Melatonin ameliorates bleomycin-induced pulmonary fibrosis via activating NRF2 and inhibiting galectin-3 expression.

Pulmonary fibrosis (PF) is a chronic interstitial lung disease with no effective therapies. Galectin-3 (Gal-3), a marker of oxidative stress, plays a key role in the pathogenesis of PF. Fibroblast-myofibroblast differentiation (FMD) is an important source of fibrotic cells in PF. Previous studies showed that melatonin (MT) exerted anti-fibrotic effect in many diseases including PF through its antioxidant activity. In the present study we investigated the relationships among Gal-3, NRF2, ROS in FMD and their regulation by MT. We established an in vitro model of FMD in TGF-ß1-treated human fetal lung fibroblast1 (HFL1) cells and a PF mouse model via bleomycin (BLM) intratracheal instillation. We found that Gal-3 expression was significantly increased both in vitro and in vivo. Knockdown of Gal-3 in HFL1 cells markedly attenuated TGF-ß1-induced FMD process and ROS accumulation. In TGF-ß1-treated HFL1 cells, pretreatment with NRF2-specific inhibitor ML385 (5 µM) significantly increased the levels of Gal-3, α-SMA and ROS, suggesting that the expression of Gal-3 was regulated by NRF2. Treatment with NRF2-activator MT (250 µM) blocked α-SMA and ROS accumulation accompanied by reduced Gal-3 expression. In BLM-induced PF model, administration of MT (5 mg·kg-1·d-1, ip for 14 or 28 days) significantly attenuated the progression of lung fibrosis through up-regulating NRF2 and down-regulating Gal-3 expression in lung tissues. These results suggest that Gal-3 regulates TGF-ß1-induced pro-fibrogenic responses and ROS production in FMD, and MT activates NRF2 to block FMD process by down-regulating Gal-3 expression. This study provides a useful clue for a clinical strategy to prevent PF. Graphic abstract of the mechanisms. MT attenuated BLM-induced PF via activating NRF2 and inhibiting Gal-3 expression.

Angstrom-Scale Electrochemistry at Electrodes with Dimensions Commensurable and Smaller than Individual Reacting Species.

In nature and technologies, many chemical reactions occur at interfaces with dimensions approaching that of a single reacting species in nano- and angstrom-scale. Mechanisms governing reactions at this ultimately small spatial regime remain poorly explored because of challenges to controllably fabricate required devices and assess their performance in experiment. Here we report how efficiency of electrochemical reactions evolves for electrodes that range from just one atom in thickness to sizes comparable with and exceeding hydration diameters of reactant species. The electrodes are made by encapsulating graphene and its multilayers within insulating crystals so that only graphene edges remain exposed and partake in reactions. We find that limiting current densities characterizing electrochemical reactions exhibit a pronounced size effect if reactant's hydration diameter becomes commensurable with electrodes' thickness. An unexpected blockade effect is further revealed from electrodes smaller than reactants, where incoming reactants are blocked by those adsorbed temporarily at the atomically narrow interfaces. The demonstrated angstrom-scale electrochemistry offers a venue for studies of interfacial behaviors at the true molecular scale.

Protective effect of dimethyl itaconate against fibroblast-myofibroblast differentiation during pulmonary fibrosis by inhibiting TXNIP.

