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1.
J Am Chem Soc ; 146(25): 17220-17229, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38861589

RESUMO

The efficient separation of C2H2 from C2H2/CO2 or C2H2/CO2/CH4 mixtures is crucial for achieving high-purity C2H2 (>99%), essential in producing contemporary commodity chemicals. In this report, we present ZNU-12, a metal-organic framework with space-partitioned pores formed by inorganic fluorinated anions, for highly efficient C2H2/CO2 and C2H2/CO2/CH4 separation. The framework, partitioned by fluorinated SiF62- anions into three distinct cages, enables both a high C2H2 capacity (176.5 cm3/g at 298 K and 1.0 bar) and outstanding C2H2 selectivity over CO2 (13.4) and CH4 (233.5) simultaneously. Notably, we achieve a record-high C2H2 productivity (132.7, 105.9, 98.8, and 80.0 L/kg with 99.5% purity) from C2H2/CO2 (v/v = 50/50) and C2H2/CO2/CH4 (v/v = 1/1/1, 1/1/2, or 1/1/8) mixtures through a cycle of adsorption-desorption breakthrough experiments with high recovery rates. Theoretical calculations suggest the presence of potent "2 + 2" collaborative hydrogen bonds between C2H2 and two hexafluorosilicate (SiF62-) anions in the confined cavities.

2.
Int J Biol Macromol ; 275(Pt 1): 133403, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38917926

RESUMO

Nasopharyngeal carcinoma (NPC), a malignant cancer originating from the epithelial cells of the nasopharynx, presents diagnostic challenges with current methods such as plasma Epstein-Barr virus (EBV) DNA testing showing limited efficacy. This study focused on identifying small extracellular vesicle (sEV) proteins as potential noninvasive biomarkers to enhance NPC diagnostic accuracy. We isolated sEVs from plasma and utilized 4D label-free proteomics to identify differentially expressed proteins (DEPs) among healthy controls (NC = 10), early-stage NPC (E-NPC = 10), and late-stage NPC (L-NPC = 10). Eighteen sEV proteins were identified as potential biomarkers. Subsequently, parallel reaction monitoring (PRM) proteomic analysis preliminarily confirmed sEV carbonic anhydrase 1 (CA1) as a highly promising biomarker for NPC, particularly in early-stage diagnosis (NC = 15; E-NPC = 10; L-NPC = 15). To facilitate this, we developed an automated, high-throughput and highly sensitive CA1 immune-chemiluminescence chip technology characterized by a broad linear detection range and robust controls. Further validation in an independent retrospective cohort (NC = 89; E-NPC = 39; L-NPC = 172) using this technology confirmed sEV CA1 as a reliable diagnostic biomarker for NPC (AUC = 0.9809) and E-NPC (AUC = 0.9893), independent of EBV-DNA testing. Notably, sEV CA1 exhibited superior diagnostic performance compared to EBV-DNA, with a significant incremental net reclassification improvement of 27.61 % for NPC and 72.11 % for E-NPC detection. Thus, this study identifies sEV CA1 as an innovative diagnostic biomarker for NPC and E-NPC independent of EBV-DNA. Additionally, it establishes an immune-chemiluminescence chip technology for the detection of sEV CA1 protein, paving the way for further validation and clinical application.

3.
Nat Microbiol ; 9(5): 1256-1270, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38649412

RESUMO

Epstein-Barr virus (EBV) can infect both B cells and epithelial cells (ECs), causing diseases such as mononucleosis and cancer. It enters ECs via Ephrin receptor A2 (EphA2). The function of interferon-induced transmembrane protein-1 (IFITM1) in EBV infection of ECs remains elusive. Here we report that IFITM1 inhibits EphA2-mediated EBV entry into ECs. RNA-sequencing and clinical sample analysis show reduced IFITM1 in EBV-positive ECs and a negative correlation between IFITM1 level and EBV copy number. IFITM1 depletion increases EBV infection and vice versa. Exogenous soluble IFITM1 effectively prevents EBV infection in vitro and in vivo. Furthermore, three-dimensional structure prediction and site-directed mutagenesis demonstrate that IFITM1 interacts with EphA2 via its two specific residues, competitively blocking EphA2 binding to EBV glycoproteins. Finally, YTHDF3, an m6A reader, suppresses IFITM1 via degradation-related DEAD-box protein 5 (DDX5). Thus, this study underscores IFITM1's crucial role in blocking EphA2-mediated EBV entry into ECs, indicating its potential in preventing EBV infection.


