Synergistic graphene-MnOx/honeycomb activated carbon (G-MnOx/HAC) and plasma technology for eradication of pathogenic microorganisms.

This paper addresses the risk for environmental transmission of pathogenic microorganisms in confined spaces and the serious health hazards for personnel, and research on efficient eradication methods for the pathogenic microorganisms was carried out to provide technical support for ensuring the health of personnel in confined spaces. A series of graphene-MnO2 (G-MnO2) catalytic materials was prepared by hydrothermal and precipitation methods, and processing parameters such as the graphene doping method, the raw material ratio and the plasma action time were optimized. It was shown that G-MnOX-P/HAC prepared by a one-step precipitation method and with a graphene doping ratio of 10% had the best bactericidal effect in a dielectric barrier discharge (DBD) reactor after 4 min of reaction. The eradication rates for Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), coronavirus and Aspergillus niger were all greater than 99.9%. The characterization techniques TEM, SEM, XRD, XPS, BET and FT-IR showed that the G-MnOX-P samples prepared by the one-step precipitation method had larger specific surface areas with more oxygen vacancies and functional groups on the surfaces, which was conducive to decomposition of the ozone generated by the dissociated plasma and formation of reactive oxygen species (ROS) for the microbial eradication process. Finally, by comparing the ozone-decomposition activity with the plasma co-catalytic performance, it was verified that efficient decomposition of the ozone facilitated the eradication of microorganisms. Based on this, an analysis of the mechanism for efficient eradication was carried out.

Macrophages as potential targets in gene therapy for cancer treatment.

Macrophages, as ubiquitous and functionally diverse immune cells, play a central role in innate immunity and initiate adaptive immunity. Especially, tumor-associated macrophages (TAMs) are crucial contributors to the tumorigenesis and development of cancer. Thus, macrophages are emerging potential targets for cancer treatment. Among the numerous targeted therapeutic options, gene therapy is one of the most potential therapeutic strategies via directly and specifically regulating biological functions of macrophages at the gene level for cancer treatment. This short review briefly introduces the characteristics of macrophage populations, the functions of TAM in the occurrence, and the progress of cancer. It also summarized some representative examples to highlight the current progress in TAM-targeted gene therapy. The review hopes to provide new insights into macrophage-targeted gene therapy for precision cancer therapy.

Preparation and characterization of graphene oxide/O-carboxymethyl chitosan (GO/CMC) composite and its unsymmetrical dimethylhydrazine (UDMH) adsorption performance from wastewater.

The removal of unsymmetrical dimethylhydrazine (UDMH) has long been a concern because of its harmful effect on the environment and humans. This study aimed to prepare a novel graphene oxide/O-carboxymethyl chitosan (GO/CMC) composite adsorbent using the solution-blending method for the removal of UDMH from wastewater. The prepared GO/CMC was systematically characterized by Fourier-transform infrared, Raman, scanning electronic microscopy, transmission electron microscopy, thermogravimetric, and zeta potential analyses. The effects of initial pH, temperature, adsorbent dosage, initial concentration, contact time, and recyclability on the UDMH adsorption behaviour of GO/CMC were studied. The adsorption kinetics was consistent with the pseudo-second-order kinetics model, and the adsorption process was mainly controlled by chemisorption. Adsorption isotherms indicated that the adsorption of UDMH by GO/CMC followed the Langmuir adsorption isotherm. The adsorption mechanisms were mainly electrostatic attraction, hydrogen bonding, and surface complexation. Furthermore, GO/CMC composites can be used as a renewable and eco-friendly adsorbent for the removal of UDMH wastewater. The designed GO/CMC composites exhibited a relatively satisfactory recyclability and removal efficiency after five adsorption-desorption cycles.

Thiourea modified low molecular polyamide as a novel room temperature curing agent for epoxy resin.

A thiourea modified low molecular weight polyamide (TLMPA) as a room temperature curing agent was synthesized by a two-step method. Firstly, a low molecular weight polyamide curing agent (LMPA) with low viscosity and high amine value was synthesized by amidation of sebacic acid with tetraethylenepentamine, then the synthesized curing agent was modified with thiourea to increase its reactivity at room temperature. The optimal reaction conditions were studied by L9(33) orthogonal experiments. The structure of the prepared curing agent was analyzed by Fourier transform infrared spectroscopy (FT-IR). The kinetics of TLMPA curing of E-51 epoxy resin was analyzed using the Kissinger method with non-isothermal differential scanning calorimetry (DSC). The activation energy of TLMPA/E-51 calculated by the Kissinger method and FWO method was 38.79 kJ mol-1 and 42.73 kJ mol-1. The nano-SiO2 filler was compounded with E-51 epoxy resin, TLMPA, allyl glycidyl ether diluent, and KH-560 coupling agent to prepare the room temperature curing epoxy resin (EP) system. L9(34) orthogonal experiments were carried out to study the effect of various factors on the mechanical properties of the cured resin systems. The best formulation of the system is that the content of nano-SiO2, curing agent, diluent, and coupling agent is 3, 35, 15, 1 wt%, respectively. With the optimal formulation, the tensile and shear strength, tensile strength, impact strength, and bending strength of the cured EP system was 13.19 MPa, 53.8 MPa, 52.16 kJ m-2, and 94.95 MPa, respectively.

