Switch-on Fluorescence Analysis of Protease Activity with the Assistance of a Nickel Ion-Nitrilotriacetic Acid-Conjugated Magnetic Nanoparticle.

Heterogeneous protease biosensors show high sensitivity and selectivity but usually require the immobilization of peptide substrates on a solid interface. Such methods exhibit the disadvantages of complex immobilization steps and low enzymatic efficiency induced by steric hindrance. In this work, we proposed an immobilization-free strategy for protease detection with high simplicity, sensitivity and selectivity. Specifically, a single-labeled peptide with oligohistidine-tag (His-tag) was designed as the protease substrate, which can be captured by a nickel ion-nitrilotriacetic acid (Ni-NTA)-conjugated magnetic nanoparticle (MNP) through the coordination interaction between His-tag and Ni-NTA. When the peptide was digested by protease in a homogeneous solution, the signal-labeled segment was released from the substrate. The unreacted peptide substrates could be removed by Ni-NTA-MNP, and the released segments remained in solution to emit strong fluorescence. The method was used to determine protease of caspase-3 with a low detection limit (4 pg/mL). By changing the peptide sequence and signal reporters, the proposal could be used to develop novel homogeneous biosensors for the detection of other proteases.

Synergistic induction of IL-6 production in human bronchial epithelial cells in vitro by nickel nanoparticles and lipopolysaccharide is mediated by STAT3 and C/EBPß.

We previously reported that delivery of nickel nanoparticles (NiNPs) and bacterial lipopolysaccharide (LPS) into the lungs of mice synergistically increased IL-6 production and inflammation, and male mice were more susceptible than female mice. The primary goal of this study was to utilize an in vitro human lung epithelial cell model (BEAS-2B) to investigate the intracellular signaling mechanisms that mediate IL-6 production by LPS and NiNPs. We also investigated the effect of sex hormones on NiNP and LPS-induced IL-6 production in vitro. LPS and NiNPs synergistically induced IL-6 mRNA and protein in BEAS-2B cells. TPCA-1, a dual inhibitor of IKK-2 and STAT3, blocked the synergistic increase in IL-6 caused by LPS and NiNPs, abolished STAT3 activation, and reduced C/EBPß. Conversely, SC144, an inhibitor of the gp130 component of the IL-6 receptor, enhanced IL-6 production induced by LPS and NiNPs. Treatment of BEAS-2B cells with sex hormones (17ß-estradiol, progesterone, or testosterone) or the anti-oxidant NAC, had no effect on IL-6 induction by LPS and NiNPs. These data suggest that LPS and NiNPs induce IL-6 via STAT3 and C/EBPß in BEAS-2B cells. While BEAS-2B cells are a suitable model to study mechanisms of IL-6 production, they do not appear to be suitable for studying the effect of sex hormones.

Ultrasensitive NO Sensor Based on a Nickel Single-Atom Electrocatalyst for Preliminary Screening of COVID-19.

A new coronavirus, SARS-CoV-2, has caused the coronavirus disease-2019 (COVID-19) epidemic. A rapid and economical method for preliminary screening of COVID-19 may help to control the COVID-19 pandemic. Here, we report a nickel single-atom electrocatalyst that can be printed on a paper-printing sensor for preliminary screening of COVID-19 suspects by efficient detection of fractional exhaled nitric oxide (FeNO). The FeNO value is confirmed to be related to COVID-19 in our exploratory clinical study, and a machine learning model that can accurately classify healthy subjects and COVID-19 patients is established based on FeNO and other features. The nickel single-atom electrocatalyst consists of a single nickel atom with N2O2 coordination embedded in porous acetylene black (named Ni-N2O2/AB). A paper-printed sensor was fabricated with the material and showed ultrasensitive response to NO in the range of 0.3-180 ppb. This ultrasensitive sensor could be applied to preliminary screening of COVID-19 in everyday life.

