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Microbiology Spectrum Jun 2024is a highly fatal fungal pathogen affecting individuals with advanced HIV disease. Molecular patterns and ultrastructural aspects of are unknown, and pathogenic models...
UNLABELLED
is a highly fatal fungal pathogen affecting individuals with advanced HIV disease. Molecular patterns and ultrastructural aspects of are unknown, and pathogenic models have not been investigated in detail. Since the cell wall of fungi is a determinant for interaction with the host and antifungal development, we characterized the ultrastructural aspects of and the general properties of cell wall components under different conditions of growth and . We also tested the pathogenic potential of in a model of infection. Transmission electron microscopy revealed the common intracellular, ultrastructural features of fungi in association with a thick cell wall. Scanning electron microscopy revealed a smooth cell surface, with no apparent decorative structures. Yeast cultures of showed the distribution of chitin, chitooligomers, and mannoproteins commonly observed in fungi. However, in mixed microenvironments containing yeast and filamenting forms of , the detection of chitooligomers was increased in comparison with isolated yeast cells, while the detection of these components in filamenting forms was markedly reduced. These observations were suggestive of the ability of to change its cell wall composition in response to different microenvironments. Although was unable to kill , this infection model allowed us to isolate infected hemocytes for further analysis of mannoproteins, chitin, and chitooligomers. Once again, the detection of chitooligomers was markedly increased. These results reveal previously unknown ultrastructural features of and suggest a high plasticity in the cell wall of this lethal pathogen.
IMPORTANCE
The epidemiology of fungal infections is very dynamic, and novel health emergencies are hard to predict. New fungal pathogens have been continuously emerging for the last few decades, and is one of these threats to human health. This complex scenario points to the need for generating knowledge about emerging pathogens so that new therapeutic strategies can be designed. In this study, we characterized the general cellular and pathogenic properties of the emerging fungal pathogen . Our results reveal that manifests some of the typical properties of fungal cells but also exhibits some unique characteristics that might be helpful for the future development of therapeutic strategies.
PubMed: 38916362
DOI: 10.1128/spectrum.00863-24 -
Reumatismo Jun 2024Nicotine has major side effects on human health through numerous mechanisms, one of which is the alteration of the immune system and its genetic components. Such... (Review)
Review
OBJECTIVE
Nicotine has major side effects on human health through numerous mechanisms, one of which is the alteration of the immune system and its genetic components. Such alteration can be a predisposing factor for autoimmune diseases such as spondyloarthritis (SpA) and rheumatoid arthritis (RA). This review aims to shed light on the effects of nicotine smoking on the pathophysiology, clinical presentation, and management of SpA and RA.
METHODS
This review looked into the studies, excluding case reports and series, which were cited by PubMed/MEDLINE.
RESULTS
Patients with established autoimmune conditions may have a different underlying pathophysiology and disease course when exposed to nicotine through cigarette smoking. Through the involvement of several cytokines, endothelial dysfunction, and epigenetic mechanisms, the severity of SpA is more prominent in smokers. The global health status, pain, and fatigue are worse in SpA patients. The evidence on the effect of nicotine smoking on the treatment of SpA is still limited. Nicotine can contribute to RA via the disruption of cellular regulatory activity, inflammatory responses, morphological, physiological, biochemical, and enzymatic responses. As such, smokers with RA have higher disease activity and are more likely to be seropositive through the citrullination of peptides. In addition, these patients are at risk of achieving a suboptimal response to tumor necrosis factor inhibitors.
CONCLUSIONS
Cigarette smoking can substantially affect the pathophysiology and clinical presentation of patients with SpA and RA. The impact of nicotine on the management of these diseases still needs to be further studied.
Topics: Humans; Arthritis, Rheumatoid; Nicotine; Spondylarthritis; Smoking
PubMed: 38916171
DOI: 10.4081/reumatismo.2024.1572 -
Frontiers in Plant Science 2024is a dominant species in the desert steppe of Northern China. Grazing is the main land use pattern of grassland, which could cause a variety of adaptive evolutionary...
