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Effective tumor regression has been observed with chimeric antigen receptor (CAR) T cells; however, the development of an affordable, safe, and effective CAR-T cell treatment remains a challenge. One of the major obstacles is that the suboptimal genetic modification of T cells reduces their yield and antitumor activity, necessitating the development of a next-generation T cell engineering approach. In this study, we developed a nonviral T cell nanoengineering system that allows highly efficient delivery of diverse functional nanomaterials into primary human T cells in a genetically stable and scalable manner. Our platform leverages the unique cell deformation and restoration process induced by the intrinsic inertial flow in a microchannel to create nanopores in the cellular membrane for macromolecule internalization, leading to effective transfection with high scalability and viability. The proposed approach demonstrates considerable potential as a practical alternative technique for improving the current CAR-T cell manufacturing process.

Biochar-derived dissolved black carbon (DBC) molecules are dependent on the BC formation temperature and affect the fate of emerging contaminants in waters, such as polyvinyl chloride microplastic (MP PVC ). However, the temperature-dependent evolution and MP PVC -interaction of DBC molecules remain unclear. Herein, we propose a novel DBC-MP PVC interaction mechanism by systematically interpreting heterogeneous correlations, sequential responses, and synergistic relationships of thousands of molecules and their linking functional groups. Two-dimensional correlation spectroscopy was proposed to combine Fourier transform-ion cyclotron resonance mass spectrometry and spectroscopic datasets. Increased temperature caused diverse DBC molecules and fluorophores, accompanied by molecular transformation from saturation/reduction to unsaturation/oxidation with high carbon oxidation states, especially for molecules with acidic functional groups. The temperature response of DBC molecules detected via negative-/positive-ion electrospray ionization sequentially occurred in unsaturated hydrocarbons → lignin-like → condensed aromatic → lipid-/aliphatic-/peptide-like → tannin-like → carbohydrate-like molecules. DBC molecular changes induced by temperature and MP PVC interaction were closely coordinated, with lignin-like molecules contributing the most to the interaction. Functional groups in DBC molecules with m / z < 500 showed a sequential MP PVC -interaction response of phenol/aromatic ether C-O, alkene C═C/amide C═O → polysaccharides C-O → alcohol/ether/carbohydrate C-O groups. These findings help to elucidate the critical role of DBCs in MP environmental behaviors.

This study investigated the effect of hydrogen (H) on the performance of amorphous In-Ga-Zn-Sn oxide ( a -In 0.29 Ga 0.35 Zn 0.11 Sn 0.25 O) thin-film transistors (TFTs). Ample H in plasma-enhanced atomic layer deposition (PEALD)-derived SiO 2 can diffuse into the underlying a -IGZTO film during the postdeposition annealing (PDA) process, which affects the electrical properties of the resulting TFTs due to its donor behavior in the a -IGZTO. The a -In 0.29 Ga 0.35 Zn 0.11 Sn 0.25 O TFTs at the PDA temperature of 400 °C exhibited a remarkably higher field-effect mobility (μ FE ) of 85.9 cm 2 /Vs, a subthreshold gate swing (SS) of 0.33 V/decade, a threshold voltage ( V TH ) of -0.49 V, and an I ON/OFF ratio of ∼10 8 ; these values are superior compared to those of unpassivated a -In 0.29 Ga 0.35 Zn 0.11 Sn 0.25 O TFTs (μ FE = 23.3 cm 2 /Vs, SS = 0.36 V/decade, and V TH = -3.33 V). In addition, the passivated a -In 0.29 Ga 0.35 Zn 0.11 Sn 0.25 O TFTs had good stability against the external gate bias duration. This performance change can be attributed to the substitutional H doping into oxygen sites (H O ) leading to a boost in n e and μ FE . In contrast, the beneficial H O effect was barely observed for amorphous indium gallium zinc oxide ( a -IGZO) TFTs, suggesting that the hydrogen-doping-enabled boosting of a -IGZTO TFTs is strongly related to the existence of Sn cations. Electronic calculations of V O and H O using density functional theory (DFT) were performed to explain this disparity. The introduction of SnO 2 in a -IGZO is predicted to cause a conversion from shallow V O to deep V O due to the lower formation energy of deep V O , which is effectively created around Sn cations. The formation of H O by H doping in the IGZTO facilitates the efficient connection of atomic states forming the conduction band more smoothly. This reduces the effective mass and enhances the carrier mobility.

The natural organic matter (NOM) properties in water from cold and hot mineral springs in South Korea are not well documented. We analyzed the characteristics of NOM in water from 25 cold and hot mineral springs located across South Korea. The NOM of each sample was concentrated using solid-phase extraction and analyzed using 15T Fourier-transform ion cyclotron resonance mass spectrometry. The origin of NOM was identified using van Krevelen diagrams. This study suggests that an analytical method to evaluate the characteristics of water in each region of South Korea can be established and used as a baseline for further research., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Discovery of ferroelectricity in HfO 2 has sparked a lot of interest in its use in memory and logic due to its CMOS compatibility and scalability. Devices that use ferroelectric HfO 2 are being investigated; for example, the ferroelectric field-effect transistor (FEFET) is one of the leading candidates for next generation memory technology, due to its area, energy efficiency and fast operation. In an FEFET, a ferroelectric layer is deposited on Si, with an SiO 2 layer of ∼1 nm thickness inevitably forming at the interface. This interfacial layer (IL) increases the gate voltage required to switch the polarization and write into the memory device, thereby increasing the energy required to operate FEFETs, and makes the technology incompatible with logic circuits. In this work, it is shown that a Pt/Ti/thin TiN gate electrode in a ferroelectric Hf 0.5 Zr 0.5 O 2 based metal-oxide-semiconductor (MOS) structure can remotely scavenge oxygen from the IL, thinning it down to ∼0.5 nm. This IL reduction significantly reduces the ferroelectric polarization switching voltage with a ∼2× concomitant increase in the remnant polarization and a ∼3× increase in the abruptness of polarization switching consistent with density functional theory (DFT) calculations modeling the role of the IL layer in the gate stack electrostatics. The large increase in remnant polarization and abruptness of polarization switching are consistent with the oxygen diffusion in the scavenging process reducing oxygen vacancies in the HZO layer, thereby depinning the polarization of some of the HZO grains.

