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One of the main objectives in wastewater treatment and sustainable energy production is to find photocatalysts that are favorably efficient and cost-effective. Transition-metal dichalcogenides (TMDs) are promising photocatalytic materials; out of all, MoS2 is extensively studied as a cocatalyst in the TMD library due to its exceptional photocatalytic activity for the degradation of organic dyes due to its distinctive morphology, adequate optical absorption, and rich active sites. However, sulfur ions on the active edges facilitate the catalytic activity of MoS2. On the basal planes, sulfur ions are catalytically inactive. Injecting metal atoms into the MoS2 lattice is a handy approach for triggering the surface of the basal planes and enriching catalytically active sites. Effective band gap engineering, sulfur edges, and improved optical absorption of Mn-doped MoS2 nanostructures are promising for improving their charge separation and photostimulated dye degradation activity. The percentage of dye degradation of MB under visible-light irradiations was found to be 89.87 and 100% for pristine and 20% Mn-doped MoS2 in 150 and 90 min, respectively. However, the degradation of MB dye was increased when the doping concentration in MoS2 increased from 5 to 20%. The kinetic study showed that the first-order kinetic model described the photodegradation mechanism well. After four cycles, the 20% Mn-doped MoS2 catalysts maintained comparable catalytic efficacy, indicating its excellent stability. The results demonstrated that the Mn-doped MoS2 nanostructures exhibit exceptional visible-light-driven photocatalytic activity and could perform well as a catalyst for industrial wastewater treatment.
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Glioblastoma is the most destructive type of malignant brain tumor in humans due to cancer relapse. Latest studies have indicated that cancer cells are more reliant on autophagy for survival than non-cancer cells. Autophagy is entitled as programmed cell death type II and studies imply that it is a comeback of cancer cells to innumerable anti-cancer therapies. To diminish the adverse consequences of chemotherapeutics, numerous herbs of natural origin have been retained in cancer treatments. Additionally, autophagy induction occurs via their tumor suppressive actions that could cause cell senescence and increase apoptosis-independent cell death. However, most of the drugs have poor solubility and thus nano drug delivery systems possess excessive potential to improve the aqueous solubility and bioavailability of encapsulated drugs. There is a pronounced need for more therapies for glioblastoma treatment and hereby, the fundamental mechanisms of natural autophagy modulators in glioblastoma are prudently reviewed in this article.
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Autofagia/efectos de los fármacos , Productos Biológicos/farmacología , Glioblastoma/tratamiento farmacológico , Nanopartículas/química , Apoptosis/efectos de los fármacos , Autofagia/genética , Productos Biológicos/química , Proliferación Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Glioblastoma/genética , Glioblastoma/patología , HumanosRESUMEN
Ubiquitin C-terminal hydrolase-1 (UCH-L1) is a specific neuronal endoprotease that cleaves the specific peptide bond between ubiquitin molecules. UCH-L1 is released in serum and cerebrospinal fluid after severe brain injury and is considered to be an important biomarker of brain injury. A common polymorphism of UCH-L1 (S18Y) is also linked to a reduced risk of Parkinson's disease. In addition to its function in neuronal tissues, UCH-L1 may also play a part in the progression of certain non-neuronal cancers. UCH-L1 is highly expressed in primary lung tumors and colo-rectal cancers, suggesting a role in tumorigenesis. We report here the development of a sensitive and accurate UCH-L1 assay based on the surface plasmon resonance (SPR) absorbance of gold nanoparticles. We created a unique UCH-L1 substrate containing a ubiquitin molecule with two terminal thiol groups. This UCH-L1 substrate interacted with gold nanoparticles via the terminal thiol groups and induced clustering of the nanoparticles, which was detected by SPR absorbance at 650 nm. UCH-L1 proteolytically cleaved the substrate and the clustered gold nanoparticles were dispersed and could be detected by a shift in the SPR absorbance to 530 nm. This change in absorbance was proportional to the concentration of UCH-L1 and can be used for the quantification of functional UCH-L1. The currently available fluorescence-based UCH-L1 assay is affected by a high background signal and a poor detection limit, especially in the presence of serum. The assay reported here can detect concentrations of UCH-L1 as low as 20 ng ml(-1) (0.8 nM) and the presence of serum had no effect on the detection limit. This assay could be adapted for the rapid determination of the severity of brain injury and could also be applied to high-throughput screening of inhibitors of UCH-L1 enzymatic activity in Parkinson's disease and cancer.
