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In this investigation, we present empirical observations detailing the manifestation of substantial negative capacitance (NC), reaching up to -1 F, within iodine-doped isomeric polythiophene (IPTh-I2). NC observed in our case is not transient but stable enough to be measured for as long as the optimum concentration of the iodine dopant is available. In contrast, undoped isomeric polythiophene (IPTh) manifests a modest positive capacitance ranging from 30 to 60 µF. The concatenation of IPTh-I2 and IPTh in the series results in an augmentation of the total capacitance of the system (â¼170 µF), exemplifying a characteristic feature of NC. Conversely, a bilayer configuration consisting of IPTh:IPTh exhibits a reduction in total capacitance by 38%. A notable amplification in the dielectric constant, escalating from 30 in IPTh to approximately 2000 in IPTh-I2, signifies extensive conformational and structural alterations arising from interactions between the doped polymer chain and various iodide species, attributing to the emergence of NC. Furthermore, we document a single-sided p-n junction diode with a low knee voltage (below 0.5 V) as a model device, illustrating the potential of IPTh as a promising material for the design and development of negative capacitance-based field-effect transistors. This research offers avenues for the scientific community to conceive low knee voltage-operating diodes, transistors, supercapacitors, and various other electronic devices based on all-organic semiconductors.
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We report the growth, structural characterization, and transport studies of Bi2Se3thin film on single crystalline silicon (Si), Si/SiO2, quartz, and glass substrates by thermal evaporation method. Our results show that 300 °C is the optimum substrate temperature to obtain thec-axis (001) oriented Bi2Se3films on all the substrates. The film grown on the Si substrate has the minimum crystalline disorder. The energy-dispersive x-ray spectroscopy results show that film on Si substrate is bismuth deficient, the film on Si/SiO2substrate is selenium deficient, and the film on quartz substrate is near perfect stoichiometric providing a way to tune the electronic properties of Bi2Se3films through substrate selection. The film grown on quartz shows the highest mobility (2.7 × 104cm2V-1s-1) which drops to 150 cm2V-1s-1for Si, 60 cm2V-1s-1for Si/SiO2, and 0.9 cm2V-1s-1for glass substrate. Carrier concentration is n-type for Bi2Se3films on Si (â¼1018cm-3), quartz (â¼1018cm-3) and Si/SiO2(â¼1019cm-3) substrate with a clear indication of frozen out effect around 50 K for Si/SiO2and Si substrate. Longitudinal resistivity of Bi2Se3film on Si/SiO2substrate shows different behavior in three different temperature regions: temperature dependent resistivity region due to electron-phonon scattering, a nearly temperature independent resistivity region due to electron-phonon and electron-ion scattering, and a quantum coherent transport region.
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A facile method based on recyclable nanoscale zero-valent iron (nZVI)-mediated photoinduced reversible deactivation radical polymerization in ionic liquid (IL) leads to the synthesis of narrow disperse poly(tert-butyl methacrylate) (PTBMA), amphiphilic PTBMA-block-poly(poly(ethylene glycol)methacrylate) diblock copolymer and double hydrophilic poly(methacrylic acid)-block-poly(poly(ethylene glycol)methacrylate) (PMAA-b-PPEGMA) diblock copolymers thereof. Stimuli response of the synthesized PMAA-b-PPEGMA diblock copolymer against variation in pH and temperature is assessed. Recyclability of the nZVI (catalyst) and IL (solvent) is established. Polymerization may be switched ON or OFF, simply by turning the UVA light irradiation ON or OFF, offering temporal control. The diblock copolymer self-aggregates into spherical nanoaggregates which are employed for encapsulation of coumarin 102 (C102, a typical hydrophobic dye), describing their potential application in drug delivery applications. The facile synthesis strategy may open up new avenues for the preparation of intelligent functional polymers for engineering and biomedical applications.
