Ascorbic acid-mediated reactive oxygen species homeostasis modulates the switch from tapetal cell division to cell differentiation in Arabidopsis.

The major antioxidant L-ascorbic acid (AsA) plays important roles in plant growth, development, and stress responses. However, the importance of AsA concentration and the regulation of AsA metabolism in plant reproduction remain unclear. In Arabidopsis (Arabidopsis thaliana) anthers, the tapetum monolayer undergoes cell differentiation to support pollen development. Here, we report that a transcription factor, DEFECTIVE IN TAPETAL DEVELOPMENT AND FUNCTION 1 (TDF1), inhibits tapetal cell division leading to cell differentiation. We identified SKEWED5-SIMILAR 18 (SKS18) as a downstream target of TDF1. Enzymatic assays showed that SKS18, annotated as a multicopper oxidase-like protein, has ascorbate oxidase activity, leading to AsA oxidation. We also show that VITAMIN C DEFECTIVE1 (VTC1), an AsA biosynthetic enzyme, is negatively controlled by TDF1 to maintain proper AsA contents. Consistently, either knockout of SKS18 or VTC1 overexpression raised AsA concentrations, resulting in extra tapetal cells, while SKS18 overexpression in tdf1 or the vtc1-3 tdf1 double mutant mitigated their defective tapetum. We observed that high AsA concentrations caused lower accumulation of reactive oxygen species (ROS) in tapetal cells. Overexpression of ROS scavenging genes in tapetum restored excess cell divisions. Thus, our findings demonstrate that TDF1-regulated AsA balances cell division and cell differentiation in the tapetum through governing ROS homeostasis.

Porous Flow Field for Next-Generation Proton Exchange Membrane Fuel Cells: Materials, Characterization, Design, and Challenges.

Porous flow fields distribute fuel and oxygen for the electrochemical reactions of proton exchange membrane (PEM) fuel cells through their pore network instead of conventional flow channels. This type of flow fields has showed great promises in enhancing reactant supply, heat removal, and electrical conduction, reducing the concentration performance loss and improving operational stability for fuel cells. This review presents the research and development progress of porous flow fields with insights for next-generation PEM fuel cells of high power density (e.g., ∼9.0 kW L-1). Materials, fabrication methods, fundamentals, and fuel cell performance associated with porous flow fields are discussed in depth. Major challenges are described and explained, along with several future directions, including separated gas/liquid flow configurations, integrated porous structure, full morphology modeling, data-driven methods, and artificial intelligence-assisted design/optimization.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels the molecular feature of M2 macrophages of head and neck squamous cell carcinoma.

The connection between head and neck squamous cell carcinoma (HNSC) and M2 tumour-associated macrophages is not yet fully understood. We gathered gene expression profiles and clinical data from HNSC patients in the TCGA database. Using Consensus Clustering, we categorized these patients into M2 macrophage-related clusters. We developed a M2 macrophage-related signature (MRS) through statistical analyses. Additionally, we assessed gene expression in HNSC cells using single-cell sequencing data (GSE139324). We identified three distinct M2 macrophage-related clusters in HNSC, each with different prognostic outcomes and immune characteristics. Patients with different MRS profiles exhibited variations in immune infiltration, genetic mutations and prognosis. FCGR2A may play a role in creating an immunosuppressive tumour microenvironment and could potentially serve as a therapeutic target for HNSC. Our study demonstrated that M2 macrophage-related genes significantly impact the development and progression of HNSC. The M2 macrophage-related model offered a more comprehensive assessment of HNSC patient prognosis, genetic mutations and immune features. FCGR2A was implicated in immunosuppressive microenvironments and may hold promise for the development of novel immunotherapeutic strategies for HNSC.

Circ-ILF2 in oral squamous cell carcinoma promotes cisplatin resistance and induces M2 polarization of macrophages.

