Currently, studies on the association between per-/polyfluoroalkyl substances (PFAS) concentrations and the renal function of residents, especially teenagers, living near fluorochemical industrial plants, are relatively rare, and not all these studies suggested associations. In this cross-sectional study, 775 local teenagers (11–15 years old) were included, and serum concentrations of 18 PFAS were measured. Perfluorooctanoic acid (PFOA) was found to be the dominant PFAS with a concentration of 22.3–3310 ng/mL (mean = 191 ng/mL), accounting for 71.5–99.1% of ΣPFAS. Statistical analyses demonstrated that internal exposure of perfluoroalkyl carboxylic acids (PFCA, C8–C10) was related to the plant. In addition, the prevalence rate of chronic kidney disease (CKD) (35.0%) in the participants was relatively high. A significantly positive association was observed between the increase in PFOA concentration and increasing risk of CKD (OR = 1.741; 95% CI: 1.004, 3.088; p = 0.048) by adjusting for gender, age, body mass index (BMI), and household income. Similar positive correlation was also observed in PFHpA with CKD (OR = 1.628, 95% CI: 1.031, 2.572; p = 0.037). However, no significant correlation was observed for concentrations of other PFAS and CKD (p > 0.05). Furthermore, linear regression analyses demonstrated that none of the PFAS concentrations were significantly correlated with estimated glomerular filtration rate (eGFR) or urine albumin/urine creatinine ratio (ACR) (p > 0.05). However, a significantly negative correlation was observed between PFOA concentration and abnormal ACR (β = −0.141, 95% CI: −0.283, 0.001; p = 0.048) after stratifying by CKD. Sensitivity analyses further confirmed these results. This cross-sectional study is the first, to our knowledge, to investigate the association between PFAS concentrations and renal function in teenagers living near a Chinese industrial plant. Further prospective and metabonomic studies are needed to interpret the results and clarify the biological mechanisms underlying this association.

Nightjars are considered human-tolerant species due to the population densities reached in strongly managed landscapes. However, no studies have been done evaluating metal-related effects on physiology, condition or fitness in any nightjar species. The main aim of this study was to evaluate how metal exposure affects physiology and condition in red-necked nightjar (Caprimulgus ruficollis) populations inhabiting three different environments in southeastern Spain: agricultural-urban area (n = 15 individuals), mining area (n = 17) and control area (n = 16).Increased plasma mineral levels (magnesium and calcium) and alkaline phosphatase (ALP) activity were observed in breeding females, and ALP was significantly higher in young birds due to bone growth and development. In the mining-impacted environment, nightjars showed decreased retinol (17.3 and 23.6 μM in the mining area and control area), uric acid (28.8 and 48.6 mg/dl in the mining area and control area) and albumin (16.2 and 19.6 g/l in the mining area and control area), probably impaired by a combination of toxic metal exposure and low prey quantity/quality in that area. Moreover, they showed increased plasma tocopherol levels (53.4 and 38.6 μM in the mining area and control area) which may be a response to cope with metal-induced oxidative stress and lipid peroxidation. Blood concentrations of toxic metals (As, Pb, Cd and Hg) were negatively associated with calcium, phosphorus, magnesium, ALP, total proteins and body condition index. This could lead to metal-related disorders in mineral metabolism and ALP activity that may potentially increase the risk of skeletal pathologies and consequent risk of fractures in the long term, compromising the survival of individuals. Further studies need to be carried out to evaluate potential metal-related effects on the antioxidant status and bone mineralization of nightjars inhabiting mining environments.

