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1.
Am J Transl Res ; 16(1): 190-199, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322577

RESUMO

OBJECTIVE: To explore the effects of positional care combined with doula delivery during childbirth in the correction of abnormal fetal position. METHODS: In this retrospective study, a total 108 pregnant women with abnormal fetal orientation were included from February 2018 to February 2021 in the Jinan City People's Hospital. Among them, 54 patients who received positional care combined with doula delivery were included in the intervention group (IG), while the other 54 patients who received routine nursing were included in the control group (CG). The data of the fetal orientation correction, delivery method and the pain score of puerpera of two groups were collected. The length of delivery, delivery fear score, the degree of neonatal asphyxia and nursing satisfaction were observed as the secondary outcomes. RESULTS: Compared with the CG, puerpera in the IG had more occipital anterior position, less occipital transverse and posterior position, higher eutocia rate, lower pain and fear scores and shorter length of delivery; the Apgar score and nursing satisfaction were higher in the IG (all P<0.05). CONCLUSION: Positional care combined with doula delivery can effectively correct abnormal fetal orientation, improve the rate of eutocia, reduce puerpera's pain and fear, shorten the length of delivery, and improve the quality of neonatal outcome and patients' satisfaction.

2.
Front Pharmacol ; 15: 1297927, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318140

RESUMO

Background: The economic impact of Complex Regional Pain Syndrome (CRPS) on both patients and the global healthcare system continues to escalate. However, the economic implications associated with management interventions for CRPS have received limited attention. Therefore, our objective is to perform a thorough examination of published economic assessments of the various management strategies utilized for CRPS. Methods: A thorough search spanning four general medical databases and three health economic databases to identify full economic evaluations on CRPS management strategies from January 1994 to June 2023 were conducted. The quality of these studies were evaluated by employing the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. To enable cross-study comparisons conducted in different countries, we adjusted the costs reported in the selected studies for inflation and converted them into 2023 US dollars. Results: A total of nine economic evaluations, consisting of eight high-quality and one medium-quality, were identified across five nations during a span of 29 years. The findings suggest that the most economically efficient intervention for CRPS are interventional approaches of Spinal Cord Stimulation (SCS) in comparison to conventional management for long periods of time. Furthermore, in situations where there is a limited time period of less than 1 year, rehabilitation therapies, particularly physical therapy, have been demonstrated to be more effective in terms of both cost and clinical outcomes. Conclusion: The interventional management strategies, particularly for severe and persistent CRPS over long periods, may offer the greatest cost efficiency. In conditions with limited timelines, rehabilitation measures, such as rehabilitation therapies, can be cost-effective. However, insufficient data for other common interventions prevents the formation of a definitive conclusion. Similarly, it is crucial to recognize that the results of these interventions might be affected by the selection of comparator and the threshold for willingness to pay.

3.
Cell Signal ; 117: 111077, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38311301

RESUMO

BACKGROUND: The exhaustion of T-cells is a primary factor contributing to immune dysfunction in cancer. Long non-coding RNAs (lncRNAs) play a significant role in the advancement, survival, and treatment of Uterine Corpus Endometrial Carcinoma (UCEC). Nevertheless, there has been no investigation into the involvement of lncRNAs associated with T-cell exhaustion (TEXLs) in UCEC. The goal of this work is to establish predictive models for TEXLs in UCEC and study their related immune features. METHODS: Using transcriptome and single-cell sequencing data from The Cancer Genome Atlas and Gene Expression Omnibus databases, we employed co-expression analysis and univariate Cox regression to identify prognostic-associated TEXLs (pTEXLs). The prognostic model was developed using the Least Absolute Contraction and Selection Operator. The immunotherapy characteristics of the prognostic model risk score were studied. Then molecular subgroups were identified through non-negative Matrix Factorization based on pTEXLs. The identification of co-expressed genes was done using a weighted correlation network analysis. Subsequently, a diagnostic model for UCEC was created. In-depth investigations, both in vitro and in vivo, were carried out to elucidate the molecular mechanism of the key gene within the diagnostic model. RESULTS: Receiver operating characteristic curve, calibration curve, and decision curve analysis proved the validity of the predictive models established according to pTEXLs. The subgroup with lower risk scores in the prognostic model has better responses to blocking immune checkpoint therapy. Single-cell analysis suggests that the expression level of MIEN1 is relatively high in immune cells among diagnostic genes. Furthermore, the targeted suppression of MIEN1 via sh-MIEN1 diminishes the proliferative, migratory, and invasive capacities of UCEC cells, potentially associated with CD8+ T cell exhaustion. CONCLUSIONS: The association between TEXLs and UCEC was methodically elucidated by our investigation. A stable pTEXLs risk prediction model and a diagnosis model for UCEC were also established.

