The new chassis in the flask: Advances in Vibrio natriegens biotechnology research.

Biotechnology has been built on the foundation of a small handful of well characterized and well-engineered organisms. Recent years have seen a breakout performer gain attention as a new entrant into the bioengineering toolbox: Vibrio natriegens. This review covers recent research efforts into making V. natriegens a biotechnology platform, using a large language model (LLM) and knowledge graph to expedite the literature survey process. Scientists have made advancements in research pertaining to the fundamental metabolic characteristics of V. natriegens, development and characterization of synthetic biology tools, systems biology analysis and metabolic modeling, bioproduction and metabolic engineering, and microbial ecology. Each of these subcategories has relevance to the future of V. natriegens for bioengineering applications. In this review, we cover these recent advancements and offer context for the impact they may have on the field, highlighting benefits and drawbacks of using this organism. From examining the recent bioengineering research, it appears that V. natriegens is on the precipice of becoming a platform bacterium for the future of biotechnology.

STAT3 inhibition induces Bax-dependent apoptosis in liver tumor myeloid-derived suppressor cells.

Immunosuppressive myeloid-derived suppressor cells (MDSC) subvert antitumor immunity and limit the efficacy of chimeric antigen receptor T cells (CAR-T). Previously, we reported that the GM-CSF/JAK2/STAT3 axis drives liver-associated MDSC (L-MDSC) proliferation and blockade of this axis rescued antitumor immunity. We extended these findings in our murine liver metastasis (LM) model, by treating tumor-bearing mice with STAT3 inhibitors (STATTIC or BBI608) to further our understanding of how STAT3 drives L-MDSC suppressive function. STAT3 inhibition caused significant reduction of tumor burden as well as L-MDSC frequencies due to decrease in pSTAT3 levels. L-MDSC isolated from STATTIC or BBI608-treated mice had significantly reduced suppressive function. STAT3 inhibition of L-MDSC was associated with enhanced antitumor activity of CAR-T. Further investigation demonstrated activation of apoptotic signaling pathways in L-MDSC following STAT3 inhibition as evidenced by an upregulation of the pro-apoptotic proteins Bax, cleaved caspase-3, and downregulation of the anti-apoptotic protein Bcl-2. Accordingly, there was also a decrease of pro-survival markers, pErk and pAkt, and an increase in pro-death marker, Fas, with activation of downstream JNK and p38 MAPK. These findings represent a previously unrecognized link between STAT3 inhibition and Fas-induced apoptosis of MDSCs. Our findings suggest that inhibiting STAT3 has potential clinical application for enhancing the efficacy of CAR-T cells in LM through modulation of L-MDSC.