Chronic cadmium (Cd) toxicity is a significant health concern, and the mechanism of long-term low-dose Cd exposure on bone has not been fully elucidated till date. This study aimed to assess the association between rat mesenchymal stem cells (MSCs) and long-term Cd exposure through 38-week intake of CdCl2 at 1 and 2 mg/kg body weight (bw). Increased gene expression of receptor activator of NF-κB ligand (RANKL) and decreased gene expression of osteoprotegerin (OPG) were observed. Fold change of RANKL gene expression (fold change = 1.97) and OPG gene expression (fold change = 1.72) showed statistically significant differences at dose 2 mg/kg bw. Decreased expression of key genes was observed during the early osteogenic differentiation of MSCs. The gene expression of Osterix in 1 mg/kg bw group was decreased by 3.70-fold, and the gene expressions of Osterix, Osteopontin, collagen type I alpha 2 chain (COL1a2) and runt-related transcription factor 2 (RUNX2) in 2 mg/kg bw group were decreased by 1.79, 1.67, 1.45 and 1.35-folds, respectively. Exposure to CdCl2 induced an increase in the renal Cd load, but only an adaptive response was observed, including increased expression of autophagy-related proteins LC3B and Beclin-1, autophagy receptor p62, and heme oxygenase 1 (HO-1), which is an inducible isoform that releases in response to stress. There were no significant changes in the urinary low molecular weight proteins including N-acetyl-b-D-glucosaminidase (NAG), β2-microglobulin and albumin (U-Alb). Urinary calcium (Ca) excretion showed no increase, and no obvious renal histological changes. Taken together, these results indicated that the chronic CdCl2 exposure directly act on MSCs through RANKL/OPG pathway and downregulate the key genes involved in osteogenic differentiation of MSCs. The toxic effect of Cd on bone may occur in parallel to nephrotoxicity.

Perfluorooctanoic acid (PFOA) toxicity is of considerable concern due to its wide application, environmental persistence, and bioaccumulation. In the current study, we used a scaffold-free three-dimensional (3D) spheroid model of mouse liver cells (AML12) to explore the toxicity of PFOA and emerging alternatives (HFPO-DA and PFO4DA). Comparing the short-term (24 and 72 h treatment) toxicity of PFOA between conventional 2D monolayer cells and 3D spheroids, we found that spheroids had higher EC₅₀ values and lower ROS levels after treatment, indicating their greater resistance to PFOA. Cell viability (i.e., adenosine triphosphate (ATP) content and lactate dehydrogenase (LDH) leakage) and liver-specific function (i.e., albumin secretion) were stable in spheroids through 28 day of culture. However, under 100 and 200 μM-PFOA treatment for 28 day, ROS levels, LDH leakage, and caspase3/7 activity all increased significantly. As a sensitive parameter, ROS showed a significant increase at 21 day, even in the 50 μM-PFOA group. Consistent with the elevation of ROS and caspase3/7, the expressions of oxidative stress- and apoptosis-related genes, including Gsta2, Nqo1, Ho-1, caspase3, p53, and p21, were induced in dose- and time-dependent manners after PFOA exposure. The peroxisome proliferator-activated receptor alpha (PPARα) pathway was also activated after treatment, with significant induction of its target genes, Fabp4 and Scd1. Similar to PFOA, both HFPO-DA and PFO4DA activated the PPARα pathway, induced ROS levels, and initiated cell damage, though at a relatively lower extent than that of PFOA. Our results imply that the 3D spheroid model is a valuable tool in chronic toxicological studies.

