Microorganisms are key players in the global biogeochemical sulfur cycle. Among them, some have garnered particular attention due to their electrical activity and ability to perform extracellular electron transfer. A growing body of research has highlighted their extensive phylogenetic and metabolic diversity, revealing their crucial roles in ecological processes. In this review, we delve into the electron transfer process between sulfate-reducing bacteria and anaerobic alkane-oxidizing archaea, which facilitates growth within syntrophic communities. Furthermore, we review the phenomenon of long-distance electron transfer and potential extracellular electron transfer in multicellular filamentous sulfur-oxidizing bacteria. These bacteria, with their vast application prospects and ecological significance, play a pivotal role in various ecological processes. Subsequently, we discuss the important role of the pili/cytochrome for electron transfer and presented cutting-edge approaches for exploring and studying electroactive microorganisms. This review provides a comprehensive overview of electroactive microorganisms participating in the biogeochemical sulfur cycle. By examining their electron transfer mechanisms, and the potential ecological and applied implications, we offer novel insights into microbial sulfur metabolism, thereby advancing applications in the development of sustainable bioelectronics materials and bioremediation technologies.

Atom-transfer radical polymerization (ATRP) is a well-known technique for controlled polymer synthesis. However, the ATRP usually employed toxic heavy metal ionas as the catalyst and was susceptible to molecular oxygen, which made it should be conducted under strictly anoxic condition. Conducting ATRP under ambient and biocompatible conditions is the major challenge. In this study, cytochrome C was explored as an efficient biocatalyst for ATRP under biocompatible conditions. The cytochrome C catalyzed ATRP showed a relatively low polymer dispersity index of 1.19. More interestingly, the cytochrome C catalyzed ATRP showed superior oxygen resistance as it could be performed under aerobic conditions with high dissolved oxygen level. Further analysis suggested that the Fe(II) embed in the cytochrome C might serve as the catalytic center and methyl radical was responsible for the ATRP catalysis. This work explored new biocompatible catalyst for aerobic ATRP, which might open new dimension for practical ATRP and application of cytochrome C protein.

The unmarked potential drug molecule azamulin has been found to be a specific inhibitor of CYP3A4 and CYP3A5 in recent years, but this molecule also shows different binding ability and affinity to the two CYP3A isoforms. In order to explore the microscopic mechanism, conventional molecular dynamics (MD) simulation methods were performed to study the dynamic interactions between two isoforms and azamulin. The simulation results show that the binding of the ligand leads to different structural properties of two CYP3A proteins. First of all, compared with apo-CYP3A4, the binding of the ligand azamulin can lead to changes in the structural flexibility of CYP3A4, i.e., holo-CYP3A4 is more flexible than apo-CYP3A4. The structural changes of CYP3A5 are just the opposite. The ligand binding increases the rigidity of CYP3A5. Furthermore, the representative structures of the production phase in the MD simulation were in details analyzed to obtain the microscopic interactions between the ligand azamulin and two CYP3A isoforms at the atomic level. It is speculated that the difference of composition and interaction of the active sites is the fundamental cause of the change of structural properties of the two proteins.Communicated by Ramaswamy H. Sarma.

Recent studies have demonstrated the crucial role of Cytochrome P450 enzymes (CYPs) in the production of secondary metabolites, phytohormones and antioxidants in plants. However, their functional characterization specifically under alkaline stress remains elusive. CYP82C4 was the key gene screened from a family of wild soybean CYPs in our previous studies. The aim of this present study was to clone the Glycine soja GsCYP82C4 gene and characterize its functions in Arabidopsis and Glycine max. The results showed that the GsCYP82C4 gene displayed a high expression in different plant tissues at mature stages compared to young stages. Further, higher temporal expression of the GsCYP82C4 gene was noted at 6, 12 and 24 h time points after alkali treatment in leaves compared to roots. In addition, overexpression of GsCYP82C4 improved alkaline stress tolerance in Arabidopsis via increased root lengths and fresh biomass and strengthened the antioxidant defense system via a reduction in superoxide radicals in transgenic lines compared to wild type (WT) and atcyp82c4 mutants. Further, the expression levels of stress-related marker genes were up-regulated in GsCYP82C4 OX lines under alkali stress. The functional analysis of GsCYP82C4 overexpression in soybean displayed better hairy root growth, increased fresh weight, higher antioxidant enzyme activities and reduced lipid peroxidation rates in OX lines compared to the soybean WT (K599) line. In total, our study displayed positive roles of GsCYP82C4 overexpression in both Arabidopsis and Glycine max to alleviate alkaline stress via altering expression abundance of stress responsive genes, stronger roots, higher antioxidant enzyme activities as well as reduced rates of lipid peroxidation and superoxide radicals.

