Functional CeOx nanoglues for robust atomically dispersed catalysts.

Single-atom catalysts1 make exceptionally efficient use of expensive noble metals and can bring out unique properties1-3. However, applications are usually compromised by limited catalyst stability, which is due to sintering3,4. Although sintering can be suppressed by anchoring the metal atoms to oxide supports1,5,6, strong metal-oxygen interactions often leave too few metal sites available for reactant binding and catalysis6,7, and when exposed to reducing conditions at sufficiently high temperatures, even oxide-anchored single-atom catalysts eventually sinter4,8,9. Here we show that the beneficial effects of anchoring can be enhanced by confining the atomically dispersed metal atoms on oxide nanoclusters or 'nanoglues', which themselves are dispersed and immobilized on a robust, high-surface-area support. We demonstrate the strategy by grafting isolated and defective CeOx nanoglue islands onto high-surface-area SiO2; the nanoglue islands then each host on average one Pt atom. We find that the Pt atoms remain dispersed under both oxidizing and reducing environments at high temperatures, and that the activated catalyst exhibits markedly increased activity for CO oxidation. We attribute the improved stability under reducing conditions to the support structure and the much stronger affinity of Pt atoms for CeOx than for SiO2, which ensures the Pt atoms can move but remain confined to their respective nanoglue islands. The strategy of using functional nanoglues to confine atomically dispersed metals and simultaneously enhance their reactivity is general, and we anticipate that it will take single-atom catalysts a step closer to practical applications.

Rapid production of kilogram-scale graphene nanoribbons with tunable interlayer spacing for an array of renewable energy.

Graphene nanoribbons (GNRs) are widely recognized as intriguing building blocks for high-performance electronics and catalysis owing to their unique width-dependent bandgap and ample lone pair electrons on both sides of GNR, respectively, over the graphene nanosheet counterpart. However, it remains challenging to mass-produce kilogram-scale GNRs to render their practical applications. More importantly, the ability to intercalate nanofillers of interest within GNR enables in-situ large-scale dispersion and retains structural stability and properties of nanofillers for enhanced energy conversion and storage. This, however, has yet to be largely explored. Herein, we report a rapid, low-cost freezing-rolling-capillary compression strategy to yield GNRs at a kilogram scale with tunable interlayer spacing for situating a set of functional nanomaterials for electrochemical energy conversion and storage. Specifically, GNRs are created by sequential freezing, rolling, and capillary compression of large-sized graphene oxide nanosheets in liquid nitrogen, followed by pyrolysis. The interlayer spacing of GNRs can be conveniently regulated by tuning the amount of nanofillers of different dimensions added. As such, heteroatoms; metal single atoms; and 0D, 1D, and 2D nanomaterials can be readily in-situ intercalated into the GNR matrix, producing a rich variety of functional nanofiller-dispersed GNR nanocomposites. They manifest promising performance in electrocatalysis, battery, and supercapacitor due to excellent electronic conductivity, catalytic activity, and structural stability of the resulting GNR nanocomposites. The freezing-rolling-capillary compression strategy is facile, robust, and generalizable. It renders the creation of versatile GNR-derived nanocomposites with adjustable interlay spacing of GNR, thereby underpinning future advances in electronics and clean energy applications.

RPGRIP1L as a new biomarker for prognosis and tumor immune of breast cancer.

The Retinitis pigmentosa GTPase regulator interacting protein 1-like (RPGRIP1L) gene encodes an important protein that performs various physiological functions. Variants of RPGRIP1L are related to a number of diseases. However, it is currently unknown whether RPGRIP1L is correlated with breast invasive carcinoma (BRCA). In BRCA tissue specimens, the expression of RPGRIP1L was found to be elevated in comparison to its levels in normal breast tissue. A notable decline in survival rates was associated with patients exhibiting heightened RPGRIP1L gene expression. Consistent with these findings, our data also show the above results. Furthermore, elevated expression of RPGRIP1L corresponded with a spectrum of unfavorable clinicopathological features, including the presence of human epidermal growth factor receptor 2 (HER2) positive, estrogen receptor (ER) positive, over 60 years old, T2, N0, and N3. At the same time, our research indicated that 50 genes and 15 proteins were positively related to RPGRIP1L, and that these proteins and genes were mostly involved in T cell proliferation, immune response, cytokine activity, and metabolic regulation. In addition, in the present study, there was a significant correlation between RPGRIP1L expression and immune cell infiltration. Finally, we found that four Chemicals could downregulate the expression of RPGRIP1L. Altogether, our results strongly indicated that RPGRIP1L might serve as a new prognostic biomarker for BRCA.

