Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 537
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 175(2): 347-359.e14, 2018 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-30290141

RESUMO

We analyze whole-genome sequencing data from 141,431 Chinese women generated for non-invasive prenatal testing (NIPT). We use these data to characterize the population genetic structure and to investigate genetic associations with maternal and infectious traits. We show that the present day distribution of alleles is a function of both ancient migration and very recent population movements. We reveal novel phenotype-genotype associations, including several replicated associations with height and BMI, an association between maternal age and EMB, and between twin pregnancy and NRG1. Finally, we identify a unique pattern of circulating viral DNA in plasma with high prevalence of hepatitis B and other clinically relevant maternal infections. A GWAS for viral infections identifies an exceptionally strong association between integrated herpesvirus 6 and MOV10L1, which affects piwi-interacting RNA (piRNA) processing and PIWI protein function. These findings demonstrate the great value and potential of accumulating NIPT data for worldwide medical and genetic analyses.


Assuntos
Povo Asiático/genética , Diagnóstico Pré-Natal/métodos , Adulto , Alelos , China , DNA/genética , Etnicidade/genética , Feminino , Frequência do Gene/genética , Testes Genéticos , Variação Genética/genética , Genética Populacional/métodos , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Migração Humana , Humanos , Gravidez , Análise de Sequência de DNA
2.
Syst Biol ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39140829

RESUMO

African antelope diversity is a globally unique vestige of a much richer world-wide Pleistocene megafauna. Despite this, the evolutionary processes leading to the prolific radiation of African antelopes are not well understood. Here, we sequenced 145 whole genomes from both subspecies of the waterbuck (Kobus ellipsiprymnus), an African antelope believed to be in the process of speciation. We investigated genetic structure and population divergence and found evidence of a mid-Pleistocene separation on either side of the eastern Great Rift Valley, consistent with vicariance caused by a rain shadow along the so-called 'Kingdon's Line'. However, we also found pervasive evidence of both recent and widespread historical gene flow across the Rift Valley barrier. By inferring the genome-wide landscape of variation among subspecies, we found 14 genomic regions of elevated differentiation, including a locus that may be related to each subspecies' distinctive coat pigmentation pattern. We investigated these regions as candidate speciation islands. However, we observed no significant reduction in gene flow in these regions, nor any indications of selection against hybrids. Altogether, these results suggest a pattern whereby climatically driven vicariance is the most important process driving the African antelope radiation, and suggest that reproductive isolation may not set in until very late in the divergence process. This has a significant impact on taxonomic inference, as many taxa will be in a gray area of ambiguous systematic status, possibly explaining why it has been hard to achieve consensus regarding the species status of many African antelopes. Our analyses demonstrate how population genetics based on low-depth whole genome sequencing can provide new insights that can help resolve how far lineages have gone along the path to speciation.

3.
Genome Res ; 31(7): 1150-1158, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34155038

RESUMO

Protein-truncating variants (PTVs) have important impacts on phenotype diversity and disease. However, their population genetics characteristics in more globally diverse populations are not well defined. Here, we describe patterns of PTVs in 1320 genes sequenced in 10,539 healthy controls and 9434 patients with psoriasis, all of Han Chinese ancestry. We identify 8720 PTVs, of which 77% are novel, and estimate 88% of all PTVs are deleterious and subject to purifying selection. Furthermore, we show that individuals with psoriasis have a significantly higher burden of PTVs compared to controls (P = 0.02). Finally, we identified 18 PTVs in 14 genes with unusually high levels of population differentiation, consistent with the action of local adaptation. Our study provides insights into patterns and consequences of PTVs.

