Introduction of the difluoromethyl group at the meta- or para-position of pyridines through regioselectivity switch.

Difluoromethyl pyridines have gained significant attention in medicinal and agricultural chemistry. The direct C-H-difluoromethylation of pyridines represents a highly efficient economic way to access these azines. However, the direct meta-difluoromethylation of pyridines has remained elusive and methods for site-switchable regioselective meta- and para-difluoromethylation are unknown. Here, we demonstrate the meta-C-H-difluoromethylation of pyridines through a radical process by using oxazino pyridine intermediates, which are easily accessed from pyridines. The selectivity can be readily switched to para by in situ transformation of the oxazino pyridines to pyridinium salts upon acid treatment. The preparation of various meta- and para-difluoromethylated pyridines through this approach is presented. The mild conditions used also allow for the late-stage meta- or para-difluoromethylation of pyridine containing drugs. Sequential double functionalization of pyridines is presented, which further underlines the value of this work.

Meta-Selective Copper-Catalyzed C-H Arylation of Pyridines and Isoquinolines through Dearomatized Intermediates.

C(sp2)-H functionalization offers an efficient strategy for the synthesis of various elaborated N-containing heteroarenes. Along these lines, oxazino pyridines that can be readily prepared from pyridines, have been introduced as powerful substrates in radical- and ionic-mediated meta-C-H functionalization. However, the regioselective meta-C-H arylation of pyridines remains a great challenge. Herein, a copper-catalyzed meta-selective C-H arylation of pyridines and isoquinolines through bench-stable dearomatized intermediates is reported. Electrophilic aryl-Cu(III) species, generated from readily accessible aryl I(III) reagents, enable the efficient meta-arylation of a broad range of pyridines and isoquinolines. The method also allows the meta-selective alkenylation of these heteroarenes using the corresponding alkenyl I(III)-reagents. Late-stage arylation of drug-derived pyridines and larger-scale experiments demonstrate the potential of this synthetic methodology.

Lower soil nitrogen-oxide emissions associated with enhanced denitrification under replacing mineral fertilizer with manure in orchard soils.

Emerging evidence suggests that replacing mineral fertilizers with organic livestock manure can effectively suppress reactive gaseous nitrogen (N) emissions from soils. However, the extent of this mitigation potential and the underlying microbial mechanisms in orchards remain unclear. To address this knowledge gap, we measured nitrous and nitric oxide (N2O and NO) emissions, microbial N cycling gene abundance, and N2O isotopomer ratios in pear and citrus orchards under three different fertilization regimes: no fertilization, mineral fertilizer, and manure plus mineral fertilizer. The results showed that although manure application caused large transient peaks of N2O, it reduced cumulative emissions of N2O and NO by an average of 20 % and 17 %, respectively, compared to the mineral fertilizer treatment. Partial replacement of mineral fertilizers with manure enhanced the contribution of AOA to nitrification and reduced the contribution of AOB, thus reducing N2O emissions from nitrification. Isotope analysis suggested that the pathway for N2O production in the soils of both orchards was dominated by bacterial denitrification and nitrifier denitrification. The manure treatment reduced the ratio of denitrification products. Additionally, the dual isotope mixing model results indicated that partially replacing mineral fertilizers with manure could promote soil denitrification, resulting in more N2O being reduced. N-oxide emissions were on average 67 % higher in the pear orchard than in the citrus orchard, probably due to the differences in soil physicochemical properties and growth habits between the two orchards. These findings underscore the potential of partially replacing mineral fertilizers with organic manure in orchards to reduce gaseous N emissions, contributing to the transition towards environmentally sustainable and climate-smart agricultural practices.

Ethyl cellulose/gelatin/ß-cyclodextrin/curcumin nanofibrous membrane with antibacterial and formaldehyde adsorbable capabilities for lightweight and high-performance air filtration.

