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1.
PLoS Pathog ; 19(6): e1011482, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37379353

RESUMEN

Wall teichoic acid (WTA) is the abundant cell wall-associated glycopolymer in Gram-positive bacteria, playing crucial roles in surface proteins retention, bacterial homeostasis, and virulence. The WTA glycosylation of Listeria monocytogenes is essential for surface anchoring of virulence factors, whereas the nature and function of the noncovalent interactions between cell wall-associated proteins and WTA are less unknown. In this study, we found that galactosylated WTA (Gal-WTA) of serovar (SV) 4h L. monocytogenes plays a key role in modulating the novel glycine-tryptophan (GW) domain-containing autolysin protein LygA through direct interactions. Gal-deficient WTA of Lm XYSN (ΔgalT) showed a dramatic reduction of LygA on the cell surface. We demonstrated that LygA binds to Gal-WTA through the GW domains, and the binding affinity is associated with the number of GW motifs. Moreover, we confirmed the direct Gal-dependent binding of the GW protein Auto from the type I WTA strain, which has no interaction with rhamnosylated WTA, indicating that the complexity of both WTA and GW proteins affect the coordination patterns. Importantly, we revealed the crucial roles of LygA in facilitating bacterial homeostasis as well as crossing the intestinal and blood-brain barriers. Altogether, our findings suggest that both the glycosylation patterns of WTA and a fixed numbers of GW domains are closely associated with the retention of LygA on the cell surface, which promotes the pathogenesis of L. monocytogenes within the host.


Asunto(s)
Listeria monocytogenes , Virulencia , Membrana Celular/metabolismo , Pared Celular/metabolismo , Factores de Virulencia/metabolismo , Proteínas de la Membrana/metabolismo , Ácidos Teicoicos/metabolismo , Proteínas Bacterianas/metabolismo
2.
J Transl Med ; 22(1): 175, 2024 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-38369542

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is the leading cancer worldwide. Microbial agents have been considered to contribute to the pathogenesis of different disease. But the underlying relevance between CRC and microbiota remain unclear. METHODS: We dissected the fecal microbiome structure and genomic and transcriptomic profiles of matched tumor and normal mucosa tissues from 41 CRC patients. Of which, the relationship between CRC-associated bacterial taxa and their significantly correlated somatic mutated gene was investigated by exome sequencing technology. Differentially expressed functional genes in CRC were clustered according to their correlation with differentially abundant species, following by annotation with DAVID. The composition of immune and stromal cell types was identified by XCELL. RESULTS: We identified a set of 22 microbial gut species associated with CRC and estimate the relative abundance of KEGG ontology categories. Next, the interactions between CRC-related gut microbes and clinical phenotypes were evaluated. 4 significantly mutated gene: TP53, APC, KRAS, SMAD4 were pointed out and the associations with cancer related microbes were identified. Among them, Fusobacterium nucleatum positively corelated with different host metabolic pathways. Finally, we revealed that Fusobacterium nucleatum modified the tumor immune environment by TNFSF9 gene expression. CONCLUSION: Collectively, our multi-omics data could help identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC.


Asunto(s)
Neoplasias Colorrectales , Microbioma Gastrointestinal , Microbiota , Humanos , Microbioma Gastrointestinal/genética , Transcriptoma/genética , Neoplasias Colorrectales/diagnóstico , Multiómica
3.
Physiol Plant ; 176(2): e14280, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38644527

RESUMEN

Inadequate reference databases in RNA-seq analysis can hinder data utilization and interpretation. In this study, we have successfully constructed a high-quality reference transcript dataset, ZjRTD1.0, for Zoysia japonica, a widely-used turfgrass with exceptional tolerance to various abiotic stress, including low temperatures and salinity. This dataset comprises 113,089 transcripts from 57,143 genes. BUSCO analysis demonstrates exceptional completeness (92.4%) in ZjRTD1.0, with reduced proportions of fragmented (3.3%) and missing (4.3%) orthologs compared to prior datasets. ZjRTD1.0 enables more precise analyses, including transcript quantification and alternative splicing assessments using public datasets, which identified a substantial number of differentially expressed transcripts (DETs) and differential alternative splicing (DAS) events, leading to several novel findings on Z. japonica's responses to abiotic stresses. First, spliceosome gene expression influenced alternative splicing significantly under abiotic stress, with a greater impact observed during low-temperature stress. Then, a significant positive correlation was found between the number of differentially expressed genes (DEGs) encoding protein kinases and the frequency of DAS events, suggesting the role of protein phosphorylation in regulating alternative splicing. Additionally, our results suggest possible involvement of serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs) in generating inclusion/exclusion isoforms under low-temperature stress. Furthermore, our investigation revealed a significantly enhanced overlap between DEGs and differentially alternatively spliced genes (DASGs) in response to low-temperature stress, suggesting a unique co-regulatory mechanism governing transcription and splicing in the context of low-temperature response. In conclusion, we have proven that ZjRTD1.0 will serve as a reliable and useful resource for future transcriptomic analyses in Z. japonica.


