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1.
PLoS One ; 19(4): e0299940, 2024.
Article in English | MEDLINE | ID: mdl-38620031

ABSTRACT

Injecting carbon dioxide is the most effective means of preventing and extinguishing fires in sealing hazardous areas, but the traditional method slowly and remotely injects carbon dioxide gas into the well after gasification on the ground, which is dependent on the complete mine pipe network without cooling effect. To inject liquid directly from the tank with vacuum interlayer and heat insulating powder for rapid inerting and cooling, a new approach using track mobile platform to go deep into the underground mine disaster area is proposed, so the liquid can be delivered to the nozzle at the end of DN40 large diameter pipe, and the continuous gasification jet can be realized. The experimental results show that: (1) The liquid volume in a tank of vacuum degree within 2.0 Pa and 200 mm interlayer reduced no more than 15.5% after 48 days; (2) Taking the pressure in the tank as the power source, because of environmental differences inside and outside the pipe after 100 m pressure holding delivery, the physical form of liquid and gas could be converted instantly; (3) The continuous discharge time without ice blocking for a tank full of 2 m3 liquid was about 10.5 min under 25 L dual mode nitrogen pressurization, which is 1/12 of injection time after ground gasification; (4) Based on the temperature decrease trend measured at different positions, the cooling characteristics on liquid gasification jet path are quantified, and the calculation formula of temperature changing with time on the center line of liquid gasification jet is obtained. Through this new approach, the integration of vacuum insulated storage, safe mobile transportation, and continuous and rapid release with large flow can be achieved for the liquid carbon dioxide.


Subject(s)
Carbon Dioxide , Fires , Fires/prevention & control , Nitrogen , Hot Temperature , Cold Temperature
2.
Cell Biol Int ; 48(4): 431-439, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38180302

ABSTRACT

Emerging evidence has suggested that N6 -methyladenosine (m6 A) regulates the pathology of Parkinson's disease (PD). Nevertheless, the function of demethylase fat mass and obesity (FTO) associated pathogenesis is still not fully elucidated. Here, this research findings revealed that m6 A-modification was decreased in PD models, meanwhile, the FTO level upregulated in the PD models. Functionally, in N-methyl-4-phenylpyridinium (MPP+) treated SH-SY5Y cells, the ferroptosis significantly upregulated and FTO silencing mitigated the ferroptosis phenotype. Moreover, in silico assays indicated that nuclear factor erythroid 2-related factor-2 (NRF2) acted as the target of FTO, and FTO demethylated the m6 A modification from NRF2 mRNA. Furthermore, FTO impaired the NRF2 mRNA stability via m6 A-dependent pathway. Thus, our findings illustrated an important role of FTO on PD through m6 A-NRF2-ferroptosis manner. Taken together, the study revealed the potential function of FTO on PD nervous system diseases.


Subject(s)
Adenine/analogs & derivatives , Ferroptosis , Neuroblastoma , Parkinson Disease , Humans , Parkinson Disease/genetics , NF-E2-Related Factor 2/genetics , Obesity/genetics , 1-Methyl-4-phenylpyridinium , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics
3.
Molecules ; 28(18)2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37764493

ABSTRACT

The FeCrMoSi amorphous coatings were fabricated on the surface of a 304 stainless steel (SS) base material using atmospheric plasma spraying. A comprehensive investigation was carried out to evaluate the structure, morphology, adhesion to base material, hardness, hydrophobicity, interfacial contact resistance, and corrosion resistance of the coatings. The results show a remarkable hardness of 1180.1 HV, a strong bond strength of up to 64.3 N/mm2, and excellent hydrophobicity with a water contact angle reaching 141.2°. Additionally, in an acidic environment with fluoride ions (0.5 M H2SO4 + 2 ppm HF, 80 °C), the FeCrMoSi amorphous coating demonstrated superior corrosion resistance compared with 304 SS while maintaining similar electroconductibility. Detailed analysis of the structural characteristics and corrosion resistance of FeCrMoSi amorphous coatings provided valuable insights into their mechanics. These promising results signify a bright future for FeCrMoSi amorphous coatings in various industrial sectors, including transportation, petroleum, and electric power industries.

