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Rainbow trout ( Oncorhynchus mykiss ) is experiencing a catastrophic pandemic. In recent years, infectious hematopoietic necrosis virus (IHNV) has spread nationwide, resulting in significant mortality. Currently, there are no available treatments or vaccines for IHNV in China. Here, the Astragalus extract was purified and characterized. Then, we developed an inactivated IHNV vaccine with purified Astragalus polysaccharide (P-APS) as an adjuvant. Safety assays showed that IHNV was successfully inactivated. After a serious IHNV challenge, the cumulative mortality rates were 76.0, 38.0, and 22.1% in control, vaccine, and P-APS + vaccine groups, respectively. P-APS + vaccine was effective at reducing head kidney damage and apoptosis after IHNV challenge by histopathological and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses. The P-APS + vaccine group showed better results in enhancing specific antibodies (IgM) and immune enzyme activities (C3, LZM, GOT, and GPT). RNA-seq revealed that many immune-related pathways were significantly enriched. TLR2 , TLR7 , C3 , IFN-γ , IgM , MHC1 , MHC2 , MX1 , and VIG1 were identified as core genes based on RNA-seq and PPI networks. Mechanistic investigations showed that P-APS + vaccine activates the immune pathway by upregulating the expression of these genes. P-ASP+vaccine induced effective innate and adaptive immune responses that were stronger than single vaccines after vaccination and IHNV challenged. Our findings will provide a promising vaccine candidate against IHNV.

Proteins are vital components in cells, biological tissues, and organs, playing a pivotal role in growth and developmental processes in living organisms. Cytochrome C (Cyt C) is a class of heme proteins found in almost all life and is involved in cellular energy metabolic processes such as respiration, mainly as electron carriers or terminal reductases. It binds cardiolipin in the inner mitochondrial membrane, leading to apoptosis. It is a challenge to design a simple and effective artificial system to mimic the complex Cyt C biological transport process. In this paper, an asymmetric biomimetic pH-driven protein gate is described by introducing arginine (Arg) at one end of an hourglass-shaped nanochannel. The nanochannel shows a sensitive protonation-driven protein gate that can be "off" at pH = 7 and "on" at pH = 2. Further studies show that differences in the binding of Arg and Cyt C at different levels of protonation lead to different switching behaviors within the nanochannels, which in turn lead to different surface charges within the nanochannels. It can be used for detecting Cyt C and as an excellent and robust gate for developing integrated circuits and nanoelectronic logic devices.

In twisted van der Waals (vdW) bilayers, intrinsic strain associated with the moiré superlattice and unintentionally introduced uniaxial strain may be present simultaneously. Both strains are able to lift the degeneracy of the E 2g phonon modes in Raman spectra. Because of the different rotation symmetry of the two types of strain, the corresponding Raman intensity exhibits a distinct polarization dependence. We compare a 2.5° twisted MoS 2 bilayer, in which the maximal intrinsic moiré strain is anticipated, and a natural MoS 2 bilayer with an intentionally introduced uniaxial strain. By analyzing the frequency shift of the E 2g doublet and their polarization dependence, we can not only determine the direction of unintentional uniaxial strain in the twisted bilayer but also quantify both strain components. This simple strain characterization method based on far-field Raman spectra will facilitate the studies of electronic properties of moiré superlattices under the influence of combined intrinsic and external strains.

Modulating anisotropic phonon polaritons (PhPs) can open new avenues in infrared nanophotonics. Promising PhP dispersion engineering through polariton hybridization has been demonstrated by coupling gated graphene to single-layer α-MoO 3 . However, the mechanism underlying the gate-dependent modulation of hybridization has remained elusive. Here, using IR nanospectroscopic imaging, we demonstrate active modulation of the optical response function, quantified in measurements of gate dependence of wavelength, amplitude, and dissipation rate of the hybrid plasmon-phonon polaritons (HPPPs) in both single-layer and twisted bilayer α-MoO 3 /graphene heterostructures. Intriguingly, while graphene doping leads to a monotonic increase in HPPP wavelength, amplitude and dissipation rate show transition from an initially anticorrelated decrease to a correlated increase. We attribute this behavior to the intricate interplay of gate-dependent components of the HPPP complex momentum. Our results provide the foundation for active polariton control of integrated α-MoO 3 nanophotonics devices.

