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1.
J Environ Sci (China) ; 149: 342-357, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39181647

RESUMO

The toxicity of PM2.5 does not necessarily change synchronously with its mass concentration. In this study, the chemical composition (carbonaceous species, water-soluble ions, and metals) and oxidative potential (dithiothreitol assay, DTT) of PM2.5 were investigated in 2017/2018 and 2022 in Xiamen, China. The decrease rate of volume-normalized DTT (DTTv) (38%) was lower than that of PM2.5 (55%) between the two sampling periods. However, the mass-normalized DTT (DTTm) increased by 44%. Clear seasonal patterns with higher levels in winter were found for PM2.5, most chemical constituents and DTTv but not for DTTm. The large decrease in DTT activity (84%-92%) after the addition of EDTA suggested that water-soluble metals were the main contributors to DTT in Xiamen. The increased gap between the reconstructed and measured DTTv and the stronger correlations between the reconstructed/measured DTT ratio and carbonaceous species in 2022 were observed. The decrease rates of the hazard index (32.5%) and lifetime cancer risk (9.1%) differed from those of PM2.5 and DTTv due to their different main contributors. The PMF-MLR model showed that the contributions (nmol/(min·m3)) of vehicle emission, coal + biomass burning, ship emission and secondary aerosol to DTTv in 2022 decreased by 63.0%, 65.2%, 66.5%, and 22.2%, respectively, compared to those in 2017/2018, which was consistent with the emission reduction of vehicle exhaust and coal consumption, the adoption of low-sulfur fuel oil used on board ships and the reduced production of WSOC. However, the contributions of dust + sea salt and industrial emission increased.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Material Particulado , Material Particulado/análise , China , Poluentes Atmosféricos/análise , Oxirredução , Cidades , Poluição do Ar/estatística & dados numéricos
2.
Transl Lung Cancer Res ; 13(8): 2000-2014, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39263017

RESUMO

Background: Accurate real-time tumor delineation is essential for achieving curative resection (R0 resection) during non-small cell lung cancer (NSCLC) surgery. The unique characteristics of lung tissue structure significantly challenge the use of video-assisted thoracoscopic surgery in the identification of lung nodules. This difficulty often results in an inability to discern the margins of lung nodules, necessitating either an expansion of the resection scope, or a transition to open surgery. Due to its high spatial resolution, ease of operation, and capacity for real-time observation, near-infrared fluorescence (NIRF) navigation in oncological surgery has emerged as a focal point of clinical research. Targeted NIRF probes, which accumulate preferentially in tumor tissues and are rapidly cleared from normal tissues, enhance diagnostic sensitivity and surgical outcomes. The imaging effect of the clinically approved NIRF probe indocyanine green (ICG) varies significantly from person to person. Therefore, we hope to develop a new generation of targeted NIRF probes targeting lung tumor-specific targets. Methods: First, the peptide iRGD (sequence: CRGDKGPDC) fluorescent tracer was synthesized, and characterized through mass spectrometry (MS), proton nuclear magnetic resonance (1H NMR), and high-performance liquid chromatography (HPLC). Fluorescence properties were tested subsequently. Safety was performed in vitro using both human normal liver cells and human normal breast cells. Second, Metabolism and optimal imaging time were determined by tail vein injection of iRGD fluorescent tracer. Finally, Orthotopic and metastatic lung tumor models were used to evaluate the targeting properties of the iRGD fluorescent tracer. Results: We successfully synthesized an iRGD fluorescent tracer specifically designed to target NSCLC. The molecular docking analyses indicated that this tracer has receptor affinity comparable to that of iRGD for αvß3 integrin, with a purity ≥98%. Additionally, the tracer is highly soluble in water, and its excitation and emission wavelengths are 767 and 799 nm, respectively, positioning it within the near-infrared spectrum. The cellular assays confirmed the tracer's minimal cytotoxicity, underscoring its excellent biosafety profile. In vivo studies further validated the tracer's capacity for specific NSCLC detection at the cellular level, alongside a prolonged imaging window of 6 days or more. Notably, the tracer demonstrated superior specificity in localizing very small lung nodules, which are otherwise clinically indiscernible, outperforming non-targeted ICG. Fluorescence intensity analyses across various organs revealed that the tracer is predominantly metabolized by the liver and kidneys, with excretion via bile and urine, and exhibits minimal toxicity to these organs as well as the lungs. Conclusions: The iRGD fluorescent tracer selectively accumulates in NSCLC tissues by specifically targeting αvß3 receptors, which are overexpressed on the surface of tumor cells. This targeted approach facilitates the real-time intraoperative localization of NSCLC, presenting an improved strategy for intraoperative tumor identification with significant potential for clinical application.

