Risk factors and a predictive model for the occurrence of adverse outcomes in patients with new-onset refractory status epilepsy.

Objectives: To determine risk factors for the occurrence of adverse outcomes in patients with new-onset refractory status epilepsy (NORSE) and to construct a concomitant nomogram. Methods: Seventy-six adult patients with NORSE who were admitted to the Department of Neurology, First Affiliated Hospital of Sun Yat-sen University between January 2016 and December 2022 were enrolled for the study. Participants were divided into two-those with good and poor functional outcomes-and their pertinent data was obtained from the hospital medical recording system. Univariate analysis was used to identify potential causes of poor outcomes in both groups and a multivariate logistic regression model was used to identify risk factors for the occurrence of poor outcomes. Using the R programming language RMS package, a nomogram was created to predict the occurrence of poor outcomes. Results: The NORSE risk of adverse outcome nomogram model included four predictors, namely duration of mechanical ventilation (OR = 4.370, 95% CI 1.221-15.640, p = 0.023), antiviral therapy (OR = 0.045, 95% CI 0.005-0.399, p = 0.005), number of anesthetics (OR = 13.428, 95% CI 2.16-83.48, p = 0.005) and neutrophil count/lymphocyte count ratio (NLR) (OR = 5.248, 95% CI 1.509-18.252, p = 0.009). The nomogram had good consistency and discrimination in predicting risk and can thus assist clinical care providers to assess outcomes for NORSE patients. Through ordinary bootstrap analyses, the results of the original set prediction were confirmed as consistent with those of the test set. Conclusion: The nomogram model of risk of adverse outcomes in NORSE adult patients developed in this study can facilitate clinicians to predict the risk of adverse outcomes in NORSE patients and make timely and reasonable interventions for patients at high risk of adverse outcomes.

Therapeutic Plasma Exchange in AChR-Ab Positive Generalized Myasthenia Gravis: A Real World Study About Its Early Response.

Background: Since there is no clear priority or selection principle in the guidelines for myasthenia crisis, therapeutic plasma exchange (TPE) and intravenous immunoglobulin are often administered randomly. However, it should be more prudent in taking TPE due to its higher cost and risk. Studying its early response factors is crucial for managing myasthenia crisis and can improve medical and economic benefits. Methods: A prospective observational study was conducted, and patients classified as having "impending myasthenia crisis" or experiencing a myasthenia crisis and treated by TPE were included. The primary endpoint was the response after TPE. Univariate logistic regression analysis and repeated measurement were performed to analyze factors related to TPE efficacy. Results: A total of 30 patients who treated with TPE as their fast-acting treatments were enrolled. After TPE, those whose QMGs and/or MGCs decreased by ≥5 points or ≥30% of the baseline were judged as "response group", accounting for 66.67% (20/30). Respiratory symptoms had a response rate of 72.00% (18/25), showing the most remarkable improvement. Meanwhile, extraocular symptoms were the least sensitive, with only 8.00% (2/25) showing efficacy. Thymoma (100.00% vs 50.00%, P=0.002) and a high concentration of AChR-Ab (37.37 nmol/L vs 25.4 nmol/L, P=0.039) were common in the early response group. Repeated measures showed significant changes in AChR-Ab and CD19+ B cells before and after TPE (all with P < 0.05). After treatment, the CD19+ B cells tended to decrease in the response group. Discussion: These results indicated that, for AChR-Ab positive generalized MG, TPE can quickly improve respiratory symptoms. Thymoma and a high concentration of AChR-Ab before TPE predict an early better response. Additionally, TPE may work by decreasing AChR-Ab levels and inducing immune regulation. Future prospective and randomized controlled studies are needed.

Organ donation after brain death from autoimmune glial fibrillary acidic protein astrocytopathy: A case report.

