Interactive network pharmacology and electrochemical analysis reveals electron transport-mediating characteristics of Chinese medicine formula Jing Guan Fang.

Background: Jing Guan Fang (JGF) is an anti-COVID-19 Chinese Medicine decoction comprised of five medicinal herbs to possess anti-inflammatory and antiviral properties for treatment. This study aims to electrochemically decipher the anti-coronavirus activity of JGF and show that microbial fuel cells may serve as a platform for screening efficacious herbal medicines and providing scientific bases for the mechanism of action (MOA) of TCMs. Methods: Electrochemical techniques (e.g., cyclic voltammetry) and MFCs were adopted as the bioenergy-based platforms to assess the bioenergy-stimulating characteristics of JGF. Phytochemical analysis correlated polyphenolic and flavonoid content with antioxidant activity and bioenergy-stimulating properties. Network pharmacology on the active compounds was employed to identify anti-inflammatory and anti-COVID-19 protein targets, and molecular docking validated in silico results. Significant findings: This first-attempt results show that JGF possesses significant reversible bioenergy-stimulation (amplification 2.02 ± 0.04) properties suggesting that its antiviral efficacy is both bioenergy-steered and electron mediated. Major flavonoids and flavone glycosides identified by HPLC (e.g., baicalein and baicalin, respectively) possess electron-shuttling (ES) characteristics that allow herbal medicines to treat COVID-19 via (1) reversible scavenging of ROS to lessen inflammation; (2) inhibition of viral proteins; and (3) targeting of immunomodulatory pathways to stimulate the immune response according to network pharmacology.

Deciphering Houttuynia cordata extract as electron shuttles with anti-COVID-19 activity and its performance in microbial fuel cells.

Background: Traditional herbal medicines usually contain electron shuttle (ES)-like structures compounds which are potential candidates for antiviral compounds selection. Houttuynia cordata is applied as a biomaterial to decipher its potential applications in bioenergy extraction in microbial fuel cells (MFCs) and anti-COVID-19 via molecular docking evaluation. Methods: H. cordata leaves extracts by water and 60% ethanol solvent were analyzed for total polyphenols, antioxidant activity, cyclic voltammetry (CV), and MFCs. The bioactive compounds of H. cordata leaves extracts were assayed via LC/MS analysis. Identification of the marker substances for potential antiviral activity using a molecular docking model was provided. Significant findings: 60% ethanol extract exhibits the highest total polyphenols and antioxidant activity compared with water extracts. Bioenergy extraction in MFCs showed that 60% ethanol extracts could give 1.76-fold more power generation compared to the blank. Flavonoids and their sugar-to-glycan ratios increased after CV scanning and they are expected to be effective ES substances. Quercitrin, from the H. cordata extract that shares an ES-like structure, was found to exhibit strong binding affinities towards ACE2 and RdRp. This indicated the potential of H. cordata leaves as a promising antiviral herb.

Interactive deciphering electron-shuttling characteristics of Coffea arabica leaves and potential bioenergy-steered anti-SARS-CoV-2 RdRp inhibitor via microbial fuel cells.

Due to the pandemics of COVID-19, herbal medicine has recently been explored for possible antiviral treatment and prevention via novel platform of microbial fuel cells. It was revealed that Coffea arabica leaves was very appropriate for anti-COVID-19 drug development. Antioxidant and anti-inflammatory tests exhibited the most promising activities for C. arabica ethanol extracts and drying approaches were implemented on the leaf samples prior to ethanol extraction. Ethanol extracts of C. arabica leaves were applied to bioenergy evaluation via DC-MFCs, clearly revealing that air-dried leaves (CA-A-EtOH) exhibited the highest bioenergy-stimulating capabilities (ca. 2.72 fold of power amplification to the blank). Furthermore, molecular docking analysis was implemented to decipher the potential of C. arabica leaves metabolites. Chlorogenic acid (-6.5 kcal/mol) owned the highest binding affinity with RdRp of SARS-CoV-2, showing a much lower average RMSF value than an apoprotein. This study suggested C. arabica leaves as an encouraging medicinal herb against SARS-CoV-2.

Interactive deciphering electron-shuttling characteristics of agricultural wastes with potential bioenergy-steered anti-COVID-19 activity via microbial fuel cells.

