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1.
Cardiovasc Diabetol ; 23(1): 160, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715043

ABSTRACT

BACKGROUND: Diabetic cardiomyopathy (DCM) is a crucial complication of long-term chronic diabetes that can lead to myocardial hypertrophy, myocardial fibrosis, and heart failure. There is increasing evidence that DCM is associated with pyroptosis, a form of inflammation-related programmed cell death. Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor ß superfamily, which regulates oxidative stress, inflammation, and cell survival to mitigate myocardial hypertrophy, myocardial infarction, and vascular injury. However, the role of GDF11 in regulating pyroptosis in DCM remains to be elucidated. This research aims to investigate the role of GDF11 in regulating pyroptosis in DCM and the related mechanism. METHODS AND RESULTS: Mice were injected with streptozotocin (STZ) to induce a diabetes model. H9c2 cardiomyocytes were cultured in high glucose (50 mM) to establish an in vitro model of diabetes. C57BL/6J mice were preinjected with adeno-associated virus 9 (AAV9) intravenously via the tail vein to specifically overexpress myocardial GDF11. GDF11 attenuated pyroptosis in H9c2 cardiomyocytes after high-glucose treatment. In diabetic mice, GDF11 alleviated cardiomyocyte pyroptosis, reduced myocardial fibrosis, and improved cardiac function. Mechanistically, GDF11 inhibited pyroptosis by preventing inflammasome activation. GDF11 achieved this by specifically binding to apoptosis-associated speck-like protein containing a CARD (ASC) and preventing the assembly and activation of the inflammasome. Additionally, the expression of GDF11 during pyroptosis was regulated by peroxisome proliferator-activated receptor α (PPARα). CONCLUSION: These findings demonstrate that GDF11 can treat diabetic cardiomyopathy by alleviating pyroptosis and reveal the role of the PPARα-GDF11-ASC pathway in DCM, providing ideas for new strategies for cardioprotection.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Cardiomyopathies , Fibrosis , Growth Differentiation Factors , Inflammasomes , Mice, Inbred C57BL , Myocytes, Cardiac , Pyroptosis , Signal Transduction , Animals , Pyroptosis/drug effects , Diabetic Cardiomyopathies/metabolism , Diabetic Cardiomyopathies/pathology , Diabetic Cardiomyopathies/prevention & control , Diabetic Cardiomyopathies/etiology , Diabetic Cardiomyopathies/physiopathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Myocytes, Cardiac/drug effects , Diabetes Mellitus, Experimental/metabolism , Cell Line , Inflammasomes/metabolism , Male , Growth Differentiation Factors/metabolism , Rats , Blood Glucose/metabolism , Mice , Glucose/metabolism , Glucose/toxicity , Bone Morphogenetic Proteins , PPAR alpha
2.
J Neuroinflammation ; 20(1): 204, 2023 Sep 07.
Article in English | MEDLINE | ID: mdl-37679787

ABSTRACT

BACKGROUND: 17ß-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown. METHODS: In this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC-MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro. RESULTS: sE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolism imbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression. CONCLUSION: These data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism.


Subject(s)
Depression , Microglia , Female , Humans , Animals , Mice , Depression/chemically induced , Brain , Estradiol/pharmacology , Cytokines , Glycerophospholipids
3.
Article in English | MEDLINE | ID: mdl-37185089

