Floating Bimetallic Catalysts for Growing 30 cm-Long Carbon Nanotube Arrays with High Yields and Uniformity.

Ultralong carbon nanotubes (CNTs) are considered as promising candidates for many cutting-edge applications. However, restricted by the extremely low yields of ultralong CNTs, their practical applications can hardly be realized. Therefore, new methodologies shall be developed to boost the growth efficiency of ultralong CNTs and alleviate their areal density decay at the macroscale level. Herein, a facile, universal, and controllable method for the in situ synthesis of floating bimetallic catalysts (FBCs) is proposed to grow ultralong CNT arrays with high yields and uniformity. Ferrocene and metal acetylacetonates serve as catalyst precursors, affording the successful synthesis of a series of FBCs with controllable compositions. Among these FBCs, the optimized FeCu catalyst increases the areal density of ultralong CNT arrays to a record-breaking value of ≈8100 CNTs mm-1 and exhibits a lifetime 3.40 times longer than that of Fe, thus achieving both high yields and uniformity. A 30-centimeters-long and high-density ultralong CNT array is also successfully grown with the assistance of FeCu catalysts. As evidenced by this kinetic model and molecular dynamics simulations, the introduction of Cu into Fe can simultaneously improve the catalyst fluidity and decrease carbon solubility, and an optimal catalytic performance will be achieved by balancing this tradeoff.

Traditional Chinese medicine improved diabetic kidney disease through targeting gut microbiota.

CONTEXT: Diabetic kidney disease (DKD) affects nearly 40% of diabetic patients, often leading to end-stage renal disease that requires renal replacement therapies, such as dialysis and transplantation. The gut microbiota, an integral aspect of human evolution, plays a crucial role in this condition. Traditional Chinese medicine (TCM) has shown promising outcomes in ameliorating DKD by addressing the gut microbiota. OBJECTIVE: This review elucidates the modifications in gut microbiota observed in DKD and explores the impact of TCM interventions on correcting microbial dysregulation. METHODS: We searched relevant articles from databases including Web of Science, PubMed, ScienceDirect, Wiley, and Springer Nature. The following keywords were used: diabetic kidney disease, diabetic nephropathy, gut microbiota, natural product, TCM, Chinese herbal medicine, and Chinese medicinal herbs. Rigorous criteria were applied to identify high-quality studies on TCM interventions against DKD. RESULTS: Dysregulation of the gut microbiota, including Lactobacillus, Streptococcus, and Clostridium, has been observed in individuals with DKD. Key indicators of microbial dysregulation include increased uremic solutes and decreased short-chain fatty acids. Various TCM therapies, such as formulas, tablets, granules, capsules, and decoctions, exhibit unique advantages in regulating the disordered microbiota to treat DKD. CONCLUSION: This review highlights the importance of targeting the gut-kidney axis to regulate microbial disorders, their metabolites, and associated signaling pathways in DKD. The Qing-Re-Xiao-Zheng formula, the Shenyan Kangfu tablet, the Huangkui capsule, and the Bekhogainsam decoction are potential candidates to address the gut-kidney axis. TCM interventions offer a significant therapeutic approach by targeting microbial dysregulation in patients with DKD.

High-Performance Airflow Sensors Based on Suspended Ultralong Carbon Nanotube Crossed Networks.

Airflow sensors are in huge demand in many fields such as the aerospace industry, weather forecasting, environmental monitoring, chemical and biological engineering, health monitoring, wearable smart devices, etc. However, traditional airflow sensors can hardly meet the requirements of these applications in the aspects of sensitivity, response speed, detection threshold, detection range, and power consumption. Herein, this work reports high-performance airflow sensors based on suspended ultralong carbon nanotube (CNT) crossed networks (SCNT-CNs). The unique topologies of SCNT-CNs with abundant X junctions can fully exhibit the extraordinary intrinsic properties of ultralong CNTs and significantly improve the sensing performance and robustness of SCNT-CNs-based airflow sensors, which simultaneously achieved high sensitivity, fast response speed, low detection threshold, and wide detection range. Moreover, the capability for encapsulation also guaranteed the practicality of SCNT-CNs, enabling their applications in respiratory monitoring, flow rate display and transient response analysis. Simulations were used to unveil the sensing mechanisms of SCNT-CNs, showing that the piezoresistive responses were mainly attributed to the variation of junction resistances. This work shows that SCNT-CNs have many superiorities in the fabrication of advanced airflow sensors as well as other related applications.