Fibroblast-myofibroblast differentiation (FMD) is a critical cellular phenotype during the occurrence and deterioration of pulmonary fibrosis (PF). FMD can increase with an elevated level of reactive oxygen species (ROS) on fibroblasts under oxidative stress. Thioredoxin-interacting protein (TXNIP) is an α-arrestin family protein that regulates the level of intracellular ROS. Nuclear factor erythroid 2-related factor 2 (Nrf2) can protect against FMD in PF. However, the relationship between Nrf2 and TXNIP in FMD remains elusive. Therefore, we established TGF-ß1-induced FMD in vitro and bleomycin (BLM)-induced mouse PF model in vivo to explore whether the activation of Nrf2 can inhibit TXNIP-mediated FMD in PF. Dimethyl itaconate (DMI) was selected to activate Nrf2. Our results showed that TXNIP was elevated and FMD was aggravated in mice lung tissues after BLM administration compared with the saline group. Inversely, Nrf2 decreased TXNIP expression and alleviated FMD in PF. In vitro, TXNIP overexpression enhanced FMD and increased the level of ROS. In contrast, TXNIP deficiency by small interfering RNA (siRNA) attenuated TGF-ß1-induced FMD and reduced ROS. An increase in ROS by H2 O2 can upregulate TXNIP expression. Moreover, Nrf2 also inhibited TGF-ß1-induced FMD and the increase of ROS, with reducing expression of TXNIP, and the inhibitory effect was better than TXNIP siRNA. These results suggest that activation of Nrf2 by DMI can protect against PF via inhibiting TXNIP expression. Our study may provide new therapeutic targets and treatment approaches for PF.

Activated AMPK by metformin protects against fibroblast proliferation during pulmonary fibrosis by suppressing FOXM1.

Pulmonary fibrosis (PF) is a progressive and devastating lung disease of unknown etiology, excessive fibroblast proliferation serves as a key event to promote PF. Transcription factor forkhead box M1 (FOXM1) is not only a well-known proto-oncogene, but also an essential driver of cell proliferation. Recently, 5'-AMP-activated protein kinase (AMPK) is reported to reduce the incidence of PF. However, it remains elusive whether have an underlying relationship between AMPK and FOXM1 in fibroblast proliferation-mediated PF. Here, the progression of lung fibroblast proliferation and the expression levels of AMPK and FOXM1 were observed by intratracheally instilled of bleomycin (BLM) and intraperitoneal injection of metformin in C57BL/6 J mice. Meanwhile, human fetal lung fibroblast1 (HFL1) cells were respectively treated with AMPK activator metformin or AMPK inhibitor Compound C, or FOXM1 depletion by transfected small interfering RNA (siRNA) to unveil roles of AMPK, FOXM1 and the link between them on platelet-derived growth factor (PDGF)-induced fibroblast proliferation. Our results demonstrated that AMPK activated by metformin could down-regulate FOXM1 and alleviate BLM-induced mouse PF model. In vitro, activation of AMPK attenuated PDGF-induced fibroblast proliferation accompanied by the down-regulation of FOXM1. In contrast, inhibition of AMPK enhanced PDGF-induced fibroblast proliferation along with activating FOXM1. These findings suggest that AMPK can ameliorate the progression of fibroblast proliferation during PF via suppressing the expression of FOXM1 and provide new insight into seek PF treatment approaches.

Cupriavidus basilensis strain r507, a toxic arsenic phytoextraction facilitator, potentiates the arsenic accumulation by Pteris vittata.

As a toxic and carcinogenic metalloid, arsenic has posed serious threat to human health. Phytoremediation has emerged as a promising approach to circumvent this problem. Arsenic uptake by Pteris vittata is largely determined by arsenic speciation and mainly occurs via roots; thus, rhizospheric microbial activities may play a key role in arsenic accumulation. The aim of this study was to investigate the potential of arsenic resistant rhizobacteria to enhance arsenic phytoextraction. A total of 49 cultivable rhizobacteria were isolated from the arsenic hyperaccumulating fern, Pteris vittata, and subjected to an initial analysis to identify potentially useful traits for arsenic phytoextraction, such as arsenic resistance and the presence of aioA(aroA)-like (arsenite oxidase-like) gene. Isolated strain r507, named as Cupriavidus basilensis strain r507, was a selected candidate for its outstanding arsenic tolerance, rapid arsenite oxidation ability, and strong colonization to P. vittata. Strain r507 was used in co-cultivation trials with P. vittata in the field for six months. Results showed that the inoculation with strain r507 potentiated As accumulation of P. vittata up to 171%. Molecular analysis confirmed that the inoculation increased the abundance of aioA-like genes in the rhizosphere, which might have facilitated arsenite oxidation and absorption. The findings of this study suggested the feasibility of co-cultivating hyperaccumulators with facilitator bacteria for practical arsenic phytoremediation.