This study was conducted to investigate mycotoxin exposure in 260 rural residents (age 18–66 years) in Nanjing, China. Paired plasma and first morning urine samples were analyzed for 26 mycotoxin biomarkers, including 12 parent mycotoxins and 14 mycotoxin metabolites, by an ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method. Mycotoxins and their metabolites were detected in 95/260 (36.5%) plasma samples and 144/260 (55.4%) urine samples. The most prevalent mycotoxin in plasma was ochratoxin A (OTA), with the incidence of 27.7% (range 0.312–9.18 μg/L), while aflatoxin B₁-lysine (AFB₁-lysine) (incidence 19.6%, range 10.5–74.5 pg/mg albumin), fumonisin B₁ (FB₁) (incidence 2.7%, range 0.305–0.993 μg/L), deoxynivalenol (DON) (incidence 2.3%, range 1.39–5.53 μg/L), zearalenone (ZEN) (incidence 6.5%, range 0.063–0.418 μg/L) and zearalanone (ZAN) (incidence 1.2%, range 0.164–0.346 μg/L) were also detected in plasma samples. Deoxynivalenol-15-glucuronide (DON-15-GlcA) was the most frequently detected urinary mycotoxin, with the incidence of 43.8% (range 0.828–37.7 μg/L). DON (incidence 10.0%, range 1.39–14.7 μg/L), DON-3-glucuronide (DON-3-GlcA) (incidence 15.8%, range 0.583–5.84 μg/L), aflatoxin M₁ (AFM₁) (incidence 10.4%, range 0.125–0.464 μg/L), ZAN (incidence 7.7%, range 0.106–1.82 μg/L), ZEN (incidence 6.9%, range 0.056–0.311 μg/L), FB₁ (incidence 3.1%, range 0.230–1.33 μg/L), T-2 toxin (incidence 2.3%, range 0.248–3.61 μg/L) and OTA (incidence 1.2%, range 0.153–0.557 μg/L) were also found in urine samples. Based on the plasma or urinary levels, the daily intakes of AFB₁, FB₁, ZEN, DON and OTA were estimated. The results showed that the investigated rural dwellers were exposed to multiple mycotoxins, especially to carcinogenic mycotoxin AFB₁ with a mean daily intake of 0.41 μg/kg·bw/day, thereby underlining a potential public health concern. To the best of our knowledge, this is the first study to evaluate human exposure to mycotoxins with direct measurements of multiple mycotoxins in paired plasma and urine samples for over 200 subjects of a single population.

The experiment was conducted to investigate the effects of Cadmium (Cd) on growth performance, blood biochemical parameters, oxidative stress, hepatocyte apoptosis and autophagy of weaned piglets. A total of 12 healthy weaned piglets were randomly assigned to the control and the Cd group, which were fed with a basal diet and the basal diet supplemented with 15 ± 0.242 mg/kg CdCl₂ for 30 d, respectively. Our results demonstrated that Cd significantly decreased final body weight, average daily feed intake (ADFI), average daily gain (ADG) and increased feed-to-gain (F/G) ratio (P < 0.05). For blood biochemical parameters, Cd treatment significantly decreased the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), total protein, albumin, copper content and iron content (P < 0.05). In addition, liver injury was observed in the Cd-exposed group. Our results also demonstrated that Cd exposure contributed to the production of ROS, activated the AMPK/PPAR-γ/NF-κB pathway (increasing the expressions of P-AMPK/AMPK, NF-κB, I-κB-β, COX-2, and iNOS, decreasing the expressions of PPAR-γ and I-κB-α), finally induced autophagy (increasing the expressions of Beclin-1, the ratio of LC3-II/LC3-I and p62), and apoptosis (increasing the expressions of Bax, Bak, Caspase-9, and Caspase-3, decreasing the expression of Bcl-2). Overall, these findings revealed the vital role of AMPK/PPAR-γ/NF-κB pathway in Cd-induced liver apoptosis and autophagy, which provided deeper insights into a better understanding of Cd-induced hepatotoxicity.

Rising tropospheric ozone concentrations in Asia affect the yield and quality of rice. This study investigated ozone-induced changes in rice grain quality in contrasting rice genotypes, and explored the associated physiological processes during the reproductive growth phase. The ozone sensitive variety Nipponbare and a breeding line (L81) containing two tolerance QTLs in Nipponbare background were exposed to 100 ppb ozone (8 h per day) or control conditions throughout their growth. Ozone affected grain chalkiness and protein concentration and composition. The percentage of chalky grains was significantly increased in Nipponbare but not in L81. Physiological measurements suggested that grain chalkiness was associated with a drop in foliar carbohydrate and nitrogen levels during grain filling, which was less pronounced in the tolerant L81. Grain total protein concentration was significantly increased in the ozone treatment, although the albumin fraction (water soluble protein) decreased. The increase in protein was more pronounced in L81, due to increases in the glutelin fraction in this genotype. Amino acids responded differently to the ozone treatment. Three essential amino acids (leucine, methionine and threonine) showed significant increases, while seven showed significant treatment by genotype interactions, mostly due to more positive responses in L81. The trend of increased grain protein was in contrast to foliar nitrogen levels, which were negatively affected by ozone. A negative correlation between grain protein and foliar nitrogen in ozone stress indicated that higher grain protein cannot be explained by a concentration effect in all tissues due to lower biomass production. Rather, ozone exposure affected the nitrogen distribution, as indicated by altered foliar activity of the enzymes involved in nitrogen metabolism, such as glutamine synthetase and glutamine-2-oxoglutarate aminotransferase. Our results demonstrate differential responses of grain quality to ozone due to the presence of tolerance QTL, and partly explain the underlying physiological processes.

