Engineered Cell Elongation Promotes Extracellular Electron Transfer of Shewanella Oneidensis.

To investigate how cell elongation impacts extracellular electron transfer (EET) of electroactive microorganisms (EAMs), the division of model EAM Shewanella oneidensis (S. oneidensis) MR-1 is engineered by reducing the formation of cell divisome. Specially, by blocking the translation of division proteins via anti-sense RNAs or expressing division inhibitors, the cellular length and output power density are all increased. Electrophysiological and transcriptomic results synergistically reveal that the programmed cell elongation reinforces EET by enhancing NADH oxidation, inner-membrane quinone pool, and abundance of c-type cytochromes. Moreover, cell elongation enhances hydrophobicity due to decreased cell-surface polysaccharide, thus facilitates the initial surface adhesion stage during biofilm formation. The output current and power density all increase in positive correction with cellular length. However, inhibition of cell division reduces cell growth, which is then restored by quorum sensing-based dynamic regulation of cell growth and elongation phases. The QS-regulated elongated strain thus enables a cell length of 143.6 ± 40.3 µm (72.6-fold of that of S. oneidensis MR-1), which results in an output power density of 248.0 ± 10.6 mW m-2 (3.41-fold of that of S. oneidensis MR-1) and exhibits superior potential for pollutant treatment. Engineering cellular length paves an innovate avenue for enhancing the EET of EAMs.

Fundamental Insights into the Direct Electron Transfer Mechanism on Ag Atomic Cluster.

The nonradical oxidation pathway for pollutant degradation in Fenton-like catalysis is favorable for water treatment due to the high reaction rate and superior environmental robustness. However, precise regulation of such reactions is still restricted by our poor knowledge of underlying mechanisms, especially the correlation between metal site conformation of metal atom clusters and pollutant degradation behaviors. Herein, we investigated the electron transfer and pollutant oxidation mechanisms of atomic-level exposed Ag atom clusters (AgAC) loaded on specifically crafted nitrogen-doped porous carbon (NPC). The AgAC triggered a direct electron transfer (DET) between the terminal oxygen (Oα) of surface-activated peroxodisulfate and the electron-donating substituents-containing contaminants (EDTO-DET), rendering it 11-38 times higher degradation rate than the reported carbon-supported metal catalysts system with various single-atom active centers. Heterocyclic substituents and electron-donating groups were more conducive to degradation via the EDTO-DET system, while contaminants with high electron-absorbing capacity preferred the radical pathway. Notably, the system achieved 79.5% chemical oxygen demand (COD) removal for the treatment of actual pharmaceutical wastewater containing 1053 mg/L COD within 30 min. Our study provides valuable new insights into the Fenton-like reactions of metal atom cluster catalysts and lays an important basis for revolutionizing advanced oxidation water purification technologies.

Bidirectional two-sample Mendelian randomization analysis identifies causal associations between migraine and five psychiatric disorders.

Background: The question of whether a correlation exists between migraine and five psychiatric disorders, including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), anorexia nervosa (AN), bipolar disorder (BIP), and schizophrenia (SCZ), remains a matter of controversy. Hence, this research aims to investigate whether there is a possible association between migraine and five psychiatric disorders. Methods: We performed a bidirectional 2-sample Mendelian randomization (MR) analysis to assess the causality between migraine and five psychiatric disorders. Genetic associations of PTSD, MDD, AN, BIP, and SCZ were obtained from the Psychiatric Genomics Consortium (PGC) database and genetic associations of migraine with aura and migraine without aura were obtained from the FinnGen dataset. We used the inverse-variance weighted (IVW), weighted median, weighted mode, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and MR Egger regression methods to evaluate the association of genetically predicted exposure with the risk of outcome. Results: MR demonstrated that MDD was associated with a high risk of migraine without aura (OR = 1.930578, 95% confidence interview (CI): 1.224510, 3.043550, p < 0.05), but BIP was related to a low risk of migraine without aura (OR = 0.758650, 95%CI: 0.639601, 0.899858, p < 0.05). According to the results of reverse MR, migraine with aura was associated with a high risk of BIP (OR = 1.019100, 95%CI: 1.002538, 1.035935, p < 0.05), and migraine without aura was associated with an increased risk of AN (OR = 1.055634, 95%CI: 1.023859, 1.088394, p < 0.05). Conclusion: Our results provide evidence of the potential causal association between migraine and some psychiatric disorders. It may contribute to the prevention of migraine and some psychiatric disorders.

