a unique molecular structure. Secondly, in eukaryotic cells they are specific to a single organelle, mitochondria, where they are also synthetized. CL are one of the most abundant lipid classes in mitochondria, mainly localized in the inner membrane. They are key determinants of mitochondrial health and homeostasis by modulating membrane integrity and fluidity, mitochondrial shapes, and metabolic pathways. Disturbances in mitochondrial CL composition can lead to tissue malfunction and diseases. It is therefore important to develop analytical tools to study the mitochondrial lipidome, and more particularly the CL. The method described here allows the quantification of cardiolipins at the sum composition level in isolated mitochondria or in liver tissue by flow injection analysis coupled to differential mobility spectrometry (FIA-DMS), also known as DMS-based shotgun lipidomics., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Endocannabinoids (ECBs) are lipid-derived endogenous molecules with important physiological roles such as regulation of energy balance, immunity, or neural development. Quantitation of ECBs helps better understand their physiological role and modulation of biological processes. This chapter presents the simultaneous quantification of 14 ECBs and related molecules in the brain, liver, and muscle, as well as white and brown adipose tissue using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dynamic range of the method has been tuned to cover the endogenous concentrations of these analytes given the fact that they are endogenously present at different orders of magnitude. Specifically, three groups are established: 0.5-5000 ng/mL for 2-oleoyl- and 2-linoleoylglycerol and arachidonic acid, 0.05-500 ng/mL for 2-arachidonoylglycerol, and 0.0005-0.5 ng/mL for anandamide, palmitoyl-, palmitoleoyl-, stearoyl-, oleoyl-, linoleoyl-, alpha-linolenoyl-, dihomo-gamma-linolenoyl-, docosahexaenoyl-, and pentadecanoylethanolamide., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale: Anabolic steroids, also known as anabolic-androgenic steroids (AAS), encompass steroidal androgens such as testosterone, as well as synthetic counterparts with similar structures and effects. The misuse of AAS has increased over the years, leading to ethical and welfare concerns in sports. The World Anti-Doping Agency (WADA) and the International Federation for Equestrian Sports (FEI) have banned AAS in relevant sports. Methandienone is one of the most identified anabolic androgenic steroids in sports drug testing, Therefore, reliable detection methods are crucial for effective doping control and maintaining the integrity of the sports., Methods: This study explores the use of homogenized camel liver for detecting methandienone metabolites in camels. The biotransformation pathways of methandienone in homogenized camel liver tissues are analyzed using Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) to identify and characterize the phase I and phase II metabolites. Chromatographic separation was achieved using a Thermo-Hypersil C18 column., Results: The study has identified 11 methandienone metabolites (M1-M11), this includes 10 phase I and one phase II metabolite. A glucuronic acid conjugate of methandienone was observed in this study, but no sulfonic acid conjugations were found. The metabolites and their possible chemical structures, along with their fragmentation patterns are confirmed using MSMS (MS2) experiments in data-independent acquisition (DIA) mode., Conclusions: These findings serve as a vital tool for the rapid detection of methandienone, combating its illicit use in camel racing. Comprehensive screenings covering both the parent drug and its metabolites are recommended to improve detection accuracy and ensure regulatory compliance in sports doping. Future research should explore methandienone's metabolite profile in administered camel samples., (© 2024 John Wiley & Sons Ltd.)

