Engineering natural molecule-triggered genetic control systems for tunable gene- and cell-based therapies.

The ability to precisely control activities of engineered designer cells provides a novel strategy for modern precision medicine. Dynamically adjustable gene- and cell-based precision therapies are recognized as next generation medicines. However, the translation of these controllable therapeutics into clinical practice is severely hampered by the lack of safe and highly specific genetic switches controlled by triggers that are nontoxic and side-effect free. Recently, natural products derived from plants have been extensively explored as trigger molecules to control genetic switches and synthetic gene networks for multiple applications. These controlled genetic switches could be further introduced into mammalian cells to obtain synthetic designer cells for adjustable and fine tunable cell-based precision therapy. In this review, we introduce various available natural molecules that were engineered to control genetic switches for controllable transgene expression, complex logic computation, and therapeutic drug delivery to achieve precision therapy. We also discuss current challenges and prospects in translating these natural molecule-controlled genetic switches developed for biomedical applications from the laboratory to the clinic.

Bioaccumulation and emission of organophosphate esters in plants affecting the atmosphere's phosphorus cycle.

The imbalance of atmospheric, terrestrial and aquatic phosphorus budgets remains a research conundrum and global concern. In this work, the uptake, distribution, bioaccumulation and emission of organophosphate esters (OPEs) by clove trees (Syzygium aromaticum), lemon trees (Citrus limon) and cape jasmine trees (Gardenia jasminoides var. fortuniana) was investigated as conduits for phosphorus transfer or sinks and sources. The objective was to assess the role OPEs in soils play as atmospheric phosphorus sources through plant bioaccumulation and emission. Results demonstrated OPEs in experimental soil plots ranging from 0.01 to 81.0 ng g-1 dry weight, were absorbed and transported through plants to the atmosphere. The total emission of OPEs varied greatly from 0.2 to 588.9 pg g-1 L-1 h-1, with a mean of 47.6 pg g-1 L-1 h-1. There was a negative linear relationship between the concentrations of total phosphorus and four OPEs, tri-iso-butyl phosphate, tri-n-butyl phosphate, tris (2-chloroisopropyl) phosphate and tripentyl phosphate. Trimethyl phosphate levels were positively correlated with total nitrogen, and the concentrations of tri-iso-butyl phosphate, tri-n-butyl phosphate, tris (2-chloroisopropyl) phosphate and tripentyl phosphate decreased along with available potassium in leaves after 72 h. There was a significantly positive linear relationship between higher emission concentrations of OPEs and the emission factor of OPEs concentration (F = 4.2, P = 0.002), with lower emissions of OPEs and the bioaccumulation of OPEs in leaves (F = 4.8, P = 0.004). OPEs releases to the atmosphere were enriched in aerosols, and participate in atmospheric chemical reactions like photolysis, thereby affecting the phosphorus balance and cycling in the atmosphere.

Electro-Oxidative C-N Bond Formation through Azolation of Indole Derivatives: An Access to 3-Substituent-2-(Azol-1-yl)indoles.

A practical protocol to synthesize 3-substituent-2-(azol-1-yl)indole derivatives has been developed via an electrochemical oxidative cross coupling process under mild conditions. This electro-oxidative C-N bond formation strategy tolerates a range of functional groups and is amenable to gram scale synthesis. Moreover, this method was applied to the late-stage functionalization of bioactive molecules.