Cisplatin (CDDP) chemoresistance is one of the predominant factors in oral squamous cell carcinoma (OSCC) treatment failure. Uncovering the mechanisms underlying CDDP resistance is of great importance in OSCC therapy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs, which are reported to participate in the progression of various diseases, including cancer. However, the function of circRNAs in CDDP resistance in OSCC remains unclear. Quantitative reverse transcription PCR was used to search for different circRNAs between OSCC cell lines and CDDP-resistant cell lines. The results showed that circ-ILF2 expression was higher in CDDP-resistant OSCC cell lines. The stability of circ-ILF2 was also confirmed using RNase R and actinomycin D assays. Functional experiments, including cytotoxicity, apoptosis and growth rate assays, showed that upregulation of circ-ILF2 contributes to CDDP resistance. Luciferase reporter-gene, RNA pull-down and quantitative real-time PCR (RT-qPCR) assays showed that circ-ILF2 functions as a microRNA sponge for miR-1252. Luciferase reporter assays, RNA pull-down, RT-qPCR and Western blotting showed that miR-1252 directly targeted and regulated the expression of KLF8. Circ-ILF2 plays an important role in CDDP resistance in OSCC. Circ-ILF2 exerts its function through the miR-1252/KLF8 pathway. In addition, tumour-associated macrophages (TAM) play important roles in cancer progressions, our results showed that circ-ILF2 in OSCC cells induced the M2 polarization of macrophages which provided new thoughts on immunotherapy. Our results suggest that circ-ILF2 may represent a potential therapeutic target in CDDP-resistant OSCC.

SP2-induced circPUM1 modulates chemoresistance and nature killer cell toxicity in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a type of tumour found in the cavity that is characterized by differentiation and metastasis to the lymph nodes. Although diagnosis strategy and clinical treatment have recently improved, the outcomes for OSCC patients remain unsatisfactory. This study verified the characteristics of circPUM1 in OSCC cells, subsequently generating dysregulated circPUM1 cell models, showing that circPUM1 promoted chemoresistance and natural killer (NK) cell toxicity. Furthermore, the transcription factor SP2 regulated the expression of circPUM1 in OSCC cells, circPUM1 acted as a molecular sponge for miR-770-5p. Moreover, Nucleosome Assembly Protein 1 Like 1 (NAP1L1) is a downstream target for miR-770-5p and essential for circPUM1-mediated cisplatin resistance and NK cell cytotoxicity in OSCC cells. The network composed of SP2, circPUM1, miR-770-5p and NAP1L1 in OSCC appears to be a promising avenue for the development of novel targets for diagnosing or treating OSCC.

Slow development allows redundant genes to restore the fertility of rpg1, a TGMS line in Arabidopsis.

Slow development has been shown to be a general mechanism to restore the fertility of thermo-sensitive and photoperiod-sensitive genic male sterile (TGMS and PGMS) lines in Arabidopsis. rpg1 is a TGMS line defective in primexine, which is essential for pollen wall pattern formation. Here, we showed that RPG1-GFP was highly expressed in microsporocytes, microspores, and pollen grains but not in the tapetum in the complemented transgenic line, suggesting that microsporocytes are the main sporophytic cells for primexine formation. Further cytological observations showed that primexine formation in rpg1 was partially restored under slow growth conditions, leading to its fertility restoration. RPG2 is the homolog of RPG1 in Arabidopsis. We revealed that the fertility recovery of rpg1 rpg2 was significantly reduced compared with that of rpg1 under low temperature. The RPG2-GFP protein was also expressed in microsporocytes in the RPG2-GFP (WT) transgenic line. These results suggest that RPG2 plays a redundant role in rpg1 fertility restoration. rpg1 plants were male sterile at the early growth stage, while their fertility was partially restored at the late developmental stage. The fertility of the rpg1 lateral branches was also partially restored. Further growth analysis showed that slow growth at the late reproductive stage or on the lateral branches led to fertility restoration. This work reveals the importance of gene redundancy in fertility restoration for TGMS lines and provides further insight into pollen wall pattern formation.

