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The present research work facilitates a ligand-mediated effective strategy to achieve different morphological surface structures of bimetallic (Ni and Co) metal-organic frameworks (MOFs) by utilizing different types of organic ligands like terephthalic acid (BDC), 2-methylimidazole (2-Melm), and trimesic acid (BTC). Different morphological structures, rectangular-like nanosheets, petal-like nanosheets, and nanosheet-assembled flower-like spheres (NSFS) of NiCo MOFs, are confirmed from the structural characterization for ligands BDC, 2-Melm, and BTC, respectively. The basic characterization studies like scanning electron microscopy, X-ray diffraction, transmission electron microscopy, and Brunauer-Emmett-Teller revealed that the NiCo MOF prepared by using trimesic acid as the ligand (NiCo MOF_BTC) with a long organic linker exhibits a three-dimensional architecture of NSFS that possesses higher surface area and pore dimensions, which enables better ion kinetics. Also, the NiCo MOF_BTC delivered the highest capacity of 1471.4 C g -1 (and 408 mA h g -1 ) at 1 A g -1 current density, compared to the other prepared NiCo MOFs and already reported different NiCo MOF structures. High interaction of trimesic acid with the metal ions confirmed from ultraviolet-visible spectroscopy and X-ray photoelectron spectroscopy leads to a NSFS structure of NiCo MOF_BTC. For practical application, an asymmetric supercapacitor device (NiCo MOF_BTC//AC) is fabricated by taking NiCo MOF_BTC and activated carbon as the positive and negative electrode, respectively, where the PVA + KOH gel electrolyte serves as a separator as well as an electrolyte. The device delivered an outstanding energy density of 78.1 Wh kg -1 at a power density of 750 W kg -1 in an operating potential window of 1.5 V. In addition, it displays a long cycle life of 5000 cycles with only 12% decay of the initial specific capacitance. Therefore, these findings manifest the morphology control of MOFs by using different ligands and the mechanism behind the different morphologies that will provide an effective way to synthesize differently structured MOF materials for future energy-storage applications.

The receptor binding domain (RBD) of SARS-CoV-2 is the primary target of neutralizing antibodies. We have previously reported the design and characterization of a mammalian cell expressed RBD derivative, mRBD1-3.2, that has higher thermal stability and greatly enhanced immunogenicity relative to the wild type mRBD. The protein is highly thermotolerant and immunogenic and is being explored for use in room temperature stable Covid-19 vaccine formulations. In the current study, we have investigated the folding pathway of both WT and stabilized RBD. It was found that chemical denaturation of RBD proceeds through a stable equilibrium intermediate. Thermal and chemical denaturation is reversible, as assayed by binding to the receptor ACE2. Unusually, in its native state, RBD binds to the hydrophobic probe ANS, and enhanced ANS binding is observed for the equilibrium intermediate state. Further characterization of the folding of mRBD1-3.2, both in solution and after reconstitution of lyophilized protein stored for a month at 37 °C, revealed a higher stability represented by higher C m , faster refolding, slower unfolding, and enhanced resistance to proteolytic cleavage relative to WT. In contrast to WT RBD, the mutant showed decreased interaction with the hydrophobic moiety linoleic acid. Collectively, these data suggest that the enhanced immunogenicity results from reduced conformational fluctuations that likely enhance in vivo half-life as well as reduce the exposure of irrelevant non-neutralizing epitopes to the immune system.

High-performance energy storage devices (HPEDs) play a critical role in the realization of clean energy and thus enable the overarching pursuit of nonpolluting, green technologies. Supercapacitors are one class of such lucrative HPEDs; however, a serious limiting factor of supercapacitor technology is its sub-par energy density. This report presents hitherto unchartered pathway of physical deformation, chemical dealloying, and microstructure engineering to produce ultrahigh-capacitance, energy-dense NiMn alloy electrodes. The activated electrode delivered an ultrahigh specific-capacitance of 2700 F/cm 3 at 0.5 A/cm 3 . The symmetric device showcased an excellent energy density of 96.94 Wh/L and a remarkable cycle life of 95% retention after 10,000 cycles. Transmission electron microscopy and atom probe tomography studies revealed the evolution of a unique hierarchical microstructure comprising fine Ni/NiMnO 3 nanoligaments within MnO 2 -rich nanoflakes. Theoretical analysis using density functional theory showed semimetallic nature of the nanoscaled oxygen-vacancy-rich NiMnO 3 structure, highlighting enhanced carrier concentration and electronic conductivity of the active region. Furthermore, the geometrical model of NiMnO 3 crystals revealed relatively large voids, likely providing channels for the ion intercalation/de-intercalation. The current processing approach is highly adaptable and can be applied to a wide range of material systems for designing highly efficient electrodes for energy-storage devices.

Over the last decades, three-dimensional (3D) organotypic skin models have received enormous attention as alternative models to in vivo animal models and in vitro two-dimensional assays. To date, most organotypic skin models have an epidermal layer of keratinocytes and a dermal layer of fibroblasts embedded in an extracellular matrix (ECM)-based biomaterial. The ECM provides mechanical support and biochemical signals to the cells. Without advancements in ECM-based biomaterials and biofabrication technologies, it would have been impossible to create organotypic skin models that mimic native human skin. In this review, the use of ECM-based biomaterials in the reconstruction of skin models, as well as the study of complete ECM-based biomaterials, such as fibroblasts-derived ECM and decellularized ECM as a better biomaterial, will be highlighted. We also discuss the benefits and drawbacks of several biofabrication processes used in the fabrication of ECM-based biomaterials, such as conventional static culture, electrospinning, 3D bioprinting, and skin-on-a-chip. Advancements and future possibilities in modifying ECM-based biomaterials to recreate disease-like skin models will also be highlighted, given the importance of organotypic skin models in disease modeling. Overall, this review provides an overview of the present variety of ECM-based biomaterials and biofabrication technologies available. An enhanced organotypic skin model is expected to be produced in the near future by combining knowledge from previous experiences and current research.

