Synaptic loss and neuron death are the underlying cause of neurodegenerative diseases such as Alzheimer's disease (AD); however, the modalities of cell death in those diseases remain unclear. Ferroptosis, a newly identified oxidative cell death mechanism triggered by massive lipid peroxidation, is implicated in the degeneration of neurons populations such as spinal motor neurons and midbrain neurons. Here, we investigated whether neurons in forebrain regions (cerebral cortex and hippocampus) that are severely afflicted in AD patients might be vulnerable to ferroptosis. To this end, we generated Gpx4BIKO mouse, a mouse model with conditional deletion in forebrain neurons of glutathione peroxidase 4 (Gpx4), a key regulator of ferroptosis, and showed that treatment with tamoxifen led to deletion of Gpx4 primarily in forebrain neurons of adult Gpx4BIKO mice. Starting at 12 weeks after tamoxifen treatment, Gpx4BIKO mice exhibited significant deficits in spatial learning and memory function versus Control mice as determined by the Morris water maze task. Further examinations revealed that the cognitively impaired Gpx4BIKO mice exhibited hippocampal neurodegeneration. Notably, markers associated with ferroptosis, such as elevated lipid peroxidation, ERK activation and augmented neuroinflammation, were observed in Gpx4BIKO mice. We also showed that Gpx4BIKO mice fed a diet deficient in vitamin E, a lipid soluble antioxidant with anti-ferroptosis activity, had an expedited rate of hippocampal neurodegeneration and behavior dysfunction, and that treatment with a small-molecule ferroptosis inhibitor ameliorated neurodegeneration in those mice. Taken together, our results indicate that forebrain neurons are susceptible to ferroptosis, suggesting that ferroptosis may be an important neurodegenerative mechanism in diseases such as AD.

AGAMOUS-Like15 (AGL15) is a MADS domain transcriptional regulator that promotes somatic embryogenesis by binding DNA and regulating gene expression. Chromatin immunoprecipitation (ChIP) analysis previously identified DNA fragments with which AGL15 associates in vivo, and a low-throughput approach revealed a role for AGL15 in gibberellic acid catabolism that is relevant to embryogenesis. However, higher throughput methods are needed to identify targets of AGL15. Here, we mapped AGL15 in vivo binding sites using a ChIP-chip approach and the Affymetrix tiling arrays for Arabidopsis thaliana and found that ;2000 sites represented in three biological replicates of the experiment are annotated to nearby genes. These results were combined with high-throughput measurement of gene expression in response to AGL15 accumulation to discriminate responsive direct targets from those further downstream in the network. LEAFY COTYLE-DON2, FUSCA3, and ABA INSENSITIVE3, which encode B3 domain transcription factors that are key regulators of embryogenesis, were identified and verified as direct target genes of AGL15. Genes identified as targets of the B3 genes are also targets of AGL15, and we found that INDOLEACETIC ACID-INDUCED PROTEIN30 is involved in promotion of somatic embryo development. The data presented here and elsewhere suggest that much cross-regulation occurs in gene regulatory networks underpinning embryogenesis.

Background: Glutathione peroxidase 4 (GPX4) is shown to be a key inhibitor of ferroptosis, a cell death mechanism involving lipid reactive oxygen species. Results: Conditional ablation of Gpx4 in neurons resulted in rapid motor neuron degeneration and paralysis in mice. Conclusion: Lack of GPX4 triggered motor neuron degeneration characterized by ferroptosis. Significance: Ferroptosis inhibition may be essential for motor neuron health and survival in vivo.

