Design and performance analysis of a mid-infrared broadband thermally tunable metamaterial absorption device based on the phase-change effect.

We propose a structurally simple, innovative, and multifunctional mid-infrared broadband thermally tunable metamaterial absorption device. The absorption device consists of a three-layer structure, from bottom to top: Ti substrate, SiO2 dielectric layer, and patterned VO2 layer. Through temperature control, the average absorption intensity of the absorption device can vary between 0.08 and 0.94. The absorption device's absorption mechanism is rooted in the thermal phase-change characteristics exhibited by the topologically patterned VO2. When the temperature is below 340 K, VO2 is in a dielectric state, resulting in near-total reflection performance in the mid-infrared range. When the temperature is above 340 K, VO2 undergoes a dielectric-to-metal transition, enabling the absorption device to achieve an average absorption rate of 94.12% in the ultra-wideband range of 6.26 µm-20.96 µm in the mid-infrared. This absorption range completely covers the atmospheric window wavelengths of 8 µm-14 µm, demonstrating high practical value. We explain the working mechanism of the absorption device from the perspective of the electromagnetic field. Subsequently, we study the variations in the absorption curve of the absorption device at different temperatures of VO2 and use the changes in the electric field at the same wavelength under different temperatures to explain the variations in absorption. Compared to previous work, our structure has only three layers in a single unit, making it easy to process and produce. Additionally, the absorption device's operating bandwidth and average absorption rate in the mid-infrared range have been significantly improved. Furthermore, the absorption device exhibits substantial incident angle tolerance and polarization insensitivity. We believe that this design has broad application potential in future optothermal conversion, infrared stealth, and thermal radiation.

Novel Flavonol Derivatives Containing 1,3,4-Thiadiazole as Potential Antifungal Agents: Design, Synthesis, and Biological Evaluation.

In order to discover novel compounds with excellent agricultural activities, novel flavonol derivatives containing 1,3,4-thiadiazole were synthesized and evaluated for their antifungal activities. The bioassay results showed that some of the target compounds had good antifungal activities against Botrytis cinerea, Phomopsis sp. and Sclerotinia sclerotiorum in vitro. It is worth noting that the half-effective concentration (EC50) value of Y18 against B. cinerea was 2.4 µg/mL, which was obviously superior to that of azoxystrobin (21.7 µg/mL). The curative activity of Y18 at 200 µg/mL (79.9%) was better than that of azoxystrobin (59.1%), and its protective activity (90.9%) was better than that of azoxystrobin (83.9%). Morphological studies by using scanning electron microscopy and fluorescence microscopy revealed that Y18 could affect the normal growth of B. cinerea mycelium. In addition, the mechanism of action studies indicated that Y18 could affect the integrity of cell membranes by inducing the production of endogenous reactive oxygen species and the release of the malondialdehyde content, leading to membrane lipid peroxidation and the release of cell contents. The inhibitory activity of flavonol derivatives containing 1,3,4-thiadiazole on plant fungi is notable, offering significant potential for the development of new antifungal agents.

Design of a delivery vehicle chitosan-based self-assembling: controlled release, high hydrophobicity, and safe treatment of plant fungal diseases.

BACKGROUND: Traditional pesticides are poorly water-soluble and suffer from low bioavailability. N-succinyl chitosan (NSCS) is a water-soluble chitosan derivative, has been recently used to encapsulate hydrophobic drugs to improve their bioavailability. However, it remains challenging to synthesize pesticides of a wide variety of water-soluble drugs and to scale up the production in a continuous manner. RESULTS: A synthetic method for preparing water-soluble nanopesticides with a polymer carrier was applied. The bioactive molecule BTL-11 was loaded into hollow NSCS to promote drug delivery, improve solubility and anti-fungal activity. The synthesized nanopesticides had well controlled sizes of 606 nm and the encapsulation rate was 80%. The release kinetics, drug toxicity and drug activity were further evaluated. The inhibitory activity of nanopesticides against Rhizoctonia solani (R. solani) was tested in vivo and in vitro. In vivo against R. solani trials revealed that BTL-11 has excellent control efficiency for cultivated rice leaf and sheath was 79.6 and 76.5%, respectively. By contrast, for BTL-11@NSCS NPs, the anti-fungal ability was strongly released and afforded significant control efficiencies of 85.9 and 81.1%. Those effects were significantly better than that of the agricultural fungicide azoxystrobin (51.5 and 66.5%). The proposed mechanism was validated by successfully predicting the synthesis outcomes. CONCLUSIONS: This study demonstrates that NSCS is a promising biocompatible carrier, which can enhance the efficacy of pesticides, synergistically improve plant disease resistance, protect crop growth, and can be used for the delivery of more insoluble pesticides.