Aberrant autophagy of the endoplasmic reticulum (reticulophagy) is engaged in diverse pathological disorders. Herein, we reported sensitive imaging of reticulophagy with ER-Green-proRed, a diad combining a solvatochromic entity of trifluoromethylated naphthalimide for long-term ER tracking by green fluorescence and an entity of rhodamine-lactam fluorogenic to lysosomal acidity. Stringently accumulated in the ER to give green fluorescence, ER-Green-proRed exhibits robust red fluorescence upon codelivery with the ER subdomain into lysosomes. The relevance of turn-on red fluorescence to reticulophagy was validated by reticulophagy modulated by starvation, reticulophagic receptors, and autophagy inhibition. This imaging method was successfully employed to discern reticulophagy induced by various pharmacological agents. These results show the potential of ER-targeted pH probes, as exemplified by ER-Green-proRed, to image reticulophagy and to identify reticulophagy inducers.

We employ time-slice and velocity map ion imaging methods to explore the quantum-state resolved dynamics in thermal N 2 O decomposition on Pd(110). We observe two reaction channels: a thermal channel that is ascribed to N 2 products initially trapped at surface defects and a hyperthermal channel involving a direct release of N 2 to the gas phase from N 2 O adsorbed on bridge sites oriented along the [001] azimuth. The hyperthermal N 2 is highly rotationally excited up to J = 52 ( v ″ = 0) with a large average translational energy of 0.62 eV. Between 35 and 79% of the estimated barrier energy (1.5 eV) released upon dissociation of the transition state (TS) is taken up by the desorbed hyperthermal N 2 . The observed attributes of the hyperthermal channel are interpreted by post-transition-state classical trajectories on a density functional theory-based high-dimensional potential energy surface. The energy disposal pattern is rationalized by the sudden vector projection model, which attributes to unique features of the TS. Applying detailed balance, we predict that in the reverse Eley-Rideal reaction, both N 2 translational and rotational excitation promote N 2 O formation.

Correlated quantum phenomena in one-dimensional (1D) systems that exhibit competing electronic and magnetic order are of strong interest for the study of fundamental interactions and excitations, such as Tomonaga-Luttinger liquids and topological orders and defects with properties completely different from the quasiparticles expected in their higher-dimensional counterparts. However, clean 1D electronic systems are difficult to realize experimentally, particularly for magnetically ordered systems. Here, we show that the van der Waals layered magnetic semiconductor CrSBr behaves like a quasi-1D material embedded in a magnetically ordered environment. The strong 1D electronic character originates from the Cr-S chains and the combination of weak interlayer hybridization and anisotropy in effective mass and dielectric screening, with an effective electron mass ratio of m X e / m Y e ∼ 50. This extreme anisotropy experimentally manifests in strong electron-phonon and exciton-phonon interactions, a Peierls-like structural instability, and a Fano resonance from a van Hove singularity of similar strength to that of metallic carbon nanotubes. Moreover, because of the reduced dimensionality and interlayer coupling, CrSBr hosts spectrally narrow (1 meV) excitons of high binding energy and oscillator strength that inherit the 1D character. Overall, CrSBr is best understood as a stack of weakly hybridized monolayers and appears to be an experimentally attractive candidate for the study of exotic exciton and 1D-correlated many-body physics in the presence of magnetic order.

Atomic-level defects in van der Waals (vdW) materials are essential building blocks for quantum technologies and quantum sensing applications. The layered magnetic semiconductor CrSBr is an outstanding candidate for exploring optically active defects because of a direct gap, in addition to a rich magnetic phase diagram, including a recently hypothesized defect-induced magnetic order at low temperature. Here, we show optically active defects in CrSBr that are probes of the local magnetic environment. We observe a spectrally narrow (1 meV) defect emission in CrSBr that is correlated with both the bulk magnetic order and an additional low-temperature, defect-induced magnetic order. We elucidate the origin of this magnetic order in the context of local and nonlocal exchange coupling effects. Our work establishes vdW magnets like CrSBr as an exceptional platform to optically study defects that are correlated with the magnetic lattice. We anticipate that controlled defect creation allows for tailor-made complex magnetic textures and phases with direct optical access.

