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Summary: The neural stem cell marker CD133 is reported to identify cells within glioblastoma (GBM) that can initiate neurosphere growth and tumor formation; however, instances of CD133− cells exhibiting similar properties have also been reported. Here, we show that some PTEN-deficient GBM tumors produce a series of CD133+ and CD133− self-renewing tumor-initiating cell types and provide evidence that these cell types constitute a lineage hierarchy. Our results show that the capacities for self-renewal and tumor initiation in GBM need not be restricted to a uniform population of stemlike cells, but can be shared by a lineage of self-renewing cell types expressing a range of markers of forebrain lineage. [Copyright &y& Elsevier]

Summary: Previously undescribed prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit markers either of proliferation or of angiogenesis and mesenchyme. Upon recurrence, tumors frequently shift toward the mesenchymal subclass. Chromosomal locations of genes distinguishing tumor subclass parallel DNA copy number differences between subclasses. Functional relevance of tumor subtype molecular signatures is suggested by the ability of cell line signatures to predict neurosphere growth. A robust two-gene prognostic model utilizing PTEN and DLL3 expression suggests that Akt and Notch signaling are hallmarks of poor prognosis versus better prognosis gliomas, respectively. [Copyright &y& Elsevier]

Vimentin, an intermediate filament protein, crucially contributes to the pathogenesis of inflammatory bowel disease (IBD) by interacting with genetic risk factors, facilitating pathogen infection, and modulating both innate and adaptive immune responses. This study aimed to demonstrate preclinical proof-of-concept for targeting vimentin therapeutically in IBD across diverse etiologies. The small molecule compound ALD-R491 was assessed for vimentin binding using microscale thermophoresis, off-target effects via Eurofins screening, and therapeutic effects in mice with dextran sulfate sodium (DSS)-induced acute colitis and in IL-10 KO with spontaneous colitis. Parameters measured included body weight, survival, disease activity, colon length, and histology. The study analyzed intestinal proinflammatory cytokines, Th17/Treg cells, and epithelial barrier molecules, along with gut microbiota profiling. ALD-R491 specifically bound vimentin with a dissociation constant (KD) of 328 ± 12.66 nM and no off-target effects. In the DSS model, orally administered ALD-R491 exhibited dose-dependent therapeutic effects, superior to 5-ASA and Tofacitinib. In the IL-10 KO model, ALD-R491 significantly delayed colitis onset and progression, with near-zero disease activity index scores over a 15-week treatment. ALD-R491 consistently showed in both models a reduced proinflammatory cytokine expression, including TNF-α, IL-1β, IL-6, IL-17, IL-22, a rebalanced Th17/Treg axis by reducing RORγt while enhancing FoxP3 expression, and an improved epithelial barrier integrity by increasing intestinal expressions of Mucin-2, ZO-1 and Claudin5. The intestinal dysbiosis was restored with enriched presence of probiotics. Targeting vimentin exhibits significant therapeutic effects on various facets of IBD pathogenesis, representing a compelling approach for the development of highly effective treatments in IBD. [Display omitted] • Novel compound ALD-R491 specifically binds to vimentin with no off-target effects. • ALD-R491 is significantly more effective than 5-ASA and Tofacitinib in DSS model. • ALD-R491 blocks the onset and progression of spontaneous colitis in IL-10 KO mice. • ALD-R491 impacts Th17/Treg, intestinal barrier, tissue fibrosis and gut microbiome. • Targeting vimentin by ALD-R491 represents a first-in-class MOA in treating IBD. [ABSTRACT FROM AUTHOR]

Treating high-strength nitrate wastewater effectively and economically has been a major challenge for some manufacturing industries. In this study, we fabricated a membrane-less two-phase bio-cathode microbial fuel cell (TPBC-MFC) by dividing the bio-cathode into a solid part (S-cathode, above the water surface) and a liquid part (L-cathode, below the water surface), on which performances and mechanisms for the treatment of pickling wastewater containing more than 1000 mg/L NO- 3-N (electron acceptor) by watermelon rind extracts (WMREs, electron donor) were explored. Results showed that the TPBC-MFC presented an excellent performance since the maximum power density, the greatest nitrate removal rate and the highest COD removal efficiency reached 16.6 mW/m2, 780 g/m3·d and 94.8%, respectively. There were identical microorganisms (unclassified- Chitinophagaceae and Comamonadaceae) predominating on all electrodes owing to WMREs as carbon sources. In addition, some special functional species were also enriched, including Anaeroarcus (3.48%, fermentation bacterium) and Desulfovibrio (12.57%, electricigen) for the anode, Thauera (5.02%, denitrifier) for the L-cathode and Chryseolinea (12.13%, denitrifier) for the S-cathode. The detection of denitrifying genes of narG, narK/S, norB and nosZ, as well as function prediction demonstrated that the anode degraded WMREs to release H+ and e− that were subsequently utilized by the cathode to reduce NO- 3-N to N 2. All these results proved that the membrane-less TPBC-MFC has a good capability in electricity generation, nitrate removal and WMREs degradation, most likely because the S-cathode benefits the promotion of mass transfer. [Display omitted] • TPBC-MFC consisting of S-cathode and L-cathode was developed. • Watermelon rinds fueled TPBC-MFC for sustainable pickling wastewater treatment. • S-cathode was vital for TPBC-MFC due to its role in promoting mass transfer. • Each of bio-electrodes possessed its own specific functional microorganisms. • Reduction of nitrate to N 2 was mainly carried out by S-cathode. [ABSTRACT FROM AUTHOR]

The overuse of antibiotics and subsequent enrichment of antibiotic resistant microbes in the natural and built environments is a severe threat to global public health. In this study, a Phanerochaete chrysosporium fungal-luffa fiber system was found to efficiently biodegrade two sulfonamides, sulfadimethoxine (SDM) and sulfadizine (SDZ), in cow urine wastewater. Biodegradation pathways were proposed on the basis of key metabolites identified using high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (HPLC-QqTOF-MS). Transcriptomic, metabolomic, and free radical analyses were performed to explore the functional groups and detailed molecular mechanisms of SDM and SDZ degradation. A total of 27 UniGene clusters showed significant differences between luffa fiber and luffa fiber-free systems, which were significantly correlated to cellulose catabolism, carbohydrate metabolism, and oxidoreductase activity. Carbohydrate-active enzymes and oxidoreductases appear to play particularly important roles in SDM and SDZ degradation. Electron paramagnetic resonance (EPR) spectroscopy revealed the generation and evolution of OH and R during the biodegradation of SDM and SDZ, suggesting that beyond enzymatic degradation, SDM and SDZ were also transformed through a free radical pathway. Luffa fiber also acts as a co-substrate to improve the activity of enzymes for the degradation of SDM and SDZ. This research provides a potential strategy for removing SDM and SDZ from agricultural and industrial wastewater using fungal-luffa fiber systems. Image 1 • The synergistic system was efficient in removing sulfonamides. • Transcriptomic, metabolites and free radical analyses were performed. • Enzymatic reactions and OH are important in sulfonamides degradation. • Luffa can improve the activity of enzymes and sulfonamides degradation efficiency. [ABSTRACT FROM AUTHOR]