Unraveling the Reaction Mystery of Li and Na with Dry Air.

Li and Na metals with high energy density are promising in application in rechargeable batteries but suffer from degradation in the ambient atmosphere. The phenomenon that in terms of kinetics, Li is stable but Na is unstable in dry air has not been fully understood. Here, we use in situ environmental transmission electron microscopy combined with theoretical simulations and reveal that the different stabilities in dry air for Li and Na are reflected by the formation of compact Li2O layers on Li metal, while porous and rough Na2O/Na2O2 layers on Na metal are a consequence of the different thermodynamic and kinetics in O2. It is shown that a preformed carbonate layer can change the kinetics of Na toward an anticorrosive behavior. Our study provides a deeper understanding of the often-overlooked chemical reactions with environmental gases and enhances the electrochemical performance of Li and Na by controlling interfacial stability.

Destriping of Remote Sensing Images by an Optimized Variational Model.

Satellite sensors often capture remote sensing images that contain various types of stripe noise. The presence of these stripes significantly reduces the quality of the remote images and severely affects their subsequent applications in other fields. Despite the existence of many stripe noise removal methods in the research, they often result in the loss of fine details during the destriping process, and some methods even generate artifacts. In this paper, we proposed a new unidirectional variational model to remove horizontal stripe noise. The proposed model fully considered the directional characteristics and structural sparsity of the stripe noise, as well as the prior features of the underlying image, to design different sparse constraints, and the ℓp quasinorm was introduced in these constraints to better describe these sparse characteristics, thus achieving a more excellent destriping effect. Moreover, we employed the fast alternating direction method of multipliers (ADMM) to solve the proposed non-convex model. This significantly improved the efficiency and robustness of the proposed method. The qualitative and quantitative results from simulated and real data experiments confirm that our method outperforms existing destriping approaches in terms of stripe noise removal and preservation of image details.

Non-pharmacological and nonsurgical interventions in male urinary incontinence: A scoping review.

AIMS: To describe and synthesize non-pharmacological and nonsurgical interventions for male urinary incontinence from the existing literature. METHODS: A scoping review was conducted following the methodology suggested by Arksey and O'Malley: (1) identification of the research questions; (2) identification of relevant studies using a three-step search recommended by JBI: an initial search within PubMed and CINAHL, a comprehensive literature search within PubMed, CINAHL, EMBASE, PsycINFO, Cochrane Library, and literature search of references lists; (3) study selection; (4) data extraction and charting; (5) collation, summarization, and reporting of the results. The PRISMA-ScR Checklist was used to report. RESULTS: A total of 4602 studies were identified, of which 87 studies were included. Approximately 78% were randomized controlled trials. More than 88% of the participants were men with prostate cancer. Exercising pelvic floor muscles 30 times per day for 12 weeks was the most frequently reported. Parameters of electrical stimulation were typically set up to 50 Hz and 300 µs for frequency and width of pulse, respectively, and lasted for 15 min. Pure pelvic floor muscle training, Pilates, Yoga, whole body vibration, diaphragm/abdominal muscle training, micturition interruption exercise, acupuncture, and auriculotherapy showed positive effects on reducing urinary incontinence. CONCLUSION: The findings suggested implementing pelvic floor muscle training alone before or after surgery can both prompt the recovery of continence in men after prostate cancer surgery. The decision to use biofeedback or electrical stimulation to enhance the therapeutic effect of pelvic floor muscle training should be approached with caution. More rigorous designed studies are needed to validate the effectiveness of Traditional Chinese Medicine techniques and diverse novel methods. RELEVANCE TO CLINICAL PRACTICE: Physicians and nurses need to be up to date on the latest evidence-based non-pharmacological and nonsurgical interventions in male urinary incontinence and select appropriate interventions based on available medical resources and patient preferences.