ABSTRACT

Four novel bacterial strains, designated RBB1W86T, RXD159T, RBB189T and RLT163T, were isolated from subtropical forest soil of the Nanling National Nature Reserve located in Guangdong Province, PR China. 16S rRNA gene phylogeny indicated their affiliation to the genus Dyella, among which strains RBB1W86T and RXD159T were closely related to Dyella halodurans CGMCC 1.15435T with 16S rRNA gene sequence similarities of 98.8 and 99.5 %, respectively, and strains RBB189T and RLT163T were closely related to Dyella tabacisoli CGMCC 1.16273T (98.8 %) and Dyella japonica JCM 21530T (99.4 %), respectively. Phylogenomic analysis based on 92 core genes showed consistent phylogeny with the 16S rRNA gene phylogeny for strains RBB1W86T, RBB189T and RLT163T, while strain RXD159T showed a closer relationship with D. tabacisoli CGMCC 1.16273T and strain RBB189T. The genome-derived average nucleotide identity (ANI) values between the newly isolated strains and their closely related species were 70.18‒90.20 %, and the corresponding digital DNA-DNA hybridization (dDDH) values were 20.80‒40.30 %. Meanwhile, the ANI and dDDH values between each pair of the newly isolated strains were 75.80‒79.77 % and 21.30‒23.30 %, respectively. They all took iso-C15 : 0 and summed feature 9 (10-methyl C16  : 0 and/or iso-C17  : 1 ω9c) as the major fatty acids. Moreover, C16 : 0, iso-C16 : 0, iso-C17 : 0 and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) were also variously distributed as major components. They all took ubiquinone 8 as the only predominant respiratory quinone and phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid as the major polar lipids. Phosphatidylmethylethanolamine was only present in strain RBB189T as another major component. Based on the results of phenotypic, genotypic and chemotaxonomic analyses, the newly isolated strains could be clearly distinguished from their closely related species and should represent four distinct novel species of the genus Dyella, for which the names Dyella humicola sp. nov. (type strain RBB1W86T=GDMCC 1.1901T=KACC 21988T), Dyella subtropica sp. nov. (type strain RXD159T=GDMCC 1.1902T=KACC 21989T), Dyella silvatica sp. nov. (type strain RBB189T=GDMCC 1.1900T=KACC 21990 T) and Dyella silvae sp. nov. (type strain RLT163T=GDMCC 1.1916T=KACC 21991T) are proposed.


Subject(s)
Fatty Acids , Xanthomonadaceae , Fatty Acids/chemistry , RNA, Ribosomal, 16S/genetics , Phylogeny , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Sequence Analysis, DNA , Phospholipids , Forests , Soil Microbiology
4.
BMC Plant Biol ; 21(1): 456, 2021 Oct 06.
Article in English | MEDLINE | ID: mdl-34615469

ABSTRACT

BACKGROUND: Leaf shape is an important agronomic trait in ornamental kale (Brassica oleracea L. var. acephala). Although some leaf shape-related genes have been reported in ornamental kale, the detailed mechanism underlying leaf shape formation is still unclear. Here, we report a lobed-leaf trait in ornamental kale, aiming to analyze its inheritance and identify the strong candidate gene. RESULTS: Genetic analysis of F2 and BC1 populations demonstrate that the lobed-leaf trait in ornamental kale is controlled by a single dominant gene, termed BoLl-1 (Brassica oleracea lobed-leaf). By performing whole-genome resequencing and linkage analyses, the BoLl-1 gene was finely mapped to a 127-kb interval on chromosome C09 flanked by SNP markers SL4 and SL6, with genetic distances of 0.6 cM and 0.6 cM, respectively. Based on annotations of the genes within this interval, Bo9g181710, an orthologous gene of LATE MERISTEM IDENTITY 1 (LMI1) in Arabidopsis, was predicted as the candidate for BoLl-1, and was renamed BoLMI1a. The expression level of BoLMI1a in lobed-leaf parent 18Q2513 was significantly higher compared with unlobed-leaf parent 18Q2515. Sequence analysis of the parental alleles revealed no sequence variations in the coding sequence of BoLMI1a, whereas a 1737-bp deletion, a 92-bp insertion and an SNP were identified within the BoLMI1a promoter region of parent 18Q2513. Verification analyses with BoLMI1a-specific markers corresponding to the promoter variations revealed that the variations were present only in the lobed-leaf ornamental kale inbred lines. CONCLUSIONS: This study identified a lobed-leaf gene BoLMI1a, which was fine-mapped to a 127-kb fragment. Three variations were identified in the promoter region of BoLMI1a. The transcription level of BoLMI1a between the two parents exhibited great difference, providing new insight into the molecular mechanism underlying leaf shape formation in ornamental kale.