PCSK9i promoting the transformation of AS plaques into a stable plaque by targeting the miR-186-5p/Wipf2 and miR-375-3p/Pdk1/Yap1 in ApoE-/- mice.

Background: Atherosclerosis (AS) is a multifaceted disease characterized by disruptions in lipid metabolism, vascular inflammation, and the involvement of diverse cellular constituents. Recent investigations have progressively underscored the role of microRNA (miR) dysregulation in cardiovascular diseases, notably AS. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) can effectively reduce circulating levels of low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp (a)], potentially fostering a more enduring phenotype for AS plaques. However, the underlying mechanisms by which PCSK9i enhances plaque stability remain unclear. In this study, we used microarray and bioinformatics techniques to analyze the regulatory impacts on gene expression pertinent to AS, thereby unveiling potential mechanisms underlying the plaque-stabilizing attributes of PCSK9i. Methods: ApoE-/- mice were randomly allocated into control, AS, PCSK9i, and Atorvastatin groups. The AS model was induced through a high-fat diet (HFD), succeeded by interventions: the PCSK9i group was subjected to subcutaneous SBC-115076 injections (8 mg/kg, twice weekly), and the Atorvastatin group received daily oral Atorvastatin (10 mg/kg) while on the HFD. Subsequent to the intervention phase, serum analysis, histological assessment using hematoxylin and eosin (H&E) and Oil Red O staining, microarray-centered miRNA analysis utilizing predictions from TargetScan and miRTarBase, and analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were executed to illuminate potential pathways. Real-time fluorescence quantitative PCR (RT-qPCR) was employed to quantify the expression levels of target genes. Results: In comparison to the control group, the AS group displayed a significant elevation in blood lipid levels. Both PCSK9i and Atorvastatin effectively attenuated blood lipid levels, with PCSK9i exhibiting a more pronounced lipid-lowering impact, particularly concerning TG and LDL-C levels. Over the course of AS progression, the expression levels of mmu-miR-134, mmu-miR-141-5p, mmu-miR-17-3p, mmu-miR-195-3p, mmu-miR-210, mmu-miR-33-5p, mmu-miR-410, mmu-miR-411-5p, mmu-miR-499, mmu-miR-672-5p, mmu-miR-675-3p, and mmu-miR-301b underwent dynamic fluctuations. PCSK9i significantly down-regulated the expression of mmu-miR-186-5p, mmu-miR-222, mmu-miR-375-3p, and mmu-miR-494-3p. Further enrichment analysis disclosed that mmu-miR-186-5p, mmu-miR-222, mmu-miR-375-3p, and mmu-miR-494-3p were functionally enriched for cardiovascular smooth muscle cell proliferation, migration, and regulation. RT-qPCR results manifested that, in comparison to the AS group, PCSK9i significantly upregulated the expression of Wipf2, Pdk1, and Yap1 (p < 0.05). Conclusion: Aberrant miRNA expression may play a pivotal role in AS progression in murine models of AS. The subcutaneous administration of PCSK9i exerted anti-atherosclerotic effects by targeting the miR-186-5p/Wipf2 and miR-375-3p/Pdk1/Yap1 axes, thereby promoting the transition of AS plaques into a more stable form.

Progress and challenges of in vivo flow cytometry and its applications in circulating cells of eyes.