Protein grass hay (PGH) was used as a new feed source for lambs to study its effect on fattening performance and meat quality. Fifty-six male lambs were allotted to four experimental groups and fed for eight weeks either alfalfa hay (AH)-based diet (control) or diets in which AH was replaced with 33 %, 66 %, or 99 % PGH. The inclusion of PGH did not affect final body weight, dry matter intake, average daily gain, feed conversion ratio, or carcass weight. Moreover, substituting AH with PGH at any level did not influence the ruminal fermentation or serum biochemical parameters, meat color, water holding capacity, shear force, or amino acid profile. However, relative liver weight was increased with 66 % substitutions. Furthermore, replacing 99 % AH with PGH decreased the meat's pH at 24 h. Higher levels of C18:3n-3, C20:5n-3, and total n-3 PUFA and a lower ratio of n-6: n-3 PUFA were also observed in meat from lambs fed PGH at 99 %. These findings suggest that PGH could be incorporated into the lamb's diet up to 99 % without compromising fattening performance and body health while improving their meat n-3 PUFA deposition., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest. We declare that our study did not involve any experimentation on human subjects., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Despite remarkable advances in Organ-on-a-chip (Organ Chip) microfluidic culture technology, recreating tissue-relevant physiological conditions, such as the region-specific oxygen concentrations, remains a formidable technical challenge, and analysis of tissue functions is commonly carried out using one analytical technique at a time. Here, we describe two-channel Organ Chip microfluidic devices fabricated from polydimethylsiloxane and gas impermeable polycarbonate materials that are integrated with multiple sensors, mounted on a printed circuit board and operated using a commercially available Organ Chip culture instrument. The novelty of this system is that it enables the recreation of physiologically relevant tissue-tissue interfaces and oxygen tension as well as non-invasive continuous measurement of transepithelial electrical resistance, oxygen concentration and pH, combined with simultaneous analysis of cellular metabolic activity (ATP/ADP ratio), cell morphology, and tissue phenotype. We demonstrate the reliable and reproducible functionality of this system in living human Gut and Liver Chip cultures. Changes in tissue barrier function and oxygen tension along with their functional and metabolic responses to chemical stimuli (e.g., calcium chelation, oligomycin) were continuously and noninvasively monitored on-chip for up to 23 days. A physiologically relevant microaerobic microenvironment that supports co-culture of human intestinal cells with living Lactococcus lactis bacteria also was demonstrated in the Gut Chip. The integration of multi-functional sensors into Organ Chips provides a robust and scalable platform for the simultaneous, continuous, and non-invasive monitoring of multiple physiological functions that can significantly enhance the comprehensive and reliable evaluation of engineered tissues in Organ Chip models in basic research, preclinical modeling, and drug development., Competing Interests: Declaration of competing interest Donald E. Ingber is a founder, board member and Scientific Advisory Board chair of, and holds equity in, Emulate Inc. The remaining authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aimed to explore the potential of a fermentation technology to reduce off-flavour perception and its underlying mechanisms. Results revealed that yeast fermentation (YF) significantly ameliorated the off-flavour of pig liver (p < 0.05). Specifically, YF pre-treatment decreased the relative abundance of α-helix and fluorescence intensity while increasing the surface hydrophobicity and SS level and loosening the microstructure of myofibrillar proteins (MPs) in pig liver. Additionally, the appropriate fermentation treatments enhanced the MP-aldehyde binding capacity by 0.25-1.30 times, demonstrating that YF-induced conformational modifications in pig liver proteins made them more prone to interacting with characteristic aldehydes. Moreover, molecular docking results confirmed that hydrophobic interactions are the primary drivers of MP-aldehyde binding. These findings suggest that YF technology holds immense promise for modulating off-flavour perception in liver products by altering protein conformation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Liver transplantation is the definitive treatment for end-stage liver failure, but the scarcity of donor organs remains a significant challenge. Leveraging organs