Epigenetic Regulation of Corneal Epithelial Differentiation by TET2.

Epigenetic DNA modification by 5-hydroxymethylcytosine (5hmC), generated by the Ten-eleven translocation (TET) dioxygenases, regulates diverse biological functions in many organ tissues, including the mammalian eye. For example, 5hmC has been shown to be involved in epigenetic regulation of retinal gene expression. However, a functional role of 5hmC in corneal differentiation has not been investigated to date. Here, we examined 5hmC and TET function in the human cornea. We found 5hmC highly expressed in MUC16-positive terminally differentiated cells that also co-expressed the 5hmC-generating enzyme TET2. TET2 knockdown (KD) in cultured corneal epithelial cells led to significant reductions of 5hmC peak distributions and resulted in transcriptional repression of molecular pathways involved in corneal differentiation, as evidenced by downregulation of MUC4, MUC16, and Keratin 12. Additionally, integrated TET2 KD RNA-seq and genome-wide Reduced Representation Hydroxymethylation Profiling revealed novel epigenetically regulated genes expressed by terminally differentiated cells, including KRT78, MYEOV, and MAL. In aggregate, our findings reveal a novel function of TET2 in the epigenetic regulation of corneal epithelial gene expression and identify novel TET2-controlled genes expressed in differentiated corneal epithelial cells. These results point to potential roles for TET2 induction strategies to enhance treatment of corneal diseases associated with abnormal epithelial maturation.

Heat-Killed Staphylococcus aureus Induces Bone Mass Loss through Telomere Erosion.

The mechanism of systemic osteoporosis caused by chronic infection is not completely clear, and there is a lack of reasonable interventions for this disease. In this study, heat-killed S. aureus (HKSA) was applied to simulate the inflammation caused by the typical clinical pathogen and to explore the mechanism of systemic bone loss caused by it. In this study, we found that the systemic application of HKSA caused bone loss in mice. Further exploration found that HKSA caused cellular senescence, telomere length shortening, and telomere dysfunction-induced foci (TIF) in limb bones. As a well-known telomerase activator, cycloastragenol (CAG) significantly alleviated HKSA-induced telomere erosion and bone loss. These results suggested that telomere erosion in bone marrow cells is a possible mechanism of HKSA-induced bone loss. CAG may protect against HKSA-induced bone loss by alleviating telomere erosion in bone marrow cells.

Effects of Roasting Conditions on Antibacterial Properties of Vietnamese Turmeric (Curcuma longa) Rhizomes.

Processing with heat treatment has been reported to alter several therapeutic effects of turmeric. In Vietnamese traditional medicine, turmeric has been long used for bacterial infections, and roasting techniques are sometimes applied with this material. However, there have been no studies investigating the effects of these thermal processes on the plant's antibacterial properties. Our study was therefore performed to examine the changes that roasting produced on this material. Slices of dried turmeric were further subjected to light-roasting (80 °C in 20 min) or dark-roasting (160 °C in 20 min) processes. Broth dilution and agar-well diffusion methods were applied to examine and compare the effects of ethanol extracts obtained from non-roasted, light-roasted and dark-roasted samples, on a set of 6 gram-positive and gram-negative bacteria. In both investigations, dark-roasted turmeric was significantly less antibacterial than non-roasted and light-roasted materials, as evident by the higher values of minimum inhibitory concentrations and the smaller diameters of induced inhibitory zones. In addition, dark-roasting was also found to clearly reduce curcumin contents, total polyphenol values and antioxidant activities of the extracts. These results suggest that non-roasting or light-roasting might be more suitable for the processing of turmeric materials that are aimed to be applied for bacterial infections.

ARHGAP21 Is Involved in the Carcinogenic Mechanism of Cholangiocarcinoma: A Study Based on Bioinformatic Analyses and Experimental Validation.

