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LSD1 (histone lysine-specific demethylase 1) has been gradually disclosed to act as an immunomodulator to enhance antitumor immune response. Despite the identification of numerous potent LSD1 inhibitors, there remains a lack of LSD1 inhibitors approved for marketing. Novel LSD1 inhibitors with different mechanisms are therefore needed. Herein, we reported a series of novel quinazoline-based LSD1 inhibitors. Among them, compound Z-1 exhibited the best LSD1 inhibitory activity (IC 50 = 0.108 μM). Z-1 also acted as a selective and cellular active as an LSD1 inhibitor. Furthermore, Z-1 promoted response of gastric cancer cells to T-cell killing effect by decreasing PD-L1 expression and further attenuated the PD-1/PD-L1 interaction. In vivo, Z-1 exhibited significant suppression effect on the growth of gastric cancer cells without obvious toxicity. Therefore, Z-1 represents a potential novel immunomodulator that targets LSD1, providing a lead compound with new function mechanism for gastric cancer treatment.

A concise and efficient method for the construction of fully substituted difluoromethylpyrazoles is achieved by a cyclization reaction between difluoroacetohydrazonoyl bromides and 2-acylacetonitrile or malononitrile. The method features advantages such as mild reaction conditions, broad substrate scope, good product yields, and high regioselectivity.

Macrophages are innate immune cells that interact with complex extracellular matrix environments, which have varied stiffness, composition, and structure, and such interactions can lead to the modulation of cellular activity. Collagen is often used in the culture of immune cells, but the effects of substrate functionalization conditions are not typically considered. Here, we show that the solvent system used to attach collagen onto a hydrogel surface affects its surface distribution and organization, and this can modulate the responses of macrophages subsequently cultured on these surfaces in terms of their inflammatory activation and expression of adhesion and mechanosensitive molecules. Collagen was solubilized in either acetic acid (Col-AA) or N -(2-hydroxyethyl)piperazine- N' -ethanesulfonic acid (HEPES) (Col-HEP) solutions and conjugated onto soft and stiff polyacrylamide (PA) hydrogel surfaces. Bone marrow-derived macrophages cultured under standard conditions (pH 7.4) on the Col-HEP-derived surfaces exhibited stiffness-dependent inflammatory activation; in contrast, the macrophages cultured on Col-AA-derived surfaces expressed high levels of inflammatory cytokines and genes, irrespective of the hydrogel stiffness. Among the collagen receptors that were examined, leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) was the most highly expressed, and knockdown of the Lair-1 gene enhanced the secretion of inflammatory cytokines. We found that the collagen distribution was more homogeneous on Col-AA surfaces but formed aggregates on Col-HEP surfaces. The macrophages cultured on Col-AA PA hydrogels were more evenly spread, expressed higher levels of vinculin, and exerted higher traction forces compared to those of cells on Col-HEP. These macrophages on Col-AA also had higher nuclear-to-cytoplasmic ratios of yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), key molecules that control inflammation and sense substrate stiffness. Our results highlight that seemingly slight variations in substrate deposition for immunobiology studies can alter critical immune responses, and this is important to elucidate in the broader context of immunomodulatory biomaterial design.

Lysine specific demethylase 1 (LSD1), a transcriptional modulator that represses or activates target gene expression, is overexpressed in many cancer and causes imbalance in the expression of normal gene networks. Over two decades, numerous LSD1 inhibitors have been reported, especially some of which have entered clinical trials, including eight irreversible inhibitors (TCP, ORY-1001, GSK-2879552, INCB059872, IMG-7289, ORY-2001, TAK-418, and LH-1802) and two reversible inhibitors (CC-90011 and SP-2577). Most clinical LSD1 inhibitors demonstrated enhanced efficacy in combination with other agents. LSD1 multitarget inhibitors have also been reported, exampled by clinical dual LSD1/histone deacetylases (HDACs) inhibitors 4SC-202 and JBI-802. Herein, we present a comprehensive overview of the combination of LSD1 inhibitors with various antitumor agents, as well as LSD1 multitarget inhibitors. Additionally, the challenges and future research directionsare also discussed, and we hope this review will provide new insight into the development of LSD1-targeted anticancer agents.

Coxiella burnetii is the causative agent of Q fever, for which there is yet to be an FDA-approved vaccine. This bacterial pathogen has both extra- and intracellular stages in its life cycle, and therefore both a cell-mediated (i.e., T lymphocyte) and humoral (i.e., antibody) immune response are necessary for effective eradication of this pathogen. However, most proposed vaccines elicit strong responses to only one mechanism of adaptive immunity, and some can either cause reactogenicity or lack sufficient immunogenicity. In this work, we aim to apply a nanoparticle-based platform toward producing both antibody and T cell immune responses against C. burnetii . We investigated three approaches for conjugation of the immunodominant outer membrane protein antigen (CBU1910) to the E2 nanoparticle to obtain a consistent antigen orientation: direct genetic fusion, high affinity tris-NTA-Ni conjugation to polyhistidine-tagged CBU1910, and the SpyTag/SpyCatcher (ST/SC) system. Overall, we found that the ST/SC approach yielded nanoparticles loaded with the highest number of antigens while maintaining stability, enabling formulations that could simultaneously co-deliver the protein antigen (CBU1910) and adjuvant (CpG1826) on one nanoparticle (CBU1910-CpG-E2). Using protein microarray analyses, we found that after immunization, antigen-bound nanoparticle formulations elicited significantly higher antigen-specific IgG responses than soluble CBU1910 alone and produced more balanced IgG1/IgG2c ratios. Although T cell recall assays from these protein antigen formulations did not show significant increases in antigen-specific IFN-γ production compared to soluble CBU1910 alone, nanoparticles conjugated with a CD4 peptide epitope from CBU1910 generated elevated T cell responses in mice to both the CBU1910 peptide epitope and whole CBU1910 protein. These investigations highlight the feasibility of conjugating antigens to nanoparticles for tuning and improving both humoral- and cell-mediated adaptive immunity against C. burnetii .

Despite the acknowledged advantages of combined immunochemotherapy for tumor treatment, the high efficiency of co-delivery of these combined agents into the targeted tumor tissue is still challenging. Herein, based on a "three-birds-with-one-stone" strategy, a facile glycyrrhizic acid (GL)-lipid hybrid nanoplatform loading triptolide (TP/GLLNP) is designed to better address the dilemma. Differing from the traditional liposomes with dual-drug co-delivery NPs, GL with a cholesterol-like structure is primarily employed to construct the lipid membrane skeleton of the GL-based lipid nanoparticle (GLLNP), and then triptolide (TP) is readily loaded in the lipid bilayer of GLLNP. The fabricated GLLNP possessed similar drug loading efficacy, particle size, and storage stability; none of the hemolysis; even higher membrane fluidity; and lower absorbed opsonin proteins compared with the conventional liposomes. Compared to TP-loaded traditional liposomes (TP/Lipo), TP/GLLNP exhibits significantly enhanced cellular uptake, cytotoxicity, and apoptosis of HepG2 cells. In addition, GLLNP could ameliorate tumor immunosuppression by promoting tumor-associated macrophage polarization from M2 to M1 phenotype. Furthermore, enhanced retention and accumulation in the tumor area of GLLNP could be found. As expected, TP/GLLNP displayed synergistic anti-hepatocellular carcinoma efficacy in vivo . In conclusion, this study provides an inspirational strategy to combine the anti-HCC benefits of GL and TP using a novel dual-drug co-delivery nanosystem.

