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"Yang, En"
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Platycodigenin as Potential Drug Candidate for Alzheimer’s Disease via Modulating Microglial Polarization and Neurite Regeneration
Neuroinflammatory microenvironment, regulating neurite regrowth and neuronal survival, plays a critical role in Alzheimer’s disease (AD). During neuroinflammation, microglia are activated, inducing the release of inflammatory or anti-inflammatory factors depending on their polarization into classical M1 microglia or alternative M2 phenotype. Therefore, optimizing brain microenvironment by small molecule-targeted microglia polarization and promoting neurite regeneration might be a potential therapeutic strategy for AD. In this study, we found platycodigenin, a naturally occurring triterpenoid, promoted M2 polarization and inhibited M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 and primary microglia. Platycodigenin downregulated pro-inflammatory molecules such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6 and nitric oxide (NO), while upregulated anti-inflammatory cytokine IL-10. Further investigation confirmed that platycodigenin inhibited cyclooxygenase-2 (Cox2) positive M1 but increased Ym1/2 positive M2 microglial polarization in primary microglia. In addition, platycodigenin significantly decreased LPS-induced the hyperphosphorylation of mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) p65 subunits. Furthermore, the inactivation of peroxisome proliferators-activated receptor γ (PPARγ) induced by LPS was completely ameliorated by platycodigenin. Platycodigenin also promoted neurite regeneration and neuronal survival after Aβ treatment in primary cortical neurons. Taken together, our study for the first time clarified that platycodigenin effectively ameliorated LPS-induced inflammation and Aβ-induced neurite atrophy and neuronal death.
Journal Article
An early warning signal for grassland degradation on the Qinghai-Tibetan Plateau
Intense grazing may lead to grassland degradation on the Qinghai-Tibetan Plateau, but it is difficult to predict where this will occur and to quantify it. Based on a process-based ecosystem model, we define a productivity-based stocking rate threshold that induces extreme grassland degradation to assess whether and where the current grazing activity in the region is sustainable. We find that the current stocking rate is below the threshold in ~80% of grassland areas, but in 55% of these grasslands the stocking rate exceeds half the threshold. According to our model projections, positive effects of climate change including elevated CO
2
can partly offset negative effects of grazing across nearly 70% of grasslands on the Plateau, but only in areas below the stocking rate threshold. Our analysis suggests that stocking rate that does not exceed 60% (within 50% to 70%) of the threshold may balance human demands with grassland protection in the face of climate change.
Livestock grazing may drive grassland degradation. Here, the authors use process-based modelling validated with empirical data to define a stocking rate threshold across grassland on the Qinghai-Tibetan Plateau, identify vulnerable areas and predict threshold shifts under future climate scenarios.
Journal Article
An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems
New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous Worldwide Integrated Assessment (WIA) in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little new information has been gathered on soil organisms. The impact on marine and coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal class (neonicotinoids and fipronil), with the potential to greatly decrease populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds, and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates and their deleterious impacts on growth, reproduction, and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota, and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al.
2015
).
Journal Article
TIMP-3 as a therapeutic target for cancer
Tissue inhibitor of metalloproteinase-3 (TIMP-3), a secreted glycoprotein, plays an important role in carcinogenesis. It can bind to many proteinases to suppress their activity and thus protect the extracellular matrix from degradation. TIMP-3 may have many anticancer properties, including apoptosis induction and antiproliferative, antiangiogenic, and antimetastatic activities. This review summarizes the structure, proteinase inhibition ability, genetic and epigenetic regulation, cancer therapy potential, and contribution to cancer development of TIMP-3. Furthermore, in this review we discuss its potential as a biomarker for predicting cancer progression and the current state of drugs that target TIMP-3, either alone or in combination with clinical treatment. In conclusion, TIMP-3 can be a biomarker of cancer and a potential target for cancer therapy. This review article can serve as a basis to understand how to modulate TIMP-3 levels as a drug target of cancers.
Journal Article
Mitigating environmental impact by development of ambient-cured EAF slag and fly ash blended geopolymer via mix design optimization
This article discusses the utilization of industrial by-products, namely, electric arc furnace slag (EAFS) and fly ash to produce cementless geopolymer binder. Taguchi-grey optimization is used for experimental design and for investigating the effects of mix design parameters. Fly ash, in the levels of 0–75% (by mass), partly replaced EAFS in the binary-blended composite system. Experiments were performed on the microstructural development, mechanical properties, and durability of ambient-cured EAFS-fly ash geopolymer paste (EFGP). The optimal mix with 75–25% composition of EAFS and fly ash produced ~ 39 MPa compressive strength accrediting to the co-existence of C-A-S–H and N-A-S–H gels. The initial and final setting times were 127 min and 581 min, respectively, owing to adequate alkali and amorphous contents in the matrix, and the flowability was 108% due to sufficient activator content and the spherical shape of fly ash particles. SEM, XRD, and FTIR results corroborated the mechanical test results.