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Líquidos Iónicos , Polímeros , Polímeros/química , Ácidos Polimetacrílicos/químicaRESUMEN
Measurements of brain deformations under injurious loading scenarios are actively sought. In this work, we report experimentally measured head kinematics and corresponding dynamic, two-dimensional brain simulant deformations in head surrogates under a blunt impact, with and without a helmet. Head surrogates used in this work consisted of skin, skull, dura, falx, tentorium, and brain stimulants. The head surrogate geometry was based on the global human body models consortium's head model. A base head surrogate consisting of skin-skull-brain was considered. In addition, the response of two other head surrogates, skin-skull-dura-brain, and skin-skull-dura-brain-falx-tentorium, was investigated. Head surrogate response was studied for sagittal and coronal plane rotations for impactor velocities of 1 and 3 m/s. Response of head surrogates was compared against strain measurements in PMHS. The strain pattern in the brain simulant was heterogenous, and peak strains were established within â¼30 ms. The choice of head surrogate affect the spatiotemporal evolution of strain. For no helmet case, peak MPS of â¼50-60% and peak MSS of â¼35-50% were seen in brain simulant corresponding to peak rotational accelerations of â¼5000-7000 rad/s2. Peak head kinematics and peak MPS have been reduced by up to 75% and 45%, respectively, with the conventional helmet and by up to 90% and 85%, respectively, with the helmet with antirotational pads. Overall, these results provide important, new data on brain simulant strains under a variety of loading scenarios-with and without the helmets.
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Dispositivos de Protección de la Cabeza , Cabeza , Humanos , Cabeza/fisiología , Cráneo/fisiología , Encéfalo , Fenómenos Biomecánicos , AceleraciónRESUMEN
Pulmonary infections contribute substantially to emergency department (ED) visits, posing a considerable health burden. Lower respiratory tract infections are prevalent, particularly among the elderly, constituting a significant percentage of infectious disease-related ED visits. Timely recognition and treatment are crucial to mitigate morbidity and mortality. Imaging studies, primarily chest radiographs and less frequently CT chests, play a pivotal role in diagnosis. This article aims to elucidate the imaging patterns of both common and rare pulmonary infections (bacterial and viral) in the post COVID-19 era, emphasizing the importance of recognizing distinct radiological manifestations. The integration of clinical and microbiological evidence aids in achieving accurate diagnoses, and guiding optimal therapeutic interventions. Despite potential overlapping manifestations, a nuanced understanding of radiological patterns, coupled with comprehensive clinical and microbiological information, enhances diagnostic precision in majority cases.
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COVID-19 , Servicio de Urgencia en Hospital , SARS-CoV-2 , Humanos , COVID-19/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Infecciones del Sistema Respiratorio/diagnóstico por imagenRESUMEN
MAIN CONCLUSION: Abiotic stresses adversely affect the productivity and production of vegetable crops. The increasing number of crop genomes that have been sequenced or re-sequenced provides a set of computationally anticipated abiotic stress-related responsive genes on which further research may be focused. Knowledge of omics approaches and other advanced molecular tools have all been employed to understand the complex biology of these abiotic stresses. A vegetable can be defined as any component of a plant that is eaten for food. These plant parts may be celery stems, spinach leaves, radish roots, potato tubers, garlic bulbs, immature cauliflower flowers, cucumber fruits, and pea seeds. Abiotic stresses, such as deficient or excessive water, high temperature, cold, salinity, oxidative, heavy metals, and osmotic stress, are responsible for the adverse activity in plants and, ultimately major concern for decreasing yield in many vegetable crops. At the morphological level, altered leaf, shoot and root growth, altered life cycle duration and fewer or smaller organs can be observed. Likewise different physiological and biochemical/molecular processes are also affected in response to these abiotic stresses. In order to adapt and survive in a variety of stressful situations, plants have evolved physiological, biochemical, and molecular response mechanisms. A comprehensive understanding of the vegetable's response to different abiotic stresses and the identification of tolerant genotypes are essential to strengthening each vegetable's breeding program. The advances in genomics and next-generation sequencing have enabled the sequencing of many plant genomes over the last twenty years. A combination of modern genomics (MAS, GWAS, genomic selection, transgenic breeding, and gene editing), transcriptomics, and proteomics along with next-generation sequencing provides an array of new powerful approaches to the study of vegetable crops. This review examines the overall impact of major abiotic stresses on vegetables, adaptive mechanisms and functional genomic, transcriptomic, and proteomic processes used by researchers to minimize these challenges. The current status of genomics technologies for developing adaptable vegetable cultivars that will perform better in future climates is also examined.
