Structure and assembly of the human IL-12 signaling complex.

Interleukin (IL)-12 is a heterodimeric pro-inflammatory cytokine. Our cryoelectron microscopy structure determination of human IL-12 in complex with IL-12Rß1 and IL-12Rß2 at a resolution of 3.75 Å reveals that IL-12Rß2 primarily interacts with the IL-12p35 subunit via its N-terminal Ig-like domain, while IL-12Rß1 binds to the p40 subunit with its N-terminal fibronectin III domain. This binding mode of IL-12 with its receptors is similar to that of IL-23 but shows notable differences with other cytokines. Through structural information and biochemical assays, we identified Y62, Y189, and K192 as key residues in IL-12p35, which bind to IL-12Rß2 with high affinity and mediate IL-12 signal transduction. Furthermore, structural comparisons reveal two distinctive conformational states and structural plasticity of the heterodimeric interface in IL-12. As a result, our study advances our understanding of IL-12 signal initiation and opens up new opportunities for the engineering and therapeutic targeting of IL-12.

Cadmium stress alleviates lipid accumulation caused by chiral penthiopyrad through regulating endoplasmic reticulum stress and mitochondrial dysfunction in zebrafish liver.

The coexistence of cadmium (Cd) can potentiate (synergism) or reduce (antagonism) the pesticide effects on organisms, which may change with chiral pesticide enantiomers. Previous studies have reported the toxic effects of chiral penthiopyrad on lipid metabolism in zebrafish (Danio rerio) liver. The Cd effects and toxic mechanism on lipid accumulation were investigated from the perspective of endoplasmic reticulum (ER) stress and mitochondrial dysfunction. The coexistence of Cd increased the concentrations of penthiopyrad and its metabolites in zebrafish. Penthiopyrad exposure exhibited significant effects on lipid metabolism and mitochondrial function-related indicators, which were verified by lipid droplets and mitochondrial damage in subcellular structures. Moreover, penthiopyrad activated the genes of ER unfolded protein reaction (UPR) and Ca2+ permeable channels, and S-penthiopyrad exhibited more serious effects on ER stress with ER hyperplasia than R-penthiopyrad. As a mitochondrial uncoupler, the coexistence of Cd could decrease lipid accumulation by alleviating ER stress and mitochondrial dysfunction, and these effects were the most significant for R-penthiopyrad. There were antagonistic effects between Cd and penthiopyrad, which could reduce the damage caused by penthiopyrad in zebrafish, thus increasing the bioaccumulation of penthiopyrad in zebrafish. These findings highlighted the importance and necessity of evaluating the ecological risks of metal-chiral pesticide mixtures.

[Determination of 13 perfluorinated and polyfluoroalkyl substances in fishes by QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry].

Perfluorinated and polyfluoroalkyl substances (PFASs) are compounds characterized by at least one perfluorinated carbon atom in an alkyl chain linked to side-chain groups. Owing to their unique chemical properties, these compounds are widely used in industrial production and daily life. However, owing to anthropogenic activities, sewage discharge, surface runoff, and atmospheric deposition, PFASs have gradually infiltrated the environment and aquatic resources. With their gradual accumulation in environmental waters, PFASs have been detected in fishes and several fish-feeding species, suggesting that they are bioconcentrated and even amplified in aquatic organisms. PFASs exhibit high intestinal absorption efficiencies, and they bioaccumulate at higher trophic levels in the food chain. They can be bioconcentrated in the human body via food (e. g., fish) and thus threaten human health. Therefore, establishing an efficient analytical technique for use in analyzing PFASs in typical fish samples and providing technical support for the safety regulation and risk assessment of fish products is necessary. In this study, by combining solvent extraction and magnetic dispersion-solid phase extraction (d-SPE), an improved QuEChERS method with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the determination of 13 PFASs in fish samples. Fe3O4-TiO2 can be used as an ideal adsorbent in the removal of sample matrix interference and a separation medium for the rapid encapsulation of other solids to be isolated from the solution. Based on the matrix characteristics of the fish products and structural properties of the target PFASs, Fe3O4-TiO2 and N-propyl ethylenediamine (PSA) were employed as adsorbents in dispersive purification. The internal standard method was used in the quantitative analyses of the PFASs. To optimize the sample pretreatment conditions of analyzing PFASs, the selection of the extraction solvent and amounts of Fe3O4-TiO2 and PSA were optimized. Several PFASs contain acidic groups that are non-dissociated in acidic environments, thus favoring their entry into the organic phase. In addition, acidified acetonitrile can denature and precipitate the proteins within the sample matrix, facilitating their removal. Finally, 2% formic acid acetonitrile was used as the extraction solvent, and 20 mg Fe3O4-TiO2, 20 mg PSA and 120 mg anhydrous MgSO4 were used as purification adsorbents. Under the optimized conditions, the developed method exhibited an excellent linearity (R≥0.9973) in the range of 0.01-50 µg/L, and the limits of detection (LODs) and quantification (LOQs) ranged from 0.001-0.023 and 0.003-0.078 µg/L, respectively. The recoveries of the 13 PFASs at low, medium, and high spiked levels (0.5, 10, and 100 µg/kg) were 78.1%-118%, with the intra- and inter-day precisions of 0.2%-11.1% and 0.8%-8.7%, respectively. This method was applied in analyzing real samples, and PFASs including perfluorooctanesulfonic acid, perfluorooctanoic acid, perfluoroundecanoic acid, perfluorododecanoic acid, and perfluorotridecanoic acid, were detected in all 11 samples evaluated. This method is simple, sensitive, and suitable for use in analyzing PFASs in fish samples.