4.
In Vitro Cell Dev Biol Anim ; 59(6): 431-442, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37474885

ABSTRACT

Family with sequence similarity 3 member A (FAM3A) is a multifunctional protein that is related to the pathological process of various disorders. FAM3A is reportedly able to affect the phenotypic change of vascular smooth muscle cells under a hypertensive state. Whether FAM3A mediates the phenotypic switch of vascular smooth muscle cells under an atherosclerotic state remains unaddressed. This work investigated the roles and mechanisms of FAM3A in mediating the phenotypic switch of human aortic smooth muscle cells (HASMCs) stimulated with oxidised low-density lipoprotein (ox-LDL) in vitro. FAM3A expression was elevated in HASMCs following ox-LDL treatment. FAM3A silencing led to a suppressive effect on ox-LDL-provoked proliferation, migration and inflammation of HASMCs, whereas FAM3A overexpression had an opposite effect. Ox-LDL elicited a change in HASMCs from a contractile phenotype to a synthetic phenotype, which was inhibited by FAM3A silencing or enhanced by FAM3A overexpression. Further investigation elucidated that FAM3A silencing repressed and FAM3A overexpression promoted ox-LDL-induced activation of the PI3K-AKT pathway in HASMCs. Reactivation of AKT reversed the suppressive effect of FAM3A silencing on the ox-LDL-induced phenotypic switch of HASMCs. Restraining AKT blocked the promoting effect of FAM3A overexpression on the ox-LDL-induced phenotypic switch of HASMCs. In summary, this work elucidates that FAM3A mediates the ox-LDL-induced phenotypic switch of HASMCs by influencing the PI3K-AKT pathway, indicating a potential role for FAM3A in atherosclerosis.


Subject(s)
Atherosclerosis , Proto-Oncogene Proteins c-akt , Humans , Atherosclerosis/genetics , Cell Movement , Cell Proliferation/genetics , Cells, Cultured , Lipoproteins, LDL/pharmacology , Lipoproteins, LDL/metabolism , Myocytes, Smooth Muscle , Phenotype , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism
5.
Mol Neurobiol ; 60(5): 2632-2643, 2023 May.
Article in English | MEDLINE | ID: mdl-36692707

ABSTRACT

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is involved in neural injury, neuroinflammation, microglia activation, and polarization, while its function in spinal cord injury (SCI) remains unclear. Thus, this study aimed to evaluate the role of MALT1 modification on SCI recovery and its underlying mechanism. SCI surgery or sham surgery was performed in Sprague-Dawley rats. Then, MALT1 knockdown or negative control lentivirus was injected into SCI rats. Subsequently, MALT1 expression, locomotor capability, neural injury, markers for microglia activation and polarization, inflammatory cytokine expressions, and nuclear factor (NF)-κB pathway were detected. SCI rats exhibited higher MALT1 expression, microglia activation and M1 polarization, neuroinflammation, and NF-κB pathway activation, while worse locomotor capacity compared to sham rats (all P < 0.05). In SCI rats, MALT1 knockdown alleviated Basso, Beattie, and Bresnahan score from 10 to 28 days and attenuated HE staining reflected neural injury (all P < 0.05). Besides, MALT1 knockdown declined the number of IBA1+ cells, IBA1+ iNOS+ cells, and IBA1+ CD86+ cells, while enhanced the number of IBA1+ Arg1+ cells and IBA1+ CD206+ cells in SCI rats (all P < 0.05). Meanwhile, MALT1 knockdown declined the expressions of IL-1ß, IL-6, and TNF-α in SCI (all P < 0.05), but did not affect IL-10 expression (P > 0.05). Furthermore, MALT1 knockdown suppressed NF-κB pathway activation validated by immunofluorescence staining and western blot assays (all P < 0.05). MALT1 knockdown improves functional recovery, attenuates microglia activation, M1 polarization, and neuroinflammation via inhibiting NF-κB pathway in SCI.


