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1.
Analyst ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258315

RESUMO

Comparison of the structural features and catalytic performance of bimetallic nanocatalysts will help to develop a unified understanding of structure-reaction relationships. The single-molecule fluorescence technique was utilized to reveal the differences in catalytic kinetics among PtRu bimetallic nanocatalysts and Pt and Ru monometallic nanocatalysts at the single particle level. The results show that bimetallic nanocatalysts have higher apparent rate constants and desorption rate constants relative to monometallic nanocatalysts, which leads to their higher catalytic activity. At the single particle level, bimetallic nanocatalysts have a wider distribution of apparent rate constants, suggesting that bimetallic nanocatalysts have higher activity heterogeneity relative to monometallic nanocatalysts. By investigating the relationship between the reaction rate and the rate of dynamic activity fluctuations, it was found that spontaneous surface restructuring and reaction-induced surface restructuring of nanoparticles occurred. The surface of bimetallic nanoparticles restructured faster, which made the bimetallic nanocatalysts more active. These findings provide new insights into the design of highly active bimetallic nanocatalysts.

2.
Adv Mater ; : e2408485, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39344562

RESUMO

Screening probiotics with specific functions is essential for advancing probiotic research. Current screening methods primarily use animal studies or clinical trials, which are inefficient and costly in terms of time, money, and labor. An intelligent intestine-on-a-chip integrating machine learning (ML) is developed to screen relief-enteritis functional probiotics. A high-throughput microfluidic chip combined with environment control systems provides a standardized and scalable intestinal microenvironment for multiple probiotic cocultures. An unsupervised ML-based score analyzer is constructed to accurately, comprehensively, and efficiently evaluate interactions between 12 Bifidobacterium strains and host cells of the colitis model in the intestine-on-a-chips. The most effective contender, Bifidobacterium longum 3-14, is discovered to relieve intestinal inflammation and enhance epithelial barrier function in vitro and in vivo. A distinct advantage of this strategy is that it can intelligently differentiate small therapeutic variations in probiotic strains and prioritize their efficacies, allowing for economical, efficient, accurate functional probiotics screening.

3.
Aging Cell ; : e14343, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39301860

RESUMO

Aging-related metabolic disorders seriously affect the lifespan of middle-aged and older people, potentially due to disruptions in the adaptive immune and gut microbial profiles. Dietary intervention offers a promising strategy for maintaining metabolic health. This study aimed to investigate the ameliorative effect of 2'-fucosyllactose (2'-FL) on aging-induced metabolic dysfunction and the underlying mechanisms. The results revealed that 2'-FL significantly relieved aging-related metabolic disorders, including weight gain, lipid deposition, dyslipidemia, glucose intolerance, systemic inflammation, and abnormal hepatic metabolism. Flow cytometry analysis revealed a significant reduction in T cytotoxic (Tc), T helper (Th), and regulatory T (Treg) cells and a significant increase in Th17 cells in aged mice, while 2'-FL relieved the aging-induced proportional changes in Th and Th17 subtypes. The aging intestinal microecology was characterized by higher Th17/Treg ratios, impaired gut barrier function, lower gut bacterial diversity, decreased abundance of beneficial genera including Ligilactobacillus, Colidextribacter, Mucispirillum, and Lachnoclostridium, and increased abundance of harmful bacteria including Turicibacter and Desulfovibrio, which was ameliorated by 2'-FL treatment. These findings highlight that 2'-FL is an ideal dietary prebiotic for improving aging-related metabolic disorders by modulating both the adaptive immune system and the gut microbial profile.