4.
Mol Biotechnol ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38305844

RESUMO

Aptamers, as a kind of small-molecule nucleic acid, have attracted much attention since their discovery. Compared with biological reagents such as antibodies, aptamers have the advantages of small molecular weight, low immunogenicity, low cost, and easy modification. At present, aptamers are mainly used in disease biomarker discovery, disease diagnosis, treatment, and targeted drug delivery vectors. In the process of screening and optimizing aptamers, it is found that there are still many problems need to be solved such as the design of the library, optimization of screening conditions, the truncation of screened aptamer, and the stability and toxicity of the aptamer. In recent years, the incidence of liver-related diseases is increasing year by year and the treatment measures are relatively lacking, which has attracted the people's attention in the application of aptamers in liver diseases. This article mainly summarizes the research status of aptamers in disease diagnosis and treatment, especially focusing on the application of aptamers in liver diseases, showing the crucial significance of aptamers in the diagnosis and treatment of liver diseases, and the use of Discovery Studio software to find the binding target and sequence of aptamers, and explore their possible interaction sites.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38349827

RESUMO

When decoding neuroelectrophysiological signals represented by Magnetoencephalography (MEG), deep learning models generally achieve high predictive performance but lack the ability to interpret their predicted results. This limitation prevents them from meeting the essential requirements of reliability and ethical-legal considerations in practical applications. In contrast, intrinsically interpretable models, such as decision trees, possess self-evident interpretability while typically sacrificing accuracy. To effectively combine the respective advantages of both deep learning and intrinsically interpretable models, an MEG transfer approach through feature attribution-based knowledge distillation is pioneered, which transforms deep models (teacher) into highly accurate intrinsically interpretable models (student). The resulting models provide not only intrinsic interpretability but also high predictive performance, besides serving as an excellent approximate proxy to understand the inner workings of deep models. In the proposed approach, post-hoc feature knowledge derived from post-hoc interpretable algorithms, specifically feature attribution maps, is introduced into knowledge distillation for the first time. By guiding intrinsically interpretable models to assimilate this knowledge, the transfer of MEG decoding information from deep models to intrinsically interpretable models is implemented. Experimental results demonstrate that the proposed approach outperforms the benchmark knowledge distillation algorithms. This approach successfully improves the prediction accuracy of Soft Decision Tree by a maximum of 8.28%, reaching almost equivalent or even superior performance to deep teacher models. Furthermore, the model-agnostic nature of this approach offers broad application potential.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38353494