Subject(s)
Microglia , Spinal Cord Injuries , Animals , Rats , Microglia/metabolism , Neuroinflammatory Diseases , NF-kappa B/metabolism , Rats, Sprague-Dawley , Spinal Cord/pathology , Spinal Cord Injuries/pathology
6.
Cell Mol Biol (Noisy-le-grand) ; 68(5): 202-206, 2022 May 31.
Article in English | MEDLINE | ID: mdl-36029493

ABSTRACT

In recent years, more and more researches has focused on "molecular targeted therapy" for basic genes and regulatory cells, but the effect is not ideal. Therefore, the discovery of new molecular targets with diagnostic and therapeutic significance can not only lay a solid foundation for molecular diagnosis and classification of lesions but also contribute to targeted therapy of glioma. This study aimed to discover the molecular mechanism of mir-218 targeting the regulation of robol expression on proliferation, invasion and migration of glioma cells and to provide a theoretical and experimental basis for finding therapeutic targets of glioma. The purpose of this study was to investigate the effect of mir-218 on gliomas by using the method of control experiment. The results showed that the number of gliomas under the action of mir-218 decreased from about 150 to about 80, and the number would tend to a fixed value range over time. In the experiment, the data decreased from about 150 to nearly 20, and compared with the control group, the control of glioma cell proliferation was very excellent.


Subject(s)
Brain Neoplasms , Glioma , MicroRNAs , Nerve Tissue Proteins , Receptors, Immunologic , Brain Neoplasms/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glioma/genetics , Humans , MicroRNAs/genetics , Neoplasm Invasiveness , Nerve Tissue Proteins/genetics , Receptors, Immunologic/genetics , Roundabout Proteins
7.
J Environ Public Health ; 2022: 5162840, 2022.
Article in English | MEDLINE | ID: mdl-36034623

ABSTRACT

In the current environment where the network and the real society are intertwined, the network public view of public emergencies has involved in reality and altered the ecology of communal public views in China. A new online court of influence has been created, and it affected the trend of events. As the main type of public emergencies, public health emergencies are directly related to people's health and life insurance. Therefore, the public often pays special attention. At present, correct media guidance plays an irreplaceable and important role in calming people's hearts and stabilizing social order. If news and public view are left unchecked, it is likely to cause panic among the people. However, in reality, public view research has always been a research object that is difficult to intelligentize and quantify. Based on such a realistic background, the article conducts a research on public view of public health emergencies based on artificial intelligence data analysis. This study designs an expert system for network public view and optimizes the algorithm for the key problem: SFC deployment. Finally, the system was put into real news and public opinion research on new coronavirus epidemic prevention, and experimental tests were carried out. The experimental results have shown that in the new coronavirus incident, the nuclear leakage incident, and the epidemic prevention policy, the data obtained by the public through the Internet are 50%, 68.06%, and 64.35%, respectively. For the system function in this study, both ICSO and IPSO are far better than the optimization results of CSO and PSO. For most of the test functions, IPSO is better than ICSO's optimization results, which better fulfills the needs of the research content. This study will make an in-depth analysis of the evolution process of online public opinion on public emergencies from the macro-, meso-, and micro-perspectives, in order to analyze the dissemination methods and internal evolution mechanism of various public emergencies of online public opinion, which provides countermeasures and suggestions for the government to guide and manage network public opinion.