Circulating inflammatory cells in eyes have emerged as early indicators of numerous major diseases, yet the monitoring of these cells remains an underdeveloped field. In vivo flow cytometry (IVFC), a noninvasive technique, offers the promise of real-time, dynamic quantification of circulating cells. However, IVFC has not seen extensive applications in the detection of circulating cells in eyes, possibly due to the eye's unique physiological structure and fundus imaging limitations. This study reviews the current research progress in retinal flow cytometry and other fundus examination techniques, such as adaptive optics, ultra-widefield retinal imaging, multispectral imaging, and optical coherence tomography, to propose novel ideas for circulating cell monitoring.

Enabling C2H2/CO2 Separation Under Humid Conditions with a Methylated Copper MOF.

As a unique subclass of metal-organic frameworks (MOFs), MOFs with open metal site (OMS) are demonstrated efficient gas separation performance through pi complexation with unsaturated hydrocarbons. However, their practical application faces the challenge of humidity that causes structure degradation and completive binding at the OMS. In this work, the effect of linker methylation of a copper MOF (BUT-155) on the C2H2/CO2 separation performance under humid condition is evaluated. The water adsorption isotherm, adsorption kinetics, and breakthrough under dry and humid conditions are performed. The BUT-155 with methylated linker exhibits lower water uptake and adsorption kinetics under humid condition (RH = 20%), in comparison with HKUST-1. Therefore, the C2H2/CO2 separation performance of BUT-155 is much less affected by water, especially under higher gas flow rate. Moreover, the dynamic C2H2/CO2 separation performance of BUT-155 can maintain five breakthrough cycles under humid conditions (RH = 20% and RH = 80%) without obvious performance degradation.

Non-CO2 greenhouse gas separation using advanced porous materials.

Global warming has become a growing concern over decades, prompting numerous research endeavours to reduce the carbon dioxide (CO2) emission, the major greenhouse gas (GHG). However, the contribution of other non-CO2 GHGs including methane (CH4), nitrous oxide (N2O), fluorocarbons, perfluorinated gases, etc. should not be overlooked, due to their high global warming potential and environmental hazards. In order to reduce the emission of non-CO2 GHGs, advanced separation technologies with high efficiency and low energy consumption such as adsorptive separation or membrane separation are highly desirable. Advanced porous materials (APMs) including metal-organic frameworks (MOFs), covalent organic frameworks (COFs), hydrogen-bonded organic frameworks (HOFs), porous organic polymers (POPs), etc. have been developed to boost the adsorptive and membrane separation, due to their tunable pore structure and surface functionality. This review summarizes the progress of APM adsorbents and membranes for non-CO2 GHG separation. The material design and fabrication strategies, along with the molecular-level separation mechanisms are discussed. Besides, the state-of-the-art separation performance and challenges of various APM materials towards each type of non-CO2 GHG are analyzed, offering insightful guidance for future research. Moreover, practical industrial challenges and opportunities from the aspect of engineering are also discussed, to facilitate the industrial implementation of APMs for non-CO2 GHG separation.

A dual-selective thermal emitter with enhanced subambient radiative cooling performance.

Radiative cooling is a zero-energy technology that enables subambient cooling by emitting heat into outer space (~3 K) through the atmospheric transparent windows. However, existing designs typically focus only on the main atmospheric transparent window (8-13 µm) and ignore another window (16-25 µm), under-exploiting their cooling potential. Here, we show a dual-selective radiative cooling design based on a scalable thermal emitter, which exhibits selective emission in both atmospheric transparent windows and reflection in the remaining mid-infrared and solar wavebands. As a result, the dual-selective thermal emitter exhibits an ultrahigh subambient cooling capacity (~9 °C) under strong sunlight, surpassing existing typical thermal emitters (≥3 °C cooler) and commercial counterparts (as building materials). Furthermore, the dual-selective sample also exhibits high weather resistance and color compatibility, indicating a high practicality. This work provides a scalable and practical radiative cooling design for sustainable thermal management.