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Ácido Cítrico/química , Oro/química , Nanopartículas/química , Resonancia por Plasmón de Superficie/métodos , Ubiquitina Tiolesterasa/sangre , Secuencia de Aminoácidos , Pruebas de Enzimas/métodos , Humanos , Límite de Detección , Modelos Moleculares , Datos de Secuencia Molecular , Ubiquitina/química , Ubiquitina/metabolismo , Ubiquitina Tiolesterasa/análisis , Ubiquitina Tiolesterasa/metabolismoRESUMEN
The rising opportunities of sustainable tourism have brought many policies to control the exploitation of the environment and increase the reach of luxurious, safe, and authentic experiences to the different segments of tourists. This study seeks to prioritize the variables influencing the development of sustainable tourism and pinpoint key success factors that align with the Sustainable Development Goals (SDGs). It adopts a tri-dimensional framework encompassing economic, social, and environmental aspects, further delineated into eleven sub-dimensions, to provide a quantitative evaluation of sustainable tourism. We conducted interviews with 26 tourism industry experts hailing from eight countries, analyzing their responses using interval type-2 fuzzy sets. The results underscore the critical role of specific components in advancing sustainable tourism. In the economic dimension, "financial resources and tourism costs" emerge as vital factors. In the social dimension, "health and safety" takes center stage, while "green infrastructure" plays a pivotal role in the environmental dimension. These findings underscore the significance of these aspects in promoting sustainable tourism. Furthermore, this study explores the strategic importance of sustainable tourism equity in shaping tourism planning and development for emerging markets.
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Turismo , Unionidae , Animales , Desarrollo SostenibleRESUMEN
Introduction: Residual hearing preservation has gained attention now which has brought round window membrane into the light, as a port for cochlear implantation. Atraumatic insertion of electrodes can be achieved by study of anatomical variations of round window and its forms which can guide the surgeon. Objective: This study was undertaken to examine the anatomical variations of round window and its adjacent structures and their impact on surgical approach during cochlear implantation. Methods: A series of 40 adult human temporal bones underwent high-resolution CT scanning and were further dissected for microscopic study of the round window. Results: The antero posterior dimensions of RW ranged from 1.22 to 2.51 mm on radiology and on dissection 1.76 mm +/- 0.3 mm. Shape of round window in 72.5% of bones was oval, and in 27.5% bones it was round shaped. As per Saint Thomas hospital classification for Round window visualization we found 82.5% bones had type I RW visualization and 17.5% had type IIa RW visualization. Area of crista fenestra on dissection was ranging from 0.41 to 0.69 mm2. Conclusion: Residual hearing preservation has become a new motto for surgeons. Therefore thorough anatomic knowledge of round window is must for careful insertion, as round window is closely related to the sensitive inner ear structures.
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OBJECTIVE: To better understand the broader experience of medical students impacted by discrimination and the support systems they engage with. DESIGN: Qualitative study using semi-structured interviews. SETTING: Four medical schools based in the UK. PARTICIPANTS: 17 medical students were recruited using volunteer and snowball sampling: all students self-identified as being impacted by discrimination. RESULTS: 5 themes were identified: feelings of isolation, imposter syndrome and exclusion; a lack of representation and positive role modelling; the importance of peer support; issues relating to the accessibility of support; building support networks through shared experiences and attempts to foster a sense of inclusion through peer and institutionally led initiatives. CONCLUSIONS: The findings of this study suggest medical schools could do more to recognise the importance of acknowledging the multiple identities at risk of discrimination held by students, perpetuating feelings of isolation and exclusion. Our research highlights the need for practical systemic initiatives to improve the sense of belonging of medical students who are impacted by discrimination. Medical educators and institutions should consider formal and informal provisions, such as creating time and space for students to meet and share experiences, access support and reporting networks, to foster a greater sense of belonging.
