Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 99
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Head Neck ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135356

RESUMO

BACKGROUND: Effective biomarkers for assessing anti-PD-1/PD-L1 therapy efficacy in patients with nasopharyngeal carcinoma (NPC) are still lacking. The human gut microbiota has been shown to influence clinical response to anti-PD-1/PD-L1 therapy in many cancers. However, the relationship between the gut microbiota and the efficacy of immunotherapy in patients with nasopharyngeal carcinoma has not been determined. METHODS: We conducted a prospective study in which fecal and blood samples from patients with NPC were subjected to 16S rDNA sequencing and survival analysis. To investigate potential differences in the gut microbiome between these groups and to identify potential biomarkers indicative of immunotherapy efficacy, patients were categorized into two groups according to their clinical response to immunotherapy, the responder group (R group) and the non-responder group (NR group). Progression-free survival (PFS) between these subgroups was analyzed using Kaplan-Meier survival analysis with the log-rank test. Additionally, we performed univariate and multivariate analyses to evaluate prognostic factors. Finally, we carried out non-targeted metabolomics to examine the metabolic effects associated with the identified microbiome. RESULTS: Our 16S rDNA sequencing results showed that the abundance of Lachnoclostridium was higher in the NR group than in the R group (p = 0.003), and alpha diversity analysis showed that the abundance of microbiota in the NR group was higher than that in the R group (p = 0.050). Patients with a lower abundance of Lachnoclostridium had better PFS (p = 0.048). Univariate (p = 0.017) and multivariate analysis (p = 0.040) showed that Lachnoclostridium was a predictor of PFS. Non-targeted metabolomics analysis revealed that Lachnoclostridium affects the efficacy of immunotherapy through the usnic acid. CONCLUSIONS: High abundance of Lachnoclostridium predicts poor prognosis in patients with NPC receiving immunotherapy.

2.
J Environ Manage ; 367: 122070, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39098068

RESUMO

Fenton-conditioning is commonly used to improve dewatering ability for municipal biological sludge, however, its application in industries is scarce. In this study, biochar (FT-BC) was successfully synthesized from a Fenton-conditioned landfill leachate biological sludge under oxygen-limited. As compared to the corresponding blank and poly ferric-pretreated biochars (BC and PF-BC), moderate Fenton conditioning of the sludge could enable good removal performance for Cr (Ⅵ) by FT-BC. It was found that the oxygen central free radicals (OCFRs) on the biochar surface was intensively promoted due to Fenton electrophilic addition of ·OH onto the oxygen-containing functional groups in biomass. The amounts of OCFRs correlated positively well with the removal efficiency, indicating these persistent free radicals (PFRs)would mainly responsible for the reductive immobilization of Cr(VI)on the FT-BC surface. This study is expected to provide a new method for reclamation of industrial biological sludges with poor agglomeration by introducing simple Fenton pre-conditioning.


Assuntos
Carvão Vegetal , Esgotos , Carvão Vegetal/química , Esgotos/química , Radicais Livres/química , Cromo/química , Poluentes Químicos da Água/química , Ferro/química , Oxigênio/química , Peróxido de Hidrogênio/química
3.
Rev Sci Instrum ; 95(8)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39189876

RESUMO

Within the beamlines of diffraction-limited storage rings, the liquid-metal-bath cooling scheme is a prevalent choice for the cooling of high-heat load mirrors. This study employs the finite element analysis method to evaluate the thermal deformations of liquid-metal-bath horizontally deflecting mirrors in the Hefei Advanced Light Facility. In particular, we introduce a novel optimization strategy to obtain the optimal thermal deformation scenario, which also satisfies mechanical design requirements. Moreover, a concurrent optimization approach across multiple structural parameters of mirrors is adopted to attain globally optimal thermal deformation. Following the optimization of the mirror's structural parameters, the curvature radius increases to 227 km, while the residual slope error decreases to 36.3 nrad at 6 eV in the meridian direction. The ray tracing analysis of the beam demonstrates a considerable reduction in the influence of thermal deformation on the beam's focal point. This work proposes an optimization method for designing cooling schemes under mechanical constraints.