Background: This first-attempt study explored indigenous herbs from agricultural waste with bioenergy and biorefinery-stimulating potentials for possible anti-COVID-19 drug development. As prior novel study revealed, medicinal herbs abundant in ortho-dihydroxyl substituents and flavonoid-bearing chemicals were likely not only electron shuttle (ES)-steered, but also virus transmission-resisted. Methods: Herbal extract preparation from agricultural wastes were implemented via traditional Chinese medicine (TCM) decoction pot. After filtration and evaporation, a crude extract obtained was used for evaluation of bioenergy-stimulating and electron-mediating characteristics via microbial fuel cells (MFCs). Combined with cyclic voltammetric analysis, MFCs provided a novel platform to distinguish electron shuttles from antioxidants with electron-transfer steered antiviral potentials of herbal extracts. Significant findings: After 50 serial cyclic voltammogram traces, considerable ES activities of herbal extracts still stably remained, indicating that possible medication-associated capabilities could be persistent. This work also extended to explore bioenergy-stimulating herbs from agricultural waste recycling for bioenergy and biorefinery applications. Water extract of Coffea arabica was more biotoxic than ethanolic extract, resulting in its lower power-generating capability. The findings revealed that water extract of Trichodesma khasianum and Euphorbia hirta could exhibit considerable bioenergy-enhancing effects. For cradle-to-cradle circular economy, agricultural waste could be specifically screened for possible regeneration of value-added anti-COVID-19 drugs via bioenergy selection.

Synergistic deciphering of bioenergy production and electron transport characteristics to screen traditional Chinese medicine (TCM) for COVID-19 drug development.

Background: Traditional Chinese medicine (TCM) has been used as an "immune booster" for disease prevention and clinical treatment since ancient China. However, many studies were focused on the organic herbal extract rather than aqueous herbal extract (AHE; decoction). Due to the COVID-19 pandemics, this study tended to decipher phytochemical contents in the decoction of herbs and derived bioactivities (e.g., anti-oxidant and anti-inflammatory properties). As prior works revealed, the efficacy of Parkinson's medicines and antiviral flavonoid herbs was strongly governed by their bioenergy-stimulating proficiency. Methods: Herbal extracts were prepared by using a traditional Chinese decoction pot. After filtration and evaporation, crude extracts were used to prepare sample solutions for various bioassays. The phytochemical content and bioactivities of AHEs were determined via ELISA microplate reader. Microbial fuel cells (MFCs) were used as a novel platform to evaluate bioenergy contents with electron-transfer characteristics for antiviral drug development. Significant findings: Regarding 18 TCM herbal extracts for the prevention of SARS and H1N1 influenza, comparison on total polyphenol, flavonoid, condensed tannins and polysaccharides were conducted. Moreover, considerable total flavonoid contents were detected for 11 herb extracts. These AEHs were not only rich in phytonutrient contents but also plentiful in anti-oxidant and anti-inflammatory activities. Herbs with high polyphenol content had higher antioxidant activity. Forsythia suspensa extract expressed the highest inhibition against nitric oxide production for anti-inflammation. MFC bioenergy-stimulating studies also revealed that top ranking COVID-19 efficacious herbs were both bioenergy driven and electron mediated. That is, electron transfer-controlled bioenergy extraction was significant to antiviral characteristics for anti-COVID-19 drug development.

Exploring community evolutionary characteristics of microbial populations with supplementation of Camellia green tea extracts in microbial fuel cells.

This first-attempt study deciphered combined characteristics of species evolution and bioelectricity generation of microbial community in microbial fuel cells (MFCs) supplemented with Camellia green tea (GT) extracts for biomass energy extraction. Prior studies indicated that polyphenols-rich extracts as effective redox mediators (RMs) could exhibit significant electrochemical activities to enhance power generation in MFCs. However, the supplementation of Camellia GT extract obtained at room temperature with significant redox capabilities into MFCs unexpectedly exhibited obvious inhibitory effect towards power generation. This systematic study indicated that the presence of antimicrobial components (especially catechins) in GT extract might significantly alter the distribution of microbial community, in particular a decrease of microbial diversity and evenness. For practical applications to different microbial systems, pre-screening criteria of selecting biocompatible RMs should not only consider their promising redox capabilities (abiotic), but also possible inhibitory potency (biotic) to receptor microbes. Although Camellia tea extract was well-characterized as GRAS energy drink, some contents (e.g., catechins) may still express inhibition towards organisms and further assessment upon biotoxicity may be inevitably required for practice.