In living systems, the adsorption of a protein on biointerfaces is a universal phenomenon, such as the specific binding of an antibody and antigen, which plays an important role in body growth and life maintenance. The exploration of a protein-selective adsorption on the biointerface is of great significance for understanding the life process and treatment in vitro. Herein, on the basis of biomimetic strategies, we fabricated a planar-chiral NH 2 -pillar[5]arene modified silicon surface ( p R-/ p S-NP5 surfaces) for a highly enantioselective adsorption of protein by taking advantage of the guest-induced planar chirality of pillar[5]arenes. Results from practical experiments and theoretical calculations show that the p R-NP5 surface possesses a high adsorption capacity and chiral selectivity for bovine serum albumin (BSA). Moreover, it was identified that the guest-induced chiral effect the generation and amplification of planar chirality, which was much beneficial for enhancing the interaction between planar-chiral pillar[5]arene host and BSA. The binding capacity of p R-NP5 and BSA is stronger than that of p S-NP5, thus promoting the chiral selective adsorption of BSA. This work affords a deeper understanding of the chiral influence of protein adsorption on biointerfaces and meanwhile provides a new perspective for chiral-sensing applications.

Active layer materials with silicone side chains have been broadly reported to have excellent long-term stability in harsh environments. However, the application of conjugated materials with silicone side chains in electron transport layers (ETLs) has rarely been reported. In this research, we synthesized for the first time a siloxane-modified perylene-diimide derivative (PDI-OSi) consisting of a side-chain substituent of siloxane and a conjugated group of perylene-diimide (PDI). The inserted siloxane functional groups not only can strengthen the light transmittance of PDI-OSi but also can remarkably expand its solubility and improve the film-forming ability and air stability of the material. Second, introducing siloxane-containing side chains can dramatically lower the work function and interfacial barrier of the electrode, thereby achieving a favorable ohmic contact. In addition, the moderate surface energy of siloxane functional groups makes PDI-OSi hydrophobic, which is conducive to forming excellent miscibility with hydrophobic active layers to promote charge transfer. When PDI-OSi is used as an ETL in organic solar cells (OSCs), operative exciton dissociation and more favorable surface morphology enable OSCs to realize a power conversion efficiency (PCE) of 13.99%. These results indicate that side-chain engineering with siloxane pendants is a facile strategy for constructing efficient OSCs.

Flexible microfluidic chips have good application prospects in situations with easy bending and complex curvature. An important factor affecting the flexible microfluidic chip is its structural complexity. For example, the hybrid chip includes flow channels, mixing chambers, and one-way valves. How to achieve the same function with as few structures as possible has become an important research topic at present. In this paper, a Tesla valve micromixer with unidirectional flow characteristics is presented. A passive laminar flow Tesla valve micromixer is fabricated through 3D printing technology and limonene dissolution method. The main process is as follows: First of all, high impact polystyrene (HIPS) material was employed to make the Tesla valve channel mold. Second, the channel mold was dissolved in the limonene solvent. The mold of Tesla micromixer is made of HIPS material, the mixing experiment displace that the Tesla valve micromixer is characterized by unidirectional flow compared with the common T-shaped planar channel. At the same time, the 5-AAC Tesla valve micromixer can increase the mixing efficiency to 87%. By using four different groove structures and different flow rates of the mixing effect experiment, the conclusion is that the mixing efficiency of the 6-AAC Tesla valve micromixer is up to 0.89 when the flow rate is 2 mL/min. The results manifest that the Tesla valve structure can effectively improve the mixing efficiency., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The reaction mechanism of the CH 3 OH synthesis by the hydrogenation of CO 2 on Cu catalysts is unclear because of the challenge in experimentally detecting reaction intermediates formed by the hydrogenation of adsorbed formate (HCOO a ). Thus, the objective of this study is to clarify the reaction mechanism of the CH 3 OH synthesis by establishing the kinetic natures of intermediates formed by the hydrogenation of adsorbed HCOO a on Cu(111). We exposed HCOO a on Cu(111) to atomic hydrogen at low temperatures of 200-250 K and observed the species using infrared reflection absorption (IRA) spectroscopy and temperature-programmed desorption (TPD) studies. In the IRA spectra, a new peak was observed upon the exposure of HCOO a on Cu(111) to atomic hydrogen at 200 K and was assigned to the adsorbed dioxymethylene (H 2 COO a ) species. The intensity of the new peak gradually decreased with heating from 200 to 290 K, whereas the IR peaks representing HCOO a species increased correspondingly. In addition, small amounts of formaldehyde (HCHO), which were formed by the exposure of HCOO a species to atomic hydrogen, were detected in the TPD studies. Therefore, H 2 COO a is formed via hydrogenation by atomic hydrogen, which thermally decomposes at ∼250 K on Cu(111). We propose a potential diagram of the CH 3 OH synthesis via H 2 COO a from CO 2 on Cu surfaces, with the aid of density functional theory calculations and literature data, in which the hydrogenation of bidentate HCOO a to H 2 COO a is potentially the rate-determining step and accounts for the apparent activation energy of the methanol synthesis from CO 2 on Cu surfaces.

