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This phase I clinical study aimed to assess the safety, tolerability, and population pharmacokinetic-pharmacodynamics (PK-PD) target attainment analysis of etimicin sulfate in healthy participants and provide scientific reference for further development of clinical breakpoints. Twenty-four healthy Chinese subjects were enrolled and received etimicin sulfate infusion in this study. A population PK model was constructed for the estimation of the PK profiles of etimicin sulfate. The area under the concentration-time curve divided by minimum inhibitory concentration (AUC0-24h/MIC) and the peak concentration divided by MIC (Cmax/MIC) were selected as the PK/PD indices. The probability of target attainment (PTA) was calculated for each designed dosing regimen using Monte Carlo Simulations. The minimum MIC value with a PTA ≥ 90% for each regimen was considered as the PK/PD cutoff values. Etimicin sulfate demonstrated safety, tolerability and predictable PK characteristics. No deaths or serious adverse events appeared, and seven treatment emergent adverse events (TEAEs) were reported by five participants. All TEAEs were minor and relieved rapidly. A two-compartment model was developed and validated for describing the PK features of etimicin sulfate among Chinese healthy participants. The diagnostic goodness-of-fit plots and visual predictive check plots showed that this developed model could describe these data well. The PTA results showed that etimicin sulfate provided clinical improvement against strains with MIC of 0.5-1 mg/l and below, and antibacterial effect against strains with MIC of 0.25 mg/l and below. However, etimicin sulfate had limited clinical efficacy for clinical isolates with MIC values > 1 mg/l.
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How to accurately assess logistics industry efficiency to identify production issues and provide support for optimizing logistics efficiency has become a current research challenge. Range adjust measure (RAM) is a method for efficiency assessment in data envelopment analysis. Currently, the RAM model only applies under the variable returns to scale condition and not to other conditions. This paper aims to establish a modified RAM (MRAM) model by revising the ranges for inputs and outputs of the RAM model. Under the constant returns to scale (CRS) condition, we first develop the RAM-CRS model. Then, by introducing radial models to define the lower bounds of inputs and the upper bounds of outputs, the MRAM is proposed. The logistics data from 18 provinces are collected to validate the practicality of the MRAM model. We compare the results of the MRAM with those of the RAM-CRS and conclude that the range bounds under RAM-CRS are too tight, which results in efficiency values at a relatively low level. The MRAM with modified bounds appropriately alleviates this restriction. We also compare the MRAM and the additive model. The results show that the efficiency of the MRAM is more accurate.
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BACKGROUND: ß-catenin, acting as the core effector of canonical Wnt signaling pathway, plays a pivotal role in controlling lineage commitment and the formation of definitive endoderm (DE) during early embryonic development. Despite extensive studies using various animal and cell models, the ß-catenin-centered regulatory mechanisms underlying DE formation remain incompletely understood, partly due to the rapid and complex cell fate transitions during early differentiation. RESULTS: In this study, we generated new CTNNB1-/- human ES cells (hESCs) using CRISPR-based insertional gene disruption approach and systematically rescued the DE defect in these cells by introducing various truncated or mutant forms of ß-catenin. Our analysis showed that a truncated ß-catenin lacking both N- and C-terminal domains (ΔN148C) could robustly rescue the DE formation, whereas hyperactive ß-catenin mutants with S33Y mutation or N-terminal deletion (ΔN90) had limited ability to induce DE lineage. Notably, the ΔN148C mutant exhibited significant nuclear translocation that was positively correlated with successful DE rescue. Transcriptomic analysis further uncovered that two weak ß-catenin mutants lacking the C-terminal transactivation domain (CTD) activated primitive streak (PS) genes, whereas the hyperactive ß-catenin mutants activated mesoderm genes. CONCLUSION: Our study uncovered an unconventional regulatory function of ß-catenin through weak transactivation, indicating that the levels of ß-catenin activity determine the lineage bifurcation from mesendoderm into endoderm and mesoderm.