Subject(s)
Brassica/anatomy & histology , Brassica/genetics , Cloning, Molecular , Phenotype , Plant Leaves/anatomy & histology , Plant Leaves/genetics , Promoter Regions, Genetic , Gene Expression Regulation, Plant , Genes, Plant , Genetic Variation , Genotype
5.
Int J Mol Sci ; 22(24)2021 Dec 08.
Article in English | MEDLINE | ID: mdl-34948024

ABSTRACT

B. oleracea Ogura CMS is an alloplasmic male-sterile line introduced from radish by interspecific hybridization and protoplast fusion. The introduction of alien cytoplasm resulted in many undesirable traits, which affected the yield of hybrids. Therefore, it is necessary to identify the composition and reduce the content of alien cytoplasm in B. oleracea Ogura CMS. In the present study, we sequenced, assembled, and compared the organelle genomes of Ogura CMS cabbage and its maintainer line. The chloroplast genome of Ogura-type cabbage was completely derived from normal-type cabbage, whereas the mitochondrial genome was recombined from normal-type cabbage and Ogura-type radish. Nine unique regions derived from radish were identified in the mitochondrial genome of Ogura-type cabbage, and the total length of these nine regions was 35,618 bp, accounting for 13.84% of the mitochondrial genome. Using 32 alloplasmic markers designed according to the sequences of these nine regions, one novel sterile source with less alien cytoplasm was discovered among 305 materials and named Bel CMS. The size of the alien cytoplasm in Bel CMS was 21,587 bp, accounting for 8.93% of its mtDNA, which was much less than that in Ogura CMS. Most importantly, the sterility gene orf138 was replaced by orf112, which had a 78-bp deletion, in Bel CMS. Interestingly, Bel CMS cabbage also maintained 100% sterility, although orf112 had 26 fewer amino acids than orf138. Field phenotypic observation showed that Bel CMS was an excellent sterile source with stable 100% sterility and no withered buds at the early flowering stage, which could replace Ogura CMS in cabbage heterosis utilization.


Subject(s)
Brassica/growth & development , Chloroplasts/genetics , Genetic Markers , Genomics/methods , Mitochondria/genetics , Plant Infertility , Plant Proteins/genetics , Brassica/classification , Brassica/genetics , Gene Expression Regulation, Plant , Genome Size , Genome, Chloroplast , Genome, Mitochondrial , High-Throughput Nucleotide Sequencing , Phenotype , Sequence Analysis, DNA , Sequence Deletion , Synteny
6.
Int J Syst Evol Microbiol ; 70(9): 4867-4873, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32749954

ABSTRACT

Two novel strains, designated 92R-1T and 9PBR-1T, were isolated from abandoned lead-zinc ore collected in Meizhou, Guangdong Province, PR China. Phylogenetic analyses based on 16S rRNA gene sequences showed that they fell into the genus of Hymenobacter and formed two distinct lineages. Strain 92R-1T was most closely related to Hymenobacter wooponensis JCM 19491T (98.7 %) and Hymenobacter gelipurpurascens LMG 21873T (98.5 %), while strain 9PBR-1T was most closely related to Hymenobacter chitinivorans LMG 21951T (99.0 %), Hymenobacter elongatus JCM 17223T (98.7 %) and Hymenobacter aquaticus JCM 31653T (98.1 %). Strain 92R-1Tshared average nucleotide identity values of 80.0-83.7 % and digital DNA-DNA hybridization values of 23.1-27.1 % with its closely related type strains, respectively, while strain 9PBR-1T shared corresponding values of 80.3-83.2 % and 23.6-26.7 % with its closely related type strains, respectively. The two novel strains could be clearly distinguished from their closely related type strains by enzyme activities and substrates assimilation, respectively. Both of them took iso-C15:0, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), summed feature 4 (iso-C17:1 I and/or anteiso-C17:1 B) and C16:1 ω5c as major fatty acids, and showed clear differences from their closely relatives in the contents of several components. They contained menaquinone 7 as the major respiratory quinone and phosphatidylethanolamine as the dominant polar lipid. The G+C contents of strains 92R-1T and 9PBR-1T were 56.7 and 59.5 mol%, respectively. The results clearly supported that strains 92R-1T and 9PBR-1T represent two distinct novel species within the genus Hymenobacter, for which the names Hymenobacter fodinae sp. nov. (type strain 92R-1T=GDMCC 1.1493T=JCM 32697T) and Hymenobacter metallicola sp. nov. (type strain 9PBR-1T=GDMCC 1.1491T=JCM 32698T) are proposed.


