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Stem-cell-based therapies can potentially reverse organ dysfunction and diseases, but the removal of impaired tissue and activation of a program leading to organ regeneration pose major challenges. In mice, a 4-day fasting mimicking diet (FMD) induces a stepwise expression of Sox17 and Pdx-1, followed by Ngn3-driven generation of insulin-producing ß cells, resembling that observed during pancreatic development. FMD cycles restore insulin secretion and glucose homeostasis in both type 2 and type 1 diabetes mouse models. In human type 1 diabetes pancreatic islets, fasting conditions reduce PKA and mTOR activity and induce Sox2 and Ngn3 expression and insulin production. The effects of the FMD are reversed by IGF-1 treatment and recapitulated by PKA and mTOR inhibition. These results indicate that a FMD promotes the reprogramming of pancreatic cells to restore insulin generation in islets from T1D patients and reverse both T1D and T2D phenotypes in mouse models. PAPERCLIP.
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Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 2/dietoterapia , Ayuno , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Dieta , Prueba de Tolerancia a la Glucosa , Humanos , Técnicas In Vitro , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Islotes Pancreáticos , Ratones , Proteínas del Tejido Nervioso/genética , Páncreas/citología , Páncreas/metabolismo , Transducción de Señal , TranscriptomaRESUMEN
Dementia is a brain disease which results in irreversible and progressive loss of cognition and motor activity. Despite global efforts, there is no simple and reliable diagnosis or treatment option. Current diagnosis involves indirect testing of commonly inaccessible biofluids and low-resolution brain imaging. We have developed a portable, wireless readout-based Graphene field-effect transistor (GFET) biosensor platform that can detect viruses, proteins, and small molecules with single-molecule sensitivity and specificity. We report the detection of three important amyloids, namely, Amyloid beta (Aß), Tau (τ), and α-Synuclein (αS) using DNA aptamer nanoprobes. These amyloids were isolated, purified, and characterized from the autopsied brain tissues of Alzheimer's Disease (AD) and Parkinson's Disease (PD) patients. The limit of detection (LoD) of the sensor is 10 fM, 1-10 pM, 10-100 fM for Aß, τ, and αS, respectively. Synthetic as well as autopsied brain-derived amyloids showed a statistically significant sensor response with respect to derived thresholds, confirming the ability to define diseased vs. nondiseased states. The detection of each amyloid was specific to their aptamers; Aß, τ, and αS peptides when tested, respectively, with aptamers nonspecific to them showed statistically insignificant cross-reactivity. Thus, the aptamer-based GFET biosensor has high sensitivity and precision across a range of epidemiologically significant AD and PD variants. This portable diagnostic system would allow at-home and POC testing for neurodegenerative diseases globally.
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Enfermedad de Alzheimer , Aptámeros de Nucleótidos , Grafito , Enfermedad de Parkinson , Humanos , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Parkinson/diagnóstico , Biomarcadores , Proteínas tauRESUMEN
Estrogen receptor α (ER) is the major driver of â¼75% of breast cancers, and multiple ER targeting drugs are routinely used clinically to treat patients with ER+ breast cancer. However, many patients relapse on these targeted therapies and ultimately develop metastatic and incurable disease, and understanding the mechanisms leading to drug resistance is consequently of utmost importance. It is now clear that, in addition to estrogens, ER function is modulated by other steroid receptors and multiple signaling pathways (e.g., growth factor and cytokine signaling), and many of these pathways affect drug resistance and patient outcome. Here, we review the mechanisms through which these pathways impact ER function and drug resistance as well as discuss the clinical implications.
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Neoplasias de la Mama/metabolismo , Receptor alfa de Estrógeno/metabolismo , Receptores de Esteroides/metabolismo , Transducción de Señal , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Citocinas/fisiología , Resistencia a Antineoplásicos , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/fisiología , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/metabolismoRESUMEN
[This corrects the article DOI: 10.1371/journal.ppat.1009885.].