4.
Small ; 20(40): e2404000, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38809060

RESUMO

Multifunctional electrocatalysts for hydrogen evolution reaction (HER), hydrogen oxidation reaction (HOR), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR) have broad application prospects; However, realization of such kinds of materials remain difficulties because it requires the materials to have not only unique electronic properties, but multiple active centers to deal with different reactions. Here, employing density functional theory (DFT) computations, it is demonstrated that by decorating the Janus-type 2D transition metal dichalcogenide (TMD) of TaSSe with the single atoms, the materials can achieve multifunctionality to catalyze the ORR/OER/HER/HOR. Out of sixteen catalytic systems, Pt-VS (i.e., Pt atom embedded in the sulfur vacancy), Pd-VSe, and Pt-VSe@TaSSe are promising multifunctional catalysts with superior stability. Among them, the Pt-VS@TaSSe catalyst exhibits the highest activity with theoretical overpotentials ηORR = 0.40 V, ηOER = 0.39 V, and ηHER/HOR = 0.07 V, respectively, better than the traditional Pt (111), IrO2 (110). The interplays between the catalyst and the reaction intermediate over the course of the reaction are then systematically investigated. Generally, this study presents a viable approach for the design and development of advanced multifunctional electrocatalysts. It enriches the application of Janus, a new 2D material, in electrochemical energy storage and conversion technology.

5.
Small ; : e2403486, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-39031678

RESUMO

The development of high-performance organic photovoltaic materials is of crucial importance for the commercialization of organic solar cells (OSCs). Herein, two structurally simple donor-π-conjugated linker-acceptor (D-π-A)-configured small-molecule donors with methyl-substituted triphenylamine as D unit, 1,1-dicyanomethylene-3-indanone as A unit, and thiophene or furan as π-conjugated linker, named DTICPT and DTICPF, are developed. DTICPT and DTICPF are facilely prepared via a two-step synthetic process with simple procedures. DTICPF with a furan π-conjugated linker exhibits stronger and broader optical absorption, deeper highest occupied molecular orbital (HOMO) energy levels, and better charge transport, compared to its thiophene analog DTICPT. As a result, vacuum-deposited OSCs based on DTICPF: C70 show an impressive power conversion efficiency (PCE) of 9.36% (certified 9.15%) with short-circuit current density (Jsc) up to 17.49 mA cm-2 (certified 17.56 mA cm-2), which is the highest Jsc reported so far for vacuum-deposited OSCs. Besides, devices based on DTICPT: C70 and DTICPF: C70 exhibit excellent long-term stability under different aging conditions. This work offers important insights into the rational design of D-π-A configured small-molecule donors for high efficient and stable vacuum-deposited OSCs.

6.
Planta ; 260(1): 33, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896325

RESUMO

MAIN CONCLUSION: γ-Aminobutyric acid alleviates acid-aluminum toxicity to roots associated with enhanced antioxidant metabolism as well as accumulation and transportation of citric and malic acids. Aluminum (Al) toxicity has become the main limiting factor for crop growth and development in acidic soils and is further being aggravated worldwide due to continuous industrial pollution. The current study was designed to examine effects of GABA priming on alleviating acid-Al toxicity in terms of root growth, antioxidant defense, citrate and malate metabolisms, and extensive metabolites remodeling in roots under acidic conditions. Thirty-seven-day-old creeping bentgrass (Agrostis stolonifera) plants were used as test materials. Roots priming with or without 0.5 mM GABA for 3 days were cultivated in standard nutrient solution for 15 days as control or subjected to nutrient solution containing 5 mM AlCl3·6H2O for 15 days as acid-Al stress treatment. Roots were sampled for determinations of root characteristics, physiological and biochemical parameters, and metabolomics. GABA priming significantly alleviated acid-Al-induced root growth inhibition and oxidative damage, despite it promoted the accumulation of Al in roots. Analysis of metabolomics showed that GABA priming significantly increased accumulations of organic acids, amino acids, carbohydrates, and other metabolites in roots under acid-Al stress. In addition, GABA priming also significantly up-regulated key genes related to accumulation and transportation of malic and citric acids in roots under acid-Al stress. GABA-regulated metabolites participated in tricarboxylic acid cycle, GABA shunt, antioxidant defense system, and lipid metabolism, which played positive roles in reactive oxygen species scavenging, energy conversion, osmotic adjustment, and Al ion chelation in roots.