Background and Objectives: Rho GTPase-activating protein (RhoGAP) is a negative regulatory element of Rho GTPases and participates in tumorigenesis. Rho GTPase-activating protein 21 (ARHGAP21) is one of the RhoGAPs and its role in cholangiocarcinoma (CCA) has never been disclosed in any publications. Materials and Methods: The bioinformatics public datasets were utilized to investigate the expression patterns and mutations of ARHGAP21 as well as its prognostic significance in CCA. The biological functions of ARHGAP21 in CCA cells (RBE and Hccc9810 cell) were evaluated by scratch assay, cell counting kit-8 assay (CCK8) assay, and transwell migration assay. In addition, the underlying mechanism of ARHGAP21 involved in CCA was investigated by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the most significant signaling pathway was identified through gene set enrichment analysis (GSEA) and the Western blot method. The ssGSEA algorithm was further used to explore the immune-related mechanism of ARHGAP21 in CCA. Results: The ARHGAP21 expression in CCA tissue was higher than it was in normal tissue, and missense mutation was the main alteration of ARHGAP21 in CCA. Moreover, the expression of ARHGAP21 had obvious differences in patients with different clinical characteristics and it had great prognostic significance. Based on cell experiments, we further observed that the proliferation ability and migration ability of the ARHGAP21-knockdown group was reduced in CCA cells. Several pathological signaling pathways correlated with proliferation and migration were determined by GO and KEGG analysis. Furthermore, the PI3K/Akt signaling pathway was the most significant one. GSEA analysis further verified that ARHGAP21 was highly enriched in PI3K/Akt signaling pathway, and the results of Western blot suggested that the phosphorylated PI3K and Akt were decreased in the ARHGAP21-knockdown group. The drug susceptibility of the PI3K/Akt signaling pathway targeted drugs were positively correlated with ARHGAP21 expression. Moreover, we also discovered that ARHGAP21 was correlated with neutrophil, pDC, and mast cell infiltration as well as immune-related genes in CCA. Conclusions: ARHGAP21 could promote the proliferation and migration of CCA cells by activating the PI3K/Akt signaling pathway, and ARHGAP21 may participate in the immune modulating function of the tumor microenvironment.

Circular RNA circFOXO3 regulates KDM2A by targeting miR-214 to promote tumor growth and metastasis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a pathological type of oral cancer, which accounts for over 90% of oral cancers. It has been widely shown that circRNA is involved in the regulation of multiple malignant oral diseases including OSCC. However, the mechanism underlying how circRNA regulates OSCC is still not clearly elucidated. In this article, we report circFOXO3 promotes tumor growth and invasion of OSCC by targeting miR-214 which specifically degrades the lysine demethylase 2A (KDM2A). CircRNA sequencing was conducted in OSCC tumor and tumor-side tissues, and the expression of circFOXO3 is found to be markedly increased in tumor tissues. CircFOXO3 is also highly expressed in several OSCC cell lines compared with human oral keratinocytes. Transwell assay and colony formation showed that knockdown of circFOXO3 prevents the invasion and proliferation of oral cancer cells. Via bioinformatic research, miR-214 was found to be the target of circFOXO3 and correlate well with circFOXO3 both in vitro and in vivo. KDM2A was then validated by database analysis and luciferase assay to be the direct target of miR-214. KDM2A helps to promote tumor invasiveness and proliferation of OSCC. Collectively, our results proved that circFOXO3 sponges miR-214 to up-regulate the expression of KDM2A, thus promotes tumor progression in OSCC.

Stem cell therapy as a promising strategy in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease that affects newborns, particularly preterm infants, and is associated with high morbidity and mortality. No effective therapeutic strategies to decrease the incidence and severity of NEC have been developed to date. Stem cell therapy has been explored and even applied in various diseases, including gastrointestinal disorders. Animal studies on stem cell therapy have made great progress, and the anti-inflammatory, anti-apoptotic, and intestinal barrier enhancing effects of stem cells may be protective against NEC clinically. In this review, we discuss the therapeutic mechanisms through which stem cells may function in the treatment of NEC.