A broadly applicable, stress-mediated bacterial death pathway regulated by the phosphotransferase system (PTS) and the cAMP-Crp cascade.

Recent work indicates that killing of bacteria by diverse antimicrobial classes can involve reactive oxygen species (ROS), as if a common, self-destructive response to antibiotics occurs. However, the ROS-bacterial death theory has been challenged. To better understand stress-mediated bacterial death, we enriched spontaneous antideath mutants of Escherichia coli that survive treatment by diverse bactericidal agents that include antibiotics, disinfectants, and environmental stressors, without a priori consideration of ROS. The mutants retained bacteriostatic susceptibility, thereby ruling out resistance. Surprisingly, pan-tolerance arose from carbohydrate metabolism deficiencies in ptsI (phosphotransferase) and cyaA (adenyl cyclase); these genes displayed the activity of upstream regulators of a widely shared, stress-mediated death pathway. The antideath effect was reversed by genetic complementation, exogenous cAMP, or a Crp variant that bypasses cAMP binding for activation. Downstream events comprised a metabolic shift from the TCA cycle to glycolysis and to the pentose phosphate pathway, suppression of stress-mediated ATP surges, and reduced accumulation of ROS. These observations reveal how upstream signals from diverse stress-mediated lesions stimulate shared, late-stage, ROS-mediated events. Cultures of these stable, pan-tolerant mutants grew normally and were therefore distinct from tolerance derived from growth defects described previously. Pan-tolerance raises the potential for unrestricted disinfectant use to contribute to antibiotic tolerance and resistance. It also weakens host defenses, because three agents (hypochlorite, hydrogen peroxide, and low pH) affected by pan-tolerance are used by the immune system to fight infections. Understanding and manipulating the PtsI-CyaA-Crp­mediated death process can help better control pathogens and maintain beneficial microbiota during antimicrobial treatment.

Efficient Interfacial Sites between Metallic and Oxidized Cobalt for Propene Hydroformylation.

Currently, the hydroformylation of short olefins is operated almost exclusively by using Rh catalysts. Considering the high cost and scarcity of rhodium resources, it is important to develop non-noble metal catalysts toward hydroformylation. Herein, we report an efficient cobalt-based catalyst rich in interfacial sites between metallic and oxidized cobalt species for the hydroformylation of short olefin, propene, under a moderate syngas pressure. The catalyst exhibited a high specific activity of 252 mol molCo-1 h-1 in toluene under 2 bar of propene and 40 bar of CO/H2 mixed gas (CO/H2 = 1:1) at 160 °C. According to mechanistic studies, the interface of metallic and oxidized cobalt species promoted the adsorption of CO and propene. Moreover, the interfacial sites lowered the energy barrier for CO* hydrogenation and C-C coupling compared with metallic cobalt.

CO-Assisted Methane Oxidation into Oxygenates over Surface Platinum-Titanium Alloyed Layers.

Methane oxidation using molecular oxygen remains a grand challenge in which the obstacle is not only the activation of methane but also the reaction with oxygen, considering the mismatch of the ground spin states. Herein, we report TiO2-supported Pt nanocrystals (Pt/TiO2) with surface Pt-Ti alloyed layers that directly convert methane into oxygenates by using O2 as the oxidant with the assistance of CO. The oxygenate yield reached 749.8 mmol gPt-1 in a H2O aqueous solution over 0.1% Pt/TiO2 under 31 bar of mixed gas (20:5:6 CH4:CO:O2) at 150 °C for 3 h, while the CH3OH selectivity was 62.3%. On the basis of the control experiments and spectroscopic results, we identified the surface Pt-Ti alloy as the active sites. Moreover, CO promoted the dissociation of O2 on the surface of Pt-Ti alloyed layers and the subsequent activation of CH4 to form oxygenated products.

Bipyridine-Confined Silver Single-Atom Catalysts Facilitate In-Plane C-O Coupling for Propylene Electrooxidation.