Hitchhiking of Cas9 with nucleus-localized proteins impairs its controllability and leads to efficient genome editing of NLS-free Cas9.

CRISPR-Cas9 is the most commonly used genome-editing tool in eukaryotic cells. To modulate Cas9 entry into the nucleus to enable control of genome editing, we constructed a light-controlled CRISPR-Cas9 system to control exposure of the Cas9 protein nuclear localization signal (NLS). Although blue-light irradiation was found to effectively control the entry of Cas9 protein into the nucleus with confocal microscopy observation, effective gene editing occurred in controls with next-generation sequencing analysis. To further clarify this phenomenon, a CRISPR-Cas9 editing system without the NLS and a CRISPR-Cas9 editing system containing a nuclear export signal were also constructed. Interestingly, both Cas9 proteins could achieve effective editing of target sites with significantly reduced off-target effects. Thus, we speculated that other factors might mediate Cas9 entry into the nucleus. However, NLS-free Cas9 was found to produce effective target gene editing even following inhibition of cell mitosis to prevent nuclear import caused by nuclear membrane disassembly. Furthermore, multiple nucleus-localized proteins were found to interact with Cas9, which could mediate the "hitchhiking" of NLS-free Cas9 into the nucleus. These findings will inform future attempts to construct controllable gene-editing systems and provide new insights into the evolution of the nucleus and compatible protein functions.

Flavonol Derivatives Containing a Quinazolinone Moiety: Design, Synthesis, and Antiviral Activity.

A series of flavonol derivatives containing quinazolinone were designed and synthesized, and their antiviral activities against tobacco mosaic virus (TMV) were evaluated. The results of the half maximal effective concentration (EC50 ) test against TMV showed that the EC50 value of curative activity of K5 was 139.6 µg/mL, which was better than that of the commercial drug ningnanmycin (NNM) 296.0 µg/mL, and the EC50 value of protective activity of K5 was 120.6 µg/mL, which was superior to that of NNM 207.0 µg/mL. The interaction of K5 with TMV coat protein (TMV-CP) was investigated using microscale thermophoresis (MST) and molecular docking and the results showed that K5 can combine with TMV-CP more strongly to TMV-CP than that NNM can. Furthermore, the assay measuring malondialdehyde (MDA) content indicated that K5 had the ability to improve the disease resistance of tobacco. Hence, this study offers strong evidence that flavonol derivatives have potential as novel antiviral agents.

Synthesis, antibacterial and antifungal activity of myricetin derivatives containing piperidine and amide fragments.

BACKGROUND: Continuous use of synthetic bactericides and fungicides is causing pathogens to develop resistance, resulting in increased use of pesticides and affecting food security. The green pesticides derived from natural products could reduce or avoid 'pesticide hazards' caused by synthetic pesticides as a result of their unique mechanism of action. Therefore, it is of great significance to create green pesticides with novel structures. RESULTS: Herein, 30 novel myricetin derivatives containing piperidine and amide fragments were designed and synthesized using active group splicing. Among them, compound Z30 had excellent inhibitory effect against Xanthomonas oryzae pv. Oryzae (Xoo) with the half effective concentration (EC50 ) of 2.7 µg mL-1 . Compound Z26 not only exhibited better antibacterial activity against Xaxonopodis pv. Citri (Xac) with EC50 of 3.9 µg mL-1 , but also displayed higher antifungal activity against Rhizoctonia solani (Rs) with EC50 of 8.3 µg mL-1 . In vivo experiments proved that Z30 against bacterial blight of rice and Z26 against rice blast exhibits significant protective and curative effect. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that Z26 and Z30 could change the integrity of cell wall and membrane of pathogen Xoo, Xac and Rs, resulting in cytoplasmic leakage and eventually death. Enzymatic assay, molecular docking and molecular dynamics simulations (MDs) indicated that Z26 could be used as a potential succinate dehydrogenase inhibitor (SDHI). CONCLUSION: Z26 and Z30 significantly reduced the pathogenicity of the pathogens, which provided a new idea and direction for the development of green pesticides. © 2023 Society of Chemical Industry.