is a dominant species in the desert steppe of Northern China. Grazing is the main land use pattern of grassland, which could cause a variety of adaptive evolutionary mechanisms in plant community composition as well as individual plant growth and morphological characteristics. However, very little is known about the morphological structure and transcriptional regulation response to different grazing intensities in . In this study, transcriptome and anatomical analyses of under different grazing intensities, including no grazing, moderate grazing, and heavy grazing, were performed. The anatomical analysis results showed that epidermis cells and xylems significantly thicken with grazing intensity, suggesting that grazing results in increasing lignification. Furthermore, the components of cell walls such as lignin, cellulose, hemicellulose, and pectin were all increased dramatically and significantly under both moderate and heavy grazing. Transcriptome analysis showed that the differentially expressed genes related to different grazing intensities were also engaged in plant cell wall formation and in photosynthesis and respiration. In addition, the activities of ATP synthase and Rubisco-activating enzyme increased significantly with enhanced grazing intensity and differed significantly between moderate and heavy grazing intensities. The trends in transcriptome and plant phenotype changes are consistent. Taken together, these results indicated that has evolved a grazing tolerance strategy under long-term grazing conditions, influencing photosynthesis and respiration in terms of its own structure and enzyme activities in the body, to maintain normal life activities under different grazing conditions.
PubMed: 38916033
DOI: 10.3389/fpls.2024.1414093 -
BioRxiv : the Preprint Server For... Jun 2024We implemented a multimodal set of functional imaging techniques optimized for deep-tissue imaging to investigate how cancer cells invade surrounding tissues and how...
We implemented a multimodal set of functional imaging techniques optimized for deep-tissue imaging to investigate how cancer cells invade surrounding tissues and how their physiological properties change in the process. As a model for cancer invasion of the extracellular matrix, we created 3D spheroids from triple-negative breast cancer cells (MDA-MB-231) and non-tumorigenic breast epithelial cells (MCF-10A). We analyzed multiple hallmarks of cancer within the same spheroid by combining a number of imaging techniques, such as metabolic imaging of NADH by Fluorescence Lifetime Imaging Microscopy (NADH-FLIM), hyperspectral imaging of a solvatochromic lipophilic dye (Nile Red) and extracellular matrix imaging by Second Harmonic Generation (SHG). We included phasor-based bioimage analysis of spheroids at three different time points, tracking both morphological and biological properties, including cellular metabolism, fatty acids storage, and collagen organization. Employing this multimodal deep-imaging framework, we observed and quantified cancer cell plasticity in response to changes in the environment composition.
PubMed: 38915530
DOI: 10.1101/2024.06.10.598307 -
Frontiers in Bioengineering and... 2024Intervertebral Disc (IVD) Degeneration (IDD) is a significant health concern, potentially influenced by mechanotransduction. However, the relationship between the IVD...
Intervertebral Disc (IVD) Degeneration (IDD) is a significant health concern, potentially influenced by mechanotransduction. However, the relationship between the IVD phenotypes and mechanical behavior has not been thoroughly explored in local morphologies where IDD originates. This work unveils the interplays among morphological and mechanical features potentially relevant to IDD through Abaqus UMAT simulations. A groundbreaking automated method is introduced to transform a calibrated, structured IVD finite element (FE) model into 169 patient-personalized (PP) models through a mesh morphing process. Our approach accurately replicates the real shapes of the patient's Annulus Fibrosus (AF) and Nucleus Pulposus (NP) while maintaining the same topology for all models. Using segmented magnetic resonance images from the former project , 169 models with structured hexahedral meshes were created employing the Bayesian Coherent Point Drift++ technique, generating a unique cohort of PP FE models under the initiative. Machine learning methods, including Linear Regression, Support Vector Regression, and eXtreme Gradient Boosting Regression, were used to explore correlations between IVD morphology and mechanics. We achieved PP models with AF and NP similarity scores of 92.06\% and 92.10\% compared to the segmented images. The models maintained good quality and integrity of the mesh. The cartilage endplate (CEP) shape was represented at the IVD-vertebra interfaces, ensuring personalized meshes. Validation of the constitutive model against literature data showed a minor relative error of 5.20%. Analysis revealed the influential impact of local morphologies on indirect mechanotransduction responses, highlighting the roles of heights, sagittal areas, and volumes. While the maximum principal stress was influenced by morphologies such as heights, the disc's ellipticity influenced the minimum principal stress. Results suggest the CEPs are not influenced by their local morphologies but by those of the AF and NP. The generated free-access repository of individual disc characteristics is anticipated to be a valuable resource for the scientific community with a broad application spectrum.
PubMed: 38915337
DOI: 10.3389/fbioe.2024.1384599 -
Frontiers in Plant Science 2024Manganese (Mn) plays a pivotal role in plant growth and development. Aside aiding in plant growth and development, Mn as heavy metal (HM) can be toxic in soil when...