from extended criteria donors (ECD) offers a potential avenue to address worldwide shortages, though these organs are more susceptible to post-reperfusion injury. This study explores the use of normothermic ex vivo liver perfusion (NEVLP) as a method for organ preservation - an approach that sustains liver metabolism and facilitates pre-transplant assessments of organ viability via bile analysis. The focal point of this study revolves on the development of analytical methods for determining the bile acid profile throughout the peritransplantation period as a potential indicator of liver function and viability., Results: The study optimized and validated a high-throughput analytical method to quantify selected bile acids in bile samples using a thin-film microextraction-liquid chromatography-mass spectrometry (TFME-LC-MS) platform. Furthermore, it introduced a solid-phase microextraction-microfluidic open interface-mass spectrometry (SPME-MOI-MS) method for rapid direct analysis of bile acid isobar groups. In the animal study, discernible variations in the concentrations of specific bile acids were observed between donors after circulatory death (DCD) and heart-beating donors (HBD), particularly following normothermic perfusion and reperfusion. Noteworthy fluctuations in individual bile acid concentrations were observed throughout the entire organ transplantation process, with taurocholic acid (TCA), glycocholic acid (GCA), and glycochenodeoxycholic acid (GCDCA) emerging as promising indicators of organ quality. The efficacy of the SPME-MOI-MS platform in corroborating these trends highlights its potential for real-time bile acid analysis during liver transplantation procedures., Significance: Our findings underscore the efficacy of NEVLP in tandem with advanced bile acid analysis methods as a reliable strategy for pre-transplant assessments of organ viability, potentially increasing the use of ECD organs and reducing organ shortages. The ability to monitor bile acid profiles in real-time provides crucial insights into liver function and ischemic injury, making significant strides in improving transplant outcomes and patient survival rates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Kamil Łuczykowski reports financial support was provided by National Science Centre Poland. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Owing to the inherent characteristics of ground beef, adulteration presents a substantial risk for suppliers and consumers alike. This study developed a robust and novel method for identifying replacement fraud in ground beef with beef liver, beef heart, and pork using Near Infrared-Hyperspectral Imaging (NIR-HSI) coupled with chemometric and other statistical methods. More specifically, NIR-HSI provided an efficient and accurate means of identifying each type of adulteration using the classification model Genetic Algorithm (GA) - Backpropagation Artificial Neural Network (BPANN), showing perfect sensitivity and specificity (a value of 1.00) for the calibration and the validation sets for all types of adulteration. As an alternative to chemometric analysis, Hyperspectral Imaging-Root Mean Square (HSI-RMS) value, based on the RMS cut-off calculation, was determined to discriminate types of adulterations without the need of resource-intensive modelling. This HSI-RMS approach provides a simple-to-use method that avoids the complexity of HSI data processing and aims to directly understand the similarity between different spectra of one sample in the pixel level. Different types of adulteration show noticeable differences reflected in the HSI-RMS value (varying from 55 to 1439), which demonstrate the potential of HSI-RMS concept as a novel and valuable alternative for assessing the HSI data and facilitating the identification of adulterants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Rationale: Silver doping of electrospray is known to increase the abundance of olefinic compounds detected by mass spectrometry. While demonstrated in targeted experiments, this has yet to be investigated in an untargeted study. Utilizing infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI-MSI), an untargeted lipidomics experiment on mouse liver was performed to evaluate the advantages of silver-doped electrospray., Methods: 10 ppm silver nitrate was doped into the IR-MALDESI solvent consisting of 60% acetonitrile and 0.2% formic acid. Using an Orbitrap mass spectrometer in positive ionization mode, MSI was performed, analyzing from m/z 150 to m/z 2000 to capture all lipids with potential silver adducts. The lipids detected in the control and silver-doped electrosprays were compared by annotating using the LIPID MAPS Structural