Perovskite solar cells (PSCs) have shown great potential for next-generation photovoltaics. One of the main barriers to their commercial use is their poor long-term stability under ambient conditions and, in particular, their sensitivity to moisture and oxygen. Therefore, several encapsulation strategies are being developed in an attempt to improve the stability of PSCs in a humid environment. The lack of common testing procedures makes the comparison of encapsulation strategies challenging. In this paper, we optimized and investigated two common encapsulation strategies: lamination-based glass-glass encapsulation for outdoor operation and commercial use (COM) and a simple glue-based encapsulation mostly utilized for laboratory research purposes (LAB). We compare both approaches and evaluate their effectiveness to impede humidity ingress under three different testing conditions: on-shelf storage at 21 °C and 30% relative humidity (RH) (ISOS-D1), damp heat exposure at 85 °C and 85% RH (ISOS-D3), and outdoor operational stability continuously monitoring device performance for 10 months under maximum power point tracking on a roof-top test site in Berlin, Germany (ISOS-O3). LAB encapsulation of perovskite devices consists of glue and a cover glass and can be performed at ambient temperature, in an inert environment without the need for complex equipment. This glue-based encapsulation procedure allowed PSCs to retain more than 93% of their conversion efficiency after 1566 h of storage in ambient atmosphere and, therefore, is sufficient and suitable as an interim encapsulation for cell transport or short-term experiments outside an inert atmosphere. However, this simple encapsulation does not pass the IEC 61215 damp heat test and hence results in a high probability of fast degradation of the cells under outdoor conditions. The COM encapsulation procedure requires the use of a vacuum laminator and the cells to be able to withstand a short period of air exposure and at least 20 min at elevated temperatures (in our case, 150 °C). This encapsulation method enabled the cells to pass the IEC 61215 damp heat test and even to retain over 95% of their initial efficiency after 1566 h in a damp heat chamber. Above all, passing the damp heat test for COM-encapsulated devices translates to devices fully retaining their initial efficiency for the full duration of the outdoor test (>10 months). To the best of the authors' knowledge, this is one of the longest outdoor stability demonstrations for PSCs published to date. We stress that both encapsulation approaches described in this work are useful for the scientific community as they fulfill different purposes: the COM for the realization of prototypes for long-term real-condition validation and, ultimately, commercialization of perovskite solar cells and the LAB procedure to enable testing and carrying out experiments on perovskite solar cells under noninert conditions.

Through the optimization of the perovskite precursor composition and interfaces to selective contacts, we achieved a p-i-n-type perovskite solar cell (PSC) with a 22.3% power conversion efficiency (PCE). This is a new performance record for a PSC with an absorber bandgap of 1.63 eV. We demonstrate that the high device performance originates from a synergy between (1) an improved perovskite absorber quality when introducing formamidinium chloride (FACl) as an additive in the "triple cation" Cs 0.05 FA 0.79 MA 0.16 PbBr 0.51 I 2.49 (Cs-MAFA) perovskite precursor ink, (2) an increased open-circuit voltage, V OC , due to reduced recombination losses when using a lithium fluoride (LiF) interfacial buffer layer, and (3) high-quality hole-selective contacts with a self-assembled monolayer (SAM) of [2-(9 H -carbazol-9-yl)ethyl]phosphonic acid (2PACz) on ITO electrodes. While all devices exhibit a high performance after fabrication, as determined from current-density voltage, J - V , measurements, substantial differences in device performance become apparent when considering longer-term stability data. A reduced long-term stability of devices with the introduction of a LiF interlayer is compensated for by using FACl as an additive in the metal-halide perovskite thin-film deposition. Optimized devices maintained about 80% of the initial average PCE during maximum power point (MPP) tracking for >700 h. We scaled the optimized device architecture to larger areas and achieved fully laser patterned series-interconnected mini-modules with a PCE of 19.4% for a 2.2 cm 2 active area. A robust device architecture and reproducible deposition methods are fundamental for high performance and stable large-area single junction and tandem modules based on PSCs.

Spatially resolved ambient mass spectrometry imaging methods have gained popularity to characterize cancer sites and their borders using molecular changes in the lipidome. This utility, however, is predicated on metabolic homogeneity at the border, which would create a sharp molecular transition at the morphometric borders. We subjected murine models of human medulloblastoma brain cancer to mass spectrometry imaging, a technique that provides a direct readout of tissue molecular content in a spatially resolved manner. We discovered a distance-dependent gradient of cancer-like lipid molecule profiles in the brain tissue within 1.2 mm of the cancer border, suggesting that a cancer-like state progresses beyond the histologic border, into the healthy tissue. The results were further corroborated using orthogonal liquid chromatography and mass spectrometry (LC-MS) analysis of selected tissue regions subjected to laser capture microdissection. LC-MS/MS analysis for robust identification of the affected molecules implied changes in a number of different lipid classes, some of which are metabolized from the essential docosahexaenoic fatty acid (DHA) present in the interstitial fluid. Metabolic molecular borders are thus not as sharp as morphometric borders, and mass spectrometry imaging can reveal molecular nuances not observed with microscopy. Caution must be exercised in interpreting multimodal imaging results stipulated on a coincidental relationship between metabolic and morphometric borders of cancer, at least within animal models used in preclinical research.

