Virulence, structure, and triadimefon sensitivity of the Puccinia striiformis f. sp. tritici population in Shaanxi Province, China.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is the most destructive fungal disease affecting wheat in China, especially in Shaanxi Province, an important epidemiological region connecting the western Pst over-summer regions and the central and eastern spring epidemic regions in the country. In the present study, 291 Pst isolates from Shaanxi Province were studied for their virulence using two sets of wheat differentials, population structure using single-nucleotide polymorphism (SNP) markers, and sensitivity to fungicide. When the isolates were tested on the Chinese differentials of 19 wheat cultivars, 72 races were identified, which belonged to three groups, including the Guinong 22 group (48.45%), Hybrid 46 group (31.62%), and Suwon 11 group (19.93%). The three most predominant races were CYR34 (15.46%), G22-14 (11.68%), and CYR32 (10.65%). When the isolates were tested on the 18 Yr single-gene differentials, 95 races were identified, but none of the isolates were virulent to either Yr5 or Yr15. Cluster analyses of the virulence data based on the two sets of differentials and the SNP marker data consistently separated the Shaanxi Pst population into two clusters in the central part and southern part of the Province. Triadimefon sensitivity testing across different concentrations showed a broad range of half-maximal effective concentration (EC50) values, from 0.03 to 5.99 µg mL-1, with a mean EC50 of 0.46 µg mL-1. The majority of isolates (90.72%) were sensitive to the fungicide. The correlation analyses of the virulence, SNP marker, and the triadimefon sensitivity data showed no significant correlations, except a logarithmic relationship between the EC50 value and the number of avirulence factors. This study is the first to determine the relationship of virulence and SNP markers with triadimefon sensitivity in a regional Pst population.The findings provide valuable insights for breeding resistant wheat cultivars and integrated management of stripe rust.

Virulence Characterization of Puccinia striiformis f. sp. tritici in China Using the Chinese and Yr Single-Gene Differentials.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most important diseases of wheat. Identifying Pst races is essential for developing resistant cultivars and managing the disease. In this study, 608 isolates collected from China in 2021 were tested with the Chinese set of 19 wheat variety differentials and the set of 18 Yr single-gene differentials. Of the 119 races detected with the Chinese set of differentials, 94 were new. A higher number (149) of races were identified using the Yr single-gene differentials. The frequencies of virulence factors to 17 of the 19 Chinese differential varieties and to 10 of the 18 Yr single-gene differentials were high (>60%). None of the isolates were virulent to the differentials Zhong 4 (Yr genes unknown) and Triticum spelta Album (Yr5) in the Chinese set and the Yr5 and Yr15 lines in the single-gene set of differentials, indicating that these genes or varieties are effective against the Pst population detected in 2021. Using Nei's genetic distance, the 16 provincial Pst populations were clustered into six groups based on the Chinese set and eight groups based on the Yr single-gene set of differentials. In addition, we found that the same races identified using the Chinese differentials could be further differentiated into different races using the Yr single-gene differentials, suggesting a higher differential capability than the Chinese set of differentials. The results provide a scientific basis for monitoring Pst populations and guiding resistance breeding in China.

Sensitivity of Puccinia triticina f. sp. tritici from China to Triadimefon and Resistance Risk Assessment.

Wheat leaf rust, caused by Puccinia triticina f. sp. tritici (Pt), is distributed widely in wheat-producing areas and results in serious yield losses worldwide. In China, leaf rust has been largely controlled with a demethylation inhibitor (DMI) fungicide, triadimefon. Although high levels of fungicide resistance in pathogens have been reported, no field failure of wheat leaf rust to DMI fungicides has been reported in China. A resistance risk assessment of triadimefon to Pt was investigated in the present study. The sensitivity of 197 Pt isolates across the country to triadimefon was determined, and the density distribution of EC50 values (concentration at which mycelial growth is inhibited by 50%) showed a continuous multimodal curve because of the extensive use of this fungicide in wheat production, with a mean value of 0.46 µg/ml. The majority of the tested Pt isolates were sensitive to triadimefon, whereas 10.2% developed varying degrees of resistance. Characterization of parasitic fitness revealed that the triadimefon-resistant isolates exhibited strong adaptive traits in urediniospore germination rate, latent period, sporulation intensity, and lesion expansion rate. No correlation was observed between triadimefon and tebuconazole and hexaconazole, which have the similar mode of action, or pyraclostrobin and flubeneteram, which have different modes of action. Overexpression of the target gene Cyp51 led to the triadimefon resistance of Pt. The risk of resistance to triadimefon in Pt may be low to moderate. This study provided important data for fungicide resistance risk management against wheat leaf rust.

Effects of Flubeneteram on Inhibiting the Development of Puccinia striiformis f. sp. tritici in Wheat Leaves.

Stripe rust caused by Puccinia striiformis f. sp. tritici (Pst) is a serious threat to wheat production, and the application of fungicides is one of the most important means for controlling the disease. The purpose of this study is to determine the effects of a new succinate dehydrogenase inhibitor (SDHI) fungicide, flubeneteram, on reducing stripe rust. The baseline sensitivity of 173 Pst isolates from 13 provinces of China to flubeneteram was determined. Flubeneteram displayed significant effects on inhibiting SDH enzymes of Pst. Histological observations showed that after flubeneteram application, the formation and development of Pst hyphae and haustoria were significantly inhibited, and the structures were destroyed. Flubeneteram primed wheat for salicylic acid-induced defenses via upregulating pathogenesis-related genes (PR1 and PR2). Altogether, our study is the first to provide evidence that flubeneteram induces wheat defense against Pst infection. The findings indicate that flubeneteram could be an effective fungicide for managing stripe rust.

Shared and unique effects of ApoEε4 and pathogenic gene mutation on cognition and imaging in preclinical familial Alzheimer's disease.

BACKGROUND: Neuropsychology and imaging changes have been reported in the preclinical stage of familial Alzheimer's disease (FAD). This study investigated the effects of APOEε4 and known pathogenic gene mutation on different cognitive domains and circuit imaging markers in preclinical FAD. METHODS: One hundred thirty-nine asymptomatic subjects in FAD families, including 26 APOEε4 carriers, 17 APP and 20 PS1 mutation carriers, and 76 control subjects, went through a series of neuropsychological tests and MRI scanning. Test scores and imaging measures including volumes, diffusion indices, and functional connectivity (FC) of frontostriatal and hippocampus to posterior cingulate cortex pathways were compared between groups and analyzed for correlation. RESULTS: Compared with controls, the APOEε4 group showed increased hippocampal volume and decreased FC of fronto-caudate pathway. The APP group showed increased recall scores in auditory verbal learning test, decreased fiber number, and increased radial diffusivity and FC of frontostriatal pathway. All three genetic groups showed decreased fractional anisotropy of hippocampus to posterior cingulate cortex pathway. These neuropsychological and imaging measures were able to discriminate genetic groups from controls, with areas under the curve from 0.733 to 0.837. Circuit imaging measures are differentially associated with scores in various cognitive scales in control and genetic groups. CONCLUSIONS: There are neuropsychological and imaging changes in the preclinical stage of FAD, some of which are shared by APOEε4 and known pathogenic gene mutation, while some are unique to different genetic groups. These findings are helpful for the early identification of Alzheimer's disease and for developing generalized and individualized prevention and intervention strategies.

A 19-Year-Old Adolescent with Probable Alzheimer's Disease.

Alzheimer's disease (AD) primarily affects older adults. In this report, we present the case of a 19-year-old male with gradual memory decline for 2 years and World Health Organization-University of California Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT) results also showing memory impairment. Positron emission tomography-magnetic resonance imaging with 18F fluorodeoxyglucose revealed atrophy of the bilateral hippocampus and hypometabolism in the bilateral temporal lobe. Examination of the patient's cerebrospinal fluid showed an increased concentration of p-tau181 and a decreased amyloid-ß 42/40 ratio. However, through whole-genome sequencing, no known gene mutations were identified. Considering the above, the patient was diagnosed with probable AD.

Predicted Immune-Related Genes and Subtypes in Systemic Lupus Erythematosus Based on Immune Infiltration Analysis.

Objective: The present investigation is aimed at identifying key immune-related genes linked with SLE and their roles using integrative analysis of publically available gene expression datasets. Methods: Four gene expression datasets pertaining to SLE, 2 from whole blood and 2 experimental PMBC, were sourced from GEO. Shared differentially expressed genes (DEG) were determined as SLE-related genes. Immune cell infiltration analysis was performed using CIBERSORT, and case samples were subjected to k-means cluster analysis using high-abundance immune cells. Key immune-related SLE genes were identified using correlation analysis with high-abundance immune cells and subjected to functional enrichment analysis for enriched Gene Ontology Biological Processes and KEGG pathways. A PPI network of genes interacting with the key immune-related SLE genes was constructed. LASSO regression analysis was performed to identify the most significant key immune-related SLE genes, and correlation with clinicopathological features was examined. Results: 309 SLE-related genes were identified and found functionally enriched in several pathways related to regulation of viral defenses and T cell functions. k-means cluster analysis identified 2 sample clusters which significantly differed in monocytes, dendritic cell resting, and neutrophil abundance. 65 immune-related SLE genes were identified, functionally enriched in immune response-related signaling, antigen receptor-mediated signaling, and T cell receptor signaling, along with Th17, Th1, and Th2 cell differentiation, IL-17, NF-kappa B, and VEGF signaling pathways. LASSO regression identified 9 key immune-related genes: DUSP7, DYSF, KCNA3, P2RY10, S100A12, SLC38A1, TLR2, TSR2, and TXN. Imputed neutrophil percentage was consistent with their expression pattern, whereas anti-Ro showed the inverse pattern as gene expression. Conclusions: Comprehensive bioinformatics analyses revealed 9 key immune-related genes and their associated functions highly pertinent to SLE pathogenesis, subtypes, and identified valuable candidates for experimental research.

Culture Effects on the Chinese Version Boston Naming Test Performance and the Normative Data in the Native Chinese-Speaking Elders in Mainland China.

Background: The Chinese version of Boston Naming Test (BNT-C) is administered in China widely. However, the neuropsychological parameter of BNT-C in native Chinese-speaking elders in mainland China has not been explored systematically. The aim of this study was to explore cultural influences on BNT-C performance and establish norms among native Chinese-speaking elders in Beijing. Methods: A total of 161 native, Chinese-speaking, cognitively normal elders aged ≥55 years were enrolled from various communities in Beijing. The BNT-C was conducted on all the participants. The internal consistency, participants' familiarity, and naming accuracy were analyzed and compared with data from Chinese areas outside the mainland and from American published previously. The influencing factors and stratified norms for BNT-C were established. Results: The BNT-C showed good internal consistency (α = 0.738). Strong correlation between naming accuracy and object familiarity was found (r = 0.962, P < 0.001). Participants' familiarity and correct naming rate for many items were notably different between the Chinese-speaking elders and English-speaking elders in America. The difference in some items' correct naming rate also existed between Beijing, Taiwan, and Hongkong. Higher education was associated with higher scores, whereas age and gender had no effect on BNT-C performance. The recommended norms of total naming scores for elders with education ≤ 9 and >9 years were 16 and 23, respectively. Conclusion: The participants' familiarity with BNT items differed between different cultures, which further affected the naming accuracy and total scores. The education stratified norms established here are helpful for the better application of BNT-C in mainland China.

Clinical Practice Guidelines for the Management of Behavioral and Psychological Symptoms of Dementia: A Systematic Review With AGREE II.

Background: High-quality clinical practice guidelines (CPGs) are important for the effective treatment of behavioral and psychological symptoms of dementia (BPSD). However, recommendations provided by different quality guidelines may lead to varied clinical practice outcomes. Objective: To assess the quality of available CPGs for the management of BPSD and summarize the best recommendations for treating BPSD. Methods: This was a systematic review of CPGs for the management of BPSD with data obtained from electronic databases and evaluated using the Appraisal of Guidelines for Research and Evaluation II instrument, consisting of six domains: "Scope and purpose", "Stakeholder involvement", "Rigor of development", "Clarity of presentation", "Applicability", and "Editorial independence". The criteria for high-quality guidelines were set as: the score of high-quality guidelines in the "Rigor of development" domain should be ≥60% and as well as a score of >60% in at least three other domains. High-quality guidelines were selected for recommendation extraction, and the final recommendations were formed in combination with the latest meta-analysis and randomized clinical-trial results. Results: In term of median scores in each domain for the six included CPGs, "Scope and purpose" (87.5%) scored better than all others, whereas "Applicability" (46.5%) was the domain with the lowest score. Four CPGs (2015 APA, 2018 NICE, 2018 CANADA, 2020 EAN) met the criteria of high-quality guidelines and were used to extract recommendations. From these four CPGs, nine specific recommendations related to the management of BPSD were summarized, of which seven were related to pharmacological treatment and two to non-pharmacological treatment. These recommendations covered the applicability of antipsychotic drugs, medication recommendations, withdrawal times, and several suitable non-pharmacological therapies. Conclusion: The quality of CPGs for the management of BPSD requires improvement, especially for the "Applicability" domain. For psychotic-like symptoms in dementia, the use of antipsychotics should be based on the individual's risk-benefit ratio, and the use of atypical antipsychotics seems to be a better choice. Non-pharmacological treatments may be suitable for emotional symptoms and sleep disorders. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020209204.