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1.
Molecules ; 29(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38543011

RESUMO

Artemisia japonica Thunb. has been used as a traditional Chinese medicine and a vegetable for thousands of years in China. However, there are few reports on the chemical composition and biological activity of its leaves. Thus, this study aimed to evaluate the chemical composition, antioxidant and anti-inflammatory effects of water extracts of A. japonica leaves and their underlying mechanisms. A total of 48 compounds were identified in the water extract using UPLC-QTOF-MS2 analysis, with phenolic acids, particularly chlorogenic acid compounds, being the predominant components. The ethyl acetate fraction (EAF) contained most of the total phenolic content (385.4217 mg GAE/g) and displayed superior antioxidant capacity with the IC50DPPH•, IC50ABTS•+, and OD0.5reducing power at 10.987 µg/mL, 43.630 µg/mL and 26.883 µg/mL, respectively. Furthermore, EAF demonstrated potent antioxidant and anti-inflammatory effects in LPS-induced RAW264.7 cells by upregulating the Nrf2/HO-1 signal pathway. These findings highlight that A. japonica leaves possess remarkable abilities to mitigate inflammation and oxidative stress, suggesting their potential utilization as medicinal agents and food additives for promoting human health.


Assuntos
Antioxidantes , Artemisia , Humanos , Animais , Camundongos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Lipopolissacarídeos/farmacologia , Extratos Vegetais/química , Artemisia/metabolismo , Transdução de Sinais , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Água/farmacologia , Células RAW 264.7
2.
Urolithiasis ; 52(1): 40, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427040

RESUMO

This retrospective study aims to examine the correlation between calcium oxalate (CaOx) stones and common clinical tests, as well as urine ionic composition. Additionally, we aim to develop and implement a personalized model to assess the accuracy and feasibility of using charts to predict calcium oxalate stones in patients with urinary tract stones. A retrospective analysis was conducted on data from 960 patients who underwent surgery for urinary stones at the First Affiliated Hospital of Soochow University from January 1, 2010, to December 31, 2022. Among these patients, 447 were selected for further analysis based on screening criteria. Multivariate logistic regression analysis was then performed to identify the best predictive features for calcium oxalate stones from the clinical data of the selected patients. A prediction model was developed using these features and presented in the form of a nomogram graph. The performance of the prediction model was assessed using the C-index, calibration curve, and decision curve, which evaluated its discriminative power, calibration, and clinical utility, respectively. The nomogram diagram prediction model developed in this study is effective in predicting calcium oxalate stones which is helpful in screening and early identification of high-risk patients with calcium oxalate urinary tract stones, and may be a guide for urologists in making clinical treatment decisions.


Assuntos
Líquidos Corporais , Cálculos Urinários , Humanos , Oxalato de Cálcio/química , Estudos Retrospectivos , Nomogramas , Cálculos Urinários/diagnóstico , Cálcio/urina
3.
Phytomedicine ; 126: 155186, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387272

