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1.
Molecules ; 29(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38731458

RESUMEN

Utilizing hydrogen as a viable substitute for fossil fuels requires the exploration of hydrogen storage materials with high capacity, high quality, and effective reversibility at room temperature. In this study, the stability and capacity for hydrogen storage in the Sc-modified C3N4 nanotube are thoroughly examined through the application of density functional theory (DFT). Our finding indicates that a strong coupling between the Sc-3d orbitals and N-2p orbitals stabilizes the Sc-modified C3N4 nanotube at a high temperature (500 K), and the high migration barrier (5.10 eV) between adjacent Sc atoms prevents the creation of metal clusters. Particularly, it has been found that each Sc-modified C3N4 nanotube is capable of adsorbing up to nine H2 molecules, and the gravimetric hydrogen storage density is calculated to be 7.29 wt%. It reveals an average adsorption energy of -0.20 eV, with an estimated average desorption temperature of 258 K. This shows that a Sc-modified C3N4 nanotube can store hydrogen at low temperatures and harness it at room temperature, which will reduce energy consumption and protect the system from high desorption temperatures. Moreover, charge donation and reverse transfer from the Sc-3d orbital to the H-1s orbital suggest the presence of the Kubas effect between the Sc-modified C3N4 nanotube and H2 molecules. We draw the conclusion that a Sc-modified C3N4 nanotube exhibits exceptional potential as a stable and efficient hydrogen storage substrate.

2.
Sci Total Environ ; 931: 172898, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38697543

RESUMEN

The production of short-chain fatty acids (SCFAs) is constrained by substrate availability and the increased fractional pressure of H2 emitted by acidogenic/fermentative bacteria during anaerobic fermentation of waste activated sludge (WAS). This study introduced a novel approach employing zero-valent iron (ZVI)-activated sulfite pretreatment combined with H2-consuming sulfate-reducing bacteria (SRB) mediation to improve SCFAs, especially acetate production from WAS fermentation. Experimental results showed that the combined ZVI-activated sulfite and incomplete-oxidative SRB (io-SRB) process achieved a peak SCFAs production of 868.11 mg COD/L, with acetate accounting for 80.55 %, which was 7.90- and 2.18-fold higher than that obtained from raw WAS fermentation, respectively. This could be firstly attributed to the SO4- and OH generated by ZVI-activated sulfite, which significantly promoted WAS decomposition, e.g., soluble proteins and carbohydrates increased 14.3- and 10.8-fold, respectively, over those in raw WAS. The biodegradation of dissolved organic matter was subsequently enhanced by the synergistic interaction and H2 transfer between anaerobic fermentation bacteria (AFB) and io-SRB. The positive and negative correlations among AFB, nitrate-reducing bacteria (NRB) and the io-SRB consortia were revealed by molecular ecological network (MEN) and Mantel test. Moreover, the expression of functional genes was also improved, for instance, in relation to acetate formation, the relative abundances of phosphate acetyltransferase and acetate kinase was 0.002 % and 0.005 % higher than that in the control test, respectively. These findings emphasized the importance of sulfate radicals-based oxidation pretreatment and the collaborative relationships of multifunctional microbes on the value-added chemicals and energy recovery from sludge fermentation.


Asunto(s)
Ácidos Grasos Volátiles , Fermentación , Aguas del Alcantarillado , Sulfitos , Eliminación de Residuos Líquidos , Aguas del Alcantarillado/microbiología , Sulfitos/metabolismo , Ácidos Grasos Volátiles/metabolismo , Eliminación de Residuos Líquidos/métodos , Sulfatos/metabolismo , Hidrógeno/metabolismo , Bacterias/metabolismo , Hierro/metabolismo
3.
Huan Jing Ke Xue ; 45(5): 3098-3106, 2024 May 08.
Artículo en Chino | MEDLINE | ID: mdl-38629570