The electrooxidation of propylene presents a promising route for the production of 1,2-propylene glycol (PG) under ambient conditions. However, the C-O coupling process remains a challenge owing to the high energy barrier. In this work, we developed a highly efficient electrocatalyst of bipyridine-confined Ag single atoms on UiO-bpy substrates (Ag SAs/UiO-bpy), which exposed two in-plane coordination vacancies during reaction for the co-adsorption of key intermediates. Detailed structure and electronic property analyses demonstrate that CH3CHCH2OH* and *OH could stably co-adsorb in a square planar configuration, which then accelerates the charge transfer between them. The combination of stable co-adsorption and efficient charge transfer facilitates the C-O coupling process, thus significantly lowering its energy barrier. At 2.4 V versus a reversible hydrogen electrode, Ag SAs/UiO-bpy achieved a record-high activity of 61.9 gPG m-2 h-1. Our work not only presents a robust electrocatalyst but also advances a new perspective on catalyst design for propylene electrooxidation.

Close Intimacy between PtIn Clusters and Zeolite Channels for Ultrastability toward Propane Dehydrogenation.

Propane dehydrogenation (PDH) serves as a pivotal intentional technique to produce propylene. The stability of PDH catalysts is generally restricted by the readsorption of propylene which can subsequently undergo side reactions for coke formation. Herein, we demonstrate an ultrastable PDH catalyst by encapsulating PtIn clusters within silicalite-1 which serves as an efficient promoter for olefin desorption. The mean lifetime of PtIn@S-1 (S-1, silicalite-1) was calculated as 37317 h with high propylene selectivity of >97% at 580 °C with a weight hourly space velocity (WHSV) of 4.7 h-1. With an ultrahigh WHSV of 1128 h-1, which pushed the catalyst away from the equilibrium conversion to 13.3%, PtIn@S-1 substantially outperformed other reported PDH catalysts in terms of mean lifetime (32058 h), reaction rates (3.42 molpropylene gcat-1 h-1 and 341.90 molpropylene gPt-1 h-1), and total turnover number (14387.30 kgpropylene gcat-1). The developed catalyst is likely to lead the way to scalable PDH applications.

T6SS nuclease effectors in Pseudomonas syringae act as potent antimicrobials in interbacterial competition.

Type VI secretion system (T6SS) is a potent weapon employed by various Pseudomonas species to compete with neighboring microorganisms for limited nutrients and ecological niches. However, the involvement of T6SS effectors in interbacterial competition within the phytopathogen Pseudomonas syringae remains unknown. In this study, we examined two T6SS clusters in a wild-type P. syringae MB03 and verified the involvement of one cluster, namely, T6SS-1, in interbacterial competition. Additionally, our results showed that two T6SS DNase effectors, specifically Tde1 and Tde4, effectively outcompeted antagonistic bacteria, with Tde4 playing a prominent role. Furthermore, we found several cognate immunity proteins, including Tde1ia, Tde1ib, and Tde4i, which are located in the downstream loci of their corresponding effector protein genes and worked synergistically to protect MB03 cells from self-intoxication. Moreover, expression of either Tde1 or C-terminus of Tde4 in Escherichia coli cells induced DNA degradation and changes in cell morphology. Thus, our results provide new insights into the role of the T6SS effectors of P. syringae in the interbacterial competition in the natural environment. IMPORTANCE: The phytopathogen Pseudomonas syringae employs an active type VI secretion system (T6SS) to outcompete other microorganisms in the natural environment, particularly during the epiphytic growth in the phyllosphere. By examining two T6SS clusters in P. syringae MB03, T6SS-1 is found to be effective in killing Escherichia coli cells. We highlight the excellent antibacterial effect of two T6SS DNase effectors, namely, Tde1 and Tde4. Both of them function as nuclease effectors, leading to DNA degradation and cell filamentation in prey cells, ultimately resulting in cell death. Our findings deepen our understanding of the T6SS effector repertoires used in P. syringae and will facilitate the development of effective antibacterial strategies.

Experimental Demonstration of Topological Catalysis for CO2 Electroreduction.

The past decade has witnessed substantial progress in understanding nontrivial band topology and discovering exotic topological materials in condensed-matter physics. Recently, topological physics has been further extended to the chemistry discipline, leading to the emergence of topological catalysis. In principle, the topological effect is detectable in catalytic reactions, but no conclusive evidence has been reported yet. Herein, by precisely manipulating the topological surface state (TSS) of Bi2Se3 nanosheets through thickness control and the application of a magnetic field, we provide direct experimental evidence to illustrate topological catalysis for CO2 electroreduction. With and without the cooperation of TSS, CO2 is mainly reduced into liquid fuels (HCOOH and H2C2O4) and CO, exhibiting high (up to 90% at -1.1 V versus reversible hydrogen electrode) and low Faradaic efficiency (FE), respectively. Theoretically, the product and FE difference can be attributed to the TSS-regulated adsorption of key intermediates and the reduced barrier of the potential-determining step. Our work demonstrates the inherent correlation between band topology and electrocatalysis, paving a new avenue for designing high-performance catalysts.