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The emergence of new variants of SARS-CoV-2 necessitates unremitting efforts to discover novel therapeutic monoclonal antibodies (mAbs). Here, we report an extremely potent mAb named P4A2 that can neutralize all the circulating variants of concern (VOCs) with high efficiency, including the highly transmissible Omicron. The crystal structure of the P4A2 Fab:RBD complex revealed that the residues of the RBD that interact with P4A2 are a part of the ACE2-receptor-binding motif and are not mutated in any of the VOCs. The pan coronavirus pseudotyped neutralization assay confirmed that the P4A2 mAb is specific for SARS-CoV-2 and its VOCs. Passive administration of P4A2 to K18-hACE2 transgenic mice conferred protection, both prophylactically and therapeutically, against challenge with VOCs. Overall, our data shows that, the P4A2 mAb has immense therapeutic potential to neutralize the current circulating VOCs. Due to the overlap between the P4A2 epitope and ACE2 binding site on spike-RBD, P4A2 may also be highly effective against a number of future variants.
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Enzima Convertidora de Angiotensina 2 , Anticuerpos Neutralizantes , COVID-19 , SARS-CoV-2 , Animales , Humanos , Ratones , Enzima Convertidora de Angiotensina 2/química , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/uso terapéutico , COVID-19/inmunología , COVID-19/terapia , Ratones Transgénicos , Pruebas de Neutralización , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
The influence of transporters on the pharmacokinetics of drugs is being increasingly recognized, and drug-drug interactions (DDIs) via modulation of transporters could lead to clinical adverse events. Organic anion-transporting polypeptide 1B (OATP1B) are liver specific uptake transporters in humans that can transport a broad range of substrates, including statins. It is a challenge to predict OATP1B-mediated DDIs using preclinical animal models because of species differences in substrate specificity and abundance levels of transporters. PXB-mice are chimeric mice with humanized livers that are highly repopulated with human hepatocytes and have been widely used for drug metabolism and pharmacokinetics studies in drug discovery. In the present study, we measured the exposure increases (blood AUC and Cmax) of ten OATP1B substrates in PXB-mice upon co-administration with rifampin, a potent OATP1B specific inhibitor. These data in PXB-mice were then compared with the observed DDIs between OATP1B substrates and single-dose rifampin in humans. Our findings suggest that the DDIs between OATP1B substrates and rifampin in PXB-mouse are comparable with the observed DDIs in the clinic. Since most OATP1B substrates are metabolized by CYPs and/or are substrates of P-glycoprotein (P-gp), we further validated the utility of PXB-mice to predict complex DDIs involving inhibition of OATP1B, CYPs and P-gp using CsA and gemfibrozil as perpetrators. Overall, the data support that the chimeric mice with humanized livers could be a useful tool for the prediction of hepatic OATP1B-mediated DDIs in humans. Significance Statement The ability of PXB-mouse with humanized liver to predict OATP1B-mediated drug-drug interactions (DDIs) in humans was evaluated. The plasma exposure increases of ten OATP1B substrates with rifampin, an OATP1B inhibitor, in PXB-mice have a good correlation with those observed in humans. More importantly, PXB-mice can predict complex DDIs including inhibition of OATP1B, CYPs and P-gp in humans. PXB-mice are a promising useful tool to assess OATP1B-mediated clinical DDIs.
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Feather waste is a highly prevalent form of keratinous waste that is generated by the poultry industry. The global daily production of feather waste has been shown to approach 5 million tons, typically being disposed of through methods such as dumping, landfilling, or incineration which contribute significantly to environmental pollutions. The proper management of these keratinous wastes is crucial to avoid environmental contamination. The study was carried out to isolate the keratinolytic fungi from the poultry disposal sites of different region of North-East India to evaluate its potential in bioremediation of the feathers wastes. Out of 12 fungal strains isolated from the sites, the fungus showing the highest zone of hydrolysis on both the skim milk and keratin agar medium was selected for the study and the molecular identification of the isolate was performed through DNA sequence analysis by amplifying the internal transcribed spacer (ITS) region. The sequence results showed higher similarity (above 95%) with Aspergillus spp. and was named Aspergillus sp. Iro-1. The strain was further analyzed for its feather degrading potential which was performed in submerged conditions under optimized conditions. The study showed that the strain could effectively degrade the feathers validated through weight loss method, and the structural deformations in the feathers were visualized through scanning electron microscopy (SEM). Aspergillus sp. Iro-1 was obtained from the southern region of Assam. It would be of great importance as the implementation of this sp. can help in the bioremediation of feathers wastes in this region. This is the first study of identification of feather degrading fungus from southern part of Assam (Barak).