Endocrine-disrupting potential was evaluated during the sewage treatment process using in vitro bioassays. Aryl hydrocarbon receptor (AhR)-, androgen receptor (AR)-, glucocorticoid receptor (GR)-, and estrogen receptor (ER)-mediated activities were assessed over five steps of the treatment process. Bioassays of organic extracts showed that AhR, AR, and GR potencies tended to decrease through the sewage treatment process, whereas ER potencies did not significantly decrease. Bioassays on reverse-phase high-performance liquid chromatography fractions showed that F5 (log K OW 2.5-3.0) had great ER potencies. Full-scan screening of these fractions detected two novel ER agonists, arenobufagin and loratadine, which are used pharmaceuticals. These compounds accounted for 3.3-25% of the total ER potencies and 4% of the ER potencies in the final effluent. The well-known ER agonists, estrone and 17β-estradiol, accounted for 60 and 17% of the ER potencies in F5 of the influent and primary treatment, respectively. Fourier transform ion cyclotron resonance mass spectrometry analysis showed that various molecules were generated during the treatment process, especially CHO and CHOS (C: carbon, H: hydrogen, O: oxygen, and S: sulfur). This study documented that widely used pharmaceuticals are introduced into the aquatic environments without being removed during the sewage treatment process.

Nanoscale polycrystalline thin-film heterostructures are central to microelectronics, for example, metals used as interconnects and high-K oxides used in dynamic random-access memories (DRAMs). The polycrystalline microstructure and overall functional response therein are often dominated by the underlying substrate or layer, which, however, is poorly understood due to the difficulty of characterizing microstructural correlations at a statistically meaningful scale. Here, an automated, high-throughput method, based on the nanobeam electron diffraction technique, is introduced to investigate orientational relations and correlations between crystallinity of materials in polycrystalline heterostructures over a length scale of microns, containing several hundred individual grains. This technique is employed to perform an atomic-scale investigation of the prevalent near-coincident site epitaxy in nanocrystalline ZrO 2 heterostructures, the workhorse system in DRAM technology. The power of this analysis is demonstrated by answering a puzzling question: why does polycrystalline ZrO 2 transform dramatically from being antiferroelectric on polycrystalline TiN/Si to ferroelectric on amorphous SiO 2 /Si?

Whole-cell-based therapy has been extensively used as an effective disease treatment approach, and it has rapidly changed the therapeutic paradigm. To fully accommodate this shift, advances in genome modification and cell reprogramming methodologies are critical. Traditionally, molecular tools such as viral and polymer nanocarriers and electroporation have been the norm for internalizing external biomolecules into cells for cellular engineering. However, these approaches are not fully satisfactory considering their cytotoxicity, high cost, low scalability, and/or inconsistent and ineffective delivery and transfection. To address these challenges, we present an approach that leverages droplet microfluidics with cell mechanoporation, bringing intracellular delivery to the next level. In our approach, cells and external cargos such as mRNAs and plasmid DNAs are coencapsulated into droplets, and as they pass through a series of narrow constrictions, the cell membrane is mechanically permeabilized where the cargos in the vicinity are internalized via convective solution exchange enhanced by recirculation flows developed in the droplets. Using this principle, we demonstrated a high level of functional macromolecule delivery into various immune cells, including human primary T cells. By utilizing droplets, the cargo consumption was drastically reduced, and near-zero clogging was realized. Furthermore, high scalability without sacrificing cell viability and superior delivery over state-of-the-art methods and benchtop techniques were demonstrated. Notably, the droplet-based intracellular delivery strategy presented here can be further applied to other mechanoporation microfluidic techniques, highlighting its potential for cellular engineering and cell-based therapies.

Calcium stannate (CaSnO 3 ) is an inorganic perovskite material with an ultrawide bandgap (4.2-4.4 eV) that is associated with its unique structural characteristics. Owing to its remarkable optical and electric properties and high physical and chemical stability, it has recently drawn significant interest for various applications such as photocatalysts for the degradation of organic compounds and hydrogen production under UV radiation, gas sensors, and thermally stable capacitors. In this study, we demonstrate a self-powered deep-UV (DUV) p-i-n photodetector consisting of CaSnO 3 thin film as an efficient DUV absorber via a low-temperature solution process. The physical, optical, and electrical properties of the as-synthesized CaSnO 3 are characterized by X-ray diffraction, Raman spectroscopy, scanning electron microscopy, high-resolution transmission electron microscopy, ultraviolet-visible spectroscopy, photoluminescence spectroscopy, space charge limited current, and four-point probe measurements. As a key component in a p-i-n DUV photodetector, the thickness of the CaSnO 3 absorber layer and operating bias are optimized to enhance charge carrier transport, light absorption, and signal-to-noise ratio. As a result, the optimized device shows a high performance at zero bias under 254 nm UV illumination: with a specific detectivity of 1.56 × 10 10 Jones, fast rise/fall time of 80/70 ms, and high 254:365 nm photocurrent rejection ratio of 5.5 along with a stable photoresponse during 100 continuous cycles initially as well as after 1 month of storage. Accordingly, this study suggests that a novel CaSnO 3 -based photodiode prepared via a solution process can be employed for many practical DUV-detection applications.

