Endothelial dysfunction and disease severity in COVID-19: Insights from circulating Tang cell counts as a potential biomarker.

BACKGROUND AND AIM: Endothelial dysfunction is a common risk factor of severe COVID-19. Angiogenic T cells (Tang cells) play a critical role in repairing endothelial injury; however, their changes and potential roles in COVID-19 remain unclear. We aimed to assess Tang cell counts in patients with COVID-19 and evaluate their association with disease severity and prognosis. METHODS: Circulating Tang cell populations in patients with COVID-19 and healthy controls were quantified using flow cytometry. Demographic and routine laboratory data were recorded. RESULTS: The Tang cell count decreased significantly with increasing disease severity and were lowest in fatal cases. Additionally, the Tang cell count was significantly decreased in patients with comorbid cardiovascular disease or hypertension. Tang cell counts were negatively correlated with inflammatory markers, kidney and myocardial injury markers, coagulation dysfunction indicators, and viral load and positively correlated with oxidative stress markers, nutritional markers, and lymphocytes. Receiver operating characteristic curves confirmed that Tang cell count could serve as a potential biomarker for predicting disease severity and patient mortality. CONCLUSIONS: Circulating Tang cell count is significantly reduced in patients with COVID-19 and is correlated with disease severity and prognosis. The Tang cell count is an important potential biomarker for COVID-19 clinical management. Additionally, these findings provide insight into the pathological features of COVID-19 endothelial injury and provide new directions for treatment.

Quasi-Ionic Liquid Enabling Single-Phase Poly(vinylidene fluoride)-Based Polymer Electrolytes for Solid-State LiNi0.6 Co0.2 Mn0.2 O2 ||Li Batteries with Rigid-Flexible Coupling Interphase.

Poly(vinylidene fluoride)-based polymer electrolytes are being intensely investigated for solid-state lithium metal batteries. However, phase separation and porous structures are still pronounced issues in traditional preparing procedure. Herein, a bottom-to-up strategy is employed to design single-phase and densified polymer electrolytes via incorporating quasi-ionic liquid with poly(vinylidene fluoride-co-hexafluoropropylene). Due to strong ion/dipole-dipole interaction, the optimized polymer electrolyte delivers high room-temperature ionic conductivity of 1.55 × 10-3 S cm-1 , superior thermal and oxidation stability of 4.97 V, excellent stretchability of over 1500% and toughness of 43 MJ cm-3 as well as desirable self-extinguishing ability. Furthermore, the superb compatibility toward Li anode enables over 3000 h cycling of Li plating/stripping and ≈98% Coulombic efficiency in Li||Cu test at 0.1 mA cm-2 . In particular, lithium metal battery Li||LiNi0.6 Co0.2 Mn0.2 O2 exhibits a room-temperature discharge retention rate of 96% after 500 cycles under a rate of 0.1 C, which is associated with the rigid-flexible coupling electrodes/electrolytes interphase. This investigation demonstrates the potential application of quasi-ionic liquid/polymer electrolytes in safe lithium metal batteries.

Diversion of metabolic flux towards 5-deoxy(iso)flavonoid production via enzyme self-assembly in Escherichia coli.