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Péptido Hidrolasas , Aves de Corral , Animales , Aves de Corral/microbiología , Péptido Hidrolasas/metabolismo , Hongos/genética , Hongos/metabolismo , Hidrólisis , Biodegradación Ambiental , Queratinas/metabolismo , Concentración de Iones de Hidrógeno , Pollos , TemperaturaRESUMEN
INTRODUCTION: Traumatic brain injury (TBI) is associated with an accelerated course of dementia, although biological relationships are incompletely understood. METHODS: The study examined 1124 participants, including 343 with Alzheimer disease (AD), 127 with AD with TBI, 266 cognitively normal adults with TBI, and 388 cognitively normal adults without TBI. Cortical thickness was quantified from T1-weighted magnetic resonance imaging data. Multiple linear regression was used to determine the interaction between AD and TBI on cortical thickness. RESULTS: Among those with AD, TBI was associated with an earlier age of AD onset but, counterintuitively, less cortical thinning in frontotemporal regions relative to non-AD controls. DISCUSSION: AD with TBI represents a distinct group from AD, likely with distinct pathologic contributions beyond gray matter loss. This finding has important implications for the diagnosis and treatment of AD in the presence of TBI and indicates that models of AD, aging, and neural loss should account for TBI history.
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Enfermedad de Alzheimer , Lesiones Traumáticas del Encéfalo , Humanos , Enfermedad de Alzheimer/diagnóstico , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/patología , Envejecimiento/patología , Imagen por Resonancia Magnética/métodosRESUMEN
The cysteine-free acyclic peptides present in marine cone snail venom have been much less investigated than their disulfide bonded counterparts. Precursor protein sequences derived from transcriptomic data, together with mass spectrometric fragmentation patterns for peptides present in venom duct tissue extracts, permit the identification of mature peptides. Twelve distinct gene superfamiles have been identified with precursor lengths between 64 and 158 residues. In the case of Conus monile, three distinct mature peptides have been identified, arising from two distinct protein precursors. Mature acyclic peptides are often post-translationally modified, with C-terminus amidation, a feature characteristic of neuropeptides. In the present study, 20 acyclic peptides from Conus monile and Conus betulinus were identified. The common modifications of C-terminus amidation, gamma carboxylation of glutamic acid (E to Ï), N-terminus conversion of Gln (Q) to a pyroglutamyl residue (Z), and hydroxylation of Pro (P) to Hyp (O) are observed in one or more peptides identified in this study. Proteolytic trimming of sequences by cleavage at the C-terminus of Asn (N) residues is established. The presence of an asparagine endopeptidase is strengthened by the identification of legumain-like sequences in the transcriptome assemblies from diverse Conus species. Such sequences may be expected to have a cleavage specificity at Asn-Xxx peptide bonds.