4.
Appl Environ Microbiol ; : e0156424, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39297664

RESUMO

Cronobacter sakazakii poses a significant threat, particularly to neonates and infants. Despite its strong pathogenicity, understanding of C. sakazakii biofilms and their role in infections remains limited. This study investigates the roles of HmsP and c-di-GMP in biofilm formation and identifies key genetic and proteomic elements involved. Gene knockout experiments reveal that HmsP and c-di-GMP are linked to biofilm formation in C. sakazakii. Comparative proteomic profiling identifies the lysozyme inhibitor protein LprI, which is downregulated in hmsP knockouts and upregulated in c-di-GMP knockouts, as a potential biofilm formation factor. Further investigation of the lprI knockout strain shows significantly reduced biofilm formation and decreased virulence in a rat infection model. Additionally, LprI is demonstrated to bind extracellular DNA, suggesting a role in anchoring C. sakazakii within the biofilm matrix. These findings enhance our understanding of the molecular mechanisms underlying biofilm formation and virulence in C. sakazakii, offering potential targets for therapeutic intervention and food production settings.IMPORTANCECronobacter sakazakii is a bacterium that poses a severe threat to neonates and infants. This research elucidates the role of the lysozyme inhibitor LprI, modulated by HmsP and c-di-GMP, and uncovers a key factor in biofilm formation and virulence. The findings offer crucial insights into the molecular interactions that enable C. sakazakii to form resilient biofilms and persist in hostile environments, such as those found in food production facilities. These insights not only enhance our understanding of C. sakazakii pathogenesis but also identify potential targets for novel therapeutic interventions to prevent or mitigate infections. This work is particularly relevant to public health and the food industry, where controlling C. sakazakii contamination in powdered infant formula is vital for safeguarding vulnerable populations.

5.
ACS Sens ; 9(9): 4934-4946, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39248698

RESUMO

This study introduces a novel deep learning framework for lung health evaluation using exhaled gas. The framework synergistically integrates pyramid pooling and a dual-encoder network, leveraging SHapley Additive exPlanations (SHAP) derived feature importance to enhance its predictive capability. The framework is specifically designed to effectively distinguish between smokers, individuals with chronic obstructive pulmonary disease (COPD), and control subjects. The pyramid pooling structure aggregates multilevel global information by pooling features at four scales. SHAP assesses feature importance from the eight sensors. Two encoder architectures handle different feature sets based on their importance, optimizing performance. Besides, the model's robustness is enhanced using the sliding window technique and white noise augmentation on the original data. In 5-fold cross-validation, the model achieved an average accuracy of 96.40%, surpassing that of a single encoder pyramid pooling model by 10.77%. Further optimization of filters in the transformer convolutional layer and pooling size in the pyramid module increased the accuracy to 98.46%. This study offers an efficient tool for identifying the effects of smoking and COPD, as well as a novel approach to utilizing deep learning technology to address complex biomedical issues.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Aprendizado Profundo , Fumar , Pulmão , Testes Respiratórios/métodos , Masculino , Olfato
6.
Int J Stroke ; : 17474930241289992, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324561

RESUMO

BACKGROUND: Routine head computed tomography (CT) is performed 24 hours post-acute stroke thrombolysis and thrombectomy, even in patients with stable or improving clinical deficits. Predicting CT results that impact management could help prioritize patients at risk and potentially reduce unnecessary imaging. METHODS: In this IRB-approved retrospective study, data from 1461 consecutive acute ischemic stroke patients at our Comprehensive Stroke Center (n=8943, 2012-2022) who received intravenous thrombolysis or endovascular therapy, exhibited stable or improving 24-hour exams, and underwent 24-hour follow-up head CT per standard acute stroke care guidelines. CT reports 24 hours post-stroke were reviewed for edema, mass effect, herniation, and hemorrhage. The primary outcome was any clinically relevant 24-hour CT finding that led to changes in antithrombotic treatment or blood pressure goals, extended ICU stays or hospitalizations, neurosurgical interventions, or administration of mannitol or hypertonic saline. Multivariable logistic regression identified independent predictors of clinically meaningful CT abnormalities. A 24-hour CT Score was developed and cross-validated. RESULTS: The mean age was 70 years, with 47% women. The median NIH Stroke Scale (NIHSS) score at admission was 12 (IQR 6-18). Stroke-related abnormalities on 24-hour CT were present in 325 patients (22.2%), with 183 (12.5%) showing clinically relevant findings. Age, admission NIHSS, and blood glucose levels were independent predictors of clinically relevant 24-hour CT findings. The final model C statistic was 0.72 (95% CI, 0.68-0.76) in the derivation cohort and 0.72 (95% CI, 0.67-0.75) in bootstrapping validation. The 24-hour CT score was developed using these predictors: NIHSS score 5-15 (+3); NIHSS score ≥16 (+5); age <75 years (+1); admission glucose ≥140mg/dL (+1). The prevalence of clinically relevant CT findings was 4.3% in the low-risk group (24-hour CT score ≤4), 11.3% in the medium-risk group (score 5), and 21.4% in the high-risk group (score ≥6). The 24-hour CT score demonstrated good calibration. CONCLUSION: In patients undergoing thrombolysis or thrombectomy who undergo routine 24-hour head CT despite remaining clinically stable or improving, only 1 in 8 prove to have 24-hour head CT findings that impact management. The 24-hour CT score provides risk stratification that may improve resource utilization.

