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1.
Sci Total Environ ; 923: 171474, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38447734

RESUMO

Manganese (Mn), a common environmental and occupational risk factor for Parkinson's disease (PD), can cause central nervous system damage and gastrointestinal dysfunction. The melatonin has been shown to effectively improve neural damage and intestinal microbiota disturbances in animal models. This research investigated the mechanism by which exogenous melatonin prevented Mn-induced neurogenesis impairment and neural damage. Here, we established subchronic Mn-exposed mice model and melatonin supplement tests to evaluate the role of melatonin in alleviating Mn-induced neurogenesis impairment. Mn induced neurogenesis impairment and microglia overactivation, behavioral dysfunction, gut microbiota dysbiosis and serum metabolic disorder in mice. All these events were reversed with the melatonin supplement. The behavioral tests revealed that melatonin group showed approximately 30 % restoration of motor activity. According to quantitative real time polymerase chain reaction (qPCR) results, melatonin group showed remarkable restoration of the expression of dopamine neurons and neurogenesis markers, approximately 46.4 % (TH), 68.4 % (DCX in hippocampus) and 48 % (DCX in striatum), respectively. Interestingly, melatonin increased neurogenesis probably via the gut microbiota and metabolism modulation. The correlation analysis of differentially expressed genes associated with hippocampal neurogenesis indicated that Firmicutes-lipid metabolism might mediate the critical repair role of melatonin in neurogenesis in Mn-exposed mice. In conclusion, exogenous melatonin supplementation can promote neurogenesis, and restore neuron loss and neural function in Mn-exposed mice, and the multi-omics results provide new research ideas for future mechanistic studies.


Assuntos
Microbioma Gastrointestinal , Melatonina , Camundongos , Animais , Melatonina/farmacologia , Melatonina/metabolismo , Manganês/metabolismo , Hipocampo/metabolismo , Neurônios Dopaminérgicos
2.
Front Immunol ; 15: 1254162, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433827

RESUMO

Cancer immunotherapies using chimeric antigen receptor (CAR) T cells have tremendous potential and proven clinical efficacy against a number of malignancies. Research and development are emerging to deepen the knowledge of CAR T cell efficacy and extend the therapeutic potential of this novel therapy. To this end, functional characterization of CAR T cells plays a central role in consecutive phases across fundamental research and therapeutic development, with increasing needs for standardization. The functional characterization of CAR T cells is typically achieved by assessing critical effector functions, following co-culture with cell lines expressing the target antigen. However, the use of target cell lines poses several limitations, including alterations in cell fitness, metabolic state or genetic drift due to handling and culturing of the cells, which would increase variabilities and could lead to inconsistent results. Moreover, the use of target cell lines can be work and time intensive, and introduce significant background due to the allogenic responses of T cells. To overcome these limitations, we developed a synthetic bead-based platform ("Artificial Targets") to characterize CAR T cell function in vitro. These synthetic microparticles could specifically induce CAR T cell activation, as measured by CD69 and CD137 (4-1BB) upregulation. In addition, engagement with Artificial Targets resulted in induction of multiple effector functions of CAR T cells mimicking the response triggered by target cell lines including cytotoxic activity, as assessed by exposure of CD107a (LAMP-1), expression and secretion of cytokines, as well as cell proliferation. Importantly, in contrast to target cells, stimulation with Artificial Targets showed limited unspecific CAR T cell proliferation. Finally, Artificial Targets demonstrated flexibility to engage multiple costimulatory molecules that can synergistically enhance the CAR T cell function and represented a powerful tool for modulating CAR T cell responses. Collectively, our results show that Artificial Targets can specifically activate CAR T cells for essential effector functions that could significantly advance standardization of functional assessment of CAR T cells, from early development to clinical applications.