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Proteómica , Verduras , Fitomejoramiento , Genómica , Productos Agrícolas , Estrés Fisiológico/genéticaRESUMEN
Various direct and indirect environmental constraints have an impact on livestock performance. The physiological parameters, such as rectal temperature, heart rate, and respiratory rate, are the primary indicators of thermal stress. Under a stressed environment temperature humidity index (THI) had established as a vital measurement to identify the thermal stress in livestock. THI in association with climatic variations can define the environmental effect as stressful or comfortable for livestock. Goats are small ruminants that adapt to a wide range of ecological variations due to their anatomical and physiological characteristics. However, the productivity of animals declines at the individual level during thermal stress. Stress tolerance can be determined through genetic studies associated with at the cellular level using physiological as well as molecular approaches. Information on genetic association with thermal stress in goats is scanty, this severely affects their survival and hence productivity of livestock. The ever-increasing demand for food across the globe needs deciphering novel molecular markers as well as stress indicators that play a vital role in livestock improvement. This review represents an analysis of current knowledge of phenotypic differences during thermal stress and signifies the importance of physiological responses and their association at the cellular level in goats. The regulation of vital genes associated with thermal stress such as Aquaporins (AQP 0, 1, 2, 4, 5, 6, 8), aquaglyceroporins (AQP3, 7, 9, and 10) and super-aquaporins (AQP 11, 12); BAX inhibitors such as PERK (PKR like ER kinase), IRE 1(inositol-requiring-1); Redox regulating genes such as NOX; Transport of Na+ and K+ such as ATPase (ATP1A1) and several heat shock proteins have been implicated in heat-stress related adaptations have been elucidated. As these changes have a significant impact on production performance as well as on livestock productivity. Such efforts may help in the development of molecular markers and will assist the breeders to develop heat-tolerant goats with improved productivity.
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Cabras , Trastornos de Estrés por Calor , Animales , Cabras/genética , Calor , Respuesta al Choque Térmico , Clima , Temperatura , Humedad , Trastornos de Estrés por Calor/genética , Trastornos de Estrés por Calor/veterinariaRESUMEN
This study was conducted in Badri cattle using a double digest restriction-site associated DNA sequencing approach. The study aimed to identify and annotate high confidence single nucleotide polymorphisms (SNPs) and their mapping in candidate genes related to production and fertility in dairy cattle. A total of 7,168,552 genome-wide SNPs were initially identified in Badri cattle by alignment with the Bos indicus reference genome. After filtration of SNPs, 65,483 high confidence SNPs were retained and further used for downstream analysis. Annotation of high confidence SNPs revealed 99.197% SNPs had modifier impact, 0.326% SNPs were low impact, 0.036% were high impact, and 0.441% were moderate impact SNPs. Most SNPs in Badri cattle were found in intergenic, transcript and intronic regions. The candidate genes for milk production PRKCE, ABCG2, GHR, EPS8, CAST and NRXN1 were found to harbour maximum high confidence variants. Among candidate genes for fertility in cattle, ATP2B1, SOX5, WDR27, ARHGAP12, CACNA1D, ANKRD6, GRIA3, ZNF521 and CAST822 have maximum high confidence variants mapped in them. The SNPs found mapped in the candidate genes will be important genetic tools in the search for phenotype-modifying nucleotide changes and will aid in formulating relevant genetic improvement programmes for dairy cattle.
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Fertilidad , Leche , Polimorfismo de Nucleótido Simple , Animales , Bovinos/genética , Fertilidad/genética , Estudio de Asociación del Genoma Completo/veterinaria , Fenotipo , Lactancia/genéticaRESUMEN
PDE9 enzyme hydrolyzes cGMP, which is involved in the regulation of synaptic plasticity through the NMDA pathway (a well-known excitotoxic target for AD) via activation of calcium/calmodulin-dependent neuronal NO synthases in the postsynaptic neurons. The inhibition of PDE9 leads to elevated cGMP levels, causing enhanced NMDA signaling and thus contributing to an increase in synaptic plasticity and stabilization. Therefore, it could be considered a pertinent target for AD drug discovery. PF-04447943 and BI-409306 targeting PDE9 are undergoing clinical trials (Phase II). The present study encompasses a pharmacophoric approach to identify potent PDE9 inhibitors using various computational methods. Pharmacophores generated from the PDB 6A3N yielded 37,554 virtual hits, which underwent drug likeliness and PAINS filtering to arrive at a few virtual leads. The leads were further subjected to extra precision docking, ADMET predictions, and molecular dynamics. The final hits, ZINC000001305675 and ZINC000000377099, showed superior docking scores of - 10.90 and - 10.30 kcal/mol and satisfactory predicted ADMET scores. The hits were subjected to molecular dynamics (MD) studies, wherein they formed stable complexes with PDE9 protein and had ligand RMSDs within acceptable limits. The processes involved in the combined ligand and structure-based strategies.
