[Retracted] MicroRNA­17­5p contributes to osteoarthritis progression by binding p62/SQSTM1.

[This retracts the article DOI: 10.3892/etm.2017.5622.].

Artificial intelligence in plant breeding.

Harnessing cutting-edge technologies to enhance crop productivity is a pivotal goal in modern plant breeding. Artificial intelligence (AI) is renowned for its prowess in big data analysis and pattern recognition, and is revolutionizing numerous scientific domains including plant breeding. We explore the wider potential of AI tools in various facets of breeding, including data collection, unlocking genetic diversity within genebanks, and bridging the genotype-phenotype gap to facilitate crop breeding. This will enable the development of crop cultivars tailored to the projected future environments. Moreover, AI tools also hold promise for refining crop traits by improving the precision of gene-editing systems and predicting the potential effects of gene variants on plant phenotypes. Leveraging AI-enabled precision breeding can augment the efficiency of breeding programs and holds promise for optimizing cropping systems at the grassroots level. This entails identifying optimal inter-cropping and crop-rotation models to enhance agricultural sustainability and productivity in the field.

Sirtuin 5-Mediated Desuccinylation of ALDH2 Alleviates Mitochondrial Oxidative Stress Following Acetaminophen-Induced Acute Liver Injury.

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury. Sirtuins 5 (SIRT5) has been implicated in the development of various liver diseases. However, its involvement in APAP-induced acute liver injury (AILI) remains unclear. The present study aimed to explore the role of SIRT5 in AILI. SIRT5 expression is dramatically downregulated by APAP administration in mouse livers and AML12 hepatocytes. SIRT5 deficiency not only exacerbates liver injury and the inflammatory response, but also worsens mitochondrial oxidative stress. Conversely, the opposite pathological and biochemical changes are observed in mice with SIRT5 overexpression. Mechanistically, quantitative succinylome analysis and site mutation experiments revealed that SIRT5 desuccinylated aldehyde dehydrogenase 2 (ALDH2) at lysine 385 and maintained the enzymatic activity of ALDH2, resulting in the suppression of inflammation and mitochondrial oxidative stress. Furthermore, succinylation of ALDH2 at lysine 385 abolished its protective effect against AILI, and the protective effect of SIRT5 against AILI is dependent on the desuccinylation of ALDH2 at K385. Finally, virtual screening of natural compounds revealed that Puerarin promoted SIRT5 desuccinylase activity and further attenuated AILI. Collectively, the present study showed that the SIRT5-ALDH2 axis plays a critical role in AILI progression and might be a strategy for therapeutic intervention.

The pivotal role of neutrophil extracellular traps in cardiovascular diseases: Mechanisms and therapeutic implications.

Cardiovascular diseases (CVDs) continue to pose a significant burden on global health, prominently contributing to morbidity and mortality rates worldwide. Recent years have witnessed an increasing recognition of the intricate involvement of neutrophil extracellular traps (NETs) in the pathology of diverse cardiovascular conditions. This review provides a comprehensive analysis of the multifaceted functions of NETs in cardiovascular diseases, shedding light on the impact on atherosclerosis, myocardial infarction, heart failure, myocarditis, atrial fibrillation, aortic stenosis, and the potential therapeutic avenues targeting NETs.

CDGT: Constructing diverse graph transformers for emotion recognition from facial videos.

Recognizing expressions from dynamic facial videos can find more natural affect states of humans, and it becomes a more challenging task in real-world scenes due to pose variations of face, partial occlusions and subtle dynamic changes of emotion sequences. Existing transformer-based methods often focus on self-attention to model the global relations among spatial features or temporal features, which cannot well focus on important expression-related locality structures from both spatial and temporal features for the in-the-wild expression videos. To this end, we incorporate diverse graph structures into transformers and propose a CDGT method to construct diverse graph transformers for efficient emotion recognition from in-the-wild videos. Specifically, our method contains a spatial dual-graphs transformer and a temporal hyperbolic-graph transformer. The former deploys a dual-graph constrained attention to capture latent emotion-related graph geometry structures among local spatial tokens for efficient feature representation, especially for the video frames with pose variations and partial occlusions. The latter adopts a hyperbolic-graph constrained self-attention that explores important temporal graph structure information under hyperbolic space to model more subtle changes of dynamic emotion. Extensive experimental results on in-the-wild video-based facial expression databases show that our proposed CDGT outperforms other state-of-the-art methods.