Polysaccharides have been successfully used as immunogens for the development of vaccines against bacterial infection; however, there are no oligosaccharide-based vaccines available to date and no previous studies of their processing and presentation. We reported here the intracellular enzymatic processing and antigen presentation of an oligosaccharide-conjugate cancer vaccine prepared from the glycan of Globo-H (GH), a globo-series glycosphingolipid (GSL). This oligosaccharide-conjugate vaccine was shown to elicit antibodies against the glycan moieties of all three globo-series GSLs that are exclusively expressed on many types of cancer and their stem cells. To understand the specificity and origin of cross-reactivity of the antibodies elicited by the vaccine, we found that the vaccine is first processed by fucosidase 1 in the early endosome of dendritic cells to generate a common glycan antigen of the GSLs along with GH for MHC class II presentation. This work represents the first study of oligosaccharide processing and presentation and is expected to facilitate the design and development of glycoconjugate vaccines based on oligosaccharide antigens.

GPR84 is a proinflammatory G protein-coupled receptor that mediates myeloid immune cell functions. Blocking GPR84 with antagonists is a promising approach for treating inflammatory and fibrotic diseases. Previously, a GPR84 antagonist 604c , with a symmetrical phosphodiester structure, has displayed promising efficacy in a mouse model of ulcerative colitis. However, the low blood exposure resulting from physicochemical properties prevented its uses in other inflammatory diseases. In this study, a series of unsymmetrical phosphodiesters with lower lipophilicity were designed and tested. The representative compound 37 exhibited a 100-fold increase in mouse blood exposure compared to 604c while maintaining in vitro activity. In a mouse model of acute lung injury, 37 (30 mg/kg, po) significantly reduced the infiltration of proinflammatory cells and the release of inflammatory cytokines and ameliorated pathological changes equally or more effectively than N -acetylcysteine (100 mg/kg, po). These findings suggest that 37 is a promising candidate for treating lung inflammation.

To eliminate internal defects of grains developed during melt-cast charging, the formation mechanism and the trend of crystal morphology of internal defects of 2,4,6-trinitrotoluene and 2,4-dinitroanisole-based melt-cast explosives under different process conditions were simulated. The effects of solidification treatment on melt-cast explosive molding quality were investigated by combining pressurized feeding, head insulation, and water bath cooling. The single pressurized treatment technology results showed that grains were exposed to layer-by-layer solidification from outside to inside, resulting in V-shaped shrink areas of the contract cavity in the core. The defect area was proportional to the treatment temperature. However, the combination of treatment technologies, such as head insulation and water bath cooling, promoted longitudinal gradient solidification of the explosive and controllable migration of its internal defects. Moreover, the combined treatment technologies effectively improved the heat transfer efficiency of the explosive with the help of a water bath to reduce the solidification time, thus achieving highly efficient equal-material manufacturing of microdefect or zero-defect grains., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Two-dimensional covalent-organic frameworks (2D COFs) have recently emerged as great prospects for their applications as new photocatalytic platforms in solar-to-hydrogen conversion; nevertheless, their inefficient solar energy capture and fast charge recombination hinder the improvement of photocatalytic hydrogen production performance. Herein, two photoactive three-component donor-π-acceptor (TCDA) materials were constructed using a multicomponent synthesis strategy by introducing electron-deficient triazine and electron-rich benzotrithiophene moieties into frameworks through sp 2 carbon and imine linkages, respectively. Compared with two-component COFs, the novel TCDA-COFs are more convenient in regulating the inherent photophysical properties, thereby realizing outstanding photocatalytic activity for hydrogen evolution from water. Remarkably, the first sp 2 carbon-linked TCDA-COF displays an impressive hydrogen evolution rate of 70.8 ± 1.9 mmol g -1 h -1 with excellent reusability in the presence of 1 wt % Pt under visible-light illumination (420-780 nm). Utilizing the combination of diversified spectroscopy and theoretical prediction, we show that the full π-conjugated linkage not only effectively broadens the visible-light harvesting of COFs but also enhances charge transfer and separation efficiency.

Double perovskites with bright emission, low toxicity, and excellent stability have drawn considerable attention. Herein, we report the hydrothermal synthesis of Mn 2+ -doped Cs 2 Na 1- x Ag x BiCl 6 double perovskites that exhibit dual emission modes. Introducing Ag + ions to Cs 2 NaBiCl 6 samples enables a bright self-trapped exciton (STE) emission in orange-red color, whereas Mn 2+ dopants induce a yellow-orange emission. Importantly, Mn 2+ doping into Cs 2 Na 1- x Ag x BiCl 6 double perovskites with an indirect bandgap enables a high photoluminescence quantum yield of 49.52 ± 2%. Density functional theory calculations reveal that bringing Ag + ions into Cs 2 NaBiCl 6 can localize wave function to the [AgCl 6 ] 5- octahedron and convert dark transitions to bright STE transitions. Moreover, the 3d orbitals of Mn 2+ dopants hybridize with Bi-6p and Cl-3p orbitals at the conduction band minimum, resulting in direct electron transfer from the host to Mn 2+ and a significant increase in photoluminescence efficiency. These results shed light on the optical physical process of Mn 2+ -doped systems, providing useful information for further improvement of the photoluminescence efficiency of double perovskites.

Metal-organic complexes with radical characteristics are unique species attracting immense attention in recent years due to their peculiar properties and promising applicability in a wide variety of innovative research fields. However, the reported complexes typically do not exceed diradicality. This study systematically investigates a series of square planar neutral Ni-bis(1,2-dithiolene) and Ni-bis(1,2-dioxolene) complexes with linear, branched, and macrocyclic configurations via ab initio calculations. The linear Ni-complexes display strong singlet diradical characters, while their branched counterparts can also exhibit moderate singlet multiradical characters. Importantly, the macrocyclic Ni-complexes can possess extremely strong singlet multiradical characters up to dodeca-radicality along with their global antiaromaticity and hence strong induced ring current in the presence of an external magnetic field, ascribed to the localization of unpaired α and β electrons residing in the highest few molecular orbitals at different molecular sites, minimizing their coupling and annihilation. Our work represents the first indication in the rational design of novel multiradical neutral antiaromatic macrocyclic complexes for potential applications in molecular machines and electronic devices.