Bisphenol A (BPA) is an industrial chemical used in the manufacture of polycarbonate plastics and epoxy resins. Due to the potential of this compound to disrupt normal endocrinal functions, concerns over human exposure to BPA have been raised. Although several studies have reported human exposure to BPA in Western nations, little is known about exposure in Asian countries. In this study, we determined total urinary BPA concentrations (free plus conjugated) in 296 urine samples (male/female: 153/143) collected from the general population in seven Asian countries, China, India, Japan, Korea, Kuwait, Malaysia, and Vietnam, using high-performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS). On the basis of urinary BPA concentrations, we estimated the total daily intake. The results indicated that BPA was detected in 94.3% of the samples analyzed, at concentrations ranging from <0.1 to 30.1 ng/mL. The geometric mean concentration of BPA for the entire sample set from seven countries was 1.20 ng/mL. The highest concentration of BPA was found in samples from Kuwait (median: 3.05 ng/mL, 2.45 μg/g creatinine), followed by Korea (2.17 ng/mL, 2.40 μg/g), India (1.71 ng/mL, 2.09 μg/g), Vietnam (1.18 ng/mL, 1.15 μg/g), China (1.10 ng/mL, 1.38 μg/g), Malaysia (1.06 ng/mL, 2.31 μg/g), and Japan (0.95 ng/mL, 0.58 μg/g). Among the five age groups studied (≤ 19, 20-29, 30-39, 40-49, and ≥ 50 years), the highest median concentration of BPA was found in urine samples from the age group of ≤ 19 years. There was no significant difference in BPA concentrations between genders (male and female) or domicile of residence (rural and urban). The estimated median daily intakes of BPA for the populations in Kuwait, Korea, India, China, Vietnam, Malaysia, and Japan were 5.19, 3.69, 2.90, 2.13, 2.01, 1.80, and 1.61 μg/day, respectively. The estimated daily intake of BPA in the seven Asian countries was significantly lower than the tolerable daily intake recommended by the U.S. Environmental Protection Agency. This is the first study to document the occurrence of and human exposure to BPA in several Asian countries.

Polychlorinated biphenyl (PCB) concentrations in air and soil, measured by various research groups from around the world, were compiled and analyzed. Data for air were available from most regions, particularly in Europe and Asia. The average air concentrations (pg/m(3)) for SigmaPCB at background sites were 70 (5.1-170) for Europe, 79 (49-120) for North America, 66 (18-110) for South America, 270 (9-670) for Central America, 59 (17-150) for Asia, and 15 (13-17) for Australia. Data for soils exhibited better global coverage compared to air and were available from most regions. The average soil concentrations (pg/g dry weight) for SigmaPCB at background sites were 7500 (47-97 000) for Europe, 4300 (110-25 000) for North America, 1400 (61-9 500) for South America, 580 (120-2 900) for Asia, 390 (94-620) for Africa, and 280 (140-540) for Australia. Based on available studies where coupled measurements of PCBs in air and soil were made, the equilibrium status of PCBs in the air-soil system was investigated for China, West Midlands of the UK, central and southern Europe, and along a latitudinal transect from the south of the UK to the north of Norway. Differences were observed in plots of the soil-air equilibrium status (expressed as the soil-air fugacity fraction, ff) for different PCB homologues. This was explained by varying contributions from primary and secondary emissions-spatially and temporally. The net effect after several decades of PCB emissions to air, preferential transport of lower molecular weight PCBs through primary and secondary emission, and reductions in emissions to air in recent decades is that the lower molecular weight PCBs have achieved (and in some cases exceeded) soil-air equilibrium in many parts of the world. The exception is remote and background sites that are still dominated by primary sources.

