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Dietary restriction (DR) is known to promote autophagy to exert its longevity effect. While SAMS-1 (S-adenosyl methionine synthetase-1) has been shown to be a key mediator of the DR response, little is known about the roles of S-adenosyl methionine (SAM) and SAM-dependent methyltransferase in autophagy and DR-induced longevity. In this study, we show that DR and SAMS-1 repress the activity of SET-2, a histone H3K4 methyltransferase, by limiting the availability of SAM. Consequently, the reduced H3K4me3 levels promote the expression and activity of two transcription factors, HLH-30/TFEB and PHA-4/FOXA, which both regulate the transcription of autophagy-related genes. We then find that HLH-30/TFEB and PHA-4/FOXA act collaboratively on their common target genes to mediate the transcriptional response of autophagy-related genes and consequently the lifespan of the animals. Our study thus shows that the SAMS-1-SET-2 axis serves as a nutrient-sensing module to epigenetically coordinate the activation of HLH-30/TFEB and PHA-4/FOXA transcription factors to control macroautophagy/autophagy and longevity in response to DR. Abbreviations: ChIP: chromatin immunoprecipitation; ChIP-seq: chromatin immuno precipitation-sequencing; COMPASS: complex of proteins associated with Set1; DR: dietary restriction; GO: gene ontology; SAM: S-adenosyl methionine; SAMS-1: S-adenosyl methionine synthetase-1; TSS: transcription start site; WT: wild-type. [ABSTRACT FROM AUTHOR]

Recent studies have shown that the reduction of sperm count is associated with sleep behaviors, including restricted/excessive sleep duration, late sleep time midpoint, and shift of sleep midpoint time (social jetlag). Chronotype is suggested to regulate sleep behaviors; however, the relationship between chronotype and human sperm count is unknown. The relationship between sleep behaviors and human sperm count, when sleep behaviors as well as chronotype are controlled is also unclear. We performed a path analysis of the data obtained from 667 Chinese men recruited into the MARHCS (Male Reproductive Health in Chongqing College Students) study. Chronotype, sleep duration, sleep time midpoint, and social jetlag were estimated by the Munich Chronotype Questionnaire. Sperm count was measured by computer-aided sperm analysis. The comprehensive relationship between chronotype, all sleep behaviors, and sperm count was tested by path analysis, in which the standardized residual of sperm count was used for adjustment of age, abstinence period, body mass index, tobacco smoking, alcohol drinking, and intake of tea, cola, and coffee. Our major findings are: (1) Chronotype negatively correlated with sleep duration (correlation coefficient (R) = −0.32, P <.001) and positively correlated with sleep midpoint (R = 0.65, P <.001) and social jetlag (R = 0.37, P <.001). (2) Sleep duration (U-shape transformed; R = −0.11, P =.005), sleep midpoint (R = −0.09, P =.021), and social jetlag (R = −0.12, P =.001), respectively, correlated with sperm count in univariate analysis. The relationship between sleep midpoint and sperm count disappeared when social jetlag was controlled. (3) Path analysis showed that chronotype is connected with sperm count through two pathways: via sleep duration (standardized path coefficient = −0.09, 95% CI: −0.17 to −0.01, P =.030) and via social jetlag (standardized path coefficient = −0.09, 95% CI: −0.17 to −0.01, P =.031). For men of earlier, intermediate, and later tertile of chronotype, the sleep-duration-related decrease of sperm count was separately estimated to be 16.3%, 12.8%, and 11.6%, while the social-jetlag-related decrease of sperm count was estimated to be 9.3%, 12.8%, and 19.2%. The total effect of sleep behaviors on sperm count was estimated to be 25.7%, 25.6%, and 30.7%, with an average of 27.4% for men of different chronotypes. The present study showed that men of earlier chronotype were prone to restricted/excessive sleep duration, while men of later chronotype were prone to social jetlag, both of which correlated with reduced sperm count, suggesting that chronotype may modulate the sleep behaviors and exert dual effects on sperm count via different sleep behaviors, leading to a ubiquitous sperm decline. Men of different chronotypes should take care to avoid different types of improper sleep behaviors, so as to prevent such deleterious effect on sperm count. [ABSTRACT FROM AUTHOR]

Dibutyl phthalate (DBP) is a widely used plasticizer that has been shown to induce germ cell apoptosis-related testicular atrophy and cause reproductive toxicity. Our previous results indicated that endoplasmic reticulum (ER) stress-activated autophagy served as a self-defense mechanism against DBP-induced germ cell apoptosis. However, the specific pathways that link ER stress and autophagy remain unclear. Here, we showed that exposure to DBP enhanced autophagic flux in mouse spermatocyte-derived GC-2 cells and that the eukaryotic translation initiation factor 2/activating transcription factor 4 pathway mediated ER stress-related autophagy independent of the mTOR and Beclin-1 pathways. Moreover, we demonstrated that DBP treatment led to the generation of reactive oxygen species (ROS) and that the inhibition of ROS by melatonin abrogated both ER stress and autophagy. The results indicated that excessive ROS production might be involved in DBP-induced ER stress and autophagy in GC-2 cells. Thus, ROS may serve as upstream mediators of ER stress and autophagy in DBP-treated GC-2 cells. [ABSTRACT FROM PUBLISHER]

Context: Smoke inhalation injury is the main cause of fatalities for fire victims. Understanding in the pathophysiology of the injury has not been fully explored in recent years. To further explore the pathophysiological mechanism, a dynamic and controllable animal model is necessary. Objective: To develop a rat model of smoke inhalation injury to simulate human victims in air-restricted vehicle cabin fires. Materials and methods: Smoke concentration, including CO, O2, VOCs and smoke temperature under different combustion conditions, were detected. Levels of COHb, respiratory function, lung wet-to-dry weight ratio and protein concentration in BALF and blood were measured. Pathological evaluations of lung in tissues were conducted at 1, 6, 24 and 48 h post-exposure. Results: Smoke concentration rose with the increase of combustion temperature and decrease of oxygen flow. Further, 215 kinds of VOCs in the smoke were detected, and the concentrations of benzene, methylbenzene, ethylbenzene, dimethylbenzene, phenylethylene and trimethyl-benzene was 32.93, 402.06, 764.03, 113.73, 1006.61 and 89.28 mg/m³, respectively. Significant hypoxemia and CO poisoning occurred in rats. The FCOHb after exposure for 14min immediately rose to (44.2 ± 12.3) % and then gradually decrease to a normal level at 300 min post-exposure. At 24 h post-exposure, Penh increased significantly (p<0.05), and high pulmonary vascular permeability and significant lung edema [p<0.05) were observed in the smoke inhalation group. Discussion and conclusion: In summary, the novel rat model of smoke inhalation injury system used in the study is dynamic and controllable, and appropriate for use in smoke inhalation injury studies of air-restricted cabins in vehicles. [ABSTRACT FROM AUTHOR]