The OsDIR55 gene increases salt tolerance by altering the root diffusion barrier.

The increased soil salinity is becoming a major challenge to produce more crops and feed the growing population of the world. In this study, we demonstrated that overexpression of OsDIR55 gene enhances rice salt tolerance by altering the root diffusion barrier. OsDIR55 is broadly expressed in all examined tissues and organs with the maximum expression levels at lignified regions in rice roots. Salt stress upregulates the expression of OsDIR55 gene in an abscisic acid (ABA)-dependent manner. Loss-function and overexpression of OsDIR55 compromised and improved the development of CS and root diffusion barrier, manifested with the decreased and increased width of CS, respectively, and ultimately affected the permeability of the apoplastic diffusion barrier in roots. OsDIR55 deficiency resulted in Na+ accumulation, ionic imbalance, and growth arrest, whereas overexpression of OsDIR55 enhances salinity tolerance and provides an overall benefit to plant growth and yield potential. Collectively, we propose that OsDIR55 is crucial for ions balance control and salt stress tolerance through regulating lignification-mediated root barrier modifications in rice.

COBL9 and COBL7 synergistically regulate root hair tip growth via controlling apical cellulose deposition.

Root hairs are cylindrical extensions of root epidermal cells that are important for the acquisition of water and minerals, interactions between plant and microbes. The deposition of cell wall materials in the tip enables root hairs to maintain elongation constantly. To date, our knowledge of the regulators that connect the architecture of cell wall and the root hair development remains very limited. Here, we demonstrated that COBL9 and COBL7, two genes of COBRA-Like family in Arabidopsis as well as their counterparts in rice, OsBC1L1 and OsBC1L8, regulate root hair growth. Single mutant cobl9, double mutants cobl7 cobl9 and double mutants osbc1l1 osbc1l8 all displayed prematurely terminated root hair elongation, though at varying levels. COBL7-YFP and COBL9-YFP accumulate prominently in the growing tips of newly emerged root hairs. Furthermore, cobl9, cobl7 cobl9 and osbc1l1 osbc1l8 mutants were defective in the enrichment of cellulose in the tips of the growing root hairs. We also discovered that overexpression of COBL9 could promote root hair elongation and salinity tolerance. Taken together, these results provide compelling evidence that the polarized COBL7 and COBL9 in the tip of the emerging root hairs have conserved roles in regulating root hair development and stress adaptation in dicots and monocots.

Decreased serum interleukin-41/Metrnl levels in patients with Graves' disease.

BACKGROUND: Interleukin (IL)-41, also known as Metrnl, is a novel immunomodulatory cytokine, which is involved in the pathogenesis of many inflammatory and metabolic diseases, but its role in thyroid autoimmune diseases is not clear. The aim of this study was to evaluate the serum IL-41 levels in patients with Graves' disease (GD) and its relationship with GD. METHODS: This study included a total of 49 GD patients and 47 age- and sex-matched healthy individuals. All baseline data were obtained by physical examination. Free triiodothyronine 3 (FT3), free triiodothyronine 4 (FT4), thyroid-stimulating hormone (TSH), anti-thyroglobulin antibodies (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) levels in plasma of GD patients were measured by chemiluminescence. The high-sensitivity C-reactive protein (CRP) and white blood cell count (WBC) were detected using automated biochemical analyzer. Serum IL-41 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum IL-41 levels in patients with GD were significantly lower than those in healthy controls (201.0 vs. 260.8 pg/mL, p < 0.05). There was a significant positive correlation between IL-41 level and CRP (r = 0.2947, p = 0.0385) and WBC (r = 0.4104, p = 0.0034) in GD patients. CRP was positively correlated with TRAb (r = 0.2874, p = 0.0452) and TSH (r = 0.3651, p = 0.0099) levels in GD patients. CONCLUSIONS: This study demonstrates that GD patients have decreased serum IL-41 levels, and IL-41 plays a potential role in abnormal immune response of GD patients.

Low levels of serum IL-39 are associated with autoimmune thyroid disease.