Conjugated polymers are promising materials for thermoelectrics as they offer good performances at near ambient temperatures. The current focus on polymer thermoelectric research mainly targets a higher power factor (PF; a product of the conductivity and square of the Seebeck coefficient) through improving the charge mobility. This is usually accomplished via structural modification in conjugated polymers using different processing techniques and doping. As a result, the structure-charge transport relationship in conjugated polymers is generally well-established. In contrast, the relationship between the structure and the Seebeck coefficient is poorly understood due to its complex nature. A theoretical framework by David Emin ( Phys. Rev. B , 1999, 59, 6205-6210) suggests that the Seebeck coefficient can be enhanced via carrier-induced vibrational softening, whose magnitude is governed by the size of the polaron. In this work, we seek to unravel this relationship in conjugated polymers using a series of highly identical pro-quinoid polymers. These polymers are ideal to test Emin's framework experimentally as the quinoid character and polaron delocalization in these polymers can be well controlled even by small atomic differences (<10 at. % per repeating unit). By increasing the polaron delocalization, that is, the polaron size, we demonstrate that both the conductivity and the Seebeck coefficient (and hence PF) can be increased simultaneously, and the latter is due to the increase in the polaron's vibrational entropy. By using literature data, we also show that this phenomenon can be observed in two closely related diketopyrrolopyrrole-conjugated polymers as well as in p-doped P3HT and PANI systems with an increasing molecular order.

Natural load-bearing mammalian tissues, such as cartilage and ligaments, contain ∼70% water yet can be mechanically stiff and strong due to the highly templated structures within. Here, we present a bioinspired approach to significantly stiffen and strengthen biopolymer hydrogels and films through the combination of nanoscale architecture and templated microstructure. Imprinted submicrometer pillar arrays absorb energy and deflect cracks. The produced chitosan hydrogels show nanofiber chains aligned by nanopillar topography, subsequently templating the microstructure throughout the film. These templated nanopillar chitosan hydrogels mechanically outperform unstructured flat hydrogels, with increases in the moduli of ∼160%, up to ∼20 MPa, and work at break of ∼450%, up to 8.5 MJ m -3 . Furthermore, the strength at break increases by ∼350%, up to ∼37 MPa, and it is one of the strongest hydrogels yet reported. The nanopillar templating strategy is generalizable to other biopolymers capable of forming oriented domains and strong interactions. Overall, this process yields hydrogel films that demonstrate mechanical performance comparable to that of other stiff, strong hydrogels and natural tissues.

The manipulation of conductive nanowires (NWs) on semiconductor platforms provides important insights into the fabrication of nanoscale electronic devices. In this work, we directly observed the electric field-induced phase transitions in atomic Au-NWs self-assembled on Ge(001) surfaces using scanning tunneling microscopy (STM). The tunneling electrons and electric fields underneath a STM tip apex can effectively trigger a phase transition in Au-NWs on Ge(001) surfaces. Such phase transitions are associated with a remarkable atomic rearrangement in the Au-NWs, thereby modifying their band structures. Moreover, directly monitoring the dynamic reconstruction of Au-NWs on Ge(001) surfaces helps us to understand the NWs' intricate atomic configurations and their electronic properties. The spatially controlled phase transition at the nanometer scale using STM shows the possibility of modulating NWs' properties at an atomic scale.

Four active partition layers and ten isolates, including (5 R )- and (5 S )-macapyrrolidone A ( 1a , 1b ), and four new alkaloids, (5 R )- and (5 S )-macapyrrolidone B ( 2a , 2b ) and macapyrrolins D, E ( 3 , 4 ), were isolated from maca ( Lepidium meyenii Walp.), an indigenous food plant from Peru. Derived from the n -hexane layer, the macamide-rich fraction exhibited pro-angiogenic activity on EPC and HUVEC cells. Anti-thrombotic activity was displayed by the polar part of maca extracts ( n -butanol and water layers). Both 75% methanol aq. (midlower polar part) and n -hexane (low polar part) layers, which showed signs of fatty acid content, markedly inhibited superoxide and elastase release in an anti-inflammatory assay. The 75% methanol aq. layer showed strong anti-allergic activity, and macapyrrolin A ( 5 ) was found active based on β-hexosaminidase release inhibition assays and a ChemGPS-NP experiment. These valuable bioactivity results suggest that maca is a food plant with good benefits for human health.

The connection between electronic structures of metal-organic frameworks (MOFs) and their building subunits is a key cornerstone for rational MOF material design. Some two-dimensional conjugated MOFs were reported to be topological insulators. However, many of them are not intrinsic as the Fermi levels are far from the topological gaps. The subunit-to-MOF electronic orbital correspondence should be established to bridge their chemical structure and physical properties, thus understanding the design rules toward intrinsic topological insulators. Herein we reveal the fundamental role of the subunit-to-MOF symmetry relation in determining their orbital interaction and hybridization and, consequently, topological characteristics. In particular, such honeycomb-kagome MOFs possess delocalized symmetry-enforced nonbonding electronic states with the topological spin-orbit gap. The nonbonding nature of these states allows tailored band structure modulation through molecular structure and strain engineering, with the potential realization of an intrinsic metal-organic topological insulator.

A novel compound zoanone A ( 1 ), together with eight new alkaloids, 3β,14α-dihydroxy-28-deoxyzoanthenamine ( 2 ), 7α-hydroxy-28-deoxyzoanthenamine ( 3 ), 3α-hydroxyzoanthenamine ( 4 ), 7β-hydroxyzoanthenamine ( 5 ), 28α-methoxyzoanthenamine ( 6 ), 28α-methoxykuroshine A ( 7 ), 30-hydroxykuroshine A ( 8 ), and 3β-hydroxy-11-deketo-kuroshine B ( 9 ), was isolated from the zoantharian Zoanthus vietnamensis . Their structures were elucidated by the comprehensive analyses of IR, mass spectrometry, NMR, and UV spectroscopic data. The absolute configuration of 1 was established by single-crystal X-ray crystallographic analysis using Cu Kα radiation. A plausible biosynthetic pathway of 1 was proposed. Antiangiogenic and antilymphangiogenic activities of the isolated metabolites were tested and evaluated. The results showed that all isolated compounds had weak antimetastatic activity.