Synthesis, Crystal Structure, Theoretical Calculations, Antibacterial Activity, Electrochemical Behavior, and Molecular Docking of Ni(II) and Cu(II) Complexes with Pyridoxal-Semicarbazone.

New Ni (II) and Cu (II) complexes with pyridoxal-semicarbazone were synthesized and their structures were solved by X-ray crystallography. This analysis showed the bis-ligand octahedral structure of [Ni(PLSC-H)2]·H2O and the dimer octahedral structure of [Cu(PLSC)(SO4)(H2O)]2·2H2O. Hirshfeld surface analysis was employed to determine the most important intermolecular interactions in the crystallographic structures. The structures of both complexes were further examined using density functional theory and natural bond orbital analysis. The photocatalytic decomposition of methylene blue in the presence of both compounds was investigated. Both compounds were active toward E. coli and S. aureus, with a minimum inhibition concentration similar to that of chloramphenicol. The obtained complexes led to the formation of free radical species, as was demonstrated in an experiment with dichlorofluorescein-diacetate. It is postulated that this is the mechanistic pathway of the antibacterial and photocatalytic activities. Cyclic voltammograms of the compounds showed the peaks of the reduction of metal ions. A molecular docking study showed that the Ni(II) complex exhibited promising activity towards Janus kinase (JAK), as a potential therapy for inflammatory diseases, cancers, and immunologic disorders.

Ab Initio Insight into the Interaction of Metal-Decorated Fluorinated Carbon Fullerenes with Anti-COVID Drugs.

We theoretically investigated the adsorption of two common anti-COVID drugs, favipiravir and chloroquine, on fluorinated C60 fullerene, decorated with metal ions Cr3+, Fe2+, Fe3+, Ni2+. We focused on the effect of fluoridation on the interaction of fullerene with metal ions and drugs in an aqueous solution. We considered three model systems, C60, C60F2 and C60F48, and represented pristine, low-fluorinated and high-fluorinated fullerenes, respectively. Adsorption energies, deformation of fullerene and drug molecules, frontier molecular orbitals and vibrational spectra were investigated in detail. We found that different drugs and different ions interacted differently with fluorinated fullerenes. Cr3+ and Fe2+ ions lead to the defluorination of low-fluorinated fullerenes. Favipiravir also leads to their defluorination with the formation of HF molecules. Therefore, fluorinated fullerenes are not suitable for the delivery of favipiravir and similar drugs molecules. In contrast, we found that fluorine enhances the adsorption of Ni2+ and Fe3+ ions on fullerene and their activity to chloroquine. Ni2+-decorated fluorinated fullerenes were found to be stable and suitable carriers for the loading of chloroquine. Clear shifts of infrared, ultraviolet and visible spectra can provide control over the loading of chloroquine on Ni2+-doped fluorinated fullerenes.

Scavenging ROS to Alleviate Acute Liver Injury by ZnO-NiO@COOH.

Currently, the incidence of acute liver injury (ALI) is increasing year by year, and infection with coronavirus disease 2019 (COVID-19) can also induce ALI, but there are still no targeted therapeutic drugs. ZnO-NiO particles is mainly used to clean up reactive oxygen species (ROS) in industrial wastewater, and it is insoluble in water. Its excellent properties are discovered and improved by adding shuttle-based bonds to make it more water-soluble. ZnO-NiO@COOH particles are synthetically applied to treat ALI. The p-n junction in ZnO-NiO@COOH increases the surface area and active sites, thereby creating large numbers of oxygen vacancies, which can quickly adsorb ROS. The content in tissues and serum levels of L-glutathione (GSH) and the GSH/oxidized GSH ratio are measured to assess the capacity of ZnO-NiO@COOH particles to absorb ROS. The ZnO-NiO@COOH particles significantly reduce the expression levels of inflammatory factors (i.e., IL-1, IL-6, and TNF-α), macrophage infiltration, and granulocyte activation. ZnO-NiO@COOH rapidly adsorb ROS in a short period of time to block the generation of inflammatory storms and gain time for the follow-up treatment of ALI, which has important clinical significance.