BACKGROUND: Interleukin (IL)-39 is a novel member of IL-12 cytokine family, but its role in autoimmune thyroid diseases (AITD) is unclear. The aim of the present study was to determine serum levels of IL-39 in Hashimoto's thyroiditis (HT) and Graves' disease (GD) patients. METHODS: A total of 48 patients with HT, 50 patients with GD, and 45 healthy controls (HCs) were recruited for this study. Levels of serum IL-39 were determined by ELISA. RESULTS: Compared with HC group, levels of serum IL-39 in patients with HT (p < 0.05) and GD (p < 0.01) were drastically reduced. Among patients with HT, serum IL-39 levels had a positive correlation with white blood cell count (WBC) count and free triiodothyronine level. Among patients with GD, the levels of IL-39 in serum were positively correlated with WBC count and C-reactive protein levels. CONCLUSIONS: IL-39 may be a new potential predictor for patients with HT and GD.

Low serum interleukin-38 levels in patients with Graves' disease and Hashimoto's thyroiditis.

BACKGROUND: Autoimmune thyroid disease (AITD) mainly includes Graves' disease (GD) and Hashimoto's thyroiditis (HT), which is caused by individual genetics, autoimmune dysfunction, and a variety of external environmental factors. Interleukin (IL)-38 is involved in a wide range of autoimmune diseases, but little is known about IL-38 expression in AITD. METHODS: Fifty patients with GD, 50 with HT, and 50 healthy controls (HC) were enrolled in this study. Basic information of the participants was obtained through a physical examination. Immunological data were obtained by an automatic chemiluminescence immunoanalyzer. C-reactive protein (CRP) concentrations and the white blood cell count were measured. Serum IL-38 levels were determined by an enzyme-linked immunosorbent assay. RESULTS: Serum IL-38 levels were significantly lower in the GD and HT groups than in the HC group (both p < 0.01). Serum CRP concentrations were significantly lower in the HT group than in the HC group (p < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve was 0.7736 (p < 0.01) for IL-38 and 0.7972 (p < 0.01) for IL-38 combined with CRP in the GD group. In the HT group, the area under the curve was 0.7276 (p < 0.01) for IL-38 and 0.7300 for IL-38 combined with CRP (p < 0.01). CONCLUSIONS: The results suggest that serum IL-38 level is a potential new diagnostic biomarker in patients with GD and HT.

OsCPL3 is involved in brassinosteroid signaling by regulating OsGSK2 stability.

Glycogen synthase kinase 3 (GSK3) proteins play key roles in brassinosteroid (BR) signaling during plant growth and development by phosphorylating various substrates. However, how GSK3 protein stability and activity are themselves modulated is not well understood. Here, we demonstrate in vitro and in vivo that C-TERMINAL DOMAIN PHOSPHATASE-LIKE 3 (OsCPL3), a member of the RNA Pol II CTD phosphatase-like family, physically interacts with OsGSK2 in rice (Oryza sativa). OsCPL3 expression was widely detected in various tissues and organs including roots, leaves and lamina joints, and was induced by exogenous BR treatment. OsCPL3 localized to the nucleus, where it dephosphorylated OsGSK2 at the Ser-222 and Thr-284 residues to modulate its protein turnover and kinase activity, in turn affecting the degradation of BRASSINAZOLE-RESISTANT 1 (BZR1) and BR signaling. Loss of OsCPL3 function resulted in higher OsGSK2 abundance and lower OsBZR1 levels, leading to decreased BR responsiveness and alterations in plant morphology including semi-dwarfism, leaf erectness and grain size, which are of fundamental importance to crop productivity. These results reveal a previously unrecognized role for OsCPL3 and add another layer of complexity to the tightly controlled BR signaling pathway in plants.

Interleukin-39 exacerbates concanavalin A-induced liver injury.

