Conspectus Organic semiconductors (OSCs) offer unique advantages with respect to mechanical flexibility, low-cost processing, and tunable properties. The optical and electrical properties of devices ...based on OSCs can be greatly improved when an OSC is coupled with graphene in a certain manner. Our research group has focused on using graphene as a growth template for OSCs and incorporating such high-quality heterostructures into optoelectronic devices. The idea is that graphene’s atomically flat surface with a uniform sp2 carbon network can serve as a perfect quasi-epitaxial template for the growth of OSCs. In addition, OSC–graphene heterostructures benefit from graphene’s unique characteristics, such as its high charge-carrier mobility, excellent optical transparency, and fascinating mechanical durability and flexibility. However, we have often found that OSC molecules assemble on graphene in unpredictable manners that vary from batch to batch. From observations of numerous research systems, we elucidated the mechanism underlying such poor repeatability and set out a framework to actually control the template effect of graphene on OSCs. In this Account, we not only present our scientific findings in this spectrum of areas but also convey our research scheme to the readers so that similar heterostructure complexes can be systematically studied. We began with experiments showing that the growth of OSCs on a graphene surface was driven by van der Waals interactions and is therefore sensitive to the cleanliness of the graphene surface. Nonetheless, we noted that, even on similarly clean graphene surfaces, the OSC thin film still varied with the underlying substrate. Thanks to the graphene-transfer method and in situ gating methods that we developed, we discovered that the decisive parameter for molecule–graphene interaction (and, hence, for the growth of OSCs on graphene) is the charge density in the graphene. Thus, to prepare a graphene template for high-quality graphene–OSC heterostructures, we controlled the charge density in the graphene to minimize the molecule–graphene interaction. Moreover, the possible charge transfer between OSC molecules and graphene, which induces additional molecule–graphene interactions, should also be taken into account. Eventually, we demonstrated a wide range of optoelectronic applications that benefitted from high-quality OSC–graphene heterostructures fabricated using our proof-of-concept systems.
Key points
The ClC‐3 2Cl−/1H+ exchanger modulates endosome pH and Cl− concentration. We investigated the relationships between ClC‐3‐mediated ion transport (steady‐state transport current, ISS), ...gating charge (Q) and cytoplasmic alkalization.
ClC‐3 transport is functionally unidirectional. ClC‐5 and ClC‐3 display indistinguishable exchange ratios, but ClC‐3 cycling is less “efficient”, as reflected by a large Q/ISS. An M531A mutation predicted to increase water‐wire stability and cytoplasmic proton supply improves efficiency.
Protonation (pH 5.0) of the outer glutamate gate (Gluext; E224) reduces Q, inhibits transport, and weakens coupling.
Removal of the central tyrosine anion gate (Y572S) greatly increases uncoupled anion current. Tyrosine –OH removal (Y572F) alters anion selectivity and impairs coupling.
E224 and Y572 act as anion barriers, and contribute to gating. The Y572 side chain and –OH regulate Q movement kinetics and voltage dependence. E224 and Y572 interact to create a “closed” inner gate conformation that maintains coupling during cycling.
We utilized plasma membrane‐localized ClC‐3 to investigate relationships between steady‐state transport current (ISS), gating charge (Q) movement, and cytoplasmic alkalization rate. ClC‐3 exhibited lower transport efficiency than ClC‐5, as reflected by a larger Q/ISS ratio, but an indistinguishable Cl−/H+ coupling ratio. External SCN− reduced H+ transport rate and uncoupled anion/H+ exchange by 80–90%. Removal of the external gating glutamate (“Gluext”) (E224A mutation) reduced Q and abolished H+ transport. We hypothesized that Methionine 531 (M531) impedes “water wire” H+ transfer from the cytoplasm to E224. Accordingly, an M531A mutation decreased the Q/ISS ratio by 50% and enhanced H+ transport. External protons (pH 5.0) inhibited ISS and markedly reduced Q while shifting the Q–voltage (V) relationship positively. The Cl−/H+ coupling ratio at pH 5.0 was significantly increased, consistent with externally protonated Gluext adopting an outward/open position. Internal “anion gate” removal (Y572S) dramatically increased ISS and impaired coupling, without slowing H+ transport rate. Loss of both gates (Y572S/E224A) resulted in a large “open pore” conductance. Y572F (removing only the phenolic hydroxide) and Y572S shortened Q duration similarly, resulting in faster Q kinetics at all voltages. These data reveal a complex relationship between Q and ion transport. Q/ISS must be assessed together with coupling ratio to properly interpret efficiency. Coupling and transport rate are influenced by the anion, internal proton supply and external protons. Y572 regulates H+ coupling as well as anion selectivity, and interacts directly with E224. Disruption of this “closed gate” conformation by internal protons may represent a critical step in the ClC‐3 transport cycle.
Key points
The ClC‐3 2Cl−/1H+ exchanger modulates endosome pH and Cl− concentration. We investigated the relationships between ClC‐3‐mediated ion transport (steady‐state transport current, ISS), gating charge (Q) and cytoplasmic alkalization.