Hanging cell culture inserts are most widely used in vitro cell culture devices, which provide a freestanding multichamber setup for various co-culture and triculture systems. Apart from being costly, the commercial inserts do not provide enough choices regarding polymer types and pore sizes. Most importantly, commercially available inserts are two-dimensional multiporous membrane-based devices. Herein, we report a one-step fabrication process of the multifunctional nanofiber-based permeable hanging cell culture insert using electrospinning. These fabricated nanofibrous membranes' attached inserts have advantages such as low cost, ready availability, easy fabrication, tunable porosity, autoclavability, and biomaterial-based nanofibrous membranes. The inserts without nanofibrous membrane can also be reused by autoclaving them and electrospun nanofibrous membrane on it according to the application. We have also confirmed its suitability for extensive use in the field of in vitro cell culture by analyzing its adherence and toxicity results on breast cancer cell line (MCF-7). These hanging cell culture inserts are thus a potent product for various cell culture assays such as cell migration for wound healing, cancer metastasis, and other tissue engineering applications., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Thermal spray coatings (TSCs) are widely utilized for limiting degradation of structural components. However, the performance of TSCs is significantly impaired by its inherent non-homogeneous microstructure, comprising of splat boundaries, porosities, secondary phase-formation, and elemental segregation. Herein, we report a simplistic approach for significantly enhancing the corrosion resistance of TSCs. Ni-Cr-5Al 2 O 3 coatings were deposited on stainless steel using high-velocity oxy-fuel technique. The microstructure of as-sprayed coating showed significant inhomogeneities in the form of isolated splats and elemental segregation. The microstructure of developed coatings was modified using a novel processing technique, known as stationary friction processing (SFP). The SFP treatment resulted in complete refinement of coating microstructure with elimination of splat boundaries and pores along with elemental homogenization. The corrosion behavior of as-sprayed and SFP treated coating was evaluated in 3.5% NaCl solution using potentiodynamic polarization and electrochemical impedance spectroscopy. The SFP treatment reduced the corrosion rate of as-sprayed coating by an order of magnitude. Long-time immersion studies showed continuously decreasing impedance of the as-sprayed coating due to the penetration of the electrolyte along the splat boundaries. In contrast, impedance for the SFP treated coating increased with the immersion time due to the removal of all microstructural defects., Competing Interests: The authors declare no competing financial interest.

Over the past decade, the available crystal structures have almost doubled in Protein Data Bank (PDB) providing the research community with a series of similar crystal structures to choose from for future docking studies. With the steady growth in the number of high-resolution three-dimensional protein structures, ligand docking-based virtual screening of chemical libraries to a receptor plays a critical role in the drug discovery process by identifying new drug candidates. Thus, identifying potential candidates among all the available structures in a database for docking studies is of utmost importance. Our work examined whether one could use the resolution of a number of known structures, without considering other parameters, to choose a good experimental structure for various docking studies to find more useful drug leads. We expected that a good experimental structure for docking studies to be the one that gave favorable docking with the largest number of ligands among the experimental structures to be selected. We chose three protein test systems for our study, all belonging to the family of MAPK: (1) JNK1, (2) JNK2, and (3) JNK3. On analysis of the results, the best resolution structures showed significant variations from the expected values in their result, whereas the poor resolution structures proved to be better candidates for docking studies., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Two-dimensional nanoporous membranes have received attention as catalysts for energy generation and membranes for liquid and gas purification but controlling their porosity and facilitating large-scale production is challenging. We show the growth and fabrication of centimeter-scale molybdenum disulfide (MoS 2 ) membranes with tunable porous areas up to ∼ 10% of the membrane and average nanopore diameters as large as ∼ 30 nm, controlled by the etch time. We also measure ionic conductance between 0.1 and 16 μS per μm 2 through variably etched nanoporous membranes. Ensuring the mechanical robustness and large-area of the membrane, bilayer and few-layer regions form a strong supporting matrix around monolayer regions, observed by aberration-corrected scanning transmission electron microscopy. During etching, nanopores form in thin, primarily monolayer areas whereas thicker multilayer regions remain essentially intact. Atomic-resolution imaging reveals that after exposure to the etchant, the number of V 1Mo vacancies increases and nanopores form along grain boundaries in monolayers, suggesting that etching starts at intrinsic defect sites. This work provides an avenue for the scalable production of nanoporous atomically thin membranes.

Multifunctional novel core-shell composites, CdSNPs@ZIF-8, have been synthesized by in situ encapsulation of different amounts of CdSNPs (150, 300, and 500 μL suspension of CdSNPs in methanol) in ZIF-8 at room temperature. These composites have been characterized by powder X-ray diffraction, X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy, high-resolution transmission electron microscopy (HRTEM), and diffuse reflectance spectroscopy techniques and Brunauer-Emmett-Teller surface analysis. XPS and HRTEM indicate the encapsulation of CdSNPs within ZIF-8 crystal without disturbing the crystal order of ZIF-8. The average size of embedded CdSNPs (determined by the particle size distribution from HRTEM) is found to be 16.34 nm. CdSNPs@ZIF-8 showed potential to be used as an antibacterial agent against the broad spectrum of bacterial strains such as Gram-positive Staphylococcus aureus and Gram-negative green fluorescent protein-expressing Escherichia coli in aqueous medium, as evident by various biophysical experiments, viz., 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, optical density and fluorescence spectroscopic studies, fluorescence and optical microscopic image analysis, disk diffusion assay, field emission scanning electron microscopy, and flow cytometry for reactive oxygen species induction assay. Further, the composite has been used as an efficient photocatalyst for the degradation of organic pollutants, such as methylene blue dye, in aqueous medium and found that the core-shell composite, CdSNPs@ZIF-8 (150 μL) (abbreviated as NC-1) (5 mg), exhibited higher photocatalytic activity (≈1.8 times) than CdSNPs for degradation of 90% of methylene blue (10 mL of 10 ppm) at pH ≥ 7 due to the synergetic effect. Therefore, in situ encapsulation of CdSNPs in ZIF-8 provides an easy executable measure for purification of wastewater effluents for the effective photocatalytic degradation of organic pollutants as well as to remove the bacterial contamination under sunlight., Competing Interests: The authors declare no competing financial interest.