3.
Cell ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39276776

RESUMO

A comprehensive understanding of physio-pathological processes necessitates non-invasive intravital three-dimensional (3D) imaging over varying spatial and temporal scales. However, huge data throughput, optical heterogeneity, surface irregularity, and phototoxicity pose great challenges, leading to an inevitable trade-off between volume size, resolution, speed, sample health, and system complexity. Here, we introduce a compact real-time, ultra-large-scale, high-resolution 3D mesoscope (RUSH3D), achieving uniform resolutions of 2.6 × 2.6 × 6 µm3 across a volume of 8,000 × 6,000 × 400 µm3 at 20 Hz with low phototoxicity. Through the integration of multiple computational imaging techniques, RUSH3D facilitates a 13-fold improvement in data throughput and an orders-of-magnitude reduction in system size and cost. With these advantages, we observed premovement neural activity and cross-day visual representational drift across the mouse cortex, the formation and progression of multiple germinal centers in mouse inguinal lymph nodes, and heterogeneous immune responses following traumatic brain injury-all at single-cell resolution, opening up a horizon for intravital mesoscale study of large-scale intercellular interactions at the organ level.

4.
Mar Environ Res ; 202: 106764, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39332317

RESUMO

Ostreococcus (Mamiellophyceae, Chlorophyta) is a cosmopolitan genus of marine pico-phytoplankton and the smallest free-living photosynthetic eukaryotes with cell size of 1-2 µm. To understand the diversity and spatio-temporal distribution of Ostreococcus in the Rongcheng coastal regions in northern China, metabarcoding analysis based on the 18S rDNA V4 molecular marker was applied to study the molecular diversity and seasonal dynamics of Ostreococcus in three typical mariculture bays (Rongcheng Bay, Lidao Bay and Sanggou Bay). A total of 103 amplicon sequence variants (ASVs) annotated as Ostreococcus were detected in these three typical mariculture bays throughout the year. The top five ASVs in terms of abundance were ASV4, ASV9, ASV14, ASV28 and ASV109, totally occupying 99.1% of Ostreococcus reads. Phylogenetic analysis showed that these five dominant ASVs represented two Ostreococcus ecotypes (OI and OII) and were grouped into four Ostreococcus clades including Ostreococcus lucimarinus (ASV9) and Ostreococcus tauri (ASV28 and ASV109) in OI, and Ostreococcus sp. RC1 (ASV4) and Ostreococcus sp. RC2 (ASV14) in OII, which provided direct evidence to support the co-existence of two ecotypes in the Rongcheng coastal regions. Five dominant ASVs in OI and OII exhibited two distinct seasonal distribution patterns. Three dominant ASVs (ASV9, ASV28 and ASV109) in OI could be detected in all four seasons of the year, exhibiting native distribution properties, while two ASVs (ASV4 and ASV14) in OII decreased sharply in winter and could not be detected in spring, exhibiting characteristics of alien inputs. The composition, succession and association of Ostreococcus community were mainly driven by water temperature in these mariculture bays. This study helps us systematically understand the molecular diversity and distribution patterns of Ostreococcus in typical mariculture bays in northern China, laying the foundation for understanding and revealing the ecological functions of pico-phytoplankton.

