Steric Engineering of Alkylthiolation Side Chains to Finely Tune Miscibility in Nonfullerene Polymer Solar Cells

Morphology and miscibility control are still a great challenge in polymer solar cells. Despite physical tools being applied, chemical strategies are still limited and complex. To finely tune blend miscibility to obtain optimized morphology, chemical steric engineering is proposed to systemically investigate its effects on optical and electronic properties, especially on a balance between crystallinity and miscibility. By changing the alkylthiol side chain orientation different steric effects are realized in three different polymers. Surprisingly, the photovoltaic device of the polymer PTBB‐m with middle steric structure affords a better power conversion efficiency, over 12%, compared to those of the polymers PTBB‐o and PTBB‐p with large or small steric structures, which could be attributed to a more balanced blend miscibility without sacrificing charge‐carrier transport. Space charge‐limited current, atomic force microscopy, grazing incidence wide angle X‐ray scattering, and resonant soft X‐ray scattering measurements show that the steric engineering of alkylthiol side chains can have significant impacts on polymer aggregation properties, blend miscibility, and photovoltaic performances. More important, the control of miscibility via the simple chemical approach has preliminarily proved its great potential and will pave a new avenue for optimizing the blend morphology.     

Long non‐coding RNA SNHG6 promotes cell proliferation and migration through sponging miR‐4465 in ovarian clear cell carcinoma

Dysregulation of small nucleolar RNA host gene 6 (SNHG6) exerts critical oncogenic effects and facilitates tumourigenesis in human cancers. However, little information about the expression pattern of SNHG6 in ovarian clear cell carcinoma (OCCC) is available, and the contributions of this long non‐coding RNA to the tumourigenesis and progression of OCCC are unclear. In the present study, we showed via quantitative real‐time PCR that SNHG6 expression was abnormally up‐regulated in OCCC tissues relative to that in unpaired normal ovarian tissues. High SNHG6 expression was correlated with vascular invasion, distant metastasis and poor survival. Further functional experiments demonstrated that knockdown of SNHG6 in OCCC cells inhibited cell proliferation, migration and invasion in vitro as well as tumour growth in vivo. Moreover, SNHG6 functioned as a competing endogenous RNA (ceRNA), effectively acting as a sponge for miR‐4465 and thereby modulating the expression of enhancer of zeste homolog 2 (EZH2). Taken together, our data suggest that SNHG6 is a novel molecule involved in OCCC progression and that targeting the ceRNA network involving SNHG6 may be a treatment strategy in OCCC.     

DDX19 Inhibits Type I Interferon Production by Disrupting TBK1-IKKε-IRF3 Interactions and Promoting TBK1 and IKKε Degradation

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Single-Cell Heterogeneity Analysis and CRISPR Screen Identify Key β-Cell-Specific Disease Genes

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Scale-down model qualification of ambr® 250 high-throughput mini-bioreactor system for two commercial-scale mAb processes

Recent advances in high-throughput (HTP) automated mini-bioreactor systems have significantly improved development timelines for early-stage biologic programs. Automated platforms such as the ambr® 250 have demonstrated the ability, using appropriate scale-down approaches, to provide reliable estimates of process performance and product quality from bench to pilot scale, but data sets comparing to large-scale commercial processes (>10,000 L) are limited. As development moves toward late stages, specifically process characterization (PC), a qualified scale-down model (SDM) of the commercial process is a regulatory requirement as part of Biologics License Application (BLA)-enabling activities. This work demonstrates the qualification of the ambr® 250 as a representative SDM for two monoclonal antibody (mAb) commercial processes at scales >10,000 L. Representative process performance and product quality associated with each mAb were achieved using appropriate scale-down approaches, and special attention was paid to pCO₂ to ensure consistent performance and product quality. Principal component analysis (PCA) and univariate equivalence testing were utilized in the qualification of the SDM, along with a statistical evaluation of process performance and product-quality attributes for comparability. The ambr® 250 can predict these two commercial-scale processes (at center-point condition) for cell-culture performance and product quality. The time savings and resource advantages to performing PC studies in a small-scale HTP system improves the potential for the biopharmaceutical industry to get products to patients more quickly.     

Pancreatic acinar cells express vesicle-associated membrane protein 2- and 8-specific populations of zymogen granules with distinct and overlapping roles in secretion

Previous studies have demonstrated roles for vesicle-associated membrane protein 2 (VAMP 2) and VAMP 8 in Ca(2+)-regulated pancreatic acinar cell secretion, however, their coordinated function in the secretory pathway has not been addressed. Here we provide evidence using immunofluorescence microscopy, cell fractionation, and SNARE protein interaction studies that acinar cells contain two distinct populations of zymogen granules (ZGs) expressing either VAMP 2 or VAMP 8. Further, VAMP 8-positive granules also contain the synaptosome-associated protein 29, whereas VAMP 2-expressing granules do not. Analysis of acinar secretion by Texas red-dextran labeling indicated that VAMP 2-positive ZGs mediate the majority of exocytotic events during constitutive secretion and also participate in Ca(2+)-regulated exocytosis, whereas VAMP 8-positive ZGs are more largely involved in Ca(2+)-stimulated secretion. Previously undefined functional roles for VAMP and syntaxin isoforms in acinar secretion were established by introducing truncated constructs of these proteins into permeabilized acini. VAMP 2 and VAMP 8 constructs each attenuated Ca(2+)-stimulated exocytosis by 50%, whereas the neuronal VAMP 1 had no effects. In comparison, the plasma membrane SNAREs syntaxin 2 and syntaxin 4 each inhibited basal exocytosis, but only syntaxin 4 significantly inhibited Ca(2+)-stimulated secretion. Syntaxin 3, which is expressed on ZGs, had no effects. Collectively, these data demonstrate that individual acinar cells express VAMP 2- and VAMP 8-specific populations of ZGs that orchestrate the constitutive and Ca(2+)-regulated secretory pathways.