To unravel the crucial components of natural organic matter that respond to the process of anthropogenic groundwater recharge (AGR) from different recharge water sources, dissolved organic matter (DOM) and base-extractable particulate organic matter (POM) in groundwater and surface water were analyzed using excitation-emission matrix spectroscopy coupled with parallel factor analysis (EEM-PARAFAC). The EEM and traditional spectral indices of samples show that the fluorescent intensity, molecular weight, and humification degree of the DOM were relatively higher than those of the POM, and the groundwater in the reclaimed water recharge area (RWRA) was more contaminated than in the south-to-north water recharge area (SNWRA). PARAFAC analysis indicates that the DOM was dominated by an allochthonous humic-like substance (C1), whereas the POM was dominated by tryptophan-like substances associated with microbial activity (C2). Partitioning of PARAFAC components between DOM and POM showed that the humic-like substances (C1 and C4) were more likely to be distributed into a dissolved phase compared to the protein-like substances (C2 and C3), which suggested the potential use of C1 and C4 as a tracking indicator. In particular, the clear gradient distributions along both the hydrogeological profile and different aquifer systems in terms of the concentration and composition of C1 also discriminated between the RWRA and SNWRA with regard to the effects of various AGRs on the groundwater. The association between C1 and water-quality indicators revealed by principal component analysis further indicated that refractory humic-like substances would track the environmental impacts of intentional AGR processes.

Cell therapy and cellular engineering begin with internalizing synthetic biomolecules and functional nanomaterials into primary cells. Conventionally, electroporation, lipofection, or viral transduction has been used; however, these are limited by their cytotoxicity, low scalability, cost, and/or preparation complexity, especially in primary cells. Thus, a universal intracellular delivery method that outperforms the existing methods must be established. Here, we present a versatile intracellular delivery platform that leverages intrinsic inertial flow developed in a T-junction microchannel with a cavity. The elongational recirculating flows exerted in the channel substantially stretch the cells, creating discontinuities on cell membranes, thereby enabling highly effective internalization of nanomaterials, such as plasmid DNA (7.9 kbp), mRNA, siRNA, quantum dots, and large nanoparticles (300 nm), into different cell types, including hard-to-transfect primary stem and immune cells. We identified that the internalization mechanism of external cargos during the cell elongation-restoration process is achieved by both passive diffusion and convection-based rapid solution exchange across the cell membrane. Using fluidic cell mechanoporation, we demonstrated a transfection yield superior to that of other state-of-the-art microfluidic platforms as well as current benchtop techniques, including lipofectamine and electroporation. In summary, the intracellular delivery platform developed in the present study enables a high delivery efficiency (up to 98%), easy operation (single-step), low material cost (<$1), high scalability (1 × 10 6 cells/min), minimal cell perturbation (up to 90%), and cell type/cargo insensitive delivery, providing a practical and robust approach anticipated to critically impact cell-based research.

A collective synthetic route for tricyclic guaiane sesquiterpenes and total syntheses of (+)-dysodensiol F, (+)-10β,14-dihydroxy- allo -aromadendrane, and (-)-dendroside C aglycon starting from a versatile hydroazulene intermediate were accomplished. The key features of these syntheses involve late-stage carbene-mediated diastereoselective cyclopropanation, construction of an unusual cis- fused-hydroazulene skeleton via intramolecular Dieckmann condensation, and highly stereoselective tandem conjugate addition/intramolecular allylic alkylation to afford a 5/7/3 tricyclic skeleton of guaiane natural products. The synthesis of (-)-dendroside C aglycon and the first total synthesis of (+)-dysodensiol F and (+)-10β,14-dihydroxy- allo -aromadendrane are described in detail. Activation of the Nrf2/ARE signaling pathway by (-)-dendroside C aglycon is also disclosed via our synthesis.

Despite the numerous studies that have investigated the occurrence and fate of plastic particles in the environment, only a limited effort has been devoted toward exploring the characteristics of dissolved organic matter (DOM) leached from microplastics. In this study, using excitation emission matrix-parallel factor analysis (EEM-PARAFAC), we explored the fluorescence signatures of plastic-derived DOM from commonly used plastic materials, which included two polymers (polyvinyl chloride (PVC) and polystyrene (PS)), two additives (diethylhexyl phthalate (DEHP) and bisphenol A (BPA)), and two commercial plastics. The exposure of the selected plastics to UV light facilitated the leaching of DOM measured in terms of dissolved organic carbon and fluorescence intensity. Four fluorescent components were identified, which included three protein/phenol-like components (C1, C3, and C4) and one humic-like component (C2). The C1 and C4 components were highly correlated with the amounts of DOM leached from DEHP and BPA, respectively, under both leaching conditions, while both C2 and C4 presented good correlations with the DOM leached from polymers under UV light. The C4 may serve as a good fluorescence proxy for DOM leached from BPA or BPA-containing plastics. This study highlights the overlooked issue of plastic-derived DOM leaching into the aquatic environment through optical characterization.

A hybrid composite of silver nanoparticles (AgNPs) and porous silicon microparticles (pSiMPs) was developed and applied for the computed tomography (CT) scanning of the lungs as an image-guided localization agent. We confirmed the grafting of AgNPs on oxidized pSiMPs template using various analytical equipment, including a scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDS). The hybrid composite showed a high CT contrast intensity (>1000 HU) that enabled us to produce and view images of the lungs. In addition, it showed the ability to maintain a strong CT signal at the injected area of the rabbit's lungs, up to an hour, without spreading. The lack of toxicity and immune response indicated that the composite could be fully utilized as a new image-guided localization agent of CT scans for lung cancer surgery.

