المؤلفون: Yujia Ye, Lihong Yang, Min Leng, Qian Wang, Jiankui Wu, Wen Wan, Huawei Wang, Longjun Li, Yunzhu Peng, Shengjie Chai, Zhaohui Meng

المصدر: Frontiers in Pharmacology, Vol 14 (2023)

مصطلحات موضوعية: luteolin, antiplatelet, collagen, GPVI, thrombus formation, platelet production, Therapeutics. Pharmacology, RM1-950

الوصف: Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo.Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca2+, and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR).Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbβ3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice.Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fphar.2023.1255069/fullTest; https://doaj.org/toc/1663-9812Test

الوصول الحر: https://doaj.org/article/35814476f571474988fc4f292e3de25bTest

المؤلفون: Wen Wan, Zheng Ren, Hongling Zhang, Qiyan Wang, Ting Wang, Yunteng Yang, Jiangtao You, Kun He, Jiang Huang, Xiaoye Jin

المصدر: Frontiers in Ecology and Evolution, Vol 10 (2023)

مصطلحات موضوعية: InDels, Dong, STR, forensic application, population genetic background, Evolution, QH359-425, Ecology, QH540-549.5

الوصف: Insertion/deletion polymorphisms (InDels) show great application values in forensic research because they own superiorities of short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs). Whereas, InDels commonly display low genetic diversities in comparison to STRs. Therefore, they may provide limited genetic information in forensic kinship testing. Here, we evaluated forensic application efficiency of a novel multiplex amplification system including two STRs, 59 InDels, and three sex-determination loci in the Guizhou Dong group. In addition, we explored the genetic background of the Guizhou Dong group in comparison to other reported populations based on 59 InDels. We found that 59 InDels displayed relatively high genetic diversities in the Guizhou Dong group. Moreover, the cumulative forensic efficiency of two STRs and 59 InDels could meet the requirement of individual identification and paternity testing in the Guizhou Dong group. For these 59 InDels, we observed that some loci exhibited relatively high genetic differentiations among different continental populations, especially for African and Non-African populations, which could be viewed as candidate ancestry informative markers in the future. Genetic structure results indicated that the Dong group had close genetic relationships with East Asian and some Southern Chinese Han populations. To sum up, we stated that the 64-plex panel could be performed for forensic application of the Guizhou Dong group.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fevo.2022.988504/fullTest; https://doaj.org/toc/2296-701XTest

الوصول الحر: https://doaj.org/article/127973c06ec74112a15f2f483fcef27dTest

المؤلفون: Wei Chen, Wen Wan, Yanlin Zhao, Qiuhong Wu, Huan He, Wenqing Peng, Xiaofan Wu, Yu Zhou, Li Wu, Senlin Xie

المصدر: Frontiers in Earth Science, Vol 10 (2022)

مصطلحات موضوعية: granite surroundings, rock mechanics parameters, effect of solution velocity, hydration corrosion, damage mechanism, Science

الوصف: In order to study the deterioration characteristics of the tunnel surrounding rock under the scouring of flowing groundwater, we ratioed similar acidic solutions based on groundwater composition. The microstructure of granite samples cored on site, deformation features, and evolution characteristics of mechanical parameters under saturations with different flow rates and various pH values were analyzed using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), nuclear magnetic resonance (NMR), and X-ray diffraction (XRD). The results indicate the following: 1) compared with the static water condition, the higher flow rate produces greater relative changes in granite’s microstructure, porosity, mass, and pH of the immersed solution. Moreover, the rate of change is relatively fast in the early stage and gradually slows down until it reaches a stable state. 2) Compared with the natural dry condition, the solution with a lower pH value causes the structural framework of the specimen to loosen, the mass loss degree to increase, and the porosity dispersion to intensify. 3) The dynamic water is more sensitive than the static water to the elastic vertical wave velocity of granite. Compared with the dry sample, the elastic longitudinal wave velocity of the sample in acidic solution with pH = 2 and flow rates of 0, 150, and 300 mm·s−1 for 49 days decreased by 8.7, 10.9, and 13.5%, respectively, which accelerates the instability and failure of the granite surroundings.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/feart.2022.927159/fullTest; https://doaj.org/toc/2296-6463Test

الوصول الحر: https://doaj.org/article/3fff36bf29e747b9a6e92ac389a4e8bcTest

المؤلفون: Xiaoying Cao, Lingxia Xu, Ludan Li, Wen Wan, Jihong Jiang

المصدر: Frontiers in Plant Science, Vol 13 (2022)

مصطلحات موضوعية: transcription factor, R2R3-MYB, taxol biosynthesis, Taxus chinensis, taxane 5α-hydroxylase, Plant culture, SB1-1110