Functionalization of bio-based nanofibers is the development tendency of high-performance air filter. However, the conventional structural optimization strategy based on high solution conductivity greatly hinders the development of fully bio-based air filter, and not conducive to sustainable development. This work fabricated fully bio-based nanofibrous membrane with formaldehyde-adsorbable and antibacterial capabilities by electrospinning low-conductivity solution for high-performance air filtration and applied to lightweight mask. The "water-like" ethyl cellulose (EC) was selected as the base polymer to "nourish" functional materials of gelatin (GE), ß-cyclodextrin (ßCD), and curcumin (Cur), thus forming a solution system with high binding energy differences and electrospinning into ultrafine bimodal nanofibers. The filtration efficiency for 0.3 µm NaCl particles, pressure drop, and quality factor were 99.25 %, 53 Pa, and 0.092 Pa-1, respectively; the bacteriostatic rates against Escherichia coli and Staphylococcus aureus were 99.9 % and 99.4 %, respectively; the formaldehyde adsorption capacity was 442 µg/g. This is the first report on antibacterial and formaldehyde-adsorbable high-performance air filter entirely made from bio-based materials. This simple strategy will greatly broaden the selection of materials for preparing high-performance multifunctional air filter, and promote the development of bio-based air filter.

Uncovering the prevalence and drivers of antibiotic resistance genes in soils across different land-use types.

The emergence and spread of antibiotic resistance genes (ARGs) in soil due to animal excreta and organic waste is a major threat to human health and ecosystems, and global efforts are required to tackle the issue. However, there is limited knowledge of the variation in ARG prevalence and diversity resulting from different land-use patterns and underlying driving factors in soils. This study aimed to comprehensively characterize the profile of ARGs and mobile genetic elements and their drivers in soil samples collected from 11 provinces across China, representing three different land-use types, using high-throughput quantitative polymerase chain reaction and 16S rRNA amplicon sequencing. Our results showed that agricultural soil had the highest abundance and diversity of ARGs, followed by tea plantation and forest land. A total of 124 unique ARGs were detected in all samples, with shared subtypes among different land-use patterns indicating a common origin or high transmission frequency. Moreover, significant differences in ARG distribution were observed among different geographical regions, with the greatest enrichment of ARGs found in southern China. Biotic and abiotic factors, including soil properties, climatic factors, and bacterial diversity, were identified as the primary drivers associated with ARG abundance, explaining 71.8% of total ARG variation. The findings of our study demonstrate that different land-use patterns are associated with variations in ARG abundance in soil, with agricultural practices posing the greatest risk to human health and ecosystems regarding ARGs. Our identification of biotic and abiotic drivers of ARG abundance provides valuable insights into strategies for mitigating the spread of these genes. This study emphasizes the need for coordinated and integrated approaches to address the global antimicrobial resistance crisis.

Coaxial Electrospun Tai Chi-Inspired Lithium-Ion Battery Separator with High Performance and Fireproofing Capacity.

Organic flame-retardant-loaded battery separator offers a new opportunity for battery safety. However, its poor thermal stability still poses serious safety issues. Inspired by Tai Chi, an "internal-cultivating and external-practicing" core-shell nanofibrous membrane was prepared by coaxial electrospinning, wherein the shell layer was a mixture of polyvinylidene fluoride, silicon dioxide (SiO2), and graphene oxide (GO) and the core layer contained triphenyl phosphate (TPP). SiO2 and GO enhanced the thermal stability and electrochemical performance. The encapsulated TPP prevented heat transfer and the degradation of electrochemical performance caused by its direct dissolution. This separator exhibited outstanding thermal stability and flame retardancy: it did not burn and remained relatively intact (91.2%) in an open flame for 15 s. The battery assembled with a composite separator showed excellent performance: the initial capacity reached 164 mA h/g and maintained 95% after 100 charge-discharge cycles. This novel strategy endows high-performance lithium batteries with relatively higher safety.

Adaptive Fuzzy Modal Matching of Capacitive Micromachined Gyro Electrostatic Controlling.

