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1.
Medicine (Baltimore) ; 103(15): e37829, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38608062

RESUMO

In this paper, our objective was to investigate the potential mechanisms of Actinidia chinensis Planch (ACP) for breast cancer treatment with the application of network pharmacology, molecular docking, and molecular dynamics. "Mihoutaogen" was used as a key word to query the Traditional Chinese Medicine Systems Pharmacology database for putative ingredients of ACP and its related targets. DrugBank, GeneCards, Online Mendelian Inheritance in Man, and therapeutic target databases were used to search for genes associated with "breast cancer." Using Cytoscape 3.9.0 we then constructed the protein-protein interaction and drug-ingredient-target-disease networks. An enrichment analysis of Kyoto encyclopedia of genes and genomes pathway and gene ontology were performed to exploration of the signaling pathways associated with ACP for breast cancer treatment. Discovery Studio software was applied to molecular docking. Finally, the ligand-receptor complex was subjected to a 50-ns molecular dynamics simulation using the Desmond_2020.4 tools. Six main active ingredients and 176 targets of ACP and 2243 targets of breast cancer were screened. There were 118 intersections of targets for both active ingredients and diseases. Tumor protein P53 (TP53), AKT serine/threonine kinase 1 (AKT1), estrogen receptor 1 (ESR1), Erb-B2 receptor tyrosine kinase 2 (ERBB2), epidermal growth factor receptor (EGFR), Jun Proto-Oncogene (JUN), and Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) selected as the most important genes were used for verification by molecular docking and molecular dynamics simulation. The primary active compounds of ACP against breast cancer were predicted preliminarily, and its mechanism was studied, thereby providing a theoretical basis for future clinical studies.


Assuntos
Actinidia , Neoplasias da Mama , Humanos , Feminino , Farmacologia em Rede , Neoplasias da Mama/tratamento farmacológico , Simulação de Acoplamento Molecular , Bases de Dados Genéticas
2.
J Med Chem ; 67(5): 4194-4224, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38442261

RESUMO

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function.


Assuntos
Corantes Fluorescentes , Células Th17 , Corantes Fluorescentes/farmacologia , Fatores de Transcrição , Regulação da Expressão Gênica , Polarização de Fluorescência , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo
3.
Nutrients ; 16(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38542820

RESUMO

Brewers' spent grain (BSG) is a fibre and protein-rich by-product of beer-brewing. Fermenting BSG with Rhizopus oligosporus can further increase its content of soluble fibre, protein and certain antioxidants. Since nutrients rich in BSG can improve postprandial glycaemic response, this study assessed the postprandial glucose response (PPGR) and postprandial insulin response (PPIR) controlling effect of consuming 30% wheat flour substituted biscuits with autoclaved BSG (ABSG) or fermented BSG (FBSG) in individuals with metabolic syndrome (MetS). The effect on postprandial lipid panel, breath hydrogen (H2) and methane (CH4) concentration and subjective appetite response was also examined. Fifteen subjects with MetS participated in this crossover randomised controlled trial, and blood was collected at 9 time-points for 4 h after consumption of control biscuits (Control), ABSG and FBSG. A significant interaction effect was observed (Pinteraction = 0.013) for the glucose time-points concentration. At 180 min, the glucose concentration was lowered after the consumption of ABSG (p = 0.010) and FBSG (p = 0.012) compared to the Control. Moreover, the FBSG resulted in a significantly lower glucose incremental area under curve (iAUC) compared to the Control (p = 0.028). Insulin level was also lowered at 180 min after the ABSG (p = 0.010) and FBSG (p = 0.051) consumption compared to the Control. However, no difference was noted for postprandial lipid panel, breath H2 and CH4 concentration and subjective appetite response. In conclusion, the consumption of BSG-incorporated biscuits can attenuate PPGR, and fermented BSG incorporation conferred a further PPGR controlling benefit.