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Rivaroxaban is a new direct oral anticoagulant, and the same dose is recommended for older and young patients. However, recent real-world studies show that older patients may need dose adjustment to prevent major bleeding. At present, the evidence for dose adjustment in older patients is extremely limited with only a few reports on older atrial fibrillation patients. The aim of this study was to review the morbidity data of adverse events and bleeding events across all indications for older and young patients treated with the same dose of rivaroxaban to provide some support for dosage adjustment in older patients. The PubMed, EMBASE, ClinicalTrials, Cochrane and Web of Science databases were searched for randomized controlled trials (RCTs) published between January 1, 2005, and October 10, 2023. The primary outcomes were the morbidity of bleeding events and efficacy-related adverse events. Summary estimates were calculated using a random effects model. Eighteen RCTs were included in the qualitative analysis. The overall morbidity of primary efficacy endpoints was higher in older patients compared to the young patients (3.37% vs. 2.60%, χ2 = 5.24, p = 0.022). Similarly, a higher morbidity of bleeding was observed in older patients compared to the young patients (4.42% vs. 6.03%, χ2 = 13.22, p < 0.001). Among all indications, deep vein thrombosis, pulmonary embolism and atrial fibrillation were associated with the highest incidence of bleeding in older patients, suggesting that these patients may be most need dose adjustment. Patients older than 75 years may require extra attention to prevent bleeding. The same dose of rivaroxaban resulted in higher bleeding morbidity and morbidity of efficacy-related adverse events in older patients compared to the young patients. An individualized dose adjustment may be preferred for older patients rather than a fixed dose that fits all.
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Colorectal cancer (CRC) is among the most common gastrointestinal malignancies worldwide. eIF3a is highly expressed in a variety of cancer types, yet its role in CRC remains unclear. We introduced ectopic eIF3a expression in CRC cells to investigate its relevance to various malignant behaviors. Further, we silenced eIF3a to explore its effect on tumor growth in a nude mouse tumor xenograft model. Finally, the molecular mechanisms through which eIF3a regulates malignancy in CRC cells were explored through bioinformatics analysis combined with the use of a specific PI3K inhibitor (LY294002). eIF3a was highly expressed in the peripheral blood and cancer tissue of CRC patients. Malignancy and tumor growth were significantly inhibited by silencing eIF3a, while overexpression promoted malignant behaviors, with a positive correlation between PI3K/AKT activation and eIF3a expression. Taken together, eIF3a plays an oncogenic role in CRC by regulating PI3K/AKT signaling and is a potential biomarker for CRC diagnosis and prognostic monitoring.
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Neoplasias Colorretais , Fator de Iniciação 3 em Eucariotos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Humanos , Fator de Iniciação 3 em Eucariotos/metabolismo , Fator de Iniciação 3 em Eucariotos/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Animais , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Nus , Linhagem Celular Tumoral , Proliferação de Células , Ensaios Antitumorais Modelo de Xenoenxerto , Feminino , Masculino , Regulação Neoplásica da Expressão GênicaRESUMO
Each year, the rising demand for palm oil generates large amounts of palm kernel shell waste. Discarded palm kernel shells can produce activated carbon, crushed shells, liquified fumes, and other derivatives; however, their indiscriminate disposal persists, raising issues related to the environment and economy. Therefore, the purpose of this study is to investigate the use of palm kernel shell as a corrosion inhibitor for thermo-mechanically treated steel in a seawater environment using gravimetric and electrochemical techniques, as well as surface tests at varying concentrations. The findings demonstrated that the palm kernel shell inhibited the cathodic and anodic processes by adsorption on the steel surface, which followed the Langmuir adsorption isotherm. The inhibitor exhibited a 98% inhibitory efficiency at 500 ppm concentration. Scanning electron microscopy analysis verified the thin films of the inhibitor on steel surface in seawater solution. Fourier transform infrared spectroscopy results show that the extract's components prevent the steel corrosion through an adsorptive mechanism. According to the inhibitor economic evaluation, employing the palm kernel shell extract is less expensive than utilizing conventional inhibitors.