Asunto(s)
Empalme Alternativo , Frío , Poaceae , Empalme Alternativo/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Poaceae/genética , Estrés Fisiológico/genética , Transcriptoma/genética
4.
Environ Res ; 250: 118446, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38367842

RESUMEN

In this paper, a multi-stage A/O mud membrane composite process with segmented influent was constructed for the first time and compared with the traditional activated sludge process and the multi-stage A/O pure membrane process with segmented influent. The nitrogen removal efficiency of the process under different influencing factors was studied. Under the optimum conditions, the highest removal rate of ammonia nitrogen can reach 99%, and the average removal rate of total nitrogen was 80%. The removal rate of COD in effluent reached 93%. The relative abundance of Proteobacteria was the highest in the multi-stage A/O mud membrane composite reactor with segmented influent. The community diversity and richness of activated sludge and biofilm in aerobic pool were the highest. Dechloromonas, Flavobacterium and Rhodobacter were dominant bacteria, and they were aerobic denitrifying bacteria that significantly contributed to the removal rate of ammonia nitrogen.


Asunto(s)
Reactores Biológicos , Nitrógeno , Nitrógeno/metabolismo , Reactores Biológicos/microbiología , Eliminación de Residuos Líquidos/métodos , Membranas Artificiales , Bacterias/metabolismo , Aguas del Alcantarillado/microbiología , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo
5.
J Neurosci ; 42(14): 3049-3064, 2022 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-35197318

RESUMEN

Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA-ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the excitability of BLA-vHPC glutamatergic projections, providing a potential target for anxiolytic therapies.SIGNIFICANCE STATEMENT Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. Here, we examined the behaviors of loss- and gain-of-function of Slack channel mice in elevated plus maze and open field tests and found the anxiolytic role of the Slack channel. By altering the Slack channel expression in the specific neuronal circuit, we demonstrated that the Slack channel played its anxiolytic role by decreasing the excitability of BLA-vHPC glutamatergic projections. Our data reveal the role of the Slack channel in the regulation of anxiety, which may provide a potential molecular target for anxiolytic therapies.


Asunto(s)
Ansiedad , Complejo Nuclear Basolateral , Proteínas del Tejido Nervioso , Canales de potasio activados por Sodio , Animales , Ansiedad/metabolismo , Complejo Nuclear Basolateral/metabolismo , Hipocampo/metabolismo , Masculino , Ratones , Ratones Noqueados , Proteínas del Tejido Nervioso/metabolismo , Canales de potasio activados por Sodio/metabolismo
6.
Environ Res ; 235: 116594, 2023 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-37467940

RESUMEN

As a biological promising wastewater treatment technology, aerobic granular sludge (AGS) technology had been widely studied in sequencing batch reactors (SBRs) for the decades. Presently, the whole processes of its granulation, long-term operation, storage, and reactivation have not been thoroughly evaluated, and also the relationships among microbial diversity, granular size, and characteristics were still not that clear. Hence, they were systematically evaluated in an AGS-SBR in this work. The results demonstrated that Proteobacteria and Bacteroidetes were the dominant phyla, Flavobacterium, Acinetobacter, Azoarcus, and Chryseobacterium were the core genera with discrepant abundances in diverse stages or granular size. Microbial immigration was significant in various stages due to microbial diversity had a line relationship with COD/MLVSS ratio (R2 = 0.367). However, microbial diversity had no line relationship with granular size (R2 = 0.001), indicating the microbial diversity in different-sized AGS was similar, although granular size had a line relationship with settleability (R2 = 0.978). Overall, compared to sludge traits (e.g., sludge size, settleability), COD/MLVSS played a key role on microbial evolution. This study revealed the relationships between granule characteristics and microbial community, and contributed to the future AGS-related studies.