Subject(s)
COVID-19 , Public Health , Artificial Intelligence , Emergencies , Humans , Public Opinion
8.
Nat Commun ; 13(1): 3787, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35778378

ABSTRACT

Spinescence is an important functional trait possessed by many plant species for physical defence against mammalian herbivores. The development of spinescence must have been closely associated with both biotic and abiotic factors in the geological past, but knowledge of spinescence evolution suffers from a dearth of fossil records, with most studies focusing on spatial patterns and spinescence-herbivore interactions in modern ecosystems. Numerous well-preserved Eocene (~39 Ma) plant fossils exhibiting seven different spine morphologies discovered recently in the central Tibetan Plateau, combined with molecular phylogenetic character reconstruction, point not only to the presence of a diversity of spiny plants in Eocene central Tibet but a rapid diversification of spiny plants in Eurasia around that time. These spiny plants occupied an open woodland landscape, indicated by numerous megafossils and grass phytoliths found in the same deposits, as well as numerical climate and vegetation modelling. Our study shows that regional aridification and expansion of herbivorous mammals may have driven the diversification of functional spinescence in central Tibetan woodlands, ~24 million years earlier than similar transformations in Africa.


Subject(s)
Ecosystem , Plants , Animals , Forests , Mammals , Phylogeny , Tibet
9.
Metab Brain Dis ; 37(5): 1351-1363, 2022 06.
Article in English | MEDLINE | ID: mdl-35486208

ABSTRACT

Cerebral ischemia is a common cerebrovascular disease with high mortality and disability rate. Exploring its mechanism is essential for developing effective treatment for cerebral ischemia. Therefore, this study aims to explore the regulatory effect and mechanism of retinoid X receptor γ (RXRγ) on cerebral ischemia-reperfusion (I/R) injury. A mouse intraluminal middle cerebral artery occlusion model was established, and PC12 cells were exposed to anaerobic/reoxygenation (A/R) as an in vitro model in this study. Cerebral I/R surgery or A/R treatment induced ferroptosis, downregulated RXRγ and GPX4 (glutathione peroxidase 4) levels, upregulated cyclooxygenase-2 (COX-2) level and increased ROS (reactive oxygen species) level in A/R induced cells or I/R brain tissues in vivo or PC12 cells in vitro. Knockdown of RXRγ downregulated GPX4 and increased COX-2 and ROS levels in A/R induced cells. RXRγ overexpression has the opposite effect. GPX4 knockdown reversed the improvement of RXRγ overexpression on COX-2 downregulation, GPX4 upregulation and ferroptosis in PC12 cells. Furthermore, chromatin immunoprecipitation (ChIP) and luciferase reporter gene assays revealed that RXRγ bound to GPX4 promoter region and activated its transcription. Overexpression of RXRγ or GPX4 alleviated brain damage and inhibited ferroptosis in I/R mice. In conclusion, RXRγ-mediated transcriptional activation of GPX4 might inhibit ferroptosis during I/R-induced brain injury.


Subject(s)
Brain Ischemia , Ferroptosis , Reperfusion Injury , Retinoid X Receptor gamma/metabolism , Animals , Brain Ischemia/metabolism , Cyclooxygenase 2/metabolism , Disease Models, Animal , Mice , Neurons/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase , Rats , Reactive Oxygen Species/metabolism , Reperfusion , Reperfusion Injury/metabolism
10.
J Mol Neurosci ; 72(3): 610-617, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34731364

ABSTRACT

Emerging evidence validates the vital roles of long noncoding RNAs (lncRNAs) in spinal cord injury (SCI), which attracts great attention. In the present study, our study investigated the function and in-depth mechanism of lncRNA Kcnq1 overlapping transcript 1 (Kcnq1ot1) in SCI. Results indicated that lncRNA Kcnq1ot1 expression upregulated in the hypoxia-administered neuronal cells (PC12 cells) and SCI rat models. Moreover, transcription factor signal transducer and activator of transcription 3 (Stat3) accelerated the transcriptional enrichment of Kcnq1ot1 in SCI cellular model. Functional experiments demonstrated that Kcnq1ot1 knockdown repressed the apoptosis of neuronal cells. Mechanistically, Kcnq1ot1 recruited EZH2 to the promoter region of p27 to repress its transcription. Taken together, our results indicate that Stat3-induced lncRNA Kcnq1ot1 regulates the apoptosis in SCI through epigenetically silencing p27, contributing to novel therapeutic target for SCI.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Spinal Cord Injuries , Animals , Apoptosis/genetics , MicroRNAs/genetics , Neurons/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Rats , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Spinal Cord Injuries/genetics , Spinal Cord Injuries/metabolism
11.
Biosens Bioelectron ; 196: 113703, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-34656853