Regulation of the hematopoietic stem cell pool by C-Kit-associated trogocytosis.

Hematopoietic stem cells (HSCs) are routinely mobilized from the bone marrow (BM) to the blood circulation for clinical transplantation. However, the precise mechanisms by which individual stem cells exit the marrow are not understood. This study identified cell-extrinsic and molecular determinants of a mobilizable pool of blood-forming stem cells. We found that a subset of HSCs displays macrophage-associated markers on their cell surface. Although fully functional, these HSCs are selectively niche-retained as opposed to stem cells lacking macrophage markers, which exit the BM upon forced mobilization. Macrophage markers on HSCs could be acquired through direct transfer by trogocytosis, regulated by receptor tyrosine-protein kinase C-Kit (CD117), from BM-resident macrophages in mouse and human settings. Our study provides proof of concept that adult stem cells utilize trogocytosis to rapidly establish and activate function-modulating molecular mechanisms.

Synergistic Sr Activation and Cr Buffering Effect on RuO2 Electronic Structures for Enhancing the Acidic Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) performance of ruthenium-based oxides strongly correlates with the electronic structures of Ru. However, the widely adopted monometal doping method unidirectionally regulates only the electronic structures, often failing to balance the activity and stability. Here, we propose an "elastic electron transfer" strategy to achieve bidirectional optimization of the electronic structures of Sr, Cr codoped RuO2 catalysts for acidic OER. The introduction of electron-withdrawing Sr intrinsically activates the Ru sites by increasing the oxidation state of Ru. Simultaneously, Cr acts as an electron buffer, donating electrons to Ru in the presence of Sr in the as-prepared catalysts and absorbing excess electrons from Sr leaching during the OER. Such a bidirectional regulation feature of Cr prevents overoxidation of Ru and maintains its high oxidation state during the OER. The optimal Ru3Cr1Sr0.175 catalyst exhibits a low overpotential (214 mV @ 10 mA cm-2) and excellent stability (over 300 h).

In situ synthesis of luminescent dsDNA-Cu NCs stained with a dsDNA-lighted fluorophore for rapid and stable detection of histamine in food.

Poisonous histamine is accumulated in stale meat and fermented foods. The rapid and stable detection of histamine is essential for food safety. Herein, a ratiometric fluorometric method for histamine detection was designed through in situ preparing double-stranded DNA­copper nanoclusters (dsDNA-Cu NCs) stained with 4',6-diamidino-2-phenylindole (DAPI). dsDNA-Cu NCs with red emission were rapidly synthesized via mixing Cu2+, ascorbate and dsDNA at room temperature for 5 min. When DAPI was added during preparation, DAPI coordinated with the Cu element accompanied by the quenched red emission of dsDNA-Cu NCs, and DAPI bound to dsDNA together with the enhanced blue emission of DAPI. Upon adding DAPI and histamine simultaneously, the coordination of histamine with the Cu element further decreased the red emission of dsDNA-Cu NCs, and drove the movement of DAPI from the Cu element to dsDNA along with the enhanced blue emission of DAPI. Significantly, ratiometric fluorescence was insensitive to variations in instrument and environment, causing stable measurement. Meanwhile, in situ synthesis integrated probe preparation with analyte detection, reducing time consumption. Additionally, this method quantified histamine in the concentration range of 7-50 µM with a detection limit of 3.6 µM. It was applied to determining histamine in food with satisfactory accuracy and precision.