A biodegradable amphiphilic poly(aminoester) dendrimer for safe and effective siRNA delivery.

Small interfering RNA (siRNA)-based therapeutics represent a novel and compelling drug modality, provided that safe and competent vectors are available for their delivery. Here, we report a biodegradable amphiphilic poly(aminoester) dendrimer for effective siRNA delivery. This dendrimer is readily biodegradable upon enzyme action, and harnesses the delivery features of both lipid and polymer vectors thanks to its lipid/dendrimer hybrid structure. This study opens new perspectives for developing biodegradable and biocompatible vectors for siRNA therapeutics.

Discovery of novel brain-penetrant GluN2B NMDAR antagonists via pharmacophore-merging strategy as anti-stroke therapeutic agents.

In this work, a novel structural series of brain-penetrant GluN2B NMDAR antagonists were designed, synthesized and biologically evaluated as anti-stroke therapeutic agents via merging the structures of NBP and known GluN2B ligands. Approximately half of them exhibited superior neuroprotective activity to NBP against NMDA-induced neurotoxicity in hippocampal neurons at 10 µM, and compound 45e and 45f exerted equipotent activity to ifenprodil, an approved GluN2B- selective NMDAR antagonist. In particular, 45e, with the most potent neuroprotective activity throughout this series, displayed dramatically enhanced activity (Ki = 3.26 nM) compared to ifenprodil (Ki = 14.80 nM) in Radioligand Competitive Binding Assay, and remarkable inhibition (IC50 = 79.32 nM) against GluN1/GluN2B receptor-mediated current in Patch Clamp Assay. Meanwhile, 45e and its enantiomers exhibited low inhibition rate against the current mediated by other investigated receptors at the concentration of 10 µM, indicating their favorable selectivity for GluN1/GluN2B. In the rat model of middle cerebral artery ischemia (MCAO), 45e exerted comparable therapeutic efficacy to ifenprodil at the same dosage. In addition to the attractive in vitro and in vivo potency, 45e displayed a favorable bioavailability (F = 63.37%) and an excellent brain exposure. In further repeated dose toxicity experiments, compound 45e demonstrated an acceptable safety profile. With the above merits, 45e is worthy of further functional investigation as a novel anti-stroke therapeutic agent.

A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer Therapy.

Despite being a mainstay of clinical cancer treatment, chemotherapy is limited by its severe side effects and inherent or acquired drug resistance. Nanotechnology-based drug-delivery systems are widely expected to bring new hope for cancer therapy. These systems exploit the ability of nanomaterials to accumulate and deliver anticancer drugs at the tumor site via the enhanced permeability and retention effect. Here, we established a novel drug-delivery nanosystem based on amphiphilic peptide dendrimers (AmPDs) composed of a hydrophobic alkyl chain and a hydrophilic polylysine dendron with different generations (AmPD KK2 and AmPD KK2K4). These AmPDs assembled into nanoassemblies for efficient encapsulation of the anti-cancer drug doxorubicin (DOX). The AmPDs/DOX nanoformulations improved the intracellular uptake and accumulation of DOX in drug-resistant breast cancer cells and increased permeation in 3D multicellular tumor spheroids in comparison with free DOX. Thus, they exerted effective anticancer activity while circumventing drug resistance in 2D and 3D breast cancer models. Interestingly, AmPD KK2 bearing a smaller peptide dendron encapsulated DOX to form more stable nanoparticles than AmPD KK2K4 bearing a larger peptide dendron, resulting in better cellular uptake, penetration, and anti-proliferative activity. This may be because AmPD KK2 maintains a better balance between hydrophobicity and hydrophilicity to achieve optimal self-assembly, thereby facilitating more stable drug encapsulation and efficient drug release. Together, our study provides a promising perspective on the design of the safe and efficient cancer drug-delivery nanosystems based on the self-assembling amphiphilic peptide dendrimer.

Photocatalytic degradation of unsymmetrical dimethylhydrazine on TiO2/SBA-15 under 185/254 nm vacuum-ultraviolet.