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BACKGROUND: Network pharmacology is a novel approach that uses bioinformatics to predict multitarget drugs and ingredient-target interactions in various diseases. A thorough search of previously published studies revealed that Hedyotis diffusa Willd (HDW) and Astragalus membranaceus (AM) possess anticancer activity. Colon cancer (CC) is one of the most common malignant tumors of the digestive tract and occurs in the colon. Herein, we explored the effect of two drugs in the treatment of CC. OBJECTIVE: The present study aimed to predict and verify the effect of these two drugs in the treatment of CC. METHODS: To explore the molecular mechanisms of the "HDW-AM" drug in the treatment of CC, we analyzed its principal efficiency in terms of ingredients, target spots, and pathways via network pharmacology, molecular docking, and experimental verification. The ingredients and their gene target sites were searched and screened through the TCMSP platform according to specific filtering conditions. Subsequently, components corresponding to the gene targets were chosen to construct the drug component-target network. The GEO (Gene Expression Omnibus) dataset was used to collect and screen for gene chips under CC and normal conditions, obtain differential genes, and construct a volcano map. The intersection genes between drug and disease targets were screened, the ".tsv" file was downloaded from the STRING platform and imported into Cytoscape 3.8.0 for visualization, a protein-protein interaction (PPI) network was constructed, the core targets were identified, and the common components with core targets were docked through Autodock Tools-1.5.6. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out through the Metascape platform to determine the major pathways. The CCK-8 (Cell Counting Kit-8) assay verified the effect of AKT1 on cell proliferation after treatment with quercetin. RESULTS: After the screening, 3658 DEGs (1841 downregulated and 1817 upregulated) were obtained from the GSE75970 gene chip; 21 active components and 220 targets were identified from the drugs. Subsequently, ten core genes (including AKT1, P53, and CASP3) and six major components were screened. GO functional analysis and KEGG analysis revealed that "HDWAM" regulates cell migration and motility through the combination of a transcription regulator complex, membrane rafts, vesicle lumen, and protein kinases via the MAPK, PI3K-Akt, and IL17 signaling pathways. The molecular docking results suggested that quercetin binds to AKT1, TP53, TNF, and CASP3. HDW-AM may exert a therapeutic effect on CC by modulating AKT1, TP53, TNF, and CASP3 and through signaling pathways. A CCK-8 cytotoxicity assay verified that quercetin affects cell viability through AKT1. CONCLUSIONS: The current study provides a theoretical basis for an in-depth investigation into the molecular mechanism of the "HDW-AM" drug in CC treatment via network pharmacology, molecular docking, and experimental verification.
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OBJECTIVE: The goal of the study is to examine the impact on the malignant biological behaviors of non-small cell lung cancer (NSCLC) of a novel coumarin derivative, ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate (C2F). It also aims to define its underlying mechanism. METHODS: NSCLC cell lines and xenograft nude mice model were conducted to explore the anti-NSCLC effects of C2F in vitro and in vivo. Then, network pharmacology analysis and molecular docking were applied to estimate the possible targets of C2F in NSCLC. Finally, the underlying mechanism of C2F against NSCLC cellular proliferation and tumor development was confirmed using inhibitors or activators of the PI3K/AKT signaling pathway. RESULTS: Our results showed that C2F was able to inhibit proliferation, migration, and invasion of NSCLC cell lines, induce cell cycle arrest and apoptosis in vitro, and prevent tumor growth in vivo. In addition, the estimated glomerular filtration rate and its downstream pathway (PI3K/AKT/mTOR) were found to be critical for the anti-NSCLC activity of C2F. CONCLUSIONS: C2F inhibits malignant biological behaviors of NSCLC by suppressing EGFR/PI3K/AKT/mTOR signaling pathway.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Pulmonares/metabolismo , Camundongos Nus , Simulação de Acoplamento Molecular , Proliferação de Células , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Acetatos/farmacologia , Linhagem Celular TumoralRESUMO
Decorating platinum (Pt) with a single atom offers a promising approach to tailoring their catalytic activity. In this study, for the first time, an innovative assistive active sites (AAS) strategy is proposed to construct high-loading (3.46wt.%) single FeâN4 as AAS, which are further hybridized with small Pt nanoparticles to enhance both oxygen reduction reaction (ORR) and methanol oxidation reaction (MOR) activities. For ORR, the target catalyst (Pt/HFeSA-HCS) exhibits a higher mass activity (MA) of 0.98 A mgPt -1 and specific activity (SA) of 1.39 mA cmPt -2 at 0.90 V versus RHE. As for MOR, Pt/HFeSA-HCS shows exceptional MA (3.21 A mgPt -1) and SA (4.27 mA cmPt -2) at peak values, surpassing commercial Pt/C by 15.3 and 11.5 times, respectively. The underlying mechanism behind this AAS strategy is to find that in MOR, FeâN4 promotes water dissociation, generating more *OH to accelerate the conversion of *CO to CO2. Meanwhile, in ORR, FeâN4 acts as a competitor to adsorb *OH, weakening PtâOH bonding and facilitating desorption of *OH on the Pt surface. Constructing AAS that can enhance dual functionality simultaneously can be seen as a successful "kill two birds with one stone" strategy.
