Per- and polyfluoroalkyl substances induce lipid metabolic impairment in fish: Integration on field investigation and laboratory study.

The biotoxicity of perfluoroalkyl and polyfluoroalkyl substances (PFASs) to aquatic organisms has been widely concerned. However, studies on toxic effects of PFASs are usually evaluated directly by using laboratory exposure rather than laboratory validation based on data obtained in the field. In this study, wild catfish (Silurus meridinalis) was explored on the relationship between PFASs bioaccumulation and lipid disorders. Nine and thirteen lipid metabolites were significantly associated with perfluorooctane sulfonate (PFOS) and 6:2/8:2Cl-PFESA (trade name F-53B) exposures, respectively; and the correlated lipid metabolites were the fatty acid (FA) and conjugates, FA esters, steroids, and glycerophosphate subclasses. The effects of PFASs on lipid metabolism of fish and its mechanism were further analyzed through exposure experiments. Zebrafish (Danio rerio) of different sexes underwent PFOS and F-53B exposures for 21 days at 100 ng/L and 100 µg/L. By determining gene expression levels, hepatic lipid contents, and histopathological change, the adverse effects order on lipid metabolism in male or female was 100 µg/L F-53B > 100 µg/L PFOS > 100 ng/L F-53B > 100 ng/L PFOS; the stress response in male was more intensive than that in female. PFOS and F-53B activated the peroxisome proliferator-activated receptor pathway, promoting the processes of FA and total cholesterol (T-CHO) transport, FA ß-oxidation, FA synthesis, and finally induced FA and T-CHO transportation from blood into liver, then accelerated FA to FA ester transformation, and CHO into steroids. Laboratory experiments confirmed the field analysis. This study innovatively explored the adverse effects of PFOS and F-53B on lipid metabolism and their mechanisms at field and laboratory levels, highlighting concerns regarding PFASs health risks.

Per- and polyfluoroalkyl substances in waterbird feathers around Poyang Lake, China: Compound and species-specific bioaccumulation.

As a nondestructive means of environmental monitoring, bird feathers have been used to analyze levels of per- and polyfluoroalkyl substances (PFASs) in specific environments. In this study, feather samples from 10 waterbird species around Poyang Lake were collected, and a pretreatment method for PFASs in feathers was optimized. The results showed that a combined cleaning method using ultrapure water and n-hexane effectively removed external PFASs. Twenty-three legacy and emerging PFASs were identified in the feathers of waterbirds, of which hexafluoropropylene oxides (HFPOs), chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), and sodium p-perfluorinated noneoxybenzene sulfonate (OBS) were reported for the first time, with their concentrations ranging from 0.060-2.4 ng·g-1 dw, 0.046-30 ng·g-1 dw, and lower than the method detection limit to 30 ng·g-1 dw, respectively. Compound- and species-specific bioaccumulation of PFASs was observed in the feathers of different waterbird species, suggesting that different PFAS types can be monitored through the selection of different species. Moreover, the concentrations of most PFCAs (except perfluorobutyric acid), perfluorooctane sulfonate (PFOS), and perfluorooctane sulfonamide (FOSA) were significantly positively correlated with δ15N (p < 0.05), while the concentrations of HFPOs, Cl-PFESAs, and OBS had significant positive correlations with δ13C. This indicates that the bioaccumulation of legacy and emerging PFASs in waterbird feathers is affected by their trophic level, feeding habits, and foraging area.

Genotype analysis of 55,281 cases of thalassemia in northern Guangxi.