Assuntos
Insulinas , Síndrome Metabólica , Humanos , Farinha , Triticum , Grão Comestível , Glucose , Lipídeos , Estudos Cross-Over
5.
Adv Mater ; 36(18): e2310673, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38284224

RESUMO

The therapy of solid tumors is often hindered by the compact and rigid tumoral extracellular matrix (TECM). Precise reduction of TECM by hyaluronidase (HAase) in combination with nanotechnology is promising for solid tumor therapeutics, yet remains an enormous challenge. Inspired by the treatment of iron poisoning, here a remotely unwrapping strategy is proposed of metal-polyphenol-packaged HAase (named PPFH) by sequentially injecting PPFH and a clinically used iron-chelator deferoxamine (DFO). The in situ dynamic disassembly of PPFH can be triggered by the intravenously injected DFO, resulting in the release, reactivation, and deep penetration of encapsulated HAase inside tumors. Such a cost-effective HAase delivery strategy memorably improves the subsequent photothermal and photodynamic therapy (PTT/PDT)-induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross-talk between tumor and tumor-draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis, and recurrence in multiple mouse cancer models. Overall, this work presents a proof-of-concept of the dynamic disassembly of metal-polyphenol nanoparticles for extracellular drug delivery as well as the modulation of TECM and immunosuppressive tumor microenvironment.


Assuntos
Hialuronoglucosaminidase , Fotoquimioterapia , Polifenóis , Animais , Hialuronoglucosaminidase/metabolismo , Camundongos , Polifenóis/química , Polifenóis/farmacologia , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/patologia , Humanos , Terapia Fototérmica , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Metais/química
6.
J Mater Chem B ; 11(47): 11265-11279, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-37974456

RESUMO

As one of the most common malignancies, oral squamous cell carcinoma (OSCC) with high rates of invasiveness and metastasis threatens people's health worldwide, while traditional therapeutic approaches have not met the requirement of its cure. Phototherapies including photothermal therapy (PTT) and photodynamic therapy (PDT) have shown great potential for OSCC treatment due to their noninvasiveness or minimal invasiveness, high selectivity and little tolerance. However, PTT or PDT alone makes it difficult to eradicate OSCC and prevent its metastasis and recurrence. Here, double-layered membrane vesicles (DMVs) were extracted from attenuated Porphyromonas gingivalis, one of the most common pathogens inside the oral region, and served as an immune adjuvant to develop a biomimetic phototherapeutic nanoagent named PBAE/IR780@DMV for OSCC treatment via combining dual PTT/PDT and robust antitumor immunity. To obtain PBAE/IR780@DMV, poly(ß-amino) ester (PBAE) was used as a carrier material to prepare the nanoparticles for loading IR780, a widely known photosensitizer possessing both PTT and PDT capabilities, followed by surface wrapping with DMVs. Upon 808 nm laser irradiation, PBAE/IR780@DMV exerted strong antitumor effects against OSCC both in vitro and in vivo, via combining PTT/PDT and specific immune responses triggered by tumor-associated antigens and DMVs. Altogether, this study provides a promising biomimetic phototherapeutic nanoagent for comprehensive treatment of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Fotoquimioterapia , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Biomimética , Neoplasias Bucais/tratamento farmacológico
7.
Orthop Surg ; 15(11): 2947-2959, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37752822