Comprehensive multi-omics investigation of sub-chronic toxicity induced by Cadmium and Triazophos Co-exposure in hook snout carps (Opsariichthys bidens).

The coexistence of heavy metals and pesticides poses a critical challenge in agricultural ecosystems. Traditional toxicity assessments often focus only on the individual impacts of either pesticides or heavy metals. Here, the untargeted metabolomics and 16 S rRNA sequencing were used to assess the individual and combined effects of cadmium (Cd) and triazophos (TRI) on hook snout carps (Opsariichthys bidens). Cd caused much more serious impacts on hepatic metabolism and gut microbiota than those in TRI. Combined Cd and TRI exposure synergistically affected hepatic metabolism, causing mitochondrial dysfunction and even oxidative damage. Simultaneously, 16 S rRNA sequencing highlighted significant variations in the composition and abundance of gut microbiota. A noteworthy connection emerged between these distinct microbiota profiles and disruptions in energy metabolism, ultimately leading to disorders in metabolites. These findings enhanced the understanding of risks posed by heavy metals and pesticides, providing insights for better environmental risk assessments of aquatic organisms.

Study on the enantioselective behaviors, activity, toxicity and mechanism of novel SDHI fungicide benzovindiflupyr to reduce the environmental risks.

Benzovindiflupyr (BEN) has emerged as one of the fastest-growing SDHI fungicides in recent years, but it is considered "very highly toxic" to aquatic fish, invertebrates and crustaceans (EC50 or LC50, 0.0035-0.056 mg/L, acute toxicity). The comprehensive study on bioactivity, toxicity, and degradation behaviors of BEN at the enantiomeric level would facilitate the development of a high-efficiency and low-risk application method. The bioactivities of 1S, 4R-(-)-BEN against five target pathogens (Alternaria alternata, Phoma multirostrata, Selerotium rolfsii, Magnaporthe oryzae, and Rhizoctonia solani) (EC50, 0.00562-0.329 mg/L, high-efficiency) were 6.7-1029 times higher than 1R, 4S-(+)-BEN, demonstrating significant enantioselectivity. For Danio rerio, 1S, 4R-(-)-BEN (LC50, 0.0360 mg/L, "very highly toxic") exhibited higher toxicity than 1 R, 4S-(+)-BEN, but the toxic interaction was concentration addition (TUrac, 0.94), indicating an enhanced toxicity in the presence of 1R, 4S-(+)-BEN. Molecular docking was employed to offer insights at the molecular level and elucidate the factors influencing enantioselectivity. The stronger binding affinity of 1S, 4R-(-)-BEN with SDH was in line with the quantitative experimental findings. The degradation of two BEN enantiomers in four different fruits followed the first-order degradation kinetics equation, and displayed enantioselectivity. The preferential degradation of 1R, 4S-(+)-BEN was found in pears and grapes, while varying enantioselectivity was found at different stages in tomatoes and watermelons. The residual concentrations of BEN in grapes were higher than the EU's MRL, which in the other three fruits were below the MRLs during the sampling. In conclusion, 1S, 4R-(-)-BEN proved to be the more effective monomer. Utilizing the pure monomer could not only reduce the dosage of racemate by about 44-59 %, but also mitigate the risk of introducing inefficient monomer into the environment (especially for fish).