RESUMEN

In recent years, the environmental pollution of microplastics in Poyang Lake has received increasing attention. Baisha Lake of Poyang Lake was selected as the study area, and samples of water and sediments of Baisha Lake and the microplastics therein were collected, and the polymer types of microplastics were identified as polyethylene (PE), polyester (PET), polypropylene (PP), and polystyrene (PS) using Fourier infrared spectroscopy. We also analyzed the structural composition of bacterial communities in water, in sediments, and on microplastic surfaces using 16S high-throughput sequencing. The species richness and diversity of bacteria on the microplastic surfaces were lower than those in the surrounding water and sediments. The results of NMDS analysis showed that the bacterial community structures on the microplastic surfaces differed greatly from those in the surrounding sediments and water. The bacterial community composition in water and sediment differed from that on the microplastic surfaces, and the dominant bacterial phyla on the microplastic surfaces were Proteobacteria and Bacteroidota, and their relative abundance on the microplastic surfaces was higher than that in sediment. The relative abundance of Proteobacteria was higher than that in water. The relative abundances of Bacteroidota and Actinobacteriota were significantly lower than that of water. Massilia and Pseudomonas were the dominant genera on the microplastic surfaces, and their relative abundances were significantly higher than those in the surrounding water and sediments. BugBase phenotype prediction revealed that the relative abundance of contains mobile elements, biofilm formation, potential pathogenicity, and stress tolerance phenotypes of microplastic bacterial communities were significantly higher than those of the surrounding water and sediments. The results revealed that microplastics may have contributed to the spread of harmful bacteria, including pathogenic bacteria, and increased the potential pathogenicity of bacterial communities. Additionally, microplastic surface bacterial communities had higher phenotypes of mobile gene element content. Revealing the potential harm of microplastic pollution to wetland ecology at the micro level may provide a scientific reference for maintaining the ecological stability of wetlands.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Plásticos/análisis , Lagos/química , Monitoreo del Ambiente , Agua/análisis , Bacterias/genética , Proteobacteria , China , Contaminantes Químicos del Agua/análisis , Sedimentos Geológicos/química
4.
Microorganisms ; 12(4)2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38674623

RESUMEN

The production of municipal sludge is steadily increasing in line with the production of sewage. A wealth of organic contaminants, including nutrients and energy, are present in municipal sludge. Anaerobic fermentation can be used to extract useful resources from sludge, producing hydrogen, methane, short-chain fatty acids, and, via further chain elongation, medium-chain fatty acids. By comparing the economic and use values of these retrieved resources, it is concluded that a high-value resource transformation of municipal sludge can be achieved via the production of medium-chain fatty acids using anaerobic fermentation, which is a hotspot for future research. In this study, the selection of the pretreatment method, the method of producing medium-chain fatty acids, the influence of the electron donor, and the technique used to enhance product synthesis in the anaerobic fermentation process are introduced in detail. The study outlines potential future research directions for medium-chain fatty acid production using municipal sludge. These acids could serve as a starting point for investigating other uses for municipal sludge.

5.
Chemosphere ; 355: 141823, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552798

RESUMEN

Chain elongation technology utilises microorganisms in anaerobic digestion to transform waste biomass into medium-chain fatty acids that have greater economic value. This innovative technology expands upon traditional anaerobic digestion methods, requiring abundant substrates that serve as electron donors and acceptors, and inoculating microorganisms with chain elongation functions. While this process may result in the production of by-products and elicit competitive responses, toxicity suppression of microorganisms by substrates and products remains a significant obstacle to the industrialisation of chain elongation technology. This study provides a comprehensive overview of existing research on widely employed electron donors and their synthetic reactions, competitive reactions, inoculum selection, toxicity inhibition of substrates and products, and increased chain elongation approaches. Additionally, it presents actionable recommendations for future research and development endeavours in this domain, intending to inspire and guide researchers in advancing the frontiers of chain elongation technology.