Asymmetric All-Metal-Oxide Supercapacitor with Superb Cycle Performance.

Metal oxides have great potential for developing high-performance supercapacitors due to their high specific capacitances. However, achieving high energy densities while maintaining good rate capability and long cycle life has proved to be challenging. We propose herein a strategy for constructing all-metal-oxide asymmetric supercapacitors (ASCs), in which both the cathode and anode are based on metal oxides, and demonstrate their outstanding electrochemical performance. We anchored SnO2 nanoparticles on the surface of reduced graphene oxide (RGO) through Sn-O-C bonds (as the cathode of ACSs), and employed low-crystalline RGO/MoO3 nanosheets as the anode, based on the large work function difference between SnO2 and MoO3 . The resulting ASC can operate stably at 1.8 V in neutral aqueous electrolyte and deliver an energy density of up to 33 W h kg-1 , which remains at 13.8 W h kg-1 even at 37.5 kW kg-1 . Moreover, the ASC exhibits a good cycling stability of 92.5 % capacitance retention after 20 000 cycles.

Coating-free, air-stable silver nanowires for high-performance transparent conductive film.

Silver nanowire (Ag NW) based films are considered as a promising alternative for traditional indium tin oxide but still suffer from some limitations, including insufficient conductivity, transparency and environmental instability. We here report a novel etching synthesis strategy to improve the performance of Ag NW films. Different from the traditional methods to synthesize high aspect ratios of NWs or employ electrically conductive coatings, we find it effective to reduce the high-reactivity defects of NWs for optimizing the comprehensive performance of Ag NW films. In this strategy etching can suppress the generation of high-reactivity defects and meanwhile the etching growth of NWs can be accomplished in an uneven ligand distribution environment. The resulting Ag NWs are uniformly straight with a sharp-edged structure. The transparent conductive film obtained exhibits simultaneous improvements in electrical conductivity, transparency and air stability. Even after exposure in air for 200 days and no protective coatings, the film can still meet the highest requirement of practical applications, with a figure of merit 361 (i.e., FoM > 350). These results not only demonstrate the importance of defect control in the synthesis of Ag NWs, but also pave a way for further optimizing the performance of Ag NW-based films.

Enhanced photocatalytic bacteriostatic activity towards Escherichia coli using 3D hierarchical microsphere BiOI/BiOBr under visible light irradiation.

A BiOI/BiOBr composite was successfully fabricated by a simple hydrothermal method. The composite was characterized by X-ray diffraction (XRD), UV-vis diffuse reflectance spectroscopy (UV-vis DRS), scanning electron microscopy (SEM), and high-resolution transmission electron microscopy (HRTEM). The BiOI/BiOBr composite exhibited enhanced photocatalytic bacteriostatic activity towards E. coli compared to the pure BiOI or BiOBr under visible light irradiation. The enhanced photocatalytic performance can be attributed to the improved separation efficiency of the photogenerated holes because of its heterojunction structure. In addition, the possible bacteriostatic mechanism of the BiOI/BiOBr composite under visible light irradiation is discussed. The hierarchical microsphere BiOI/BiOBr showed enhanced photocatalytic bacteriostasis towards Escherichia coli under visible light.

Tuning the Mechanical Properties of 3D-Printed Objects by Mixing Chain Transfer Agents in Norrish Type†I Photoinitiated RAFT Polymerization.

Photoinduced 3D printing via photocontrolled reversible-deactivation radical polymerization (photoRDRP) techniques has emerged as a robust technique for creating polymeric materials. However, methods for precisely adjusting the mechanical properties of these materials remain limited. In this study, we present a facile approach for adjusting the mechanical properties of 3D-printed objects by adjusting the polymer dispersity within a Norrish type I photoinitiated reversible addition-fragmentation chain transfer (NTI-RAFT) polymerization-based 3D printing process. We investigated the effects of varying the concentrations and molar ratios of trithiocarbonate (BTPA) and xanthate (EXEP) on the mechanical properties of the printed materials. Our findings demonstrate that increased concentrations of RAFT agents or higher proportions of the more active BTPA lead to a decrease in Young's modulus and glass transition temperatures, along with an increase in elongation at break, which can be attributed to the enhanced homogeneity of the polymer network. Using a commercial LCD printer, the NTI-RAFT-based 3D printing system effectively produced materials with tailored mechanical properties, highlighting its potential for practical applications.