Assuntos
Micropartículas Derivadas de Células , Linhagem Celular , Proliferação de Células , Técnicas de Cocultura , Citocinas
3.
Contemp Clin Trials ; 140: 107505, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38521384

RESUMO

Oncology drug research in the last few decades has been driven by the development of targeted agents. In the era of targeted therapies, basket trials are often used to test the antitumor activity of a novel treatment in multiple indications sharing the same genomic alteration. As patient population are further fragmented into biomarker-defined subgroups in basket trials, novel statistical methods are needed to facilitate cross-indication learning to improve the statistical power in basket trial design. Here we propose a robust Bayesian model averaging (rBMA) technique for the design and analysis of phase II basket trials. We consider the posterior distribution of each indication (basket) as the weighted average of three different models which only differ in their priors (enthusiastic, pessimistic and non-informative). The posterior weights of these models are determined based on the effect of the experimental treatment in all the indications tested. In early phase oncology trials, different binary endpoints might be chosen for different indications (objective response, disease control or PFS at landmark times), which makes it even more challenging to borrow information across indications. Compared to previous approaches, the proposed method has the flexibility to support cross-indication learning in the presence of mixed endpoints. We evaluate and compare the performance of the proposed rBMA approach to competing approaches in simulation studies. R scripts to implement the proposed method are available at https://github.com/xwang317/rBMA.

4.
J Agric Food Chem ; 72(8): 4426-4432, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38353981

RESUMO

A pair of positively charged stable isotope labeling (SIL) agents, (4-carbonochloridoylphenyl)-trimethylazanium iodide (d0-CCPTA) and d6-CCPTA, were designed and synthesized. These agents were employed in the precolumn labeling of advanced glycation end products (AGEs) within 5 min under mild conditions. Through derivatization, the mass spectrometry response of the AGEs was enhanced by approximately 2 orders of magnitude. The detection and quantitation limits were in the ranges of 3.1-7.1 and 10.0-23.7 ng/kg, respectively. The recoveries were in the range of 90.1-94.3%, and the matrix effect ranged from -6.6 to -3.5%. CCPTA produced "CCPTA-specific production ions", and all analytes were analyzed by common multiple reaction monitoring (MRM) parameters. The common MRM parameters were applied to the semitarget analysis of 41 types of AGE candidates in the absence of standards, with 13 AGEs identified.


Assuntos
Produtos Finais de Glicação Avançada , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Marcação por Isótopo , Padrões de Referência
5.
Enzyme Microb Technol ; 175: 110408, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38309052

RESUMO

Alginate lyases with unique characteristics for degrading alginate into size-defined oligosaccharide fractions, were considered as the potential agents for disrupting Pseudomonas aeruginosa biofilms. In our study, a novel endolytic PL-7 alginate lyase, named AlyG2, was cloned and expressed through Escherichia coli. This enzyme exhibited excellent properties: it maintained more than 85% activity at low temperatures of 4 °C and high temperatures of 70 °C. After 1 h of incubation at 4 °C, it still retained over 95% activity, demonstrating the ability to withstand low temperature. The acid-base and salt tolerance properties shown it preserves more than 50% activity in the pH range of 5.0 to 11.0 and in a high salt environment at 3000 mM NacCl, indicating its high stability in several aspects. More importantly, AlyG2 in our research was revealed to be effective at removing mature biofilms and inhibiting biofilm formation produced by Pseudomonas aeruginosa, and the inhibition and disruption rates were 47.25 ± 4.52% and 26.5 ± 6.72%, respectively. Additionally, the enzyme AlyG2 promoted biofilm disruption in combination with antibiotics, particularly manifesting the synergistic effect with erythromycin (FIC=0.5). In all, these results offered that AlyG2 with unique characteristics may be an effective technique for the clearance or disruption of biofilm produced by P. aeruginosa.


Assuntos
Biofilmes , Flavobacteriaceae , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genética , Polissacarídeo-Liases/genética , Polissacarídeo-Liases/química , Alginatos
6.
J Microbiol Immunol Infect ; 57(2): 300-308, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38350840

RESUMO

PURPOSES: This study determined the synergy of polymyxin B (POLB) and colistin (COL) with 16 other tested antimicrobial agents in the inhibition of multidrug-resistant Acinetobacter baumannii (MDR-AB). METHODS: We used chequerboard assays to determine synergy between the drugs against 50 clinical MDR-AB from a tertiary hospital in the Zhejiang province in 2019, classifying combinations as either antagonistic, independent, additive, or synergistic. The efficacy of hit combinations which showed highest synergistic rate were confirmed using time-kill assays. RESULTS: Both POLB and COL displayed similar bactericidal effects when used in combination with these 16 tested drugs. Antagonism was only observed for a few strains (2%) exposed to a combination of POLB and cefoperazone/sulbactam (CSL). A higher percentage of synergistic combinations with POLB and COL were observed with rifabutin (RFB; 90%/96%), rifampicin (RIF; 60%/78%) and rifapentine (RFP; 56%/76%). Time-kill assays also confirmed the synergistic effect of POLB and rifamycin class combinations. 1/2 MIC rifamycin exposure can achieve bacterial clearance when combined with 1/2 MIC POLB or COL. CONCLUSION: Nearly no antagonism was observed when combining polymyxins with other drugs by both chequerboard and time-kill assays, suggesting that polymyxins may be effective in combination therapy. The combinations of POLB/COL with RFB, RIF, and RFP displayed neat synergy, with RFB showing the greatest effect.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Humanos , Colistina/farmacologia , Colistina/uso terapêutico , Polimixina B/farmacologia , Sinergismo Farmacológico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla
7.
Inflammation ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38316671