Assuntos
Agrostis , Alumínio , Antioxidantes , Malatos , Raízes de Plantas , Ácido gama-Aminobutírico , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Antioxidantes/metabolismo , Ácido gama-Aminobutírico/metabolismo , Alumínio/toxicidade , Agrostis/efeitos dos fármacos , Agrostis/metabolismo , Agrostis/fisiologia , Malatos/metabolismo , Ácido Cítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos
7.
Mol Ecol ; 33(2): e17205, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37971141

RESUMO

Genomic studies of species threatened by extinction are providing crucial information about evolutionary mechanisms and genetic consequences of population declines and bottlenecks. However, to understand how species avoid the extinction vortex, insights can be drawn by studying species that thrive despite past declines. Here, we studied the population genomics of the muskox (Ovibos moschatus), an Ice Age relict that was at the brink of extinction for thousands of years at the end of the Pleistocene yet appears to be thriving today. We analysed 108 whole genomes, including present-day individuals representing the current native range of both muskox subspecies, the white-faced and the barren-ground muskox (O. moschatus wardi and O. moschatus moschatus) and a ~21,000-year-old ancient individual from Siberia. We found that the muskox' demographic history was profoundly shaped by past climate changes and post-glacial re-colonizations. In particular, the white-faced muskox has the lowest genome-wide heterozygosity recorded in an ungulate. Yet, there is no evidence of inbreeding depression in native muskox populations. We hypothesize that this can be explained by the effect of long-term gradual population declines that allowed for purging of strongly deleterious mutations. This study provides insights into how species with a history of population bottlenecks, small population sizes and low genetic diversity survive against all odds.


Assuntos
Metagenômica , Resiliência Psicológica , Humanos , Animais , Recém-Nascido , Evolução Biológica , Genômica , Ruminantes/genética , Variação Genética/genética
8.
Langmuir ; 40(27): 14099-14109, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38920408

RESUMO

With the wide application of lithium-ion batteries (LIBs) in different fields, safety accidents occur frequently. Therefore, it is necessary to monitor the thermal runaway gas for an early warning. In this article, the adsorption properties of the characteristic gases of LIBs thermal runaway gases are studied by density functional theory (DFT). The adsorption structure of TM (Co/Rh/Ir)-decorated HfS2 (TM@HfS2) is established, and its adsorption properties for C2H4, CH4, and CO are studied. The adsorption energy, charge transfer, band, DOS, charge difference density, work function, and recovery time are discussed in detail. The results show that Ir@HfS2 has the strongest adsorption performance for C2H4 and CO, so C2H4 and CO can be stably adsorbed on the surface of the Ir@HfS2 monolayer. The adsorption energy of CH4 on Co@HfS2 is stronger than those of Rh@HfS2 and Ir@HfS2, but the adsorption energy is still very small. By applying biaxial strain to Co@HfS2, we found that the adsorption energy increases with the increase in negative strain. This study provides a theoretical basis for the regulation of the adsorption properties of HfS2 by different transition metals.