5.
Small Methods ; : e2400989, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39348097

RESUMO

In recent years, the rapid development of brain-inspired neuromorphic systems has created an imperative demand for artificial photonic synapses that operate with low power consumption. In this study, a self-driven memristor synapse based on gallium oxide (Ga2O3) nanowires is proposed and demonstrated successfully. This memristor synapse is capable of emulating a range of functionalities of biological synapses when exposed to 255 nm light stimulation. These functionalities encompass peak time-dependent plasticity, pulse facilitation, and memory learning capabilities. It exhibits an ultrahigh paired-pulse facilitation index of 158, indicating exceptional learning performance. The transition from short-term memory to long-term memory can be attributed to the remarkable relearning capabilities. Furthermore, the potential applications of the memristor synapse is showcased through the successful manipulation of a humanoid intelligent robot. Upon establishing artificial intelligence (AI) systems, the control commands originating from the synaptic device can drive the humanoid robot to perform various actions. Based on the memristor synapses, the autonomous feedback system of the humanoid robot facilitates a good collaboration between robotic actions and bio-inspired light perception. Therefore, this research opens up an effective way to advance the development of neuromorphic computing technologies, AI systems, and intelligent robots that demand ultra-low energy consumption.

6.
J Mater Chem B ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39189074

RESUMO

The combination therapy of targeted treatments and immune checkpoint blockade (ICB) holds great promise for hepatocellular carcinoma (HCC) treatment. However, challenges such as immunogenicity, off-target toxicity of ICB antibodies, low drug co-delivery efficiency, and lack of effective biomarkers to monitor treatment response limit the efficacy of existing targeted immunotherapies. Herein, we synthesized iRGD-modified pH-sensitive liposomal nanoparticles co-encapsulating lenvatinib (Len) and the small molecule PD-1/PD-L1 inhibitor BMS-202 (iRGD-lip@Len/BMS-202) to address issues related to inadequate tumor enrichment and distinct pharmacokinetics of these drugs. Furthermore, intravoxel incoherent motion-magnetic resonance imaging (IVIM-MRI), which is calculated using a biexponential model, can simultaneously reflect both the diffusion of water molecules within the tissue and the microcirculatory perfusion of capillaries. Consequently, we further assessed the feasibility of using IVIM-MRI to monitor the cancer treatment response in nanodrug therapy. These results demonstrated that the iRGD-targeted liposomal nanodrug effectively accumulated in tumors and released in acidic microenvironments. The sustained release of Len facilitated tumor vascular normalization, decreased the presence of Tregs and MDSCs and activated the IFN-γ signaling pathway. This led to increased PD-L1 expression in tumor cells, enhancing the sensitivity of BMS-202. Consequently, there was a synergistic amplification of antitumor immune therapy, resulting in the shrinkage of subcutaneous and orthotopic HCC and inhibition of lung metastasis. Furthermore, IVIM-MRI technology facilitated the non-invasive monitoring of the tumor microenvironment (TME), revealing critical therapeutic response indicators such as the normalization of tumor blood vessels and the degree of hypoxia. Collectively, the combination of Food and Drug Administration (FDA)-approved drugs with iRGD-modified liposomes presents a promising strategy for HCC treatment. Simultaneously, IVIM-MRI provides a non-invasive method to accurately predict the response to this nanodrug.

7.
Sci Rep ; 14(1): 19215, 2024 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160177

RESUMO

The aim of this study was to develop a medical imaging and comprehensive stacked learning-based method for predicting high- and low-risk thymoma. A total of 126 patients with thymomas and 5 patients with thymic carcinoma treated at our institution, including 65 low-risk patients and 66 high-risk patients, were retrospectively recruited. Among them, 78 patients composed the training cohort, while the remaining 53 patients formed the validation cohort. We extracted 1702 features each from the patients' arterial-, venous-, and plain-phase images. Pairwise subtraction of these features yielded 1702 arterial-venous, arterial-plain, and venous-plain difference features each. The Mann‒Whitney U test and least absolute shrinkage and selection operator (LASSO) and SelectKBest methods were employed to select the best features from the training set. Six models were built with a stacked learning algorithm. By applying stacked ensemble learning, three machine learning algorithms (XGBoost, multilayer perceptron (MLP), and random forest) were combined by XGBoost to produce the the six basic imaging models. Then, the XGBoost algorithm was applied to the six basic imaging models to construct a combined radiomic model. Finally, the radiomic model was combined with clinical information to create a nomogram that could easily be used in clinical practice to predict the thymoma risk category. The areas under the curve (AUCs) of the combined radiomic model in the training and validation cohorts were 0.999 (95% CI 0.988-1.000) and 0.967 (95% CI 0.916-1.000), respectively, while those of the nomogram were 0.999 (95% CI 0.996-1.000) and 0.983 (95% CI 0.990-1.000). This study describes the application of CT-based radiomics in thymoma patients and proposes a nomogram for predicting the risk category for this disease, which could be advantageous for clinical decision-making for affected patients.