7.
Materials (Basel) ; 17(16)2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39203107

RESUMO

Cathodic plasma electrolytic treatment (CPET) is an emerging surface modification and coating preparation technology. By utilizing plasma discharge induced through electrolysis and the cooling impact of electrolyte, metal cleaning, saturation, and coating preparation are efficiently achieved. In this review, the principle, application, and development of the CPET process are briefly summarized based on the past literature. Detailed insights are provided into the influence of electrolyte parameters (pH, metal salt concentration, and temperature), electrical parameters (voltage, duty cycle, and frequency), and process parameters (electrode area ratio, material, roughness, and deposition time) on plasma discharge and coating formation for metal coatings. The interaction mechanism between plasma and material surfaces is also investigated. Recommendations and future research avenues are suggested to propel CPET and its practical implementations. This review is expected to provide assistance and inspiration for researchers engaged in CPET.

8.
Nat Commun ; 15(1): 7329, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187549

RESUMO

Manipulation of confined water dynamics by voltage keeps great importance for diverse applications. However, limitations on the membrane functions, voltage-control range, and unclear dynamics need to be addressed. Herein, we report an anomalous electrically controlled gating phenomenon on cation-intercalated multi-layer Ti3C2 membranes and reveal the confined water dynamics. The water permeation rate was improved rapidly following the application and rise of voltage and finally reached a maximum rate at 0.9 V. The permeation rate starts to decrease from 0.9 V. Below 0.9 V, the electric field affects the charge and polarity of water molecules and then leads to ordered and denser rearrangement in the two-dimensional (2D) channel to accelerate the permeation rate. Above 0.9 V, with the assistance of metal cations, the surge in current induced aggregation of water molecules into clusters, thereby limiting the water mobility. Based on these findings, a high-performance humidity sensor was developed by simultaneously optimizing the response and recovery speeds through electric manipulation. This work provides flexible strategies in intelligent membrane design and nanofluidic sensing.

9.
J Agric Food Chem ; 72(33): 18697-18707, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39165163

RESUMO

Cronobacter sakazakii is a notorious foodborne opportunistic pathogen, particularly affecting vulnerable populations such as premature infants, and poses significant public health challenges. This study aimed to elucidate the role of the envZ/ompR genes in environmental tolerance, pathogenicity, and protein regulation of C. sakazakii. An envZ/ompR knockout mutant was constructed and assessed for its impact on bacterial growth, virulence, environmental tolerance, and protein regulation. Results demonstrate that deletion of envZ/ompR genes leads to reduced growth rate and attenuated virulence in animal models. Additionally, the knockout strain exhibited compromised environmental tolerance, particularly in desiccation and oxidative stress conditions, along with impaired adhesion and invasion abilities in epithelial cells. Proteomic analysis revealed significant alterations in protein expression and phosphorylation patterns, highlighting potential compensatory mechanisms triggered by gene deletion. Furthermore, investigation into protein deamidation and glucose metabolism uncovered a link between envZ/ompR deletion and energy metabolism dysregulation. Interestingly, the downregulation of MalK and GrxC proteins was identified as contributing factors to altered desiccation tolerance and disrupted redox homeostasis, respectively, providing mechanistic insights into the phenotypic changes observed. Overall, this study enhances understanding of the multifaceted roles of envZ/ompR in C. sakazakii physiology and pathogenesis, shedding light on potential targets for therapeutic intervention and food safety strategies.