Complete genome sequence of Pseudomonas moorei strain m318 isolated from rhizosphere of Pteris multifida in high-arsenic-content soil.

Pseudomonas moorei strain m318 is an arsenite-oxidizing rhizobacterium isolated from the rhizosphere of an arsenic hyperaccumulator plant, beneficial for arsenic phytoremediation. Here, we report the complete genome sequence of this strain, which consists of a circular chromosome assembled using long reads sequenced on Nanopore and polished with Illumina paired-end reads.

Surface diffusion enhanced ion transport through two-dimensional nanochannels.

Fast ion permeation in nanofluidic channels has been intensively investigated in the past few decades because of their potential uses in separation technologies and osmotic energy harvesting. Mechanisms governing ion transport at this ultimately small spatial regime remain to be understood, which can only be achieved in nanochannels that are controllably fabricated. Here, we report the fabrication of two-dimensional nanochannels with their top and bottom walls consisting of atomically flat graphite and mica crystals, respectively. The distinct wall structures and properties enable us to investigate interactions between ions and interior surfaces. We find an enhanced ion transport within the channels that is orders of magnitude faster than that in the bulk solutions. The result is attributed to the highly dense packing of adsorbed cations at mica surfaces, where they diffuse in-plane. Our work provides insights into surface effects on ion transport at the nanoscale.

Metformin attenuates fibroblast activation during pulmonary fibrosis by targeting S100A4 via AMPK-STAT3 axis.

Fibroblasts activation is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis pathogenesis, and transforming growth factor (TGF)-ß1 plays a key regulatory role in fibroblast activation. It has been reported that metformin (MET) alleviated bleomycin (BLM)-induced pulmonary fibrosis (PF) by regulating TGF-ß1-induced fibroblasts activation, but the underlying mechanisms still deserve further investigations. In this study, MET blocked α-smooth muscle actin (α-SMA) accumulation in vivo accompanied with S100A4 expression and STAT3 phosphorylation inhibition, resulting in attenuating the progression of lung fibrosis after BLM administration. We determined that S100A4 plays critical roles in fibroblasts activation in vitro, evidenced by siRNA knockdown of S100A4 expression downregulated TGF-ß1 induced α-SMA production in Human fetal lung fibroblast (HFL1) cells. Importantly, we found for the first time that the expression of S100A4 in fibroblasts was regulated by STAT3. Stattic, an effective small molecule inhibitor of STAT3 phosphorylation, reduced S100A4 level in TGF-ß1- treated HFL1 cells accompanied with less α-SMA production. We further found that MET, which inhibits STAT3 phosphorylation by AMPK activation, also inhibits fibroblasts activation by targeting S100A4 in vitro. Together all these results, we conclude that S100A4 contributes to TGF-ß1- induced pro-fibrogenic function in fibroblasts activation, and MET was able to protect against TGF-ß1-induced fibroblasts activation and BLM-induced PF by down-regulating S100A4 expression through AMPK-STAT3 axis. These results provide a useful clue for a clinical strategy to prevent PF.

Empirical Evidence of Arsenite Oxidase Gene as an Indicator Accounting for Arsenic Phytoextraction by Pteris vittata.

Arsenic (As) is a toxic semi-metallic element that is ubiquitous in the environment and poses serious human health risks. Phytoextraction by Pteris vittata is considered a low-cost and environmentally friendly approach to treat As-contaminated soil. P. vittata mainly absorbs arsenate thus the bioavailability of As to P. vittata depends on the chemical form of As. Microbial redox of As contributes to the biogeochemical cycling of As, and rhizobacterium-assisted phytoextraction by P. vittata was proposed. In this study, this microbe-assisted phytoextraction was applied to two fields, and the effectiveness of phytoextraction was evaluated. The results revealed that P. vittata was able to grow in temperate and subarctic climate zones. The biomass was influenced by the weather, and the As concentration in plants was dependent on the As content in the soil. The ratio of arsenite oxidase genes (aioA-like genes) to 16S rRNA genes was employed to evaluate the effect of As phytoextraction, and the results exhibited that the ratio was related to the As concentration in P. vittata. Our results showed that arsenite oxidation in the rhizosphere might not be achieved by single-strain inoculation, while this study provided empirical evidence that the rhizospheric aioA-like genes could be an indicator for evaluating the effectiveness of As phytoextraction.

Low-cost gel-filled microwell array device for screening marine microbial consortium.

In order to exploit the microbes present in the environment for their beneficial resources, effective selection and isolation of microbes from environmental samples is essential. In this study, we fabricated a gel-filled microwell array device using resin for microbial culture. The device has an integrated sealing mechanism that enables high-density isolation based on the culture of microorganisms; the device is easily manageable, facilitating observation using bright-field microscopy. This low-cost device made from polymethyl methacrylate (PMMA)/polyethylene terephthalate (PET) has 900 microwells (600 µm × 600 µm × 700 µm) filled with a microbial culture gel medium in glass slide-sized plates. It also has grooves for maintaining the moisture content in the micro-gel. The partition wall between the wells has a highly hydrophobic coating to inhibit microbial migration to neighboring wells and to prevent exchange of liquid substances. After being hermetically sealed, the device can maintain moisture in the agarose gels for 7 days. In the bacterial culture experiment using this device, environmental bacteria were isolated and cultured in individual wells after 3 days. Moreover, the isolated bacteria were then picked up from wells and re-cultured. This device is effective for the first screening of microorganisms from marine environmental samples.

Cation-Gated Ion Transport at Nanometer Scale for Tunable Power Generation.

Gated ion channels in biological cell membranes allow efficient tuning of cross-membrane ion transport with enhanced permeation and selectivity, converting ionic signals into various forms of electrical signals and energies on demands, which functionalities though are still difficult to achieve in artificial membranes. Here, we report cation-gated ion transport through synthesized porous aromatic films containing nanometer-scale ionic channels together with -NH2 groups at interiors. Ion selectivity and permeability is greatly tuned by gating cations, up to 2 orders of magnitude, and as a consequence, the membrane efficiently produces switchable electricity output from salinity gradients. The results are attributed to positively charged cations binding at -NH2 groups, which screens the intrinsic negative surface charge at channels' interiors and inverts charge polarity there. Our work adds understanding to ion gating effects at nanoscale and offers strategies of developing smart membranes and their heterostructures for separation, energy conversion, cell membrane mimics, and related technologies.

Rhizospheric plant-microbe synergistic interactions achieve efficient arsenic phytoextraction by Pteris vittata.

Phytoextraction is a cost-effective and eco-friendly technology to remove arsenic (As) from contaminated soil using plants and associated microorganisms. Pteris vittata is the most studied As hyperaccumulator, which effectively takes up inorganic arsenate via roots. Arsenic solubilization and speciation occur prior to plant absorption in the rhizosphere, which play a key role in As phytoextraction by P. vittata. This study investigated the metabolomic correlation of P. vittata and associated rhizospheric microorganisms during As phytoextraction. Three-month pot cultivation of P. vittata in As polluted soil was conducted. In rhizosphere, an increase of water-soluble As concentration and a decrease of pH was observed in the second month, suggesting acidic metabolites as a possible cause of As solubilization. A correlation network was built to elucidate the interactions among metabolites, bacteria and fungi in the rhizosphere of P. vittata. Our results demonstrate that the plant is the major driving force of rhizospheric microbiota generation, and both microbial community and metabolites in rhizosphere of P. vittata correlate to increased bioavailable As. Multi-omics analysis revealed that pterosins enrich microbes that potentially promote As phytoextraction. This study extends the current view of rhizospheric plant-microbes synergistic effects of hyperaccumulators on phytoextraction, which provides clues for developing efficient As phytoremediation approaches.