Graphical Abstract
Journal Article
Compression Helps Deep Learning in Image Classification
The impact of JPEG compression on deep learning (DL) in image classification is revisited. Given an underlying deep neural network (DNN) pre-trained with pristine ImageNet images, it is demonstrated that, if, for any original image, one can select, among its many JPEG compressed versions including its original version, a suitable version as an input to the underlying DNN, then the classification accuracy of the underlying DNN can be improved significantly while the size in bits of the selected input is, on average, reduced dramatically in comparison with the original image. This is in contrast to the conventional understanding that JPEG compression generally degrades the classification accuracy of DL. Specifically, for each original image, consider its 10 JPEG compressed versions with their quality factor (QF) values from 100,90,80,70,60,50,40,30,20,10. Under the assumption that the ground truth label of the original image is known at the time of selecting an input, but unknown to the underlying DNN, we present a selector called Highest Rank Selector (HRS). It is shown that HRS is optimal in the sense of achieving the highest Top k accuracy on any set of images for any k among all possible selectors. When the underlying DNN is Inception V3 or ResNet-50 V2, HRS improves, on average, the Top 1 classification accuracy and Top 5 classification accuracy on the whole ImageNet validation dataset by 5.6% and 1.9%, respectively, while reducing the input size in bits dramatically—the compression ratio (CR) between the size of the original images and the size of the selected input images by HRS is 8 for the whole ImageNet validation dataset. When the ground truth label of the original image is unknown at the time of selection, we further propose a new convolutional neural network (CNN) topology which is based on the underlying DNN and takes the original image and its 10 JPEG compressed versions as 11 parallel inputs. It is demonstrated that the proposed new CNN topology, even when partially trained, can consistently improve the Top 1 accuracy of Inception V3 and ResNet-50 V2 by approximately 0.4% and the Top 5 accuracy of Inception V3 and ResNet-50 V2 by 0.32% and 0.2%, respectively. Other selectors without the knowledge of the ground truth label of the original image are also presented. They maintain the Top 1 accuracy, the Top 5 accuracy, or the Top 1 and Top 5 accuracy of the underlying DNN, while achieving CRs of 8.8, 3.3, and 3.1, respectively.
Journal Article
Sublethal Dosage of Imidacloprid Reduces the Microglomerular Density of Honey Bee Mushroom Bodies
The dramatic loss of honey bees is a major concern worldwide. Previous studies have indicated that neonicotinoid insecticides cause behavioural abnormalities and have proven that exposure to sublethal doses of imidacloprid during the larval stage decreases the olfactory learning ability of adults. The present study shows the effect of sublethal doses of imidacloprid on the neural development of the honey bee brain by immunolabelling synaptic units in the calyces of mushroom bodies. We found that the density of the synaptic units in the region of the calyces, which are responsible for olfactory and visual functions, decreased after being exposed to a sublethal dose of imidacloprid. This not only links a decrease in olfactory learning ability to abnormal neural connectivity but also provides evidence that imidacloprid damages the development of the nervous system in regions responsible for both olfaction and vision during the larval stage of the honey bee.
Journal Article
Unravelling the progression of the zebrafish primary body axis with reconstructed spatiotemporal transcriptomics
Background
Elucidating the spatiotemporal dynamics of gene expression is essential for understanding complex physiological and pathological processes. Current spatial transcriptomics techniques are hindered by low read depths and limited gene detection.
Results
Here, we introduce Palette, a pipeline that infers detailed spatial gene expression patterns from bulk RNA-seq data, utilizing existing spatial transcriptomics data as the sole reference. This method identifies more precise expression patterns by smoothing, imputing and adjusting gene expressions. We apply Palette to reconstruct the zebrafish SpatioTemporal Expression Profiles (zSTEP) by integrating 53-slice serial bulk RNA-seq data from three developmental stages with existing spatial transcriptomics and image references. zSTEP provides a comprehensive cartographic resource for examining gene expression and investigating developmental events within zebrafish embryos. Utilizing machine learning-based screening, we identify key morphogens and transcription factors essential for anteroposterior axis development and characterized their dynamic distribution throughout embryogenesis. In addition, among these transcription factors, Hox family genes are found to be pivotal in anteroposterior axis refinement. Their expression is closely correlated with cellular anteroposterior identities, and
hoxb
genes may act as central regulators in this process.
Conclusions
This study presents Palette, a pipeline for integrating bulk RNA-seq data and spatial transcriptomics data, and zSTEP, a comprehensive cartographic resource for investigating zebrafish early embryonic development. In addition, key morphogens and transcriptional factors essential for anteroposterior axis establishment and refinement are identified.
Journal Article
Impaired Olfactory Associative Behavior of Honeybee Workers Due to Contamination of Imidacloprid in the Larval Stage
The residue of imidacloprid in the nectar and pollens of the plants is toxic not only to adult honeybees but also the larvae. Our understanding of the risk of imidacloprid to larvae of the honeybees is still in a very early stage. In this study, the capped-brood, pupation and eclosion rates of the honeybee larvae were recorded after treating them directly in the hive with different dosages of imidacloprid. The brood-capped rates of the larvae decreased significantly when the dosages increased from 24 to 8000 ng/larva. However, there were no significant effects of DMSO or 0.4 ng of imidacloprid per larva on the brood-capped, pupation and eclosion rates. Although the sublethal dosage of imidacloprid had no effect on the eclosion rate, we found that the olfactory associative behavior of the adult bees was impaired if they had been treated with 0.04 ng/larva imidacloprid in the larval stage. These results demonstrate that a sublethal dosage of imidacloprid given to the larvae affects the subsequent associative ability of the adult honeybee workers. Thus, a low dose of imidacloprid may affect the survival condition of the entire colony, even though the larvae survive to adulthood.
Journal Article