RESUMO

BACKGROUND: Racial and ethnic disparities exist in the outcomes following surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). However, it is unclear whether hospital racial composition contributes to these racial disparities. METHODS: We analyzed the National Inpatient Sample (NIS) database from 2015 to 2019 to identify patients with aortic stenosis (AS) who received SAVR and TAVI. The Racial/Ethnic Diversity Index (RDI) was used to assess hospital racial composition as the proportion of nonwhite patients to total hospital admissions. Hospitals were categorized into RDI quintiles. Textbook outcome (TO) was defined as no in-hospital mortality, no postoperative complications and no prolonged length of stay (LOS). Multivariable mixed generalized linear models were conducted to assess the association between RDI and post-SAVR and post-TAVI outcomes. Moreover, quantile regression was used to assess the additional cost and length of stay associated with the RDI quintile. RESULTS: The study included 82,502 SAVR or TAVI performed across 3285 hospitals, with 47.4% isolated SAVR and 52.5% isolated TAVI. After adjustment, quintiles 4 and 5 demonstrated significantly lower odds of TO than the lowest RDI quintile in both the SAVR cohort (quintile 4, 0.79 [95% CI, 0.73-0.85]; quintile 5, 0.79 [95% CI, 0.73-0.86]) and TAVI cohort (quintile 4, 0.88 [95% CI, 0.82-0.95]; quintile 5, 0.80 [95% CI, 0.74-0.86]). Despite non-observable differences in in-hospital mortality across all RDI quintiles, the rate of AKI and blood transfusion increased with increasing RDI for both cohorts. Further, Higher RDI quintiles were associated with increased costs and longer LOS. From 2015 to 2019, post-TAVI outcomes improved across all RDI quintiles. CONCLUSIONS: Hospitals with a higher RDI experienced lower TO achievements, increased AKI, and blood transfusion, along with extended LOS and higher costs. Importantly, post-TAVI outcomes improved from 2015 to 2019 across all RDI groups.

7.
J Hazard Mater ; 466: 133648, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38306835

RESUMO

The precise identification viable pathogens hold paramount significance in the prevention of foodborne diseases outbreaks. In this study, we integrated machine vision and learning with single microsphere to develop a phage and Clostridium butyricum Argonaute (CbAgo)-mediated fluorescence biosensor for detecting viable Salmonella typhimurium (S. typhimurium) without convoluted DNA extraction and amplification procedures. Phage and lysis buffer was utilized to capture and lyse viable S. typhimurium, respectively. Subsequently, CbAgo can cleave the bacterial DNA to obtain target DNA that guides a newly targeted cleavage of fluorescent probes. After that, the resulting fluorescent signal accumulates on the streptavidin-modified single microsphere. The overall detection process is then analyzed and interpreted by machine vision and learning algorithms, achieving highly sensitive detection of S. typhimurium with a limit of detection at 40.5 CFU/mL and a linear range of 50-107 CFU/mL. Furthermore, the proposed biosensor demonstrates standard recovery rates and coefficients of variation at 93.22% - 106.02% and 1.47% - 12.75%, respectively. This biosensor exhibits exceptional sensitivity and selectivity, presenting a promising method for the rapid and effective detection of foodborne pathogens. ENVIRONMENTAL IMPLICATION: Bacterial pathogens exist widely in the environment and seriously threaten the safety of human life. In this study, we developed a phage and Clostridium butyricum Argonaute-mediated fluorescence biosensor for the detection of viable Salmonella typhimurium in environmental water and food samples. Compared with other Salmonella detection methods, this method does not need complex DNA extraction and amplification steps, which reduces the use of chemical reagents and experimental consumables in classic DNA extraction kit methods.


Assuntos
Técnicas Biossensoriais , Humanos , Técnicas Biossensoriais/métodos , Salmonella typhimurium/genética , Alimentos , DNA , DNA Bacteriano/genética
8.
Neurochem Res ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38366208