Asunto(s)
Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Aguas del Alcantarillado/microbiología , Eliminación de Residuos Líquidos/métodos , Reactores Biológicos/microbiología , Aerobiosis , Aguas Residuales , Nitrógeno
7.
Environ Res ; 216(Pt 2): 114591, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36272586

RESUMEN

Coal pyrolysis wastewater (CPW) contained all kinds of toxic and harmful components, which would seriously threaten the natural environment and human health. However, the traditional advanced oxidation processes frequently failed to remove phenolic substances. An A2BO4-type perovskite (La2CuO4) was successfully synthesized through sol-gel process and first applied in the treatment of CPW. More than 90% of 3, 5-dimethylphenol (DMP) was removed within 200 min at neutral conditions. Moreover, La2CuO4 also displayed excellent catalytic activity and stability in the actual CPW treatment process. Results demonstrated that DMP was removed through the attack of ∙OH, ∙O2- and 1O2 in La2CuO4/H2O2 system. The La2CuO4 were more favorable for H2O2 activation and have a lower adsorption energy than LaFeO3. XPS of fresh and spent La2CuO4 illustrated that the decomposition of hydrogen peroxide (H2O2) was mainly due to the redox cycle between surface copper and oxygen species. Moreover, the possible degradation pathway of DMP was deduced by identifying degradation products and analyzing density functional theory (DFT) calculations. This research provided a novel strategy for the development of perovskite-based catalytic materials on the treatment of practical CPW.


Asunto(s)
Peróxido de Hidrógeno , Aguas Residuales , Humanos , Carbón Mineral/análisis , Cobre , Pirólisis , Óxidos , Oxidación-Reducción
8.
Sensors (Basel) ; 23(2)2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36679799

RESUMEN

Superpixel decomposition could reconstruct an image through meaningful fragments to extract regional features, thus boosting the performance of advanced computer vision tasks. To further optimize the computational efficiency as well as segmentation quality, a novel framework is proposed to generate superpixels from the perspective of hybridizing two existing linear clustering frameworks. Instead of conventional grid sampling seeds for region clustering, a fast convergence strategy is first introduced to center the final superpixel clusters, which is based on an accelerated convergence strategy. Superpixels are then generated from a center-fixed online average clustering, which adopts region growing to label all pixels in an efficient one-pass manner. The experiments verify that the integration of this two-step implementation could generate a synergistic effect and that it becomes more well-rounded than each single method. Compared with other state-of-the-art superpixel algorithms, the proposed framework achieves a comparable overall performance in terms of segmentation accuracy, spatial compactness and running efficiency; moreover, an application on image segmentation verifies its facilitation for traffic scene analysis.


Asunto(s)
Algoritmos , Semántica , Análisis por Conglomerados
9.
Environ Monit Assess ; 195(10): 1195, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37698675

RESUMEN

The widespread contamination of the environment by polyhalogenated carbazoles (PHCZs) has been increasingly observed during the past decade. Among numerous PHCZ congeners, 3,6-dichlorocarbazole (36-CCZ) is often among the most frequently detected at higher concentrations. Although the environmental level of the legacy pesticide p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) has been declining, it continues to be ubiquitously detected. These two compounds were found to interfere with each other during analyses using gas chromatography (GC) coupled with single- or triple-quadrupole low-resolution mass spectrometry (MS or MS/MS). The base peak in the mass spectra was that of m/z 235 for both compounds. In MS/MS with multiple reaction monitoring (MRM), the same transitions (235 → 200 and 235 → 165) were often used. Under the same GC operating conditions, the SH-I-5MS capillary column used in this work did not resolve the two compounds at baseline. Pre-treatment using cleanup column chromatography can fractionate the sample extract, with the two compounds separated in different fractions before instrumental analyses. Reversed-phase HPLC columns also work for resolving 36-CCZ and p,p'-DDT. Possible overlaps in GC retention and similarity in MS spectra might have caused data inaccuracy for 36-CCZ as well as p,p'-DDT in some studies published to date, and steps to avoid the interference should be taken into quality control protocols in future research and environmental monitoring.