Structural determinants of spike infectivity in bat SARS-like coronaviruses RsSHC014 and WIV1.

The recurrent spillovers of coronaviruses (CoVs) have posed severe threats to public health and the global economy. Bat severe acute respiratory syndrome (SARS)-like CoVs RsSHC014 and WIV1, currently circulating in bat populations, are poised for human emergence. The trimeric spike (S) glycoprotein, responsible for receptor recognition and membrane fusion, plays a critical role in cross-species transmission and infection. Here, we determined the cryo-electron microscopy (EM) structures of the RsSHC014 S protein in the closed state at 2.9 Å, the WIV1 S protein in the closed state at 2.8 Å, and the intermediate state at 4.0 Å. In the intermediate state, one receptor-binding domain (RBD) is in the "down" position, while the other two RBDs exhibit poor density. We also resolved the complex structure of the WIV1 S protein bound to human ACE2 (hACE2) at 4.5 Å, which provides structural basis for the future emergence of WIV1 in humans. Through biochemical experiments, we found that despite strong binding affinities between the RBDs and both human and civet ACE2, the pseudoviruses of RsSHC014, but not WIV1, failed to infect 293T cells overexpressing either human or civet ACE2. Mutagenesis analysis revealed that the Y623H substitution, located in the SD2 region, significantly improved the cell entry efficiency of RsSHC014 pseudoviruses, which is likely accomplished by promoting the open conformation of spike glycoproteins. Our findings emphasize the necessity of both efficient RBD lifting and tight RBD-hACE2 binding for viral infection and underscore the significance of the 623 site of the spike glycoprotein for the infectivity of bat SARS-like CoVs. IMPORTANCE: The bat SARS-like CoVs RsSHC014 and WIV1 can use hACE2 for cell entry without further adaptation, indicating their potential risk of emergence in human populations. The S glycoprotein, responsible for receptor recognition and membrane fusion, plays a crucial role in cross-species transmission and infection. In this study, we determined the cryo-EM structures of the S glycoproteins of RsSHC014 and WIV1. Detailed comparisons revealed dynamic structural variations within spike proteins. We also elucidated the complex structure of WIV1 S-hACE2, providing structural evidence for the potential emergence of WIV1 in humans. Although RsSHC014 and WIV1 had similar hACE2-binding affinities, they exhibited distinct pseudovirus cell entry behavior. Through mutagenesis and cryo-EM analysis, we revealed that besides the structural variations, the 623 site in the SD2 region is another important structural determinant of spike infectivity.

Establishment of a scoring model for predicting clinical outcomes in patients with unilateral primary aldosteronism after superselective adrenal artery embolization.

OBJECTIVE: Superselective adrenal arterial embolization (SAAE) is a potential alternative treatment for patients with unilateral primary aldosteronism (PA) who refuse unilateral adrenalectomy. Therefore, we aimed to establish a scoring model to differentiate between hypertensive remission after SAAE. METHODS: This prospective cohort study involved 240 patients who underwent SAAE for unilateral PA. Patients were randomly divided into a model training set and a validation set at a ratio of 7:3. The clinical outcome was a response to hypertension remission, defined as complete, partial, or absent success at 6 months after SAAE. Multivariate logistic regression was performed to identify independent parameters and develop a nomogram to predict clinical outcomes after SAAE. The discrimination, calibration efficacy, and clinical utility of the predictive model were assessed. RESULTS: Five independent predictors were identified: female sex, duration of hypertension, defined daily dose of antihypertensive medication, diabetes, and target organ damage. The above five independent predictors were put into a predictive model that was presented as a nomogram. Using bootstrapping for internal validation, the C-statistic for the predictive model was 0.866 (95% confidence interval [CI]: 0.834 to 0.898). In the validation cohort, the area under the curve (AUC) of the nomogram for predicting hypertension remission after SAAE was 0.809. CONCLUSION: The present model is the first nomogram-based score that specifically predicts hypertension remission after SAAE in patients with unilateral PA using conventional parameters. This is an effective risk stratification tool that can be used by clinicians for timely and tailored preoperative risk discussions.