Asunto(s)
Reactores Biológicos , Ácidos Grasos , Fermentación , Biomasa
6.
Clin Transl Med ; 14(1): e1556, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38279874

RESUMEN

BACKGROUND: Human papillomavirus (HPV) integration into the host genome is an important factor in HPV(+)OPSCC carcinogenesis, in conjunction with HPV oncoproteins E6/E7. However, a well-studied investigation about virus-host interaction still needs to be completed. Our objective is to characterise HPV integration to investigate potential mechanisms of tumourigenesis independent of E6/E7 oncoproteins. MATERIALS AND METHODS: High-throughput viral integration detection was performed on 109 HPV(+)OPSCC tumours with relevant clinicopathological information. Of these tumours, 38 tumours underwent targeted gene sequencing, 29 underwent whole exome sequencing and 26 underwent RNA sequencing. RESULTS: HPV integration was detected in 94% of tumours (with a mean integration count of 337). Tumours occurring at the tonsil/oropharyngeal wall that exhibit higher PD-L1 expression demonstrated increased integration sites (p = .024). HPV exhibited a propensity for integration at genomic sites located within specific fragile sites (FRA19A) or genes associated with functional roles such as cell proliferation and differentiation (PTEN, AR), immune evasion (CD274) and glycoprotein biosynthesis process (FUT8). The viral oncogenes E2, E4, E6 and E7 tended to remain intact. HPV fragments displayed enrichment within host copy number variation (CNV) regions. However, insertions into genes related to altered homologous recombination repair were infrequent. Genes with integration had distinct expression levels. Fifty-nine genes whose expression level was affected by viral integration were identified, for example, EPHB1, which was reported to be involved in cellular protein metabolic process. CONCLUSIONS: HPV can promote oncogenesis through recurrent integration into functional host genome regions, leading to subsequent genomic aberrations and gene expression disruption. This study characterises viral integrations and virus-host interactions, enhancing our understanding of HPV-related carcinogenesis mechanisms.


Asunto(s)
Neoplasias de Cabeza y Cuello , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Virus del Papiloma Humano , Infecciones por Papillomavirus/genética , Variaciones en el Número de Copia de ADN , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Carcinogénesis/genética
7.
Huan Jing Ke Xue ; 45(1): 470-479, 2024 Jan 08.
Artículo en Chino | MEDLINE | ID: mdl-38216496

RESUMEN

Contaminants such as microplastics (MPs) and heavy metals are commonly found in soils, both of which are extremely difficult to degrade and can easily form compound contamination, altering the physicochemical properties of the soil and thus potentially changing the growth and physiological and ecological characteristics of plants. In order to study the effects of the combined contamination of soil MPs and heavy metals on soil properties and plant growth, polystyrene microplastics (PS-MPs) with a particle size of 3 µm and the heavy metal cadmium were selected in the study. The changes in the physicochemical properties of soil and their effects on lettuce (Lactuca sativa) seed germination and seedling growth were studied at various exposure concentrations of PS-MPs (0, 10, 50, 100, 200, and 400 mg·kg-1) and combined with different Cd contamination concentrations (0, 1.2, and 6.0 mg·kg-1), respectively. The results showed that soil organic matter (SOM), available phosphorus (AP), alkali-hydrolysable nitrogen (AHN), and available kalium (AK) showed significant decreases as the intensity of PS-MPs combined with Cd contamination increased. Simultaneously, PS-MPs combined with Cd contamination also significantly reduced the germination rate of lettuce seeds, but low concentrations of PS-MPs slowed down the effect of Cd (6.0 mg·kg-1) contamination on lettuce seeds, and high concentrations of PS-MPs enhanced the effect of Cd (6.0 mg·kg-1). The fresh weight, dry weight, and plant height of lettuce seedlings showed an increasing and then decreasing trend with increasing exposure to PS-MPs. Chlorophyll content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) showed a decreasing trend, whereas malondialdehyde (MDA) content showed an overall increasing trend under different Cd concentrations. The main physicochemical indicators of the soil were negatively correlated with MDA of lettuce seedlings, whereas other indicators of the seedlings were positively correlated. The combined contamination of PS-MPs and Cd could affect the germination of plant seeds and the physiological and ecological characteristics of seedlings by changing the physicochemical properties of the soil. Both exposure to single PS-MPs contaminants and the combination of PS-MPs with Cd inhibited the germination of lettuce seeds and affected the physiological activities of their seedlings, and the inhibition was significantly increased with increasing exposure. Low exposure to PS-MPs or the combination of PS-MPs with Cd contamination exhibited a promotive effect on lettuce seedling growth. High exposure to PS-MPs combined with Cd contamination exhibited significant ecological effects on lettuce seedlings, and high exposure to PS-MPs exacerbated the ecotoxicological effects of Cd contaminants on lettuce seedlings, and PS-MPs and Cd exhibited synergistic effects. The results can provide some reference for assessing the ecological effects of MPs and heavy metal pollution in soil-plant systems.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Cadmio/toxicidad , Cadmio/metabolismo , Microplásticos , Lactuca , Plásticos , Poliestirenos , Suelo , Metales Pesados/metabolismo , Plantones , Contaminantes del Suelo/análisis
8.
Nat Genet ; 56(1): 112-123, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38177344

