Aptamer-Linked Photonic Crystal Assay for High-Throughput Screening of HIV and SARS-CoV-2.

We present a microplate assay for the detection of HIV and SARS-CoV-2 which involves the preadsorption of carboxy-modified polystyrene microspheres to the microplate wells and their self-assembly leading to the formation of a photonic crystal colloidal array (PCCA). PCCA is then cross-linked with amino-modified aptamers selected for viral cell surface glycoproteins, i.e., S1-protein of SARS-CoV-2 and gp120 of the human immunodeficiency virus (HIV), to develop an aptamer-linked photonic crystal assay (ALPA). ALPA is then utilized as a proof-of-concept method for the detection of S1-protein, gp120, and two whole viruses, i.e., SARS-CoV-2 and HIV, as well. The aptamers are stable at room temperature and can bind with the viruses' proteins via hydrogen bonding. This binding leads to color generation from PCCA, and the signal can easily be measured and quantified by a UV/vis spectrometer. The assay carries the advantage of a two-step detection process by the addition of the virus sample directly to a 96-well microplate and incubation of 5 min followed by convenient detection through a UV/vis-spectrometer. The assay does not require any additional reagents and can be customized for similar viruses utilizing specific aptamers targeting their cell surface receptors.

Ferulic acid attenuated difenoconazole-induced immunotoxicity in carp by inhibiting TRAF/TAK1/NF-κB, Nrf2 and p53 pathways.

Difenoconazole (DFZ) is a classical triazole fungicide that causes immunosuppression in non-target organisms. Ferulic acid (FA) is a polyphenolic molecule found in nature that has antioxidant and anti-inflammatory activities. The purpose of this investigation was to see if FA could prevent DFZ-induced immunosuppression and to identify the potential mechanisms. Carp were exposed to 1/10 LC50 of DFZ as well as fed normal feed or feed containing dietary additive FA for 30 d. It was found that DFZ-induced immunosuppression could be improved by FA, as evidenced by upregulation of Hb, C3 and IgM and downregulation of LDH. It was then investigated that FA could ameliorate DFZ-induced splenic injury through p53-mediated apoptosis. At the same time, enhancing the levels of CAT, GSH and T-AOC in spleen and transcription levels Nrf2 signaling pathway related genes indicated that FA reduced oxidative damage caused by DFZ by blocking the Nrf2 signaling pathway. In addition, FA inhibited the inflammatory response triggered by TRAF/TAK1/NF-κB signaling pathway, downregulated the transcript levels of pro-inflammatory factors (il-1ß, tnf-α, il-6) and the level of NLRP3 inflammasome (NRLP3, ASC, Caspase 1), and upregulated the transcript levels of anti-inflammatory factors (tgf-ß1, il-10). In conclusion, the above results suggested that FA mediated TRAF/TAK1/NF-κB, Nrf2, and p53 pathways to attenuate DFZ-induced inflammation, oxidative stress, and apoptosis thereby enhancing the immune capacity of carp.

Strong External Electric Fields Reduce Explosive Sensitivity: A Theoretical Investigation into the Reaction Selectivity in NH2NO2∙∙∙NH3.

Controlling the selectivity of a detonation initiation reaction of explosive is essential to reduce sensitivity, and it seems impossible to reduce it by strengthening the external electric field. To verify this, the effects of external electric fields on the initiation reactions in NH2NO2∙∙∙NH3, a model system of the nitroamine explosive with alkaline additive, were investigated at the MP2/6-311++G(2d,p) and CCSD(T)/6-311++G(2d,p) levels. The concerted effect in the intermolecular hydrogen exchange is characterized by an index of the imaginary vibrations. Due to the weakened concerted effects by the electric field along the -x-direction opposite to the "reaction axis", the dominant reaction changes from the intermolecular hydrogen exchange to 1,3-intramolecular hydrogen transference with the increase in the field strengths. Furthermore, the stronger the field strengths, the higher the barrier heights become, indicating the lower sensitivities. Therefore, by increasing the field strength and adjusting the orientation between the field and "reaction axis", not only can the reaction selectivity be controlled, but the sensitivity can also be reduced, in particular under a super-strong field. Thus, a traditional concept, in which the explosive is dangerous under the super-strong external electric field, is theoretically broken. Compared to the neutral medium, a low sensitivity of the explosive with alkaline can be achieved under the stronger field. Employing atoms in molecules, reduced density gradient, and surface electrostatic potentials, the origin of the reaction selectivity and sensitivity change is revealed. This work provides a new idea for the technical improvement regarding adding the external electric field into the explosive system.