Sulfur doped-graphene for enhanced acetaminophen degradation via electro-catalytic activation: Efficiency and mechanism.

Although graphene exhibited excellent performance, its capability of electrochemical catalytic oxidation would significantly improve by modification via sulfur (S)-doping. However, due to the complicated doping species of heteroatoms, the detailed mechanism was still remained open for discussion. Thus, this first-attempt study tended to decipher such mechanism behind the direct and indirect oxidation by analyzing S species in S-graphene. The density functional theory (DFT) was adopted for reactive center calculation and confirmation of secondary active species, to discuss the degradation pathway. As the experimental and calculation results, the thiophene structure S was more favorable for electron acceptation in direct oxidation. Chloride reactive species, as the most effective secondary functionalities (rather than •OH), were favorably generated on the edge doped S position than thiophene structured S in defects, to further trigger the indirect oxidation. However, the extensive contents of reactive functionalities could act as trap for self-annihilation of chloride reactive species, resulting in poor electrocatalytic degradation of the pollutants. This study deepened the understanding of heteroatoms doping for electrochemical catalytic oxidation.

Revealing microbial mechanism associated with volatile fatty acids production in anaerobic acidogenesis of waste activated sludge enhanced by freezing/thawing pretreatment.

This study investigated the association of volatile fatty acid (VFA) production with microbial mechanism in waste activated sludge (WAS) anaerobic acidogenesis enhanced by freezing/thawing (F/T) pretreatment. WAS solubilization was enhanced with 955.4 ± 10.0 mg/L soluble chemical oxygen demand (SCOD) release by a 50-h F/T pretreatment at -24 °C. The highest level of VFAs (4852 ± 156 mg COD/L) was obtained after a 12-day fermentation. Moreover, phyla of Proteobacteria, Bacteroidetes, Firmicutes, and Ignavibacteriae played vital roles in VFA generation, while high genera abundance of Clostridium, Macellibacteroides, Prevotella, and Megasphaera were positively associated with high yields of short-chain (C2-C5) fatty acids. A schematic diagram was drawn to illustrate the microbial mechanism of enhanced VFA generation by F/T pretreatment during WAS fermentation. This study provides an in-depth exploration of promoting bio-resource recycling from WAS with a low-cost approach (specially in high latitudes) and bring about some new thinking on future WAS management.

Deciphering Electron-Shuttling Characteristics of Neurotransmitters to Stimulate Bioelectricity-Generating Capabilities in Microbial Fuel Cells.

This first-attempt study used electrochemical methods to quantitatively assess electron-shuttling capabilities of different neurotransmitters crucial to catecholamine biosynthesis in human brain. As prior studies mentioned, aromatics bearing ortho- or para-dihydroxybenzenes could reveal promising electroactivities to stimulate bioenergy generation in microbial fuel cells (MFCs). This feasibility study extended to investigate the electrochemical characteristics of catecholamines and trace amines (e.g., 14 model compounds selected from neurotransmitters) synthesized by human brain via cyclic voltammetry methods (CVs) and MFCs. Dopamine (DA), levodopa (L-DOPA), epinephrine (EP), norepinephrine (NP), and 3,4-dihydroxyphenylacetic acid (DOPAC) would perform the electron-shuttling characteristics, and the rest would not. In particular, DA formed by decarboxylation of L-DOPA could exhibit relatively higher electrochemical activities than their precursors. In addition, carboxylic acids formed by deamination and carboxylation of trace monoamines would reveal more significant reductive potential (Epc); however, their oxidative electric currents seemed to be reduced. That is, chemical structure significantly influenced whether the electrochemical characteristics could be effectively expressed. This work also clearly revealed that neurotransmitters with ortho-dihydroxybenzenes exhibited promising stimulation to bioelectricity-generating capabilities of MFCs in the ranking of DA ~ EP > NP > L-DOPA > DOPAC. This was consistent with ES behaviors as CV analyses indicated.