Asunto(s)
DDT , Espectrometría de Masas en Tándem , Cromatografía de Gases y Espectrometría de Masas , Monitoreo del Ambiente , Carbazoles
10.
Cancer Sci ; 113(6): 1955-1967, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35363928

RESUMEN

Neutrophils are the first defenders of the innate system for injury and infection. They have gradually been recognized as important participants in tumor initiation and development due to their heterogeneity and plasticity. In the tumor microenvironment (TME), neutrophils can exert antitumor and protumor functions, depending on the surroundings. Tumor cells systemically alter intracellular amino acid (AA) metabolism and extracellular AA distribution to meet their proliferation need, leading to metabolic reprogramming and TME reshaping. However, the underlying mechanisms that determine how altered AAs affect neutrophils in TME are less-explored. Here, we identified that abundant glutamate releasing from tumor cells blunted neutrophils' cell-killing effects toward tumor cells in vitro and in vivo. Mass spectrometric detection, flow cytometry, and western blot experiments proved that increased levels of pSTAT3/RAB10/ARF4, mediated by glutamate, were accompanied with immunosuppressive phenotypes of neutrophils in TME. We also discovered that riluzole, an FDA-approved glutamate release inhibitor, significantly inhibited tumor growth by restoring neutrophils' cell-killing effects and decreasing glutamate secretion from tumor cells. These findings highlight the importance of tumor-released glutamate on neutrophil transformation in TME, providing new possible cancer treatments targeting altered glutamate metabolism.


Asunto(s)
Neoplasias , Microambiente Tumoral , Apoptosis , Ácido Glutámico , Humanos , Neoplasias/patología , Neutrófilos/metabolismo
11.
Hum Genomics ; 15(1): 30, 2021 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-34034810

RESUMEN

UDP-glucuronosyltransferases (UGTs) are the main phase II drug-metabolizing enzymes mediating the most extensive glucuronidation-binding reaction in the human body. The UGT1A family is involved in more than half of glucuronidation reactions. However, significant differences exist in the distribution of UGT1As in vivo and the expression of UGT1As among individuals, and these differences are related to the occurrence of disease and differences in metabolism. In addition to genetic polymorphisms, there is now interest in the contribution of epigenetics and noncoding RNAs (especially miRNAs) to this differential change. Epigenetics regulates UGT1As pretranscriptionally through DNA methylation and histone modification, and miRNAs are considered the key mechanism of posttranscriptional regulation of UGT1As. Both epigenetic inheritance and miRNAs are involved in the differences in sex expression and in vivo distribution of UGT1As. Moreover, epigenetic changes early in life have been shown to affect gene expression throughout life. Here, we review and summarize the current regulatory role of epigenetics in the UGT1A family and discuss the relationship among epigenetics and UGT1A-related diseases and treatment, with references for future research.


Asunto(s)
Epigénesis Genética/genética , Glucuronosiltransferasa/genética , Inactivación Metabólica/genética , Glucuronosiltransferasa/metabolismo , Humanos , MicroARNs/genética , Familia de Multigenes/genética
12.
Environ Res ; 211: 113045, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35248560

RESUMEN

The extensive use of antibiotics leads to the occurrences of antibiotic resistance genes (ARGs) in aquatic environment. As an emerging environmental pollutant, its pollution in aquatic environment has aroused widespread concern. However, the residues of antibiotics and antibiotic resistance genes in drinking water distribution system were barely reported up to now. Here, we studied the correlation and coordination between chlorine resistance mechanism and antibiotic resistance mechanism of chlorine-resistant bacteria. Antibiotics induce the resistance of chlorine-resistant bacteria (CRB) to NaClO, so that low-dose disinfectants can not inactivate CRB. We put forward a strategy to control the growth of CRB by controlling the concentration of biodegradable dissolved organic carbon (BDOC) in the front section of the water network. Moreover, We screened two strains of chlorine-resistant bacteria with different antibiotic resistance after mixed culture, the results showed that antibiotic resistance could spread horizontally among different kinds of bacteria. Then, the non-pathogenic bacteria can be used as a carrier, causing the pathogen to become resistant to antibiotic, and ultimately pose harm to human health. Generally, the antibiotic, antibiotic resistant genes, and the chlorine disinfectants added in water treatment plants will interact with bacteria in the water supply pipe network, which causes pollution to drinking water.


