Precise Chemical Control Research Articles

Small-molecule activators specific to adenine base editors through blocking the canonical TGF-β pathway.

Adenine base editors (ABEs) catalyze A-to-G conversions, offering therapeutic options to treat the major class of human pathogenic single nucleotide polymorphisms (SNPs). However, robust and precise editing at diverse genome loci remains challenging. Here, using high-throughput chemical screening, we identified and validated SB505124, a selective ALK5 inhibitor, as an ABE activator. Treating cells with SB505124 enhanced on-target editing at multiple genome loci, including epigenetically refractory regions, and showed little effect on off-target conversion on the genome. Furthermore, SB505124 facilitated the editing of disease-associated genes in vitro and in vivo. Intriguingly, SB505124 served as a specific activator by selectively promoting ABE activity. Mechanistically, SB505124 promotes ABE editing, at least in part, by enhancing ABE expression and modulating DNA repair-associated genes. Our findings reveal the role of the canonical transforming growth factor-β pathway in gene editing and equip ABEs with precise chemical control.

The largest aluminum molecular rings: Phenol‐thermal synthesis, photoluminescence, and optical limiting

AbstractIt is of great interest to modulate the photophysical properties by atomically precise chemical control. The incorporation of conjugated ligands into crystalline materials provides a platform for molecular‐level interpretation of the structure‐activity relationship. Herein, we reported the phenol‐thermal and scale‐up synthesis of a new family of remarkably stable aluminum molecular rings. They are assembled by twenty AlIII ions with large conjugated ligands and phenols, representing the currently largest sizes (up to 4 nm in diameter) in the field of main group metal oxo clusters. Phenols are not only reaction medium but also auxiliary bridging ligands on the surface of macrocyclic molecules. In addition, they are either parallel to the center of the molecular ring or inserted into the molecular ring, or form dimers/tetramers that bind macrocyclic molecules to form supramolecular structures. These macrocyclic rings are hydrophobic and ultra‐stable, evidenced by retaining their morphology and crystalline when exposed to air for more than a year. Compared with the pristine conjugated ligands, they exhibit coordination‐enhanced fluorescence. By dispersing them into a polydimethylsiloxane (PDMS) matrix, we prepared transparent and flexible PDMS thin films for coupling flexible display and nonlinear optical application. Our discovery of such atomically precise rings provides a platform for the fine‐tuning of photo‐related performances.

Dynamic Distribution of Adult Thrips hawaiiensis Morgan During Banana Flowering Stage and Its Precise Chemical Control in Banana Plantation

Dynamic Distribution of Adult Thrips hawaiiensis Morgan During Banana Flowering Stage and Its Precise Chemical Control in Banana Plantation

Monofunctionalized Gold Nanoparticles: Fabrication and Applications.

An overview of various approaches to synthesize gold nanoparticles (AuNPs) bearing one single chemically addressable unit and their diverse fields of application is presented. This comprehensive review not only describes the strategies pursued to obtain monofunctionalized AuNPs, but also reports their behavior as 'massive' molecules in wet chemical protocols and the scope of their applications. The latter reaches from site-specific labels in biomolecules over mechanical barriers in superstructures to building blocks in hybrid nano-architectures. The complementing physical properties of AuNPs combined with precise chemical control of their attachment makes these objects promising building blocks for numerous proof-of-concept experiments and applications.

Systematically Tuning the Electronic Structure of Gold Nanoclusters through Ligand Derivatization.

While the ability to crystallize metal nanoclusters has revealed their geometric structure, the lack of a similarly precise measure of their electronic structure has hampered the development of synthetic design rules to precisely engineer their electronic properties. We track the evolution of highly-resolved electronic absorption spectra of gold nanoclusters with precisely mass-selected chemical composition in a controlled environment. Simple derivatization of the ligands yields larger spectral changes than varying the overall atomic composition of the cluster for two clusters with similar symmetry and size. The nominally metal-localized HOMO-LUMO transition of these nanoclusters lowers in energy linearly with increasing electron donation from the exterior of the ligand shell for both cluster sizes. Very weak surface interactions, such as binding of He or N2 , yield significant state-dependent shifts, identifying states with significant interfacial character. These observations demonstrate a pathway for deliberate tuning of interfacial chemistry for chemical and technological applications.

3-D Image-Driven Morphological Crop Analysis: A Novel Method for Detection of Sunflower Broomrape Initial Subsoil Parasitism.