Synthesis of Metal-Nitrogen-Carbon Electrocatalysts with Atomically Regulated Nitrogen-Doped Polycyclic Aromatic Hydrocarbons.

Tuning the active site structure of metal-nitrogen-carbon electrocatalysts has recently attracted increasing interest. Herein, we report a bottom-up synthesis strategy in which atomically regulated N-doped polycyclic aromatic hydrocarbons (N-PAHs) of NxC42-x (x = 1, 2, 3, 4) were used as ligands to allow tuning of the active site's structures of M-Nx and establish correlations between the structures and electrocatalytic properties. Based on the synthesis process, detailed characterization, and DFT calculation results, active structures of Nx-Fe1-Nx in Fe1-Nx/RGO catalysts were constructed. The results demonstrated that the extra uncoordinated N atoms around the Fe1-N4 moieties disrupted the π-conjugated NxC42-x ligands, which led to more localized electronic state in the Fe1-N4 moieties and superior catalytic performance. Especially, the Fe1-N4/RGO exhibited optimized performance for ORR with E1/2 increasing by 80 mV and Jk at 0.85 V improved 18 times (compared with Fe1-N1/RGO). This synthesis strategy utilizing N-PAHs holds significant promise for enhancing the controllability of metal-nitrogen-carbon electrocatalyst preparation.

Screening seven-electron boron-centered radicals for dinitrogen activation.

The activation of dinitrogen is significant as nitrogen-containing compounds play an important role in industries. However, the inert NN triple bond caused by its large HOMO-LUMO gap (10.8 eV) and high bond dissociation energy (945 kJ mol-1 ) renders its activation under mild conditions particularly challenging. Recent progress shows that a few main group species can mimic transition metal complexes to activate dinitrogen. Here, we demonstrate that a series of seven-electron (7e) boron-centered radical can be used to activate N2 via density functional theory calculations. It is found that boron-centered radicals containing amine ligand perform best on the thermodynamics of dinitrogen activation. In addition, when electron-donating groups are introduced at the boron atom, these radicals can be used to activate N2 with low reaction barriers. Further analysis suggests that the electron transfer from the boron atom to the π* orbitals of dinitrogen is essential for its activation. Our findings suggest great potential of 7e boron radicals in the field of dinitrogen activation.

Multiparametric US for Identifying Metabolic Dysfunction-associated Steatohepatitis: A Prospective Multicenter Study.

Background Noninvasive evaluation of metabolic dysfunction-associated fatty liver disease (MAFLD) with multiparametric US is essential, but multicenter studies are lacking. Purpose To evaluate the ability of multiparametric US with attenuation imaging (ATI) and two-dimensional (2D) shear-wave elastography (SWE) for predicting metabolic dysfunction-associated steatohepatitis (MASH) in participants with MAFLD, regardless of hepatitis B virus infection status. Materials and Methods This prospective cross-sectional multicenter study of consecutive adults with MAFLD who underwent multiparametric US with ATI and 2D SWE, as well as liver biopsy, from September 2020 to June 2022 was conducted in 12 tertiary hospitals in China. Multivariable logistic regression was performed to assess risk factors associated with MASH. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate diagnostic performance in predicting MASH in training and validation groups (6:4 ratio of participants), and for a post hoc subgroup analysis of hepatitis B virus infection and diabetes. Results A total of 424 participants (median age, 47 years; IQR, 34-59 years; 244 male) were evaluated, including 332 participants (78%) with MASH and 92 (22%) without. Attenuation coefficient (AC) (odds ratio [OR], 3.32 [95% CI: 1.94, 5.71]; P < .001), alanine aminotransferase (ALT) level (OR, 4.42 [95% CI: 1.78, 10.94]; P = .001), and international normalized ratio (INR) (OR, 0.59 [95% CI: 0.37, 0.95]; P = .03) were independently associated with MASH. A combined model (AC, ALT, and INR) had AUCs of 0.85 (95% CI: 0.79, 0.91) and 0.77 (95% CI: 0.69, 0.85) for predicting MASH in the training and validation groups, respectively. AUC values for the subgroups with and without diabetes were 0.83 (95% CI: 0.72, 0.94) and 0.81 (95% CI: 0.75, 0.87) and for the subgroups with and without hepatitis B were 0.82 (95% CI: 0.74, 0.90) and 0.79 (95% CI: 0.71, 0.87), respectively. Conclusion A model combining AC, ALT level, and INR showed good discrimination ability for predicting MASH in participants with MAFLD. Clinical trial registration no. NCT04551716 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Reuter in this issue.