ClC‐3 transport is functionally unidirectional. ClC‐5 and ClC‐3 display indistinguishable exchange ratios, but ClC‐3 cycling is less “efficient”, as reflected by a large Q/ISS. An M531A mutation predicted to increase water‐wire stability and cytoplasmic proton supply improves efficiency.
Protonation (pH 5.0) of the outer glutamate gate (Gluext; E224) reduces Q, inhibits transport, and weakens coupling.
Removal of the central tyrosine anion gate (Y572S) greatly increases uncoupled anion current. Tyrosine –OH removal (Y572F) alters anion selectivity and impairs coupling.
E224 and Y572 act as anion barriers, and contribute to gating. The Y572 side chain and –OH regulate Q movement kinetics and voltage dependence. E224 and Y572 interact to create a “closed” inner gate conformation that maintains coupling during cycling.
Cancer—one of the most life-threatening human diseases—can be treated with surgery, chemotherapy, and radiotherapy. Despite the negative side effects, conventional chemotherapy which contains ...doxorubicin is widely used in cancer treatment. Drug delivery carriers, an alternative cancer treatment, can be used to target tumor site by vectorizing anti-cancer drug and minimize the drug quantities. Due to unique physical and chemical properties, superparamagnetic iron oxide nanoparticles are researched and documented. This work investigates how magnetic drug delivery carriers are synthesized, how the carriers are characterized and quantified, the mechanisms of drug loading/releasing of the carriers including kinetics and thermodynamic parameters, and the future research topics of magnetic drug delivery carriers for loading and releasing doxorubicin.
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Selenate adsorption onto metal oxide surfaces is a cost-effective method to remove the toxin from drinking water systems. However, the low selectivity of metal oxides requires ...frequent sorbent replacement. The design of selective adsorbents is stymied because the surface factors controlling selenate adsorption remain unknown. We calculate adsorption energies of selenate on the (012) α-Al2O3 surface using density functional theory to unravel the physics that controls adsorption. Our model is validated against experiment by correctly predicting selenate removal efficiency as a function pH. We find that the selenate adsorption energy on the anhydrous α-Al2O3 surface is surprisingly anti-correlated with the fully solvated adsorption energy; therefore, the direct interaction between adsorbate and sorbent is eliminated as the controlling mechanism. Rather, the change in number of surface hydrogen bonds after adsorption is the factor most correlated with the adsorption energy (R2 > 0.8); and is thus determined to be the factor controlling selenate adsorption. We find that pH affects adsorption by controlling the number of surface protons available for H-bonding to selenate. This work demonstrates that adsorption prediction should not be made based on gas phase sorption energies and suggests that surface engineering which increases surface protonation may be an effective strategy for increasing selenate sorption.
Rice husk is one of the most abundant biomass resources in the world, yet it is not effectively used. This study focuses on the sustainably rice-husk-extracted lignin, nano-lignin (n-Lignin), ...lignin-capped silver nanoparticles (LCSN), n-Lignin-capped silver nanoparticles (n-LCSN), and lignin-capped silica-silver nanoparticles (LCSSN), and using them for antibacterial activities. The final n-Lignin-based products had a sphere-like structure, of which the size varied between 50 and 80 nm. We found that while n-Lignin and lignin were less effective against Escherichia coli than against Staphylococcus aureus, n-Lignin/lignin-based hybrid materials, i.e., n-LCSN, LCSN, and LCSSN, were better against E. coli than against S. aureus. Interestingly, the antimicrobial behaviors of n-LCSNs could be further improved by decreasing the size of n-Lignin. Considering the facile, sustainable, and eco-friendly method that we have developed here, it is promising to use n-Lignin/lignin-based materials as highly efficient antimicrobials without environmental concerns.
Therapeutic antibodies are decorated with complex-type N-glycans that significantly affect their biodistribution and bioactivity. The N-glycan structures on antibodies are incompletely processed in ...wild-type CHO cells due to their limited glycosylation capacity. To improve N-glycan processing, glycosyltransferase genes have been traditionally overexpressed in CHO cells to engineer the cellular N-glycosylation pathway by using random integration, which is often associated with large clonal variations in gene expression levels. In order to minimize the clonal variations, we used recombinase-mediated-cassette-exchange (RMCE) technology to overexpress a panel of 42 human glycosyltransferase genes to screen their impact on antibody N-linked glycosylation. The bottlenecks in the N-glycosylation pathway were identified and then released by overexpressing single or multiple critical genes. Overexpressing B4GalT1 gene alone in the CHO cells produced antibodies with more than 80% galactosylated bi-antennary N-glycans. Combinatorial overexpression of B4GalT1 and ST6Gal1 produced antibodies containing more than 70% sialylated bi-antennary N-glycans. In addition, antibodies with various tri-antennary N-glycans were obtained for the first time by overexpressing MGAT5 alone or in combination with B4GalT1 and ST6Gal1. The various N-glycan structures and the method for producing them in this work provide opportunities to study the glycan structure-and-function and develop novel recombinant antibodies for addressing different therapeutic applications.