Asunto(s)
Desinfectantes , Agua Potable , Purificación del Agua , Antibacterianos/farmacología , Bacterias/genética , Cloro/análisis , Cloro/farmacología , Desinfectantes/farmacología , Desinfección , Farmacorresistencia Microbiana/genética , Humanos
13.
Environ Res ; 213: 113601, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35660564

RESUMEN

In this study, lignite activated coke (LAC) was used as the carrier for the first time, Fe3O4-CuO composite metal oxide was used as the main active material, and the nano-scale magnetic supported composite metal oxide Fe3O4-CuO@LAC catalyst was synthesized for the first time, which can effectively activate the active oxygen in peroxodisulfate (PS). XRD, FTIR, BET, SEM, XPS and other analysis results showed that there was particulate matter with spherical structure on the surface of the active coke, and its diffraction peaks matched well with the characteristic peaks of Fe3O4 and CuO, and it was a mesoporous structure with a specific surface area of 619.090 m2 g-1. By optimizing the experimental conditions, the results showed that more than 92% of hydroquinone can be removed under the conditions of hydroquinone concentration of 50 mg/L, pH = 5, adding 0.1 g/L catalyst and 3 mmol/L PS. EPR and quenching experiments proved that there were four reactive oxygen species in the reaction system ·OH, SO4-·, O2-· and 1O2. According to the degradation products of hydroquinone detected by LC-MS, the possible degradation path was deduced which laid a foundation for solving the problem of difficult treatment of phenol-containing wastewater in coal chemical industry.


Asunto(s)
Coque , Contaminantes Químicos del Agua , Industria Química , Carbón Mineral/análisis , Coque/análisis , Cobre , Hidroquinonas/análisis , Óxidos/análisis , Fenoles/análisis , Aguas Residuales/análisis , Contaminantes Químicos del Agua/análisis
14.
Water Sci Technol ; 85(6): 1813-1823, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35358073

RESUMEN

In this study, we investigated using the main composition of pipe deposits from water distribution networks as catalyst to activate dual-oxidant H2O2/Na2S2O8 system to produce radicals for perchloroethylene and chloramphenicol removal. According to the results, the degradation efficiency of perchloroethylene by H2O2/Na2S2O8 system was 92.05% within 8 h. Due to the slow conversion between ≡Fe3+ and ≡Fe2+, the hydroxylamine was introduced to reduce reaction time. As for the results, the degradation efficiency of chloramphenicol in the H2O2/Na2S2O8 system with hydroxylamine assistance was 73.31% within 100 min. Meanwhile, several key affecting factors and the kinetic models were investigated. The primary radicals were identified by electron paramagnetic resonance and radical scavenging tests. Eleven degradation products were confirmed by high-resolution liquid chromatography-mass spectrometry. The result of this study provided the theoretical basis for resource utilization of pipe deposits in water treatment in case of emerging contamination events.


Asunto(s)
Contaminantes Ambientales , Compuestos de Hierro , Peróxido de Hidrógeno/química , Hierro/química , Abastecimiento de Agua
15.
Sheng Li Xue Bao ; 74(3): 489-494, 2022 Jun 25.
Artículo en Zh | MEDLINE | ID: mdl-35770646

RESUMEN

High level noise can damage cochlear hair cells, auditory nerve and synaptic connections between cochlear hair cells and auditory nerve, resulting in noise-induced hearing loss (NIHL). Recent studies have shown that animal cochleae have circadian rhythm, which makes them different in sensitivity to noise throughout the day. Cochlear circadian rhythm has a certain relationship with brain-derived neurotrophic factor and glucocorticoids, which affects the degree of hearing loss after exposure to noise. In this review, we summarize the research progress of the regulation of cochlear sensitivity to noise by circadian rhythm and prospect the future research direction.


