Tunable electronic and magnetic properties of Cr2Ge2Te6monolayer by organic molecular adsorption.

Recently, two-dimensional materials are widely concerned because of their novel physical properties. Cr2Ge2Te6(CGT) has been studied extensively due to its intrinsic ferromagnetism and ferromagnetic order. In this investigation, the electronic and magnetic performances of organic molecules (TCNE, TCNQ and TTF) adsorbed on CGT monolayer were studied based on the first-principles calculations systematically. The results demonstrate that the CGT presents pronounced tunable electronic and magnetic properties by the adsorption of these macromolecules. Furthermore, the Curie temperature of CGT monolayer can be enhanced significantly by the TTF adsorption. This work can provide a magnetic regulation method for CGT and explore the promising applications of the CGT for spin devices.

Colorimetric tyrosinase assay based on catechol inhibition of the oxidase-mimicking activity of chitosan-stabilized platinum nanoparticles.

It is found that catechol inhibits the oxidase-mimicking activity of chitosan-protected platinum nanoparticles (Chit-PtNPs) by competing with the substrate for the active site of the Ch-PtNPs. The inhibition mechanism of catechol is different from that of ascorbic acid in that it neither reacts with O2•- nor reduces the oxidized 3,3',5,5'-tetramethylbenzidine (TMB). Tyrosinase (TYRase) catalyzes the oxidation of catechol, thus restoring the activity of oxidase-mimicking Chit-PtNPs. By combining the Chit-PtNP, catechol, and TYRase interactions with the oxidation of TMB to form a yellow diamine (maximal absorbance at 450 nm), a colorimetric analytical method was developed for TYRase determination and inhibitor screening. The assay works in the 0.5 to 2.5 U·mL-1 TYRase activity range, and the limit of detection is 0.5 U·mL-1. In our perception, this new assay represents a powerful approach for determination of TYRase activity in biological samples. Graphical abstract Schematic representation of a colorimetric method for tyrosinase (TYRase) detection and inhibitor screening. It is based on the fact that catechol can inhibit the oxidase-like activity of chitosan-stabilized platinum nanoparticles (Ch-PtNPs) by competing with the substrate for the active sites and TYRase can catalyze the oxidation of catechol.

Alkaline peroxidase activity of cupric oxide nanoparticles and its modulation by ammonia.

We herein report the intrinsic alkaline peroxidase-like activity exhibited by CuO nanoparticles when 3-(4-hydroxyphenyl)propionic acid was employed as a substrate. Based on this observation, a fluorometric assay method with a low detection limit of 0.81 µM was established for H2O2 determination under alkaline conditions. Notably, ammonia was found to inhibit the alkaline peroxidase-like activity of the CuO nanoparticles. Thus, a sensing platform for the determination of urea and urease was successfully constructed, with the limits of detection for urea and urease being 27 µM and 2.6 U L-1, respectively. This platform was then applied for the detection of urea in human urine and urease in soil, which yielded satisfactory results. These results suggest that it is possible to extend the catalytic potential of peroxidase and its mimetics from acidic and neutral conditions to include activity in alkaline media as well. Furthermore, this strategy is a novel method for the analysis of urea and urease. The assay developed in this work is facile, inexpensive, convenient, and highly selective and sensitive. Therefore, it is expected that this system can serve as a template for the development of similar enzyme nano-mimics.

Effect of graphene oxide on sodium alginate hydrogel as a carrier triggering release of ibuprofen.

The design and preparation of safe wound dressings with antibacterial and controlled drug release abilities is valuable in medicine. This research focuses on the fabrication of a hydrogel carrier with graphene oxide (GO)-triggered ibuprofen (IBU) release to control inflammation. The hydrogel was prepared by cross-linking the base polymer sodium alginate (SA) and functionalized GO. The morphology of the gel was observed by a scanning electron microscope (SEM), and its structure was analyzed through X-ray diffraction (XRD) and Fourier transform infrared reflection (FTIR) spectroscopy. The effects of GO on swelling capacity, IBU release behavior and antibacterial activity were investigated by using the prepared GO/SA hydrogel as a drug carrier and IBU as a drug model. In vitro studies confirmed that the GO/SA hydrogel had good antimicrobial activity and excellent cytotoxicity. The analysis of cumulative IBU release rates revealed that the addition of GO could promote the release of IBU, and the change in GO content did not have a prominent effect on IBU release. At the same time, the rate of IBU release from the GO/SA hydrogel was affected by near-infrared light. Under a light source, the release rate of IBU increased, and the release amount of IBU showed a clear stepwise increase under light on-off conditions. These results suggest that the GO/SA hydrogel could be a potential antibacterial and anti-inflammatory wound dressing.