The ethyl acetate extract of an endophyte Epicoccum sorghinum exhibited anti-inflammatory activity at a concentration of <10 μg/mL. By bioassay-guided fractionation, one new compound, named epicorepoxydon A ( 1 ), and one unusual bioactive compound, 6-(hydroxymethyl)benzene-1,2,4-triol ( 6 ), together with six known compounds, were isolated from E. sorghinum . The structures of all isolates were established by spectroscopic analyses. The relative configuration of 1 was deduced by the NOESY spectrum and its absolute configuration was determined by X-ray single-crystal analysis. The biological activities of all isolates were evaluated using four types of bioassays including cytotoxicity, anti-inflammatory, antiplatelet aggregation, and antiangiogenesis activities. Compounds 4 and 6 showed potent anti-inflammatory activity, compound 2 possessed potent antiplatelet aggregation and antiangiogenesis activities, and compound 6 demonstrated antiangiogenesis activity. This fungal species can cause a human hemorrhagic disorder known as onyalai. In this study, we identified the active components with antiplatelet aggregation and antiangiogenesis activities, which may be related to the hemorrhagic disorder caused by this fungus. Moreover, we proposed a biosynthetic pathway of the isolated polyketide secondary metabolites and investigated their structure-activity relationship (SAR). Our results suggested that E. sorghinum is a potent source of biologically active compounds that can be developed as antiplatelet aggregation and anti-inflammatory agents., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Density functional theory calculations with a Hubbard U correction were used to investigate the selective oxidation of propylene on Cu 2 O(111) and Cu 2 O(110) surfaces, and the mechanism for the selective oxidation of propylene was discussed. On both surfaces, acrolein can be generated by two H-stripping reactions in the allylic hydrogen stripping path, while propylene oxide (PO), propanal, and acetone can be created through the propylene oxametallacycle intermediates in the epoxidation path. Our calculation results indicated that Cu 2 O has a high crystal plane-controlled phenomenon for the selective oxidation of propylene. It was found that the formations of propanal and acetone are unfavorable kinetically and acrolein is the main product on the (111) surface. On the (110) surface, the activation barrier of acrolein formation is too high to produce and PO becomes the favored product, which is different from the case of the (111) surface. Moreover, energetic span model analysis was carried out to discuss the selective oxidation of propylene on these two surfaces and confirm the above calculations. The present study can help people to design the proper crystal plane catalyst to get the target product of PO with high selectivity and activity in the selective oxidation of propylene., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

This study aims to investigate the photothermal oxidation removal of Hg 0 in simulated flue gases using photothermal catalysts at relatively low temperatures of 120-160 °C in two phases: the first phase applied the sol-gel method to prepare TiO 2 and CeO 2 /TiO 2 photothermal catalysts and characterized surface properties by specific surface area analysis, X-ray diffraction, X-ray photoelectron spectroscopy (XPS), and photoluminescence spectroscopy. The second phase investigated the effects of operating parameters on Hg 0 oxidation efficiency at lower temperatures of 100-160 °C. The operating parameters included reaction temperatures and modified concentrations of CeO 2 . Experimental results indicated that TiO 2 prepared by the sol-gel method was mainly in the anatase phase. XPS analysis showed that Ce mostly existed in the form of Ce 4+ . The content of surface-chemisorbed oxygen increased with the modification amount of CeO 2 . Photothermal catalytic oxidation results indicated that CeO 2 /TiO 2 had a much higher oxidation efficiency of Hg 0 at 120-160 °C than neat TiO 2 , which increased from 30-60 to >90%. 7%CeO 2 /TiO 2 not only had the best photothermal performance but also maintained high efficiency at a relatively higher reaction temperature of 160 °C., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Stimuli-responsive polymers are an efficient means of targeted therapy. Compared to conventional agents, they increase bioavailability and efficacy. In particular, polymer hydrogel nanoparticles (NPs) can be designed to respond when exposed to a specific environmental stimulus such as pH or temperature. However, targeting a specific metabolite as the trigger for stimuli response could further elevate selectivity and create a new class of bioresponsive materials. In this work we describe an N-isopropylacrylamide (NIPAm) NP that responds to a specific metabolite, characteristic of a hypoxic environment found in cancerous tumors. NIPAm NPs were synthesized by copolymerization with an oxamate derivative, a known inhibitor of lactate dehydrogenase (LDH). The oxamate-functionalized NPs (OxNP) efficiently sequestered LDH to produce an OxNP-protein complex. When exposed to elevated concentrations of lactic acid, a substrate of LDH and a metabolite characteristic of hypoxic tumor microenvironments, OxNP-LDH complexes swelled (65%). The OxNP-LDH complexes were not responsive to structurally related small molecules. This work demonstrates a proof of concept for tuning NP responsiveness by conjugation with a key protein to target a specific metabolite of disease.

Combining both density functional theory and the cluster expansion method, we investigate 3 binary MXene alloy systems of semiconducting Ti 2 CO 2 , Zr 2 CO 2 , and Hf 2 CO 2 , where the transition metals substitute one another (i.e., Ti 2(1- x) Zr 2 x CO 2 , Ti 2(1- x) Hf 2 x CO 2 , and Zr 2(1- x) Hf 2 x CO 2 ). We show that this group of MXene alloys forms the solid-solution phase across all compositions. Special quasirandom structures are generated to model the solid-solution phase of these alloys, using which we demonstrate how their structural, mechanical, electronic, and optical properties are tuned via stoichiometry engineering. These alloys exhibit outstanding mechanical strength and stability. They possess indirect band gaps of 1.25-1.80 eV. For Ti 2(1- x) Zr 2 x CO 2 and Ti 2(1- x) Hf 2 x CO 2 , they display higher absorbance in the solar spectrum than their constituent Zr 2 CO 2 and Hf 2 CO 2 , respectively. Most of the MXene alloys also show appropriately aligned band edges for water splitting. We predict the Ti 2(1- x) Zr 2 x CO 2 alloy with x = 0.2778 to be the most promising water-splitting photocatalyst among the MXenes studied here, outperforming its constituents, Ti 2 CO 2 and Zr 2 CO 2 , when solar absorbance performance and band-edge alignments are simultaneously considered. This work demonstrates that alloying can be used to effectively tune photocatalytic performance.

Extraordinary progress has been achieved in polymer-based thermoelectric materials in recent years. New emerging π-conjugated transition-metal coordination polymers are one of the best n-type polymer-based thermoelectric materials. However, the microscopic descriptions on geometric structures, orbital characteristics, and most importantly, thermoelectric properties remain elusive, which has seriously hampered the experimentalists to draw a straightforward design strategy for new n-type polymer-based thermoelectric materials. Herein, we assess the n-type thermoelectric properties of 20 π-conjugated d 8 metal center coordination polymers and rationalize their thermoelectric properties in terms of molecular geometry, orbital nature, and electron-phonon coupling based on first-principles calculations. An explicit screening rule for high-performance n-type π-conjugated transition-metal coordination polymeric thermoelectric materials was found, i.e., smaller metal center d orbital component ratio in the conduction band minimum, weaker electron-phonon coupling, higher intrinsic mobility, and thereby higher thermoelectric power factor can be achieved. Guided by this rule, poly(Pd-C 2 S 4 ) and poly(Ni-C 2 Se 4 ) show very high power factors. We built a map of high-performance π-conjugated transition-metal coordination polymers for n-type thermoelectric applications, which will help to accelerate the screening and design of innovative n-type thermoelectric polymers.