Nanoconfinement steers nonradical pathway transition in single atom fenton-like catalysis for improving oxidant utilization.

The introduction of single-atom catalysts (SACs) into Fenton-like oxidation promises ultrafast water pollutant elimination, but the limited access to pollutants and oxidant by surface catalytic sites and the intensive oxidant consumption still severely restrict the decontamination performance. While nanoconfinement of SACs allows drastically enhanced decontamination reaction kinetics, the detailed regulatory mechanisms remain elusive. Here, we unveil that, apart from local enrichment of reactants, the catalytic pathway shift is also an important cause for the reactivity enhancement of nanoconfined SACs. The surface electronic structure of cobalt site is altered by confining it within the nanopores of mesostructured silica particles, which triggers a fundamental transition from singlet oxygen to electron transfer pathway for 4-chlorophenol oxidation. The changed pathway and accelerated interfacial mass transfer render the nanoconfined system up to 34.7-fold higher pollutant degradation rate and drastically raised peroxymonosulfate utilization efficiency (from 61.8% to 96.6%) relative to the unconfined control. It also demonstrates superior reactivity for the degradation of other electron-rich phenolic compounds, good environment robustness, and high stability for treating real lake water. Our findings deepen the knowledge of nanoconfined catalysis and may inspire innovations in low-carbon water purification technologies and other heterogeneous catalytic applications.

Ultrathin cobalt-based nanosheets containing surface oxygen promoted near-complete nitrate removal.

Electrocatalytic nitrate removal offers a sustainable approach to alleviate nitrate pollution and to boost the anthropogenic nitrogen cycle, but it still suffers from limited removal efficiency at high rates, especially at low levels of nitrate. Herein, we report the near-complete removal of low-level nitrate (10-200 ppm) within 2 h using ultrathin cobalt-based nanosheets (CoNS) containing surface oxygen, which was fabricated from in-situ electrochemical reconstruction of conventional nanosheets. The average nitrate removal of 99.7 % with ammonia selectivity of 98.2 % in 9 cyclic runs ranked in the best of reported catalysts. Powered by a solar cell under the winter sun, the full-cell nitrate electrolysis system, equipped with ultrathin CoNS, achieved 100 % nitrogen gas selectivity and 99.6 % total nitrogen removal. The in-situ Fourier Transform Infrared included experiments and theoretical computations revealed that in-situ electrochemical reconstruction not only increased electrochemical active surface area but also constructed surface oxygen in active sites, leading to enhanced stabilization of nitrate adsorption in a symmetry breaking configuration and charge transfer, contributing to near-complete nitrate removal on ultrathin CoNS. This work provides a strategy to design ultrathin nanocatalysts for nitrate removal.

Genome mining of sulfonated lanthipeptides reveals unique cyclic peptide sulfotransferases.

Although sulfonation plays crucial roles in various biological processes and is frequently utilized in medicinal chemistry to improve water solubility and chemical diversity of drug leads, it is rare and underexplored in ribosomally synthesized and post-translationally modified peptides (RiPPs). Biosynthesis of RiPPs typically entails modification of hydrophilic residues, which substantially increases their chemical stability and bioactivity, albeit at the expense of reducing water solubility. To explore sulfonated RiPPs that may have improved solubility, we conducted co-occurrence analysis of RiPP class-defining enzymes and sulfotransferase (ST), and discovered two distinctive biosynthetic gene clusters (BGCs) encoding both lanthipeptide synthetase (LanM) and ST. Upon expressing these BGCs, we characterized the structures of novel sulfonated lanthipeptides and determined the catalytic details of LanM and ST. We demonstrate that SslST-catalyzed sulfonation is leader-independent but relies on the presence of A ring formed by LanM. Both LanM and ST are promiscuous towards residues in the A ring, but ST displays strict regioselectivity toward Tyr5. The recognition of cyclic peptide by ST was further discussed. Bioactivity evaluation underscores the significance of the ST-catalyzed sulfonation. This study sets up the starting point to engineering the novel lanthipeptide STs as biocatalysts for hydrophobic lanthipeptides improvement.