Assuntos
Aprendizado de Máquina , Timoma , Neoplasias do Timo , Tomografia Computadorizada por Raios X , Humanos , Timoma/diagnóstico por imagem , Timoma/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/patologia , Adulto , Estudos Retrospectivos , Idoso , Medição de Risco/métodos , Algoritmos , Nomogramas , Radiômica
8.
Food Chem X ; 23: 101582, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39045224

RESUMO

Sweet potato pulp water (SPPW) is a kind of sweet potato starch processing by-product with rich nutrition but low utilization. The impacts of different proportions of Coriolus versicolor (C. versicolor, CV) fermented sweet potato pulp water (CV-SPPW) on the physicochemical, structural and metabolic properties of yogurt were investigated. Compared with 0% group, the hardness index, elasticity index and cohesion of the 10% sample group increased by 1.9-fold, 55.7% and 1.39-fold, respectively. When CV-SPPW was added at an amount of 10%, the microstructure and sensory scores of yogurts were considered as the optimal. Metabolic pathway analysis indicated that the changes of yogurts were mainly involved in sugar metabolism and amino acid metabolism, and that the carbohydrate metabolites produced mainly included cellobiose, maltitol, d-trehalose and d-maltose. The CV-SPPW improved the structural characteristics of yogurts to varying degrees and the fermented yogurts exhibited better viscosity properties.

10.
Sci Rep ; 14(1): 13577, 2024 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866828

RESUMO

Zinc finger MIZ-type containing 1 (ZMIZ1) is a transcriptional coactivator related to the protein inhibitors of activated STATs (PIAS) family. Mounting evidence suggests that ZMIZ1 plays a crucial role in the occurrence and development of cancers. The function of ZMIZ1 in tongue squamous cell carcinoma (TSCC) and the mechanisms underpinning its role in this disease have not been fully clarified. We performed qualitative ZMIZ1 protein expression analyses using immunohistochemistry in 20 patient-derived, paraffin-embedded TSCC tissue sections. We used RNAi to knock down ZMIZ1 expression in the CAL-27 TSCC cell line and quantified the impact of ZMIZ1 knock down on proliferation, migration and apoptosis via CCK-8, scratch assay and flow cytometry, respectively. We used qRT-PCR and western blotting to investigate the role of ZMIZ1 in this cell line. Finally, we established a model of lung metastasis in nude mice to replicate the in vitro results. ZMIZ1 protein was significantly more abundant in TSCC case tissue samples. ZMIZ1 knockdown reduced the invasion and metastases of TSCC tumor cells and promoted apoptosis. ZMIZ1 knockdown was associated with the down-regulation of Notch signaling pathway related factors Jagged1 and Notch1, and invasion and metastasis related factors MKP-1, SSBP2 and MMP7 in vitro and in vivo, at the mRNA level. In vitro and in vivo data suggest that knock down of ZMIZ1 may inhibit TSCC invasion and metastasis by modulating Notch signaling. ZMIZ1 inhibition may therefore represent a new therapeutic target for TSCC.


Assuntos
Apoptose , Carcinoma de Células Escamosas , Proliferação de Células , Receptor Notch1 , Transdução de Sinais , Neoplasias da Língua , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Proteína Jagged-1/metabolismo , Proteína Jagged-1/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Camundongos Nus , Receptor Notch1/metabolismo , Receptor Notch1/genética , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia , Neoplasias da Língua/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Ensaios Antitumorais Modelo de Xenoenxerto
11.
J Hazard Mater ; 476: 134967, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38936190

