Directional Formation of Reactive Oxygen Species Via a Non-Redox Catalysis Strategy That Bypasses Electron Transfer Process.

A broad range of chemical transformations driven by catalytic processes necessitates the electron transfer between catalyst and substrate. The redox cycle limitation arising from the inequivalent electron donation and acceptance of the involved catalysts, however, generally leads to their deactivation, causing substantial economic losses and environmental risks. Here, a "non-redox catalysis" strategy is provided, wherein the catalytic units are constructed by atomic Fe and B as dual active sites to create tensile force and electric field, which allows directional self-decomposition of peroxymonosulfate (PMS) molecules through internal electron transfer to form singlet oxygen, bypassing the need of electron transfer between catalyst and PMS. The proposed catalytic approach with non-redox cycling of catalyst contributes to excellent stability of the active centers while the generated reactive oxygen species find high efficiency in long-term catalytic pollutant degradation and selective organic oxidation synthesis in aqueous phase. This work offers a new avenue for directional substrate conversion, which holds promise to advance the design of alternative catalytic pathways for sustainable energy conversion and valuable chemical production.

Structure-Based Identification of Kelch-like ECH-Associated Protein 1 as a Pharmacological Target of Electrophile-Containing Catechol-O-Methyltransferase Inhibitors.

Entacapone and nitecapone are electrophile-containing catechol-O-methyltransferase (COMT) inhibitors that are used to treat Parkinson's disease in combination with L-DOPA. It is desirable to investigate whether they can covalently bind to cellular protein targets using their reactive electrophilic warheads. We identified Kelch-like ECH-associated protein 1 (KEAP1), a sensor for oxidative and electrophilic stress, as a potential pharmacological target of both drugs by performing covalent-based reverse docking. We confirmed that both drugs activate nuclear factor erythroid 2-related factor 2 (NRF2) by reversibly modifying C151 on KEAP1. Both drugs can enhance the expression of growth differentiation factor 15 (GDF15) and NRF2 downstream antioxidant response element (ARE) genes, both in vitro and in vivo. Furthermore, both drugs exhibit anti-inflammatory effects in an NRF2-dependent acute gout model. Our findings suggest that these two drugs could be repurposed for the treatment of NRF2-modulated inflammatory diseases, and the 3-methylene-acetylacetone group of nitecapone could serve as a new reversible covalent warhead.

Asymmetrically Coordinated CoB1 N3 Moieties for Selective Generation of High-Valence Co-Oxo Species via Coupled Electron-Proton Transfer in Fenton-like Reactions.

High-valence metal species generated in peroxymonosulfate (PMS)-based Fenton-like processes are promising candidates for selective degradation of contaminants in water, the formation of which necessitates the cleavage of OH and OO bonds as well as efficient electron transfer. However, the high dissociation energy of OH bond makes its cleavage quite challenging, largely hampering the selective generation of reactive oxygen species. Herein, an asymmetrical configuration characterized by a single cobalt atom coordinated with boron and nitrogen (CoB1 N3 ) is established to offer a strong local electric field, upon which the cleavage of OH bond is thermodynamically favored via a promoted coupled electron-proton transfer process, which serves an essential step to further allow OO bond cleavage and efficient electron transfer. Accordingly, the selective formation of Co(IV)O in a single-atom Co/PMS system enables highly efficient removal performance toward various organic pollutants. The proposed strategy also holds true in other heteroatom doping systems to configure asymmetric coordination, thus paving alternative pathways for specific reactive species conversion by rationalized design of catalysts at atomic level toward environmental applications and more.

Generation of iodinated trihalomethanes during chloramination in the presence of solid copper corrosion products.