Discovery of a novel anti-osteoporotic agent from marine fungus-derived structurally diverse sirenins.

Thirteen new sirenin derivatives named eupenicisirenins C-O (1-13), along with a biosynthetically related known one (14), were isolated from the mangrove sediment-derived fungus Penicillium sp. SCSIO 41410. The structures, which possessed a rare cyclopropane moiety, were confirmed by extensive analyses of the spectroscopic data, quantum chemical calculations, and X-ray diffraction. Among them, eupenicisirenin C (1) exhibited the strongest NF-κB inhibitory activities, as well as suppressing effects on cGAS-STING pathway. Moreover, 1 showed the significant inhibitory effect on RANKL-induced osteoclast differentiation in bone marrow macrophages cells, and also displayed the therapeutic potential on prednisolone-induced zebrafish osteoporosis. Transcriptome analysis and the following verification tests suggested that its anti-osteoporotic mechanism is related to the extracellular matrix receptor interaction-related pathways. This study provided a promising marine-derived anti-osteoporotic agent for the treatment of skeletal disease.

A novel TWIK2 channel inhibitor binds at the bottom of the selectivity filter and protects against LPS-induced experimental endotoxemia in vivo.

TWIK2 channel plays a critical role in NLRP3 inflammasome activation and mice deficient in TWIK2 channel are protected from sepsis and inflammatory lung injury. However, inhibitors of TWIK2 channel are currently in an early stage of development, and the molecular determinants underlying the chemical modulation of TWIK2 channel remain unexplored. In this study, we identified NPBA and the synthesized derivative NPBA-4 potently and selectively inhibited TWIK2 channel by using whole-cell patch clamp techniques. Furthermore, the mutation of the last residues of the selectivity filter in both P1 and P2 (i.e., T106A, T214A) of TWIK2 channel substantially abolished the effect of NPBA on TWIK2 channel. Our data suggest that NPBA blocked TWIK2 channel through binding at the bottom of the selectivity filter, which was also supported by molecular docking prediction. Moreover, we found that NPBA significantly suppressed NLRP3 inflammasome activation in macrophages and alleviated LPS-induced endotoxemia and organ injury in vivo. Notably, the protective effects of NPBA against LPS-induced endotoxemia were abolished in Kcnk6-/- mice. In summary, our study has uncovered a series of novel inhibitors of TWIK2 channel and revealed their distinct molecular determinants interacting TWIK2 channel. These findings provide new insights into the mechanisms of pharmacological action on TWIK2 channel and opportunities for the development of selective TWIK2 channel modulators to treat related inflammatory diseases.

Multi-responsive and conductive bilayer hydrogel and its application in flexible devices.

Multi-stimuli-responsive hydrogels are intelligent materials that present advantages for application in soft devices compared with conventional machines. In this paper, we prepared a bilayer hydrogel consisting of a poly(2-(dimethylamino)ethyl methacrylate) layer and a poly(N-isopropylacrylamide) layer. The hydrogel responded to temperature, pH, NaCl, and ethanol by undergoing bending deformation. At 40 °C, it only took 23 s for the hydrogel to bend nearly 300°. Carbon black was also introduced into the hydrogel network to render it conductive. Based on its multi-stimuli-responsive properties and conductivity, the hydrogel was used to construct a 4-arm gripper, thermistor, and finger movement monitor. The time required to grip and release an object was 141 s. The resistance changed with temperature, which affected the brightness of an LED. Finger motions were monitored, and the bending angle could be distinguished.

Novel DCPIB analogs as dual inhibitors of VRAC/TREK1 channels reduced cGAS-STING mediated interferon responses.