4.
Water Res ; 263: 122198, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39098158

RESUMO

The cycling processes of elemental manganese (Mn), including the redox reactions of dissolved Mn(III) (dMn(III)), directly and indirectly influences the biogeochemical processes of many elements. Though increasing evidence indicates the widespread presence of dMn(III) mediates the fate of many elements, its role may be currently underestimated. There is both a lack of clear understanding of the historical research framework of dMn(III) and a systematic overview of its geochemical properties and detection methods. Therefore, the primary aim of this review is to outline the understanding of dMn(III) in multiple fields, including soil science, analytical chemistry, biochemistry, geochemistry, and water treatment, and summarize the formation pathways, species forms, and detection methods of dMn(III) in aquatic systems. This review considers how the characteristics of dMn(III), the intermediate formed in the single-electron reaction processes of Mn(II) oxidation and Mn(IV) reduction, determines its participation in environmental geochemical processes. Its widespread presence in diverse water systems and active redox properties coupling with various elements confirm its significant role in natural elemental geochemistry cycle and artificial water treatment processes. Therefore, further investigation into the role of dissolved Mn(III) in aquatic systems is warranted to unravel unexplored coupled elemental redox reaction processes mediated by dissolved Mn(III), filling in the gaps in our understanding of manganese environmental geochemistry, and providing a theoretical basis for recognizing the role of dMn(III) role in water treatment technologies.


Assuntos
Manganês , Manganês/química , Oxirredução , Poluentes Químicos da Água/química , Meio Ambiente
5.
ACS Appl Mater Interfaces ; 16(31): 41321-41331, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39051622

RESUMO

The clearance of urea poses a formidable challenge, and its excessive accumulation can cause various renal diseases. Urease demonstrates remarkable efficacy in eliminating urea, but cannot be reused. This study aimed to develop a composite vector system comprising microcrystalline cellulose (MCC) immobilized with urease and metal-organic framework (MOF) UiO-66-NH2, denoted as MCC@UiO/U, through the dynamic defect generation strategy. By utilizing competitive coordination, effective immobilization of urease into MCC@UiO was achieved for efficient urea removal. Within 2 h, the urea removal efficiency could reach up to 1500 mg/g, surpassing an 80% clearance rate. Furthermore, an 80% clearance rate can also be attained in peritoneal dialyzate from patients. MCC@UiO/U also exhibits an exceptional bioactivity even after undergoing 5 cycles of perfusion, demonstrating remarkable stability and biocompatibility. This innovative approach and methodology provide a novel avenue and a wide range of immobilized enzyme vectors for clinical urea removal and treatment of kidney diseases, presenting immense potential for future clinical applications.


Assuntos
Celulose , Enzimas Imobilizadas , Estruturas Metalorgânicas , Ureia , Urease , Urease/química , Urease/metabolismo , Ureia/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Celulose/química , Estruturas Metalorgânicas/química , Humanos
6.
Environ Sci Technol ; 58(28): 12430-12440, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38968084

RESUMO

Soil organic carbon (SOC) is pivotal for both agricultural activities and climate change mitigation, and biochar stands as a promising tool for bolstering SOC and curtailing soil carbon dioxide (CO2) emissions. However, the involvement of biochar in SOC dynamics and the underlying interactions among biochar, soil microbes, iron minerals, and fresh organic matter (FOM, such as plant debris) remain largely unknown, especially in agricultural soils after long-term biochar amendment. We therefore introduced FOM to soils with and without a decade-long history of biochar amendment, performed soil microcosm incubations, and evaluated carbon and iron dynamics as well as microbial properties. Biochar amendment resulted in 2-fold SOC accrual over a decade and attenuated FOM-induced CO2 emissions by approximately 11% during a 56-day incubation through diverse pathways. Notably, biochar facilitated microbially driven iron reduction and subsequent Fenton-like reactions, potentially having enhanced microbial extracellular electron transfer and the carbon use efficiency in the long run. Throughout iron cycling processes, physical protection by minerals could contribute to both microbial carbon accumulation and plant debris preservation, alongside direct adsorption and occlusion of SOC by biochar particles. Furthermore, soil slurry experiments, with sterilization and ferrous iron stimulation controls, confirmed the role of microbes in hydroxyl radical generation and biotic carbon sequestration in biochar-amended soils. Overall, our study sheds light on the intricate biotic and abiotic mechanisms governing carbon dynamics in long-term biochar-amended upland soils.