Copper water pipelines are widely used in water distribution systems, but the effects of solid copper corrosion products (CCPs) including CuO, Cu2O and Cu2(OH)2CO3 on the generation of iodinated trihalomethanes (I-THMs) during chloramination remain unknown. This study found that the formation of I-THMs during chloramination of humic acid (HA) was inhibited by the presence of CuO and Cu2O, but promoted with the addition of Cu2(OH)2CO3. The negative effect of CuO and Cu2O is mainly exerted by promoting the decay of both NH2Cl and HOI. Although Cu2(OH)2CO3 also accelerated the decomposition of NH2Cl and HOI, it was found that the complexes formed between Cu2(OH)2CO3 and HA facilitated, through carboxyl functional groups, the reaction between HA and HOI, leading to an enhancement of I-THM generation during chloramination, which was further confirmed by model compound experiments. Additionally, this study demonstrated that the effects of solid CCPs on I-THM generation during chloramination were solid CCP- and HA-concentration dependent, but almost unaffected by different initial I- and Br- concentrations. This study provides new insights into the health risks caused by the corrosion of copper water pipelines, especially in areas intruded by sea water.

Carbon nanotubes mediated chemical and biological decolorization of azo dye: Understanding the structure-activity relationship.

Chemical structure of azo dyes molecules showed significant influence on their decolorization rate, while the structure-activity relationship between chemical structure and their reduction decolorization rate is not fully understand. In this study, we found that azo dye molecule with closer position for electron-withdrawing substituent to azo bond resulted in faster chemical and biotic reduction rate with or without presence of carbon nanotubes (CNTs), while electron-repulsive substituent closer to azo bond leading to slower azo dye chemical and biotic reduction rate no matter with or without presence of CNTs. Additionally, galvanic cell experiments implied that electron transfer process may play important roles for both chemical and biological reduction decolorization of azo dyes, and CV results indicated that the higher (azo bond breakage) reduction wave potential corresponding to a faster azo dye chemical decolorization reaction. Finally, the results of Lowest Unoccupied Molecular Orbital (LUMO) energy established that lower LUMO energy for azo dye corresponding to a faster chemical decolorization reaction. This study not only offer systematized relationships between structure property of azo dye and their decolorization rate, but also provide a universal and propagable reduction rules.

Advances in interfacial engineering for enhanced microbial extracellular electron transfer.

The extracellular electron transfer (EET) efficiency between electroactive microbes (EAMs) and electrode is a key factor determining the development of microbial electrochemical technology (MET). Currently, the low EET efficiency of EAMs limits the application of MET in the fields of organic matter degradation, electric energy production, seawater desalination, bioremediation and biosensing. Enhancement of the interaction between EAMs and electrode by interfacial engineering methods brings bright prospects for the improvement of the EET efficiency of EAMs. In view of the research in recent years, this mini-review systematically summarizes various interfacial engineering strategies ranging from electrode surface modification to hybrid biofilm formation, then to single cell interfacial engineering and intracellular reformation for promoting the electron transfer between EAMs and electrode, focusing on the applicability and limitations of these methodologies. Finally, the possible key directions, challenges and opportunities for future interfacial engineering to strengthen the microbial EET are proposed in this mini-review.

Mixed-culture biocathodes for acetate production from CO2 reduction in the microbial electrosynthesis: Impact of temperature.

The temperature effect on bioelectrochemical reduction of CO2 to acetate with a mixed-culture biocathode in the microbial electrosynthesis was explored. The results showed that maximum acetate amount of 525.84 ± 1.55 mg L-1 and fastest acetate formation of 49.21 ± 0.49 mg L-1 d-1 were obtained under mesophilic conditions. Electron recovery efficiency for CO2 reduction to acetate ranged from 14.50 ± 2.20% to 64.86 ± 2.20%, due to propionate, butyrate and H2 generation. Mesophilic conditions were demonstrated to be more favorable for biofilm formation on the cathode, resulting in a stable and dense biofilm. At phylum level, the relative abundance of Bacteroidetes phylum in the biofilm remarkably increased under mesophilic conditions, compared with that at psychrophilic and thermophilic conditions. At genus level, the Clostridium, Treponema, Acidithiobacillus, Acetobacterium and Acetoanaerobium were found to be dominated genera in the biofilm under mesophilic conditions, while genera diversity decreased under psychrophilic and thermophilic conditions.

Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals.

