Covalent and Noncovalent Loading of Doxorubicin by Folic Acid-Carbon Dot Nanoparticles for Cancer Theranostics.

With special properties such as excellent fluoresce features, low toxicity, good biocompatibility, permeability, and easy clearance from the body, carbon dot (CD)-based nanoparticles (NPs) have the potential to deliver drugs and use in vivo diagnostics through molecular imaging. In this work, folic acid-CD (FA-CD) NPs were prepared to deliver doxorubicin (Dox) covalently and noncovalently as cancer theranostics. FA was conjugated to the surface of CDs for targeting cancer cells with overexpressing folate receptors. CDs prepared with various amounts of precursors lead to their associated NPs with different photoluminescence properties and drug release profiles. The loading of Dox and its releasing data depends on the linkage of drug Dox to FA-CD and CD composition. All NPs were characterized by UV-vis, Fourier transform infrared spectroscopy, and dynamic light scattering. The noncovalent FA-CD-Dox NPs were preferred with a simple preparation process, excellent photoluminescence, and in vitro drug release properties. The noncovalent FA-CD-Dox showed the best efficacy against MDA-MB-231 compared to the CD-Dox and covalent FA-CD-Dox.

Grammatical Evolution of Complex Digital Circuits in SystemVerilog.

The evolution of complex circuits remains a challenge for the Evolvable Hardware field in spite much effort. There are two major issues: the amount of testing required and the low evolvability of representation structures to handle complex circuitry, at least partially due to the destructive effects of genetic operators. A 64-bit × 64-bit add-shift multiplier circuit modelled at register-transfer level in SystemVerilog would require approximately 33,200 gates when synthesized using Yosys Open SYnthesis Suite tool. This enormous gate count makes evolving such a circuit at the gate-level difficult. We use Grammatical Evolution (GE) and SystemVerilog, a hardware description language (HDL), to evolve fully functional parameterized Adder, Multiplier, Selective Parity and Up-Down Counter circuits at a more abstract level other than gate level-register transfer level. Parameterized modules have the additional benefit of not requiring a re-run of evolutionary experiments if multiple instances with different input sizes are required. For example, a 64-bit × 64-bit and 128-bit × 128-bit multipliers etc., can be instantiated from  a fully evolved functional and parameterized N-bit × N-bit multiplier. The Adder (6.4 × ), Multiplier (10.7 × ) and Selective Parity (6.7 × ) circuits are substantially larger than the current state of the art for evolutionary approaches. We are able to scale so dramatically because of the use of a HDL, which permits us to operate at a register-transfer level. Furthermore, we adopt a well known technique for reducing testing from digital circuit design known as corner case testing. Skilled circuit designers rely on this to avoid time-consuming exhaustive testing. We demonstrate a simple way to identify and use corner cases for evolutionary testing and show that it enables the generation of massively complex circuits. All circuits were successfully evolved without resorting to the use of any standard decomposition methods, due to our ability to use programming constructs and operators available in SystemVerilog.

Investigating Ghanaian Allium Species for Anti-Infective and Resistance-Reversal Natural Product Leads to Mitigate Multidrug-Resistance in Tuberculosis.

The bulbs of Allium species are a known source of antibacterial phytochemicals. Anti-infective, efflux pump and biofilm inhibitory activities of bulb extracts of selected Ghanaian shallots Allium cepa var aggregatum were evaluated using the HT-SPOTi assay and other whole-cell phenotypic screening techniques to determine their possible mechanisms of action. Ethanol and aqueous extracts of white A. cepa inhibited the growth of Mycobacterium smegmatis mc2 155 and Escherichia coli, respectively. The majority of the Allium extracts significantly (p < 0.05) exhibited efflux pump inhibitory activity against all the acid-fast, Gram-positive and Gram-negative strains used. Hexane and chloroform extract of the pink A. cepa and the aqueous extract of the white A. cepa significantly inhibited M. smegmatis biofilm formation. For Pseudomonas aeruginosa, the inhibition was observed at 250 µg/mL for the aqueous extract (~77.34%) and 125 µg/mL for the hexane extract (~76.51%). The results suggest that Ghanaian shallots could potentially be useful when further developed to tackle antimicrobial resistance, particularly in tuberculosis (TB).