Globally, hepatocellular carcinoma (HCC) is the sixth most common cancer. In this study, the correlation between mitophagy and HCC prognosis was evaluated using data from The Cancer Genome Atlas (TCGA). Clinical and transcriptomic data of HCC patients were downloaded from TCGA dataset, and mitophagy-related gene (MRG) datasets were obtained from the Molecular Signature Database. Then, a consensus clustering analysis was performed to classify the patients into two clusters. Furthermore, tumor prognosis, clinicopathological features, functional analysis, immune infiltration, immune checkpoint (IC)-related gene expression level, tumor stem cells, ferroptosis status, and N6-methyladenosine analysis were compared between the two clusters. Finally, a mitophagy-related signature was developed. Two clusters (C1 and C2) were identified using the consensus clustering analysis based on the MRG signature. Patients with the C1 subtype exhibited upregulated pathways with better liver function, downregulated cancer-related pathways, lower cancer stem cell scores, lower Tumor Immune Dysfunction and Exclusion scores (TIDE), different ferroptosis status, and better prognosis compared with the patients with the C2 subtype. The C2 subtype was characterized by the increased grade of HCC, as well as the increased number of immune-related pathways and m⁶A-related genes. Higher immune scores were also observed for the C2 subtype. A signature containing four MRGs (PGAM5, SQSTM1, ATG9A, and GABARAPL1) which can accurately predict the prognosis of HCC patients was then identified. This four-gene signature exhibited a predictive effect in five other cancer types, namely glioma, uveal melanoma, acute myeloid leukemia, adrenocortical carcinoma, and mesothelioma. The mitophagy-associated subtypes of HCC were closely related to the immune microenvironment, immune checkpoint-related gene expression, cancer stem cells, ferroptosis status, m⁶A, prognosis, and HCC progression. The established MRG signature could predict prognosis in patients with HCC.

Exposure to mild early-life stresses can slow down aging, and protein phosphorylation might be an essential regulator in this process. However, the mechanisms of phosphorylation-based signaling networks during mild early-life stress remain elusive. Herein, we systematically analyzed the phosphoproteomes of Caenorhabditis elegans, which were treated with three mild temperatures (15 °C, 20 °C, and 25 °C) in two different short-term groups (10 min and 60 min). By utilizing an iTRAQ-based quantitative phosphoproteomic approach, 18,187 phosphosites from 3330 phosphoproteins were detected in this study. Volcano plots illustrated that the phosphorylation abundance of 374 proteins and 347 proteins, were significantly changed at 15 °C and 25 °C, respectively. Gene ontology, KEGG pathway and protein-protein interaction network analyses revealed that these phosphoproteins were primarily associated with metabolism, translation, development, and lifespan determination. A motif analysis of kinase substrates suggested that MAPK, CK, and CAMK were most likely involved in the adaption processes. Moreover, 16 and 14 aging-regulated proteins were found to undergo phosphorylation modifications under the mild stresses of 15 °C and 25 °C, respectively, indicating that these proteins might be important for maintaining long-term health. Further lifespan experiments confirmed that the candidate phosphoproteins, e.g., EGL-27 and XNP-1 modulated longevity at 15 °C, 20 °C, and 25 °C, and they showed increased tolerance to thermal and oxidative stresses. In conclusion, our findings offered data that supports understanding of the phosphorylation mechanisms involved in mild early-life stresses in C. elegans. Data are available via ProteomeXchange with identifier PXD021081.