Liver disease has become a growing health burden, and little is known about the impairment of liver function caused by exposure to organophosphate esters (OPEs) in adolescents aged 12–19 years in the United States. To investigate the relationship between urinary metabolites of OPEs including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(1-chloroethyl) phosphate (BCPP), bis(2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP) and liver function in US adolescents aged 12–19 years. Liver function tests (LFTs) include aspartate aminotransferase (AST), albumin (ALB), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin (TBIL), total protein (TP), and AST/ALT. Meanwhile, potential confounding and interaction effects were assessed. The study sample included 592 adolescents aged 12–19 from two consecutive NHANES cycles (2011–2012, 2013–2014). A composite statistical strategy combining traditional linear regression with advanced multi-pollutant models quantile based g-computation (QGC) and eXtreme Gradient Boosting (XGBoost) regression was used to analyze the joint effects of multiple OPEs on liver function indicators, and to describe the interaction between different OPEs in detail. 592 adolescent participants were 15 (14–17) years old, with similar numbers of males and females (304 vs. 288). The analysis results showed that (1) in the linear regression model, individual DPHP, BCEP exposure and ALP changes, BCEP and AST/ALT changes were positively associated. DPHP, BDCPP were negatively associated with TP changes. (2) The combined effects of various OPEs on ALB, ALT, ALP, GGT, TBIL, TP, and AST/ALT were statistically significant. (3) There is no potential interaction between different OPEs. Several OPEs and their combinations are closely related to the 8 LFT indicators. In addition, data suggest that exposure to OPEs in adolescents may be associated with liver damage. Due to limited evidence in the literature and potential limitations of the current study, our findings require more studies to confirm.

Environmental lead exposure has been linked with reduced kidney function. However, evidence about its role in diabetic kidney damage, especially when considering the nutritional status of vitamin D, is sparse. In this observational study, we investigated the association between low-level lead exposure and urinary albumin-to-creatinine ratio (UACR) and assessed potential impact of vitamin D among 4033 diabetic patients in Shanghai, China. Whole blood lead was measured by graphite furnace atomic absorption spectrometry. Serum 25-hydroxyvitamin D [25(OH)D] was tested using a chemiluminescence immunoassay. The associations of blood lead with UACR and albuminuria, defined as UACR ≥30 mg/g, according to 25(OH)D levels were analyzed using linear and Poisson regression models. A doubling of blood lead level was associated with a 10.7% higher UACR (95% CI, 6.19%–15.5%) in diabetic patients with 25(OH)D < 50 nmol/L, whereas the association was attenuated toward null (2.03%; 95% CI, −5.18% to 9.78%) in those with 25(OH)D ≥ 50 nmol/L. Similarly, the risk ratios of prevalent albuminuria per doubling of blood lead level between the two groups were 1.09 (95% CI, 1.03–1.15) and 0.99 (95% CI, 0.86–1.14), respectively. Joint analysis demonstrated that a combination of high blood lead and low 25(OH)D corresponded to significantly higher UACR. Among diabetic patients with 25(OH)D < 50 nmol/L, the increment of UACR relative to blood lead was more remarkable in those with reduced estimated glomerular filtration rate (<60 mL/min/1.73 m²). These results suggested that higher blood lead levels were associated with increased urinary albumin excretion in diabetic patients with vitamin D deficiency. Further prospective studies are needed to validate our findings and to determine whether vitamin D supplementation yields a benefit.