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Estudiantes de Medicina , Humanos , Facultades de Medicina , Investigación Cualitativa , Grupo Paritario , Reino UnidoRESUMEN
Malignant brain tumors remain a major cause of concern and mortality as successful treatment is hindered due to the poor transport and low penetration of chemotherapeutics across the blood-brain barrier (BBB). In this study, a nano formulation composed of chlorotoxin (CTX)-conjugated morusin loaded PLGA nanoparticles (PLGA-MOR-CTX) was devised against Glioblastoma Multiforme (GBM) and its anti-proliferative effects were evaluated in vitro. The synthesized nanoparticles were loaded with morusin, a naturally derived chemotherapeutic drug, and surface conjugated with CTX, a peptide derived from scorpion venom, highly specific for chloride channels (CIC-3) expressed in glioma tumor cells, as well as for matrix metalloproteinase (MMP-2), which is up regulated in the tumor microenvironment. Subsequently, the anti-cancer potential of the NPs was assessed in U87 and GI-1 (human glioblastoma) cells. Antiproliferative, cell apoptosis, and other cell-based assays demonstrated that the PLGA-MOR-CTX NPs resulted in enhanced inhibitory effects on U87 and GI-1 glioma cells. Prominent cytotoxicity parameters such as ROS generation, enhanced caspase activity, cytoskeletal destabilization, and inhibition of MMP-activity were observed in glioblastoma cells upon PLGA-MOR-CTX NP treatment. The cytocompatibility observed with normal human neuronal cells (HCN-1A) and the enhanced lethal effects in glioblastoma cells highlight the potential of PLGA-MOR-CTX nanoparticles as promising therapeutic nanocarriers towards GBM.
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Portadores de Fármacos/química , Flavonoides/química , Glioblastoma/tratamiento farmacológico , Terapia Molecular Dirigida , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Venenos de Escorpión/química , Autofagia/efectos de los fármacos , Transporte Biológico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Liberación de Fármacos , Glioblastoma/patología , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Venenos de Escorpión/farmacologíaRESUMEN
Glioblastoma multiforme (GBM), one of the most lethal Brain tumors, characterized by its high invasive nature and increased mortality rates forms a major bottleneck in transport of therapeutics across the Blood Brain Barrier (BBB). Matrix metalloproteinases (MMPs) are classified as enzymes, which are found to be up regulated in the Glioma tumor microenvironment and thus can be considered as a target for inhibition for curbing GBM. Many chemotherapeutics and techniques have been employed for inhibiting MMPs till now but all of them failed miserably and were withdrawn in clinical trials due to their inability in restricting the tumor growth or increasing the overall survival rates. Thus, the quest for finding the suitable MMP inhibitor is still on and there is a critical need for identification of novel compounds which can alter the BBB permeability, restrain tumor growth and prevent tumor recurrence. Currently, naturally derived substances are gaining widespread attention as tumor inhibitors and many studies have been reported by far highlighting their importance in restricting MMP expression thus serving as chemotherapeutics for cancer due to their minimal toxicity. These substances may serve as probable candidates for inhibiting MMP expression in GBM. However, targeting and delivering the inhibitor to its target site is an issue that needs to be overcome in order to attain maximum specificity and sustained release. The birth of nanotechnology served as a boon in delivering drugs to the most complicated areas thus paving way for Nano drug delivery. An efficient Nano carrier with ability to cross the BBB and competently kill the Glioma cells forms the prerequisite for GBM chemotherapy. Vesicular drug delivery systems are one such class of carriers, which have the capacity to release the drug at a predetermined rate at the target site thus minimizing any undesirable side effects. Exploiting vesicular systems as promising Nano drug carriers to formulate naturally derived substances, that can bypass the BBB and act as an inhibitor against MMPs in GBM is the main theme of this review.
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Antineoplásicos/administración & dosificación , Productos Biológicos/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Glioblastoma/tratamiento farmacológico , Inhibidores de la Metaloproteinasa de la Matriz/administración & dosificación , Animales , Humanos , Metaloproteinasas de la Matriz/metabolismo , Microambiente TumoralRESUMEN
Morusin, a water-insoluble prenylated flavonoid is known for its numerous medicinal properties. It manifests its anticancer potential by suppression of genes involved in tumor progression. However, poor solubility of the drug results in low bioavailability and rapid degradation thus hindering its clinical utilization. In order to overcome this, we have synthesized a niosome system composed of non-ionic surfactant span 60 and cholesterol using a thin-layer evaporation technique to improve the aqueous-phase solubility of the drug. Highly cytocompatible niosomes of 479 nm average size with smooth and uniform spherical morphology were synthesized in a facile manner. Unlike free morusin, nanomorusin was found to be freely dispersible in aqueous media. Having an extremely high drug entrapment efficiency (97%), controlled and sustained release of morusin resulting in enhanced therapeutic efficacy was observed in cancer cell lines of 4 different lineages. The results demonstrate that the morusin-niosome system is a promising strategy for enhanced anti-cancer activity against multiple cancer types and could be an indispensable tool for future targeted chemotherapeutic strategies.