In light of the importance of and challenges inherent in realizing a wearable healthcare platform for simultaneously recognizing, preventing, and treating diseases while tracking vital signs, the development of simple and customized functional devices has been required. Here, we suggest a new approach for making a stretchable light waveguide which can be combined with integrated functional devices, such as organic photodetectors (PDs) and nanowire-based heaters, for multifunctional healthcare monitoring. Controlling the reflection condition of the medium gave a solid design rule for strong light emission in our stretchable waveguides. Based on this rule, the stretchable light waveguide (up to 50% strain) made of polydimethylsiloxane was successfully demonstrated with strong emissions. We also incorporated highly sensitive organic PDs and silver nanowire-based heaters with the stretchable waveguide for the detection of vital signs, including the heart rate, deep breathing, coughs, and blood oxygen saturation. Through these multifunctional performances, we have successfully demonstrated that our stretchable light waveguide has a strong potential for multifunctional healthcare monitoring.

Effect-directed analysis was used to identify previously unidentified aryl hydrocarbon receptor (AhR) agonists in sediments collected from a highly industrialized area of Ulsan Bay, Korea. The specific objectives were to (i) investigate potent fractions of sediment extracts using the H4IIE- luc bioassay, (ii) determine the concentrations of known AhR agonists (polycyclic aromatic hydrocarbons (PAHs) and styrene oligomers (SOs)), (iii) identify previously unreported AhR agonists in fractions by use of GC-QTOFMS, and (iv) evaluate contributions of individual compounds to overall AhR-mediated potencies, found primarily in fractions containing aromatics with log K ow 5-8. Greater concentrations of PAHs and SOs were also found in those fractions. On the basis of GC-QTOFMS and GC-MSD analyses, 16 candidates for AhR agonists were identified in extracts of sediments. Of these, seven compounds, including 1-methylchrysene, benzo[ j ]fluoranthene, 3-methylchrysene, 5-methylbenz[ a ]anthracene, 11 H -benzo[ b ]fluorene, benzo[ b ]naphtho[2,3- d ]furan, and benzo[ b ]naphtho[2,1- d ]thiophene, exhibited significant AhR activity. Relative potency values of newly identified AhR agonists were found to be greater than or comparable to that of benzo[ a ]pyrene (BaP). The potency balance analysis showed that newly identified AhR agonists explained 0.07-16% of bioassay-derived BaP-EQs. These chemicals were widely distributed in industrial sediments; thus, it is of immediate importance to conduct studies on sources and potential effects of those chemicals.

Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1α, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure-activity relationship of ring-truncated deguelin analogs in HIF-1α inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1α inhibitory activity, with an IC 50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-1α inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1α inhibitors that can be used in lieu of a chromene ring.

WS9326H (1), a new cyclic peptide, was isolated from a mudflat-derived Streptomyces strain. Based on analysis by 1D/2D NMR, UV spectroscopy, and mass spectrometry, compound 1 was determined to have the gross structure of a cyclic heptapeptide bearing an unprecedented pyrazolone ring connected to a d-arabinitol via an amide bond. The absolute configuration of 1 was established by multistep chemical derivatizations, comprehensive NMR, and LC/MS analyses of the derivatives and quantum mechanics-based computational methods. WS9326H (1) displayed significant antiangiogenesis activity.

The adsorption behaviors of different constituents within bulk humic substances (HS) on two nanoparticles, TiO 2 and ZnO, were examined by using two-dimensional correlation size exclusion chromatography (2D-CoSEC) and excitation emission matrix-parallel factor analysis (EEM-PARAFAC), which separated bulk HS into different size fractions and fluorescent components, respectively. Subtle changes in the size distributions of HS with increasing adsorbents were successfully identified and tracked via the 2D-CoSEC. From adsorption isotherm experiments, three different HS constituent groups with respect to sizes and fluorescence features were identified by the 2D-CoSEC and EEM-PARAFAC, respectively. The chromatographically separated HS size groups presented dissimilar adsorption behaviors in terms of adsorption affinity and isotherm nonlinearity. The sequence orders of adsorption, interpreted from the 2D-CoSEC, was consistent with those of the isotherm model parameters individually calculated for different HS size subfractions, signifying the promising application of 2D-CoSEC in obtaining an insight into the heterogeneous adsorption of HS in terms of molecular sizes. EEM-PARAFAC results also supported the major finding of the 2D-CoSEC as shown by the preferential adsorption of the fluorescent components associated with large molecular sizes.

Flexible and stretchable optoelectronic devices can be potentially applied in displays, biosensors, biomedicine, robotics, and energy generation. The use of nanomaterials with superior optical properties such as quantum dots (QDs) is important in the realization of wearable displays and biomedical devices, but specific structural design as well as selection of materials should preferentially accompany this technology to realize stretchable forms of these devices. Here, we report stretchable optoelectronic sensors manufactured using colloidal QDs and integrated with elastomeric substrates, whose optoelectronic properties are stable under various deformations. A graphene electrode is adopted to ensure extreme bendability of the devices. Ultrathin QD light-emitting diodes and QD photodetectors are transfer-printed onto a prestrained elastomeric layout to form wavy configurations with regular patterns. The layout is mechanically stretchable until the structure is converted to a flat configuration. The emissive and active area itself can be stretched or compressed by buckled structures, which are applicable to wearable electronic devices. We demonstrate that these stretchable optoelectronic sensors can be used for continuous monitoring of blood waves via photoplethysmography signal recording. These and related systems create important and unconventional opportunities for stretchable and foldable optoelectronic devices with health-monitoring capability and, thus, meet the demand for wearable and body-integrated electronics.

