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1.
Adv Sci (Weinh) ; : e2405210, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984453

RESUMO

The modulation of the chemical microenvironment surrounding metal nanoparticles (NPs) is an effective means to enhance the selectivity and activity of catalytic reactions. Herein, a post-synthetic modification strategy is developed to modulate the hydrophobic microenvironment of Ru nanoparticles encapsulated in a metal-organic framework (MOF), MIP-206, namely Ru@MIP-Fx (where x represents perfluoroalkyl chain lengths of 3, 5, 7, 11, and 15), in order to systematically explore the effect of the hydrophobic microenvironment on the electrocatalytic activity. The increase of perfluoroalkyl chain length can gradually enhance the hydrophobicity of the catalyst, which effectively suppresses the competitive hydrogen evolution reaction (HER). Moreover, the electrocatalytic production rate of ammonia and the corresponding Faraday efficiency display a volcano-like pattern with increasing hydrophobicity, with Ru@MIP-F7 showing the highest activity. Theoretical calculations and experiments jointly show that modification of perfluoroalkyl chains of different lengths on MIP-206 modulates the electronic state of Ru nanoparticles and reduces the rate-determining step for the formation of the key intermediate of N2H2 *, leading to superior electrocatalytic performance.

2.
Future Med Chem ; 16(12): 1185-1203, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989989

RESUMO

Aim: Synthesis of novel bis-Schiff bases having potent inhibitory activity against phosphodiesterase (PDE-1 and -3) enzymes, potentially offering therapeutic implications for various conditions. Methods: Bis-Schiff bases were synthesized by refluxing 2,4-dihydroxyacetophenone with hydrazine hydrate, followed by treatment of substituted aldehydes with the resulting hydrazone to obtain the product compounds. After structural confirmation, the compounds were screened for their in vitro PDE-1 and -3 inhibitory activities. Results: The prepared compounds exhibited noteworthy inhibitory efficacy against PDE-1 and -3 enzymes by comparing with suramin standard. To clarify the binding interactions between the drugs, PDE-1 and -3 active sites, molecular docking studies were carried out. Conclusion: The potent compounds discovered in this study may be good candidates for drug development.


[Box: see text].


Assuntos
Acetofenonas , Nucleotídeo Cíclico Fosfodiesterase do Tipo 1 , Simulação de Acoplamento Molecular , Inibidores de Fosfodiesterase , Acetofenonas/química , Acetofenonas/farmacologia , Acetofenonas/síntese química , Inibidores de Fosfodiesterase/farmacologia , Inibidores de Fosfodiesterase/síntese química , Inibidores de Fosfodiesterase/química , Humanos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 1/antagonistas & inibidores , Nucleotídeo Cíclico Fosfodiesterase do Tipo 1/metabolismo , Relação Estrutura-Atividade , Estrutura Molecular , Bases de Schiff/química , Bases de Schiff/farmacologia , Bases de Schiff/síntese química , Domínio Catalítico
3.
Artigo em Inglês | MEDLINE | ID: mdl-38996406

RESUMO

The current study involves the synthesis of Schiff bases based on 1,2,4-triazoles skeleton and assessing their α-amylase and α-glucosidase profile. Furthermore, the precise structures of the synthesized derivatives were elucidated using various spectroscopic methods such as 1H-NMR, 13C-NMR and HREI-MS. Using glimepiride as the reference standard, the in vitro α-glucosidase and α-amylase inhibitory activities of the synthesized compounds were evaluated in order to determine their potential anti-diabetic properties. All analogues showed varied range of inhibitory activity having IC50 values ranging from 17.09 ± 0.72 to 45.34 ± 0.03 µM (α-amylase) and 16.35 ± 0.42 to 42.31 ± 0.09 µM (α-glucosidase), respectively. Specifically, the compounds 1, 7 and 8 were found to be significantly active with IC50 values of 17.09 ± 0.72, 19.73 ± 0.42, and 23.01 ± 0.04 µM (against α-amylase) and 16.35 ± 0.42, 18.55 ± 0.26, and 20.07 ± 0.02 µM (against α-glucosidase) respectively. The obtained results were compared with the Glimepiride reference drug having IC50 values of 13.02 ± 0.11 µM (for α-glucosidase) and 15.04 ± 0.02 µM (for α-amylase), respectively. The structure-activity relationship (SAR) studies were conducted based on differences in substituent patterns at varying position of aryl rings A and B may cause to alter the inhibitory activities of both α-amylase and α-glucosidase enzymes. Additionally, the molecular docking study was carried out to explore the binding interactions possessed by most active analogues with the active sites of targeted α-amylase and α-glucosidase enzymes.