It is generally deemed that doping is a must for polymeric materials to achieve their high thermoelectric performance. We herein present the first report that intrinsically metallic behaviors and high-performance thermoelectric power factors can coexist within doping-free linear-backbone conducting polymers, poly(nickel-ethylenetetrathiolate) and its analogs. On the basis of density functional calculations, we have corroborated that four crystalline π- d conjugated transition-metal coordination polymers, including poly(Ni-C 2 S 4 ), poly(Ni-C 2 Se 4 ), poly(Pd-C 2 S 4 ) and poly(Pt-C 2 S 4 ) exhibit intrinsically metallic behavior arising from the formation of dense intermolecular interaction networks between sulfur/selenium atoms. They show moderate carrier concentrations (10 19 -10 21 cm -3 ) and decent conductivities (10 3 -10 4 S cm -1 ), among which, poly(Ni-C 2 S 4 ), poly(Ni-C 2 Se 4 ) and poly(Pd-C 2 S 4 ) possess high power factors (∼10 3 μW m -1 K -2 ).

Van der Waals structures formed by aligning monolayer graphene with insulating layers of hexagonal boron nitride exhibit a moiré superlattice that is expected to break sublattice symmetry. Despite an energy gap of several tens of millielectronvolts opening in the Dirac spectrum, electrical resistivity remains lower than expected at low temperature and varies between devices. While subgap states are likely to play a role in this behavior, their precise nature is unclear. We present a scanning gate microscopy study of moiré superlattice devices with comparable activation energy but with different charge disorder levels. In the device with higher charge impurity (∼10 10 cm -2 ) and lower resistivity (∼10 kΩ) at the Dirac point we observe current flow along the graphene edges. Combined with simulations, our measurements suggest that enhanced edge doping is responsible for this effect. In addition, a device with low charge impurity (∼10 9 cm -2 ) and higher resistivity (∼100 kΩ) shows subgap states in the bulk, consistent with the absence of shunting by edge currents.

Integration of strain engineering of two-dimensional (2D) materials in order to enhance device performance is still a challenge. Here, we successfully demonstrated the thermally strained band gap engineering of transition-metal dichalcogenide bilayers by different thermal expansion coefficients between 2D materials and patterned sapphire structures, where MoS 2 bilayers were chosen as the demonstrated materials. In particular, a blue shift in the band gap of the MoS 2 bilayers can be tunable, displaying an extraordinary capability to drive electrons toward the electrode under the smaller driven bias, and the results were confirmed by simulation. A model to explain the thermal strain in the MoS 2 bilayers during the synthesis was proposed, which enables us to precisely predict the band gap-shifted behaviors on patterned sapphire structures with different angles. Furthermore, photodetectors with enhancement of 286% and 897% based on the strained MoS 2 on cone- and pyramid-patterned sapphire substrates were demonstrated, respectively.

Efficient delivery of antigens is of paramount concern in immunotherapies. We aimed to target antigen presenting cells (APCs) by conjugating CpG oligonucleotides to an E2 protein nanoparticle surface (CpG-PEG-E2). Compared to E2 alone, we observed ~4-fold increase of in vitro APC uptake of both CpG-PEG-E2 and E2 conjugated to non-CpG DNA. Furthermore, compared to E2-alone or E2 functionalized solely with polyethylene glycol (PEG), the CpG-PEG-E2 showed enhanced lymph node retention up to at least 48 hr and 2-fold increase in APC uptake in vivo , parameters which are advantageous for vaccine success. This suggests that enhanced APC uptake of nanoparticles mediated by oligonucleotide display may help overcome delivery barriers in vaccine development.

Hydrophobic interactions often dominate the associative forces between biomacromolecules. A synthetic affinity reagent must be able to exploit and optimize these interactions. We describe synthesis of abiotic affinity reagents that sequester biomacromolecules with lipid-like domains. NIPAm-based copolymer nanoparticles (NPs) containing C4-C8 hydrophobic groups were evaluated for their affinity for lipopolysaccharides (LPS), the lipophilic component of the outer membrane of Gram-negative bacteria. Optimal affinity was found for NPs incorporating a linear C4 hydrocarbon group. 1D and 2D (1)H NMR studies revealed that in water, the longer chain (C6 and C8) alkyl groups in the hydrogel NPs were engaged in intrachain association, rendering them less available to interact with LPS. Optimal LPS-NP interaction requires maximizing hydrophobicity, while avoiding side chain aggregation. Polymer compositions with high LPS binding were grafted onto agarose beads and evaluated for LPS clearance from solution; samples containing linear C4 groups also showed the highest LPS clearance capacity.

Hepatocellular carcinoma (HCC) has become one of most common malignancies and a leading cause of cancer mortality worldwide. Previous study has shown that 4-acetylantroquinonol B (4AAQB) isolated from Antrodia cinnamomea (or niu-chang-chih) was observed to inhibit HepG2 cell proliferation via affecting cell cycle. However, the in vivo effects and antimetastatic activity of 4AAQB have not yet been addressed. This study found that 4AAQB inhibited HepG2 and HuH-7 hepatoma cell growth in both in vitro and in vivo models and exhibited pronounced inhibitory effects on HuH-7 tumor growth in xenograft and orthotopic models. 4AAQB efficiently inhibited the phosphorylation of mTOR and its upstream kinases and the downstream effectors and decreased the production of VEGF and activity of Rho GTPases in HuH-7 cells. Furthermore, 4AAQB inhibited in vitro HuH-7 cell migration and in vivo pulmonary metastasis. The results suggested that 4AAQB is a potential candidate for HCC therapy.

A new electron acceptor 6-alkylpyrrolo[3,4-d]pyridazine-5,7-dione (PPD) with a very low LUMO level has been synthesized via a challenging inverse electron demand Diels-Alder reaction between thiophene and furan-decorated tetrazine substrates and an electron-deficient 1-alkyl-1H-pyrrole-2,5-dione unit. The PPD monomer has been incorporated into a series of donor-acceptor-type conjugated polymers as electrochromic materials with good optical contrast, fast switching speed, and high coloration efficiency.