Atomic-defect engineering in thin membranes provides opportunities for ionic and molecular filtration and analysis. While molecular-dynamics (MD) calculations have been used to model conductance through atomic vacancies, corresponding experiments are lacking. We create sub-nanometer vacancies in suspended single-layer molybdenum disulfide (MoS 2 ) via Ga + ion irradiation, producing membranes containing ∼300 to 1200 pores with average and maximum diameters of ∼0.5 and ∼1 nm, respectively. Vacancies exhibit missing Mo and S atoms, as shown by aberration-corrected scanning transmission electron microscopy (AC-STEM). The longitudinal acoustic band and defect-related photoluminescence were observed in Raman and photoluminescence spectroscopy, respectively. As the irradiation dose is increased, the median vacancy area remains roughly constant, while the number of vacancies (pores) increases. Ionic current versus voltage is nonlinear and conductance is comparable to that of ∼1 nm diameter single MoS 2 pores, proving that the smaller pores in the distribution display negligible conductance. Consistently, MD simulations show that pores with diameters <0.6 nm are almost impermeable to ionic flow. Atomic pore structure and geometry, studied by AC-STEM, are critical in the sub-nanometer regime in which the pores are not circular and the diameter is not well-defined. This study lays the foundation for future experiments to probe transport in large distributions of angstrom-size pores.

Early detection is the critical phase in the prognostic strategy of various life-threatening maladies like infectious diseases and cancer. The mortality rate caused by these diseases could be considerably reduced if they were diagnosed in the early stages of disease development. Carbon dots (C-dots), a relatively new and promising candidate in the fluorescent nanomaterial category, possess a perceptible impact on various bioapplications. Herein, we report a one-step facile hydrothermal synthesis that yields a novel surface-passivated carbon dot (CDP) from curcumin (as a green substrate) displaying high aqueous solubility. The physico-chemical characterization of thus synthesized C-dots was accomplished by an UV-visible spectrophotometer, fluorescence spectrophotometer, zetasizer, TEM, and FE-SEM to understand the formation of carbon dots with a 4-5 nm size near spherical nanoparticle with high colloidal stability. E. coli DH5α was engaged as the Gram-negative test organism and S. aureus as the Gram-positive in the biolabeling of bacteria. Cancer cell lines including colon cancer (HCT-15), lung cancer (A549), and mouse fibroblast (NIH 3T3) were evaluated and resulted in good biolabeling potential and less cytotoxicity. Zebrafish (ASWT) embryos as an animal model system were bioimaged, and in vivo toxicity was inferred. Moreover, the synthesized C-dots were shown to have free radical scavenging activity in a dose-dependent manner. The unpassivated C-dots (CD) were found to sense ferric ions at the micromolar concentration level. The findings of our study suggest that the multifunctional potentiality of CDPs serves as high-performance optical nanoprobes and can be a suitable alternative for various biolabeling and contrasting agents., Competing Interests: The authors declare no competing financial interest.

The fabrication of polymeric nanofibers and its potential versatility instigated to foster smart hybrid nanomaterials for the removal of environmental pollutants. In this pursuit, in this research work, polyacrylonitrile (PAN)-based two-dimensional (2D) nanofibrous mats with polyethyleneimine (PEI)/Fe and quaternary ammonium (QA)/Fe as hybrid fillers were prepared by the electrospinning process for the effective dye removal and bacterial disinfection. The characteristics of the fabricated nanomaterials were extensively explored by several analytical techniques such as field emission-scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and Brunauer-Emmett-Teller analysis. Magnetic and thermal properties were investigated by superconducting quantum interference device and thermogravimetric measurements. The kinetic and isothermal models affirmed the adsorption behavior of the PAN-PEI/Fe nanofibers, and further regenerative studies substantiated the sustainability of the mats for the removal of industrial dye effluents. Subsequently, the magnetic-QA-loaded PAN nanofiber mats exhibited bactericidal killing efficacy of 99 and 89.5% in both Staphylococcus aureus and green fluorescence protein expressing Escherichia coli bacterial models evaluated from the conventional quantitative bacterial colony-counting assay. Disk diffusion method and microscopic investigations corroborated the disinfection efficacy with zone of inhibitions of ∼23 and 33 mm, respectively. Interestingly, in vitro cell culture studies conducted in BHK-21 and NIH 3T3 cell lines demonstrated the cytocompatibility, and the in vivo toxicity investigations using the zebrafish models necessitated the real-time application of these nanofibrous mats. Therefore, the comprehensive study of the fabricated PAN-templated functionalized 2D nanofibrous mats affirmed to be competent for the remediation of industrial dye effluents and bacteria in water bodies., Competing Interests: The authors declare no competing financial interest.

A tunable band gap in phosphorene extends its applicability in nanoelectronic and optoelectronic applications. Here, we propose to tune the band gap in phosphorene by patterning antidot lattices, which are periodic arrays of holes or nanopores etched in the material, and by exploiting quantum confinement in the corresponding nanoconstrictions. We fabricated antidot lattices with radii down to 13 nm in few-layer black phosphorus flakes protected by an oxide layer and observed suppression of the in-plane phonon modes relative to the unmodified material via Raman spectroscopy. In contrast to graphene antidots, the Raman peak positions in few-layer BP antidots are unchanged, in agreement with predicted power spectra. We also use DFT calculations to predict the electronic properties of phosphorene antidot lattices and observe a band gap scaling consistent with quantum confinement effects. Deviations are attributed primarily to self-passivating edge morphologies, where each phosphorus atom has the same number of bonds per atom as the pristine material so that no dopants can saturate dangling bonds. Quantum confinement is stronger for the zigzag edge nanoconstrictions between the holes as compared to those with armchair edges, resulting in a roughly bimodal band gap distribution. Interestingly, in two of the antidot structures an unreported self-passivating reconstruction of the zigzag edge endows the systems with a metallic component. The experimental demonstration of antidots and the theoretical results provide motivation to further scale down nanofabrication of antidots in the few-nanometer size regime, where quantum confinement is particularly important.