9.
Physiol Plant ; 176(4): e14433, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994561

RESUMO

Cadmium (Cd) is a leading environmental issue worldwide. The current study was conducted to investigate Cd tolerance of 10 commercial white clover (Trifolium repens) cultivars during seed germination and to further explore differences in lipid remodelling, glycometabolism, and the conversion of lipids into sugars contributing to Cd tolerance in the early phase of seedling establishment as well as the accumulation of Cd in seedlings and mature plants. The results show that Cd stress significantly reduced seed germination of 10 cultivars. Compared to Cd-sensitive Sulky, Cd-tolerant Pixie accelerated amylolysis to produce more glucose, fructose, and sucrose by maintaining higher amylase and sucrase activities under Cd stress. Pixie maintained higher contents of various lipids, higher DGDG/MGDG ratio, and lower unsaturation levels of lipids, which could be beneficial to membrane stability and integrity as well as signal transduction in cells after being subjected to Cd stress. In addition, Pixie upregulated expression levels of key genes (TrACX1, TrACX4, TrSDP6, and TrPCK1) involved in the conversion of lipids into sugars for early seedling establishment under Cd stress. These findings indicate that lipid remodelling, enhanced glycometabolism, and accelerated conversion of lipids into sugars are important adaptive strategies for white clover seed germination and subsequent seedling establishment under Cd stress. In addition, Pixie not only accumulated more Cd in seedlings and mature plants than Sulky but also had significantly better growth and phytoremediation efficiency under Cd stress. Pixie could be used as a suitable and critical germplasm for the rehabilitation and re-establishment of Cd-contaminated areas.


Assuntos
Cádmio , Germinação , Sementes , Trifolium , Cádmio/toxicidade , Germinação/efeitos dos fármacos , Trifolium/efeitos dos fármacos , Trifolium/metabolismo , Trifolium/genética , Trifolium/crescimento & desenvolvimento , Trifolium/fisiologia , Sementes/efeitos dos fármacos , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Açúcares/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos
10.
Fish Shellfish Immunol ; 153: 109822, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39117128

RESUMO

T-cell/transmembrane immunoglobulin and mucin domain-containing (TIM) protein family has attracted particular attention because of their broad immune functions and the response to viral infections. TIM-1, a member of the TIM family, has been demonstrated to play an important role in viral infections. However, its roles during fish nodavirus infection still remained largely unknown. In this study, a homolog of TIM-1 from orange-spotted grouper (Epinephelus coioides) (EcTIM-1) was identified, and characterized. EcTIM-1 encoded a 217-amino acids protein, containing one Immunoglobulin domain. Homology analysis showed that EcTIM-1 shared 98.62 % and 42.99 % identity to giant grouper (E. lanceolatus) and human (Homo sapiens). Quantitative Real-time PCR analyses indicated that EcTIM-1 was expressed in all examined tissues, with higher expression in liver, spleen, skin, and heart, and was significantly up-regulated in response to red-spotted grouper nervous necrosis virus (RGNNV) infection. EcTIM-1 was distributed in the cytoplasm, and partly co-localized with Golgi apparatus and lysosomes in vitro. The ectopic expression of EcTIM-1 promoted RGNNV replication by increasing the level of viral genes transcription and protein synthesis. Besides, overexpression of EcTIM-1 decreased the luciferase activity of type I interferon (IFN1), interferon stimulated response elements (ISRE) and nuclear factor kappa-B (NF-κB) promoters, as well as the transcription of pro-inflammatory factors and interferon related genes. EcTIM-1 significantly suppressed the luciferase activity of IFN1, ISRE and NF-κB promoters evoked by Epinephelus coioides melanoma differentiation-associated gene 5 (EcMDA5), mitochondrial antiviral signaling protein (EcMAVS), stimulator of IFN genes (EcSTING) or TANK-binding kinase 1 (EcTBK1). Collectively, EcTIM-1 negatively regulated interferon and inflammatory response to promote RGNNV infection. These results provide a basis for a better understanding of the innate immune response of TIM-1 in fish.


