Search

De novo truncations in Interferon Regulatory Factor 2 Binding Protein Like (IRF2BPL) lead to severe childhood-onset neurodegenerative disorders. To determine how loss of IRF2BPL causes neural dysfunction, we examined its function in Drosophila and zebrafish. Overexpression of either IRF2BPL or Pits, the Drosophila ortholog, represses Wnt transcription in flies. In contrast, neuronal depletion of Pits leads to increased wingless (wg) levels in the brain and is associated with axonal loss, whereas inhibition of Wg signaling is neuroprotective. Moreover, increased neuronal expression of wg in flies is sufficient to cause age-dependent axonal loss, similar to reduction of Pits. Loss of irf2bpl in zebrafish also causes neurological defects with an associated increase in wnt1 transcription and downstream signaling. WNT1 is also increased in patient-derived astrocytes, and pharmacological inhibition of Wnt suppresses the neurological phenotypes. Last, IRF2BPL and the Wnt antagonist, CKIα, physically and genetically interact, showing that IRF2BPL and CkIα antagonize Wnt transcription and signaling.

This study investigated whether artemisinin (ART) exerts a neuroprotective effect against cerebral ischemia/reperfusion (I/R) injury. Hypoxia-glucose deprivation and reoxygenation (OGD/R) of SH-SY5Y cells were used as the I/R injury model in vitro. Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and lactate dehydrogenase (LDH) release was measured. Cell apoptosis and apoptosis-associated protein expression were determined via flow cytometry and western blotting, respectively. The levels of glutathione peroxidase, superoxide dismutase, catalase, and malondialdehyde were determined. The secretion of tumor necrosis factor-α and interleukin-1β was measured using ELISA. The activation of the nuclear factor kappa B (NF-κB) pathway was also determined. The indicated ART concentrations (0, 25, 50, 75, and 100 μM) had no significant effect on SH-SY5Y cell viability and LDH activity. ART promoted cell viability, reduced cell apoptosis, repressed cellular inflammation, and inhibited cellular oxidative stress and NF-κB signaling pathway in OGD/R-induced SH-SY5Y cells. In addition, all the protective effects of ART on OGD/R-induced SH-SY5Y cell injury were significantly reversed by an NF-κB agonist. In conclusion, ART protects neurons from OGD/R-induced damage in vitro by inhibiting the NF-κB signaling pathway. These results suggest that ART may be a potential agent for the treatment of cerebral I/R injury.

BackgroundAs the second primary type of cognitive impairment worldwide, vascular cognitive impairment (VCI) is closely associated with cerebrovascular risks, which imposes a heavy burden on the society and families. Early diagnosis and treatment are important for intervening and reversing VCI. And formulating high-quality clinical guidelines is an effective way to improve diagnosis and treatment levels of VCI.ObjectiveTo assess the quality of guidelines for VCI, aiming at offering support for making clinical decisions for VCI.MethodsFrom August to November 2021, we searched literature databases and websites in China and abroad to identify guidelines for VCI, and assessed them using the Appraisal of Guidelines for Research & Evaluation (AGREE) Ⅱ.ResultsA total of 18 guidelines were enrolled, 12 of which are Chinese guidelines and 6 are foreign guidelines; 9 of which are evidence-based guidelines, and the other 9 are not. The intraclass correlation coefficient was 0.935, indicating a high degree of agreement between raters. The overall quality of these guidelines was relatively low, since in the six domains, only the average score of Clarity of Presentation was greater than 60% (64.04%) , and the average scores of Scope and Purpose (52.31%) and Editorial Independence (42.01%) were between 30% and 60%, and those for other three domains, Stakeholder Involvement (27.24%) , Rigor of Development (20.05%) and Applicability (13.83%) , were all less than 30%. The grade of recommendation for 6 guidelines was B, and that for other 12 guidelines was C.ConclusionThe overall quality of the included guidelines was rated relatively low, especially their average score for each of the three domains, Stakeholder Involvement, Rigor of Development, and Applicability, was below the average level. It is suggested to enhance the quality of VCI guidelines via improving the details of guidelines strictly under the evidence-based principle.

The mitochondrial distribution and morphology family 33 gene (MDM33) regulates mitochondrial homeostasis by mediating the mitochondrial fission process in yeast. The wheat head blight Fusarium graminearum contains an FgMdm33 protein that is orthologous to Saccharomyces cerevisiae Mdm33, albeit its function remains unknown. We have reported here the roles of FgMdm33 in regulating fungal morphogenesis, mitochondrial morphology, autophagy, apoptosis, and fungal pathogenicity. The ΔFgmdm33 mutants generated through a homologous recombination strategy in this study exhibited defects in terms of mycelial growth, conidia production, and virulence. Hyphal cells lacking FgMDM33 displayed elongated mitochondria and a dispensable respiratory-deficient growth phenotype, indicating the possible involvement of FgMDM33 in mitochondrial fission. The ΔFgmdm33 mutants displayed a remarkable reduction in the proteolysis of GFP-FgAtg8, whereas the formation of autophagic bodies in the hyphal cells of mutants was recorded under the induction of mitophagy. In addition, the transcriptional expression of the apoptosis-inducing factor 1 gene (FgAIF1) was significantly upregulated in the ΔFgmdm33 mutants. Cumulatively, these results indicate that FgMDM33 is involved in mitochondrial fission, non-selective macroautophagy, and apoptosis and that it regulates fungal growth, conidiation, and pathogenicity of the head blight pathogen. [ABSTRACT FROM AUTHOR]

Tea leaf spot caused by Didymella segeticola is an important disease that threatens the healthy growth of tea plants (Camellia sinensis) and results in reductions in the productivity and quality of tea leaves. Early diagnosis of the disease is particularly important for managing the infection. Loop-mediated isothermal amplification (LAMP) assay is an efficient diagnostic technique with the advantages of simplicity, specificity, and sensitivity. In this study, we developed a rapid, visual, and high-sensitivity LAMP assay for D. segeticola detection based on sequence-characterized amplified regions. Two pairs of amplification primers (external primers F3 and B3 and internal primers FIP and BIP) were designed based on a specific sequence in D. segeticola (NCBI accession number: OR987684). Compared to common pathogens of other genera in tea plants and other species in the Didymella genus (Didymella coffeae-arabicae, Didymella pomorum, and Didymella sinensis), the LAMP method is specific for detecting the species D. segeticola. The assay was able to detect D. segeticola at a minimal concentration of 1 fg/μL genomic DNA at an optimal reaction temperature of 65 °C for 60 min. When healthy leaves were inoculated with D. segeticola in the laboratory, the LAMP method successfully detected D. segeticola in diseased tea leaves at 72 h post inoculation. The LAMP assays were negative when the DNA samples were extracted from healthy leaves. Leaf tissues with necrotic lesions from 18 germplasms of tea plants tested positive for the pathogen by the LAMP assay. In summary, this study established a specific, sensitive, and simple LAMP method to detect D. segeticola, which provides reliable technical support for estimating disease prevalence and facilitates sustainable management of tea leaf spot. [ABSTRACT FROM AUTHOR]

Soil acidification has emerged as a critical limiting factor for the sustainable development of the tea industry. In this article, a comprehensive review of 63 original research articles focusing on the impact of amendments on the pH in tea plantations soil was conducted. Through meta-analysis, the effect of applying soil amendments to increase the pH of tea plantation soil and its influencing factors were investigated. The results revealed that lime had a significant impact, increasing the pH by 18% in tea plantation soil, while rapeseed cake had a minimal (2%) effect. It was observed that as the quantity of amendments and pH levels increased, so did their impact on the pH of tea plantation soil. Subgroup analysis within biochar showed varying effects, depending on soil pH, with an 11% increase in acidic soil. Among these amendments, biochar produced at pyrolysis temperature ranging from 501–600 °C and derived from animal waste demonstrated significant effect on increasing soil pH in tea plantations by 9% and 12%, respectively. This study offers valuable insights into improving and ensuring the health and sustainability of tea plantations. [ABSTRACT FROM AUTHOR]

The herringbone multi-ribbed reticulated shell concrete structure (HMRSCS) was a new type of structure similar in appearance to a traditional sloping roof structure, but the elimination of the tension beams below the folded slab for supporting the members results in different dynamic characteristics from those of the conventional structure. In order to study the dynamic characteristics of HMRSCSs, a new simplified equivalent model was proposed for HMRSCSs based on the action of the vertex loading method in the traditional classical model. A vertex loading test was carried out on HMRSCS to identify the modal parameters of the model and to verify the applicability of the model. The results showed that the numerical model of HMRSCS was established and the experimental and numerical results were in good agreement. The traditional classical model based on the assumption of rigid floor slab was not fully applicable to HMRSCS, while the new simplified equivalent model could truly and accurately reflect the structural frequency and vibration mode of the new structure.