Database and eliminating false positives using the metabolite annotation confidence score., Results: Silver-doped electrospray allowed for the detection of such ions of lipid molecules as [M + H] + or [M + NH 4 ] + and as [M + Ag] + . Among the ions seen as [M + H] + or [M + NH 4 ] + , the signal was comparable between the control and silver-doped electrosprays. The silver-doped electrospray led to a 10% increase in the number of detected lipids, all of which contained a bay region increasing the interaction between silver and alkenes. Silver preferentially interacted with lipids that did not contain hard bases such as phosphates., Conclusions: Silver-doped electrospray enabled detection of 10% more olefinic lipids, all containing bay regions in their putative structures. This technique is valuable for detecting previously unobserved lipids that have the potential to form bay regions, namely fatty acyls, glycerolipids, prenol lipids, and polyketides., (© 2024 The Author(s). Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Background: Lipids such as phosphatidic acids (PAs) and cardiolipins (CLs) present strongly tailing peaks in reversed phase liquid chromatography, which entails low detectability. They are usually analyzed by hydrophilic interaction liquid chromatography (HILIC), which hampers high-throughput lipidomics. Thus, there is a great need for improved analytical methods in order to obtain a broader coverage of the lipidome in a single chromatographic method. We investigated the effect of ammonium bicarbonate (ABC) on peak asymmetry and detectability, in comparison with ammonium formate (AFO) on both a conventional BEH C18 column and an HST-CSH C18 column., Results: The combination of 2.5 mM ABC buffer pH 8 with an HST-CSH C18 column produced significantly improved results, reducing the asymmetry factor at 10 % peak height of PA 16:0/18:1 from 8.4 to 1.6. Furthermore, on average, there was up to a 54-fold enhancement in the peak height of its [M - H] - ion compared to AFO and the BEH C18 column. We confirmed this beneficial effect on other strongly tailing lipids, with accessible phosphate moieties e.g., cardiolipins, phosphatidylinositol phosphate, phosphatidylinositol bisphosphate, phosphorylated ceramide and phosphorylated sphingosine. Furthermore, we found an increased detectability of phospho- and sphingolipids up to 28 times in negative mode when using an HST-CSH C18 column. The method was successfully applied to mouse liver samples, where previously undetected endogenous phospholipids could be analyzed with improved chromatographic separation., Significance: In conclusion, the use of 2.5 mM ABC substantially improved the peak shape of PAs and enhanced the detectability of the lipidome in negative mode on an RPLC-ESI-Q-TOF-MS system on both BEH C18 and HST-CSH C18 columns. This method provides a wider coverage of the lipidome with one single injection for future lipidomic applications in negative mode., Competing Interests: Declaration of competing interest There is no conflict of interest from the authors of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Data-independent acquisition (DIA) techniques such as sequential window acquisition of all theoretical mass spectra (SWATH) acquisition have emerged as the preferred strategies for proteomic analyses. Our study optimized the SWATH-DIA method using a narrow isolation window placement approach, improving its proteomic performance. We optimized the acquisition parameter combinations of narrow isolation windows with different widths (1.9 and 2.9 Da) on a ZenoTOF 7600 (Sciex); the acquired data were analyzed using DIA-NN (version 1.8.1). Narrow SWATH (nSWATH) identified 5916 and 7719 protein groups on the digested peptides, corresponding to 400 ng of protein from mouse liver and HEK293T cells, respectively, improving identification by 7.52 and 4.99%, respectively, compared to conventional SWATH. The median coefficient of variation of the quantified values was less than 6%. We further analyzed 200 ng of benchmark samples comprising peptides from known ratios of Escherichia coli , yeast, and human peptides using nSWATH. Consequently, it achieved accuracy and precision comparable to those of conventional SWATH, identifying an average of 95,456 precursors and 9342 protein groups across three benchmark samples, representing 12.6 and 9.63% improved identification compared to conventional SWATH. The nSWATH method improved identification at various loading amounts of benchmark samples, identifying 40.7% more protein groups at 25 ng. These results demonstrate the improved performance of nSWATH, contributing to the acquisition of deeper proteomic data from complex biological samples.