Asunto(s)
Ritmo Circadiano , Pérdida Auditiva Provocada por Ruido , Animales , Umbral Auditivo , Cóclea , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Células Ciliadas Auditivas , Ruido/efectos adversos
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(7): 792-796, 2022 Jul 15.
Artículo en Zh | MEDLINE | ID: mdl-35894195

RESUMEN

OBJECTIVES: To study the characteristics of UGT1A1 gene mutations in Dong neonates in Sanjiang County of Liuzhou and its association with the pathogenesis of hyperbilirubinemia in Dong neonates. METHODS: A prospective analysis was performed on 84 neonates who were diagnosed with unexplained hyperbilirubinemia in the Department of Neonatology, Sanjiang County People's Hospital, from January 2021 to January 2022. Sixty healthy neonates born during the same period were enrolled as the control group. Peripheral blood genomic DNA was extracted for both groups, and UGT1A1 exon 1 was amplified by PCR and sequenced. RESULTS: In the case group, 33 neonates were found to have G71R missense mutation, with a mutation rate of 39%. The case group had a significantly higher frequency of A allele than the healthy control group (21% vs 10%, P<0.05). The risk of hyperbilirubinemia in Dong neonates carrying G71R missense mutation was 2.588 times as high as that in healthy neonates carrying wild-type UGT1A1 gene (P<0.05). Hardy-Weinberg equilibrium testing showed that the UGT1A1 G71R locus was in genetic equilibrium in both groups (P>0.05). CONCLUSIONS: UGT1A1 G71R mutation is a high-frequency gene mutation type in Dong neonates in Sanjiang County, and G71R missense mutation is associated with hyperbilirubinemia in Dong neonates.


Asunto(s)
Glucuronosiltransferasa , Hiperbilirrubinemia Neonatal , Pueblo Asiatico/genética , China , Exones , Glucuronosiltransferasa/genética , Humanos , Hiperbilirrubinemia Neonatal/genética , Recién Nacido , Mutación
17.
Environ Sci Technol ; 55(22): 15400-15411, 2021 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-34738465

RESUMEN

Ubiquitous oxygen vacancies (Vo) existing in metallic compounds can activate peroxymonosulfate (PMS) for water treatment. However, under environmental conditions, especially oxygenated surroundings, the interactions between Vo and PMS as well as the organics degradation mechanism are still ambiguous. In this study, we provide a novel insight into the PMS activation mechanism over Vo-containing Fe-Co layered double hydroxide (LDH). Experimental results show that Vo/PMS is capable of selective degradation of organics via a single-electron-transfer nonradical pathway. Moreover, O2 is firstly demonstrated as the most critical trigger in this system. Mechanistic studies reveal that, with abundant electrons confined in the vacant electron orbitals of Vo, O2 is thermodynamically enabled to capture electrons from Vo to form O2•- under the imprinting effect and start the activation process. Simultaneously, Vo becomes electron-deficient and withdraws the electrons from organics to sustain the electrostatic balance and achieve organics degradation (32% for Bisphenol A without PMS). Different from conventional PMS activation, under the collaboration of kinetics and thermodynamics, PMS is endowed with the ability to donate electrons to Vo as a reductant other than an oxidant to form 1O2. In this case, 1O2 and O2•- act as the indispensable intermediate species to accelerate the circulation of O2 (as high as 14.3 mg/L) in the micro area around Vo, and promote this nano-confinement electron-recycling process with 67% improvement of Bisphenol A degradation. This study provides a brand-new perspective for the nonradical mechanism of PMS activation over Vo-containing metallic compounds in natural environments.


Asunto(s)
Oxígeno , Peróxidos , Electrones , Hidróxidos
18.
J Nanobiotechnology ; 19(1): 111, 2021 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-33874945

RESUMEN

BACKGROUND: Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of amphiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy. RESULTS: The multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized (< 20 nm) nanoparticles, promoting deep penetration and distribution in tumor tissues. Furthermore, MPNs exhibited not only an excellent stable nanostructure for antitumor doxorubicin (DOX) loading, but rapid dissociation of the nanostructure under an intracellular reductive environment. With the capacity of long blood circulation, deep tumor penetration and fast intracellular drug release, the DOX-loaded multi-pocket nanoparticles demonstrated superior antitumor activities against large 4T1 tumor (~ 250 mm3) bearing mice with reduced side effect. CONCLUSIONS: Our facile fabrication of multi-pocket nanoparticles provided a promising way in improving solid tumor penetration and achieving a great therapeutic efficacy.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Nanopartículas/química , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Ácido Tióctico/química , Ácido Tióctico/farmacocinética , Animales , Doxorrubicina/química , Doxorrubicina/farmacología , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Femenino , Ratones , Ratones Endogámicos BALB C , Nanoestructuras , Tamaño de la Partícula , Polietilenglicoles/química , Polietilenglicoles/farmacología , Solubilidad
19.
J Appl Toxicol ; 41(7): 1063-1075, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33094525