Subject(s)
Cytophagaceae/classification , Mining , Phylogeny , Bacterial Typing Techniques , Base Composition , China , Cytophagaceae/isolation & purification , DNA, Bacterial/genetics , Fatty Acids/chemistry , Lead , Nucleic Acid Hybridization , Phosphatidylethanolamines/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Vitamin K 2/analogs & derivatives , Vitamin K 2/chemistry , Zinc
7.
Int J Syst Evol Microbiol ; 70(4): 2867-2872, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32207677

ABSTRACT

A novel pink-pigmented strain, designated 6HR-1T, was isolated from tungsten mine tailings in Jiangxi Province, PR China. Cells were Gram-stain-negative, aerobic, non-spore-forming, rod-shaped and motile with a polar flagellum (monotrichous). It could not utilize methanol, methylamine, formaldehyde or formate as a sole carbon source. The methanol dehydrogenase mxaF gene was absent but the xoxF gene was present. Phylogenomic and 16S rRNA gene phylogenetic analyses clearly showed that strain 6HR-1T was affiliated to the genus Methylobacterium and closely related to 'Methylobacterium terrae' 17Sr1-28T (98.6 %), Methylobacterium platani JCM 14648T (97.7 %), Methylobacterium variabile DSM 16961T (97.7 %) and Methylobacterium currus KACC 19662T (97.4 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain 6HR-1T and its closely related type species were 87.4-88.7 and 33.2-36.3 %, respectively. It had summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) as the major fatty acid and ubiquinone 10 as the predominant respiratory quinone. Polyphasic characterization supported that strain 6HR-1T represents a novel species of the genus Methylobacterium, for which the name Methylobacterium nonmethylotrophicum sp. nov. is proposed with the type strain 6HR-1T (=GDMCC 1.662T=KCTC 42760T).


Subject(s)
Methylobacterium/classification , Mining , Phylogeny , Tungsten , Bacterial Typing Techniques , Base Composition , China , DNA, Bacterial/genetics , Fatty Acids/chemistry , Genes, Bacterial , Methylobacterium/isolation & purification , Nucleic Acid Hybridization , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Ubiquinone/analogs & derivatives , Ubiquinone/chemistry
8.
Int J Syst Evol Microbiol ; 70(4): 2901-2906, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32223836

ABSTRACT

A novel bacterial strain, designated FGD1T, was isolated from subtropical forest soil of the Nanling National Forest Park located in Guangdong Province, P.R. China. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain FGD1T was most closely related to Novosphingobium lindaniclasticum DSM 25049T (98.8 %), followed by N. barchaimii DSM 25411T (98.7 %), N. guangzhouense DSM 32207T (98.2 %), N. panipatense DSM 22890T (98.1 %) and other species of Novosphingobium (<98 %). The draft genome sequence was 4.58 Mb in length with a G+C content of 65.1 mol%. The calculated average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain FGD1T and closely related type strains were 77.7‒79.6 % and 21.7-22.9 %, respectively. Major fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C14 : 0 2-OH and C16 : 0. The predominant respiratory quinone was ubiquinone 10 and the major polyamine was spermidine. Polar lipids were composed of sphingoglycolipid, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, diphosphatidylglycerol, an unidentified phospholipid and lipid. The polyphasic taxonomic results indicated that strain FGD1T represents a novel species of the genus Novosphingobium, for which the name Novosphingobium silvae sp. nov. is proposed. The type strain is FGD1T (=GDMCC 1.1761T=KACC 21283T).