BACKGROUND: Interleukin (IL)-39 is a novel member of IL-12 family and has been reported to play a pro-inflammatory role in lupus-like mice, but its function in concanavalin A (ConA)-induced liver injury is currently unclear. MATERIALS AND METHODS: In this study, we investigated the effects of IL-39 expression in a mouse model of ConA induced-hepatitis. We first showed that delivery of plasmid DNA encoding mouse IL-39 using the hydrodynamic tail vein injection method increased IL-39 mRNA and protein levels in the liver. We then administrated mice with IL-39 plasmid before ConA injection and measured serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, inflammatory infiltration, and hepatocyte necrosis in the liver. Additionally, we further explored the potential mechanism of IL-39 in ConA-induced liver injury by measuring several inflammatory mediators. RESULTS: We found that ectopic IL-39 expression promoted the ConA-induced increase in serum ALT and AST levels, inflammatory infiltration, and hepatocyte necrosis in the liver. We also observed that IL-39 plasmid administration significantly increased serum and liver interferon-γ, tumor necrosis factor-α, and IL-17A levels, but did not affect serum and liver IL-10 levels in ConA-induced hepatitis. CONCLUSION: Our results suggest that IL-39 can exacerbate ConA-induced hepatitis and may be a therapeutic target in inflammatory liver disease.

Genome-wide identification and expression profiling analysis of DIR gene family in Setaria italica.

Dirigent (DIR) proteins play essential roles in regulating plant growth and development, as well as enhancing resistance to abiotic and biotic stresses. However, the whole-genome identification and expression profiling analysis of DIR gene family in millet (Setaria italica (Si)) have not been systematically understood. In this study, we conducted genome-wide identification and expression analysis of the S. italica DIR gene family, including gene structures, conserved domains, evolutionary relationship, chromosomal locations, cis-elements, duplication events, gene collinearity and expression patterns. A total of 38 SiDIR members distributed on nine chromosomes were screened and identified. SiDIR family members in the same group showed higher sequence similarity. The phylogenetic tree divided the SiDIR proteins into six subfamilies: DIR-a, DIR-b/d, DIR-c, DIR-e, DIR-f, and DIR-g. According to the tertiary structure prediction, DIR proteins (like SiDIR7/8/9) themselves may form a trimer to exert function. The result of the syntenic analysis showed that tandem duplication may play the major driving force during the evolution of SiDIRs. RNA-seq data displayed higher expression of 16 SiDIR genes in root tissues, and this implied their potential functions during root development. The results of quantitative real-time PCR (RT-qPCR) assays revealed that SiDIR genes could respond to the stress of CaCl2, CdCl, NaCl, and PEG6000. This research shed light on the functions of SiDIRs in responding to abiotic stress and demonstrated their modulational potential during root development. In addition, the membrane localization of SiDIR7/19/22 was confirmed to be consistent with the forecast. The results above will provide a foundation for further and deeper investigation of DIRs.

Circulating interleukin-39 as a potential biomarker for rheumatoid arthritis diagnosis.

BACKGROUND: Imbalances in cytokine networks have been shown to be a possible cause of rheumatoid arthritis (RA). The interleukin (IL)-12 family is involved in the pathogenesis of autoimmune diseases including RA, while IL-39 is a newly discovered member of the IL-12 family, although its role in RA remains unclear. The purpose of the present study was to detect the expression of IL-39 in the sera of patients with RA and its relationship with RA activity. METHODS: We recruited 46 patients with RA and 35 healthy controls at Ningbo Sixth Hospital. Blood samples were collected for biochemical analysis, and disease activity scores of 28 joints based on C-reactive protein were monitored. Serum concentrations of IL-39 were determined using an enzyme-linked immunosorbent assay. The Pearson correlation test was used to analyze the association between serum IL-39 levels and clinical indicators. RESULTS: Serum levels of IL-39 were significantly higher in patients with RA compared with healthy controls (p < 0.0001). IL-39 levels positively correlated with rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and IgM; RF positively correlated with ESR. Receiver operating characteristic curve analysis showed that IL-39 has diagnostic value for RA (p < 0.0001). CONCLUSIONS: The significant increase of IL-39 levels in serum of patients with RA and its positive correlation with clinical indicators suggest that IL-39 may serve as biomarker for the diagnosis of RA.

Increased serum IL-41 is associated with disease activity in rheumatoid arthritis.