Topologically protected states in combination with superconductivity hold great promise for quantum computing applications, but the progress on electrical transport measurements in such systems has been impeded by the difficulty of fabricating devices with reliable electrical contacts. We find that superconductivity can be patterned directly into Bi 2 Se 3 nanostructures by local doping with palladium. Superconducting regions are defined by depositing palladium on top of the nanostructures using electron beam lithography followed by in situ annealing. Electrical transport measurements at low temperatures show either partial or full superconducting transition, depending on the doping conditions. Structural characterization techniques indicate that palladium remains localized in the targeted areas, making it possible to pattern superconducting circuits of arbitrary shapes in this topological material.

Two-dimensional materials are promising for a range of applications, as well as testbeds for probing the physics of low-dimensional systems. Tungsten disulfide (WS 2 ) monolayers exhibit a direct band gap and strong photoluminescence (PL) in the visible range, opening possibilities for advanced optoelectronic applications. Here, we report the realization of two-dimensional nanometer-size pores in suspended monolayer WS 2 membranes, allowing for electrical and optical response in ionic current measurements. A focused electron beam was used to fabricate nanopores in WS 2 membranes suspended on silicon-based chips and characterized using PL spectroscopy and aberration-corrected high-resolution scanning transmission electron microscopy. It was observed that the PL intensity of suspended WS 2 monolayers is ∼10-15 times stronger when compared to that of substrate-supported monolayers, and low-dose scanning transmission electron microscope viewing and drilling preserves the PL signal of WS 2 around the pore. We establish that such nanopores allow ionic conductance and DNA translocations. We also demonstrate that under low-power laser illumination in solution, WS 2 nanopores grow slowly in size at an effective rate of ∼0.2-0.4 nm/s, thus allowing for atomically controlled nanopore size using short light pulses.

Black phosphorus (BP) is a highly anisotropic allotrope of phosphorus with great promise for fast functional electronics and optoelectronics. We demonstrate the controlled structural modification of few-layer BP along arbitrary crystal directions with sub-nanometer precision for the formation of few-nanometer-wide armchair and zigzag BP nanoribbons. Nanoribbons are fabricated, along with nanopores and nanogaps, using a combination of mechanical-liquid exfoliation and in situ transmission electron microscopy (TEM) and scanning TEM nanosculpting. We predict that the few-nanometer-wide BP nanoribbons realized experimentally possess clear one-dimensional quantum confinement, even when the systems are made up of a few layers. The demonstration of this procedure is key for the development of BP-based electronics, optoelectronics, thermoelectrics, and other applications in reduced dimensions.

We report the synthesis of an amphiphilic triblock copolymer composed of a hydrophilic poly(ethylene glycol) (PEG) block, a central poly(acrylic acid) (PAA) block, and a hydrophobic poly(methyl methacrylate) (PMMA) block using atom transfer radical polymerization technique. We examined the self-assembly of PEG-b-PAA-b-PMMA copolymers in aqueous solutions forming nanosized micelles and their ability to encapsulate hydrophobic guest molecules such as Nile Red (NR) dye and cabazitaxel (CTX, an anticancer drug). We used 2,2β'-(propane-2,2-diylbis(oxy))-diethanamine to react with the carboxylic acid groups of the central PAA block forming acid-labile, shell cross-linked micelles (SCLM). We investigated the loading efficiency and release of different guest molecules from non-cross-linked micelles (NSCLM) and shell cross-linked micelles (SCLM) prepared by reacting 50% (SCLM-50) and 100% (SCLM-100) of the carboxylic acid groups in the PAA in physiologic (pH 7.4) and acidic (pH 5.0) buffer solutions as a function of time. We examined the uptake of NR-loaded NSCLM, SCLM-50, and SCLM-100 micelles into PC-3 and C4-2B prostate cancer cells and the effect of different micelle compositions on membrane fluidity of both cell lines. We also investigated the effect of CTX-loaded NSCLM, SCLM-50, and SCLM-100 micelles on the viability of PC-3 and C4-2B cancer cells compared to free CTX as a function of drug concentration. Results show that PEG-b-PAA-b-PMMA polymers form micelles at concentrations ≥11 μg/mL with an average size of 40-50 nm. CTX was encapsulated in PEG-b-PAA-b-PMMA micelles with 55% loading efficiency in NSCLM. In vitro release studies showed that 30% and 85% of the loaded CTX was released from SCLM-50 micelles in physiologic (pH 7.4) and acidic (pH 5.0) buffer solutions over 30 h, confirming micelles' sensitivity to solution pH. Results show uptake of NSCLM and SCLM into prostate cancer cells delivering their chemotherapeutic cargo, which triggered efficient cancer cell death. PEG-b-PAA-b-PMMA micelles were not hemolytic and did not cause platelet aggregation, which indicate their biocompatibility.

Heparan sulfates are implicated in a wide range of biological processes. A major challenge in deciphering their structure and activity relationship is the synthetic difficulties to access diverse heparan sulfate oligosaccharides with well-defined sulfation patterns. In order to expedite the synthesis, a divergent synthetic strategy was developed. By integrating chemical synthesis and two types of O-sulfo transferases, seven different hexasaccharides were obtained from a single hexasaccharide precursor. This approach combined the flexibility of chemical synthesis with the selectivity of enzyme-catalyzed sulfations, thus simplifying the overall synthetic operations. In an attempt to establish structure activity relationships of heparan sulfate binding with its receptor, the synthesized oligosaccharides were incorporated onto a glycan microarray, and their bindings with a growth factor FGF-2 were examined. The unique combination of chemical and enzymatic approaches expanded the capability of oligosaccharide synthesis. In addition, the well-defined heparan sulfate structures helped shine light on the fine substrate specificities of biosynthetic enzymes and confirm the potential sequence of enzymatic reactions in biosynthesis.