5-Deoxy(iso)flavonoids are structural representatives of phenylpropanoid-derived compounds and play critical roles in plant ecophysiology. Recently, 5-deoxy(iso)flavonoids gained significant interest due to their potential applications as pharmaceuticals, nutraceuticals, and food additives. Given the difficulties in their isolation from native plant sources, engineered biosynthesis of 5-deoxy(iso)flavonoids in a microbial host is a highly promising alternative approach. However, the production of 5-deoxy(iso)flavonoids is hindered by metabolic flux imbalances that result in a product profile predominated by non-reduced analogues. In this study, GmCHS7 (chalcone synthase from Glycine max) and GuCHR (chalcone reductase from Glycyrrhizza uralensis) were preliminarily utilized to improve the CHR ratio (CHR product to total CHS product). The use of this enzyme combination improved the final CHR ratio from 39.7% to 50.3%. For further optimization, a protein-protein interaction strategy was employed, basing on the spatial adhesion of GmCHS7:PDZ and GuCHR:PDZlig. This strategy further increased the ratio towards the CHR-derived product (54.7%), suggesting partial success of redirecting metabolic flux towards the reduced branch. To further increase the total carbon metabolic flux, 15 protein scaffolds were programmed with stoichiometric arrangement of the three sequential catalysts GmCHS7, GuCHR and MsCHI (chalcone isomerase from Medicago sativa), resulting in a 1.4-fold increase in total flavanone production, from 69.4 mg/L to 97.0 mg/L in shake flasks. The protein self-assembly strategy also improved the production and direction of the lineage-specific compounds 7,4'-dihydroxyflavone and daidzein in Escherichia coli. This study presents a significant advancement of 5-deoxy(iso)flavonoid production and provides the foundation for production of value-added 5-deoxy(iso)flavonoids in microbial hosts.

Improve the Biosynthesis of Baicalein and Scutellarein via Manufacturing Self-Assembly Enzyme Reactor In Vivo.

Baicalein and scutellarein are bioactive flavonoids isolated from the traditional Chinese medicine Scutellaria baicalensis Georgi; however, there is a lack of effective strategies for producing baicalein and scutellarein. In this study, we developed a sequential self-assembly enzyme reactor involving two enzymes in the baicalein pathway with a pair of protein-peptide interactions in E. coli. These domains enabled us to optimize the stoichiometry of two baicalein biosynthetic enzymes recruited to be an enzymes complex. This strategy reduces the accumulation of intermediates and removes the pathway bottleneck. With this strategy, we successfully promoted the titer of baicalein by 6.6-fold (from 21.6 to 143.5 mg/L) and that of scutellarein by 1.4-fold (from 84.3 to 120.4 mg/L) in a flask fermentation, respectively. Furthermore, we first achieved the de novo biosynthesis of baicalein directly from glucose, and the strain was capable of producing 214.1 mg/L baicalein by fed-batch fermentation. This work provides novel insights for future optimization and large-scale fermentation of baicalein and scutellarein.

Recent Advances in Metabolic Engineering, Protein Engineering, and Transcriptome-Guided Insights Toward Synthetic Production of Taxol.

The diterpenoid paclitaxel (Taxol®) is a blockbuster anticancer agent that was originally isolated from the Pacific yew (Taxus brevifolia) five decades ago. Despite the wealth of information gained over the years on Taxol research, there still remains supply issues to meet increasing clinical demand. Although alternative Taxol production methods have been developed, they still face several drawbacks that cause supply shortages and high production costs. It is highly desired to develop biotechnological production platforms for Taxol, however, there are still gaps in our understanding of the biosynthetic pathway, catalytic enzymes, regulatory and control mechanisms that hamper production of this critical drug by synthetic biology approaches. Over the past 5 years, significant advances were made in metabolic engineering and optimization of the Taxol pathway in different hosts, leading to accumulation of taxane intermediates. Computational and experimental approaches were leveraged to gain mechanistic insights into the catalytic cycle of pathway enzymes and guide rational protein engineering efforts to improve catalytic fitness and substrate/product specificity, especially of the cytochrome P450s (CYP450s). Notable breakthroughs were also realized in engineering the pathway in plant hosts that are more promising in addressing the challenging CYP450 chemistry. Here, we review these recent advances and in addition, we summarize recent transcriptomic data sets of Taxus species and elicited culture cells, and give a bird's-eye view of the information that can be gleaned from these publicly available resources. Recent mining of transcriptome data sets led to discovery of two putative pathway enzymes, provided many lead candidates for the missing steps and provided new insights on the regulatory mechanisms governing Taxol biosynthesis. All these inferences are relevant to future biotechnological production of Taxol.