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Bioelectrochemical system (BES) is a unique biotechnology for wastewater treatment and energy recovery, and extracellular electron transfer (EET) between microbe and electrode is the key to optimize the performance of BESs. Resazurin is an effective artificial compound that can promote EET in BESs, but the way how it transports electrons is not fully understood. In this study differential pulse voltammetry revealed that the redox potential of resorufin (RR) (intermediate of resazurin reduction, actual electron mediator) within Geobacter sulfurreducens biofilm was positively shifted by 100 mV than that of free RR, and this shift was attenuated by the mutation of outer-membrane cytochrome gene omcE but not by omcS and omcZ mutation, indicating that RR specifically interacted with OmcE. By using heterologously expressed OmcE monomers in Escherichia coli, it was found that RR bonded with OmcE monomers with a moderate intensity (dissociation constant of 720 nM), and their interaction obviously increased the content of α helix in OmcE monomers. Biomolecular analysis indicated that heme II of OmcE monomer might be the binding site for RR (binding energy of -7.01 kJ/mol), which were favorable for electron transfer within OmcE-RR complex. Comparative transcriptomics showed that RZ addition significantly upregulated the expression of omcE, periplasmic cytochrome gene ppcB, and outer-membrane genes omaB, ombB and omcB, thus, it was hypothesized that OmcE-bound RR might serve as potential electron acceptor of OmbB-OmaB-OmcB porin complex which passes electrons across outer membrane. Our work demonstrated a new pathway of artificial electron mediators in facilitating EET in Geobacter species, which may guide the application of electron mediator in improving the performance of BESs.

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Caproate production by microbial fermentation gained the advantages of sustainability and eco-friendliness, but challenged by sterile fermentation environment, necessity of organic electron donors. Here, a single-step electro-fermentation (EF) process of mixed culture was proposed for caprate production from rice straw. At the optimal potential of -0.8 V, caproate concentration, yield and selectivity in the neutral red (NR)-mediated EF system were 2.4 g/L, 0.2 g/g and 26.6%. Long-term operation accumulated 5.3 g/L caproate with the yield and selectivity of 0.2 g/g and 34.2% in the EF+NR system. Bioaugmentation by dosing chain-elongation microbial consortium further improved the caproate production, yield and selectivity to 9.1 g/L, 0.3 g/g and 41.5%, respectively. The improved caproate production in the bioaugmented EF+NR system was likely due to the enhanced interspecies electron transfer, reconstructed microbial community, multiple electron donors and suitable pH environment. Present study offers a feasible strategy for cost-effective caprate production directly from waste biomass.

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Humic electron mediators can facilitate the reductive dehalogenation of organohalogenated compounds by accelerating electron transfer. To investigate the effect of humic electron mediators on the microbial anaerobic reductive dechlorination of Polychlorinated biphenyls (PCBs), three types of humic electron mediators, humin (HM), humic acid (HA), and anthraquinone-2,6-disulfonic acid (AQDS, HA analogs), were added to PCB dechlorination cultures enriched from different sources in terrestrial and marine environments (T and M cultures). The results showed that meta- and para-site dechlorination occurred in the M culture, while only meta-site dechlorination occurred in the T culture. The dechlorination process N and the dechlorination process H or H' are presented in both cultures. HM enhanced PCB dechlorination metabolic activity in both cultures mainly by promoting meta-site dechlorination. HA showed a weak promoting effect on the M culture by promoting para-chlorine removal but inhibited the dechlorination metabolism of the terrestrial-origin culture, inhibiting meta-chlorine removal. AQDS showed inhibitory effects on both cultures by inhibiting the microbial removal of meta-chlorine. High-throughput sequencing and qPCR results suggest that HM is not a carbon source for the potential dechlorinating metabolism of Dehalococcoides but may promote reductive dechlorination by changing the community structure, and AQDS may inhibit anaerobic reductive dechlorination of PCBs by inhibiting the growth of Dehalococcoides. This study provides insights into the mechanism of enhancing PCB microbial dechlorination mediated by humic substances and plays a significant role in extending the application prospects of PCBs bioremediation technology.