Collagen is the most abundant protein in extracellular matrices and is commonly used as a tissue engineering scaffold. However, collagen and other biopolymers from native sources can exhibit limitations when tuning mechanical and biological properties. Cysteines do not naturally occur within the triple-helical region of any native collagen. We utilized a novel modular synthesis strategy to fabricate variants of recombinant human collagen that contained 2, 4, or 8 non-native cysteines at precisely defined locations within each biopolymer. This bottom-up approach introduced capabilities using sulfhydryl chemistry to form hydrogels and immobilize bioactive factors. Collagen variants retained their triple-helical structure and supported cellular adhesion. Hydrogels were characterized using rheology, and the storage moduli were comparable to fibrillar collagen gels at similar concentrations. Furthermore, the introduced cysteines functioned as anchoring sites, with TGF-β1-conjugated collagens promoting myofibroblast differentiation. This approach demonstrates the feasibility to produce custom-designed collagens with chemical functionality not available from native sources.

Ambient fine particulate matter (PM2.5) is a leading environmental risk factor for premature mortality. We use aerosol optical depth (AOD) retrieved from two satellite instruments, MISR and SeaWiFS, to produce a unified 15-year global time series (1998-2012) of ground-level PM2.5 concentration at a resolution of 1° x 1°. The GEOS-Chem chemical transport model (CTM) is used to relate each individual AOD retrieval to ground-level PM2.5. Four broad areas showing significant, spatially coherent, annual trends are examined in detail: the Eastern U.S. (-0.39 ± 0.10 μg m(-3) yr(-1)), the Arabian Peninsula (0.81 ± 0.21 μg m(-3) yr(-1)), South Asia (0.93 ± 0.22 μg m(-3) yr(-1)) and East Asia (0.79 ± 0.27 μg m(-3) yr(-1)). Over the period of dense in situ observation (1999-2012), the linear tendency for the Eastern U.S. (-0.37 ± 0.13 μg m(-3) yr(-1)) agrees well with that from in situ measurements (-0.38 ± 0.06 μg m(-3) yr(-1)). A GEOS-Chem simulation reveals that secondary inorganic aerosols largely explain the observed PM2.5 trend over the Eastern U.S., South Asia, and East Asia, while mineral dust largely explains the observed trend over the Arabian Peninsula.

Tumor metastasis is the major obstacle for cancer treatment. Previous studies have shown that butein exhibits antiangiogenesis property and anticancer effects in different kinds of human cancer cells. However, the effects of butein on metastasis and energy metabolism of cancer cells are mostly unknown. This study showed that butein significantly inhibited invasion of cancer cells without acting in a cytotoxic fashion. It was further demonstrated that butien dramatically suppressed cancer metastasis by an in vivo CAM-intravasation model. Additionally, butein concentration-dependently repressed the expression and activity of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA). The study indicated that butein may repress MMP-9 and uPA proteolytic activities and subsequently inhibit cancer metastasis via Akt/mTOR/p70S6K translational machinery. Moreover, butein may partly suppress cancer metastasis by down-regulating ATP synthesis via both oxidative and glycolytic metabolism. The results suggest that butein is a potential antimetastatic agent worthy of further development for cancer treatment.

Many current cancer vaccine strategies suffer from the inability to mount a CD8 T cell response that is strong enough to overcome the low immunogenicity of tumors. Viruses naturally possess the sizes, geometries, and physical properties for which the immune system has evolved to recognize, and mimicking those properties with nanoparticles can produce robust platforms for vaccine design. Using the nonviral E2 core of pyruvate dehydrogenase, we have engineered a viral-mimicking vaccine platform capable of encapsulating dendritic cell (DC)-activating CpG molecules in an acid-releasable manner and displaying MHC I-restricted SIINFEKL peptide epitopes. Encapsulated CpG activated bone marrow-derived DCs at a 25-fold lower concentration in vitro when delivered with the E2 nanoparticle than with unbound CpG alone. Combining CpG and SIINFEKL within a single multifunctional particle induced ∼3-fold greater SIINFEKL display on MHC I by DCs over unbound peptide. Importantly, combining CpG and SIINFEKL to the E2 nanoparticle for simultaneous temporal and spatial delivery to DCs showed increased and prolonged CD8 T cell activation, relative to free peptide or peptide-bound E2. By codelivering peptide epitopes and CpG activator in a particle of optimal DC-uptake size, we demonstrate the ability of a noninfectious protein nanoparticle to mimic viral properties and facilitate enhanced DC activation and cross-presentation.

The major challenge in current chemotherapy is to increase local effective therapeutic concentration of drugs as well as to minimize toxicity and side effects for patients. The targeted delivery of drugs to their desired site of action in a controlled manner plays an essential role in the development of drug formulations. A photocage refers to a caged molecule rendered biologically inert by a photolabile protecting group. Molecules are illuminated with light to liberate the caged group and then become active forms. In this study, we formulate upconversion nanoparticles (UCNPs) as the NIR-triggered targeting and drug delivery vehicles that successfully deliver in vitro and in vivo for near-infrared light photocontrolled targeting, bioimaging, and chemotherapy. It is noted that there has been no report on the systemic administration UCNP-based drug delivery agents for evaluation of bioimaging and chemotherapy. To achieve phototargeting, the tumor-homing agent (i.e., folic acid) has been constructed as a photoresponsive molecule. For the chemotherapeutic effect, the antitumor drug doxorubicin is thiolated on the surface of UCNPs, forming a disulfide bond that can be cleaved by lysosomal enzymes within the cells. The caged UNCPs can serve as a platform for the improvement of selective targeting and possible reduction of adverse side effects from chemotherapy.

The physical and electronic properties of single-walled carbon nanotubes (SWCNTs) are determined by their chirality. The chirality selection mechanism in SWCNT growth is not fully understood. In this study, the interaction between near-armchair (n,5), where n = 6, 7, 8, and 9, zigzag (9,0), and armchair (5,5) nanotubes and a fully relaxed Ni(55) metal cluster during the early stage of growth is studied by density functional theory calculations. We found that kink sites at the end edge of (n,5) nanotubes are more reactive than other sites based on the charge transfer analysis at the Ni-C interface. The frontier orbitals of the (6,5) and (7,5) caps are localized on their kink-step sites, which stretch outward from the carbon cap surface, having typical 2p(z) orbital feature of carbon atom with high reactivity. Such favorable frontier orbital spatial orientation and location is ideal to incorporate more carbon species. These reactive sites may lead to the faster growth rate, resulting in the chirality selectivity toward the (6,5) and (7,5) nanotubes. In contrast, the frontier orbitals of (8,5) and (9,5) caps spread over the entire carbon cap surface. Adding carbon species at these sites may lead to the chirality change or formation of other carbon structures. Our results showed that the spatial distribution and orientation of frontier orbitals is useful in explaining the chiral selectivity. Engineering catalyst clusters to control these reactive sites has high potential to further improve chirality control in SWCNT synthesis.