Nanofiber scaffold's ability to foster seemingly nonexistent interface with the cells enables them to effectively deliver various bioactive molecules to cells in the vicinity. Among such bioactive molecules, therapeutically active nucleic acid has been the most common candidate. In spite of such magnanimous efforts in this field, it remains a paradox that suicide gene delivery by nanofibers has never been sought for anticancer application. To investigate such a possibility, in the present work, a composite core-shell nanofiberous scaffold has been realized which could efficiently transfect suicide gene into cancer cells and simultaneously deliver prodrug, 5-Fluorocytosine (5-FC) in a controlled and sustained manner. The scaffold's ability to instigate apoptosis by suicide gene therapy in nonsmall lung cancer cells (A549) was ascertained at both phenotypic and genotypic levels. A cascade of events starting from suicide gene polyplex release from nanofibers, transfection, and expression of cytosine deaminase-uracil phosphoribosyltransferase (CD::UPRT) suicide gene by A549; subsequent prodrug release; and its metabolic conversion into toxic intermediates which finally culminates in host cells apoptosis has been monitored in a time-dependent manner. This work opens up new application avenues for nanofiber-based scaffolds which can effectively manage cancer prognosis.

CoCr alloy is commonly used in various cardiovascular medical devices for its excellent physical and mechanical properties. However, the formation of blood clots on the alloy surfaces is a serious concern. This research is focused on the surface modification of CoCr alloy using varying concentrations (1, 25, 50, 75, and 100 mM) of phosphoric acid (PA) and phosphonoacetic acid (PAA) to generate various surfaces with different wettability, chemistry, and roughness. Then, the adsorption of blood plasma proteins such as albumin and fibrinogen and the adhesion, activation, and aggregation of platelets with the various surfaces generated were investigated. Contact angle analysis showed PA and PAA coatings on CoCr provided a gradient of hydrophilic surfaces. FTIR showed PA and PAA were covalently bound to CoCr surface and formed different bonding configurations depending on the concentrations of coating solutions used. AFM showed the formation of homogeneous PA and PAA coatings on CoCr. The single and dual protein adsorption studies showed that the amount of albumin and fibrinogen adsorbed on the alloy surfaces strongly depend on the type of PA and PAA coatings prepared by different concentrations of coating solutions. All PA coated CoCr showed reduced platelet adhesion and activation when compared to control CoCr. Also, 75 and 100 mM PA-CoCr showed reduced platelet aggregation. For PAA coated CoCr, no significant difference in platelet adhesion and activation was observed between PAA coated CoCr and control CoCr. Thus, this study demonstrated that CoCr can be surface modified using PA for potentially reducing the formation of blood clots and improving the blood compatibility of the alloy.

We study translocations of gold nanoparticles and nanorods through silicon nitride nanopores and present a method for determining the surface charge of nanorods from the magnitude of the ionic current change as nanorods pass through the pore. Positively charged nanorods and spherical nanoparticles with average diameters 10 nm and average nanorod lengths between 44 and 65 nm were translocated through 40 nm thick nanopores with diameters between 19 and 27 nm in 1, 10, or 100 mM KCl solutions. Nanorod passage through the nanopores decreases ion current in larger diameter pores, as in the case of typical Coulter counters, but it increases ion current in smaller diameter nanopores, likely because of the interaction of the nanopore's and nanoparticle's double layers. The presented method predicts a surface charge of 26 mC/m(2) for 44 nm long gold nanorods and 18 mC/m(2) for 65 nm long gold nanorods and facilitates future studies of ligand coverage and surface charge effects in anisotropic particles.

A cellular activity-based screen on Mycobacterium tuberculosis (Mtb) H37Rv using a focused library from the AstraZeneca corporate collection led to the identification of 2-phenylindoles and arylsulphonamides, novel antimycobacterial scaffolds. Both the series were bactericidal in vitro and in an intracellular macrophage infection model, active against drug sensitive and drug resistant Mtb clinical isolates, and specific to mycobacteria. The scaffolds showed promising structure-activity relationships; compounds with submicromolar cellular potency were identified during the hit to lead exploration. Furthermore, compounds from both scaffolds were tested for inhibition of known target enzymes or pathways of antimycobacterial drugs including InhA, RNA polymerase, DprE1, topoisomerases, protein synthesis, and oxidative-phosphorylation. Compounds did not inhibit any of the targets suggesting the potential of a possible novel mode of action(s). Hence, both scaffolds provide the opportunity to be developed further as leads and tool compounds to uncover novel mechanisms for tuberculosis drug discovery.

4-Aminoquinolone piperidine amides (AQs) were identified as a novel scaffold starting from a whole cell screen, with potent cidality on Mycobacterium tuberculosis (Mtb). Evaluation of the minimum inhibitory concentrations, followed by whole genome sequencing of mutants raised against AQs, identified decaprenylphosphoryl-β-d-ribose 2'-epimerase (DprE1) as the primary target responsible for the antitubercular activity. Mass spectrometry and enzyme kinetic studies indicated that AQs are noncovalent, reversible inhibitors of DprE1 with slow on rates and long residence times of ∼100 min on the enzyme. In general, AQs have excellent leadlike properties and good in vitro secondary pharmacology profile. Although the scaffold started off as a single active compound with moderate potency from the whole cell screen, structure-activity relationship optimization of the scaffold led to compounds with potent DprE1 inhibition (IC50 < 10 nM) along with potent cellular activity (MIC = 60 nM) against Mtb.