RESUMEN

Aminoglycoside antibiotics are widely used for many life-threatening infections. The use of aminoglycosides is often comprised by their deleterious side effects to the kidney and inner ear. A novel semisynthetic antibiotic, etimicin, has good antimicrobial activity against both gram-positive and gram-negative bacteria. But its toxicity profile analysis is still lacking. In the present study, we compared the in vivo toxic effects of three aminoglycosides, gentamicin, amikacin, and etimicin, in zebrafish embryos. We examined the embryotoxicity, nephrotoxicity, and the damage to the neuromast hair cells. Our results revealed that etimicin and amikacin exhibit more developmental toxicities to the young embryos than gentamicin. But at subtoxic doses, etimicin and amikacin show significantly reduced toxicities towards kidney and neuromast hair cells. We further demonstrated that fluorescently conjugated aminoglycosides (gentamicin-Texas red [GTTR], amikacin-Texas red [AMTR], and etimicin-Texas red [ETTR]) all enter the hair cells properly. Inside the hair cells, gentamicin, not etimicin and amikacin, displays robust reactive oxygen species generation and induces apoptosis. Our data support that the different intracellular cytotoxicity underlies the different ototoxicity of the three aminoglycosides and that etimicin is a new aminoglycoside with reduced risk of nephrotoxicity and ototoxicity.


Asunto(s)
Aminoglicósidos/toxicidad , Antibacterianos/toxicidad , Aminoglicósidos/efectos adversos , Animales , Embrión no Mamífero , Gentamicinas/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Células Ciliadas Auditivas/efectos de los fármacos , Riñón/efectos de los fármacos , Ototoxicidad , Insuficiencia Renal/inducido químicamente , Xantenos , Pez Cebra
20.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2298-2303, 2021 May.
Artículo en Zh | MEDLINE | ID: mdl-34047133

RESUMEN

Child Compound Endothelium Corneum(CCEC)has the effects in invigorating the spleen and appetizing the appetite, and dissolving the accumulation of food. The recent studies have proved that it could improve gastrointestinal motility, restore physiological gastrointestinal peristalsis, increase gastrointestinal digestive motility, and enhance appetite. This trial aimed to evaluate its clinical efficacy and safety in the treatment of children's anorexia(spleen-stomach disharmony). A total of 240 children with anorexia in line with the inclusion and exclusion criteria were selected and randomly divided into experimental group and control group, with 120 in each group. Patients in the experimental group took CCEC and Erpixing Granules simulant. Patients in the control group took Erpi-xing Granules and CCEC simulant. After 21 days of treatment, there was no statistical difference in the recovery rate of anorexia, reduced food intake, eating time, weight change, traditional Chinese medicine syndrome effect, single symptom effect, and trace element Zn recovery rate between the two groups. Based on the non-inferiority test, the experimental group was not inferior to the control group in efficacy. How-ever, the effect of CCEC in reducing appetite in children with anorexia was better than that of control drugs(P<0.05). There was no statistical difference in the incidence of adverse events and adverse reactions between the two groups during the trial. This experiment confirmed the efficacy and safety of CCEC in the treatment of children's anorexia(spleen-stomach disharmony), with a safety and re-liability in clinical application. In addition, it was a better choice for children with anorexia who were mainly manifested by reduced appetite. Meanwhile, compared with granule, chewable tablets were more convenient to take in clinic. Therefore, the efficacy and safety of CCEC for the treatment of children's anorexia(spleen-stomach disharmony) were not inferior to those of Erpixing Granules, with a safety and reliability in clnic. However, due to the small sample size of this trial, the efficacy results only show a trend. It is suggested to further carry out a large-sample-size clinical study to define the clinical advantages of CCEC.


Asunto(s)
Anorexia , Bazo , Anorexia/tratamiento farmacológico , Niño , Método Doble Ciego , Endotelio , Humanos , Reproducibilidad de los Resultados , Estómago , Resultado del Tratamiento
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