RESUMEN

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.


Asunto(s)
Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Porcinos/genética , Animales , Humanos , Genotipo , Fenotipo , Análisis de Secuencia de ARN
9.
Mol Biol Evol ; 41(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38266195

RESUMEN

The cross-species characterization of evolutionary changes in the functional genome can facilitate the translation of genetic findings across species and the interpretation of the evolutionary basis underlying complex phenotypes. Yet, this has not been fully explored between cattle, sheep, goats, and other mammals. Here, we systematically characterized the evolutionary dynamics of DNA methylation and gene expression in 3 somatic tissues (i.e. brain, liver, and skeletal muscle) and sperm across 7 mammalian species, including 3 ruminant livestock species (cattle, sheep, and goats), humans, pigs, mice, and dogs, by generating and integrating 160 DNA methylation and transcriptomic data sets. We demonstrate dynamic changes of DNA hypomethylated regions and hypermethylated regions in tissue-type manner across cattle, sheep, and goats. Specifically, based on the phylo-epigenetic model of DNA methylome, we identified a total of 25,074 hypomethylated region extension events specific to cattle, which participated in rewiring tissue-specific regulatory network. Furthermore, by integrating genome-wide association studies of 50 cattle traits, we provided novel insights into the genetic and evolutionary basis of complex phenotypes in cattle. Overall, our study provides a valuable resource for exploring the evolutionary dynamics of the functional genome and highlights the importance of cross-species characterization of multiomics data sets for the evolutionary interpretation of complex phenotypes in cattle livestock.


Asunto(s)
Bovinos , Metilación de ADN , Cabras , Ovinos , Animales , Bovinos/genética , Perros , Humanos , Masculino , Ratones , Estudio de Asociación del Genoma Completo , Cabras/genética , Herencia Multifactorial , Ovinos/genética , Porcinos
10.
Org Lett ; 25(49): 8792-8796, 2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-38059767

RESUMEN

A heterobifunctional cross-linker with one sulfhydryl-reactive dinitroimidazole end and another amine-reactive N-hydroxysuccinimide (NHS) ester end was designed and synthesized. The two motifs of this cross-linker, dinitroimidazole and NHS ester, proved to react with thiol and amine, respectively, in an orthogonal way. The cross-linker was further applied to construct stapled peptides of different sizes and mono- and dual functionalization (including biotinylation, PEGylation, and fluorescence labeling) of protein.


Asunto(s)
Cisteína , Lisina , Nitroimidazoles , Péptidos , Aminas , Reactivos de Enlaces Cruzados , Imidazoles/química , Péptidos/química , Proteínas , Compuestos de Sulfhidrilo , Nitroimidazoles/química
11.
Oral Dis ; 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37846172