Antiproliferative drugs such as paclitaxel and sirolimus are delivered from stents to inhibit the growth of smooth muscle cells (SMCs) for preventing neointimal hyperplasia. However, these drugs delay the growth of endothelial cells (ECs) as well and cause late stent thrombosis. We recently demonstrated the use of Vitamin-C (l-ascorbic acid, l-AA) over paclitaxel and sirolimus for inhibiting SMCs growth and promoting EC growth simultaneously. In this study, we have investigated the delivery of l-AA from CoCr alloy surfaces for potential use in stents. A polymer-free phosphoric acid (PA) platform and a polymer-based poly(lactic-co-glycolic acid) (PLGA) platform were used for coating l-AA onto CoCr surfaces. For the PA platform, FTIR confirmed that the PA was coated on CoCr, while the AFM showed that the PA coating on the CoCr surface was homogeneous. The successful deposition of l-AA on PA-coated CoCr was also confirmed by FTIR. The uniform distribution of l-AA crystals on PA-coated CoCr was shown by SEM, optical profilometer, and AFM. The drug release studies showed that l-AA (276 μg/cm(2)) was burst released from the PA platform by 1 h. For the PLGA platform, SEM showed that the l-AA incorporated polymer films were smoothly and uniformly coated on CoCr. FTIR showed that l-AA was incorporated into the bulk of the PLGA film. DSC showed that the l-AA was present in an amorphous form and formed an intermolecular bonding interaction with PLGA. The drug release studies showed that l-AA was sustained released from the PLGA coated CoCr for up to 24 h. The SEM, FTIR, and DSC characterizations of samples collected post drug release shed light on the mechanism of l-AA release from PLGA coated CoCr. Thus, this study demonstrated the delivery of l-AA from biomaterial surfaces for potential applications in stents and other implantable medical devices.

Myelin-specific proteins are either integral or peripheral membrane proteins that, in complex with lipids, constitute a multilayered proteolipid membrane system, the myelin sheath. The myelin sheath surrounds the axons of nerves and enables rapid conduction of axonal impulses. Myelin proteins interact intimately with the lipid bilayer and play crucial roles in the assembly, function, and stability of the myelin sheath. Although myelin proteins have been investigated for decades, their structural properties upon membrane surface binding are still largely unknown. In this study, we have used simplified model systems consisting of synthetic peptides and membrane mimics, such as detergent micelles and/or lipid vesicles, to probe the conformation of peptides using synchrotron radiation circular dichroism spectroscopy (SRCD). Additionally, oriented circular dichroism spectroscopy (OCD) was employed to examine the orientation of myelin peptides in macroscopically aligned lipid bilayers. Various representative peptides from the myelin basic protein (MBP), P0, myelin/oligodencrocyte glycoprotein, and connexin32 (cx32) were studied. A helical peptide from the central immunodominant epitope of MBP showed a highly tilted orientation with respect to the membrane surface, whereas the N-terminal cytoplasmic segment of cx32 folded into a helical structure that was only slightly tilted. The folding of full-length myelin basic protein was, furthermore, studied in a bicelle environment. Our results provide information on the conformation and membrane alignment of important membrane-binding peptides in a membrane-mimicking environment, giving novel insights into the mechanisms of membrane binding and stacking by myelin proteins.

The use of self-assembled monolayers (SAMs) as a polymer-free platform to deliver an antiproliferative drug, paclitaxel (PAT), from a stent material cobalt-chromium (CoCr) alloy has been previously demonstrated. In this study, the interaction of human aortic endothelial cells (ECs) and human aortic smooth muscle cells (SMCs) with CoCr alloy surfaces coated with SAMs- (SAMs-CoCr) and PAT-deposited SAMs (PAT-SAMs-CoCr) was investigated. A polished CoCr with no coatings was used as a control. The viability, proliferation, morphology, and phenotype of ECs and SMCs were investigated on these samples. SAMs-CoCr significantly enhanced the growth of ECs. Also, the ECs were well spreading with its typical morphological features and showed stronger PECAM-1 expression on SAMs-CoCr. This showed that the SAMs-CoCr surface is conducive to endothelialization. For PAT-SAMs-CoCr, although the adhesion of ECs was lower, the cells continued to proliferate with some degree of spreading and limited PECAM-1 expression. For SMCs, a significant decrease in the cell proliferation was observed on SAMs-CoCr when compared with that of Control-CoCr. PAT-SAMs-CoCr showed maximum inhibitory effect on the proliferation of SMCs. Also, the SMCs on PAT-SAMs-CoCr displayed a poorly spread discoid morphology with disarranged α-actin filaments. This showed that the PAT released from the SAMs platform successfully inhibited the growth of SMCs. Thus, this study showed the interaction of ECs and SMCs with SAMs-CoCr and PAT-SAMs-CoCr for potential uses in stents and other cardiovascular medical devices.

Cobalt-chromium (Co-Cr) alloys have extensive biomedical applications including drug-eluting stents (DES). This study investigates the use of eight different microrough Co-Cr alloy surfaces for delivering paclitaxel (PAT) for potential use in DES. The eight different surfaces include four bare microrough and four self-assembled monolayer (SAM) coated microrough surfaces. The bare microrough surfaces were prepared by grit blasting Co-Cr with glass beads (50 and 100 μm in size) and Al(2)O(3) (50 and 110 μm). The SAM coated surfaces were prepared by depositing a -COOH terminated phosphonic acid monolayer on the different microrough surfaces. PAT was then deposited on all the bare and SAM coated microrough surfaces. The surfaces were characterized using scanning electron microscopy (SEM), 3D optical profilometry, and Fourier transform infrared spectroscopy (FTIR). SEM showed the different morphologies of microrough surfaces without and with PAT coating. An optical profiler showed the 3D topography of the different surfaces and the changes in surface roughness and surface area after SAM and PAT deposition. FTIR showed ordered SAMs were formed on glass bead grit blasted surfaces, while the molecules were disordered on Al(2)O(3) grit blasted surfaces. Also, FTIR showed the successful deposition of PAT on these surfaces. The PAT release was investigated for up to two weeks using high performance liquid chromatography. Al(2)O(3) grit blasted bare microrough surfaces showed sustained release profiles, while the glass bead grit blasted surfaces showed burst release profiles. All SAM coated surfaces showed biphasic drug release profiles, which is an initial burst release followed by a slow and sustained release. SAM coated Al(2)O(3) grit blasted surfaces prolonged the sustained release of PAT in a significant amount during the second week of drug elution studies, while this behavior was not observed for any other surfaces used in this study. Thus, this study demonstrates the use of different microrough Co-Cr alloy surfaces for delivering PAT for potential applications in DES and other medical devices.

