Tenbrio molitor (T. molitor) is a widely utilized feed ingredient, though it is deficient in long-chain omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To address this, dietary supplements containing EPA and DHA in ethyl ester and triglyceride forms were administered to investigate the lipid metabolism and bioenhancement potential of T. molitor. The larvae exhibited normal growth across all treatment groups. EPA/DHA levels were significantly elevated in T. molitor-enriched diets, with newly identified phospholipid species including phosphatidylcholine 18:1_20:5 (PC 18:1_20:5) and phosphatidylethanolamine 18:0_20:5 (PE 18:0_20:5). KEGG pathway analysis revealed that glycerol phospholipid metabolism (ko00564), endogenous cannabinoid signaling (ko04723), and cell division (ko04148) were the core pathways that promoted phospholipid synthesis and oxidative lipid conversion (such as peroxide value-phosphatidylcholine, POV-PC). T. molitor activates glycerophospholipid metabolism, converting EPA/DHA into more bioavailable medium- and short-chain phospholipids, thereby enhancing its nutritional value and providing a new strategy for the development of functional foods/feeds.

Due to their high nutritional value and a lower environmental impact, Tenebrio molitor (T. molitor) larvae are regarded as an alternative protein and lipid source in food industries, animal husbandry, and fishery. This study aimed to investigate the effect of ω-3 PUFA intake on the nutritional value and gut microbiota of T. molitor larvae. Tenebrio molitor (T. molitor) larvae were reared with wheat bran at 20–32 °C for 4 weeks to screen for a suitable temperature. EPA ethyl esters (EE), DHA ethyl esters (ED), DHA triglycerides (TG), and krill oil (KO) were supplemented in wheat bran to rear larvae for 4 weeks, and the compositions including moisture, carbohydrates, crude protein, and crude fats were analyzed. Gut microbiome was analyzed using 16S rRNA amplicon sequencing. Larvae reared on wheat bran showed optimal growth at 28 °C. ω-3 PUFA supplements increased crude protein (1.07–1.16 fold) and crude fat (1.12–1.22 fold) contents without affecting survival. Gut microbiota composition shifted significantly in all ω-3 supplemented groups, altering over 10 genera. Bacteria with changed abundance (e.g., Clostridium), known for roles in protein/lipid metabolism, likely contributed to the enhanced nutritional contents. These findings demonstrate the benefits of ω-3 PUFA supplementation in T. molitor rearing and identify associated gut bacteria.

Background/Objectives: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with a poor prognosis and limited therapeutic options. This study aimed to repurpose methylstat, a selective histone demethylase inhibitor, as a novel anti-glioma agent. We characterized its anti-proliferative efficacy, elucidated mechanisms of cell cycle regulation, and evaluated its blood–brain barrier (BBB) permeability potential. Methods: Compounds with transcriptional profiles enriched for cell cycle arrest and tumor-suppressive pathways were identified via Connectivity Map (CMAP) analysis. Methylstat was selected based on its high connectivity score and favorable physicochemical properties. In vitro assays were performed to evaluate its effects on cell viability, proliferation, cell cycle progression, and expression of related molecular markers in U251 and HOG glioma cell lines. Molecular docking and 200 ns molecular dynamics (MD) simulations were performed to evaluate the binding mode and stability of the Methylstat–JMJD2A complex. An in vitro BBB model was established to assess the ability of Methylstat to cross the BBB. Results: Methylstat significantly inhibited glioma cell proliferation in a dose-dependent manner without inducing apoptosis. It caused G1-phase arrest in U251 cells and G2-phase arrest in HOG cells. Mechanistically, methylstat downregulated cyclins and cyclin-dependent kinases via the p53/p21 pathway. Additionally, methylstat reduced the expression of JMJD2A and its downstream targets, including PDK1, AKT, and mTOR. Molecular docking studies and 200 ns MD simulations confirmed the stable binding of methylstat to the catalytic pocket of JMJD2A, effectively inhibiting its enzymatic activity. HPLC analysis confirmed that methylstat could penetrate the in vitro BBB model to varying extents. Conclusions: Methylstat is a promising small-molecule agent that effectively suppresses glioma cell growth by modulating key cell cycle regulators. Its ability to cross the BBB highlights its potential as a novel therapeutic strategy for GBM and other brain tumors.

In peripheral nervous system (PNS), immature Schwann cells differentiate into two functionally distinct types of mature Schwann cells: myelinating Schwann cells, which establish a one-to-one relationship with large-diameter axons and initiate the complex myelination program that enables the rapid saltatory conduction of nerve impulses, and non-myelinating Schwann cells, which envelop multiple small-diameter axons without forming myelin, but support axon survival and maintain microenvironment homeostasis. Here, we demonstrate that discoidin domain receptor 1 (DDR1) signaling plays a pivotal role in Schwann cell maturation and peripheral nerve myelination. Ddr1^−/− mice of both sexes exhibited fewer myelinating Schwann cells and profound hypomyelination, reduced nerve conduction velocity, and apparent motor dysfunction. Expression of myelin markers was markedly reduced in the mutants accompanied by the formation of abnormal myelin ultrastructure resembling “onion bulbs”. Mechanistically, Ddr1 deficiency impaired Schwann cell myelination through the marked hyperactivation of the MAPK/ERK signaling pathway. These findings establish DDR1 as a novel regulator of Schwann cell myelination and highlight its potential as a therapeutic target for demyelinating neuropathies.