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Enfermedad de Alzheimer , Enfermedad de Alzheimer/tratamiento farmacológico , Calcio/uso terapéutico , Calmodulina/uso terapéutico , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , N-Metilaspartato/uso terapéutico , Inhibidores de Fosfodiesterasa/farmacología , Inhibidores de Fosfodiesterasa/uso terapéuticoRESUMEN
Structure-based drug design (SBDD) is an important in silico technique, used for the identification of enzyme inhibitors. Acetylcholinesterase (AChE), obtained from Electrophorus electricus (ee), is widely used for the screening of AChE inhibitors. It shares structural homology with the AChE of human and other organisms. Till date, the three-dimensional crystal structure of enzyme from ee is not available that makes it challenging to use the SBDD approach for the identification of inhibitors. A homology model was developed for eeAChE in the present study, followed by its structural refinement through energy minimisation. The docking protocol was developed using a grid dimension of 84 × 66 × 72 and grid point spacing of 0.375 Å for eeAChE. The protocol was validated by redocking a set of co-crystallised inhibitors obtained from mouse AChE, and their interaction profiles were compared. The results indicated a poor performance of the Autodock scoring function. Hence, a batch of machine learning-based scoring functions were developed. The validation results displayed an accuracy of 81.68 ± 1.73% and 82.92 ± 3.05% for binary and multiclass classification scoring function, respectively. The regression-based scoring function produced [Formula: see text] and [Formula: see text] values of 0.94, 0.635 and 0.634, respectively.
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Acetilcolinesterasa , Inhibidores de la Colinesterasa , Acetilcolinesterasa/química , Animales , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Diseño de Fármacos , Electrophorus , Aprendizaje Automático , RatonesRESUMEN
BACKGROUND: Hepatocyte nuclear factor 4α (HNF4α) and glucocorticoid receptor (GR), master regulators of liver metabolism, are down-regulated in fatty liver diseases. The present study aimed to elucidate the role of down-regulation of HNF4α and GR in fatty liver and hyperlipidemia. METHODS: Adult mice with liver-specific heterozygote (HET) and knockout (KO) of HNF4α or GR were fed a high-fat-high-sugar diet (HFHS) for 15 days. Alterations in hepatic and circulating lipids were determined with analytical kits, and changes in hepatic mRNA and protein expression in these mice were quantified by real-time PCR and Western blotting. Serum and hepatic levels of bile acids were quantified by LC-MS/MS. The roles of HNF4α and GR in regulating hepatic gene expression were determined using luciferase reporter assays. RESULTS: Compared to HFHS-fed wildtype mice, HNF4α HET mice had down-regulation of lipid catabolic genes, induction of lipogenic genes, and increased hepatic and blood levels of lipids, whereas HNF4α KO mice had fatty liver but mild hypolipidemia, down-regulation of lipid-efflux genes, and induction of genes for uptake, synthesis, and storage of lipids. Serum levels of chenodeoxycholic acid and deoxycholic acid tended to be decreased in the HNF4α HET mice but dramatically increased in the HNF4α KO mice, which was associated with marked down-regulation of cytochrome P450 7a1, the rate-limiting enzyme for bile acid synthesis. Hepatic mRNA and protein expression of sterol-regulatory-element-binding protein-1 (SREBP-1), a master lipogenic regulator, was induced in HFHS-fed HNF4α HET mice. In reporter assays, HNF4α cooperated with the corepressor small heterodimer partner to potently inhibit the transactivation of mouse and human SREBP-1C promoter by liver X receptor. Hepatic nuclear GR proteins tended to be decreased in the HNF4α KO mice. HFHS-fed mice with liver-specific KO of GR had increased hepatic lipids and induction of SREBP-1C and PPARγ, which was associated with a marked decrease in hepatic levels of HNF4α proteins in these mice. In reporter assays, GR and HNF4α synergistically/additively induced lipid catabolic genes. CONCLUSIONS: induction of lipid catabolic genes and suppression of lipogenic genes by HNF4α and GR may mediate the early resistance to HFHS-induced fatty liver and hyperlipidemia.