RESUMO

Chronic asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Previous studies have shown that mesenchymal stromal/stem cells (MSCs) exert anti-inflammatory effects on asthma via regulation of the immune cells. However, the therapeutic mechanism of MSCs, especially the mechanism of airway remodeling in chronic asthma, remains to be elucidated. Here, we aimed to investigate the therapeutic effect of MSCs on airway remodeling in chronic asthma and explored the mechanisms by analyzing the polarization phenotype of macrophages in the lungs. We established a mouse model of chronic asthma induced by ovalbumin (OVA) and evaluated the effect of MSCs on airway remodeling. The data showed that MSCs treatment before the challenge exerted protective effects on OVA-induced chronic asthma, i.e., decreased the inflammatory cell infiltration, Th2 cytokine levels, subepithelial extracellular matrix deposition, and transforming growth factor ß (TGF-ß)/Smad signaling. Additionally, we found that MSCs treatment markedly suppressed macrophage M2 polarization in lung tissue. At the same time, MSCs treatment inhibited NF-κB p65 nuclear translocation, ER stress, and oxidative stress in the OVA-induced chronic allergic airway remodeling mice model. In conclusion, these results demonstrated that MSCs treatment prevents OVA-induced chronic airway remodeling by suppressing macrophage M2 polarization, which may be associated with the dual inhibition of ER stress and oxidative stress. This discovery may provide a new theoretical basis for the future clinical application of MSCs.

8.
J Environ Sci (China) ; 140: 157-164, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38331497

RESUMO

Homogenous molecular photocatalysts for CO2 reduction, especially metal complex-based photosensitizer‒catalyst assemblages, have been attracting extensive research interests due to their efficiency and customizability. However, their low durability and recyclability limit practical applications. In this work, we immobilized the catalysts of metal terpyridyl complexes and the photosensitizer of [Ru(bpy)3]Cl2 onto the surface of carbon nanotubes through covalent bonds and electrostatic interactions, respectively, transforming the homogeneous system into a heterogeneous one. Our characterizations prove that these metal complexes are well dispersed on CNTs with a high loading (ca. 12 wt.%). Photocatalytic measurements reveal that catalytic activity is remarkably enhanced when the molecular catalysts are anchored, which is three times higher than that of homogeneous molecular catalysts. Moreover, when the photosensitizer of [Ru(bpy)3]Cl2 is immobilized, the side reaction of hydrogen evolution is completely suppressed and the selectivity for CO production reaches 100%, with its durability also significantly improved. This work provides an effective pathway for constructing heterogeneous photocatalysts based on rational assembly of efficient molecular photosensitizers and catalysts.


Assuntos
Complexos de Coordenação , Nanotubos de Carbono , Dióxido de Carbono , Fármacos Fotossensibilizantes , Hidrogênio
9.
Clin Implant Dent Relat Res ; 26(2): 385-401, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38214435