A review of psoriasis image analysis based on machine learning.

Machine Learning (ML), an Artificial Intelligence (AI) technique that includes both Traditional Machine Learning (TML) and Deep Learning (DL), aims to teach machines to automatically learn tasks by inferring patterns from data. It holds significant promise in aiding medical care and has become increasingly important in improving professional processes, particularly in the diagnosis of psoriasis. This paper presents the findings of a systematic literature review focusing on the research and application of ML in psoriasis analysis over the past decade. We summarized 53 publications by searching the Web of Science, PubMed and IEEE Xplore databases and classified them into three categories: (i) lesion localization and segmentation; (ii) lesion recognition; (iii) lesion severity and area scoring. We have presented the most common models and datasets for psoriasis analysis, discussed the key challenges, and explored future trends in ML within this field. Our aim is to suggest directions for subsequent research.

Female urinary incontinence in China after 15 years' efforts: Results from large-scale nationwide surveys.

Urinary incontinence (UI) is a disease that quietly yet seriously impacts women's health and represents a global health burden that is often neglected. This study aims to systematically assess the prevalence and dynamics of female UI in China, and can inform further policies and have international implications. This study used three nationwide investigations: A national cross-sectional survey in 2021; another nationwide cross-sectional survey in 2006; and data regarding the institutions and physicians providing pelvic floor rehabilitation services from 2005 to 2019. The weighted prevalence of female UI and its subtypes, including stress UI (SUI), urgency UI (UUI), and mixed UI (MUI), were estimated as primary outcomes. Knowledge, attitude and care-seeking behaviors of UI were evaluated. It was found that the weighted prevalence of female UI was 16.0 % (95% CI, 13.3 %-19.1%) with SUI remaining the predominant subtype (7.0%) in 2021, followed by MUI (6.5%) and UUI (1.9%). The estimated absolute number of Chinese adult women with UI was 85.8 million in 2021. 52.7% (95% CI, 45.9%-59.4 %) of women were aware that UI was a medical condition, and only 10.1% of women with UI sought health care. After 15 years of development, there were 8400 pelvic floor rehabilitation institutions and nearly 10,000 relevant physicians in China-they were found to be associated with UI prevalence. The UI prevalence in China was significantly lower in 2021 compared to that in 2006. Despite the achievement, UI remains a public health problem, especially given China's fast aging and three-child policy. More innovations, especially those that can facilitate care seeking, are needed to address this prevalent yet treatable condition.

Investigating the impact of the inflammatory immune microenvironment and steroids or COX-2 inhibitors usage on immunotherapy in advanced esophageal squamous cell carcinoma (ESCC): a propensity score matched analysis.

PURPOSE: The research aimed to evaluate the connection between pre-treatment inflammatory biomarkers and clinical results in advanced esophageal squamous cell carcinoma (ESCC) receiving immune checkpoint inhibitors. MATERIALS AND METHODS: Between 2019 and 2022, we analyzed 354 individuals diagnosed with metastatic ESCC who underwent immunotherapy. The study sought to evaluate the impact of specific inflammatory biomarkers (Neutrophil/Lymphocyte Ratio (NLR), C-reactive protein to albumin ratio (CRP/ALB) and Glasgow Prognostic Score (GPS), Cyclooxygenase-2 (COX-2) inhibitors or steroids usage on the effectiveness and survival outcomes of immunotherapy in advanced ESCC. The research utilized Kaplan‒Meier and Cox regression models alongside propensity score matching for analysis. RESULTS: The findings revealed that elevated pre-treatment NLR (11.0 vs. 14.6 months, p = 0.021) and CRP/ALB (11.4 vs. 14.6 months, p = 0.022) levels were significantly associated with poorer overall survival (OS) outcomes, while the use of steroids did not show a significant difference in OS (15.5 vs. 15.4 months, p = 0.685) between groups. Similarly, no notable disparity in OS was observed between patients treated withCOX-2 inhibitors and those who were not (13.8 vs. 11.0 months, p = 0.054). CONCLUSION: Lower levels of NLR and CRP/ALB prior to treatment were linked to better effectiveness and OS in immunotherapy for advanced ESCC. The study did not identify a significant relationship between OS in patients with esophageal cancer and the use of either steroids or COX-2 inhibitors.