RESUMO

Spinal cord injury (SCI) encompasses various pathological processes, notably neuroinflammation and apoptosis, both of which play significant roles. CTLA-4, a well-known immune molecule that suppresses T cell-mediated immune responses, is a key area of research and a focal point for targeted therapy development in treating tumors and autoimmune disorders. Despite its prominence, the impact of CTLA-4 inhibition on inflammation and apoptosis subsequent to SCI remains unexplored. This study aimed to investigate the influence of CTLA-4 on SCI. A weight-drop technique was used to establish a rat model of SCI. To examine the safeguarding effect of CTLA-4 on the restoration of motor function in rats with SCI, the Basso-Beattie-Bresnahan (BBB) scale and inclined plane test were employed to assess locomotion. Neuronal degeneration and apoptosis were assessed using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and Fluoro-Jade B labeling, respectively, and the activity of microglial cells was examined by immunofluorescence. To evaluate the impact of CTLA4 on SCI, the levels of inflammatory markers were measured. After treatment with the CTLA-4 inhibitor ipilimumab, the rats showed worse neurological impairment and more severe neuroinflammation after SCI. Furthermore, the combination therapy with ipilimumab and durvalumab after SCI had more pronounced effects than treatment with either inhibitor alone. These findings indicate that CTLA-4 contributes to neuroinflammation and apoptosis after SCI, presenting a promising new therapeutic target for this traumatic condition.

9.
Carcinogenesis ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38366384

RESUMO

In recent decades, considerable evidence has emerged indicating the involvement of tRNA-derived fragments (tRFs) in cancer progression through various mechanisms. However, the biological effects and mechanisms of tRFs in lung adenocarcinoma (LUAD) remain unclear. In this study, we screen out tRF-29-79, a 5'-tRF derived from tRNAGlyGCC, through profiling the tRF expressions in three pairs of LUAD tissues. We show that tRF-29-79 is down-regulated in LUAD and down-regulation of tRF-29-79 is associated with poorer prognosis. In vivo and in vitro assay reveal that tRF-29-79 inhibits proliferation, migration, and invasion of LUAD cells. Mechanistically, we discovered that tRF-29-79 interacts with the RNA-binding protein PTBP1 and facilitates the transportation of PTBP1 from nucleus to cytoplasm, which regulates alternative splicing in the 3' untranslated region (UTR) of SLC1A5 pre-mRNA. Given that SLC1A5 is a core transporter of glutamine, we proved that tRF-29-79 mediate glutamine metabolism of LUAD through affecting the stability of SLC1A5 mRNA, thus exerts its anticancer function. In summary, our findings uncover the novel mechanism that tRF-29-79 participates in glutamine metabolism through interacting with PTBP1 and regulating alternative splicing in the 3' UTR of SLC1A5 pre-mRNA.

10.
Nat Commun ; 15(1): 1409, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360850

RESUMO

The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis-expression quantitative trait loci (cis-eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression.


Assuntos
Artrite , Estudo de Associação Genômica Ampla , Humanos , Estudo de Associação Genômica Ampla/métodos , Predisposição Genética para Doença/genética , Regulação da Expressão Gênica , Cromatina/genética , Membrana Sinovial , Artrite/genética , Polimorfismo de Nucleotídeo Único
11.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385873

RESUMO

Lysine lactylation (Kla) is a newly discovered posttranslational modification that is involved in important life activities, such as glycolysis-related cell function, macrophage polarization and nervous system regulation, and has received widespread attention due to the Warburg effect in tumor cells. In this work, we first design a natural language processing method to automatically extract the 3D structural features of Kla sites, avoiding potential biases caused by manually designed structural features. Then, we establish two Kla prediction frameworks, Attention-based feature fusion Kla model (ABFF-Kla) and EBFF-Kla, to integrate the sequence features and the structure features based on the attention layer and embedding layer, respectively. The results indicate that ABFF-Kla and Embedding-based feature fusion Kla model (EBFF-Kla), which fuse features from protein sequences and spatial structures, have better predictive performance than that of models that use only sequence features. Our work provides an approach for the automatic extraction of protein structural features, as well as a flexible framework for Kla prediction. The source code and the training data of the ABFF-Kla and the EBFF-Kla are publicly deposited at: https://github.com/ispotato/Lactylation_model.