RESUMO

OBJECTIVES: To assess the accuracy of autonomous robotic and fully guided static computer-assisted implant surgery (sCAIS) performed on models and patients. MATERIALS AND METHODS: This study was divided into in vitro and in vivo sections. In vitro, 80 operators were assigned to two groups randomly. Forty operators performed forty autonomous robotic implant (ARI group) surgeries and the remaining forty operators carried out forty fully guided sCAIS (FGI group) surgeries on maxillary models, respectively. Each operator placed an implant in one maxillary model. In vivo, 60 patients with 113 implants from 2019 to 2023 (ARI group: 32 patients, 58 implants; FGI group: 28 patients, 55 implants) receiving implant surgeries were incorporated in this retrospective research. The preoperative and postoperative cone beam computer tomographs (CBCTs) were utilized to estimate the linear deviations and angular deviations in two-dimensional (2D) and three-dimensional (3D) space. The Pearson's chi-square test, Shapiro-Wilk test, Student's t test, Mann-Whitney U test and mixed models were applied, and p <0.05 was considered statistically significant. RESULTS: In vitro, a total of 80 implants were enrolled and significant differences were found between the two groups (p < 0.001): The 3D deviation at the platform of ARI and FGI group was 0.58 ± 0.60 mm and 1.50 ± 1.46 mm, respectively, at the apex was 0.58 ± 0.60 mm and 1.78 ± 1.35 mm, respectively, and angle was 1.01 ± 0.87° and 2.93 ± 1.59°, respectively. Also, except for mesiodistal deviation at the implant platform, the rest linear and angular deviations in the ARI group were significantly lower than those in the FGI group in 2D space (p < 0.001). In vivo, a significantly lower mean of angular deviation (0.95 ± 0.50°, p < 0.001) and the linear deviation at both platform (0.45 ± 0.28 mm, p < 0.001) and apex (0.47 ± 0.28 mm, p < 0.001) were observed in ARI group when compared to the FGI group (4.31 ± 2.60°; 1.45 ± 1.27 mm; 1.77 ± 1.14 mm). CONCLUSIONS: The use of autonomous robotic technology showed significantly higher accuracy than the fully guided sCAIS.


Assuntos
Implantes Dentários , Procedimentos Cirúrgicos Robóticos , Cirurgia Assistida por Computador , Humanos , Implantação Dentária Endóssea/métodos , Estudos Retrospectivos , Desenho Assistido por Computador , Cirurgia Assistida por Computador/métodos , Computadores , Tomografia Computadorizada de Feixe Cônico , Imageamento Tridimensional
10.
iScience ; 27(1): 108618, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38197055

RESUMO

Nicotinamide adenine dinucleotide (NAD), a nucleotide-containing metabolite, can be incorporated into the RNA 5'-terminus to result in NAD-capped RNA (NAD-RNA). Since NAD has been heightened as one of the most essential metabolites in cells, its linkage to RNA represents a critical but poorly studied modification at the epitranscriptomic level. Here, we design a highly sensitive method, DO-seq, to capture NAD-RNAs. Using Drosophila, we identify thousands of previously unexplored NAD-RNAs and their dynamics in the fly life cycle, from embryo to adult. We show the evidence that chromosomal clustering might be the structural basis by which co-expression can couple with NAD capping on physically and functionally linked genes. Furthermore, we note that NAD capping of cuticle genes inversely correlates with their gene expression. Combined, we propose NAD-RNA epitranscriptome as a hidden layer of regulation that underlies biological processes. DO-seq empowers the identification of NAD-capped RNAs, facilitating functional investigation into this modification.

11.
BMC Cardiovasc Disord ; 24(1): 72, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267838

RESUMO

BACKGROUND: Cancer and coronary artery disease (CAD) is reported to often co-exist in same individuals, however, whether cancer is directly associated with anatomical severity of CAD is rarely studied. The present study aimed to observe the relationship between newly diagnosed cancer and anatomical severity of CAD, moreover, to investigate effect of inflammation on the relationship of cancer with CAD. METHODS: 374 patients with newly diagnosed cancer who underwent coronary angiography (CAG) were enrolled. Through 1:3 propensity score matching (PSM) to cancer patients based on the age and gender among 51,106 non-cancer patients who underwent CAG, 1122 non-cancer patients were selected as control patients. Anatomical severity of CAD was assessed using SYNTAX score (SXscore) based on coronary angiographic image. SXscore ≤ 22 (highest quartile) was defined as SX-low, and SXscore > 22 as SX-high. The ratio of neutrophil to lymphocyte count (NLR) was used to describe inflammation level. Association between cancer and the anatomical severity of CAD was investigated using logistic regression. RESULTS: Univariate logistic regression analysis showed a correlation between cancer and anatomical severity of CAD (OR: 1.419, 95% CI: 1.083-1.859; P = 0.011). Cancer was associated with increased risk of SX-high after adjusted for common risk factors of CAD (OR: 1.598, 95% CI: 1.172-2.179, P = 0.003). Significant association between cancer and SX-high was revealed among patients with high inflammation (OR: 1.656, 95% CI: 1.099-2.497, P = 0.016), but not among patients with low inflammation (OR: 1.530, 95% CI: 0.973-2.498, P = 0.089). CONCLUSIONS: Cancer was associated with severity of CAD, however, the association between the two diseases was significant among patients with high inflammation rather than among patients with low inflammation.