Antiviral activity evaluation and action mechanism of myricetin derivatives containing thioether quinoline moiety.

A variety of myricetin derivatives containing thioether quinoline moiety were designed and synthesized. Their structures of title compounds were determined by 1H NMR, 13C NMR, 19F NMR, and HRMS. Single-crystal X-ray diffraction experiments were carried out with B4. Antiviral activity indicated that some of the target compounds exhibited remarkable anti-tobacco mosaic virus (TMV) activity. In particular, compound B6 possessed significant activity. The half maximal effective concentration (EC50) value of the curative activity of compound B6 was 169.0 µg/mL, which was superior to the control agent ningnanmycin (227.2 µg/mL). Meanwhile, the EC50 value of the protective activity of compound B6 was 86.5 µg/mL, which was better than ningnanmycin (179.2 µg/mL). Microscale thermophoresis (MST) indicated that compound B6 had a strong binding capability to the tobacco mosaic virus coat protein (TMV-CP) with a dissociation constant (Kd) value of 0.013 µmol/L, which was superior to that of myricitrin (61.447 µmol/L) and ningnanmycin (3.215 µmol/L). And the molecular docking studies were consistent with the experimental results. Therefore, these novel myricetin derivatives containing thioether quinoline moiety could become potential alternative templates for novel antiviral agents.

Synthesis and biological activities of novel chalcone derivatives containing pyrazole oxime ethers.

A series of novel chalcone derivatives containing pyrazole oxime ethers were designed and synthesized. The structures of all the target compounds were determined by NMR and HRMS. The structure of H5 was further confirmed via single-crystal X-ray diffraction analysis. The results of biological activity test showed that some of the target compounds exhibited significant antiviral and antibacterial activities. The test results of EC50 value against tobacco mosaic virus showed that H9 had the best curative and protective effect, and the EC50 value of curative activity of H9 was 166.9 µg/mL, which was superior to ningnanmycin (NNM) 280.4 µg/mL, the EC50 value of protective activity of H9 was 126.5 µg/mL, which was superior to ningnanmycin 227.7 µg/mL. Microscale thermophoresis (MST) experiments demonstrated that H9 (Kd = 0.0096 ± 0.0045 µmol/L) exhibited a strong binding ability with tobacco mosaic virus capsid protein (TMV-CP), which was far superior to ningnanmycin (Kd = 1.2987 ± 0.4577 µmol/L). In addition, molecular docking results showed that the affinity of H9 to TMV protein was significantly higher than ningnanmycin. The results of against bacterial activity showed that H17 has a good inhibiting effect against Xanthomonas oryzae pv. oryzae (Xoo), the EC50 value of H17 was 33.0 µg/mL, which was superior to the commercial drugs thiodiazole copper (68.1 µg/mL) and bismerthiazol (81.6 µg/mL), and the antibacterial activity of H17 was verified by scanning electron microscopy (SEM).

Design, synthesis and bioactivity of myricetin derivatives for control of fungal disease and tobacco mosaic virus disease.

A series of myricetin derivatives containing isoxazole were designed and synthesized. All the synthesized compounds were characterized by NMR and HRMS. In terms of antifungal activity, Y3 had a good inhibitory effect on Sclerotinia sclerotiorum (Ss), and the median effective concentration (EC50) value was 13.24 µg mL-1, which was better than azoxystrobin (23.04 µg mL-1) and kresoxim-methyl (46.35 µg mL-1). Release of cellular contents and cell membrane permeability experiments further revealed that Y3 causes the destruction of the cell membrane of the hyphae, which in turn plays an inhibitory role. The anti-tobacco mosaic virus (TMV) activity in vivo showed that Y18 had the best curative and protective activities, with EC50 values of 286.6 and 210.1 µg mL-1 respectively, the effect was better than ningnanmycin. Microscale thermophoresis (MST) data showed that Y18 had a strong binding affinity with tobacco mosaic virus coat protein (TMV-CP), with a dissociation constant (K d) value of 0.855 µM, which was better than ningnanmycin (2.244 µM). Further molecular docking revealed that Y18 interacts with multiple key amino acid residues of TMV-CP, which may hinder the self-assembly of TMV particles. Overall, after the introduction of isoxazole on the structure of myricetin, its anti-Ss and anti-TMV activities have been significantly improved, which can be further studied.

Design, Synthesis, and Bioactivity of Chalcone Derivatives Containing Indanone.

A series of chalcone derivatives containing indanone were designed and synthesized by aldehyde-ketone condensation and etherification. The activity test demonstrated that the majority of the compounds had good therapeutic and protective activities against tobacco mosaic virus (TMV) at a concentration of 500 µg/mL when being tested. Among them, the target compounds N2 and N7 showed good therapeutic activities against TMV with EC50 values of 70.7 and 89.9 µg/mL, respectively, which were better than that of ningnanmycin (158.3 µg/mL). N2 and N10 showed better protective activities against TMV with EC50 values of 60.8 and 120.3 µg/mL, which were superior to that of ningnanmycin (175.6 µg/mL). A hydrogen bond interaction was observed between N2 and ARG-341 with a bond length of 3.08 Å and a hydrogen bond was observed between ningnanmycin and ASP-66 with a bond length of 3.72 Å. In contrast, the hydrogen bond length of compound N2 was shorter and its binding was closer. Meanwhile, when the heartleaf tobacco was being treated with N2, its increasing rate of malondialdehyde slowed and its content of defense enzymes significantly increased, again reflecting the good activity of N2 against TMV.

Design, Synthesis, and Biological Evaluation of Novel 1,4-Pentadien-3-one Derivatives Containing a Sulfonamide Moiety.

Novel 1,4-pentadien-3-one derivatives containing a sulfonamide moiety were synthesized, and their antifungal, antibacterial, and antiviral activities were verified. These compounds exhibited better activity against five bacteria, with EC50 values ranging from 9.6 to 60.1 µg/mL, prominently, which are superior to those of the commercial agent. A great amount of compounds had excellent fungicidal activity in vitro at 100 µg/mL. Strikingly, compound E6 exhibited moderate activity against Phytophthora litchii than azoxystrobin, with the EC50 value of compound E6 (0.5 µg/mL) drawing near azoxystrobin (0.3 µg/mL). Furthermore, compound E17 had a marked impact on in vivo anti-tobacco mosaic virus, according to the data of microscale thermophoresis, with a Kd value of the intermolecular binding force of 0.002 ± 0.001 µM, which was better than the commercial agent of ningnanmycin (Kd = 0.121 ± 0.031 µM). In addition, the results of these studies suggest that the use of active splicing can improve the biological activity of natural compounds and provide further complement to the development of novel pesticides.

Music Literacy and Soundscape Perception: A Study Based on the Soundwalk Method of Soundscapes.

To explore a method of promoting college aesthetic education through campus environments, the Aesthetic Education Center of the Beijing Institute of Technology Zhuhai (BITZH-AEC) used the soundwalk method of soundscapes to carry out an experiment on students' soundscape perceptions on campus. Half of the students who participated in the experiment (n = 42) had musical instrument learning experience and musical literacy. The research work used conventional statistical analysis methods and "Soundscapy", newly developed by the British soundscape research team, to process the experimental data. It was found that the soundscape perception evaluation of students with musical literacy was different from that of ordinary students. This included a difference in the overall evaluation of the three experimental areas and a difference in the degree of dispersion of the soundscape evaluation of all six experimental areas. The study also found that there was no correlation between the acoustic noise level and the students' evaluations of soundscape perception. BITZH-AEC proposes that aesthetic educators should pay attention to the idea of inspiring students to stimulate cultural imagination through soundscape perception.