Link Brain-Wide Projectome to Neuronal Dynamics in the Mouse Brain.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.

Modularized Engineering of Shewanella oneidensis MR-1 for Efficient and Directional Synthesis of 5-Aminolevulinic Acid.

Shewanella oneidensis MR-1 has found widespread applications in pollutant transformation and bioenergy production, closely tied to its outstanding heme synthesis capabilities. However, this significant biosynthetic potential is still unexploited so far. Here, we turned this bacterium into a highly-efficient bio-factory for green synthesis of 5-Aminolevulinic Acid (5-ALA), an important chemical for broad applications in agriculture, medicine, and the food industries. The native C5 pathway genes of S. oneidensis was employed, together with the introduction of foreign anti-oxidation module, to establish the 5-ALA production module, resulting 87-fold higher 5-ALA yield and drastically enhanced tolerance than the wild type. Furthermore, the metabolic flux was regulated by using CRISPR interference and base editing techniques to suppress the competitive pathways to further improve the 5-ALA titer. The engineered strain exhibited 123-fold higher 5-ALA production capability than the wild type. This study not only provides an appealing new route for 5-ALA biosynthesis, but also presents a multi-dimensional modularized engineering strategy to broaden the application scope of S. oneidensis.

Phthalates Boost Natural Transformation of Extracellular Antibiotic Resistance Genes through Enhancing Bacterial Motility and DNA Environmental Persistence.

The environmental dissemination of extracellular antibiotic resistance genes (eARGs) in wastewater and natural water bodies has aroused growing ecological concerns. The coexisting chemical pollutants in water are known to markedly affect the eARGs transfer behaviors of the environmental microbial community, but the detailed interactions and specific impacts remain elusive so far. Here, we revealed a concentration-dependent impact of dimethyl phthalate (DMP) and several other types of phthalate esters (common water pollutants released from plastics) on the natural transformation of eARGs. The DMP exposure at an environmentally relevant concentration (10 µg/L) resulted in a 4.8-times raised transformation frequency of Acinetobacter baylyi but severely suppressed the transformation at a high concentration (1000 µg/L). The promotion by low-concentration DMP was attributed to multiple mechanisms, including increased bacterial mobility and membrane permeability to facilitate eARGs uptake and improved resistance of the DMP-bounded eARGs (via noncovalent interaction) to enzymatic degradation (with suppressed DNase activity). Similar promoting effects of DMP on the eARGs transformation were also found in real wastewater and biofilm systems. In contrast, higher-concentration DMP suppressed the eARGs transformation by disrupting the DNA structure. Our findings highlight a potentially underestimated eARGs spreading in aquatic environments due to the impacts of coexisting chemical pollutants and deepen our understanding of the risks of biological-chemical combined pollution in wastewater and environmental water bodies.

Transcriptomic Insights into Metabolism-Dependent Biosynthesis of Bacterial Nanocellulose.

Bacterial nanocellulose (BNC) is an attractive green-synthesized biomaterial for biomedical applications and various other applications. However, effective engineering of BNC production has been limited by our poor knowledge of the related metabolic processes. In contrast to the traditional perception that genome critically determines biosynthesis behaviors, here we discover that the glucose metabolism could also drastically affect the BNC synthesis in Gluconacetobacter hansenii. The transcriptomic profiles of two model BNC-producing strains, G. hansenii ATCC 53582 and ATCC 23769, which have highly similar genomes but drastically different BNC yields, were compared. The results show that their BNC synthesis capacities were highly related to metabolic activities such as ATP synthesis, ion transport protein assembly, and carbohydrate metabolic processes, confirming an important role of metabolism-related transcriptomes in governing the BNC yield. Our findings provide insights into the microbial biosynthesis behaviors from a transcriptome perspective, potentially guiding cellular engineering for biomaterial synthesis.