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The bioreduction of toxic chromium(VI) to sparingly soluble chromium(III) represents an environmentally friendly and cost-effective method for remediating Cr contamination. Usually, this bioreduction process is slow and requires the addition of quinone compounds as electron shuttles to enhance the reaction rate. However, the dissolved quinone compounds are susceptible to loss with water flow, thereby limiting their effectiveness. To address this challenge, this study loaded anthraquinone-2,6-disulfonate (AQDS), a typical quinone compound, onto biochar (BC) to create a novel solid-phase electron mediator (BC-AQDS) that can sustainably promote Cr(VI) bioreduction. The experimental results demonstrated that BC-AQDS significantly promoted the bioreduction of Cr(VI), where the reaction rate constant increased by 4.81 times, and the reduction extent increased by 38.31%. X-ray photoelectron spectroscopy and Fourier-Transform Infrared Spectroscopy analysis revealed that AQDS replaced the -OH functional groups on the BC surface to form BC-AQDS. Upon receiving electrons from Shewanella putrefaciens CN32, BC-AQDS was reduced to BC-AH2DS, which subsequently facilitated the reduction of Cr(VI) to Cr(III). This redox cycle between BC-AQDS and BC-AH2DS effectively enhanced the bioreduction rate of Cr(VI). Our study also found that a lower carbonization temperature of BC resulted in a higher surface -OH functional group content, enabling a greater load of AQDS and a more pronounced enhancement effect on the bioreduction of Cr(VI). Additionally, a smaller particle size of BC and a higher dosage of BC-AQDS further contributed to the enhancement of Cr(VI) bioreduction. The preparation of BC-AQDS in this study effectively improve the utilization of quinone compounds and offer a promising approach for enhancing the bioreduction of Cr(VI). It provides a more comprehensive reference for understanding and solving the problem of Cr pollution in groundwater.

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Escalating global water pollution exacerbated by textile-dyeing wastewater (TDW) poses significant environmental and health concerns due to the insufficient treatment methods being utilized. Thus, it is imperative to implement more effective treatment solutions to address such issues. In this research, different environmentally-friendly strategies involving effluent recirculation (ER) and Rubia cordifolia plant-derived purpurin electron mediator (EM) were introduced to enhance the treatment of real TDW and bioelectricity generation performance of an anti-gravity flow microbial fuel cell (AGF-MFC). The results revealed that optimum performance was achieved with a combination of hydraulic retention time (HRT) of 48 h with a recirculation ratio of 1, where the reduction efficiency of biochemical oxygen demand (BOD5), chemical oxygen demand (COD), ammonium (NH4+), nitrate (NO3-), sulphate (SO42-), ammonia nitrogen (NH3-N), colour and turbidity were 82.17 %, 82.15 %, 85.10 %, 80.52 %, 75.91 %, 59.52 %, 71.02 % and 93.10 %, respectively. In terms of bioelectricity generation performance, AGF-MFC showed a maximum output voltage and power density of 404.72 mV and 65.16 mW/m2, respectively. Moreover, the results also signified that higher treatment performance of TDW was obtained with natural purpurin from Rubia cordifolia plant than synthetic purpurin as EM. The reduced reactivity of highly stable synthetic purpurin EM for mediating the electron transfer was a contributing factor to the outperformance of plant-derived purpurin. Additionally, detailed electron-mediating mechanisms of purpurin were proposed to unravel the underlying electron transfer pathway involved in AGF-MFC. This research offers insight into the development of more sustainable solutions for managing TDW, and consequently reducing environmental pollution.

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The quinoid component of humic acids (HAs) had been studied as exogenous electron mediators (EMs), but the redox-mediating abilities of other functional groups remained unclear. This study evaluated the effects of various HAs functional groups on cellular respiration and extracellular electron transfer. The three EMs increased the current density compared to the control. Current density increased significantly after adding ultraviolet-irradiated HAs (UV-HAs), suggesting that nitrogenous group-mediated redox reactions contributed to high-density current generation. Structural equation model (SEM) results indicated that the contribution of nitrogen-containing groups to electron transfer could exceed 20%. This study proposed a synergistic mechanism: in the soil microbial fuel cells (soil-MFCs), HAs accelerated their component evolution through irreversible redox reactions and promoted extracellular electron transfer. Additionally, HAs-induced high expression of c-Cyts could further enhance high-density current generation. This study demonstrates that humic acids enhance electron transfer and current in bioelectrochemical systems, aiding sustainable energy optimization.