Synthetic Mimics of Antimicrobial Peptides for the Targeted Therapy of Multidrug-Resistant Bacterial Infection.

Antibacterial materials are highly demanded in treatment of bacterial infection, especially severe ones with multidrug-resistance. Herein, pH-responsive polypeptide, i.e., poly-L-lysine modified by 1-(propylthio)acetic acid-3-octylimidazolium and citraconic anhydride (PLL-POIM-CA), is synthesized by post-polymerization modification of poly-L-lysine (PLL) with 1-(propylthio)acetic acid-3-octylimidazolium (POIM) and citraconic anhydride (CA). It is observed that PLL-POIM-CA is stable under normal physiological condition, while CA cleaves rapidly at weakly acidic environment like bacterial infectious sites. The hydrolyzed PLL-POIM-CA exhibits excellent broad-spectrum antibacterial activities against Gram-negative bacteria of Escherichia coli and Gram-positive bacteria of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). In particular, the minimum inhibitory concentration (MIC) against multidrug-resistant bacteria like MRSA is as low as 7.8 µg mL-1 . Moreover, PLL-POIM-CA exhibits good biocompatibility with mouse fibroblast cells (L929) in vitro and improved hemocompatibility with an HC50 exceeding 5000 µg mL-1 . Therefore, PLL-POIM-CA displays an excellent bacteria versus cells selectivity (HC50 /MIC) over 534, which is 53 times higher than natural antimicrobial peptide of indolicidin. It is further demonstrated in vivo that the antimicrobial polypeptide effectively accelerates MRSA-infected wound healing by relieving local inflammatory response. Therefore, this targeted antimicrobial polypeptide has broad application prospects for the treatment of multidrug-resistant bacterial infection.

Efficient Editing of an Adenoviral Vector Genome with CRISPR/Cas9.

Immunotherapy based on genetic modification of T cells has played an important role in the treatment of tumors and viral infections. Moreover, adenoviral vectors engineered with improved safety due to their inability to integrate into the host genome have been key in the clinical application of T cell therapy. However, the commonly used adenoviral vector Ad5 exhibits low efficiency of infection of human T cells and the details of the intracellular trafficking pathway of adenoviral vectors in human primary T cells remains unclear. Resolution of these issues will depend on successful modification of the adenoviral vector. To this end, here we describe the successful establishment of a simple and efficient method for editing adenoviral vectors in vitro using the CRISPR-Cas9 gene editing system to target the adenoviral fiber gene.

Development of a Self-Restricting CRISPR-Cas9 System to Reduce Off-Target Effects.

Development of the CRISPR-Cas9 gene-editing system has given rise to a new era of gene editing with wide applications in biology, medicine, agriculture, and other fields. However, the overexpression of Cas9 nuclease causes off-target effects and may trigger an immune response in vivo. Therefore, we constructed a self-restricting CRISPR-Cas9 system, where the target gene sequence corresponding to the guide RNA (gRNA) is inserted on either end of the Cas9 promoter. When double-strand breaks (DSBs) are induced in the target gene sequence, the Cas9 promoter is cut off and transcription ceases. With this system, expression of Cas9 protein at 60 h after transfection is only 10% that of the wild-type system, with about 70% promoter deletion efficiency. The target site editing efficiency and homologous recombination efficiency of the self-restricting system remain at about 50% and 30%, respectively, while the frequency of off-target indel formation decreased by 76.7%. Further, the number of indel types was also reduced from 13 to 2. Because this system does not include additional gRNA sequences, the possibility of introducing new off-target mutations is decreased. Importantly, this system is composed of a single plasmid, which could potentially be easily introduced in vivo using a viral vector or nanoparticles.