RESUMO

OBJECTIVE: Disuse osteoporosis is known to be primarily caused by a lack of exercise. However, the causal relationships between zinc and immunity and disuse osteoporosis remain unknown. This study investigated these relationships and their potential mechanisms. METHODS: This study was an integrative study combining genome-wide association studies and transcriptomics. Two-sample Mendelian randomization analysis (MR) was used to analyze the causal relationships between exposures (zinc, immunity, physical activity) and the outcome (osteoporosis) with the aid of single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Four models, MR-Egger, inverse variance weighted, weighted median and MR-Pleiotrophy RESidual Sum and Outlier (MRPRESSO), were used to calculate odds ratio values. Sensitivity and heterogeneity analyses were also performed using MRPRESSO and MR-Egger methods. The mRNA transcriptomic analysis was subsequently conducted. Zinc metabolism scores were acquired through single-sample Gene Set Enrichment Analysis algorithms. Stromal scores were obtained using the R Package "estimate" algorithms. Important Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathways were also derived through gene set variation analysis. Cytoscape software helped construct the transcription factor (TF)-mRNA-microRNA (miRNA) network. Virtual screening and molecular docking were performed. Polymerase chain reaction validation was also carried out in vivo. RESULTS: Causal relationships were demonstrated between zinc and exercise (95% confidence interval [CI] = 1.30-2.95, p = 0.001), exercise and immunity (95% CI = 0.36-0.80, p = 0.002), exercise and osteoporosis (95% CI = 0.97-0.99, p = 0.0007), and immunity disorder and osteoporosis (95% CI = 1.30-2.03, p = 0.00002). One hundred and seventy-nine mRNAs in important modules were screened. Combining the differential expressional genes (DEGs) and the Boruta selection, six DEGs were screened (AHNAK, CSF2, ADAMTS12, SRA1, RUNX2, and SLC39A14). TF HOXC10 and miRNA hsa-miR-204 were predicted. Then, the TF-mRNA-miRNA network was successfully constructed. RUNX2 and SLC39A14 were identified as hub mRNAs in the TF-mRNA-miRNA network. Eventually, the novel small drug C6O4NH5 was designed according to the pharmacophore structure of SLC39A14. The docking energy for the novel drug was -5.83 kcal/mol. SLC39A14 and RUNX2 were downregulated (of statistical significance p-value < 0.05) in our animal experiment. CONCLUSION: This study revealed that zinc had a protective causal relationship with disuse osteoporosis by promoting exercise and immunity. SLC39A14 and RUNX2 mRNA participated in this zinc-related mechanism.


Assuntos
MicroRNAs , Osteoporose , Animais , Subunidade alfa 1 de Fator de Ligação ao Core , Zinco , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Simulação de Acoplamento Molecular , Transcriptoma , Osteoporose/genética , RNA Mensageiro , Polimorfismo de Nucleotídeo Único
8.
Front Public Health ; 11: 1136494, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483945

RESUMO

Background: Despite the fact that an increasing number of older adults are addicted to smartphones, the existing addiction literature still focuses primarily on adolescents. To address this issue, this study draws from the perspectives of subjective cognitive decline and family relationship conflict to examine older adults' smartphone addiction based on their key characteristics. Methods: This study investigates the effects of subjective cognitive decline and family relationship conflict on older adults' smartphone addiction through a survey of 371 subjects in China. Results: The results show that subjective cognitive decline and family relationship conflict affect older adults' smartphone addiction through a sense of alienation. In addition, older adults' perceived power moderates the relationship between alienation and smartphone addiction. Discussion: This study offers new perspectives on the study of smartphone addiction from the perspective of older adults, and sheds light on how to improve the older adults' quality of life in their later years.


Assuntos
Transtorno de Adição à Internet , Qualidade de Vida , Adolescente , Humanos , Idoso , Emoções , Smartphone , China
9.
Ginekol Pol ; 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37162143