Hydrogels have attracted widespread attention for breaking the bottlenecks faced during facile drug delivery. To date, the preparation of jelly carriers for hydrophobic drugs remains challenging. In this study, by evaporating ethanol to drive the formation of hydrogen bonds, hydrophilic poly(vinyl alcohol) (PVA) and certain hydrophobic compounds [luteolin (LUT), quercetin (QUE), and myricetin (MYR)] were rapidly prepared into supramolecular hydrogel within 10 min. The gelation performance of these three hydrogels changed regularly with the changing sequence of LUT, QUE, and MYR. An investigation of the gelation pathway of these hybrid gels reveals that the formation of this type of gel follows a simple supramolecular self-assembly process, called "hydrophobe-hydrophile crosslinked gelation". Because the hydrogen bond between PVA and the drug is noncovalent and reversible, the hydrogel has good plasticity and self-healing properties, while the drugs can be controllably released by tuning the output stimuli. Using a rat sidewall-cecum abrasion adhesion model, the as-prepared hydrogel was highly efficient and safe in preventing postsurgical adhesion. This work provides a useful archetypical template for researchers interested in the efficient delivery and controllable release of hydrophobic drugs.

The spreading of pesticide droplets on the surface of superhydrophobic plants is an important process, which can prevent the inadequate retention such as bouncing, splashing, and drifting, thereby improving the efficiency of pesticide utilization and reducing soil and groundwater pollution. Herein, we report an approach to fabricate a supramolecular amphiphilic system that significantly contributes to this issue. The hydrophilic amino-pillar[5]arene was synthesized, which could form vesicles with the hydrophobic long-chain guest. This host-guest complex decreased the surface tension, which greatly promotes the spreading of droplets. This study provides a new strategy for prolonging pesticide retention and reducing pesticide loss.

MnBi 2 Te 4 represents a new class of magnetic topological insulators in which novel quantum phases emerge at temperatures higher than those found in magnetically doped thin films. Here, we investigate how couplings between electron, spin, and lattice are manifested in the phonon spectra of few-septuple-layer thick MnBi 2 Te 4 . After categorizing phonon modes by their symmetries, we study the systematic changes in frequency, line width, and line shape of a spectrally isolated A 1g mode. The electron-phonon coupling increases in thinner flakes as manifested in a broader phonon line width, which is likely due to changes of the electron density of states. In 4- and 5-septuple thick samples, the onset of magnetic order below the Néel temperature is concurrent with a transition to an insulating state. We observe signatures of a reduced electron-phonon scattering across this transition as reflected in the reduced Fano parameter. Finally, spin-lattice coupling is measured and modeled from temperature-dependent phonon frequency.

With the growth of demand for flexible devices, the development of flexible electrodes used in energy storage devices has attracted much attention of researchers. In this work, a thin flexible cathode of Prussian blue analogue@polyaniline rooted in carbon cloth has been fabricated. The Prussian blue analogue (PBA) is an electrochemically active material grafted on flexible carbon cloth substrates, which had been precoated with polyaniline. Polyaniline as an intermediate layer can not only improve the overall electronic conductivity of the electrode but also enhance the adhesion and load of the PBAs. The electrochemical properties of the flexible cathode with a "sandwich" structure were determined in half-cells, with a superior capacity of 151 mA h·g -1 and a striking cyclability with 96% capacity retention over 100 cycles at 100 mA h·g -1 . This work proposes a novel perspective for the structural construction and material synthesis of flexible positive electrodes and gives new options for the practical application of flexible batteries.

Enantiomers of various drug molecules have a specific effect on living organisms. Accordingly, developing a sample method for the efficient and rapid recognition of chiral drug enantiomers is of great industrial value and physiological significance. Here, inspired by the structure of ion channels in living organisms, we developed a chiral nanosensor based on an artificial tip-modified nanochannel system that allows efficient selective recognition of chiral drugs. In this system, l-alanine-pillar[5]arenes as selective receptors were introduced on the tip side of conical nanochannels to form an enantioselective "gate". The selective coefficient of our system toward R -propranolol is 4.96, which is higher than the traditional fully modified nanochannels in this work.

