Energy sensor AMPK gamma regulates translation via phosphatase PPP6C independent of AMPK alpha.

Maintenance of energy level to drive movements and material exchange with the environment is a basic principle of life. AMP-activated protein kinase (AMPK) senses energy level and is a major regulator of cellular energy responses. The gamma subunit of AMPK senses elevated ratio of AMP to ATP and allosterically activates the alpha catalytic subunit to phosphorylate downstream effectors. Here, we report that knockout of AMPKγ, but not AMPKα, suppressed phosphorylation of eukaryotic translation elongation factor 2 (eEF2) induced by energy starvation. We identified PPP6C as an AMPKγ-regulated phosphatase of eEF2. AMP-bound AMPKγ sequesters PPP6C, thereby blocking dephosphorylation of eEF2 and thus inhibiting translation elongation to preserve energy and to promote cell survival. Further phosphoproteomic analysis identified additional targets of PPP6C regulated by energy stress in an AMPKγ-dependent manner. Thus, AMPKγ senses cellular energy availability to regulate not only AMPKα kinase, but also PPP6C phosphatase and possibly other effectors.

ZJUSAH Classification: A New Classification for Primary Brainstem Hemorrhage.

To analyze and improve ZJUSAH classification for primary brainstem hematoma, we retrospectively reviewed 211 patients with primary brainstem hemorrhage who were admitted to our institution between January 2014 and October 2020. The primary clinical outcomes were the 30-day survival rate and 90-day consciousness recovery rate, which were evaluated using the National Institutes of Health Stroke Scale score. Univariate logistic regression and multivariate Cox regression analyses were performed to evaluate the prognostic model. The overall 30-day survival rate of the 211 patients was 69.7%. The 30-day survival rate was 95% among Type 1 patients, 77.8% among Type 2 patients, and 63.2% among Type 3 patients. The 90-day consciousness recovery rate was 63.2% among Type 1 patients, 61.9% among Type 2 patients, and 30.2% among Type 3 patients. Our findings suggest that ZJUSAH classification can be optimized according to hematoma volume, with Type 3 patients with a hematoma larger than 12.4 mL tending to have a worse state of consciousness. Additionally, we discovered that ZJUSAH classification is valuable in predicting 30-day survival rates in conservative treatment patients. In conclusion, our study established and optimized a new CT-based hematoma classification system for primary brainstem hematoma, which facilitates treatment selection and prognostic prediction.

Prognostic models for survival and consciousness in patients with primary brainstem hemorrhage.

Objectives: Primary brainstem hemorrhage (PBSH) is one of the most catastrophic spontaneous intracerebral hemorrhage diseases, with a mortality rate of 70-80%. We explored the predictive factors for survival and consciousness in patients with PBSH (ClinicalTrials.gov ID: NCT04910490). Methods: We retrospectively reviewed 211 patients with PBSH admitted to our institution between January 2014 and October 2020. Clinical outcomes included the 30-day survival rate and the 90-day consciousness rate as evaluated by the National Institutes of Health Stroke Scale score. Multiple logistic regression analysis was performed. Results: The overall 30-day survival rate of 211 patients with PBSH was 70%. Several predictive factors including hematoma volume, hematoma location, activated partial thromboplastin time (APTT) upon admission, and therapeutic strategy were significantly related to 30-day survival. Compared with conservative treatment, stereotactic aspiration in our prediction model is strongly associated with improved 30-day survival (odds ratio, 6.67; 95% confidence interval, 3.13-14.29; P < 0.001). The prognosis prediction model of 90-day consciousness including factors such as mydriasis, APTT value, hematoma location, and hematoma volume upon admission has a good predictive effect (AUC, 0.835; 95% confidence interval, 0.78-0.89; P < 0.001). Conclusion: In patients with PBSH, conscious state upon admission, coagulation function, hematoma volume, hematoma location, and therapeutic strategy were significantly associated with prognosis. Stereotactic aspiration could significantly reduce the 30-day mortality rate.

Corrigendum: Prognostic models for survival and consciousness in patients with primary brainstem hemorrhage.

[This corrects the article DOI: 10.3389/fneur.2023.1126585.].