BACKGROUND: Interleukin (IL)-41 is upregulated in the synovial tissue of rheumatoid arthritis (RA) patients, but its serum level has not been reported. The present study aimed to determine IL-41 expression in serum from RA patients and to clarify the relationships between IL-41 and disease-related parameters in RA patients. METHODS: The study included 46 RA patients and 32 healthy controls (HC). Baseline data were obtained by routine physical examinations and immune-related parameters were measured by an automated chemiluminescent immunoassay analyzer. The correlations between IL-41 and disease activity score in 28 joints (DAS28) and serum clinical data were analyzed using the Pearson correlation test. RESULTS: Serum IL-41 concentrations were higher in RA patients than in HC. Serum IL-41 was positively correlated with DAS28 based on C-reactive protein (DAS28-CRP), CRP, erythrocyte sedimentation rate (ESR), mean platelet volume (MPV), and CRP-to-albumin ratio (CAR) and negatively correlated with platelet count, while rheumatoid factor was significantly correlated with ESR, CRP, and CAR. Receiver operating characteristic curve analysis showed that IL-41 had diagnostic value for RA, especially when combined with MPV. CONCLUSIONS: The present findings suggest that IL-41 is increased in the serum of RA patients and may be a potential new diagnostic biomarker for RA.

Clinical significance of elevated serum IL-36γ levels in patients with early-stage Hashimoto's thyroiditis.

OBJECTIVES: Hashimoto's thyroiditis (HT) is the predominant cause of primary hypothyroidism. Interleukin (IL)-36γ is a member of the IL-36 family. Recently, IL-36γ was shown to possess proinflammatory properties in autoimmune diseases. However, the role of IL-36γ in HT is insufficiently understood. The purpose of the present study was to investigate the potential relationship between IL-36γ and HT. DESIGN & METHODS: We included 100 subjects, among whom, 52 had early-stage HT and 48 were healthy controls (HC). The subjects' basic clinical information was obtained through physical examination and clinical histories of signs and symptoms. Thyroid function and measurements of thyroid-stimulating hormone (TSH), free triiodothyronine 3, free triiodothyronine 4 (FT4), thyroid peroxidase antibody (TPO-Ab), and thyroid globulin antibody were measured using a fully automated chemiluminescent immunoassay analyzer. The expression levels of serum IL-36γ were determined using an enzyme-linked immunosorbent assay. RESULTS: The serum IL-36γ level in the HT group was significantly higher compared with that of the HC group [91.91 (67.52, 130.90) pg/mL vs 62.50 (44.61, 91.53) pg/mL, P < 0.0001]. Correlation analysis showed a negative correlation between serum IL-36γ and TPO-Ab titers in the HT group (r = -0.3507, P = 0.0054). According to receiver operating characteristic curve analysis, the area under the curve (AUC) for IL-36γ was 0.7278 (P < 0.0001), and the AUC for IL-36γ combined with TSH and FT4 was 0.8109 (P < 0.0001). CONCLUSIONS: The present study indicates that serum IL-36γ expression is increased in patients with HT and negatively correlates with TPO-Ab. Our findings suggest that IL-36γ may be involved in the development of HT and may therefore serve as a potential new diagnostic biomarker for HT.

Rice BIG gene is required for seedling viability.

Arabidopsis BIG (AtBIG) gene encodes an enormous protein that is required for auxin transport. Loss of AtBIG function not only profoundly changes plant architecture but also alters plant adaptability to environmental stimuli. A putative homolog of AtBIG exists in the rice genome, but no function has been ascribed to it. In this study, we focus on the characterization of the gene structure and function of OsBIG. Sequence and phylogenetic analysis shows that the homologs of OsBIG have high amino acid conservation in several domains across species. Transgenic rice plants in which the expression of OsBIG was disrupted through the CRISPR/Cas9 system-mediated genome editing were used for phenotypic analysis. The Osbig/- plants show high levels of cell death, enhanced electrolyte leakage and membrane lipid peroxidation, and reduced chlorophyll content, which likely accounted for the seedling lethality. Moreover, gene expression between Osbig/- and wild-type plants analyzed by RNA-seq indicates that a number of metabolic and hormonal pathways including ribosome, DNA replication, photosynthesis, and chlorophyll metabolism were significantly perturbed by OsBIG deficiency. In summary, OsBIG gene is integral to the normal growth and development in rice.