Assuntos
Lisina , Processamento de Linguagem Natural , Sequência de Aminoácidos , Domínios Proteicos , Processamento de Proteína Pós-Traducional
12.
Microbiol Spectr ; : e0234223, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38391229

RESUMO

Seed metabolites are the combination of essential compounds required by an organism across various potential environmental conditions. The seed metabolites screening framework based on the network topology approach can capture important biological information of species. This study aims to identify comprehensively the relationship between seed metabolites and pathogenic bacteria. A large-scale data set was compiled, describing the seed metabolite sets and metabolite sets of 124,192 pathogenic strains from 34 genera, by constructing genome-scale metabolic models. The enrichment analysis method was used to screen the specific seed metabolites of each species/genus of pathogenic bacteria. The metabolites of pathogenic microorganisms database (MPMdb) (http://qyzhanglab.hzau.edu.cn/MPMdb/) was established for browsing, searching, predicting, or downloading metabolites and seed metabolites of pathogenic microorganisms. Based on the MPMdb, taxonomic and phylogenetic analyses of pathogenic bacteria were performed according to the function of seed metabolites and metabolites. The results showed that the seed metabolites could be used as a feature for microorganism chemotaxonomy, and they could mirror the phylogeny of pathogenic bacteria. In addition, our screened specific seed metabolites of pathogenic bacteria can be used not only for further tapping the nutritional resources and identifying auxotrophies of pathogenic bacteria but also for designing targeted bactericidal compounds by combining with existing antimicrobial agents.IMPORTANCEMetabolites serve as key communication links between pathogenic microorganisms and hosts, with seed metabolites being crucial for microbial growth, reproduction, external communication, and host infection. However, the large-scale screening of metabolites and the identification of seed metabolites have always been the main technical bottleneck due to the low throughput and costly analysis. Genome-scale metabolic models have become a recognized research paradigm to investigate the metabolic characteristics of species. The developed metabolites of pathogenic microorganisms database in this study is committed to systematically predicting and identifying the metabolites and seed metabolites of pathogenic microorganisms, which could provide a powerful resource platform for pathogenic bacteria research.

13.
Front Endocrinol (Lausanne) ; 15: 1304512, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38379860

RESUMO

Background: Previous research has indicated a vital association between hypertension, intraocular pressure (IOP), and diabetic retinopathy (DR); however, the relationship has not been elucidated. In this study, we aim to investigate the causal association of hypertension, IOP, and DR. Methods: The genome-wide association study (GWAS) IDs for DR, hypertension, and IOP were identified from the Integrative Epidemiology Unit (IEU) Open GWAS database. There were 33,519,037 single-nucleotide polymorphisms (SNPs) and a sample size of 1,030,836 for DR. There were 16,380,466 SNPs and 218,754 participants in the hypertension experiment. There were 9,851,867 SNPs and a sample size of 97,465 for IOP. Univariable, multivariable, and bidirectional Mendelian randomization (MR) studies were conducted to estimate the risk of hypertension and IOP in DR. Moreover, causality was examined using the inverse variance weighted method, and MR results were verified by numerous sensitivity analyses. Results: A total of 62 SNPs at the genome-wide significance level were selected as instrumental variables (IVs) for hypertension-DR. The results of univariable MR analysis suggested a causal relationship between hypertension and DR and regarded hypertension as a risk factor for DR [p = 0.006, odds ratio (OR) = 1.080]. A total of 95 SNPs at the genome-wide significance level were selected as IVs for IOP-DR. Similarly, IOP was causally associated with DR and was a risk factor for DR (p = 0.029, OR = 1.090). The results of reverse MR analysis showed that DR was a risk factor for hypertension (p = 1.27×10-10, OR = 1.119), but there was no causal relationship between DR and IOP (p > 0.05). The results of multivariate MR analysis revealed that hypertension and IOP were risk factors for DR, which exhibited higher risk scores (p = 0.001, OR = 1.121 and p = 0.030, OR = 1.124, respectively) than those in univariable MR analysis. Therefore, hypertension remained a risk factor for DR after excluding the interference of IOP, and IOP was still a risk factor for DR after excluding the interference of hypertension. Conclusion: This study validated the potential causal relationship between hypertension, IOP, and DR using MR analysis, providing a reference for the targeted prevention of DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Oftalmopatias , Hipertensão , Humanos , Pressão Intraocular , Retinopatia Diabética/etiologia , Retinopatia Diabética/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Hipertensão/etiologia , Hipertensão/genética
14.
ACS Nano ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385433