5.
Sensors (Basel) ; 24(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39000893

RESUMO

This paper discusses the design and implementation of a portable IoT station. Communication and data synchronization issues in several installations are addressed here, making possible a detailed analysis of the entire system during its operation. The system operator requires a synchronized data stream, combining multiple communication protocols into one single time stamp. The hardware selected for the portable IoT station complies with the International Electrotechnical Commission (IEC) industrial standards. A short discussion regarding interface customization shows how easily the hardware can be modified so that it is integrated with almost any system. A programmable logic controller enables the Node-RED to be utilized. This open-source middleware defines operations for each global variable nominated in the Modbus register. Two applications are presented and discussed in this paper; each application has a distinct methodology utilized to publish and visualize the acquired data. The portable IoT station is highly customizable, consisting of a modular structure and providing the best platform for future research and development of dedicated algorithms. This paper also demonstrates how the portable IoT station can be implemented in systems where time-based data synchronization is essential while introducing a seamless implementation and operation.

6.
Cureus ; 16(6): e62356, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39006567

RESUMO

Introduction Hypoglycemia is a critical concern in neonatal care, particularly among preterm infants. This study aims to investigate the frequency of hypoglycemia within the first 24 hours of life in preterm neonates, considering factors such as gestational age (GA), birth weight, and gender. Materials and methods A cross-sectional study was conducted from February to August 2021. The sample comprised 186 preterm infants selected through consecutive sampling. Data collection involved demographic information, glucose level monitoring, and symptom assessment. Results Of the 186 preterm neonates, 31.7% (n=59) experienced hypoglycemia within the first 24 hours, with feeding refusal being the predominant symptom. There was a significant difference in hypoglycemia occurrence between infants born before and after 32 weeks of gestation (p<0.05). Males were slightly more affected than females, although not statistically significant. Infants weighing less than 2 kg showed a higher susceptibility to hypoglycemia. Conclusion The early detection and management of hypoglycemia are crucial in preterm neonatal care. Close monitoring, especially in the initial four hours, is essential to prevent complications. Larger studies are warranted to confirm these findings and improve understanding and management strategies for hypoglycemia in preterm neonates, particularly within the first 24 hours of life.

7.
Chem Asian J ; : e202400314, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014972

RESUMO

Stainless steel mesh (SSM) has emerged as a cornerstone in electrochemical applications owing to its exemplary versatility, electrical conductivity, mechanical robustness, and corrosion resistance. This state-of-the-art review delves into the diverse roles of SSM across a spectrum of electrochemical domains, including energy conversion and storage devices, water treatment technologies, electrochemical sensors, and catalysis. We meticulously explore its deployment in supercapacitors, batteries, and fuel cells, highlighting its utility as a current collector, electrode, and separator. The review further discusses the critical significance of SSM in water treatment processes, emphasizing its efficacy in supporting membranes and facilitating electrocoagulation, as well as its novel uses in electrochemical sensing and catalysis, which include electrosynthesis and bioelectrochemistry. Each section delineates the recent advancements, identifies the inherent challenges, and suggests future directions for leveraging SSM in electrochemical technologies. This comprehensive review showcases the current state of knowledge and articulates the novel integration of SSM with emerging materials and technologies, thereby establishing a new paradigm for sustainable and efficient electrochemical applications. Through critical analysis and insightful recommendations, this review positions itself as a seminal contribution, paving the way for researchers and practitioners to harness the full potential of SSM in advancing the electrochemistry frontiers.