The enzyme cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA and catalyzes the formation of 2'3'-cyclic-GMP-AMP (cGAMP), which in turn triggers interferon (IFN) production. Inappropriate activation of cGAS and production of cGAMP have been linked to a diversity of autoimmune diseases. The volume-regulated anion channels (VRACs) have been recently demonstrated to permeate cGAMP, thus making the channel essential for the activation of the cGAS-cGAMP-STING axis. DCPIB, a prominent inhibitor of VRAC channel, has been recently reported to also significantly activate TREK1 channel. Herein, in this study, we have designed and synthesized a series of novel DCPIB derivatives and investigated their potential regulatory effects on VRAC/TREK1 channels. Our results manifested that compound 6u was a dual inhibitor of VRAC/TREK1 channels with IC50s of 7.11 ± 0.94 µM and 4.43 ± 0.90 µM, respectively. On top of that, our data demonstrated that 6u impaired interferon production in a concentration-dependently manner by dampening cGAS-cGAMP-STING pathway without any cytotoxicity when it comes to herpes simplex virus type 1 (HSV1) infection. To sum up, our study not only discovered a novel DCPIB analog with dual inhibitory effects on VRAC/TREK1 channels but also provided a new strategy for the design and development of newly potent VRAC inhibitors, which benefits the treatment of cGAS-STING related autoimmune and inflammatory diseases.

Sodium Alginate Modified Platinum Nanozymes With Highly Efficient and Robust Oxidase-Like Activity for Antioxidant Capacity and Analysis of Proanthocyanidins.

Platinum nanozymes exhibiting highly efficient and robust oxidase-like activity are successfully synthesized and modified using sodium alginate (SA-PtNPs). According to a steady-state dynamic assay, Michaelis-Menton constant (K m ) is calculated as 11.6 µM, indicating that the affinity of SA-PtNPs toward the substrate, 3, 3', 5, 5'-tetramethylbenzidine (TMB), is high. It shows in the paper that SA-PtNPs exhibit a significant oxidant effect on substrate-O2 to produce O 2 • - as an oxidase mimic. Moreover, the oxidase-like activity fluctuated slightly under changes in environmental pH and incubation time, implying that SA can increase the dispersibility and stability of PtNPs. A colorimetric assay for oligomeric proanthocyanidins (OPC) was realized given how few explorations of the former there are. We found that the significant inhibitory effect of OPC on the oxidase-like activity is due to the competitive effect between OPC and TMB for binding to the active site of SA-PtNPs, resulting in a color change. Under optimal conditions, the logarithmic value of the chromogenic difference (ΔA450nm) to OPC concentration was linear (4-32.5 µM, r = 0.999) with a limit of detection (LOD) of 2.0 µM. The antioxidant capacity of OPC obtained by the Soxhlet extraction method from grape seeds was 2.85 U/mg. The recovery from the experiment in which OPC was added to grape seeds ranged from 97.0 to 98.6% (RSDs of 0.5-3.4%), suggesting a high accuracy in OPC detection. These findings are important because OPC is an internationally recognized antioxidant that eliminates free radicals in the human body and, therefore, may prevent a variety of diseases. Thus, we envisage that this Pt nanozyme-based assay may be prevalent for antioxidant capacity evaluation and analytical applications.

Heparin-platinum nanozymes with enhanced oxidase-like activity for the colorimetric sensing of isoniazid.

In this study, a colorimetric sensing assay of isoniazid based on excellent oxidase-like activity of heparin sodium stabilized platinum nanoparticles (HS-PtNPs) has been demonstrated. The newly prepared HS-PtNPs exhibit a great dispersion with an average size distribution of 4.8 ± 0.6 nm, and maintain more than 90% catalytic activity under strong acid and alkali or long-term storage conditions, indicating a robust nanomaterial with attractive potential. The HS-PtNPs show distinct oxidase-like activity with an ultrahigh affinity (Km = 0.01012 mM) for 3, 3', 5, 5'-tetramethylbenzidine (TMB). More significantly, we found that the pyridine ring of isoniazid has a strong reductive hydrazyl substitution, which can compete with TMB for the catalytic site of HS-PtNPs resulting in a colorless solution. Accordingly, a colorimetric sensing of isoniazid was fabricated. A linear relationship for isoniazid was achieved in 2.5 × 10-6 to 2.5 × 10-4 M (R2 = 0.998) with a low limit of detection 1.7 × 10-6 M (S/N = 3). Recovery experiments in drug tablets show that the standard recovery rates were 95%-103%. The quantitative detection data for isoniazid in drug tablets calculated respectively from the standard method and this method exhibited a high correlation coefficient (a slope of 0.9995), suggesting that high accuracy in isoniazid detection.