As a passive cooling strategy, radiative cooling is becoming an appealing approach to dissipate heat from terrestrial emitters to the outer space. However, the currently achieved cooling performance is still underperforming due to considerable solar radiation absorbed by the emitter and nonradiative heat transferred from the surroundings. Here, we proposed a mechanically robust and spectrally selective convection shield composed of nanoporous composite fabric (NCF) to achieve daytime subambient radiative cooling. By selectively reflecting ∼95% solar radiation, transmitting ∼84% thermal radiation, and suppressing the nonradiative heat transferred from warmer surroundings, the NCF-based radiative cooler demonstrated an average daytime temperature reduction of ∼4.9 °C below the ambient temperature, resulting in an average net radiative cooling power of ∼48 W/m 2 over a 24 h measurement. In addition, we also modeled the potential cooling capacity of the NCF-based radiative cooler and demonstrated that it can cover the cooling demands of energy-efficient residential buildings in most regions of China. Excellent spectral selectivity, mechanical strength, and weatherability of the NCF cover enable a much broader selection for the emitters, which is promising in the real-world deployment of direct daytime subambient radiative cooling.

Artemisinin and its derivatives are of great research value in biology. In this work, we study their chiral and optical properties. The multidimensional multifunction analysis method is used to analyze the linear and nonlinear optical processes (one-photon and two-photon absorption: OPA and TPA), electronic circular dichroism (ECD), and Raman optical activity (ROA) mechanisms under light excitation. Transition dipole moments (TDMs) and charge difference density (CDD) are used to describe the electromagnetic interaction between ECD and ROA when a substance is excited by light. The theoretical research results of the study show that the dioxygen atoms provide an intermediary for the transfer between charges and also enhance the role of the TDMs. This generalized chiral theory can not only explain the traditional sources of chirality but also distinguish whether the molecule has chirality when the chiral center is not obvious. By analyzing ROA and different vibration modes, we can clearly observe that each part of the molecule responds differently when excited., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Highly confined and low-loss hyperbolic phonon polaritons in hexagonal boron nitride possess properties analogous to surface plasmon polaritons, but with enhanced confinement and lower loss. Their properties have been so far mostly studied on dielectric substrates, which provide an asymmetric environment for polariton propagation, and add to damping. In this work, we investigate hyperbolic phonon polaritons over suspended hexagonal boron nitride, showing remarkable properties, including elongated polariton wavelength and reduced damping, up to 18% lower compared to dielectric-backed samples. We use real-space nanoimaging of the polaritons in hexagonal boron nitride to demonstrate and visualize these effects. Our results indicate that suspended boron nitride offers better figures of merit for polariton transport, which are generalizable to other polaritonic materials, and they may be explored in heterostructures for advanced nanophotonic applications.

The self-assembly of macroscopic droplets on interfaces has attracted much attention and shown promising potential in the field of materials as a sensing or delivery system. Herein, we reported a new strategy to construct a d-tartaric acid-functionalized pillar[5]arene (d-TP5) interface for macroscopic differentiation of histidine enantiomers. At the molecular level, it has been proved that d-TP5 has the ability to distinguish between l-Histidine and d-Histidine ( K L / K D = 4.6). Furthermore, a functional d-TP5 surface was constructed by a click reaction and characterized by contact angle measurements and attenuated total reflection-Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses. The d-TP5 surface exhibited the selective dynamic adhesion of l-His droplets on the tilted interface. It means that a d-TP5 surface can distinguish histidine enantiomers at a macrolevel. The amount of d/l-His absorbed by a d-TP5 surface and the morphology of His particles formed by removing the solvent have been investigated to prove that the self-assembly of His occurs on the d-TP5 surface. The possible mechanism has been discussed from host-guest interaction and chiral recognition. The proposed chiral material displays rapidly remarkable selectivity and is convenient to be utilized, which should be suitable for comprehending chiral recognition processing and applied to chiral recognition detection of histidine in a living body.

Low-cost manganese hexacyanoferrate (NMHCF) possesses many favorable advantages including high theoretical capacity, ease of preparation, and robust open channels that enable faster Na + diffusion kinetics. However, high lattice water and low electronic conductivity are the main bottlenecks to their pragmatic realization. Here, we present a strategy by anchoring NMHCF on reduced graphene oxide (RGO) to alleviate these problems, featuring a specific discharge capacity of 161/121 mA h g -1 at a current density of 20/200 mA g -1 . Moreover, the sodiation process is well revealed by ex situ X-ray diffraction, EIS and Car-Parrinello molecular dynamics simulations. At a rate of 20 mA g -1 , the hard carbon//NMHCF/RGO full cell affords a stable discharge capacity of 84 mA h g -1 (based on the weights of cathode mass) over 50 cycles, thus highlighting NMHCF/RGO an alternative cathode for sodium-ion batteries.

