The tRNA methyltransferase Mettl1 governs ketogenesis through translational regulation and drives metabolic reprogramming in cardiomyocyte maturation.

After birth, the heart undergoes a shift in energy metabolism and cytoarchitecture to enhance efficient energy production and cardiac contraction, which is essential for postnatal development and growth. However, the precise mechanisms regulating this process remain elusive. Here we show that the RNA modification enzyme Mettl1 is a critical regulator of postnatal metabolic reprogramming and cardiomyocyte maturation in mice, primarily through its influence on the translation of the rate-limiting ketogenesis enzyme Hmgcs2.

Hope for Others: Research Results from the University of Pittsburgh Rapid Autopsy Program for Breast Cancer.

Breast cancer affects 1/8 of women throughout their lifetimes, with 90% of cancer deaths being caused by metastasis. However, metastasis poses unique challenges to research, as complex changes in the microenvironment in different metastatic sites and difficulty obtaining tissue for study hinder the ability to examine in depth the changes that occur during metastasis. Rapid autopsy programs thus fill a unique need in advancing metastasis research.

Response Trajectories and Temporal Trends of Viloxazine Treatment for Young People With ADHD: A Meta-Analysis.

Importance: Viloxazine is a novel nonstimulant medication approved for the treatment of attention-deficit/hyperactivity disorder (ADHD).

Objectives: To investigate the whether viloxazine is associated with effective and acceptable outcomes when treating children and adolescents with ADHD and to evaluate these outcomes' associations with viloxazine doses and duration of treatment.

Data Sources: The MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, PsycINFO, and ClinicalTrial.

Progressive transcriptomic shifts in evolved yeast strains following gene knockout.

Gene knockout disrupts cellular homeostasis, altering gene expression, and phenotypes. We investigated whether cells return to their pre-knockout transcriptomic state through adaptive evolution experiments on and yeast strains. Analysis revealed that genes with higher expression levels and more physical interaction partners in wild-type strains were more likely to be restored, suggesting that genes of significant functional importance have increased resilience to genetic perturbations.

Metabolic Control of Glycosylation Forms for Establishing Glycan-Dependent Protein Interaction Networks.

Protein-protein interactions (PPIs) provide essential insights into the complex molecular mechanisms and signaling pathways within cells that regulate development and disease-related phenotypes. However, for membrane proteins, the impact of various forms of glycosylation has often been overlooked in PPI studies. In this study, we introduce a novel approach, glycan-dependent affinity purification followed by mass spectrometry (GAP-MS), to assess variations in PPIs for any glycoprotein of interest under different glycosylation conditions.

Hepatic arterial infusion chemotherapy in combination with lenvatinib and durvalumab versus standard first-line treatment gemcitabine and cisplatin plus durvalumab in advanced intrahepatic cholangiocarcinoma.

In patients with advanced intrahepatic cholangiocarcinoma (ICC), clinical outcomes remain unsatisfactory despite the recommended first-line treatment of gemcitabine with cisplatin and durvalumab (GCD). We recently reported that hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib and durvalumab (HLD) exhibited promising antitumor activity and manageable adverse events in patients with unresectable ICC. Here, we aimed to compare HLD with GCD in patients with advanced ICC.

Antagonism of the ATP-gated P2X7 receptor inhibits the proliferation of hepatocellular carcinoma cells.

The P2X7 receptor, an ATP-gated ion channel which belongs to the P2X receptor family, plays critical roles in recognizing extracellular adenosine 5'-triphosphate (ATP) and is widely expressed in most tumor cells as well as inflammatory cells. Previously, the P2X7 receptor has been demonstrated to modulate the progression of various malignancies, including glioblastoma, pancreatic cancer, lung cancer, leukemia, and lymphoma. However, the biological function and prognostic values of P2X7 receptor in hepatocellular carcinoma remain to be determined.

Integrin β6/Annexin A2 axis triggers autophagy to orchestrate hepatocellular carcinoma radioresistance.

Radiotherapy (RT) is one of the main therapies for hepatocellular carcinoma (HCC), but its effectiveness has been constrained due to the resistance effect of radiation. Thus, the factors involved in radioresistance are evaluated and the underlying molecular mechanisms are also done. In this present study, we identified Integrin β6 (ITGB6) as a potential radioresistant gene through an integrative analysis of transcriptomic profiles, proteome datasets and survival using HCC cases treated with IR.