Assuntos
Doença da Artéria Coronariana , Neoplasias , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Angiografia Coronária , Inflamação , Fatores de Risco
12.
Environ Pollut ; 341: 122908, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37952916

RESUMO

Manganese (Mn) is considered as an important environmental risk factor for Parkinson's disease. Excessive exposure to Mn can damage various neural cells and affect the neurogenesis, resulting in neurological dysfunction. However, the specific mechanisms of Mn exposure affecting neurogenesis have not been well understood, including compositional changes and heterogeneity of various neural cells. Zebrafish have been successfully used as a neurotoxicity model due to its homology with mammals in several key regions of the brain, as well as its advantages such as small size. We performed single-cell RNA sequencing of zebrafish brains from normal and Mn-exposed groups. Our results suggested that low levels of Mn exposure activated neurogenesis in the zebrafish brain, including promoting the proliferation of neural progenitor cells and differentiation to newborn neurons and oligodendrocytes, while high levels of Mn exposure inhibited neurogenesis and neural function. Mn could affect neurogenesis through specific molecular pathways. In addition, Mn regulated intercellular communication and affected cellular communication in neural cells through specific signaling pathways. Taken together, our study elucidates the cellular composition of the zebrafish brain and adds to the understanding of the mechanisms involved in Mn-induced neurogenesis damage.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Manganês , Animais , Manganês/toxicidade , Manganês/metabolismo , Peixe-Zebra , Neurogênese , Encéfalo/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Perfilação da Expressão Gênica , Mamíferos
13.
Nurse Educ Today ; 133: 106042, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37984053

RESUMO

INTRODUCTION: Midwifery undergraduate students' core competencies directly affect the quality of midwifery services and overall quality of midwifery teams. However, limited research has explored the core competencies of undergraduate midwifery students in China. OBJECTIVES: This study aimed to describe the level of core competencies among undergraduate midwifery students in China and investigated possible associated factors. DESIGN: This was a cross-sectional descriptive study. SETTINGS AND PARTICIPANTS: The study population comprised third- and fourth-year undergraduate midwifery students at Zunyi Medical University in Guizhou Province in southwest China (n = 207, response rate 94.1 %). METHODS: Data were collected using an online survey that included a general information questionnaire, a general self-efficacy scale, and a core competencies self-assessment questionnaire for midwifery undergraduates. Data were statistically analyzed using SPSS 18.0. Pearson's correlation analysis was used to explore the relationship between self-efficacy and the core competencies. Stepwise multiple linear regression was used to explore influencing factors. RESULTS: The total score for the core competencies among midwifery undergraduates was 118.46 (8.97). The highest mean score was for professional attitude, 4.21 (0.43), and the lowest was for professional skills, 3.70 (0.30). We found a positive association between self-efficacy and core competencies (r = 0.251, P < 0.01). Grade (ß = 0.261, P < 0.01), scholarship (ß = -0.231, P < 0.01), work intention (ß = -0.135, P < 0.05), and self-efficacy (ß = 0.207, P < 0.01) significantly influenced undergraduate midwifery students' core competencies (R2 = 0.189, adjusted R2 = 0.173, F = 11.775, P < 0.001). CONCLUSIONS: Undergraduate midwifery students showed moderate core competencies, indicating room for improvement. Fourth-grade midwifery students had higher core competencies than third-grade students. Additionally, scholarship, work intention, and self-efficacy were significant influencing factors. Midwifery educators should examine students' core competencies and explore targeted interventions, particularly for those with low self-efficacy and core competencies.


