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.

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.

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.

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.

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.

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.

Copper ion-stimulated McoA-laccase production and enzyme characterization in Proteus hauseri ZMd44.

The novel bioelectricity-generating bacterium of Proteus hauseri ZMd44 has been first identified to produce McoA-laccase (EC 1.10.3.2) induced by copper sulphate. The optimal concentration of copper is 3 mM as supplementation at the beginning of culture or early exponential growth phase, during which laccase is predominantly synthesized. Moreover, the whole cellular and intracellular activities of laccase increase in the degrees of inducible copper concentrations. A possible mechanism for this phenomenon is that copper ions enhance the laccase genetic transcription level during the laccase synthesis thus granting this strain in copper tolerance. McoA-laccase belongs to typical type 1 (T1) Cu site laccase by electron paramagnetic resonance (EPR) analysis of intracellular enzyme. From our results, the optimal temperature and pH are 60°C and pH 2.2, respectively. The kinetic profiles show that this enzyme is stable under 50°C and in the slightly acidic environment, making it a potentially useful enzyme in dye decolorization, paper-pulp bleaching and bioremediation industries.

Waste brick's potential for use as a pozzolan in blended Portland cement.

This study investigated the pozzolanic reactions and engineering properties of waste brick-blended cements in relation to various replacement ratios (0-50%). The waste brick consisted of SiO(2) (63.21%), Al(2)O(3) (16.41%), Fe(2)O(3) (6.05%), Na(2)O (1.19%), K(2)O (2.83%) and MgO (1.11%), and had a pozzolanic activity index of 107%. The toxic characteristic leaching procedure (TCLP) results demonstrate that the heavy-metal content in waste bricks met the Environmental Protection Agency regulatory limits. Experimental results indicate that 10, 20, 30, 40 and 50% of cement can be replaced by waste brick, which causes the initial and final setting times to increase. Compressive strength development was slower in waste brick-blended cement (WBBC) pastes in the early ages; however, strength at the later ages increased significantly. Species analyses demonstrate that the hydrates in WBBC pastes primarily consisted of Ca(OH)(2) and calcium silicate hydrate (C-S-H) gel, like those found in ordinary Portland cement (OPC) paste. Pozzolanic reaction products formed in the WBBC pastes, in particular, various reaction products, including hydrates of calcium silicates (CSH), aluminates (CAH) and aluminosilicates (CASH), formed as expected, resulting in consumption of Ca(OH)(2) during the late ages of curing. The changes in the properties of WBBC pastes were significant as blend ratio increased, due to the pores of C-S-H gels and CAH filling via pozzolanic reactions. This filling of gel pores resulted in densification and subsequently enhanced the gel/space ratio and degree of hydration. Experimental results demonstrate waste brick can be supplementary cementitious material.

Optimal biostimulation strategy for phenol degradation with indigenous rhizobium Ralstonia taiwanensis.

This study provides a first attempt from a perspective of Gaden's classification of fermentation and phase-plane to put forward phenol degradation using various augmented nutrient media for biostimulation. It aimed to identify the most promising nutrient source(s) to attenuate synergistic interactions with phenol for optimal phenol degradation. Therefore, the growth association of phenol degradation using various nutrient media in place of combined toxic interactions was established via Gaden's classification scheme of fermentation and phase-plane analysis. In cultures grown on medium bearing dual carbon sources (glycerol and phenol) or phenol alone, phenol was found to be firstly biodegraded for microbial growth (i.e., growth-associated degradation). In contrast, when yeast extract or acetate was supplemented, a diauxic growth behavior was observed as the augmented nutrient was primarily utilized while phenol degradation was repressed. Moreover, using glycerol as the nutrient source, phenol degradation seemed to be enhanced simultaneously during the consumption of glycerol for cellular growth after ca. 2h response lag in growth. Although gluconic acid could enhance cell growth as well as phenol degradation, the phenol degradation performance was still not as good as that of glycerol. Thus, biostimulation with glycerol appeared to show the most favorable metabolic characteristics against phenol toxicity on Ralstonia taiwanensis, leading to better degradation efficiency of the toxic pollutant. Phase-plane trajectories also clearly confirmed that glycerol was the optimal biostimulating nutrient source for phenol degradation.

Understanding biotoxicity for reusability of municipal solid waste incinerator (MSWI) ash.

This feasibility study using Escherichia coli DH5alpha as a reporter microorganism tended to disclose toxicity ranking of various ashes of municipal solid waste incinerator (MSWI) in comparison with typical toxic chemicals for reusability in further applications. Previous study indicated that growth inhibition to bacterial cells occurred at concentrations above 0.156, 0.625 and 0.0195g/L for bottom ash (BA), cyclone ash (CA), scrubber ash (SA), respectively, suggesting the toxicity ranking of SA>BA>CA. This follow-up study clearly stated that compared to cadmium(II) and chromium(II) SA seemed to be the most toxic species to DH5alpha. Large amounts of supplemented lime (CaO) were used for neutralization of acid gas in incinerator, SA was thus contained high-levels of sulfate, chloride and nitrate salts. Therefore, compared to other ashes a marked increase in toxicity was observed in SA. Regarding soluble cations and anions in ashes, nitrite ion seemed to stimulate instead of repress cell growth. In contrast, nitrate ion showed so-called "sufficient challenge" characteristics for growth enhancement and inhibition at low and high concentration, respectively. Low solubility of metallic ions (e.g., Pb(II) and Cu(II)) in ashes likely resulted in low mobility in the environment and low risk to humans. The findings showed that toxicity attenuation of SA will be inevitably required as SA is even more toxic than Cr(II) and Cd(II).

Phenol degradation and toxicity assessment upon biostimulation to an indigenous Rhizobium Ralstonia taiwanensis.

This study provides a first attempt from a toxicological perspective to put forward, in general terms and explanations, combined toxic interactions and biostimulation strategy upon nutrient medium to Ralstonia taiwanensis for bioremediation. Dose-response analysis clearly revealed that most of the supplemented nutrients tested (except for gluconic acid) synergistically interact with chronic toxicity to phenol, especially at low doses. Acute toxicity based upon adaptation lag is a more appropriate indicator for comparative analysis of toxicity due to similar toxic ranking at almost all effective concentrations. In addition, comparison upon acute and chronic toxicity for various nutrient media also suggests in parallel that acute toxicity is more significant than chronic toxicity possibly as the result of a more sensitive response of adaptation lag to growth in different media. Feasibility of adding extra nutrient substrates (e.g., phenol, gluconic acid, yeast extract, pyruvic acid, acetic acid, and glycerol) to stimulate proliferation of phenol degraders for better phenol degradation performance was also assessed. The results show that using acetic acid as the augmented nutrient source might be the most feasible biostimulation strategy for phenol degradation.