OBJECTIVE: To understand the genotype and distribution of thalassemia in northern Guangxi. METHODS: The study subjects were 55,281 individuals who came to the Affiliated Hospital of Guilin Medical University for genetic diagnosis of thalassemia from January 2012 to August 2023. All of their household registration was in the precincts of Guibei District and its affiliated counties. Red blood cell parameters and hemoglobin analysis were used for thalassemia screening. Gap-PCR, PCR-reverse dot blot hybridization (PCR-RDB), and multicolor melting curve analysis (MMCA) were used to identify common thalassemia genes. Multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, and third-generation single-molecule real-time (SMRT) sequencing were employed to identify rare thalassemia genes. RESULTS: Among the 55,281 samples, 16,442 (29.74%) were diagnosed with thalassemia. The detection rates of α, ß, and α combined ß-thalassemia were 18.57%, 9.99% and 1.18%, respectively. Among ethnical groups, allele mutation frequency of thalassemia was the highest in Zhuang (44.97%), followed by Yao (40.11%), Dong (31.33%), Han (29.85%), Miao (24.31%), and Hui (20.6%). A total of 11,659 alleles (21.09%) of 8 types of α-thalassemia were identified in 55,281 samples, primarily --SEA (53.9%), followed by -α3.7 (21.3%), including rare alleles: --THAI (0.45%) and HKαα (0.38%). A total of 6367 (11.52%) and 14 types of ß-thalassemia alleles were identified, mainly CD41-42 (50.12%), followed by CD17 (22.22%), including rare alleles: ßCD37 (0.16%) and Gγ+ (Aγδß)0/ßN (0.05%). A total of 31 genotypes were detected in 10,264 cases of α-thalassemia, and the main types were --SEA/αα (53.23%), -α3.7/αα (19.15%), and -α4.2/αα (7.21%). A total of 34 genotypes were detected in 5525 cases of ß-thalassemia, and the main types were ßCD41-42/ßN (50.53%), ßCD17/ßN (21.77%), and ßIVS-II-654/ßN (12.16%). A total of 78 gene types were detected in 653 cases of α- and ß-thalassemia, and the main types were --SEA/αα, ßCD41-42/ßN (18.68%) and -α3.7/αα, ßCD41-42/ßN (13.02%). There were 580 cases (5.65%) of HbH disease (α0/α+), and 4 cases of Hemoglobin Bart's Hydrops Foetus syndrome (--SEA/--SEA). In addition, there were 92 cases (1.67%) of intermedia or severe types of ß-thalassemia (ß0/ß0, ß0/ß+, ß+/ß+), including 23 cases of combined α-thalassemia. Among the samples screened negative for thalassemia, 3.7% of them were found to carry thalassemia genes, and 91.35% of the genotypes were αWSα/αα, -α3.7/αα, and -α4.2/αα. In addition, 40.26% of αWSα/αα, 22.89% of -α3.7/αα, and 18.51% of -α4.2/αα had no hematological phenotype. CONCLUSION: The population in northern Guangxi exhibited rich ethnic diversity, with high allelic carrying rates among the Zhuang, Yao and Dong ethnic groups. Thalassemia gene mutations are diverse, encompassing a variety of gene types, with α thalassemia predominating, notably the --SEA/αα gene type. The prevalence of intermedia or severe types of thalassemia is not low, but there are still some carriers of thalassemia in people who are initially tested negative.

Effects of single and combined exposure to zinc and two tetracycline antibiotics on zebrafish at the early stage.

Tetracycline antibiotics (TCs) and heavy metals are commonly used in livestock and poultry farming, leading to their coexistence in the aquatic environment. This coexistence causes combined toxicity to aquatic organisms. Here, zebrafish embryos were exposed to chlortetracycline (CTC), oxytetracycline (OTC), zinc chloride (ZnCl2), and their combinations for 120 h to evaluate their adverse effects on the growth, antioxidant system, immune system, and endocrine system during the early stage of life. OTC/ZnCl2 combined exposure significantly reduced the body weight, whereas the TCs/ZnCl2 combination significantly increased the heart rate of zebrafish larvae, suggesting growth impairment induced by TCs and ZnCl2. Further, combined groups showed more prominent toxicity to the antioxidant system than single groups, as revealed by related levels of enzyme activity and gene expression. In addition, the levels of most pro-inflammatory genes were downregulated, and those of NF-κB-related genes were upregulated in all treatment groups, indicating an immunosuppressive response and the potential role of NF-κB signaling, while the combined treatment was not more toxic than TCs or ZnCl2 alone. Similarly, hormone and endocrine related gene levels were determined. Although both single and combined exposures caused certain endocrine-disrupting effects, the combined exposure did not result in higher toxicity than a single exposure. Our findings showed that a mixture of TCs and ZnCl2 might exert greater toxic effects as compared to a single compound on some systems, providing fundamental data on the toxic effects of single and combined TC and ZnCl2 exposure on aquatic organisms, although studies are needed to explore the underlying mechanisms.

The role of exercise intensity on fatty liver in rats.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is often caused by obesity. Currently, moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) are two effective treatments for reducing fat mass in patients with obesity and NAFLD. However, the comparative fat-reducing effects and underlying molecular mechanisms of MICT and HIIT remain unclear. This comprehensive study was performed on male Wistar rats treated with standard diet, high-fat diet, MICT, and HIIT to explore their comparative fat-reducing effects and corresponding molecular mechanisms. HIIT had a greater effect on hepatic vacuolation density and lipid content reduction than MICT, and triglyceride and total cholesterol levels in the serum and the liver demonstrated different sensitivities to different exercise training programs. At the molecular level, both MICT and HIIT altered the processes of fatty acid synthesis, fatty acid transport, fatty acid ß-oxidation, and cholesterol synthesis, wherein the transcriptional and translational levels of signaling molecules peroxisome proliferator-activated receptors (PPARs) regulating fatty acid and cholesterol synthesis were strongly changed. Moreover, the metabolic pathways of amino acids, bile acids, and carbohydrates were also affected according to transcriptome analysis, and the changes in the above-mentioned processes in the HIIT group were greater than those in the MICT group. In combination with the search tool for the retrieval of interacting genes/proteins (STRING) analysis and the role of PPARs in lipid metabolism, as well as the expression pattern of PPARs in the MICT and HIIT groups, the MICT-and HIIT-induced fat loss was mediated by the PPAR pathway, causing feedback responses in fatty acid, steroid, amino acid, bile acid, and carbohydrate metabolism, and HIIT had a better fat-reducing effect, which may be initiated by PPAR-α. This study provides a theoretical basis for targeted therapy of patients with obesity and NAFLD.