Consensus Receptor-Binding Domain-Targeted Aptamer Selection and Designing of a Photonic Crystal-Decorated Aptasensor for SARS-CoV-2.

The frequent emergence of variants of concern (VOC) of SARS-CoV-2 necessitates a sensitive and all-inclusive detection platform that remains viable despite the virus mutations. In this context, we targeted the receptor-binding domain (RBD) of glycoprotein (S-protein) of all VOC and constructed a consensus RBD (cRBD) based on the conserved amino acids. Then, we selected a high-affinity ssDNA novel aptamer specific for the cRBD by an in silico approach. The selected aptamer is utilized to fabricate a photonic crystal (PC)-decorated aptasensor (APC-sensor), which consists of polystyrene nanoparticles polymerized within a polyacrylamide hydrogel. cRBD-responsive ssDNA aptamers are crosslinked in the hydrogel network, which selectively bind to the cRBD and SARS-CoV-2 in saliva samples. The binding response can be visually monitored by swelling of the hydrogel and color generation by diffraction of light from PCs and can be quantified by the diffraction ring diameter or a spectrometer. The sensor delivers a LOD of 12.7 ± 0.55 ng mL-1 for the cRBD and 3 ± 18.8 cells mL-1 for SARS-CoV-2 in saliva samples, with a rapid response of 5 min. The sensor can be stored and regenerated without loss of activity. It can be utilized as a point-of-care testing (POCT) for SARS-CoV-2 diagnosis.

In Vivo Imaging of Exosomes Labeled with NIR-II Polymer Dots in Liver-Injured Mice.

Mesenchymal stem cell-derived exosomes (MSC-Exos) are emerging as a promising platform for treating various intractable diseases and organ injuries. Monitoring their migration, homing, and therapeutic capability in vivo is essential to develop exosome-based theranostics. Here, we designed fluorescent semiconductor polymer dots (Pdots) in the second near-infrared window (NIR-II) for bright labeling and tracking of MSC-Exos. Glucose-coated Pdots (Pdots-Glu) were able to label MSC-Exos without changing their biological properties. The NIR-II fluorescent Pdots allow for high labeling brightness and long-term in vivo tracking of MSC-Exos. We investigated the biodistributions and therapeutic functions of these labeled MSC-Exos in liver-resected mice. In vivo and ex vivo imaging demonstrated that the Pdot-labeled MSC-Exos injected via the tail vein mainly accumulated in the residual liver tissue. In terms of the therapeutic effect, MSC-Exos may accelerate postoperative liver function recovery by inhibiting inflammatory responses, promoting cell proliferation, and resisting apoptosis. Our results indicated that MSC-Exos therapeutic systems hold promising applications in liver regenerative medicine.

Responsive hydrogel-based three-dimensional photonic crystal sensor for lactic acid detection.

The determination of lactic acid content has a guiding significance for disease diagnosis or food supervision. Herein, a hydrogel-based three-dimensional photonic crystal (PC) sensor for specific detection of lactic acid is introduced. The hydrogel was prepared by one-step copolymerization of N-isopropylacrylamide and acrylamide in the presence of oxamate derivative 2-((6-acrylamidohexyl) amino)-2-oxoacetic acid (AOA). An obvious color change from orange-red to purple and a 45-nm redshift of the reflection peak were obtained in 3 min when lactic acid concentration increased from 0 to 20 mM. The detection limit was confirmed as 0.1 mM, and the prepared sensor can be reused more than 20 times. Moreover, the affinity and selectivity of AOA to lactic acid were proven by both the interaction energy from density functional theory (DFT) study and the comparison to those of pyruvate and propionic acid. This sensor was proven to be cost-effective and convenient with rapid response time, good reusability, and selectivity.