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Bacillus subtilis is an important part of the gut microbiota and a commonly used probiotic. In the present study, to assess the biological characteristics and probiotic properties of B. subtilis derived from mink, we isolated B. subtilis MG-1 isolate from mink fecal samples, characterized its biological characteristics, optimized the hydrolysis of casein by its crude extract, and comprehensively analyzed its potential as a probiotic in combination with whole-genome sequencing. Biological characteristics indicate that, under low-pH conditions (pH 2), B. subtilis MG-1 can still maintain a survival rate of 64.75%; under the conditions of intestinal fluid, gastric acid, and a temperature of 70 °C, the survival rate was increased by 3, 1.15 and 1.17 times compared with the control group, respectively. This shows that it can tolerate severe environments. The results of hydrolyzed casein in vitro showed that the crude bacterial extract of isolate MG-1 exhibited casein hydrolyzing activity (21.56 U/mL); the enzyme activity increased to 32.04 U/mL under optimized reaction conditions. The complete genome sequencing of B. subtilis MG-1 was performed using the PacBio third-generation sequencing platform. Gene annotation analysis results revealed that B. subtilis MG-1 was enriched in several Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways, and most genes were related to Brite hierarchy pathways (1485-35.31%) and metabolism pathways (1395-33.17%). The egg-NOG annotation revealed that most genes were related to energy production and conversion (185-4.10%), amino acid transport and metabolism (288-6.38%), carbohydrate transport and metabolism (269-5.96%), transcription (294-6.52%), and cell wall/membrane/envelope biogenesis (231-5.12%). Gene Ontology (GO) annotation elucidated that most genes were related to biological processes (8230-45.62%), cellular processes (3582-19.86%), and molecular processes (6228-34.52%). Moreover, the genome of B. subtilis MG-1 was predicted to possess 77 transporter-related genes. This study demonstrates that B. subtilis MG-1 has potential for use as a probiotic, and further studies should be performed to develop it as a probiotic additive in animal feed to promote animal health.
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Urinary 1,5-anhydroglucitol (1, 5-AG), 6-α-D-glucopyranosyl-maltotriose (Glc4) and maltotetraose (M4) are important biomarkers for glycogen storage disease (types Ib and â ¡). This study aimed to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to detect these three urinary saccharide metabolites. Urine samples were diluted and then analyzed. Chromatographic separation was performed on an Acquity™ UPLC Amide column (2.1 × 100 mm, 1.7 µm) with gradient elution. The quantitation of analytes was achieved on a 5500 Qtrap mass spectrometer using negative multiple reaction monitoring (MRM) mode. The calibration curves for all analytes were linear over the range of 0.500 to 100 µg/mL with a correlation coefficient, R2 ≥ 0.999. The percent relative standard deviations (RSD%) were ≤12.8%, and the percent relative errors (RE%) were in the range of -11.7%-11.0%. The relative matrix effects of all analytes were between 87.2% and 104% with RSD% < 3.10% across three concentrations. The developed analytical method was simple, accurate, and reliable for rapid and simultaneous analysis of these three urinary saccharide metabolites. It was applied to healthy volunteers and patients. To our knowledge, it was the first validated assay for urinary maltotetraose quantification. This work provides support for exploring the potential of maltotetraose as a biomarker for Pompe disease.
