Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.873
Filtrar
1.
Plant Methods ; 20(1): 103, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003455

RESUMO

BACKGROUND: Genotyping of individuals plays a pivotal role in various biological analyses, with technology choice influenced by multiple factors including genomic constraints, number of targeted loci and individuals, cost considerations, and the ease of sample preparation and data processing. Target enrichment capture of specific polymorphic regions has emerged as a flexible and cost-effective genomic reduction method for genotyping, especially adapted to the case of very large genomes. However, this approach necessitates complex bioinformatics treatment to extract genotyping data from raw reads. Existing workflows predominantly cater to phylogenetic inference, leaving a gap in user-friendly tools for genotyping analysis based on capture methods. In response to these challenges, we have developed GeCKO (Genotyping Complexity Knocked-Out). To assess the effectiveness of combining target enrichment capture with GeCKO, we conducted a case study on durum wheat domestication history, involving sequencing, processing, and analyzing variants in four relevant durum wheat groups. RESULTS: GeCKO encompasses four distinct workflows, each designed for specific steps of genomic data processing: (i) read demultiplexing and trimming for data cleaning, (ii) read mapping to align sequences to a reference genome, (iii) variant calling to identify genetic variants, and (iv) variant filtering. Each workflow in GeCKO can be easily configured and is executable across diverse computational environments. The workflows generate comprehensive HTML reports including key summary statistics and illustrative graphs, ensuring traceable, reproducible results and facilitating straightforward quality assessment. A specific innovation within GeCKO is its 'targeted remapping' feature, specifically designed for efficient treatment of targeted enrichment capture data. This process consists of extracting reads mapped to the targeted regions, constructing a smaller sub-reference genome, and remapping the reads to this sub-reference, thereby enhancing the efficiency of subsequent steps. CONCLUSIONS: The case study results showed the expected intra-group diversity and inter-group differentiation levels, confirming the method's effectiveness for genotyping and analyzing genetic diversity in species with complex genomes. GeCKO streamlined the data processing, significantly improving computational performance and efficiency. The targeted remapping enabled straightforward SNP calling in durum wheat, a task otherwise complicated by the species' large genome size. This illustrates its potential applications in various biological research contexts.

2.
Int J Mol Sci ; 25(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39000490

RESUMO

Ischemic stroke followed by reperfusion (IR) leads to extensive cerebrovascular injury characterized by neuroinflammation and brain cell death. Inhibition of matrix metalloproteinase-3 (MMP-3) emerges as a promising therapeutic approach to mitigate IR-induced stroke injury. We employed middle cerebral artery occlusion with subsequent reperfusion (MCAO/R) to model ischemic stroke in adult mice. Specifically, we investigated the impact of MMP-3 knockout (KO) on stroke pathophysiology using RNA sequencing (RNA-seq) of stroke brains harvested 48 h post-MCAO. MMP-3 KO significantly reduced brain infarct size following stroke. Notably, RNA-seq analysis showed that MMP-3 KO altered expression of 333 genes (252 downregulated) in male stroke brains and 3768 genes (889 downregulated) in female stroke brains. Functional pathway analysis revealed that inflammation, integrin cell surface signaling, endothelial- and epithelial-mesenchymal transition (EndMT/EMT), and apoptosis gene signatures were decreased in MMP-3 KO stroke brains. Intriguingly, MMP-3 KO downregulated gene signatures more profoundly in females than in males, as indicated by greater negative enrichment scores. Our study underscores MMP-3 inhibition as a promising therapeutic strategy, impacting multiple cellular pathways following stroke.


Assuntos
Infarto Cerebral , Modelos Animais de Doenças , AVC Isquêmico , Metaloproteinase 3 da Matriz , Camundongos Knockout , Animais , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Masculino , Feminino , Camundongos , AVC Isquêmico/genética , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , Infarto Cerebral/genética , Infarto Cerebral/patologia , Infarto Cerebral/metabolismo , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Camundongos Endogâmicos C57BL , Transcriptoma , Regulação da Expressão Gênica , Encéfalo/metabolismo , Encéfalo/patologia
3.
Bioelectrochemistry ; 160: 108769, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38955054