RESUMO

The clinical treatment efficacy for implant-associated infections (IAIs), particularly those caused by Methicillin-resistant Staphylococcus aureus (MRSA), remains unsatisfactory, primarily due to the formation of biofilm barriers and the resulting immunosuppressive microenvironment, leading to the chronicity and recurrence of IAIs. To address this challenge, we propose a light-induced immune enhancement strategy, synthesizing BSA@MnO2@Ce6@Van (BMCV). The BMCV exhibits precise targeting and adhesion to the S. aureus biofilm-infected region, coupled with its capacity to catalyze oxygen generation from H2O2 in the hypoxic and acidic biofilm microenvironment (BME), promoting oxygen-dependent photodynamic therapy efficacy while ensuring continuous release of manganese ions. Notably, targeted BMCV can penetrate biofilms, producing ROS that degrade extracellular DNA, disrupting the biofilm structure and impairing its barrier function, making it vulnerable to infiltration and elimination by the immune system. Furthermore, light-induced reactive oxygen species (ROS) around the biofilm can lyse S. aureus, triggering bacterium-like immunogenic cell death (ICD), releasing abundant immune costimulatory factors, facilitating the recognition and maturation of antigen-presenting cells (APCs), and activating adaptive immunity. Additionally, manganese ions in the BME act as immunoadjuvants, further amplifying macrophage-mediated innate and adaptive immune responses and reversing the immunologically cold BME to an immunologically hot BME. We prove that our synthesized BMCV elicits a robust adaptive immune response in vivo, effectively clearing primary IAIs and inducing long-term immune memory to prevent recurrence. Our study introduces a potent light-induced immunomodulatory nanoplatform capable of reversing the biofilm-induced immunosuppressive microenvironment and disrupting biofilm-mediated protective barriers, offering a promising immunotherapeutic strategy for addressing challenging S. aureus IAIs.

15.
Int J Nanomedicine ; 19: 1629-1644, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38406605

RESUMO

Background: Dendrobium, with profound botanical importance, reveals a rich composition of bioactive compounds, including polysaccharides, flavonoids, alkaloids, and diverse amino acids, holding promise for skin regeneration. However, the precise mechanism remains elusive. Seeking a potent natural remedy for wound healing, exocyst vesicles were successfully isolated from Dendrobium. Aims of the Study: This investigation aimed to employ bioinformatics and in vivo experiments to elucidate target genes of Dendrobium-derived nanovesicles in skin wound healing, focusing on immune infiltration and senescence characteristics. Materials and Methods: C57 mice experienced facilitated wound healing through Dendrobium-derived nanovesicles (DDNVs). Bioinformatics analysis and GEO database mining identified crucial genes by intersecting immune-related, senescence-related, and PANoptosis-associated genes. The identified genes underwent in vivo validation. Results: DDNVs remarkably accelerated skin wound healing in C57 mice. Bioinformatics analysis revealed abnormal expression patterns of immune-related, senescence-related, and pan-apoptosis-related genes, highlighting an overexpressed IL-1ß and downregulated IL-18 in the model group, Exploration of signaling pathways included IL-17, NF-kappa B, NOD-like receptor, and Toll-like receptor pathways. In vivo experiments confirmed DDNVs' efficacy in suppressing IL-1ß expression, enhancing wound healing. Conclusion: Plant-derived nanovesicles (PDNV) emerged as a natural, reliable, and productive approach to wound healing. DDNVs uptake by mouse skin tissues, labeled with a fluorescent dye, led to enhanced wound healing in C57 mice. Notably, IL-1ß overexpression in immune cells and genes played a key role. DDNVs intervention effectively suppressed IL-1ß expression, accelerating skin wound tissue repair.