Introduction: Endovascular therapy is the standard of care for severe acute ischemic stroke caused by large‐vessel occlusion in the anterior circulation, but there is a debate on the optimal anesthetic approach during this therapy. Meta‐analyses of observational studies suggest that general anesthesia increases disability and death compared with conscious sedation However, their results are conflicting. This meta‐analysis study was performed to assess the relationship between the effects of general anesthesia compared to conscious sedation during endovascular therapy for acute ischemic stroke.Methods: Through a systematic literature search up to August 2020, 18 studies included 4,802 subjects at baseline with endovascular therapy for acute ischemic stroke and reported a total of 1,711 subjects using general anesthesia and 1,961 subjects using conscious sedation were found. They recorded relationships between the effects of general anesthesia compared to conscious sedation during endovascular therapy for acute ischemic stroke. Odds ratio (OR) or Mean differences (MD) with 95% confidence intervals (CIs) were calculated between the effect of general anesthesia compared to conscious sedation during endovascular therapy for acute ischemic stroke using the dichotomous or contentious methods with a random or fixed‐effect model.Results: No significant difference were found between general anesthesia and conscious sedation during the endovascular therapy for acute ischemic stroke in functional independence at 90 days (OR, 0.78; 95% CI, 0.44–1.40, p = 40); successful recanalization at 24 hr (OR, 1.23; 95% CI, 0.62–2.41, p = 55); mortality at 90 days (OR, 1.36; 95% CI, 0.83–2.24, p = .22); interventional complication (OR, 1.24; 95% CI, 0.76–2.02, p = .40); symptomatic intracranial hemorrhage (OR, 0.64; 95% CI, 0.41–0.99, p = .05); aspiration pneumonia (OR, 0.96; 95% CI, 0.58–1.58, p = .87); and National Institute of Health Stroke Scale score after 24 hr (MD, 0.38; 95% CI, −1.15–1.91, p = .62); with relative relationship favoring general anesthesia only in decreasing the symptomatic intracranial hemorrhage.Conclusions: General anesthesia has no independent relationship compared to conscious sedation during the endovascular therapy for acute ischemic stroke with a relative relationship favoring general anesthesia only in decreasing the symptomatic intracranial hemorrhage.This relationship encouraged us to recommend either anesthetic strategy during the endovascular therapy for acute ischemic stroke with no possible fear of higher complication.

The germin-like protein (GLP) family plays vital roles for plant growth, stress adaptation, and defense; however, its evolutionary dynamics and functional diversity in halophytes remain poorly characterized. Here, we present the genome-wide analysis of the GLP family in the halophytic forage alkaligrass (Puccinellia tenuiflora), which identified 54 PutGLPs with a significant expansion compared to other plant species. Phylogenetic analysis revealed monocot-specific clustering, with 41.5% of PutGLPs densely localized to chromosome 7, suggesting tandem duplication as a key driver of family expansion. Collinearity analysis confirmed evolutionary conservation with monocot GLPs. Integrated gene structure and motif analysis revealed conserved cupin domains (BoxB and BoxC). Promoter cis-acting elements analysis revealed stress-responsive architectures dominated by ABRE, STRE, and G-box motifs. Tissue-/organ-specific expression profiling identified root- and flower-enriched PutGLPs, implying specialized roles in stress adaptation. Dynamic expression patterns under salt-dominated stresses revealed distinct regulatory pathways governing ionic and alkaline stress responses. Functional characterization of PutGLP37 demonstrated its cell wall localization, dual superoxide dismutase (SOD) and oxalate oxidase (OXO) enzymatic activities, and salt stress tolerance in Escherichia coli, yeast (Saccharomyces cerevisiae INVSc1), and transgenic Arabidopsis. This study provides critical insights into the evolutionary innovation and stress adaptive roles of GLPs in halophytes.

β-thalassemia is a hematologic disease that may be associated with significant morbidity and mortality. Increased expression of HBG1/2 can ameliorate the severity of β-thalassemia. Compared to the unaffected population, some β-thalassemia patients display elevated HBG1/2 expression levels in their red blood cells. However, the magnitude of up-regulation does not reach the threshold of self-healing, and thus, the molecular mechanism underlying HBG1/2 expression in the context of HBB-deficiency requires further elucidation. Here, we performed a multi-omics study examining chromatin accessibility, transcriptome, proteome, and phosphorylation patterns in the HBB homozygous knockout of the HUDEP2 cell line (HBB-KO). We found that up-regulation of HBG1/2 in HBB-KO cells was not induced by the H3K4me3-mediated genetic compensation response. Deletion of HBB in human erythroid progenitor cells resulted in increased ROS levels and production of oxidative stress, which led to an increased rate of apoptosis. Furthermore, in response to oxidative stress, slower cell cycle progression and proliferation were observed. In addition, stress erythropoiesis was initiated leading to increased intracellular HBG1/2 expression. This molecular model was also validated in the single-cell transcriptome of hematopoietic stem cells from β-hemoglobinopathy patients. These findings further the understanding of HBG1/2 gene regulatory networks and provide novel clinical insights into β-thalassemia phenotypic diversity.