RESUMO

The structure and surface physicochemical properties of anode play a crucial role in microbial fuel cells (MFCs). To enhance the enrichment of exoelectrogen and facilitate extracellular electron transfer (EET), a three-dimensional macroporous graphene aerogel with polydopamine coating was successfully introduced to modify carbon brush (PGA/CB). The three-dimensional graphene aerogel (GA) with micrometer pores improved the space utilization efficiency of microorganisms. Polydopamine (PDA) coating enhanced the physicochemical properties of the electrode surface by introducing abundant functional groups and nitrogen-containing active sites. MFCs equipped with PGA/CB anodes (PGA/CB-MFCs) demonstrated superior power generation compared to GA/CB-MFCs and CB-MFCs (MFCs with GA/CB and CB anodes respectively), including a 23.0 % and 30.1 % reduction in start-up time, and an increase in maximum power density by 2.43 and 1.24 times respectively. The higher bioelectrochemical activity exhibited by the biofilm of PGA/CB anode and the promoted riboflavin secretion by PGA modification imply the enhanced EET efficiency. 16S rRNA high-throughput sequence analysis of the biofilms revealed successful enrichment of Geobacter on PGA/CB anodes. These findings not only validate the positive impact of the synergistic effects between GA and PDA in promoting EET and improving MFC performance but also provide valuable insights for electrode design in other bioelectrochemical systems.

4.
Methods Mol Biol ; 2826: 117-129, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39017889

RESUMO

Memory B cells are central to the establishment of immunological memory, providing long-term protection against specific pathogens and playing a vital role in the efficacy of vaccines. Understanding how memory B cell formation is disrupted during persistent infection is essential for new therapeutics. Lymphocytic choriomeningitis virus (LCMV) is an ideal model for investigating memory B cells in acute versus chronic infection. This protocol details techniques to isolate, enrich, and examine LCMV-specific memory B cells in both acute and chronic LCMV infection. Using an antigen tetramer enrichment system and flow cytometry, this method assesses low-frequency, polyclonal antigen-specific memory B cells.


Assuntos
Antígenos Virais , Citometria de Fluxo , Coriomeningite Linfocítica , Vírus da Coriomeningite Linfocítica , Células B de Memória , Vírus da Coriomeningite Linfocítica/imunologia , Animais , Camundongos , Coriomeningite Linfocítica/imunologia , Coriomeningite Linfocítica/virologia , Citometria de Fluxo/métodos , Antígenos Virais/imunologia , Células B de Memória/imunologia , Células B de Memória/metabolismo , Memória Imunológica , Linfócitos B/imunologia , Linfócitos B/metabolismo
5.
Eur J Cancer ; 208: 114201, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018630

RESUMO

Precision cancer medicine brought the promise of improving outcomes for patients with cancer. High-throughput molecular profiling of tumors at treatment failure aims to direct a patient to a treatment matched to the tumor profile. In this way, improved outcome has been achieved in a small number of patients whose tumors exhibit unique targetable oncogenic drivers. Most cancers, however, contain multiple genetic alterations belonging to and of various hallmarks of cancer; for most of these alterations, there is limited knowledge on the level of evidence, their hierarchical roles in oncogenicity, and utility as biomarkers for response to targeted treatment(s). We developed a proof-of-concept trial that explores new treatment strategies in a molecularly-enriched tumor-agnostic, pediatric population. The evaluation of novel agents, including first-in-child molecules, alone or in combination, is guided by the available understanding of or hypotheses for the mechanisms of action of the diverse cancer events. Main objectives are: to determine 1) recommended phase 2 doses, 2) activity signals to provide the basis for disease specific development, and 3) to define new predictive biomarkers. Here we outline concepts, rationales and designs applied in the European AcSé-ESMART trial and highlight the feasibility but also complexity and challenges of such innovative platform trials.