RESUMO

OBJECTIVES: To explore the relationship between the distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy and placenta previa. MATERIAL AND METHODS: A prospective cohort study of women who underwent pregnancy examination in Weifang People's Hospital or Sunshine Union Hospital from January 2020 to June 2021. The distance from the lower edge of the gestational sac to the internal cervical os was measured at 5-6 weeks' gestation. There were 86 women with distance < 2.5 cm, and 105 women with distance ≥ 2.5 cm were randomly selected. There were 92 cases of scarred uterus and 99 cases of non-scarred uterus among the 191 women. They were divided into six groups according to the distance: (1) < 1.0 cm; (2) 1.0 cm to < 1.5 cm; (3) 1.5 cm to < 2.0cm; (4) 2.0 cm to < 2.5 cm; (5) 2.5 cm to < 3.0 cm; (6) ≥ 3.0 cm. All included women were followed-up during pregnancy and pregnancy outcome, and the likelihood ratio of different distances in early pregnancy was calculated and risk stratification was performed, and ROC curve was constructed. RESULTS: There were 15 women in the included studies who were lost to follow-up, 47 had a scarred uterus with placenta previa and 29 had a non-scarred uterus with placenta previa after delivery at 28 weeks or later. The distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy of the scarred uterus < 1.5 cm, and the likelihood ratio was ∞; and the distance ≥ 3.0 cm, the likelihood ratio was 0. The distance from the lower edge of the non-scarred gestational sac to the internal cervical os < 1.0 cm, and the likelihood ratio was ∞; and the distance ≥ 3.0 cm, the likelihood ratio was 0. The ROC curve showed that when the area AUC under the curve was 87%, the optimal diagnostic cut-off value was 2.4 cm. CONCLUSIONS: When the distance from the lower edge of the gestational sac to the internal cervical os was < 1.5 cm and the distance between the non-scarred uterus was < 1.0 cm, it eventually developed into placenta previa; the distance from the lower edge of the gestational sac to the internal cervical os in the first trimester of pregnancy between the scarred uterus and the non-scarred uterus was ≥ 3.0 cm, and it would hardly develop into placenta previa. When the distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy was ≤ 2.4 cm, it could be used as a predictor of placenta previa.

10.
Rev Sci Instrum ; 94(3): 035111, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37012830

RESUMO

Magnetic interferential compensation plays a vital role in geomagnetic vector measurement applications. Traditional compensation accounts for only the permanent interferences, induced field interferences, and eddy-current interferences. However, nonlinear magnetic interferences are found, which also have a great impact on measurement, and it cannot be fully characterized by a linear compensation model. This paper proposes a new compensation method based on a back propagation neural network, which can reduce the influence of the linear model on compensation accuracy due to its good nonlinear mapping capabilities. The high-quality network training requires representative datasets, yet it is a common problem in the engineering field. To provide adequate data, this paper adopts a 3D Helmholtz coil to restore the magnetic signal of a geomagnetic vector measurement system. A 3D Helmholtz coil is more flexible and practical than the geomagnetic vector measurement system itself when generating abundant data under different postures and applications. Simulations and experiments are both conducted to prove the superiority of the proposed method. According to the experiment, the proposed method can reduce the root mean square errors of north, east, and vertical components and the total intensity from 73.25, 68.54, 70.45, and 101.77 nT to 23.35, 23.58, 27.42, and 29.72 nT, respectively, compared with the traditional method.

11.
Chemosphere ; 322: 138209, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36822518

RESUMO

Triazole antifungal pesticides work by inhibiting the activity of lanosterol-14-α-demethylase, a member of cytochrome P450 enzymes (CYPs), but this effect is non-specific. Bile acids (BAs) are important physical surfactants for lipids absorption in intestine, and synthesized by CYPs 7A1/27A1. Thus, we presume that triazole exposure might influence the therapeutic effect or safety of oral medication through disturbing the BAs pool, even though the exposure is under an acceptable daily intake (ADI) dose. Short- and long-term of ADI dose tebuconazole (TEB) exposure animal models were established through various routes, and statins with different hydrophilic and lipophilic properties were gavaged. It exhibited that the activity of CYP7A1/27A1 was indeed inhibited but the expression was up-regulated, the BAs pool was changed either the content and the composition, and the absorption behavior of statins with strong and medium degree of lipid-solubility were significantly changed. A series of experiments performed on models of intestinal mucus, Caco-2 cell monolayer and Caco-2/HT29 co-culture system revealed that the TEB-exposure induced BAs disturbance made impacts on drug absorption in many aspects, including drug solubility and the structure of intestinal barriers. This study suggests us to be more alert about the hazard of pesticides residues for elderly and chronically ill groups.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Praguicidas , Humanos , Animais , Ácidos e Sais Biliares , Células CACO-2 , Nível de Efeito Adverso não Observado
12.
Plant Cell Environ ; 46(3): 918-930, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597190