RESUMO

BACKGROUND & AIMS: The effect fraction of Bletilla striata (Thunb.) Reichb.f. (EFBS), a phenolic-rich extract, has significant protective effects on lipopolysaccharide (LPS)-induced acute lung injury (ALI), but its composition and molecular mechanisms are unclear. This study elucidated its chemical composition and possible protective mechanisms against LPS-induced ALI from an antioxidant perspective. METHODS: EFBS was prepared by ethanol extraction, enriched by polyamide column chromatography, and characterized using ultra-performance liquid chromatography/time-of-flight mass spectrometry. The LPS-induced ALI model and the RAW264.7 model were used to evaluate the regulatory effects of EFBS on oxidative stress, and transcriptome analysis was performed to explore its possible molecular mechanism. Then, the pathway by which EFBS regulates oxidative stress was validated through inhibitor intervention, flow cytometry, quantitative PCR, western blotting, and immunofluorescence techniques. RESULTS: A total of 22 compounds in EFBS were identified. The transcriptome analyses of RAW264.7 cells indicated that EFBS might reduce reactive oxygen species (ROS) production by inhibiting the p47phox/NADPH oxidase 2 (NOX2) pathway and upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Both in vitro and in vivo data confirmed that EFBS significantly inhibited the expression and phosphorylation of p47phox protein, thereby weakening the p47phox/NOX2 pathway and reducing ROS production. EFBS significantly increased the expression of Nrf2 in primary peritoneal macrophages and lung tissue and promoted its nuclear translocation, dose-dependent increase in HO-1 levels, and enhancement of antioxidant activity. In vitro, both Nrf2 and HO-1 inhibitors significantly reduced the scavenging effects of EFBS on ROS, further confirming that EFBS exerts antioxidant effects at least partially by upregulating the Nrf2/HO-1 pathway. CONCLUSIONS: EFBS contains abundant phenanthrenes and dibenzyl polyphenols, which can reduce ROS production by inhibiting the p47phox/NOX2 pathway and enhance ROS clearance activity by upregulating the Nrf2/HO-1 pathway, thereby exerting regulatory effects on oxidative stress and improving LPS-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Lipopolissacarídeos , Humanos , Lipopolissacarídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NADPH Oxidase 2/metabolismo , Heme Oxigenase-1/metabolismo , Transdução de Sinais , Estresse Oxidativo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/metabolismo
4.
Small ; : e2307323, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349049

RESUMO

Layered zeolitic silicates and corresponding interlayer-expanded porous materials exhibit attractive application potential in wide fields. Nonetheless, designable synthesis and structure analysis of layered silicates remain challenging. Herein, two kinds of layered silicates are synthesized using different di-quaternary ammonium-type organic structure-directing agents (OSDAs). Their crystal structures are analyzed and verified by 3D electron diffraction (3D ED) and high-resolution TEM imaging. The suitable configurations of OSDA can lead to desirable interlayer states. Additionally, two new zeolite structures both with 12-membered ring (MR) channels intersected by 8 MR channels and larger interlayer spaces are constructed from layered silicate precursors by interlayer silylation. The new zeolitic material exhibits potential application in adsorption of organic pollution and catalytic reaction. This study is expected to develop versatile ways for the design and synthesis of layered silicates even zeolites and provide references in characterizing layered materials and zeolites as well.

5.
Heliyon ; 10(2): e24654, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38304769

RESUMO

The importance of flexible employment has been highlighted at the policy level in China. In the process of implementing the employment priority strategy, the number of flexible workers in China has exceeded 200 million. Platform-based flexible employment has shown great potentiality in stabilising employment, but as a new form of employment, its employment quality still needs to be improved. Based on the research data, this study identified 14 effective factors influencing the employment quality of platform-based flexible workers and constructed a five-level interpretative structural model (ISM) for the employment quality of platform-based flexible workers. According to the characteristics of different platform types, platform-based flexible employment was divided into business-type and labour-type flexible employment. Then hierarchical logistic regression analysis was conducted on the quality of the two types of flexible workers respectively. The results showed that working hours only had a significant positive effect on the employment quality of business-type flexible workers, while salary and employment injury insurance only had a significant positive effect on the employment quality of labour-type flexible workers. This paper proposed policy recommendations to achieve high-quality employment for flexible workers on different platforms.