Assuntos
Antígenos de Diferenciação , Efrina-A2 , Células Epiteliais , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Receptor EphA2 , Internalização do Vírus , Humanos , Herpesvirus Humano 4/fisiologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Células Epiteliais/virologia , Células Epiteliais/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/metabolismo , Receptor EphA2/metabolismo , Efrina-A2/metabolismo , Efrina-A2/genética , Antígenos de Diferenciação/metabolismo , Antígenos de Diferenciação/genética , Animais , Células HEK293 , Ligação Proteica , Camundongos , Linhagem Celular
4.
Chem Sci ; 15(15): 5653-5659, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38638230

RESUMO

Since ethylene (C2H4) is important feedstock in the chemical industry, developing economical and energy-efficient adsorption separation techniques based on ethane (C2H6)-selective adsorbents to replace the energy-intensive cryogenic distillation is highly demanded, which however remains a daunting challenge. While previous anionic boron cluster hybrid microporous materials display C2H4-selective features, we herein reported that the incorporation of a neutral para-carborane backbone and aliphatic 1,4-diazabicyclo[2.2.2]octane (DABCO) enables the reversed adsorption of C2H6 over C2H4. The generated carborane-hybrid microporous material ZNU-10 (ZNU = Zhejiang Normal University) is highly stable in humid air and maintains good C2H6/C2H4 separation performance under high humidity. Gas loaded single crystal structure and density-functional theory (DFT) calculations revealed that the weakly polarized carborane and DABCO within ZNU-10 induce more specific C-Hδ+⋯Hδ--B dihydrogen bonds and other van der Waals interactions with C2H6, while the suitable pore space allows the high C2H6 uptake. Approximately 14.5 L kg-1 of polymer grade C2H4 can be produced from simulated C2H6/C2H4 (v/v 10/90) mixtures under ambient conditions in a single step, comparable to those of many popular materials.

5.
Tohoku J Exp Med ; 263(1): 17-25, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38267060

RESUMO

MicroRNAs (miRNAs) are related to the regulation of bone metabolism. Delayed fracture healing (DFH) is a common complication after fracture surgery. The study attempted to examine the role of miR-98-5p and bone morphogenetic protein (BMP)-2 with the onset of DFH. A total of 140 patients with femoral neck fracture were recruited, including 80 cases with normal fracture healing (NFH) and 60 cases with DFH. MC3T3-E1 cells were induced cell differentiation for cell function experiments. Real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to test mRNA levels. Cell proliferation and apoptosis were determined via CCK-8 and flow cytometry assay. Luciferase reporter assay was done to verify the targeted regulatory relationship of miR-98-5p with BMP-2. In comparison with NFH cases, DFH patients owned high levels of serum miR-98-5p and low concentration of BMP-2, and the levels of the two indexes are significantly negatively correlated. Both miR-98-5p and BMP-2 had the ability to predict DFH, while their combined diagnostic value is the highest. BMP-2 was demonstrated to be the target gene of miR-98-5p. Overexpression of BMP-2 reversed the role of miR-98-5p in MC3T3-E1 cell proliferation, apoptosis and differentiation. Increased miR-98-5p and decreased BMP-2 serve as potential biomarkers for the diagnosis of DFH. MiR-98-5p overexpression inhibits osteoblast proliferation and differentiation via targeting BMP-2.


Assuntos
Apoptose , Proteína Morfogenética Óssea 2 , Proliferação de Células , Consolidação da Fratura , MicroRNAs , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Apoptose/genética , Sequência de Bases , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 2/genética , Diferenciação Celular/genética , Linhagem Celular , Fraturas do Colo Femoral/metabolismo , Fraturas do Colo Femoral/genética , Consolidação da Fratura/genética , MicroRNAs/genética , MicroRNAs/metabolismo
6.
Adv Mater ; 36(11): e2311140, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38061391

RESUMO

Separating propyne/propadiene to produce pure propadiene is extremely challenging in industry due to their similar properties. Herein, a novel ZrF6 2- anion pillared cage-like metal-organic framework (termed as CuZrF6 -TPA) for highly efficient propyne/propadiene separation is reported. It exhibits high propyne capacity (177.4/188.6 cm3 /cm3 at 0.5/1.0 bar and 298 K), benchmark separation selectivity (6.0), and remarkable separation potential (5.7 mol L-1 ) simultaneously. Record propadiene productivity (≈4.7 mol L-1 ) is achieved through a single adsorption process in breakthrough experiments with excellent recycle stability even under humid conditions. Based on the structure of propyne-loaded single crystals, two binding sites are identified, including a major propyne trapping site at the windows and a minor binding site located in the large cages. Modelling studies further confirm that the contracted cage windows surrounded with rotating Lewis basic F atoms and aromatic rings are the optimal bonding sites to capture propyne with multiple hydrogen bonding and π···π interactions.