Lubricating Microneedles System with Multistage Sustained Drug Delivery for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is a typical joint degenerative disease that is prevalent worldwide and significantly affects the normal activities of patients. Traditional treatments using diclofenac (DCF) as an anti-inflammatory drug by oral administration and transdermal delivery have many inherent deficiencies. In this study, a lubricating microneedles (MNs) system for the treatment of osteoarthritis with multistage sustained drug delivery and great reduction in skin damage during MNs penetration is developed. The bilayer dissolvable MNs system, namely HA-DCF@PDMPC, is prepared by designating the composite material of hyaluronic acid (HA) and covalently conjugated drug compound (HA-DCF) as the MNs tips and then modifying the surface of MNs tips with a self-adhesive lubricating copolymer (PDMPC). The MNs system is designed to achieve sustained drug release of DCF via ester bond hydrolysis, physical diffusion from MNs tips, and breakthrough of lubrication coating. Additionally, skin damage is reduced due to the presence of the lubrication coating on the superficial surface. Therefore, the lubricating MNs with multistage sustained drug delivery show good compliance as a transdermal patch for OA treatment, which is validated from anti-inflammatory cell tests and therapeutic animal experiments, down-regulating the expression levels of pro-inflammatory factors and alleviating articular cartilage destruction.

Simultaneous Inhibition of Conduction Loss and Enhancement of Polarization Intensity of Polyetherimide Dielectrics for High-Temperature Capacitive Energy Storage.

Polymer dielectrics with excellent high-temperature capacitive energy storage performance are in urgent demand for modern power electronic devices and high-voltage electrical systems. Nevertheless, the energy storage capability usually degrades dramatically at increased temperatures, owing to the exponentially increased conduction loss. Herein, a trace of commercially available aluminum nitride (AlN) nanoparticles is incorporated into the poly(ether imide) (PEI) matrix to inhibit the conduction loss. The nanostructured AlN component with a large specific surface area can provide abundant sites for the collision of carriers. More importantly, the generated new trap energy levels can immobilize the carriers, accordingly contributing to the reduction in leakage current. From this, the discharged energy density at 150 °C of PEI composites increases by 82.13% from 2.63 J/cm3 for pristine PEI to 4.79 J/cm3 for PEI composites. This work establishes a facile approach to enhancing the high-temperature capacitive performance of polymer dielectrics.

Unifying and Suppressing Conduction Losses of Polymer Dielectrics for Superior High-Temperature Capacitive Energy Storage.

Superior high-temperature capacitive performance of polymer dielectrics is critical for the modern film capacitor demanded in the harsh-environment electronic and electrical systems. Unfortunately, the capacitive performance degrades rapidly at elevated temperatures owing to the exponential growth of conduction loss. The conduction loss is mainly composed of electrode and bulk-limited conduction. Herein, the contribution of surface and bulk factors is unified to conduction loss, and the loss is thoroughly suppressed. The experimental results demonstrate that the polar oxygen-containing groups on the surface of polymer dielectrics can act as the charge trap sites to immobilize the injected charges from electrode, which can in turn establish a built-in field to weaken the external electric field and augment the injection barrier height. Wide bandgap aluminum oxide (Al2 O3 ) nanoparticle fillers can serve as deep traps to constrain the transport of injected or thermally activated charges in the bulk phase. From this, at 200 °C, the discharged energy density with a discharge-charge efficiency of 90% increases by 1058.06% from 0.31 J cm-3 for pristine polyetherimide to 3.59 J cm-3 for irradiated composite film. The principle of simultaneously inhibiting the electrode and bulk-limited conduction losses could be easily extended to other polymer dielectrics for high-temperature capacitive performance.

Systematic Study of Heteroarene Stacking Using a Congeneric Set of Molecular Glues for Procaspase-6.