Assuntos
Carbono , Ferro , Microbiologia do Solo , Solo , Solo/química , Ferro/química , Ferro/metabolismo , Carvão Vegetal/química , Dióxido de Carbono/metabolismo
7.
Sci Total Environ ; 946: 174528, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38971243

RESUMO

Soil aggregates are crucial for soil organic carbon (OC) accumulation. This study, utilizing a 32-year fertilization experiment, investigates whether the core microbiome can elucidate variations in carbon content and decomposition across different aggregate sizes more effectively than broader bacterial and fungal community analyses. Employing ensemble learning algorithms that integrate machine learning with network inference, we found that the core microbiome accounts for an average increase of 26 % and 20 % in the explained variance of PCoA and Adonis analyses, respectively, in response to fertilization. Compared to the control, inorganic and organic fertilizers decreased the decomposition index (DDI) by 31 % and 38 %, respectively. The fungal core microbiome predominantly influenced OC content and DDI in larger macroaggregates (>2000 µm), explaining over 35 % of the variance, while the bacterial core microbiome had a lesser impact, explaining <30 %. Conversely, in smaller aggregates (<2000 µm), the bacterial core microbiome significantly influenced DDI (R2 > 0.2), and the fungal core microbiome more strongly affected OC content (R2 > 0.3). Mantel tests showed that pH is the most significant environmental factor affecting core microbiome composition across all aggregate sizes (Mantel's r > 0.8, P < 0.01). Linear correlation analysis further confirmed that the core microbiome's community structure could accurately predict OC content and DDI in aggregates (R2 > 0.8, P < 0.05). Overall, our findings suggested that the core microbiome provides deeper insights into the variability of aggregate organic carbon content and decomposition, with the bacterial core microbiome playing a particularly pivotal role within the soil aggregates.


Assuntos
Carbono , Aprendizado de Máquina , Microbiota , Microbiologia do Solo , Solo , Carbono/metabolismo , Carbono/análise , Solo/química , Algoritmos , Fungos/metabolismo , Bactérias/metabolismo , Fertilizantes
8.
Acta Otolaryngol ; 144(4): 325-332, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39033361

RESUMO

BACKGROUND: Keratinizing squamous cell carcinoma (KSCC) is recognized as WHO I nasopharyngeal carcinoma (NPC). Current guidelines for treating nasopharyngeal cancer do not delineate specific strategies for individual pathologic subtypes. OBJECTIVES: To explore the optimal treatment for KSCC of the nasopharynx. MATERIAL AND METHODS: Data on patients were extracted from the SEER database. Survival differences between patients treated with radiotherapy alone and combined surgery were assessed using Kaplan-Meier and Cox regression models and compared using propensity score matching (PSM). In addition, we explored the survival differences between the two groups of patients in different risk stratifications. RESULTS: In our study, 165 patients underwent surgical intervention, while 1238 patients did not. In both univariate (CSS: p = .001, HR = 0.612; OS: p < .001, HR = 0.623) and multivariate (CSS: p = .004, HR = 0.655; OS: p < .001, HR = 0.655) analyses, combined surgery was identified as a significant prognostic factor. These findings were consistent after PSM. Using RPA, patients were categorized into two groups. CSS improved in the high-risk group, whereas the difference in low-risk patients was not significant. CONCLUSIONS AND SIGNIFICANCE: For patients diagnosed with WHO I nasopharyngeal carcinoma, the combination of radiotherapy and surgery has significant clinical advantages, especially for patients at high risk.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/cirurgia , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/cirurgia , Idoso , Adulto , Terapia Combinada , Estudos Retrospectivos , Programa de SEER , Estimativa de Kaplan-Meier
10.
Regen Biomater ; 11: rbae045, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38845854