7.
J Ethnopharmacol ; 323: 117675, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38159819

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pill has been utilized to treat cancer for more than three hundred years in China. The molecular mechanisms of Xihuang pill in treating glioblastoma remains unclear. AIM OF THE STUDY: This study aimed to explore the core molecular mechanisms of Xihuang pill in treating glioblastoma by an integrative pharmacology-based investigation. MATERIALS AND METHODS: The main active compounds of Xihuang pill were identified from TCMSP, BATMAN-TCM, TCMID and CNKI. Glioblastoma-related therapeutic targets were retrieved from GeneCards and UniProt. Subsequently, a protein-protein interaction (PPI) network analysis was constructed using STRING. GO and KEGG enrichment were performed to analyze the intersection targets between the active compounds of Xihuang pill and glioblastoma. Based on the above analysis, we built a CTP network. The in vitro and in vivo experiments were further performed to validate the crucial molecular targets of Xihuang pill for the treatment of glioblastoma. RESULTS: A total of sixty active compounds of Xihuang pill and ten potential targets related to glioblastoma were found. Based on topological analysis, fourteen ingredients were selected as the main active compounds, and MY11 might be the most important metabolite in Xihuang pill. PI3K/Akt signaling pathway and receptor tyrosine kinases were considered as crucial targets for Xihuang pill against glioblastoma through KEGG enrichment and CTP analysis. The present experiments indicated that Xihuang pill suppressed the activation of PI3K/Akt/mTOR signaling pathway in glioblastoma cells and mouse xenografts via modulating the expression of PTEN and Rheb proteins, the interaction between TSC2 and Rheb, and the production of PIP3. Meanwhile, after glioblastoma cells treatment with Xihuang pil, the release of IL-1ß, INF-γ was increased and the production of IL-10, TGF-ß1 was decreased in glioblastoma cells after incubated with Xihuang pill. In addition, the activation of the upstream positive modulators of PI3K/Akt/mTOR pathway including PDGF/PDGFR and FGF/FGFR signaling were down-regulated in glioblastoma cells and mouse xenografts after treatment with Xihuang pill. CONCLUSION: Taken together, Xihuang pill inhibiting glioblastoma cell growth might be partly through down-regulating the activation of PDGF/PDGFR or FGF/FGFR-PI3K/Akt/mTOR signaling axis and improving immuno-suppressive micro-environment of glioblastoma.


Assuntos
Medicamentos de Ervas Chinesas , Glioblastoma , Humanos , Animais , Camundongos , Glioblastoma/tratamento farmacológico , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Microambiente Tumoral
8.
Viruses ; 15(9)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37766321

RESUMO

This study aimed to develop a model using Epstein-Barr virus (EBV)-associated hub genes in order to predict the prognosis of nasopharyngeal carcinoma (NPC). Differential expression analysis, univariate regression analysis, and machine learning were performed in three microarray datasets (GSE2371, GSE12452, and GSE102349) collected from the GEO database. Three hundred and sixty-six EBV-DEGs were identified, 25 of which were found to be significantly associated with NPC prognosis. These 25 genes were used to classify NPC into two subtypes, and six genes (C16orf54, CD27, CD53, CRIP1, RARRES3, and TBC1D10C) were found to be hub genes in NPC related to immune infiltration and cell cycle regulation. It was shown that these genes could be used to predict the prognosis of NPC, with functions related to tumor proliferation and immune infiltration, making them potential therapeutic targets. The findings of this study could aid in the development of screening and prognostic methods for NPC based on EBV-related features.

