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Background Dermatophytosis is a superficial fungal infection caused by a group of pathogenic keratinophilic fungi. The increase in the incidence of superficial fungal infections, combined with the emergence of antifungal resistance, represents both a global health challenge and a considerable economic burden. Recent years have witnessed a surge in dermatophytosis cases, accompanied by the emergence of antifungal-resistant strains. This study aimed to analyze the in vitro antifungal susceptibility patterns and determine the minimum inhibitory concentrations (MIC) of antifungal drugs among isolated species using the broth microdilution method. Methodology This cross-sectional study was conducted between September 2021 and August 2022. Patients with symptoms or clinical features of fungal infection, including skin, hair, and nail lesions indicative of Tinea infections, were included. Samples underwent processing, including potassium hydroxide (KOH) mounting, direct microscopic examination, and culture on Sabouraud Dextrose Agar (SDA) with antibiotics. Antifungal susceptibility testing was subsequently conducted. Results Trichophyton mentagrophytes emerged as the most common isolate among patients with Tinea infections. MIC values of various drugs were analyzed, with itraconazole exhibiting a minimum MIC of 0.03 µg/ml and a maximum of 0.50 µg/ml. Terbinafine showed an MIC of 0.010 µg/ml and a maximum of 1.00 µg/ml. Ketoconazole had a minimum MIC of 0.03 µg/ml and a maximum of 0.50 µg/ml. Fluconazole exhibited a minimum MIC of 0.10 µg/ml and a maximum of 1.00 µg/ml. Lastly, miconazole demonstrated a minimum MIC of 0.03 µg/ml and a maximum of 2.00 µg/ml. Conclusion Accurate diagnosis is crucial for fungal infections to enable early treatment and reduce transmission. With an increasing trend in resistance among dermatophytes, there is a growing need to conduct susceptibility testing of antifungal agents, particularly in cases of long-term infections, recurrent infections, and individuals who do not respond to medication.
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Cadmium, a heavy metal, disrupts cellular homeostasis and is highly toxic, with no effective treatments currently available against its toxicity. According to studies, phytochemicals provide a promising strategy for mitigating cadmium toxicity. Naringenin (NG), a potent antioxidant found primarily in citrus fruits, showed protective properties against cadmium toxicity in rats. Nonetheless, the precise mechanism of cadmium cytotoxicity in fibroblasts remains unknown. This study evaluated NG against cadmium (CdCl2) toxicity utilizing network pharmacology and in silico molecular docking, and was further validated experimentally in rat fibroblast F111 cells. Using network pharmacology, 25 possible targets, including the top 10 targets of NG against cadmium, were identified. Molecular docking of interleukin 6 (IL6), the top potential target with NG, showed robust binding with an inhibition constant (Ki) of 58.76 µM, supporting its potential therapeutic potential. Pathway enrichment analysis suggested that "response to reactive oxygen species" and "negative regulation of small molecules metabolic process" were the topmost pathways targeted by NG against cadmium. In vitro analysis showed that NG (10 µM) attenuated CdCl2-induced oxidative stress by reducing altered intracellular ROS, mitochondrial mass, and membrane potential. Also, NG reversed CdCl2-mediated nuclear damage, G2/M phase arrest, and apoptosis. GC/MS-based metabolomics of F111 cells revealed CdCl2 reduced cholesterol levels, which led to alterations in primary bile acid, steroid and steroid hormone biosynthesis pathways, whereas, NG restored these alterations. In summary, combined in silico and in vitro analysis suggested that NG protected cells from CdCl2 toxicity by mitigating oxidative stress and metabolic pathway alterations, providing a comprehensive understanding of its protective mechanisms against cadmium-induced toxicity.
