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Furthermore, we find that the improved H2O2 reinforces silibinin-induced glycolysis dysfunction. Collectively, autophagy contributes to silibinin-induced glioma cell death via promotion of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF.Dietary microRNAs have been shown to be absorbed by mammals and regulate host gene expression, but the absorption mechanism remains unknown. Here, we show that SIDT1 expressed on gastric pit cells in the stomach is required for the absorption of dietary microRNAs. SIDT1-deficient mice show reduced basal levels and impaired dynamic absorption of dietary microRNAs. Notably, we identified the stomach as the primary site for dietary microRNA absorption, which is dramatically attenuated in the stomachs of SIDT1-deficient mice. Mechanistic analyses revealed that the uptake of exogenous microRNAs by gastric pit cells is SIDT1 and low-pH dependent. Furthermore, oral administration of plant-derived miR2911 retards liver fibrosis, and this protective effect was abolished in SIDT1-deficient mice. Our findings reveal a major mechanism underlying the absorption of dietary microRNAs, uncover an unexpected role of the stomach and shed light on developing small RNA therapeutics by oral delivery.Double-stranded RNA (dsRNA)-dependent protein kinase R (PKR) activation via autophosphorylation is the central cellular response to stress that promotes cell death or apoptosis. However, the key factors and mechanisms behind the simultaneous activation of pro-survival signaling pathways remain unknown. We have discovered a novel regulatory mechanism for the maintenance of cellular homeostasis that relies on the phosphorylation interplay between sphingosine kinase 1 (SPHK1) and PKR during exogenous stress. We identified SPHK1 as a previously unrecognized PKR substrate. Phosphorylated SPHK1, a central kinase, mediates the activation of PKR-induced pro-survival pathways by the S1P/S1PR1/MAPKs/IKKα signal axis, and antagonizes PKR-mediated endoplasmic reticulum (ER) stress signal transduction under stress conditions. Otherwise, phosphorylated SPHK1 also acts as the negative feedback factor, preferentially binding to the latent form of PKR at the C-terminal kinase motif, inhibiting the homodimerization of PKR, suppressing PKR autophosphorylation, and reducing the signaling strength for cell death and apoptosis. Our results suggest that the balance of the activation levels between PKR and SPHK1, a probable hallmark of homeostasis maintenance, determines cell fate during cellular stress response.

Although previous studies have shown a decreased incidence of prostate cancer in men with HIV/AIDS, the consensus has not been reached. Our aim is to conduct a systematic review and meta-analysis to assess the risk of prostate cancer among people with HIV/AIDS.

We systematically searched PubMed, Web of Science, Embase, and Cochrane Library until March 2020. Cohort studies were included if they compared the prostate cancer risk between people with HIV/AIDS and uninfected controls or the general population. The summary standardized incidence ratio (SIR) and 95% confidence interval (CI) were calculated using a random-effects model.

A total of 27 studies were included for analysis, with more than 2780 males with HIV/AIDS developing prostate cancer. The results showed that HIV infection was associated with a decreased risk of prostate cancer incidence (SIR, 0.76; 95% CI, 0.64-0.91; P = 0.003), with significant heterogeneity (P < 0.001; I

 = 91.6%). A range of sensitivity analyzes did not significantly change the results.

Our study shows that people with HIV/AIDS have a lower incidence of prostate cancer compared with the general population. However, significant heterogeneity exists among the included studies. Further prospective studies with better designs are needed to elucidate the association between HIV infection and prostate cancer.

Our study shows that people with HIV/AIDS have a lower incidence of prostate cancer compared with the general population. However, significant heterogeneity exists among the included studies. Further prospective studies with better designs are needed to elucidate the association between HIV infection and prostate cancer.

Consensus regarding optimal glucagon dosing for management or diagnosis of neonatal/infant hypoglycemia has not been established.

To investigate glycemic effects of glucagon dosed ≤0.2 mg/kg (Gn

) vs. >0.2 mg/kg (Gn

) in neonatal/infant hypoglycemia.

Retrospective, observational, cohort study.

Glucagon administration at any dose resulted in 75/77 (97.4%) samples meeting criteria for normoglycemia (plasma glucose >60 mg/dL), and plasma glucose increases of >30 mg/dL occurred in 74.2% vs. 63% (NS) of samples in the Gn

and Gn

groups, respectively. Despite equivalent glucagon dosing, there was a trend toward smaller (<2500 g) patients achieving post-glucagon plasma glucose increases of >30 mg/dL less often than their bigger (≥2500 g) counterparts (60% vs. 74.1%, NS).

Glucagon is highly effective in raising plasma glucose levels in neonatal/infant hypoglycemia. No differences in glycemic effects were noted between either dosing regimen. However, glycemic effects may be diminished in lower weight patients.

Glucagon is highly effective in raising plasma glucose levels in neonatal/infant hypoglycemia. No differences in glycemic effects were noted between either dosing regimen. Levofloxacin However, glycemic effects may be diminished in lower weight patients.

To examine interhospital variation in admissions to neonatal intensive care units (NICU) and reasons for the variation.

2010-2012 linked birth certificate and hospital discharge data from 35 hospitals in California on live births at 35-42 weeks gestation and ≥1500 g birth weight were used. Hospital variation in NICU admission rates was assessed by coefficient of variation. Patient/hospital characteristics associated with NICU admissions were identified by multivariable regression.

Among 276,489 newborns, 6.3% were admitted to NICU with 34.5% of them having mild diagnoses. There was high interhospital variation in overall risk-adjusted rate of NICU admission (coefficient of variation = 26.2) and NICU admission rates for mild diagnoses (coefficient of variation 46.4-74.0), but lower variation for moderate/severe diagnoses (coefficient of variation 8.8-14.1). Births at hospitals with more NICU beds had a higher likelihood of NICU admission.

Interhospital variation in NICU admissions is mostly driven by admissions for mild diagnoses, suggesting potential overuse.