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Grasas de la Dieta , Azúcares de la Dieta , Factor Nuclear 4 del Hepatocito , Metabolismo de los Lípidos , Receptores de Glucocorticoides , Animales , Cromatografía Liquida , Grasas de la Dieta/metabolismo , Azúcares de la Dieta/metabolismo , Hígado Graso/genética , Hígado Graso/metabolismo , Factor Nuclear 4 del Hepatocito/genética , Factor Nuclear 4 del Hepatocito/metabolismo , Factores Nucleares del Hepatocito/metabolismo , Metabolismo de los Lípidos/genética , Metabolismo de los Lípidos/fisiología , Lípidos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , ARN Mensajero/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Espectrometría de Masas en TándemRESUMEN
Scrub typhus is the oldest known vector-borne zoonotic infectious disease in the world which is life-threatening for all age groups as it presents acute febrile illness along with multi-organ involvements and spread with the biting of infectious 'Trombiculid mite' (chigger mite). The pathogen of this disease is an obligatory coccobacillus gram-negative rickettsial bacteria Orientia tsutsugamushi. Scrub typhus disease was previously confined geographically only to the Asia Pacific region (tsutsugamushi triangle), but in recent years it has crossed its limit and has spread in other countries beyond the tsutsugamushi triangle and has become more hazardous for the community. The objective of this study is to explore the scrub typhus disease outbreak trends with existing information in southern Rajasthan state, India. This study concluded that scrub typhus disease is being re-emerged again and again in various Indian geographical regions with new species of vectors. The disease has been raised in tremendous amounts in Rajasthan within the last five years especially in the hilly zone and has led to major public health problems with other zoonotic diseases.
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Orientia tsutsugamushi , Tifus por Ácaros , Trombiculidae , Animales , Humanos , Tifus por Ácaros/epidemiología , Salud Pública , India/epidemiología , Zoonosis , Trombiculidae/microbiologíaRESUMEN
The discovery of fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) provided a profound new insight into physiological and metabolic functions. FGF has a large family by having divergent structural elements and enable functional divergence and specification. FGF and FGFRs are highly expressed during kidney development. Signals from the ureteric bud regulate morphogenesis, nephrogenesis, and nephron progenitor survival. Thus, FGF signaling plays an important role in kidney progenitor cell aggregation at the sites of new nephron formation. This review will summarize the current knowledge about functions of FGF signaling in kidney development and their ability to promote regeneration in injured kidneys and its use as a biomarker and therapeutic target in kidney diseases. Further studies are essential to determine the predictive significance of the various FGF/FGFR deviations and to integrate them into clinical algorithms.
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Factores de Crecimiento de Fibroblastos/metabolismo , Enfermedades Renales/terapia , Riñón/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Animales , Humanos , Enfermedades Renales/metabolismo , Nefronas/metabolismo , Transducción de Señal/fisiologíaRESUMEN
A novel dual pH/thermoresponsive amphiphilic poly(histidine methacrylamide)-block-hydroxyl-terminated polybutadiene-block-poly(histidine methacrylamide) (PHisMAM-b-PB-b-PHisMAM) triblock copolymer biohybrid, composed of hydrophobic PB and ampholytic PHisMAM segments, is developed via direct switching from living anionic polymerization to recyclable nanoparticle catalyst-mediated reversible-deactivation radical polymerization (RDRP). The transformation involved in situ postpolymerization modification of living polybutadiene-based carbanionic species, end-capped with ethylene oxide, into dihydroxyl-terminated polybutadiene and a subsequent reaction with 2-bromo-2-methylpropionyl bromide resulting in a telechelic ATRP macroinitiator (Br-PB-Br). Br-PB-Br was used to mediate RDRP of an l-histidine-derived monomer, HisMAM, yielding a series of PHisMAM-b-PB-b-PHisMAM triblock copolymers. The copolymer's stimuli response was assessed against pH and temperature changes. The copolymer is capable of switching among its zwitterionic, anionic, and cationic forms and exhibited unique antifouling properties in its zwitterionic form. These novel triblock copolymers are expected to be show promising potential in biomedical applications.