An efficient and straightforward four-component synthetic protocol has been developed to synthesize imidazo[1,2-a]pyridines and imidazo[1,2,3-ij][1,8]naphthyridine derivatives incorporating medicinally privileged heterosystems from heterocyclic ketene aminals, aldehydes, diketene, and amines via cascade reactions, including diketene ring-opening, Knoevenagel condensation, aza-ene reaction, imine-enamine tautomerization, cyclocondensation, and intramolecular S(N)Ar. This strategy can provide an alternative approach for easy access to the highly substituted imidazo[1,2-a]pyridine derivatives in moderate to good yields using four simple and readily available building blocks under mild conditions. Importantly, the unusual splitting peaks in the (1)H NMR spectra of the products derived from heterocyclic ketene aminals with an o-halogen atom on the aryl ring were explained reasonably by varying the temperature in NMR analysis.

Even though metal-organic frameworks (MOFs) derived from antiferromagnetic dimeric-Cu(II) building units and nonmagnetic molecular linkers are known to exhibit unexpected ferromagnetic behavior, a comprehensive understanding of the underlying mechanism remains elusive. Using a combined theoretical and experimental approach, here we reveal the origin of the long-range ferromagnetic coupling in a series of MOFs, constructed from antiferromagnetic dimeric-Cu(II) building blocks. Our studies show that the strong localization of copper vacancy states favors spontaneous spin polarization and formation of local moment. These copper vacancy-induced moments are coupled via the itinerant electrons in the conjugated aromatic linkers to establish a long-range ferromagnetic ordering. The proposed mechanism is supported by direct experimental evidence of copper vacancies and the magnetic hysteresis (M-H) loops.

The development of restenosis involves migration and hyperproliferation of vascular smooth muscle cells (VSMCs). Platelet-derived growth factor (PDGF) is one of the major factors. Butein modulates inflammatory pathways and affects the proliferation and invasion of the tumor. We investigated the hypothesis that butein might prevent the restenosis process via a similar pathway. Our results demonstrated that butein inhibited PDGF-induced VSMC proliferation and migration as determined by BrdU proliferation and two-dimensional migration scratch assay. Butein also concentration-dependently repressed PDGF-induced phosphorylation of PDGF-receptor β, mitogen-activated protein kinases, phosphoinositide 3-kinase/Akt, and phopholipase Cγ/c-Src in VSMCs. In addition, in vivo results showed that butein attenuated neointima formation in balloon-injured rat carotid arteries. These results indicate that butein may inhibit PDGF-induced VSMC proliferation and migration, resulting in attenuation of neointima formation after percutaneous transluminal coronary angioplasty. Our study demonstrates for the first time that systemic administration of butein is able to reduce neointima formation after vascular injury.

Atomic force microscopy (AFM) studies under aqueous buffer probed the role of chemical affinity between liposomes, consisting of large unilamellar vesicles, and substrate surfaces in driving vesicle rupture and tethered lipid bilayer membrane (tLBM) formation on Au surfaces. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-poly(ethylene glycol)-2000-N-[3-(2-pyridyldithio) propionate] (DSPE-PEG-PDP) was added to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) vesicles to promote interactions via Au-thiolate bond formation. Forces induced by an AFM tip leading to vesicle rupture on Au were quantified as a function of DSPE-PEG-PDP composition with and without osmotic pressure. The critical forces needed to initiate rupture of vesicles with 2.5, 5, and 10 mol % DSPE-PEG-PDP are approximately 1.1, 0.8, and 0.5 nN, respectively. The critical force needed for tLBM formation decreases from 1.1 nN (without osmotic pressure) to 0.6 nN (with an osmotic pressure due to 5 mM of CaCl(2)) for vesicles having 2.5 mol % DSPE-PEG-PDP. Forces as high as 5 nN did not lead to LBM formation from pure POPC vesicles on Au. DSPE-PEG-PDP appears to be important to anchor and deform vesicles on Au surfaces. This study demonstrates how functional lipids can be used to tune vesicle-surface interactions and elucidates the role of vesicle-substrate interactions in vesicle rupture.

Self-assembling protein nanocapsules can be engineered for various bionanotechnology applications. Using the dodecahedral scaffold of the E2 subunit from pyruvate dehydrogenase, we introduced non-native surface cysteines for site-directed functionalization. The modified nanoparticle's structural, assembly, and thermostability properties were comparable to the wild-type scaffold (E2-WT), and after conjugation of poly(ethylene glycol) (PEG) to these cysteines, the nanoparticle remained intact and stable up to 79.7 ± 1.8 °C. PEGylation of particles reduced uptake by human monocyte-derived macrophages and MDA-MB-231 breast cancer cells, with decreased uptake as PEG chain length is increased. In vitro C4-depletion and C5a-production assays yielded 97.6 ± 10.8% serum C4 remaining and 40.1 ± 6.0 ng/mL C5a for E2-WT, demonstrating that complement activation is weak for non-PEGylated E2 nanoparticles. Conjugation of PEG to these particles moderately increased complement response to give 79.7 ± 6.0% C4 remaining and 87.6 ± 10.1 ng/mL C5a. Our results demonstrate that PEGylation of the E2 protein nanocapsules can modulate cellular uptake and induce low levels of complement activation, likely via the classical/lectin pathways.

Superparamagnetic iron oxide (SPIO) nanoparticles show promise as labels for cellular magnetic resonance imaging (MRI) in the application of stem cell-based therapy. However, the unaddressed concerns about the impact of SPIO nanoparticles on stem cell attributes make the feasibility of SPIO labeling uncertain. Here, we show that the labeling of human mesenchymal stem cells (hMSCs) with ferucarbotran can induce epidermal growth factor receptor (EGFR) overexpression. Labeled hMSCs with their overexpressed EGFR were attracted by tumorous EGF and more effectively migrated toward tumor than unlabeled cells, resulting in more potent intrinsic antitumor activity. Moreover, the captured binding of tumorous EGF by overexpressed EGFR of labeled hMSCs blocked EGF/EGFR signaling-derived tumor growth, tumorous angiogenesis, and tumorous VEGF expression also responsible for tumor progression and development. Our results show that the impact of SPIO nanoparticles on stem cell attributes is not necessarily harmful but can be cleverly used to be beneficial to stem cell-based therapy.

Developing Janus kinase 2 (Jak2) inhibitors has become a significant focus for small molecule drug discovery programs in recent years due to the identification of a Jak2 gain-of-function mutation in the majority of patients with myeloproliferative disorders (MPD). Here, we describe the discovery of a thienopyridine series of Jak2 inhibitors that culminates with compounds showing 100- to >500-fold selectivity over the related Jak family kinases in enzyme assays. Selectivity for Jak2 was also observed in TEL-Jak cellular assays, as well as in cytokine-stimulated peripheral blood mononuclear cell (PBMC) and whole blood assays. X-ray cocrystal structures of 8 and 19 bound to the Jak2 kinase domain aided structure-activity relationship efforts and, along with a previously reported small molecule X-ray cocrystal structure of the Jak1 kinase domain, provided structural rationale for the observed high levels of Jak2 selectivity.