A fuzzy PI controller was utilized to realize the modal matching between a driving and detecting model. A simulation model was built to study electrostatic decoupling controlling technology. The simulation results show that the modal matching can be gained by the fuzzy PI controller. The frequency difference between the driving mode and the detection mode is less than 1 Hz, and the offset of the input DC is smaller than 0.6 V. The optimal proportionality factor and integral coefficient are 1.5 and 20, respectively. The fuzzy PI controlling technology provides a good way for the parameter optimization to gain modal matching of micro gyro, via which the detecting accuracy and stability can be improved greatly.

Effect of fertilizer type on antibiotic resistance genes by reshaping the bacterial community and soil properties.

Conventional and bio-organic fertilizers play an important role in maintaining soil health and promoting crop growth. However, the effect of organic fertilizers on the prevalence of antibiotic resistance genes (ARGs) in the vegetable cropping system has been largely overlooked. In this study, we investigated the impacts of soil properties and biotic factors on ARG profiles by analyzing ARG and bacterial communities in vegetable copping soils with a long-term history of manure and bio-organic fertilizer application. The ARG abundance in the soil was significantly increased by 116% with manure application compared to synthetic NPK fertilizer application. This finding was corroborated by our meta-analysis that the longer the duration of manure application, the greater the response of increased soil ARG abundance. However, bio-organic fertilizers containing Trichoderma spp. Significantly reduced ARG contamination by 31% compared to manure application. About half of the ARG variation was explained by changes in bacterial abundance and structure, followed by soil properties. The mitigation of ARG by Trichoderma spp. Is achieved by altering the structure of the bacterial community and weakening the close association between bacteria and ARG prevalence. Taken together, these findings shed light on the contribution of bio-organic fertilizers in mitigating ARG contamination in agricultural soils, which can help manage the ecological risk posed by ARG inputs associated with manure application.

A C-H activation-based enantioselective synthesis of lower carbo[n]helicenes.

The three-dimensional structure of carbohelicenes has fascinated generations of molecular chemists and has been exploited in a wide range of applications. Their strong circularly polarized luminescence has attracted considerable attention in recent years due to promising applications in new optical materials. Although the enantioselective synthesis of fused carbo- and heterohelicenes has been achieved, a direct catalytic enantioselective method allowing the synthesis of lower, non-fused carbo[n]helicenes (n = 4-6) is still lacking. We report here that Pd-catalysed enantioselective C-H arylation in the presence of a unique bifunctional phosphine-carboxylate ligand provides a simple and general access to these lower carbo[n]helicenes. Computational mechanistic studies indicate that both the C-H activation and reductive elimination steps contribute to the overall enantioselectivity. The observed enantio-induction seems to arise from a combination of non-covalent interactions and steric repulsion between the substrate and ligand during the two key reductive elimination steps. The photophysical and chiroptical properties of the synthesized scalemic [n]helicenes have been systematically studied.

PGF2α facilitates pathological retinal angiogenesis by modulating endothelial FOS-driven ELR+ CXC chemokine expression.

The pathological retinal angiogenesis often causes blindness. Current anti-angiogenic therapy for proliferative retinopathy targets the vascular endothelial growth factor (VEGF), but many patients do not radically benefit from this therapy. Herein, we report that circulating prostaglandin (PG) F2α metabolites were increased in type 2 diabetic patients with proliferative retinopathy, and the PGF2α receptor (Ptgfr) was upregulated in retinal endothelial cells (ECs) from a mouse model of oxygen-induced retinopathy (OIR). Further, disruption of the PTGFR receptor in ECs attenuated OIR in mice. PGF2α promoted the proliferation and tube formation of human retinal microvascular endothelial cells (HRMECs) via the release of ELR+ CXC chemokines, such as CXCL8 and CXCL2. Mechanistically, the PGF2α /PTGFR axis potentiated ELR+ CXC chemokine expression in HRMECs through the Gq /CAMK2G/p38/ELK-1/FOS pathway. Upregulated FOS-mediated ELR+ CXC chemokine expression was observed in retinal ECs from PDR patients. Moreover, treatment with PTGFR inhibitor lessened the development of OIR in mice in a CXCR2-dependent manner. Therefore, inhibition of PTGFR may represent a new avenue for the treatment of retinal neovascularization, particularly in PDR.