ABSTRACT

A sandwiched photoelectrochemical (PEC) immunosensor based on BiOI/Bi2S3/Ag2S was designed for the quantitative detection of cytokeratin-19 fragments (CYFRA21-1) in serum. In this work, due to the intervention of the narrow band gap Bi2S3, the absorption of the light source by the BiOI/Bi2S3 heterostructure has been significantly enhanced. Meanwhile, the matched band structure of BiOI, Bi2S3 and Ag2S promoted the rapid transfer of electrons between the conduction bands and effectively inhibited the recombination of electron-hole pairs, thus enhanced the photoelectric signals. Sulfur and nitrogen co-doped carbon quantum dots (S,N-CQDs) with up-conversion luminescence properties provided more light energy for the base materials. On the other hand, S,N-CQDs were combined with Ab2 through polydopamine (PDA), as secondary antibody labels, further enhanced the sensitivity of the sensor. Herein, the linear range of the sensor was from 0.001 to 100 ng mL-1 and the detection limit was 1.72 pg mL-1. In addition, the sensor provides a feasible way for the detection of tumor markers due to its excellent selectivity, repeatability and good stability.


Subject(s)
Antigens, Neoplasm/blood , Biosensing Techniques , Keratin-19/blood , Quantum Dots , Carbon , Electrochemical Techniques , Humans , Immunoassay , Limit of Detection , Nitrogen , Sulfur
12.
Molecules ; 26(21)2021 Oct 27.
Article in English | MEDLINE | ID: mdl-34770898

ABSTRACT

Human dipeptidyl-peptidase III (hDPP III) is capable of specifically cleaving dipeptides from the N-terminal of small peptides with biological activity such as angiotensin II (Ang II, DRVYIHPF), and participates in blood pressure regulation, pain modulation, and the development of cancers in human biological activities. In this study, 500 ns molecular dynamics simulations were performed on free-hDPP III (PDB code: 5E33), hDPP III-Ang II (PDB code: 5E2Q), and hDPP III-IVYPW (PDB code: 5E3C) to explore how these two peptides affect the catalytic efficiency of enzymes in terms of the binding mode and the conformational changes. Our results indicate that in the case of the hDPP III-Ang II complex, subsite S1 became small and hydrophobic, which might be propitious for the nucleophile to attack the substrate. The structures of the most stable conformations of the three systems revealed that Arg421-Lys423 could form an α-helix with the presence of Ang II, but only part of the α-helix was produced in hDPP III-IVYPW. As the hinge structure in hDPP III, the conformational changes that took place in the Arg421-Lys423 residue could lead to the changes in the shape and space of the catalytic subsites, which might allow water to function as a nucleophile to attack the substrate. Our results may provide new clues to enable the design of new inhibitors for hDPP III in the future.


