Brain capillaries are crucial for cognitive functions by supplying oxygen and other nutrients to and removing metabolic wastes from the brain. Recent studies have demonstrated that constriction of ...brain capillaries is triggered by beta-amyloid (Aβ) oligomers via endothelin-1 (ET1)-mediated action on the ET1 receptor A (ETRA), potentially exacerbating Aβ plaque deposition, the primary pathophysiology of Alzheimer’s disease (AD). However, direct evidence is still lacking whether changes in brain capillaries are causally involved in the pathophysiology of AD. Using APP/PS1 mouse model of AD (AD mice) relative to age-matched negative littermates, we identified that reductions of density and diameter of hippocampal capillaries occurred from 4 to 7 months old while Aβ plaque deposition and spatial memory deficit developed at 7 months old. Notably, the injection of ET1 into the hippocampus induced early Aβ plaque deposition at 5 months old in AD mice. Conversely, treatment of ferulic acid against the ETRA to counteract the ET1-mediated vasoconstriction for 30 days prevented reductions of density and diameter of hippocampal capillaries as well as ameliorated Aβ plaque deposition and spatial memory deficit at 7 months old in AD mice. Thus, these data suggest that reductions of density and diameter of hippocampal capillaries are crucial for initiating Aβ plaque deposition and spatial memory deficit at the early stages, implicating the development of new therapies for halting or curing memory decline in AD.
Autism spectrum disorder (ASD) is a complex disease involving multiple genes and multiple sites, and it is closely related to environmental factors. It has been gradually revealed that long noncoding ...RNAs (lncRNAs) may regulate the pathogenesis of ASD at the epigenetic level. In neuronal cells, the lncRNA moesin pseudogene 1 antisense (MSNP1AS) forms a double‐stranded RNA with moesin (MSN) to suppress moesin protein expression. MSNP1AS overexpression can activate the RhoA pathway and inhibit the Rac1 and PI3K/Akt pathways; however, the regulation of Rac1 by MSNP1AS is not associated with MSN, and the effect on the RhoA pathway may also be associated with other factors. MSNP1AS can decrease the number and length of neurites, inhibit neuronal cell viability and migration, and promote apoptosis. Downregulation of MSN expression functions similarly to MSNP1AS, and its overexpression can block the above functions of MSNP1AS. In addition, in vivo experiments show that MSN improves social interactions and reduces repetitive behaviors in BTBR mice, decreases the activity of RhoA and restores the activity of PI3K/Akt pathway. Therefore, the abnormal expression of MSNP1AS in ASD patients might influence the structure and survival of neuronal cells through the regulation of moesin protein expression to facilitate the development and progression of ASD. These findings provide new evidence for studying the mechanisms of lncRNAs in ASD.
Lay Summary
Autism spectrum disorder (ASD) is a common neurodevelopmental disease and its neurodevelopmental mechanisms have not been elucidated. More and more studies have found that long noncoding RNAs (lncRNAs) can regulate the development of central nervous system in many ways and affect the pathogenic process of ASD. Moesin pseudogene 1 antisense (MSNP1AS) is an up‐regulated lncRNA in ASD patients. In‐depth functional experiments showed that MSNP1AS inhibited moesin protein expression and regulated the activation of multiple signaling pathways, thus decreasing the number and length of neurites, inhibiting neuronal cell viability and migration, and promoting apoptosis. Therefore, MSNP1AS is an important lncRNA related to ASD and can regulate the biological function of neurons.
The dentinogenic ghost cell tumor (DGCT), a locally invasive benign neoplasm, is one of the rarest odontogenic tumors, usually developing in the maxilla or mandible. It can be classified into 2 ...types: intraosseous (central) and extraosseous (peripheral). Here, we describe the first case of a peripheral DGCT located in the ethmoid sinus.
An 8-year-old boy presented to our department with a longer than 7-month history of nasal obstruction, purulent secretion, and reduction in sense of smell in the right nasal cavity.
The patient was diagnosed with peripheral DGCT of the ethmoid sinus based on computed tomography scan and pathology.
Functional endoscopic sinus surgery was performed.
With 2 years of follow-up, there was no evidence of recurrence.
Peripheral DGCT can occur in the paranasal sinus and the need to consider this entity as a possible diagnosis by the clinicians.
Epstein–Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum IgA antibodies against early antigen (EA‐IgA) and viral capsid antigen (VCA‐IgA) are the most commonly used ...to screen for NPC in endemic areas. However, the prognostic value of serum EA‐IgA and VCA‐IgA in patients with NPC is less clear. We hypothesize that serum EA‐IgA and VCA‐IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non‐metastatic NPC and undetectable pEBV DNA were included. Serum EA‐IgA and VCA‐IgA were determined by ELISA. After analysis, serum EA‐IgA and VCA‐IgA loads correlated positively with T, N, and overall stage (all P < 0.05). Serum EA‐IgA was not associated with survival outcome in univariable analyses. But patients with serum VCA‐IgA >1:120 had significantly inferior 5‐year progression‐free survival (80.4% vs 89.6%, P = 0.025), distant metastasis‐free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse‐free survival (88.4% vs 95.6%, P = 0.023; log–rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA‐IgA became insignificant. Further analyses revealed that serum VCA‐IgA was not an independent prognostic factor in early N (N0–1) or advanced N (N2–3) stage NPC. In summary, although both EA‐IgA and VCA‐IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA.
To the best of our knowledge, the current study is the first large‐scale study to demonstrate the impact of EBV antibodies on the prognosis of patients with non‐metastatic NPC from a population with a high prevalence of both EBV infection and NPC. Our study findings did not confirm the role of EA‐IgA and VCA‐IgA as prognostic biomarkers in patients with NPC and undetectable pEBV DNA. However, it is plausible that EA‐IgA and VCA‐IgA may enhance patient stratification by providing an additional layer of information on disease burden. In support of this suggestion, EA‐IgA and VCA‐IgA were positively associated with T stage, N stage and overall stage.
A thorough knowledge of the consolidation behavior of highly saturated soil under time-dependent stress is essential for the design and construction of abandoned-soil dump sites in the soft soil ...regions of China. In this study, one-dimensional consolidation analytical solutions are derived for such soil under one-way and two-way drainage conditions, accommodating the time-dependent stress created by various dumping protocols. Representative soil samples are obtained, and consolidation tests are conducted with various saturation degrees (one-way drainage) and loading protocols (two-way drainage), to verify the consolidation equation and determine its range of applicability to various saturation degrees. The effects of layer thickness, dumping type, and compaction degree on the consolidation behaviors of highly saturated abandoned-soil dumps are investigated. The one-dimensional consolidation equation is applicable to soil with saturation degree not lower than 75% under instantaneous stress, stepped stress, and linear stress. The pore pressure distribution with depth is not symmetrical; the eccentric distance of consolidation degree increases with increasing layer thickness in the stress application stage and is approximately zero in the stress keeping stage. The pore pressure at middle of the soil layer increases with increasing layer thickness and decreases with increasing dumping rate from the completion of soil dumping. With increasing compaction degree, the middle pore pressure increases, while the surface settlement decreases. In the premise of the stability of an abandoned-soil dump, where the goals are to reduce post-construction settlement and to shorten the consolidation process of the entire soil layer, the important factors are smaller layer thickness, higher dumping rate, and larger compaction degree.
•1D consolidation model was established for highly saturated abandoned-soil dumps.•The model was validated by conducting large-scale consolidation tests.•The model was applied to an abandoned-soil dump via sensitivity analysis.•The model is applicable for soil with Sr>75% under instantaneous, stepped, linear stresses.•Smaller layer thickness, higher dumping rate, larger compaction degree benefits such dumps.
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18–25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the ...biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA–target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA–target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.
PagWOX11/12a is induced by drought stress, and transgenic poplar overexpressing PagWOX11/12a exhibited increased root elongation and biomass growth, leading to enhanced drought tolerance. PagERF35 ...can bind to the PagWOX11/12a promoter and activate its expression.
Abstract
In plants, a large root system improves the uptake of water and nutrients, and is important for responding to drought stress. The poplar WUSCHEL-related homeobox (WOX) transcription factor promotes adventitious rooting, but its regulation of root growth in response to drought stress remains elusive. In this study, we found that PagWOX11/12a from hybrid poplar 84K (Populus alba×Populus glandulosa) is expressed predominantly in the roots and is strongly induced by drought stress. Compared with non-transgenic 84K plants, transgenic poplar plants overexpressing PagWOX11/12a displayed increased root biomass and enhanced drought tolerance, while opposite phenotypes were observed for PagWOX11/12a dominant repression plants. PagWOX11/12a functions as a nuclear transcriptional activator with a transactivation domain at the C-terminus. In addition, PagERF35 was found to specifically bind to a dehydration-responsive element (DRE) within the PagWOX11/12a promoter and activate PagWOX11/12a gene expression. These results indicate that PagERF35 may activate PagWOX11/12a expression in response to drought stress by promoting root elongation and biomass, thereby increasing drought tolerance of poplar.
Abstract
Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we ...functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.
•We establish an improved model to represent the microstructure forming process of polyacrylate polymer modified mortars.•We specify the chemical reactions between PA polymer and cement hydrates.•We ...design a simulation test to identify the reactions products in polymer modified mortars.•The influence of PA polymer on the mechanical performance and pore structure was enlightened.
The microstructure forming process of polyacrylate (PA) latex modified cement-based materials was investigated from mixing to hardening. Owing to the chemical reaction between PA particles and calcium ions in the pore solution, PA polymer will not uniformly disperse in cement mortar due to its adsorption on cement particles or hydrates. As a result, PA polymer should exist in cement mortars through different morphologies. The early age mechanical properties of PA modified mortars are lower than those of unmodified mortars, while a rapid progress of the compressive strength and fracture energy can be recognized from the PA modified mortars. It was found that PA polymer addition will refine the small pores but induce big pores to cement mortar. SEM and EDX analysis proves that PA polymer is localized at some places within PA modified mortar which can be named as the localization of polymer modification. The physical and chemical influence of PA polymer on cement-based materials was integrated into an improved model.
A useful approach is developed for the synthesis of various structurally interesting spirocyclic sultams and heterobiaryls using a cross-dehydrogenative coupling strategy that features high atom and ...step economy. This method employs Cp*RhCl22 as a catalyst and N-sulfonylimine, a weak coordinating group, as an efficient directing group to assist C–H activation. A number of the coupled products were converted into interesting molecules through further synthetic transformations.
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