Key message
Key message Three major QTLs for resistance to downy mildew were located within an 0.78 Mb interval on chromosome 8 in foxtail millet.
Downy mildew, a disease caused by
Sclerospora ...graminicola
, is a serious problem that jeopardizes the yield and quality of foxtail millet. Breeding resistant varieties represents one of the most economical and effective solutions, yet there is a lack of molecular markers related to the resistance. Here, a mapping population comprising of 158 F
6:7
recombinant inbred lines (RILs) was constructed from the crossing of G1 and JG21. Based on the specific locus amplified fragment sequencing results, a high-density linkage map of foxtail millet with 1031 bin markers, spanning 1041.66 cM was constructed. Based on the high-density linkage map and the phenotype data in four environments, a total of nine quantitative trait loci (QTL) associated with resistance to downy mildew were identified. Further BSR-seq confirmed the genomic regions containing the potential candidate genes related to downy mildew resistance. Interestingly, a 0.78-Mb interval between C8M257 and C8M268 on chromosome 8 was highlighted because of its presence in three major QTL,
qDM8_1
,
qDM8_2
, and
qDM8_4
, which contains 10 NBS-LRR genes. Haplotype analysis in RILs and natural population suggest that 9 SNP loci on
Seita8G.199800
,
Seita8G.195900
,
Seita8G.198300
, and
Seita.8G199300
genes were significantly correlated with disease resistance. Furthermore, we found that those genes were taxon-specific by collinearity analysis of pearl millet and foxtail millet genomes. The identification of these new resistance QTL and the prediction of resistance genes against downy mildew will be useful in breeding for resistant varieties and the study of genetic mechanisms of downy mildew disease resistance in foxtail millet.
Alzheimer's disease is pathologically defined by accumulation of extracellular amyloid-β (Aβ). Approximately 25 mutations in β-amyloid precursor protein (APP) are pathogenic and cause autosomal ...dominant Alzheimer's disease. To date, the mechanism underlying the effect of APP mutation on Aβ generation is unclear. Therefore, investigating the mechanism of APP mutation on Alzheimer's disease may help understanding of disease pathogenesis. Thus, APP mutations (A673T, A673V, E682K, E693G, and E693Q) were transiently co-transfected into human embryonic kidney cells. Western blot assay was used to detect expression levels of APP, beta-secretase 1, and presenilin 1 in cells. Enzyme-linked immunosorbent assay was performed to determine Aβ1-40 and Aβ1-42 levels. Liquid chromatography-tandem mass chromatography was used to examine VVIAT, FLF, ITL, VIV, IAT, VIT, TVI, and VVIA peptide levels. Immunofluorescence staining was performed to measure APP and early endosome antigen 1 immunoreactivity. Our results show that the protective A673T mutation decreases Aβ42/Aβ40 rate by downregulating IAT and upregulating VVIA levels. Pathogenic A673V, E682K, and E693Q mutations promote Aβ42/Aβ40 rate by increasing levels of CTF99, Aβ42, Aβ40, and IAT, and decreasing VVIA levels. Pathogenic E693G mutation shows no significant change in Aβ42/Aβ40 ratio because of inhibition of γ-secretase activity. APP mutations can change location from the cell surface to early endosomes. Our findings confirm that certain APP mutations accelerate Aβ generation by affecting the long Aβ cleavage pathway and increasing Aβ42/40 rate, thereby resulting in Alzheimer's disease.
•There has been little research on the association between childhood maltreatment and murderous ideation and behaviors in general adolescents population.•Murderous ideation and behaviors as a series ...of psychological possess, including ideation, plans, preparation and attempts were examined.•Each type of childhood maltreatment was significantly increasing the risks of murderous ideation and behaviors among adolescents and a dose-response relationship between them.
Previous research has revealed associations between childhood maltreatment (CM) and adverse health behaviors. However, little is known about the relationship between CM and adolescent murderous ideation and behaviors. A total of 5726 middle and high school students completed the Childhood Trauma Questionnaire-Short Form and the Murderous Ideation and Behaviors Questionnaire. The findings revealed that the prevalence rates for murderous ideation, plans, preparation, and attempts were 9.9%, 2.8%, 1.3%, and 0.6%, respectively. The results of multinomial logistic regression models indicated that adolescents who experienced CM were more likely to exhibit murderous ideation and behaviors, with adjusted odds ratios (AORs) ranging from 2.55 to 22.31. Additionally, a significant dose-response relationship was found between the number of CM types experienced and murderous ideation and behaviors (AORs ranging from 1.52 to 2.45). The odds of participants who had experienced three or five types of CM were significantly associated with murderous ideation and behaviors, with AORs ranging from 4.55 to 28.30 and from 5.26 to 85.45, respectively. The findings highlighted that adolescents who engaged in murderous ideation and behaviors were more likely to have a personal history of CM and revealed a dose-response relationship between the number of CM types and murderous ideation and behaviors.
