Thanks for your amazing talk and results! I have some questions, as follows: 1) You propose that mtIDH compensates for LDH loss under hypoxia by providing an alternative NAD⁺ regeneration pathway, so I wonder whether you have quantified intracellular NAD⁺/NADH and NADP⁺/NADPH ratios in mtIDH-expressing vs LDH-deficient glioma cells, and how do these values compare to in vivo glioma samples from TCGA or patient-derived xenografts? 2) How do you comprehend the observed inverse correlation between mtIDH and LDH expression with the well-established “Warburg effect” in gliomas? Could mtIDH tumors represent a distinct metabolic subtype that preferentially uses glutamine or alternative substrates under hypoxia, and have isotope-tracing experiments been performed to map carbon flux? 3) In your hypoxia survival assays, have you examined whether mtIDH expression impacts HIF1α stabilization or transcriptional activity, given that α-KG and 2-HG differentially regulate prolyl hydroxylases?   Thanks and congrats again!

Thanks for your amazing talk and results! I have some questions, as follows: 1) Since HOTTIP and FIRRE are overexpressed across all phenotypes, do you hypothesize they act as general PD-related neuroinflammatory regulators, and have you explored whether their upregulation correlates with circulating cytokine levels or immune cell activation markers? 2) From a translational perspective, do you foresee lncRNA-based blood signatures serving as reliable liquid biopsy biomarkers for PD diagnosis and subtyping in clinical practice, considering challenges of specificity (neurodegeneration vs systemic inflammation) and stability of circulating lncRNAs? Thanks and congrats again!

Thanks for your amazing talk and results! I have some questions, as follows: 1) Given the temporal changes in CpG methylation you observed, have you assessed whether these epigenetic modifications also happen at the transcriptional or protein level of SLC6A4 to establish functional consequences beyond methylation signatures? In addition, did you explore whether the CpG-specific methylation differences cluster within known transcription factor binding sites or regulatory motifs of the SLC6A4 promoter, and could these site-specific changes differentially impact serotonin transporter regulation? 2) How do you distinguished methylation changes due to prematurity itself from those potentially driven by external perinatal stressors (e.g., oxygen therapy, corticosteroids, NICU handling, maternal stress), and have you controlled for these in your analyses? 3) From a translational perspective, do you envision that SLC6A4 methylation profiling at birth could serve as a biomarker for identifying preterm infants at higher risk of later neurodevelopmental disorders, and what are the ethical implications of early-life epigenetic risk stratification in neonatology? Thanks and congrats again!  

Thanks for your amazing talk and results! I have some questions, as follows: 1) You demonstrated the downregulation of MMP2/9/11 transcripts after cirsimarin exposure, so I wonder if these transcript changes translate into reduced proteolytic activity in the extracellular milieu, for instance, and have you measured their active vs. pro-forms (e.g., by zymography or activity assays)? 2) There is a notable difference in effective concentrations between your 2D (1–40 μM) and 3D (160 μM) assays. How do you interpret this in terms of compound diffusion, binding to ECM components, local aggregation/solubility, or compound stability within spheroids? 3) Which upstream signalling pathways do you hypothesize link cirsimarin to MMP transcriptional repression — for example, FAK/ERK, NF-κB, or TGF-β/EMT regulators?

Thanks for your amazing talk and results! I have some questions, as follows: 1) Did you identify subtype-specific methylation patterns (e.g., yolk sac vs dysgerminoma vs immature teratoma), and if so, do these overlap with known methylation “imprints” in primordial germ cell development or pluripotency pathways? 2) Since resistance to cisplatin is a major clinical issue, have you explored whether methylation changes in DNA repair genes (e.g., MGMT, MLH1, or other repair-associated promoters) correlate with high-risk or resistant cases in your cohort? 3) Considering the reliance on tumor markers and histopathology in GCT diagnosis, do you envision that DNA methylation profiling could be translated into a minimally invasive diagnostic approach (for instance, via circulating tumor DNA methylation in plasma) and how would you address challenges of sensitivity and specificity in children? Thanks and congrats again!