Assuntos
Tocologia , Estudantes de Enfermagem , Gravidez , Humanos , Feminino , Estudos Transversais , Inquéritos e Questionários , Intenção
14.
Inflammation ; 47(1): 30-44, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37603227

RESUMO

Activated microglia-induced inflammation in the hippocampus plays an important role in perioperative neurocognitive disorders. Previous studies have shown that sialic acid-binding immunoglobulin-like lectin 3 (hSiglec-3, ortholog of mouse Siglec-E) engagement in microglia and its glycan ligands on neurons contributes to inflammatory homeostasis through an endogenous negative regulation pathway. This study aimed to explore whether the glycan ligand alteration on neurons plays a role in sevoflurane-induced perioperative neurocognitive disorders. This study's data has shown that a slight Siglec-E ligands' expression decrease does not induce inflammation homeostasis disruption. We also demonstrated that the ligand level on neurons was decreased with age, and the reduced Siglec-E ligand expression on neurons caused via sevoflurane was induced by neuraminidase 1. Furthermore, this study has shown that the Siglec-E ligand expression decline caused by age and sevoflurane treatment could decrease the ligands' level, thus leading to inflammatory homeostasis disruption. This research provided a novel mechanism for perioperative neurocognitive disorder susceptibility in the elderly.


Assuntos
Inflamação , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico , Humanos , Camundongos , Animais , Idoso , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Ligantes , Sevoflurano/efeitos adversos , Regulação para Baixo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Neurônios/metabolismo , Polissacarídeos/metabolismo , Hipocampo/metabolismo
15.
Sci Total Environ ; 912: 169515, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38154651

RESUMO

Nanoplastics pose several health hazards, especially vascular toxicity. Transfer RNA-derived small RNAs (tsRNAs) are novel noncoding RNAs associated with different pathological processes. However, their biological roles and mechanisms in aberrant vascular smooth muscle cell (VSMC) plasticity and vascular injury are unclear. This study investigated the potent effects of tsRNAs on vascular injury induced by short- and long-term exposure to polystyrene nanoplastics (PS-NPs). Mice were exposed to PS-NPs (100 nm) at different doses (10-100 µg/mL) for 30 or 180 days. High-throughput sequencing was used to analyze tsRNA expression patterns in arterial tissues obtained from an in vivo model. Additionally, quantitative real-time polymerase chain reaction, fluorescent in situ hybridization assays, and dual-luciferase reporter assays were performed to measure the expression and impact of tiRNA-Glu-CTC on VSMCs exposed to PS-NPs. Short-term (≥50 µg/mL, moderate concentration) and long-term (≥10 µg/mL, low concentration) PS-NP exposure induced vascular injury in vivo. Cellular experiments showed that the moderate concentration of PS-NPs induced VSMC phenotypic switching, whereas a high concentration of PS-NPs (100 µg/mL) promoted VSMC apoptosis. PS-NP induced severe mitochondrial damage in VSMCs, including overexpression of reactive oxygen species, accumulation of mutated mtDNA, and dysregulation of genes related to mitochondrial synthesis and division. Compared with the control group, 13 upregulated and 12 downregulated tRNA-derived stress-induced RNAs (tiRNAs) were observed in the long-term PS-NP (50 µg/mL) exposure group. Bioinformatics analysis indicated that differentially expressed tiRNAs targeted genes that were involved in vascular smooth muscle contraction and calcium signaling pathways. Interestingly, tiRNA-Glu-CTC was overexpressed in vivo and in vitro following PS-NP exposure. Functionally, the tiRNA-Glu-CTC inhibitor mitigated VSMC phenotypic switching and mitochondrial damage induced by PS-NP exposure, whereas tiRNA-Glu-CTC mimics had the opposite effect. Mechanistically, tiRNA-Glu-CTC mimics induced VSMC phenotypic switching by downregulating Cacna1f expression. PS-NP exposure promoted VSMC phenotypic switching and vascular injury by targeting the tiRNA-Glu-CTC/Cacna1f axis.


Assuntos
Lesões do Sistema Vascular , Camundongos , Animais , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologia , Músculo Liso Vascular/metabolismo , Microplásticos/metabolismo , Hibridização in Situ Fluorescente , Proliferação de Células , RNA/metabolismo , Células Cultivadas
16.
J Environ Manage ; 350: 119655, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38039703