Mono-Sized Anion-Exchange Magnetic Microspheres for Protein Adsorption.

In this study, mono-sized anion-exchange microspheres with polyglycidylmethacrylate were engineered and processed to introduce magnetic granules by penetration-deposition approaches. The obtained magnetic microspheres showed a uniform particle diameter of 1.235 µm in average and a good spherical shape with a saturation magnetic intensity of 12.48 emu/g by VSM and 12% magnetite content by TGA. The magnetic microspheres showed no cytotoxicity when the concentration was below 10 µg/mg. The magnetic microspheres possess respective adsorption capacity for three proteins including Bovine albumin, Hemoglobin from bovine blood, and Cytochrome C. These magnetic microspheres are also potential biomaterials as targeting medicine carriers or protein separation carriers at low concentration.

Comparative Thermal Research on Energetic Molecular Perovskite Structures.

Molecular perovskites are promising practicable energetic materials with easy access and outstanding performances. Herein, we reported the first comparative thermal research on energetic molecular perovskite structures of (C6H14N2)[NH4(ClO4)3], (C6H14N2)[Na(ClO4)3], and (C6H14ON2)[NH4(ClO4)3] through both calculation and experimental methods with different heating rates such as 2, 5, 10, and 20 °C/min. The peak temperature of thermal decompositions of (C6H14ON2)[NH4(ClO4)3] and (C6H14N2) [Na(ClO4)3] were 384 and 354 °C at the heating rate of 10 °C/min, which are lower than that of (C6H14N2)[NH4(ClO4)3] (401 °C). The choice of organic component with larger molecular volume, as well as the replacement of ammonium cation by alkali cation weakened the cubic cage skeletons; meanwhile, corresponding kinetic parameters were calculated with thermokinetics software. The synergistic catalysis thermal decomposition mechanisms of the molecular perovskites were also investigated based on condensed-phase thermolysis/Fourier-transform infrared spectroscopy method and DSC-TG-FTIR-MS quadruple technology at different temperatures.

Comparative Studies on Thermal Decompositions of Dinitropyrazole-Based Energetic Materials.

Dinitropyrazole is an important structure for the design and synthesis of energetic materials. In this work, we reported the first comparative thermal studies of two representative dinitropyrazole-based energetic materials, 4-amino-3,5-dinitropyrazole (LLM-116) and its novel trimer derivative (LLM-226). Both the experimental and theoretical results proved the active aromatic N-H moiety would cause incredible variations in the physicochemical characteristics of the obtained energetic materials. Thermal behaviors and kinetic studies of the two related dinitropyrazole-based energetic structures showed that impressive thermal stabilization could be achieved after the trimerization, but also would result in a less concentrated heat-release process. Detailed analysis of condensed-phase systems and the gaseous products during the thermal decomposition processes, and simulation studies based on ReaxFF force field, indicated that the ring opening of LLM-116 was triggered by hydrogen transfer of the active aromatic N-H moiety. In contrast, the initial decomposition of LLM-226 was caused by the rupture of carbon-nitrogen bonds at the diazo moiety.

An enhanced gas sensor based on SiO2@mesoporous MCM-41 core-shell nanocomposites for SO2 visual detection.