In this work, TiO2/SBA-15 was synthesized via an in situ hydrothermal method and was used for vacuum-ultraviolet (VUV) photocatalytic degradation of unsymmetrical dimethylhydrazine (UDMH) for the first time. Compared with photocatalysis under UV irradiation, VUV photocatalysis exhibited higher photodegradation efficiency due to the synergetic effect of direct photolysis, indirect photooxidation and photocatalytic oxidation. The synthesized TiO2/SBA-15 catalysts exhibited ordered mesoporous structure and anatase phase TiO2. Titanium content, initial pH and substrate concentration impacted degradation efficiency of UDMH in the VUV photocatalysis process. Among the prepared catalysts, TiO2/SBA-15 with the molar ratio of Ti/Si = 1 : 3 (TS-2) showed the best photocatalytic activity under VUV light, with the rate constant of 0.02511 min-1, which is 1.91 times that with VUV/P25. The superior photocatalytic activity of TS-2 is mainly related to the good balance between the specific surface area and TiO2 contents. The photodegradation efficiency decreases with the increase in the initial UDMH concentration and the maximum degradation rate was obtained at pH 9.0. In the VUV/TS-2 process, ˙OH played a more important role in the degradation of UDMH than ˙O2 - and the degradation pathways contained bond breaking, amidation, isomerisation and oxidation reactions. The TS-2 also showed good reusability with the rate constant maintained at above 90% after five cycles and exhibited satisfactory degradation efficiency in tap water.

Discovery of talmapimod analogues as polypharmacological anti-inflammatory agents.

Twenty novel talmapimod analogues were designed, synthesised and evaluated for the in vivo anti-inflammatory activities. Among them, compound 6n, the most potent one, was selected for exploring the mechanisms underlying its anti-inflammatory efficacy. In RAW264.7 cells, it effectively suppressed lipopolysaccharides-induced (LPS-induced) expressions of iNOS and COX-2. As illustrated by the western blot analysis, 6n downregulated both the NF-κB signalling and p38 MAPK phosphorylation. Further enzymatic assay identified 6n as a potent inhibitor against both p38α MAPK (IC50=1.95 µM) and COX-2 (IC50=0.036 µM). By virtue of the concomitant inhibition of p38α MAPK, its upstream effector, and COX-2, along with its capability to downregulate NF-κB and MAPK-signalling pathways, 6n, a polypharmacological anti-inflammatory agent, deserves further development as a novel anti-inflammatory drug.

Design, synthesis, biological evaluation and docking study of novel indole-2-amide as anti-inflammatory agents with dual inhibition of COX and 5-LOX.

In this work, a series of novel indole-2-amide compounds were designed, synthesized, characterized and the anti-inflammatory activity in vivo were evaluated. Compounds 8a, 10b, 12h, and 12l exhibited marked anti-inflammatory activity in 2,4-Dinitrofluorobenzenethe (DNFB) - induced mice auricle edema model. Further, compounds 8a, 10b and 12h exhibited potential in vitro COX-2 inhibitory activity (IC50 = 21.86, 23.3 and 23.21 nM, respectively), while the reference drug celecoxib was 11.20 nM. The most promising compound 10b was exhibited the highest selectivity for COX-2 (selectivity index (COX-1/COX-2) = 17.45) and moderate 5-LOX inhibitory activity (IC50 = 66 nM), which comparable to positive controlled zileuton (IC50 = 38.91 nM). In addition, the test results showed compounds 10b and 12h no significant cytotoxic activity on normal cells (RAW264.7). Further, at the active sites of the COX-1, COX-2 co-crystals, 3b and 4l showed higher binding forces in the molecular docking study, which consistent with the results of in vitro experiments. These results demonstrated that these compounds had dual inhibitory activity of COX/5-LOX, providing clues for further searching for safer and more effective anti-inflammatory drugs.

Design, synthesis, and biological evaluation of tetrahydroisoquinoline-based diaryl urea derivatives for suppressing VEGFR-2 signaling.

A novel structural series of tetrahydroisoquinoline-based compounds that incorporate the diaryl urea moiety was designed, synthesized, and biologically evaluated as suppressors of VEFGR-2 signaling. As a consequence, compounds 9k and 9s exhibited comparable or superior cytotoxic activity to that of gefitinib against the tested three cell lines, including A549, MCF-7, and PC-3. Importantly, both of them downregulated the expression of VEGFR-2, and inhibited VEGFR-2 phosphorylation at the concentration of 0.5 or 1.0 µmol/l. Besides, they suppressed human umbilical vein endothelial cell tube formation at the concentration of 4.0 µmol/l. Considering their capability of down-regulating VEGFR-2 expression and inhibiting VEGFR-2 phosphorylation, 9k and 9s may serve as suppressors of angiogenesis for further investigation.