Benzophenones and benzotriazoles are widely used as ultraviolet (UV) light filters and stabilizers in cosmetics, skin creams, and body lotions and as corrosion inhibitors in building materials, automobile components, and automotive antifreeze cooling systems. Benzophenones and benzotriazoles have been reported to occur in the environment. Some of these UV filters have been reported to possess significant estrogenic activity. Despite this, very few studies have examined their occurrence and profiles in the environment. In this work, we determined five benzophenone-type UV filters and two benzotriazole-type corrosion inhibitors, namely, 2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4-dihydroxybenzophenone (2,4OH-BP), 2,2'-dihydroxy-4-methoxybenzophenone (2,2'OH-4MeO-BP), 2,2',4,4'-tetrahydroxybenzophenone (2,2',4,4'OH-BP), 4-hydroxybenzophenone (4OH-BP), 1H-benzotriazole (1H-BT), and 5-methyl-1H-benzotriazole (5Me-1H-BT), in sediment and sewage sludge samples, using liquid-liquid extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, four benzotriazole-type UV stabilizers, namely, 2-(3-t-butyl-2-hydroxy-5-methylphenyl)-5-chlorobenzotriazole (UV-326), 2,4-di-t-butyl-6-(5-chloro-2H-benzotriazole-2-yl) phenol (UV-327), 2-(2H-benzotriazole-2yl)-4,6-di-t-pentylphenol (UV-328), and 2-(5-t-butyl-2-hydroxyphenyl) benzotriazole (TBHPBT) were determined by gas chromatography (GC)-mass spectrometry (MS). The limits of quantitation (LOQ) were in the ranges of 0.06-0.33 ng g⁻¹ dry weight (dw) and 0.1-1.65 ng g⁻¹ dw for sediment and sludge samples, respectively. Recoveries of target compounds spiked into sample matrices and passed through the entire analytical procedure ranged from 70% to 116% (RSD: 3.32-13.8%) and from 82% to 106% (RSD: 2.89-8.09%) for the compounds analyzed by LC-MS/MS and GC-MS, respectively. The methods were applied to the analysis of sediment samples from the Songhua, Saginaw, and Detroit Rivers; the sum concentrations of target compounds were 3.29-9.93, 5.81-22.5, and 190-389 ng g⁻¹ dw, respectively. Five sludge samples collected from five wastewater treatment plants in northeastern China contained the sum concentrations of target compounds in the range of 104-6370 ng g⁻¹ dw. The concentration of UV-328 in sludge was the highest (mean: 1300 ng g⁻¹ dw) among the target compounds. To our knowledge, this is the first work to report the occurrence of 2OH-4MeO-BP, 2,4OH-BP, 2,2'OH-4MeO-BP, 2,2',4,4'OH-BP, and 4OH-BP in sediment and sludge samples.

Polychlorinated biphenyl (PCB) concentrations in surface soil samples (0-20 cm) from 52 sites (4 background, 39 rural, and 9 urban) across China in 2005 are presented. The average concentration of total PCBs among all the sites was 515 pg/g dry weight (dw), approximately one-tenth of that in global background soil in 1998. Differences of less than 1 order of magnitude were found between all background and rural sites, indicating a generally uniform distribution of PCBs in Chinese background/rural surface soil. While the major PCB homologue group in global background soil is hexa-PCB followed by penta-PCB, the major PCB homologue group in Chinese background/rural soil is tri-PCB followed by di-PCB, indicating a rather fresh signature in comparison to the much weathered PCBs in global surface soil. The correlation between sigmaPCBs and also each PCB homologue group per soil organic carbon (SOC) content in background/rural soil with longitude from 80 degrees to 122 degrees East was studied. The results indicated the strong influence of PCBs concentrations in Chinese background/rural soil by proximity to source region and SOC content, and also provided evidence for urban fractionation effect of PCBs in soil in the city of Shanghai and the longitudinal fractionation of PCBs in Chinese background/ rural soil from east to west. This work is the first comprehensive and spatial study of its kind for PCBs in Chinese surface soil on a national scale, and the data presented in this study can provide baseline information for establishing a long-term PCBs monitoring program in China.

The highly chlorinated flame retardant, Dechlorane Plus (DP), was measured in air across 97 Chinese urban and rural sites. DP was detected in 51 of these sites, with a mean air concentration in urban centers (15.6 ( 15.1 pg m -3 ) approximately 5 times greater than those measured in rural areas (3.5 ( 5.6 pg m -3 ). These DP levels were likely attributable to local sources rather than trans-boundary influences. Elevated urban levels were measured along the southeastern coast and in southcentral China; the highest concentration was observed in the city of Kunming (66 pg m -3 ). Few of the urban samples (7%) and a majority of the rural samples (62%) were below the method detection limit, notably areas in rural central and northeastern China. The mean fractional abundance of the syn-DP isomer (f syn ) in all samples was 0.33 ( 0.10, values indistinguishable from that of a commercial mixture (f syn ) 0.35). This paper represents the first report on DP levels in Chinese air, together with isomeric ratio profiles from urban and rural sites.