Can biochar application improve the net economic benefits of tea plantations?

Biochar applied to the soil can contribute to the sustainability of agriculture by promoting ecosystem services. Tea production contributes to addressing hunger and poverty in developing countries. However, little is known about the impact of biochar amendment on ecosystem services in tea plantations. We evaluated ecosystem services from an economic assessment perspective to better understand the effects of biochar on ecosystem services and dis-services. We conducted field experiments in two subtropical tea plantations with three treatments: no fertilizer and compound fertilizers applied without and with biochar. Results showed that biochar increased the net ecosystem carbon budget by 17-fold through direct carbon addition, thus increasing regulating services. Compared to compound fertilizer alone, biochar application reduced total reactive nitrogen loss by an average of 1.8 % due to an average reduction of 16.2 % and 21.5 % in nitrous oxide and nitric oxide emissions, respectively. However, the high cost of biochar, the low environmental benefits due to the low carbon price, and the fact that biochar did not provide additional economic profit made the net ecosystem economic benefits unsatisfactory. For comparison, we set up an optimistic scenario based on the increased carbon price ($160/ton CO2-equivalent) and the documented effects of biochar on yield (+9.6 %), nitrogen leaching/runoff (-24 %), and ammonia volatilization (+14 %). The scenario analysis showed that increased yields and higher carbon prices could contribute to the increase in net ecosystem economic benefits. Taken together, our findings suggest that the impact of biochar on yield benefits is the key to biochar application and that a market-regulated carbon price accompanied by appropriate ecological compensation is necessary to effectively promote biochar application by farmers.

Metagenomic-based characterization of the gut virome in patients with polycystic ovary syndrome.

Background: Polycystic ovary syndrome (PCOS) is a complex disease that afflicts women of reproductive age, and its pathological mechanism has not been well explained. The gut microbiota is believed to be closely related to the development of PCOS. Although an important component of the gut microbiome, the role of the gut virome in the development of PCOS is still unclear. Methods: In this study, we profiled and compared the gut viral community of 50 patients with PCOS and 43 healthy women based on the analysis of their fecal whole-metagenome dataset. Results: The gut virome of PCOS patients exhibited a significant decrease in within-sample viral diversity and a remarkable alteration of the overall virome composition compared with that of healthy controls. At the family level, Siphoviridae was significantly depleted in the gut virome of patients, while Quimbyviridae was enriched. We identified 1,089 viral operational taxonomic units (vOTUs) that differed in relative abundance between the two groups, of which 455 vOTUs were enriched in PCOS patients (including numerous Bacteroidaceae phages) and 634 were enriched in controls (including numerous viruses predicted to infect Oscillospiraceae, Prevotellaceae, and Ruminococcaceae). Functional comparison of the PCOS-enriched and control-enriched vOTUs uncovered the viral functional signatures associated with PCOS. Furthermore, we demonstrated gut viral signatures for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of 0.938, demonstrating the potential of the gut virome in the prediction of PCOS. Conclusion: Our findings reveal specific alterations in viral diversity and taxonomic and functional compositions of the gut virome of PCOS patients. Further studies on the etiology of PCOS and the gut viral community will offer new prospects for treating and preventing PCOS and its related diseases.

PGE2 -EP3 axis promotes brown adipose tissue formation through stabilization of WTAP RNA methyltransferase.