6.
BMC Urol ; 24(1): 5, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172816

RESUMO

OBJECTIVES: The aim of this study was to use deep learning (DL) of intraoperative images of urinary stones to predict the composition of urinary stones. In this way, the laser frequency and intensity can be adjusted in real time to reduce operation time and surgical trauma. MATERIALS AND METHODS: A total of 490 patients who underwent holmium laser surgery during the two-year period from March 2021 to March 2023 and had stone analysis results were collected by the stone laboratory. A total of 1658 intraoperative stone images were obtained. The eight stone categories with the highest number of stones were selected by sorting. Single component stones include calcium oxalate monohydrate (W1), calcium oxalate dihydrate (W2), magnesium ammonium phosphate hexahydrate, apatite carbonate (CH) and anhydrous uric acid (U). Mixed stones include W2 + U, W1 + W2 and W1 + CH. All stones have intraoperative videos. More than 20 intraoperative high-resolution images of the stones, including the surface and core of the stones, were available for each patient via FFmpeg command screenshots. The deep convolutional neural network (CNN) ResNet-101 (ResNet, Microsoft) was applied to each image as a multiclass classification model. RESULTS: The composition prediction rates for each component were as follows: calcium oxalate monohydrate 99% (n = 142), calcium oxalate dihydrate 100% (n = 29), apatite carbonate 100% (n = 131), anhydrous uric acid 98% (n = 57), W1 + W2 100% (n = 82), W1 + CH 100% ( n = 20) and W2 + U 100% (n = 24). The overall weighted recall of the cellular neural network component analysis for the entire cohort was 99%. CONCLUSION: This preliminary study suggests that DL is a promising method for identifying urinary stone components from intraoperative endoscopic images. Compared to intraoperative identification of stone components by the human eye, DL can discriminate single and mixed stone components more accurately and quickly. At the same time, based on the training of stone images in vitro, it is closer to the clinical application of stone images in vivo. This technology can be used to identify the composition of stones in real time and to adjust the frequency and energy intensity of the holmium laser in time. The prediction of stone composition can significantly shorten the operation time, improve the efficiency of stone surgery and prevent the risk of postoperative infection.


Assuntos
Cálculos Renais , Cálculos Urinários , Humanos , Oxalato de Cálcio , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Ácido Úrico , Apatitas , Aprendizado de Máquina , Carbonatos
7.
J Environ Manage ; 351: 119687, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38061097

RESUMO

Ridge-furrow with full film mulching has been widely applied to increase crop yield and water productivity on the Loess Plateau, but it may stimulate carbon (C) mineralization. How to integrate other technological benefits based on this technology for long-term maintenance of high yield and soil fertility is a pressing issue. With the local farmers' practice (FP) as a control, three integrated soil-crop system management (ISSM) practices integrating fertilizer rates, fertilizer types and planting densities (ISSM-N1, ISSM-N2 and ISSM-MN) were established to improve maize yield and soil quality. Compared with the FP, the maize yield increased by 13.34%, 21.83% and 30.24%, and the soil quality index (SQI) increased by 9.66%, 14.91% and 38.38% for ISSM-N1, ISSM-N2 and ISSM-MN, respectively. However, ISSM-N1 did not significantly increase yield, and ISSM-N2 increased residual soil nitrate and decreased nitrogen (N) partial factor productivity significantly. Compared to the FP, ISSM practices increased soil organic carbon (SOC), labile organic C fractions (LOCFs) and potassium permanganate organic C fractions in the topsoil to varying degrees, but only ISSM-MN reached significant levels for most C fractions. The sensitivity index indicated very easily oxidizable C (24.6%), easily oxidizable C (24.7%), hot-water extractable C (30.8%), labile organic C (24.7%) and particulate organic C (57.3%) were more sensitive than SOC (22.7%). ISSM-MN sequestered significantly higher C than the other treatments. The results of the relative importance analysis and the structural equation model indicated that LOCFs were the direct contributors to yield, while recalcitrant C (CO) was the indirect contributor, revealing the underlying mechanism that CO decomposed to replenish LOCFs and the total N pool with the water soluble C pool as the transit station. Overall, ISSM-MN is the most promising strategy to improve crop yield and soil fertility in the long term on the Loess Plateau.


Assuntos
Agricultura , Solo , Solo/química , Agricultura/métodos , Carbono/análise , Fertilizantes/análise , Zea mays , Nitrogênio/análise , Água/análise , China
8.
Shock ; 61(2): 311-321, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38150369