We investigated the antioxidative properties of (2R,3S,2″R,3″R)-manniflavanone (MF) using in vitro assays and examined its effects on myogenesis and lactate-induced oxidative stress in C2C12 cells. MF was purified from Garcinia buchananii stem bark. H 2 O 2 and oxygen radical absorbance capacity assays demonstrated that MF is a powerful antioxidant. This finding was supported by diphenylpicrylhydrazine radical scavenging activity of MF. MF was less cytotoxic to C2C12 cells compared to ascorbic acid and myricetin. Moreover, MF accelerated myotube formation in the differentiated C2C12 cells by up-regulating myogenic proteins such as MyoG and myosin heavy chain. Furthermore, MF rescued late differentiation of myoblast suppressed by lactate treatment and up-regulated the expression levels of Nrf2 in lactate-induced oxidative stress, indicating that MF stimulates antioxidative activity inside C2C12 cells. Collectively, MF is a potent antioxidant with a higher safety profile than ascorbic acid and myricetin. It reduces oxidative stress-induced delaying of skeletal muscle differentiation by scavenging reactive oxygen species and regulating myogenic proteins factors.

Methylmercury (MeHg) accumulation in marine organisms poses serious ecosystem and human health risk, yet the sources of MeHg in the surface and subsurface ocean remain uncertain. Here, we report the first MeHg mass budgets for the Western Pacific Ocean estimated based on cruise observations. We found the major net source of MeHg in surface water to be vertical diffusion from the subsurface layer (1.8-12 nmol m -2  yr -1 ). A higher upward diffusion in the North Pacific (12 nmol m -2  yr -1 ) than in the Equatorial Pacific (1.8-5.7 nmol m -2  yr -1 ) caused elevated surface MeHg concentrations observed in the North Pacific. We furthermore found that the slope of the linear regression line for MeHg versus apparent oxygen utilization in the Equatorial Pacific was about 2-fold higher than that in the North Pacific. We suggest this could be explained by redistribution of surface water in the tropical convergence-divergence zone, supporting active organic carbon decomposition in the Equatorial Pacific Ocean. On the basis of this study, we predict oceanic regions with high organic carbon remineralization to have enhanced MeHg concentrations in both surface and subsurface waters.

Three-dimensional (3-D) fin-structured carbon nanotube field-effect transistors (CNT-FETs) with purified 99.9% semiconducting CNTs were demonstrated on a large scale 8 in. silicon wafer. The fabricated 3-D CNT-FETs take advantage of the 3-D geometry and exhibit enhanced electrostatic gate controllability and superior charge transport. A trigated structure surrounding the randomly networked single-walled CNT channel was formed on a fin-like 3-D silicon frame, and as a result, the effective packing density increased to almost 600 CNTs/μm. Additionally, highly sensitive controllability of the threshold voltage (V TH ) was achieved using a thin back gate oxide in the same silicon frame to control power consumption and enhance performance. Our results are expected to broaden the design margin of CNT-based circuit architectures for versatile applications. The proposed 3-D CNT-FETs can potentially provide a desirable alternative to silicon based nanoelectronics and a blueprint for furthering the practical use of emerging low-dimensional materials other than CNTs.

Adsorption isotherms of extracellular polymeric substances (EPS) on graphene oxide (GO) and reduced GO (rGO) were studied using fluorescence excitation-emission matrix-parallel factor analysis (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2D-COS) combined with Fourier transform infrared spectroscopy (FTIR). Chemical reduction of GO resulted in a greater extent of carbon adsorption with a higher degree of isotherm nonlinearity, suggesting that heterogeneous adsorption sites were additionally created by GO reduction. Two protein-like and two humic-like components were identified from EPS by EEM-PARAFAC. Adsorption of protein-like components was greater than that of humic-like components, and the preferential adsorption was more pronounced for GO versus rGO. Adsorption of protein-like components was more governed by site-limiting mechanisms than humic-like components as shown by the higher isotherm nonlinearity. 2D-COS provided further information on the adsorption of secondary protein structures. Adsorption of the EPS structures related to amide I and aromatic C-C bands was greater for rGO versus GO. Protein structures of EPS were more favorable for adsorption in the order of α-helix → amide II → β-sheet structures with increasing site limitation. Our results revealed successful applicability of EEM-PARAFAC and 2D-COS in examining the adsorption behavior of heterogeneous biological materials on graphene materials.

A vertically integrated junctionless field-effect transistor (VJ-FET), which is composed of vertically stacked multiple silicon nanowires (SiNWs) with a gate-all-around (GAA) structure, is demonstrated on a bulk silicon wafer for the first time. The proposed VJ-FET mitigates the issues of variability and fabrication complexity that are encountered in the vertically integrated multi-NW FET (VM-FET) based on an identical structure in which the VM-FET, as recently reported, harnesses a source and drain (S/D) junction for its operation and is thus based on the inversion mode. Variability is alleviated by bulk conduction in a junctionless FET (JL-FET), where current flows through the core of the SiNW, whereas it is not mitigated by surface conduction in an inversion mode FET (IM-FET), where current flows via the surface of the SiNW. The fabrication complexity is reduced by the inherent JL structure of the JL-FET because S/D formation is not required. In contrast, it is very difficult to dope the S/D when it is positioned at each floor of a tall SiNW with greater uniformity and with less damage to the crystalline structure of the SiNW in a VM-FET. Moreover, when the proposed VJ-FET is used as nonvolatile flash memory, the endurance and retention characteristics are improved due to the above-mentioned bulk conduction.