Glycopolymers with large galactose units are attractive in biological processes because of their ability to selectively recognize lectin proteins. Recently, thermoresponsive double-hydrophilic block glycopolymers (TDHBGs) have been designed, which allow sugar residues to expose or hide via the lower critical solution temperature (LCST)-type phase transition. In this work, we first synthesize a new type of TDHBGs, composed of a thermoresponsive poly(di(ethylene glycol)methyl ether methacrylate) block and a galactose-functionalized, poly(6- O-vinyladipoyl-d-galactose) (POVNG) block. The LCST can be tuned by varying the size of the POVNG block. Then, we have systematically investigated their thermoresponsive self-assembly behavior, using static and dynamic light scattering techniques, combined with transmission electron microscopy (TEM) imaging. It is found that the TDHBGs possess both micellization and LCST-type transition, and there exist strong interactions between them, depending on the concentration and structure of the TDHBGs. It is particularly interesting that for the same type of TDHBGs under different conditions, such interactions result in rich morphologies of the formed micelles (or nanoparticles) such as spheres, hollow spheres, prolate ellipsoids, crystal-like, and so on, thus potentially enriching their biological applications by noting that they are hepatoma-targeting glycopolymers.

High expression of glutaminyl cyclase (QC) contributes to the initiation of Alzheimer's disease (AD) by catalyzing the generation of neurotoxic pyroglutamate (pE)-modified β-amyloid (Aβ) peptides. Preventing the generation of pE-Aβs by QC inhibition has been suggested as a novel approach to a disease-modifying therapy for AD. In this work, a series of diphenyl conjugated imidazole derivatives (DPCIs) was rationally designed and synthesized. Analogues with this scaffold exhibited potent inhibitory activity against human QC (hQC) and good in vitro blood-brain barrier (BBB) permeability. Further assessments corroborated that the selected hQC inhibitor 28 inhibits the activity of hQC, dramatically reduces the generation of pE-Aβs in cultured cells and in vivo, and improves the behavior of AD mice.

Compared to pure organic amphiphiles, metalloamphiphiles display distinctive features, including luminescence, magnetism and catalytic properties. However, the self-organization of metalloamphiphiles is commonly driven by solvophobic effects. Alkyl chains and oligomeric ethylene glycol moieties are thus the most frequently used aggregation units to drive the self-assembly of metalloamphiphiles. We expect novel metallo-supramolecular structures with exciting functions to be created if additional noncovalent interaction modes are incorporated. In this work, a new type of metalloamphiphile, consisting of a Tb(III) complex head and a cholesteryl unit (TbL 3+ (I)), was designed and synthesized. TbL 3+ (I) spontaneously self-assembles into helical nanofibers (d = 6 nm) in water. This synthetic multivalent nanoscale binding array displays powerful capability for the recognition of DNA conformations through a turn-on luminescence sensing mechanism. ssDNA-kit1 triggered a 26-fold increase in the luminescence intensity of TbL 3+ (I). Its corresponding G-quadruplex structure (G-quadruplex-kit1), however, induced a 6.6-fold enhancement under the same conditions. Consequently, TbL 3+ (I) nanofibers can monitor DNA folding. In contrast, neither ssDNA-kit1 nor G-quadruplex-kit1 markedly promoted the luminescence of molecularly dispersed TbL 3+ (II), illustrating that the multivalent electrostatic interactions between the phosphate groups on the backbone of DNA and TbL 3+ (I) self-assembled into nanofibers could greatly improve the efficiency of the energy transfer between the guanine units and the organized TbL 3+ (I). The TbL 3+ (I) nanofibers could bind and distinguish not only the kit1-ssDNA/G-quadruplex but also the conformations of other G-rich DNA, such as spb1, htelo, and intermolec-htelo. The self-assembly of luminescent metalloamphiphiles thus provides a general and convenient strategy for the efficient recognition and conversion of molecular information.

