Assessment of phylogenetic relationships and genetic diversity of Sagittaria trifolia using phenotypic traits and SNP markers.

The aquatic perennial herb Sagittaria trifolia L. commonly known as arrowhead, has been utilized in China both as a culinary vegetable and in traditional medicines. Characterizing the phylogenetic relationships and genetic diversity of arrowheads is crucial for improved management, conservation, and efficient utilization of the germplasm resources associated with this species. Herein, we presented the phenotypic traits and genome-wide DNA marker-based analyses of 111 arrowhead accessions, most of which were from China. Cluster analysis revealed that arrowhead could be categorized into two clusters based on 11 phenotypic traits, with Cluster 1 comprising two subclusters. All accessions were clustered into three sub-clusters based primarily on leaf shape and tuber weight. A set of 759,237 high-quality single-nucleotide polymorphisms was identified and used to assess the phylogenetic relationships. Population structure and phylogenetic tree analyses suggested that the accessions could be classified into two major groups, Group I was further subdivided into two subgroups, aligning with the clusters identified through morphological classification. By employing Sagittaria lichuanensis as an outgroup, the rooted tree revealed that the evolutionary relationships within the three groups followed a progression from Group I-1 to Group I-2 and finally to Group II. The landraces were clustered into one group along with the remaining wild accessions. The level of genetic diversity for Group I (π = 0.26) was slightly lower than that which was estimated for Group II (π = 0.29). The lowest pairwise differentiation levels (Fst, 0.008) were obtained from the comparison between groups I-2 and II, indicating that the two groups were the most closely related. This study provides novel insights into germplasm classification, evolutionary relationships, genomics and arrowhead breeding.

Wear Resistance and Biocompatibility of Co-Cr Dental Alloys Fabricated with CAST and SLM Techniques.

Cobalt-chromium (Co-Cr) alloys have been widely used as dental-restoration materials for many years. This study sought to investigate whether selective laser melting (SLM) is a more appropriate process than traditional casting (CAST) for fabricating dental Co-Cr alloys. Metallurgical microscopy, X-ray photoelectron spectroscopy (XPS), Vickers hardness and nanoindentation tests, and friction and wear tests were used to evaluate the microstructure, surface compositions, mechanical properties, and wear resistance, respectively. Additionally, the biocompatibilities and cell adhesion of the alloys were evaluated with L-929 fibroblasts via CCK-8 assay, Live/Dead staining, flow cytometric analysis, scanning electron microscopy (SEM) observation and real-time PCR (RT-PCR) assay. The XPS results showed that the two alloys were all mainly comprised of Co, Cr, and O. The hardness in the CAST group equaled 7.15 ± 0.48 GPa, while in the SLM group, it equaled 9.06 ± 0.49 GPa. The friction coefficient of SLM alloys remained at approximately 0.46, but the CAST specimens fluctuated significantly. SLM alloys exhibited shallower wear scars and less wear debris compared with CAST alloys, simultaneously. Additionally, there were higher survival and expression of cell-adhesion-related genes on SLM alloys of L-929 cells, which meant that the deleterious effect on L-929 cells was significantly reduced compared with that for the CAST alloys. Overall, the wear resistances and biocompatibilities of the Co-Cr dental alloys were dramatically affected by the fabrication technique. The SLM technique is advantageous over the CAST technique for fabricating Co-Cr dental alloys.

Influence of Blanching on the Gene Expression Profile of Phenylpropanoid, Flavonoid and Vitamin Biosynthesis, and Their Accumulation in Oenanthe javanica.

Field blanching is a process used in agriculture to obtain sweet, delicious, and tender stems of water dropwort by obstructing sunlight. The nutritional and transcriptomic profiling of blanched water dropwort has been investigated in our previous studies. However, the effect of blanching on the production of secondary metabolites and different vitamins in water dropwort has not been investigated at the transcriptomic level. This study explored the transcriptomic variations in the phenylpropanoid biosynthesis, flavonoid biosynthesis, and different vitamin biosynthesis pathways under different blanching periods in the water dropwort stems (pre-blanching, mid-blanching, post-blanching, and control). The results show that polyphenol and flavonoid contents decreased; however, the contents of vitamins (A, B1, B2, and C) and antioxidant activity increased significantly after blanching. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of blanched water dropwort showed the downregulation of many important genes involved in phenylpropanoid and flavonoid biosynthesis pathways, and the downregulation of these genes might be the reason for the reduction in polyphenol and flavonoid contents. We also examined and highlighted the genes involved in the higher vitamin content, antioxidant activity, pale color, tenderness, and sweetness of the blanched stem of water dropwort. In conclusion, the present study explored the role of phenylpropanoid and vitamin biosynthesis, and it will provide a basis for future investigation and application in the blanch cultivation of water dropwort.