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Plant diseases pose a significant threat to agricultural productivity worldwide. Convolutional neural networks (CNNs) have achieved state-of-the-art performances on several plant disease detection tasks. However, the manual development of CNN models using an exhaustive approach is a resource-intensive task. Neural Architecture Search (NAS) has emerged as an innovative paradigm that seeks to automate model generation procedures without human intervention. However, the application of NAS in plant disease detection has received limited attention. In this work, we propose a two-stage meta-learning-based neural architecture search system (ML NAS) to automate the generation of CNN models for unseen plant disease detection tasks. The first stage recommends the most suitable benchmark models for unseen plant disease detection tasks based on the prior evaluations of benchmark models on existing plant disease datasets. In the second stage, the proposed NAS operators are employed to optimize the recommended model for the target task. The experimental results showed that the MLNAS system's model outperformed state-of-the-art models on the fruit disease dataset, achieving an accuracy of 99.61%. Furthermore, the MLNAS-generated model outperformed the Progressive NAS model on the 8-class plant disease dataset, achieving an accuracy of 99.8%. Hence, the proposed MLNAS system facilitates faster model development with reduced computational costs.
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This study demonstrated the correlation of molecular structures of Peroxisome proliferator-activated receptor gamma (PPARγ) modulators and their biological activities. Bayesian classification, and recursive partitioning (RP) studies have been applied to a dataset of 323 PPARγ modulators with diverse scaffolds. The results provide a deep insight into the important sub-structural features modulating PPARγ. The molecular docking analysis again confirmed the significance of the identified sub-structural features in the modulation of PPARγ activity. Molecular dynamics simulations further underscored the stability of the complexes formed by investigated modulators with PPARγ. Overall, the integration of many computational approaches unveiled key structural motifs essential for PPARγ modulatory activity that will shed light on the development of effective modulators in the future.
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Alzheimer's disease (AD) is the most prevalent cause of dementia and is characterized by low levels of acetyl and butyrylcholine, increased oxidative stress, inflammation, accumulation of metals, and aggregations of Aß and tau proteins. Current treatments for AD provide only symptomatic relief without impacting the pathological hallmarks of the disease. In our ongoing efforts to develop naturally inspired novel multitarget molecules for AD, through extensive medicinal chemistry efforts, we have developed 13a, harboring the key functional groups to provide not only symptomatic relief but also targeting oxidative stress, able to chelate iron, inhibiting NLRP3, and Aß1-42 aggregation in various AD models. 13a exhibited promising anticholinesterase activity against AChE (IC50 = 0.59 ± 0.19 µM) and BChE (IC50 = 5.02 ± 0.14 µM) with excellent antioxidant properties in DPPH assay (IC50 = 5.88 ± 0.21 µM) over ferulic acid (56.49 ± 0.62 µM). The molecular docking and dynamic simulations further corroborated the enzyme inhibition studies and confirmed the stability of these complexes. Importantly, in the PAMPA-BBB assay, 13a turned out to be a promising molecule that can efficiently cross the blood-brain barrier. Notably, 13a also exhibited iron-chelating properties. Furthermore, 13a effectively inhibited self- and metal-induced Aß1-42 aggregation. It is worth mentioning that 13a demonstrated no symptom of cytotoxicity up to 30 µM concentration in PC-12 cells. Additionally, 13a inhibited the NLRP3 inflammasome and mitigated mitochondrial-induced reactive oxygen species and mitochondrial membrane potential damage triggered by LPS and ATP in HMC-3 cells. 13a could effectively reduce mitochondrial and cellular reactive oxygen species (ROS) in the Drosophila model of AD. Finally, 13a was found to be efficacious in reversing memory impairment in a scopolamine-induced AD mouse model in the in vivo studies. In ex vivo assessments, 13a notably modulates the levels of superoxide, catalase, and malondialdehyde along with AChE and BChE. These findings revealed that 13a holds promise as a potential candidate for further development in AD management.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Inhibidores de la Colinesterasa , Ácidos Cumáricos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/síntesis química , Ácidos Cumáricos/farmacología , Humanos , Péptidos beta-Amiloides/metabolismo , Antioxidantes/farmacología , Antioxidantes/síntesis química , Diseño de Fármacos , Ratones , Ratas , Simulación del Acoplamiento Molecular , Estrés Oxidativo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/síntesis química , Butirilcolinesterasa/metabolismo , Butirilcolinesterasa/efectos de los fármacos , Células PC12 , Fragmentos de Péptidos/metabolismo , Acetilcolinesterasa/metabolismo , Acetilcolinesterasa/efectos de los fármacosRESUMEN