Tetrahedral Occupied V Ions Enabling Reversible Three-Electron Redox of Cr3+ /Cr6+ in Layered Cathode Materials for Potassium-Ion Batteries.

Reversible three-electron redox of Cr3+ /Cr6+ in layered cathode materials for rechargeable batteries is very attractive in layered cathode materials, which leads to high capacity and energy density for rechargeable batteries. However, the poor reversibility and Cr-ion migration make it very challenging. In this work, by introducing V ions into tetrahedral sites of layer-structured NaCrO2 , reversible three-electron redox of Cr3+ /Cr6+ is realized successfully in NaCr0.92 V0.05 O2 (NCV05) cathode for potassium-ion batteries with a cut-off voltage of 4.0 V. V ions can weaken the attraction of Cr to electrons, leading to enhanced valence change of Cr ions. On the other hand, V in tetrahedral sites can facilitate the reversible migration of Cr between octahedral and tetrahedral sites via coulombic repulsion to realize the reversible redox between Cr3+ and Cr6+ during charge and discharge processes. In addition, V ions can inhibit the phase transition from O3 phase to O'3 phase during the charge process by adjusting the crystal lattices. As a result, the NaCr0.92 V0.05 O2 cathode exhibits a high reversible capacity of 130 mAh g-1 with promising cycle stability and rate capability. The strategy opens new opportunity for developing high-capacity cathode materials for potassium-ion batteries.

Second Near-Infrared Macrophage-Biomimetic Nanoprobes for Photoacoustic Imaging of Neuroinflammation.

Neuroinflammation is a significant pathological event involving the neurodegenerative process associated with many neurological disorders. Diagnosis and treatment of neuroinflammation in its early stage are essential for the prevention and management of neurological diseases. Herein, we designed macrophage membrane-coated photoacoustic (PA) probes (MSINPs), with targeting specificities based on naturally existing target-ligand interactions for the early diagnosis of neuroinflammation. The second near-infrared dye, IR1061, was doped into silica as the core and was encapsulated with a macrophage membrane. In vitro as well as in vivo, the MSINPs could target inflammatory cells via the inflammation chemotactic effect. PA imaging was used to trace the MSINPs in a neuroinflammation mouse model and showed a great targeted effect of MSINPs in the prefrontal cortex. Therefore, the biomimetic nanoprobe prepared in this study offers a new strategy for PA molecular imaging of neuroinflammation, which can enhance our understanding of the evolution of neuroinflammation in specific brain regions.

RNA sequencing of the thalamus and rostral ventral medulla in rats with chronic orofacial pain.

Diagnosing and treating chronic orofacial pain is challenging due to its complex structure and limited understanding of its causes and mechanisms. In this study, we used RNA sequencing to identify differentially expressed genes (DEGs) in the rostral ventral medulla (RVM) and thalamus of rats with persistent orofacial pain, aiming to explore its development. DEGs were functionally analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results showed a significant association between immune response and pain in this model. Key DEG mRNA expression trends were further validated using real-time quantitative polymerase chain reaction (RT-PCR), confirming their crucial roles in chronic orofacial pain. After injecting complete Freund's adjuvant (CFA) into the bilateral temporomandibular joint cavity for 14 days, we observed 293 upregulated genes and 14 downregulated genes in the RVM, and 1086 upregulated genes and 37 downregulated genes in the thalamus. Furthermore, we identified 27 common DEGs with altered expression (upregulation) in both the thalamus and RVM, including Cd74, C3, Cxcl13, C1qb, Itgal, Fcgr2b, C5ar1, and Tlr2, which are pain-associated genes. Protein-protein interaction (PPI) analysis using Cytoscape revealed the involvement of Toll-like receptors, complement system, differentiation clusters, and antigen presentation-related proteins in the interaction between the thalamus and RVM. The results of this study show that the immune system seems to have a more significant influence on chronic orofacial pain. There may be direct or indirect influence between the thalamus and RVM, which may participate in the regulation of chronic orofacial pain.

Al(OTf)3-Catalyzed Regioselective N2-Arylation of Tetrazoles with Diazo Compounds.

Regioselective methods to access alkylated tetrazoles still remain a challenging goal. Herein, we describe a novel regioselective protocol for N2-arylation of tetrazoles with diazo compounds using inexpensive Al(OTf)3. This reaction could be conducted under mild conditions to access a diverse array of alkylated tetrazoles with 2-substituted tetrazoles as the major products, demonstrating a comprehensive range of substrate compatibility and excellent functional group compatibility. Mechanistic studies revealed a carbene-free process in this reaction procedure. Furthermore, the scale-up reaction and transformations of the N2-arylation of tetrazole products demonstrated the potential of this strategy.

Synthesis of 2,4-Disubstituted Oxazoles and Thiazoles via Brønsted Acid-Catalyzed Cyclization of α-diazoketones with Amides.

A novel method is described for the synthesis of 2,4-disubstituted oxazole and thiazole derivates via the coupling of α-diazoketones with (thio)amides or thioureas using trifluoromethanesulfonic acid (TfOH) as a catalyst. This protocol is characterized by mild reaction conditions, metal-free, and simplicity and also features good functional group tolerance, good to excellent yields, and a broad substrate scope with more than 40 examples. Experimental studies suggest a mechanism involving 2-oxo-2-phenylethyl trifluoromethanesulfonate as the key intermediate.

An LC-MS/MS method for serum cystatin C quantification and its comparison with two commercial immunoassays.

OBJECTIVES: The standardization of cystatin C (CysC) measurement has received increasing attention in recent years due to its importance in estimating glomerular filtration rate (GFR). Mass spectrometry-based assays have the potential to provide an accuracy base for CysC measurement. However, a precise, accurate and sustainable LC-MS/MS method for CysC is still lacking. METHODS: The developed LC-MS/MS method quantified CysC by detecting signature peptide (T3) obtained from tryptic digestion. Stable isotope labeled T3 peptide (SIL-T3) was spiked to control matrix effects and errors caused by liquid handling. The protein denaturation, reduction and alkylation procedures were combined into a single step with incubation time of 1 h, and the digestion lasted for 3.5 h. In the method validation, digestion time-course, imprecision, accuracy, matrix effect, interference, limit of quantification (LOQ), carryover, linearity, and the comparability to two routine immunoassays were evaluated. RESULTS: No significant matrix effect or interference was observed with the CysC measurement. The LOQ was 0.21 mg/L; the within-run and total imprecision were 1.33-2.05 % and 2.18-3.90 % for three serum pools (1.18-5.34 mg/L). The LC-MS/MS method was calibrated by ERM-DA471/IFCC and showed good correlation with two immunoassays traceable to ERM-DA471/IFCC. However, significant bias was observed for immunoassays against the LC-MS/MS method. CONCLUSIONS: The developed LC-MS/MS method is robust and simpler and holds the promise to provide an accuracy base for routine immunoassays, which will promote the standardization of CysC measurement.

Aberrant HO-1/NQO1-Reactive Oxygen Species-ERK Signaling Pathway Contributes to Aggravation of TPA-Induced Irritant Contact Dermatitis in Nrf2-Deficient Mice.

NF-erythroid 2-related factor 2 (Nrf2) is a major transcription factor to protect cells against reactive oxygen species (ROS) and reactive toxicants. Meanwhile, Nrf2 can inhibit contact dermatitis through redox-dependent and -independent pathways. However, the underlying mechanisms of how Nrf2 mediates irritant contact dermatitis (ICD) are still unclear. In this article, we elucidated the role of Nrf2 in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute ICD. Our study demonstrated that the ear thickness, redness, swelling, and neutrophil infiltration were significantly increased, accompanied by increased expression of inflammatory cytokines (IL-1α, IL-1ß, IL-6, etc.) and decreased expression of antioxidant genes (HO-1 and NQO1) in Nrf2 knockout mice. Moreover, ERK phosphorylation was elevated in mouse embryonic fibroblasts (MEFs) from Nrf2 knockout mouse. Inhibition of ERK significantly alleviated TPA-induced cutaneous inflammation and ROS accumulation in MEFs derived from mouse. Conversely, ROS scavenging inhibited the ERK activation and TPA-induced inflammation in MEFs. Taken together, the findings illustrate the key role of the Nrf2/ROS/ERK signaling pathway in TPA-induced acute ICD.