A colorimetric sulfur dioxide (SO2) gas sensor based on a core-shell composite was developed. The composite was fabricated with a silicon dioxide core and a mesoporous MCM-41 shell (SiO2@MCM-41), and further loaded with a mixture of zinc chloride (ZnCl2), sodium nitroprusside (SNP) and hexamine as an SO2 indicator. The sensing properties of SiO2@MCM-41 toward SO2 were measured in solid powder, discs and a gas detection tube (GDT), respectively. Each of these sensing configurations showed a distinct color change from pale yellow to red, which indicates good potential for naked-eye detection of SO2. The limit of detection (LOD) is 2 ppm for SiO2@MCM-41 discs, which indicates high sensitivity to SO2. The performance of GDT suggested a linear relationship between the SO2 concentration and the response length of the red portions in a range of 100-1000 ppm. This work shows promising potential of SiO2@MCM-41 as an easy, effective and rapid response sensing material for the in situ detection of SO2.

Short-Term Rental Forecast of Urban Public Bicycle Based on the HOSVD-LSTM Model in Smart City.

As a kind of transportation in a smart city, urban public bicycles have been adopted by major cities and bear the heavy responsibility of the "last mile" of urban public transportation. At present, the main problem of the urban public bicycle system is that it is difficult for users to rent a bike during peak h, and real-time monitoring cannot be solved adequately. Therefore, predicting the demand for bicycles in a certain period and performing redistribution in advance is of great significance for solving the lag of bicycle system scheduling with the help of IoT. Based on the HOSVD-LSTM prediction model, a prediction model of urban public bicycles based on the hybrid model is proposed by transforming the source data (multiple time series) into a high-order tensor time series. Furthermore, it uses the tensor decomposition technology (HOSVD decomposition) to extract new features (kernel tenor) from higher-order tensors. At the same time, these kernel tenors are directly used to train tensor LSTM models to obtain new kernel tenors. The inverse tensor decomposition and high-dimensional, multidimensional, and tensor dimensionality reduction were introduced. The new kernel tenor obtains the predicted value of the source sequence. Then the bicycle rental amount is predicted.

Flexible construction of cellulose photonic crystal optical sensing nano-materials detecting organic solvents.

We developed a simple and efficient method to construct 3D and 2D opal and inverse opal cellulose photonic crystal films (CPCF) by embedding 3D or 2D polymethyl methacrylate (PMMA) colloidal arrays into carboxymethyl cellulose (CMC), respectively. The morphology and optical performance of CPCFs were characterized by SEM, diffraction spectra, Debye rings, and structural color. The brilliant structural colors of CPCFs are visible to the eye in the entire visible spectrum, and can be tuned by changing the particle diameters or the pore sizes. Attributed to decreased particle spacing and lower average refractive index caused by air spheres instead of polymer spheres, the stopbands of the inverse opal CPCFs blue-shifted. To the contrary, the particle spacing of 2D inverse opal CPCFs increased due to the losing of the connection force of 2D arrays, along with decreasing of Debye ring diameters. By alternately being exposed to organic solvents of methanol, acetonitrile, butanol, dioxane, and carbon tetrachloride, the 3D inverse opal CPCFs displayed an excellent sensing performance with instantaneously reversible color changes from violet to red. Their high stability and flexibility, efficient visual detection, and wide range of analytes promises a new opportunity for optical switching and sensing applications.

Acetylcholinesterase-functionalized two-dimensional photonic crystal for the sensing of G-series nerve agents.

G-series nerve agents, such as sarin, tabun, and soman, would cause tremendous harm in military and terrorist attacks, so it is necessary to develop a simple method for the rapid and efficient detection of these hazardous substances. We have developed a tunable acetylcholinesterase (AChE)-functionalized two-dimensional photonic crystal (2D PhC) for the detection of a real nerve agent, sarin. In accordance with the 2D PhC previously prepared by our group, the AChE-functionalized 2D PhC was optimized by adjustment of the amount of monomer in the hydrogel, which not only increased the sensitivity of the 2D PhC, with the detection limit decreasing by two orders of magnitude, but also ensured the structural color spanned the whole visible region in the detection range. A linear relationship between the logarithm of the sarin concentration and the particle spacing of the AChE-functionalized 2D PhC was observed from 7.1 × 10-17 to 7.1 × 10-4 mol/L. The AChE-functionalized 2D PhC also responded to mimics of G-series nerve agents, including dimethyl methylphosphonate, diisopropyl methylphosphonate, and isodipropyl methylphosphonate, to various degrees. The proposed 2D-PhC hydrogel has potential for low-cost, trace-level, and on-site monitoring of other G-series nerve agents. Graphical abstract.