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Doença de Depósito de Glicogênio , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , BiomarcadoresRESUMO
In this work, the one-dimensional (1D) Ni-Co-Se nanowire arrays with rich grain-boundaries were prepared through the solvothermal method and gas-phase selenizaiton. The results showed that the structure and crystallization of the Ni-Co-Se nanowire arrays could be modulated through the optimization of selenizaiton time. The optimal Ni-Co-Se electrode sample displayed an area specific capacitance of 242.6µAh cm-2at 30 mA cm-2with a current retention rate of 68.34%. The assembled Ni-Co-Se/Active carbon (AC) electrode-based asymmetric supercapacitor (ASC) showed the area specific capacitances of 329.2µAh cm-2and 225.8µAh cm-2at 3 mA cm-2and 30 mA cm-2, respectively. A 73.33% retention rate of capacitance was observed after 8000 charge/discharge cycles. Besides, the further fabricated all-solid ASC delivered the power densities of 342.94 W kg-1and 3441.33 W kg-1at the energy densities of 37.62 Wh kg-1and 25.81 Wh kg-1, respectively. Those results suggested the potentials of the obtained Ni-Co-Se nanowire arrays as electrode material for the high-performance pseudocapacitors.
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Glucose tetrasaccharide (Glc4) and maltotetraose (M4) are important biomarkers for Pompe disease and other glycogen storage diseases (GSDs). With the development of new treatments for GSDs, more specific and sensitive bioanalytical methods are needed to determine biomarkers. In recent years, differential mobility spectrometry (DMS) has become an effective analytical technique with high selectivity and specificity. This study aimed to develop an efficient analytical method for the two urinary tetrasaccharide metabolites using DMS and apply it to patients with GSDs (type Ib and II). Urine samples were directly diluted and injected into liquid chromatography-differential mobility spectrometry tandem mass spectrometry (LC-DMS-MS/MS). Chromatographic separation was performed on an Acquity™ UPLC BEH Amide column (2.1 × 50 mm, 1.7 µm) with a short gradient elution of 2.6 min. DMS-MS/MS was used to detect two urinary tetrasaccharide metabolites in a negative multiple reaction monitoring mode with isopropanol as a modifier. A total of 20 urine samples from 6 healthy volunteers and 10 patients with GSDs (type Ib and II) were collected for analysis. The method was linear over a concentration range of 0.5~100.0 µg/mL for each urinary tetrasaccharide (r≥0.99). The intra- and inter-day precision RSD% were less than 14.3%, and the accuracy RE% were in the range of -14.3~13.4%. The relative matrix effect was between 86.6 and 114.3%. No carryover or interference was observed. Patients with GSDs (type Ib and II) had significantly higher median urinary Glc4 (P=0.001) and M4 (P=0.012) excretion than healthy subjects. The developed method was simple, rapid, sensitive, and specific. It was successfully applied to healthy volunteers and patients with GSDs (type Ib and II). DMS technology greatly improved analysis efficiency and provided high sensitivity and specificity.