RESUMEN

OBJECTIVES: Antiangiogenic inhibitors have been shown to synergize with immune checkpoint blockade, but the underlying mechanisms of the synergistic response are not fully understood. PATIENTS AND METHODS: We investigate the impact of VEGFR2 inhibition on tumor-infiltrating immune cells in vivo and the activity of the combination of apatinib and anti-PD-1 in synergistic mouse model of HNSCC. A patient with squamous cell carcinoma of the left tongue with cervical lymph node were received with combined induction treatment of camrelizumab and apatinib to validate the efficacy of neoadjuvant immunotherapy before surgery. RESULTS: We found that apatinib increased the infiltration of CD8+ T cells and decreased the population of Tregs in a preclinical syngeneic mouse model. The proportions of CD8+ PD1+ T cells were significantly increased in apatinib-treated tumors. The combined treatment of apatinib and anti-PD-1 demonstrated better therapeutic benefit than each treatment alone. The patient with squamous cell carcinoma of the left tongue with cervical lymph node achieved major pathologic response (MPR) after two cycles of combined induction treatment. CONCLUSION: Our study demonstrated that apatinib therapy synergized with an anti-PD-1 antibody in preclinical cancer models and in patient with advanced HNSCC. These results provide a new rationale for advancing this neoadjuvant immunotherapy in large scale of clinical trials of HNSCC.

12.
Cell Genom ; 3(10): 100385, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37868035

RESUMEN

Many quantitative trait loci (QTLs) are in non-coding regions. Therefore, QTLs are assumed to affect gene regulation. Gene expression and RNA splicing are primary steps of transcription, so DNA variants changing gene expression (eVariants) or RNA splicing (sVariants) are expected to significantly affect phenotypes. We quantify the contribution of eVariants and sVariants detected from 16 tissues (n = 4,725) to 37 traits of ∼120,000 cattle (average magnitude of genetic correlation between traits = 0.13). Analyzed in Bayesian mixture models, averaged across 37 traits, cis and trans eVariants and sVariants detected from 16 tissues jointly explain 69.2% (SE = 0.5%) of heritability, 44% more than expected from the same number of random variants. This 69.2% includes an average of 24% from trans e-/sVariants (14% more than expected). Averaged across 56 lipidomic traits, multi-tissue cis and trans e-/sVariants also explain 71.5% (SE = 0.3%) of heritability, demonstrating the essential role of proximal and distal regulatory variants in shaping mammalian phenotypes.

13.
Nat Commun ; 14(1): 5974, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37749093

RESUMEN

Enzymes achieve high catalytic activity with their elaborate arrangements of amino acid residues in confined optimized spaces. Nevertheless, when exposed to complicated environmental implementation scenarios, including high acidity, organic solvent and high ionic strength, enzymes exhibit low operational stability and poor activity. Here, we report a metal-organic frameworks (MOFs)-based artificial enzyme system via second coordination sphere engineering to achieve high hydrolytic activity under mild conditions. Experiments and theoretical calculations reveal that amide cleavage catalyzed by MOFs follows two distinct catalytic mechanisms, Lewis acid- and hydrogen bonding-mediated hydrolytic processes. The hydrogen bond formed in the secondary coordination sphere exhibits 11-fold higher hydrolytic activity than the Lewis acidic zinc ions. The MOFs exhibit satisfactory degradation performance of toxins and high stability under extreme working conditions, including complicated fermentation broth and high ethanol environments, and display broad substrate specificity. These findings hold great promise for designing artificial enzymes for environmental remediation.