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Conotoxinas , Caracol Conus , Animales , Venenos de Moluscos/química , Venenos de Moluscos/genética , Venenos de Moluscos/metabolismo , Conotoxinas/química , Péptidos/química , Caracol Conus/química , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismoRESUMEN
BACKGROUND: Bacterial panicle blight, incited by Burkholderia glumae, has impacted rice production globally. Despite its significance, knowledge about the disease and the virulence pattern of the causal agent is very limited. Bacterial panicle blight is a major challenge in the rice-growing belts of North-western India, resulting in yield reduction. However, the management of B. glumae has become a challenge due to the lack of proper management strategies. METHODOLOGY AND RESULTS: Twenty-one BG strains have been characterized using the 16S rRNA and the gyrB gene-based sequence approach in the present study. The gyrB gene-based phylogenetic analysis resulted in geographic region-specific clustering of the BG isolates. The virulence screening of twenty-one BG strains by inoculating the pathogenic bacterial suspension of 1 × 10-8 cfu/ml at the booting stage (55 DAT) revealed the variation in the disease severity and the grain yield of rice plants. The most virulent BG1 strain resulted in the highest disease incidence (82.11%) and lowest grain yield (11.12 g/plant), and the least virulent BG10 strain resulted in lowest disease incidence of 18.94% and highest grain yield (24.62 g/plant). In vitro evaluation of various biocontrol agents and nano copper at different concentrations by agar well diffusion method revealed that nano copper at 1000 mg/L inhibited the colony growth of B. glumae. Under net house conditions, nano copper at 1000 mg/L reduced the disease severity to 21.23% and increased the grain yield by 20.91% (31.76 g per plant) compared to the positive control (COC 0.25% + streptomycin 200 ppm). Remarkably, pre-inoculation with nano copper at 1000 mg/L followed by challenge inoculation with B. glumae enhanced the activity of enzymatic antioxidants viz., Phenyl ammonia-lyase (PAL), Polyphenol oxidase (PPO) and Peroxidase (POX) and non-enzymatic antioxidant phenol. Additionally, we observed a substantial transcript level upregulation of six defense-related genes to several folds viz., OsPR2, OsPR5, OsWRKY71, OsPAL1, OsAPX1, and OsPPO1 in comparison to the pathogen control and healthy control. CONCLUSIONS: Overall, our study provides valuable insights into the potential and practical application of nano copper for the mitigation of bacterial panicle blight, offering promising prospects for commercial utilization in disease management.
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Burkholderia , Oryza , Oryza/genética , Filogenia , ARN Ribosómico 16S/genética , Burkholderia/genética , Antioxidantes , Cobre , Grano ComestibleRESUMEN
OBJECTIVES: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses. METHODS: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2-years follow-up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits. RESULTS: Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively. CONCLUSIONS: The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.
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Enfermedad de Alzheimer , Trastornos Cerebrovasculares , Disfunción Cognitiva , Enfermedad de Parkinson , Humanos , Estudios Transversales , Enfermedad de Parkinson/psicología , Estudios Longitudinales , Disfunción Cognitiva/psicología , Enfermedad de Alzheimer/psicología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Trastornos Cerebrovasculares/complicaciones , Pruebas NeuropsicológicasRESUMEN
AIMS: The study aimed to determine the pathogenicity of Fusarium species currently prevalent in tomato fields having history of chemical fungicide applications and determine the bio-efficacy of Bacillus subtilis NBRI-W9 as a potent biological control agent. METHODS AND RESULTS: Fusarium was isolated from surface-sterilized infected tomato plants collected from fields. Pathogenicity of 30 Fusarium isolates was determined by in vitro and in vivo assays. Following Koch's postulates, F. chlamydosporum (FOL7) was identified as a virulent pathogen. The biological control of FOL 7 by B. subtilis NBRI-W9 (W9) and the colonization potential of W9 were established using spontaneous rifampicin-resistant mutants. W9 showed 82% inhibition of FOL7 on a dual-culture plate and colonization levels in tomato plants of â¼5.5, â¼3.3, and â¼2.2 log10 CFU/g in root, stem, and leaf tissue, respectively. Antagonistic activity was shown by scanning electron microscopy (SEM) and cell-wall-degradative enzymes. W9 reduced FOL7 infection in net-house and field experiments by 60% and 41%, respectively. Biochemical investigation, defence enzymes, defence gene expression analysis, SEM, and field studies provide evidence of hyperparasitism and induced resistance as the mode of biological control. The study also demonstrates that the potent biocontrol agent W9, isolated from Piper, can colonize tomato plants, control fungal disease by inducing induced systemic resistance (ISR) and systemic acquired resistance (SAR) simultaneously, and increase crop yield by 21.58% under field conditions. CONCLUSIONS: This study concludes that F. chlamydosporum (NBRI-FOL7) is a potent, fungicide-resistant pathogen causing wilt in tomatoes. NBRI-W9 controlled FOL7 through mycoparasitism and simultaneously activated ISR and SAR in plants, providing an attractive tool for disease control that acts at multiple levels.