Hybrid Molecular Container Based on Glycoluril and Triptycene: Synthesis, Binding Properties, and Triggered Release.

We designed and synthesized a "hybrid" molecular container 1, which is structurally related to both cucurbit[n]uril (CB[n]) and pillar[n]arene type receptors. Receptor 1 was fully characterized by 1 H NMR, 13 C NMR, IR, MS and X-ray single crystal diffraction. The self-association behavior, host-guest recognition properties of 1, and the [salt] dependence of Ka were investigated in detail by 1 H NMR and isothermal titration calorimetry (ITC). Optical transmittance and TEM measurements provide strong evidence that receptor 1 undergoes co-assemble with amphiphilic guest C10 in water to form supramolecular bilayer vesicles (diameter 25.6±2.7 nm, wall thickness ≈3.5 nm) that can encapsulate the hydrophilic anticancer drug doxorubicin (DOX) and the hydrophobic dye Nile red (NR). The release of encapsulated DOX or NR from the vesicles can be triggered by hexamethonium (8 c) or spermine (10) which leads to the disruption of the supramolecular vesicles.

A glycoluril dimer-triptycene hybrid receptor: synthesis and molecular recognition properties.

The strategic combination of the methylene bridged glycoluril dimer and triptycene skeletons delivers acyclic water soluble hybrid receptor 1 which is analogous to cucurbit[6]uril. The molecular recognition properties of host 1 toward hydrophobic cationic guests are investigated in detail by a combination of 1H NMR spectroscopy and isothermal titration calorimetry (ITC) studies. The fluorescence emission of 1 can be selectively and efficiently quenched upon the formation of 1·26 and 1·28 complexes.

Therapeutic Considerations and Conjugated Polymer-Based Photosensitizers for Photodynamic Therapy.

Conjugated polymers have recently attracted a great deal of attention for applications in photodynamic therapy (PDT) because of their light-harvesting capability, efficient energy transfer, and singlet oxygen generation properties. This review describes recent advances in PDT development, including therapeutic mechanisms of PDT in cancer treatments, light excitation methods, and especially recent advances of conjugated polyelectrolytes and conjugated polymer nanoparticles as photosensitizers. The future direction on PDT and further development of conjugated polymer photosensitizers are discussed. The aim of this review is to stimulate innovative ideas to synthesize a new generation of conjugated polymer photosensitizers and promote their translation to clinical applications of PDT.

Peptide-Coated Semiconductor Polymer Dots for Stem Cells Labeling and Tracking.

Stem cell therapy is rapidly moving toward translation to clinical application. To elucidate the therapeutic effect, a robust method that allows tracking of the stem cells over an extended period of time is required. Herein, semiconducting polymer dots (Pdots) are demonstrated for their use in bright labeling and tracking of human mesenchymal stem cells (MSCs) in vitro and in vivo. The Pdots coated with a cell-penetrating peptide (R8) showed remarkable endocytic uptake efficiency that was 15 times higher than that of carboxyl Pdots and more than 200 times than that of bare Pdots. The Pdot-labeled MSCs can be traced for 15 generations in vitro and tracked over 2 weeks in vivo after subcutaneous transplantation. The labeled MSCs administered through the tail vein were preferentially accumulated in the lung; this was distinctive from the distribution of free Pdots, which were primarily distributed in the liver. Based on the properties of bright labeling, excellent tracking capability, and great biocompatibility, the Pdots will be valuable in the applications of stem cell biology and regenerative medicine.

Self-assembly of the polymer brush-grafted silica colloidal array for recognition of proteins.