Lipid-albumin nanoparticles (LAN) were synthesized for delivery of RX-0047, an antisense oligonucleotide (ASO) against the hypoxia inducible factor-1 alpha (HIF-1α) to solid tumor. These lipid nanoparticles (LNs) incorporated a human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate, which is cationic and can form electrostatic complexes with negatively charged oligonucleotides. The delivery efficiency of LAN-RX-0047 was investigated in KB cells and a KB murine xenograft model. When KB cells were treated with LAN-RX-0047, significant HIF-1α downregulation and enhanced cellular uptake were observed compared to LN-RX-0047. LN-RX-0047 and LAN-RX-0047 showed similar cytotoxicity against KB cells with IC50 values of 19.3 ± 3.8 and 20.1 ± 4.2 μM, respectively. LAN-RX-0047 was shown to be taken up by the cells via the macropinocytosis and caveolae-mediated endocytosis pathways while LN-RX-0047 was taken up by cells via caveolae-mediated endocytosis. In the KB xenograft tumor model, LAN-RX-0047 exhibited tumor suppressive activity and significantly reduced intratumoral HIF-1α expression compared to LN-RX-0047. Furthermore, LAN-RX-0047 greatly increased survival time of mice bearing KB-1 xenograft tumors at doses of either 3 mg/kg or 16 mg/kg. These results indicated that LAN-RX-0047 is a highly effective vehicle for therapeutic delivery of antisense agents to tumor.

A mitochondria-targeted approach was developed to increase the cellular bioactivities of thioredoxin reductase (TrxR) inhibitors. By being conjugated with a triphenylphosphine (TPP) motif to a previously found TrxR inhibitor 2a, the resulted compound TPP2a can target subcellular mitochondria and efficiently inhibit cellular TrxR, leading to remarkably increased cellular ROS level and mitochondrial apoptosis of HeLa cancer cells. The cellular bioactivities of TPP2a, including its cytotoxicity against a panel of cancer cell lines, dramatically elevated compared with its parental compound 2a. The selectively and covalently interaction of TPP2a with subcellular mitochondrial TrxR was validated by fluorescent microscopy. Moreover, a nonspecific signal quenching coupled strategy was proposed based on the environmentally sensitive fluorescence of TPP2a, which makes it possible to label TrxR by removing the nonspecific backgrounds caused by TPP2a under complex biosettings such as cellular lysates and living cells, implicating a potential of TPP2a for TrxR-specific labeling.

CD33-targeted lipid nanoparticles (aCD33LNs) were synthesized for delivery of GTI-2040, an antisense oligonucleotide (ASO) against the R2 subunit of ribonucleotide reductase, to acute myelogenous leukemia (AML). These LNs incorporated a deoxycholate-polyethylenimine (DOC-PEI) conjugate, which has shown significant activity to facilitate oligonucleotide delivery. Anti-CD33 scFv (aCD33) was added as a targeting ligand. The delivery efficiency of this system was investigated both in vitro and in vivo. When cells were treated with aCD33LN/GTI-2040, significant uptake was observed in CD33 positive Kasumi-1 cells. aCD33LNs loaded with GTI-2040 induced significant down-regulation of R2 mRNA and protein levels in AML cells. Moreover, aCD33LN/GTI-2040 showed a 15-fold reduction in the IC50 of antileukemic drug Ara-C in Kasumi-1 cells. In Kasumi-1 xenograft model, aCD33LN/GTI-2040 showed significant R2 downregulation compared to LN/GTI-2040. Furthermore, aCD33LN/GTI-2040 coadministered with Ara-C was shown to be highly effective in tumor growth inhibition and to greatly increase survival time of mice bearing Kasumi-1 xenograft tumors. The conjugate DOC-PEI has shown an ability to include calcein release from lipid nanoparticles, suggesting a potential mechanism contributing to efficient endosome release by DOC-PEI2K. These results indicate that aCD33LNs are a highly effective vehicle for the therapeutic delivery of antisense agents to AML.

The subsurface urban heat island (SubUHI) is one part of the overall UHI specifying the relative warmth of urban ground temperatures against the rural background. To combat the challenge on measuring extensive underground temperatures with in situ instruments, we utilized satellite-based moderate-resolution imaging spectroradiometer data to reconstruct the subsurface thermal field over the Beijing metropolis through a three-time-scale model. The results show the SubUHI's high spatial heterogeneity. Within the depths shallower than 0.5 m, the SubUHI dominates along the depth profiles and analyses imply the moments for the SubUHI intensity reaching first and second extremes during a diurnal temperature cycle are delayed about 3.25 and 1.97 h per 0.1 m, respectively. At depths shallower than 0.05 m in particular, there is a subsurface urban cool island (UCI) in spring daytime, mainly owing to the surface UCI that occurs in this period. At depths between 0.5 and 10 m, the time for the SubUHI intensity getting to its extremes during an annual temperature cycle is lagged 26.2 days per meter. Within these depths, the SubUHI prevails without exception, with an average intensity of 4.3 K, varying from 3.2 to 5.3 K.

