Low-Density Silk Nanofibrous Aerogels: Fabrication and Applications in Air Filtration and Oil/Water Purification.

A method was developed to fabricate light, water-insoluble silk fibroin nanofibrous aerogels (SNFAs) through solvent welding of lyophilized silk nanofibrous 3D networks at the junction points while converting silk structures from random-coils to ß-sheets (water insoluble). Aromatic alcohols, especially phenethyl alcohol (PEA), supported robust solvent welding and the structural conversion of silk. PEA vapor treatment was a better approach than solvent infusion to retain volume, density, and mechanical strength of the SNFAs. The mechanical properties of highly orientated SNFAs were superior to randomly distributed fibers. The SNFAs had a low density (3.5 mg/cm3), high hydrophobicity (140.9°), and a porous surface morphology on the individual nanofibers, resulting in high efficiency and selectivity for absorbing particulate matter and oils. Compared with commonly used inorganic aerogels, the SNFAs developed in this study are biocompatible, easily functionalized, environmentally friendly, and low-cost and therefore have potential for air and water purification, biosensors, drug delivery, and tissue engineering.

BCL2 Amplicon Loss and Transcriptional Remodeling Drives ABT-199 Resistance in B Cell Lymphoma Models.

Drug-tolerant "persister" tumor cells underlie emergence of drug-resistant clones and contribute to relapse and disease progression. Here we report that resistance to the BCL-2 targeting drug ABT-199 in models of mantle cell lymphoma and double-hit lymphoma evolves from outgrowth of persister clones displaying loss of 18q21 amplicons that harbor BCL2. Further, persister status is generated via adaptive super-enhancer remodeling that reprograms transcription and offers opportunities for overcoming ABT-199 resistance. Notably, pharmacoproteomic and pharmacogenomic screens revealed that persisters are vulnerable to inhibition of the transcriptional machinery and especially to inhibition of cyclin-dependent kinase 7 (CDK7), which is essential for the transcriptional reprogramming that drives and sustains ABT-199 resistance. Thus, transcription-targeting agents offer new approaches to disable drug resistance in B-cell lymphomas.