RESUMO

Selective removal of ultra-high low-density lipoprotein (LDL) from the blood of hyperlipemia patients using hemoperfusion is considered an efficient method to prevent the deterioration of atherosclerotic cardiovascular disease. Based on the exceptional structure-function properties of multistimulus-responsive materials, we developed a magnetic photorenewable nanoadsorbent (Fe3O4@SiO2@Azo-COOH) with outstanding selectivity and regenerative characteristics, featuring functionalized azobenzene as the ligand. The dual-stimulus response endowed Fe3O4@SiO2@Azo-COOH with rapid separation and photoregenerative properties. The adsorbent demonstrated excellent removal efficiency of LDL with an adsorption capacity of 15.06 mg/g, and highly repetitive adsorption performance (≥5 cycles) under irradiation. Fe3O4@SiO2@Azo-COOH also exhibited remarkable adsorption properties and selectivity in human serum, with adsorption capacities of 10.93, 21.26 and 9.80 mg/g for LDL, total cholesterol and triglycerides and only 0.77 mg/g for high-density lipoprotein (HDL), resulting in a 93% selective adsorption difference (LDL/HDL). Complete green regeneration of the nanoadsorbent was achieved through a simple regeneration process, maintaining a recovery rate of 99.4% after five regeneration experiments. By combining dynamic perfusion experiment with micromagnetic microfluidics, the LDL content decreased by 16.6%. Due to its superior adsorption capacity and regenerative properties, the dual stimulus-responsive nanosorbent is considered a potential hemoperfusion adsorbent.

11.
J Nanobiotechnology ; 22(1): 231, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720360

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation. METHODS: To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis. CONCLUSIONS: This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis.


Assuntos
Biomarcadores Tumorais , Membrana Celular , Separação Celular , Nanopartículas de Magnetita , Células Neoplásicas Circulantes , Células Neoplásicas Circulantes/patologia , Células Neoplásicas Circulantes/metabolismo , Humanos , Nanopartículas de Magnetita/química , Separação Celular/métodos , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Membrana Celular/química , Biomarcadores Tumorais/sangue , Receptor ErbB-2 , Molécula de Adesão da Célula Epitelial/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Neoplasias
12.
Small Methods ; : e2400159, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697928

RESUMO

Regular blood glucose monitoring and control is necessary for people with type 1 or advanced type 2 diabetes, yet diagnosing and treating patients with diabetes in an accurate, sustained and patient-friendly manner remains limited. Here, a glucose-responsive bifunctional nanosystem (PGOxMns) is constructed via one-pot biomineralisation of manganese dioxide with glucose oxidase and ε-poly-L-lysine. Under hyperglycaemic conditions, the cascade reactions that occur when glucose interacts with PGOxMns can trigger the production of Mn(II), which enhances the magnetic resonance imaging signal. Simultaneously, manganese dioxide catalyses the decomposition of toxic hydrogen peroxide into oxygen, which also maintains glucose oxidase (GOx) activity. In an in vivo model of diabetes, PGOxMns is used to monitor glucose levels (0-20 mm) and allowed identification of diabetic mice via T1-weighted MRI. Furthermore, PGOxMns is found to have a high insulin-loading capacity (83.6%), likely due to its positive charge. A single subcutaneous injection of insulin-loaded nanosystem (Ins-PGOxMns) into diabetic mice resulted in a rapid and efficient response to a glucose challenge and prolonged blood glucose level control (< 200 mg dL-1) for up to 50 h. Overall, this proof-of-concept study demonstrates the feasibility of using biomineralised nanosystems to develop patient-friendly strategies for glucose monitoring and control.