9.
Angew Chem Int Ed Engl ; 62(37): e202309925, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37458603

RESUMO

Separation of acetylene (C2 H2 ) from carbon dioxide (CO2 ) or ethylene (C2 H4 ) is industrially important but still challenging so far. Herein, we developed two novel robust metal organic frameworks AlFSIX-Cu-TPBDA (ZNU-8) with znv topology and SIFSIX-Cu-TPBDA (ZNU-9) with wly topology for efficient capture of C2 H2 from CO2 and C2 H4 . Both ZNU-8 and ZNU-9 feature multiple anion functionalities and hierarchical porosity. Notably, ZNU-9 with more anionic binding sites and three distinct cages displays both an extremely large C2 H2 capacity (7.94 mmol/g) and a high C2 H2 /CO2 (10.3) or C2 H2 /C2 H4 (11.6) selectivity. The calculated capacity of C2 H2 per anion (4.94 mol/mol at 1 bar) is the highest among all the anion pillared metal organic frameworks. Theoretical calculation indicated that the strong cooperative hydrogen bonds exist between acetylene and the pillared SiF6 2- anions in the confined cavity, which is further confirmed by in situ IR spectra. The practical separation performance was explicitly demonstrated by dynamic breakthrough experiments with equimolar C2 H2 /CO2 mixtures and 1/99 C2 H2 /C2 H4 mixtures under various conditions with excellent recyclability and benchmark productivity of pure C2 H2 (5.13 mmol/g) or C2 H4 (48.57 mmol/g).

10.
Heliyon ; 9(7): e18055, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37519692

RESUMO

Background: Traditional Chinese medicine (TCM) has been used to prevent and treat type 2 diabetes (T2DM) for thousands of years. The holistic view of TCM and the "multitarget" characteristics of Chinese medicine have unique advantages in the prevention and treatment of T2DM. TCM syndrome differentiation and treatment are effective for T2DM; however, currently, the therapeutic effect of TCM is generally evaluated by asking for patients' subjective feelings, or by checking the changes in relevant indicators. The main problems are that the patient's descriptions are unclear and subjective, and although the self-reported symptoms may have improved significantly, the relevant indicators are sometimes not obvious, which cannot truly reflect the therapeutic effect of TCM. Therefore, it is urgent to develop a novel, sensitive, and noninvasive method to quantitatively evaluate the therapeutic effect of TCM. Methods: In this study, ultra-weak photon emission (UPE) was measured at four sites of hands of T2DM patients with Qi-Yin deficiency before treatment and after 1 and 2 weeks of treatment with TCM. The UPE intensity and spectral distribution were calculated and analyzed using the results measured at these four sites. Spearman's correlation coefficient was used to quantify the correlation between the UPE parameters and the syndrome scores of TCM. Results: The UPE intensity of T2DM patients with Qi-Yin deficiency decreased gradually with the course of the treatment and was significantly lower than that before the treatment. The ratio of photon counts between the wavelength ranges of 495-550 nm and 550-610 nm after the treatment was higher than that before the treatment and negatively correlated with the corresponding syndrome scores so that the degree of symptoms improvement could be characterized by the ratio (495-550 nm/550-610 nm). Conclusions: The therapeutic effect of TCM in T2DM patients with Qi-Yin deficiency can be shown at the level of UPE. UPE is a potential and noninvasive tool for evaluating the therapeutic effect of TCM in patients with T2DM.

11.
Langmuir ; 39(25): 8638-8645, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37320857

RESUMO

Acetylene (C2H2) is an important and widely used raw material in various industries (such as petrochemical). Generally, a product yield is proportional to the purity of C2H2; however, C2H2 from a typical industrial gas-production process is commonly contaminated by CO2. So far, the achievement of high-purity C2H2 separated from a CO2/C2H2 mixture is still challenging due to their very close molecular dimensions and boiling temperatures. Taking advantage of their quadrupoles with opposite signs, here, we show that the graphene membrane embedded with crown ether nanopores can achieve an unprecedented separation efficiency of CO2/C2H2. Combining the molecular dynamics simulation and the density functional theory (DFT) approaches, we discovered that the electrostatic gas-pore interaction favorably allows the fast transport of CO2 through crown ether nanopores while completely prohibiting C2H2 transport, which yields a remarkable permeation selectivity. In particular, the utilized crown ether pore is capable of allowing the individual transport of CO2 while completely rejecting the passage of C2H2, independent of the applied pressures, fed gases ratios, and exerted temperatures, featuring the superiority and robustness of the crown pore in CO2/C2H2 separation. Further, DFT and PMF calculations demonstrate that the transport of CO2 through the crown pore is energetically more favorable than the transport of C2H2. Our findings reveal the potential application of graphene crown pore for CO2 separation with outstanding performance.

