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"Wei, Chengwen"
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Cytospyrone and Cytospomarin: Two New Polyketides Isolated from Mangrove Endophytic Fungus, Cytospora sp
Two new polyketides, cytospyrone (1), cytospomarin (2), together with three known metabolites dimethoxyphtalide (3), integracin A (4) and integracin B (5), were isolated from the culture of Cytospora sp. from the Chinese mangrove Ceriops tagal. Their structures were elucidated by extensive spectroscopic analyses and time dependent density functional theory (TDDFT), calculation of electronic circular dichroism (ECD) and optical rotation (OR) data. Compound 2 displayed weak inhibitory activity against Escherichia coli GIM1.201 (minimum inhibitory concentration (MIC) value of 0.35 mM). Compounds 4 and 5 displayed significant cytotoxicity against human cancer cell line HepG2 (IC50 values of 5.98 ± 0.12 µM and 9.97 ± 0.06 µM, respectively), more potent than the positive control 5-fluorouracil (IC50 value of 43.50 ± 3.69 µM).
Journal Article
Dysfunction of Trio GEF1 involves in excitatory/inhibitory imbalance and autism-like behaviors through regulation of interneuron migration
Autism spectrum disorders (ASDs) are a group of highly inheritable neurodevelopmental disorders. Functional mutations in TRIO, especially in the GEF1 domain, are strongly implicated in ASDs, whereas the underlying neurobiological pathogenesis and molecular mechanisms remain to be clarified. Here we characterize the abnormal morphology and behavior of embryonic migratory interneurons (INs) upon Trio deficiency or GEF1 mutation in mice, which are mediated by the Trio GEF1-Rac1 activation and involved in SDF1α/CXCR4 signaling. In addition, the migration deficits are specifically associated with altered neural microcircuit, decreased inhibitory neurotransmission, and autism-like behaviors, which are reminiscent of some features observed in patients with ASDs. Furthermore, restoring the excitatory/inhibitory (E/I) imbalance via activation of GABA signaling rescues autism-like deficits. Our findings demonstrate a critical role of Trio GEF1 mediated signaling in IN migration and E/I balance, which are related to autism-related behavioral phenotypes.
Journal Article
Epigenetic Manipulation Induced Production of Immunosuppressive Chromones and Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48
A mangrove endophytic fungus Phomopsis asparagi DHS-48 was found to be particularly productive with regard to the accumulation of substantial new compounds in our previous study. In order to explore its potential to produce more unobserved secondary metabolites, epigenetic manipulation was used on this fungus to activate cryptic or silent genes by using the histone deacetylase (HDAC) inhibitor sodium butyrate and the DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-Aza). Based on colony growth, dry biomass, HPLC, and 1H NMR analyses, the fungal chemical diversity profile was significantly changed compared with the control. Two new compounds, named phaseolorin J (1) and phomoparagin D (5), along with three known chromones (2–4) and six known cytochalasins (6–11), were isolated from the culture treated with sodium butyrate. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD and 13C NMR calculations. The immunosuppressive and cytotoxic activities of all isolated compounds were evaluated. Compounds 1 and 8 moderately inhibited the proliferation of ConA (concanavalin A)-induced T and LPS (lipopolysaccharide)-induced B murine spleen lymphocytes. Compound 5 exhibited significant in vitro cytotoxicity against the tested human cancer cell lines Hela and HepG2, which was comparative to the positive control adriamycin and fluorouracil. Our finding demonstrated that epigenetic manipulation should be an efficient strategy for the induction of new metabolites from mangrove endophytic fungi.
Journal Article
Four New Chromones from the Endophytic Fungus Phomopsis asparagi DHS-48 Isolated from the Chinese Mangrove Plant Rhizophora mangle
Four new chromones, phomochromenones D–G (1–4), along with four known analogues, diaporchromone A (5), diaporchromanone C (6), diaporchromanone D (7), and phomochromenone C (8), were isolated from the culture of Phomopsis asparagi DHS-48 from Chinese mangrove Rhizophora mangle. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. The absolute configurations of 1 and 4 were assigned on the basis of experimental and calculated electronic circular dichroism (ECD) data, and those of enantiomers 2 and 3 were determined by a modified Mosher’s method and basic hydrolysis. To the best of our knowledge, phomochromenones D–F (1–4) possessing a 3-substituted-chroman-4-one skeleton are rarely found in natural sources. Diaporchromone A (5) showed moderate to weak immunosuppressive activity against T and/or B lymphocyte cells with IC50 of 34 μM and 117 μM.
Journal Article
Immunosuppressive Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48
Three new cytochalasins, phomoparagins A-C (1–3), along with five known analogs (4–8), were isolated from Phomopsis asparagi DHS-48, a mangrove-derived endophytic fungus. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD techniques. Notably, 1 possessed an unprecedented 5/6/5/8/5-fused pentacyclic skeleton. These compounds were tested for their inhibitory activity against concanavalin A (ConA)/lipopolysaccharide (LPS)-induced spleen lymphocyte proliferation and calcineurin (CN) enzyme. Several metabolites (2 and 4–6) exhibited fascinating inhibitory activities with a relatively low toxicity. Furthermore, 2 was demonstrated to inhibit ConA-stimulated activation of NFAT1 dephosphorylation and block NFAT1 translocation in vitro, subsequently inhibiting the transcription of interleukin-2 (IL-2). Our results provide evidence that 2 may, at least partially, suppress the activation of spleen lymphocytes via the CN/NFAT signaling pathway, highlighting that it could serve as an effective immunosuppressant that is noncytotoxic and natural.
Journal Article
Spatio-Temporal Characteristics of Land Subsidence and Driving Factors Analysis in Shenzhen
Analyzing land subsidence using Multi-temporal Interferometric Synthetic Aperture Radar (MT-InSAR) technology holds significant importance for the secure development of urban areas. Shenzhen, being a crucial component of the Pearl River Delta, faces the threat of land subsidence, similar to most deltaic cities. Numerous studies have already indicated the presence of severe land subsidence in certain localities of Shenzhen. However, due to limitations in data scope and research methodologies, the comprehensive spatial-temporal distribution of land subsidence across the entire city of Shenzhen remains unclear. This study initially employed MT-InSAR technology to process a total of 534 Sentinel-1A SAR images from three different frames (P11F71, P113F71, P11F65), covering the entire city of Shenzhen. This processing resulted in the generation of subsidence rate maps and subsidence time series. Subsequently, the temporal evolution patterns of the subsidence were analyzed while significant subsidence regions were identified. By integrating information from optical images reflecting human activities on the Earth’s surface, the study deduced the subsidence mechanisms in various significant subsidence areas. Research findings indicate that land subsidence in Shenzhen is primarily caused by construction activities, with a concentration in the western coastal areas of Shenzhen, reaching a maximum rate of 80 mm/yr, located at the estuary of Dongbao River (113.770385, 22.745305). The cumulative subsidence from March 2017 to June 2023 amounts to 500 mm. The expansion of the Qinglinjing Reservoir has led to an increased demand for water, resulting in a significant rise in formation pressure and subsequent land subsidence. InSAR land subsidence monitoring and analysis in urban areas can address the spatial and temporal resolution limitations of traditional subsidence monitoring methods, providing effective recommendations for widespread subsidence prevention and control.
Journal Article
Microstructure, Densification, Microhardness and Antioxidant Properties of Ti2AlN/TiN FGM Fabricated by Hot-pressing
Ti2AlN/TiN functionally graded materials（FGM） were successfully fabricated by vacuum hotpressing. Bulk density of the sintered samples was measured by Archimedes principle. The sample sintered at 1 300 ℃ for 2h has the maximum final density and lowest open porosity. SEM coupled with EDS was utilized to investigate the phase composition and microstructure, and well-formed boundary was found between the layers. The microhardness tests suggest that Vickers’ hardness of Ti2AlN/TiN FGM increases monotonically with the volume fraction content of TiN increases. Corrosion results are that the corrosion resistance of Ti2AlN/TiN FGM is much better than that of Ti2AlN in acid, but quite the opposite in alkali. Constant temperature oxidation study shows that the oxidation kinetics of Ti2AlN/TiN FGM at 900 °C follows the parabolic law closely.
Journal Article
An improved deep learning approach and its applications on colonic polyp images detection
Background
Colonic polyps are more likely to be cancerous, especially those with large diameter, large number and atypical hyperplasia. If colonic polyps cannot be treated in early stage, they are likely to develop into colon cancer. Colonoscopy is easily limited by the operator’s experience, and factors such as inexperience and visual fatigue will directly affect the accuracy of diagnosis. Cooperating with Hunan children’s hospital, we proposed and improved a deep learning approach with global average pooling (GAP) in colonoscopy for assisted diagnosis. Our approach for assisted diagnosis in colonoscopy can prompt endoscopists to pay attention to polyps that may be ignored in real time, improve the detection rate, reduce missed diagnosis, and improve the efficiency of medical diagnosis.
Methods
We selected colonoscopy images from the gastrointestinal endoscopy room of Hunan children’s hospital to form the colonic polyp datasets. And we applied the image classification method based on Deep Learning to the classification of Colonic Polyps. The classic networks we used are VGGNets and ResNets. By using global average pooling, we proposed the improved approaches: VGGNets-GAP and ResNets-GAP.
Results
The accuracies of all models in datasets exceed 98%. The TPR and TNR are above 96 and 98% respectively. In addition, VGGNets-GAP networks not only have high classification accuracies, but also have much fewer parameters than those of VGGNets.
Conclusions
The experimental results show that the proposed approach has good effect on the automatic detection of colonic polyps. The innovations of our method are in two aspects: (1) the detection accuracy of colonic polyps has been improved. (2) our approach reduces the memory consumption and makes the model lightweight. Compared with the original VGG networks, the parameters of our VGG19-GAP networks are greatly reduced.
Journal Article