Metabolomics and physio-chemical analyses of mulberry plants leaves response to manganese deficiency and toxicity reveal key metabolites and their pathways in manganese tolerance.
INTRODUCTION
Manganese (Mn) plays a pivotal role in plant growth and development. Aside aiding in plant growth and development, Mn as heavy metal (HM) can be toxic in soil when applied in excess. is an economically significant plant, capable of adapting to a range of environmental conditions and possessing the potential for phytoremediation of contaminated soil by HMs. The mechanism by which tolerates Mn stresses remains obscure.
METHODS
In this study, Mn concentrations comprising sufficiency (0.15 mM), higher regimes (1.5 mM and 3 mM), and deficiency (0 mM and 0.03 mM), were applied to in pot treatment for 21 days to understand Mn tolerance. Mn stress effects on the net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), intercellular CO concentration (Ci), chlorophyll content, plant morphological traits, enzymatic and non-enzymatic parameters were analyzed as well as metabolome signatures via non-targeted LC-MS technique.
RESULTS
Mn deficiency and toxicity decrease plant biomass, Pn, Ci, Gs, Tr, and chlorophyll content. Mn stresses induced a decline in the activities of catalase (CAT) and superoxide dismutase (SOD), while peroxidase (POD) activity, and leaf Mn content, increased. Soluble sugars, soluble proteins, malondialdehyde (MDA) and proline exhibited an elevation in Mn deficiency and toxicity concentrations. Metabolomic analysis indicates that Mn concentrations induced 1031 differentially expressed metabolites (DEMs), particularly amino acids, lipids, carbohydrates, benzene and derivatives and secondary metabolites. The DEMs are significantly enriched in alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, galactose metabolism, pantothenate and CoA biosynthesis, pentose phosphate pathway, carbon metabolism, etc.
DISCUSSION AND CONCLUSION
The upregulation of Galactinol, Myo-inositol, Jasmonic acid, L-aspartic acid, Coproporphyrin I, Trigonelline, Pantothenol, and Pantothenate and their significance in the metabolic pathways makes them Mn stress tolerance metabolites in . Our findings reveal the fundamental understanding of DEMs in 's response to Mn nutrition and the metabolic mechanisms involved, which may hold potential significance for the advancement of genetic improvement initiatives and phytoremediation programs.
PubMed: 38911982
DOI: 10.3389/fpls.2024.1349456 -
Regenerative Therapy Jun 2024With over 9 million fatalities per year expected by 2030, infectious diseases will remain a significant burden on the world economy and cause high mortality rates. An...
With over 9 million fatalities per year expected by 2030, infectious diseases will remain a significant burden on the world economy and cause high mortality rates. An excellent method to increase the bioactivity of levofloxacin (LEV) in pediatric abdominal wound repair is the finding of a stimuli-based drug delivery system (DDS). We designed and developed an LEV incorporated with zeolite imidazole framework-8 (ZIF-8) as a promising nanocarrier for wound healing applications. The spectral analysis and morphological analysis confirm the formation of our newly fabricated composites. Mouse embryonic fibroblast NIH3T3 cells, the cytotoxicity, cytocompatibility, and cell proliferation characteristics of LEV@ZIF-8 were evaluated in vitro. LEV@ZIF-8 composite considerably improved the biocompatibility against NIH3T3 cells after 72-h of exposure, according to in vitro experiments. Under acidic circumstances, the pH-responsive drug release studies exhibit superior LEV release, and in physiological circumstances, there is no unintended drug release. The LEV@ZIF-8 composite-treated cells demonstrate the most remarkable cell growth and migration method in a very short time, according to the results of the wound scratch experiment. The composite exposure concentration depended on inhibition against various microorganisms in the antibacterial activity testing. According to the study, LEV@ZIF-8 are appropriate and effective DDS for stimuli-based pediatric abdominal wound repair.
PubMed: 38911026
DOI: 10.1016/j.reth.2024.05.003 -
APL Bioengineering Jun 2024Previous lung-on-chip devices have facilitated significant advances in our understanding of lung biology and pathology. Here, we describe a novel lung-on-a-chip model in...