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Fungicidas Industriales , Fusarium , Solanum lycopersicum , Bacillus subtilis , Resistencia Sistémica Adquirida de la Planta , Plantas , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiologíaRESUMEN
Oral cancer is a common malignant tumor of the oral cavity that affects many countries with a prevalent distribution in the Indian subcontinent, with poor prognosis rate on account of locoregional metastases. Gain-of-function mutations in p53 and overexpression of its related transcription factor, p63 are both widely reported events in oral cancers. However, targeting these alterations remains a far-achieved aim due to lack of knowledge on their downstream signaling pathways. In the present study, we characterize the isoforms of p63 and using knockdown strategy, decipher the functions and oncogenic signaling of p63 in oral cancers. Using Microarray and Chromatin Immunoprecipitation experiments, we decipher a novel transcriptional regulatory axis between p63 and Activin A and establish its functional significance in migration of oral cancer cells. Using an orally bioavailable inhibitor of the Activin A pathway to attenuate oral cancer cell migration and invasion, we further demonstrate the targetability of this signaling axis. Our study highlights the oncogenic role of ΔNp63 - Activin A - SMAD2/3 signaling and provides a basis for targeting this oncogenic pathway in oral cancers.
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Activinas , Neoplasias de la Boca , Factores de Transcripción , Proteínas Supresoras de Tumor , Humanos , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Línea Celular Tumoral , Técnicas de Silenciamiento del Gen , Movimiento Celular , Transducción de Señal , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Activinas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
This study presents a novel blend of synthesis techniques for shape-controlled ZnS nanoparticles. Zinc sulfide (ZnS) nanoparticles with distinct morphologies cauliflower-like microstructures (â¼4.5 µm) and uniform nanospheres (200-700 nm) were synthesized through an innovative blend of precipitation and hydrothermal techniques. Capping with polyvinylpyrrolidone (PVP) significantly decreased crystallite size (3.93 nm-2.36 nm), modulated the band gap (3.57 eV-3.71 eV), and dramatically influenced morphology, highlighting the novelty of shape-controlled synthesis and its impact on optoelectronic and functional properties. X-ray diffraction confirmed crystallinity and revealed the size-controlling influence of PVP. UV-vis spectroscopy suggested potential tuning of optical properties due to band gap widening upon PVP capping. Field-emission scanning electron microscopy (FESEM) unveiled distinct morphologies: cauliflower-like microstructures for ZnS and uniform nanospheres (200-700 nm) for PVP-ZnS. Both structures were composed of smaller spherical nanoparticles, demonstrating the role of PVP in promoting controlled growth and preventing agglomeration. High-resolution transmission electron microscope (HRTEM) images depicted that the majority of nanoparticles maintain a spherical shape, though slight deviations from perfect sphericity can be discerned. Fourier-transform infrared (FTIR) spectroscopy confirmed that successful PVP encapsulation is crucial for shaping nanospheres and minimizing aggregation through steric hindrance. Photocatalytic activity evaluation using methylene blue (MB) dye degradation revealed significantly faster degradation by PVP-ZnS under ultraviolet (UV) irradiation (within 60 min as compared to 120 min for ZnS), showcasing its superior performance. This improvement can be attributed to the smaller size, higher surface area, and potentially optimized band gap of PVP-ZnS. Additionally, PVP-ZnS exhibited promising antibacterial activity against S. aureus and P. aeruginosa, with increased activity at higher nanoparticle concentrations.