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Incrustaciones Biológicas , Histidina , Incrustaciones Biológicas/prevención & control , Micelas , Polimerizacion , PolímerosRESUMEN
Herein we have reported for the first time a one-pot, one step methodology to synthesize isomeric polythiophene (IPTh) possessing 2,2, 2,4 and 5,4 linkages. The method of polymerization of thiophene to IPTh involved reacting thiophene with DDQ in the presence of concentrated H2SO4 at 40 °C and the polymerization is completed in 10 minutes. The synthesized IPTh was characterized by various spectroscopic and microscopic techniques. The formation of polaron and bipolaron in an iodine doped sample (IPTh-I2) has been confirmed by IR, Raman and UV-Vis spectra. The electrical conductivity of the synthesized IPTh and IPTh-I2 have been studied by impedance spectroscopy and found to be â¼10-5 and 10-3 S cm-1 respectively. IPTh exhibits an excellent thermal stability up to 150 °C, and low optical band gap of 3.49 eV suitable for photovoltaic applications. The weight average molecular weight of IPTh has been found to be 18.636 kDa, and it has a better post functionalization capability and hence wider scope than polythiophene (PTh).
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A novel triple stimuli sensitive block copolymer is prepared by magnetically separable and reusable (up to multiple cycles) Ni-Co alloy nanoparticles mediated reversible deactivation radical polymerization (RDRP) at 25 °C, that responds to changes in temperature, pH, and light. Design of this block copolymer constitutes a temperature-sensitive N-isopropylacrylamide (NIPAM), an acid-sensitive lysine methacrylamide (LysMAM), and a light responsive umbelliferone (UMB) end group. The stimuli response, in response to one stimulus as well as combinations of stimuli, has been evaluated. Responsiveness to light allows the construction of self-healing materials. Density functional theory calculations rationalize the underlying mechanism of the polymerization.
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Aleaciones , Nanopartículas , Micelas , Polimerizacion , Polímeros , TemperaturaRESUMEN
There are several potential side and adverse effects are found to be associated with the anti-inflammatory drugs in clinical practice. The long-term use of these clinical agents highly unsafe. It encouraged the development of novel heterocyclic compounds with potential anti-inflammatory activity and low to no toxicity. In present investigation, a total of 12 indole functionalized pyrazole and oxadiazole derivatives were designed, synthesized and evaluated for the in-vivo anti-inflammatory and analgesic potential. These compounds displayed comparable anti-inflammatory and analgesic potential to the reference drugs. Finally, molecular docking analysis was performed considering different anti-inflammatory targets to determine the mechanistic target of the designed molecules. Detailed analysis suggested that the molecules inhibit COX-2, preferably over other anti-inflammatory targets. The results suggested that two compounds (15c and 15f) were found promising candidates for the development of novel anti-inflammatory agents.
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Analgésicos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Indoles/farmacología , Oxadiazoles/farmacología , Pirazoles/farmacología , Analgésicos/síntesis química , Analgésicos/química , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Antioxidantes/síntesis química , Antioxidantes/química , Compuestos de Bifenilo/antagonistas & inhibidores , Carragenina , Bovinos , Ciclooxigenasa 2/metabolismo , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Edema/tratamiento farmacológico , Femenino , Humanos , Indoles/química , Masculino , Estructura Molecular , Oxadiazoles/síntesis química , Oxadiazoles/química , Picratos/antagonistas & inhibidores , Pirazoles/síntesis química , Pirazoles/química , Ratas , Ratas Wistar , Relación Estructura-ActividadRESUMEN
RNA interference molecules have tremendous potential for cancer therapy but are limited by insufficient potency after i.v. administration. We previously found that Chol-DsiRNA polyplexes formed between cholesterol-modified dicer-substrate siRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase the activity of Chol-DsiRNA against a stably expressed reporter mRNA in primary murine syngeneic breast tumors after daily i.v. dosing. Here, we provide a more thorough preliminary preclinical study of Chol-DsiRNA polyplexes against the therapeutically relevant target protein, STAT3. We found that Chol-DsiSTAT3 polyplexes greatly increase plasma exposure, distribution, potency, and therapeutic activity of Chol-DsiSTAT3 in primary murine syngeneic 4T1 breast tumors after i.v. administration. Furthermore, inactive Chol-DsiCTRL polyplexes are well tolerated by healthy female BALB/c mice after chronic i.v. administration at 50â¯mg Chol-DsiCTRL/kg over 28â¯days. Thus, Chol-DsiRNA polyplexes may be a good candidate for Phase I clinical trials to improve the treatment of breast cancer and other solid tumors.