الوصف: Paclitaxel (Taxol), a highly modified diterpene agent mainly obtained from Taxus species, is the most widely used anticancer drug. Abscisic acid (ABA) is a well-known stress hormone that plays important roles in the secondary metabolism of plants, and it can also induce the accumulation of taxol in Taxus cell suspension cultures. However, the mechanism behind the regulation of taxol biosynthesis by ABA remains largely unknown. In previous research, a R2R3 MYB transcription factor (TF) TcMYB29a was observed to show a significant correlation with taxol biosynthesis, indicative of its potential role in the taxol biosynthesis. In this study, the TcMYB29a encoded by its gene was further characterized. An expression pattern analysis revealed that TcMYB29a was highly expressed in the needles and roots. Overexpression of TcMYB29a in Taxus chinensis cell suspension cultures led to an increased accumulation of taxol, and upregulated expression of taxol-biosynthesis-related genes, including the taxadiene synthase (TS) gene, the taxane 5α-hydroxylase (T5OH) gene, and the 3′-N-debenzoyl-2′-deoxytaxol-N-benzoyltransferase (DBTNBT) gene as compared to the controls. Chromatin immunoprecipitation (ChIP) assays, yeast one-hybrid (Y1H) assays, electrophoretic mobility shift assays (EMSAs), and dual-luciferase reporter assays verified that TcMYB29a could bind and activate the promoter of TcT5OH. Promoter sequence analysis of TcMYB29a revealed that its promoter containing an AERB site from -313 to -319 was a crucial ABA-responsive element. Subsequently, the ABA treatment assay showed that TcMYB29a was strongly upregulated at 6 h after ABA pretreatment. Furthermore, TcMYB29a was strongly suppressed at 3 h after the methyl jasmonate (MeJA) treatment and was depressed to the platform at 12 h. Taken together, these results reveal that TcMYB29a is an activator that improves the accumulation of taxol in Taxus chinensis cells through an ABA-medicated signaling pathway which is different from JA-medicated signaling pathways for the accumulation of taxol. These findings provide new insights into the potential regulatory roles of MYBs on the expression of taxol biosynthetic genes in Taxus.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fpls.2022.804593/fullTest; https://doaj.org/toc/1664-462XTest

الوصول الحر: https://doaj.org/article/237d79db5c9144f58877498891e9e826Test

المؤلفون: Wei Chen, Wenqing Peng, Wen Wan, Xianqing Wang, Qiuhong Wu, Yu Zhou, Senlin Xie

المصدر: Frontiers in Materials, Vol 9 (2022)

مصطلحات موضوعية: deep high humidity condition, water-rock interaction, ageing characteristics, damage mechanism, rock mechanics, Technology

الوصف: The paper studies the uniaxial compression mechanical properties of pillars under the deep and high-humidity environment. We make the pillars cored from the −750 m mine room of Wengfu Phosphate Mine into the standard dolomite samples and test with a humidity control device developed by ourselves. Combining with uniaxial compression tests and microstructure inspections, we study the mechanical deterioration rule and damage mechanism of the dry samples and the wet ones that have been placed in a high-humidity condition (90% RH) for 30, 60 and 90 d, respectively. The results show that: 1) When the sample is placed in the humidity device, its original layered or sheet crystal morphology will change into sponge-like or flocculent morphology. As the placement time increases, the structure of the sample becomes looser and the boundaries between layers become blurred. The numbers of micro-cracks and micro-pores increase. 2) In the initial stage of water molecule intrusion (0–30 d), the strength and mass damages of the rock sample are less, and the damage rate is low. As high-humidity action time increases (30–90 d), the damage rates of both strength and mass gradually grow. 3) The failure modes of dolomites include shear failure and tensile/shear mixed failure, which are controlled by the storage time under high-humidity condition. As time goes by, more macroscopic cracks appear and the failure mode of the rock changes from shear to tensile. 4) Based on the X-ray diffraction and scanning electron microscopy analysis on mineral components, together with the principle of chemical kinetics, we discuss the chemical reaction process between dolomite and gaseous water molecules, and summarize the chemical damage mechanism of rocks during the water-rock interaction. The research has a certain guiding significance for the durability and stability prediction of pillars under deep high-humidity conditions.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmats.2022.812738/fullTest; https://doaj.org/toc/2296-8016Test

الوصول الحر: https://doaj.org/article/2fd7e814fb714502b58b230804e98d24Test

المؤلفون: Wei Chen, Wen Wan, Yanlin Zhao, Senlin Xie, Bing Jiao, Zhenming Dong, Xianqing Wang, Shuailong Lian

المصدر: Frontiers in Physics, Vol 8 (2020)

مصطلحات موضوعية: rock mechanics, acidification erosion, mechanics damage, aging characteristics, strength model, Physics, QC1-999

الوصف: Acidic fluids will cause rock erosion and further endanger the safety of rock engineering. To explore the aging characteristics of the mechanical damage under acid condition, diorite specimens were saturated in neutral water and acid solutions with pH values of 3 and 5 for 49 days. The masses and sizes of the specimens and the pH values of the acidic solution were tracked and measured. Besides, the specimens before and after saturations were observed by an electron microscope scanner. Meanwhile, triaxial compression tests were carried out under neutral water, pH = 5 and pH = 3 hydrochloric acid solutions, respectively. The mass damage features and mechanical properties of diorite specimens saturated in solutions with different pH values were analyzed. The results show: 1) after acidic saturation, the original lamellar structures and crystal forms were spongy or flocculent. The structure loosened and the boundary between layers became fuzzy. Meanwhile, the number of micro-cracks and micro-pores increased, which weakened the macro-mechanical performances of diorite; 2) the acid condition with pH value of 3 could be used to simulate the long-term effect of the weakly acidic environment in nature; 3) internal friction angle of diorite was more sensitive to acidic solutions than its cohesion; 4) at the initial stage of saturation, diorite broke rapidly. With increasing saturation time, the damage rate slowed down and finally stabilized. The established damage strength model considering acidification could properly describe the test results.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fphy.2020.553643/fullTest; https://doaj.org/toc/2296-424XTest

الوصول الحر: https://doaj.org/article/3205868e3b4a408b9b40ca0d70fd17e0Test

المؤلفون: Jie Liu, Wen Wan, Yanlin Zhao, Xiang Fan

المصدر: Frontiers in Physics, Vol 8 (2020)

مصطلحات موضوعية: effective shear fracture toughness, failure process, confining stress, crack propagation, fluctuation, Physics, QC1-999

الوصف: The discrete element method is adopted to investigate the failure process in punch-through shear tests. The numerical tests agree well with the laboratory tests on crack propagation sequence and the influence of confining stress on effective shear fracture toughness. More importantly, the numerical tests indicate that the increase in axial force first causes stress concentrations. When the stresses reach critical values, cracks initiate and the concentrated stresses dissipate. With further increase in axial displacement, the axial force may fluctuate, accompanied with crack development. In addition, the increase in confining stress promotes the critical values of the concentrated stresses before crack propagation. Thus, the numerical tests show that the increase in confining stress promotes the effective shear fracture toughness and restrains the propagation of tensile cracks.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fphy.2020.00327/fullTest; https://doaj.org/toc/2296-424XTest

الوصول الحر: https://doaj.org/article/b37d70db706440b6a7104f895425b031Test

المؤلفون: Huawei Wang, Yujia Ye, Wen Wan, Luqiao Wang, Ruijie Li, Longjun Li, Lihong Yang, Lai Yang, Yajuan Gu, Ling Dong, Zhaohui Meng

المصدر: Frontiers in Pharmacology, Vol 10 (2019)

مصطلحات موضوعية: Xinmailong, platelet, thrombosis, α II bβ3, traditional medicine, Therapeutics. Pharmacology, RM1-950

الوصف: Background: Xinmailong (XML), a bioactive composite extracted from Periplaneta americana, has been widely used to treat cardiovascular diseases such as congestive heart failure. However, it is unclear whether XML has antiplatelet and antithrombotic effects.Methods: The effects of XML on agonist-induced platelet aggregation, adhesion and spreading, granule secretion, integrin α II bβ3 activation, and thrombus formation were evaluated. Phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK signaling molecules was also studied on agonist-induced platelets. In addition, the antithrombotic effects of XML were observed in vivo using an acute pulmonary thrombosis mouse model.Results: XML dose-dependently inhibited in vitro platelet aggregation and granule secretion induced by thrombin, collagen, and arachidonic acid (AA). XML also greatly reduced platelet adhesion and spreading on both collagen- and fibrinogen-coated surfaces. Biochemical analysis revealed that XML inhibited thrombin-, collagen-, and AA-induced phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK. Additionally, XML significantly inhibited in vivo thrombus formation in a collagen–epinephrine-induced acute pulmonary thrombosis mouse model.Conclusions and General Significance: Here, we provide the first report showing that XML inhibits platelet function and that it possesses antithrombotic activity. This suggests that XML could be a potential therapeutic candidate to prevent or treat platelet-related cardiovascular diseases.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fphar.2019.00923/fullTest; https://doaj.org/toc/1663-9812Test

الوصول الحر: https://doaj.org/article/be3345d09bf4405bad3c3452c733d087Test

المؤلفون: Yi-Ling Cheng, Chiao-Hsuan Chao, Yen-Chung Lai, Kun-Han Hsieh, Jen-Ren Wang, Shu-Wen Wan, Hong-Jyun Huang, Yung-Chun Chuang, Woei-Jer Chuang, Trai-Ming Yeh

المصدر: Frontiers in Immunology, Vol 13 (2022)

مصطلحات موضوعية: COVID-19, dengue virus, SARS-CoV-2, diagnosis, antibody-dependent enhancement, Immunologic diseases. Allergy, RC581-607

الوصف: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since December 2019. Several studies reported that SARS-CoV-2 infections may produce false-positive reactions in dengue virus (DENV) serology tests and vice versa. However, it remains unclear whether SARS-CoV-2 and DENV cross-reactive antibodies provide cross-protection against each disease or promote disease severity. In this study, we confirmed that antibodies against the SARS-CoV-2 spike protein and its receptor-binding domain (S1-RBD) were significantly increased in dengue patients compared to normal controls. In addition, anti-S1-RBD IgG purified from S1-RBD hyperimmune rabbit sera could cross-react with both DENV envelope protein (E) and nonstructural protein 1 (NS1). The potential epitopes of DENV E and NS1 recognized by these antibodies were identified by a phage-displayed random peptide library. In addition, DENV infection and DENV NS1-induced endothelial hyperpermeability in vitro were inhibited in the presence of anti-S1-RBD IgG. Passive transfer anti-S1-RBD IgG into mice also reduced prolonged bleeding time and decreased NS1 seral level in DENV-infected mice. Lastly, COVID-19 patients’ sera showed neutralizing ability against dengue infection in vitro. Thus, our results suggest that the antigenic cross-reactivity between the SARS-CoV-2 S1-RBD and DENV can induce the production of anti-SARS-CoV-2 S1-RBD antibodies that cross-react with DENV which may hinder dengue pathogenesis.

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.941923/fullTest; https://doaj.org/toc/1664-3224Test; https://doaj.org/article/1593d7bfd4814c728ffc08e8dce945ceTest

الإتاحة: https://doi.org/10.3389/fimmu.2022.941923Test
https://doaj.org/article/1593d7bfd4814c728ffc08e8dce945ceTest

المؤلفون: Wen-Wan Chao, Yueh-Hsiung Kuo, Bi-Fong Lin

المصدر: Frontiers in Pharmacology, Vol 12 (2021)

مصطلحات موضوعية: Andrographis paniculata, antiviral activity, cytopathic effect, enterovirus 71, rhabdomyosarcoma cells, Therapeutics. Pharmacology, RM1-950

الوصف: Aim:Andrographis paniculata (Burm. f.) Nees (also known as Chuanxinlian in Chinese) of Acanthaceae family is one of the Chinese herbs reputed to be effective in the treatment of inflammation, infection, cold, and fever. Enterovirus 71 (EV71) is one of the most important enteroviruses that cause hand, foot, and mouth disease (HFMD) accompanied with neurological complication.Methods: To explore an anti-infective Chinese herb medicine, pure compounds isolated or synthesized analogues from A. paniculata (AP) ethyl acetate (EtOAc) extract are used to explore their anti-EV71-induced cytotoxicity. The antiviral activity was determined by cytopathic effect (CPE) reduction, and sub-G1 assays were used for measuring lysis and apoptosis of EV71-infected rhabdomyosarcoma (RD) cells. IFNγ-driven luciferase reporter assay was used to evaluate their potential roles in activation of immune responses.Results: Our data showed that EV71-induced sub-G1 phase of RD cells was dose dependently increased. Highly apoptotic EV71-infected RD cells were reduced by AP extract treatment. Ergosterol peroxide (4) has the most anti-apoptotic effect among these seven compounds. In addition, 3,19-O-acetyl-14-deoxy-11,12-didehydroandrographolide (8) synthesized from acetylation of compound 7 showed significantly better antiviral activity and the lowest sub-G1 phase of 6%–18%. Further investigation of IFNγ-inducer activity of these compounds showed that compounds 3, 6, 10, 11, and 12 had significantly higher IFNγ luciferase activities, suggesting their potential to promote IFNγ expression and thus activate immune responses for antivirus function.Conclusion: Our study demonstrated that bioactive compounds of AP and its derivatives either protecting EV71-infected RD cells from sub-G1 arrest or possessing IFNγ-inducer activity might be feasible for the development of anti-EV71 agents.

العلاقة: https://www.frontiersin.org/articles/10.3389/fphar.2021.762285/fullTest; https://doaj.org/toc/1663-9812Test; https://doaj.org/article/c5c9c3ee3fdb4a5db9dac23af9cdd69fTest

الإتاحة: https://doi.org/10.3389/fphar.2021.762285Test
https://doaj.org/article/c5c9c3ee3fdb4a5db9dac23af9cdd69fTest