Nucleus-Targeting Photosensitizers Enhance Neutrophil Extracellular Traps for Efficient Eradication of Multidrug-Resistant Bacterial Infections.

Neutrophil extracellular traps (NETs) are web-like complexes of DNA and proteins that are extruded by activated neutrophils and play critical roles as major components of the innate immune response against pathogen invasion. However, some microbes have developed strategies to evade NET attacks, leading to impaired immune defenses and persistent infections. In this study, an engineered neutrophil strategy for enhancing the antibacterial activity of NETs is developed.

Cellular mechanisms of combining innate immunity activation with PD-1/PD-L1 blockade in treatment of colorectal cancer.

PD-1/PD-L1 blockade therapies have displayed extraordinary clinical efficacy for melanoma, renal, bladder and lung cancer; however, only a minority of colorectal cancer (CRC) patients benefit from these treatments. The efficacy of PD-1/PD-L1 blockade in CRC is limited by the complexities of tumor microenvironment. PD-1/PD-L1 blockade immunotherapy is based on T cell-centered view of tumor immunity.

Three-Dimensional Imaging of Aortic Tissues in Atherosclerosis.

Recent research has advanced the understanding of atherosclerosis as a transmural chronic inflammatory disease involving all three layers of the arterial wall, including the intima plaque, the media, and the adventitia, which forms the outer connective tissue coat of arteries. Our recent studies have suggested that the adventitia is used by the peripheral nervous system as a conduit for reaching all tissue cells. We also found that the peripheral nervous system, that is, the sensory and sympathetic nervous system, undergoes major remodeling processes involving the neogenesis of axon networks adjacent to atherosclerotic plaques.

Metabolomics and lipidomics in pectus excavatum: preliminary screening of biomarkers for early diagnosis.

Background: Pectus excavatum (PE) is the most common chest wall deformity, characterized by an insidious onset, gradual progression, and challenges in early diagnosis. It is often accompanied by emaciation and distinctive metabolic traits, which may provide valuable insights into its internal physiological and biochemical mechanisms. Our study attempted to screen out biomarkers by identifying the metabolic characteristics of PE, and the results provide a scientific basis for the early diagnosis of PE.

Nanocarriers for intracellular delivery of proteins in biomedical applications: strategies and recent advances.

Protein drugs are of great importance in maintaining the normal functioning of living organisms. Indeed, they have been instrumental in combating tumors and genetic diseases for decades. Among these pharmaceutical agents, those that target intracellular components necessitate the use of therapeutic proteins to exert their effects within the targeted cells.

Mismatched unrelated donors allogeneic hematopoietic stem cell transplantation with antithymocyte globulin for hematological malignancies: a multicenter retrospective study in China.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) utilizing mismatched unrelated donors (MMUD) present a vital option for patients with hematologic malignancies without human leukocyte antigen (HLA)-matched donors. This multicenter retrospective study encompassed 211 adults with hematological malignancies receiving allo-HSCT with antithymocyte globulin (ATG) from ≥1 HLA locus MMUD. The findings revealed cumulative incidences of II-IV acute graft-versus-host disease (GVHD) at 180 days at 26.

The unique functions of Runx1 in skeletal muscle maintenance and regeneration are facilitated by an ETS interaction domain.

The conserved Runt-related (RUNX) transcription factor family are master regulators of developmental and regenerative processes. Runx1 and Runx2 are expressed in satellite cells (SCs) and in skeletal myotubes. Here, we examined the role of Runx1 in mouse satellite cells to determine the role of Runx1 during muscle differentiation.

Protease activated receptor 2 deficiency retards progression of abdominal aortic aneurysms by modulating phenotypic transformation of vascular smooth muscle cells via ERK signaling.

Abdominal aortic aneurysm (AAA) is characterized by localized structural deterioration of the aortic wall, leading to progressive dilatation and rupture. Protease activated receptor 2 (PAR2) dependent signaling has been implicated in the pathophysiology of atherosclerosis through the regulation of smooth muscle cell function. However, its role in AAA remains unclear.