Given the increased extraction of trace elements for use by new and emerging technologies, monitoring the environmental fate and potential effects of these compounds within the aquatic environment has never been more critical. Here, hepatic trace element concentrations were assessed in a key sentinel predator, the common dolphin (Delphinus delphis), using a long-term dataset. Variation in concentrations were assessed in relation to other elements, time period, decomposition state, sex, age, total body length, sexual maturity and nutritional status, and cause of death. Additionally, mercury toxicity thresholds for evaluating risk were reviewed and employed. Concentrations of elements which bioaccumulate, THg, MeHg, Cd, and Pb, in addition to Se and V, were strongly correlated with age, and/or body length. An association was observed between Zn concentrations and disease status, with significantly higher concentrations measured in individuals that died from infectious disease, compared to other causes. Strong inter-elemental relationships were detected, namely between Hg and Se, MeHg and Se, Cd and Se, and Cu and Zn. While THg:Se molar ratio values were observed to increase with age and body length, approaching equimolarity. THg was largely comprised of inorganic Hg in older individuals, potentially bound to Se, therefore the effects from THg toxicity may possibly be less important than originally assumed. In contrast, higher MeHg:Hg ratio values were reported in juveniles, suggesting a poorer efficiency in demethylation and a higher sensitivity. The generation of data on proportions of hepatic MeHg and inorganic Hg is highly informative to both future toxicity threshold assessments within pollutant indicator assessments, and to understanding the ultimate fate of mercury in the marine web., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Due to the close correlation between choline, L-carnitine, betaine and their intestinal microbial metabolites, including trimethylamine (TMA) and trimethylamine N-oxide (TMAO), and creatinine, there has been an increasing interest in the study of these compounds in vivo., Methods: In this study, a rapid stable isotope dilution (SID)-UHPLC-MS/MS method was developed for the simultaneous determination of choline, L-carnitine, betaine, TMA, TMAO and creatinine in plasma, liver and feces of rats. The method was validated using quality control (QC) samples spiked at low, medium and high levels. Second, we applied the method to quantify the effects of Rosa Roxburghii Tratt juice (RRTJ) on plasma, liver, and fecal levels of choline, L-carnitine, betaine, TMA, TMAO, and creatinine in high-fat diet-induced hyperlipidemic rats, demonstrating the utility of the method., Results: The limits of detection (LOD) were 0.04-0.027 µM and the limits of quantification (LOQ) were 0.009-0.094 µM. The linear ranges for each metabolite in plasma were choline1.50-96 µM; L-carnitine: 2-128 µM; betaine: 3-192 µM; TMA: 0.01-40.96 µM; TMAO: 0.06-61.44 µM and creatinine: 1-64 µM (R 2  ≥ 0.9954). The linear ranges for each metabolite in liver were Choline: 12-768 µM; L-carnitine: 1.5-96 µM; betaine: 10-640 µM; TMA: 0.5-32 µM; TMAO: 0.02-81.92 µM and creatinine: 0.2-204.8 µM (R 2  ≥ 0.9938). The linear ranges for each metabolite in feces were choline: 1.5-96 µM; L-carnitine: 0.01-40.96 µM; Betaine: 1.5-96 µM; TMA: 1-64 µM; TMAO: 0.02-81.92 µM and Creatinine: 0.02-81.92 µM (R 2  ≥ 0.998). The intra-day and inter-day coefficients of variation were < 8 % for all analytes. The samples were stabilized after multiple freeze-thaw cycles (3 freeze-thaw cycles), 24 h at room temperature, 24 h at 4 °C and 20 days at -80 °C. The samples were stable. The average recovery was 89 %-99 %. This method was used to quantify TMAO and its related metabolites and creatinine levels in hyperlipidemic rats. The results showed that high-fat diet led to the disorder of TMAO and its related metabolites and creatinine in rats, which was effectively improved after the intervention of Rosa Roxburghii Tratt juice（RRTJ）., Conclusions: A method for the determination of choline, L-carnitine, betaine, TMA, TMAO and creatinine in plasma, liver and feces samples was established, which is simple, time-saving, high precision, accuracy and recovery., Competing Interests: Declaration of competing interest The authors declare no competing financial interest.., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Glufosinate is a widely and increasingly used non-selective, broad-spectrum herbicide. Although cases of glufosinate poisoning are frequently reported, they are rarely documented in forensic case reports, particularly in fatal instances. The