A vertically integrated multiple channel-based field-effect transistor (FET) with the highest number of nanowires reported ever is demonstrated on a bulk silicon substrate without use of wet etching. The driving current is increased by 5-fold due to the inherent vertically stacked five-level nanowires, thus showing good feasibility of three-dimensional integration-based high performance transistor. The developed fabrication process, which is simple and reproducible, is used to create multiple stiction-free and uniformly sized nanowires with the aid of the one-route all-dry etching process (ORADEP). Furthermore, the proposed FET is revamped to create nonvolatile memory with the adoption of a charge trapping layer for enhanced practicality. Thus, this research suggests an ultimate design for the end-of-the-roadmap devices to overcome the limits of scaling.

Metal thin film electrodes on flexible polymer substrates are inherently unstable against humidity and mechanical stresses because of their poor adhesion properties. We introduce a novel approach for improving the adhesion characteristics of metal-polymer interface based on the nanostructuring of the polymer substrate by using nanoimprint lithography. The adhesion characteristics of metal-polymer interface were measured by accelerated test, cyclic bending test and double cantilever beam (DCB) test. The interface of Au/Ti dual layer thin film and nanoimprinted PMMA substrate shows over 2.03 and 1.95 times higher adhesion energy (G(c)) than that of Au/Ti dual layer thin film and plane PMMA substrate in air and wet environments, respectively. The adhesion energy between metal thin film and polymer substrate was dramatically improved by the increased surface roughness and mechanical interlocking effect of numerous nanoscale anchors at the edges of nanoimprinted surface, which was verified by both experiment and numerical analysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious cutaneous adverse reactions. We mined the approved labels in Drugs@FDA, identified the SJS/TEN list of 259 small molecular drugs and biologics, and conducted systems pharmacological network analyses. Pharmacological network analysis revealed that drugs with treatment-related SJS and/or TEN are pharmacologically diverse and that the largest subnetwork is associated with antiepileptic drugs and their pharmacological targets. Our pharmacological network analysis identified CTNNB1 [catenin (cadherin-associated protein), beta 1, 88 kDa] as a significant intermediator. This protein is involved in maintaining the functional integrity of the epithelium through regulating cell growth and adhesion between cells in various organs, including the skin. Leveraging a publicly accessible genome-wide transcriptional expression database, we found that human leukocyte antigen-related (HLA) genes were significantly perturbed by various SJS/TEN-inducing drugs. Notably, carbamazepine (CBZ) perturbed several HLA genes, among which HLA-DQB1*0201 was reportedly shown to be associated with CBZ-induced SJS/TEN in caucasians. In short, systems analysis by leveraging a publicly accessible knowledge base and databases could produce meaningful results for further mechanistic investigation. Our study sheds light on the utility of systems pharmacology analysis for gaining insight into clinical drug toxicity.

We investigated systematic modulation of the Dirac point voltage of graphene transistors by changing the type of ionic liquid used as a main gate dielectric component. Ion gels were formed from ionic liquids and a non-triblock-copolymer-based binder involving UV irradiation. With a fixed cation (anion), the Dirac point voltage shifted to a higher voltage as the size of anion (cation) increased. Mechanisms for modulation of the Dirac point voltage of graphene transistors by designing ionic liquids were fully understood using molecular dynamics simulations, which excellently matched our experimental results. It was found that the ion sizes and molecular structures play an essential role in the modulation of the Dirac point voltage of the graphene. Through control of the position of their Dirac point voltages on the basis of our findings, complementary metal-oxide-semiconductor (CMOS)-like graphene-based inverters using two different ionic liquids worked perfectly even at a very low source voltage (V(DD) = 1 mV), which was not possible for previous works. These results can be broadly applied in the development of low-power-consumption, flexible/stretchable, CMOS-like graphene-based electronic devices in the future.

Conductive hydrogels are a class of composite materials that consist of hydrated and conducting polymers. Due to the mechanical similarity to biointerfaces such as human skin, conductive hydrogels have been primarily utilized as bioelectrodes, specifically neuroprosthetic electrodes, in an attempt to replace metallic electrodes by enhancing the mechanical properties and long-term stability of the electrodes within living organisms. Here, we report a conductive, smart hydrogel, which is thermoplastic and self-healing owing to its unique properties of reversible liquefaction and gelation in response to thermal stimuli. In addition, we demonstrated that our conductive hydrogel could be utilized to fabricate bendable, stretchable, and patternable electrodes directly on human skin. The excellent mechanical and thermal properties of our hydrogel make it potentially useful in a variety of biomedical applications such as electronic skin.

The goal of this study was to integrate systems pharmacology and biochemical flux to delineate drug-induced rhabdomyolysis by leveraging prior knowledge and publicly accessible data. A list of 211 rhabdomyolysis-inducing drugs (RIDs) was compiled and curated from multiple sources. Extended pharmacological network analysis revealed that the intermediators directly interacting with the pharmacological targets of RIDs were significantly enriched with functions such as regulation of cell cycle, apoptosis, and ubiquitin-mediated proteolysis. A total of 78 intermediators were shown to be significantly connected to at least five RIDs, including estrogen receptor 1 (ESR1), synuclein gamma (SNCG), and janus kinase 2 (JAK2). Transcriptomic analysis of RIDs profiled in Connectivity Map on the global scale revealed that multiple pathways are perturbed by RIDs, including ErbB signaling and lipid metabolism pathways, and that carnitine palmitoyl transferase 2 (CPT2) was in the top 1 percent of the most differentially perturbed genes. CPT2 was downregulated by nine drugs that perturbed the genes significantly enriched in oxidative phosphorylation and energy-metabolism pathways. With statins as the use case, biochemical pathway analysis on the local scale implicated a role for CPT2 in statin-induced perturbation of energy homeostasis, which is in agreement with reports of statin-CPT2 interaction. Considering the complexity of human biology, an integrative multiple-approach analysis composed of a biochemical flux network, pharmacological on- and off-target networks, and transcriptomic signature is important for understanding drug safety and for providing insight into clinical gene-drug interactions.