Biological upcycling of nickel and sulfate as electrocatalyst from electroplating wastewater.

Upcycling nickel (Ni) to useful catalyst is an appealing route to realize low-carbon treatment of electroplating wastewater and simultaneously recovering Ni resource, but has been restricted by the needs for costly membranes or consumption of large amount of chemicals in the existing upcycling processes. Herein, a biological upcycling route for synchronous recovery of Ni and sulfate as electrocatalysts, with certain amount of ferric salt (Fe3+) added to tune the product composition, is proposed. Efficient biosynthesis of bio-NiFeS nanoparticles from electroplating wastewater was achieved by harnessing the sulfate reduction and metal detoxification ability of Desulfovibrio vulgaris. The optimal bio-NiFeS, after further annealing at 300 °C, served as an efficient oxygen evolution electrocatalyst, achieving a current density of 10 mA·cm-1 at an overpotential of 247 mV and a Tafel slope of 60.2 mV·dec-1. It exhibited comparable electrocatalytic activity with the chemically-synthesized counterparts and outperformed the commercial RuO2. The feasibility of the biological upcycling approach for treating real Ni-containing electroplating wastewater was also demonstrated, achieving 99.5 % Ni2+removal and 41.0 % SO42- removal and enabling low-cost fabrication of electrocatalyst. Our work paves a new path for sustainable treatment of Ni-containing wastewater and may inspire technology innovations in recycling/ removal of various metal ions.

Echinacoside exerts neuroprotection via suppressing microglial α-synuclein/TLR2/NF-κB/NLRP3 axis in parkinsonian models.

BACKGROUND: Echinacoside (ECH), a natural active compound, was found to exert neuroprotection in Parkinson's disease (PD). However, the underlying molecular mechanisms remain controversial. PURPOSE: This study aimed to explore the roles of ECH in PD and its engaged mechanisms. CONCLUSION: In vivo, MPTP was adapted to construct subacute PD mouse model to explore the regulation of ECH on NLRP3 inflammasome. In vitro, α-synuclein (α-syn)/MPP+ was used to mediate the activation of NLRP3 inflammasome in BV2 cells, and the mechanism of ECH regulation of it was explored with molecular docking, immunofluorescence, Western blotting, and small molecule inhibitors. CONCLUSION: The activation of microglial NLRP3 inflammasome could be evoked by MPTP in vitro, but its toxic metabolite MPP+ alone cannot trigger the activation of NLRP3 inflammasome in vitro, which requires α-synuclein (α-syn) priming. Exogenous α-syn could evoke microglial TLR2/NF-κB/NLRP3 axis, playing the priming role in MPP+ -mediated NLRP3 inflammasome activation. ECH can suppress the upregulation of α-syn in MPTP-treated mice and BV2 microglia. It can also suppress the activation of the TLR2/NF-κB/NLRP3 axis induced by α-syn. CONCLUSION: ECH exerts neuroprotective effects by downregulating the TLR2/NF-κB/NLRP3 axis via reducing the expression of α-syn in the PD models.

Direct ammonia oxidation (Dirammox) is favored over cell growth in Alcaligenes ammonioxydans HO-1 to deal with the toxicity of ammonium.