14.
Ying Yong Sheng Tai Xue Bao ; 34(7): 1968-1974, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37694481

RESUMEN

As a new type of pollutant, microplastics accumulate continuously in the environment. The environmental problems caused by microplastics have attracted wide attention. In this study, we collected water, sediment and four types of microplastics (film, foam, fiber and fragment) from wetland in East Lake area of Poyang Lake. We used high-throughput sequencing technology to analyze the bacterial diversity and community structure of water, sediment, and microplastics surface. The results showed that the bacterial richness and diversity of water and sediment were significantly higher than that on microplastics, and the bacterial richness of foaming microplastics was significantly lower than that of the other three types of microplastics. There were significant differences of bacterial communities between water, sediment, and microplastics. There were significant differences cross different types of microplastics. Proteobacteria, Bacteroidetes, and Actinobacteria were the main bacterial communities of water, sediment, and microplastics. The relative abundance of Bacteroidetes and Actinobacteria in water was higher than that in sediments and microplastics, while the relative abundance of Bacteroidetes and Actinobacteria in foaming microplastics was higher than that in other three types. At the genus level, the dominant ones included Massilia, Flavobacteria, and Pseudomonas. The relative abundance of Massilia and Pseudomonas in water and sediments was lower than that on microplastics, and the relative abundance of Flavobacteria was not different among water, sediment and microplastics. The relative abundance of Massilia in microplastics followed an order of fragment>fiber>film>foam, and that of Pseudomonas was film>fiber>foam>fragment. The results of metabolic pathway prediction analysis showed that except for foaming microplastics, the bacterial metabolic pathways on the surface of the other three types of microplastics were significantly different from those in water and sediment. The cellular processes, organismal systems, environmental information processing, and human diseases in bacterial metabolic pathways on microplastics surface were significantly higher than those in water and sediment. Our results suggested that microbial community structure on the surface of microplastics was significantly different from that in water and sediment, and that the morphology type of microplastics affected microbial community structure on the surface.


Asunto(s)
Actinobacteria , Contaminantes Ambientales , Humanos , Microplásticos , Plásticos , Humedales
15.
Huan Jing Ke Xue ; 44(9): 5063-5070, 2023 Sep 08.
Artículo en Chino | MEDLINE | ID: mdl-37699824

RESUMEN

Plastic particles smaller than 5 mm in size are known as microplastics which are widespread in the environment and can cause several negative effects. Moreover, only a few studies have focused on the relationship between microplastics and microbes in the natural wetland ecosystem. In this study, microplastics were collected from sediment, water, and sediment flooded and non-flooded conditions in the lake wetland of Poyang Lake as the study area. The structural distribution of bacterial community on sediment, water, and microplastics were analyzed using 16S high-throughput sequencing. The results of the α-diversity analysis showed that the bacterial abundance and diversity on the surface of microplastics were significantly different from those in the environment and were lower than those in the surrounding environment in both flooded and non-flooded conditions. The results of the principal co-ordinates analysis indicated that the bacterial community on the surface of microplastics was more influenced by the sediment in non-flooded conditions and by the water in flooded conditions. The structure of the bacterial community on the microplastic surface also showed significant differences from the surrounding environment, with the sediment mainly consisting of several other bacterial genera with <1% abundance, whereas the bacterial community on the microplastics had clearly dominant species. The relative abundance of Proteobacteria on the microplastic surfaces increased significantly in the non-flooded condition compared to that in the water and sediment samples, whereas the relative abundance of Bacteroidota on the microplastic surface increased in the flooded condition. The genus Flavobacterium, Massilia, and Pseudomonas were the most abundant in the non-flooded state, and the genus Flavobacterium was the most abundant in the flooded state. In this study, Pseudomonas spp. was the focus of future research on plastic biodegradation. This study can further improve the understanding of microplastic pollution in wetland ecosystems and provide a theoretical basis for lake environmental management.


Asunto(s)
Microplásticos , Humedales , Plásticos , Ecosistema , Lagos , Biodegradación Ambiental , Pseudomonas , Agua
16.
Pak J Pharm Sci ; 36(4(Special)): 1325-1330, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37606023

RESUMEN

Assessment and prognostic value of serum uric acid (SUA) and neuron-specific enolase (NSE) on the efficacy of intravenous thrombolytic therapy in cerebral infarction. A retrospective analysis was performed on clinical data of 159 patients with acute cerebral infarction who received rt-PA intravenous thrombolytic therapy from 2015 to 2020 and patients with an mRS>2 points were assigned to the poor prognosis group and with mRS≤2 to the good prognosis group. The receiver operating characteristic curve (ROC) was used to examine the prognostic value of SUA and NSE in intravenous thrombolytic therapy for acute cerebral infarction, and logistic regression analysis was utilized to elucidate the predictive features. SUA levels were adversely correlated with prognosis, whereas NSE was positively correlated with prognosis (r=0.465 and -0.501, P=0.000 and 0.000). The ROC curve showed that the predictive accuracy of SUA was 77.4% and of NSE was 71%. SUA≤337.5 mmol/l and NSE≥24.50 ng/ml are considered viable criteria to predict the curative effect and prognostic value of intravenous thrombolytic therapy for acute cerebral infarction. SUA and NSE demonstrate great potential to accurately predict the therapeutic effect and prognosis of intravenous thrombolytic therapy for acute cerebral infarction.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Ácido Úrico , Pronóstico , Estudios Retrospectivos , Fibrinolíticos , Terapia Trombolítica , Infarto Cerebral/tratamiento farmacológico , Fosfopiruvato Hidratasa
17.
Sci Adv ; 9(27): eadg7943, 2023 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-37406110