Subject(s)
Forests , Phylogeny , Soil Microbiology , Sphingomonadaceae/classification , Bacterial Typing Techniques , Base Composition , China , DNA, Bacterial/genetics , Fatty Acids/chemistry , Nucleic Acid Hybridization , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Sphingomonadaceae/isolation & purification , Ubiquinone/analogs & derivatives , Ubiquinone/chemistry
9.
Int J Syst Evol Microbiol ; 70(3): 1644-1647, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31909705

ABSTRACT

Phylogenetic analysis of the genus Sphingobium had shown that the type strains of Sphingobium paulinellae, Sphingobium algicola and Sphingobium limneticum shared a very close relationship between each other. The 16S rRNA gene sequences similarity values between each other ranged from 99.65 to 99.93 %. Whole genome sequencing was performed and genomic relatedness values between each pair of the species were 97.49-100 % (ANI) and 79.3-100 % (dDDH), respectively, all higher than the threshold values of 95-96 % ANI and 70 % dDDH suggested for species discrimination, and implicated that the type strains should belong to the same species of the genus Sphingobium. The phenotypic and chemotaxonomic characterizations performed in the original descriptions of S. paulinellae and S. algicola also supported the same conclusion. Due to priority of publication Sphingobium paulinellae and Sphingobium algicola Lee and Jeon 2017, should be taken as two later heterotypic synonyms of Sphingobium limneticum Chen et al. 2013. Correspondingly, the species description of Sphingobium limneticum was emended based on this study.


Subject(s)
Phylogeny , Sphingomonadaceae/classification , Bacterial Typing Techniques , DNA, Bacterial/genetics , Nucleic Acid Hybridization , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Whole Genome Sequencing
10.
Int J Syst Evol Microbiol ; 69(8): 2214-2219, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31066661

ABSTRACT

A novel slowly growing member of the genus Sphingomonas, designated 1PNM-20T, was isolated from an abandoned lead-zinc mine in Meizhou, Guangdong Province, PR China. A polyphasic taxonomic study was performed to characterize the novel strain. Growth occurred on Reasoner's 2A (R2A) agar and peptone-yeast extract (PYE) agar, but not in liquid R2A or PYE media. Cells were Gram-stain-negative, aerobic, non-spore-forming, rod-shaped and motile with a polar flagellum (monotrichous). 16S rRNA gene sequence comparison showed that it shared the highest similarity with Sphingomonas carriPR0302T (97.2 %), followed by Sphingomonas spermidinifaciens 9NM-10T (97.0 %), Sphingomonas floccifaciens FQM01T (97.0 %) and other species of Sphingomonas (<97 %). Phylogenetic analyses clearly showed that strain 1PNM-20T fell into the cluster of Sphingomonas, and was most closely related to S. carri. The draft genome sequence was 3.76 Mb in length with a DNA G+C content of 69.8 mol%. Major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and 11-methyl C18 : 1ω7c, with C14 : 0 2-OH as the main hydroxy fatty acid. Ubiquinone 10 (Q-10) was the predominant respiratory quinone, and sym-homospermidine was displayed as the major polyamine. The polar lipids were composed of sphingoglycolipid, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an unidentified phospholipid and an unidentified glycolipid. The phenotypic, phylogenetic and chemotaxonomic results supported the hypothesis that strain 1PNM-20T represents a novel species of the genus Sphingomonas, for which the name Sphingomonas lenta sp. nov. is proposed. The type strain is 1PNM-20T (=GDMCC 1.660T=DSM 27572T).


Subject(s)
Phylogeny , Soil Microbiology , Sphingomonas/classification , Bacterial Typing Techniques , Base Composition , China , DNA, Bacterial/genetics , Fatty Acids/chemistry , Glycolipids/chemistry , Lead , Mining , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Spermidine/analogs & derivatives , Spermidine/chemistry , Sphingomonas/isolation & purification , Ubiquinone/chemistry , Zinc
11.
Biomed Microdevices ; 20(4): 91, 2018 10 25.
Article in English | MEDLINE | ID: mdl-30361769