Bacteria capable of direct ammonia oxidation (Dirammox) play important roles in global nitrogen cycling and nutrient removal from wastewater. Dirammox process, NH3 → NH2 OH → N2 , first defined in Alcaligenes ammonioxydans HO-1 and encoded by dnf gene cluster, has been found to widely exist in aquatic environments. However, because of multidrug resistance in Alcaligenes species, the key genes involved in the Dirammox pathway and the interaction between Dirammox process and the physiological state of Alcaligenes species remain unclear. In this work, ammonia removal via the redistribution of nitrogen between Dirammox and microbial growth in A. ammonioxydans HO-1, a model organism of Alcaligenes species, was investigated. The dnfA, dnfB, dnfC, and dnfR genes were found to play important roles in the Dirammox process in A. ammonioxydans HO-1, while dnfH, dnfG, and dnfD were not essential genes. Furthermore, an unexpected redistribution phenomenon for nitrogen between Dirammox and cell growth for ammonia removal in HO-1 was revealed. After the disruption of the Dirammox in HO-1, more consumed NH4 + was recovered as biomass-N via rapid metabolic response and upregulated expression of genes associated with ammonia transport and assimilation, tricarboxylic acid cycle, sulfur metabolism, ribosome synthesis, and other molecular functions. These findings deepen our understanding of the molecular mechanisms for Dirammox process in the genus Alcaligenes and provide useful information about the application of Alcaligenes species for ammonia-rich wastewater treatment.

Coagulation/co-catalytic membrane integrated system for fouling-resistant and efficient water purification.

Low-pressure catalytic membranes allow efficient rejection of particulates and simultaneously removing organics pollutant in water, but the accumulation of dissolved organic matters (DOM) on membrane surface, which cover the catalytic sites and cause membrane fouling, challenges their stable operation in practical wastewater treatment. Here we propose a ferric salt-based coagulation/co-catalytic membrane integrated system that can effectively mitigate the detrimental effects of DOM. Ferric salt (Fe3+) serving both as a DOM coagulant to lower the membrane fouling and as a co-catalyst with the membrane-embedded MoS2 nanosheets to drive perxymonosulfate (PMS) activation and pollutant degradation. The membrane functionalized with 2H-phased MoS2 nanosheets showed improved hydrophilicity and fouling resistance relative to the blank polysulfone membrane. Attributed to the DOM coagulation and co-catalytic generation of surface-bound radicals for decontamination at membrane surface, the catalytic membrane/PMS/ Fe3+ system showed much less membrane fouling and 2.6 times higher pollutant degradation rate in wastewater treatment than the catalytic membrane alone. Our work imply a great potential of coagulation/co-catalytic membrane integrated system for water purification application.

Exploring the potential mechanism of Kaixinsan powder for the same pathogenesis of PTSD and anxiety based on network pharmacology and molecular docking: A review.

BACKGROUND: Post-traumatic stress disorder (PTSD) and anxiety are common mental illnesses and there are many similar pathogenesis and clinical manifestations between PTSD and anxiety. Kaixinsan powder (KXS), a commonly used prescription in traditional Chinese medicine, has been widely used to treat PTSD and anxiety. This study aims to explore the potential mechanisms of KXS for the same pathogenesis of PTSD and anxiety using a network pharmacology approach. METHODS: The bioactive components and relevant target genes of KXS were obtained from the database about Traditional Chinese Medicine. The key genes of PTSD and anxiety were derived from disease databases. Subsequently, the network of protein-protein interaction and a network of "drug-components-disease-targets" was constructed. In order to treat PTSD and anxiety, gene ontology enrichment and signaling pathway enrichment were analyzed by using R language and components-core targets associated were validated by molecular docking. RESULTS: One hundred three targets of KXS in treating PTSD and anxiety were identified. The results of protein-protein interaction analysis and molecular docking indicated that AKT1 and IL-6 were crucial targets. Moreover, KEGG analysis has shown that neuroactive ligand-receptor interaction, calcium signaling pathway, and cAMP signaling pathway may play crucial roles in treating PTSD and anxiety. Ten biological process, 10 molecular function, and 10 cellular component were revealed via gene ontology analysis. CONCLUSIONS: The network pharmacology study and molecular docking indicated that KXS treated anxiety and PTSD by multiple components, targets, and signaling pathways. These results provide an important reference for subsequent basic research on PTSD and anxiety.

Nonsterilized Fermentation of Crude Glycerol for Polyhydroxybutyrate Production by Metabolically Engineered Vibrio natriegens.