RESUMO

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disorder with significant health implications. N6-methyladenosine (m6A) methyltransferase is known to exert regulatory functions in liver-related diseases. This study investigates the intricate role of RNA binding motif protein 15 (RBM15) in modulating inflammation and oxidative stress in NAFLD. An NAFLD model was induced in mice (male, C57BL/6J, 72 mice in the sham group) through a high-fat diet for 9 weeks, and hepatocytes were exposed to long chain-free fatty acids. The expression levels of RBM15, ring finger protein 5 (RNF5), and rho-kinase 1 (ROCK1) were assessed. RBM15 expression was intervened (injection of AAV9 virus at week 9 and detection at week 11). Liver damage was evaluated using staining assays, along with assessments of weight changes and lipid levels. Notably, RBM15 (decreased approximately 40%/60%) and RNF5 (decreased approximately 60%/75%) were poorly expressed while ROCK1 (increased approximately 2.5-fold) was highly expressed in liver tissues and cells. RBM15 overexpression mitigated liver damage, inflammation, and oxidative stress in NAFLD mice, resulting in reduced liver-to-body weight ratio (20%) and decreased levels of alanine aminotransferase (54%), aspartate aminotransferase (36%), total cholesterol (30%), and triglycerides (30%), and inhibited inflammation and oxidative stress levels. Mechanistically, RBM15 upregulated RNF5 expression through m6A methylation modification, and RNF5 suppressed ROCK1 protein levels through ubiquitination modification. RNF5 knockdown or ROCK1 overexpression accelerated inflammation and oxidative stress in NAFLD. Taken together, RBM15 upregulated RNF5 expression through m6A methylation modification. RNF5 inhibited ROCK1 expression through ubiquitination modification to mitigate NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Masculino , Camundongos , Modelos Animais de Doenças , Ácidos Graxos , Inflamação , Proteínas de Membrana , Metiltransferases , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ubiquitina-Proteína Ligases/genética
9.
J Environ Manage ; 351: 119854, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128212

RESUMO

Controlled-release urea application and straw incorporation have been conducted in recent years as environmental-friendly and sustainable farming strategies, but the long-term effects of controlled-release urea application and combination with straw on the dryland maize yield, soil fertility and the environment under future climate scenarios remain unclear. Hence, based on a six-year field experiment, four treatments were used to calibrate and validate the DeNitrification-DeComposition (DNDC) model, including non-nitrogen (CK), split applications of conventional urea (UR), single basal application of conventional urea and controlled-release urea at a ratio of 2:1 (CU), and CU combined with straw (CUS). Subsequently, coupled the well-validated model with future climate to evaluate suitable agricultural production practices under two shared socioeconomic pathways (SSP)-SSP245 and SSP585. The validation results indicated a good fit between the simulated and observed data of greenhouse gas emissions, soil organic carbon (SOC) contents and maize yields. With the anticipation of warmer temperatures and increased precipitation in the future, the yields of UR, CU, and CUS treatment significantly rose. Under SSP585 scenario, the positive impacts of CU treatment on maize yields reduced after the 2050s, exhibiting an average decline of 12.03%. Compared with the UR treatment, the CU treatment markedly reduced cumulative N2O emissions, and both treatments maintained the original state of SOC storages in the 2030s, furthermore, the CUS treatment reduced N2O emissions by 47.10%, 35.07%, 23.80% and 10.04% in the 2030s, 2050s, 2070s and 2090s, respectively. SOC storages for the CUS treatment gradually increased with an average of 464.58, 350.22, 250.87 and 177.75 kg C ha-1 y-1 for two SSP scenarios in the 2030s, 2050s, 2070s and 2090s, which excellently offset the CO2 equivalent of emissions caused by N2O emissions. Therefore, in dryland maize production, combined controlled-release urea with straw incorporation could achieve the best comprehensive effect among increase of yield, improvement of SOC storages and alleviation of greenhouse gas emissions under future climate scenario.