Risk factors and a predictive model for left ventricular hypertrophy in young adults with salt-sensitive hypertension.

Salt-sensitive hypertension is common among individuals with essential hypertension, and the prevalence of left ventricular hypertrophy (LVH) has increased. However, data from early identification of the risk of developing LVH in young adults with salt-sensitive hypertension are lacking. Thus, the present study aimed to design a nomogram for predicting the risk of developing LVH in young adults with salt-sensitive hypertension. A retrospective analysis of 580 patients with salt-sensitive hypertension was conducted. The training set consisted of 70% (n = 406) of the patients, while the validation set consisted of the remaining 30% (n = 174). Based on multivariate analysis of the training set, predictors for LVH were extracted to develop a nomogram. Discrimination curves, calibration curves, and clinical utility were employed to assess the predictive performance of the nomogram. The final simplified nomogram model included age, sex, office systolic blood pressure, duration of hypertension, abdominal obesity, triglyceride-glucose index, and estimated glomerular filtration rate (eGFR). In the training set, the model demonstrated moderate discrimination, as indicated by an area under the receiver operating characteristic (ROC) curve of 0.863 (95% confidence interval: 0.831-0.894). The calibration curve exhibited good agreement between the predicted and actual probabilities of LVH in the training set. Additionally, the validation set further confirmed the reliability of the prediction nomogram. In conclusions, the simplified nomogram, which consists of seven routine clinical variables, has shown good performance and clinical utility in identifying young adults with salt-sensitive hypertension who are at high risk of LVH at an early stage.

Transfer and risk assessment of fipronil in laying hen tissues and eggs.

Fipronil is a persistent insecticide known to transfer into hen eggs from exposure from animal drinking water and feed, but some questions remain regarding its transfer behavior and distribution characteristics. Therefore, the dynamic metabolism, residue distribution and transfer factor (TF) of fipronil were investigated in 11 edible tissues of laying hens and eggs over 21 days. After a continuous low-dose drinking water exposure scenario, the sum of fipronil and all its metabolites (defined as fipronilT) quickly transferred to each edible tissue and gradually increased with exposure time. FipronilT residue in eggs first appeared at 3 days and then gradually increased. After a single high-dose feed exposure scenario, fipronilT residue in edible tissues first appeared after 2 h, quickly peaked at 1 day, and then gradually decreased. In eggs, fipronilT residue first appeared at 2 days, peaked 6-7 days and then gradually decreased. The TF values followed the order of the skin (0.30-0.73) > egg yolk (0.30-0.71) > bottom (0.21-0.59) after drinking water exposure, and the order of the skin (1.01-1.59) > bottom (0.75-1.1) > egg yolk (0.58-1.10) for feed exposure. Fipronil sulfone, a more toxic compound, was the predominant metabolite with higher levels distributed in the skin and bottom for both exposure pathways. FipronilT was distributed in egg yolks rather than in albumen owing to its lipophilicity, and the ratio of egg yolk to albumen may potentially reflect the time of exposure. The distinction is that the residues after feed exposure were much higher than that after drinking water exposure in edible tissues and eggs. The study highlights the residual characteristics of two exposure pathways, which would contribute to the tracing of contamination sources and risk assessment.

Native T1-mapping as a predictor of progressive renal function decline in chronic kidney disease patients.

BACKGROUND: To investigate the potential of Native T1-mapping in predicting the prognosis of patients with chronic kidney disease (CKD). METHODS: We enrolled 119 CKD patients as the study subjects and included 20 healthy volunteers as the control group, with follow-up extending until October 2022. Out of these patients, 63 underwent kidney biopsy measurements, and these patients were categorized into high (25-50%), low (< 25%), and no renal interstitial fibrosis (IF) (0%) groups. The study's endpoint event was the initiation of renal replacement therapy, kidney transplantation, or an increase of over 30% in serum creatinine levels. Cox regression analysis determined factors influencing unfavorable kidney outcomes. We employed Kaplan-Meier analysis to contrast kidney survival rates between the high and low T1 groups. Additionally, receiver-operating characteristic (ROC) curve analysis assessed the predictive accuracy of Native T1-mapping for kidney endpoint events. RESULTS: T1 values across varying fibrosis degree groups showed statistical significance (F = 4.772, P < 0.05). Multivariate Cox regression pinpointed 24-h urine protein, cystatin C(CysC), hemoglobin(Hb), and T1 as factors tied to the emergence of kidney endpoint events. Kaplan-Meier survival analysis revealed a markedly higher likelihood of kidney endpoint events in the high T1 group compared to the low T1 value group (P < 0.001). The ROC curves for variables (CysC, T1, Hb) tied to kidney endpoint events demonstrated area under the curves(AUCs) of 0.83 (95%CI: 0.75-0.91) for CysC, 0.77 (95%CI: 0.68-0.86) for T1, and 0.73 (95%CI: 0.63-0.83) for Hb. Combining these variables elevated the AUC to 0.88 (95%CI: 0.81-0.94). CONCLUSION: Native T1-mapping holds promise in facilitating more precise and earlier detection of CKD patients most at risk for end-stage renal disease.