14.
Am J Pathol ; 194(6): 975-988, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38423356

RESUMO

Radiation-induced enteritis, a significant concern in abdominal radiation therapy, is associated closely with gut microbiota dysbiosis. The mucus layer plays a pivotal role in preventing the translocation of commensal and pathogenic microbes. Although significant expression of REGγ in intestinal epithelial cells is well established, its role in modulating the mucus layer and gut microbiota remains unknown. The current study revealed notable changes in gut microorganisms and metabolites in irradiated mice lacking REGγ, as compared to wild-type mice. Concomitant with gut microbiota dysbiosis, REGγ deficiency facilitated the infiltration of neutrophils and macrophages, thereby exacerbating intestinal inflammation after irradiation. Furthermore, fluorescence in situ hybridization assays unveiled an augmented proximity of bacteria to intestinal epithelial cells in REGγ knockout mice after irradiation. Mechanistically, deficiency of REGγ led to diminished goblet cell populations and reduced expression of key goblet cell markers, Muc2 and Tff3, observed in both murine models, minigut organoid systems and human intestinal goblet cells, indicating the intrinsic role of REGγ within goblet cells. Interestingly, although administration of broad-spectrum antibiotics did not alter the goblet cell numbers or mucin 2 (MUC2) secretion, it effectively attenuated inflammation levels in the ileum of irradiated REGγ absent mice, bringing them down to the wild-type levels. Collectively, these findings highlight the contribution of REGγ in counteracting radiation-triggered microbial imbalances and cell-autonomous regulation of mucin secretion.


Assuntos
Enterite , Microbioma Gastrointestinal , Células Caliciformes , Homeostase , Camundongos Knockout , Mucina-2 , Complexo de Endopeptidases do Proteassoma , Animais , Humanos , Camundongos , Disbiose/microbiologia , Disbiose/metabolismo , Enterite/microbiologia , Enterite/metabolismo , Enterite/patologia , Células Caliciformes/patologia , Células Caliciformes/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Camundongos Endogâmicos C57BL , Mucina-2/metabolismo , Proteínas Associadas a Pancreatite/metabolismo , Lesões por Radiação/metabolismo , Lesões por Radiação/microbiologia , Lesões por Radiação/patologia , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/microbiologia , Fator Trefoil-3/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/efeitos da radiação , Autoantígenos/genética , Autoantígenos/metabolismo , Autoantígenos/efeitos da radiação
15.
ACS Biomater Sci Eng ; 10(3): 1494-1506, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38414275

RESUMO

The use of hemoperfusion adsorbents for the removal of bilirubin in patients with liver failure has become a critical treatment. However, the insufficient clearance of bilirubin and the possibility of bacterial infection during hemoperfusion limit the application. In this work, we designed a novel antibacterial bilirubin adsorbent (PSVT) through the suspension polymerization reaction between double-bond functionalized TiO2 nanoparticles and styrene. PSVT showed an excellent bilirubin adsorption ability and antibacterial performance, ensuring efficient clearance of bilirubin in liver failure patients during hemoperfusion and preventing bacterial infection. The experimental results indicated that TiO2 was uniformly dispersed in the microspheres, which improved the mesoporous structure and increased the specific surface area. Composite adsorbent PSVT showed an exceptional bilirubin adsorption capacity, with the maximum adsorption capacity reaching 24.3 mg/g. In addition, the introduction of TiO2 endowed PSVT with excellent antibacterial ability; the ultimate antibacterial rates against Escherichia coli and Staphylococcus aureus reached 97.31 and 96.47%, respectively. In summary, PSVT served as a novel antibacterial bilirubin adsorbent with excellent bilirubin clearance capacity and antibacterial performance, providing excellent application prospects for treating liver failure patients.