Monoclonal antibodies (mAbs) eliminate cancer cells via various effector mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which ...are influenced by the N-glycan structures on the Fc region of mAbs. Manipulating these glycan structures on mAbs allows for optimization of therapeutic benefits associated with effector functions. Traditional approaches such as gene deletion or overexpression often lead to only all-or-nothing changes in gene expression and fail to modulate the expression of multiple genes at defined ratios and levels. In this work, we have developed a CHO cell engineering platform enabling modulation of multiple gene expression to tailor the N-glycan profiles of mAbs for enhanced effector functions. Our platform involves a CHO targeted integration platform with two independent landing pads, allowing expression of multiple genes at two pre-determined genomic sites. By combining with internal ribosome entry site (IRES)-based polycistronic vectors, we simultaneously modulated the expression of α-mannosidase II (MANII) and chimeric β-1,4-N-acetylglucosaminyl-transferase III (cGNTIII) genes in CHO cells. This strategy enabled the production of mAbs carrying N-glycans with various levels of bisecting and non-fucosylated structures. Importantly, these engineered mAbs exhibited different degrees of effector cell activation and CDC, facilitating the identification of mAbs with optimal effector functions. This platform was demonstrated as a powerful tool for producing antibody therapeutics with tailored effector functions via precise engineering of N-glycan profiles. It holds promise for advancing the field of metabolic engineering in mammalian cells.
This review is dedicated to various functional nanoarchitectonic nanocomposites based on molecular octahedral metal atom clusters (Nb
6
, Mo
6
, Ta
6
, W
6
, Re
6
). Powder and film nanocomposites ...with two-dimensional, one-dimensional and zero-dimensional morphologies are presented, as well as film matrices from organic polymers to inorganic layered oxides. The high potential and synergetic effects of these nanocomposites for biotechnology applications, photovoltaic, solar control, catalytic, photonic and sensor applications are demonstrated. This review also provides a basic level of understanding how nanocomposites are characterized and processed using different techniques and methods. The main objective of this review would be to provide guiding significance for the design of new high-performance nanocomposites based on transition metal atom clusters.
The purpose of this study was to investigate the effect of reducing diabetes-induced lysyl oxidase (LOX) overexpression on vascular cell apoptosis and blood-retinal barrier (BRB) characteristics in ...diabetic rats.
Nondiabetic rats, diabetic rats, and diabetic rats intravitreally (IV) injected with LOX siRNA or scrambled (scram) siRNA were used in the study. One month after the onset of diabetes, intravitreal injections were initiated at monthly intervals for up to three times. At the end of study, retinal capillary networks were isolated, stained with periodic acid-Schiff (PAS) and hematoxylin, and assessed for acellular capillaries (AC) and pericyte loss (PL). To assess vascular leakage, extravasation of FITC-dextran was evaluated in retinal capillaries after tail vein injection of FITC-dextran. Western blot analysis was performed to determine retinal LOX level and confirm LOX downregulation via LOX siRNA intravitreal injection.
LOX expression was significantly upregulated in retinas of diabetic rats compared with that of nondiabetic rats. Diabetic rats injected with LOX siRNA showed a significant decrease in retinal LOX expression compared with those of diabetic rats or scram siRNA-injected rats. In diabetic retinas, AC and PL were significantly increased compared with those of nondiabetic retinas. Importantly, diabetic rats treated with LOX siRNA exhibited a significant decrease in AC and PL counts compared with those of untreated diabetic rats. Furthermore, diabetic rats treated with LOX siRNA showed significant decrease in retinal vascular permeability compared with that of untreated diabetic rats.
Findings suggest LOX siRNA intravitreal injection may be effective against diabetes-induced LOX overexpression in preventing apoptosis and vascular leakage associated with diabetic retinopathy.
Human skin plays a critical role in a person communicating with his or her environment through diverse activities such as touching or deforming an object. Various electronic skin (E‐skin) devices ...have been developed that show functional or geometrical superiority to human skin. However, research into stretchable E‐skin that can simultaneously distinguish materials and textures has not been established yet. Here, the first approach to achieving a stretchable multimodal device is reported, that operates on the basis of various electrical properties of piezoelectricity, triboelectricity, and piezoresistivity and that exceeds the capabilities of human tactile perception. The prepared E‐skin is composed of a wrinkle‐patterned silicon elastomer, hybrid nanomaterials of silver nanowires and zinc oxide nanowires, and a thin elastomeric dielectric layer covering the hybrid nanomaterials, where the dielectric layer exhibits high surface roughness mimicking human fingerprints. This versatile device can identify and distinguish not only mechanical stress from a single stimulus such as pressure, tensile strain, or vibration but also that from a combination of multiple stimuli. With simultaneous sensing and analysis of the integrated stimuli, the approach enables material discrimination and texture recognition for a biomimetic prosthesis when the multifunctional E‐skin is applied to a robotic hand.
Fingerpad‐inspired multimodal electronic skin (E‐skin) is developed by mimicking functional and geometrical properties of a human finger. This multifunctional device can identify and distinguish not only mechanical stress from a single stimulus such as pressure, tensile strain, or vibration but also that to a combination of multiple stimuli, enabling material discrimination and texture recognition for a biomimetic prosthesis.
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