present study examined six cases of glufosinate poisoning, including a fatal case involving a 25-year-old female found deceased by the roadside, with an empty 1000 mL bottle labeled "glufosinate" by her side. Biological specimens such as plasma or cardiac blood, gastric contents, and liver tissues were collected for quantitative analysis of glufosinate levels using LC-MS/MS. In five cases of acute glufosinate poisoning, glufosinate plasma concentrations ranged from 0.62 to 3.92 μg/mL. In the fatal case, the concentrations of glufosinate in cardiac blood, gastric contents, and liver tissues were 8.41 μg/mL, 31.25 μg/mL, and 66.1 μg/g, respectively. The pathological autopsy concluded that the cause of death was acute cardio-respiratory failure due to glufosinate poisoning, characterized by multi-organ congestion without specific pathological findings. The toxicological data provided in this study aim to serve as a critical reference for future clinical treatment and forensic validation of glufosinate poisoning-related deaths., (Copyright © 2024 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

From organs to subcellular organelles, trace element (TE) homeostasis is fundamental for many physiological processes. While often overlooked in early stages, manifested TE disbalance can have severe health consequences, particularly in the context of aging or pathological conditions. Monitoring TE concentrations at the mitochondrial level could identify organelle-specific imbalances, contributing to targeted diagnostics and a healthier aging process. However, mitochondria isolation from frozen tissue is challenging, as it poses the risk of TE losses from the organelles due to cryodamage, but would significantly ease routine laboratory work. To address this, a novel method to isolate an enriched mitochondria fraction (EMF) from frozen tissue was adapted from already established protocols. Validation of manganese (Mn), iron (Fe), and copper (Cu) quantification via inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) showed sufficiently low quantification limits for EMF TE analysis. Successful mitochondrial enrichment from frozen liver samples was confirmed via immunoblots and transmission electron microscopy (TEM) revealed sufficient structural integrity of the EMFs. No significant differences in EMF TEs between frozen and fresh tissue were evident for Mn and Cu and only slight decreases in EMF Fe. Consequently, EMF TEs were highly comparable for isolates from both tissue states. In application, this method effectively detected dietary differences in EMF Fe of a murine feeding study and identified the disease status in a Wilson disease rat model based on drastically increased EMF Cu. In summary, the present method is suitable for future applications, facilitating sample storage and high-throughput analyses of mitochondrial TEs., (© 2024. The Author(s).)

Measuring trace element concentrations in tissue can be a valuable approach to monitor animal health status. Temporal variation in the absorption, transport, and storage of elements between different tissues can, however, complicate the assessment of element-health relationships. Here, we measured concentrations of selected essential (copper (Cu), zinc (Zn), selenium (Se)) and non-essential (arsenic (As), cadmium (Cd), lead (Pb)) trace elements within blood, liver, kidney, and hair of fallow deer (Dama dama; N=20) and red deer (Cervus elaphus; N=21). Using multivariate regression and structural equation models, we estimated direct and indirect linkages between tissue-specific trace element profiles and long- (body condition) and short-term (serum protein biomarkers for acute inflammation, infection, and malnutrition) health indicators. Trace element concentrations varied markedly and were weakly correlated among tissues, with the exception of Se. After accounting for sex- and site-differences in trace element concentrations, body condition of red deer was directly, and positively, associated to trace element status in liver and hair, but not in kidney. For both deer species, trace element status in blood was directly linked to serum protein status with an indirect positive association to deer body condition. For fallow deer, no direct association between trace element status and body condition was detected in any of the tissues, possibly because of elemental homeostasis, and because all individuals were in good clinical health. This study shows that hair can serve as an effective, non-invasive, biomarker in deer health assessments, yet, to fully uncover trace element-health relationships a variety of sample matrices is preferred., (© 2023. The Author(s).)