RESUMO

Hg2+ contamination poses a serious threat to the environment and human health. Although gold nanoclusters (Au NCs) have been utilized as fluorescence probes or colorimetric nanozymes for performing Hg2+ assays by using a single method, designing multifunctional nanoclusters as fluorescent nanozyme remains challenging. Herein, Ce-aggregated gold nanoclusters (Ce-Au NCs) were reported with "three in one" functions to generate strong fluorescence, excellent peroxidase-like activity, and the highly specific recognition of Hg2+ via its metallophilic interaction. A portable fluorescence and colorimetric dual-mode sensing device based on Ce-Au NCs was developed for on-site visual analysis of Hg2+. In the presence of Hg2+, fluorescence was effectively quenched and the paper-based chips gradually darkened from green till they became completely absent, while peroxidase-like activity was significantly enhanced. Two independent signals were captured by one identification unit, which provided self-validation to improve reliability and accuracy. Therefore, this work presents a simple synthesis of a multifunctional fluorescent nanozyme, and the developed portable device for on-site visual detection has considerable potential for application in the rapid on-site analysis of heavy metal ions in the environment.


Assuntos
Cério , Corantes Fluorescentes , Ouro , Mercúrio , Nanopartículas Metálicas , Mercúrio/análise , Mercúrio/química , Ouro/química , Nanopartículas Metálicas/química , Cério/química , Corantes Fluorescentes/química , Colorimetria/métodos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Espectrometria de Fluorescência , Fluorescência
12.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124695, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38936212

RESUMO

The extraction process plays a crucial role in the production of Tibetan medicines. This study focused on assembling a set of online near-infrared (NIR) spectroscopy detection devices for the extraction of medicinal herbs. The original infrared device was transformed into an online detection system. After evaluating the stability of the system, we applied online NIR spectroscopy monitoring to the flavonoid contents (total flavonoids, quercetin-3-O-sophoroside, and luteolin) of Meconopsis quintuplinervia Regel. during the ultrasonic extraction process and determined the extraction endpoint. Nine batches of samples were employed to construct quantitative and discriminant models, half of the remaining two batches of samples are used for external verification. Our research shows that the residual predictive deviation (RPD) values of total flavonoids, quercetin-3-O-sophoroside and luteolin models exceeded 2.5. The R values for external verification of the three ingredients were above 0.9, with RPD values generally exceeding 2 and RSEP values within 10 %, demonstrating the model's strong predictive performance. Most of the extraction endpoints of the flavonoid components in M. quintuplinervia ranged from 18 to 58 min, with high consistency between the predicted extraction endpoints of the external validation, suggesting accurate determination of extraction endpoints based on predicted values. This study can provide a reference for the online NIR spectroscopy quality monitoring of the extraction process of Chinese and Tibetan herbs.


Assuntos
Flavonoides , Medicina Tradicional Tibetana , Espectroscopia de Luz Próxima ao Infravermelho , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Flavonoides/análise , Flavonoides/isolamento & purificação , Quimiometria/métodos
13.
J Proteome Res ; 23(7): 2323-2331, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38865581

RESUMO

The Chromosome-Centric Human Proteome Project (C-HPP) aims to identify all proteins encoded by the human genome. Currently, the human proteome still contains approximately 2000 PE2-PE5 proteins, referring to annotated coding genes that lack sufficient protein-level evidence. During the past 10 years, it has been increasingly difficult to identify PE2-PE5 proteins in C-HPP approaches due to the limited occurrence. Therefore, we proposed that reanalyzing massive MS data sets in repository with newly developed algorithms may increase the occurrence of the peptides of these proteins. In this study, we downloaded 1000 MS data sets via the ProteomeXchange database. Using pFind software, we identified peptides referring to 1788 PE2-PE5 proteins. Among them, 11 PE2 and 16 PE5 proteins were identified with at least 2 peptides, and 12 of them were identified using 2 peptides in a single data set, following the criteria of the HPP guidelines. We found translation evidence for 16 of the 11 PE2 and 16 PE5 proteins in our RNC-seq data, supporting their existence. The properties of the PE2 and PE5 proteins were similar to those of the PE1 proteins. Our approach demonstrated that mining PE2 and PE5 proteins in massive data repository is still worthy, and multidata set peptide identifications may support the presence of PE2 and PE5 proteins or at least prompt additional studies for validation. Extremely high throughput could be a solution to finding more PE2 and PE5 proteins.