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Neoplasias de la Mama/terapia , ARN Helicasas DEAD-box/genética , Polietilenglicoles/química , Polilisina/análogos & derivados , ARN Interferente Pequeño/química , Tratamiento con ARN de Interferencia/métodos , Ribonucleasa III/genética , Animales , Línea Celular Tumoral , Colesterol/química , Femenino , Técnicas de Transferencia de Gen , Humanos , Ratones Endogámicos BALB C , Micelas , Terapia Molecular Dirigida , Polilisina/química , Interferencia de ARN , Factor de Transcripción STAT3/metabolismo , Distribución TisularRESUMEN
In this review article, we will discuss the gamut of abnormalities involving the ureters. In the emergency department, ureterolithiasis is the most common indication for imaging abdomen and pelvis. However, spectrum of ureteral abnormalities including congenital, infectious and inflammatory, primary and secondary ureteral malignancies, retroperitoneal fibrosis rare described in this article may be encountered. Thus, we will describe acute subacute as well as chronic conditions that may affect ureter. Knowledge of common, as well as rare entities and their imaging features, is of utmost importance to enable appropriate management.
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Uréter , Cálculos Ureterales , Abdomen , Humanos , Pelvis , Radiólogos , Uréter/diagnóstico por imagen , UrografíaRESUMEN
PURPOSE: To measure the diagnostic accuracy and inter-observer agreement with the use of COVID-19 Reporting and Data System (CO-RADS) for detection of COVID-19 on CT chest imaging. METHODS: This retrospective study included 164 consecutive patients with clinical suspicion of COVID-19 in whom a CT chest examination was performed at a single institution between April 2020 and July 2020. Of them, 101 patients was RT-PCR positive for COVID-19. Six readers with varying radiological experience (two each of chest radiologists, general radiologists, and radiologists in training) independently assigned a CO-RADS assessment category for each CT chest study. The Fleiss' K was used to quantify inter-observer agreement. The inter-observer agreement was also assessed based on the duration of onset of symptoms to CT scan. ROC curve analysis was used to determine the diagnostic accuracy of CO-RADS. The area under curve was calculated to determine the reader accuracy for detection of COVID-19 lung involvement with RT-PCR as reference standards. The data sets were plotted in ROC space, and Youden's J statistic was calculated to determine the threshold cut-off CO-RADS category for COVID-19 positivity. RESULTS: There was overall moderate inter-observer agreement between all readers (Fleiss' K 0.54 [95% CI 0.54, 0.54]), with substantial agreement among chest radiologists (Fleiss' K 0.68 [95% CI 0.67, 0.68]), general radiologists (Fleiss' K 0.61 [95% CI 0.61, 0.61]), and moderate agreement among radiologists-in-training (Fleiss' K 0.56 [95% CI 0.56, 0.56]). There was overall moderate inter-observer agreement in early disease (stages 1 and 2), with cumulative Fleiss' K 0.45 [95% CI 0.45, 0.45]). The overall AUC for CO-RADS lexicon scheme to accurately diagnose COVID-19 yielded 0.92 (95% CI 0.91, 0.94) with strong concordance within and between groups, of chests radiologists with AUC of 0.91 (95% CI 0.88, 0.94), general radiologists with AUC 0.96 (95% CI 0.94, 0.98), and radiologists in training with AUC of 0.90 (95% CI 0.87, 0.94). For detecting COVID-19, ROC curve analysis yielded CO-RADS > 3 as the cut-off threshold with sensitivity 90% (95% CI 0.88, 0.93), and specificity of 87% (95% CI 0.83, 0.91). CONCLUSION: Readers across different levels of experience could accurately identify COVID-19 positive patients using the CO-RADS lexicon with moderate inter-observer agreement and high diagnostic accuracy.