Heteroaromatic stacking interactions are important in drug binding, supramolecular chemistry, and materials science, making protein-ligand model systems of these interactions of considerable interest. Here we studied 30 congeneric ligands that each present a distinct heteroarene for stacking between tyrosine residues at the dimer interface of procaspase-6. Complex X-ray crystal structures of 10 analogs showed that stacking geometries were well conserved, while high-accuracy computations showed that heteroarene stacking energy was well correlated with predicted overall ligand binding energies. Empirically determined KD values in this system thus provide a useful measure of heteroarene stacking with tyrosine. Stacking energies are discussed in the context of torsional strain, the number and positioning of heteroatoms, tautomeric state, and coaxial orientation of heteroarene in the stack. Overall, this study provides an extensive data set of empirical and high-level computed binding energies in a versatile new protein-ligand system amenable to studies of other intermolecular interactions.

Membranous nephropathy: Mechanistic insights and therapeutic perspectives.

Membranous nephropathy (MN) is one of the most common causes of non-diabetic nephrotic syndrome in adults. About 80% of cases are renal limited (primary MN) and 20% are associated with other systemic diseases or exposures (secondary MN). Autoimmune reaction is the main pathogenic factor of MN, and the discovery of autoantigens including the phospholipase A2 receptor and thrombospondin type-1 domain-containing protein 7A has led to new insights into the pathogenesis, they can induce humoral immune responses led by IgG4 makes them suitable for the diagnosis and monitoring of MN. In addition, complement activation, genetic susceptibility genes and environmental pollution are also involved in MN immune response. In clinical practice, due to the spontaneous remission of MN, the combination of supportive therapy and pharmacological treatment is widely used. Immunosuppressive drugs are the cornerstone of MN treatment, and the dangers and benefits of this approach vary from person to person. In summary, this review provides a more comprehensive review of the immune pathogenesis, interventions and unresolved issues of MN in the hope of providing some new ideas for clinical and scientific researchers in the treatment of MN.

Synthesis of Ultralong Carbon Nanotubes with Ultrahigh Yields.

Ultralong carbon nanotubes (CNTs) are in huge demand in many cutting-edge fields due to their macroscale lengths, perfect structures, and extraordinary properties, while their practical application is limited by the difficulties in their mass production. Herein, we report the synthesis of ultralong CNTs with a dramatically increased yield by a simple but efficient substrate interception and direction strategy (SIDS), which couples the advantages of floating-catalyst chemical vapor deposition with the flying-kite-like growth mechanism of ultralong CNTs. The SIDS-assisted approach prominently improves the catalyst utilization and significantly increases the yield. The areal density of the ultralong CNT arrays with length of over 1 cm reached a record-breaking value of ∼6700 CNTs mm-1, which is 2-3 orders of magnitude higher than the previously reported values obtained by traditional methods. The SIDS provides a solution for synthesizing high-quality ultralong CNTs with high yields, laying the foundation for their mass production.

Scalable Structural Coloration of Carbon Nanotube Fibers via a Facile Silica Photonic Crystal Self-Assembly Strategy.

The coloration of carbon nanotube (CNT) fibers (CNTFs) is a long-lasting challenge because of the intrinsic black color and chemically inert surfaces of CNTs, which cannot satisfy the aesthetic and fashion requirements and thus significantly restrict their performance in many cutting-edge fields. Recently, a structural coloration method of CNTFs was developed by our group using atomic layer deposition (ALD) technology. However, the ALD-based structural coloration method of CNTFs is expensive, time-consuming, and not suitable for the large-scale production of colorful CNTFs. Herein, we developed a very simple and scalable liquid-phase method to realize the structural coloration of CNTFs. A SiO2/ethanol dispersion containing SiO2 nanospheres with controllable sizes was synthesized. The SiO2 nanospheres could self-assemble into photonic crystal layers on the surface of CNTFs and exhibited brilliant colors. The colors of SiO2 nanoparticle-coated CNTFs could be easily changed by tuning the sizes of SiO2 nanospheres. This method provides a simple, effective, and promising way for the large-scale production of colorful CNTFs.