Previous lung-on-chip devices have facilitated significant advances in our understanding of lung biology and pathology. Here, we describe a novel lung-on-a-chip model in which human induced pluripotent stem cell-derived alveolar epithelial type II cells (iAT2s) form polarized duct-like lumens alongside engineered perfused vessels lined with human umbilical vein endothelium, all within a 3D, physiologically relevant microenvironment. Using this model, we investigated the morphologic and signaling consequences of the KRAS mutation, a commonly identified oncogene in human lung adenocarcinoma (LUAD). We show that expression of the mutant KRAS isoform in iAT2s leads to a hyperproliferative response and morphologic dysregulation in the epithelial monolayer. Interestingly, the mutant epithelia also drive an angiogenic response in the adjacent vasculature that is mediated by enhanced secretion of the pro-angiogenic factor soluble uPAR. These results demonstrate the functionality of a multi-cellular platform capable of modeling mutation-specific behavioral and signaling changes associated with lung adenocarcinoma.
PubMed: 38911024
DOI: 10.1063/5.0207228 -
Scientific Reports Jun 2024This study explores the utilization of eight readily available agricultural waste varieties in Nigeria-sugarcane bagasse, corn husk, corn cob, wheat husk, melina,...
This study explores the utilization of eight readily available agricultural waste varieties in Nigeria-sugarcane bagasse, corn husk, corn cob, wheat husk, melina, acacia, mahogany, and ironwood sawdust-as potential sources of cellulose. Gravimetric analysis was employed to assess the cellulose content of these wastes, following which two selected wastes were combined based on their cellulose content and abundance to serve as the raw material for the extraction process. Response Surface Methodology, including Box-Behnken design, was applied to enhance control over variables, establish an optimal starting point, and determine the most favorable reaction conditions. The cellulose extracted under various conditions was comprehensively examined for content, structure, extent of crystallinity, and morphological properties. Characterization techniques such as X-ray Diffraction, Scanning Electron Microscopy, and Fourier Transform Infrared Spectroscopy were employed for detailed analysis. Compositional analysis revealed sugarcane bagasse and corn cob to possess the highest cellulose content, at 41 ± 0.41% and 40 ± 0.32% respectively, with FTIR analysis confirming relatively low C=C bond intensity in these samples. RSM optimization indicated a potential 46% isolated yield from a hybrid composition of sugarcane bagasse and corn cob at NaOH concentration of 2%, temperature of 45 °C, and 10 ml of 38% HO. However, FTIR analyses revealed the persistence of non-cellulosic materials in this sample. Further analysis demonstrated that cellulose isolated at NaOH concentration of 10%, temperature of 70 °C, and 20 ml of 38% HO was of high purity, with a yield of 42%. Numerical optimization within this extraction condition range predicted a yield of 45.6% at NaOH concentration of 5%, temperature of 45 °C, and 20 ml of 38% HO. Model validation confirmed an actual yield of 43.9% at this condition, aligning closely with the predicted value. These findings underscore the significant potential of combinning and utilizing agricultural wastes as a valuable source of cellulose, paving the way for sustainable and resource-efficient practices in various industrial applications.
PubMed: 38906961
DOI: 10.1038/s41598-024-65229-4 -
The Science of the Total Environment Jun 2024Eukaryotic communities in groundwater may be particularly sensitive to disturbance because they are adapted to stable environmental conditions and often have narrow...
Eukaryotic communities in groundwater may be particularly sensitive to disturbance because they are adapted to stable environmental conditions and often have narrow spatial distributions. Traditional methods for characterising these communities, focussing on groundwater-inhabiting macro and meiofauna (stygofauna), are challenging because of limited taxonomic knowledge and expertise (particularly in less-explored regions), and the time and expense of morphological identification. The primary objective of this study was to evaluate the vulnerability of eukaryote communities in shallow groundwater to mine water discharge containing elevated concentrations of magnesium (Mg) and sulfate (SO). The study was undertaken in a shallow sand bed aquifer within a wet-dry tropical setting. The aquifer, featuring a saline mine water gradient primarily composed of elevated Mg and SO, was sampled from piezometers in the creek channel upstream and downstream of the mine water influence during the dry season when only subsurface water flow was present. Groundwater communities were characterised using both morphological assessments of stygofauna from net samples and environmental DNA (eDNA) targeting the 18S rDNA and COI mtDNA genes. eDNA data revealed significant shifts in community composition in response to mine waters, contrasting with findings from traditional morphological composition data. Changes in communities determined using eDNA data were notably associated with concentrations of SO, Mg, Na, and water levels in the piezometers. This underscores the importance of incorporating molecular approaches in impact assessments, as relying solely on traditional stygofauna sampling methods in similar environments may lead to inaccurate conclusions about the responses of the assemblage to studied impacts.
PubMed: 38906296
DOI: 10.1016/j.scitotenv.2024.174101