Transcriptional regulation lies at the core of the circadian clockwork, but how the clock-related transcription machinery controls the circadian phase is not understood. Here, we show both in human cells and in mice that RuvB-like ATPase 2 (RUVBL2) interacts with other known clock proteins on chromatin to regulate the circadian phase. Pharmacological perturbation of RUVBL2 with the adenosine analog compound cordycepin resulted in a rapid-onset 12-hour clock phase-shift phenotype at human cell, mouse tissue, and whole-animal live imaging levels. Using simple peripheral injection treatment, we found that cordycepin penetrated the blood-brain barrier and caused rapid entrainment of the circadian phase, facilitating reduced duration of recovery in a mouse jet-lag model. We solved a crystal structure for human RUVBL2 in complex with a physiological metabolite of cordycepin, and biochemical assays showed that cordycepin treatment caused disassembly of an interaction between RUVBL2 and the core clock component BMAL1. Moreover, we showed with spike-in ChIP-seq analysis and binding assays that cordycepin treatment caused disassembly of the circadian super-complex, which normally resides at E-box chromatin loci such as PER1, PER2, DBP, and NR1D1 Mathematical modeling supported that the observed type 0 phase shifts resulted from derepression of E-box clock gene transcription.

A Review of FoxO1-Regulated Metabolic Diseases and Related Drug Discoveries.

FoxO1 is a conserved transcription factor involved in energy metabolism. It is tightly regulated by modifications on its mRNA and protein and responds to environmental nutrient signals. FoxO1 controls the transcription of downstream genes mediating metabolic regulation. Dysfunction of FoxO1 pathways results in several metabolic diseases, including diabetes, obesity, non-alcoholic fatty liver disease, and atherosclerosis. Here, we summarize the mechanism of FoxO1 regulation behind these diseases and FoxO1-related drug discoveries.

Identification, genomic organization and expression pattern of glutathione transferase in Pardosa pseudoannulata.

The pond wolf spider, Pardosa pseudoannulata, is one of the dominant natural enemies in farmlands and plays important roles in controlling a range of insect pests. The spider is less sensitive to many insecticides than the target pests such as the brown planthopper, Nilaparvata lugens. The different sensitivity to a certain insecticide between species is mostly attributed to the differences in both molecular targets and detoxification enzymes. As one of the most important detoxification enzymes, glutathione transferases (GSTs) play a key role as phase II enzyme in the enzymic detoxification in organisms. Until now, there are few studies on spiders' GSTs, limiting the understanding of insecticide selectivity between insect pests and natural enemy spiders. In this study, based on the transcriptome and genome sequencing of P. pseudoannulata, thirteen full-length transcripts encoding GSTs were identified and analyzed. Interestingly, Delta family, which is thought to be specific to the Insecta, was identified in P. pseudoannulata. Further, vertebrate/mammalian-specific Mu family was also identified in P. pseudoannulata. The mRNA expression levels of cytosolic GSTs in different tissues were determined, and most GST genes were abundant in the gut and the fat body. To investigate GST candidates involving in insecticide detoxification, the mRNA levels of cytosolic GSTs were tested after spiders' exposure to either imidacloprid or deltamethrin. The results showed that PpGSTD3 and PpGSTT1 responded to at least one of these two insecticides. The present study helped understand the function of GSTs in P. pseudoannulata and enriched the genetic information of natural enemy spiders.

Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1.

Recent studies have established the involvement of the fat mass and obesity-associated gene (FTO) in metabolic disorders such as obesity and diabetes. However, the precise molecular mechanism by which FTO regulates metabolism remains unknown. Here, we used a structure-based virtual screening of U.S. Food and Drug Administration-approved drugs to identify entacapone as a potential FTO inhibitor. Using structural and biochemical studies, we showed that entacapone directly bound to FTO and inhibited FTO activity in vitro. Furthermore, entacapone administration reduced body weight and lowered fasting blood glucose concentrations in diet-induced obese mice. We identified the transcription factor forkhead box protein O1 (FOXO1) mRNA as a direct substrate of FTO, and demonstrated that entacapone elicited its effects on gluconeogenesis in the liver and thermogenesis in adipose tissues in mice by acting on an FTO-FOXO1 regulatory axis.

Fto Deficiency Reduces Anxiety- and Depression-Like Behaviors in Mice via Alterations in Gut Microbiota.