Three-dimensional photonic crystal sensors are attractive platforms for autonomous chemical sensing and colorimetric bioassays. At present, the photonic crystal sensors with inverse opal structure were extensively studied, which swells or shrinks in response to the analytes. However, the fabrication of inverse opal sensors still remains a major challenge. Herein, we propose a simple and versatile approach to fabricate 3D opal photonic sensors. This photonic crystal is fabricated via assembly of monodispersed silica particles grafted with linear polymeric ligands (SiO2@LPs). Acrylic acid (negatively charged monomer) and N-tert-butylacrylamide (hydrophobic monomer) were incorporated with N-isopropylacrylamide to achieve strong affinity between the designed polymer ligands and proteins. The proposed photonic crystal displays a maximum redshift of 23 nm in response to 2 mg/mL lysozyme, accompanied by the structure color change from blue to green. Compared to the cross-linked polymers, the linear polymer with flexible structure allows the colloidal array to recognize lysozyme with higher sensitivity (as low as 5 µg/mL) and broader linearity (from 5 to 2000 µg/mL in aqueous media). In the future, this photonic crystal sensor can be used as universal tools for the detection of a broad range of analytes. Graphical abstract Colloidal array self-assembled by polymer brush-grafted silica for proteins detection.

Separation of 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane and 1,3,5-trinitro-1,3,5- triazacyclohexane by molecularly imprinted solid-phase extraction.

Synthesis of 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane and 1,3,5-trinitro-1,3,5-triazacyclohexane by the Bachmann process leads to a mixture of both. The separation of 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane and 1,3,5-trinitro-1,3,5-triazacyclohexane from their mixture is difficult because the sizes and physical properties of these homologous compounds are similar. For this purpose, seven molecularly imprinted polymers have been synthesized for each explosive, and a selective solid-phase extraction procedure has been developed. A molecularly imprinted polymer, synthesized with 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane as the template, methacrylic acid as the monomer and trimethylolpropane trimethacrylate as the cross-linking agent in a molar ratio of 1:8:8 showed the best separation capability. A packed cartridge containing this polymer can be reused for 23 solid-phase extraction cycles without repacking, and the total separation capability toward 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane reached 6.81 mg per gram of polymer. 1,3,5-Trinitro-1,3,5-triazacyclohexane was not detected in the separated 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane by high-performance liquid chromatography and vice versa. This newly developed method had the advantages of high recovery (100%) and purity, environmental friendliness, and room temperature operability. This study showed that some molecularly imprinted polymers that cannot absorb target analytes well in the solvent in which the polymers were polymerized might have high-binding capacity for the analytes and show imprinting effects in other solvents.

Understanding the relationships between molecule structure and imprinting effect of two acetyl-nitrogen heterocyclic compounds.

The molecularly imprinted polymers (MIPs) for two structural analogs, 1,3,5-triacetyl-1,3,5-triazacyclohexane (TRAT) and 1,3,5,7-tetraacetyl-1,3,5,7-tetraazacyclooctane (TAT), have been synthesized respectively under the same conditions. The TAT-MIP showed excellent imprinting effect, whereas the TRAT-MIP did not. To understand the different imprinting effects of the MIPs prepared from these two templates, the geometric structures and energetic properties of complexes formed around TAT and TRAT were studied computationally. The results indicate that in liquid phase, for the complexes formed with TAT and its nearest neighbor molecules, the magnitude of the binding energy increases with the number of surrounding TAT, methacrylic acid, and acetonitrile (ACT), whereas for the cases of TRAT, the magnitude of the binding energy increases with the number of surrounding TRAT and trimethylolpropane trimethacrylate. The studied systems form stronger and thus more stable networks encapsulating TAT than with TRAT. ACT may also play an important role in the polymerization phase in stabilizing the shapes of the cavities that TATs reside in. We propose these as the major factors that affect the different imprinting effects of the two MIPs. Copyright © 2016 John Wiley & Sons, Ltd.