8.
PLoS One ; 19(7): e0304472, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39024335

RESUMO

Fruit flies of genus Bactrocera are important insect pests of commercially cultivated mangos in Pakistan limiting its successful production in the country. Despite the economic risk, the genetic diversity and population dynamics of this pest have remained unexplored. This study aimed to morphologically identify Bactrocera species infesting Mango in major production areas of the country and to confirm the results with insect DNA barcode techniques. Infested mango fruits from the crop of 2022, were collected from 46 locations of 11major production districts of Punjab and Sindh provinces, and first-generation flies were obtained in the laboratory. All 10,653 first generation flies were morphologically identified as two species of Bactrocera; dorsalis and zonata showing geography-based relative abundance in the two provinces; Punjab and Sindh. Morphological identification was confirmed by mitochondrial cytochrome oxidase gene subunit I (mt-COI) based DNA barcoding. Genetic analysis of mtCOI gene region of 61 selected specimens by the presence of two definite clusters and reliable intraspecific distances validated the results of morphological identification. This study by morphological identification of a large number of fruit fly specimens from the fields across Pakistan validated by insect DNA barcode reports two species of Bactrocera infesting mango in the country.


Assuntos
Código de Barras de DNA Taxonômico , Complexo IV da Cadeia de Transporte de Elétrons , Variação Genética , Mangifera , Tephritidae , Animais , Tephritidae/genética , Tephritidae/classificação , Paquistão , Mangifera/parasitologia , Mangifera/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Filogenia
9.
Expert Opin Ther Pat ; 34(8): 723-732, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38965930

RESUMO

INTRODUCTION: Boswellic acids (BAs) are a group of pentacyclic triterpenoids of the ursane and oleanane type. They have shown very interesting biological properties that have led to the development of a number of synthesis protocols. Both natural BAs and their synthetic derivatives may be useful in the treatment of a variety of cancers, viral infections and inflammatory diseases. AREAS COVERED: This review covers patents relating to the therapeutic activities of natural BAs and their synthetic derivatives. The latest patented studies of boswellic acids (are summarized by using the keywords 'boswellic acid,' in SciFinder, PubMed, and Google Patents and databases in the year from 2016 to 2023. EXPERT OPINION: Boswellic acids have shown potent antiviral, anticancer and anti-inflammatory potential. Few BAs analogues have been prepared by modification at the C24-CO2H functional groups. In particular, the C-24 amide and amino analogues have shown enhanced anticancer effects compared to the parent AKBA. In addition, BAs have the ability to form conjugates with other antiviral, anti-inflammatory and anticancer drugs that synergistically enhance their biological efficacy. In addition, this conjugation strategy will increase the solubility and bioavailability of BAs, which is one of the most important issues in the development of BAs.


Assuntos
Anti-Inflamatórios , Antivirais , Desenvolvimento de Medicamentos , Neoplasias , Patentes como Assunto , Triterpenos , Humanos , Triterpenos/farmacologia , Triterpenos/química , Animais , Antivirais/farmacologia , Anti-Inflamatórios/farmacologia , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Inflamação/tratamento farmacológico , Viroses/tratamento farmacológico , Disponibilidade Biológica
10.
ACS Omega ; 9(22): 23355-23363, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38854579

RESUMO

An increase in cocaine abuse has been observed globally since the past decade. Cocaine is among the commonly abused stimulants used for recreational purposes. In this study, the SPE-UHPLC-MS/MS method was developed and validated to be applied on real specimens of 20 chronic cocaine abusers to quantify cocaine/metabolites in conventional as well as alternative biological matrices. Cocaine was extracted from biological specimens using solid-phase extraction followed by liquid chromatography tandem mass spectrometry analysis. Chromatographic separation was achieved on a Poroshell120EC-18 column (2.1 mm × 50 mm, 2.7 µm particle size) using water-acetonitrile in 0.1% formic acid as a mobile phase in gradient elution mode. The flow rate of the mobile phase was 0.5 mL/min with a gradient varying the percentage of acetonitrile linearity ranging 15-95% in 6.0 min acquisition time, and the injection volume was set at 5 µL. Positive electrospray ionization with multireaction ion monitoring mode using two ion transitions for cocaine/metabolites and one for cocaine-d3 was employed. The quantification method demonstrated good linear ranges of 0.025-250 ng/mL in blood, urine, and oral fluid (ng/mg for hair and nail) with a ≥0.991% determination coefficient. The detection limit and lower quantification limit were 0.005 and 0.025 ng/mL in all matrices, respectively. The mean extraction recovery and ionization suppression ranged from 89.3 to 99.8% and -4.6 to -14.4% in the studied matrices. Within-run and between-days precisions were 1.8-7.2% and 1.9-6.1%, respectively. This study will not only help in quantifying cocaine/metabolites in alternative specimens (hair, nail, and oral fluid) but also guide clinical and forensic toxicologists in interpretation of exhumation cases. Furthermore, multiple specimens' analyses can be of significance in estimating the time/manner of drug exposure, in confirming the results of laboratories in cases of doubtful clinical histories, or in aiding medico-legal investigations.

11.
PeerJ Comput Sci ; 10: e2000, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855256

RESUMO

Immersive technology, especially virtual reality (VR), transforms education. It offers immersive and interactive learning experiences. This study presents a systematic review focusing on VR's integration with educational theories in higher education. The review evaluates the literature on VR applications combined with pedagogical frameworks. It aims to identify effective strategies for enhancing educational experiences through VR. The process involved analyzing studies about VR and educational theories, focusing on methodologies, outcomes, and effectiveness. Findings show that VR improves learning outcomes when aligned with theories such as constructivism, experiential learning, and collaborative learning. These integrations offer personalized, immersive, and interactive learning experiences. The study highlights the importance of incorporating educational principles into VR application development. It suggests a promising direction for future research and implementation in education. This approach aims to maximize VR's pedagogical value, enhancing learning outcomes across educational settings.

12.
Sci Rep ; 14(1): 13520, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866825

RESUMO

This study aims to explore the precise resolution of the nonlinear Benjamin Bona Mahony Burgers (BBMB) equation, which finds application in a variety of nonlinear scientific disciplines including fluid dynamics, shock generation, wave transmission, and soliton theory. Within this paper, we employ two versatile methodologies, specifically the extended exp ( - Ψ ( χ ) ) expansion technique and the novel Kudryashov method, to identify the exact soliton solutions of the nonlinear BBMB equation. The solutions we discovered involve trigonometric functions, hyperbolic functions, and rational functions. The uniqueness of this research lies in uncovering the bright soliton, kink wave solution, and periodic wave solution, and conducting stability analysis. Furthermore, the solutions' graphical characteristics were explored through the utilization of the mathematical software Maple 2022 ( https://maplesoft.com/downloads/selectplatform.aspx?hash=61ab59890f2313b2241fde3423fd975e ). The system's physical interpretation is defined through various types of graphs, including contour graphs, 3D-surface graphs, and line graphs, which use appropriate parameter values. These recommended techniques hold significant importance and are applicable in diverse nonlinear evolutionary equations found in the field of nonlinear sciences for illustrating nonlinear physical models.