Alleviative effects of foraging exercise on depressive-like behaviors in chronic mild stress-induced ischemic rat model.

BACKGROUND: Poststroke depression (PSD) is a common complication that seriously affects the functional recovery and prognosis of an individual. As some patients with PSD fail to respond to drug therapy, it is urgent to find a viable alternative treatment. METHODS: An active exercise program known as foraging exercise (FE), using food as bait, was designed. First, focal ischemia and chronic unpredictable mild stress (CUMS) were used to establish a PSD model in rats. FE was then performed for 4 weeks. Body weight and behavioral assessments were conducted at the end of the 4th and 8th weeks. RESULTS: After 8 weeks, the results revealed that, compared with the PSD group, the behavioral scores of the rats in the PSD/FE group were significantly improved, the expression of Iba-1 in the affected frontal lobe and striatum was decreased, and serum levels of IL-6 and the IL-6/IL-10 ratio were downregulated. However, the ratio of residual brain volume in rats that had experienced CUMS was significantly less than that in the stroke group. CONCLUSION: FE can alleviate the behavioral scores of PSD rats, and its mechanism may be related to a modulation of the immune-inflammation response of microglia. Furthermore, chronic, persistent stress may increase the volume of cerebral infarction after stroke.

Repression of CRNDE enhances the anti-tumour activity of CD8 + T cells against oral squamous cell carcinoma through regulating miR-545-5p and TIM-3.

Immunotherapy has been identified a promising treatment of cancers, including Oral squamous cell carcinoma (OSCC). CRNDE is highly overexpressed in various cancers. Many lncRNAs have been reported in CD8 T lymphocytes. Little is investigated about their effects in the functions of CD8 + T cells in OSCC. Currently, the influence of lncRNA CRNDE on the function of CD8 + T cells in OSCC progression was investigated. Here, CRNDE was obviously elevated and negatively correlated with IFN-γ production in tumour-infiltrating CD8 + T cells isolated from OSCC patients. CRNDE can exhibit a crucial role in activating CD8 + T-cell exhaustion. Mechanistically, CRNDE specifically sponged miR-545-5p to induce T-cell immunoglobulin and mucin domain-3 (TIM-3), thus contributing to CD8 + T-cell exhaustion. The function of miR-545-5p on T-cell function remains poorly known. TIM-3 is a significant immune checkpoint, and it inhibits cancer immunity. TIM-3 can demonstrate an important role in CD8 + T-cell exhaustion. In summary, loss of CRNDE could induce miR-545-5p and inhibit TIM3 expression, thus significantly activated the anti-tumour effect of CD8 + T cells.

Targeting the ABC transporter ABCB5 sensitizes glioblastoma to temozolomide-induced apoptosis through a cell-cycle checkpoint regulation mechanism.

Glioblastoma multiforme (GBM) is a malignant brain tumor with a poor prognosis resulting from tumor resistance to anticancer therapy and a high recurrence rate. Compelling evidence suggests that this is driven by subpopulations of cancer stem cells (CSCs) with tumor-initiating potential. ABC subfamily B member 5 (ABCB5) has been identified as a molecular marker for distinct subsets of chemoresistant tumor-initiating cell populations in diverse human malignancies. In the current study, we examined the potential role of ABCB5 in growth and chemoresistance of GBM. We found that ABCB5 is expressed in primary GBM tumors, in which its expression was significantly correlated with the CSC marker protein CD133 and with overall poor survival. Moreover, ABCB5 was also expressed by CD133-positive CSCs in the established human U-87 MG, LN-18, and LN-229 GBM cell lines. Antibody- or shRNA-mediated functional ABCB5 blockade inhibited proliferation and survival of GBM cells and sensitized them to temozolomide (TMZ)-induced apoptosis in vitro Likewise, in in vivo human GBM xenograft experiments with immunodeficient mice, mAb treatment inhibited growth of mutant TP53, WT PTEN LN-229 tumors, and sensitized LN-229 tumors to TMZ therapy. Mechanistically, we demonstrate that ABCB5 blockade inhibits TMZ-induced G2/M arrest and augments TMZ-mediated cell death. Our results identify ABCB5 as a GBM chemoresistance marker and point to the potential utility of targeting ABCB5 to improve current GBM therapies.