RESUMO

Best management practices (BMPs) have been extensively employed in effective watershed management for non-point source pollution. The weights of objective functions and the restrictive conditions of combined BMPs are the vital requirements for BMPs allocation. Therefore, it is more beneficial to explore that a spatial optimal allocation method considering multi-attribute decision making and multiple BMPs random combination. Here is the novel framework based on Soil and Water Assessment Tool (SWAT) and the Non-dominated Sorting Genetic Algorithm II (NSGA-Ⅱ), which considers multiple objectives in deriving watershed-scale pollution control practices by considering BMPs cost and combined reduction rates of total nitrogen (TN) and total phosphorus (TP). The framework also integrates combined Entropy Weight method (EWM) and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) to solve the weights of TN and TP, and considers the attributes of the sub-basin itself, which is more local suitability. Four categories of BMPs, tillage management, nutrient management, vegetative filter strips, and landscape management, were evaluated in the Jing River Basin (JRB) and resulted in reduction rates of 9.77%, 10.53%, 16.40%, and 14.27% averagely, respectively. BMP allocation schemes, derived from multi-objective optimization, are stratified into three financial scenarios. Low-cost scenario, costing up to 2 billion RMB, primarily targets the grain for green program in 28.81% of sub-basins. Medium-cost scenario, between 2 and 6 billion RMB, predominantly utilizes the grain for green in areas with a slope greater than 15°, accounting for 20.00% of sub-basins. High-cost scenario exceeds 6 billion RMB, mainly due to the implementation of multiple combination measures. The three configuration scenarios can provide decision-makers with a trade-off between measure costs and reduction efficiency. Overall, the innovative framework not only facilitates cost-effective implementation but provides a beneficial methodology for selecting cost-effective conservation practices in other regions.


Assuntos
Poluição Ambiental , Poluição Difusa , Poluição Difusa/análise , Solo , Tomada de Decisões , Fósforo , Agricultura/métodos , Nitrogênio/análise
17.
Anal Biochem ; 685: 115401, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-37981176

RESUMO

Flavin adenine dinucleotide (FAD) binding sites play an increasingly important role as useful targets for inhibiting bacterial infections. To reveal protein topological structural information as a reasonable complement for the identification FAD-binding sites, we designed a novel fusion technology according to sequence and complex network. The specially designed feature vectors were combined and fed into CatBoost for model construction. Moreover, due to the minority class (positive samples) is more significant for biological researches, a random under-sampling technique was applied to solve the imbalance. Compared with the previous methods, our methods achieved the best results for two independent test datasets. Especially, the MCC obtained by FADsite and FADsite_seq were 14.37 %-53.37 % and 21.81 %-60.81 % higher than the results of existing methods on Test6; and they showed improvements ranging from 6.03 % to 21.96 % and 19.77 %-35.70 % on Test4. Meanwhile, statistical tests show that our methods significantly differ from the state-of-the-art methods and the cross-entropy loss shows that our methods have high certainty. The excellent results demonstrated the effectiveness of using sequence and complex network information in identifying FAD-binding sites. It may be complementary to other biological studies. The data and resource codes are available at https://github.com/Kangxiaoneuq/FADsite.


Assuntos
Flavina-Adenina Dinucleotídeo , Proteínas , Sítios de Ligação , Proteínas/química
18.
Pestic Biochem Physiol ; 197: 105685, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38072542

RESUMO

Cyantraniliprole is a highly effective diamide insecticide used to control of Laodelphax striatellus (Fallén). This study aimed to assess the insecticide resistance risk of L. striatellus and its metabolic resistance mechanisms. After 25 continuous generations of selection, the resistance of L. striatellus to cyantraniliprole increased by 17.14-fold. The realistic heritability of resistance was 0.0751. After successive rearing for five generations without exposure to insecticides, the resistance ratio for the resistant strain of L. striatellus decreased by 3.47-fold, and the average resistance decline rate per generation was 0.0266. Cyantraniliprole-resistant strains did not exhibit cross-resistance to triflumezopyrim, pymetrozine, flonicamid, sulfoxaflor, dinotefuran, clothianidin, thiamethoxam, nitenpyram, or imidacloprid. Compared to those of the sensitive strain, the 2nd, 3rd, and 4th instars, nymphal stage durations, total preoviposition period, and average generation time of the resistant strain were markedly reduced. Furthermore, the activity of cytochrome P450 monooxygenase (P450) and carboxylesterase (CarE) were markedly increased. The upregulation of CYP419A1v2 expression was most evident among the P450 genes, with a 6.10-fold increase relative to that in the sensitive strain. The CarE gene LsCarE5 was significantly upregulated by 1.94-fold compared with that in the sensitive strain. With the continuous use of cyantraniliprole, L. striatellus may develop resistance to this insecticide. This resistance may be related to the increase in metabolic enzyme activities regulated by the overexpression of P450 and CarE genes.