Comparative Transcriptomic Analysis Provides Novel Insights into the Blanched Stem of Oenanthe javanica.

In the agricultural field, blanching is a technique used to obtain tender, sweet, and delicious water dropwort stems by blocking sunlight. The physiological and nutritional parameters of blanched water dropwort have been previously investigated. However, the molecular mechanism of blanching remains unclear. In the present study, we investigated transcriptomic variations for different blanching periods in the stem of water dropwort (pre, mid, post-blanching, and control). The results showed that many genes in pathways, such as photosynthesis, carbon fixation, and phytohormone signal transduction as well as transcription factors (TFs) were significantly dysregulated. Blanched stems of water dropwort showed the higher number of downregulated genes in pathways, such as photosynthesis, antenna protein, carbon fixation in photosynthetic organisms, and porphyrin and chlorophyll metabolism, which ultimately affect the photosynthesis in water dropwort. The genes of hormone signal transduction pathways (ethylene, jasmonic acid, brassinosteroid, and indole-3-acetic acid) showed upregulation in the post-blanched water dropwort plants. Overall, a higher number of genes coding for TFs, such as ERF, BHLH, MYB, zinc-finger, bZIP, and WRKY were overexpressed in blanched samples in comparison with the control. These genes and pathways participate in inducing the length, developmental processes, pale color, and stress tolerance of the blanched stem. Overall, the genes responsive to blanching, which were identified in this study, provide an effective foundation for further studies on the molecular mechanisms of blanching and photosynthesis regulations in water dropwort and other species.

Corrigendum: Phenotypic, Nutritional, and Antioxidant Characterization of Blanched Oenanthe javanica for Preferable Cultivar.

[This corrects the article DOI: 10.3389/fpls.2021.639639.].

Comparison of iguratimod and conventional cyclophosphamide with sequential azathioprine as treatment of active lupus nephritis: study protocol for a multi-center, randomized, controlled clinical trial (iGeLU study).

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that can involve multiple organs or systems. Lupus nephritis (LN) is associated with high mortality and morbidity. However, plenty of patients do not respond to present treatment or relapse. Iguratimod (IGU) is a new small molecular, anti-rheumatic drug and has shown the potential for drug repurposing from rheumatoid arthritis (RA) to LN treatment. It has been approved for treating RA in northeast Asia. Beyond expectation in a recent observational study, over 90% of thirteen refractory LN patients responded to iguratimod monotherapy in 24 weeks, with no steroids dose increasing or any other medication add-on during the entire follow-up. METHODS/DESIGN: This study is a multi-center, randomized, 52-week parallel positive drug-controlled study. The study was designed as a head-to-head comparison between the iguratimod and present first-line therapy on LN patients. A total of 120 patients (60 patients each group) is in the enrolling plan. All enrolled patients are assigned randomly into trial and control groups. The patients will be selected from six study sites in China and will all have biopsy-proven active lupus nephritis. In the first 24 weeks of the trial, IGU is compared with cyclophosphamide as an induction therapy, and in the second 24 weeks, IGU is compared with azathioprine as a maintenance therapy. The primary outcome is renal remission rate including both complete remission and partial remission at week 52, which will be analyzed using a non-inferiority hypothesis test. DISCUSSION: Most patients diagnosed with SLE will develop LN within 5 years and LN remains a major cause of morbidity and death for SLE patients. Although some medications are proven effective for the treatment of this condition, at least 20-35% LN patients have to suffer from relapse or ineffective treatment and medication intolerance is also frequent. This trial is designed to demonstrate whether iguratimod can be used as an alternative induction or maintenance therapy in subjects who have lupus nephritis. Data from this study will provide an evidence on whether or not iguratimod should be recommended to active LN patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02936375 . Registered on October 18, 2016.

Effect of Salt Stress on Growth, Physiological Parameters, and Ionic Concentration of Water Dropwort (Oenanthe javanica) Cultivars.

Salt stress is an important environmental limiting factor. Water dropwort (Oenanthe javanica) is an important vegetable in East Asia; however, its phenotypic and physiological response is poorly explored. For this purpose, 48 cultivars of water dropwort were grown hydroponically and treated with 0, 50, 100, and 200 mm NaCl for 14 days. Than their phenotypic responses were evaluated, afterward, physiological studies were carried out in selected sensitive and tolerant cultivars. In the present study, the potential tolerant (V11E0022) and sensitive (V11E0135) cultivars were selected by screening 48 cultivars based on their phenotype under four different levels of salt concentrations (0, 50, 100, and 200 mm). The results depicted that plant height, number of branches and leaves were less effected in V11E0022, and most severe reduction was observed in V11E0135 in comparison with others. Than the changes in biomass, ion contents, accumulation of reactive oxygen species, and activities of antioxidant enzymes and non-enzymatic antioxidants were determined in the leaves and roots of the selected cultivars. The potential tolerant cultivar (V11E0022) showed less reduction of water content and demonstrated low levels of Na+ uptake, malondialdehyde, and hydrogen peroxide (H2O2) in both leaves and roots. Moreover, the tolerant cultivar (V11E0022) showed high antioxidant activities of ascorbate peroxidase (APX), superoxide dismutase, peroxidase, catalase (CAT), reduced glutathione (GSH), and high accumulation of proline and soluble sugars compared to the sensitive cultivar (V11E0135). These results suggest the potential tolerance of V11E0022 cultivar against salt stress with low detrimental effects and a good antioxidant defense system. The observations also suggest good antioxidant capacity of water dropwort against salt stress. The findings of the present study also suggest that the number of branches and leaves, GSH, proline, soluble sugars, APX, and CAT could serve as the efficient markers for understanding the defense mechanisms of water dropwort under the conditions of salt stress.

Uncovering phylogenetic relationships and genetic diversity of water dropwort using phenotypic traits and SNP markers.

The water dropworts Oenanthe linearis Wall. ex DC. and O. javanica (Blume) DC. are aquatic perennial herbs that have been used in China as vegetables and traditional medicines. However, their phylogenetic relationships and genetic diversity are poorly understood. Here, we presented the phenotypic traits and genome-wide DNA marker-based analysis of 158 water dropwort accessions representing both species. The analysis revealed that Oenanthe linearis was readily segregated into linear-leaf and deep-cleft leaf water dropworts according to their leaf shapes at flowering. Oenanthe javanica was classified by clustering analysis into two clusters based mainly on the morphological characteristics of their ultimate segments (leaflets). A set of 11 493 high-quality single-nucleotide polymorphisms was identified and used to construct a phylogenetic tree. There was strong discrimination between O. linearis and O. javanica, which was consistent with their phenotype diversification. The population structure and phylogenetic tree analyses suggested that the O. linearis accessions formed two major groups, corresponding to the linear-leaf and deep-cleft leaf types. The most obvious phenotypic differences between them were fully expressed at the reproductive growth stage. A single-nucleotide polymorphism-based analysis revealed that the O. javanica accessions could be categorized into groups I andII. However, this finding did not entirely align with the clusters revealed by morphological classification. Landraces were clustered into one group along with the remaining wild accessions. Hence, water dropwort domestication was short in duration. The level of genetic diversity for O. linearis (π = 0.1902) was slightly lower than that which was estimated for O. javanica (π = 0.2174). There was a low level of genetic differentiation between O. linearis and O. javanica (Fst = 0.0471). The mean genetic diversity among accessions ranged from 0.1818 for the linear-leaf types to 0.2318 for the groupII accessions. The phenotypic traits and the single-nucleotide polymorphism markers identified here lay empirical foundation for future genomic studies on water dropwort.

The ubiquitin ligase Peli1 inhibits ICOS and thereby Tfh-mediated immunity.

T follicular helper (Tfh) cells are crucial for regulating autoimmune inflammation and protective immunity against viral infection. However, the molecular mechanism controlling Tfh cell differentiation is poorly understood. Here, through two mixed bone marrow chimeric experiments, we identified Peli1, a T cell-enriched E3 ubiquitin ligase, as an intrinsic regulator that inhibits Tfh cell differentiation. Peli1 deficiency significantly promoted c-Rel-mediated inducible T-cell costimulator (ICOS) expression, and PELI1 mRNA expression was negatively associated with ICOS expression on human CD4+ T cells. Mechanistically, increased ICOS expression on Peli1-KO CD4+ T cells enhanced the activation of PI3K-AKT signaling and thus suppressed the expression of Klf2, a transcription factor that inhibits Tfh differentiation. Therefore, reconstitution of Klf2 abolished the differences in Tfh differentiation and germinal center reaction between WT and Peli1-KO cells. As a consequence, Peli1-deficient CD4+ T cells promoted lupus-like autoimmunity but protected against H1N1 influenza virus infection in mouse models. Collectively, our findings established Peli1 as a critical negative regulator of Tfh differentiation and indicated that targeting Peli1 may have beneficial therapeutic effects in Tfh-related autoimmunity or infectious diseases.

Phenotypic, Nutritional, and Antioxidant Characterization of Blanched Oenanthe javanica for Preferable Cultivar.

Blanching is a technique used in blocking sunlight for the production of tender, sweet, and delicious stems in the field. This technique is also used in water dropwort (Oenanthe javanica), an important vegetable in East Asia. In China, the steamed stems of water dropwort are prepared with boiled rice. However, the effect of blanching on the nutritional level and antioxidant capacity of water dropwort has not been explored yet. The current study aims to determine the nutrient contents and antioxidant capacities of five cultivars and select the best cultivar. They were mainly compared in terms of phenotypic, physiological, nutritional, and antioxidant levels after blanch cultivation. Results indicate that blanching significantly influenced the phenotype, physiology, and nutritional level of water dropwort in all cultivars. Although few parameters decreased with blanching, starch, sugars, vitamins, minerals, and antioxidant activities increased significantly in the blanched stems in mid- and post-blanching periods. The most noticeable changes were detected in post-blanching samples. Furthermore, the best cultivar (V11E0012) was identified among them. Therefore, blanched water dropwort could be consumed for achieving more nutraceuticals and antioxidants, and cultivar V11E0012 could be recommend for blanching cultivation.

Cytoplasmic DNA sensing by KU complex in aged CD4+ T cell potentiates T cell activation and aging-related autoimmune inflammation.

Aging is associated with DNA accumulation and increased homeostatic proliferation of circulating T cells. Although these attributes are associated with aging-related autoimmunity, their direct contributions remain unclear. Conventionally, KU complex, the regulatory subunit of DNA-dependent protein kinase (DNA-PK), together with the catalytic subunit of DNA-PK (DNA-PKcs), mediates DNA damage repair in the nucleus. Here, we found KU complex abundantly expressed in the cytoplasm, where it recognized accumulated cytoplasmic DNA in aged human and mouse CD4+ T cells. This process enhanced T cell activation and pathology of experimental autoimmune encephalomyelitis (EAE) in aged mice. Mechanistically, KU-mediated DNA sensing facilitated DNA-PKcs recruitment and phosphorylation of the kinase ZAK. This activated AKT and mTOR pathways, promoting CD4+ T cell proliferation and activation. We developed a specific ZAK inhibitor, which dampened EAE pathology in aged mice. Overall, these findings demonstrate a KU-mediated cytoplasmic DNA-sensing pathway in CD4+ T cells that potentiates aging-related autoimmunity.

Activation status of CD56dim natural killer cells is associated with disease activity of patients with systemic lupus erythematosus.

OBJECTIVES: Decreased natural killer (NK) cells have been reported in systemic lupus erythematosus (SLE) patients. However, the role of NK cells in the pathogenesis of SLE is not well understood. In this study, we aimed to characterize NK cell subsets, phenotypes, and cytokine-secreting functions and investigate the clinical relevance of NK cells in SLE patients. METHODS: Peripheral blood samples from 81 SLE patients and 59 healthy donors (HDs) were collected. The frequency and phenotype of NK cells were measured by flow cytometry. Intracellular interferon-γ (IFN-γ) production by NK cells was evaluated by flow cytometry after stimulation with interleukin-12 (IL-12) and IL-18. RESULTS: The percentages of NK cells in the peripheral blood of SLE patients were significantly lower than those in HDs, and the percentages of CD56dim NK cells among total NK cells showed a trend toward decrease. The CD56dim NK cells in SLE patients showed increased production of IFN-γ and displayed relatively activated phenotypic characteristics, including significant increases in NKp44, NKp46, and CD69 and decreased expression of CD16 and CD158a/h/g. Furthermore, CD56dim NK cells in active SLE patients had higher percentages of NKp44+ cells and lower percentages of CD158a/h/g+ cells than those in inactive SLE patients. The percentages of CD158a/h/g+ cells among CD56dim NK cells were negatively correlated with the systemic lupus erythematosus disease activity index (SLEDAI) and positively correlated with C3 and C4 levels. CONCLUSION: CD56dim NK cells in SLE patients show a reduced proportion tendency among total NK cells and are activated, which partially reflects the disease activity. CD158a/h/g expression on CD56dim NK cells may be considered an index of disease activity. Key Points • In patients with SLE, the proportion of CD56dim NK cells showed a decreased trend and CD56dim NK cells were phenotypically activated which partially reflects the disease activity. • CD158a/h/g expression on CD56dim NK cells were decreased which may be used as an indicator for evaluating disease activity in SLE patients.

Genetic diversity and population structure of eddoe taro in China using genome-wide SNP markers.

Taro (Colocasia esculenta) is an important root and tuber crop cultivated worldwide. There are two main types of taro that vary in morphology of corm and cormel, 'dasheen' and 'eddoe'. The eddoe type (Colocasia esculenta var. antiquorium) is predominantly distributed throughout China. Characterizing the genetic diversity present in the germplasm bank of taro is fundamental to better manage, conserve and utilize the genetic resources of this species. In this study, the genetic diversity of 234 taro accessions from 16 provinces of China was assessed using 132,869 single nucleotide polymorphism (SNP) markers identified by specific length amplified fragment-sequencing (SLAF-seq). Population structure and principal component analysis permitted the accessions to be categorized into eight groups. The genetic diversity and population differentiation of the eight groups were evaluated using the characterized SNPs. Analysis of molecular variance showed that the variation among eight inferred groups was higher than that within groups, while a relatively small variance was found among the two morphological types and 16 collection regions. Further, a core germplasm set comprising 41 taro accessions that maintained the genetic diversity of the entire collection was developed based on the genotype. This research is expected to be valuable for genetic characterization, germplasm conservation, and breeding of taro.

Investigation of an Antioxidative System for Salinity Tolerance in Oenanthe javanica.

Abiotic stress, such as drought and salinity, severely affect the growth and yield of many plants. Oenanthe javanica (commonly known as water dropwort) is an important vegetable that is grown in the saline-alkali soils of East Asia, where salinity is the limiting environmental factor. To study the defense mechanism of salt stress responses in water dropwort, we studied two water dropwort cultivars, V11E0022 and V11E0135, based on phenotypic and physiological indexes. We found that V11E0022 were tolerant to salt stress, as a result of good antioxidant defense system in the form of osmolyte (proline), antioxidants (polyphenols and flavonoids), and antioxidant enzymes (APX and CAT), which provided novel insights for salt-tolerant mechanisms. Then, a comparative transcriptomic analysis was conducted, and Gene Ontology (GO) analysis revealed that differentially expressed genes (DEGs) involved in the carbohydrate metabolic process could reduce oxidative stress and enhance energy production that can help in adaptation against salt stress. Similarly, lipid metabolic processes can also enhance tolerance against salt stress by reducing the transpiration rate, H2O2, and oxidative stress. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs involved in hormone signals transduction pathway promoted the activities of antioxidant enzymes and reduced oxidative stress; likewise, arginine and proline metabolism, and flavonoid pathways also stimulated the biosynthesis of proline and flavonoids, respectively, in response to salt stress. Moreover, transcription factors (TFs) were also identified, which play an important role in salt stress tolerance of water dropwort. The finding of this study will be helpful for crop improvement under salt stress.

BACH2 regulates the function of human CD4+ CD45RA- Foxp3l ° cytokine-secreting T cells and promotes B-cell response in systemic lupus erythematosus.

Although CD4+ CD45RA- Foxp3l ° cytokine-secreting T cells (Fr.III cells) have been reported to be increased in systemic lupus erythematosus (SLE), their function and effects on response of B cells are still unclear. Here, we dissect how BACH2 regulates Fr.III cells function and promotes B-cell response in active SLE patients. We measured cytokines and BACH2 expression, and found that Fr.III cells from SLE patients produce much more inflammatory cytokines and were more able to promote B- cell proliferation, IgG, IgA, and TNF-α production than controls in a co-culture system. Fr.III cells expressed high levels of ICOS and CD154, but a low level of Tfr and BACH2, BACH2 expression was negatively correlated with SLE Disease Activity Index. Overexpressed of BACH2 in Fr.III cells, decreased cytokines expression and reduced B-cell response. Furthermore, we identified a reduction of H3K27ac level binding at the BACH2 locus in the SLE Fr.III cells and SLE serum stimulation decreased H3K27ac binding at the BACH2 locus, which could be restored using trichostatin A (TSA). In conclusion, BACH2 was associated with SLE disease activity, regulated the function of Fr.III cells, and promoted B-cells response. Targeting BACH2 may be a new immune intervention therapy of SLE.

Genetic Diversity and DNA Fingerprints of Three Important Aquatic Vegetables by EST-SSR Markers.

Twenty-two sacred lotus (Nelumbo nucifera), 46 taros (Colocasia esculenta) and 10 arrowheads (Sagittaria trifolia) were used as materials and combined with EST-SSR (expressed sequence tag-simple sequence repeats) primers developed by our laboratory. Core primers were screened from a large number of primers that were able to distinguish all materials with a high frequency of polymorphisms. Six pairs, twenty pairs and three pairs of core primers were screened from sacred lotus, taro, and arrowhead, respectively. The SSR fingerprints of these three important aquatic vegetables, producing 17-, 87- and 14-bit binary molecular identity cards, respectively, were separately determined by using the core primers. Since there were few core primers of sacred lotus and arrowhead, 3 and 9 primer pairs with higher polymorphic information content (PIC), respectively, were selected as candidate primers. These core and candidate primers were used to identify the purities of No.36 space lotus, Shandong 8502 taro and Wuhan arrowhead, which were 93.3% (84/90), 98.9% (89/90) and 100.0% (90/90), respectively. The fingerprints, displayed as binary molecular identification cards of three important aquatic vegetables, were obtained, and their purity was successfully determined with EST-SSR labeling technology. Phylogenetic trees were also constructed to analyze the genetic diversity of 22 sacred lotus, 46 taros and 10 arrowheads. This study classifies and identifies germplasm resources and is an important reference to test the authenticity and variety purity of other aquatic vegetables in the future.

Higher activation of the interferon-gamma signaling pathway in systemic lupus erythematosus patients with a high type I IFN score: relation to disease activity.

Increased IFN-γ levels have been associated with systemic lupus erythematosus (SLE). However, the relationships among IFN-γ, type I interferons (IFNs) and clinical features have not been extensively studied. Peripheral blood samples from 44 SLE patients and 36 healthy donors (HDs) were collected. Quantitative real-time PCR was used to assess the mRNA expression of IFNG, type II IFN-inducible genes (IRF1, GBP1, CXCL9, CXCL10, and SERPING1, which are used for the type II IFN score), type I IFN-inducible genes (IRF7, MX1, ISG15, and ISG20, which are used for the type I IFN score), TBX21, and EOMES in peripheral blood mononuclear cells. Flow cytometry was used to measure the IFN-γ levels in lymphocytes. The mRNA levels of type II IFN-inducible genes, IFNG, TBX21, and EOMES were significantly higher in SLE patients than those in HDs. Similarly, the percentages of IFN-γ-producing cells in lymphocytes and their subsets in SLE patients were significantly increased. Linear regression indicated that IFNG expression levels and type II IFN scores were positively correlated with anti-double-stranded DNA autoantibody levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. Compared with patients with low type I IFN scores, patients with high type I IFN scores showed increased type II IFN scores and SLEDAI scores. Type II IFN scores were positively associated with type I IFN scores. The IFN-γ signaling pathway is activated in SLE patients and may be considered an index of disease activity. IFN-γ, together with type I IFNs, promotes the pathogenesis of SLE.

Peli1 negatively regulates noncanonical NF-κB signaling to restrain systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by uncontrolled secretion of autoantibodies by plasma cells. Although the functional importance of plasma cells and autoantibodies in SLE has been well established, the underlying molecular mechanisms of controlling autoantibody production remain poorly understood. Here we show that Peli1 has a B cell-intrinsic function to protect against lupus-like autoimmunity in mice. Peli1 deficiency in B cells induces autoantibody production via noncanonical NF-κB signaling. Mechanically, Peli1 functions as an E3 ligase to associate with NF-κB inducing kinase (NIK) and mediates NIK Lys48 ubiquitination and degradation. Overexpression of Peli1 inhibits noncanonical NF-κB activation and alleviates lupus-like disease. In humans, PELI1 levels negatively correlate with disease severity in SLE patients. Our findings establish Peli1 as a negative regulator of the noncanonical NF-κB pathway in the context of restraining the pathogenesis of lupus-like disease.

Oxcarbazepine oral suspension in young pediatric patients with partial seizures and/or generalized tonic-clonic seizures in routine clinical practice in China: a prospective observational study.

BACKGROUND: This study aimed to assess efficacy and safety of oxcarbazepine (OXC) oral suspension in pediatric patients aged 2-5 years with partial seizures (PS) and/or generalized tonic-clonic seizures (GTCS) in real-world clinical practice in China. METHODS: This 26-week, prospective, single-arm, multicenter, observational study recruited pediatric patients aged 2-5 years with PS or GTCS suitable for OXC oral suspension treatment based on physicians' judgments from 11 medical centers in China. Enrolled subjects started OXC oral suspension treatment as monotherapy or in combination with other antiepileptic drugs. Primary efficacy outcome was the percentage of pediatric subjects achieving ≥ 50% seizure frequency reduction at the end of the 26-week treatment. Secondary efficacy-related parameters and safety parameters such as adverse events (AEs) and serious AEs (SAEs) were also monitored during the 26-week treatment period. RESULTS: Six hundred and six pediatric patients were enrolled and 531 (87.6%) completed the study. After 26 weeks of treatment, 93.3% subjects achieved ≥ 50% seizure frequency reduction, and 81.8% achieved 100% seizure frequency reduction compared to baseline. Among different seizure types, OXC was effective in all subjects with simple PS and in > 90% of subject with other type of seizure present in the study. AEs were observed in 49 (8.1%) subjects. Only three subjects experienced SAE. Rash (n = 18, 2.97%) was the most common AE. Only 17 subjects discontinued due to AEs. CONCLUSION: This study, reporting the real-world data, further confirms the efficacy and good safety profile of OXC oral suspension in Chinese pediatric patients aged 2-5 years with PS and/or GTCS.

Phenotypic and functional alterations of pDCs in lupus-prone mice.

Plasmacytoid dendritic cells (pDCs) were considered to be the major IFNα source in systemic lupus erythematosus (SLE) but their phenotype and function in different disease status have not been well studied. To study the function and phenotype of pDCs in lupus-prone mice we used 7 strains of lupus-prone mice including NZB/W F1, NZB, NZW, NZM2410, B6.NZM(Sle1/2/3), MRL/lpr and BXSB/Mp mice and C57BL/6 as control mice. Increased spleen pDC numbers were found in most lupus mice compared to C57BL/6 mice. The IFNα-producing ability of BM pDCs was similar between lupus and C57BL/6 mice, whereas pDCs from the spleens of NZB/W F1 and NZB mice produced more IFNα than pDCs from the spleens of C57BL/6 mice. Furthermore, spleen pDCs from MRL-lpr and NZM2410 mice showed increased responses to Tlr7 and Tlr9, respectively. As the disease progressed, IFN signature were evaluated in both BM and spleen pDC from lupus prone mice and the number of BM pDCs and their ability to produce IFNα gradually decreased in lupus-prone mice. In conclusion, pDC are activated alone with disease development and its phenotype and function differ among lupus-prone strains, and these differences may contribute to the development of lupus in these mice.