Effective control of the parasitic weed sunflower broomrape (Orobanche cumana Wallr.) can be achieved by herbicides application in early parasitism stages. However, the growing environmental concerns associated with herbicide treatments have motivated the adoption of precise chemical control approaches that detect and treat infested areas exclusively. The main challenge in developing such control practices for O. cumana lies in the fact that most of its life-cycle occurs in the soil sub-surface and by the time shoots emerge and become observable, the damage to the crop is irreversible. This paper approaches early O. cumana detection by hypothesizing that its parasitism already impacts the host plant morphology at the sub-soil surface developmental stage. To validate this hypothesis, O. cumana- infested sunflower and non-infested control plants were grown in pots and imaged weekly over 45-day period. Three-dimensional plant models were reconstructed using image-based multi-view stereo followed by derivation of their morphological parameters, down to the organ-level. Among the parameters estimated, height and first internode length were the earliest definitive indicators of infection. Furthermore, the detection timing of both parameters was early enough for herbicide post-emergence application. Considering the fact that 3-D morphological modeling is nondestructive, is based on commercially available RGB sensors and can be used under natural illumination; this approach holds potential contribution for site specific pre-emergence managements of parasitic weeds and as a phenotyping tool in O. cumana resistant sunflower breeding projects.

Mass‐Production of Mesoporous MnCo2O4 Spinels with Manganese(IV)‐ and Cobalt(II)‐Rich Surfaces for Superior Bifunctional Oxygen Electrocatalysis

AbstractA mesoporous MnCo2O4 electrode material is made for bifunctional oxygen electrocatalysis. The MnCo2O4 exhibits both Co3O4‐like activity for oxygen evolution reaction (OER) and Mn2O3‐like performance for oxygen reduction reaction (ORR). The potential difference between the ORR and OER of MnCo2O4 is as low as 0.83 V. By XANES and XPS investigation, the notable activity results from the preferred MnIV‐ and CoII‐rich surface. The electrode material can be obtained on large‐scale with the precise chemical control of the components at relatively low temperature. The surface state engineering may open a new avenue to optimize the electrocatalysis performance of electrode materials. The prominent bifunctional activity shows that MnCo2O4 could be used in metal–air batteries and/or other energy devices.

Mass-Production of Mesoporous MnCo2 O4 Spinels with Manganese(IV)- and Cobalt(II)-Rich Surfaces for Superior Bifunctional Oxygen Electrocatalysis.

A mesoporous MnCo2 O4 electrode material is made for bifunctional oxygen electrocatalysis. The MnCo2 O4 exhibits both Co3 O4 -like activity for oxygen evolution reaction (OER) and Mn2 O3 -like performance for oxygen reduction reaction (ORR). The potential difference between the ORR and OER of MnCo2 O4 is as low as 0.83 V. By XANES and XPS investigation, the notable activity results from the preferred MnIV - and CoII -rich surface. The electrode material can be obtained on large-scale with the precise chemical control of the components at relatively low temperature. The surface state engineering may open a new avenue to optimize the electrocatalysis performance of electrode materials. The prominent bifunctional activity shows that MnCo2 O4 could be used in metal-air batteries and/or other energy devices.

Investigation of the Influence of Glucose Concentration on Cancer Cells by Using a Microfluidic Gradient Generator without the Induction of Large Shear Stress.

A microfluidic device capable of precise chemical control is helpful to mimic tumor microenvironments in vitro, which are closely associated with malignant progression, including metastasis. Cancer cells under a concentration gradient of oxygen and other sustenance materials inside a tumor in vivo have recently been reported to increase the probability of metastasis. The influence of glucose concentration on cancer cells has not been measured well, whereas that of oxygen concentration has been thoroughly examined using microfluidic devices. This is because glucose concentrations can be controlled using microfluidic concentration gradient generators, which trade off temporal stability of the glucose concentration and shear stress on the cells; by contrast, oxygen concentration can be easily controlled without microfluidic device-induced shear stresses. To study cell division and migration responses as a function of glucose concentration, we developed a microfluidic device to observe cell behaviors under various chemical conditions. The device has small-cross-section microchannels for generating a concentration gradient and a large-cross-section chamber for cell culture. With this design, the device can achieve both a cell culture with sufficiently low shear stress on cell activity and a stable glucose concentration gradient. Experiments revealed that a low glucose concentration increased the total migration length of HeLa cells and that HeLa cells under a glucose concentration gradient exhibit random motion rather than chemotaxis.

Controlled Chemical Derivatisation of Carbon Nanotubes with Imaging, Targeting, and Therapeutic Capabilities.

In drug delivery, carbon nanotubes (CNTs) hold a great potential as carriers because of their ability to easily cross biological barriers and be internalised into cells. Their high aspect ratio allows multi-functionalisation and their development as a multimodal platform for targeted therapy. In this article, we report the controlled covalent derivatisation of triple-functionalised CNTs with the anticancer drug gemcitabine, folic acid as a targeting ligand and fluorescein as a probe. The anticancer activity of gemcitabine was maintained after covalent grafting onto the CNTs. The functionalised nanotubes were internalised into both folate-positive and negative cells, suggesting the passive diffusion of CNTs. Overall, our approach is versatile and offers a precise chemical control of the sidewall functionalisation of CNTs and the possibility to manoeuvre the types of functionalities required on the nanotubes for a multimodal therapeutic strategy.