6.
Environ Pollut ; 359: 124540, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004208

RESUMO

Microplastic pollution poses a global threat to freshwater ecosystems, with laboratory experiments indicating potential toxic impacts through chemical toxicity, physical abrasion, and false satiation. Bioplastics have emerged as a potential greener alternative to traditional oil-based plastics. Yet, their environmental effects remain unclear, particularly at scales relevant to the natural environment. Additionally, the interactive impacts of microplastics with other environmental stressors, such as nutrient enrichment, are poorly understood and rarely studied. Under natural conditions organisms might be able to mitigate the toxic effects of microplastics by shifting their diet, but this ability may be compromised by other stressors. This study combines an outdoor mesocosm experiment and stable isotope analysis to determine changes in the trophic niches of three freshwater invertebrate species exposed to conventional (HDPE) and bio-based biodegradable (PLA) microplastics at two concentrations, both independently and combined with nutrient enrichment. Exposure to microplastics altered the isotopic niches of two of the invertebrate species, with nutrient enrichment mediating this effect. Moreover, the effects of microplastics were consistent regardless of their type or concentration. Under enriched conditions, two of the species exposed to microplastics shifted to a specialised diet compared with controls, whereas little difference was observed between the isotopic niches of those exposed to microplastic and controls under ambient nutrient conditions. Additionally, PLA was estimated to support 24 % of the diet of one species, highlighting the potential assimilation of bioplastics by biota and possible implications. Overall, these findings suggest that the toxic effects of microplastics suggested from laboratory studies might not manifest under real-world conditions. However, this study does demonstrate that subtle sublethal effects occur even at environmentally realistic microplastic concentrations. The crucial role of nutrient enrichment in mediating microplastic effects underscores the importance of considering microplastic pollution in the context of other environmental stressors.

7.
ACS Appl Mater Interfaces ; 16(28): 36462-36470, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38956932

RESUMO

Artificial photosynthesis is an effective way of converting CO2 into fuel and high value-added chemicals. However, the sluggish interfacial electron transfer and adsorption of CO2 at the catalyst surface strongly hamper the activity and selectivity of CO2 reduction. Here, we report a photocathode attaching zeolitic imidazolate framework-8 (ZIF-8) onto a ZnTe surface to mimic an aquatic leaf featuring stoma and chlorophyll for efficient photoelectrochemical conversion of CO2 into CO. ZIF-8 possessing high CO2 adsorption capacity and diffusivity has been selected to enrich CO2 into nanocages and provide a large number of catalytic active sites. ZnTe with high light-absorption capacity serves as a light-absorbing layer. CO2 molecules are collected in large nanocages of ZIF-8 and delivered to the ZnTe surface. As evidenced by scanning electrochemical microscopy, the interface can effectively boost interfacial electron transfer kinetics. The ZIF-8/ZnTe photocathode with unsaturated Zn-Nx sites exhibits a high Faradaic efficiency for CO production of 92.9% and a large photocurrent of 6.67 mA·cm-2 at -2.48 V (vs Fc/Fc+) in a nonaqueous electrolyte at AM 1.5G solar irradiation (100 mW·cm-2).

8.
Epigenetics ; 19(1): 2375022, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38967555

RESUMO

Infinium Methylation BeadChip arrays remain one of the most popular platforms for epigenome-wide association studies, but tools for downstream pathway analysis have their limitations. Functional class scoring (FCS) is a group of pathway enrichment techniques that involve the ranking of genes and evaluation of their collective regulation in biological systems, but the implementations described for Infinium methylation array data do not retain direction information, which is important for mechanistic understanding of genomic regulation. Here, we evaluate several candidate FCS methods that retain directional information. According to simulation results, the best-performing method involves the mean aggregation of probe limma t-statistics by gene followed by a rank-ANOVA enrichment test using the mitch package. This method, which we call 'LAM,' outperformed an existing over-representation analysis method in simulations, and showed higher sensitivity and robustness in an analysis of real lung tumour-normal paired datasets. Using matched RNA-seq data, we examine the relationship of methylation differences at promoters and gene bodies with RNA expression at the level of pathways in lung cancer. To demonstrate the utility of our approach, we apply it to three other contexts where public data were available. First, we examine the differential pathway methylation associated with chronological age. Second, we investigate pathway methylation differences in infants conceived with in vitro fertilization. Lastly, we analyse differential pathway methylation in 19 disease states, identifying hundreds of novel associations. These results show LAM is a powerful method for the detection of differential pathway methylation complementing existing methods. A reproducible vignette is provided to illustrate how to implement this method.