Assuntos
Bass , Doenças dos Peixes , Proteínas de Peixes , Imunidade Inata , Nodaviridae , Filogenia , Infecções por Vírus de RNA , Animais , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/veterinária , Nodaviridae/fisiologia , Bass/imunologia , Bass/genética , Imunidade Inata/genética , Regulação da Expressão Gênica/imunologia , Inflamação/imunologia , Inflamação/veterinária , Inflamação/genética , Sequência de Aminoácidos , Perfilação da Expressão Gênica/veterinária , Alinhamento de Sequência/veterinária
11.
Phys Chem Chem Phys ; 26(3): 2082-2092, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38131401

RESUMO

Nitrogen fixation using electrochemical methods on the surface of single-atom catalysts (SACs) provides a highly feasible strategy for green and low-energy-consumption ammonia (NH3) production. Herein, using density functional theory (DFT) calculations, we explored in detail the potential of monolayer BC3N2 SACs supported with 3d transition metal (TM) atoms (TM@BC3N2) to facilitate nitrogen reduction. The results revealed that the TM@BC3N2 systems exhibited remarkable catalytic activity in the nitrogen-reduction reaction (NRR). The fine NRR activity was related to the just-right bonding/antibonding orbital interactions between the 2π* of N2 and the d orbitals of the TM ions. The nitrogen-adsorption configurations were found to have different activation mechanisms. In addition, the effects of convectively formed convex nitrogen defects (VN) on the interaction between N2 and VN-TM@BC3N2 and the NRR process of VN-TM@BC3N2 were studied, and it was found that VN could fine-tune the reaction efficiency of the eNRR because after N atom dissociation to form VN, the interaction of TM-C3 was enhanced, and the activation of nitrogen and adsorption of NH3 by the TM-active centers were weakened. The present study can be used as a motivation for further experimental and theoretical research of 2D monolayers as NRR electrocatalysts.

12.
Nutr J ; 23(1): 93, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148075

RESUMO

BACKGROUND: Cardiovascular disease (CVD) remains the foremost cause of mortality globally. Taurine, an amino acid, holds promise for cardiovascular health through mechanisms such as calcium regulation, blood pressure reduction, and antioxidant and anti-inflammatory effects. Despite these potential benefits, previous studies have yielded inconsistent results. This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the existing evidence on the quantitative effects of taurine on hemodynamic parameters and cardiac function grading, which are indicative of overall cardiovascular health and performance. METHODS: We conducted an electronic search across multiple databases, including Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, from their inception to January 2, 2024. Our analysis focused on key cardiovascular outcomes, such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) Functional Classification. Meta-regression was applied to explore dose-dependent relationships based on the total taurine dose administered during the treatment period. A subgroup analysis, stratified according to the baseline disease status of patients, was also conducted. RESULTS: The analysis included a pooled sample of 808 participants from 20 randomized controlled trials. Taurine demonstrated a significant reduction in HR (weighted mean difference [WMD] = -3.579 bpm, 95% confidence interval [CI] = -6.044 to -1.114, p = 0.004), SBP (WMD = -3.999 mm Hg, 95% CI = -7.293 to -0.706, p = 0.017), DBP (WMD: -1.435 mm Hg, 95% CI: -2.484 to -0.386, p = 0.007), NYHA (WMD: -0.403, 95% CI: -0.522 to -0.283, p < 0.001), and a significant increase in LVEF (WMD: 4.981%, 95% CI: 1.556 to 8.407, p = 0.004). Meta-regression indicated a dose-dependent reduction in HR (coefficient = -0.0150 per g, p = 0.333), SBP (coefficient = -0.0239 per g, p = 0.113), DBP (coefficient = -0.0089 per g, p = 0.110), and NYHA (coefficient = -0.0016 per g, p = 0.111), and a positive correlation with LVEF (coefficient = 0.0285 per g, p = 0.308). No significant adverse effects were observed compared to controls. In subgroup analysis, taurine significantly improved HR in heart failure patients and healthy individuals. Taurine significantly reduced SBP in healthy individuals, heart failure patients, and those with other diseases, while significantly lowered DBP in hypertensive patients It notably increased LVEF in heart failure patients and improved NYHA functional class in both heart failure patients and those with other diseases. CONCLUSIONS: Taurine showed noteworthy effects in preventing hypertension and enhancing cardiac function. Individuals prone to CVDs may find it advantageous to include taurine in their daily regimen.