Assuntos
Gases de Efeito Estufa , Solo , Zea mays , Carbono , Preparações de Ação Retardada , Óxido Nitroso/análise , Agricultura/métodos , Fertilizantes/análise , China
10.
Sci Total Environ ; 912: 169576, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38145665

RESUMO

Anaerobic methanotrophic archaea (ANME) belonging to the family Methanoperedenaceae are crucial for the global carbon cycle and different biogeochemical processes, owing to their metabolic versatility to couple anaerobic oxidation of methane (AOM) with different electron acceptors. A universal feature of Methanoperedenaceae is the abundant genes encoded in their genomes associated with extracellular electron transfer (EET) pathways. Candidatus. 'Methanoperedens manganicus', an archaeon belonging to the family Methanoperedenaceae, was recently enriched in a bioreactor performing AOM coupled with Mn (IV) reduction. Using this EET-capable ANME, we tested the hypothesis in this study that ANME can catalyse the humic-dependent AOM for growth. A two-year incubation showed that AOM activity can be sustained by Ca. 'M. manganicus' consortium in a bioreactor fed only with humic acids and methane. An isotopic mass balance batch test confirmed that the observed AOM was coupled to the reduction of humic acids. The increase of relative abundance of Ca. 'M. manganicus', and the total archaea population in the microbial community suggested that Ca. 'M. manganicus' can grow on methane and humic acids. The observation of humic-dependent AOM led to a subsequent hypothesis that humic acids could be used as the electron shuttle to mediate the EET in dissimilatory Mn (IV) reduction by Ca. 'M. manganicus'. We tested this hypothesis by adding humic acids to a Ca. 'M. manganicus' dominated-culture, which showed that the AOM rate was doubled by the addition of humic acids. X-ray photoelectron spectroscopy (XPS) showed that quinone moieties were consumed when humic acids worked as electron acceptors while remaining stable when functioning as a shuttle for electron transfer. The results of our study suggest that humic acids may serve as electron shuttles to allow ANME to access more electron acceptors through long-range EET.


Assuntos
Substâncias Húmicas , Metano , Anaerobiose , Metano/metabolismo , Elétrons , Archaea/metabolismo , Oxirredução , Oxidantes
11.
Nano Lett ; 23(24): 11569-11577, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38078629

RESUMO

Creating customizable metallic nanostructures in a simple and controllable manner has been a long-standing goal in nanoscience. In this study, we use DNA origami as a letterpress printing plate and gold nanoparticles as ink to produce predesigned gold nanostructures. The letterpress plate is reusable, enabling the repetitive production of predesigned gold nanostructures. Furthermore, by modifying the DNA origami letterpress plate on magnetic beads, we can simplify the printing processes. We have successfully printed gold nanoparticle dimers, trimers, straight and quadrilateral tetramers, and other nanostructures. Our approach improves the flexibility and stability of metallic nanostructures, simplifying both their design and their operation. It promises universal applicability in the fabrication of metamaterials, biosensors, and surface plasma nanooptics.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Ouro/química , Nanopartículas Metálicas/química , Nanoestruturas/química , DNA/química , Impressão Tridimensional , Nanotecnologia
12.
Urol Int ; 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38081150

RESUMO

INTRODUCTION: Bladder cancer (BC) is a major health concern that poses a significant threat to the population, with an increasing incidence rate and a high risk of recurrence and progression. The primary clinical method for diagnosing bladder cancer is cystoscopy, but due to the limitations of traditional white light cystoscopy and inadequate clinical experience among junior physicians, its detection rate for bladder tumor, especially small and flat lesions, is relatively low. However, recent years have seen remarkable advancements in the application of artificial intelligence (AI) technology in the field of medicine. This has led to the development of numerous AI algorithms that have been successfully integrated into medical practices, providing valuable assistance to clinicians. The purpose of this study is to develop a cystoscopy algorithm that is real-time, cost-effective, high-performing, and accurate, with the aim of enhancing the detection rate of bladder tumors during cystoscopy. MATERIALS AND METHODS: For this study, a dataset of 3500 cystoscopic images obtained from 100 patients diagnosed with bladder cancer was collected, and a deep learning model was developed utilizing the U-Net algorithm within a convolutional neural network for training purposes. RESULTS: This study randomly divided 3,500 images from 100 bladder cancer patients into training and validation groups, and each patient's pathology result was confirmed. In the validation group, the accuracy of tumor recognition by the U-Net algorithm reached 98%. Compared to primary urologists, with greater accuracy and faster detection speed. CONCLUSION: This study highlights the potential of U-Net-based deep learning techniques in the detection of bladder tumors. The establishment and optimization of the U-Net model is a significant breakthrough and it provides a valuable reference for future research in the field of medical image processing.