Assuntos
Metilação de DNA , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas , Feminino , Estudo de Associação Genômica Ampla/métodos , Epigênese Genética
9.
Heliyon ; 10(12): e32415, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39005908

RESUMO

Pasta, a globally popular dish, serves as a complete meal around the world. This research aims to improve the nutritional value of pasta by enriching it with vitamin E. Firstly, vitamin E and sesame oil were mixed in different ratios (1:10, 1:5, 10:10) and dissolved in an aqueous medium at 50 °C with different concentrations of Tween 80 (10 %, 20 %, 30 %). Coarse emulsions were formed by gradual addition of the oil phase to the aqueous phase, followed by equilibration using an Ultratrax mixer at 15,000 rpm for 5 min. The target nanoemulsions were then produced using an ultrasonic system. After 30 days of storage, the most stable nanoemulsions containing 10 % Tween 80 and a 1:10 ratio of vitamin E to sesame oil showed minimal changes. In addition, nanoemulsions with 10 % Tween 80 and a 10:10 ratio of vitamin E to sesame oil showed less turbidity than those with 20 % and 30 % Tween 80. Evaluation of enriched pasta for physical, chemical and sensory properties compared to non-enriched samples showed no significant differences in properties such as pH, ash, total solids, texture and colour characteristics (P < 0.05). Enriched pasta samples showed an increase in moisture content of 0.94 % and a decrease in weight loss of 2.13 % compared to the control, with improved brightness (L) and yellowness (b) due to the addition of nanoemulsion. Sensory evaluation showed higher scores for pasta samples enriched with nanoemulsions containing vitamin E compared to control samples. This pioneering study introduces nanoemulsion technology to improve the nutritional profile of pasta by enriching it with vitamin E. The research demonstrates the successful formulation of stable nanoemulsions and their positive effects on pasta properties, suggesting promising avenues for improving public health through innovative pasta enrichment methods.

10.
Mol Pharm ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008633

RESUMO

Amorphous solid dispersions (ASDs) can be used to enhance the solubility and bioavailability of poorly soluble drugs. An ASD is often a ternary system containing a drug, a surfactant, and a polymer. Recent work on binary ASDs has observed significant differences between surface and bulk compositions, with impacts on wettability and stability. Here we investigate a ternary ASD composed of the antifungal posaconazole, the surfactant Span 80, and a dispersion polymer (PVP or PVP/VA). The surfactant loading was fixed at the typical level of 5 wt %, and the drug/polymer ratio was varied. We observed strong surface enrichment of the surfactant and simultaneous depletion of the drug. This effect is already pronounced in the binary drug-surfactant system and is enhanced by the addition of the polymers. Between the two polymers, the more hydrophilic PVP causes a stronger enhancement of the surface enrichment effect. These results demonstrate the impact of component interactions on the surface composition of ASDs and the performance.

11.
Environ Int ; 190: 108879, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39008919

RESUMO

Perfluorooctanoic acid (PFOA), a member of per- and polyfluoroalkyl substances (PFASs), has been widely used in manufacturing for decades. Currently, PFOA is strictly regulated, but due to its high stability and persistence, it is detected in both environmental as well as in human matrices. To elucidate mechanisms of PFOA toxicity in humans, we determined the genome-wide transcriptomic changes of peripheral blood mononuclear cells (PBMC) responding to PFOA exposure in a sex-stratified analysis. This work employed samples from 145 female and 143 male participants of the CELSPAC: YA study to characterize PFOA-associated transcripts in a broader context using computational analysis. PFOA-associated gene expression differed significantly between men and women, as only 2 % of mapped genes were expressed in both sexes. Disease-specific enrichment analysis revealed cancer and immune-related disease terms as those most enriched in male and female populations. Patterns of enriched terms within the gene set enrichment analysis indicated three main targets of PFOA toxicity: i) lipid metabolism for women; ii) cell cycle regulation for men; and iii) immune system response for both sexes. In summary, our genome-wide transcriptomics analysis described sex-specific differences in PFOA-associated gene expression and provided evidence about biological pathways underlying PFOA toxicity in humans.