Assuntos
Bases de Dados de Proteínas , Proteoma , Software , Humanos , Proteoma/análise , Proteoma/genética , Algoritmos , Espectrometria de Massas/métodos , Proteômica/métodos , Peptídeos/genética , Peptídeos/análise , Peptídeos/química , Genoma Humano
14.
J Adv Res ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38750695

RESUMO

INTRODUCTION: Crohn's Disease (CD) is a chronic inflammatory condition characterized by intestinal fibrosis, severely impacting patient quality of life. The molecular mechanisms driving this fibrosis remain inadequately understood. Recent evidence implicates mesenteric adipose tissue (MAT) in CD pathogenesis, particularly through its exosome secretion, which may influence fibrogenic pathways. Understanding the role of MAT-derived exosomes is crucial for unraveling these molecular processes. OBJECTIVES: This study aims to elucidate the role of MAT-derived exosomes in CD-related intestinal fibrosis. We focus on investigating their molecular composition and the potential impact on fibrosis progression, with an emphasis on identifying novel therapeutic targets. METHODS: We induced chronic intestinal inflammation in mice using dinitrobenzene sulfonic acid (DNBS), simulating CD-like fibrosis. Exosomes were isolated from DNBS-treated mice (MG) and normal controls (NG) for characterization using electron microscopy and proteomic analysis. Additionally, human colonic fibroblasts were exposed to exosomes from CD patients and healthy individuals, with subsequent assessment of fibrogenesis through proteomic and RNA sequencing analyses. RESULTS: Proteomic analyses revealed a significant activation of the TGF-ß signaling pathway in MG-treated mice compared to controls, correlating with enhanced intestinal fibrosis. In vitro experiments demonstrated that colonic fibroblasts exposed to CD patient-derived exosomes exhibited increased fibrogenic activity. Protein docking and co-immunoprecipitation studies suggested a critical interaction between TINAGL1 and SMAD4, enhancing fibrosis. Importantly, in vivo experiments corroborated that recombinant TINAGL1 protein exacerbated DNBS-induced intestinal fibrosis. CONCLUSION: Our findings highlight the pivotal role of MAT-derived exosomes, particularly those carrying TINAGL1, in the progression of intestinal fibrosis in CD. The involvement of the TGF-ß signaling pathway, especially the SMAD4 protein, offers new insights into the molecular mechanisms of CD-related fibrosis and presents potential targets for therapeutic intervention.

15.
Transl Stroke Res ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38740617

RESUMO

Stroke in China is distinguished by its high rates of morbidity, recurrence, disability, and mortality. The ultra-early administration of rtPA is essential for restoring perfusion in acute ischemic stroke, though it concurrently elevates the risk of hemorrhagic transformation. High-mobility group box 1 (HMGB1) emerges as a pivotal player in neuroinflammation after brain ischemia and ischemia-reperfusion. Released passively by necrotic cells and actively secreted, including direct secretion of HMGB1 into the extracellular space and packaging of HMGB1 into intracellular vesicles by immune cells, glial cells, platelets, and endothelial cells, HMGB1 represents a prototypical damage-associated molecular pattern (DAMP). It is intricately involved in the pathogenesis of atherosclerosis, thromboembolism, and detrimental inflammation during the early phases of ischemic stroke. Moreover, HMGB1 significantly contributes to neurovascular remodeling and functional recovery in later stages. Significantly, HMGB1 mediates hemorrhagic transformation by facilitating neuroinflammation, directly compromising the integrity of the blood-brain barrier, and enhancing MMP9 secretion through its interaction with rtPA. As a systemic inflammatory factor, HMGB1 is also implicated in post-stroke depression and an elevated risk of stroke-associated pneumonia. The role of HMGB1 extends to influencing the pathogenesis of ischemia by polarizing various subtypes of immune and glial cells. This includes mediating excitotoxicity due to excitatory amino acids, autophagy, MMP9 release, NET formation, and autocrine trophic pathways. Given its multifaceted role, HMGB1 is recognized as a crucial therapeutic target and prognostic marker for ischemic stroke and hemorrhagic transformation. In this review, we summarize the structure and redox properties, secretion and pathways, regulation of immune cell activity, the role of pathophysiological mechanisms in stroke, and hemorrhage transformation for HMGB1, which will pave the way for developing new neuroprotective drugs, reduction of post-stroke neuroinflammation, and expansion of thrombolysis time window.

16.
J Ethnopharmacol ; 332: 118362, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38768838

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In ancient times, ginseng was used for hyperuricemia treatment as described in the classic traditional Chinese medical text Shang Han Lun. Recent studies have shown that common ginsenosides and rare ginsenosides (RGS) are the main active compounds in ginseng. RGS have higher activity and are less studied in the treatment of hyperuricemia. AIM OF THE STUDY: To determine whether RGS prevents and ameliorates potassium oxonate(PO)-induced hyperuricemia and concomitant spermatozoa damage in mice and the possible underlying mechanisms. MATERIALS AND METHODS: Potassium oxonate (PO, 300 mg/kg) induced hyperuricemia in mice via the oral administration of RGS (50, 100, or 200 mg/kg) or allopurinol (ALL, 5 mg/kg) for 35 days. Uric acid (UA) and xanthine oxidase (XO) levels were measured to assess the degree of histopathological damage in the liver, kidney, and testis, and renal creatinine (CRE), urea nitrogen (BUN), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and inflammatory factor (IL-1ß) levels were measured to calculate the sperm density. Mechanisms were also explored based on blood and urine metabolomics and the gut microbiota. RESULTS: In this study, we demonstrated that RGS containing Rg3, Rk1, Rg6, and Rg5 could reduce serum UA levels, inhibit serum and hepatic XO activity, reduce renal CRE and BUN levels, further restore renal SOD and GSH activities, reduce the accumulation of MDA in the kidneys, and attenuate the production of renal IL-1ß. RGS was able to restore sperm density. Metabolomic analysis revealed that RGS improved sphingolipid metabolism, pyrimidine metabolism, and other metabolic pathways. 16S rDNA sequencing revealed that RGS could increase gut microbial diversity, restore the Firmicutes/Bacteroidetes (F/B) ratio, and adjust the intestinal microbial balance. Spearman's correlation analysis revealed a correlation between differentially metabolites and the gut microbiota. Lactobacillus and Akkermansia are the core genera. CONCLUSION: RGS can be a candidate for the prevention and amelioration of hyperuricemia and concomitant sperm damage. Its mechanism of action is closely related to sphingolipid metabolism, pyrimidine metabolism, and the modulation of gut microbiota, such as Lactobacillus and Akkermansia.


Assuntos
Microbioma Gastrointestinal , Ginsenosídeos , Hiperuricemia , Metabolômica , Espermatozoides , Animais , Masculino , Hiperuricemia/tratamento farmacológico , Ginsenosídeos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Camundongos , Ácido Oxônico , Xantina Oxidase/metabolismo , Ácido Úrico/sangue , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia
17.
Small ; 20(28): e2310642, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38708896

RESUMO

Neutral electrolysis to produce hydrogen is prime challenging owing to the sluggish kinetics of water dissociation for the electrochemical reduction of water to molecular hydrogen. An ion-enriched electrode/electrolyte interface for electrocatalytic reactions can efficiently obtain a stable electrolysis system. Herein, we found that interfacial accumulated fluoride ions and the anchored Pt single atoms/nanoparticles in catalysts can improve hydrogen evolution reaction (HER) activity of NiFe-based hydroxide catalysts, prolonging the operating stability at high current density in neutral conditions. NiFe hydroxide electrode obtains an outstanding performance of 1000 mA cm-2 at low overpotential of 218 mV with 1000 h operation at 100 mA cm-2. Electrochemical experiments and theoretical calculations have demonstrated that the interfacial fluoride contributes to promote the adsorption of Pt to proton for sustaining a large current density at low potential, while the Pt single atoms/nanoparticles provide H adsorption sites. The synergy effect of F and Pt species promotes the formation of Pt─H and F─H bonds, which accelerate the adsorption and dissociation process of H2O and promote the HER reaction with a long-term durability in neutral conditions.

18.
Food Chem X ; 22: 101376, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38665636

RESUMO

The aim of this study was to investigate the effect of Ganoderma lucidum fermentation on antioxidant and anti-glycemic activities of Tartary buckwheat. Xylanase, total cellulase (CMCase and FPase) and ß-glucosidase in fermented Tartary buckwheat (FB) increased significantly to 242.06 U/g, 17.99 U/g and 8.67 U/g, respectively. And the polysaccharides, total phenols, flavonoids and triterpenoids, which is increased by 122.19%, 113.70%, 203.74%, and 123.27%, respectively. Metabolite differences between non-fermented Tartary buckwheat (NFB) and FB pointed out that 445 metabolites were substantially different, and were involved in related biological metabolic pathways. There was a considerable rise in the concentrations of hesperidin, xanthotoxol and quercetin 3-O-malonylglucoside by 240.21, 136.94 and 100.77 times (in Fold Change), respectively. The results showed that fermentation significantly increased the antioxidant and anti-glycemic activities of buckwheat. This study demonstrates that the fermentation of Ganoderma lucidum provides a new idea to enhance the health-promoting components and bioactivities of Tartary buckwheat.

19.
Talanta ; 275: 126086, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38663071

RESUMO

Laser-induced breakdown spectroscopy (LIBS), as an elemental composition analysis technique, has many unique advantages and great potential for applications in water detection. However, the quality of LIBS spectral signals, such as signal-to-noise ratio and stability, is often poor due to the matrix effects of water, limiting its practical performance. To effectively remove the inherent weak radiation in experimental spectral data that can be easily mistaken for noise, this paper proposes a denoising algorithm for processing spectral data using a self-built blank sample spectral database of deionized water samples, and designs a complete data processing workflow. It includes steps such as blank sample data screening, internal standard correction, blank sample correction, and spectral smoothing. Against the backdrop of marine applications, experimental spectral data for target elements Na, Mg, Ca, K, Sr, and Li were processed with this algorithm. The results show that after algorithm processing, the spectral quality was significantly improved, with the signal-to-noise ratio and detection limits of various elements improved by at least one order of magnitude. The signal-for Li increased by up to 36 times, and the detection limit for K decreased by up to 25.2 times. Additionally, tiny spectral peaks that could not be observable in the original spectral data could be effectively extracted after processing. From a technical implementation perspective, the database establishment and data process are simple and practical, with universal applicability. Therefore, this method has good potential and wide foregrounds in many other water sample LIBS detection technologies.

20.
Brain Behav ; 14(2): e3413, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38578197

RESUMO

OBJECTIVES: Early detection of cognitive impairment is essential for timely intervention. Currently, most widely used cognitive screening tests are influenced by language and cultural differences; therefore, there is a need for the development of a language-neutral, visual-based cognitive assessment tool. The Visual Cognitive Assessment Test (VCAT), a 30-point test that assesses memory, executive function, visuospatial function, attention, and language, has demonstrated its utility in a multilingual population. In this study, we evaluated the reliability, validity, and diagnostic performance of the VCAT for screening early cognitive impairment in Chongqing, China METHODS: A total of 134 individuals (49 healthy controls (HCs), 52 with mild cognitive impairment (MCI), and 33 with mild dementia) completed the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), VCAT, and domain-specific neuropsychological assessments. The diagnostic performances of MMSE, MoCA, and VCAT were evaluated using the area under the curve (AUC), sensitivity, and specificity. Construct validity of the VCAT was assessed with well-established domain-specific cognitive assessments. Reliability was measured using Cronbach's alpha. RESULTS: The VCAT and its subdomains demonstrated both good construct validity and internal consistency (α = 0.577). The performance of VCAT was comparable to that of MoCA and MMSE in differentiating mild dementia from nondemented groups (AUC: 0.940 vs. 0.902 and 0.977, respectively; p = .098 and .053) and in distinguishing cognitive impairment (CI) from HC (AUC: 0.929 vs. 0.899 and 0.891, respectively; p = .239 and .161), adjusted for education level. The optimal score range for VCAT in determining dementia, MCI, and HC was 0-14, 15-19, and 20-30, respectively. CONCLUSION: The VCAT proves to be a reliable screening test for early cognitive impairment within our cohort. Being both language and cultural neutral, the VCAT has the potential to be utilized among a wider population within China.


Assuntos
Disfunção Cognitiva , Demência , Humanos , Reprodutibilidade dos Testes , Disfunção Cognitiva/psicologia , Demência/diagnóstico , Demência/epidemiologia , Testes Neuropsicológicos , Cognição
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