13.
Chem Sci ; 14(46): 13446-13452, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38033904

RESUMO

Developing new and understanding multicomponent reactions (MCRs) is an appealing but challenging task. Herein, Rh(iii)-catalyzed multicomponent double C-H annulations of cyclic diimines (or diketones and acetone), alkynes, and ammonium acetate to assemble functionalized 1,1'-biisoquinolines and C-bridged 1,1'-bisisoquinolines with controllable 14N/15N editing in one shot has been developed. Through a combination of isotopic-labeling (2H, 18O, and 15N) experiments, crystallography, and time-dependent ESI-MS, the reaction process was studied in detail. Ammonium acetate accounts for two rounds of Hofmann elimination and iminization, thus leading to an unprecedented imine dance, cyclic imine → N-alkenyl imine → NH imine. The N-alkenyl imine can immediately guide a C-H annulation (N-retention channel), and some of it is converted into NH-imine to trigger another annulation (N-exchange channel). The channels and 15N ratios can be regulated by the reaction mode and acidity. Moreover, the resulting 1,1'-biisoquinolines are a privileged ligand scaffold which is exemplified herein by a hydrazine-iodine exchange reaction to form drug-like benzo[c]cinnolines.

14.
Front Plant Sci ; 14: 1266218, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37905168

RESUMO

Over the years, the microbial community of maize (Zea mays) rhizosphere has been extensively studied; however, the role of microdiversity sustain rhizosphere-associated microbial species distribution from root surface to bulk soil in mature maize is still unclear. Although operational taxonomic units (OTUs) have been used to classify species, amplicon sequence variants (ASVs) have been shown to be effective in representing microdiversity within OTUs at a finer genetic scale. Therefore, the aim of this study was to examine the role of microdiversity in influencing the distribution of rhizosphere-associated microbial species across environmental gradients from root surface to bulk soil at the OTU and ASV levels. Here, the microbial community structures of bulk, loosely bound, and tightly bound soil samples from maize rhizosphere were examined at OTU and ASV levels. The results showed that OTU and ASV methods exhibited similar microbial community structures in rhizosphere. Additionally, different ecotypes with varying distributions and habitat preferences were observed within the same bacterial OTU at the ASV level, indicating a rich bacterial microdiversity. In contrast, the fungal community exhibited low microdiversity, with no significant relationship between fungal microdiversity and persistence and variability. Moreover, the ecotypes observed within the bacterial OTUs were found to be positively or negatively associated with environmental factors, such as soil organic carbon (SOC), NO3 --N, NH4 +-N contents, and pH. Overall, the results showed that the rich microdiversity could sustain the distribution of rhizosphere-associated bacterial species across environmental gradients from root surface to bulk soil. Further genetic analyses of rhizosphere-associated bacterial species could have considerable implications for potential mediation of microdiversity for sustainable crop production.

15.
ACS Nano ; 17(18): 18114-18127, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37695697

RESUMO

In personalized cancer immunotherapy, developing an effective neoantigen nanovaccine with high immunogenicity is a significant challenge. Traditional nanovaccine delivery systems often require nanocarriers, which can hinder the delivery of the neoantigen and cause significant toxicity. In this study, we present an innovative strategy of carrier-free nanovaccine achieved through direct self-assembly of 2'-fluorinated CpG (2'F-CpG) with melanoma neoantigen peptide (Obsl1). Molecular dynamics simulations demonstrated that the introduction of a fluorine atom into CpG increases the noncovalent interaction between 2'F-CpG and Obsl1, which enhanced the loading of Obsl1 on 2'F-CpG, resulting in the spontaneous formation of a hybrid 2'F-CpG/Obsl1 nanovaccine. This nanovaccine without extra nanocarriers showed ultrahigh Obsl1 loading up to 83.19 wt %, increasing the neoantigen peptide uptake by antigen-presenting cells (APCs). In C57BL/6 mice models, we demonstrated the long-term preventive and therapeutic effects of the prepared 2'F-CpG/Obsl1 nanovaccine against B16F10 melanoma. Immunocellular analysis revealed that the nanovaccine activated innate and adaptive immune responses to cancer cells. Hence, this study established a simple, safe, and effective preparation strategy for a carrier-free neoantigen nanovaccine, which could be adapted for the future design of personalized cancer vaccines in clinical settings.