Depression and obesity have high concurrence within individuals, which may be explained by sharing the same risk factors, including disruption of the intestinal microbiota. However, evidence that delineated the causal connections is extremely scarce. Methods: Mice lacking fat mass- and obesity-associated gene (Fto) were generated. Fto-deficient and wild-type control mice were subjected to novel conditions with or without chronic unpredictable mild stress (CUMS) for 6 weeks. Some mice were treated with antibiotics via their drinking water for 6 weeks in order to deplete their microbiota. Behavioral tests were performed to evaluate anxiety- and depression-like behaviors. 16S rRNA amplicon and metagenomic sequencing were employed to analyse fecal microbiota. Plasma levels of inflammatory cytokines and lipopolysaccharides (LPS) were also compared. Results: Deletion of Fto led to lower body weight and decreased anxiety- and depression-like behaviors, Fto+/- mice were also less susceptible to stress stimulation, highlighting the essential role of Fto in pathogenesis of depression. With regard to gut microbiota, Fto deficiency mice harbored specific bacterial signature of suppressing inflammation, characterized with higher abundance of Lactobacillus, lower Porphyromonadaceae and Helicobacter. Critically, behavioral alterations of Fto+/- mice are mediated by shift in gut microbiota, as such changes can be partially attenuated using antibiotics. Exposure to CUMS increased serum IL-6 level while Fto deficiency reduced its level, which may be explained by a lower LPS concentration. Conclusion: Together, our findings uncover the roles of Fto on depression and provide insights into microbiota-related biological mechanisms underlying the association between obesity and depression.

Ammonia sensing by closely packed WO3 microspheres with oxygen vacancies.

Ammonia (NH3), is a precursor for the formation of atmospheric fine particulate matter (PM2.5), and thus establishing efficient and cost-effective methods to detect ammonia emission is highly desired. Transition metal oxide semiconductors-based sensors for electrochemical gas sensing have been extensively explored. Among various types of semiconductors, tungsten oxide (WO3) possesses an anisotropic layered crystalline structure and is recognized as a promising material for gas sensing. However, the performance of commercial WO3 is unsatisfactory because of its high impedance and low charge transportation efficiency. Thus, the modification of commercial WO3 is needed to make it an efficient ammonia sensor material. In this work, closely packed WO3 microspheres with oxygen vacancies were synthesized successfully through a novel two-step hydrothermal route. Our WO3 showed a good selectivity to ammonia sensing, and its response intensity was 2.6 times higher than that of commercial WO3 because of its optimized conductivity. Moreover, the mechanism behind its robust ammonia sensing performance was elucidated. The effectiveness of the as-prepared WO3 microspheres for ammonia sensing also suggests a new strategy for modifying transition metal oxide materials.

A novel enzyme-linked immunosorbent assay for detection of Escherichia coli O157:H7 using immunomagnetic and beacon gold nanoparticles.

This paper presents a functional nanoparticle-enhanced enzyme-linked immunosorbent assay (FNP-ELISA) for detection of enterohemorrhagic Escherichia coli (EHEC) O157:H7. Immunomagnetic nanoparticles (IMMPs) conjugated with monoclonal anti-O157:H7 antibody were used to capture E. coli O157:H7. Beacon gold nanoparticles (B-GNPs) coated with polyclonal anti-O157:H7 and biotin single-stranded DNA (B-DNA) were then subjective to immunoreaction with E. coli O157:H7, which was followed by streptavidin-horseradish peroxidase (Strep-HRP) conjugated with B-GNPs based on a biotin-avidin system. The solutions containing E. coli O157:H7, IMMPs, B-GNPs, and Strep-HRP were collected for detecting color change. The signal was significantly amplified with detection limits of 68 CFU mL(-1) in PBS and 6.8 × 10(2) to 6.8 × 10(3) CFU mL(-1) in the food samples. The FNP-ELISA method developed in this study was two orders of magnitude more sensitive than immunomagnetic separation ELISA (IMS-ELISA) and four orders of magnitude more sensitive than C-ELISA. The entire detection process of E. coli O157:H7 lasted only 3 h, and thus FNP-ELISA is considered as a time-saving method.