The small GTPase Rheb binds and activates mTORC1, which plays a pivotal role in diverse cellular physiologies. To increase our understanding of how Rheb regulates mTORC1 signaling, we set out to identify Rheb binding proteins using shotgun proteomics approaches. In this study, we characterized HSP70, one of the identified proteins, as a new Rheb binding protein. The present study showed that Rheb forms a complex with HSP70 in intact cells. Interestingly, the binding of Rheb to mTORC1 was abolished by HSP70. Furthermore, DNA Repair inhibitor of Rheb is dramatically decreased by HSP70, and this degradation is proteasome-dependent. As a result, Rheb-dependent mTORC1 activation was decreased by HSP70. Taken together, HSP70 dissociates Rheb from mTORC1 and induces proteasome-dependent degradation, leading to the inhibition of mTORC1 signaling. Our findings suggest that HSP70 is a negative regulator of mTORC1 signaling via interaction with Rheb.Sphingomyelin synthase 2 (SMS2) regulates sphingomyelin synthesis and contributes to obesity and hepatic steatosis. Here, we investigated the effect of SMS2 deficiency on liver fibrosis in mice fed with choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) or injected with carbon tetrachloride (CCl4), respectively. #link# SMS2 deficiency suppressed hepatic steatosis, but exacerbated fibrosis induced by CDAHFD feeding. Sphingosine 1-phosphate (S1P), which is a key lipid mediator induces fibrosis in various organs, was increased in the liver of mice fed with CDAHFD. The increase of S1P became prominent by SMS2 deficiency. Meanwhile, SMS2 deficiency had no impact on CCl4-induced liver injury, fibrosis and S1P levels. Our findings demonstrated that SMS2 deficiency suppresses steatosis but worsens fibrosis in the liver in a specific condition with CDAHFD feeding.The mechanisms underlying the antidepressant activity of quercetin are unknown. We investigated the effect of a quercetin-enriched diet (2 g/kg and 0.5 g/kg doses) on chronic social defeat stress (CSDS)-induced depressive-like behaviors in mice. The 2 g/kg quercetin-enriched diet attenuated depressive-like behaviors when introduced before CSDS (long-term). The long-term 0.5 g/kg quercetin-enriched diet showed a trend toward behavioral improvement. The frequencies of spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs) in the mPFC and hippocampus were significantly higher in mice fed the long-term 2 g/kg quercetin-enriched diet compared with the normal diet; no difference was found in the amygdala. Quercetin-enriched diets administered concurrently and after stress induction failed to trigger these effects. A1-specific astrocyte reactivity was markedly suppressed in the microglia and astrocytes isolated from the mPFC and hippocampus of mice fed the long-term quercetin-enriched diet, but not in those who received quercetin supplementation concurrently or after CSDS. To confirm the role of astrocytes in the neuroprotective effect of quercetin, we activated astrocytes by injecting a chemogenic AAV stimulus into the mPFC and hippocampus and found that astrocyte activation during administration of the long-term quercetin-enriched diet significantly deceased the frequency of sEPSCs and sIPSCs in the mPFC and hippocampus and further attenuated quercetin-induced behavioral improvements. These findings highlight the key role of astrocyte reactivation in the regulation of quercetin neuroprotective activity and suggest that a diet high in quercetin, whether as a fruit- and vegetable-rich diet or food additive may help cope with stress.

As a primary source of added sugars, sugar-sweetened beverage consumption contributes to obesity. This study systematically synthesizes the scientific evidence regarding the impact of sugar-sweetened beverage warning labels on consumer behaviors and intentions.

A keyword/reference search was performed in 2019 in Cochrane Library, PubMed, Web of Science, CINAHL, Scopus, and Google Scholar. Meta-analysis was conducted in 2020 to estimate the effect of sugar-sweetened beverage warning labels on consumers’ purchase decisions.

A total of 23 studies (13 RCTs, 9 nonrandomized experiments, and 1 computer simulation study) met the eligibility criteria and were included. Labels were classified into 6 categories (1) symbol with nutrient profile, (2) symbol with health effect, (3) text of nutrient profile, (4) text of health effect, (5) graphic with health effect, and (6) graphic with nutrient profile. Compared with the no-label control group, sugar-sweetened beverage warning label use was associated with reduced oct labels showed the largest impact. Future studies should delineate the psychosocial pathways linking sugar-sweetened beverage warning labels to purchase decisions, recruit socioeconomically diverse participants, and design experiments in naturalistic settings.

Smoking-cessation interventions can increase successful quitting, reduce healthcare costs, and enhance patients’ health and well-being. This study assesses changes in the availability of hospital-affiliated smoking-cessation programs over time in the U.S. and examines the hospital characteristics associated with such programs.

Data were obtained from the American Hospital Association annual surveys. Joinpoint regressions were used to estimate the trends in having hospital-affiliated cessation programs between 2000 and 2018. A logit regression was used to estimate the association between hospital characteristics (bed size, location, teaching status, ownership) and having any hospital-affiliated cessation program. Analyses were conducted in 2019.

The percentage of U.S. hospitals with any tobacco-cessation program increased from 23.8% (95% CI=22.7, 24.9) in 2000 to 45.5% (95% CI=44.2, 46.7) in 2018. There were sharp increases in the cessation programs between 2000 and 2002 but no change between 2015 and 20Further efforts to promote and support hospital-affiliated cessation programs could be beneficial, especially among smaller, rural, nonteaching, and private for-profit hospitals.

In young women, EOC is a rare disease with an uncertain genetic and biological substrate.

We report a long follow-up of EOC patients treated at Gustave Roussy between 1990 and 2009. We matched young patients aged ≤30years to randomly selected older patients aged ≥40years according to known prognostic factors (i.e. FIGO stage, histology and surgical residual disease) and the date of diagnosis with a threshold at the year 2000 to balance the treatment procedures.

EOC was diagnosed in 68 patients aged ≤30years matched with 111 patients aged ≥40years. Low-grade (LG) (i.e. serous and endometrioid) (52%, n=35) and mucinous (i.e. 23%, n=16 infiltrative and 12% n=8 expansile) tumors are prevalent. High-grade (HG) tumors are rare (7%, n=5). Early stage diseases (53%, n=36 FIGO I/II) are predominant. Response to platinum based chemotherapy is observed to be inferior in young patients as compared to matched older patients (ORR, 29 vs 84% p=0.0002). For HG tumors the PFS is of 0% at 5 and 10years in younger as compared to 30% in older patients.