Polyhydroxybutyrate (PHB) is an attractive biodegradable polymer that can be produced through the microbial fermentation of organic wastes or wastewater. However, its mass production has been restricted by the poor utilization of organic wastes due to the presence of inhibitory substances, slow microbial growth, and high energy input required for feedstock sterilization. Here, Vibrio natriegens, a fast-growing bacterium with a broad substrate spectrum and high tolerance to salt and toxic substances, was genetically engineered to enable efficient PHB production from nonsterilized fermentation of organic wastes. The key genes encoding the PHB biosynthesis pathway of V. natriegens were identified through base editing and overexpressed. The metabolically engineered strain showed 166-fold higher PHB content (34.95 wt %) than the wide type when using glycerol as a substrate. Enhanced PHB production was also achieved when other sugars were used as feedstock. Importantly, it outperformed the engineered Escherichia coli MG1655 in PHB productivity (0.053 g/L/h) and tolerance to toxic substances in crude glycerol, without obvious activity decline under nonsterilized fermentation conditions. Our work demonstrates the great potential of engineered V. natriegens for low-cost PHB bioproduction and lays a foundation for exploiting this strain as a next-generation model chassis microorganism in synthetic biology.

Genome Sequence of a Heavy Metal-Detoxifying Actinomycete, Microbacterium proteolyticum ustc.

A complete genome is presented for Microbacterium proteolyticum ustc, a member of the Gram-positive order Micrococcales of the phylum Actinomycetota that is resistant to high concentrations of heavy metals and participates in metal detoxification. The genome consists of one plasmid and one chromosome.

Biogenic Copper Selenide Nanoparticles for Near-Infrared Photothermal Therapy Application.

Near-infrared (NIR) photothermal therapy (PTT) is attractive for cancer treatment but is currently restricted by limited availability and insufficient NIR-II photoactivity of photothermal agents, for which artificial nanomaterials are usually used. Here, we report the first use of biogenic nanomaterials for PTT application. A fine-controlled extracellular biosynthesis of copper selenide nanoparticles (bio-Cu2-xSe) by Shewanella oneidensis MR-1 was realized. The resulting bio-Cu2-xSe, with fine sizes (∼35.5 nm) and high product purity, exhibited 76.9% photothermal conversion efficiency under 1064 nm laser irradiation, outperforming almost all the existing counterparts. The protein capping also imparted good biocompatibility to bio-Cu2-xSe to favor a safe PTT application. The in vivo PTT with injected bio-Cu2-xSe in mice (without extraction nor further modification) showed 87% tumor ablation without impairing the normal organisms. Our work not only opens a green route to synthesize the NIR-II photothermal nanomaterial but may also lay a basis for the development of bacteria-nanomaterial hybrid therapy technologies.

Distinguishing homogeneous advanced oxidation processes in bulk water from heterogeneous surface reactions in organic oxidation.

Clarifying the reaction pathways at the solid-water interface and in bulk water solution is of great significance for the design of heterogeneous catalysts for selective oxidation of organic pollutants. However, achieving this goal is daunting because of the intricate interfacial reactions at the catalyst surface. Herein, we unravel the origin of the organic oxidation reactions with metal oxide catalysts, revealing that the radical-based advanced oxidation processes (AOPs) prevail in bulk water but not on the solid catalyst surfaces. We show that such differing reaction pathways widely exist in various chemical oxidation (e.g., high-valent Mn3+ and MnOX) and Fenton and Fenton-like catalytic oxidation (e.g., Fe2+ and FeOCl catalyzing H2O2, Co2+ and Co3O4 catalyzing persulfate) systems. Compared with the radical-based degradation and polymerization pathways of one-electron indirect AOP in homogeneous reactions, the heterogeneous catalysts provide unique surface properties to trigger surface-dependent coupling and polymerization pathways of a two-electron direct oxidative transfer process. These findings provide a fundamental understanding of catalytic organic oxidation processes at the solid-water interface, which could guide the design of heterogeneous nanocatalysts.