Subject(s)
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/chemistry , Molecular Docking Simulation , Molecular Dynamics Simulation , Binding Sites , Catalysis , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Ligands , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Protein Binding , Protein Conformation , Structure-Activity Relationship , Substrate Specificity
13.
Anal Chim Acta ; 1188: 339190, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34794572

ABSTRACT

In this paper, we constructed a sandwich-type photoelectrochemical (PEC) immunosensor for the quantitative detection of procalcitonin (PCT) based on the sensitization of Mn2+ doped CdS (CdS:Mn) nanocomposites to Bi2WO6 and the signal amplification effect of an upconversion material NaYF4:Yb,Tm. Bi2WO6 was synthesized with a three-dimensional flowered structure. CdS:Mn reduced the recombination of photogenerated carriers, and significantly improved photocurrent response. Lanthanide-doped upconversion nanomaterials were used as the label of secondary antibody. NaYF4:Yb,Tm have two functions, not only connected with the secondary antibody, but also can further amplify the photocurrent response. The proposed immunosensor for detecting PCT provided a desired linear range of 0.5 pg mL-1-100 ng mL-1 and a detection limit of 0.13 pg mL-1 under optimal experimental conditions. Besides, the PEC immunosensor demonstrated good reproducibility, specificity and stability. The results of determination of PCT in real human serum samples were satisfactory. Thus, the immunosensor may be applied in the clinical diagnosis of PCT and other biomarkers.


Subject(s)
Biosensing Techniques , Cadmium Compounds , Nanocomposites , Electrochemical Techniques , Humans , Immunoassay , Limit of Detection , Procalcitonin , Reproducibility of Results
14.
Front Psychol ; 12: 758967, 2021.
Article in English | MEDLINE | ID: mdl-34650498

ABSTRACT

Text sentiment classification is a fundamental sub-area in natural language processing. The sentiment classification algorithm is highly domain-dependent. For example, the phrase "traffic jam" expresses negative sentiment in the sentence "I was stuck in a traffic jam on the elevated for 2 h." But in the domain of transportation, the phrase "traffic jam" in the sentence "Bread and water are essential terms in traffic jams" is without any sentiment. The most common method is to use the domain-specific data samples to classify the text in this domain. However, text sentiment analysis based on machine learning relies on sufficient labeled training data. Aiming at the problem of sentiment classification of news text data with insufficient label news data and the domain adaptation of text sentiment classifiers, an intelligent model, i.e., transfer learning discriminative dictionary learning algorithm (TLDDL) is proposed for cross-domain text sentiment classification. Based on the framework of dictionary learning, the samples from the different domains are projected into a subspace, and a domain-invariant dictionary is built to connect two different domains. To improve the discriminative performance of the proposed algorithm, the discrimination information preserved term and principal component analysis (PCA) term are combined into the objective function. The experiments are performed on three public text datasets. The experimental results show that the proposed algorithm improves the sentiment classification performance of texts in the target domain.

15.
Int Immunopharmacol ; 101(Pt B): 108279, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34715574

ABSTRACT

MicroRNA-124-3p (miR-124-3p) and dipeptidyl peptidase-4 (DPP4) are closely related to the development of inflammation. Allergic rhinitis (AR) models in mice and HNEpC cells were established. AR progression was assessed assessing by the frequency of nasal rubbing and sneezing, hematoxylin and eosin (HE), and TUNEL staining. Tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), eotaxin, and MUC5AC were assessed by enzyme-linked immunosorbent assay and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Apoptosis in HNEpC cells was assessed using flow cytometry. DPP4, activated-caspase-3, and pro-caspase-3 protein expression were evaluated by western blotting. In addition, we clarified the influence of miR-124-3p-targeted DPP4 on AR inflammation and cell injury. MiR-124-3p was downregulated in AR nasal mucosa tissue. Upregulation of miR-124-3p reduced the frequency of nasal rubbing and sneezing, pathological changes, eosinophil number, and apoptosis of nasal mucosa, TNF-α and IL-6 protein and mRNA levels in serum and HNEpC cells, and MUC5AC, eotaxin, and GM-CSF levels in HNEpC cells. Downregulation of miR-124-3p has the opposite effect. Therefore, the miR-124-3p /DPP4 axis may be an attractive target for AR therapy.