In situ synchrotron radiation photoemission study of ultrathin surface oxides of Ge(111)-c(2 × 8) induced by supersonic O2 beams

We investigated the surface oxidation on a Ge(111)-c(2 × 8) surface at room temperature using supersonic oxygen beams as a function of the translational energy of the incident oxygen molecules ranging from 26 meV to 2.3 eV. In situ synchrotron photoemission spectroscopy performed during the oxidation revealed that the surface oxidation terminated with the formation of a sub-monolayer oxide of at most 0.52 ML, for all the beam energies examined. In addition, the oxidation state of the surface oxides was found to depend on the translational energy. These results demonstrate the precise chemical control of the ultrathin surface oxides of Ge(111)-c(2 × 8).

High-throughput tracking of single yeast cells in a microfluidic imaging matrix.

Time-lapse live cell imaging is a powerful tool for studying signaling network dynamics and complexity and is uniquely suited to single cell studies of response dynamics, noise, and heritable differences. Although conventional imaging formats have the temporal and spatial resolution needed for such studies, they do not provide the simultaneous advantages of cell tracking, experimental throughput, and precise chemical control. This is particularly problematic for system-level studies using non-adherent model organisms such as yeast, where the motion of cells complicates tracking and where large-scale analysis under a variety of genetic and chemical perturbations is desired. We present here a high-throughput microfluidic imaging system capable of tracking single cells over multiple generations in 128 simultaneous experiments with programmable and precise chemical control. High-resolution imaging and robust cell tracking are achieved through immobilization of yeast cells using a combination of mechanical clamping and polymerization in an agarose gel. The channel and valve architecture of our device allows for the formation of a matrix of 128 integrated agarose gel pads, each allowing for an independent imaging experiment with fully programmable medium exchange via diffusion. We demonstrate our system in the combinatorial and quantitative analysis of the yeast pheromone signaling response across 8 genotypes and 16 conditions, and show that lineage-dependent effects contribute to observed variability at stimulation conditions near the critical threshold for cellular decision making.

Reversing the size-dependence of surface plasmon resonances

The size-dependence of surface plasmon resonances (SPRs) is poorly understood in the small particle limit due to complex physical/chemical effects and uncertainties in experimental samples. In this article, we report an approach for synthesizing an ideal class of colloidal Ag nanoparticles with highly uniform morphologies and narrow size distributions. Optical measurements and theoretical analyses for particle diameters in the d approximately 2-20 nm range are presented. The SPR absorption band exhibits an exceptional behavior: As size decreases from d approximately 20 nm it blue-shifts but then turns over near d approximately 12 nm and strongly red-shifts. A multilayer Mie theory model agrees well with the observations, indicating that lowered electron conductivity in the outermost atomic layer, due to chemical interactions, is the cause of the red-shift. We corroborate this picture by experimentally demonstrating precise chemical control of the SPR peak positions via ligand exchange.

Nanoscale organization of β 2-adrenergic receptor-Venus fusion protein domains on the surface of mammalian cells

Adrenergic receptors are a key component of nanoscale multiprotein complexes that are responsible for controlling the beat rate in a mammalian heart. We demonstrate the ability of near-field scanning optical microscopy (NSOM) to visualize β 2-adrenergic receptors (β 2AR) fused to the GFP analogue Venus at the nanoscale on HEK293 cells. The expression of the β 2AR-Venus fusion protein was tightly controlled using a tetracycline-induced promoter. Both the size and density of the observed nanoscale domains are dependent on the level of induction and thus the level of protein expression. At concentrations between 100 and 700 ng/ml of inducer doxycycline, the size of domains containing the β 2AR-Venus fusion protein appears to remain roughly constant, but the number of domains per cell increase. At 700 ng/ml doxycycline the functional receptors are organized into domains with an average diameter of 150 nm with a density similar to that observed for the native protein on primary murine cells. By contrast, larger micron-sized domains of β 2AR are observed in the membrane of the HEK293 cells that stably overexpress β 2AR-GFP and β 2AR-eYFP. We conclude that precise chemical control of gene expression is highly advantageous for the use β 2AR-Venus fusion proteins as models for β 2AR function. These observations are critical for designing future cell models and assays based on β 2AR, since the receptor biology is consistent with a relatively low density of nanoscale receptor domains.

Precise Chemical Control of Algae in Ponds

The objective of this study was to investigate the behavior of copper sulfate in ponds, especially when applied in granulated form, for the control of algae. The study used the atomic absorption technique for direct, rapid analysis of water. Study results indicate that present dosages of copper sulfate are adequate for algae control. The concentration obtained by use of these dosages, however, may not reach recommended levels in some ponds. This is because copper sulfate goes out of solution very rapidly in some ponds, and much more precise and in some cases higher dosage rates may have to be used.