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BACKGROUND: The prevalence of infections with multidrug-resistant organism (MDRO) pose great challenges for anti-infective therapy. Previous research on MDRO infections after cardiac surgery was limited. Therefore, understanding and mastering the clinical characteristics and risk predictors of MDRO infection after cardiac surgery is of great significance for standardized management of perioperative patients. METHODS: The medical records of adult patients with MDRO infection after cardiac surgery from January 2018 to October 2021 were collected, and patients were divided into MDR infection group (n = 176) and non-MDR infection group (n = 233). Univariate and multivariate regression analysis of variables was performed to determine the risk predictors of MDRO infection. RESULTS: The incidence of MDRO infection was 8.6%. Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common, accounting for 37.3%, 23.5% and 18.0%, respectively. The main infection type were lower respiratory tract infection (LTRI = 29.0%). Univariate analysis showed that underwent coronary artery bypass graft (CABG) (P = 0.001) and secondary operation (P = 0.008), pre-infection exposure to vancomycin (P < 0.001) and linezolid (P = 0.002), combination antibiotics (P < 0.001), four antibiotics in combination (P = 0.005), glucocorticoid use (P = 0.029), preoperative hypoalbuminemia (P = 0.003) were risk factors for post-operative MDRO infection. Multivariate regression analysis showed that underwent CABG (OR = 1.228, 95%CI = 1.056â½1.427, P = 0.008), secondary operation (OR = 1.910, 95%CI = 1.131â½3.425, P = 0.015) and pre-infection exposure to linezolid (OR = 3.704, 95%CI = 1.291â½10.629, P = 0.005) were independent risk predictors for MDRO infection. The risk of MDRO infection increased with the length of stay in the ICU (P < 0.001) and the length of stay before diagnosis of infection (P = 0.003), and the difference was statistically significant. Meanwhile, the length of stay after infection (P = 0.005) and the total length of hospital stay (P < 0.001) were significantly longer in the MDRO infection group, and the all-cause mortality was numerically higher in the MDRO infection group (31.3% versus 23.2%). CONCLUSIONS: The morbidity and mortality of MDRO infection was high in adult cardiac surgery, and many risk factors influence the occurrence of MDRO infection. In the future, clinicians should focus on high-risk patients, strengthen multidisciplinary collaboration on infection prevention and control measures, reduce the morbidity and mortality of MDRO infection, and improve the prognosis of in-hospital patients.
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Infecções Bacterianas , Procedimentos Cirúrgicos Cardíacos , Humanos , Adulto , Farmacorresistência Bacteriana Múltipla , Linezolida , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Pacientes Internados , Fatores de Risco , Antibacterianos/uso terapêuticoRESUMO
According to current research, the primary active ingredients of Radix Astragali (RA), such as saponins, flavonoids, and polysaccharides, play an important role in anti-inflammatory effects. However, the exact molecular mechanism underlying the action was not elucidated to date. Our research attempted to determine the active components in RA and to investigate the interaction between the active components and targets involved in the anti-inflammation activity by network pharmacology and molecular docking. The active components and targets of RA were screened out by TCMSP. Thereafter, through the "anti-inflammation effect" and "inflammation" as the keywords, disease targets were obtained from the GeneCards database. The PPI network was constructed with Cytoscape 3.8.0 software to screen core targets. The GO function and KEGG analysis were enriched and analyzed through the Metascape platform, obtaining the 3-dimensional view of the core targets from the PDB database, and then, performing molecular docking in AutoDock Vina, a heatmap was constructed using the binding free energies in GraphPad Prism 8. The Discovery Studio software was used for docking analysis, and eventually, the docking results were visualized. We also explored the targets and signaling pathways of Astragaloside IV acting on anti-inflammatory effects via constructing compound-disease-target-pathway network. 18 active components and 45 targets of RA were screened out. The main anti-inflammatory active components of RA were quercetin, Astragaloside IV, kaempferol, 7-O-methylisomucronulatol, and formononetin, and the strongly interacting core proteins were TNF, IL6, IL1B, TLR4, CXCL8, CCL2, IL10, VEGFA, and MMP9. The signal pathways mainly involved include Lipid and atherosclerosis, IL-17 signaling pathway, Chagas disease, leishmaniasis, and TNF signaling pathway. Moreover, molecular docking showed that the 2 most active compounds, Astragaloside IV and kaempferol, could efficiently bind with the targets TNF, TLR4, and IL10. Astragaloside IV may play a part in anti-inflammatory effects through pathways such as HIF-1 signaling pathway, Inflammatory bowel disease and Hepatitis B ect. RA exhibits the characteristic of multicomponent and multitarget synergistic effects in exerting anti-inflammatory effects and the effective component of RA is Astragaloside IV, targeting TNF, TLR4, and IL10.