Subject(s)
Rhinitis, Allergic/pathology , Animals , Chemokine CCL11 , Cytokines/metabolism , Dipeptidyl-Peptidase IV Inhibitors , Down-Regulation , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Inflammation/metabolism , Male , Mice , MicroRNAs/genetics , Mucin 5AC , Nasal Mucosa/pathology , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation
16.
Front Chem ; 9: 711242, 2021.
Article in English | MEDLINE | ID: mdl-34527658

ABSTRACT

There are multiple drugs for the treatment of type 2 diabetes, including traditional sulfonylureas biguanides, glinides, thiazolidinediones, α-glucosidase inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase IV (DPP-4) inhibitors, and sodium-glucose cotransporter 2 (SGLT2) inhibitors. α-Glucosidase inhibitors have been used to control postprandial glucose levels caused by type 2 diabetes since 1990. α-Glucosidases are rather crucial in the human metabolic system and are principally found in families 13 and 31. Maltase-glucoamylase (MGAM) belongs to glycoside hydrolase family 31. The main function of MGAM is to digest terminal starch products left after the enzymatic action of α-amylase; hence, MGAM becomes an efficient drug target for insulin resistance. In order to explore the conformational changes in the active pocket and unbinding pathway for NtMGAM, molecular dynamics (MD) simulations and adaptive steered molecular dynamics (ASMD) simulations were performed for two NtMGAM-inhibitor [de-O-sulfonated kotalanol (DSK) and acarbose] complexes. MD simulations indicated that DSK bound to NtMGAM may influence two domains (inserted loop 1 and inserted loop 2) by interfering with the spiralization of residue 497-499. The flexibility of inserted loop 1 and inserted loop 2 can influence the volume of the active pocket of NtMGAM, which can affect the binding progress for DSK to NtMGAM. ASMD simulations showed that compared to acarbose, DSK escaped from NtMGAM easily with lower energy. Asp542 is an important residue on the bottleneck of the active pocket of NtMGAM and could generate hydrogen bonds with DSK continuously. Our theoretical results may provide some useful clues for designing new α-glucosidase inhibitors to treat type 2 diabetes.

17.
J Cell Mol Med ; 25(16): 7720-7733, 2021 08.
Article in English | MEDLINE | ID: mdl-34173716

ABSTRACT

Glioma is a common malignant tumour of the brain. In this study, we aimed to investigate diagnostic biomarkers and its role in glioma. Weighted gene co-expression network analysis (WGCNA) and Cytoscape software were used to screen the marker genes in glioma. RT-qPCR and Western blotting methods were performed to determine the expression of PAICS, ERCC1 and XPA genes in glioma tissues. Expression level of PAICS in different grades of glioma was examined by immunohistochemistry. CCK8 and Colony formation assays were used to detect cell proliferation. Cell adhesion assay was used to detect adhesion ability. Wound healing and transwell tests were used to detect cell migration ability. Flow cytometry was used to detect cell cycle and apoptosis. According to the predicted co-expression network, we identified the hub gene PAICS. Furthermore, we observed that PAICS expression level was up-regulated in glioma tissues compared with normal tissues, and the expression level was correlated with the grade of glioma. Moreover, we found PAICS can promote glioma cells proliferation and migration in vitro. Flow cytometry results showed that si-PAICS cells were stalled at the G1 phase compared with the si-NC cells and knocking down PAICS expression can increase apoptotic rate. PAICS can regulate the mRNA and protein levels of nucleotide excision repair pathway core genes ERCC1 and XPA. l-aspartic acid can affect the expression of PAICS and then inhibit glioma cell proliferation. Our results indicated that PAICS can promote glioma proliferation and migration. PAICS may act as a potential diagnostic marker and a therapeutic target for glioma.