Brown adipose tissue (BAT) functions as a thermogenic organ and is negatively associated with cardiometabolic diseases. N6 -methyladenosine (m6 A) modulation regulates the fate of stem cells. Here, we show that the prostaglandin E2 (PGE2 )-E-prostanoid receptor 3 (EP3) axis was activated during mouse interscapular BAT development. Disruption of EP3 impaired the browning process during adipocyte differentiation from pre-adipocytes. Brown adipocyte-specific depletion of EP3 compromised interscapular BAT formation and aggravated high-fat diet-induced obesity and insulin resistance in vivo. Mechanistically, activation of EP3 stabilized the Zfp410 mRNA via WTAP-mediated m6 A modification, while knockdown of Zfp410 abolished the EP3-induced enhancement of brown adipogenesis. EP3 prevented ubiquitin-mediated degradation of WTAP by eliminating PKA-mediated ERK1/2 inhibition during brown adipocyte differentiation. Ablation of WTAP in brown adipocytes abrogated the protective effect of EP3 overexpression in high-fat diet-fed mice. Inhibition of EP3 also retarded human embryonic stem cell differentiation into mature brown adipocytes by reducing the WTAP levels. Thus, a conserved PGE2 -EP3 axis promotes BAT development by stabilizing WTAP/Zfp410 signaling in a PKA/ERK1/2-dependent manner.

Effects of nanopolystyrene addition on nitrogen fertilizer fate, gaseous loss of N from the soil, and soil microbial community composition.

Nanoplastics and microplastics are the degradation products of plastics waste and have become a dominant pollutant in the environment. However, little is known about the ecological impacts of nanoplastic particles in the agroecosystem. We conducted a mesocosm experiment to examine nanopolystyrene effects on fertilizer nitrogen (N) fate, N gaseous losses and soil microbial communities using Chinese cabbage (Brassica Campestris ssp.) as the model plant. The two-factorial experiment was designed as the addition of 15N-labeled urea exposed without and with ~50 nm nanopolystyrene (0, 0.05%, and 0.1%). Nanopolystyrene addition had a detectable effect on soil mineral N content. The 15N uptake of plants was reduced in aboveground biomass but enhanced in roots with increasing nanopolystyrene concentration. Nanopolystyrene addition decreased soil nitrous oxide and ammonia emissions by 27% and 37%, respectively. Nanopolystyrene addition consistently reduced the abundance of ammonia oxidizer genes but showed contrasting effects on denitrifying genes. Metagenomic sequencing data revealed no significant effects of nanopolystyrene on the N-cycle pathway, while it significantly altered the composition of bacterial and fungal communities. This study provided the first insights into the nanopolystyrene induced linkage of root growth with more root N uptake and less gaseous N losses and the associated changes in the microbial community.

Sulfonamide antibiotics alter gaseous nitrogen emissions in the soil-plant system: A mesocosm experiment and meta-analysis.

Veterinary antibiotics are widely used in many countries worldwide to treat diseases and protect the health of animals. However, the effects of sulfonamide antibiotics introduced via manure and wastewater irrigation on nitrogen (N) loss in the soil-plant system remain poorly understood. Here, we conducted a pot experiment to assess the effects of sulfamethazine (SMZ) and its degradation product (2-amino-4,6-dimethylpyrimidine, ADPD) at four concentration gradients (i.e., 0, 1, 10, 100 mg kg-1) on nitrous oxide (N2O) and ammonia (NH3) emissions, and the abundances of N-cycling functional genes and sulfonamide resistance genes. We also collated 350 observations from 62 published papers and performed a meta-analysis of antibiotic addition effects on N2O emission and soil net nitrification and denitrification. Antibiotics additions showed an inhibitory effect on N2O emissions, which accords with the trend of our meta-analysis showing a significant decrease of 32%. The decreased N2O emissions were attributed to the significant reduction in the abundances of total bacterial communities, ammonia oxidizers, and nir-type denitrifiers and to the resultant changes in soil inorganic N. N2O emissions did not differ between non-environmentally relevant concentrations for SMZ but lowered with increasing ADPD concentrations. This discrepancy can be explained by differential responses of the gene abundances of ammonia oxidizers and nirK-type denitrifiers and the development of antibiotic resistance genes in the highest concentration following antibiotic additions. Antibiotic additions increased soil NH3 volatilization but did not affect vegetable yield. Therefore, these findings provide insight into how the prevalence of antibiotics in soils could alter the N-cycling process and associated gas emissions, with implications for understanding the ecological risks of antibiotics in agriculture.

