It was previously reported that three dsRNA segments, designated L, M and S, were isolated from Sclerotinia sclerotiorum strain Ep-1PN and that the M dsRNA segment was coincident with hypovirulence and debilitation of the fungal host. Here, the complete nucleotide sequence of the M dsRNA of 5419 nt, excluding the poly(A) tail, was determined. Sequence analysis revealed the occurrence of a single open reading frame (nt 93-5195) encoding a protein with significant similarity to the replicases of the 'alphavirus-like' supergroup of positive-strand RNA viruses. The M dsRNA-encoded putative replicase protein contained the conserved methyl transferase, helicase and RNA-dependent RNA polymerase (RdRp) domains characteristic of the replicases of potex-like plant viruses (flexiviruses) and Botrytis virus F (BVF), a flexuous rod mycovirus infecting the phytopathogenic fungus Botrytis cinerea. Furthermore, convincing evidence is presented showing that ascospore descendents derived from the debilitated strain Ep-1PN were devoid of dsRNA and exhibited normal colony morphology. Moreover, it was demonstrated that the debilitation phenotype was transmitted from the parental debilitated strain to its normal ascospore progeny via hyphal anastomosis. These results suggest that the M dsRNA from strain Ep-1PN is derived from the genomic RNA of a positive-strand RNA virus, which we designated Sclerotinia sclerotiorum debilitation-associated RNA virus (SsDRV). Although phylogenetic analysis of the conserved RdRp motifs verified that SsDRV is closely related to BVF and to the allexiviruses in the family Flexiviridae, SsDRV is distinct from these viruses, mainly based on the lack of coat protein and movement protein. INTRODUCTIONHypovirulent or debilitated strains of plant-pathogenic fungi that carry transmissible viruses have attracted much interest because of their potential exploitation as biological control agents, as well as their use as probes for deciphering mechanisms of fungal pathogenesis. Evidence of a viral aetiology for the debilitating disease of the plant-pathogenic fungus Cochliobolus (Helminthosporium) victoriae, the causal agent of Victoria blight of oats (Lindberg, 1959), was recently presented (Ghabrial, 2001;Ghabrial et al., 2002). Hypovirulent strains of Cryphonectria (Endothia) parasitica, the highly destructive chestnut blight fungus, were first reported in 1965 (Grente, 1965) and were later utilized successfully to control chestnut blight in Europe (Anagnostakis, 1982). The development of an infectious cDNA-based reverse genetics system for hypoviruses has significantly facilitated the undertaking of fundamental studies on various aspects of hypovirus-Cryphonectria parasitica interactions (Dawe & Nuss, 2001). There are several other examples of mycovirusassociated hypovirulence/debilitation including the mitoviruses in Ophiostoma novo-ulmi (Hong et al., 1999) and Sclerotinia homoeocarpa (Deng & Boland, 2004;Deng et al., 2003) and the unclassified mycoviruses infecting Diaporthe ambigua (Preisig et al., 2000), Fu...

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BackgroundThe Global Burden of Diseases, Injuries, and Risk Factors Study 2019 called for innovation in addressing age-related disabilities. Our study aimed to identify and validate a urinary peptidomic profile (UPP) differentiating healthy from unhealthy ageing in the general population, to test the UPP predictor in independent patient cohorts, and to search for targetable molecular pathways underlying age-related chronic diseases. MethodsIn this prospective population study, we used data from participants in the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO), done in northern Belgium from 1985 to 2019, and invited participants to a follow-up examination in 2005-10. Participants were eligible if their address was within 15 km of the examination centre and if they had not withdrawn consent in any of the previous examination cycles (1985-2004). All participants (2005-10) were also invited to an additional follow-up examination in 2009-13. Participants who took part in both the 2005-10 follow-up examination and in the additional 2009-13 follow-up visit constituted the derivation dataset, which included their 2005-10 data, and the time-shifted internal validation dataset, which included their 2009-13 data. The remaining participants who only had 2005-10 data constituted the synchronous internal validation dataset. Participants were excluded from analyses if they were incapacitated, had not undergone UPP, or had either missing or outlying (three SDs greater than the mean of all consenting participants) values of body-mass index, plasma glucose, or serum creatinine. The UPP was assessed by capillary electrophoresis coupled with mass spectrometry. The multidimensional UPP signature reflecting ageing was generated from the derivation dataset and validated in the time-shifted internal validation dataset and the synchronous validation dataset. It was further validated in patients with diabetes, COVID-19, or chronic kidney disease (CKD). In FLEMENGHO, the mortality endpoints were all-cause, cardiovascular, and non-cardiovascular mortality; other endpoints were fatal or non-fatal cancer and musculoskeletal disorders. Molecular pathway exploration was done using the Reactome and Kyoto Encyclopedia of Genes and Genomes databases. Findings 778 individuals (395 [51%] women and 383 [49%] men; aged 16•2-82•1 years; mean age 50•9 years [SD 15•8]) from the FLEMENGHO cohort had a follow-up examination between 2005 and 2010, of whom 559 participants had a further follow-up from Oct 28, 2009, to March 19, 2013, and made up the derivation (2005-10) and time-shifted internal validation (2009-13) datasets. 219 were examined once and constituted the synchronous internal validation dataset (2005-10). With correction for multiple testing and multivariable adjustment, chronological age was associated with 210 sequenced peptides mainly showing downregulation of collagen fragments. The trained model relating chronological age to UPP, derived by elastic net regression, included 54 peptides from 17 proteins. The UPP-age pred...

It is very vital to construct the dense hot spots for the strong surface-enhanced Raman scattering (SERS) signals. We take full advantage of the MoS edge-active sites induced from annealing the Ag film on the surface of the MoS. Furthermore, the composite structure of Au-Ag bi-metal nanoparticles (NPs)/MoS hybrid with pyramid structure is obtained by the in situ grown AuNPs around AgNPs, which serves the optimal SERS performance (enhancement factor is ~9.67 × 10) in experiment. Due to the introduction of AuNPs with the simple method, the denser hot spots contribute greatly to the stronger local electric field, which is also confirmed by the finite-different time-domain (FDTD) simulation. Therefore, the ultralow limit of detection (the LOD of 10 and 10 M respectively for the resonant R6G and non-resonant CV), quantitative detection and excellent reproducibility are achieved by the proposed SERS substrate. For practical application, the melamine molecule is detected with the LOD of 10 M using the proposed SERS substrate that has the potential to be a food security sensor.

BackgroundChildhood Takayasu’s arteritis (c-TA) is scarcely reported but is characterized by devastating morbidity and mortality. This study aims to investigate the clinical course of c-TA and prognostic factors associated with rehospitalization and events including vascular complications, flares, and death.MethodsAn ambispective study of 101 c-TA patients satisfying the American College of Rheumatology (ACR) criteria and/or the European League against Rheumatism (EULAR)/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS) criteria was conducted from January 2002 to December 2017. Data on demographic, clinical, laboratory, imaging, and therapeutic features were collected. Event-free survival, complication-free survival, flare-free survival, rehospitalization-free survival, and associated prognostic factors were assessed by Kaplan-Meier survival curve and propensity score analysis.ResultsThe median age at c-TA onset was 14 (interquartile range (IQR) 12–16) years and 76.2% were female. Hypertension (70.3%), blood pressure discrepancy (55.4%), bruits (51.5%), and pulse deficits (37.6%) were core presentations. Major vascular involvement included the renal artery (62.4%), abdominal aorta (42.6%), subclavian artery (43.6%), and carotid artery (42.6%). Glucocorticoids (78.2%), antihypertensive drugs (72.3%), antiplatelet agents (72.3%), and revascularization (57.4%) were made up the majority administered. At a median 2.4 (IQR 0.7–6.1) years of follow-up, events, rehospitalization, vascular complications, flares and death were observed in 44.6%, 37.6%, 44.6%, 26.7%, and 3%, respectively. The 5-year event-free survival, rehospitalization-free survival, vascular complication-free survival, and flare-free survival were 42.8%, 55.8%, 45.9%, and 62.3%, respectively. Body mass index (BMI) (hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.30–0.81, p = 0.005), stroke (HR = 7.37, 95% CI 2.35–23.1, p = 0.001), and revascularization (HR = 0.51, 95% CI 0.27–0.94, p = 0.032) were independent prognostic predictors of events. Predictors for rehospitalization include age at admission (HR = 0.81, 95% CI 0.69–0.94, p = 0.006), renal artery involvement (HR = 0.49, 95% CI 0.25–0.96, p = 0.037), and elevated C-reactive protein (CRP; HR = 2.50, 95% CI 1.24–5.00, p = 0.01). BMI level (p = 0.024) and renal artery involvement (p = 0.015) were also associated with vascular complications, while revascularization (p = 0.002) independently correlated with re-flares.ConclusionsThis large ambispective study of c-TA revealed an early 3% mortality at the first year and around 50% morbidity within 5 years after diagnosis. Hypertension, renal artery involvement, and revascularization based on anti-inflammation, antihypertension, and antiplatelet medications dominated c-TA with indications for optimistic prognosis. Patients with initial lower BMI level, a younger age at admission, stroke, and elevated CRP have a high risk of poor outcomes, requiring close c-TA monitoring and more aggressiv...

Rheumatoid arthritis (RA) and periodontal disease (PD) are chronic inflammatory diseases that share similar osteoclasia, human leukocyte antigen-DR4 allelic genes and immunological profile, and characteristic cytokines. Smoking can contribute to more severe RA and PD; secretion of pro-inflammatory mediators destroys the soft synovial membrane and periodontium, respectively. Anti-citrullinated protein antibodies and anti-α-enolase antibody are characteristic of these two diseases. Some studies suggest that PD may be associated with RA. Anti-Porphyromonas gingivalis (P. gingivalis) antibody, but no P. gingivalis bacterium can be detected in RA patients' joint fluid. Anti-P. gingivalis antibody has been seen as a biomarker of RA. Both diseases share some nosogenesis and common pathological pathways. However, there are differing views on the connection between the two diseases. Interferon-inducible-16 (IFI16) is a genic marker of RA; moreover, the association between IFI16 and PD is rare. Some studies suggest PD is related to periodontal parameters and patient's pathological status rather than RA. Disease frequency in men and women differ between these two diseases. The expression of interleukin-17 (IL-17) receptor only associates with different genders in PD (PD of different sexes have different IL-17 expressions). Periodontal local treatment only affects clinical periodontal status, and it does not alter circulating levels of IL-6, tumor necrosis factor-alpha or C-reactive protein which are associated with RA. This review examines the similarities and differences between these two diseases and explores possible interactions. Importantly, we will discuss whether PD is a feature of RA and whether this knowledge provides helpful information in future treatment of both diseases.

Rationale: Vaginal stone is a rare condition that is often misdiagnosed due to its low incidence. It can be divided into 2 types, primary vaginal and secondary vaginal, based on the etiology of the disease. Vaginal stones involve pathologic calcification. The formation of vaginal stones is mainly due to stasis and urine infection. We describe a procedure for the safe extraction of vaginal stones. Patient concerns: We report a case of a 25-year-old female patient with congenital genitourinary malformation and urethrovaginal fistula. A urogenital tract malformation repair operation was performed before she was 21 years old. Frequency of urination occurred before and after menstruation for 9 years, and dyspareunia occurred for 1 year. Diagnoses: B ultrasound examination showed a 59 × 55 × 23 mm fusiform region of increased signal intensity in the vagina followed by a sound shadow. We performed a gynecologic examination and found that the long diameter of the vaginal opening was 20 mm. A brown substance observed in her vagina had a hard texture and felt like a stone, and a palpation hand test revealed the size was approximately 60 × 50 mm. A cystoscope was inserted into the urethra and revealed that the broken end of the urethra was connected to the vagina. The proximal broken end of the urethra was 20 mm from the distal end. Interventions: The purpose of this operation was to make a definite diagnosis and remove the stones. We performed vaginal stone removal surgery and cystoscopy under anesthesia. Outcomes: We removed the stone successfully. The patient was discharged from the hospital after a smooth recovery without any complications. Follow-up was conducted 1 month after the operation and then every 3 months. Lessons: Although vaginal stones are rare, we must pay attention to this disease, especially in patients with congenital genitourinary malformations and urethrovaginal or vesicovaginal fistulas. Obstruction of urine discharge combined with repeated urinary tract infection is the main cause of vaginal stone formation. For these patients, follow-up every 3 months, including a physical examination, B-mode ultrasonography of the urinary system and cystoscopy if necessary, can avoid the occurrence of the disease.

The comparison with other detection methods shows the superior performance of this method, which indicates its potential for detecting seizure events in clinical practice. Additionally, much larger amounts of true continuous EEG data will be used to test the proposed method further in the future work.