The hepatitis C virus core protein (HCVc) forms the viral nucleocapsid and is involved in viral persistence and pathogenesis, possibly by interacting with host factors to modulate viral replication and cellular functions. Here, we identified 36 cellular protein candidates by one-dimensional SDS-PAGE and LC-MS/MS-based proteomics after affinity purification with HCVc174, a matured form of HCVc from HCV-1b genotype, tagged with biotin and calmodulin-binding peptide/protein A at N- and C-termini, respectively. By pull-down and confocal imaging techniques, we confirmed that heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1), nuclear factor 45 (NF45), and C14orf166 are novel HCVc174-interacting host proteins, known to participate in mRNA metabolism, gene regulation, and microtubule organization, respectively. Unlike the other 2 proteins, NF45 interacted with HCVc174 in an RNA-dependent manner. These 3 proteins colocalized with ectopic HCVc-1b in both the cytoplasm and nucleus, which demonstrated their spatial interaction with naturally translocated HCVc174 after HCVc biogenesis. Such colocalization, however, shifted to the cytoplasm in cells with replicating virus of 1b or 2a genotype, indicating that active viral replication confined these interacting proteins in the cytoplasm. Collectively, our findings suggest that spatial interactions of hnRNPH1, NF45, and C14orf166 with HCVc174 likely modulate HCV or cellular functions during acute and chronic HCV infection.

Two-dimensional non-close-packed crystals of the protein streptavidin, grown on phospholipid membranes, can serve as nanoscale templates capable of directing the formation of ordered nanoparticle arrays through site-specific electrostatic adsorption. Here we examine the effects of both interparticle and nanoparticle/lipid membrane electrostatic interactions on the degree of structural order exhibited by the templated nanoparticle array. Interparticle electrostatic repulsion is shown to have only marginal influence on nanoparticle ordering. In contrast, the degree of order exhibited by the templated array can be tuned by controlling the charge on the lipid membrane. Analysis of the local and global structure of arrays generated with negatively charged gold nanoparticles (∼6 nm) indicate improved long-range order when the lipid membrane supporting the protein crystal is derived from cationic lipid molecules as opposed to zwitterionic phospholipids. Furthermore, as nanoparticle size is reduced (∼3 nm), the presence of a charged lipid membrane is found to be essential, as smaller particles do not adhere to streptavidin crystals grown on zwitterionic membranes. These findings demonstrate that the composition of the lipid support can influence the efficacy of directed-assembly processes which utilize protein templates and are important results toward enhancing control over bottom-up nanofabrication applications., (© 2011 American Chemical Society)

Lipid vesicles are designed with functional chemical groups to promote vesicle fusion on template-stripped gold (TS Au) surfaces that does not spontaneously occur on unfunctionalized Au surfaces. Three types of vesicles were exposed to TS Au surfaces: (1) vesicles composed of only 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids; (2) vesicles composed of lipid mixtures of 2.5 mol % of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-poly(ethylene glycol)-2000-N-[3-(2-pyridyldithio)propionate] (DSPE-PEG-PDP) and 97.5 mol % of POPC; and (3) vesicles composed of 2.5 mol % of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG) and 97.5 mol % POPC. Atomic force microscopy (AFM) topography and force spectroscopy measurements acquired in a fluid environment confirmed tethered lipid bilayer membrane (tLBM) formation only for vesicles composed of 2.5 mol % DSPE-PEG-PDP/97.5 mol % POPC, thus indicating that the sulfur-containing PDP group is necessary to achieve tLBM formation on TS Au via Au-thiolate bonds. Analysis of force-distance curves for 2.5 mol % DSPE-PEG-PDP/97.5 mol % POPC tLBMs on TS Au yielded a breakthrough distance of 4.8 ± 0.4 nm, which is about 1.7 nm thicker than that of POPC lipid bilayer membrane formed on mica. Thus, the PEG group serves as a spacer layer between the tLBM and the TS Au surface. Fluorescence microscopy results indicate that these tLBMs also have greater mechanical stability than solid-supported lipid bilayer membranes made from the same vesicles on mica. The described process for assembling stable tLBMs on Au surfaces is compatible with microdispensing used in array fabrication.

Bird species from the order Procellariiformes or petrels, including the northern fulmar (Fulmarus glacialis), produce high lipid and high energy content stomach oils from the prey they consume, which enables them to exploit distant marine food sources. Stomach oils are also used as a food source for chicks and for defensive purposes. Samples of stomach oils from two Arctic colonies, St. George Island Alaska, USA and Cape Vera, Devon Island Nunavut, Canada, were collected and analyzed for organochlorine contaminants. SigmaPCB concentrations ranged from 13 to 236 ng g(-1) wet weight (ww) and SigmaDDT concentrations from 5 to 158 ng g(-1) ww and were similar in both sites, though differences in chemical signatures were apparent. Stomach oils are a rich energy source; however, they may also provide a higher dose of contaminants per unit energy than the direct consumption of prey items, as illustrated using mass and energy balance calculations to estimate chick exposure to SigmaDDT for hypothetical stomach oil and whole prey diets. The results of this study suggest that stomach oils are an important vector of organochlorine contaminants to chicks and should be considered in future risk assessments of northern fulmars and other species of petrels. To our knowledge this is the first study of stomach oils as an overlooked vector of organochlorine contaminants to chicks and as a potentially valuable medium for dietary analysis and noninvasive biomonitoring both of petrel dietary exposure and of marine contaminant concentrations.

Long, stable, and free-standing linear atomic carbon wires (carbon chains) have been carved out from graphene recently [Meyer et al. Nature (London) 2008, 454, 319; Jin et al. Phys. Rev. Lett. 2009, 102, 205501]. They can be considered as extremely narrow graphene nanoribbons or extremely thin carbon nanotubes. It might even be possible to make use of high-strength and identical (without chirality) carbon wires as a transport channel or on-chip interconnects for field-effect transistors. Here we investigate electron transport properties of linear atomic carbon wire-graphene junctions by combining nonequilibrium Green's function with density functional theory. For short wires, linear ballistic transport is observed in wires consisting of odd numbers of carbon atoms but not in those consisting of even numbers of carbon atoms. For wires longer than 2.1 nm as fabricated above, however, the ballistic conductance of carbon wire-graphene junctions is independent of the structural distortion, structural imperfections, and hydrogen impurity adsorbed on the linear carbon wires, except for oxygen impurity adsorption under a low bias. As such, the epoxy groups might be the origin of experimentally observed low conductance in the carbon chain. Moreover, double-atomic carbon chains exhibit a negative differential resistance effect.