Assuntos
Dendrobium , Animais , Camundongos , Dendrobium/metabolismo , Cicatrização/genética , Pele/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais
16.
Small ; : e2400254, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38402432

RESUMO

Pyroptosis, a new mode of regulatory cell death, holds a promising prospect in tumor therapy. The occurrence of pyroptosis can trigger the release of damage-associated molecular patterns (DAMPs) and activate the antitumor immune response. Moreover, enhancing intracellular reactive oxygen species (ROS) generation can effectively induce pyroptosis. Herein, an integrated nanoplatform (hCZAG) based on zeolitic imidazolate framework-8 (ZIF-8) with Cu2+ and Zn2+ as active nodes and glucose oxidase (GOx) loading is constructed to evoke pyroptosis. GOx can effectively elevate intracellular hydrogen peroxide (H2 O2 ) levels to regulate the unfavorable tumor microenvironment (TME). Cu2+ can be reduced to Cu+ by endogenous overexpressed GSH and both Cu2+ and Cu+ can exert Fenton-like activity to promote ROS generation and amplify oxidative stress. In addition, the accumulation of Cu2+ leads to the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), thus resulting in cuproptosis. Notably, the outburst of ROS induced by hCZAG activates Caspase-1 proteins, leads to the cleavage of gasdermin D (GSDMD), and induces pyroptosis. Pyroptosis further elicits an adaptive immune response, leading to immunogenic cell death (ICD). This study provides effective strategies for triggering pyroptosis-mediated immunotherapy and achieving improved therapeutic effects.

17.
Eur J Med Chem ; 267: 116205, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38350361

RESUMO

In this study, a series of novel 4-Aryl-4H-chromene derivatives (D1-D31) were designed and synthesized by integrating quinoline heterocycle to crolibulin template molecule based on the strategy of molecular hybridization. One of these compounds D19 displayed positive antiproliferative activity against U87 cancer cell line (IC50 = 0.90 ± 0.03 µM). Compound D19 was verified as the microtubule-targeting agent through downregulating tubulin related genes of U87 cells, destroying the cytoskeleton of tubulins and interacting with the colchicine-binding site to inhibit the polymerization of tubulins by transcriptome analysis, immune-fluorescence staining, microtubule dynamics and EBI competition assays as well as molecular docking simulations. Moreover, compound D19 induced G2/M phase arrest, resulted in cell apoptosis and inhibited the migration of U87 cells by flow cytometry analysis and wound healing assays. Significantly, compound D19 dose-dependently inhibited the tumor growth of orthotopic glioma xenografts model (GL261-Luc) and effectively prolonged the survival time of mice, which were extremely better than those of positive drug temozolomide (TMZ). Compound D19 exhibited potent in vivo antivascular activity as well as no observable toxicity. Furthermore, the results of in silico simulation studies and P-gp transwell assays verified the positive correlation between compound D19's Blood-Brain Barrier (BBB) permeability and its in vivo anti-GBM activity. Overall, compound D19 can be used as a promising anti-GBM lead compound for the treatment of glioblastoma.


Assuntos
Antineoplásicos , Glioblastoma , Humanos , Camundongos , Animais , Glioblastoma/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia , Benzopiranos/farmacologia , Benzopiranos/uso terapêutico , Proliferação de Células
18.
J Phys Chem Lett ; 15(7): 1975-1984, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38346356

RESUMO

Colloidal quantum dots (QDs) consist of an inorganic core and organic surface ligands. Surface ligands play a dominant role in maintaining the colloidal stability of QDs and passivating the surface defects of QDs. However, the original ligands introduced in the synthetic process of QDs cannot meet the requirements for diverse applications; therefore, ligand exchanges with functional ligands are mandatory. Understanding the ligand exchange process requires a comprehensive combination of the concepts and techniques of surface chemistry. In this Perspective, the ligand exchange process is discussed in detail. Specifically, we elaborate on the thermodynamics that can reveal the feasibility and mechanism of ligand exchange. It depicts a critical physical picture of the surface of QDs along with the following ligand exchange.