RESUMEN

An understanding of protein conformational ensembles is essential for revealing the underlying mechanisms of interpeptide recognition and association. However, experimentally resolving multiple simultaneously existing conformational substates remains challenging. Here, we report the use of scanning tunneling microscopy (STM) to analyze the conformational substate ensembles of ß sheet peptides with a submolecular resolution (in-plane <2.6 Å). We observed ensembles of more than 10 conformational substates (with free energy fluctuations between several kBTs) in peptide homoassemblies of keratin (KRT) and amyloidal peptides (-5Aß42 and TDP-43 341-357). Furthermore, STM reveals a change in the conformational ensemble of peptide mutants, which is correlated with the macroscopic properties of peptide assemblies. Our results demonstrate that the STM-based single-molecule imaging can capture a thorough picture of the conformational substates with which to build an energetic landscape of interconformational interactions and can rapidly screen conformational ensembles, which can complement conventional characterization techniques.


Asunto(s)
Amiloide , Péptidos , Conformación Proteica en Lámina beta , Péptidos/química , Conformación Proteica , Entropía
18.
Biomolecules ; 13(7)2023 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-37509173

RESUMEN

Butyrate contributes epigenetically to the changes in cellular function and tissue development of the rumen in ruminant animals, which might be achieved by its genetic or epigenetic regulation of gene expression. To explore the role of butyrate on bovine rumen epithelial function and development, this study characterized genome-wide H3K27ac modification changes and super-enhancer profiles in rumen epithelial primary cells (REPC) induced with butyrate by ChIP-seq, and analyzed its effects on gene expression and functional pathways by integrating RNA-seq data. The results showed that genome-wide acetylation modification was observed in the REPC with 94,675 and 48,688 peaks in the butyrate treatment and control group, respectively. A total of 9750 and 5020 genes with increased modification (H3K27ac-gain) and decreased modification (H3K27ac-loss) were detected in the treatment group. The super-enhancer associated genes in the butyrate-induction group were involved in the AMPK signaling pathway, MAPK signaling pathway, and ECM-receptor interaction. Finally, the up-regulated genes (PLCG1, CLEC3B, IGSF23, OTOP3, ADTRP) with H3K27ac gain modification by butyrate were involved in cholesterol metabolism, lysosome, cell adhesion molecules, and the PI3K-Akt signaling pathway. Butyrate treatment has the role of genome-wide H3K27ac acetylation on bovine REPC, and affects the changes in gene expression. The effect of butyrate on gene expression correlates with the acetylation of the H3K27ac level. Identifying genome-wide acetylation modifications and expressed genes of butyrate in bovine REPC cells will expand the understanding of the biological role of butyrate and its acetylation.


Asunto(s)
Epigénesis Genética , Histonas , Bovinos , Animales , Histonas/metabolismo , Acetilación , Butiratos/farmacología , Butiratos/metabolismo , Rumen/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo
19.
ACS Cent Sci ; 9(7): 1480-1487, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37521785

RESUMEN

Deciphering the conformations and interactions of peptides in their assemblies offers a basis for guiding the rational design of peptide-assembled materials. Here we report the use of scanning tunneling microscopy (STM), a single-molecule imaging method with a submolecular resolution, to distinguish 18 types of coexisting conformational substates of the ß-strand of the 8-37 segment of human islet amyloid polypeptide (hIAPP 8-37). We analyzed the pairwise peptide-peptide interactions in the hIAPP 8-37 assembly and found 82 interconformation interactions within a free energy difference of 3.40 kBT. Besides hIAPP 8-37, this STM method validates the existence of multiple conformations of other ß-sheet peptide assemblies, including mutated hIAPP 8-37 and amyloid-ß 42. Overall, the results reported in this work provide single-molecule experimental insights into the conformational ensemble and interpeptide interactions in the ß-sheet peptide assembly.