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Quempferóis , Farmacologia em Rede , Humanos , Simulação de Acoplamento Molecular , Quempferóis/farmacologia , Interleucina-10 , Receptor 4 Toll-Like , Anti-Inflamatórios/farmacologiaRESUMO
A simple and sensitive direct immersion thin-film microextraction (DI-TFME) method based on MIL-101(Cr) modified with carbon nanofibers supported in cellulose acetate (CA-MIL-101(Cr)@CNFs) polymeric membrane was developed for the extraction and preconcentration of parabens in environmental water samples. A high-performance liquid chromatography-diode array detector (HPLC-DAD) was used for the determination and quantification of methylparaben (MP) and propylparaben (PP). The factors affecting the DI-TFME performance were investigated using central composite design (CCD). The linearity of the DI-TFME/HPLC-DAD method obtained under optimal conditions was 0.04-0.04-500 µg/L with a correlation coefficient (R2) greater than 0.99, respectively. The limits of detection (LOD) and quantification (LOQ) for methylparaben were 11 ng/L and 37 ng/L; for propylparaben, they were 13 ng/L and 43 ng/L, respectively. The enrichment factors were 93.7 and 123 for methylparaben and propylparaben. The intraday (repeatability) and interday (reproducibility) precisions expressed as relative standard deviations (%RSD) were less than 5%. Furthermore, the DI-TFME/HPLC-DAD method was validated using real water samples spiked with known concentrations of the analytes. The recoveries ranged from 91.5 to 99.8%, and intraday and interday trueness values were less than ±15%. The DI-TFME/HPLC-DAD approach was effectively used for the preconcentration and quantification of parabens in river water and wastewater samples.
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Parabenos , Água , Parabenos/análise , Porosidade , Reprodutibilidade dos Testes , Imersão , Cromatografia Líquida de Alta Pressão/métodos , Limite de DetecçãoRESUMO
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition with an unfavorable prognosis. As the pathogenesis of ARDS remains unclear, we aimed to identify the core genes associated with ARDS and the mechanisms by which competing endogenous RNAs (ceRNAs) regulate the disease's progression. METHODS: Three mRNA microarray datasets (GSE17355, GSE48787, and GSE130936), derived from the Gene Expression Omnibus (GEO) database, were selected. Common differentially expressed genes (DEGs) related to acute lung injury (ALI) were identified and subjected to enrichment analysis. Then, hub genes were figured out through the protein-protein interaction (PPI) network and functional analysis, and targeted miRNAs and lncRNAs were predicted. Finally, the ceRNA networks associated with ALI were constructed and validated experimentally. RESULTS: A total of 155 upregulated and 93 downregulated DEGs were identified in the three datasets. The TNF signaling pathway and IL-17 signaling pathway were the most enriched pathways. Then, eleven DEGs enriched in the IL-17 signaling pathway were selected as the hub genes. Three miRNAs (mmu-mir-155-5p, mmu-mir-21a-5p, and mmu-mir-122-5p), which were located in the lung tissue and predicted to bind the hub genes at the same time, and two lncRNAs (Neat1 and Tug1), which have binding sites for the aforementioned miRNAs, were filtered. With qPCR verification, we identified a ceRNA network composed of NEAT1, miR-21-5p, MMP9, and CXCL5. NEAT1 knockdown promoted the migration and reduced the expression of pro-inflammatory factor and reactive oxygen species (ROS) in lung epithelial cells. We eventually confirmed that NEAT1/miR-21-5p/CXCL5/MMP9 played a pivotal role in regulating the inflammatory response in ALI. CONCLUSION: The IL-17 signaling pathway is of great importance in the pathogenesis of ARDS. NEAT1/miR-21-5p is involved in the inflammation of ALI by regulating CXCL5 and MMP9.