SLC30A9: an evolutionarily conserved mitochondrial zinc transporter essential for mammalian early embryonic development.

SLC30A9 (ZnT9) is a mitochondria-resident zinc transporter. Mutations in SLC30A9 have been reported in human patients with a novel cerebro-renal syndrome. Here, we show that ZnT9 is an evolutionarily highly conserved protein, with many regions extremely preserved among evolutionarily distant organisms. In Drosophila melanogaster (the fly), ZnT9 (ZnT49B) knockdown results in acutely impaired movement and drastic mitochondrial deformation. Severe Drosophila ZnT9 (dZnT9) reduction and ZnT9-null mutant flies are pupal lethal. The phenotype of dZnT9 knockdown can be partially rescued by mouse ZnT9 expression or zinc chelator TPEN, indicating the defect of dZnT9 loss is indeed a result of zinc dyshomeostasis. Interestingly, in the mouse, germline loss of Znt9 produces even more extreme phenotypes: the mutant embryos exhibit midgestational lethality with severe development abnormalities. Targeted mutagenesis of Znt9 in the mouse brain leads to serious dwarfism and physical incapacitation, followed by death shortly. Strikingly, the GH/IGF-1 signals are almost non-existent in these tissue-specific knockout mice, consistent with the medical finding in some human patients with severe mitochondrial deficiecny. ZnT9 mutations cause mitochondrial zinc dyshomeostasis, and we demonstrate mechanistically that mitochondrial zinc elevation quickly and potently inhibits the activities of respiration complexes. These results reveal the critical role of ZnT9 and mitochondrial zinc homeostasis in mammalian development. Based on our functional analyses, we finally discussed the possible nature of the so far identified human SLC30A9 mutations.

Fe,Ce Co-Doped Ni3S2/NiS Polymorphism Nanosheets with Improved Electrocatalytic Activity and Stability for Water Oxidation.

Balancing the relationship between electrocatalytic activity and stability of sulfide catalysts during oxygen evolution reaction (OER) has been attracting extensive research interest. Here, a simple electrodeposition-vulcanization two-step route was designed to successfully construct nickel foam supported sheet-like Fe,Ce-codoped Ni3S2/NiS polymorphism catalyst (labeled as Fe,Ce-Ni3S2/NiS/NF). Electrochemical measurements showed that the as-obtained Fe,Ce-Ni3S2/NiS/NF electrode presented excellent OER electrocatalytic performances. In 1 M KOH solution, merely 173 and 234 mV of overpotentials were required to deliver the current densities of 10 and 100 mA cm-2, respectively. Further investigations revealed that the Fe,Ce co-doping regulated the electron density around Ni, which promoted the conversion of Ni towards the higher valence state and simultaneously, avoided the stability decrease of the catalyst caused by excessive oxidation corrosion. Moreover, the defects generated during vulcanization also contributed to promoting water oxidation. The present work provides a facile and feasible approach to balance the relationship between the stability and the activity of sulfide catalysts for OER.

Highly stretchable, self-healing, antibacterial, conductive, and amylopectin-enhanced hydrogels with gallium droplets loading as strain sensors.