12.
Plants (Basel) ; 12(11)2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37299088

RESUMO

Leaf traits reflect the ecological strategy in heterogeneous contexts and are widely used to explore the adaption of plant species to environmental change. However, the knowledge of short-term effect of canopy management on understorey plant leaf traits is still limited. Here, we studied the short-term effect of crown-thinning on the leaf morphological traits of bamboo (Chimonobambusa opienensis), an important understorey plant and staple food for the giant panda (Ailuropoda melanoleuca) of Niba Mountain. Our treatments were two crown-thinnings (spruce plantation, CS, and deciduous broad-leaved forest, CB) and two controls (broad-leaved forest canopy, FC, and the bamboo grove of clearcutting, BC). The results showed that: the CS enhanced the annual leaf length, width, area, and thickness, CB decreased almost all annual leaf traits, and perennial leaf traits in CS and CB were the opposite. The log-transformed allometric relationships of length vs. width, biomass vs. area were significantly positive while those of specific leaf area vs. thickness were significantly negative, which varied largely in treatments and age. The leaf traits and allometric relationships suggested that the CS created a more suitable habitat for bamboo growth. This study highlighted that the understorey bamboo leaf traits could adapt the improved light environment induced by crown-thinning rapidly.

13.
Cancer Med ; 12(11): 12608-12621, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37097161

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with high incidence in China. The molecular mechanisms of vasculogenic mimicry (VM) and angiogenesis are not fully elucidated in NPC. More specially, it has seldomly been reported that Epstein-Barr virus-encoded miRNA can regulate VM and angiogenesis in NPC. The aim of this study was to investigate the function and molecular mechanism of a targeting exosome system (iRGD-exo-antagomiR) against VM and angiogenesis in NPC, and to provide new approaches for improving the comprehensive treatment of NPC. METHODS: Exosomes were isolated by differential ultracentrifugation. Dynamic light scattering, transmission electron microscopy and western blotting were performed to characterize the exosomes. The 3D-Culture assay, tube formation assay, chicken chorioallantoic membrane assay, Matrigel plug assay, mouse xenograft tumor modeling and immunohistochemical staining were applied to evaluate the anti-VM and anti-angiogenic effects of the targeting exosome system in vitro and in vivo. Western blot was performed to detect the changes of downstream regulated networks following interference and recovery of the target gene. RESULTS: In vitro or in vivo treatment with iRGD-tagged exosome containing antagomiR-BART1-5p specifically suppressed VM and angiogenesis in NPC. EBV-miR-BART1-5p promoted VM and angiogenesis in vitro and in vivo by regulating VEGF, PI3K, Akt, mTOR and HIF1-α in a Spry2-dependent manner. CONCLUSIONS: Our findings demonstrated that targeting exosomes enveloped EBV-miR-BART1-5p-antagomiRs in a Spry2-dependent manner for NPC therapy through both anti-VM and anti-angiogenesis in vitro and in vivo.


Assuntos
Infecções por Vírus Epstein-Barr , Exossomos , MicroRNAs , Neoplasias Nasofaríngeas , Humanos , Animais , Camundongos , Carcinoma Nasofaríngeo/patologia , Herpesvirus Humano 4/genética , Antagomirs , Infecções por Vírus Epstein-Barr/diagnóstico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Exossomos/patologia , MicroRNAs/genética , Linhagem Celular Tumoral
14.
Micromachines (Basel) ; 14(3)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36985032

RESUMO

Due to the strong plasticity of Inconel 718 and the significant size effect of micromachining, a large number of burrs will be produced in traditional processing. The addition of ultrasonic vibration during machining can reduce the burr problem. The mechanism of burr generation in traditional micromilling (TMM) and ultrasonic vibration-assisted micromilling (UVAMM) was analyzed by simulation, and verified by corresponding experiments. It is found that applying high-frequency ultrasonic vibration in the milling feed direction can reduce cutting temperature and cutting force, improve chip breaking ability, and reduce burr formation. When the cutting thickness will reach the minimum cutting thickness hmin, the chip will start to form. When A/ƒz > 1/2, the tracks of the two tool heads start to cut, and the chips are not continuous. Some of the best burr suppression effects were achieved under conditions of low cutting speed (Vc), feed per tooth (ƒz), and large amplitude (A). When A is 6 µm, the size and quantity of burr is the smallest. When ƒz reaches 6 µm, large continuous burrs appear at the top of the groove. The experimental results further confirm the accuracy of the simulation results and provide parameter reference.

15.
Mol Biol Rep ; 50(4): 3469-3478, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36765018

RESUMO

BACKGROUND: Metformin, a first-line oral anti-diabetic drug, has recently been reported to exert protective effect on various cardiovascular diseases. However, the potential role of metformin in ethanol-induced cardiomyocyte injury is still unknown. Therefore, this study was aimed to investigate the effect of metformin on ethanol-induced cardiomyocyte injury and its underlying mechanism. METHODS AND RESULTS: H9c2 cardiomyocytes were exposed to ethanol for 24 h to establish an ethanol-induced cardiomyocyte injury model, and followed by treatment with metformin in the presence or absence of Lapatinib (an ErbB2 inhibition). CCK8 and LDH assays demonstrated that metformin improved cell viability in cardiomyocytes exposed to ethanol. Furthermore, metformin suppressed cardiomyocyte apoptosis and reduced the expressions of apoptosis-related proteins (Bax and C-CAS-3). In addition, our results showed that metformin activated the AKT/Nrf2 pathway, and then promoted Nrf2 nuclear translocation and the transcription of its downstream antioxidant genes (HO-1, CAT and SOD2), thereby inhibiting oxidative stress. Interestingly, we found that ErbB2 protein expression was significantly inhibited in ethanol-treated cardiomyocytes, which was markedly reversed by metformin. In contrast, Lapatinib largely abrogated the activation of AKT/Nrf2 signaling by metformin, accompanied by the increases in oxidative stress and cardiomyocyte apoptosis, indicating that metformin prevented ethanol-induced cardiomyocyte injury in an ErbB2-dependent manner. CONCLUSION: In summary, our study provides the first evidence that metformin protects cardiomyocyte against ethanol-induced oxidative stress and apoptosis by activating ErbB2-mediated AKT/Nrf2 signaling. Thus, metformin may be a potential novel treatment approach for alcoholic cardiomyopathy.


Assuntos
Metformina , Miócitos Cardíacos , Apoptose , Linhagem Celular , Etanol/farmacologia , Lapatinib/farmacologia , Metformina/farmacologia , Metformina/metabolismo , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/metabolismo
16.
Chem Sci ; 14(2): 298-309, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36687342

RESUMO

Propyne/propylene (C3H4/C3H6) separation is an important industrial process yet challenged by the trade-off of selectivity and capacity due to the molecular similarity. Herein, record C3H4/C3H6 separation performance is achieved by fine tuning the pore structure in anion pillared MOFs. SIFSIX-Cu-TPA (ZNU-2-Si) displays a benchmark C3H4 capacity (106/188 cm3 g-1 at 0.01/1 bar and 298 K), excellent C3H4/C3H6 IAST selectivity (14.6-19.3) and kinetic selectivity, and record high C3H4/C3H6 (10/90) separation potential (36.2 mol kg-1). The practical C3H4/C3H6 separation performance is fully demonstrated by breakthroughs under various conditions. 37.8 and 52.9 mol kg-1 of polymer grade C3H6 can be produced from 10/90 and 1/99 C3H4/C3H6 mixtures. 4.7 mol kg-1 of >99% purity C3H4 can be recovered by a stepped desorption process. Based on the in situ single crystal analysis and DFT calculation, an unprecedented entropy-enthalpy balanced adsorption pathway is discovered. MD simulation further confirmed the thermodynamic-kinetic synergistic separation of C3H4/C3H6 in ZNU-2-Si.

17.
Nat Commun ; 14(1): 401, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36697390

RESUMO

Ethylene (C2H4) purification from multi-component mixtures by physical adsorption is a great challenge in the chemical industry. Herein, we report a GeF62- anion embedded MOF (ZNU-6) with customized pore structure and pore chemistry for benchmark one-step C2H4 recovery from C2H2 and CO2. ZNU-6 exhibits significantly high C2H2 (1.53 mmol/g) and CO2 (1.46 mmol/g) capacity at 0.01 bar. Record high C2H4 productivity is achieved from C2H2/CO2/C2H4 mixtures in a single adsorption process under various conditions. The separation performance is retained over multiple cycles and under humid conditions. The potential gas binding sites are investigated by density functional theory (DFT) calculations, which suggest that C2H2 and CO2 are preferably adsorbed in the interlaced narrow channel with high aff0inity. In-situ single crystal structures with the dose of C2H2, CO2 or C2H4 further reveal the realistic host-guest interactions. Notably, rare C2H2 clusters are formed in the narrow channel while two distinct CO2 adsorption locations are observed in the narrow channel and the large cavity with a ratio of 1:2, which accurately account for the distinct adsorption heat curves.