Decreased Methane Emissions Associated with Methanogenic and Methanotrophic Communities in a Pig Manure Windrow Composting System under Calcium Superphosphate Amendment.

With the rapid growth of livestock breeding, manure composting has evolved to be an important source of atmospheric methane (CH4) which accelerates global warming. Calcium superphosphate (CaSSP), as a commonly used fertilizer, was proposed to be effective in reducing CH4 emissions from manure composting, but the intrinsic biological mechanism remains unknown. Methanogens and methanotrophs both play a key role in mediating CH4 fluxes, therefore we hypothesized that the CaSSP-mediated reduction in CH4 emissions was attributed to the shift of methanogens and methanotrophs, which was regulated by physicochemical parameter changes. To test this hypothesis, a 60-day pig manure windrow composting experiment was conducted to investigate the response of CH4 emissions to CaSSP amendment, with a close linkage to methanogenic and methanotrophic communities. Results showed that CaSSP amendment significantly reduced CH4 emissions by 49.5% compared with the control over the whole composting period. The decreased mcrA gene (encodes the α-subunit of methyl-coenzyme M reductase) abundance in response to CaSSP amendment suggested that the CH4 emissions were reduced primarily due to the suppressed microbial CH4 production. Illumina MiSeq sequencing analysis showed that the overall distribution pattern of methanogenic and methanotrophic communities were significantly affected by CaSSP amendment. Particularly, the relative abundance of Methanosarcina that is known to be a dominant group for CH4 production, significantly decreased by up to 25.3% accompanied with CaSSP addition. Only Type I methanotrophs was detected in our study and Methylocaldum was the dominant methanotrophs in this composting system; in detail, CaSSP amendment increased the relative abundance of OTUs belong to Methylocaldum and Methylobacter. Moreover, the increased SO42- concentration and decreased pH acted as two key factors influencing the methanogenic and methanotrophic composition, with the former has a negative effect on methanogenesis growth and can later promote CH4 oxidation at a low level. This study deepens our understanding of the interaction between abiotic factors, function microbiota and greenhouse gas (GHG) emissions, as well as provides implication for practically reducing composting GHG emissions.

Congestive heart failure in COX2 deficient rats.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin (PG) formation by targeting cyclooxygenase (COX) 1 and 2. Long-term use of NSAIDs that selectively inhibit COX2 increases the risk for thrombotic events, cardiac failure, and hypertension. However, the underlying mechanisms remain unclear. In this study, COX1- and COX2-deficient rats were created via Cas9/RNA-mediated gene targeting. DNA genotyping and Western blot analysis confirmed successful generation of COX1-/-and COX2-/- rats. Adult COX1-/- rats grew normally, while more than 70% of COX2-/- rats after wean died within 2 months. Echocardiography showed markedly reduced left ventricular ejection fraction and fractional shortening in adult COX2-/- rats compared to those in wildtype (WT) controls. Histological analysis revealed accumulation of inflammatory cells and severe interstitial and perivascular fibrosis in COX2-/- cardiac tissues. Moreover, cardiac ATP and acetyl-CoA production was dramatically decreased in COX2-/- rats. Consistently, the expression of genes related to mitochondrial oxidation, such as those that encode for subunits of pyruvate dehydrogenase complex and acyl CoA dehydrogenases, were downregulated, while glycolytic hexokinase 1 (HK1) was upregulated in COX2-/- heart tissues. These observations indicate that COX2-deficient rats developed spontaneously heart failure, likely as a result of dysregulated cardiac energy metabolism.