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Exploring low-cost visible light photocatalysts for CO2 reduction to produce proportionally adjustable syngas is of great significance for meeting the needs of green chemical industry. A S-Scheme CeO2/g-C3N4 (CeO2/CN) heterojunction was constructed by using a simple two-step calcination method. During the photocatalytic CO2 reduction process, the CeO2/CN heterojunction can present a superior photocatalytic performance, and the obtained CO/H2 ratios in syngas can be regulated from 1 : 0.16 to 1 : 3.02. In addition, the CO and H2 production rate of the optimal CeO2/CN composite can reach 1169.56 and 429.12 µmol g-1 h-1, respectively. This superior photocatalytic performance is attributed to the unique S-Scheme photogenerated charge transfer mechanism between CeO2 and CN, which facilitates rapid charge separation and migration, while retaining the excellent redox capacity of both semiconductors. Particularly, the variable valence Ce3+/Ce4+ can act as electron mediator between CeO2 and CN, which can promote electron transfer and improve the catalytic performance. This work is expected to provide a new useful reference for the rational construction of high efficiency S-Scheme heterojunction photocatalyst, and improve the efficiency of photocatalytic reduction of CO2, promoting the photocatalytic reduction of CO2 into useful fuels.

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Assembling functional molecules on the surface of an enzyme electrode is the most basic technique for constructing a biosensor. However, precise control of electron transfer interface or electron mediator on the electrode surface remains a challenge, which is a key step that affects the stability and sensitivity of enzyme-based biosensors. In this study, we propose the use of controllable free radical polymerization to grow stable 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) polymer as electron mediator on enzyme surface for the first time. Through scanning electron microscopy (SEM), Raman spectroscopy, electrode surface coverage measurement, static contact angle (SCA), and a series of electrochemical methods, it has been demonstrated that the TEMPO-based enzyme electrode exhibits a uniform hydrophilic morphology and stable electrochemical performance. Furthermore, the results show that the sensor demonstrates high sensitivity for detecting glucose biomolecules in artificial sweat and serum. Attributing to the quantitative and controllable radical polymerization of TEMPO redox assembled enzyme electrode surface, the as-proposed biosensor providing a use, storage, and inter-batch sensing stability, providing a vital platform for wearable/implantable biochemical sensors.

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To enhance the removal efficiencies of polycyclic aromatic hydrocarbons (PAHs) in sediments and to elucidate the mechanisms by which microbial electrochemical action aids in the degradation of PAHs, humic acid was used as an electron mediator in the microbial electrochemical system in this study. The results revealed that the addition of humic acids led to increases in the removal efficiencies of naphthalene, phenanthrene, and pyrene by 45.91%, 97.83%, and 85.56%, respectively, in areas remote from the anode, when compared to the control group. The investigation into the microbial community structure and functional attributes showed that the presence of humic acid did not significantly modify the microbial community composition or its functional expression at the anode. However, an examination of humic acid transformations demonstrated that humic acid extended the electron transfer range in sediment via the redox reactions of quinone and semiquinone groups, thereby facilitating the PAHs degradation within the sediment.

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Hydrogen sulfide (H2S), a toxic gas abundant in natural gas fields and refineries, is currently being removed mainly via the Claus process. However, the emission of sulfur-containing pollutants is hard to be prevented and the hydrogen element is combined to water. Herein, we report an electron-mediated off-field electrocatalysis approach (OFEC) for complete splitting of H2S into H2 and S under ambient conditions. Fe(III)/Fe(II) and V(II)/V(III) redox mediators are used to fulfill the cycles for H2S oxidation and H2 production, respectively. Fe(III) effectively removes H2S with almost 100% conversion during its oxidation process. The H+ ions are reduced by V(II) on a nonprecious metal catalyst, tungsten carbide. The mediators are regenerated in an electrolyzer at a cell voltage of 1.05 V, close to the theoretical potential difference (1.02 V) between Fe(III)/Fe(II) and V(II)/V(III). In a laboratory bench-scale plant, the energy consumption for the production of H2 from H2S is estimated to be 2.8 kWh Nm-3 H2 using Fe(III)/Fe(II) and V(II)/V(III) mediators and further reduced to about 0.5 kWh Nm-3 H2 when employing well-designed heteropolyacid/quinone mediators. OFEC presents a cost-effective approach for the simultaneous production of H2 and elemental sulfur from H2S, along with the complete removal of H2S from industrial processes. It also provides a practical platform for electrochemical reactions involving solid precipitation and organic synthesis.