The biological signaling molecule nitric oxide (NO) has recently emerged as a metabolic precursor for the creation of microbial natural products with diversified structures and biological activities. Within the biosynthetic gene clusters (BGCs) of these compounds, genes associated with NO production pathways have been pinpointed. In this study, we employ a nitric oxide synthase (NOS)-guided genome mining strategy for the targeted discovery of NO-derived bacterial natural products and NO-utilizing biocatalysts. We show that a conserved NOS-containing BGC, distributed across several actinobacterial genomes, is responsible for the biosynthesis of lajollamycin, a unique nitro-tetraene-containing antibiotic whose biosynthetic mechanism remains elusive. Through a combination of in vivo and in vitro studies, we unveil the first cytochrome P450 enzyme capable of catalyzing olefin nitration in natural product biosynthesis. These results not only expand the current knowledge about biosynthetic nitration processes but also offer an efficient way for targeted identification of NO-utilizing metabolic pathways and novel nitrating biocatalysts.

Siloxanes have been commonly used as additives in a variety of industrial and consumer products. Media and government investigations have revealed that defoamers containing siloxanes are used in the effluent of thermal power plants in Korea. However, investigations of the source impact of siloxane contamination from the discharge of thermal power plants into coastal environments are scarce. In this study, sediment and invertebrates were collected around a thermal power plant to assess source impact, seasonal variation, and a potential for bioaccumulation. Although siloxanes were detectable in sediment and invertebrates, the spatial distribution and composition (which differed between the siloxanes found in sediment and invertebrates and those in defoamer used in the plant) suggest they were likely transported by long-distance migration as well as the discharge of thermal power plant. Seasonal differences might affect sedimentary contamination and the bioaccumulation potential of siloxanes. Specifically, octamethylcyclotetrasiloxane (D4) may have limited adsorption capacity and potential for long-distance migration, as its contribution in sediment far from the coastline was greater than that of decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6). However, higher D5 accumulation in invertebrates, and D5 has a potential bioaccumulation. A molecular docking analysis showed that the binding affinity between D5 and the cytochrome enzyme in invertebrates was weaker than that with other siloxanes, which could lead to higher D5 accumulation in invertebrates.

Herb medicine has a long history of application and is still used worldwide. With the development of complementary and alternative medicine, the interaction between herb and drugs has attracted more and more attention. Herb-drug interactions (HDI) could cause decreased efficiency, increased toxicity, and affect the drug absorption and disposition processes due to the interference of their pharmacological or pharmacokinetic effects. Hence, the mechanisms and results of herb-pharmacokinetic interactions should be comprehensively summarized. Here, we have summarized the mechanisms of HDI and pharmacokinetic interactions in the last ten years based on searching on PubMed, Science Direct, and Web of Science with different keywords. Besides, the pharmacokinetic interactions were related to nine commonly used herbs and drugs, including Ginseng, Salvia miltiorrhiza, Ginkgo biloba, Garlic, Coptis chinensis, St. John\'s wort, Ginger, Licorice, Silythistle and Fructus Schisandrae. This review provides an overview of HDI to provide a reference for the rational and safe clinical use of herbs and drugs.