Graphene has received considerable attention in both scientific and technological areas due to its extraordinary material properties originating from the atomically single- or small number-layered structure. Nevertheless, in most scalable solution-based syntheses, graphene suffers from severe restacking between individual sheets and thus loses its material identity and advantages. In the present study, we have noticed the intercalated water molecules in the dried graphene oxide (GO) as a critical mediator to such restacking and thus eliminated the hydrogen bonding involving the intercalated water by treating GO with melamine resin (MR) monomers. Upon addition of MR monomers, porous restacking-inhibited GO sheets precipitated, leading to the carbonaceous composite with an exceptionally large surface area of 1040 m(2)/g after a thermal treatment. Utilizing such high surface area, the final graphene composite exhibited excellent electrochemical performance as a supercapacitor electrode material: specific capacitance of 210 F/g, almost no capacitance loss for 20,000 cycles, and ~7 s rate capability. The current study delivers a message that various condensation reactions engaging GO sheets can be a general synthetic approach for restacking-inhibited graphene in scalable solution processes.

We report a nanoparticle-based probe that can be used for a "turn-on" theragnostic agent for simultaneous Raman imaging/diagnosis and photothermal therapy. The agent consists of a 10 nm spherical gold nanoparticle (NP) with pH-responsive ligands and Raman probes on the surface. They are engineered to exhibit the surface with both positive and negative charges upon mildly acidic conditions, which subsequently results in rapid aggregations of the gold NPs. This aggregation simultaneously provides hot spots for the SERS probe with the enhancement factor reaching 1.3 × 10(4) and shifts the absorption to far-red and near-infrared (which is optimal for deep tissue penetration) by the coupled plasmon resonances; this shift was successfully exploited for low-threshold photothermal therapy. The theragnostic gold NPs are cancer-specific because they aggregate rapidly and accumulate selectively in cancerous cells. As the result, both Raman imaging and photothermal efficacy were turned on under a cancerous local environment. In addition, the relatively small hydrodynamic size can have the potential for better access to targeted delivery in vivo and facilitated excretion after therapy.

We report the structural behavior for mixtures of two differently sized ("bidisperse") silica microspheres at the air-water interface under three different size ratio conditions (alpha (identical with R(S)/R(L)) = 0.375, 0.500, and 0.579). These bidisperse silica monolayers were studied via measurement of the surface pressure-area isotherm and optical microscopy at various particle surface coverages (theta identical with theta(S) + theta(L)) during compression. The silica colloids used in these trials were found to possess purely repulsive pair interactions at the air-water interface, which was confirmed by the pair correlation function calculated from the analysis of many optical images of the particles taken at dilute concentrations. The results revealed that, at certain mixture compositions (beta identical with theta(L)/theta(S)), compression can lead to the formation of 2D binary crystal structures. Specifically, at a particle size ratio of alpha = 0.375, LS1 crystal domains were observed at a surface coverage of theta approximately 0.619 when beta = 7.00 and 3.50, although this LS1 structure was not observed at higher total particle densities (where the system became phase-separated). At a size ratio of alpha = 0.579, compression produced 2D LS2 binary crystals at particle surface coverages (theta) above 0.641 when beta = 3.00, 1.50, or 1.00. However, at a size ratio of alpha = 0.500, compression triggered macroscopic phase separation, leading to the formation of two separate hexagonal-close-packed domains consisting purely of either large or small particles. In general, when the mixture composition (beta) was too different from the stoichiometric ratio needed for the formation of LS1 or LS2 superlattices, the bidisperse monolayer was observed to remain in an amorphous state rather than evolving to an ordered phase under compression. These findings suggest that, in two dimensions, contrary to what has been speculated in the literature, (1) purely repulsive pair potentials can give rise to LS1 and LS2 binary crystals under compression and also (2) perfectly spherical particles can form LS2 crystals. This discrepancy between our results and the predictions of previous simulations might indicate that the capillary interaction and/or the many-body effects play a significant role in determining the structure of bidisperse colloids at the air-water interface.

We have functionalized core-shell CdSe/ZnS quantum dots (QDs) with a photosensitive monolayer, rendering them solution processable and photopatternable. Upon exposure to ultraviolet radiation, films composed of this material were found to polymerize, forming interconnected arrays of QDs. The photoluminescence properties of the nanocrystal films increased with photocuring. The material was found to be suitable for spin casting and was used as the active layer in a green electroluminescent device. The electroluminescence efficiency of devices containing a photocured active layer was found to be largely enhanced when compared to devices containing nonphotocured active layers. The material also showed excellent adhesion to both organic and inorganic substrates because of the unique combination of a siloxane and a photopatternable layer as ligands. The pristine functionalized nanocrystals could easily be used for two-dimensional patterning on organic and inorganic substrates. The photopatternable quantum dots were uniformly dispersed into a photopolymerizable resin to fabricate QD embedded three-dimensional microstructures.