circ_0001461 promotes oral squamous cell carcinoma progression through miR-145/TLR4/NF-κB axis.

Circular RNAs (circRNAs) have been widely reported to participate in progression of various cancers, including oral cancer. Previous study showed circ_0001461 was aberrantly expressed in oral squamous cell carcinoma (OSCC), while its role in tumorigenesis of OSCC remains largely unclear. In this study, we confirmed that circ_0001461 was highly expressed in OSCC cell lines and tumor tissues. Knocking down of circ_0001461 suppressed cell proliferation, migration and invasion in vitro, and repress xenograft tumor growth in vivo. Mechanistically, we found circ_0001461 regulates OSCC cell proliferation, migration and invasion through sponging miR-145. Furthermore, circ_0001461 promotes the resistance of TNF-α-induced apoptosis of OSCC cells by modulating miR-145/TLR4/NF-κB pathway. In general, our study demonstrated a novel regulatory mechanism that circ_0001461/miR-145/TLR4/NF-κB axis modulates oral squamous cell carcinoma progression.

The Impact of ANxA6 Gene Polymorphism on the Efficacy of Methotrexate Treatment in Psoriasis Patients.

BACKGROUND: There are great interindividual variations in the clinical efficacy of methotrexate (MTX) treatment and patients' genetic background seems promising in its explanation. OBJECTIVES: The study aimed to test whether the polymorphism of annexin A6 (ANxA6) gene, a susceptibility factor for psoriasis, was associated with the clinical response to MTX therapy. METHODS: A total of 325 patients enrolled in the study received oral MTX treatment, of whom 310 completed the 1-year study and performed the genotype analysis. They were defined as responders (a reduction of Psoriasis Area and Severity Index [PASI] score ≥75%) and nonresponders (a reduction of PASI <50%) compared to baseline after 12 weeks of short-time therapy. On 1-year treatment, they were defined as responders if they achieved PASI75 and absolute PASI ≤3, otherwise as nonresponders. The genotypes of 4 single-nucleotide polymorphisms (SNPs) in the ANxA6 gene were verified using the Sequenom platform. Potential predictors associated with the treatment outcome of MTX were assessed by binary logistic regression. RESULTS: We found significant associations for the ANxA6 SNPs of rs11960458, rs960709, and rs13168551 with psoriasis severity. Patients with rs11960458 CC genotype and rs960709 GG genotype showed higher percentages of PASI75 and improvement rates of PASI at 12 weeks. And on 1-year treatment, statistical difference occurred in rs11960458 rather than other SNPs compared between responders and nonresponders that the frequency of CC genotype was higher in responders (p = 0.019). After adjustment for potential confounders, patients with rs11960458 TT/CT genotype (at 12 weeks: OR 0.483, 95% CI 0.245-0.951, p = 0.035; at 1 year: OR 0.483, 95% CI 0.280-0.833, p = 0.009) were significantly more likely to not respond to MTX both on the short-term and long-term treatment, while rs960709 and rs13168551 polymorphisms were only associated with the short-term efficacy of MTX (p = 0.018 and p = 0.036, respectively). CONCLUSIONS: The CC ge-notype of ANxA6 (rs11960458) was significantly associated with a better response when compared to those patients with the TT/CT genotype, thus being a potential predictor for the clinical efficacy of MTX.