Risperidone (Ris) is a second-generation antipsychotic that belongs to the chemical class of benzisoxazole derivatives. 9-Hydroxy (9OH-) Ris is well known among the six reported metabolites of Ris and had been examined using not only blood but also other matrices, but the other five metabolites reported such as benzisoxazole ring-cleaved Ris (c-Ris) and c-9OH-Ris had been detected only in blood, urine and feces. In the present work, large peaks of c-Ris and c-9OH-Ris were detected in the liver, kidney, cerebrum, blood, pericardial fluid, bile and urine obtained from two cadavers. There is a potential that c-Ris and c-9OH-Ris will be good markers to prove Ris consumption in forensic toxicology cases. For example, the peak ratios of c-Ris against the parent Ris in the kidney and blood were as high as 3.9 and 3.6 in cadaver 1; and 7.0 and 7.9 in cadaver 2, respectively. In addition to the previously reported six metabolites, five new metabolites such as dehydrogenated-Ris, 7-keto-Ris and three benzisoxazole ring-cleaved metabolites were disclosed in the present work, and the pathways for the totally eleven metabolites detected in human solid tissues and body fluids have also been proposed, because such pathways were neither reported nor discussed previously., Competing Interests: Declaration of Competing Interest The authors declare that there are no financial or other relationships that could lead to a conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Wolverines are facultative scavengers that feed near the top of terrestrial food chains. We characterized concentrations of mercury and other trace elements in tissues of wolverine from a broad geographic area, representing much of their contemporary distribution in northwestern North America. We obtained tissues from 504 wolverines, from which mercury was measured on muscle (n = 448), kidney (n = 222), liver (n = 148), hair (n = 130), and brain (n = 52). In addition, methylmercury, seven trace elements (arsenic, cadmium, chromium, cobalt, lead, nickel, selenium), and arsenic compounds were measured on a subset of samples. Concentrations of mercury and other trace elements varied between tissues and were generally highest in kidney compared to brain, liver and muscle. Mercury was predominately as methylmercury in brain and muscle, but largely as inorganic mercury in liver and kidney. Mercury concentrations of hair were moderately correlated with those of internal tissues (Pearson r = 0.51-0.75, p ≤ 0.004), making hair a good non-lethal indicator of broad spatial or temporal differences in mercury exposure to wolverine. Arsenobetaine was the dominant arsenic compound identified in tissues, and arsenite, arsenocholine and dimethylarsinic acid were also detected. A preliminary risk assessment suggested the cadmium, lead, mercury, and selenium concentrations in our sample of wolverines were not likely to pose a risk of overt toxicological effects. This study generated a comprehensive dataset on mercury and other trace elements in wolverine, which will support future contaminants study of this northern terrestrial carnivore., (© 2024. Crown.)

Concentrations of one metalloid (As) and eight metals (Cd, Cr, Cu, Hg, Mn, Ni, Pb, and Zn) were determined in tissues (muscle, liver, and kidney) of eight snake species (Bothrops neuwiedi, Crotalus durissus, Dipsas mikanii, Epicrates crassus, Helicops modestus, Micrurus carvalhoi, Oxyrhopus guibei, and Oxyrhopus trigeminus) from Lagoa Santa Karst. Except for Cu and Zn, all other analyzed elements were detected in concentrations within the ranges previously reported for snakes inhabiting polluted areas, emphasizing Hg (specific Hg mean concentrations varied from 0.87 to 9.76 μg g -1 d.w). The highest mean concentrations of all elements except Zn were found in muscle samples of the false corals O. guibei (means ranged from 2.01 [Pb] to 9.76 [Hg]). The highest Zn mean concentration (13.77 μg g -1 d.w) was detected in the kidney of the water snake H. modestus. No significant correlation was found between element concentrations and body size for all species. Significant interorgan differences were observed for As, Cr, Cu, Hg, Mn, Pb, and Zn concentrations in the three tissues in H. modestus. Significant interspecific differences were found in at least one organ for all elements. Significant pairwise differences were found between diet specialist species and between these species and broader diet species, while no significant difference was found between the broader diet species. The bioaccumulation of As and metals in snakes from Lagoa Santa Karst could be associated with natural rock dissolution and erosion processes but also with the wide-scale mining in the region and the increased agriculture and urbanization., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)