We investigated, by experiment and theory, the lateral structure of a weak polyelectrolyte brush at various added salt concentrations and chain grafting densities. Model poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes with grafting density gradients were developed for this study by using a novel "Langmuir-Blodgett-deposition-under-compression" (LB\C) method. Fluid AFM images of these brushes indicate that the lateral structure of the brush system is sensitive to both added salt concentration and grafting density. Under low salt conditions, 0-20 mM NaCl, the brush structure shows strong microscopic lateral heterogeneities at high grafting densities; both the width and height of the heterogeneities increase with increasing grafting density but are independent of the salt concentration. As the bulk salt concentration is increased to an intermediate regime, 60-100 mM NaCl, these heterogeneities become smaller in size and number, coexisting with smooth homogeneous regions. At high enough concentrations, 300-500 mM NaCl, the entire surface becomes homogeneous. A simple free energy-based Flory-type argument is presented which explains the essential features of the thermodynamic behavior of the brush system. In the zero-salt limit, relatively few monomers are charged, and the hydrophobicity of the backbone chain drives the collapse/aggregation of the chains. At high salt concentrations, the brush chains become sufficiently charged to overcome the hydrophobic nature of the monomers and stabilize the homogeneous state. However, at intermediate salt concentrations, it is found that the osmotic pressure of the counterions surrounding the charged polymer moieties can be decreased by collapsing the chain structure while simultaneously decreasing the number of charges along the backbone and releasing small ions into the bulk solution. This effect, which we term "osmotic instability", serves to destabilize the homogeneous brush configuration.

Changes in selected spectroscopic and chromatographic characteristics of water-soluble organic matter (WSOM) extracted from leaf litter and its ability to bind pyrene were monitored throughout 14 day microbial incubation experiments. To provide additional insight into the microbial transformation of the WSOM, incubation experiments were similarly conducted with controlled-composition mixtures of glucose and dissolved humic substances (HS) that were base extracted from the same leaf litter source. Microbial transformation increased the specific ultraviolet absorbance and number-average molecular weight of residual WSOM while polydispersity values decreased. Fluorescence measurements revealed loss of protein-like fluorescence and enhancement of fulvic- and humic-like fluorescence in residual WSOM. Overall, the incubation results suggest that nonaromatic and smaller sized carbon structures were being degraded while the microbial activity produced humic-like aromatic components in solution. Together, these changes resulted in enhanced pyrene binding by the altered WSOM. Consistent findings resulted from mixtures of glucose and the leaf litter HS. Changes in measured operational descriptors were more pronounced for mixtures containing a higher percentage of glucose, suggesting that utilization of labile constituents may be necessary for formation of unknown structures associated with high pyrene binding capabilities. Simple mass balance, end member mixing models often failed to predict changes in pyrene binding brought about by microbial transformation, suggesting that microbial utilization of labile constituents is not the predominant process governing the enhanced pyrene binding.

In this paper, we demonstrate that two-dimensional (2D) periodic patterns of polyelectrolyte multilayers (PEMs) can be used as surface templates for assembling highly ordered 2D colloidal microarrays. We report detailed structural features of the 2D colloid crystals produced by depositing silica microspheres onto periodic micrometer-scale PEM patterns arrayed in a square or hexagonal lattice with a pattern pitch (approximately) twice the pattern diameter. Analysis of the images of these 2D colloid monolayers reveals that the distributions of the distances by which the adsorbed particles deviate from the corresponding PEM pattern centers are typically bell-shaped, with the majority of the deposited particles located within a relatively short distance from the respective pattern centers. We show that this behavior reflects the effect of the electrostatic focusing force that (occurs because of the finite size of the PEM pattern and) becomes effective when the depositing particle approaches the pattern site to a small distance. Also, in these 2D colloid crystals, the orientations of the off-center displacements of the deposited particles are strongly correlated spatially over the entire sample size. We present experimental evidence that this unusually long-ranged orientational correlation is due to the close spacing of the patterns, which causes an overlap of the excluded volumes between the neighboring deposited particles.

Changes in pyrene binding by dissolved and mineral-associated humic substances (HS) due to HS adsorptive fractionation processes were examined in model environmental systems using purified Aldrich humic acid (PAHA) and Suwannee River fulvic acid (SRFA). For PAHA, carbon-normalized pyrene binding coefficients for nonadsorbed, residual fractions (Koc(res)) were different from the original dissolved PAHA Koc value (Koc(orig)) prior to contact with the mineral suspensions. A strong positive correlation between pyrene log Koc(res) and log weight-average molecular weight (MWw) for residual PAHA fractions was observed, which was relatively independent of the specific mineral adsorbent used and hypothesized fractionation processes. A strong positive correlation between log Koc(ads) and log MWw was also found for PAHA fractions adsorbed to kaolinite at low mass fraction organic carbon levels, although the relationship was statistically different from the one found with residual PAHA fractions. The same trends and correlations found for PAHA were not observed with SRFA, suggesting that the impacts of HS adsorptive fractionation on changes in hydrophobic organic contaminants binding are also influenced by the source and other biogeochemical characteristics of HS.

The heterogeneity within a bulk humic substance (HS) was investigated for ultrafiltration (UF) fractions of purified Aldrich humic acid (PAHA) using specific ultraviolet absorbance (SUVA), weight- and number-average molecular weights (MWw and MWn), and organic carbon-normalized pyrene binding coefficients (Koc). As expected, variations in these selected operational descriptors were found for the PAHA UF fractions, but the variations were smaller than the ranges observed for a small subset of different aquatic and terrestrial HS. In general, correlations among the operational descriptors for the different HS failed to predict the correct trends for the PAHA UF fractions. More variation in Koc was observed for the different HS versus the PAHA UF fractions despite comparable molecular weight ranges, suggesting that the extent of pyrene binding is more strongly influenced by HS source and chemical structure than merely by physical structural features. Size-exclusion chromatography (SEC) confirmed the structural stability of PAHA UF fractions, as demonstrated by a near-identical mathematical reconstruction of the original bulk chromatogram from a weighted summation of the individual UF fraction chromatograms. An ideal mixture model accurately predicted some operational descriptors of PAHA properties (i.e., SUVA and MWw), but failed to predict the PAHA reactivity for pyrene binding. Our Koc results at pH 4 and 7 suggest that the relative contribution of two mechanisms, partitioning and specific interactions, may account for the interactions between HS and pyrene.