Acetic acid bacteria (AAB) are a group of bacteria that can oxidize many substrates such as alcohols and sugar alcohols and play important roles in industrial biotechnology. A majority of industrial processes that involve AAB are related to their dehydrogenases, including PQQ/FAD-dependent membrane-bound dehydrogenases and NAD(P)+-dependent cytoplasmic dehydrogenases. These cofactor-dependent dehydrogenases must effectively regenerate their cofactors in order to function continuously. For PQQ, FAD and NAD(P)+ alike, regeneration is directly or indirectly related to the electron transport chain (ETC) of AAB, which plays an important role in energy generation for aerobic cell growth. Furthermore, in changeable natural habitats, ETC components of AAB can be regulated so that the bacteria survive in different environments. Herein, the progressive cascade in an application of AAB, including key dehydrogenases involved in the application, regeneration of dehydrogenase cofactors, ETC coupling with cofactor regeneration and ETC regulation, is systematically reviewed and discussed. As they have great application value, a deep understanding of the mechanisms through which AAB function will not only promote their utilization and development but also provide a reference for engineering of other industrial strains.

UNASSIGNED: Avitinib is the first third-generation epithelial growth factor receptor (EGFR) inhibitor independently developed in China and is mainly used for treating non-small cell lung cancer. However, pharmacokinetic details are limited. This study explored the in vivo and in vitro effects of avitinib on cytochrome CYP450 enzymes metabolic activity.
UNASSIGNED: A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for determining six probe substrates and their metabolites. Avitinib influence on activity levels of CYP isozymes was examined in vitro using human and rat liver microsomes (HLMs/RLMs). For in vivo studies, rats were pretreated with 30 mg/kg avitinib once daily for 7 days (avitinib multiple-doses group), 30 mg/kg avitinib on day 7 (avitinib single-dose group), or an equivalent amount of CMC-Na once daily for 7 days (control group), followed by intragastrical administration of the probe substrates (1 mg/kg tolbutamide and 10 mg/kg phenacetin, bupropion, chlorzoxazone, dextromethorphan, and midazolam). Plasma pharmacokinetics and IC50 values of the probe substrates were then compared. Pharmacokinetic parameters were determined using non-compartmental analysis implemented in a pharmacokinetic program.
UNASSIGNED: In vitro experiments revealed different inhibitory effects of avitinib on the six probe substrates with various IC50 values (bupropion, 6.39/22.64 μM; phenacetin, 15.79/48.36 μM; chlorzoxazone, 23.15/57.09 μM; midazolam, 27.64/59.6 μM; tolbutamide, 42.18/6.91 μM; dextromethorphan, 44.39/56.57 μM, in RLMs and HLMs respectively). In vivo analysis revealed significant differences (P <0.05) in distinct pharmacokinetic parameters (AUC(0-t), AUC (0-∞), Cmax, MRT(0-t), MRT (0-∞), and CLz/F) for the six probe substrates after avitinib pretreatment.
UNASSIGNED: A sensitive and reliable UPLC-MS/MS method was established to determine the concentration of six probe substrates in rat plasma. Avitinib had inhibitory effects on CYP450 enzymes, especially cyp2b1, cyp1a2 in RLMs, CYP2C9 in HLMs, and cyp1a2, cyp2b1, cyp2d1, and cyp2e1 in vivo. Our data recommend caution when avitinib was taken simultaneously with drugs metabolized by CYP450 enzymes.

Electroactive microorganisms (EAMs) are ubiquitous in nature and have attracted considerable attention as they can be used for energy recovery and environmental remediation via their extracellular electron transfer (EET) capabilities. Although the EET mechanisms of Shewanella and Geobacter have been rigorously investigated and are well characterized, much less is known about the EET mechanisms of other microorganisms. For EAMs, efficient EET is crucial for the sustainable economic development of bioelectrochemical systems (BESs). Currently, the low efficiency of EET remains a key factor in limiting the development of BESs. In this review, we focus on the EET mechanisms of different microorganisms, (i.e., bacteria, fungi, and archaea). In addition, we describe in detail three engineering strategies for improving the EET ability of EAMs: (1) enhancing transmembrane electron transport via cytochrome protein channels; (2) accelerating electron transport via electron shuttle synthesis and transmission; and (3) promoting the microbe-electrode interface reaction via regulating biofilm formation. At the end of this review, we look to the future, with an emphasis on the cross-disciplinary integration of systems biology and synthetic biology to build high-performance EAM systems.