•There has been little research on the association between school bullying and murder-related psychological behaviors among adolescents.•Murderous ideation and behaviors as a series of psychological ...possess, including murderous ideation, plans, preparation and attempts were examined.•Both primary and secondary school bullying, especially cyber forms, were more likely to have murder-related psychological behaviors among adolescents and a dose-response relationship was found in the current study.
Little is known about the relationship between precollege school bullying and murder-related psychological behaviors. The present study aims to examine that relationship in Chinese college students using a cross-sectional study. Self-report data were collected from 4034 college students in Anhui Province using a proportional stratified cluster sampling method. Four types of school bullying (i.e., physical, verbal, relational, and cyber) with bullies and victims and two periods (i.e., primary and secondary) were measured. The prevalence rates of murderous ideation, plans, preparation, and attempts were 6.9%, 2.5%, 1.8%, 1.4%, respectively. Different stages of precollege cyber bullying were associated with murder-related psychological behaviors for both bullies (primary: AORs = 2.78 to 15.67; secondary: AORs = 2.43 to 9.99; both periods: AORs = 2.26 to 14.04) and victims (primary: AORs = 2.87 to 16.57; secondary: AORs = 1.89 to 4.49; both periods: AORs = 3.68 to 21.48). A dose-response relationship was found, such that college students with a bullying perpetration index of two types and more were more likely to have murder-related psychological behaviors than those who were not bullied. Notably, both primary and secondary school bullying, especially cyber forms, were more likely to be associated with murder-related psychological behaviors. Therefore, it is necessary to develop school bullying preventive measures beginning in primary school.
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•The probe P-1 can selectively detect H2O2 with colorimetric change.•the P-1can be used for on-site and visual detection of H2O2.•The P-1 can image H2O2 in cells and distinguish ...cancer cells and normal cells.•The P-1 probe was applied to monitor H2O2 of tumor in mice.
We designed and developed the probe P-1 for detecting H2O2. The probe can selectively detect H2O2 with colorimetric change. In addition, the combination of portable test strips with a smartphone platform provided great convenience for on-site and visual detection of H2O2 with satisfactory sensitivity and reliability. The P-1 can image exogenous and endogenous H2O2 in cells and distinguish cancer cells and normal cells by fluorescence image of H2O2 and flow cytometry. Meanwhile, the P-1 probe has been successfully applied to monitor H2O2 levels of tumor in mice, and the results showed the level of H2O2 in tumor tissue increased significantly. Therefore, P-1 provided a potential chemical tool to understand pathological and physiological mechanisms of diseases by imaging H2O2.
Emerging evidence suggests that long non-coding RNAs (lncRNA) play critical roles in the development and progression of diverse cancers including hepatocellular carcinoma (HCC), but the underlying ...molecular mechanisms of lncRNAs that are involved in hepatocarcinogenesis have not been fully explored.
In this study, we profiled lncRNA expression in 127 pairs of HCC and nontumor liver tissues (a Discovery Cohort) using a custom microarray. The expression and clinical significance of lncCSMD1-1 were then validated with qRT-PCR and COX regression analysis in a Validation Cohort (n=260) and two External Validation Cohorts (n=92 and n=124, respectively). In vitro and
assays were performed to explore the biological effects of lncCSMD1-1 on HCC cells. The interaction of lncCSMD1-1 with MYC was identified by RNA pull-down and RNA immunoprecipitation. The role of LncCSMD1-1 in the degradation of MYC protein was also investigated.
With microarray, we identified a highly upregulated lncRNA, lncCSMD1-1, which was associated with tumor progression and poor prognosis in the Discovery Cohort, and validated in another 3 HCC cohorts. Consistently, ectopic expression of lncCSMD1-1 notably promotes cell proliferation, migration, invasion, tumor growth and metastasis of HCC cells in
and
experiments. Gene expression profiling on HCC cells and gene sets enrichment analysis indicated that the MYC target gene set was significantly enriched in HCC cells overexpressing lncCSMD1-1, and lncCSMD1-1 was found to directly bind to MYC protein in the nucleus of HCC cells, which resulted in the elevation of MYC protein. Mechanistically, lncCSMD1-1 interacted with MYC protein to block its ubiquitin-proteasome degradation pathway, leading to activation of its downstream target genes.
lncCSMD1-1 is upregulated in HCC and promotes progression of HCC by activating the MYC signaling pathway. These results provide the evidence that lncCSMD1-1 may serve as a novel prognostic marker and potential therapeutic target for HCC.
Downy mildew caused by
is a systemic infectious disease affecting foxtail millet production in Africa and Asia.
-infected leaves could be decomposed to a state where only the veins remain, resulting ...in a filamentous leaf tissue symptom. The aim of the present study was to investigate how
influences the formation of the filamentous leaf tissue symptoms in hosts at the morphological and molecular levels. We discovered that vegetative hyphae expanded rapidly, with high biomass accumulated at the early stages of
infection. In addition,
could affect spikelet morphological development at the panicle branch differentiation stage to the pistil and stamen differentiation stage by interfering with hormones and nutrient metabolism in the host, resulting in hedgehog-like panicle symptoms.
could acquire high amounts of nutrients from host tissues through secretion of β-glucosidase, endoglucanase, and pectic enzyme, and destroyed host mesophyll cells by mechanical pressure caused by rapid expansion of hyphae. At the later stages,
could rapidly complete sexual reproduction through tryptophan, fatty acid, starch, and sucrose metabolism and subsequently produce numerous oospores. Oospore proliferation and development further damage host leaves via mechanical pressure, resulting in a large number of degraded and extinct mesophyll cells and, subsequently, malformed leaves with only veins left, that is, "filamentous leaf tissue." Our study revealed the
expansion characteristics from its asexual to sexual development stages, and the potential mechanisms via which the destructive effects of
on hosts occur at different growth stages.
ObjectivesTo develop and validate a nomogram model to predict chronic kidney disease (CKD) stages 3–5 prognosis.DesignA retrospective cohort study. We used univariate and multivariate Cox regression ...analysis to select the relevant predictors. To select the best model, we evaluated the prediction models’ accuracy by concordance index (C-index), calibration curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). We evaluated the clinical utility by decision curve analysis.SettingChronic Disease Management (CDM) Clinic in the Nephrology Department at the Guangdong Provincial Hospital of Chinese Medicine.ParticipantsPatients with CKD stages 3–5 in the derivation and validation cohorts were 459 and 326, respectively.Primary outcome measureRenal replacement therapy (haemodialysis, peritoneal dialysis, renal transplantation) or death.ResultsWe built four models. Age, estimated glomerular filtration rate and urine protein constituted the most basic model A. Haemoglobin, serum uric acid, cardiovascular disease, primary disease, CDM adherence and predictors in model A constituted model B. Oral medications and predictors in model A constituted model C. All the predictors constituted model D. Model B performed well in both discrimination and calibration (C-index: derivation cohort: 0.881, validation cohort: 0.886). Compared with model A, model B showed significant improvement in the net reclassification and integrated discrimination (model A vs model B: NRI: 1 year: 0.339 (−0.011 to 0.672) and 2 years: 0.314 (0.079 to 0.574); IDI: 1 year: 0.066 (0.010 to 0.127), p<0.001 and 2 years: 0.063 (0.008 to 0.106), p<0.001). There was no significant improvement between NRI and IDI among models B, C and D. Therefore, we selected model B as the optimal model.ConclusionsWe constructed a prediction model to predict the prognosis of patients with CKD stages 3–5 in the first and second year. Applying this model to clinical practice may guide clinical decision-making. Also, this model needs to be externally validated in the future.Trial registration numberChiCTR1900024633 (http://www.chictr.org.cn).
The high mortality rate of immunocompromised patients with fungal infections and the limited availability of highly efficacious and safe agents demand the development of new antifungal therapeutics. ...To rapidly discover such agents, we developed a high-throughput synergy screening (HTSS) strategy for novel microbial natural products. Specifically, a microbial natural product library was screened for hits that synergize the effect of a low dosage of ketoconazole (KTC) that alone shows little detectable fungicidal activity. Through screening of almost equal to20,000 microbial extracts, 12 hits were identified with broad-spectrum antifungal activity. Seven of them showed little cytotoxicity against human hepatoma cells. Fractionation of the active extracts revealed beauvericin (BEA) as the most potent component, because it dramatically synergized KTC activity against diverse fungal pathogens by a checkerboard assay. Significantly, in our immunocompromised mouse model, combinations of BEA (0.5 mg/kg) and KTC (0.5 mg/kg) prolonged survival of the host infected with Candida parapsilosis and reduced fungal colony counts in animal organs including kidneys, lungs, and brains. Such an effect was not achieved even with the high dose of 50 mg/kg KTC. These data support synergism between BEA and KTC and thereby a prospective strategy for antifungal therapy.
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