The nuclear factor kappa B signaling pathway is a master regulator of renal fibrosis.

Renal fibrosis is increasingly recognized as a global public health problem. Acute kidney injury (AKI) and chronic kidney disease (CKD) both result in renal fibrosis. Oxidative stress and inflammation play central roles in progressive renal fibrosis. Oxidative stress and inflammation are closely linked and form a vicious cycle in which oxidative stress induces inflammation through various molecular mechanisms. Ample evidence has indicated that a hyperactive nuclear factor kappa B (NF-ƙB) signaling pathway plays a pivotal role in renal fibrosis. Hyperactive NF-ƙB causes the activation and recruitment of immune cells. Inflammation, in turn, triggers oxidative stress through the production of reactive oxygen species and nitrogen species by activating leukocytes and resident cells. These events mediate organ injury through apoptosis, necrosis, and fibrosis. Therefore, developing a strategy to target the NF-ƙB signaling pathway is important for the effective treatment of renal fibrosis. This Review summarizes the effect of the NF-ƙB signaling pathway on renal fibrosis in the context of AKI and CKD (immunoglobulin A nephropathy, membranous nephropathy, diabetic nephropathy, hypertensive nephropathy, and kidney transplantation). Therapies targeting the NF-ƙB signaling pathway, including natural products, are also discussed. In addition, NF-ƙB-dependent non-coding RNAs are involved in renal inflammation and fibrosis and are crucial targets in the development of effective treatments for kidney disease. This Review provides a clear pathophysiological rationale and specific concept-driven therapeutic strategy for the treatment of renal fibrosis by targeting the NF-ƙB signaling pathway.

Bioinspired Self-Adhesive Lubricated Coating for the Surface Functionalization of Implanted Biomedical Devices.

The lubrication property of implanted biomedical devices is of great significance as it affects the clinical performance owing to direct contact with soft tissues. In the present study, a bioinspired copolymer with dual functions of both self-adhesion and lubrication was synthesized with N-(3-aminopropyl) methacrylamide hydrochloride, gallic acid, and 3-[dimethyl-[2-(2-methylprop-2-enoyloxy) ethyl] azaniumyl] propane-1-sulfonate by free radical polymerization and a carbodiimide coupling reaction. The copolymer was further modified on the surface of poly(vinyl chloride) (PVC) samples using a simple dip-coating method and was characterized by different evaluations including Fourier transform infrared spectroscopy, the water contact angle, X-ray photoelectron spectroscopy, optical interferometry, and atomic force microscopy. Additionally, the results of a series of tribological tests at the microscopic level demonstrated that the friction coefficient of the copolymer-coated PVC samples was significantly reduced compared to that of the bare PVC samples. Furthermore, the pull out test at the macroscopic level was performed using copolymer-coated PVC catheters on a poly(dimethylsiloxane)-based test rig, and the result showed that the copolymer-coated PVC catheters were endowed with a greatly decreased and much more stable pull out force compared with that of the bare PVC catheters. In conclusion, the bioinspired self-adhesive lubricated coating developed herein may be applied as a universal and versatile method to enhance the lubrication performance of implanted biomedical devices.

Bioinspired Surface Functionalization of Poly(ether ether ketone) for Enhancing Osteogenesis and Bacterial Resistance.