Assuntos
Pressão Sanguínea , Doenças Cardiovasculares , Ensaios Clínicos Controlados Aleatórios como Assunto , Taurina , Taurina/farmacologia , Taurina/administração & dosagem , Humanos , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
13.
J Chem Phys ; 160(21)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38828804

RESUMO

Fullerene-chromophore dyads have attracted a great deal of research interest because these complexes can be potentially designed as nanoscale artificial photosynthetic centers, in which the chromophore and fullerene function as the electron donor and acceptor, respectively. The basic operation of this dyad-type artificial reaction center is photoinduced electron transfer from the donor to the acceptor. The fullerene and chromophore are usually covalently linked so that sufficient electronic coupling between these two moieties can facilitate the electron transfer. However, other deactivation pathways for the chromophore excited state, such as energy transfer to the fullerene, may reduce the quantum yield of the photoinduced electron transfer. Here, a series of C60-perylene dyads is exploited to interrogate the effect of the linkage on deactivation mechanisms of the chromophore excited state. For the C60-perylene dyads with a single or double bond bridge, we find that the decay of the singlet state of the chromophore is dominated by the electron transfer, and the corresponding time constant is determined to be 45 ps. On the other hand, for the dyad with a triple bond bridge, the singlet state of the chromophore is quickly quenched through energy transfer to fullerene, and the time constant is as short as 7.9 ps. Our finding suggests that the bond order of the bridge in the fullerene-chromophore dyads can be utilized to control the deactivation pathways of the excited state.

14.
Ergonomics ; : 1-19, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781044

RESUMO

Technological breakthroughs such as artificial intelligence and sensors make human-robot collaboration a reality. Robots with highly reliable, specialised skills gain informal status in collaborative teams, but factors such as unstructured work environments and task requirements make robot error inevitable. So how do status differences of errant robots affect the desire for contact, and do team characteristics also have an impact? This paper describes an intergroup experiment using the Experimental Vignette Method (EVM), based on the Expectation Violation Theory, 214 subjects were invited to test the following hypotheses: (1) Errant robot status has an influence on employees' desire for contact and support for robotics research through negative emotions; (2) Team interdependence is a boundary condition for the effect of errant robot status on negative emotions. This paper contributes to the literature on employee reactions to robot errors in human-robot collaboration and provides suggestions for robot status design.


Complex human-robot collaboration inevitably leads to the phenomenon of robot errors. Based on this, we used an Experimental Vignette Method and found that differences in robot status design and human-robot team design features significantly affect employees' cognitive psychology after robot errors and reduce the negative consequences.

15.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2117-2127, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38812227

RESUMO

Piperlongumine(PL), a natural alkaloid extracted from Piperis Longi Fructus, has attracted much attention in recent years because of its strong anti-tumor activity, little toxicity to normal cells, and excellent sensitizing effect combined with chemotherapy and radiotherapy, which endow PL with unique advantages as an anti-tumor drug. However, similar to other alkaloids, PL has low water solubility and poor bioavailability. To improve the application of PL in the clinical treatment of tumors, researchers have constructed various nano-drug delivery systems to increase the efficiency of PL delivery. This paper reviewed the physicochemical properties, anti-tumor mechanism, combined therapies, and nano-drug delivery systems of PL in recent years. The review aimed to provide a reference for further research on the anti-tumor effect and nano-drug delivery system of PL. Moreover, this review is expected to provide a reference for the development and application of PL in the anti-tumor therapies.