Subject(s)
Biomarkers, Tumor/genetics , Brain Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Glioma/pathology , Peptide Synthases/genetics , Biomarkers, Tumor/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Cycle , Cell Line, Tumor , Cell Movement , Cell Proliferation , Computational Biology/methods , Databases, Genetic , Glioma/genetics , Glioma/metabolism , Humans , Neoplasm Invasiveness , Peptide Synthases/metabolism , Signal Transduction
18.
Orphanet J Rare Dis ; 16(1): 225, 2021 05 17.
Article in English | MEDLINE | ID: mdl-34001193

ABSTRACT

BACKGROUND: Relapsing polychondritis (RPC) is a rare autoimmune disease and its early diagnosis remains challenging. Defining the clinical patterns and disease course may help early recognition of RPC. RESULTS: Sixty-six males and 60 females were included in this study. The average age at onset were 47.1 ± 13.8 years and the median follow-up period was 18 months. Correlation analysis revealed a strong negative correlation between airway involvement and auricular chondritis (r = - 0.75, P < 0.001). Four distinct clinical patterns were identified: Ear pattern (50.8%), Airway pattern (38.9%), Overlap pattern (4.8%) and Airway-Ear negative pattern (5.6%), and patients with Ear pattern and Airway pattern were further divided into limited and systemic form of RPC (27.8% with limited form of Ear pattern and 24.6% with limited form of Airway pattern initially). During follow-up, a minority of patients with Ear pattern and Airway pattern progressed into Overlap pattern, and some Airway-Ear negative pattern patients progressed into Ear pattern. While a large majority of limited RPC patients remained limited form during follow-up, a minority of limited RPC patients progressed into systemic form. Patients with Ear pattern had the highest survival rate and relatively lower inflammatory status. CONCLUSIONS: RPC patients can be categorized as 4 different clinical patterns and 2 distinct presenting forms (limited and systemic) based on organ involvement. The clinical patterns and presenting forms may evolve during follow-up. Our findings may facilitate early recognition of this rare disease.


Subject(s)
Autoimmune Diseases , Polychondritis, Relapsing , China , Early Diagnosis , Female , Humans , Male , Polychondritis, Relapsing/diagnosis , Retrospective Studies
19.
Plant Divers ; 43(2): 142-151, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33997547

ABSTRACT

Compressed materials of fossil foliage described here as Itea polyneura sp. nov. (Iteaceae) were collected from the Oligocene of Wenshan, Yunnan Province, southwestern China. The identification is based on the following characters: eucamptodromous secondary veins, strict scalariform tertiary veins, irregular tooth with setaceous apex. The leaf morphology of all modern and fossil species was compared with the new species from Wenshan and show that I. polyneura is most similar to the extant East Asian species Itea omeiensis, which inhabits subtropical forests of southern China. This discovery represents the first unambiguous leaf fossil record of Itea in East Asia. Together with other species in the Wenshan flora and evidence from several other flora in southern China, these findings demonstrate that Itea from East Asia arose with the Paleogene modernization.

20.
Oncol Res ; 28(6): 683-684, 2021 Mar 16.
Article in English | MEDLINE | ID: mdl-33731249

ABSTRACT

Glioma is the most common and lethal malignant intracranial tumor. Long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in the tumorigenesis of glioma. However, the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in glioma genesis is still unknown. The purpose of this study was to investigate the underlying function of UCA1 on glioma genesis. The results demonstrated that UCA1 was upregulated in glioma tissue and indicated a poor prognosis. UCA1 knockdown induced by si-UCA1 significantly suppressed the proliferative, migrative, and invasive activities of glioma cell lines (U87 and U251). Bioinformatics analysis and luciferase reporter assay verified the complementary binding within UCA1 and miR-122 at the 3-UTR. Functional experiments revealed that UCA1 acted as an miR-122 sponge to modulate glioma cell proliferation, migration, and invasion via downregulation of miR-122. Overall, the present study demonstrated that lncRNA UCA1 acts as an endogenous sponge of miR-122 to promote glioma cell proliferation, migration, and invasion, which provides a novel insight and therapeutic target in the tumorigenesis of glioma.

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