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1.
PLoS One ; 19(8): e0307026, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39110681

RESUMO

This study examines the role of intellectual property protection (IPP) in enhancing radical technological innovation (RTI) within national research project teams, using an innovation-driven theory and an ability-motivation-opportunity (AMO) perspective. This study utilizes a sample of 336 national research project team members from various Chinese universities, research institutes, and corporations to analyze the theoretical model. Additionally, a two-stage hybrid partial least squares structural equation modeling (PLS-SEM) approach, combined with artificial neural network techniques (ANN), is employed to evaluate the hypotheses. The empirical findings of this study reveal a positive association between the intensity of IPP and RTI within national research project teams. Research and development investment intensity (R&DII) is identified as the primary predictor, while integrated leadership (IL) and group potential (GP) play crucial moderating roles. These groundbreaking findings extend the scope of innovation-driven and AMO theories, providing a proactive model for national research project teams to propose improvements to the IPP system, ultimately enhancing the realization of RTI.


Assuntos
Propriedade Intelectual , Invenções , Redes Neurais de Computação , Humanos , Análise dos Mínimos Quadrados , Pesquisa , Modelos Teóricos , China
2.
Drug Metab Dispos ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39214665

RESUMO

Compound probiotics have been widely used and commonly co-administered with other drugs for treating various chronic illnesses, yet their effects on drug pharmacokinetics remain underexplored. This study elucidated the impact of VSL#3 on the metabolism of probe drugs for cytochrome P450 enzymes (CYP450s), specifically omeprazole, tolbutamide, midazolam, metoprolol, phenacetin and chlorzoxazone. Male Wistar rats were administered with drinking water containing VSL#3 or not for 14 days and then intragastrically administered a CYP450s probe cocktail; This was done to investigate the host CYP450s metabolic phenotype. Stool, liver/jejunum and serum samples were collected for 16S rRNA sequencing, RNA sequencing, and bile acid profiling. The results indicated significant differences in both alpha and beta diversity of intestinal microbial composition between the probiotic and vehicle groups in rats. In the probiotic group, the bioavailability of omeprazole increased by 269.9%, whereas those of tolbutamide and chlorpropamide decreased by 28.1% and 27.4%, respectively. The liver and jejunum exhibited 1,417 and 4,004 differentially expressed genes, respectively, between the two groups. In the probiotic group, most of CYP450s genes were upregulated in the liver but downregulated in the jejunum. The expression of genes encoding metabolic enzymes and drug transporters also changed. The serum conjugated bile acids in the probiotic group were significantly reduced. Shorter duodenal villi and longer ileal villi were found in the probiotic group. In summary, VSL#3 administration altered the gut microbiota, host drug-processing gene expression, and the intestinal structure in rats, which could be reasons for pharmacokinetic changes. Significance Statement This study focused on the effects of the probiotic VSL#3 on the pharmacokinetic profile of CYP450s probe drugs and the expression of host drug metabolism genes. Compared with previous studies, the current study provides a comprehensive explanation for the host drug metabolism profile modified by probiotics, here combined with the bile acid profile and histopathological analysis.

3.
Molecules ; 29(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731462

RESUMO

A novel and efficient method for functionalizing organosulfones has been established, utilizing a visible-light-driven intermolecular radical cascade cyclization of α-allyl-ß-ketosulfones. This process employs fac-Ir(ppy)3 as the photoredox catalyst and α-carbonyl alkyl bromide as the oxidizing agent. Via this approach, the substrates experience intermolecular addition of α-carbonyl alkyl radicals to the alkene bonds, initiating a sequence of C-C bond formations that culminate in the production of organosulfone derivatives. Notably, this technique features gentle reaction conditions and an exceptional compatibility with a wide array of functional groups, making it a versatile and valuable addition to the field of organic synthesis.

4.
Obes Surg ; 34(4): 1185-1195, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38388967

RESUMO

PURPOSE: Obesity is a risk factor for many chronic diseases. This study aimed to investigate the effect of bariatric surgery on the gut microbiota from patients with obesity. MATERIALS AND METHODS: The microbiota composition from stool samples before and after bariatric surgery were identified using bacterial 16S rRNA gene sequencing. Based on the speed of weight loss, patients were classified as the slow-loss group and fast-loss group. The ɑ- and ß-diversity analysis was done to compare the species richness, evenness, and overall structure of the microbiota between different groups. Next, linear discriminant analysis effect size (LEfSe) and receiver operating characteristic (ROC) analysis were implemented to identify high-dimensional biomarkers and significantly different species of microbial taxa between different groups. Finally, the pathway analysis was inferred using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict the functional profiling of microbial communities. RESULTS: ß-diversity analysis suggested that species diversity of preoperative samples of slow-loss group was significantly higher than the fast-loss group. High levels of Oscillospira and Abiotrophia in the preoperative gut microbiota may lead to poor postoperative weight loss. For patients with poor postoperative weight loss due to changes in gut microbiota, the gut microbiota is mainly composed of Lactobacillus. For patients with good postoperative results, the gut microbiota is mainly composed of Escherichia, Robinsonella, and Dialister. In addition, multiple metabolic-related pathways were significantly different between the four groups. CONCLUSION: This comparative study revealed biomarker species based on microfloral composition in patients with obesity before and after bariatric surgery.


Assuntos
Cirurgia Bariátrica , Microbioma Gastrointestinal , Obesidade Mórbida , Humanos , RNA Ribossômico 16S/genética , Genes de RNAr , Filogenia , Obesidade Mórbida/cirurgia , Obesidade/cirurgia , Cirurgia Bariátrica/métodos , Fezes/microbiologia , Redução de Peso/genética
5.
Materials (Basel) ; 16(23)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38068247

RESUMO

With the continuous expansion of the application range of gob-side entry retaining technology, the depth, height, and advancing speed of coal seams also increase, which brings great problems to the stability control of surrounding rock structures of gob-side entry retaining. As one of the main bearing structures of the surrounding rock, the stability of the roadway-side support body is a key factor for the success of gob-side entry retaining. In order to study the deformation characteristics and instability mechanism of roadway-side support body, based on the roadway-side support materials of gob-side entry retaining, the dynamic expansion test of back-filling concrete cracks under uniaxial compression was carried out. The YOLOv5 algorithm was applied to establish the fine identification and quantitative characterization method of macroscopic cracks of the samples, and the dynamic expansion rule of roadway-side support body cracks and its dimensional effect were revealed by combining the fractal theory. The results show that the F1 value and average precision mean of the intelligent dynamic crack identification model reached 75% and 71%, respectively, the GIoU loss value tends to fit around 0.038, and the model reached the overall optimal solution. During the uniaxial compression process, micro cracks on the surface of the back-filling concrete first initiated at the end, and after reaching the yield stress, the macroscopic cracks developed significantly. Moreover, several secondary cracks expanded, pooled, and connected from the middle of the specimen to the two ends, inducing the overall instability of the specimen. The surface crack expansion rate, density, and fractal dimension all show stage change characteristics with the increase in stress, and the main crack expansion rate has obvious precursor characteristics. With the increase in the size, the decrease in crack density after back-filling concrete failures gradually decreases from 93.19% to 4.08%, the surface crack network develops from complex to simple, and the failure mode transits from tensile failure to shear failure. The above research results provide a basic experimental basis for design optimization and instability prediction of a roadway-side support body for engineering-scale applications.

6.
Sci Total Environ ; 880: 163320, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37028655

RESUMO

The Anaerobic-oxic-anoxic (AOA) process is a carbon-saving and high-efficiency way to treat municipal wastewater and gets more attention. Recent reports suggest that in the AOA process, well-performed endogenous denitrification (ED), conducted by glycogen accumulating organisms (GAOs), is crucial to advanced nutrient removal. However, the consensuses about starting up and optimizing AOA, and in-situ enriching GAOs, are still lacking. Hence, this study tried to verify whether AOA could be established in an ongoing anaerobic-oxic (AO) system. For this aim, a lab-scale plug-flow reactor (working volume of 40 L) previously operated under AO mode for 150 days, during that 97.87 % of ammonium was oxidized to nitrate and 44.4 % of orthophosphate was absorbed. Contrary to expectations, under AOA mode, little nitrate reduction (only 6.3 mg/L within 5.33 h) indicated the failure of ED. According to high-throughput sequencing analysis, GAOs (Candidatus_Competibacter and Defluviicoccus) were enriched within the AO period (14.27 % and 3 %) and then still dominated during the AOA period (13.9 % and 10.07 %) but contributed little to ED. Although apparent alternate orthophosphate variations existed in this reactor, no typical phosphorus accumulating organisms were abundant (< 2 %). More than that, within the long-term AOA operation (109 days), the nitrification weakened (merely 40.11 % of ammonium been oxidized) since the dual effects of low dissolved oxygen and long unaerated duration. This work reveals the necessity of developing practical strategies for starting and optimizing AOA, and then three aspects in future studying are pointed out.


Assuntos
Compostos de Amônio , Eliminação de Resíduos Líquidos , Desnitrificação , Nitratos , Anaerobiose , Reatores Biológicos , Fosfatos , Fósforo , Nutrientes , Nitrogênio , Esgotos
7.
Front Endocrinol (Lausanne) ; 14: 1049484, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36998473

RESUMO

Background: Laparoscopic sleeve gastrectomy (LSG) is a sustainable technique that effectively treats morbid obesity. However, the molecular mechanisms underlying the improvement of metabolic health following this process warrants more investigation. This study investigates LSG-related molecules and uses bulk RNA-sequencing high-throughput analysis to unravel their regulatory mechanisms. Methods: Peripheral blood mononuclear cells (PBMC) were collected from ten obese patients with BMI ≥ 32.5 kg/m2 in the Department of General Surgery of Kunming First People's Hospital. After LSG, patients were followed up for one month, and blood samples were retaken. Blood samples from ten patients before and after LSG and bulk RNA-Seq data were analyzed in this study. LSG-associated gene expression was detected by weighted gene coexpression network analysis (WGCNA) and differential analysis. Subsequently, essential signature genes were identified using logistic least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) algorithms. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were utilized to reveal the potential functions of the target genes. Furthermore, the Pearson correlation of signature genes with leptin and lipocalin was also explored. Finally, we constructed a robust endogenous RNA (ceRNA) network based on miRWalk and starBase databases. Results: We identified 18 overlapping genes from 91 hub genes, and 165 differentially expressed mRNAs (DE-mRNA), which were revealed to be significantly associated with immune cells, immune response, inflammatory response, lipid storage, and localization upon functional enrichment analysis. Three signature genes, IRF1, NFKBIA, and YRDC, were identified from the 18 overlapping genes by LASSO and SVM-REF algorithms. The logistic regression model based on the three signature genes highlighted how robustly they discriminated between samples. ssGSEA indicated these genes to be involved in lipid metabolism and degradation pathways. Moreover, leptin levels were significantly reduced in patients undergoing LSG, and NFKBIA significantly negatively correlated with leptin. Finally, we identified how the long non-coding RNA (lncRNA) ATP2B1-AS1 regulated the expression of the signature genes by competitively binding to six microRNAs (miRNAs), which were hsa-miR-6509-5p, hsa-miR-330-5P, hsa-miR-154-5P, hsa-miR-145-5P, hsa-miR4726-5P and hsa-miR-134-5P. Conclusion: This study identified three critical regulatory genes significantly differentiated between patients before and after LSG treatment and highlighted their potentially crucial role after bariatric surgery. This provides novel insights to increase our understanding of the underlying mechanisms of weight loss and associated metabolic improvement after bariatric surgery.


Assuntos
Laparoscopia , MicroRNAs , Obesidade Mórbida , Humanos , Leptina , Leucócitos Mononucleares , Transcriptoma , População do Leste Asiático , Obesidade Mórbida/genética , Obesidade Mórbida/cirurgia , Proteínas de Ligação a RNA , Proteínas de Ligação ao GTP , ATPases Transportadoras de Cálcio da Membrana Plasmática
8.
Chem Asian J ; 17(24): e202200963, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36332196

RESUMO

An efficient and environmentally-friendly method for carbon-centered radical cyclization of olefins via visible light photoredox catalysis to afford pyrrolo[3,2-c]-quinolines, oxindoles and quinoline-2,4-diones is described. This novel reaction successfully activated the α C-H bonds in one-carbon units such as esters, chlorinated hydrocarbons and cyano compounds via HAT (hydrogen atom transfer) process by means of aryldiazonium salts. The transformation features good functional group tolerance, broad substrate scope, high atom economy, no need for transition metal or high temperature.


Assuntos
Carbono , Quinolinas , Ciclização , Carbono/química , Catálise , Radicais Livres/química , Quinolinas/química , Metais
9.
Front Bioeng Biotechnol ; 10: 972933, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051580

RESUMO

The past decade has become an important strategy in precision medicine for the targeted therapy of many diseases, expecially various types of cancer. As a promising targeted element, nucleic acid aptamers are single-stranded functional oligonucleotides which have specific abilities to bind with various target molecules ranging from small molecules to entire organisms. They are often named 'chemical antibody' and have aroused extensive interest in diverse clinical studies on account of their advantages, such as considerable biostability, versatile chemical modification, low immunogenicity and quick tissue penetration. Thus, aptamer-embedded drug delivery systems offer an unprecedented opportunity in bioanalysis and biomedicine. In this short review, we endeavor to discuss the recent advances in aptamer-based targeted drug delivery platforms for cancer therapy. Some perspectives on the advantages, challenges and opportunities are also presented.

10.
Materials (Basel) ; 15(16)2022 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-36013908

RESUMO

The back-filling body in the gob-side entry retaining is subject to continuous disturbance due to repeated mining. In this study, uniaxial and cyclical loading tests of back-filling concrete samples were carried out under laboratory conditions to study damage evolution characteristics with respect to microscopic hydration, deformation properties, and energy evolution. The results showed that, due to the difference in the gradation of coarse and fine aggregates, the cemented structure was relatively loose, and the primary failure modes under cyclical loading were tensile and shearing failure, which significantly decreased its strength. With an increasing number of loadings, a hysteresis loop appeared for the axial strain, and the area showed a pattern of decrease-stabilization-increase. This trend, to a certain extent, reflected the evolution of the cracks in the back-filling concrete samples. The axial, radial, and volumetric plastic strain curves of the back-filling concrete samples showed a "U" shape. The plastic strain changed in three stages, i.e., a rapid decrease, stabilization, and a rapid increase. A damage parameter was defined according to the plastic strain increment to accurately characterize the staged failure of the samples. The plastic strain and energy dissipation of the samples were precursors to sample failure. Prior to the failure of the back-filling samples, the amount and speed of change of both the plastic strain and energy parameters increased significantly. Understanding the characteristics of plastic strain, damage evolution, and energy dissipation rate of the back-filling samples are of great reference value for realizing real-time monitoring of back-filling concrete in the gob-side entry retaining and providing early warning of failure.

11.
J Phys Chem A ; 113(11): 2584-90, 2009 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-19236049

RESUMO

By combining a large pi-conjugated bidentate ligand L: 3,6-dipyrazole-N-ethylcarbazole with HgI(2), an extraordinary supramolecular coordination polymer, [Hg(4)L(2)I(8)](infinity), has been prepared. The crystal structures of the ligand and its coordination polymer were determined by X-ray crystallography, which shows three varied coordination modes especially the rare asymmetric quadruply bridged trinuclear moieties in [Hg(4)L(2)I(8)](infinity). Density functional theory (DFT) calculations (ADF) performed on model dimers show the roles of covalent and noncovalent interactions in establishing the three-dimensional architecture.

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