Polyphenolic compounds as electron shuttles for sustainable energy utilization.

For renewable and sustainable bioenergy utilization with cost-effectiveness, electron-shuttles (ESs) (or redox mediators (RMs)) act as electrochemical "catalysts" to enhance rates of redox reactions, catalytically accelerating electron transport efficiency for abiotic and biotic electrochemical reactions. ESs are popularly used in cellular respiratory systems, metabolisms in organisms, and widely applied to support global lives. Apparently, they are applicable to increase power-generating capabilities for energy utilization and/or fuel storage (i.e., dye-sensitized solar cell, batteries, and microbial fuel cells (MFCs)). This first-attempt review specifically deciphers the chemical structure association with characteristics of ESs, and discloses redox-mediating potentials of polyphenolics-abundant ESs via MFC modules. Moreover, to effectively convert electron-shuttling capabilities from non-sustainable antioxidant activities, environmental conditions to induce electrochemical mediation apparently play critical roles of great significance for bioenergy stimulation. For example, pH levels would significantly affect electrochemical potentials to be exhibited (e.g., alkaline pHs are electrochemically favorable for expression of such electron-shuttling characteristics). Regarding chemical structure effect, chemicals with ortho- and para-dihydroxyl substituents-bearing aromatics own convertible characteristics of non-renewable antioxidants and electrochemically catalytic ESs; however, ES capabilities of meta-dihydroxyl substituents can be evidently repressed due to lack of resonance effect in the structure for intermediate radical(s) during redox reaction. Moreover, this review provides conclusive remarks to elucidate the promising feasibility to identify whether such characteristics are non-renewable antioxidants or reversible ESs from natural polyphenols via cyclic voltammetry and MFC evaluation. Evidently, considering sustainable development, such electrochemically convertible polyphenolic species in plant extracts can be reversibly expressed for bioenergy-stimulating capabilities in MFCs under electrochemically favorable conditions.

Exploring biostimulation of plant hormones and nitrate supplement to effectively enhance biomass growth and lutein production with thermo-tolerant Desmodesmus sp. F51.

In this study, the interactive effect of plant hormone-salicylic acid and succinic acid on biomass growth, lutein content, and productivity of Desmodesmus sp. F51 were investigated. The results demonstrated that the synergistic action of salicylic acid and succinic acid could effectively enhance the assimilation of nitrate and significantly improve lutein production. The maximal lutein content 7.01 mg/g and productivity 5.11 mg/L/d could be obtained with a supplement of 100 µM salicylic acid and 2.5 mM succinic acid in batch culture. Furthermore, operation strategy of nitrate fed-batch coupled with supplementation for succinic acid and salicylic acid resulted in further enhancement of lutein content and productivity by 7.50 mg/g and 5.78 mg/L/d, respectively. The performance is better than most of the previously reported values.

Unraveling interactive characteristics of microbial community associated with bioelectric energy production in sludge fermentation fluid-fed microbial fuel cells.

This first-attempt study deciphered the interactive characteristics of anodophilic microbial community-associated bioelectricity production in waste activated sludge (WAS) fermentation fluid-fed microbial fuel cells (MFCs). A novel schematic elucidation for illustrating synergistic interactions in anodic microbial consortia towards electrogenesis was proposed. Moreover, the specific genera of Pseudomonas, Desulfovibrio, Phyllobacterium, Desulfuromonas, Chelatococcus and Aminivibrio were dominant in anodic biofilms, leading to an electrogenesis efficiency of 1.254 kWh/kg COD and peak power density of 0.182 W/m2 (at feeding level of 1.20 g COD/L). It was apparently higher than those MFCs fed with glucose/acetate. The fermentative species contributed positively in reorganizing microbial community structure in anodic biofilms, positively relating to electrogenesis via interactions with exoeletrogens in MFCs. Finally, a more electrogenesis was positively associated to larger anodic microbial diversity, relatively medium anodic community evenness, together with higher abundance of functional genes related to electrogenesis in functional species in MFCs fed with WAS fermentation fluid.

Deciphering optimal biostimulation strategy of supplementing anthocyanin-abundant plant extracts for bioelectricity extraction in microbial fuel cells.