A unified strategy toward the asymmetric facile construction of the [6.7.6.5]oxapentacyclic skeleton of cortistatins is reported, featuring intramolecular Diels-Alder (IMDA), oxidative dearomatization, and an oxy-Michael addition reaction.

One-pot and diastereoselective syntheses of diverse chromeno[3,4-c]pyrrole-3,4-diones from readily available starting materials were achieved via sequential Ugi-4CR and intramolecular Michael addition.

Benzo[e]isoindole-1,3-dione derivatives were synthesized, and the effects on GSK-3beta activity and zebrafish embryo growth were evaluated. A series of derivatives show obvious inhibitory activity against GSK-3beta. The most potent inhibitor, 7,8-dimethoxy-5-methylbenzo[e]isoindole-1,3-dione (8a), shows nanomolar IC(50) and obvious phenotype on zebrafish embryo growth associated with the inhibition of GSK-3beta at low micromolar concentration. The interaction mode between 8a and GSK-3beta was characterized by computational modeling.

An unexpected R(2)AlCl-mediated ring-opening reaction of oxacycles for the formation of all-carbon quaternary centers was discovered, and a possible mechanism is proposed. The developed chemistry provides a concise approach to synthesize structural diverse of dolastane-type compounds.

A concise and modular approach to synthesize a new type of cyclopentene-based diaminocyclitol library from D-serine and L-serine has been developed, and key steps in this synthesis are an aza-Claisen rearrangement, a ring-closing metathesis, and a Baylis-Hillman reaction. The developed chemistry may offer a unique way to investigate the neuraminidase (NA) mutation by systematically mapping the changes within its binding sites.

The unusual regioselectivity in the Diels-Alder reactions of pyranoquinone 1 with (4,4-dimethoxybuta-1,3-dien-2-yloxy)trimethylsilane 2 are explored by both computations and experiments. The regioselectivity is controlled by the electrostatic interaction of the lactone ring-oxygen and the vicinal quinone oxygen on the transition structure, which can be tuned by the terminal methyl group of the butadienes.

Response surface methodology was successfully employed to optimize lipase-catalyzed synthesis of feruloyl butyryl glycerides (FBGs). The effects of the reaction parameters, including the reaction time, reaction temperature, enzyme concentration, substrate molar ratio, and water activity, and the interaction parameters were examined. The analysis suggested that the conversion of the FBGs was significantly (p < 0.05) affected by independent factors of reaction time, reaction temperature, substrate molar ratio, and water activity as well as interactive terms of reaction temperature/reaction time, reaction temperature/enzyme concentration, substrate molar ratio/reaction temperature, water activity/reaction temperature, reaction time/enzyme concentration, and enzyme concentration/water activity. The highest conversion yield of FBGs was 81.2% at the following optimized reaction conditions: reaction temperature of 53.6 degrees C, reaction time of 5.5 days, enzyme concentration of 50.8 mg/mL, water activity of 0.14, and substrate molar ratio of 2.9. The conversion is higher as compared to that at the conditions before optimization.

An efficient and rapid solution-phase combinatorial synthesis of the SAG library was developed. The salient features for this library synthesis is the application of carbothioamide-derived palladacycle-catalyzed Suzuki coupling reactions for the parallel synthesis of a series of pyridine-based biaryl aldehydes under aerobic conditions and a direct N-alkylation of carbamates using NaH as base in DMF in the presence of catalytic amount of water. The resultant library has been submitted to biological screening to evaluate their potential role in the regulation of Hedgehog pathway.

Lewis acid Zn(OTf)(2)-catalyzed tandem annulations of isonitriles and allenic esters which lead to efficient and flexible syntheses of a range of biologically significant maleimides and carbazoles and related compounds are reported. A mechanistic rationale is proposed to account for the observed reactivity.

[reaction: see text] A single-step chirality transfer method for the synthesis of axially chiral biaryl compounds by construction of the second aromatic ring via a Diels-Alder/retro-Diels-Alder cascade reaction is reported. This methodology should find broad application in the synthesis of natural products and asymmetric catalysts.