Assuntos
Proteínas de Bactérias , Cronobacter sakazakii , Regulação Bacteriana da Expressão Gênica , Cronobacter sakazakii/genética , Cronobacter sakazakii/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Virulência , Humanos , Animais , Infecções por Enterobacteriaceae/microbiologia , Camundongos , Estresse Oxidativo
10.
CNS Neurosci Ther ; 30(8): e70004, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39169599

RESUMO

BACKGROUND AND OBJECTIVE: Metformin pretreatment might have neuroprotective effects. We aimed to determine the therapeutic effects of the antidiabetic medication metformin on ischemic stroke severity and discharge outcomes. METHODS: We analyzed data on 1303 ischemic stroke patients who were on antidiabetic medications from the Massachusetts General Hospital (MGH) Advanced Comprehensive Stroke Center dataset (n = 8943, 2012-2022). We applied propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses to investigate the effect of current usage of metformin (versus alternate antidiabetic treatment) on acute stroke clinical severity and discharge outcomes. RESULTS: Of the 1303 patients who were on antidiabetic medications at the time of stroke admission, 730 (56%) were taking metformin. Metformin users were younger and more frequently had hypertension, whereas less frequently had prior CAD, AFib, and chronic kidney disease. The clinical features and laboratory values of the two groups were evenly distributed after PSM. Metformin-treated patients had statistically significant lower stroke severity on admission [National Institutes of Health Stroke Scale (NIHSS) (median, interquartile range) 3.0 (1.0-8.0) vs. 4.0 (2.0-11.3), p = 0.011], better functional independence at discharge (modified Rankin scale score 0-2, 36.3% vs. 25.4%, p < 0.001) and less in-hospital mortality (4.5% vs. 11.3%, p = 0.018). IPTW analysis results were consistent with PSM results. CONCLUSIONS: Among diabetic patients with acute ischemic stroke, metformin appears to confer neuroprotection. Our results extend previous findings to the general stroke population. Stroke patients with diabetes mellitus who were treated with metformin prior to stroke, even when combined with additional antidiabetic medications, experienced less severe strokes upon admission and had better functional outcomes during hospitalization.


Assuntos
Hipoglicemiantes , Metformina , Pontuação de Propensão , Índice de Gravidade de Doença , Humanos , Metformina/uso terapêutico , Masculino , Feminino , Idoso , Hipoglicemiantes/uso terapêutico , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , AVC Isquêmico/tratamento farmacológico , Resultado do Tratamento , Acidente Vascular Cerebral/tratamento farmacológico , Estudos Retrospectivos
11.
Opt Lett ; 49(16): 4759-4762, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146154

RESUMO

Multi-dimensional orbital angular momentum (OAM) mode multiplexing provides a promising route for enlarging communication capacity and establishing comprehensive networks. While multi-dimensional multiplexing has gained advancements, the cross-connection of these multiplexed channels, especially involving modes and polarizations, remains challenging due to the needs for multi-mode interconversion and on-demand polarization control. Herein, we propose an OAM mode-polarization cross-transformation solution via cascaded partitioned phase modulation, which enables the divergently separated OAM modes to be independently phase-imposed within distinct spatial regions, leading to the synergistic conversion operation of mode and polarization channels. In demonstrations, we implemented the cross-connection of three OAM modes and two polarization multiplexed channels, achieving the mode purity that exceeds 0.951 and polarization contrast up to 0.947. The measured mode insertion losses and polarization conversion losses are below 3.42 and 3.54 dB, respectively. Consequently, 1.2 Tbit/s quadrature phase shift keying signals were successfully exchanged, yielding the bit-error-rates close to 10-6. Incorporating with increased partitioned phase treatments, this approach shows promise in accommodating massive mode-polarization multiplexed channels, which hold the potential to augment networking capability of large-scale OAM mode multiplexing communication networks.

