Detailed studies on Egr1 and Arc expression revealed HDAC enrichment at their promoter regions. HDAC inhibition with trichostatin A (TSA) before PEE rescued H3ac/H4ac levels and prevented CC3 formation. Antagonism/null mutation of cannabinoid receptor type-1 (CB1R) before PEE to inhibit CC3 production prevented Egr1 and Arc loss via epigenetic events. TSA administration before PEE prevented PE-induced loss of Egr1 and Arc expression and neurobehavioral defects in adult mice via epigenetic remodeling. In adult mice, three-day TSA administration attenuated PEE-induced behavioral defects. CONCLUSIONS These findings demonstrate that CB1R/HDAC-mediated epigenetic remodeling disrupts gene expression and is a critical step in FASD-associated cognitive decline but is reversed by restoration of histone acetylation in the brain. Published by Oxford University Press on behalf of CINP 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.CONTEXT Unlike other commonly used invasive blood glucose monitoring methods, saliva detection prevents patients from suffering the physical uneasiness. However, there are few studies on saliva 1,5-anhydroglucitol (1,5-AG) in patients with diabetes mellitus (DM). OBJECTIVE This study aimed to evaluate the effectiveness of saliva 1,5-AG in diabetes screening in a Chinese population. DESIGN AND PARTICIPANTS This was a population-based cross-sectional study. A total of 641 subjects without a valid diabetic history were recruited from September 2018 to June 2019. Saliva 1,5-AG was measured with liquid chromatography-mass spectrometry. RESULTS Saliva 1,5-AG levels in DM subjects were lower than those in non-diabetes mellitus subjects (both P less then 0.05). Saliva 1,5-AG was positively correlated with serum 1,5-AG and negatively correlated with blood glucose and glycated hemoglobin (HbA1c) (all P less then 0.05). The optimal cutoff points of saliva 1,5-AG0 and 1,5-AG120 for diabetes screening were 0.436 μg/mL (sensitivity 63.58%, specificity 60.61%) and 0.438 μg/mL (sensitivity 62.25%, specificity 60.41%), respectively. Fasting plasma glucose (FPG) combined with fasting saliva 1,5-AG reduced the proportion of people who required an OGTT by 47.22% compared with FPG alone. CONCLUSION Saliva 1,5-AG combined with FPG or HbA1c improved the efficiency of diabetes screening. Saliva 1,5-AG is robust in nonfasting measurements and a noninvasive and convenient tool for diabetes screening. see more © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Increasing atmospheric carbon dioxide concentration ([CO2]) directly impacts C3 plant photosynthesis and productivity, and the rate at which [CO2] is increasing is greater than initially predicted by worst-case scenario climate models. Thus, it is increasingly important to assess the physiological responses of C3 plants, especially those that serve as important crops, to [CO2] beyond the mid-range levels used in traditional experiments. Here, we grew the C3 crop soybean (Glycine max) at eight different [CO2] levels spanning sub-ambient (340 ppm) to the highest level thought plausible (~2000 ppm) in chambers for five weeks. Physiological development was delayed and plant height and total leaf area increased at [CO2] levels higher than ambient conditions with very little difference in these parameters among the elevated [CO2] treatments >900 ppm. Daily photosynthesis initially increased with rising [CO2] but began to level off around 1000 ppm CO2. Similar results occurred in biomass accumulation. Thus, as [CO2] continues to match or exceed the worst-case emission scenarios, these results indicate carbon gain, growth, and potentially yield increases will diminish, thereby ultimately constraining the positive impact continuing increases in atmospheric [CO2] could have on crop productivity and global terrestrial carbon sinks. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email journals.permissions@oup.com.CONTEXT Different phenotypical features of women with hypothalamic hypogonadism (HH), also known as World Health Organization-1 anovulation, including ovarian morphology, have been scarcely described in large cohorts. Some studies have reported increased levels of anti-Müllerian hormone (AMH) in women with HH. OBJECTIVE To assess whether women with HH, compared with healthy controls, have increased serum levels of AMH and what proportion of these women erroneously meet the Rotterdam Criteria for Polycystic Ovarian Syndrome (PCOS). DESIGN, SETTING AND PARTICIPANTS Retrospective cohort study in a Dutch academic medical center including 83 women with neither anovulation nor menstrual cycle disorders (healthy controls), 159 women with HH and 3640 women with PCOS. Age matching was used between the HH and PCOS group (12 ratio) to create a second group consisting of 318 age-matched women with PCOS. INTERVENTION None. MAIN OUTCOME MEASURES AMH levels and ovarian morphology. RESULTS Median AMH serum levels for the HH group were 3.8 ( less then 0.1-19.8), compared with 7.5 ( less then 0.1-81.0) in the PCOS group and 1.9 ( less then 0.1-21.5) in the control group (P  less then  0.001). In the HH group, 58 (36%) erroneously met the Rotterdam Criteria for PCOS (meeting 2 of 3 criteria). CONCLUSIONS AMH levels are increased in women with HH. We hypothesize that this increase, although there was no increase in follicle count, may be explained by the presence of a relatively large pool of antral follicles smaller than 2 mm in diameter, that are undetectable by transvaginal ultrasound. This study highlights the importance of measuring gonadotropins and estradiol before diagnosing a patient with PCOS. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Cyclic-G/AMP (cGAMP) synthase (cGAS) triggers host innate immune responses against cytosolic double-stranded (ds)DNA arising from genotoxic stress and pathogen invasion. The canonical activation mechanism of cGAS entails dsDNA-binding and dimerization. Here, we report an unexpected activation mechanism of cGAS in which Mn2+ activates monomeric cGAS without dsDNA. Importantly, the Mn2+-mediated activation positively couples with dsDNA-dependent activation in a concerted manner. Moreover, the positive coupling between Mn2+ and dsDNA length-dependent activation requires the cognate ATP/GTP substrate pair, while negative-cooperativity suppresses Mn2+ utilization by either ATP or GTP alone. Additionally, while Mn2+ accelerates the overall catalytic activity, dsDNA length-dependent dimerization specifically accelerates the cyclization of cGAMP. Together, we demonstrate how the intrinsic allostery of cGAS efficiently yet precisely tunes its activity. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.