Assuntos
Dioxolanos , Neoplasias , Dioxolanos/química , Humanos , Animais , Neoplasias/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/administração & dosagem , Sistemas de Liberação de Fármacos por Nanopartículas/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Piperidonas
16.
Zhongguo Zhong Yao Za Zhi ; 49(17): 4658-4671, 2024 Sep.
Artigo em Zh | MEDLINE | ID: mdl-39307804

RESUMO

The preparation processes of iron-based organic framework(FeMOF) MIL-100(Fe) and MIL-101(Fe) with two different ligands were optimized and screened, and the optimized FeMOF was loaded with piperlongumine(PL) to enhance the biocompatibility and antitumor efficacy of PL. The MIL-100(Fe) and MIL-101(Fe) were prepared by solvent thermal method using the optimized reaction solvent. With particle size, polymer dispersity index(PDI), and yield as indexes, the optimal preparation processes of the two were obtained by using the definitive screening design(DSD) experiment and establishing a mathematical model, combined with the Derringer expectation function. After characterization, the best FeMOF was selected to load PL by solvent diffusion method, and the process of loading PL was optimized by a single factor combined with an orthogonal experiment. The CCK-8 method was used to preliminarily evaluate the biological safety of blank FeMOF and the antitumor effect of the drug-loaded nano preparations. The experimental results showed that the optimal preparation process of MIL-100(Fe) was as follows: temperature at 127.8 ℃, reaction time of 14.796 h, total solvent volume of 11.157 mL, and feed ratio of 1.365. The particle size of obtained MIL-100(Fe) nanoparticles was(108.84±2.79)nm; PDI was 0.100±0.023, and yield was 36.93%±0.79%. The optimal preparation process of MIL-101(Fe) was as follows: temperature at 128.1 ℃, reaction time of 6 h, total solvent volume of 10.005 mL, and feed ratio of 0.500. The particle size of obtained MIL-101(Fe) nanoparticles was(254.04±22.03)nm; PDI was 0.289±0.052, and yield was 44.95%±0.45%. The optimal loading process of MIL-100(Fe) loaded with PL was as follows: the feed ratio of MIL-100(Fe) to PL was 1∶2; the concentration of PL solution was 7 mg·mL~(-1), and the ratio of DMF to water was 1∶5. The drug loading capacity of obtained MIL-100(Fe)/PL nanoparticles was 68.86%±1.82%; MIL-100(Fe) was nontoxic to HepG2 cells at a dose of 0-120 µg·mL~(-1), and the half-inhibitory concentration(IC_(50)) of free PL for 24 h treatment of HepG2 cells was 1.542 µg·mL~(-1). The IC_(50) value of MIL-100(Fe)/PL was 1.092 µg·mL~(-1)(measured by PL). In this study, the optimal synthesis process of MIL-100(Fe) and MIL-101(Fe) was optimized by innovatively using the DSD to construct a mathematical model combined with the Derringer expectation function. The optimized preparation process of MIL-100(Fe) nanoparticles and the PL loading process were stable and feasible. The size and shape of MIL-100(Fe) particles were uniform, and the crystal shape was good, with a high drug loading capacity, which could significantly enhance the antitumor effect of PL. This study provides a new method for the optimization of the nano preparation process and lays a foundation for the further development and research of antitumor nano preparations of PL.


Assuntos
Antineoplásicos , Dioxolanos , Ferro , Estruturas Metalorgânicas , Humanos , Dioxolanos/química , Estruturas Metalorgânicas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Ferro/química , Linhagem Celular Tumoral , Tamanho da Partícula , Nanopartículas/química , Portadores de Fármacos/química , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos/métodos , Proliferação de Células/efeitos dos fármacos , Piperidonas
17.
Angew Chem Int Ed Engl ; : e202413582, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39422656