BACKGROUND: Microbial fuel cells (MFCs) are effective biofuel devices that use indigenous microbes to directly convert chemical energy from organics oxidation into bioelectric energy. To maximize energy-converting efficiency for bioelectricity generation in MFCs, redox mediators (RMs) (e.g., extracts obtained from plant resource-Camellia green tea) have been explored for optimal stimulation upon electron transfer (ET) capabilities. Anthocyanins are natural antioxidants widely used in food science and medicinal industry. This first-attempt study revealed optimal strategies to augment extracts of anthocyanin-rich herbs (Lycium ruthenicum Murr., Clitoria ternatea Linn. and Vaccinium Spp.) as biofuel sources of catalytic RMs for stimulating bioenergy extraction in MFCs. RESULTS: This work showed that extracts of anthocyanin-rich herbs were promising electroactive RMs. The maximal power density of MFCs supplemented with extract of L. ruthenicum Murr. was achieved, suggesting that extract of L. ruthenicum Murr. would be the most electrochemically appropriate RMs. Compared to C. ternatea Linn. and Vaccinium Spp., L. ruthenicum Murr. evidently owned the most significant redox-mediating capability to stimulate bioenergy extraction likely due to significantly high contents of polyphenols (e.g., anthocyanin). Evidently, increases in adenosine triphosphate (ATP) content directly responded to supplementation of anthocyanin-rich herbal extracts. It strongly suggested that the electron-shuttling characteristics of RMs upon electroactive microorganisms could effectively promote the electron transfer capability to maximize bioenergy extraction in MFCs. CONCLUSION: Anthocyanin as the main water-soluble vacuolar pigments in plant products were very electroactive for not only excellent antioxidant activities, but also promising electron-shuttling capabilities for renewable biofuel applications. This work also suggested the electron-shuttling mechanism of RMs that could possibly promote electron transport phenomena through microbial cell membrane, further influencing the electron transport chain for efficient bioenergy generation.

Exploring the glyphosate-degrading characteristics of a newly isolated, highly adapted indigenous bacterial strain, Providencia rettgeri GDB 1.

This study explored the characteristics of a newly isolated glyphosate (GLYP)-degrading bacterium Providencia rettgeri GDB 1, for GLYP bioremediation. Due to the serial selection pressure of high GLYP concentrations for enriched isolation, this highly tolerant GLYP biodegrader shows very promising capabilities for GLYP removal (approximately 71.4% degradation efficiency) compared to previously reported strains. High performance liquid chromatography analyses showed aminomethylphosphonic acid (AMPA) rather than sarcosine (SAR) to be the sole intermediate of GLYP decomposition via the AMPA formation pathway. Moreover, GLYP biodegradation was biochemically favorable in aerobic cultures due to its strong growth-associated characteristics. To the best of our knowledge, this is the first report to indicate that bacterial strains in the Providencia genus could demonstrate highly promising GLYP-degrading characteristics in environments with high GLYP contents.

Novel inspection of sugar residue and origin in honey based on the 13C/12C isotopic ratio and protein content.

Regarding the honey industry, market prices are strongly affected by the origin and composition of products. In particular, the adulteration of honey can be divided into cases of honey being mixed with artificial syrup, the different origin of the adulteration and the presence of cane sugar residue. Unfortunately, recent studies mentioned that most honey is mixed with artificial syrups. Thus, determining such unnaturally present sugar is necessary to maintain the trust of the consuming populations. To investigate the possibility of syrup augmentation, this study first clarifies two points of great importance. First, long-term feeding of cane sugar to honey bee colonies in winter and the continuous harvest of honey were investigated to evaluate the C4 sugar ratio in spring through inspection of the 13C/12C isotopic ratio. As the results indicated, C4 sugar was detected as "sugar residue" in honey samples when the honey bee colonies were fed with cane sugar in winter and when the honey was collected in the first and second harvests in March. As indicated from the samples of 89 Taiwanese longan honeys, 54 Thai longan honeys, and 20 Taiwanese non-longan honeys for analysis, such "sugar residues" were in 40% (8/20) of the Taiwanese non-longan honeys, 15% (3/20) of 2017 Taiwanese longan honeys and 20% (4/20) of 2017 Thai longan honeys; these samples were classified as adulterated honey (C4% > 7). Second, as revealed in the honeys' protein contents, statistically significant differences were found between Taiwanese (>1.00 mg/g) and Thai longan honeys (<1.00 mg/g). Apparently, this significant difference could be used to classify the difference in origins of longan honeys. This novel inspection of "sugar residue" and "origin" in honey could represent the first attempt for a protocol to guarantee both the quality and quantity assurance of honey in the marketplace.