Covalent surface attachment of carbohydrate moieties using maleimide-sulfhydril reaction was characterized by surface-selective vibrational sum-frequency generation (VSFG) spectroscopy. The comparative VSFG spectra of the precursor maleimide-terminated SAM and the product glucose adlayer reveal the high efficiency of the surface coupling reaction (>90%) and the details of the molecular organization of the formed carbohydrate adlayer. The glucose groups are orientationally well ordered, as judged by their sharp C-H stretch bands. The chemical structure of the linker can significantly affect the orientation of the carbohydrate moiety at the surface. Two alkanethiol linkers of different chain lengths (11 and 16 carbons) yield similar orientations of the glucose in the adlayer whereas the cysteine-containing linker produces markedly different relative peak intensities of the glucose C-H stretch bands in the VSFG spectra, suggesting a significantly different orientation with respect to the surface plane.

Collagen, though widely used as a core biomaterial in many clinical applications, is often limited by its rapid degradability which prevents full exploitation of its potential in vivo. Polyamidoamine (PAMAM) dendrimer, a highly branched macromolecule, possesses versatile multiterminal amine surface groups that enable them to be tethered to collagen molecules and enhance their potential. In this study, we hypothesized that incorporation of PAMAM dendrimer in a collagen matrix through cross-linking will result in a durable, cross-linked collagen biomaterial with free -NH 2 groups available for further multi-biomolecular tethering. The aim of this study was to assess the physicochemical properties of a G1 PAMAM cross-linked collagen matrix and its cellular sustainability in vitro. Different amounts of G1 PAMAM dendrimer (5 or 10 mg) were integrated into bovine-derived collagen matrices through a cross-linking process, mediated by 5 or 25 mM 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) in 5 mM N-hydroxysuccinimide (NHS) and 50 mM 2-morpholinoethane sulfonic acid buffer at pH 5.5. The physicochemical properties of resultant matrices were investigated with scanning electron microscopy (SEM), collagenase degradation assay, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectra, and ninhydrin assay. Cellular sustainability of the matrices was assessed with Alamar Blue assay and SEM. There was no significant difference in cellular behavior between the treated and nontreated groups. However, the benefit of incorporating PAMAM in the cross-linking reaction was limited when higher concentrations of either agent were used. These results confirm the hypothesis that PAMAM dendrimer can be incorporated in the collagen cross-linking process in order to modulate the properties of the resulting cross-linked collagen biomaterial with free -NH 2 groups available for multi-biomolecular tethering.

Methyl- and hydroxyl-terminated phosphonic acid self-assembled monolayers (SAMs) were coated on Ti from aqueous solution. Dodecyl phosphate and dodecyltrichlorosilane SAMs were also coated on Ti using solution-phase deposition. The stability of SAMs on Ti was investigated in Tris-buffered saline (TBS) at 37 degrees C using X-ray photoelectron spectroscopy, contact angle goniometry, and atomic force microscopy. For comparison purposes, a hydroxyl-terminated thiol SAM was coated on Au, and its stability was also investigated under similar conditions. In TBS, a significant proportion of phosphonic acid or phosphate molecules were desorbed from the Ti surface within 1 day, while the trichlorosilane SAM on Ti or thiol SAM on Au was stable for up to 7 days under similar conditions. The stability of hydroxyl-terminated phosphonic acid SAM coated Ti and thiol SAM coated Au was investigated in ambient air and ultraviolet (UV) light. In ambient air, the phosphonic acid SAM on Ti was stable for up to 14 days, while the thiol SAM on Au was not stable for 1 day. Under UV-radiation exposure, the alkyl chains of the phosphonic acid SAM were decomposed, leaving only the phosphonate groups on the Ti surface after 12 h. Under similar conditions, decomposition of alkyl chains of the thiol SAM was observed on the Au surface accompanied by oxidation of thiolates.

Considering the importance of quantitative structure-toxicity relationship (QSTR) studies in the field of aquatic toxicology from the viewpoint of ecological safety assessment, fish toxicity of various benzene derivatives has been modeled by the multiple regression technique using recently introduced extended topochemical atom (ETA) indices. The toxicity data have also been modeled using other selected topological descriptors and physicochemical variables, and the best ETA model has been compared to the non-ETA ones. Principal component factor analysis was used as the data preprocessing step to reduce the dimensionality of the data matrix and identify the important variables that are devoid of collinearities. All-possible-subsets regression was also applied on the parameters to cross-check the variable selection for the best model. Multiple linear regression analyses show that the best non-ETA model involves 1chi, ALogP98, and LUMO (energy) as predictor variables and the quality of the relation is as follows: n = 92, Q2 = 0.718, Ra2 = 0.730, R2 = 0.738, R = 0.859, F = 82.8 (df 3, 88), s = 0.340. On the other hand, the best ETA model has the following quality: n = 92, Q2 = 0.865, Ra2 = 0.876, R2 = 0.885, R = 0.941, F = 92.6 (df 7, 84), s = 0.230. The ETA relations showed positive contributions of molecular bulk (size), chloro and hydroxy substitutions in the benzene ring, and the simultaneous presence of methyl and nitro substitutions to the toxicity. Further, the presence of fluoro and ether functionality, amino or nitro functionality in an otherwise unsubstituted ring, and nitro functionality that is ortho to a chloro substituent decreases toxicity. An attempt to use non-ETA descriptors along with ETA ones did not improve the quality in comparison to the best ETA model. Interestingly, the ETA model developed presently for the fish toxicity is better than the previously reported models on the same data set. Thus, it appears that ETA descriptors have significant potential in QSAR/QSPR/QSTR studies, which warrants extensive evaluation.