Innovative recovery of matrix layered double hydroxide from simulated acid mine wastewater for the removal of copper and cadmium from wastewater.

This study innovatively added biochar to optimize regulation in the neutralization process of simulated acid mine drainage (AMD) and recovered a new type of matrix layered double hydroxides (MLDH), which can be used to remove copper (Cu(II)) and cadmium (Cd(II)) from wastewater. A series of batch experiments show that MLDH with strong selective removal ability of Cu(II) and Cd(II) can be successfully obtained by adding biochar (BC) at pH = 5 end in the neutralization process. Kinetic and isotherm modeling studies indicated that the removal of Cu(II) and Cd(II) by the MLDH was a chemical multilayer adsorption process. The removal mechanism of Cu(II) and Cd(II) was further analyzed through related characterization analysis with contribution rate calculation: the removal rates of Cu(II) and Cd(II) by ion exchange were 42.7% and 26%, while that by precipitation were 34.5% and 49.9%, respectively. This study can provide a theoretical reference and experimental basis for the recovery and utilization of valuable by-products in AMD and the treatment of heavy metal wastewater.

6PPD induced cardiac dysfunction in zebrafish associated with mitochondrial damage and inhibition of autophagy processes.

The compound 6PPD is widely acknowledged for its antioxidative properties; however, concerns regarding its impact on aquatic organisms have spurred comprehensive investigations. In our study, we advanced our comprehension by revealing that exposure to 6PPD could induce cardiac dysfunction, myocardial injury and DNA damage in adult zebrafish. Furthermore, our exploration unveiled that the exposure of cardiomyocytes to 6PPD resulted in apoptosis and mitochondrial injury, as corroborated by analyses using transmission electron microscopy and flow cytometry. Significantly, our study demonstrated the activation of the autophagy pathway in both the heart of zebrafish and cardiomyocytes, as substantiated by transmission electron microscopy and immunofluorescent techniques. Importantly, the increased the expression of P62 in the heart and cardiomyocytes suggested an inhibition of the autophagic process. The reduction in autophagy flux was also verified through in vivo experiments involving the infection of mCherry-GFP-LC3. We further identified that the fusion of autophagosomes and lysosomes was impaired in the 6PPD treatment group. In summary, our findings indicated that the impaired fusion of autophagosomes and lysosomes hampered the autophagic degradation process, leading to apoptosis and ultimately resulting in cardiac dysfunction and myocardial injury. This study discovered the crucial role of the autophagy pathway in regulating 6PPD-induced cardiotoxicity. SYNOPSIS: 6PPD exposure inhibited the autophagic degradation process and induced mitochondrial injury and apoptosis in the heart of adult zebrafish.

Effect of ultrasonic treatment during fermentation on the quality of fortified sweet wine.

The present study aimed to investigate the potential of ultrasonic treatment during fermentation for enhancing the quality of fortified wines with varying time and power settings. Chemical analysis and sensory evaluation were conducted to assess the impact of ultrasonic treatment on wine quality. Results showed that ultrasonic treatment could increase total anthocyanin and total phenol content, reduce anthocyanin degradation rate, and improve color stability. Moreover, ethyl carbamate content was lower in the ultrasonic group after aging compared to non-ultrasonic group. A combination of 200 W for 20 min resulted in higher sensory scores and more coordinated taste, while a combination of 400 W for 40 min produced higher levels of volatile compounds (21860.12 µg/L) leading to a richer and more elegant aroma. Therefore, ultrasound can be used as a potential technology to improve the quality of wine.