In orthopedics, developing functionalized biomaterials to enhance osteogenesis and bacterial resistance is crucial. Although poly(ether ether ketone) (PEEK) is regarded as an important engineering plastic for biomedical material with excellent mechanical properties and biocompatibility, its biological inertness has greatly compromised its application in biomedical engineering. Inspired by the catecholamine chemistry of mussels, we propose a universal and versatile approach for enhancing the osteogenesis and antibacterial performances of PEEK based on surface functionalization of polydopamine-modified nanohydroxyapatite and lysozyme simultaneously. The characterizations of surface morphology and elemental composition revealed that the composite coating was successfully added to the PEEK surface. Additionally, the in vitro cell experiment and biomineralization assay indicated that the composite coating-modified PEEK was biocompatible with significantly improved bioactivity to promote osteogenesis and biomineralization compared with the untreated PEEK. Furthermore, the antibacterial test demonstrated that the composite coating had a strongly destructive effect on two bacteria (Staphylococcus aureus and Escherichia coli) with antibacterial ratios of 98.7% and 96.1%, respectively. In summary, the bioinspired method for surface functionalization can enhance the osteogenesis and bacterial resistance of biomedical materials, which may represent a potential approach for designing functionalized implants in orthopedics.

Cooperative Spectrum Sensing Based on Multi-Features Combination Network in Cognitive Radio Network.

Cognitive radio, as a key technology to improve the utilization of radio spectrum, acquired much attention. Moreover, spectrum sensing has an irreplaceable position in the field of cognitive radio and was widely studied. The convolutional neural networks (CNNs) and the gate recurrent unit (GRU) are complementary in their modelling capabilities. In this paper, we introduce a CNN-GRU network to obtain the local information for single-node spectrum sensing, in which CNN is used to extract spatial feature and GRU is used to extract the temporal feature. Then, the combination network receives the features extracted by the CNN-GRU network to achieve multifeatures combination and obtains the final cooperation result. The cooperative spectrum sensing scheme based on Multifeatures Combination Network enhances the sensing reliability by fusing the local information from different sensing nodes. To accommodate the detection of multiple types of signals, we generated 8 kinds of modulation types to train the model. Theoretical analysis and simulation results show that the cooperative spectrum sensing algorithm proposed in this paper improved detection performance with no prior knowledge about the information of primary user or channel state. Our proposed method achieved competitive performance under the condition of large dynamic signal-to-noise ratio.

1-Hydroxypyrene mediates renal fibrosis through aryl hydrocarbon receptor signalling pathway.

BACKGROUND AND PURPOSE: In chronic kidney disease (CKD), patients inevitably reach end-stage renal disease and require renal transplant. Evidence suggests that CKD is associated with metabolite disorders. However, the molecular pathways targeted by metabolites remain enigmatic. Here, we describe roles of 1-hydroxypyrene in mediating renal fibrosis. EXPERIMENTAL APPROACH: We analysed 5406 urine and serum samples from patients with Stage 1-5 CKD using metabolomics, and 1-hydroxypyrene was identified and validated using longitudinal and drug intervention cohorts as well as 5/6 nephrectomised and adenine-induced rats. KEY RESULTS: We identified correlations between the urine and serum levels of 1-hydroxypyrene and the estimated GFR in patients with CKD onset and progression. Moreover, increased 1-hydroxypyrene levels in serum and kidney tissues correlated with decreased renal function in two rat models. Up-regulated mRNA expression of aryl hydrocarbon receptor and its target genes, including CYP1A1, CYP1A2 and CYP1B1, were observed in patients and rats with progressive CKD. Further we showed up-regulated mRNA expression of aryl hydrocarbon receptor and its three target genes, plus up-regulated nuclear aryl hydrocarbon receptor protein levels in mice and HK-2 cells treated with 1-hydroxypyrene, which caused accumulation of extracellular matrix components. Treatment with aryl hydrocarbon receptor short hairpin RNA or flavonoids inhibited mRNA expression of aryl hydrocarbon receptor and its target genes in 1-hydroxypyrene-induced HK-2 cells and mice. CONCLUSION AND IMPLICATIONS: Metabolite 1-hydroxypyrene was demonstrated to mediate renal fibrosis through activation of the aryl hydrocarbon receptor signalling pathway. Targeting aryl hydrocarbon receptor may be an alternative therapeutic strategy for CKD progression.