Engineering a New Chloroplastic Photorespiratory Bypass to Increase Photosynthetic Efficiency and Productivity in Rice.

Over the past few years, three photorespiratory bypasses have been introduced into plants, two of which led to observable increases in photosynthesis and biomass yield. However, most of the experiments were carried out using Arabidopsis under controlled environmental conditions, and the increases were only observed under low-light and short-day conditions. In this study, we designed a new photorespiratory bypass (called GOC bypass), characterized by no reducing equivalents being produced during a complete oxidation of glycolate into CO2 catalyzed by three rice-self-originating enzymes, i.e., glycolate oxidase, oxalate oxidase, and catalase. We successfully established this bypass in rice chloroplasts using a multi-gene assembly and transformation system. Transgenic rice plants carrying GOC bypass (GOC plants) showed significant increases in photosynthesis efficiency, biomass yield, and nitrogen content, as well as several other CO2-enriched phenotypes under both greenhouse and field conditions. Grain yield of GOC plants varied depending on seeding season and was increased significantly in the spring. We further demonstrated that GOC plants had significant advantages under high-light conditions and that the improvements in GOC plants resulted primarily from a photosynthetic CO2-concentrating effect rather than from improved energy balance. Taken together, our results reveal that engineering a newly designed chloroplastic photorespiratory bypass could increase photosynthetic efficiency and yield of rice plants grown in field conditions, particularly under high light.

Chitosan-stabilized platinum nanoparticles as effective oxidase mimics for colorimetric detection of acid phosphatase.

Capping molecules on the surface of nanomaterials not only enhance the dispersion and stability of nanomaterials but also greatly facilitate their surface modification and biological applications. However, most capping molecules can severely block the active sites of the catalytic core, thereby decreasing the enzymatic activity of nanomaterial-based enzyme mimics. This work demonstrates the superiority of chitosan (Ch) as a capping molecule for synthesizing catalytic platinum nanoparticles (PtNPs). The experimental results show that Ch simultaneously exhibits an excellent stabilizing effect and enhances the oxidase-like activity of PtNPs. Kinetic studies indicate that Ch-PtNPs have a higher affinity for 3,3',5,5'-tetramethylbenzidine (TMB) than other kinds of oxidase mimics. Furthermore, the TMB chromogenic reaction catalyzed by Ch-PtNPs is found to be much faster in an acidic medium, thus adapting well to the optimal pH for acid phosphatase (ACP). Therefore, a novel colorimetric approach for ACP determination is developed for the first time, which is based on the Ch-PtNP-catalyzed oxidation of TMB, the inhibitory effect of ascorbic acid (AA) on the oxidase-like activity of Ch-PtNPs, and the ACP-catalyzed hydrolysis of AA 2-phosphate (AAP) into AA. The linear range for ACP is 0.25-2.5 U L-1 and the limit of detection is measured to be 0.016 U L-1. This new colorimetric method is utilized to detect ACP in real biological samples and to screen ACP inhibitors. We believe that these new PtNPs, which exhibit high colloidal stability, excellent catalytic performance, good biocompatibility, simple preparation, and easy modification, can be promising candidates for a broad range of applications in optical sensing, environmental monitoring, clinical diagnosis, and drug discovery.

Self-cascade reaction catalyzed by CuO nanoparticle-based dual-functional enzyme mimics.

It is desirable but challenging to assemble various biomimetic properties into a functional catalytic cascade system. In this work, cupric oxide nanoparticles were investigated as oxidase mimics for the aerobic oxidation of cysteine to cystine with the generation of hydrogen peroxide. Coupling this property with the peroxidase-like activity of CuO nanoparticles, we constructed a self-organized cascade reaction system based on a single-component nanozyme, which includes the oxidation of cysteine to yield cystine and hydrogen peroxide and the hydrogen peroxide-mediated oxidation of terephthalic acid to produce a fluorescence change. Based on this artificial enzymatic cascade reaction system, a fluorometric assay method with a low detection limit of 6.6nM was established for cysteine determination. This platform was then applied for the detection of cysteine in pharmaceutical products and human plasma, which yielded satisfactory results. Our investigations open up a new route and holds promise for the development and applications of multifunctional nanomaterials as enzyme mimics.