ABSTRACT

A rapid, sensitive and quantitative biomarker detection platform is of great importance to the small clinic or point-of-care (POC) diagnosis. In this work, we realize that an automated diagnostic platform mainly includes two components: (1) an instrument that can complete all steps of the chemiluminescence immunoassay automatically and (2) an integrated microfluidic chip which is disposable and harmless. In the instrument, we adopt vacuum suction cups which are driven by linear motor to realize a simple, effective and convenient control. The method of acridine esterification chemiluminescence is adopted to achieve a quantitative detection, and a photomultiplier tube is used to detect photons from acridine ester producing in alkaline conditions. We use the laser cutting machine and hot press machine to accomplish the product of microfluidic chips. The automated microfluidics-based system is demonstrated by implementation of a chemiluminescence immunoassay for quantitative detection of ferritin. We observe alinear relationship between CL intensity and the concentration of ferritin from 5.1 to 1300 ng mL -1and the limit of detection (LoD) is 2.55 ng mL -1. At the same time, we also used the automated microfluidics-based system to test clinical serum samples. The whole process of chemiluminescence experiment can complete within 45 min. We realize that this lab-on-a-chip chemiluminescence immunoassay platform with features of automation and quantitation provides a promising strategy for POC diagnosis.


Subject(s)
Biomarkers/analysis , Immunoassay/instrumentation , Lab-On-A-Chip Devices , Luminescent Measurements/instrumentation , Automation , Costs and Cost Analysis , Ferritins/analysis , Lab-On-A-Chip Devices/economics
12.
IEEE Trans Cybern ; PP2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39231065

ABSTRACT

This article considers an observer-based optimal backstepping security control for nonlinear systems using reinforcement learning (RL) strategy. The main challenge faced is the design of optimal contoller under the deception attacks. Therefore, this article introduces an improved security RL algorithm based on neural network technology under the design framework of critic-actor to resist attacks and optimize the entire system. Second, compared with some existing results, how to relax the general assumption about deception attack is also a difficult research topic. In this article, an unusual observer that uses the attacked system output is designed to estimate the real unavailable states caused by deception attacks, so that the impact of deception attacks is eliminated and the output feedback control is also achieved. By selecting the virtual controllers and the real controller as corresponding optimized controllers within the framework of the RL algorithm, the control strategy can ensure that all signals in the closed-loop system are semi-globally ultimately bounded. Finally, two simulation experiments will be run to demonstrate the effectiveness of the strategy.

13.
IEEE Trans Cybern ; PP2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990743

ABSTRACT

This article presents a new event-triggered adaptive finite-time control strategy using a fuzzy state observer for a class of nonlinear cyber-physical systems (CPSs) under malicious deception attacks with a more general form. Compared with the traditional assumptions on the deception attacks in the existing results, a more general assumption on deception attacks is given in this article. During the design process, real system states are initially estimated by developing an improved state observer, which effectively addresses the problem of state unavailability. Then, a coordinate transformation technology, in which the estimated states of observer are considered, is presented to stabilize the studied system. By constructing the singularity-free finite time virtual controls, the singularity problem in the traditional finite time design algorithms is cleverly avoided. Furthermore, to minimize communication overhead, a final finite-time controller is established by using a relative threshold event-triggered scheme. The developed event-triggered adaptive finite-time control strategy guarantees that all signals in the closed-loop system are semi-globally bounded in finite time without Zeno behavior. Finally, the correctness of the proposed control strategy is validated through two simulation results.

14.
Eur J Pharmacol ; 983: 177000, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39278311

ABSTRACT

Postmenopausal osteoporosis (PMOP) is closely related to the pathogenesis of osteoclasts, with the Cathepsin K (CTSK) protein playing a crucial role. Our study aimed to screen small molecule compounds targeting CTSK and evaluate their impact on PMOP. Through molecular docking, we identified NVP-BHG712 as significantly inhibiting osteoclast differentiation and bone resorption. NVP-BHG712 also effectively suppressed CTSK activity and exhibited strong binding affinity to CTSK protein. Furthermore, NVP-BHG712 regulated the expression of inflammatory factors and modulated the balance between M1 and M2 macrophage polarization. In the mouse model of ovariectomy-induced osteoporosis, NVP-BHG712 rescued bone loss by inhibiting excessive osteoclast activation. These findings suggest that NVP-BHG712 may be a promising treatment for pathological osteoporosis by alleviating osteoclast function.