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Microbial biofilms are behind microbiologically influenced corrosion (MIC). Sessile cells in biofilms are many times more concentrated volumetrically than planktonic cells in the bulk fluids, thus providing locally high concentrations of chemicals. More importantly, "electroactive" sessile cells in biofilms are capable of utilizing extracellularly supplied electrons (e.g., from elemental Fe) for intracellular reduction of an oxidant such as sulfate in energy metabolism. MIC directly caused by anaerobic biofilms is classified into two main types based on their mechanisms: extracellular electron transfer MIC (EET-MIC) and metabolite MIC (M-MIC). Sulfate-reducing bacteria (SRB) are notorious for their corrosivity. They can cause EET-MIC in carbon steel, but they can also secrete biogenic H2S to corrode other metals such as Cu directly via M-MIC. This study investigated the use of conductive magnetic nanowires as electron mediators to accelerate and thus identify EET-MIC of C1020 by Desulfovibrio vulgaris. The presence of 40 ppm (w/w) nanowires in ATCC 1249 culture medium at 37 °C resulted in 45 % higher weight loss and 57 % deeper corrosion pits after 7-day incubation. Electrochemical tests using linear polarization resistance and potentiodynamic polarization supported the weight loss data trend. These findings suggest that conductive magnetic nanowires can be employed to identify EET-MIC. The use of insoluble 2 µm long nanowires proved that the extracellular section of the electron transfer process is a bottleneck in SRB MIC of carbon steel.

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Sonocatalysis has emerged as a promising technology for addressing environmental pollution issues. However, the efficacy of sonocatalytic processes is primarily hindered by challenges related to the sluggish flow rate of photogenerated electrons. This study presents a novel approach to address this issue by developing an improved Z-scheme NiFe2O4/MXene/Bi2WO6 (NMB) composite that exhibits exceptional sonocatalytic activity for ciprofloxacin (CIP) degradation. In particular, the NiFe2O4/MXene (5 wt%)/Bi2WO6 composite could achieve high CIP (at 10 mg/L) degradation efficiency (97.39 %) after 60 min of ultrasonic irradiation. The exceptional sonocatalytic activity of the composite was attributed to the synergistic interaction of the Z-scheme heterojunction charge transfer route and the electron mediator of Ti3C2-MXene, which enhances light collection capacity, separates photogenerated carriers efficiently, and improves redox activity of the composite. The scavenging experiments reveal that the sonocatalytic degradation of CIP was driven by holes (h+), hydroxyl radicals (•OH), and superoxide anion radicals (•O2-), with the former playing a dominant role. The results of reuse experiments demonstrate the outstanding sonocatalytic stability of the catalyst, as well as its uncomplicated recovery. The developed NMB Z-scheme composite shows promise for sonocatalytic treatment of antibiotics in industrial wastewaters, particularly those with high turbidity and/or low transparency. The findings also open up avenues for developing efficient and cost-effective sonocatalysts with good recyclability and remarkable performance.

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The construction of a novel Z-scheme system which possesses superior charge separation and high redox ability is highly desirable for efficient photocatalytic degradation of organic pollutants. Herein, a carbon quantum dots (CQDs) modified g-C3N4 (GCN) and BiVO4 (BVO) composite (GCN-CQDs/BVO) was fabricated via an initial loading of CQDs on GCN, and a subsequent combination with BVO during its hydrothermal synthesis. Physical characterization (e.g. TEM, XRD, XPS) verified the intimate heterojunction structure of the composite, while CQDs improved its light absorption. The band structures of GCN and BVO were evaluated, displaying the feasibility for Z-scheme formation. In comparison with GCN, BVO, and GCN/BVO, GCN-CQDs/BVO generated the highest photocurrent and lowest charge transfer resistance, inferring the prominently improved charge separation. Under visible light irradiation, GCN-CQDs/BVO exhibited the significantly enhanced activity in degrading the typical Paraben pollutant--benzyl paraben (BzP), achieving the removal of 85.7% in 150 min. The effects of various parameters were explored, demonstrating that neutral pH was optimal, while coexisting ions (CO32-, SO42-, NO3-, K+, Ca2+, Mg2+) and humic acid impacted the degradation negatively. Meanwhile, trapping experiments and electron paramagnetic resonance (EPR) technique revealed that superoxide radicals (•O2-) and hydroxyl radical (•OH) were primarily responsible for BzP degradation by GCN-CQDs/BVO. In particular, with the assistance of CQDs, the generation of •O2- and •OH was notably augmented. Based on these results, a Z-scheme photocatalytic mechanism was proposed for GCN-CQDs/BVO, where CQDs acted as electron mediators to combine the holes from GCN and electrons from BVO, resulting in significantly improved charge separation and maximized redox ability. Moreover, the toxicity of BzP was remarkably reduced during the photocatalytic process, emphasizing its great potential in abating the risk of Paraben pollutants.

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The electrochemical degradation of air pollutants, particularly volatile organic compounds (VOCs), at their gaseous state is a promising method. However, it remains at an infant stage due to sluggish solid-gas electron transfers at room temperature. We established a triphase reaction condition using a semi-solid electrolyte layer between the electrode and membrane to enhance the electron transfer at room temperature. A polyvinyl alcohol (PVA) gel layer was inserted between a bimetallic layered CuNi(CN)4 complex coated Cu foam electrode (TCNi-Cu) and Nafion 324 membrane for the degradation of gaseous toluene. The cyclic voltammetry of TCNi-Cu using a sodium hydroxide-coated copper mesh electrode at a triphase showed Cu1+ and Ni1+ stabilization at -0.7 and -0.9 V, respectively, which was similar to the liquid phase electron transfer behavior. The degradation capacity of gaseous toluene without using electrogenerated TCNi-Cu + PVA gel was 0.54 mg cm2 min-1, whereas that of TCNi-Cu + PVA gel layers was 1.17 mg cm-2min-1, which revealed the mediation effect at a triphase condition. Toluene was converted into oxygen-containing products, such as butanol, propanol, and acetone (without reduction products), which revealed that indirect oxidation occurred at the cathode using an in-situ generated oxidant, such as OH˙ radical. As an electron-mediator, Cu1+ was used to form oxidants for the degradation of toluene at -0.7 V. The toluene removal rate reached 1.4 µmol h-1, with an energy efficiency of 0.15 Wh L-1. This study is the first attempt to describe a liquid-electrolyte-free cathodic half-cell in electrochemical application to VOCs degradation, highlighting the electron transfer at room temperature.

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Recent studies have found that green hydrogen production and biomass utilization technologies can be combined to efficiently produce both hydrogen and value-added chemicals using biomass as an electron and proton source. However, the majority of them have been limited to proof-of-concept demonstrations based on batch systems. Here the authors report the design of modular flow systems for the continuous depolymerization and valorization of lignin and low-voltage hydrogen production. A redox-active phosphomolybdic acid is used as a catalyst to depolymerize lignin with the production of aromatic compounds and extraction of electrons for hydrogen production. Individual processes for lignin depolymerization, byproduct separation, and hydrogen production with catalyst reactivation are modularized and integrated to perform the entire process in the serial flow. Consequently, this work enabled a one-flow process from biomass conversion to hydrogen gas generation under a cyclic loop. In addition, the unique advantages of the fluidic system (i.e., effective mass and heat transfer) substantially improved the yield and efficiency, leading to hydrogen production at a higher current density (20.5 mA cm-2 ) at a lower voltage (1.5 V) without oxygen evolution. This sustainable eco-chemical platform envisages scalable co-production of valuable chemicals and green hydrogen for industrial purposes in an energy-saving and safe manner.

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Traditional bioelectrochemical systems (BESs) coupled with stripping units for ammonia recovery suffer from an insufficient supply of electron acceptors due to the low solubility of oxygen. In this study, we proposed a novel strategy to efficiently transport the oxidizing equivalent provided at the stripping unit to the cathode by introducing a highly soluble electron mediator (EM) into the catholyte. To validate this strategy, we developed a new kind of iron complex system (tartrate-EDTA-Fe) as the EM. EDTA-Fe contributed to the redox property with a midpoint potential of -0.075 V (vs. standard hydrogen electrode, SHE) at pH 10, whereas tartrate acted as a stabilizer to avoid iron precipitation under alkaline conditions. At a ratio of the catholyte recirculation rate to the anolyte flow rate (RC-A) of 12, the NH4 +-N recovery rate in the system with 50 mM tartrate-EDTA-Fe complex reached 6.9 ±â€¯0.2 g N m-2 d-1, approximately 3.8 times higher than that in the non-EM control. With the help of the complex, our system showed an NH4 +-N recovery performance comparable to that previously reported but with an extremely low RC-A (0.5 vs. 288). The strategy proposed here may guide the future of ammonia recovery BES scale-up because the introduction of an EM allows aeration to be performed only at the stripping unit instead of at every cathode, which is beneficial for the system design due to its simplicity and reliability.

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Humin, an insoluble fraction of humic substances at any pH, has been reported to be an extracellular electron mediator (EEM) that functions in carbon dioxide (CO2 )-fixing acetogenesis. Here, we show that humin promotes the microbial electrosynthesis (MES) of acetate from CO2 using Moorella thermoacetica. Yeast extract, essential for the reaction of M. thermoacetica, resulted in the heterotrophic production of organic acids including acetate, hydrogen, and methane. Excluding the effect of yeast extract, MES with 13 g/L of suspended humin poised at -510 mV (vs. Ag/AgCl) achieved a CO2 -fixing acetate production of 24.2 mg-acetate/L/day (1.9 mg-acetate/day/g-humin); this is 10-folds higher than the humin-free MES, with 90.3% of the coulombic efficiency. Although M. thermoacetica is an electroactive bacterium, it obtains electrons for acetogenesis mostly via humin. The suspended humin-assisted MES poised at -810 mV (vs. Ag/AgCl) increased the acetate production rate to 39.3 mg-acetate/L/day using electrons mainly from electrolyzed hydrogen and humin. Immobilization increased the humin's EEM efficiency, as indicated by the acetate production rate of 20.8 mg-acetate/L/day (6.9 mg-acetate/day/g-humin) with a 98.7% coulombic efficiency in MES with 3 g/L of immobilized humin poised at -510 mV (vs. Ag/AgCl). These results suggest that humin-assisted MES has high potential for microbial CO2 fixation.

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The amendment of biochar for soil bioremediation can improve soil conditions, influence soil microbial community, and achieve co-application of biochar-microbe to promote the removal of pollutants. This paper summarizes the positive effects of biochar on microorganisms, including acting as a shelter, providing nutrients, and improving soil conditions (soil aggregation, pH, cation exchange capacity (CEC), and enzymatic activity). These effects will cause variations in microbial abundance, activity, and community structure. Biochar can act as an electron mediator to promote electron transfer in the process of microbial degradation. And the application of biochar in soil bioremediation is also introduced. Nevertheless, toxic substances carried by biochar that may threaten microbial community shouldn't be overlooked. With this review, we can better understand biochar's involvement in soil bioremediation, which will help us choose and modify biochar in a targeted manner for the desired purpose in practical applications.

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This study systematically evaluated the effects of bentonite as a possible additive to alleviate the "inhibited steady-state" induced by ammonia and acid accumulation during anaerobic digestion. Continuous stirred tank reactors fed with poultry manure were operated at 35 ± 1 °C either with bentonite or not. The results demonstrate that bentonite amendment increased average specific methane production by 35% as suffered from steady-state at an organic loading rate of 6.25 g VS/L·d. 16S rRNA gene amplicon sequencing revealed that the relative abundance of electron-donating Sedimentibacter and Syntrophomonas, and electrophilic Methanosarcina was increased by 110%, 91%, and 49%, respectively. The genera were identified as crucial for alleviating "inhibited steady-state", through establishment of a more robust syntrophic pathway of methanogenic acetate degradation. The enhancement might result from the accelerated electron transfer by bentonite, which is qualified for serving as an exogenetic electron mediator due to containing abundant redox-active metal elements.

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Clinical situations arise in which blood for transfusion becomes scarce or unavailable. Considerable demand for a transfusion alternative persists because of various difficulties posed by blood donation and transfusion systems. Hemoglobin-vesicles (Hb- V) are artificial oxygen carriers being developed for use as a transfusion alternative. Just as biomembranes of red blood cells (RBCs) do, phospholipid vesicles (liposomes) for Hb encapsulation can protect the human body from the toxic effects of molecular Hb. The main HbV component, Hb, is obtained from discarded human donated blood. Therefore, HbV can be categorized as a biologic agent targeting oxygen for peripheral tissues. The purification procedure strictly eliminates the possibility of viral contamination. It also removes all concomitant unstable enzymes present in RBC for utmost safety from infection. The deoxygenated HbVs, which are storable for over the years at ambient temperature, can function as an alternative to blood transfusion for resuscitation from hemorrhagic shock and O2 therapeutics. Moreover, a recent study clarified beneficial effects for anti- oxidation and anti-inflammation by carbon monoxide (CO)-bound HbVs. Autoxidation of HbV (HbO2 → metHb + O2 -.) is unavoidable after intravenous administration. Co-injection of methylene blue can extract the intraerythrocytic glycolytic electron energy effectively and reduce metHb. Other phenothiazine dyes can also function as electron mediators to improve the functional life span of HbV. This review paper summarizes recent progress of the research and development of HbV, aimed at clinical applications.

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