Stimuli-responsive electrospun nanofibers from poly(N-isopropylacrylamide)-co-poly(acrylic acid) copolymer and polyurethane.

A thermo- and pH-sensitive copolymer of poly(N-isopropylacrylamide)-co-poly(acrylic acid) (P(NIPAAm-co-AAc)) with an adjusted lower critical solution temperature (LCST)(at 37 °C) in an aqueous medium and pH of 7.4 was synthesized by a radical copolymerization, and was characterized by Fourier-transform infrared (FTIR) spectroscopy and 1H nuclear magnetic resonance (1H-NMR) spectroscopy. Then, nanofibers composed of P(NIPAAm-co-AAc) and polyurethane (PU) were fabricated by the single-spinneret electrospinning technique and used as drug carriers by co-spinning with the water insoluble drug nifedipine (NIF). The thermo-responsive behavior of the nanofibers was detected by contact angle (CA) measurements. The release behavior of the NIF from nanofibers was observed by scanning electron microscopy (SEM) and demonstrated by UV-vis spectroscopy. It was found that the wettability of the P(NIPAAm-co-AAc) nanofibers could be switched, due to the incorporation of PU. The release amount of NIF from the nanofibers could be controlled effectively by adjusting the temperature or pH value of the aqueous medium and incorporating the hydrophobic PU.

Self-assembly and controlled release behaviour of the water-insoluble drug nifedipine from electrospun PCL-based polyurethane nanofibres.

OBJECTIVES: Electrospun micro- and nanofibres are increasingly being investigated for drug delivery. The components of nanofibres are important influences on the drug release behaviour. The aim of this study was to investigate the self-assembly and release behaviour of drug from nanofibres. METHODS: Water-insoluble drug nifedipine (NIF)-loaded nanofibres with polymeric carrier of polycaprolactone (PCL)-based polyurethane (PU) were fabricated by electrospinning. The morphology of the nanofibres and the composite nanofibres with NIF were examined by scanning electron microscopy (SEM). The interactions between NIF and PU were followed by Fourier-transform infrared spectroscopy, and the elemental composition on the surface of the nanofibres was characterized by X-ray photoelectron spectroscopy. The release behaviour of NIF from nanofibres was observed by SEM (contacted with or without a drop of ethanol), and demonstrated by UV-Vis spectroscopy. KEY FINDINGS: In-vitro drug release studies revealed that a self-assembly process of NIF particles might be achieved within the body of the nanofibres. The electrospun nanofibre was an ideal drug carrier compared with a spin-coated film and could achieve controlled release of drug. CONCLUSIONS: The electrospinning technique could be used to fabricate a polymeric carrier that might have potential applications in the biomedical field.

Controllable drug release of electrospun thermoresponsive poly(N-isopropylacrylamide)/poly(2-acrylamido-2- methylpropanesulfonic acid) nanofibers.

Electrospinning micro- and nanofibers are being increasingly investigated for drug delivery. The components and their stimuli-responsive properties of fibers are important factors influencing the drug release behavior. The aim of this study is to fabricate thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm)/poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) nanofibers by single-spinneret electrospinning technique. The electrospun nanofibers are used as a drug carrier by cospinning with nifedipine (NIF), and the release behaviors of NIF from the thermoresponsive nanofibers can be controlled by the response of nanofibers with temperature. The morphology of the nanofibers and its composites with NIF was determined by scanning electron microscopy (SEM). The hydrogen bond interactions between PNIPAAm/PAMPS and the water-insoluble drug of NIF were introduced and confirmed by Fourier-transform infrared spectroscopy and energy dispersive spectrometer. The thermoresponsive properties of nanofibers were investigated by contact angle (CA) measurements. The release behaviors of NIF from the PNIPAAm/PAMPS nanofibers were observed by SEM and demonstrated by UV-vis spectroscopy. It was found that uniform fibers of NIF and PNIPAAm/PAMPS could be fabricated without particles on the surface. The release of NIF from nanofibers could be controlled effectively by the changes of hydrogen bonds between PNIPAAm/PAMPS and NIF, and by adjusting temperatures of the thermoresponsive nanofibers.