18.
Nat Prod Res ; 37(23): 3971-3976, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36600488

RESUMO

Asini Corii Colla (ACC) and Taurus Corii Colla (TCC) are well-known for their high nutritional value, especially for medicinal purposes. However, the aforementioned are also potential candidates for adulteration because of their low yield and high price. A UPLC-MS/MS approach based on the specific peptide was proposed to detect adulterated gelatin with possible mixed animal species. To explore the antioxidant activity, the peptides were separated to evaluate their effect on ·OH radical and DPPH· scavenging activity, together with PI3K-AKT pathway activation. The results showed that the peptides had excellent DPPH· and ·OH radical scavenging effects, and could alleviate H2O2-induced oxidative stress by promoting the phosphorylation of PI3K and AKT. According to the results of MALDI-TOF/MS, the shared mass-to-charge ratio (m/z) 1466, 1744 and 2382 may serve as a material basis for the antioxidant activity of both ACC and TCC, and contribute to their traditional tonic effects.


Assuntos
Antioxidantes , Espectrometria de Massas em Tandem , Animais , Antioxidantes/farmacologia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Cromatografia Líquida/métodos , Peróxido de Hidrogênio , Peptídeos
19.
Zhonghua Nan Ke Xue ; 29(10): 874-880, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-38639655

RESUMO

OBJECTIVE: To explor the potential mechanisms of ferroptosis involvement in non-obstructive azoospermia based on bioinformatics and machine learning methods. METHODS: To obtain disease-related datasets and ferroptosis-related genes, we utilized the GEO database and FerrDb database, respectively. Using the R software, the disease dataset was subjected to normalization, differential analysis, and GO and KEGG enrichment analysis. The differentially expressed genes from the disease dataset were then intersected with the ferroptosis-related genes to identify common genes. Core genes were selected using three machine learning algorithms, namely LASSO, SVM-RFE, and random forest. Further analysis included exploring immune infiltration correlation, predicting target drugs, and conducting molecular docking simulations. RESULTS: The differential analysis of the GSE45885 dataset yielded 1751 differentially expressed genes, while the GSE145467 dataset yielded 4358 differentially expressed genes. The intersection of these two gene sets resulted in a disease-related gene set consisting of 508 genes. Taking the intersection of the disease-related gene set and the ferroptosis-related gene set, we obtained 17 disease-related ferroptosis genes. After machine learning-based screening, three core genes were identified: GPX4, HSF1, and KLHDC3. CONCLUSION: The mechanism underlying the involvement of ferroptosis in non-obstructive azoospermia may be linked to the downregulation of GPX4, HSF1, and KLHDC3 expression. This finding provides a basis for subsequent in-depth mechanistic and therapeutic studies.


Assuntos
Azoospermia , Ferroptose , Masculino , Humanos , Azoospermia/genética , Ferroptose/genética , Simulação de Acoplamento Molecular , Biologia Computacional , Aprendizado de Máquina
20.
Angew Chem Int Ed Engl ; 61(18): e202200947, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35199908

RESUMO

Propyne/propylene (C3 H4 /C3 H6 ) separation is an important but challenging industrial process to produce polymer-grade C3 H6 and recover high-purity C3 H4 . Herein, we report an ultrastable TiF6 2- anion cross-linked metal-organic framework (ZNU-2) with precisely controlled pore size, shape and functionality for benchmark C3 H4 storage (3.9/7.7 mmol g-1 at 0.01/1.0 bar and 298 K) and record high C3 H4 /C3 H6 (10/90) separation potential (31.0 mol kg-1 ). The remarkable C3 H4 /C3 H6 (1/99, 10/90, 50/50) separation performance was fully demonstrated by simulated and experimental breakthroughs under various conditions with excellent recyclability and high productivity (42 mol kg-1 ) of polymer-grade C3 H6 from a 1/99 C3 H4 /C3 H6 mixture. A modelling study revealed that the symmetrical spatial distribution of six TiF6 2- on the icosahedral cage surface provides two distinct binding sites for C3 H4 adsorption: one serves as a tailored single C3 H4 molecule trap and the other boosts C3 H4 accommodation by cooperative host-guest and guest-guest interactions.

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