Salicylic Acid Is Involved in the Growth Inhibition Caused by Excessive Ammonium in Oilseed Rape (Brassica napus L.).

Rapeseed (Brassica napus L.) is extremely sensitive to excessive NH4+ toxicity. There remains incomplete knowledge of the causal factors behind the growth suppression in NH4+-nourished plants, with limited studies conducted specifically on field crop plants. In this study, we found that NH4+ toxicity significantly increased salicylic acid (SA) accumulation by accelerating the conversion of SA precursors. Moreover, exogenous SA application significantly aggravated NH4+ toxicity symptoms in the rapeseed shoots. Genome-wide differential transcriptomic analysis showed that NH4+ toxicity increased the expression of genes involved in the biosynthesis, transport, signaling transduction, and conversion of SA. SA treatment significantly increased shoot NH4+ concentrations by reducing the activities of glutamine synthase and glutamate synthase in NH4+-treated rapeseed plants. The application of an SA biosynthesis inhibitor, ABT, alleviated NH4+ toxicity symptoms. Furthermore, SA induced putrescine (Put) accumulation, resulting in an elevated ratio of Put to [spermidine (Spd) + spermine (Spm)] in the NH4+-treated plants, while the opposite was true for ABT. The application of exogenous Put and its biosynthesis inhibitor DFMA induced opposite effects on NH4+ toxicity in rapeseed shoots. These results indicated that the increased endogenous SA contributed noticeably to the toxicity caused by the sole NH4+-N supply in rapeseed shoots. This study provided fresh perspectives on the mechanism underlying excessive NH4+-induced toxicity and the corresponding alleviating strategies in plants.

A systemic lupus erythematosus patient with persistent elevated conjugated bilirubin as the initial symptom: A case report.

RATIONALE: While some systemic lupus erythematosus (SLE) patients may experience varying degrees of liver function abnormalities, only a small portion of these cases have clinical significance, and the majority of patients typically exhibit low levels of serum bilirubin. However, in this article, we present a case of a middle-aged female patient with SLE who exhibited persistent skin jaundice as her initial symptom, offering a fresh perspective on diagnosing and treating patients who exhibit unexplained liver dysfunction and SLE combined with liver injury. PATIENT CONCERNS: A 45-year-old woman was initially admitted to the hospital due to yellowing of the skin and sclera, and her symptoms did not improve significantly during treatment. The results were abnormal after relevant immunological tests. DIAGNOSES: Persistent non-conjugated bilirubin elevation due to lupus hepatitis. INTERVENTIONS: The use of methylprednisolone sodium succinate (40 mg/Qd) and mycophenolate mofetil (0.75 g/d) suppressed immunity, polyolefin choline (20 mL/d) and glutathione (0.6 g/Qd) improved liver function, and nutritional support therapy. OUTCOMES: After 2 weeks of treatment, a significant decrease in the yellow skin and sclera of the patient was observed. LESSONS: Most clinicians overlook that liver function abnormalities are the main manifestation of SLE, resulting in many patients not receiving timely treatment. This study highlights the importance that SLE is also a cause of abnormal liver function.

Three cases of systemic lupus erythematosus presenting with ischemic stroke as the initial symptom: Case reports and literature review.

BACKGROUND: Ischemic stroke constitutes a grave complication within the context of systemic lupus erythematosus (SLE), typically manifesting several years postdiagnosis of SLE. Incidents where ischemic stroke precedes and acts as an initial symptom of SLE are comparatively rare in its early stages, and such presentations are frequently misdiagnosed as ischemic cerebrovascular diseases, posing significant diagnostic challenges. CASE REPORTS: This article presents three cases of young females in whom ischemic stroke emerged as the initial manifestation of SLE. It incorporates a review of 17 case reports published over the past two decades, focusing on patients with SLE where ischemic stroke was a primary symptom. This discussion encompasses the clinical presentation, outcomes, and therapeutic approaches for these patients. CONCLUSION: In young patients, particularly females presenting with ischemic stroke and especially in cases accompanied by hematologic or multisystemic involvement, there should be heightened vigilance for SLE-induced ischemic stroke. Early diagnosis and treatment significantly enhance patients' quality of life and survival rates.

Differential Morpho-Physiological, Ionomic, and Phytohormone Profiles, and Genome-Wide Expression Profiling Involving the Tolerance of Allohexaploid Wheat (Triticum aestivum L.) to Nitrogen Limitation.

Common wheat (Triticum aestivum L.) is a global staple food, while nitrogen (N) limitation severely hinders plant growth, seed yield, and grain quality of wheat. Genetic variations in the responses to low N stresses among allohexaploid wheat (AABBDD, 2n = 6x = 42) genotypes emphasize the complicated regulatory mechanisms underlying low N tolerance and N use efficiency (NUE). In this study, hydroponic culture, inductively coupled plasma mass spectrometry, noninvasive microtest, high-performance liquid chromatography, RNA-seq, and bioinformatics were used to determine the differential growth performance, ionome and phytohormone profiles, and genome-wide expression profiling of wheat plants grown under high N and low N conditions. Transcriptional profiling of NPFs, NRT2s, CLCs, SLACs/SLAHs, AAPs, UPSs, NIAs, and GSs characterized the core members, such as TaNPF6.3-6D, TaNRT2.3-3D, TaNIA1-6B, TaGLN1;2-4B, TaAAP14-5A/5D, and TaUPS2-5A, involved in the efficient transport and assimilation of nitrate and organic N nutrients. The low-N-sensitivity wheat cultivar XM26 showed obvious leaf chlorosis and accumulated higher levels of ABA, JA, and SA than the low-N-tolerant ZM578 under N limitation. The TaMYB59-3D-TaNPF7.3/NRT1.5-6D module-mediated shoot-to-root translocation and leaf remobilization of nitrate was proposed as an important pathway regulating the differential responses between ZM578 and XM26 to low N. This study provides some elite candidate genes for the selection and breeding of wheat germplasms with low N tolerance and high NUE.

Pectin demethylation-mediated cell wall Na+ retention positively regulates salt stress tolerance in oilseed rape.

KEY MESSAGE: Integrated phenomics, ionomics, genomics, transcriptomics, and functional analyses present novel insights into the role of pectin demethylation-mediated cell wall Na+ retention in positively regulating salt tolerance in oilseed rape. Genetic variations in salt stress tolerance identified in rapeseed genotypes highlight the complicated regulatory mechanisms. Westar is ubiquitously used as a transgenic receptor cultivar, while ZS11 is widely grown as a high-production and good-quality cultivar. In this study, Westar was found to outperform ZS11 under salt stress. Through cell component isolation, non-invasive micro-test, X-ray energy spectrum analysis, and ionomic profile characterization, pectin demethylation-mediated cell wall Na+ retention was proposed to be a major regulator responsible for differential salt tolerance between Westar and ZS11. Integrated analyses of genome-wide DNA variations, differential expression profiling, and gene co-expression networks identified BnaC9.PME47, encoding a pectin methylesterase, as a positive regulator conferring salt tolerance in rapeseed. BnaC9.PME47, located in two reported QTL regions for salt tolerance, was strongly induced by salt stress and localized on the cell wall. Natural variation of the promoter regions conferred higher expression of BnaC9.PME47 in Westar than in several salt-sensitive rapeseed genotypes. Loss of function of AtPME47 resulted in the hypersensitivity of Arabidopsis plants to salt stress. The integrated multiomics analyses revealed novel insights into pectin demethylation-mediated cell wall Na+ retention in regulating differential salt tolerance in allotetraploid rapeseed genotypes. Furthermore, these analyses have provided key information regarding the rapid dissection of quantitative trait genes responsible for nutrient stress tolerance in plant species with complex genomes.

Aortic sinus aneurysm invading ventricular septum and dissection caused by Behcet's disease: a case report and literature review.

Few case reports have mentioned the aortic sinus aneurysm invading ventricular septum and dissection caused by Behcet's disease. Here, we reported a 36-year-old male patient with an aortic sinus aneurysm invading the ventricular septum and dissection caused by Behcet's disease, who manifested as recurrent chest tightness and shortness of breath. Cardiac ultrasound showed the rupture of the right aortic sinus and the formation of ventricular septal dissection. Ascending aortic valve prosthesis replacement, mitral valvuloplasty with ring implantation and tricuspid valvuloplasty were performed. Postoperatively, he was treated with hormones, hydroxychloroquine sulfate, mycophenolate mofetil tablets, thalidomide and warfarin, and his symptoms were relieved. This is a rare case easily being misdiagnosed and missed, early diagnosis and in-time treatment are crucial to avoid surgical complications. The diagnostic and therapeutic approaches of this patient were reported and related literature was reviewed in this case report.

Predictors of response of rituximab in rheumatoid arthritis by weighted gene co-expression network analysis.

PURPOSE: The purpose of this study was to identify a biomarker that can predict the efficacy of rituximab (RTX) in the treatment of rheumatoid arthritis (RA) patients. METHODS: Utilized weighted gene co-expression network analysis (WGCNA) and LASSO regression analysis of whole blood transcriptome data (GSE15316 and GSE37107) related to RTX treatment for RA from the GEO database, the critical modules, and key genes related to the efficacy of RTX treatment for RA were found. The biological functions were further explored through enrichment analysis. The area under the ROC curve (AUC) was validated using the GSE54629 dataset. RESULTS: WGCNA screened 71 genes for a dark turquoise module that were correlated with the efficacy of RTX treatment for RA (r = 0.42, P < 0.05). Through the calculation of gene significance (GS) and module membership (MM), 12 important genes were identified; in addition, 21 important genes were screened by the LASSO regression model; two key genes were obtained from the intersection between the important genes. Then, BANK1 (AUC = 0.704, P < 0.05) was identified as a potential biomarker to predict the efficacy of RTX treatment for RA by ROC curve evaluation of the treatment and validation groups. BANK1 gene expression was significantly decreased after RTX treatment, and a statistically significant difference was found (log FC = - 2.08, P < 0.05). Immune cell infiltration analysis revealed that the infiltration of CD4 + T cell memory subset was increased in the group with high BANK1 expression, and a statistically significant difference was found (P < 0.05). CONCLUSIONS: BANK1 can be used as a potential biomarker to predict the response of RTX treatment in RA patients. Key Points • Identifying the hub genes BANK1 as a potential biomarker to predict the response of RTX treatment in RA patients and confirming it in validation data. • Using the WGCNA approach and LASSO analyses to identify the BANK1 in a data set consisting of two GEO data merged and assessing the correlations between BANK1 and immune infiltration by CIBERSORT algorithm.

Low iron ameliorates the salinity-induced growth cessation of seminal roots in wheat seedlings.

Wheat plants are ubiquitously simultaneously exposed to salinity and limited iron availability caused by soil saline-alkalisation. Through this study, we found that both low Fe and NaCl severely inhibited the growth of seminal roots in wheat seedlings; however, sufficient Fe caused greater growth cessation of seminal roots than low Fe under salt stress. Low Fe improved the root meristematic division activity, not altering the mature cell sizes compared with sufficient Fe under salt stress. Foliar Fe spray and split-root experiments showed that low Fe-alleviating the salinity-induced growth cessation of seminal roots was dependent on local low Fe signals in the roots. Ionomics combined with TEM/X-ray few differences in the root Na+ uptake and vacuolar Na+ sequestration between two Fe levels under salt stress. Phytohormone profiling and metabolomics revealed salinity-induced overaccumulation of ACC/ethylene and tryptophan/auxin in the roots under sufficient Fe than under low Fe. Differential gene expression, pharmacological inhibitor addition and the root growth performance of transgenic wheat plants revealed that the rootward auxin efflux and was responsible for the low Fe-mediated amelioration of the salinity-induced growth cessation of seminal roots. Our findings will provide novel insights into the modulation of crop root growth under salt stress.

Case Report: Vesicorectal Fistula Caused by Intestinal Tuberculosis Complicated with Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) are prone to various infections due to autoimmune defects and long-term use of immunosuppressive agents. Mycobacterium tuberculosis (TBC) infection is a common infection in patients with SLE, especially in developing countries such as China. SLE and TBC may overlap and confuse a clinical picture, bringing great difficulties for the diagnosis and treatment. This article reports a case of vesicorectal fistula caused by intestinal TBC complicated with SLE, where the manifestation was recurrent diarrhea, initially treated as lupus-associated intestinal vasculitis without notable response. This case suggests that we should pay attention to close monitoring of tuberculosis-related indicators during the follow-up period of SLE patients, especially in endemic areas, and early diagnosis and treatment of TBC can reduce tuberculosis-related complications and significantly improve the quality of life of patients.

Genome-Scale Investigation of GARP Family Genes Reveals Their Pivotal Roles in Nutrient Stress Resistance in Allotetraploid Rapeseed.

The GARP genes are plant-specific transcription factors (TFs) and play key roles in regulating plant development and abiotic stress resistance. However, few systematic analyses of GARPs have been reported in allotetraploid rapeseed (Brassica napus L.) yet. In the present study, a total of 146 BnaGARP members were identified from the rapeseed genome based on the sequence signature. The BnaGARP TFs were divided into five subfamilies: ARR, GLK, NIGT1/HRS1/HHO, KAN, and PHL subfamilies, and the members within the same subfamilies shared similar exon-intron structures and conserved motif configuration. Analyses of the Ka/Ks ratios indicated that the GARP family principally underwent purifying selection. Several cis-acting regulatory elements, essential for plant growth and diverse biotic and abiotic stresses, were identified in the promoter regions of BnaGARPs. Further, 29 putative miRNAs were identified to be targeting BnaGARPs. Differential expression of BnaGARPs under low nitrate, ammonium toxicity, limited phosphate, deficient boron, salt stress, and cadmium toxicity conditions indicated their potential involvement in diverse nutrient stress responses. Notably, BnaA9.HHO1 and BnaA1.HHO5 were simultaneously transcriptionally responsive to these nutrient stresses in both hoots and roots, which indicated that BnaA9.HHO1 and BnaA1.HHO5 might play a core role in regulating rapeseed resistance to nutrient stresses. Therefore, this study would enrich our understanding of molecular characteristics of the rapeseed GARPs and will provide valuable candidate genes for further in-depth study of the GARP-mediated nutrient stress resistance in rapeseed.

Genome-Wide Identification and Functional Characterization Reveals the Pivotal Roles of BnaA8.ATG8F in Salt Stress Tolerance and Nitrogen Limitation Adaptation in Allotetraploid Rapeseed.

Autophagy is a common physiological process in organisms, including higher plants. The ATG8 subfamily, the core member of the autophagy-related gene (ATG) family, plays a key role in plant growth and development and nutrient stress responses. However, the core ATG8 homologs and their roles in stress resistance remain elusive in allotetraploid rapeseed (AACC, Brassica napus L.). In this study, we identified 29 ATG8 subgroup members, consisting of three phylogenetic clades, based on the analysis of genomic annotation and conserved motifs. Differential transcriptional responses of BnaATG8s to salt stress, nitrogen limitation, and other nutrient stresses were investigated, and we identified BnaA8.ATG8F as the core ATG8 member through gene co-expression network analysis. Decreased BnaA8.ATG8F expression repressed the salt tolerance of transgenic rapeseed plants by significantly reducing the root Na+ retention under salt stress. Moreover, downregulation of BnaA8.ATG8F increased nitrogen (N) limitation sensitivity of transgenic rapeseed plants through decreasing N uptake, translocation, and enhancing N remobilization under nitrogen starvation. In summary, we identified the core ATG8 homologs and characterized their physiological and molecular mechanisms underlying salt stress tolerance and nitrogen limitation adaptation. Our results may provide elite genetic resources for the genetic improvement of nutrient stress tolerance in rapeseed.

Transcriptomic Dissection of Allotetraploid Rapeseed (Brassica napus L.) in Responses to Nitrate and Ammonium Regimes and Functional Analysis of BnaA2.Gln1;4 in Arabidopsis.

Plant roots acquire nitrogen predominantly as two inorganic forms, nitrate (NO3-) and ammonium (NH4+), to which plants respond differentially. Rapeseed (Brassica napus L.) is an important oil-crop species with very low nitrogen-use efficiency (NUE), the regulatory mechanism of which was elusive due to the vastness and complexity of the rapeseed genome. In this study, a comparative transcriptomic analysis was performed to investigate the differential signatures of nitrogen-starved rapeseed in responses to NO3- and NH4+ treatments and to identify the key genes regulating rapeseed NUE. The two nitrogen sources differentially affected the shoot and root transcriptome profiles, including those of genome-wide nitrogen transporter and transcription factor (TF)-related genes. Differential expression profiling showed that BnaA6.NRT2;1 and BnaA7.AMT1;3 might be the core transporters responsible for efficient NO3- and NH4+ uptake, respectively; the TF genes responsive to inorganic nitrogen, specifically responding to NO3-, and specifically responsive to NH4+ were also identified. The genes which were commonly and most significantly affected by both NO3- and NH4+ treatments were related to glutamine metabolism. Among the glutamine synthetase (GS) family genes, we found BnaA2.Gln1;4, significantly responsive to low-nitrogen conditions and showed higher transcription abundance and GS activity in the leaf veins, flower sepals, root cortex and stele, silique petiole and stem tissues. These characters were significantly different from those of AtGln1;4. The heterologous overexpression of BnaA2.Gln1;4 in Arabidopsis increased plant biomass, NUE, GS activity and total amino acid concentrations under both sufficient- and low-nitrogen conditions. Overall, this study provided novel information about the genes involved in the adaptation to different nitrogen regimes and identified some promising candidate genes for enhancing NUE in rapeseed.

Linkage of calprotectin with inflammation, activity and treatment response of rheumatoid arthritis: a meta-analysis.

Aim: This meta-analysis aimed to investigate the clinical value of calprotectin in rheumatoid arthritis (RA) patients. Methods: The data regarding blood calprotectin levels in RA patients were retrieved from PubMed, Embase, Web of Science and Cochrane databases. Results: Thirty-one eligible articles were included. Calprotectin was increased in RA patients compared with healthy controls (mean difference [MD] = 1.48, 95% CI: 1.16-1.79). Calprotectin was positively associated with C-reactive protein (correlation coefficient [CC] = 0.58, 95% CI: 0.53-0.63) and disease activity score (CC = 0.48, 95% CI: 0.38-0.58) in RA patients. Interestingly, calprotectin showed an increased trend in RA responders compared with nonresponders, but without statistical significance (MD = 0.38, 95% CI: -0.09-0.85). Conclusion: Blood calprotectin relates to disease risk, inflammation and activity in RA patients.

This meta-analysis included published data about blood calprotectin levels in rheumatoid arthritis (RA) patients. After integrated analyses, it was observed that blood calprotectin levels were higher in RA patients compared with healthy subjects; calprotectin was positively related to systemic inflammation and disease activity in RA patients. However, blood calprotectin levels failed to predict treatment outcomes in RA patients.