12.
Sci Total Environ ; : 174768, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39009147

RESUMO

Wastewater Treatment Plants (WWTP) are a major repository and entrance path of nanoparticles (NP) in the environment and hence play a major role in the final fate and toxicity to biota of NP in the aquatic environment. Studies on silver nanoparticles (AgNP) transport via the WWTP system and uptake by aquatic biota have so far been carried out using unrealistically high AgNP concentrations, unlikely to be encountered in the aquatic environment. The use of high AgNP concentrations is necessitated by both the low sensitivity of the detection methods used and the need to distinguish background Ag from spiked AgNP. In this study, isotopically enriched 109AgNP were synthesized to overcome these shortcomings and characterized by a broad range of methods including transmission electron microscopy, dynamic and electrophoretic light scattering. 109AgNP and gold NP (AuNP) were spiked to a pilot wastewater treatment plant fed with municipal wastewater for up to 21 days. AuNP were used as chemically less reactive tracer. The uptake of the pristine and transformed NP present in the effluent was assessed using the benthic amphipod Hyalella azteca in fresh- and brackish water exposures at environmentally relevant concentrations of 30 to 500 ng Au/L and 39 to 260 ng Ag/L. The unique isotopic signature of the 109AgNP allowed to detect the material at environmentally relevant concentrations in the presence of a much higher natural Ag background. The results show that the transformations reduce the NP uptake at environmentally relevant exposure concentrations. For 109Ag, lower accumulation factors (AF) were obtained after exposure to transformed NP (250-350) compared to the AF values obtained for pristine 109AgNP (750-840). The reduced AF values observed for H. azteca exposed to effluent from the AuNP-spiked WWTP indicate that biological transformation processes (e.g. eco-corona formation) seem to be involved in addition to chemical transformation.

13.
Cancers (Basel) ; 16(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39001403

RESUMO

B cells are central to the adaptive immune response and provide long-lasting immunity after infection. B cell activation is mediated by the surface membrane-bound B cell receptor (BCR) following recognition of a specific antigen. The BCR has been challenging to analyse using mass spectrometry (MS) due to the difficulty of isolating and enriching this membrane-bound protein complex. There are approximately 120,000 BCRs on the B cell surface; however, depending on the B cell activation state, there may be hundreds-of-millions to billions of proteins in a B cell. Consequently, advanced proteomic techniques such as MS workflows that use purified proteins to yield structural and protein-interaction information have not been published for the BCR complex. This paper describes a method for enriching the BCR complex that is MS-compatible. The method involves a Protein G pull down on agarose beads using an intermediary antibody to each of the BCR complex subcomponents (CD79a, CD79b, and membrane immunoglobulin). The enrichment process is shown to pull down the entire BCR complex and has the advantage of being readily compatible with further proteomic study including MS analysis. Using intermediary antibodies has the potential to enrich all isotypes of the BCR, unlike previous methods described in the literature that use protein G-coated beads to directly pull down the membrane IgG (mIgG) but cannot be used for other mIg isotypes.

14.
Sci Total Environ ; 947: 174696, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38997032

RESUMO

Plastic pollution of the soil is a global issue of increasing concern, with far-reaching impact on the environment and human health. To fully understand the medium- and long-term impact of plastic dispersal in the environment, it is necessary to define its interaction with the residing microbial communities and the biochemical routes of its degradation and metabolization. However, despite recent attention on this problem, research has largely focussed on microbial functional potential, failing to clearly identify collective adaptation strategies of these communities. Our study combines genome-centric metagenomics and metatranscriptomics to characterise soil microbial communities adapting to high polyethylene and polyethylene terephthalate concentration. The microbiota were sampled from a landfill subject to decades-old plastic contamination and enriched through prolonged cultivation using these microplastics as the only carbon source. This approach aimed to select the microorganisms that best adapt to these specific substrates. As a result, we obtained simplified communities where multiple plastic metabolization pathways are widespread across abundant and rare microbial taxa. Major differences were found in terms of expression, which on average was higher in planktonic microbes than those firmly adhered to plastic, indicating complementary metabolic roles in potential microplastic assimilation. Moreover, metatranscriptomic patterns indicate a high transcriptional level of numerous genes in emerging taxa characterised by a marked accumulation of genomic variants, supporting the hypothesis that plastic metabolization requires an extensive rewiring in energy metabolism and thus provides a strong selective pressure. Altogether, our results provide an improved characterisation of the impact of microplastics derived from common plastics types on terrestrial microbial communities and suggest biotic responses investing contaminated sites as well as potential biotechnological targets for cooperative plastic upcycling.