Assuntos
Infecções Bacterianas , Hemoperfusão , Falência Hepática , Nanocompostos , Humanos , Bilirrubina/química , Poliestirenos/química , Hemoperfusão/métodos , Nanocompostos/uso terapêutico
16.
J Hazard Mater ; 466: 133557, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38309168

RESUMO

The reactive oxygen species (ROS) photochemically generated from natural iron minerals have gained significant attention. Amidst the previous studies on the impact of heavy metal ions on ROS generation, our study addresses the role of the anion Cr(VI), with its intrinsic photoactivity, in influencing ROS photochemical generation with the co-presence of minerals. We investigated the transformation of inorganic/organic pollutants (Cr(VI) and benzoic acid) at the ferrihydrite interface, considering sunlight-mediated conversion processes (300-1000 nm). Increased photochemical reactivity of ferrihydrite was observed in the presence of aqueous Cr(VI), acting as a photosensitizer. Meanwhile, a positive correlation between hydroxyl radical (•OH) production and concentrations of aqueous Cr(VI) was observed, with a 650% increase of •OH generation at 50 mg L-1 Cr(VI) compared to systems without Cr(VI). Our photochemical batch experiments elucidated three potential pathways for •OH photochemical production under varying wet chemistry conditions: (1) ferrihydrite hole-mediated pathway, (2) chromium intermediate O-I-mediated pathway, and (3) chromium intermediates CrIV/V-mediated pathway. Notably, even in the visible region (> 425 nm), the promotion of aqueous Cr(VI) on •OH accumulation was observed in the presence of ferrihydrite and TiO2 suspensions, attributed to Cr(VI) photosensitization at the mineral interface. This study sheds light on the overlooked role of aqueous Cr(VI) in the photochemical reactivity of minerals, thereby enhancing our understanding of pollutant fate in acid mining-impacted environments.

17.
Nat Cell Biol ; 26(2): 263-277, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38238450

RESUMO

Human in vitro fertilized embryos exhibit low developmental capabilities, and the mechanisms that underlie embryonic arrest remain unclear. Here using a single-cell multi-omics sequencing approach, we simultaneously analysed alterations in the transcriptome, chromatin accessibility and the DNA methylome in human embryonic arrest due to unexplained reasons. Arrested embryos displayed transcriptome disorders, including a distorted microtubule cytoskeleton, increased genomic instability and impaired glycolysis, which were coordinated with multiple epigenetic reprogramming defects. We identified Aurora A kinase (AURKA) repression as a cause of embryonic arrest. Mechanistically, arrested embryos induced through AURKA inhibition resembled the reprogramming abnormalities of natural embryonic arrest in terms of the transcriptome, the DNA methylome, chromatin accessibility and H3K4me3 modifications. Mitosis-independent sequential activation of the zygotic genome in arrested embryos showed that YY1 contributed to human major zygotic genome activation. Collectively, our study decodes the reprogramming abnormalities and mechanisms of human embryonic arrest and the key regulators of zygotic genome activation.


Assuntos
Aurora Quinase A , Multiômica , Humanos , Aurora Quinase A/genética , Blastocisto , Cromatina/genética , Citoesqueleto , Desenvolvimento Embrionário/genética
18.
Molecules ; 28(18)2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37764514

RESUMO

Phthalic acid esters (PAEs), which are widespread environmental contaminants, can be efficiently biodegraded, mediated by enzymes such as hydrolases. Despite great advances in the characterization of PAE hydrolases, which are the most important enzymes in the process of PAE degradation, their molecular catalytic mechanism has rarely been systematically investigated. Acinetobacter sp. LUNF3, which was isolated from contaminated soil in this study, demonstrated excellent PAE degradation at 30 °C and pH 5.0-11.0. After sequencing and annotating the complete genome, the gene dphAN1, encoding a novel putative PAE hydrolase, was identified with the conserved motifs catalytic triad (Ser201-Asp295-His325) and oxyanion hole (H127GGG130). DphAN1 can hydrolyze DEP (diethyl phthalate), DBP (dibutyl phthalate) and BBP (benzyl butyl phthalate). The high activity of DphAN1 was observed under a wide range of temperature (10-40 °C) and pH (6.0-9.0). Moreover, the metal ions (Fe2+, Mn2+, Cr2+ and Fe3+) and surfactant TritonX-100 significantly activated DphAN1, indicating a high adaptability and tolerance of DphAN1 to these chemicals. Molecular docking revealed the catalytic triad, oxyanion hole and other residues involved in binding DBP. The mutation of these residues reduced the activity of DphAN1, confirming their interaction with DBP. These results shed light on the catalytic mechanism of DphAN1 and may contribute to protein structural modification to improve catalytic efficiency in environment remediation.


Assuntos
Acinetobacter , Hidrolases , Acinetobacter/genética , Simulação de Acoplamento Molecular , Clonagem Molecular
19.
Sci Adv ; 9(26): eadg6004, 2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-37379385

RESUMO

Recent discoveries of methyl-coenzyme M reductase-encoding genes (mcr) in uncultured archaea beyond traditional euryarchaeotal methanogens have reshaped our view of methanogenesis. However, whether any of these nontraditional archaea perform methanogenesis remains elusive. Here, we report field and microcosm experiments based on 13C-tracer labeling and genome-resolved metagenomics and metatranscriptomics, revealing that nontraditional archaea are predominant active methane producers in two geothermal springs. Archaeoglobales performed methanogenesis from methanol and may exhibit adaptability in using methylotrophic and hydrogenotrophic pathways based on temperature/substrate availability. A five-year field survey found Candidatus Nezhaarchaeota to be the predominant mcr-containing archaea inhabiting the springs; genomic inference and mcr expression under methanogenic conditions strongly suggested that this lineage mediated hydrogenotrophic methanogenesis in situ. Methanogenesis was temperature-sensitive , with a preference for methylotrophic over hydrogenotrophic pathways when incubation temperatures increased from 65° to 75°C. This study demonstrates an anoxic ecosystem wherein methanogenesis is primarily driven by archaea beyond known methanogens, highlighting diverse nontraditional mcr-containing archaea as previously unrecognized methane sources.


Assuntos
Archaea , Fontes Termais , Archaea/genética , Archaea/metabolismo , Ecossistema , Metano/metabolismo , Temperatura , Filogenia
20.
Environ Sci Technol ; 57(26): 9843-9853, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37342885

RESUMO

The association of arsenic (As) with colloidal particles could facilitate its transport to adjacent water systems or alter its availability in soil-rice systems. However, little is known about the size distribution and composition of particle-bound As in paddy soils, particularly under changing redox conditions. Here, we incubated four As-contaminated paddy soils with distinctive geochemical properties to study the mobilization of particle-bound As during soil reduction and subsequent reoxidation. Using transmission electron microscopy-energy dispersive spectroscopy and asymmetric flow field-flow fractionation, we identified organic matter (OM)-stabilized colloidal Fe, most likely in the form of (oxy)hydroxide-clay composite, as the main arsenic carriers. Specifically, colloidal As was mainly associated with two size fractions of 0.3-40 and >130 kDa. Soil reduction facilitated the release of As from both fractions, whereas reoxidation caused their rapid sedimentation, coinciding with solution Fe variations. Further quantitative analysis demonstrated that As concentrations positively correlated with both Fe and OM concentrations at nanometric scales (0.3-40 kDa) in all studied soils during reduction and reoxidation, yet the correlations are pH-dependent. This study provides a quantitative and size-resolved understanding of particle-bound As in paddy soils, highlighting the importance of nanometric Fe-OM-As interactions in paddy As geochemical cycling.


Assuntos
Arsênio , Oryza , Poluentes do Solo , Arsênio/química , Poluição Ambiental/análise , Solo/química , Coloides/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA