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"Zhao, Jianjun"
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Isoliquiritin ameliorates depression by suppressing NLRP3-mediated pyroptosis via miRNA-27a/SYK/NF-κB axis
by
Yong, Jingjiao
,
Tong, Yue
,
Li, Yuanjie
in
Adenosine triphosphate
,
Animal cognition
,
Animal models
2021
Background
The NLRP3-mediated pyroptosis, which could be regulated by miRNA-27a, is a key player in the development of depression. Isoliquiritin is a phenolic flavonoid compound that has been demonstrated to suppress NLRP3-mediated pyroptosis. However, it is still unknown whether isoliquiritin could confer antidepressant activity via decreasing NLRP3-mediated pyroptosis by stimulating miRNA-27a. Thus, in the current study, we explored the antidepressant activity of isoliquiritin and its underlying mechanism.
Methods
Expression of miRNA-27a in depressed patients or mice was measured using qRT-PCR. Luciferase reporter assay was performed to illustrate the link between miRNA-27a and SYK. Lipopolysaccharide (LPS) and chronic social defeat stress (CSDS) depression models were established to investigate the antidepressant actions of isoliquiritin. Changes in miRNA-27a/SYK/NF-κB axis and NLRP3-mediated pyroptosis were also examined. The role of miRNA-27a in isoliquiritin-related antidepressant effect was further investigated by using miRNA-27a inhibitors and mimics of miRNA-27a.
Results
Our results showed the miRNA-27a expression was downregulated in the serum of depressed patients, and decreased serum and hippocampus expression of miRNA-27a were observed in rodent models of depression. SYK gene expression was significantly reduced by miRNA-27a mimic incubation. Isoliquiritin profoundly attenuated LPS or CSDS-induced depressive symptoms, as well as CSDS-induced anxiety behavior. In the hippocampus, LPS and CSDS decreased miRNA-27a mRNA expression; increased the protein levels of SYK, p-NF-κB, and NLRP3: cleaved Caspase-1, IL-1β, and GSDMD-N: and elevated the concentration of IL-1β, IL-6, and TNF-α, which were all restored by isoliquiritin administration. Meanwhile, isoliquiritin upregulated the hippocampal NeuN protein level, improved the survival and morphology of neurons, and decreased pyroptosis-related neuronal cell death. Moreover, isoliquiritin protected primary microglia against LPS and adenosine triphosphate (ATP) elicited NLRP3 inflammasome activation in vitro, evidenced by declined protein levels of p-NF-κB, NLRP3; cleaved Caspase-1, IL-1β, and GSDMD-N; upregulated miRNA-27a mRNA expression; and decreased the mRNA and protein levels of SYK. Nevertheless, miRNA-27a inhibitors significantly reversed isoliquiritin-generated therapeutic efficacy in CSDS mice and in vitro. Furthermore, the cytoprotective effect of isoliquiritin was similar to that of miRNA-27a mimics in LPS and ATP-treated primary microglia.
Taken together, these findings suggest that isoliquiritin possesses potent antidepressant property, which requires miRNA-27a/SYK/NF-κB axis controlled decrease of pyroptosis via NLRP3 cascade.
Journal Article
Multiple Receptors Involved in Invasion and Neuropathogenicity of Canine Distemper Virus: A Review
2022
The canine distemper virus (CDV) is a morbillivirus that infects a broad range of terrestrial carnivores, predominantly canines, and is associated with high mortality. Similar to another morbillivirus, measles virus, which infects humans and nonhuman primates, CDV transmission from an infected host to a naïve host depends on two cellular receptors, namely, the signaling lymphocyte activation molecule (SLAM or CD150) and the adherens junction protein nectin-4 (also known as PVRL4). CDV can also invade the central nervous system by anterograde spread through olfactory nerves or in infected lymphocytes through the circulation, thus causing chronic progressive or relapsing demyelination of the brain. However, the absence of the two receptors in the white matter, primary cultured astrocytes, and neurons in the brain was recently demonstrated. Furthermore, a SLAM/nectin-4-blind recombinant CDV exhibits full cell-to-cell transmission in primary astrocytes. This strongly suggests the existence of a third CDV receptor expressed in neural cells, possibly glial cells. In this review, we summarize the recent progress in the study of CDV receptors, highlighting the unidentified glial receptor and its contribution to pathogenicity in the host nervous system. The reviewed studies focus on CDV neuropathogenesis, and neural receptors may provide promising directions for the treatment of neurological diseases caused by CDV. We also present an overview of other neurotropic viruses to promote further research and identification of CDV neural receptors.
Journal Article
Roles of Reactive Oxygen Species and Mitochondria in Seed Germination
by
Farooq, Muhammad Awais
,
Ma, Wei
,
Zhang, Xiaomeng
in
Abiotic stress
,
Abscisic acid
,
Biomolecules
2021
Seed germination is crucial for the life cycle of plants and maximum crop production. This critical developmental step is regulated by diverse endogenous [hormones, reactive oxygen species (ROS)] and exogenous (light, temperature) factors. Reactive oxygen species promote the release of seed dormancy by biomolecules oxidation, testa weakening and endosperm decay. Reactive oxygen species modulate metabolic and hormone signaling pathways that induce and maintain seed dormancy and germination. Endosperm provides nutrients and senses environmental signals to regulate the growth of the embryo by secreting timely signals. The growing energy demand of the developing embryo and endosperm is fulfilled by functional mitochondria. Mitochondrial matrix-localized heat shock protein GhHSP24.7 controls seed germination in a temperature-dependent manner. In this review, we summarize comprehensive view of biochemical and molecular mechanisms, which coordinately control seed germination. We also discuss that the accurate and optimized coordination of ROS, mitochondria, heat shock proteins is required to permit testa rupture and subsequent germination.
Journal Article
Single-cell transcriptome reveals dominant subgenome expression and transcriptional response to heat stress in Chinese cabbage
by
Liu, Mengyang
,
Ma, Wei
,
Zhang, Xiaomeng
in
Animal Genetics and Genomics
,
Bioinformatics
,
Biomedical and Life Sciences
2022
Background
Chinese cabbage (Brassica rapa ssp. pekinensis) experienced a whole-genome triplication event and thus has three subgenomes: least fractioned, medium fractioned, and most fractioned subgenome. Environmental changes affect leaf development, which in turn influence the yield. To improve the yield and resistance to different climate scenarios, a comprehensive understanding of leaf development is required including insights into the full diversity of cell types and transcriptional networks underlying their specificity.
Results
Here, we generate the transcriptional landscape of Chinese cabbage leaf at single-cell resolution by performing single-cell RNA sequencing of 30,000 individual cells. We characterize seven major cell types with 19 transcriptionally distinct cell clusters based on the expression of the reported marker genes. We find that genes in the least fractioned subgenome are predominantly expressed compared with those in the medium and most fractioned subgenomes in different cell types. Moreover, we generate a single-cell transcriptional map of leaves in response to high temperature. We find that heat stress not only affects gene expression in a cell type-specific manner but also impacts subgenome dominance.
Conclusions
Our study highlights the transcriptional networks in different cell types and provides a better understanding of transcriptional regulation during leaf development and transcriptional response to heat stress in Chinese cabbage.
Journal Article
Morphology, Carbohydrate Composition and Vernalization Response in a Genetically Diverse Collection of Asian and European Turnips (Brassica rapa subsp. rapa)
2014
Brassica rapa displays enormous morphological diversity, with leafy vegetables, turnips and oil crops. Turnips (Brassica rapa subsp. rapa) represent one of the morphotypes, which form tubers and can be used to study the genetics underlying storage organ formation. In the present study we investigated several characteristics of an extensive turnip collection comprising 56 accessions from both Asia (mainly Japanese origin) and Europe. Population structure was calculated using data from 280 evenly distributed SNP markers over 56 turnip accessions. We studied the anatomy of turnip tubers and measured carbohydrate composition of the mature turnip tubers of a subset of the collection. The variation in 16 leaf traits, 12 tuber traits and flowering time was evaluated in five independent experiments for the entire collection. The effect of vernalization on flowering and tuber formation was also investigated. SNP marker profiling basically divided the turnip accessions into two subpopulations, with admixture, generally corresponding with geographical origin (Europe or Asia). The enlarged turnip tuber consists of both hypocotyl and root tissue, but the proportion of the two tissues differs between accessions. The ratio of sucrose to fructose and glucose differed among accessions, while generally starch content was low. The evaluated traits segregated in both subpopulations, with leaf shape, tuber colour and number of shoots per tuber explaining most variation between the two subpopulations. Vernalization resulted in reduced flowering time and smaller tubers for the Asian turnips whereas the European turnips were less affected by vernalization.
Journal Article
Effect of bottom ash powder replacement rate, water cement ratio and sand cement ratio on alkali activated slag mortar
2025
The main objective of this study is to clarify the effect of bottom ash (BA) powder replacement rate, water-cement ratio, and sand-cement ratio on alkali-activated slag mortar (AASM) by comprehensively investigating the following parameters: fluidity, consistency, setting time, pH, compressive strength, and flexural strength, as well as observing the microstructure by XRD and SEM. Finally, the relationship between the parameters was explored by means of correlation coefficient heatmaps in concert with scatter plots (including quadratic polynomial linear fitting). The results show that it is feasible to use up to 60% of BA powder to replace slag for AASM. Meanwhile, it is suggested that the AASM with a water-cement ratio of 0.44 and a sand-cement ratio of 2.6 can obtain better workability, mechanical properties, and a denser microstructure. The incorporation of BA powder produces the unique hydration product Magadiite. In addition, the mechanical models of compressive strength and flexural strength of AASM were proposed
. This study provides a reference for the application of BA powder in the alkali-activated system, which is beneficial for resource recycling.
Journal Article
Instability mechanism of loess-mudstone landslides under rainfall infiltration conditions
2025
The evolution of seepage field in large loess-mudstone landslides is significantly influenced by rainfall infiltration, which is a critical factor affecting their stability. This paper presented a case study of the Hongya Village landslide in Huzhu County, Qinghai Province, to better understand the impact of rainfall infiltration on the triggering mechanism of loess-mudstone landslides. A combination of field investigations, high-density electrical resistivity surveys, and numerical simulations was employed to systematically analyze the temporal and spatial distribution of pore water pressure, volumetric water content, and shear strain within the landslide mass under rainfall infiltration conditions. The results indicated that the rainfall infiltration markedly alters the seepage characteristics of the landslide mass, leading to a sharp increase in pore water pressure and a significant reduction in shear strength, which consequently reduced the overall stability of the landslide. The stability analysis identified a stepwise instability process in the landslide, characterized by “shear displacement-tensile failure-pulling effect” triggered by rainfall infiltration. The findings provide a comprehensive understanding of the instability mechanisms of loess-mudstone landslides under rainfall conditions, thereby offering valuable scientific guidance and technical support for the prevention and mitigation of similar landslide hazards.
Journal Article
HBV integrations reshaping genomic structures promote hepatocellular carcinoma
2024
ObjectiveHepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further.DesignHere, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic rearrangement. We also conducted a clustered regularly interspaced short palindromic repeat (CRISPR)-based gain-of-function genetic screen in mouse hepatocytes. We individually activated each candidate gene in the mouse model to uncover HBV integration-mediated oncogenic aberration that elicits tumourigenesis in mice.ResultsThese HBV-mediated rearrangements are significantly enriched in a bridge-fusion-bridge pattern and interchromosomal translocations, and frequently led to a wide range of aberrations including driver copy number variations in chr 4q, 5p (TERT), 6q, 8p, 16q, 9p (CDKN2A/B), 17p (TP53) and 13q (RB1), and particularly, ultra-early amplifications in chr8q. Integrated HBV frequently contains complex structures correlated with the translocation distance. Paired breakpoints within each integration event usually exhibit different microhomology, likely mediated by different DNA repair mechanisms. HBV-mediated rearrangements significantly correlated with young age, higher HBV DNA level and TP53 mutations but were less prevalent in the patients subjected to prior antiviral therapies. Finally, we recapitulated the TONSL and TMEM65 amplification in chr8q led by HBV integration using CRISPR/Cas9 editing and demonstrated their tumourigenic potentials.ConclusionHBV integrations extensively reshape genomic structures and promote hepatocarcinogenesis (graphical abstract), which may occur early in a patient’s life.
Journal Article
Embedded Feature Selection and Machine Learning Methods for Flash Flood Susceptibility-Mapping in the Mainstream Songhua River Basin, China
2022
Mapping flash flood susceptibility is effective for mitigating the negative impacts of flash floods. However, a variety of conditioning factors have been used to generate susceptibility maps in various studies. In this study, we proposed combining logistic regression (LR) and random forest (RF) models with embedded feature selection (EFS) to filter specific feature sets for the two models and map flash flood susceptibility in the mainstream basin of the Songhua River. According to the EFS results, the optimized feature sets included 32 and 28 features for the LR and RF models, respectively, and the composition of the two optimal feature sets was similar and distinct. Overall, the relevant vegetation cover and river features exhibit relatively high effects overall for flash floods in the study area. The LR and RF models provided accurate and reliable flash flood susceptibility maps (FFSMs). The RF model (accuracy = 0.8834, area under the curve (AUC) = 0.9486) provided a better prediction capacity than the LR model (accuracy = 0.8634, AUC = 0.9277). Flash flood-prone areas are mainly distributed in the south and southwest and areas close to rivers. The results obtained in this study is useful for flash flood prevention and control projects.
Journal Article
Influence of different mining locations on deformation characteristics of overlying strata on gently anti-dip high-steep mining slope
2024
High-steep gently inclined mining slopes, prevalent globally, often suffer significant deformation, leading to landslides due to numerous goafs. This research investigates the critical role of goaf location in controlling deformation, failure mechanisms, and disaster evolution, vital for safe mining practices. Through field investigations and model generalization in Guizhou, a physical model test method was used to study three positions of goafs: under the shoulder and foot of the slope, under the slope shoulder, and within the slope. Findings highlight the stronger influence of the goaf’s mutual position with the slope shoulder on slope and overburden deformation and failure compared to the slope toe. Deformation and failure modes evolve from collapse toppling to collapse slip and collapse settlement as the goaf shifts from the near slope surface to inside of the slope. Statistical analysis of fracture distribution in the goaf’s overlying strata reveals damage increase with larger goafs, following a Gaussian distribution, with concentrated damage in the middle. The study identifies the maximum damage area, influenced by the horizontal distance between the goaf center and slope shoulder. These insights advance understanding of overburden rock deformation in gently inclined high-steep mining slopes.
Journal Article