Deciphering synergistic characteristics of redox mediators-stimulated echinenone production of Gordonia terrae TWIH01.

This first-attempt study tended to decipher synergistic interactions of model redox mediators (RMs) to echinenone production for electrochemically-steered fermentation (ESF). The findings indicated that supplement of RMs could significantly stimulate the production performance of fermentation (e.g., 36% for 4-aminophenol) which was parallel with stimulation of bioelectricity generation in microbial fuel cells (MFCs) as prior studies mentioned. Although redox mediators could usually enhance electron transport extracellular compartment, the mechanisms of bioelectricity generation in MFCs and echinenone production in ESF were very likely functioned in the extracellular and the intracellular compartment, respectively. In MFCs, electron transfer towards biofilm anode for bioelectricity generation must be taken place. However, for ESF echinenone accumulation was very likely occurred in the intracellular compartment, thus electron transfer was predominantly implemented in the intracellular, not the extracellular compartment.

Exploring optimal supplement strategy of medicinal herbs and tea extracts for bioelectricity generation in microbial fuel cells.

This first-attempt study used extracts of appropriate antioxidant abundant Camellia and non-Camellia tea and medicinal herbs as model ESs to stably intensify bioelectricity generation performance in microbial fuel cells (MFCs). As electron shuttles (ESs) could stimulate electron transport phenomena by significant reduction of electron transfer resistance, the efficiency of power generation for energy extraction in microbial fuel cells (MFCs) could be appreciably augmented. Using environmentally friendly natural bioresource as green bioresource of ESs is the most promising to sustainable practicability. As comparison of power-density profiles indicated, supplement of Camellia tea extracts would be the most appropriate, then followed non-Camellia Chrysanthemum tea and medicinal herbs. Antioxidant activities, total phenolic contents and power stimulating activities were all electrochemically associated. In particular, the extract of unfermented Camellia tea (i.e., green tea) was the most promising ESs to augment bioenergy extraction compared to other refreshing medicinal herb extracts.

Correction: Surface modification of carbon cloth anodes for microbial fuel cells using atmospheric-pressure plasma jet processed reduced graphene oxides.

[This corrects the article DOI: 10.1039/C7RA11914C.].

Revealing Pesticide Residues Under High Pesticide Stress in Taiwan's Agricultural Environment Probed by Fresh Honey Bee (Hymenoptera: Apidae) Pollen.

Significant pesticide residues are among the most serious problems for sustainable agriculture. In the beekeeping environment, pesticides not only impact a honey bee's survival, but they also contaminate bee products. Taiwan's agricultural environment has suffered from pesticide stress that was higher than that found in Europe and America. This study deciphered problems of pesticide residues in fresh honey bee pollen samples collected from 14 monitoring apiaries in Taiwan, which reflected significant contaminations within the honey bee population. In total, 155 pollen samples were screened for 232 pesticides, and 56 pesticides were detected. Among the residues, fluvalinate and chlorpyrifos showed the highest concentrations, followed by carbendazim, carbaryl, chlorfenapyr, imidacloprid, ethion, and flufenoxuron. The average frequency of pesticide residues detected in pollen samples was ca. 74.8%. The amounts and types of pesticides were higher in winter and in southwestern Taiwan. Moreover, five of these pollen samples were contaminated with 11-15 pesticides, with average levels between 1,560 and 6,390 µg/kg. Compared with the literature, this study emphasized that pollen gathered by honey bee was highly contaminated with more pesticides in Taiwan than in the America, France, and Spain. The ubiquity of pesticides in the pollen samples was likely due to the field applications of common pesticides. Recently, the Taiwanese government began to improve the pesticide policy. According to the resurvey data in 2016, there were reductions in several pesticide contamination parameters in pollen samples from west to southwest Taiwan. A long-term investigation of pollen pesticide residues should be conducted to inspect pesticides usage in Taiwan's agriculture.