Assuntos
Hemípteros , Inseticidas , Animais , Inseticidas/farmacologia , Tiametoxam , Pirazóis/farmacologia , ortoaminobenzoatos/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Resistência a Inseticidas/genética , Hemípteros/metabolismo
19.
Chin Med ; 18(1): 161, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072948

RESUMO

BACKGROUND: Salvianolic acid B (Sal B), a water-soluble phenolic compound derived from Salvia miltiorrhiza Bunge, is commonly used in Traditional Chinese Medicine to treat cardiovascular disease. In our previous study, Sal B protected against myocardial fibrosis induced by diabetic cardiomyopathy (DCM). This study aimed to investigate the ameliorative effects and potential mechanisms of Sal B in mitigating myocardial fibrosis induced by DCM. METHODS: Various methods were used to investigate the effects of Sal B on myocardial fibrosis induced by DCM in vivo and in vitro. These methods included blood glucose measurement, echocardiography, HE staining, Masson's trichrome staining, Sirius red staining, cell proliferation assessment, determination of hydroxyproline levels, immunohistochemical staining, evaluation of fibrosis-related protein expression (Collagen-I, Collagen-III, TGF-ß1, p-Smad3, Smad3, Smad7, and α-smooth muscle actin), analysis of Smad7 gene expression, and analysis of Smad7 ubiquitin modification. RESULTS: The animal test results indicated that Sal B significantly improved cardiac function, inhibited collagen deposition and phenotypic transformation, and ameliorated myocardial fibrosis in DCM by upregulating Smad7, thereby inhibiting the TGF-ß1 signaling pathway. In addition, cell experiments demonstrated that Sal B significantly inhibited the proliferation, migration, phenotypic transformation, and collagen secretion of cardiac fibroblasts (CFs) induced by high glucose (HG). Sal B significantly decreased the ubiquitination of Smad7 and stabilized the protein expression of Smad7, thereby increasing the protein expression of Smad7 in CFs and inhibiting the TGF-ß1 signaling pathway, which may be the potential mechanism by which Sal B mitigates myocardial fibrosis induced by DCM. CONCLUSION: This study revealed that Sal B can improve myocardial fibrosis in DCM by deubiquitinating Smad7, stabilizing the protein expression of Smad7, and blocking the TGF-ß1 signaling pathway.

20.
Ann Clin Microbiol Antimicrob ; 22(1): 107, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072972

RESUMO

OBJECTIVE: To evaluate effect of inoculum size of extended-spectrum ß-Lactamase (ESBL)-producing-, AmpC-producing-, and KPC-producing Escherichia coli and Klebsiella pneumoniae on the in vitro antibacterial effects of imipenem/relebactam (IMR) and ceftazidime/avibactam (CZA). METHODS: We compared the impact of inoculum size on IMR and CZA of sixteen clinical isolates and three standard isolates through antimicrobial susceptibility tests, time-kill assays and in vitro PK/PD studies. RESULTS: When inoculum size increased from 105 to 107 CFU/mL, an inoculum effect was observed for 26.3% (5/19) and 52.6% (10/19) of IMR and CZA, respectively; time-kill assays revealed that the concentration of CZA increased from ≥ 4 × MIC to 16 × MIC to reach 99.9% killing rate against K. pneumoniae ATCC-BAA 1705 (KPC-2-, OXA-9- and SHV-182-producing) and 60,700 (SHV-27- and DHA-1-producing). While for IMR, a concentration from 1 × MIC to 4 × MIC killed 99.9% of the four strains. When the inoculum size increased to 109 CFU/mL, neither IMR nor CZA showed a detectable antibacterial effect, even at a high concentration. An in vitro PK/PD study revealed a clear bactericidal effect when IMR administered as 1.25 g q6h when inoculum size increased. CONCLUSION: An inoculum effect on CZA was observed more frequent than that on IMR. Among the ß-lactamase-producing strains, the inoculum effect was most common for SHV-producing and KPC-producing strains.


Assuntos
Ceftazidima , Klebsiella pneumoniae , Humanos , Ceftazidima/farmacologia , Escherichia coli , Proteínas de Bactérias/genética , Antibacterianos/farmacologia , beta-Lactamases/genética , Combinação de Medicamentos , Imipenem/farmacologia , Testes de Sensibilidade Microbiana
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