Ni2+ Catalyzed Cleavage of TrpLE-Fused Small Transmembrane Peptides.

In addition to a membrane anchor, the transmembrane domain (TMD) of single-pass transmembrane proteins (SPTMPs) recently has shown essential roles in the cross-membrane activity or receptor assembly/clustering. However, these small TMD peptides are generally hydrophobic and dynamic, difficult to be expressed and purified. Here, we have integrated the power of TrpLE fusion protein and a sequence-specific nickel-assisted cleavage (SNAC)-tag to produce small TMD peptides in a highly efficient way under mild conditions, which uses Ni2+ as the cleavage reagent, avoiding the usage of toxic cyanogen bromide (CNBr). Furthermore, this method simplifies the downstream protein purification and reconstitution. Two representative TMDs, including the Spike-TMD from severe acute respiratory syndrome coronavirus 2 (SARS2), were successfully produced with high-quality nuclear magnetic resonance (NMR) spectra. Therefore, our study provides a more efficient and practical approach for general structural characterization of the small TM proteins.

Ultra-fast, high throughput and inexpensive detection of SARS-CoV-2 seroconversion using Ni2+ magnetic beads.

To monitor the levels of protecting antibodies raised in the population in response to infection and/or to immunization with SARS-CoV-2, we need a technique that allows high throughput and low-cost quantitative analysis of human IgG antibodies reactive against viral antigens. Here we describe an ultra-fast, high throughput and inexpensive assay to detect SARS-CoV-2 seroconversion in humans. The assay is based on Ni2+ magnetic particles coated with His tagged SARS-CoV-2 antigens. A simple and inexpensive 96 well plate magnetic extraction/homogenization process is described which allows the simultaneous analysis of 96 samples and delivers results in 7 min with high accuracy.

Diet Intervention Study through Telemedicine Assistance for Systemic Nickel Allergy Syndrome Patients during the COVID-19 Pandemic.

BACKGROUND: Restrictions due to the COVID-19 pandemic limited patients' access to hospital care. The aims of this study were to assess dietary nutritional status, quality of life (QoL), and adherence to dietary therapy before and after 30-day personalized diet therapy through telenutrition tools in patients with systemic nickel allergic syndrome (SNAS). METHODS: Each SNAS patient underwent the following allergological procedures: (a) face-to-face visit (nutritional visit and QoL evaluation) with prescription of one out of five personalized and balanced dietary plans different for calorie intake, (b) video call visit for dietary evaluation and assessment of adherence to diet after 15 days, and (c) video call visit for dietary and QoL evaluation and assessment of adherence to diet therapy after 30 days (end of study). RESULTS: We enrolled 20 SNAS patients. After 15 and 30 days, we found a statistically significant improvement in anthropometric findings after diet therapy, a significant adherence rate to low-nickel diet (60% and 80%, respectively), and an improvement in QoL with an increase in almost all psychometric indices. CONCLUSIONS: Our study demonstrates that telenutrition can be a valid tool to monitor nutritional status and adherence to balanced low-Ni diet positively affecting QoL in SNAS patients during the COVID-19 pandemic.

Nickel-Catalyzed Asymmetric Synthesis of α-Arylbenzamides.

A nickel-catalyzed asymmetric reductive hydroarylation of vinyl amides to produce enantioenriched α-arylbenzamides is reported. The use of a chiral bisimidazoline (BIm) ligand, in combination with diethoxymethylsilane and aryl halides, enables the regioselective introduction of aryl groups to the internal position of the olefin, forging a new stereogenic center α to the N atom. The use of neutral reagents and mild reaction conditions provides simple access to pharmacologically relevant motifs present in anticancer, SARS-CoV PLpro inhibitors, and KCNQ channel openers.