Assuntos
Melanoma , Camundongos , Animais , Camundongos Endogâmicos C57BL , Melanoma/terapia , Células Apresentadoras de Antígenos , Transporte Biológico , Peptídeos
16.
J Proteomics ; 288: 104959, 2023 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-37478968

RESUMO

Danshen, belongs to the Lamiaceae family, and its scientific name is Salvia miltiorrhiza Bunge. It is a valuable medicinal plant to prevent and treat cardiovascular and cerebrovascular diseases. Lysine succinylation, a widespread modification found in various organisms, plays a critical role in regulating secondary metabolism in plants. The hairy roots of Salvia miltiorrhiza were subject to proteomic analysis to identify lysine succinylation sites using affinity purification and HPLC-MS/MS in this investigation. Our findings reveal 566 lysine succinylation sites in 348 protein sequences. We observed 110 succinylated proteins related to secondary metabolism, totaling 210 modification sites. Our analysis identified 53 types of enzymes among the succinylated proteins, including phenylalanine ammonia-lyase (PAL) and aldehyde dehydrogenase (ALDH). PAL, a crucial enzyme involved in the biosynthesis of rosmarinic acid and flavonoids, displayed succinylation at two sites. ALDH, which participates in the phenylpropane metabolic pathway, was succinylated at 8 eight sites. These observations suggest that lysine succinylation may play a vital role in regulating the production of secondary metabolites in Salvia miltiorrhiza. Our study may provide valuable insights for further investigation on plant succinylation, specifically as a reference point. SIGNIFICANCE: Salvia miltiorrhiza Bunge is a valuable medicinal plant that prevents and treats cardiovascular and cerebrovascular diseases. Lysine succinylation plays a critical role in regulating secondary metabolism in plants. The hairy roots of Salvia miltiorrhiza were subject to proteomic analysis to identify lysine succinylation sites using affinity purification and HPLC-MS/MS in this investigation. These observations suggest that lysine succinylation may act as a vital role in regulating the production of secondary metabolites in Salvia miltiorrhiza. Our study may provide valuable insights for further investigation on succinylation in plants, specifically as a reference point.


Assuntos
Salvia miltiorrhiza , Metabolismo Secundário , Salvia miltiorrhiza/metabolismo , Lisina/metabolismo , Proteoma/metabolismo , Espectrometria de Massas em Tandem , Proteômica
17.
Food Res Int ; 170: 112960, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37316006

RESUMO

Gluten accumulation damages the proximal small intestine and causes celiac disease (CeD) which has not been effectively treated except by using a gluten-free diet. In this study, strain Bacillus subtilis LZU-GM was isolated from Pakistani traditional fermented sourdough and could degrade 73.7% of gluten in 24 h in vitro. Strain LZU-GM was employed for practical application to investigate gluten degradation in mice models. The results showed that strain LZU-GM was colonized in mice and the survival rate was around 0.95 % (P < 0.0001). The gluten degradation was 3-fold higher in the small intestine of the strain LZU-GM treated mice group remaining 1511.96 ng/mL of gluten peptides than the untreated mice group (6500.38 ng/mL). Immunochemical analysis showed that gluten-treated mice established positive antigliadin antibodies (AGA) in serum (IgA, IgG, and anti-TG2 antibodies) as compared to the strain LZU-GM treatment group. Furthermore, the number of IFN-γ, TNF-α, IL-10, and COX-2 cells decrease in the lamina propria of the strain LZU-GM treatment group (P < 0.0001). Microbial community bar plot analysis showed that Lactobacillus, Dubosiella, and Enterococcus genera were restored and stabilized in the LZU-GM treatment group while Blautia and Ruminococcus were found lower. The oral gavage of probiotic strain LZU-GM might be useful for gluten metabolism in the intestine during digestion and would be a long-term dietary treatment for CeD management.