19.
Water Res ; 253: 121270, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38359598

RESUMO

Sulfidated zero-valent iron (S-ZVI) is an attractive material of permeable reactive barriers (PRBs) for the remediation of contaminated groundwater. However, S-ZVI is prone to be passivated due to the oxidation of reactive and conductive iron sulfide (FeSx) shell and the formation of inactive and non-conductive ferric (hydr)oxides, which serve as electron transfer barriers to hinder the electron flow from Fe° core to contaminants. This study thus proposed a novel approach for in-situ reactivation and reuse of micronsized S-ZVI (S-mZVI) in PRB using sulfate-reducing bacteria (SRB) enriched culture to realize long-lasting remediation of Cr(VI)-contaminated groundwater. S-mZVI were passivated after reactions with Cr(VI) due to the formation of electron transfer barriers (mainly inactive and non-conductive Fe(III) (hyd)oxides, which increased the polarization resistance from 16.38 to 27.38 kΩ cm2 and hindered the electron transfer from the Fe° core. Interestingly, the passivated S-mZVI was efficiently reactivated by providing the SRB-enriched culture and organic carbon within 12 h, and the Cr(VI) removal capacity of S-mZVI in the three use cycles increased to 37.4 mg Cr/g, which was 2.1 times higher than that of the virgin S-mZVI. After biological reactivation, the Rp of reactivated S-mZVI decreased to 12.30 kΩ cm2. SRB-mediated reactivation removed the electron transfer barriers via biotic and abiotic reduction of Fe(III) (hyd)oxides. Especially, the microbial Fe(III) reduction mediated by FmnA-dmkA-fmnB-pplA-ndh2-eetAB-dmkB protein family enhanced the Fe2+ release from the surface and the subsequent re-formation of reactive and conductive FeSx shell. A long-term PRB column test further demonstrated the feasibility of in-situ biological reactivation and reuse of S-mZVI for enhanced Cr(VI)-contaminated groundwater remediation. Within 64 days, the Cr(VI) removal capacity of S-mZVI in the four use cycles increased by 3.2 times, compared to the virgin one. The bio-reactivation using the SRB-enriched culture and sulfate locally-available in groundwater will reduce the chemical and maintenance costs associated with the frequent replacement of reactive ZVI-based materials. The PRB technology based on the bio-renewable S-mZVI can be a sustainable alternative to the conventional PRBs for the long-lasting and low-cost remediation of groundwater contaminated by oxidative pollutants.

20.
Front Psychol ; 15: 1290233, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348248

RESUMO

Introduction: Moral disengagement is an essential concept in organizational behavioral ethics, as it is strongly related to employee behaviors and attitudes. What is not clear, however, is which leader traits are directly associated with employees' moral disengagement and which are indirectly associated with unethical behavior. This study draws on a social cognitive perspective that links leaders' other-oriented perfectionism (LOOP) with unethical employee behavior. Specifically, we propose that LOOP provides employees with excuses and encouragement to engage in unethical pro-organizational behavior (UPB). Methods: We analyzed data collected from 266 full-time employees at two-time points, and used mediated and moderated structural equation models to test the hypotheses, and the findings largely support our claims. Results: The results suggest that LOOP effectively promotes employees' involvement in UPB. Moderated mediation tests suggest that the positive indirect impact of LOOP on employees' unethical behavior via moral disengagement was attenuated by higher employees' moral identity. Discussion: In summary, the results indicate that when leaders emphasize only perfection and make unrealistic demands on their employees, the latter perceive that engaging in unethical behavior is demanded by the leader, that the responsibility is not theirs, and thus they are more willing to engage in unethical behavior. This study discusses the implications of these findings from both practical and theoretical perspectives.

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