In this study, we address the challenge of developing highly conductive hydrogels with enhanced stretchability for use in wearable sensors, which are critical for the precise detection of human motion and subtle physiological strains. Our novel approach utilizes amylopectin, a biopolymer, for the uniform integration of liquid metal gallium into the hydrogel matrix. This integration results in a conductive hydrogel characterized by remarkable elasticity (up to 7100 % extensibility) and superior electrical conductance (Gauge Factor = 31.4), coupled with a minimal detection limit of less than 0.1 % and exceptional durability over 5000 cycles. The hydrogel demonstrates significant antibacterial activity, inhibiting microbial growth in moist environments, thus enhancing its applicability in medical settings. Employing a synthesis process that involves ambient condition polymerization of acrylic acid, facilitated by a hydrophobic associative framework, this hydrogel stands out for its rapid gelation and robust mechanical properties. The potential applications of this hydrogel extend beyond wearable sensors, promising advancements in human-computer interaction through technologies like wireless actuation of robotic systems. This study not only introduces a viable material for current wearable technologies but also sets a foundation for future innovations in bio-compatible sensors and interactive devices.

Transcriptomic and proteomic elucidation of Z chromosome dosage compensation in Helicoverpa armigera.

Transcriptomic data have been used to study sex chromosome dosage compensation (SCDC) in approximately 10 Lepidoptera ZW species, yielding a consensus compensation pattern of Z ≈ ZZ < AA . $$ \approx \mathrm{ZZ}<\mathrm{AA}. $$ It remains unclear whether this compensation pattern holds when examining more Lepidoptera ZW species and/or using proteomic data to analyse SCDC. Here we combined transcriptomic and proteomic data as well as transcriptional level of six individual Z genes to reveal the SCDC pattern in Helicoverpa armigera, a polyphagous lepidopteran pest of economic importance. Transcriptomic analysis showed that the Z chromosome expression of H. armigera was balanced between male and female but substantially reduced relative to autosome expression, exhibiting an SCDC pattern of Z ≈ ZZ < AA $$ \approx \mathrm{ZZ}<\mathrm{AA} $$ . When using H. amigera midgut proteomic data, the SCDC pattern of this species changed from Z ≈ ZZ < AA $$ \approx \mathrm{ZZ}<\mathrm{AA} $$ at transcriptomic level to Z = ZZ = AA at the proteomic level. RT-qPCR analysis of transcript abundance of six Z genes found that compensation for each Z gene could vary from no compensation to overcompensation, depending on the individual genes and tissues tested. These results demonstrate for the first time the existence of a translational compensation mechanism, which is operating in addition to a translational mechanism, such as has been reported in other lepidopteran species. And the transcriptional compensation mechanism functions to accomplish Z chromosome dosage balance between the sexes (M = F on the Z chromosome), whereas the translation compensation mechanism operates to achieve dosage compensation between Z chromosome and autosome (Z = AA).

Associations between oral health and depression and anxiety: A cross-sectional and prospective cohort study from the UK Biobank.

AIM: To investigate the associations between oral health and depression, anxiety and their comorbidity in the UK Biobank cohort. MATERIALS AND METHODS: Oral health problems were self-reported at baseline. Symptoms of depression and anxiety were assessed using the Mental Health Questionnaire (PHQ-4) in a cross-sectional study. In the cohort study, diagnoses of depression and anxiety disorders were based on hospital records. Logistic regression and Cox regression models were used to analyse the association between oral health and depression/anxiety. RESULTS: A total of 305,188 participants were included in the cross-sectional study, and multivariate analysis showed that periodontal disease was associated with depression and/or anxiety (odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.73-1.86). In the prospective cohort study involving 264,706 participants, periodontal disease was significantly associated with an increased risk of depression and/or anxiety (hazard ratio [HR]: 1.14, 95% CI: 1.10-1.19), depression (HR: 1.19, 95% CI: 1.13-1.25) and anxiety (HR: 1.13, 95% CI: 1.07-1.19). Periodontal disease was also significantly associated with comorbid depression and anxiety (HR: 1.27, 95% CI: 1.16-1.38). Multiple mediation analysis using baseline inflammatory factors showed that white blood cell count and C-reactive protein explained 3.07% and 3.15% of the association between periodontal disease and depression and anxiety, respectively. However, the results of longitudinal multiple mediation analysis of inflammatory factors at first follow-up (N = 10,673) were not significant. CONCLUSIONS: Periodontal disease was found to be consistently associated with an increased risk of depression, anxiety and their comorbidity.

PoSnf1 affects cellulose utilization through interaction with cellobiose transporter in Pleurotus ostreatus.

Pleurotus ostreatus is one of the most cultivated edible fungi worldwide, but its lignocellulose utilization efficiency is relatively low (<50 %), which eventually affects the biological efficiency of P. ostreatus. Improving cellulase production and activity will contribute to enhancing the lignocellulose-degrading capacity of P. ostreatus. AMP-activated/Snf1 protein kinase plays important roles in regulating carbon and energy metabolism. The Snf1 homolog (PoSnf1) in P. ostreatus was obtained and analyzed using bioinformatics. The cellulose response of PoSnf1, the effect of the phosphorylation level of PoSnf1 on the expression of cellulose degradation-related genes, the putative proteins that interact with the phosphorylated PoSnf1 (P-PoSnf1), the cellobiose transport function of two sugar transporters (STP1 and STP2), and the interactions between PoSnf1 and STP1/STP2 were studied in this research. We found that cellulose treatment improved the phosphorylation level of PoSnf1, which further affected cellulase activity and the expression of most cellulose degradation-related genes. A total of 1, 024 proteins putatively interacting with P-PoSnf1 were identified, and they were enriched mainly in the substances transport and metabolism. Most of the putative cellulose degradation-related protein-coding genes could respond to cellulose. Among the P-PoSnf1-interacting proteins, the functions of two sugar transporters (STP1 and STP2) were further studied, and the results showed that both could transport cellobiose and were indirectly regulated by P-PoSnf1, and that STP2 could directly interact with PoSnf1. The results of this study indicated that PoSnf1 plays an important role in regulating the expression of cellulose degradation genes possibly by affecting cellobiose transport.

Enhanced stability and biocompatibility of HIPEs stabilized by cyclodextrin-metal organic frameworks with inclusion of resveratrol and soy protein isolate for ß-carotene delivery.

High internal phase Pickering emulsions (HIPEs) constitute a significant research domain within colloid interface chemistry, addressing the demand for robust emulsion systems across various applications. An innovative nanoparticle, synthesized from a cyclodextrin metal-organic framework encapsulated with a composite of resveratrol and soy isolate protein (RCS), was employed to fortify a high internal phase emulsion. The emulsion's three-dimensional printing capabilities, alongside the encapsulated delivery efficacy for ß-carotene, were thoroughly examined. Cyclodextrin metal-organic frameworks (CD-MOFs), facilitated by cellulose nanofibrils, were synthesized to yield particles at the nanoscale, maintaining a remarkable 97.67 % cellular viability at an elevated concentration of 1000 µg/ml. The RCS nanoparticles demonstrated thermal stability and antioxidant capacities surpassing those of CD-MOF. The integration of soybean isolate protein augmented both the hydrophobicity (from 21.95 ± 0.64° to 59.15 ± 0.78°) and the interfacial tension (from 14.36 ± 0.46 mN/m to 5.34 ± 0.81 mN/m) of the CD-MOF encapsulated with resveratrol, thereby enhancing the RCS nanoparticles' adsorption at the oil-water interface with greater stability. The durability of the RCS-stabilized high internal phase emulsions was contingent upon the RCS concentration. Emulsions stabilized with 5 wt%-RCS exhibited optimal physical and chemical robustness, demonstrating superior performance in emulsion 3D printing and ß-carotene encapsulation delivery. This investigation furnishes a novel perspective on the amalgamation of food customization and precision nutrition.