RESUMO

ß-Glucosidase is validated as an elicitor for early immune responses in plants and it was detected in the salivary glands of Frankliniella occidentalis in previous research. Seven differentially expressed genes encoding ß-glucosidase were obtained by comparing the transcriptomes of F. occidentalis adults grown under two different CO2 concentrations (800 vs. 400 ppm), which might be associated with the differences in the interaction between F. occidentalis adults and its host plant, Phaseolus vulgaris under different CO2 levels. To verify this speculation, changes in defense responses based on the production and elimination of reactive oxygen species (ROS) in P. vulgaris leaves treated with three levels of ß-glucosidase activity under ambient CO2 (aCO2 ) and elevated CO2 (eCO2 ) were measured in this study. According to the results, significantly higher levels of ROS were noticed under eCO2 compared to aCO2 , which was caused by the increased ß-glucosidase activity in thrips due to increased cellulose content in P. vulgaris leaves under eCO2 . Together with the lower activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) in injured leaves under eCO2 , P. vulgaris leaves would be negatively affected on redox-based defense by eCO2 , thus facilitating thrips damage under climate change.


Assuntos
Celulases , Phaseolus , Tisanópteros , Animais , Phaseolus/genética , Dióxido de Carbono , Espécies Reativas de Oxigênio , Flores , Oxirredução
13.
ACS Omega ; 7(48): 43923-43933, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36506201

RESUMO

A broad linear range of ionic flexible sensors (IFSs) with high sensitivity is vital to guarantee accurate pressure acquisition and simplify back-end circuits. However, the issue that sensitivity gradually decreases as the applied pressure increases hinders the linearity over the whole working range and limits its wide-ranging application. Herein, we design a two-scale random microstructure ionic gel film with rich porosity and a rough surface. It increases the buffer space during compression, enabling the stress deformation to be more uniform, which makes sure that the sensitivity maintains steady as the pressure loading. In addition, we develop electrodes with multilayer graphene produced by a roll-to-roll process, utilizing its large interlayer spacing and ion-accessible surface area. It benefits the migration and diffusion of ions inside the electrolyte, which increases the unit area capacitance and sensitivity, respectively. The IFS shows ultra-high linearity and a linear range (correlation coefficient ∼ 0.9931) over 0-1 MPa, an excellent sensitivity (∼12.8 kPa-1), a fast response and relaxation time (∼20 and ∼30 ms, respectively), a low detection limit (∼2.5 Pa), and outstanding mechanical stability. This work offers an available path to achieve wide-range linear response, which has potential applications for attaching to soft robots, followed with sensing slight disturbances induced by ships or submersibles.

14.
Biomaterials ; 289: 121796, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36108581

RESUMO

Generally, autophagy/mitophagy, as a highly conserved lysosomal-based catabolic pathway, compromises the photodynamic therapy (PDT) efficiency by increasing the adaptation of tumor cells toward reactive oxygen species (ROS)-triggered protein damages and mitochondrial destruction. On the other hand, excessively activated autophagy/mitophagy cascades can provoke autophagic cell death and promote the endogenous antigens release of dying cells, thus playing a vital role in initiating the antitumor immune responses. To harness the exquisite immunomodulating effect of pro-death autophagy/mitophagy, we rationally constructed a MnO2 shell-coated multifunctional porphyrinic metal-organic framework (MOF) to load carbonyl cyanide 3-chlorophenylhydrazone (CCCP). The wrapped MnO2 shell could not only prevent premature release of CCCP during blood circulation but also conquer tumor hypoxia by catalyzing the decomposition of intratumoral H2O2. After entering tumor cells, the MnO2 shell could scavenge over-expressed glutathione (GSH), resulting in burst CCCP release and GSH-depletion/O2-generation enhanced PDT. More importantly, the released CCCP acts as a mitochondrial uncoupler can elicit mitochondrial depolarization and mitophagy, which could significantly boost the autophagy/mitophagy levels generated during PDT and consequently convert the pro-survival autophagy/mitophagy to pro-death, leading tumor cells to autophagic and immunogenic cell death. In vivo results reveal that the CCCP synergistic PDT could induce excessive immunostimulatory autophagy/mitophagy associated with T-cell responses and immunological memory, leading to complete ablation of primary tumors and prevention of tumor recurrence and lung metastasis. The effectiveness of this strategy may highlight the pro-death role and immunomodulating effect of autophagy/mitophagy in cancer therapy, providing a novel yet versatile avenue to enhance the efficacy of cancer treatments.


Assuntos
Estruturas Metalorgânicas , Mitofagia , Autofagia , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Glutationa , Peróxido de Hidrogênio/farmacologia , Compostos de Manganês/farmacologia , Estruturas Metalorgânicas/farmacologia , Mitofagia/fisiologia , Óxidos/farmacologia , Espécies Reativas de Oxigênio/metabolismo
15.
Nanoscale ; 14(23): 8463-8473, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35662311

RESUMO

Auxetic materials are highly desirable for advanced applications because of their negative Poisson's ratios, which are rather scarce in two-dimensional materials. Motivated by the elemental mutation method, we predict a new class of monolayer IV-VI semiconductors, namely, δ-IV-VI monolayers (GeS, GeSe, SiS and SiSe). Distinctly different from the previously predicted IV-VI monolayers, the newly predicted δ-MX (X = Ge and Si; M = S and Se) monolayers exhibit a puckered unit cell with a space group of Pca21. Their stabilities were confirmed by first-principles lattice dynamics and molecular dynamics calculations. In particular, all these MX monolayers possess a large bandgap in the range of 2.08-2.65 eV and pronounced anisotropic mechanical properties, which are demonstrated by direction-dependent in-plane Young's moduli and Poisson's ratios. Furthermore, all these 2D MX monolayers possess negative Poisson's ratios (even up to about -0.3 for SiSe). Strong optical absorption is observed in these δ-IV-VI monolayers. These interesting physical properties will stimulate the development of 2D flexible devices based on IV-VI semiconductor monolayers.

16.
Comput Math Methods Med ; 2022: 4914727, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602340

RESUMO

Disused osteoporosis is a kind of osteoporosis, a common age-related disease. Neurological disorders are major risk factors for osteoporosis. Though there are many studies on disuse osteoporosis, the genetic mechanisms for the association between glutathione metabolism and ferroptosis in osteoblasts with disuse osteoporosis are still unclear. The purpose of this study is to explore the key genes and other related mechanism of ferroptosis and glutathione metabolism in osteoblast differentiation and disuse osteoporosis. By weighted gene coexpression network analysis (WGCNA), the process of osteoblast differentiation-related genes was studied in GSE30393. And the related functional pathways were found through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. By combining GSE1367 and GSE100933 together, key genes which were separately bound up with glutathione metabolism and ferroptosis were located. The correlation of these key genes was analyzed by the Pearson correlation coefficient. GSTM1 targeted agonist glutathione (GSH) selected by connectivity map (CMap) analysis was used to interfere with the molding disused osteoporosis process in MC3T3-E1 cells. RT-PCR and intracellular reactive oxygen species (ROS) were performed. Two important pathways, glutathione metabolism and ferroptosis pathways, were found. GSTM1 and TFRC were thought as key genes in disuse osteoporosis osteoblasts with the two mechanisms. The two genes have a strong negative correlation. Our experiment results showed that the expression of TFRC was consistent with the negative correlation with the activation process of GSTM1. The strong relationship between the two genes was proved. Glutathione metabolism and ferroptosis are important in the normal differentiation of osteoblasts and the process of disuse osteoporosis. GSTM1 and TFRC were the key genes. The two genes interact with each other, which can be seen as a bridge between the two pathways. The two genes participate in the process of reducing ROS in disuse osteoporosis osteoblasts.


Assuntos
Ferroptose , Osteoporose , Ferroptose/genética , Glutationa/metabolismo , Humanos , Osteoblastos/metabolismo , Osteoporose/genética , Espécies Reativas de Oxigênio/metabolismo
17.
Nanotechnology ; 33(34)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35561655

RESUMO

Recently, a new two-dimensional allotrope of carbon named biphenylene has been experimentally synthesized. First-principles calculations are preformed to investigate the electronic properties of biphenylene and the doping effect is also considered to tune its electronic, magnetic, and catalytic properties. The metallic nature with an n-type Dirac cone is observed in the biphenylene. The magnetism can be induced by Fe, Cl, Cr, and Mn doping. More importantly, the doping position dependence of hydrogen evolution reaction (HER) performance of biphenylene is addressed, which can be significantly improved by atomic doping. In particular, the barrier for HER of Fe doping case is only -0.03 eV, denoting its great potential in HER catalysis.

18.
Front Psychol ; 13: 770879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295395

RESUMO

While prior literature has widely acknowledged that the entrepreneurial environment significantly fertilizes entrepreneurship, the impact of workplace receives limited attention, and the vital role of organizations in linking social entrepreneurial environment and employee entrepreneurship has been largely ignored. Therefore, this study aims to unfold how multiple entrepreneurial environments (i.e., social, organizational, and interpersonal factors) shape employee entrepreneurship and then further reveal how such relationships vary with employees' risk propensity. Drawn on the theoretical lens of mindsponge process, which offers an explanation of why and how organizations and individuals adopt new values through the cost-benefit analysis, we proposed a research model to explain the influence mechanisms of the social entrepreneurial environment on the cost-benefit analysis of both organizations and individual employees. Specifically, given that organizations deeply embedded in the society need to balance the costs and benefits under the pressure of the social entrepreneurial environment, the social entrepreneurial environment affects the organizational entrepreneurial environment (i.e., organizational hostility toward employee entrepreneurship). Similarly, employees' cost-benefit analysis under the pressure of organizational hostility will influence their entrepreneurial intentions. Through analyzing the data collected from a two-wave survey with 220 employees, we showed that organizational hostility toward employee entrepreneurship plays a mediating role between social entrepreneurial environment and employees' entrepreneurial intentions. In addition, such mediation relationship is moderated by coworkers' unethical behaviors during their entrepreneurship and employees' risk propensity, which are expected to influence organizations' and employees' cost-benefit analysis, respectively.

19.
Front Psychol ; 12: 767876, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803849

RESUMO

Given that "cross-border e-commerce + live streaming" has become an important driver of global trade but limited attention has been paid to this area, this study examines the impacts of live streaming features on the consumers' cross-border purchase intention from the perspectives of consumers' overall perceived value and overall perceived uncertainty based on the SOR theory. In addition, through investigating the moderating effects of saving money, this study reveals the impacts of amazing bargains in live streaming commerce. A total of 272 samples were collected by a questionnaire survey to test the proposed research model. The results show that live streaming features significantly increase consumers' overall perceived value and purchase intention, and significantly reduce consumers' overall perceived uncertainty; in addition, saving money further increases the impact of live streaming features on consumers' overall perceived value. This study provides a theoretical basis and reference for cross-border e-commerce platforms and merchants to effectively leverage live streaming to influence consumers' perception and purchase intention.

20.
Phys Chem Chem Phys ; 23(43): 24915-24921, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34726209

RESUMO

Two-dimensional (2D) materials with a moderate bandgap and high carrier mobility are useful for applications in optoelectronics. In this work, we present a systematic investigation of the mechanical, electronic and optical properties of a B2P6 monolayer using first-principles calculations. Monolayer B2P6 was estimated to be an anisotropic material from direction-dependent in-plane Young's moduli and Poisson's ratios. Also, B2P6 exhibits an ultrahigh electron mobility of ∼5888 cm2 V-1 s-1, showing advantages for application in high-speed optoelectronic devices. More importantly, for the B2P6 monolayer, a desirable transformation from an indirect to direct band gap was observed at a biaxial tensile strain of ∼4%. Increasing the biaxial strain reduces the gap and preserves the suitable band edge positions for photocatalytic water splitting in the observed strain range of 1-8%. The decreased gap also enhances the visible light absorption of the B2P6 monolayer. These findings indicate that the B2P6 monolayer has promising applications in photocatalytic and photovoltaic devices.

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