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A new area of biotechnology is nanotechnology. Nanotechnology is an emerging field that aims to develope various substances with nano-dimensions that have utilization in the various sectors of pharmaceuticals, bio prospecting, human activities and biomedical applications. An essential stage in the development of nanotechnology is the creation of nanoparticles. To increase their biological uses, eco-friendly material synthesis processes are becoming increasingly important. Recent years have shown a lot of interest in nanostructured materials due to their beneficial and unique characteristics compared to their polycrystalline counterparts. The fascinating performance of nanomaterials in electronics, optics, and photonics has generated a lot of interest. An eco-friendly approach of creating nanoparticles has emerged in order to get around the drawbacks of conventional techniques. Today, a wide range of nanoparticles have been created by employing various microbes, and their potential in numerous cutting-edge technological fields have been investigated. These particles have well-defined chemical compositions, sizes, and morphologies. The green production of nanoparticles mostly uses plants and microbes. Hence, the use of microbial nanotechnology in agriculture and plant science is the main emphasis of this review. The present review highlights the methods of biological synthesis of nanoparticles available with a major focus on microbially synthesized nanoparticles, parameters and biochemistry involved. Further, it takes into account the genetic engineering and synthetic biology involved in microbial nanobiosynthesis to the construction of microbial nanofactories.
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Nanopartículas , Nanotecnología , Nanotecnología/métodos , Nanopartículas/química , Bacterias/metabolismo , Bacterias/genética , Biotecnología/métodos , Biología Sintética/métodos , Nanoestructuras/químicaRESUMEN
Ideally, the morphology of atrial appendages should solely be used to identify and differentiate patients with isomeric right and left atrial appendages. However, in clinical practice, the segregation is often indirectly based on the arrangement of thoraco-abdominal structures. The correlation between thoraco-abdominal arrangement and atrial appendages, however, is imperfect. In this study, we sought to clarify the cardiovascular malformations in patients with isomeric atrial appendages with an emphasis on atrial-thoracic-abdominal disharmony. A retrospective review of all patients who underwent cardiac CT angiography between January 2014 and June 2023 and identified to have isomeric atrial appendages was performed. Of the 366 cases (median age: 2 years [interquartile range: 11 months-7 years]), 247 (67.5%) patients had isomeric right atrial appendages while 119 (32.5%) patients had isomeric left atrial appendages. In 316 (86.3%) patients, the thoraco-abdominal arrangement was as per atrial appendage morphology while the remaining 50 (13.6%) patients had disharmonious patterns. Compared to isomeric left atrial appendages, the disharmonious pattern was more frequent with isomeric right atrial appendages (5.9% vs. 17.4%; p 0.003). Irrespective of the type of isomerism, disharmony was mostly confined to the level of the abdomen. Not all patients with isomeric atrial appendages have a harmonious thoraco-abdominal arrangement. The atrial-bronchial-abdominal disharmony is more frequent with isomeric right atrial appendages and is mostly present at the level of the abdomen. A detailed sequential segmental analysis with an independent description of each organ system is, therefore, essential for the complete evaluation of patients with isomeric atrial appendages.
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Pineapple (Ananas comosus), the succulent and vibrant tropical fruit, is a symbol of exoticism and sweetness that captures the hearts and palates of people around the world. The pineapple peel, often considered as waste, has garnered attention for its potential applications. The pineapple peel is rich in essential nutrients, including calcium, potassium, vitamin C, carbohydrates, dietary fiber, and water, making it beneficial for the digestive system, weight management, and overall balanced nutrition. It contains significant amounts of sugars such as sucrose, glucose, and fructose, along with citric acid as the predominant organic acid. The peel also contains bromelain, a proteolytic enzyme known for its digestive properties. Studies have highlighted the pharmacological properties of pineapple peel, such as its potential anti-parasitic effects, alleviation of constipation, and benefits for individuals with irritable bowel syndrome (IBS). Efforts are being made to promote the utilization of pineapple peel as a valuable resource rather than mere waste. Its applications range from the production of vinegar, alcohol, and citric acid to the development of various food products, including squash, syrup, jelly, and pickles. Further research and innovation are required to fully explore the potential of pineapple peel and establish sustainable practices for its utilization, contributing to waste reduction and the development of value-added products.