Intermolecular Palladium(0)-Catalyzed Atropo-enantioselective C-H Arylation of Heteroarenes.

Atropisomeric (hetero)biaryls are motifs with increasing significance in ligands, natural products, and biologically active molecules. The straightforward construction of the stereogenic axis by efficient C-H functionalization methods is extremely rare and challenging. An intermolecular and highly enantioselective C-H arylation of relevant heteroarenes providing an efficient access to atropisomeric (hetero)biaryls is reported. The use of a Pd(0) complex equipped with H8-BINAPO as a chiral ligand enables the direct functionalization of a broad range of 1,2,3-triazoles and pyrazoles in excellent yields and selectivities of up to 97.5:2.5 er. The method also allows for an atroposelective double C-H arylation for the construction of two stereogenic axes with >99.5:0.5 er.

Arced Multi-Nozzle Electrospinning Spinneret for High-Throughput Production of Nanofibers.

The stable and continuous ejection of multiple jets with high densities is the key to the application of electrospinning technology. An arced multi-nozzle spinneret was designed to increase the production efficiency of electrospinning. The distribution of the electrical field was simulated to optimize the nozzles' distribution of the spinneret. When the nozzles were arranged in an arc array, a relatively uniform electrical field could be obtained, which was beneficial for the weakening of electrical interference among the nozzles. Under the optimized electrical field, multiple jets from each nozzle could be ejected in a stable and continuous way. With the increase of the applied voltage, the electrical stretching force became larger, and there were fewer bonding structures. The average diameter of the electrospun nanofibers decreased with the increase of the applied voltage. When the distance between the inner nozzle and the collector increased, the charged jets suffered a larger stretching effect, resulting in the decrease of the average diameter of the electrospun nanofibers. The electrospinning current increased with the applied voltage and decreased with the distance between the inner nozzle and the collector, which is an important aspect for the monitoring of electrospinning jets. This work provides an effective way to promote the production efficiency of electrospun nanofibrous membranes.

2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes injury-induced vascular neointima formation in mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental pollutant that causes cardiovascular toxicity. The phenotypic transformation of vascular smooth muscle cells (VSMCs) from the contractile to the synthetic phenotype is a hallmark of vascular response to injury. However, the precise role and molecular mechanism of TCDD in vascular remodeling remains unknown. In the present study, we found that TCDD treatment promoted VSMC phenotypic transition from contractile to synthetic phenotype and exaggerated vascular neointimal hyperplasia after wire injury in mice. TCDD treatment enhanced VSMC entry into cell cycle from G0/G1 phase to S and G2/M phase. The expression of cyclin D1, cyclin-dependent kinase 4 (CDK4), and its phosphorylation were coordinately increased in response to TCDD treatment. Knocking down of aryl hydrocarbon receptor (AHR) inhibited VSMC phenotypic transition induced by TCDD and promoted S/G2 phase cell cycle arrest. TCDD treatment markedly increased oncogenic c-Jun gene expression in VSMCs. ChIP assay revealed the direct binding of AHR on the promoter of c-Jun to up-regulate the mRNA expression of c-Jun. Silencing of c-Jun gene enhanced the expression of p53 and p21, whereas attenuated the expression of CDK4 and cyclin D1 leading to the decrease in the TCDD-stimulated VSMC proliferation and synthetic phenotype transition in vitro. In vivo study showed that genetic ablation of c-Jun in VSMCs restricted injury-induced neointimal hyperplasia in TCDD-treated mice. Thus, TCDD exposure exaggerated injury-induced vascular remodeling by the activation of AHR and up-regulation of the expression of its target gene c-Jun, indicating that inhibition of AHR may be a promising prevention strategy for TCDD-associated cardiovascular diseases.-Guo, S., Zhang, R., Liu, Q., Wan, Q., Wang, Y., Yu, Y., Liu, G., Shen, Y., Yu, Y., Zhang, J. 2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes injury-induced vascular neointima formation in mice.