BACKGROUND: Studies attempted to estimate MASLD-related advanced fibrosis (AF) and cirrhosis (MC) prevalence utilized tests with low positive predictive value (PPV) which overestimates prevalence. AGILE3 + and 4 scores were developed to increase the PPV of both; respectively. In this study, we used these scores to assess the prevalence of AF and MC. METHODS: Participants aged ≥ 18 years with VCTE exam in the NHANES 2017-2018 cycle were included. We excluded pregnant women, patients with excessive alcohol intake, hepatitis B/C, and ALT or AST > 500 IU/L. MASLD was defined with CAP score > 248 dB/m. MASLD subjects with AGILE 3 + score of ≥ 0.68 and AGILE 4 score of ≥ 0.57 were considered to have advanced fibrosis and cirrhosis; respectively. AGILE 3 + of 0.45-0.67 and AGILE 4 of 0.25-0.57 were grey zone, whereas AGILE 3 + < 0.45 and AGILE 4 < 0.25 were considered a rule-out. RESULTS: 1244 subjects were included in the final analysis. The Median age was 53 (51.4-54.6) years, 55.6% were male, median BMI was 33.8 kg/m2 and 41.1% had T2DM. Based on AGILE 3+, 80.3% of the MASLD population were at low risk for AF and 11.5% were in grey zone. The prevalence of AF due to MASLD was 8.1% corresponding to 4.5 million Americans. Based on AGILE 4 score, 96.5% of the MASLD population were at low risk for cirrhosis and 2.4% were in the grey zone. The prevalence of MASLD-cirrhosis was 1.1% corresponding to 610,000 Americans. CONCLUSION: Our results suggest that approximately 4.5 million people in the U.S. have AF and 0.6 million have cirrhosis due to MASLD.
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Cirrosis Hepática , Encuestas Nutricionales , Humanos , Femenino , Masculino , Persona de Mediana Edad , Prevalencia , Cirrosis Hepática/epidemiología , Estados Unidos/epidemiología , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , AdultoRESUMEN
Background Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. Chronic plaque psoriasis, or psoriasis vulgaris, is the most common form of psoriasis. Present available preparations for mild to moderate chronic plaque psoriasis for topical use are local corticosteroids, coal tar, dithranol, tazarotene, calcipotriol, tapinarof, and calcineurin inhibitors. However, every preparation has its disadvantages. Calcipotriol, an active form of vitamin D, is available in topical form for dermatological use. Chronic plaque psoriasis is the chief medical use of calcipotriol for mild to moderate form. Methotrexate has dramatic results in psoriasis when used systemically. Now, topical formulation is being advocated in localized psoriasis, which is not associated with the side effects of the systemic form. Therefore, this study aimed to compare the effectiveness of topical calcipotriol and topical methotrexate on the basis of the psoriasis area severity index (PASI) in patients of chronic plaque psoriasis and compare their safety in terms of adverse effects. Methodology The total number of patients included in the study was 60. They were divided into two groups, with 30 patients each. One group was prescribed ointment calcipotriol 0.005% twice daily local application (Group C). The other group was prescribed methotrexate gel 1% twice daily local application (Group M). The patients were followed up on the fourth and eighth weeks, and at each time, thorough clinical examinations were conducted for all patients. The PASI score was calculated in each patient every time. Safety was assessed by biochemical parameters, and tolerability was assessed by the incidence of adverse effects. All the patients included in the study were investigated at baseline, fourth week, and eighth week. The data collected were transferred to a master chart and analyzed. Results For the patients in group C, the mean PASI score at 0 week was 5.93 ± 2.62, while at four weeks, the mean PASI score declined to 1.67 ± 1.13, and at eight weeks, the mean PASI score further declined to 0.67 ± 0.68. For the patients in group M, the mean PASI score at 0 week was 5.91 ± 2.22, while at four weeks, the mean PASI score declined to 1.91 ± 1.11, and at eight weeks, the mean PASI score further declined to 0.89 ± 0.72. Furthermore, there was no significant difference in the mean PASI score at various time points when compared between the two groups (p-value = 0.761, 0.296, 0.079, respectively). Thus, both drugs seem to be effective in treating mild- to moderate-grade chronic plaque psoriasis. Most of the patients in both groups showed marked clearance of the lesions. However, there were six patients in the calcipotriol group showing complete clearance of the lesions having mild-degree plaque psoriasis, as compared to three patients in the methotrexate group. In the present study, based on the comparison of safety and tolerability, four out of 30 patients (13.3%) in the calcipotriol group suffered skin irritation, whereas six out of 30 patients (20%) in the methotrexate group complained of a burning sensation. The adverse effects seen in the patients were transient and mild. Conclusion Topical calcipotriol and methotrexate were effective in reducing lesions in patients with chronic mild to moderate plaque psoriasis. Both drugs were well tolerated with mild and transient adverse effects and did not alter hematological and biochemical parameters.
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In the quest to improve energy efficiency and design better thermal insulators, various engineering strategies have been extensively investigated to minimize heat transfer through a material. Yet, the suppression of thermal transport in a material remains elusive because heat can be transferred by multiple energy carriers. Here, the realization of Anderson localization of phonons in a random 3D elastic network of graphene is reported. It is shown that thermal conductivity in a cellular graphene aerogel can be drastically reduced to 0.9 mW m-1 K-1 by the application of compressive strain while keeping a high metal-like electrical conductivity of 120 S m-1 and ampacity of 0.9 A. The experiments reveal that the strain can cause phonon localization over a broad compression range. The remaining heat flow in the material is dominated by charge transport. Conversely, electrical conductivity exhibits a gradual increase with increasing compressive strain, opposite to the thermal conductivity. These results imply that strain engineering provides the ability to independently tune charge and heat transport, establishing a new paradigm for controlling phonon and charge conduction in solids. This approach will enable the development of a new type of high-performance insulation solutions and thermally superinsulating materials with metal-like electrical conductivity.
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A thiazole-based probe, N'-((2-aminothiazol-5-yl)methylene)benzohydrazide (TBH), has been efficiently synthesized and characterized for the selective and sensitive detection of the neurotransmitter epinephrine (EP). The sensing strategy is based on the use of TBH for sequential colorimetric sensing of Ag+ and EP via in situ formation of Ag nanoparticles (Ag NPs) from the TBH-Ag+ complex. The generated Ag NPs lead to a bathochromic shift in absorption maximum and a change in color of the solution from light brown to reddish brown. TBH-Ag+ shows remarkable selectivity toward EP versus other drugs, common cations, anions, and some biomolecules. Moreover, TBH-Ag+ has a low detection limit for EP at 1.2 nM. The coordination of TBH-Ag+ has been proposed based on Job's plot, Fourier transform infrared spectroscopy (FT-IR), high-resolution mass spectrometry (HRMS), 1H NMR titration, X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray analysis (EDAX), and density functional theory (DFT) studies. The composition and morphology of the generated Ag NPs have been analyzed by XPS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The proposed sensing mechanism for EP has been supported by XPS of Ag after the reaction. Further, the sensitivity of TBH-Ag+ toward EP in brain tissues of an Alzheimer's disease model of mouse has been evaluated. A thorough comparison was done for evaluation of the proposed method.
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Enfermedad de Alzheimer , Encéfalo , Colorimetría , Epinefrina , Plata , Tiazoles , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/metabolismo , Plata/química , Animales , Ratones , Epinefrina/análisis , Tiazoles/química , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Ensayo de Materiales , Modelos Animales de Enfermedad , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Tamaño de la Partícula , Nanopartículas del Metal/química , Estructura Molecular , Iones/químicaRESUMEN
The efficient patient-independent and interpretable framework for electroencephalogram (EEG) epileptic seizure detection (ESD) has informative challenges due to the complex pattern of EEG nature. Automated detection of ES is crucial, while Explainable Artificial Intelligence (XAI) is urgently needed to justify the model detection of epileptic seizures in clinical applications. Therefore, this study implements an XAI-based computer-aided ES detection system (XAI-CAESDs), comprising three major modules, including of feature engineering module, a seizure detection module, and an explainable decision-making process module in a smart healthcare system. To ensure the privacy and security of biomedical EEG data, the blockchain is employed. Initially, the Butterworth filter eliminates various artifacts, and the Dual-Tree Complex Wavelet Transform (DTCWT) decomposes EEG signals, extracting real and imaginary eigenvalue features using frequency domain (FD), time domain (TD) linear feature, and Fractal Dimension (FD) of non-linear features. The best features are selected by using Correlation Coefficients (CC) and Distance Correlation (DC). The selected features are fed into the Stacking Ensemble Classifiers (SEC) for EEG ES detection. Further, the Shapley Additive Explanations (SHAP) method of XAI is implemented to facilitate the interpretation of predictions made by the proposed approach, enabling medical experts to make accurate and understandable decisions. The proposed Stacking Ensemble Classifiers (SEC) in XAI-CAESDs have demonstrated 2% best average accuracy, recall, specificity, and F1-score using the University of California, Irvine, Bonn University, and Boston Children's Hospital-MIT EEG data sets. The proposed framework enhances decision-making and the diagnosis process using biomedical EEG signals and ensures data security in smart healthcare systems.
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Electroencefalografía , Epilepsia , Procesamiento de Señales Asistido por Computador , Humanos , Electroencefalografía/métodos , Epilepsia/diagnóstico , Epilepsia/fisiopatología , Inteligencia Artificial , Niño , Diagnóstico por Computador/métodos , Algoritmos , Adolescente , Preescolar , Masculino , Adulto , FemeninoRESUMEN
Alzheimer's disease (AD) is the most common cause of dementia, which arises due to low levels of acetyl and butyrylcholines, an increase in oxidative stress, inflammation, metal dyshomeostasis, Aß and tau aggregations. The currently available drugs for AD treatment can provide only symptomatic relief without interfering with pathological hallmarks of the disease. In our ongoing efforts to develop naturally inspired novel multifunctional molecules for AD, systematic SAR studies on EJMC-4e were caried out to improve its multifunctional properties. The rigorous medicinal efforts led to the development of 12o, which displayed a 15-fold enhancement in antioxidant properties and a 2-fold increase in the activity against AChE and BChE over EJMC-4e. Molecular docking and dynamics studies revealed the binding sites and stability of the complex of 12o with AChE and BChE. The PAMPA-BBB assay clearly demonstrated that 12o can easily cross the blood-brain barrier. Interestingly, 12o also expresses promising metal chelation activity, while EJMC-4e was found to be devoid of this property. Further, 12o inhibited metal-induced or self Aß1-42 aggregation. Observing the neuroprotection ability of 12o against H2O2-induced oxidative stress in the PC-12 cell line is noteworthy. Furthermore, 12o also inhibited NLRP3 inflammasome activation and attenuated mitochondrial-induced ROS and MMP damage caused by LPS and ATP in HMC-3 cells. In addition, 12o is able to effectively reduce mitochondrial and cellular oxidative stress in the AD Drosophila model. Finally, 12o could reverse memory impairment in the scopolamine-induced AD mice model, as evident through in vivo and ex vivo studies. These findings suggest that this compound may act as a promising candidate for further improvement in the management of AD.
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Enfermedad de Alzheimer , Ácidos Cumáricos , Ratones , Ratas , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Inflamasomas , Péptidos beta-Amiloides/metabolismo , Inhibidores de la Colinesterasa/química , Simulación del Acoplamiento Molecular , Proteína con Dominio Pirina 3 de la Familia NLR , Peróxido de Hidrógeno , Metales , Células PC12 , Acetilcolinesterasa/metabolismoRESUMEN
The exposure to high altitude and cold stress poses challenges in maintaining normal physiological standards and body homeostasis in non-native animals. To enhance our understanding of the physiology of native and non-native goats in high-altitude environments, we conducted a comparative study to examine the impact of natural hypoxic and cold stress conditions on their feed intake (FIT) and associated changes in physiological responses, including plasma glucose concentration (PGC). The study took place at an altitude of 3505.2 m above mean sea level and involved twenty-two healthy females from two different breeds of goats. This study was conducted over a period of 56 days after the arrival of non-native Black Bengal goats (BBN) and compared with native Changthangi (CHAN) goats. Both groups were extensively reared in a natural high-altitude and cold-stress environment in Leh, India, and were subjected to defined housing and management practices. The parameters evaluated included FIT, PGC, respiration rate, heart rate, pulse rate, and rectal temperature. High altitudes had a significant (p < 0.05) impact on FIT, PGC, respiration rate, heart rate, pulse rate, and rectal temperature in BBN, whereas these parameters remained stable in CHAN throughout the study period. Additionally, the detrimental effects of high-altitude stress were more pronounced in non-native goats compared to native goats. These findings suggest that physiological responses in non-native goats tend to stabilize after an initial period of adverse effects in high-altitude environments. Based on the physiological responses and glucose concentration, it is recommended to pay special attention to the nutrition of non-native goats for up to the third week (21 days) after their arrival in high-altitude areas.
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Altitud , Glucemia , Animales , Femenino , Cabras/fisiología , Ambiente , Ingestión de AlimentosRESUMEN
Two-dimensional transition metal dichalcogenides (TMDs) have drawn immense interest due to their strong spin-orbit coupling and unique layer number dependence in response to spin-valley coupling. This leads to the possibility of controlling the spin degree of freedom of the ferromagnet (FM) in thin film heterostructures and may prove to be of interest for next-generation spin-based devices. Here, we experimentally demonstrate the odd-even layer dependence of WS2 nanolayers by measurements of the ultrafast magnetization dynamics in WS2/Co3FeB thin film heterostructures by using time-resolved Kerr magnetometry. The fluence (photon energy per unit area) dependent magnetic damping (α) reveals the existence of broken symmetry and the dominance of inter- and intraband scattering for odd and even layers of WS2, respectively. The higher demagnetization time, τm, in 3 and 5 layers of WS2 is indicative of the interaction between spin-orbit and spin-valley coupling due to the broken symmetry. The lower τm in even layers as compared to the bare FM layer suggests the presence of a spin transport. By correlating τm and α, we pinpointed the dominant mechanisms of ultrafast demagnetization. The mechanism changes from spin transport to spin-flip scattering for even layers of WS2 with increasing fluence. A fundamental understanding of the two-dimensional material and its odd-even layer dependence at ultrashort timescales provides valuable information for designing next-generation spin-based devices.
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A diarylethene-based probe (Z)-N'-((2-amino-5-chlorophenyl)(phenyl)methylene)-2-hydroxy benzohydrazide (KBH) has been proficiently developed and its structure has been confirmed by single crystal X-ray diffraction technique. It displays a selective and sensitive colorimetric sensing of Cu2+ ions in aqueous medium with a naked eye colour change from colourless to yellow. It exhibits a significantly low limit of detection as 1.5 nM. A plausible binding mechanism has been proposed using Job's plot, FT-IR, 1H NMR titration, HRMS and DFT studies. The chemosensor is effectively reversible and reusable with EDTA. Test strip kit and real water sample analysis have been shown to establish its practical applicability. Further, the potential of KBH for the early diagnosis of Cu2+ ion-induced amyloid toxicity has been investigated in eye imaginal disc of Alzheimer's disease model of Drosophila 3rd instar larvae. The in-vivo interaction of KBH with Cu2+ in gut tissues of Drosophila larvae establishes its sensing capability in biological system. Interestingly, the in-vivo detection of Cu2+ has been done using bright field imaging which eliminates the necessity of a fluorescent label, hence making the method highly economical.
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Senescence is a complicated, multi-factorial, irreversible cell cycle halt that has a tumor-suppressing effect in addition to being a significant factor in aging and neurological diseases. Damaged DNA, neuroinflammation, oxidative stress and disrupted proteostasis are a few of the factors that cause senescence. Senescence is triggered by DNA damage which initiates DNA damage response. The DNA damage response, which includes the formation of DNA damage foci containing activated H2AX, which is a key factor in cellular senescence, is provoked by a double strand DNA break. Oxidative stress impairs cognition, inhibits neurogenesis, and has an accelerated aging effect. Senescent cells generate pro-inflammatory mediators known as senescence-associated secretory phenotype (SASP). These pro-inflammatory cytokines and chemokines have an impact on neuroinflammation, neuronal death, and cell proliferation. While it is tempting to think of neurodegenerative diseases as manifestations of accelerated aging and senescence, this review will present information on brain ageing and neurodegeneration as a result of senescence and DNA damage response.
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Neoplasias del Cuello Uterino , Femenino , Humanos , Frotis Vaginal , Detección Precoz del Cáncer , Tamizaje MasivoRESUMEN
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare fatal autosomal recessive disorder of immune dysregulation. The disease presents most commonly in the first year of life; however, symptomatic presentation throughout childhood and adulthood has also been identified. Biallelic mutation in the perforin gene is present in 20%50% of all cases of FHL. Secondary hemophagocytic lymphohistiocytosis (HLH) in association with hematological malignancies is known; however, whether mutations in HLH-associated genes can be associated with FHL and hematolymphoid neoplasms is not well documented. Also, EpsteinBarr-virus- (EBV) positive systemic T-cell lymphoproliferative disease (SE-LPD) in the setting of FHL is not clearly understood. Here, we present the case of a young boy who presented with typical features of childhood FHL harboring the perforin gene (PRF1) mutation, and had SE-LPD diagnosed on autopsy, along with evidence of recent EBV infection. The patient expired due to progressive disease. Five siblings died in the second or third decade of life with undiagnosed disease. Genetic counseling was provided to the two surviving siblings and parents, but they could not afford genetic testing. One surviving sibling has intermittent fever and is on close follow-up for possible bone marrow transplantation.
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Humanos , Masculino , Adolescente , Antígenos Nucleares del Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica/patología , Autopsia , Resultado Fatal , Perforina , LinfomaRESUMEN
Abstract Increasing urbanisation is widely associated with decline in biodiversity of all forms. The aim of the present study was to answer two questions: (i) Does rapid urbanization in Delhi (India) affect biodiversity of arbuscular mycorrhizal (AM) fungi? (ii) If so, how? We measured the AM fungal diversity at nine sites located in Delhi forests, which had different types of urban usage in terms of heavy vehicular traffic pollution, littering, defecation and recreational activities. The study revealed a significant decrease in AM fungal diversity (alpha diversity) and abundance measured as spore density, biovolume, mean infection percentage (MIP) in roots, soil hyphal length and easily extractable glomalin related soluble proteins (EE-GRSP) at polluted sites. Non-metric multidimensional scaling (NMDS) and nested PERMANOVA, revealed significant differences in AM fungal community structure which could be correlated with variations in soil moisture, temperature, pH, carbon, and nitrogen and phosphorus levels. BEST (biota and environmental matching) analysis of biological and environmental samples revealed that soil temperature and moisture accounted for 47.6 % of the total variations in the samples. The study demonstrated how different forms of human activities in urban ecosystems of Delhi are detrimental to the diversity and abundance of AM fungi.(AU)
Resumen El incremento en la urbanización está ampliamente asociado con una disminución de la biodiversidad de todas las formas. El objetivo del presente estudio fue responder dos preguntas: (i) ¿Afecta la urbanización rápida en Delhi (India) la biodiversidad de hongos micorrízicos arbusculares (MA)?, y (ii) si es así, ¿Cómo? Medimos la diversidad de hongos MA en nueve sitios ubicados en los bosques de Delhi, los cuales tenían diferentes tipos de uso urbano en términos de contaminación por alto tráfico vehicular, basura, defecación y actividades recreacionales. El estudio reveló una disminución significativa en la diversidad de hongos MA (diversidad alfa) y abundancia medida como densidad de esporas, biovolumen, porcentaje medio de infección (PMI) en raíces, longitud de las hifas del suelo y glomalina fácilmente extraible relacionada con proteínas solubles (EE-GRSP) en sitios contaminados. Análisis de escalamiento multidimensional no métrico (NMDS) y PERMANOVA anidados revelaron diferencias significativas en la estructura de hongos MA, que puede estar relacionada con la variación en humedad, temperatura, pH y niveles de carbono, nitrógeno y fósforo del suelo. El análisis BEST (biota y correspondencia ambiental) de muestras biológicas y ambientales mostró que la temperatura y humedad del suelo explican un 47.6 % del total de la variación en las muestras. Este estudio demostró cómo las diferentes actividades humanas en ecosistemas urbanos de Delhi son perjudiciales para la diversidad y abundancia de hongos MA.(AU)