Assuntos
Doença Celíaca , Microbioma Gastrointestinal , Microbiota , Animais , Camundongos , Bacillus subtilis , Glutens , Aditivos Alimentares
18.
Nat Commun ; 14(1): 2661, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37160866

RESUMO

Oral dihydroxyphenylalanine (Dopa) administration to replenish neuronal dopamine remains the most effective treatment for Parkinson's disease (PD). However, unlike the continuous and steady dopamine signaling in normal neurons, oral Dopa induces dramatic fluctuations in plasma Dopa levels, leading to Dopa-induced dyskinesia. Herein, we report a functional nucleic acid-based responsive artificial enzyme (FNA-Fe3O4) for in situ continuous Dopa production. FNA-Fe3O4 can cross the blood-brain barrier and target diseased neurons relying on transferrin receptor aptamer. Then, FNA-Fe3O4 responds to overexpressed α-synuclein mRNA in diseased neurons for antisense oligonucleotide treatment and fluorescence imaging, while converting to tyrosine aptamer-based artificial enzyme (Apt-Fe3O4) that mimics tyrosine hydroxylase for in situ continuous Dopa production. In vivo FNA-Fe3O4 treatment results in recovery of Dopa and dopamine levels and decrease of pathological overexpressed α-synuclein in PD mice model, thus ameliorating motor symptoms and memory deficits. The presented functional nucleic acid-based responsive artificial enzyme strategy provides a more neuron friendly approach for the diagnosis and treatment of PD.


Assuntos
Ácidos Nucleicos , Doença de Parkinson , Animais , Camundongos , Doença de Parkinson/tratamento farmacológico , Di-Hidroxifenilalanina , alfa-Sinucleína/genética , Dopamina
19.
ACS Appl Mater Interfaces ; 15(23): 28116-28124, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37253068

RESUMO

An MFI-topology nanosheet zeolite with a highly a-axis-oriented structure has rarely been reported but with a great potential for industrial applications. Theoretical calculations on the interaction energies between the MFI skeleton and ionic liquid molecules indicated the possibility of preferential crystal growth along a specific direction, according to which highly a-oriented ZSM-5 nanosheets were synthesized from commercially available 1-(2-hydroxyethyl)-3-methylimidazolium and layered silicate sources. The imidazolium molecules directed the structure formation and meanwhile acted as zeolite growth modifiers to restrict the crystal growth perpendicular to the MFI bc plane, which induced unique a-axis-orientated thin sheets with ∼12 nm thickness. The a-oriented ZSM-5 exhibited more competitive propylene selectivity and longer lifetime than bulky crystals in methanol-to-propylene (MTP) reaction. This research would provide a versatile protocol for the rational design and synthesis of shape-selective zeolite catalysts with promising applications.

20.
Nano Lett ; 23(8): 3326-3333, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37026788

RESUMO

On-chip photonic systems play crucial roles in nanoscience and nanoapplications, but coupling external light to these subwavelength devices is challenging due to a large mode mismatch. Here, we establish a new scheme for realizing highly miniaturized couplers for efficiently exciting on-chip photonic devices in a controllable way. Relying on both resonant and Pancharatnam-Berry mechanisms, our meta-device can couple circularly polarized light to a surface plasmon, which is then focused into a spot placed with a target on-chip device. We experimentally demonstrate two meta-couplers. The first can excite an on-chip waveguide (with a 0.1λ × 0.2λ cross section) with an absolute efficiency of 51%, while the second can achieve incident spin-selective excitation of a dual-waveguide system. Background-free excitation of a gap-plasmon nanocavity with the local field enhanced by >1000 times is numerically demonstrated. Such a scheme connects efficiently propagating light in free space and localized fields in on-chip devices, being highly favored in many integration-optics applications.

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