Review of fruits flavor deterioration in postharvest storage: Odorants, formation mechanism and quality control.

Fruits flavor deterioration is extremely likely to occur during post-harvest storage, which not only damages quality but also seriously affects its market value. This work focuses on the study of fruits deterioration odorants during storage by describing their chemical compositions (i.e., alcohols, aldehydes, acids, and sulfur-containing compounds). Besides, the specific flavor deterioration mechanisms (i.e., fermentation metabolism, lipid oxidation, and amino acid degradation) inducing by factors (temperature, oxygen, microorganisms, ethylene) are summarized. Moreover, quality control strategies to mitigate fruits flavor deterioration by physical (temperature control, hypobaric treatment, UV-C, CA) and chemical (1-MCP, MT, NO, MeJA) techniques are also proposed. This review will provide useful references for fruits flavor control technologies development.

Development and comprehensive SBSE-GC/Q-TOF-MS analysis optimization, comparison, and evaluation of different mulberry varieties volatile flavor.

Optimization of seven parameters of stir bar sorptive extraction (SBSE) on mulberry volatile components for the first time. A total of 347 volatile components were identified and quantified in 14 mulberry varieties, predominantly encompassing esters, aldehydes, terpenoids, hydrocarbons, ketones, alcohols, heterocyclics, acids, and phenols. Hexanal and (E)-2-hexenal were the dominant volatiles. Furthermore, 79 volatile compounds characterized by odor activity values (OAVs) > 1 were identified, making a significant contribution to the distinctive mulberry flavor. "Green" notes were the most intense, followed by "fatty" and "fruity". Utilizing odor ring charts, the volatile flavor characteristics of the 14 mulberry varieties could be intuitively distinguished. This study not only established a viable methodology for differentiating mulberry varieties but also laid a theoretical foundation for the quality evaluation and variety breeding of mulberry flavor.

Potential effects of individual and combined exposure to tetraconazole and cadmium on zebrafish from the perspective of enantioselectivity and intestinal microbiota.

As the wide use of pesticides, they could form combined pollution with heavy metals, which would affect their environmental behaviors and toxic effects. Particularly, the effects would be more intricate for chiral pesticides. In this study, the accumulation and dissipation trends of tetraconazole enantiomers in zebrafish were investigated by individual and combined exposure of cadmium (Cd) and tetraconazole (including racemate and enantiomers) after confirming the absolute configuration of tetraconazole enantiomer. For the enantiomer treatments, Cd enhanced the accumulation of S-(+)-tetraconazole, but declined the concentrations of R-(-)-tetraconazole in zebrafish. The dissipation half-lives of tetraconazole enantiomers were extended by 1.65-1.44 times after the combined exposure of Cd and enantiomers. The community richness and diversity of intestinal microbiota were reduced in all treatments, and there were significant differences in R + Cd treatment. There was synergistic effect between Cd and S-(+)-tetraconazole for the effects on the relative abundances of Fusobacteria, Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. For R-(-)-tetraconazole, Cd mainly exhibited antagonistic effects. In the combined exposure of Cd and S-(+)-tetraconazole, the relative abundance changes of Cetobacterium (Fusobacteria, increase) and Edwardsiella (Proteobacteria, decrease) might affect the carbohydrate metabolism and energy metabolism, and led to the increase of S-(+)-tetraconazole bioaccumulation concentration. In the combined exposure of Cd and R-(-)-tetraconazole, Cd could increase the relative abundance of Edwardsiella (Proteobacteria), and affect the amino acid metabolism, which might reduce the bioaccumulation concentration of R-(-)-tetraconazole. This study reported for the first time that the abundance of intestinal microbiota in zebrafish might affect the bioaccumulation and dissipation of tetraconazole enantiomers, and would provide new insight for the study of combined pollutions.

Enzymatic and transcriptional level changes induced by the co-presence of lead and procymidone in hook snout carp (Opsariichthys bidens).

Understanding the interactions between different environmental pollutants is necessary in ecotoxicology since environmental contaminants never appear as single components but rather in combination with other substances. Heavy metals and pesticides are commonly detected in the environment, but the characterization of their mixture toxicity has been inadequately explored. This research aimed to elucidate the mixture impacts of the heavy metal lead (Pb) and the pesticide procymidone (PCM) on the hook snout carp (Opsariichthys bidens) using an array of biomarkers. The data showed that Pb and PCM possessed almost equivalent acute toxicity to the animals, with 4-days LC50 values of 120.9 and 85.15 mg L-1, respectively. Combinations of Pb and PCM generated acute synergistic effects on O. bidens. The contents of malondialdehyde (MDA), antioxidative (SOD), apoptotic (caspase-9), and detoxifying enzymes glutathione S-transferase (GST) and cytochrome P450 (CYP450) significantly changed after most of the mixture exposures compared with the baseline level and the corresponding individual exposures. This suggests the induction of oxidative stress, cell damage, and detoxification dysfunction. The expressions of eight genes (mn-sod, cu-sod, p53, cas3, erß1, esr, ap, and klf2α) associated with oxidative stress, cell apoptosis, immune response, and hormonal functions exhibited pronounced changes when challenged with the mixture compared to the individual treatments. This indicates the occurrence of immune dysregulation and endocrine disorder. These findings provide an overall understanding of fish upon the challenge of sublethal toxicity between Pb and PCM and can be adopted to evaluate the complicated toxic mechanisms in aquatic vertebrates when exposed to heavy metal and pesticide mixtures. Additionally, these results might guide environmental regulation tactics to protect the population of aquatic vertebrates in natural ecosystems.

Integrated QuEChERS combined with LC-MS/MS for high-throughput analysis of per- and polyfluoroalkyl substances in milk.

In this study, an integrated QuEChERS method was developed for the rapid determination of 22 per- and polyfluoroalkyl substances (PFASs) in milk by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The extraction and purification processes were combined into one step with this method. Meanwhile, the solid-liquid separation was carried out by magnetic suction (Fe3O4-SiO2) instead of the centrifugal process. The primary experimental parameters were optimized, including the type of extraction solvent, the amounts of magnetic nanomaterials (Fe3O4-SiO2), and the purification materials (ZrO2 and C18). The developed method exhibits high precision (RSDs < 9.9%), low limits of detection (0.004-0.079 µg/kg) and limits of quantitation (0.01-0.26 µg/kg), and acceptable recovery (71.7-116%) under optimized conditions. The developed integrated QuEChERS method had clear superiority in terms of sample pretreatment time, operating procedures, reagent amount, and recovery. This makes it an excellent alternative analytical technique for PFAS residue measurement at low micrograms-per-kilogram ranges with desirable sensitivity.

Intraprocedural Cortisol Measurement Increases Adrenal Vein Cannulation Success Rate in Primary Aldosteronism: A Systematic Review and Meta-analysis.

BACKGROUND: This study aimed to explore the effectiveness of intraprocedural cortisol measurement (IPCM) for the technical success rates of bilateral adrenal vein, right adrenal vein (RAV), and left adrenal vein (LAV) cannulation during adrenal vein sampling (AVS). METHODS: Systematic searches of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were performed from database inception to May 10, 2023, without any restrictions. We estimated the overall effect estimates of outcomes using the Mantel-Haenszel random-effects model. We conducted subgroup analyses, meta-regression, and sensitivity analysis to explore the possible sources of between-study heterogeneity. RESULTS: In total, 3,485 patients from 11 studies (three prospective and eight retrospective) were enrolled. Bilateral selectivity in patients who underwent IPCM during AVS was significantly higher than that in patients who underwent a routine AVS procedure (84% vs. 64%, RR 1.42, 95% confidence interval [CI]: 1.27-1.59, P < 0.01), with significant heterogeneity (I2 = 68%). A 42% relative risk reduction in the failure rate of bilateral adrenal vein cannulation was found in the IPCM group. Moreover, pooled analysis showed a significant increase in the success rates of RAV cannulation (84% vs. 72%, RR 1.21, 95% CI 1.12-1.31, P < 0.01, I2 = 33%) and LAV cannulation (89% vs. 84%, RR 1.05, 95% CI 1.02-1.08, P < 0.01, I2 = 4%) when IPCM was implemented during the AVS procedure compared to the routine AVS procedure. CONCLUSIONS: An IPCM-based strategy during AVS appears to have a significant beneficial effect on improving the success rate of bilateral cannulation, RAV cannulation and LAV cannulation.