Gas permeation through graphdiyne-based nanoporous membranes.

Nanoporous membranes based on two dimensional materials are predicted to provide highly selective gas transport in combination with extreme permeance. Here we investigate membranes made from multilayer graphdiyne, a graphene-like crystal with a larger unit cell. Despite being nearly a hundred of nanometers thick, the membranes allow fast, Knudsen-type permeation of light gases such as helium and hydrogen whereas heavy noble gases like xenon exhibit strongly suppressed flows. Using isotope and cryogenic temperature measurements, the seemingly conflicting characteristics are explained by a high density of straight-through holes (direct porosity of ∼0.1%), in which heavy atoms are adsorbed on the walls, partially blocking Knudsen flows. Our work offers important insights into intricate transport mechanisms playing a role at nanoscale.

One-Atom-Thick Crystals as Emerging Proton Sieves.

Two-dimensional (2D) crystals, despite their atomic thickness, have long been considered as impermeable membranes to all molecules and atoms under ambient conditions: even the smallest of atoms, hydrogen, is expected to take billions of years to penetrate the 2D lattice covered with dense electron clouds. Recently it has been found that monolayer graphene, hexagonal boron nitride, and some other one-atom-thick crystals are highly permeable to protons, raising fundamental questions about the details of the transport process. In this Perspective, we review the mechanism of proton transport through 2D crystals and the related room-temperature quantum effects; the potential applications of 2D membranes in proton-related separation and sieving techniques, including proton exchange membranes and hydrogen isotope separation; and factors that enhance proton permeation and in turn influence 2D membrane design.

A Bifunctional-Modulated Conformal Li/Mn-Rich Layered Cathode for Fast-Charging, High Volumetric Density and Durable Li-Ion Full Cells.

Lithium- and manganese-rich (LMR) layered cathode materials hold the great promise in designing the next-generation high energy density lithium ion batteries. However, due to the severe surface phase transformation and structure collapse, stabilizing LMR to suppress capacity fade has been a critical challenge. Here, a bifunctional strategy that integrates the advantages of surface modification and structural design is proposed to address the above issues. A model compound Li1.2Mn0.54Ni0.13Co0.13O2 (MNC) with semi-hollow microsphere structure is synthesized, of which the surface is modified by surface-treated layer and graphene/carbon nanotube dual layers. The unique structure design enabled high tap density (2.1 g cm-3) and bidirectional ion diffusion pathways. The dual surface coatings covalent bonded with MNC via C-O-M linkage greatly improves charge transfer efficiency and mitigates electrode degradation. Owing to the synergistic effect, the obtained MNC cathode is highly conformal with durable structure integrity, exhibiting high volumetric energy density (2234 Wh L-1) and predominant capacitive behavior. The assembled full cell, with nanographite as the anode, reveals an energy density of 526.5 Wh kg-1, good rate performance (70.3% retention at 20 C) and long cycle life (1000 cycles). The strategy presented in this work may shed light on designing other high-performance energy devices.

Improved stability of up-flow anaerobic sludge blanket reactor treating starch wastewater by pre-acidification: Impact on microbial community and metabolic dynamics.

Poor processing stability has been cited as the fatal shortcoming of the up-flow anaerobic sludge blanket (UASB) reactor treating starch wastewater (SW). In this study, the SW treatment performance in a one-stage UASB reactor and a pre-acidification equipped UASB process were evaluated together with the microbial dynamics. The results revealed that the pre-acidification provided improvements in terms of the substrate utilization diversity and the stability of the microbial community structure on the UASB reactor. Anaerolineaceae/Methanosaeta was the core functional microbiota in the pre-acidification equipped UASB reactor, indicated the superior abilities on the acetogenic methanogenesis of granules. The genus of Methanobacterium, a hydrogenotrophic methanogen was dominant in the archaeal community in the one-stage UASB reactor. The granules performed very strong hydrogen affinity in methane production, a small amount of propionate was detected in the effluent. These were abnormal, which suggested the high hydrogen turn-over rate in the one-stage UASB reactor.