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MicroRNAs , RNA Longo não Codificante , Síndrome do Desconforto Respiratório , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Metaloproteinase 9 da Matriz/genética , Interleucina-17/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Síndrome do Desconforto Respiratório/genética , Redes Reguladoras de GenesRESUMO
The advanced manufacturing industry is located at the top of the manufacturing value chain. Its development is restricted by supply chain collaboration (SCC), the level of which is affected by many factors. Few studies comprehensively summarize what influences SCC and distinguish the impact level of each factor. Practitioners have difficulty isolating the primary factors that affect SCC and managing them effectively. Therefore, based on synergetics and the theory of comparative advantage, this study analyzes what influences SCC in the advanced manufacturing industry and how these influencing factors work, using data from 94 manufacturing enterprises and the Haken model to identify the influencing factors. The results show that China's advanced manufacturing supply chain underwent a phase change and entered a new stage during 2017-2018. In the new stage, the competitive advantages of enterprises are one order parameter (slow variable) and are primary factors affecting SCC. The interest demands of enterprises are a fast variable and are secondary factors affecting SCC. The competitive advantages of enterprises dominate the interests of enterprises in affecting the collaboration level of China's advanced manufacturing supply chain. In addition, in the process of influencing SCC, there is a positive correlation between the competitive advantages of enterprises and the interest demands of enterprises, and the two factors have a positive feedback mechanism. Finally, when the enterprises in the supply chain cooperate based on their differential advantages, the collaboration capability of the supply chain is at the highest level, and the overall operation of the supply chain is orderly. In terms of theoretical contribution, this study is the first to propose a collaborative motivation framework that conforms to the characteristics of sequential parameters, which provides a theoretical reference for subsequent studies on SCC. In addition, the theory of comparative advantage and synergetics are linked for the first time in this study, and both of them are enriched and developed. Equally importantly, this study compares the bidirectional influence between firms' competitive advantages and firms' interest demands and the ability of both to influence SCC, enriching previous validation studies of unidirectional influence. In terms of practical implications, this study guides top managers to focus on the management practice of collaborative innovation in the supply chain and advises purchasing managers and sales managers on selecting supply chain partnerships.
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Comércio , Indústria Manufatureira , Motivação , Registros , ChinaRESUMO
The rational design and controllable synthesis of high-performance energy storage materials are important measures to address the growing demand for energy storage devices. This work involves the growth of a fishnet-like Fe2O3 nanorod@oxygen-rich carbon layer structure directly onto carbon fiber cloth as a binder-free electrode for symmetric capacitors. The growth of Fe2O3 nanorods provided a large specific surface area, and the coating of an oxygen-rich carbon layer protected the Fe2O3 nanorods as an active substance. Furthermore, oxidation treatment created rich electrochemically active sites by loading oxygen-containing functional groups onto the composite surface. As a result, the optimal OC@Fe2O3-ACC sample exhibited a high areal specific capacitance of 1687 mF cm-2 at a current density of 1 mA cm-2. Meanwhile, an excellent capacity retention rate of 58.7% was achieved at 15 mA cm-2. Finally, the long-term cycling stability was verified with an 80% retention rate of the initial capacitance after 12 000 cycles.
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In the process of developing low-cost and high-performance bifunctional electrocatalysts, rational selection of catalytic components and tuning of their electronic structures to achieve synergistic effects is a feasible approach. In this work, CeO2 was composited into Fe/N-doped carbon foam by a molten salt method to improve the electrocatalytic performance of the composite catalyst for the oxygen evolution reaction (OER). The results showed that the excitation of oxygen vacancies in CeO2 accelerated the migration of oxygen species and enhanced the oxygen storage/release capacity of the as-prepared catalyst. Meanwhile, the size effect of CeO2 particles enabled the timely discharge of gas bubbles from the reaction system and thus improved the OER kinetics. In addition, a large number of pyridine-N species were induced by CeO2-doping and sequentially anchored in the carbon matrix. As a result, the Fe2N active state was formed through the strengthened binding of Fe-N elements. Benefiting from the strong electronic interaction between Fe2N and CeO2 components, the optimal CeO2-Fe2N/NFC-2 catalyst sample showed a good OER performance (Ej=10 = 266 mV) and ORR electrocatalytic activity (E1/2 = 0.87 V). The practical feasibility tests indicated that the Zn-air battery assembled by the CeO2-Fe2N/NFC-2 catalyst exhibited a large energy density and an excellent long-term cycling stability.