20.
J Anim Sci ; 1012023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-37366074

RESUMEN

Considering that artificial insemination is the most widely used assisted reproductive technique in the dairy industry, the semen quality of bulls is very important for selecting excellent stud bulls. Sperm motility is one of the important traits of semen quality, and related genes may be regulated by environmental factors. Seminal plasma can affect sperm cell transcriptome and further affect sperm motility through exosome or other processes. However, the molecular regulation mechanism of bull sperm motility has not been studied by combining the sperm cell transcriptome with seminal plasma metabolome. The number of motile sperm per ejaculate (NMSPE) is an integrated indicator for assessing sperm motility in stud bulls. In the present study, we selected 7 bulls with higher NMSPE (5,698.55 million +/- 945.40 million) as group H and 7 bulls with lower NMSPE (2,279.76 million +/- 1,305.69 million) as group L from 53 Holstein stud bulls. The differentially expressed genes (DEGs) in sperm cells were evaluated between the two groups (H vs. L). We conducted gene co-expression network analysis (WGCNA) on H and L groups of bulls, as well as two monozygotic twin Holstein bulls with different NMSPE values, to screen candidate genes for NMSPE. The regulatory effect of seminal plasma metabolome on the candidate genes of NMSPE was also investigated. A total of 1,099 DEGs were identified in the sperm cells of H and L groups. These DEGs were primarily concentrated in energy metabolism and sperm cell transcription. The significantly enriched Kyoto encyclopedia of genes and genomes (KEGG) pathways of the 57 differential metabolites were the aminoacyl-tRNA biosynthesis pathway and vitamin B6 metabolism pathway. Our study discovered 14 genes as the potential candidate markers for sperm motility, including FBXO39. We observed a broad correlation between transcriptome of sperm cells and seminal plasma metabolome, such as three metabolites, namely, mesaconic acid, 2-coumaric acid, and 4-formylaminoantipyrine, might regulate FBXO39 expression through potential pathways. The genes related to seminal plasma metabolites expressed in sperm cells are not only located near the quantitative trait loci of reproductive traits, but also enriched in the genome-wide association study signal of sire conception rate. Collectively, this study was the first to investigate the interplays among transcriptome of sperm cells and seminal plasma metabolome from Holstein stud bulls with different sperm motility.


A Holstein stud bull can produce thousands of doses of frozen semen, which are used to distribute its selected genetics to dairy herds all over the world. The semen quality of stud bulls has an impact on the economics of the breeding centers. Our previous study found that monozygotic twin stud bulls showed different semen quality traits and different transcriptomic profiles in sperm cells. The number of motile sperm per ejaculate (NMSPE) is an integrated trait for assessing sperm motility in stud bulls, which is one of the most important semen quality traits. In the present study, we selected 7 stud bulls that had a high NMSPE (named as H group) and 7 stud bulls with low NMSPE (named as L group) from a Chinese Holstein bull population based on 9 yr of semen quality records. In this study, we investigated the sperm cells transcriptomic differences between the two groups and observed the influences of seminal plasma metabolites on the transcriptomic profiles of the sperm cells. The results showed that the expression level of the differentially expressed genes in the sperm cells is closely related to NMSPE. Our study discovered 14 genes as the potential candidate markers for sperm motility, including FBXO39. Our data provide new insights into the improvement of bovine semen quality traits.


Asunto(s)
Análisis de Semen , Semen , Masculino , Bovinos , Animales , Semen/fisiología , Análisis de Semen/veterinaria , Motilidad Espermática/fisiología , Estudio de Asociación del Genoma Completo/veterinaria , Transcriptoma , Espermatozoides/fisiología , Metaboloma
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