12.
Nutrients ; 16(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38999886

RESUMO

Alcoholic liver damage is caused by long-term or heavy drinking, and it may further progress into alcoholic liver diseases (ALD). Probiotic supplements have been suggested for the prevention or improvement of liver damage. This study was designed to consider the ameliorative effects of Lactobacillus rhamnosus NKU FL1-8 isolated from infant feces against alcoholic liver damage. The mice were gavaged with a 50% ethanol solution and treated with 109 CFU of L. rhamnosus NKU FL1-8 suspension. The factors for liver function, oxidative stress, inflammation, gut microbiota composition, and intestinal barrier integrity were measured. The results showed that L. rhamnosus NKU FL1-8 could decrease the levels of aspartate aminotransferase (AST) to 61% and alanine aminotransferase (ALT) to 50% compared with ethanol given by gavage. It could inhibit the expression level of malondialdehyde (MDA), increase superoxide dismutase (SOD), glutathione (GSH) to relieve oxidative stress, and down-regulate the cytokines to decrease hepatic inflammation. After treatment, the level of triglycerides was reduced, and the expression levels of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and the peroxisome proliferators-activated receptor-α (PPAR-α) pathway were up-regulated. Additionally, the 16S rRNA sequencing analysis showed that L. rhamnosus NKU FL1-8 increased the relative abundance of Lactobacillus, Ruminococcaceae, etc. At the same time, L. rhamnosus NKU FL1-8 could significantly reduce lipopolysaccharides (LPS) and enhance intestinal tight junction proteins. These results demonstrated that L. rhamnosus NKU FL1-8 could reduce the level of oxidative stress, fat accumulation, and liver inflammation caused by alcohol in the host. The underlying mechanism could be that L. rhamnosus NKU FL1-8 inhibits LPS by regulating the gut microbiota and repairing the intestinal barrier. Thereby, these findings support L. rhamnosus NKU FL1-8 as a potential functional food for the relief of ALD.


Assuntos
Fezes , Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Hepatopatias Alcoólicas , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Probióticos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Fezes/microbiologia , Estresse Oxidativo/efeitos dos fármacos , Hepatopatias Alcoólicas/prevenção & controle , Probióticos/farmacologia , Camundongos , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Masculino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lactente , Etanol , Modelos Animais de Doenças
13.
Front Nutr ; 11: 1421848, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962449

RESUMO

Introduction: Dietary advanced lipoxidation end products (ALEs), which are abundant in heat-processed foods, could induce lipid metabolism disorders. However, limited studies have examined the relationship between maternal ALEs diet and offspring health. Methods: To investigate the transgenerational effects of ALEs, a cross-generation mouse model was developed. The C57BL/6J mice were fed with dietary ALEs during preconception, pregnancy and lactation. Then, the changes of glycolipid metabolism and gut microbiota of the offspring mice were analyzed. Results: Maternal ALEs diet not only affected the metabolic homeostasis of dams, but also induced hepatic glycolipid accumulation, abnormal liver function, and disturbance of metabolism parameters in offspring. Furthermore, maternal ALEs diet significantly upregulated the expression of TLR4, TRIF and TNF-α proteins through the AMPK/mTOR/PPARα signaling pathway, leading to dysfunctional glycolipid metabolism in offspring. In addition, 16S rRNA analysis showed that maternal ALEs diet was capable of altered microbiota composition of offspring, and increased the Firmicutes/Bacteroidetes ratio. Discussion: This study has for the first time demonstrated the transgenerational effects of maternal ALEs diet on the glycolipid metabolism and gut microbiota in offspring mice, and may help to better understand the adverse effects of dietary ALEs.

14.
Toxics ; 12(7)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39058168

RESUMO

Hexafluoropropylene Oxide Dimer Acid (HFPO-DA or GenX) is a pervasive perfluorinated compound with scant understood toxic effects. Toxicological studies on GenX have been conducted using animal models. To research deeper into the potential toxicity of GenX in humans and animals, we undertook a comprehensive analysis of transcriptome datasets across different species. A rank-in approach was utilized to merge different transcriptome datasets, and machine learning algorithms were employed to identify key genetic mechanisms common among various species and humans. We identified seven genes-TTR, ATP6V1B1, EPHX1, ITIH3, ATXN10, UBXN1, and HPX-as potential variables for classification of GenX-exposed samples, and the seven genes were verified in separate datasets of human, mouse, and rat samples. Bioinformatic analysis of the gene dataset further revealed that mitochondrial function and metabolic processes may be modulated by GenX through these key genes. Our findings provide insights into the underlying genetic mechanisms and toxicological impacts of GenX exposure across different species and offer valuable references for future studies using animal models to examine human exposure to GenX.

15.
Nano Lett ; 24(31): 9666-9674, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39072504

RESUMO

Herein, we report a high-density dual-structure single-atom catalyst (SAC) by creating a large number of vacancies of O and Ti in two-dimensional (2D) Ti3C2 to immobilize Pt atoms (SA Pt-Ti3C2). The SA Pt-Ti3C2 showed excellent performance toward the pH-universal electrochemical hydrogen evolution reaction (HER) and multimodal sensing. For HER catalysis, compared to the commercial 20 wt % Pt/C, the Pt mass activities of SA Pt-Ti3C2 at the overpotentials of ∼30 and 110 mV in acid and alkaline media are 45 and 34 times higher, respectively. More importantly, during the alkaline HER process, an interesting synergetic effect between Pt-C and Pt-Ti sites that dominated the Volmer and Heyrovsky steps, respectively, was revealed. Moreover, the SA Pt-Ti3C2 catalyst exhibited high sensitivity (0.62-2.65 µA µM-1) and fast response properties for the multimodal identifications of ascorbic acid, dopamine, uric acid, and nitric oxide under the assistance of machine learning.

16.
Adv Mater ; 36(32): e2304867, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38837502

RESUMO

A disordered crystal structure is an asymmetrical atomic lattice resulting from the missing atoms (vacancies) or the lattice misarrangement in a solid-state material. It has been widely proven to improve the electrocatalytic hydrogen evolution reaction (HER) process. In the present work, due to the special physical properties (the low evaporation temperature of below 900 °C), Zn is utilized as a sacrificial component to create senary PtIrNiCoFeZn high-entropy alloy (HEA) with highly disordered lattices. The structure of the lattice-disordered PtIrNiCoFeZn HEA is characterized by the thermal diffusion scattering (TDS) in transmission electron microscope. Density functional theory calculations reveal that lattice disorder not only accelerates both the Volmer step and Tafel step during the HER process but also optimizes the intensity and distribution of projected density of states near the Fermi energy after the H2O and H adsorption. Anomalously high alkaline HER activity and stability are proven by experimental measurements. This work introduces a novel approach to preparing irregular lattices offering highly efficient HEA and a TDS characterization method to reveal the disordered lattice in materials. It provides a new route toward exploring and developing the catalytic activities of materials with asymmetrically disordered lattices.

17.
Adv Sci (Weinh) ; 11(28): e2309084, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38704694

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a prevalent gastrointestinal cancer characterized by high mortality and an unfavorable prognosis. While combination therapies involving surgery, chemotherapy, and radiation therapy are advancing, targeted therapy for ESCC remains underdeveloped. As a result, the overall five-year survival rate for ESCC is still below 20%. Herein, ESCC-specific DNA aptamers and an innovative aptamer-modified nano-system is introduced for targeted drug and gene delivery to effectively inhibit ESCC. The EA1 ssDNA aptamer, which binds robustly to ESCC cells with high specificity and affinity, is identified using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). An EA1-modified nano-system is developed using a natural egg yolk lipid nanovector (EA1-EYLNs-PTX/siEFNA1) that concurrently loads paclitaxel (PTX) and a small interfering RNA of Ephrin A1 (EFNA1). This combination counters ESCC's proliferation, migration, invasion, and lung metastasis. Notably, EFNA1 is overexpressed in ESCC tumors with lung metastasis and has an inverse correlation with ESCC patient prognosis. The EA1-EYLNs-PTX/siEFNA1 nano-system offers effective drug delivery and tumor targeting, resulting in significantly improved therapeutic efficacy against ESCC tumors. These insights suggest that aptamer-modified nano-systems can deliver drugs and genes with superior tumor-targeting, potentially revolutionizing targeted therapy in ESCC.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/metabolismo , Animais , Camundongos , Paclitaxel/uso terapêutico , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos/métodos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Técnica de Seleção de Aptâmeros/métodos
18.
J Hazard Mater ; 473: 134434, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38762983

RESUMO

The behavior of As is closely related to trans(formation) of ferrihydrite, which often coprecipitates with extracellular polymeric substances (EPS), forming EPS-mineral aggregates in natural environments. While the effect of EPS on ferrihydrite properity, mineralogy reductive transformation, and associated As fate in sulfate-reducing bacteria (SRB)-rich environments remains unclear. In this research, ferrihydrite-EPS aggregates were synthesized and batch experiments combined with spectroscopic, microscopic, and geochemical analyses were conducted to address these knowledge gaps. Results indicated that EPS blocked micropores in ferrihydrite, and altered mineral surface area and susceptibility. Although EPS enhanced Fe(III) reduction, it retarded ferrihydrite transformation to magnetite by inhibiting Fe atom exchange in systems with low SO42-. As a result, 16% of the ferrihydrite was converted into magnetite in the Fh-0.3 treatment, and no ferrihydrite transformation occurred in the Fh-EPS-0.3 treatment. In systems with high SO42-, however, EPS promoted mackinawite formation and increased As mobilization into the solution. Additionally, the coprecipitated EPS facilitated As(V) reduction to more mobilized As(III) and decreased conversion of As into the residual phase, enhancing the potential risk of As contamination. These findings advance our understanding on biogeochemistry of elements Fe, S, and As and are helpful for accurate prediction of As behavior.


Assuntos
Arsênio , Matriz Extracelular de Substâncias Poliméricas , Compostos Férricos , Compostos Férricos/química , Arsênio/química , Arsênio/metabolismo , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Matriz Extracelular de Substâncias Poliméricas/química , Poluentes Químicos da Água/química
19.
Front Microbiol ; 15: 1341303, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572242

RESUMO

Understanding the interactions between fish gut microbiota and the aquatic environment is a key issue for understanding aquatic microorganisms. Environmental microorganisms enter fish intestines through feeding, and the amount of invasion varies due to different feeding habits. Traditional fish feeding habitat preferences are determined by fish morphology or behavior. However, little is known about how the feeding behavior of fish relative to the vertical structure in a shallow lake influences gut microbiota. In our study, we used nitrogen isotopes to measure the trophic levels of fish. Then high-throughput sequencing was used to describe the composition of environmental microbiota and fish gut microbiota, and FEAST (fast expectation-maximization for microbial source tracking) method was used to trace the source of fish gut microbiota. We investigated the microbial diversity of fish guts and their habitats in Lake Sanjiao and verified that the sediments indeed played an important role in the assembly of fish gut microbiota. Then, the FEAST analysis indicated that microbiota in water and sediments acted as the primary sources in half of the fish gut microbiota respectively. Furthermore, we classified the vertical habitat preferences using microbial data and significant differences in both composition and function of fish gut microbiota were observed between groups with distinct habitat preferences. The performance of supervised and unsupervised machine learning in classifying fish gut microbiota by habitat preferences actually exceeded classification by fish species taxonomy and fish trophic level. Finally, we described the stability of fish co-occurrence networks with different habitat preferences. Interestingly, the co-occurrence network seemed more stable in pelagic fish than in benthic fish. Our results show that the preferences of fish in the vertical structure of habitat was the main factor affecting their gut microbiota. We advocated the use of microbial interactions between fish gut and their surrounding environment to reflect fish preferences in vertical habitat structure. This approach not only offers a novel perspective for understanding the interactions between fish gut microbiota and environmental factors, but also provides new methods and ideas for studying fish habitat selection in aquatic ecosystems.

20.
J Agric Food Chem ; 72(9): 4765-4776, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38393978

RESUMO

Akkermansia muciniphila is a potential candidate for ulcerative colitis prevention. Considering that it utilizes 2'-fucosyllactose (2'FL) for growth, 2'FL can be used to enrich the abundance of A. muciniphila in feces. However, whether the crosswalk between 2'FL and A. muciniphila can promote the intestinal colonization of A. muciniphila remains unclear. In this study, we explored the effect and the underlying mechanism of 2'FL on the colonization of A. muciniphila in vitro and in vivo as well as its alleviating effect on colitis. Our results revealed that 2'FL can serve as a carbon source of A. muciniphila to support the growth and increase cell-surface hydrophobicity and the expression of the genes coding fibronectin-binding autotransporter adhesin to promote the adhesion to Caco2/HT29 methotrexate (MTX) cells but not of galactooligosaccharides (GOS) and glucose. Moreover, 2'FL could increase the host mucin formation to promote the adhesion of A. muciniphila to Caco2/HT29 MTX cells but not of GOS and glucose. Furthermore, 2'FL could significantly increase the colonization of A. muciniphila in the gut to alleviate colitis in mice. Overall, the interplay between A. muciniphila and 2'FL is expected to provide an advantageous ecological niche for A. muciniphila so as to confer further health benefits against colitis.


Assuntos
Colite Ulcerativa , Trissacarídeos , Animais , Humanos , Camundongos , Akkermansia , Células CACO-2 , Colite Ulcerativa/metabolismo , Glucose/metabolismo
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