Subject(s)
Cathepsin K , Osteoclasts , Osteogenesis , Ovariectomy , Animals , Mice , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteogenesis/drug effects , Cathepsin K/metabolism , Cathepsin K/genetics , Female , RAW 264.7 Cells , Cell Differentiation/drug effects , Molecular Docking Simulation , Osteoporosis/drug therapy , Osteoporosis/metabolism , Bone Resorption/drug therapy , Bone Resorption/pathology , Humans , Mice, Inbred C57BL , Osteoporosis, Postmenopausal/drug therapy , Osteoporosis, Postmenopausal/pathology , Osteoporosis, Postmenopausal/metabolism , Disease Models, Animal
15.
IEEE Trans Cybern ; 53(10): 6562-6570, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36219655

ABSTRACT

This work concentrates on the adaptive resilient dynamic surface controller design problem for uncertain nonlinear lower triangular stochastic cyber-physical systems (CPSs) subject to unknown deception attacks based on a switching threshold event-triggered mechanism. The adverse effect of deception attacks on the stochastic CPSs is that the exact system state variables become unavailable. Furthermore, it should be emphasized that the coexistence of unknown nonlinearities, stochastic perturbations, and unknown sensor and actuator attacks makes it a very difficult and challenging event to implement the control design. To get the desired controller, radial basis function (RBF) neural networks (NNs) are introduced so that the design obstacle caused from the unknown nonlinearities can be easily solved. On this basis, in order to save resources and effectively transmit, the event-triggered control scheme based on a switching threshold strategy is further considered. In the backstepping design process, the dynamic surface control (DSC) technique is presented to deal with the issue of "explosion of complexity." By skillfully designing a new coordinate transformation and the attack compensators, the problem of unknown deception attacks is successfully handled. Under our proposed control scheme, all the closed-loop signals are bounded in probability and the stabilization errors converge to an adjustable neighborhood of the origin in probability. Finally, the simulation results on the double chemical reactor show the validity of the proposed design scheme.

16.
Sci Rep ; 12(1): 20128, 2022 Nov 22.
Article in English | MEDLINE | ID: mdl-36418378

ABSTRACT

Seismic fault displacement is the main factor leading to local buckling failure of the buried pipeline, especially crossing the oblique-reverse fault. The local buckling behavior of the buried pipeline is complex under the 3-D displacement of the oblique-reverse fault. In this work, the pipe local buckling mechanism was discussed, then a shell and solid element nonlinear contact coupling model of the pipeline crossing oblique-reverse fault was established based on the ABAQUS program. The local buckling behavior (potential local buckling locations, developing process) of the pipeline under oblique-reverse fault displacement was systematically analyzed, comparing against the same under single fault displacement. Subsequently, the influence of internal pressure, diameter thickness ratio and burial depth on the local buckling behavior of the pipeline were discussed. The numerical results revealed two potential locations and three stages of the local buckling, then the potential local buckling locations and three stages of the local buckling under different internal pressure, diameter thickness ratio and burial depth were obtained. It proves that the local buckling of the pipeline is more sensitive to the oblique-reverse fault displacement than single fault displacement and provides a reference for the aseismic design and reinforcement of the pipeline crossing the oblique-reverse fault.

17.
Article in English | MEDLINE | ID: mdl-35622809

ABSTRACT

In this article, the asymptotic tracking control problem for a class of nonlinear multi-agent systems (MASs) is researched by the combination of radial basis function neural networks (RBF NNs) and an improved dynamic surface control (DSC) technology. It's important to emphasize that the MASs studied in this article are nonlinear and nonstrict-feedback systems, where the nonlinear functions are unknown. In order to satisfy the requirement that all items in the controller must be available, the unknown nonlinearities in the system are flexibly approximated by utilizing RBF NNs technique. Moreover, the issue of ``complexity explosion'' in the backstepping procedure is handled by improving the traditional DSC technology, and meanwhile, the influences of the boundary layers caused by the filters in the DSC procedure are eliminated skillfully through the compensation terms. In addition, the relative threshold event-triggered strategy is developed for the designed controllers to reduce the waste of communication resources, where Zeno phenomenon is successfully avoided. It is observed that the new presented control strategy ensures that all the closed-loop systems variables are uniformly ultimately bounded (UUB), and furthermore all the outputs of followers are able to track the output of the leader with zero tracking errors. Finally, the simulation results are presented to show the effectiveness of the obtained design scheme.

18.
Front Cell Dev Biol ; 10: 1028510, 2022.
Article in English | MEDLINE | ID: mdl-36393869

ABSTRACT

Human female fecundity decreases irreversibly as chronological age rises, adversely affecting oocyte quality, consequently worsening pregnancy outcomes and increasing the extent of birth defects. The first-line type 2 diabetes treatment metformin has been associated with delayed aging and reduction of oxidative stress; yet it remains unclear if metformin confers any benefits for oocytes from aged mice, particularly in the context of the assisted human reproductive technology (ART) known as in vitro maturation (IVM). Here, we found that adding metformin into the M16 culture medium of oocytes from aged mice significantly improved both oocyte maturation and early embryonic development. This study showed that metformin reduced the extent of meiotic defects and maintained a normal distribution of cortical granules (CGs). RNA-seq analysis of metformin-treated oocytes revealed genes apparently involved in the reduction of mitochondrial ROS. Further, the results supported that the metformin improved mitochondrial function, reduced apoptosis, increased the extent of autophagy, and reduced mitochondrial ROS via SIRT3-mediated acetylation status of SOD2K68 in oocytes from aged mice. Thus, this finding demonstrated a protective effect for metformin against the decreased quality of oocytes from aged mice to potentially improve ART success rates and illustrated a potential strategy to prevent or delay reproductive aging.

19.
IEEE Trans Cybern ; PP2022 Sep 28.
Article in English | MEDLINE | ID: mdl-36170392

ABSTRACT

In this article, two novel adaptive fault-tolerant control schemes for a class of nonlinear strict-feedback cyber-physical systems (CPSs) with deception attacks are presented. Deception attacks, such as false data-injection attacks, which destroy sensor networks, make the outputs and states of the CPSs unavailable. It is very difficult and challenging for a designer to achieve the tracking control under the circumstance of cyberattacks. To realize the tracking control for the studied CPSs, we propose a new coordinate transformation technology without precedent, where it takes the attack gains into account and uses the compromised states to design the corresponding controllers. In the backstepping design process, Nussbaum functions are presented to alleviate the influence of the unknown attack gains. Furthermore, we consider the actuator faults problem, which includes the loss of effectiveness and the bias fault. By skillfully designing the adaptive laws, the effect of actuator faults is completely eliminated. It is theoretically proved that the first proposed tracking control scheme can guarantee all signals in the closed-loop system are bounded and the output can track the desired reference signal. In addition, the second adaptive control scheme is also developed for the CPSs under the actuator faults and a more general assumption on the deception attacks is proposed simultaneously. Finally, the feasibility of the new proposed methods is verified by MATLAB simulation analysis.

20.
Plants (Basel) ; 11(10)2022 May 21.
Article in English | MEDLINE | ID: mdl-35631797

ABSTRACT

Cabbage (Brassica oleracea L. var. capitata) self-incompatibility is important for heterosis. However, the seed production of elite hybrid cannot be facilitated by honey bees due to the cross-incompatibility of the two parents. In this study, the self-compatibility of 58 winter cabbage inbred lines was identified by open-flower self-pollination (OS) and molecular techniques. Based on the NCBI database, a new class I S-haplotype-specific marker, PKC6F/PKC6R, was developed. Verification analyses revealed 9 different S-haplotypes in the 58 cabbage inbred lines; of these lines, 46 and 12 belonged to class I (S6, S7, S12, S14, S33, S45, S51, S68) and class II (S15) S-haplotypes, respectively. The coincidence rate between the self-compatibility index and S-haplotype was 91%. This study developed a Tri-Primer-PCR amplification method to rapidly select plants with specific S-haplotypes in biased segregated S-locus populations. Furthermore, it established an S-haplotype identification system based on these nine S-haplotypes. To overcome parental cross-incompatibility (18-503 and 18-512), an inbred line (18-2169) with the S15 haplotype was selected from the sister lines of self-incompatible 18-512 (S68, class I S-haplotype). The inbred line (18-2169) showed self-compatibility and cross-compatibility with 18-503. This study provides guidance for self-compatibility breeding in cabbage and predicts parental cross-incompatibility in elite combinations.

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