15.
Animals (Basel) ; 14(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38998015

RESUMO

Good zoo animal welfare is commonly promoted with environmental enrichment; however, some species are less likely to be offered enrichment than others. This study tested the effect of enrichment on a group of scarlet ibises from Zoomarine Algarve, Portugal. The study consisted of a first baseline condition, followed by four types of enrichment displays with individual presentations, a post-enrichment condition, and a post-enrichment with all enrichment types presented simultaneously. The enrichment types chosen were physical, with a tidal simulation in the lakes of the enclosure; nutritional, presenting mussels in a plastic mesh tube; sensory, by playing scarlet ibises calls; and tactile, with brushes through the habitat. The data collection was performed for 21 days between January and March 2021, 3 times a day, using scan sampling and instantaneous time sampling every 2 min. The comparison between conditions revealed that most behaviors showed similarity between the baseline and post-enrichment conditions, suggesting that after removing the enrichment, the behaviors returned to their initial baseline. It was also found that each enrichment influenced different types of behaviors and these behaviors also changed depending on the time of day. Exploratory behavior was only associated with the presence of enrichment, and vocalizations were only heard after the sensory enrichment was performed. This study demonstrates that the use of physical and tactile enrichments increased activity and decreased stationary behaviors in this group of ibises and may be used to improve their lives in zoological contexts if included in the housing and husbandry protocols.

16.
Animals (Basel) ; 14(13)2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38998110

RESUMO

Domesticated animals have undergone significant changes in their behavior, morphology, and physiological functions during domestication. To identify the changes in gene expression associated with domestication, we collected the RNA-seq data of pigs, chickens, wild boars, and red junglefowl from public databases and performed a meta-analysis. Gene expression was quantified, and the expression ratio between domesticated animals and their wild ancestors (DW-ratio) was calculated. Genes were classified as "upregulated", "downregulated", or "unchanged" based on their DW-ratio, and the DW-score was calculated for each gene. Gene set enrichment analysis revealed that genes upregulated in pigs were related to defense from viral infection, whereas those upregulated in chickens were associated with aminoglycan and carbohydrate derivative catabolic processes. Genes commonly upregulated in pigs and chickens are involved in the immune response, olfactory learning, epigenetic regulation, cell division, and extracellular matrix. In contrast, genes upregulated in wild boar and red junglefowl are related to stress response, cell proliferation, cardiovascular function, neural regulation, and energy metabolism. These findings provide valuable insights into the genetic basis of the domestication process and highlight potential candidate genes for breeding applications.

17.
Int J Hyg Environ Health ; 261: 114417, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38968837

RESUMO

BACKGROUND: Epidemiological studies on heavy metal exposure and liver injury are predominantly cross-sectional, lacking longitudinal data and exploration of potential mechanisms. METHOD: We conducted a repeated-measures study in Northeast China from 2016 to 2019, involving 322 participants. Linear mixed models (LMM) and Bayesian kernel machine regression (BKMR) were employed to explore the associations between individual and mixed blood metal concentrations [chromium (Cr), cadmium (Cd), vanadium (V), manganese (Mn), lead (Pb)] and liver function biomarkers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), globulin (GLB), total protein (TP)]. Mediation and enrichment analyses were used to determine whether the inflammatory response is a critical pathway for heavy metal-induced liver damage. RESULT: We obtained a total of 958 observations. The results from LMM and BKMR indicated significant associations between individual and mixed heavy metals and liver function biomarkers. Longitudinal analysis revealed associations between Cd and the annual increase rate of ALT (ß = 2.61; 95% CI: 0.97, 4.26), the annual decrease rate of ALB (ß = -0.21; 95% CI: -0.39, -0.03), Mn and the annual increase rate of GLB (ß = 0.38; 95% CI: 0.05, 0.72), and V and the annual decrease rate of ALB/GLB (ß = -1.15; 95% CI: -2.00, -0.31). Mediation analysis showed that high-sensitivity C-reactive protein (hsCRP) mediated the associations between Cd and AST, TP, with mediation effects of 27.7% and 13.4%, respectively. Additionally, results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses supported the role of inflammatory response pathways. CONCLUSION: Our findings indicate that heavy metal exposure leads to liver damage, with the inflammatory response potentially serving as a crucial pathway in this process. This study offers a novel perspective on understanding heavy metal-induced liver injury and provides insights for preventive measures against the health damage caused by heavy metals.

18.
Heliyon ; 10(12): e32691, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38988570

RESUMO

This empirical research study endeavors to analyze the indirect association between oppression and corruption in 147 nations around the globe to answer one question: "Why does oppression drive corruption in many nations?" The author used secondary data from two different resources. The first source is the Corruption Perception Index (CPI), created by Transparency International (TI) in 2020, and the Human Freedom Index (HFI), co-published by the Cato Institute. In addition, the second source is the Political Stability Index in 2020 to test the three research hypotheses using the R-square, and Anova shows that the model is personal and economic oppression explains 53.5 percent of the variance. In addition, the Weighted Least Squares Regression Analyses imply that there is a positive and meaningful connection between personal oppression (ß = 3.028, p < 0.000) and corruption and economic oppression and corruption (5.203, p < 0.000). This study's findings confirmed the theoretical and conceptual relationship between oppression and bribery and identified personal and economic oppression factors as the leading causes of corruption in many countries. The study findings also contribute to the literature and the industry as well. Theoretically, the study results help researchers to understand why oppression causes corruption at the country level. Practically, the study results help policymakers, educators, and international business planners to consider roots when making successful strategic decisions in the era of the globalized world. The author also discussed the research limitations and practical and theoretical implications.

19.
AIMS Neurosci ; 11(2): 103-117, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988883

RESUMO

The central nervous system (CNS) and the immune system collectively coordinate cellular functionalities, sharing common developmental mechanisms. Immunity-related molecules exert an influence on brain development, challenging the conventional view of the brain as immune-privileged. Chronic inflammation emerges as a key player in the pathophysiology of Alzheimer's disease (AD), with increased stress contributing to the disease progression and potentially exacerbating existing symptoms. In this study, the most significant gene signatures from selected RNA-sequencing (RNA-seq) data from AD patients and healthy individuals were obtained and a functional analysis and biological interpretation was conducted, including network and pathway enrichment analysis. Important evidence was reported, such as enrichment in immune system responses and antigen processes, as well as positive regulation of T-cell mediated cytotoxicity and endogenous and exogenous peptide antigen, thus indicating neuroinflammation and immune response participation in disease progression. These findings suggest a disturbance in the immune infiltration of the peripheral immune environment, providing new challenges to explore key biological processes from a molecular perspective that strongly participate in AD development.

20.
F1000Res ; 13: 123, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974941

RESUMO

Background: Zoos use environmental enrichments, including scents, which may have applications to improve breeding success for taxa, such as lemurs, which rely heavily on olfactory communication. We aimed to develop novel, biologically-relevant scent enrichments to trigger mating behaviours of zoo-housed lemur species, which are critically endangered in the wild and show a low success rate in captive breeding programmes. Methods: We examined anogenital odour secretions, released by female gentle ( Hapalemur alaotrensis) and ruffed ( Varecia variegata) lemurs, using solid-phase microextraction and gas chromatography-mass spectrometry techniques. We identified the key compounds distinguishing the volatile chemical profile of female lemurs during the breeding season and used them to develop species-specific scent enrichments. We then tested the scent enrichments, made up of synthesized mixtures conveying information about female lemur fertility, on unsuccessful breeding pairs of lemurs hosted in European zoos. We evaluated the effects of the newly designed scent enrichments on their target species by combining behavioural observations with faecal endocrinology. Results: We identified and reproduced fertility-specific signals associated with female scents. These scent mixtures triggered male sexual behaviours, including mating, during and after the enrichment condition. We also found effects on faecal testosterone levels, with increased levels after the enrichment condition albeit not statistically significant. Conclusions: Our findings suggest that biologically-relevant scent enrichments may trigger natural species-specific behaviours, with potential implications for conservation breeding of zoo-based endangered lemur species, and highlight that combining more assessment methods may assist with evaluating the impact of environmental enrichments.


Assuntos
Animais de Zoológico , Cruzamento , Lemur , Odorantes , Animais , Animais de Zoológico/fisiologia , Feminino , Odorantes/análise , Lemur/fisiologia , Masculino , Comportamento Sexual Animal/fisiologia , Lemuridae/fisiologia , Cromatografia Gasosa-Espectrometria de Massas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA