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1.
Brief Bioinform ; 24(1)2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36528806

RESUMO

Determining the pathogenicity and functional impact (i.e. gain-of-function; GOF or loss-of-function; LOF) of a variant is vital for unraveling the genetic level mechanisms of human diseases. To provide a 'one-stop' framework for the accurate identification of pathogenicity and functional impact of variants, we developed a two-stage deep-learning-based computational solution, termed VPatho, which was trained using a total of 9619 pathogenic GOF/LOF and 138 026 neutral variants curated from various databases. A total number of 138 variant-level, 262 protein-level and 103 genome-level features were extracted for constructing the models of VPatho. The development of VPatho consists of two stages: (i) a random under-sampling multi-scale residual neural network (ResNet) with a newly defined weighted-loss function (RUS-Wg-MSResNet) was proposed to predict variants' pathogenicity on the gnomAD_NV + GOF/LOF dataset; and (ii) an XGBOD model was constructed to predict the functional impact of the given variants. Benchmarking experiments demonstrated that RUS-Wg-MSResNet achieved the highest prediction performance with the weights calculated based on the ratios of neutral versus pathogenic variants. Independent tests showed that both RUS-Wg-MSResNet and XGBOD achieved outstanding performance. Moreover, assessed using variants from the CAGI6 competition, RUS-Wg-MSResNet achieved superior performance compared to state-of-the-art predictors. The fine-trained XGBOD models were further used to blind test the whole LOF data downloaded from gnomAD and accordingly, we identified 31 nonLOF variants that were previously labeled as LOF/uncertain variants. As an implementation of the developed approach, a webserver of VPatho is made publicly available at http://csbio.njust.edu.cn/bioinf/vpatho/ to facilitate community-wide efforts for profiling and prioritizing the query variants with respect to their pathogenicity and functional impact.


Assuntos
Aprendizado Profundo , Humanos , Mutação com Ganho de Função , Genoma
2.
Plant Physiol ; 195(1): 566-579, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38345864

RESUMO

The formation of multi-pistil flowers reduces the yield and quality in Japanese apricot (Prunus mume). However, the molecular mechanism underlying the formation of multi-pistil flowers remains unknown. In the current study, overexpression of PmKNAT2/6-a, a class I KNOTTED1-like homeobox (KNOX) member, in Arabidopsis (Arabidopsis thaliana) resulted in a multi-pistil phenotype. Analysis of the upstream regulators of PmKNAT2/6-a showed that AGAMOUS-like 24 (PmAGL24) could directly bind to the PmKNAT2/6-a promoter and regulate its expression. PmAGL24 also interacted with Like Heterochromatin Protein 1 (PmLHP1) to recruit lysine trimethylation at position 27 on histone H3 (H3K27me3) to regulate PmKNAT2/6-a expression, which is indirectly involved in multiple pistils formation in Japanese apricot flowers. Our study reveals that the PmAGL24 transcription factor, an upstream regulator of PmKNAT2/6-a, regulates PmKNAT2/6-a expression via direct and indirect pathways and is involved in the formation of multiple pistils in Japanese apricot.


Assuntos
Arabidopsis , Flores , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Flores/genética , Flores/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Plantas Geneticamente Modificadas , Prunus/genética , Prunus/metabolismo , Prunus armeniaca/genética , Prunus armeniaca/metabolismo , Regiões Promotoras Genéticas/genética
3.
Plant Physiol ; 193(1): 466-482, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37204822

RESUMO

Japanese apricot (Prunus mume Sieb. et Zucc.) is a traditional fruit tree with a long history. Multiple pistils (MP) lead to the formation of multiple fruits, decreasing fruit quality and yield. In this study, the morphology of flowers was observed at 4 stages of pistil development: undifferentiated stage (S1), predifferentiation stage (S2), differentiation stage (S3), and late differentiation stage (S4). In S2 and S3, the expression of PmWUSCHEL (PmWUS) in the MP cultivar was significantly higher than that in the single-pistil (SP) cultivar, and the gene expression of its inhibitor, PmAGAMOUS (PmAG), also showed the same trend, indicating that other regulators participate in the regulation of PmWUS during this period. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) showed that PmAG could bind to the promoter and the locus of PmWUS, and H3K27me3 repressive marks were also detected at these sites. The SP cultivar exhibited an elevated level of DNA methylation in the promoter region of PmWUS, which partially overlapped with the region of histone methylation. This suggests that the regulation of PmWUS involves both transcription factors and epigenetic modifications. Also, the gene expression of Japanese apricot LIKE HETEROCHROMATIN PROTEIN (PmLHP1), an epigenetic regulator, in MP was significantly lower than that in SP in S2 to 3, contrary to the trend in expression of PmWUS. Our results showed that PmAG recruited sufficient PmLHP1 to maintain the level of H3K27me3 on PmWUS during the S2 of pistil development. This recruitment of PmLHP1 by PmAG inhibits the expression of PmWUS at the precise time, leading to the formation of 1 normal pistil primordium.


Assuntos
Frutas , Prunus armeniaca , Frutas/genética , Frutas/metabolismo , Prunus armeniaca/metabolismo , Histonas/genética , Histonas/metabolismo , Proteínas do Grupo Polycomb/genética , Proteínas do Grupo Polycomb/metabolismo , Flores/genética , Flores/metabolismo , Morfogênese
4.
Environ Sci Technol ; 58(19): 8464-8479, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38701232

RESUMO

Microplastics threaten soil ecosystems, strongly influencing carbon (C) and nitrogen (N) contents. Interactions between microplastic properties and climatic and edaphic factors are poorly understood. We conducted a meta-analysis to assess the interactive effects of microplastic properties (type, shape, size, and content), native soil properties (texture, pH, and dissolved organic carbon (DOC)) and climatic factors (precipitation and temperature) on C and N contents in soil. We found that low-density polyethylene reduced total nitrogen (TN) content, whereas biodegradable polylactic acid led to a decrease in soil organic carbon (SOC). Microplastic fragments especially depleted TN, reducing aggregate stability, increasing N-mineralization and leaching, and consequently increasing the soil C/N ratio. Microplastic size affected outcomes; those <200 µm reduced both TN and SOC contents. Mineralization-induced nutrient losses were greatest at microplastic contents between 1 and 2.5% of soil weight. Sandy soils suffered the highest microplastic contamination-induced nutrient depletion. Alkaline soils showed the greatest SOC depletion, suggesting high SOC degradability. In low-DOC soils, microplastic contamination caused 2-fold greater TN depletion than in soils with high DOC. Sites with high precipitation and temperature had greatest decrease in TN and SOC contents. In conclusion, there are complex interactions determining microplastic impacts on soil health. Microplastic contamination always risks soil C and N depletion, but the severity depends on microplastic characteristics, native soil properties, and climatic conditions, with potential exacerbation by greenhouse emission-induced climate change.


Assuntos
Carbono , Clima , Microplásticos , Nitrogênio , Solo , Nitrogênio/análise , Solo/química , Carbono/análise , Poluentes do Solo/análise
5.
Environ Res ; 252(Pt 2): 118945, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38631466

RESUMO

Microplastics pollution and climate change are primarily investigated in isolation, despite their joint threat to the environment. Greenhouse gases (GHGs) are emitted during: the production of plastic and rubber, the use and degradation of plastic, and after contamination of environment. This is the first meta-analysis to assess underlying causal relationships and the influence of likely mediators. We included 60 peer-reviewed empirical studies; estimating GHGs emissions effect size and global warming potential (GWP), according to key microplastics properties and soil conditions. We investigated interrelationships with microbe functional gene expression. Overall, microplastics contamination was associated with increased GHGs emissions, with the strongest effect (60%) on CH4 emissions. Polylactic-acid caused 32% higher CO2 emissions, but only 1% of total GWP. Phenol-formaldehyde had the greatest (175%) GWP via 182% increased N2O emissions. Only polystyrene resulted in reduced GWP by 50%, due to N2O mitigation. Polyethylene caused the maximum (60%) CH4 emissions. Shapes of microplastics differed in GWP: fiber had the greatest GWP (66%) whereas beads reduced GWP by 53%. Films substantially increased emissions of all GHGs: 14% CO2, 10% N2O and 60% CH4. Larger-sized microplastics had higher GWP (125%) due to their 9% CO2 and 63% N2O emissions. GWP rose sharply if soil microplastics content exceeded 0.5%. Higher CO2 emissions, ranging from 4% to 20%, arose from soil which was either fine, saturated or had high-carbon content. Higher N2O emissions, ranging from 10% to 95%, arose from soils that had either medium texture, saturated water content or low-carbon content. Both CO2 and N2O emissions were 43%-56% higher from soils with neutral pH. We conclude that microplastics contamination can cause raised GHGs emissions, posing a risk of exacerbating climate-change. We show clear links between GHGs emissions, microplastics properties, soil characteristics and soil microbe functional gene expression. Further research is needed regarding underlying mechanisms and processes.


Assuntos
Aquecimento Global , Gases de Efeito Estufa , Microplásticos , Poluentes do Solo , Microplásticos/análise , Gases de Efeito Estufa/análise , Poluentes do Solo/análise , Mudança Climática , Solo/química , Poluentes Atmosféricos/análise
6.
Luminescence ; 39(5): e4758, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38712530

RESUMO

The ability of heterogeneous photocatalysis to effectively remove organic pollutants from wastewater has shown great promise as a tool for environmental remediation. Pure zinc ferrites (ZnFe2O4) and magnesium-doped zinc ferrites (Mg@ZnFe2O4) with variable percentages of Mg (0.5, 1, 3, 5, 7, and 9 mol%) were synthesized via hydrothermal route and their photocatalytic activity was checked against methylene blue (MB) taken as a model dye. FTIR, XPS, BET, PL, XRD, TEM, and UV-Vis spectroscopy were used for the identification and morphological characterization of the prepared nanoparticles (NPs) and nanocomposites (NCs). The 7% Mg@ZnFe2O4 NPs demonstrated excellent degradation against MB under sunlight. The 7% Mg@ZnFe2O4 NPs were integrated with diverse contents (10, 50, 30, and 70 wt.%) of S@g-C3N4 to develop NCs with better activity. When the NCs were tested to degrade MB dye, it was revealed that the 7%Mg@ZnFe2O4/S@g-C3N4 NCs were more effective at utilizing solar energy than the other NPs and NCs. The synergistic effect of the interface formed between Mg@ZnFe2O4 and S@g-C3N4 was primarily responsible for the boosted photocatalytic capability of the NCs. The fabricated NCs may function as an effective new photocatalyst to remove organic dyes from wastewater.


Assuntos
Compostos Férricos , Azul de Metileno , Compostos de Nitrogênio , Energia Solar , Poluentes Químicos da Água , Zinco , Catálise , Poluentes Químicos da Água/química , Compostos Férricos/química , Azul de Metileno/química , Zinco/química , Magnésio/química , Fotólise , Processos Fotoquímicos , Corantes/química , Nanocompostos/química , Grafite/química , Águas Residuárias/química , Nitrilas/química
7.
Luminescence ; 39(3): e4724, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38523053

RESUMO

For white light-rendering research activities, interpretation by using colored emitting materials is an alternative approach. But there are issues in designing the white color emitting materials. Particularly, differences in thermal and decay properties of discrete red, green, and blue emitting materials led to the quest for the search of a single-phased material, able to emit primary colors for white light generation. The current study is an effort to design a simple, single-phase, and cost-effective material with the tunable emission of primary colors by a series of Mg1-xBaxAl2O4:Mn2+ nanopowders. Doping of manganese ion (Mn2+) in the presence of the larger barium cation (Ba2+) at tetrahedral-sites of the spinel magnesium aluminate (MgAl2O4) structure led to the creation of antisite defects. Doped samples were found to have lower bandgaps compared with MgAl2O4, and hybridization of 3d-orbitals of Mn2+ with O(2p), Mg(2s)/Al(2s3p) was found to be responsible for narrowing the bandgap. The distribution of cations at various sites at random results in a variety of electronic transitions between the valance band and oxygen vacancies as well as electron traps produced the antisite defects. The suggested compositions might be used in white light applications since they have three emission bands with centers at 516 nm (green), 464 nm (blue) and 622 nm (red) at an excitation wavelength of 380 nm. A detailed discussion to analyze the effects of the larger cationic radius of Ba2+ on the lattice strain, unit cell parameters, and cell volumes using X-ray diffraction analysis is presented.


Assuntos
Óxido de Alumínio , Óxido de Magnésio , Cristalografia por Raios X , Eletrônica
8.
Luminescence ; 39(6): e4799, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38858760

RESUMO

In this study, tellurium-doped and undoped metal oxide nanoparticles (NPs) (ZnO, Mn3O4, SnO2) are compared, and a practical method for their synthesis is presented. Nanocomposites were created using the coprecipitation process, and comparisons between the three material categories under study were made using a range of characterization methods. The produced materials were subjected to structural, morphological, elemental composition, and functional group analyses using XRD, FESEM in combination with EDS, and FTIR. The optical characteristics in terms of cutoff wavelength were evaluated using UV-visible spectroscopy. Catalyzing the breakdown of methylene blue (MB) dye, the isolated nanocomposites demonstrated very consistent behavior when utilized as catalysts. Regarding both doped and undoped ZnO NPs, the maximum percentage of degradation was found to be 98% when exposed to solar Escherichia coli and Staphylococcus aureus, which stand for gram-positive and gram-negative bacteria, respectively, and were chosen as model strains for both groups using the disk diffusion technique in the context of in vitro antibacterial testing. Doped and undoped ZnO NPs exhibited greater antibacterial efficacy, with significant inhibition zones measuring 31.5 and 37.8 mm, compared with other metal oxide NPs.


Assuntos
Antibacterianos , Escherichia coli , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Telúrio , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Telúrio/química , Telúrio/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Catálise , Nanopartículas Metálicas/química , Escherichia coli/efeitos dos fármacos , Processos Fotoquímicos , Azul de Metileno/química , Azul de Metileno/farmacologia , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Manganês/química , Manganês/farmacologia , Estanho/química , Estanho/farmacologia , Tamanho da Partícula , Óxidos/química , Óxidos/farmacologia
9.
Luminescence ; 39(2): e4693, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38403841

RESUMO

The construction of SnO2 nanoparticles (NPs), specifically Te-doped SnO2 NPs, using a simple and economical co-precipitation technique has been thoroughly described in this work. NH3 served as the reducing agent in this procedure, whilst polyethylene glycol served as the capping agent. The primary goals of our work were to investigate the physicochemical properties of the synthesized SnO2 NPs and assess their potential use as antibacterial agents and photocatalysts. Scanning electron microscopy-energy dispersive X-ray, ultraviolet light, Fourier transform infrared spectroscopy, X-ray diffraction (XRD), and other analytical techniques were used to thoroughly analyze the NPs. Based on the full width at half maximum of the most noticeable peaks in the XRD spectrum, the Debye-Scherrer equation was used to calculate the crystallite sizes, which indicated the presence of a single tetragonal SnO2 phase. Particularly noteworthy was the exceptional photocatalytic activity of graphene-assisted Te-doped SnO2 NPs, achieving an impressive decomposition efficiency of up to 98% in the photo-oxidation of methylene blue. Furthermore, our investigation delved into the antibacterial attributes of the synthesized SnO2 NPs against Escherichia coli and Staphylococcus aureus, demonstrating inhibitory effects on both bacteria strains. This suggests potential applications for these NPs in various environmental and medical contexts.


Assuntos
Nanopartículas Metálicas , Azul de Metileno , Fotólise , Azul de Metileno/química , Telúrio , Nanopartículas Metálicas/química , Antibacterianos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
10.
Environ Geochem Health ; 46(5): 175, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619636

RESUMO

Alpine lakes are aquatic ecosystems that maintain and regulate water supply for the downstream streams, rivers, and other reservoirs. This study examined the water characteristics of various alpine lakes in Gilgit-Baltistan, Northern Pakistan. For this purpose, water was sampled and investigated for basic parameters, anions, and cations using the multi-parameter analyzers and atomic absorption spectrophotometer. Physicochemical parameters of alpine lakes were noted under the World Health Organization water guidelines, except for fluoride (F-) and turbidity in 4.3% and 36% of samples, respectively. Water quality index (WQI) classified samples (93%) as excellent and good quality (7%). Results showed maximum chronic daily intake values (0.14 ± 0.01 mg/kg-day) for nitrate (NO3-) and hazard quotient (0.80 ± 0.24) for F- in children via water intake from Upper Kachura and Shausar Lakes, respectively. Statistical analyses of Piper and Gibbs's plots revealed that the water quality is mainly characterized by bedrock geology.


Assuntos
Ecossistema , Qualidade da Água , Criança , Humanos , Lagos , Abastecimento de Água , Fluoretos
11.
Brief Bioinform ; 22(6)2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34058752

RESUMO

Understanding how a mutation might affect protein stability is of significant importance to protein engineering and for understanding protein evolution genetic diseases. While a number of computational tools have been developed to predict the effect of missense mutations on protein stability protein stability upon mutations, they are known to exhibit large biases imparted in part by the data used to train and evaluate them. Here, we provide a comprehensive overview of predictive tools, which has provided an evolving insight into the importance and relevance of features that can discern the effects of mutations on protein stability. A diverse selection of these freely available tools was benchmarked using a large mutation-level blind dataset of 1342 experimentally characterised mutations across 130 proteins from ThermoMutDB, a second test dataset encompassing 630 experimentally characterised mutations across 39 proteins from iStable2.0 and a third blind test dataset consisting of 268 mutations in 27 proteins from the newly published ProThermDB. The performance of the methods was further evaluated with respect to the site of mutation, type of mutant residue and by ranging the pH and temperature. Additionally, the classification performance was also evaluated by classifying the mutations as stabilizing (∆∆G ≥ 0) or destabilizing (∆∆G < 0). The results reveal that the performance of the predictors is affected by the site of mutation and the type of mutant residue. Further, the results show very low performance for pH values 6-8 and temperature higher than 65 for all predictors except iStable2.0 on the S630 dataset. To illustrate how stability and structure change upon single point mutation, we considered four stabilizing, two destabilizing and two stabilizing mutations from two proteins, namely the toxin protein and bovine liver cytochrome. Overall, the results on S268, S630 and S1342 datasets show that the performance of the integrated predictors is better than the mechanistic or individual machine learning predictors. We expect that this paper will provide useful guidance for the design and development of next-generation bioinformatic tools for predicting protein stability changes upon mutations.


Assuntos
Biologia Computacional/métodos , Mutação de Sentido Incorreto , Estabilidade Proteica , Proteínas/química , Proteínas/genética , Software , Algoritmos , Bases de Dados de Proteínas , Evolução Molecular , Aprendizado de Máquina , Modelos Moleculares , Conformação Proteica , Proteínas/metabolismo , Reprodutibilidade dos Testes , Relação Estrutura-Atividade
12.
Opt Express ; 31(8): 12789-12801, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37157432

RESUMO

Metalenses of adjustable power and ultrathin flat zoom lens system have emerged as a promising and key photonic device for integrated optics and advanced reconfigurable optical systems. Nevertheless, realizing an active metasurface retaining lensing functionality in the visible frequency regime has not been fully explored to design reconfigurable optical devices. Here, we present a focal tunable metalens and intensity tunable metalens in the visible frequency regime through the control of the hydrophilic and hydrophobic behavior of freestanding thermoresponsive hydrogel. The metasurface is comprised of plasmonic resonators embedded on the top of hydrogel which serves as dynamically reconfigurable metalens. It is shown that the focal length can be continuously tuned by adjusting the phase transition of hydrogel, the results reveal that the device is diffraction limited in different states of hydrogel. In addition, the versatility of hydrogel-based metasurfaces is further explored to design intensity tunable metalens, that can dynamically tailor the transmission intensity and confined it into the same focal spot under different states, i.e., swollen and collapsed. It is anticipated that the non-toxicity and biocompatibility make the hydrogel-based active metasurfaces suitable for active plasmonic devices with ubiquitous roles in biomedical imaging, sensing, and encryption systems.

13.
Genomics ; 114(5): 110451, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35988654

RESUMO

Japanese apricot is an imperative stone fruit plant with numerous processing importance. The failure of reproductive system is the most common cause of fruit loss, through which pistil abortion is the fundamental one. To understand this mechanism, we used a combination of transcriptomic and metabolomic approaches to investigate the biochemical and molecular basis of flavonoid biosynthesis. Due to the regulated expression of flavonoid pathway-related genes in plants, flavonoid biosynthesis is largely regulated at the transcriptional level. A total of 2272 differently expressed genes and 215 differential metabolites were found. The expression of the genes and metabolites encoding flavonoid biosynthesis was lower in abnormal pistils that are in line with the flavonoid quantification from abnormal pistils. Besides, a couple of genes were also detected related to MYB, MADS, NAC and bHLH transcription factors. Remarkably, we found 'hydroxycinnamoyl transferase (LOC103323133)' and flavonoid related metabolite '2-hydroxycinnamic acid' was lower expressed in abnormal pistil, proposing the cause of pistil abortion. Collectively, the present study delivers inclusive transcriptional and metabolic datasets that proposed valuable prospects to unravel the genetic mechanism underlying pistil abortion.


Assuntos
Prunus armeniaca , Transcriptoma , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Ácidos Cumáricos/metabolismo , Flavonoides , Flores/metabolismo , Frutas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Prunus armeniaca/genética , Prunus armeniaca/metabolismo , Transferases/genética , Transferases/metabolismo
14.
Saudi Pharm J ; 31(11): 101823, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37965293

RESUMO

Thymidine phosphorylase (TP) is an angiogenic enzyme. It is crucial for the development, invasion and metastasis of tumors as well as angiogenesis. In our current research, we examine how structurally changing bis-thiadiazole bearing bis-schiff bases affects their ability to inhibit TP. Through the oxidative cyclization of pyridine-based bis-thiosemicarbazone with iodine, a series of fourteen analogs of bis-thiadiazole-based bis-imines with pyridine moiety were developed. Newly synthesized scaffolds were assessed in vitro for their thymidine phosphorylase inhibitory potential and showed moderate to good inhibition profile. Eleven scaffolds such as 4a-4d,4f-4 h and 4j-4 m were discovered to be more effective than standard drug at inhibiting the thymidine phosphorylase enzyme with IC50 values of 1.16 ± 1.20, 1.77 ± 1.10, 2.48 ± 1.30, 12.54 ± 1.60, 14.63 ± 1.70, 15.53 ± 1.80, 17.47 ± 1.70, 18.98 ± 1.70, 19.53 ± 1.50, 22.73 ± 2.40 and 24.87 ± 2.80 respectively, while remaining three analogs such as 4n, 4i and 4ewere found to be more potent, but they were less potent than the standard drug. All analogs underwent SAR studies based on the pattern of substitutions around the aryl part of the bis-thiadiazole skeleton. The most active analogs in the synthesized series were then molecular docking study performed to investigate their interactions of active part of enzyme. The results showed that remarkable interactions were exhibited by these analogs with the targeted enzymes active sites. Furthermore, to confirm the structure of synthesized analogs by employing spectroscopic tools such as HREI-MS and NMR.

15.
Small ; 18(8): e2105585, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34889027

RESUMO

Emerging nonvolatile resistive switching, also known as the memristor, works with a distinct concept that relies mainly on the change in the composition of the active materials, rather than to store the charge. Particularly for oxide-based memristors, the switching is often governed by the random and unpredicted temporal/spatial migration of oxygen defects, resulting in possessing limitations in terms of control over conduction channel formation and inability to regulate hysteresis loop opening. Therefore, site specific dynamic control of defect concentration in the active materials can offer a unique opportunity to realize on-demand regulation of memory storage and artificial intelligence capabilities. Here, high-performance, site-specific spatially scalable memristor devices are fabricated by stabilizing the conduction channel via manipulation of oxygen defects using electron-beam irradiation. Specifically, the memristors exhibit highly stable and electron-beam dose-regulated multilevel analog hysteresis loop opening with adjustable switching ratios even higher than 104 . Additionally, broad modulation of neural activities, including short- and long-term plasticity, paired-pulse facilitation, spike-timing-dependent plasticity, and dynamic multipattern memory processing, are demonstrated. The work opens a new possibility to regulate the resistive switching behavior and control mimicking of neural activities, providing a hitherto unseen tunability in two-terminal oxide-based memristors.


Assuntos
Inteligência Artificial , Sinapses , Elétrons , Redes Neurais de Computação
16.
Bioorg Med Chem Lett ; 57: 128520, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34965467

RESUMO

The sulfonamide-based thiadiazole derivatives (STDs) with different hydrophobic/hydrophilic substitutions were synthesized to investigate their potentials in carbonic anhydrase inhibition (CAI). The CAI activity of the STDs (4a-4h) and the mechanism of the inhibition kinetics were determined. STD 4f contained both methoxy and Cl groups at benzene ring in STD 4f showed the lowest IC50 value. The molecular docking study confirmed that STDs bind strongly with the active sites of the target protein PDBID 1V9E. With the help of Lineweaver-Burk plots, inhibition kinetics of PDBIR 1V9E protein with STDs were determined. Cytotoxicity was checked against human keratinocyte cell lines and the anticancer properties were determined against MCF-7 cell lines. The electrochemical method was used to investigate the binding study with DNA and CA enzymes. Anticancer studies showed that STDs have weak bonding ability to DNA and strong binding ability with CA. It is concluded that anticancer activity is through CAI rather than by DNA binding.


Assuntos
Antineoplásicos/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Sulfonamidas/farmacologia , Tiadiazóis/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Biocatálise , Anidrase Carbônica II/química , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/metabolismo , Domínio Catalítico , Bovinos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Ligação Proteica , Sulfonamidas/síntese química , Sulfonamidas/metabolismo , Tiadiazóis/síntese química , Tiadiazóis/metabolismo
17.
J Chem Inf Model ; 62(17): 4270-4282, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-35973091

RESUMO

An essential step in engineering proteins and understanding disease-causing missense mutations is to accurately model protein stability changes when such mutations occur. Here, we developed a new sequence-based predictor for the protein stability (PROST) change (Gibb's free energy change, ΔΔG) upon a single-point missense mutation. PROST extracts multiple descriptors from the most promising sequence-based predictors, such as BoostDDG, SAAFEC-SEQ, and DDGun. RPOST also extracts descriptors from iFeature and AlphaFold2. The extracted descriptors include sequence-based features, physicochemical properties, evolutionary information, evolutionary-based physicochemical properties, and predicted structural features. The PROST predictor is a weighted average ensemble model based on extreme gradient boosting (XGBoost) decision trees and an extra-trees regressor; PROST is trained on both direct and hypothetical reverse mutations using the S5294 (S2647 direct mutations + S2647 inverse mutations). The parameters for the PROST model are optimized using grid searching with 5-fold cross-validation, and feature importance analysis unveils the most relevant features. The performance of PROST is evaluated in a blinded manner, employing nine distinct data sets and existing state-of-the-art sequence-based and structure-based predictors. This method consistently performs well on frataxin, S217, S349, Ssym, S669, Myoglobin, and CAGI5 data sets in blind tests and similarly to the state-of-the-art predictors for p53 and S276 data sets. When the performance of PROST is compared with the latest predictors such as BoostDDG, SAAFEC-SEQ, ACDC-NN-seq, and DDGun, PROST dominates these predictors. A case study of mutation scanning of the frataxin protein for nine wild-type residues demonstrates the utility of PROST. Taken together, these findings indicate that PROST is a well-suited predictor when no protein structural information is available. The source code of PROST, data sets, examples, and pretrained models along with how to use PROST are available at https://github.com/ShahidIqb/PROST and https://prost.erc.monash.edu/seq.


Assuntos
Mutação de Sentido Incorreto , Transferência Intratubária do Zigoto , Estabilidade Proteica , Proteínas/química , Software
18.
Fam Process ; 61(1): 326-341, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33937988

RESUMO

Couple relationship standards (beliefs about what makes for a satisfying couple relationship) have not included standards held about religion, which is surprising given how important religion is in many parts of the world. In the current study, we developed the Importance of Religion in Couple Relationships Scale (IRCRS) with the aim of having a scale suitable for use across different cultural and religious groups. The IRCRS was administered to three samples: 354 Pakistani residents (178 females, 176 males) who identified as Muslim; 274 Thai residents (157 females, 117 males) who identified as Buddhist; and 165 Westerners (resident in Australia or the United States, 60 males, 105 females) who identified as either not religious (n = 74) or Christian (n = 91). We developed a 13-item measure with a two level structure yielding an overall importance of religion score. The items in the IRCRS had acceptable cross-cultural structural invariance in a multi-group confirmatory factor analysis of the Pakistani Muslims, Thai Buddhists, and Westerners. Pakistani Muslims endorsed IRCRS standards most strongly, Western Christians next most strongly, Thai Buddhists next, and Westerners with no religion least strongly. There were no gender differences, and only very small differences by relationship status. The IRCRS can be used in future research to investigate the association of religious relationship standards with couple relationship satisfaction and might be a useful clinical tool to assess the importance of religion to couples.


Los estándares de las relaciones de pareja (las creencias acerca de lo que conduce a una relación de pareja satisfactoria) no han incluido los estándares relacionados con la religión, lo cual es sorprendente teniendo en cuenta cuán importante es la religión en muchas partes del mundo. En el presente estudio desarrollamos la Escala de la Importancia de la Religión en las Relaciones de Pareja (IRCRS, por sus siglas en inglés) con el objetivo de tener una escala apta para el uso en diferentes grupos religiosos y culturales. Se administró la IRCRS a tres muestras: 354 residentes pakistaníes (178 mujeres, 176 hombres) que se identificaron como musulmanes; 274 residentes tailandeses (157 mujeres, 117 hombres) que se identificaron como budistas; y 165 occidentales (residentes en Australia o en EE. UU., 60 hombres, 105 mujeres) que se identificaron como irreligiosos (n = 74) o como cristianos (n = 91). Desarrollamos una escala de 13 ítems con una estructura de dos niveles que da un puntaje de la importancia general de la religión. Los ítems de la IRCRS tuvieron una invarianza estructural intercultural aceptable en un análisis factorial confirmatorio multigrupo de los musulmanes pakistaníes, los budistas tailandeses y los occidentales. Los musulmanes pakistaníes confirmaron los estándares de la IRCRS más marcadamente, luego le siguieron los cristianos occidentales, los budistas tailandeses y finalmente los occidentales irreligiosos. No hubo diferencias de género y solo muy pequeñas diferencias según el estado civil. La IRCRS puede utilizarse en investigaciones futuras para averiguar la asociación de los estándares religiosos de las relaciones con la satisfacción con la relación de pareja, y podría ser una herramienta clínica útil para evaluar la importancia de la religión para las parejas.


Assuntos
Budismo , Islamismo , Povo Asiático , Análise Fatorial , Feminino , Humanos , Masculino , Satisfação Pessoal
19.
Molecules ; 27(19)2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36235210

RESUMO

The present work was aimed at studying the biosorption of two important heavy metals, viz. Pb and Cr, using defatted seed residue of Cucumis melo as biosorbent. As this study for the biosorption of the selected biosorbent is being carried out for the first time, optimization of the% sorption was carried out with the help of Taguchi method. Three most influential experimental factors were taken into account for this purpose, including the amount of sorbent, amount of sorbate and shaking time. For Pb, maximum% sorption was found to be 94.1%, using 2 g of sorbent and 5 ppm of sorbate after 2 h of shaking. Similarly, for Cr, maximum% sorption was 92.5% using 2 g of sorbent, 10 ppm of sorbate and 3 h of shaking. For Pb, the highest% contribution, which was determined by ANOVA, was given by the amount of sorbate (54.7%) followed by the amount of sorbent (38.8%) and the least contribution was given by the shaking time (6.47%). Similarly, for Cr, the highest% contribution, which was determined by ANOVA, was given by the amount of sorbate (75%) followed by the amount of sorbent (16%) and the least contribution was given by the shaking time (8.65%). Kinetic and isothermal studies were also performed to understand the nature of adsorption mechanism. For this purpose, linear and non-linear forms of three sorption isotherms were employed including Freundlich, Langmuir and Dubnin-Radushkevich isotherm. From these observations, it can be concluded that the defatted seed residue of Cucumis melo can be regarded as a novel, renewable, green and cost-effective biosorbent for removal of heavy metals from wastewater.


Assuntos
Cucumis melo , Metais Pesados , Poluentes Químicos da Água , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Chumbo , Metais Pesados/análise , Sementes/química , Águas Residuárias , Poluentes Químicos da Água/análise
20.
Molecules ; 27(14)2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35889240

RESUMO

Suaeda fruticosa Forssk. Ex J.F.Gmel is traditionally used for inflammatory and digestive disorders, as a carminative, and for diarrhea. This plant is widely distributed in Asia, Africa, and the Mediterranean region. Aqueous methanolic extract of S. fruticosa (Sf.Cr) was prepared and screened for phytoconstituents through qualitative and GC-MS analysis. Quantification of total phenolic and flavonoid contents was performed, while antioxidant capacity was determined by DPPH, CUPRAC, FRAP, and ABTS assays. The gastroprotective activity was assessed in an ethanol-induced ulcer model. Gastric secretory parameters and macroscopic ulcerated lesions were analyzed and scored for ulcer severity. After scoring, histopathology was performed, and gastric mucus contents were determined. Oral pre-treatment of Sf.Cr demonstrated significant gastroprotection. The gastric ulcer severity score and ulcer index were reduced while the %-inhibition of ulcer was increased dose-dependently. The Sf.Cr significantly elevated the pH of gastric juice, while a decrease in total acidity and gastric juice volume was observed. Histopathology demonstrated less oedema and neutrophil infiltration in gastric mucosa of rats pre-treated with the Sf.Cr in comparison to ethanol-intoxicated animals. Furthermore, the gastric mucus contents were increased as determined by alcian blue binding. Sf.Cr showed marked gastroprotective activity, which can be attributed to antioxidant, antisecretory, and cytoprotective effects.


Assuntos
Antiulcerosos , Chenopodiaceae , Úlcera Gástrica , Animais , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Antioxidantes/metabolismo , Etanol/metabolismo , Mucosa Gástrica , Extratos Vegetais/química , Folhas de Planta/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Úlcera/tratamento farmacológico
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