Background: No reports of organ donation have been documented in patients suffering from severe autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Case presentation: A 27-year-old male patient developed a fever and headache, followed a week later by weakness and unsteadiness in his limbs. He attended his local hospital, but no cause was found. Thirteen days later, he became unconscious and was promptly moved to the intensive care unit for symptomatic support treatment, with no improvement. He was then transferred to our hospital, where he suffered a cardiac arrest on the same day. The family abandoned treatment and opted for organ donation, for financial reasons. Cell-based assays demonstrated GFAP antibodies in the cerebrospinal fluid. Two kidney recipients and one liver recipient showed no abnormal reactions 15 months after receiving organ transplants. Conclusions: We report a case of organ donation following brain death in a patient diagnosed with GFAP astrocytopathy, highlighting the need for vigilance regarding the potential occurrence of cardiac arrest in patients with this condition. Considering the potential of GFAP astrocytopathy is crucial when observing deteriorating symptoms, seizures, and consciousness disturbances subsequent to a suspected viral infection. Successful organ donation from patients with GFAP astrocytopathy may be feasible given the exclusion of systemic infection and the absence of peripheral organ involvement.

Thymoma-associated autoimmune encephalitis with myasthenia gravis: Case series and literature review.

OBJECTIVES: This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their clinical characteristics. METHODS: Clinical records of 3 AE patients in the first affiliated hospital of Sun Yat-sen University were reviewed. All of them were diagnosed with AE between 1 November 2021 and 1 March 2022, and clinical evidence about thymoma and MG was found. All published case reports were searched for comprehensive literature from January 1990 to June 2022. RESULTS: A total of 18 cases diagnosed with thymoma-associated autoimmune encephalitis (TAAE) and thymoma-associated myasthenia gravis (TAMG) were included in this complication, wherein 3 cases were in the first affiliated hospital of Sun Yat-sen University and the other 15 were published case reports. 5/18 patients had alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody (AMPAR-Ab) in their serum and cerebrospinal fluid (CSF). All of them had positive anti-acetylcholine receptor antibody (AChR-Ab). And 12/18 patients showed a positive response to thymectomy and immunotherapy. Besides, thymoma recurrences were detected because of AE onset. And the shortest interval between operation and AE onset was 2 years in patients with thymoma recurrence. CONCLUSIONS: There was no significant difference in the clinical manifestations between these patients and others with only TAMG or TAAE. TAAE was commonly associated with AMPAR2-Ab. Significantly, AE more commonly heralded thymoma recurrences than MG onset. And the intervals of thymectomy and MG or AE onset had different meanings for thymoma recurrence and prognoses of patients.

Environmental factors affecting the risk of generalization for ocular-onset myasthenia gravis: a nationwide cohort study.

BACKGROUND: The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. AIM: To investigate the association between specific environmental factors and the generalization of OMG. DESIGN: The cohort study was conducted in China based on a nationwide multicenter database. METHODS: Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. RESULTS: A total of 1396 participants were included. During a median follow-up of 5.15 (interquartile range [IQR] 3.37-9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10-15.66) years. Latitude of 20-50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity <0.001). Living in areas with lower PDI had 1.28-2.11 times higher risk of generalization. No significant association was observed with education or smoking. CONCLUSIONS: Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.

Study of serum exosome miRNA as a biomarker for early onset adult ouclar myastthenia gravis.

BACKGROUND: By extracting and sequencing miRNAs from serum exosomes of patients with early-onset ocular myasthenia gravis (OMG), generalized myasthenia gravis (GMG) and healthy controls, we screened differentially expressed miRNAs and explored the possibility as potential biomarkers for early-onset OMG. METHODS: Peripheral blood samples were collected from patients with early-onset OMG, early-onset GMG, and age-matched healthy subjects, with 6 samples in each group. All these patients were diagnosed as MG for the first time and did not undergo any treatment. Exosomes miRNAs were extracted from the serum and performed deep sequencing; the differentially expressed miRNAs were compared and analyzed between OMG, GMG, and healthy control groups using edgeR. The differential expression standard was set to | log2FC |>1, p < 0.05. Target prediction of mRNAs were performed using miRTarBase, TargetScan, and miRDB databases, and a protein-protein interaction (PPI) network was constructed subsequently. The miRNAs with a significant difference were validated using RT-qPCR (10 early-onset OMG patients, 10 early-onset GMG patients and 10 age-sex-matched healthy subjects), and the value of the area under the ROC curve (AUC) was used to assess the diagnostic accuracy and evaluate clinical prognostic value. RESULTS: In total, one upregulated (miR-130a-3p) miRNA was obtained through the upregulated intersection between control vs OMG and OMG vs GMG; four downregulated (miR-4712-3p; miR-6752-5p; miR-320d; miR-3614-3p) miRNAs were obtained through the downregulated intersection between control vs OMG and OMG vs GMG. A total of 408 target genes were predicted for the five differentially expressed miRNAs. The mTOR signaling pathway and Rap1 signaling pathway were significantly enriched based on the enrichment results. RT-qPCR findings revealed that for the OMG, the expression of miR-320d, miR-4712-3p and miR-3614-3p was markedly up-/down-regulated as compared to GMG and healthy control group. The AUC for the three miRNAs between OMG and healthy control groups were 0.78, 0.79 and 0.79 respectively; the AUC between OMG and GMG was 0.84. CONCLUSIONS: The present study identified three novel miRNAs as candidate biomarkers for early-onset OMG patients and it was expected to provide a possibility and a new orientation for serum exosomal miRNAs as OMG diagnostic biomarkers.

Transfer of patient's peripheral blood mononuclear cells (PBMCs) disrupts blood-brain barrier and induces anti-NMDAR encephalitis: a study of novel humanized PBMC mouse model.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neuropsychiatric disease. Brain access of anti-NMDAR autoantibody through the blood-brain barrier (BBB) is essential for pathogenesis. Most previous animal models limit the investigation of etiologies of BBB damage in patients. METHODS: In this study, we established a novel humanized mouse model of anti-NMDAR encephalitis by intraperitoneal injection of patients' peripheral blood mononuclear cells (PBMCs) into BALB/c Rag2-/-Il2rg-/-SirpαNODFlk2-/- mice. RESULTS: We found that engraftment of patients' PBMCs not only produced potent anti-GluN1 autoantibodies, but also disrupted BBB integrity to allow brain access of autoantibodies, resulting in a hyperactive locomotor phenotype, anxiety- and depressive-like behaviors, cognitive deficits, as well as functional changes in corresponding brain regions. Transcriptome analysis suggested an exaggerated immune response and impaired neurotransmission in the mouse model and highlighted Il-1ß as a hub gene implicated in pathological changes. We further demonstrated that Il-1ß was produced by endothelial cells and disrupted BBB by repressing tight junction proteins. Treatment with Anakinra, an Il-1 receptor antagonist, ameliorated BBB damage and neuropsychiatric behaviors. CONCLUSIONS: Our study provided a novel and clinically more relevant humanized mouse model of anti-NMDAR encephalitis and revealed an intrinsic pathogenic property of the patient's lymphocytes.

Clinical use of dimethyl fumarate in multiple sclerosis treatment: an update to include China, using a modified Delphi method.

Dimethyl fumarate (DMF) is a widely used oral disease-modifying therapy for multiple sclerosis (MS). Its efficacy and safety profiles are supported by over a decade of experience. Differences exist between Asia and Europe/United States in the prevalence and characteristics of MS; most data for DMF are derived from populations outside Asia. DMF was recently (2021) approved for use in China. The objectives of this review were to evaluate the evidence for DMF's profile, to provide an update to healthcare providers on current knowledge surrounding its use and to assess the relevance of existing data to use in China. This study used a modified Delphi method based on the insights of a scientific Steering Committee (SC), with a structured literature review conducted to assess the data of DMF. The literature review covered all papers in English (from 01 January 2011 to 21 February 2022) that include 'dimethyl fumarate' and 'multiple sclerosis', and their MeSH terms, on PubMed, supplemented by EMBASE and Citeline searches. Papers were categorized by topic and assessed for relevance and quality, before being used to formulate statements summarizing the literature on each subject. SC members voted on/revised statements, requiring ⩾80% agreement and ⩽10% disagreement for inclusion. Statements not reaching this level were discussed further until agreement was reached or until there was agreement to remove the statement. A total of 1030 papers were retrieved and used to formulate the statements and evidence summaries considered by the SC members. A total of 45 statements were agreed by the SC members. The findings support the positive efficacy and safety profile of DMF in treating patients with MS. Limited Chinese patient data are an ongoing consideration; however, based on current evidence, the statements are considered applicable to both the global and Chinese populations. DMF is a valuable addition to address unmet MS treatment needs in China. Registration: Not applicable.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Corrigendum: Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients.

[This corrects the article DOI: 10.3389/fneur.2022.961628.].

mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study.

Whether metagenomic next-generation sequencing (mNGS) could benefit patients with suspected severe central nervous system (CNS) infection in terms of diagnosis and antibiotic treatment remains unknown. We retrospectively analyzed 79 patients with suspected CNS infection and undertook mNGS. The value of mNGS was investigated in terms of identification of pathogen and guidance for the adjustment of antibiotic treatment. The relationship between the time of initiating mNGS since onset and the Glasgow Outcome Scale (GOS) score after 90-day follow-up were analyzed. Fifty out of 79 cases with suspicious severe CNS infection were finally diagnosed. Despite previous routine laboratory tests, mNGS further promoted the accurate identification of pathogens in 23 cases (47.9%). The sensitivity, specificity, and accuracy of mNGS test in this study were 84.0, 79.3, and 82.3%, respectively. Furthermore, mNGS facilitated the adjustment of empirical antibiotic treatments in 38 cases (48.1%). The time of taking mNGS since onset had an insignificant weak positive correlation with GOS after 90-day follow-up (r = -0.73, P = 0.08). mNGS facilitated the accurate identification of pathogens in suspicious severe CNS infections and promoted the accurate antibiotic therapy even empirical antibiotics were administrated. It should be taken as early as possible to improve the clinical outcome of patients with suspicious severe CNS infection.

The Protective Role of Scorias spongiosa Polysaccharide-Based Microcapsules on Intestinal Barrier Integrity in DSS-Induced Colitis in Mice.

Scorias spongiosa, a type of edible fungus, is beneficial for intestinal health. However, the mechanisms by which polysaccharides derived from S. spongiosa contribute to the integrity of the intestinal barrier have been little investigated. In the present study, 40 C57BL/6J mice were assigned into five groups: (1) Normal; (2) Dextran sulfate sodium (DSS)Administration; (3) DSS + Uncapped polysaccharides; (4) DSS + Low microcapsules; (5) DSS + High microcapsules. After one week of administration of S. spongiosa polysaccharides, all mice, excluding the Normal group, had free access to the drinking water of 3.5% DSS for seven days. Serum and feces were then taken for analysis. Scanning electron microscopy analysis indicated the structure of the micro-capped polysaccharides with curcumin was completed with a rough surface, which differs from the uncapped polysaccharides. Noticeably, S. spongiosa polysaccharides enhanced intestinal barrier integrity as evidenced by increasing the protein levels of Claudin-1, ZO-1 and ZO-2. Low-capped polysaccharides mitigated the DSS-induced oxidative stress by increasing catalase (CAT) concentration and decreasing malondialdehyde (MDA) and myeloperoxidase (MPO) concentrations. Besides, DSS treatment caused a disturbance of inflammation and the contents of IL-1ß, IL-6, TNF-α and CRP were downregulated and the contents of IL-4, IL-10 and IFN-γ were upregulated by S. spongiosa polysaccharides. Research on the potential mechanisms indicated that S. spongiosa polysaccharides inhibited the DSS-triggered activation of NF-κB signaling. Moreover, the JAK/STAT1 and MAPK pathways were suppressed by S. spongiosa polysaccharides in DSS-challenged mice, with Lcap showing the strongest efficacy. 16S rDNA amplicon sequencing revealed that the richness and diversity of the microbial community were reshaped by S. spongiosa polysaccharide ingestion. Therefore, our study substantiated that S. spongiosa polysaccharides exhibited protective effects against colitis mice by reshaping the intestinal microbiome and maintaining the balance of intestinal barrier integrity, antioxidant capacity and colonic inflammation through regulation of the NF-κB-STAT1-MAPK axis.

Nomogram for the acute exacerbation of acetylcholine receptor antibody-positive generalized myasthenia gravis.

BACKGROUND AND OBJECTIVE: An acute exacerbation of myasthenia gravis (MG) can lead to the life-threatening myasthenia crisis which can increase the in-hospital mortality. This study aimed to clarify the correlative factor of the severity and activity of MG and the predictors of its exacerbation. METHODS: A prospective study was conducted to compare the clinical characteristics of acetylcholine receptor antibody (AChR-Ab)-positive generalized MG during acute exacerbation (AE) and in a stable state (SS). Logistic regression was used to determine risk factors, and a nomogram was developed. RESULTS: A total of 97 AChR-Ab MG patients were enrolled, of whom 44 had AE and 53 were in SS. The concentrations of AChR-Ab were 35.24 (23.26, 42.52) nmol/L and 19.51 (8.30, 36.93) nmol/L in the AE and SS groups (P = 0.005), respectively. The receiver operating characteristic curve showed that a single AChR-Ab predicted severity and acute exacerbation, with an area under the curve (AUC) of 0.679. Logistic regression analysis showed that, in addition to AChR-Ab (P = 0.018), bulbar symptoms (P = 0.001), interleukin (IL)-6 (P = 0.025), CD4+/CD8+ T cell ratio (P = 0.031), and CD19+ B cell proportion (P = 0.019) were independent risk factors for acute exacerbation of MG. The developed nomogram had an AUC of 0.878. The Hosmer and Lemeshow chi-square test was 4.37 (P = 0.929). CONCLUSION: AChR-Ab concentration was positively correlated with the severity and activity of MG. AChR-Ab concentration, alongside bulbar symptoms, IL-6 concentration, CD4+/CD8+ T cell ratio, and CD19+ B cell proportion can predict the acute exacerbation of MG.

Prevalence of multiple sclerosis in Guangzhou, China: A population-based case-finding prospective study.

BACKGROUND: Multiple sclerosis (MS) is rare in China, and the prevalence previously reported may be biased. Currently, few studies that have investigated the prevalence of MS in China based on the latest diagnostic criteria. METHODS: Through a population-based survey from August 8, 2021 to December 31, 2021, we calculated the prevalence of multiple sclerosis in 18,676,605 residents of Guangzhou, China. MS patients were identified through the health insurance system of the Guangzhou Health Insurance Bureau, and we surveyed 17 large tertiary hospitals using a case-finding approach. All MS patients were diagnosed according to the 2017 McDonald criteria. RESULTS: A total of 143 patients in the resident population of Guangzhou were diagnosed with MS, with a crude prevalence of 0.77 per 100,000 (95% confidence interval (CI): 0.65-0.90), and the prevalence was higher in in females (1.14/100,000) than in males (0.44/100,000). The age-adjusted prevalence was 0.92 per 100,000 (95% CI: 0.77-1.10). The prevalence peaked at the age of 25-29 years (2.86/100,000) for both males and females (1.44/100,000 and 4.42/100,000, respectively). CONCLUSIONS: This is the first study to report the prevalence of MS in Guangzhou, China, according to the criteria. Our study shows that the prevalence of MS in Guangzhou is lower than that in other cities in China.

Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients.

We previously found that leflunomide combined with low-dose prednisone rapidly improved the clinical symptoms of myasthenia gravis (MG), but we had not investigated the mechanism of this phenomenon. This study documents the effect of leflunomide combined with low-dose prednisone on pro-inflammatory T cells in MG patients. We compared 32 treated MG patients with 18 controls. We collected peripheral blood before treatment and 4, 8, and 12 weeks after treatment. We extracted peripheral blood mononuclear cells (PBMCs) and stimulated them with phorbol 12-myristate 13-acetate (PMA) + ionomycin and quantified IFN-γ, IL-4, IL-17, and IL-9 secretion through ELISA. We quantified T helper (Th) cells Th1 (CD3+CD4+IFN-γ+), Th2 (CD3+CD4+IL-4+), Th17 (CD3+CD4+IL-17A+) and Th9 (CD3+CD4+IL-9+) among PBMCs. The treatment significantly reduced IL-17 and IL-9 secretion in peripheral blood but did not affect IFN-γ levels. Significant decreases in IL-17 and IL-9 appeared at week 12, and the trend of change was similar to that of the MG composite score. Flow cytometry indicated that leflunomide combined with low-dose prednisone significantly reduced the frequency of Th1 and Th17 cells. These findings demonstrate the potential of this treatment as an alternative immunosuppressive therapy for MG.

Multisystem Involvement Induced by Human Parvovirus B19 Infection in a Non-immunosuppressed Adult: A Case Report.

Background: Human parvovirus B19 (B19V) infection is usually symptomless and occurs in the childhood. While in immunocompromised adults, B19V infection also presents various clinical symptoms due to the host's immune status. The classic symptoms include erythema, anemia, arthropathy, and edema, but neurological involvement is rare. Case Presentation: In this report, we present a case of B19V infection caused multiple organ dysfunction in a non-immunosuppressed adult. Metagenomic next-generation sequencing (mNGS) was used and successfully detected the pathogen in multiple types of samples, including blood, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid (BALF). The diagnosis was subsequently confirmed by polymerase chain reaction (PCR). He was treated with intravenous gamma globulin, resulting in a significant resolution of symptoms after 1 month. Conclusion: Multisystem involvement induced by B19V infection was found in this case report. mNGS performed great advantages in rapidly and accurately diagnosing B19V infection in multiple types of samples, which helps the timely adjustment of treatment and improves the prognosis.

First two mitochondrial genomes for the order Filobasidiales reveal novel gene rearrangements and intron dynamics of Tremellomycetes.

In the present study, two mitogenomes from the Filobasidium genus were assembled and compared with other Tremellomycetes mitogenomes. The mitogenomes of F. wieringae and F. globisporum both comprised circular DNA molecules, with sizes of 27,861 bp and 71,783 bp, respectively. Comparative mitogenomic analysis revealed that the genetic contents, tRNAs, and codon usages of the two Filobasidium species differed greatly. The sizes of the two Filobasidium mitogenomes varied greatly with the introns being the main factor contributing to mitogenome expansion in F. globisporum. Positive selection was observed in several protein-coding genes (PCGs) in the Agaricomycotina, Pucciniomycotina, and Ustilaginomycotina species, including cob, cox2, nad2, and rps3 genes. Frequent intron loss/gain events were detected to have occurred during the evolution of the Tremellomycetes mitogenomes, and the mitogenomes of 17 species from Agaricomycotina, Pucciniomycotina, and Ustilaginomycotina have undergone large-scale gene rearrangements. Phylogenetic analyses based on Bayesian inference and the maximum likelihood methods using a combined mitochondrial gene set generated identical and well-supported phylogenetic trees, wherein Filobasidium species had close relationships with Trichosporonales species. This study, which is the first report on mitogenomes from the order Filobasidiales, provides a basis for understanding the genomics, evolution, and taxonomy of this important fungal group.

Scorias spongiosa Polysaccharides Promote the Antioxidant and Anti-Inflammatory Capacity and Its Effect on Intestinal Microbiota in Mice.

Scorias spongiosa, as an edible fungus, has multiple health benefits. However, the effects of S. spongiosa on intestinal health are rarely explored. Hence, our study aims to elaborate on the influences of S. spongiosa polysaccharides (SSPs) on antioxidant, anti-inflammatory, and intestinal microflora in C57BL/6J mice. In the present study, 18 male mice were randomly distributed into three groups: (1) Control group (CON); (2) Low dose SSPs group (LSSP); (3) High dose SSPs group (HSSP). After 14-day administration, the jejunum and serum samples were collected for detection. The results showed that SSPs exert no effects on the growth performance of mice regardless of doses. Meanwhile, SSPs administration reduced the serum pro-inflammatory cytokines and elevated the anti-inflammatory cytokines. Moreover, the antioxidant capacity was elevated by SSPs administration, as evidenced by the increased contents of T-AOC, GSH-Px, and the decreased content of MDA. Mechanistically, the administration of SSPs enhanced the protein abundances of p-Nrf2, Keap1, and HO-1 in mice. The results of 16S rDNA demonstrated that the microbial community and composition were altered by SSPs administration. To summarize, SSPs benefit intestinal health in C57BL/6J mice via a mechanism that involves elevating antioxidant and anti-inflammatory activities and regulating intestinal microbiota.