13.
Sci Rep ; 14(1): 13585, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866857

RESUMO

In this study, Delonix regia seed pods (DRSPs) as a locally available material were refluxed in 90% H2SO4 to yield a novel D. regia seed pods biochar-sulfur oxide (DRB-SO). FTIR, BET, BJH, SEM, EDX, XRD, DSC and TGA were applied to investigate the characterizations of the prepared DRB-SO. Various adsorption parameters like pH effect, dye concentration effect, adsorbent dose, reaction time isotherm and kinetic study were carried out to explain the process of adsorption of methyl orange (MO) and methyl red (MR) onto DRB-SO. Langmuir's adsorption model perfectly explained the adsorption process onto the surface of DRB-SO as a monolayer. The maximum adsorption efficiency of DRB-SO was (98%) and (99.6%) for MO and MR respectively which attained after 150 min with an adsorbent dose of 0.75 g/L. The pseudo-second-order kinetic model best explained the process of adsorption of MO and MR dyes by DRB-SO. The highest observed adsorption amount was as high as 144.9 mg/g for MO dye and 285.7 mg/g for MR dye, comparable with other reported materials based on activated carbon materials. All of the outcomes signposted a prodigious perspective of the fabricated biochar composite material in wastewater treatment. Using the regenerating DRB-SO through an acid-base regeneration process, six cycles of adsorption/desorption were examined. Over the course of the cycles, there was a minor decrease in the adsorption and desorption processes. Also, it was revealed what the most plausible mechanism was for DRB-SO to absorb the ions of the MO and MR dyes.

14.
PLoS One ; 19(6): e0304018, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38905213

RESUMO

Fractional order algorithms demonstrate superior efficacy in signal processing while retaining the same level of implementation simplicity as traditional algorithms. The self-adjusting dual-stage fractional order least mean square algorithm, denoted as LFLMS, is developed to expedite convergence, improve precision, and incurring only a slight increase in computational complexity. The initial segment employs the least mean square (LMS), succeeded by the fractional LMS (FLMS) approach in the subsequent stage. The latter multiplies the LMS output, with a replica of the steering vector (R) of the intended signal. Mathematical convergence analysis and the mathematical derivation of the proposed approach are provided. Its weight adjustment integrates the conventional integer ordered gradient with a fractional-ordered. Its effectiveness is gauged through the minimization of mean square error (MSE), and thorough comparisons with alternative methods are conducted across various parameters in simulations. Simulation results underscore the superior performance of LFLMS. Notably, the convergence rate of LFLMS surpasses that of LMS by 59%, accompanied by a 49% improvement in MSE relative to LMS. So it is concluded that the LFLMS approach is a suitable choice for next generation wireless networks, including Internet of Things, 6G, radars and satellite communication.


Assuntos
Algoritmos , Processamento de Sinais Assistido por Computador , Análise dos Mínimos Quadrados , Simulação por Computador , Modelos Teóricos
15.
Acta Vet Hung ; 72(2): 133-139, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38900584

RESUMO

This study investigated the sero-epidemiology of bluetongue in ruminants in North-Western Pakistan. A total of 3,173 serum samples were collected from small (n = 1,651) and large (n = 1,522) ruminants being reared by farmers in 14 districts. Antibodies to bluetongue virus (BTV) were detected using competitive ELISA. The overall prevalence of BTV antibodies was 65%. A significant association (P < 0.05) between the prevalence of BTV antibodies and the risk factors including sex, species, age, area, husbandry practices and breed was shown by univariate analysis. In multivariate analysis, the seroprevalence was 6.5 (95% CL = 3.7-11.4), 5.9 (95% CL = 3.8-9.4) and 2.4 (95% CL = 1.5-3.7) times higher in buffaloes, cattle and goats than sheep, respectively. The seroprevalence was 1.4 (95% CL = 1.1-1.7) times higher in local breeds than in cross/exotic breeds. The seroprevalence was 1.6 (95% CL = 1.1 to 2.3) times higher in sedentary animals than in nomadic animals. The seroprevalence was significantly associated with age. Further work is required to determine the BTV serotypes prevalent in the study area for effective control of the disease.


Assuntos
Vírus Bluetongue , Bluetongue , Doenças das Cabras , Animais , Paquistão/epidemiologia , Estudos Soroepidemiológicos , Bluetongue/epidemiologia , Bluetongue/virologia , Vírus Bluetongue/imunologia , Feminino , Masculino , Doenças das Cabras/epidemiologia , Doenças das Cabras/virologia , Ovinos , Cabras , Bovinos , Anticorpos Antivirais/sangue , Ruminantes/virologia , Fatores de Risco , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/virologia , Criação de Animais Domésticos , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/virologia , Prevalência
16.
Future Med Chem ; : 1-15, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940451

RESUMO

Aim: To synthesize aurone (Ar) derivatives and to demonstrate their effects against diabetes mellitus (DM) and neurodegeneration. Materials & methods: Five Ar (A-E) derivatives were synthesized, characterized by proton NMR and screened for antioxidant, anti-diabetic and anti-cholinesterase activities. They were further evaluated for neuroprotective effects in streptozotocin (STZ)-induced neurodegenerative model. Results: Among the aurone derivatives ArE demonstrated significant reversal of cognitive impairment, oxidative stress and neuroinflammation. Biochemical analysis revealed anti-diabetic and neuroprotective effects, possibly through downregulation of inflammatory markers and upregulation of antioxidant enzymes. Conclusion: Synthesized Ar (A-E) exhibits promising therapeutic potential against STZ-induced neurodegeneration and DM by modulating inflammatory and oxidative pathways, suggesting a novel avenue for disease management.


[Box: see text].

17.
Biodivers Data J ; 12: e123405, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919771

RESUMO

Cinnamomumparthenoxylon is an endemic and endangered species with significant economic and ecological value in Vietnam. A better understanding of the genetic architecture of the species will be useful when planning management and conservation. We aimed to characterize the transcriptome of C.parthenoxylon, develop novel molecular markers, and assess the genetic variability of the species. First, transcriptome sequencing of five trees (C.parthenoxylon) based on root, leaf, and stem tissues was performed for functional annotation analysis and development of novel molecular markers. The transcriptomes of C.parthenoxylon were analyzed via an Illumina HiSeqTM 4000 sequencing system. A total of 27,363,199 bases were generated for C.parthenoxylon. De novo assembly indicated that a total of 160,435 unigenes were generated (average length = 548.954 bp). The 51,691 unigenes were compared against different databases, i.e. COG, GO, KEGG, KOG, Pfam, Swiss-Prot, and NR for functional annotation. Furthermore, a total of 12,849 EST-SSRs were identified. Of the 134 primer pairs, 54 were randomly selected for testing, with 15 successfully amplified across nine populations of C.parthenoxylon. We uncovered medium levels of genetic diversity (PIC = 0.52, Na = 3.29, Ne = 2.18, P = 94.07%, Ho = 0.56 and He = 0.47) within the studied populations. The molecular variance was 10% among populations and low genetic differentiation (Fst = 0.06) indicated low gene flow (Nm = 2.16). A reduction in the population size of C.parthenoxylon was detected using BOTTLENECK (VP population). The structure analysis suggested two optimal genetic clusters related to gene flow among the populations. Analysis of molecular variance (AMOVA) revealed higher genetic variation within populations (90%) than among populations (10%). The UPGMA approach and DAPC divided the nine populations into three main clusters. Our findings revealed a significant fraction of the transcriptome sequences and these newlydeveloped novel EST-SSR markers are a very efficient tool for germplasm evaluation, genetic diversity and molecular marker-assisted selection in C.parthenoxylon. This study provides comprehensive genetic resources for the breeding and conservation of different varieties of C.parthenoxylon.

18.
Chem Asian J ; : e202400341, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38923319

RESUMO

The development of efficient supercapacitors hinges on the innovation of superior electrodes, which are pivotal in augmenting their energy storage capabilities. Supercapacitors, recognized for their high-power density and extended cycle life, play a crucial role as sustainable solutions in addressing energy storage challenges. A fundamental aspect of supercapacitor functionality involves the electrode material, which works in concert with other key components such as the current collector, separator, and electrolyte. This study focuses on evaluating the impact of the current collector material on the performance of symmetric supercapacitors. We investigated the electropolymerization of polyaniline on woven steel mesh current collectors of varying mesh sizes, ranging from 20 to 200 mesh per inch, using assorted deposition conditions. The electrochemically modified woven steel meshes were utilized to construct symmetric supercapacitors. The electrochemical performance of the assembled supercapacitors, configured in a two-electrode system, was investigated using a variety of electrochemical techniques to better understand the kinetics of electrolyte ion migration. Notably, the 20-mesh size, characterized by the fewest pores per inch, demonstrated superior performance with an optimum capacitance of 4730 mF/cm2, an energy density of 317.8 µWh/cm2, and a power density of 400 µW/cm2 at a current density of 1 mA/cm2.

19.
Aging Dis ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38913039

RESUMO

Alzheimer's disease (AD) manifests as a complex systems pathology with intricate interplay among various genes and biological processes. Traditional differential gene expression (DEG) analysis, while commonly employed to characterize AD-driven perturbations, does not sufficiently capture the full spectrum of underlying biological processes. Utilizing single-nucleus RNA-sequencing data from postmortem brain samples across key regions-middle temporal gyrus, superior frontal gyrus, and entorhinal cortex-we provide a comprehensive systematic analysis of disrupted processes in AD. We go beyond the DEG-centric analysis by integrating pathway activity analysis with weighted gene co-expression patterns to comprehensively map gene interconnectivity, identifying region- and cell-type-specific drivers of biological processes associated with AD. Our analysis reveals profound modular heterogeneity in neurons and glia as well as extensive AD-related functional disruptions. Co-expression networks highlighted the extended involvement of astrocytes and microglia in biological processes beyond neuroinflammation, such as calcium homeostasis, glutamate regulation, lipid metabolism, vesicle-mediated transport, and TOR signaling. We find limited representation of DEGs within dysregulated pathways across neurons and glial cells, suggesting that differential gene expression alone may not adequately represent the disease complexity. Further dissection of inferred gene modules revealed distinct dynamics of hub DEGs in neurons versus glia, suggesting that DEGs exert more impact on neurons compared to glial cells in driving modular dysregulations underlying perturbed biological processes. Interestingly, we observe an overall downregulation of astrocyte and microglia modules across all brain regions in AD, indicating a prevailing trend of functional repression in glial cells across these regions. Notable genes from the CALM and HSP90 families emerged as hub genes across neuronal modules in all brain regions, suggesting conserved roles as drivers of synaptic dysfunction in AD. Our findings demonstrate the importance of an integrated, systems-oriented approach combining pathway and network analysis to comprehensively understand the cell-type-specific roles of genes in AD-related biological processes.

20.
Am J Ophthalmol ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38871269

RESUMO

PURPOSE: To assess the safety and efficacy of AAV5-hRKp.RPGR in participants with retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (XLRP). DESIGN: Open-label, phase 1/2 dose escalation/expansion study (NCT03252847). METHODS: Males (≥5 years old) with XLRP-RPGR were evaluated. In the dose escalation phase, subretinal AAV5-hRKp.RPGR (low: 1.0×1011 vg/ml; intermediate: 2.0×1011 vg/ml; high: 4.0×1011 vg/ml) was administered to the poorer-seeing eye (n = 10). Dose confirmation (intermediate dose) was carried out in 3 pediatric participants. In the dose expansion phase, 36 participants were randomized 1:1:1 to immediate (low or intermediate dose) or deferred (control) treatment. The primary outcome was safety. Secondary efficacy outcomes included static perimetry, microperimetry, vision-guided mobility, best corrected visual acuity, and contrast sensitivity. Safety and efficacy outcomes were assessed for 52 weeks for immediate treatment participants and 26 weeks for control participants. RESULTS: AAV5-hRKp.RPGR was safe and well tolerated, with no reported dose-limiting events. Most adverse events (AEs) were transient and related to the surgical procedure, resolving without intervention. Two serious AEs were reported with immediate treatment (retinal detachment, uveitis). A third serious AE (increased intraocular pressure) was reported outside the reporting period. All ocular inflammation-related AEs responded to corticosteroids. Treatment with AAV5-hRKp.RPGR resulted in improvements in retinal sensitivity and functional vision compared with the deferred group at Week 26; similar trends were observed at Week 52. CONCLUSIONS: AAV5-hRKp.RPGR demonstrated an anticipated and manageable AE profile through 52 weeks. Safety and efficacy findings support investigation in a phase 3 trial.

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