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Ananas , Humanos , Ananas/química , Frutas/química , Valor Nutritivo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ácido Ascórbico/química , Potasio/química , Carbohidratos/químicaRESUMEN
For early diabetes identification and management, the progression of an uncomplicated and exceedingly responsive glucose testing technology is crucial. In this study, we present a new sensor incorporating a composite of metal organic framework (MOF) based on cobalt, coated with boronic acid to facilitate selective glucose binding. Additionally, we successfully employed a highly sensitive electro-optical immunosensor for the detection of subtle changes in concentration of the diabetes biomarker glycated haemoglobin (HbA1c), using zeolitic imidazolate framework-67 (ZIF-67) coated with polydopamine which further modified with boronic acid. Utilizing the polymerization characteristics of dopamine and the NH2 groups, a bonding structure is formed between ZIF-67 and 4-carboxyphenylboronic acid. ZIF-67 composite served as an effective substrate for immobilising 4-carboxyphenylboronic acid binding agent, ensuring precise and highly selective glucose identification. The sensing response was evaluated through both electrochemical and optical methods, confirming its efficacy. Under optimized experimental condition, the ZIF-67 based sensor demonstrated a broad detection range of 50-500 mg dL-1, a low limit of detection (LOD) of 9.87 mg dL-1 and a high correlation coefficient of 0.98. Furthermore, the 4-carboxyphenylboronic acid-conjugated ZIF-67-based sensor platform exhibited remarkable sensitivity and selectivity in optical-based detection for glycated haemoglobin within the clinical range of 4.7-11.3%, achieving a LOD of 3.7%. These findings highlight the potential of the 4-carboxyphenylboronic acid-conjugated ZIF-67-based electro-optical sensor as a highly sensitive platform for diabetes detection.
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Glucemia , Ácidos Borónicos , Diabetes Mellitus , Hemoglobina Glucada , Imidazoles , Límite de Detección , Estructuras Metalorgánicas , Zeolitas , Ácidos Borónicos/química , Zeolitas/química , Estructuras Metalorgánicas/química , Imidazoles/química , Humanos , Hemoglobina Glucada/análisis , Glucemia/análisis , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Nanopartículas/química , Técnicas Biosensibles/métodos , Indoles/química , Polímeros/química , Técnicas Electroquímicas/métodosRESUMEN
Detection and characterization of hidden defects, impurities, and damages in homogeneous materials like aluminum die casting materials, as well as composite materials like Fiber-Metal Laminates (FML), is still a challenge. This work discusses methods and challenges in data-driven modeling of automated damage and defect detectors using measured X-ray single- and multi-projection images. Three main issues are identified: Data and feature variance, data feature labeling (for supervised machine learning), and the missing ground truth. It will be shown that simulation of synthetic measuring data can deliver a ground truth dataset and accurate labeling for data-driven modeling, but it cannot be used directly to predict defects in manufacturing processes. Noise has a significant impact on the feature detection and will be discussed. Data-driven feature detectors are implemented with semantic pixel Convolutional Neural Networks. Experimental data are measured with different devices: A low-quality and low-cost (Low-Q) X-ray radiography, a typical industrial mid-quality X-ray radiography and Computed Tomography (CT) system, and a state-of-the-art high-quality µ-CT device. The goals of this work are the training of robust and generalized data-driven ML feature detectors with synthetic data only and the transition from CT to single-projection radiography imaging and analysis. Although, as the title implies, the primary task is pore characterization in aluminum high-pressure die-cast materials, but the methods and results are not limited to this use case.
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INTRODUCTION: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases. METHODS: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative. RESULTS: PVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH. DISCUSSION: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia. HIGHLIGHTS: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS's effect on executive function was mediated by GFAP and white matter disease.