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Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence ...is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA) as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: −0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recent studies suggest that perfluoroalkyl substances (PFAS) and PFAS alternatives can cross the placental barrier. However, little is known on the differential patterns of trans-placental transfer ...(TPT) among conventional PFAS and PFAS alternatives in epidemiological study.
We aimed to characterize comprehensive TPT patterns in conventional PFAS and PFAS alternatives using matched maternal-cord blood serum from a birth cohort.
A total of 424 mother-fetus pairs were recruited from the Maoming Birth Cohort during 2015–2018. We detected 20 PFAS in cord and maternal serum using an ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). TPT of PFAS was calculated via cord to maternal serum concentration ratios.
Both of PFOS alternatives (chlorinated polyfluorinated ether sulfonates, Cl-PFESAs) and PFOA short-chain alternative (perfluorobutanoic acid, PFBA) were widely detected in the cord and maternal serum. In cord serum, the predominant PFAS was PFOS (1.93 ng/mL), followed by PFBA (1.45 ng/mL), PFOA (0.75 ng/mL) and 6:2 Cl-PFESA (0.32 ng/mL). We found that the PFAS alternatives had higher TPT than PFOS and PFOA, such as PFBA vs. PFOA (median: 1.41 vs. 0.73, P < 0.001) and 8:2 Cl-PFESA vs. PFOS (median: 0.98 vs. 0.42, P < 0.001). Moreover, the TPT of 8:2 Cl-PFESA was higher than the precursor, linear and isomeric PFOS, respectively (P < 0.01). Furthermore, we found a U-shaped pattern for TPT in perfluorocarboxylic acid compounds (PFCAs) across different length of carbon chain.
Our findings suggest that PFAS alternatives may be more easily across the placenta than conventional PFAS. Given the widespread usage of PFAS alternatives, our results indicate that more research is needed to assess the potential health risks of prenatal exposure to PFAS alternatives in children.
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•Examined trans-placental transfer (TPT) of PFAS and the alternatives systematically•PFAS alternatives were widely detected in maternal and cord serum.•Higher TPT was observed in the PFAS alternatives than those in PFOS and PFOA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
In transition metal compounds, due to the interplay of charge, spin, lattice and orbital degrees of freedom, many intertwined orders exist with close energies. One of the commonly observed ...states is the so-called nematic electron state, which breaks the in-plane rotational symmetry. This nematic state appears in cuprates, iron-based superconductor, etc. Nematicity may coexist, affect, cooperate or compete with other orders. Here we show the anisotropic in-plane electronic state and superconductivity in a recently discovered kagome metal CsV
3
Sb
5
by measuring
c
-axis resistivity with the in-plane rotation of magnetic field. We observe a twofold symmetry of superconductivity in the superconducting state and a unique in-plane nematic electronic state in normal state when rotating the in-plane magnetic field. Interestingly these two orders are orthogonal to each other in terms of the field direction of the minimum resistivity. Our results shed new light in understanding non-trivial physical properties of CsV
3
Sb
5
.
Abstract
The pairing mechanism in cuprates remains as one of the most challenging issues in condensed matter physics. Recently, superconductivity was discovered in thin films of the infinite-layer ...nickelate Nd
1-x
Sr
x
NiO
2
(x = 0.12–0.25) which is believed to have the similar
3d
9
orbital electrons as that in cuprates. Here we report single-particle tunneling measurements on the superconducting nickelate thin films. We find predominantly two types of tunneling spectra, one shows a V-shape feature which can be fitted well by a
d
-wave gap function with gap maximum of about 3.9 meV, another one exhibits a full gap of about 2.35 meV. Some spectra demonstrate mixed contributions of these two components. Combining with theoretical calculations, we attribute the
d
-wave gap to the pairing potential of the
$${\mathrm{Ni - }}3d_{x^2 - y^2}$$
Ni-
3
d
x
2
−
y
2
orbital. Several possible reasons are given for explaining the full gap feature. Our results indicate both similarities and distinctions between the newly found Ni-based superconductors and cuprates.
Colorectal cancer is one of the most common cancers in the world. Although genomic mutations and single nucleotide polymorphisms have been extensively studied, the epigenomic status in colorectal ...cancer patient tissues remains elusive. Here, together with genomic and transcriptomic analysis, we use ChIP-Seq to profile active enhancers at the genome wide level in colorectal cancer paired patient tissues (tumor and adjacent tissues from the same patients). In total, we sequence 73 pairs of colorectal cancer tissues and generate 147 H3K27ac ChIP-Seq, 144 RNA-Seq, 147 whole genome sequencing and 86 H3K4me3 ChIP-Seq samples. Our analysis identifies 5590 gain and 1100 lost variant enhancer loci in colorectal cancer, and 334 gain and 121 lost variant super enhancer loci. Multiple key transcription factors in colorectal cancer are predicted with motif analysis and core regulatory circuitry analysis. Further experiments verify the function of the super enhancers governing PHF19 and TBC1D16 in regulating colorectal cancer tumorigenesis, and KLF3 is identified as an oncogenic transcription factor in colorectal cancer. Taken together, our work provides an important epigenomic resource and functional factors for epigenetic studies in colorectal cancer.
Obtaining a high-performance nonprecious electrocatalyst for oxygen and hydrogen evolution reactions (OER and HER) under mild conditions is highly desirable yet challenging. Transition metal nitrides ...are emerging as cost-effective substitutes for state-of-the-art noble metal based catalysts, but large OER overpotentials plague these nitrides. Herein, we developed the heterostructure of CoO-domain-anchored Co4N nanowhiskers as an effective bifunctional electrocatalyst for both OER and HER in neutral media. The exterior CoO targets OER, and the CO4N matrix is active for HER. The periodically-aligned {111} crystalline planes between Co4N and CoO provide good electron transport through their interface. The heterostructure performs dual functions of elevating activity and diminishing interior resistance of the catalyst. Moreover, the porous metallic Co4N nanowhiskers were integrated on a nickel foam, and this configuration contributes an arterial channel for collecting current as well as a spacious surface area for increasing the reaction cross section for heterocatalysis. These advantages actuate our bifunctional 3D catalytic electrode to achieve low OER and HER overpotentials in neutral systems. It finally provides an unprecedentedly low cell voltage (1.79 V for 10 mA cm−2) for catalyzing overall water splitting in neutral media.
•Few human studies reported the associations of Cl-PFESAs exposure with birth outcomes.•A birth cohort study was conducted in China to assess these associations.•Cl-PFESAs was significantly ...associated with lower birth weight and preterm birth.•The adverse effects of Cl-PFESAs on birth outcomes were similar with PFAS.•PFOS alternatives (Cl-PFESAs) may be reproductive toxicants in human populations.
Experimental studies show that chlorinated polyfluorinated ether sulfonic acids (Cl-PFESA 6:2 and 8:2), one of perfluoroalkyl substances (PFAS) used as perfluorooctane sulfonate (PFOS) alternatives, are reproductive toxicants in vivo and in vitro. However, the associations between gestational exposure to Cl-PFESAs and birth outcomes are unknown.
We investigated associations between 6:2 Cl-PFESA and 8:2 Cl-PFESA in maternal serum and birth outcomes.
We measured four PFAS, including 6:2 Cl-PFESA, 8:2 Cl-PFESA, PFOS, and perfluorooctanoic acid (PFOA) in third-trimester maternal serum collected from 372 mother-child dyads participating in the Guangzhou Birth Cohort Study. Characteristics of mothers and infants were gathered from medical records and by interviewer-administered questionnaires.
PFOS was the most abundant PFAS in maternal serum (median: 7.15 ng/mL), followed by 6:2 Cl-PFESA (median: 2.41 ng/mL). Greater maternal serum levels of all PFAS alternatives were significantly associated with lower birth weight, adjusted for confounding variables. For example, each ln-ng/mL greater concentration of 6:2 Cl-PFESA and 8:2 Cl-PFESA was associated with a 54.44 g 95% confidence interval (CI): −95.66, −13.22 and 21.15 g (95% CI: −41.44, −0.86) lower birth weight, respectively. Greater continuous maternal serum 6:2 Cl-PFESA (OR: 2.67, 95% CI: 1.73, 4.15) and PFOS (OR: 2.03, 95% CI: 1.24, 3.32) were also associated with higher risks for preterm birth, adjusted for confounders, with a possible threshold effect at the highest quartile of 6:2 Cl-PFESA.
For the first time, we report associations between maternal serum 6:2 Cl-PFESA and 8:2 Cl-PFESA concentrations and adverse birth outcomes. Our findings suggest that PFOS alternatives may be reproductive toxicants in human populations and should be considered with caution before widespread use. Given the preliminary nature of our results, additional epidemiological and toxicological investigations are needed to more definitively assess the risks.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is dysregulated in various cancers, and its upregulation strongly correlates with an invasive phenotype and poor ...prognosis in patients with nasopharyngeal carcinomas. However, the underlying mechanism of Bmi-1-mediated invasiveness remains unknown. In the current study, we found that upregulation of Bmi-1 induced epithelial-mesenchymal transition (EMT) and enhanced the motility and invasiveness of human nasopharyngeal epithelial cells, whereas silencing endogenous Bmi-1 expression reversed EMT and reduced motility. Furthermore, upregulation of Bmi-1 led to the stabilization of Snail, a transcriptional repressor associated with EMT, via modulation of PI3K/Akt/GSK-3beta signaling. Chromatin immunoprecipitation assays revealed that Bmi-1 transcriptionally downregulated expression of the tumor suppressor PTEN in tumor cells through direct association with the PTEN locus. This in vitro analysis was consistent with the statistical inverse correlation detected between Bmi-1 and PTEN expression in a cohort of human nasopharyngeal carcinoma biopsies. Moreover, ablation of PTEN expression partially rescued the migratory/invasive phenotype of Bmi-1-silenced cells, indicating that PTEN might be a major mediator of Bmi-1-induced EMT. Our results provide functional and mechanistic links between the oncoprotein Bmi-1 and the tumor suppressor PTEN in the development and progression of cancer.
•Few studies have explored the associations between Cl-PFESAs and serum lipids.•A large population-based study was conducted in China to assess these associations.•Perfluorooctane sulfonate ...alternatives were adversely associated with serum lipids.•That such associations were similar to those between legacy PFASs and TC.
Chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs), a group of perfluorooctane sulfonate (PFOS) alternatives, can be widely observed in humans and environmental matrices. However, associations between exposure to Cl-PFESAs and serum lipid levels in adults are unknown.
To explore the relationships between Cl-PFESA levels and serum lipid levels in adults.
We analyzed 1238 adults from the Isomers of C8 Health Project, a cross-sectional study conducted in China from July 2015 to October 2016. The average age of the participants was 61.98 ± 14.40 years. We quantified two select legacy per- and perfluoroalkyl substances perfluorooctanoic acid (PFOA) and PFOS and their alternatives (6:2 and 8:2 Cl-PFESAs). We also measured four serum lipids: low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). We used generalized linear models to estimate the associations between PFASs and serum lipids, with PFASs defined as either a categorical variable divided into quartiles or as a continuous variable.
We found that 6:2 Cl-PFESA was positively associated with serum TC and LDL-C. For instance, LDL-C levels in the highest quartile of 6:2 Cl-PFESA exposure (Q4) were significantly higher than those in the lowest quartile (Q1) β: 0.19, 95% confidence interval (CI): 0.08, 0.30. Further analysis showed that one ln-ng/mL increase in 6:2 Cl-PFESA exposure corresponded to a 0.10 mmol/L (95% CI: 0.05, 0.16) LDL-C increase, and that exposure to 8:2 Cl-PFESA was negatively correlated with HDL-C (β: −0.03, 95% CI: −0.05, −0.01). TC had a similar relationship with both 6:2 Cl-PFESA and legacy PFASs. Participants with a BMI ≥ 25 kg/m2 exhibited a stronger association between 6:2 Cl-PFESA and TC.
Our findings make the novel suggestion that exposure to Cl-PFESAs are adversely associated with serum lipid levels, and that such associations are also observed in legacy PFASs. Increased investigation into the effects of Cl-PFESAs exposure on human health is warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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