The programmability of Watson-Crick base pairing, combined with a decrease in the cost of synthesis, has made DNA a widely used material for the assembly of molecular structures and dynamic molecular ...devices. Working in cell-free settings, researchers in DNA nanotechnology have been able to scale up system complexity and quantitatively characterize reaction mechanisms to an extent that is infeasible for engineered gene circuits or other cell-based technologies. However, the most intriguing applications of DNA nanotechnology - applications that best take advantage of the small size, biocompatibility and programmability of DNA-based systems - lie at the interface with biology. Here, we review recent progress in the transition of DNA nanotechnology from the test tube to the cell. We highlight key successes in the development of DNA-based imaging probes, prototypes of smart therapeutics and drug delivery systems, and explore the future challenges and opportunities for cellular DNA nanotechnology.
With the prevalence of antibiotic-resistant bacteria, novel antibacterial strategies are urgently needed. In recent years, several antibiotics-independent physical approaches have attracted high ...attention and interests. Among those approaches, photothermal therapy (PTT), a novel non-invasive therapeutic technique, has exhibited great potentials in dealing with drug-resistant bacteria and bacterial biofilms. Photothermal agents (PTAs), which are either nanomaterials themselves or small molecules loaded in nanoparticles, are the essential element for PTT. How to deliver PTAs in a controlled manner is of great importance for high-efficiency and low-toxicity PTT. Therefore, a comprehensive understanding of various PTAs is required for the better application of PTT in antibacterial treatment. Herein, the physicochemical properties and antibacterial PTT of five types of PTAs are summarized. In addition, the PTT-involved multifunctional theranostics nanoplatforms and the potential approaches for reducing the side effects of PTT (such as targeted delivery and controlled release of PTAs) are also discussed.
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The evolution of photoelectrochemical (PEC) bioanalysis has resulted in substantial progress in its analytical performance and biodetection applications. The aim of this review is to provide a ...panoramic snapshot of the state of the art in this dynamically developing field, with special emphasis on PEC DNA analysis, immunoassay, enzymatic biosensing and cell-related detection. The future prospects in this area are also evaluated and discussed. This work will serve as a useful source to inform the interested audience of the latest developments and applications in the field of PEC bioanalysis.
Electrogenerated chemiluminescence, also known as electrochemiluminescence (ECL), is an electrochemically induced production of light by excited luminophores generated during redox reactions. It can ...be used to sense the charge transfer and related processes at electrodes
via
a simple visual readout; hence, ECL is an outstanding tool in analytical sensing. The traditional ECL approach measures averaged electrochemical quantities of a large ensemble of individual entities, including molecules, microstructures and ions. However, as a real system is usually heterogeneous, the study of single entities holds great potential in elucidating new truths of nature which are averaged out in ensemble assays or hidden in complex systems. We would like to review the development of ECL intensity and imaging based single entity detection and place emphasis on the assays of small entities including single molecules, micro/nanoparticles and cells. The current challenges for and perspectives on ECL detection of single entities are also discussed.
We summarize the history and recent development that has been made in the ECL detection of single entities.
Covalent organic frameworks (COFs) show great promise as heterogeneous photocatalysts, but they have not yet been explored for asymmetric photocatalysis, which is important for the sustainable ...production of pharmaceuticals and fine chemicals. We report here a pair of twofold interpenetrated 3D COFs adopting a rare (3,4)-connected
ffc
topology for photocatalytic asymmetric reactions by imine condensation of rectangular and trigonal building blocks. Both COFs containing a photoredox triphenylamine moiety are efficient photocatalysts for the cross-dehydrogenative coupling reactions and asymmetric α-alkylation of aldehydes integrated with a chiral imidazolidinone catalyst. Under visible-light irradiation, the targeted chiral products are produced in satisfactory yields with up to 94% enantiomeric excess, which are comparable to those of reported reactions using molecular metal complexes or organic dyes as photosensitizers. Whereas the COFs became amorphous after catalysis, they can be recrystallized through solvent-assisted linker exchange and reused without performance loss. This is the first report utilizing COFs as photocatalysts to promote enantioselective photochemical reactions.
Covalent organic frameworks (COFs) show great promise as heterogeneous photocatalysts, but they have not yet been explored for asymmetric photocatalysis, which is important for the sustainable production of pharmaceuticals and fine chemicals.
We report a photodynamic therapy driven by electrochemiluminescence (ECL). The luminescence generated by Ru(bpy)32+ and co‐reactant tripropylamine (TPA) pair acts as both optical readout for ECL ...imaging, and light source for the excitation of photosensitizer to produce reactive oxygen species (ROS) in photodynamic therapy (PDT) system. The ECL‐driven PDT (ECL‐PDT) relies on the effective energy transfer from ECL emission to photosensitizer chlorin e6 (Ce6), which sensitizes the surrounding O2 into ROS. The dynamic process of gradual morphological changes, the variation of cell‐matrix adhesions, as well as the increase of cell membrane permeability in the process of ECL‐PDT were monitored under ECL microscopy (ECLM) with good spatiotemporal resolution. Combining real‐time imaging with ECL‐PDT, this new strategy provides not only new insights into dynamic cellular processes, but also promising potential of ECL in clinical applications.
A system for photodynamic therapy driven by electrochemiluminescence (ECL) is reported. The ECL generated by the Ru(bpy)32+/TPA pair acts as both the optical readout for the monitoring of the dynamic cellular processes and the light source for the excitation of a photosensitizer to produce cytotoxic ROS.
Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health ...Organization (WHO) in 2011.
We conducted a phase 3 noninferiority trial in participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides. Participants were randomly assigned, in a 2:1 ratio, to receive a short regimen (9 to 11 months) that included high-dose moxifloxacin or a long regimen (20 months) that followed the 2011 WHO guidelines. The primary efficacy outcome was a favorable status at 132 weeks, defined by cultures negative for
at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome. An upper 95% confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority.
Of 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population. Favorable status was reported in 79.8% of participants in the long-regimen group and in 78.8% of those in the short-regimen group - a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% confidence interval CI, -7.5 to 9.5) (P = 0.02 for noninferiority). The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, -0.7 percentage points; 95% CI, -10.5 to 9.1). An adverse event of grade 3 or higher occurred in 45.4% of participants in the long-regimen group and in 48.2% in the short-regimen group. Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia's formula) to 500 msec occurred in 11.0% of participants in the short-regimen group, as compared with 6.4% in the long-regimen group (P = 0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively.
In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety. (Funded by the U.S. Agency for International Development and others; Current Controlled Trials number, ISRCTN78372190; ClinicalTrials.gov number, NCT02409290.).
Better than expected: With a regular boronic acid as the functional monomer, a general and facile approach for glycoprotein imprinting exhibited several highly favorable features that are beyond ...normal expectation, which make the prepared MIPs feasible for the recognition of trace glycoproteins in complicated real samples.
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