Comprehensive analysis of the Spartina alterniflora WD40 gene family reveals the regulatory role of SaTTG1 in plant development.

Introduction: The WD40 gene family, prevalent in eukaryotes, assumes diverse roles in cellular processes. Spartina alterniflora, a halophyte with exceptional salt tolerance, flood tolerance, reproduction, and diffusion ability, offers great potential for industrial applications and crop breeding analysis. The exploration of growth and development-related genes in this species offers immense potential for enhancing crop yield and environmental adaptability, particularly in industrialized plantations. However, the understanding of their role in regulating plant growth and development remains limited. Methods: In this study, we conducted a comprehensive analysis of WD40 genes in S. alterniflora at the whole-genome level, delving into their characteristics such as physicochemical properties, phylogenetic relationships, gene architecture, and expression patterns. Additionally, we cloned the TTG1 gene, a gene in plant growth and development across diverse species. Results: We identified a total of 582 WD40 proteins in the S. alterniflora genome, exhibiting an uneven distribution across chromosomes. Through phylogenetic analysis, we categorized the 582 SaWD40 proteins into 12 distinct clades. Examining the duplication patterns of SaWD40 genes, we observed a predominant role of segmental duplication in their expansion. A substantial proportion of SaWD40 gene duplication pairs underwent purifying selection through evolution. To explore the functional aspects, we selected SaTTG1, a homolog of Arabidopsis TTG1, for overexpression in Arabidopsis. Subcellular localization analysis revealed that the SaTTG1 protein localized in the nucleus and plasma membrane, exhibiting transcriptional activation in yeast cells. The overexpression of SaTTG1 in Arabidopsis resulted in early flowering and increased seed size. Discussion: These outcomes significantly contribute to our understanding of WD40 gene functions in halophyte species. The findings not only serve as a valuable foundation for further investigations into WD40 genes in halophyte but also offer insights into the molecular mechanisms governing plant development, offering potential avenues in molecular breeding.

Factor XII and prekallikrein promote microvascular inflammation and psoriasis in mice.

BACKGROUND AND PURPOSE: Psoriasis is an autoimmune inflammatory skin disease, featuring microvascular abnormalities and elevated levels of bradykinin. Contact activation of Factor XII can initiate the plasma kallikrein-kinin cascade, producing inflammation and angioedema. The role of Factor XII in psoriasis is unknown. EXPERIMENTAL APPROACH: The effects of deficiency of Factor XII or its enzymatic substrate, prekallikrein, were examined in the imiquimod-induced mouse model of psoriasis. Skin microcirculation was assessed using intravital confocal microscopy and laser Doppler flowmeter. A novel antibody blocking Factor XII activation was evaluated for psoriasis prevention. KEY RESULTS: Expression of Factor XII was markedly up-regulated in human and mouse psoriatic skin. Genetic deletion of Factor XII or prekallikrein, attenuated imiquimod-induced psoriatic lesions in mice. Psoriatic induction increased skin microvascular blood perfusion, causing vasodilation, hyperpermeability and angiogenesis. It also promoted neutrophil-vascular interaction, inflammatory cytokine release and enhanced Factor XII / prekallikrein enzymatic activity with elevated bradykinin. Factor XII or prekallikrein deficiency ameliorated these microvascular abnormalities and abolished bradykinin increase. Antagonism of bradykinin B2 receptors reproduced the microvascular protection of Factor XII / prekallikrein deficiency, attenuated psoriatic lesions, and prevented protection by Factor XII / prekallikrein deficiency against psoriasis. Furthermore, treatment of mice with Factor XII antibody alleviated experimentally induced psoriasis and suppressed microvascular inflammation. CONCLUSION AND IMPLICATIONS: Activation of Factor XII promoted psoriasis via prekallikrein-dependent formation of bradykinin, which critically mediated psoriatic microvascular inflammation. Inhibition of contact activation represents a novel therapeutic strategy for psoriasis.