RESUMO

Hole transport materials (HTMs) are essential for improving the stability and efficiency of perovskite solar cells (PSCs). In this study, we have designed and synthesized a novel organic small molecule HTM, cor-(DPA)5, characterized by a bowl-shaped core with symmetric five diphenylamine groups. Compared to already-known HTMs, the bowl-shaped and relatively compact structure of cor-(DPA)5 facilitates intermolecular π-π interactions, promotes film formations, and enhances charge transport. Consequently, the cor-[DPA(2)]5 HTM exhibits high charge mobility, exceptional hydrophobicity, and a significantly elevated glass transition temperature. Superior to previously reported HTMs such as spiro-OMeTAD and cor-OMePTPA, our newly synthesized cor-(DPA)5 HTM is free from any ionic dopants. As a result, the dopant-free cor-[DPA(2)]5-based PSC demonstrates an impressive efficiency of 24.01%, and exhibits outstanding operational stability. It retains 96% after continuous exposure to 1 sun irradiation for 800 hours under MPP (maximum power point) tracking in ambient air. These findings present a structurally compact novel HTM and exemplify a new approach to the molecular design of HTM for the development of stable and effective PSCs.

18.
J Cell Sci ; 134(24)2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34817059

RESUMO

The disruption of endosomal actin architecture negatively affects endocytic recycling. However, the underlying homeostatic mechanisms that regulate actin organization during recycling remain unclear. In this study, we identified a synergistic endosomal actin assembly restricting mechanism in C. elegans involving WTS-1, the homolog of LATS kinases, which is a core component of the Hippo pathway. WTS-1 resides on the sorting endosomes and colocalizes with the actin polymerization regulator PTRN-1 [the homolog of the calmodulin-regulated spectrin-associated proteins (CAMSAPs)]. We observed an increase in PTRN-1-labeled structures in WTS-1-deficient cells, indicating that WTS-1 can limit the endosomal localization of PTRN-1. Accordingly, the actin overaccumulation phenotype in WTS-1-depleted cells was mitigated by the associated PTRN-1 loss. We further demonstrated that recycling defects and actin overaccumulation in WTS-1-deficient cells were reduced by the overexpression of constitutively active UNC-60A(S3A) (a cofilin protein homolog), which aligns with the role of LATS as a positive regulator of cofilin activity. Altogether, our data confirmed previous findings, and we propose an additional model, that WTS-1 acts alongside the UNC-60A-mediated actin disassembly to restrict the assembly of endosomal F-actin by curbing PTRN-1 dwelling on endosomes, preserving recycling transport.


Assuntos
Actinas , Proteínas de Caenorhabditis elegans , Proteínas Serina-Treonina Quinases , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Endossomos , Proteínas dos Microfilamentos/genética
19.
Mol Genet Genomics ; 298(4): 823-836, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37059908

RESUMO

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19.


Assuntos
COVID-19 , Ácidos Nucleicos Livres , Humanos , COVID-19/diagnóstico , Ácidos Nucleicos Livres/genética
20.
Small ; 19(12): e2206662, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36587975

RESUMO

The development of high-performance lead-free dielectric ceramic capacitors is essential in the field of advanced electronics and electrical power systems. A huge challenge, however, is how to simultaneously realize large recoverable energy density (Wrec ), ultrahigh efficiency (η), and satisfactory temperature stability to effectuate next-generation high/pulsed power capacitors applications. Here, a strategy of utilizing nanoscale polarization heterogeneous regions is demonstrated for high-performance dielectric capacitors, showing comprehensive properties of large Wrec (≈6.39 J cm-3 ) and ultrahigh η (≈94.4%) at 700 kV cm-1 accompanied by excellent thermal endurance (20-160 °C), frequency stability (5-200 Hz), cycling reliability (1-105 cycles) at 500 kV cm-1 , and superior charging-discharging performance (discharge rate t0.9 ≈ 28.4 ns, power density PD ≈161.3 MW cm-3 ). The observations reveal that constructing the polarization heterogeneous regions in a linear dielectric to form novel relaxor ferroelectrics produces favorable microstructural characters, including extremely small polar nanoregions with high dynamics and multiphase coexistence and stable local structure symmetry, which enables large breakdown strength and ultralow polarization switching hysteresis, hence synergistically contributing to high-efficient capacitive energy storage. This study thus opens up a novel strategy to design lead-free dielectrics with comprehensive high-efficient energy storage performance for advanced pulsed power capacitors applications.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA