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1.
FASEB J ; 38(13): e23701, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38941193

RESUMO

Zearalenone (ZEN) is a mycotoxin known for its estrogen-like effects, which can disrupt the normal physiological function of endometrial cells and potentially lead to abortion in female animals. However, the precise mechanism by which ZEN regulates endometrial function remains unclear. In this study, we found that the binding receptor estrogen receptors for ZEN is extensively expressed across various segments of the uterus and within endometrial cells, and a certain concentration of ZEN treatment reduced the proliferation capacity of goat endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs). Meanwhile, cell cycle analysis revealed that ZEN treatment leaded to cell cycle arrest in goat EECs and ESCs. To explore the underlying mechanism, we investigated the mitochondrial quality control systems and observed that ZEN triggered excessive mitochondrial fission and disturbed the balance of mitochondrial fusion-fission dynamics, impaired mitochondrial biogenesis, increased mitochondrial unfolded protein response and mitophagy in goat EECs and ESCs. Additionally, ZEN treatment reduced the activities of mitochondrial respiratory chain complexes, heightened the production of hydrogen peroxide and reactive oxygen species, and caused cellular oxidative stress and mitochondrial dysfunction. These results suggest that ZEN has adverse effects on goat endometrium cells by disrupting the mitochondrial quality control system and affecting cell cycle and proliferation. Understanding the underlying molecular pathways involved in ZEN-induced mitochondrial dysfunction and its consequences on cell function will provide critical insights into the reproductive toxicity of ZEN and contribute to safeguarding the health and wellbeing of animals and humans exposed to this mycotoxin.


Assuntos
Proliferação de Células , Endométrio , Cabras , Mitocôndrias , Zearalenona , Animais , Feminino , Endométrio/citologia , Endométrio/metabolismo , Endométrio/efeitos dos fármacos , Zearalenona/toxicidade , Zearalenona/farmacologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Cultivadas , Dinâmica Mitocondrial/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/efeitos dos fármacos , Células Estromais/citologia
2.
PLoS Comput Biol ; 20(6): e1011882, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38838038

RESUMO

In embryonic development and organogenesis, cells sharing identical genetic codes acquire diverse gene expression states in a highly reproducible spatial distribution, crucial for multicellular formation and quantifiable through positional information. To understand the spontaneous growth of complexity, we constructed a one-dimensional division-decision model, simulating the growth of cells with identical genetic networks from a single cell. Our findings highlight the pivotal role of cell division in providing positional cues, escorting the system toward states rich in information. Moreover, we pinpointed lateral inhibition as a critical mechanism translating spatial contacts into gene expression. Our model demonstrates that the spatial arrangement resulting from cell division, combined with cell lineages, imparts positional information, specifying multiple cell states with increased complexity-illustrated through examples in C.elegans. This study constitutes a foundational step in comprehending developmental intricacies, paving the way for future quantitative formulations to construct synthetic multicellular patterns.


Assuntos
Redes Reguladoras de Genes , Modelos Biológicos , Animais , Redes Reguladoras de Genes/genética , Caenorhabditis elegans/genética , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/crescimento & desenvolvimento , Divisão Celular/fisiologia , Divisão Celular/genética , Biologia Computacional , Desenvolvimento Embrionário/fisiologia , Desenvolvimento Embrionário/genética , Linhagem da Célula , Simulação por Computador , Regulação da Expressão Gênica no Desenvolvimento/genética
3.
Brief Bioinform ; 23(6)2022 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-36384071

RESUMO

Emerging evidence suggests that circular RNA (circRNA) is an important regulator of a variety of pathological processes and serves as a promising biomarker for many complex human diseases. Nevertheless, there are relatively few known circRNA-disease associations, and uncovering new circRNA-disease associations by wet-lab methods is time consuming and costly. Considering the limitations of existing computational methods, we propose a novel approach named MNMDCDA, which combines high-order graph convolutional networks (high-order GCNs) and deep neural networks to infer associations between circRNAs and diseases. Firstly, we computed different biological attribute information of circRNA and disease separately and used them to construct multiple multi-source similarity networks. Then, we used the high-order GCN algorithm to learn feature embedding representations with high-order mixed neighborhood information of circRNA and disease from the constructed multi-source similarity networks, respectively. Finally, the deep neural network classifier was implemented to predict associations of circRNAs with diseases. The MNMDCDA model obtained AUC scores of 95.16%, 94.53%, 89.80% and 91.83% on four benchmark datasets, i.e., CircR2Disease, CircAtlas v2.0, Circ2Disease and CircRNADisease, respectively, using the 5-fold cross-validation approach. Furthermore, 25 of the top 30 circRNA-disease pairs with the best scores of MNMDCDA in the case study were validated by recent literature. Numerous experimental results indicate that MNMDCDA can be used as an effective computational tool to predict circRNA-disease associations and can provide the most promising candidates for biological experiments.


Assuntos
Redes Neurais de Computação , RNA Circular , Humanos , Algoritmos
4.
Brief Bioinform ; 23(2)2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35037026

RESUMO

There is a lack of robust generalizable predictive biomarkers of response to immune checkpoint blockade in multiple types of cancer. We develop hDirect-MAP, an algorithm that maps T cells into a shared high-dimensional (HD) expression space of diverse T cell functional signatures in which cells group by the common T cell phenotypes rather than dimensional reduced features or a distorted view of these features. Using projection-free single-cell modeling, hDirect-MAP first removed a large group of cells that did not contribute to response and then clearly distinguished T cells into response-specific subpopulations that were defined by critical T cell functional markers of strong differential expression patterns. We found that these grouped cells cannot be distinguished by dimensional-reduction algorithms but are blended by diluted expression patterns. Moreover, these identified response-specific T cell subpopulations enabled a generalizable prediction by their HD metrics. Tested using five single-cell RNA-seq or mass cytometry datasets from basal cell carcinoma, squamous cell carcinoma and melanoma, hDirect-MAP demonstrated common response-specific T cell phenotypes that defined a generalizable and accurate predictive biomarker.


Assuntos
Imunoterapia , Melanoma , Biomarcadores , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Linfócitos T
5.
Immunol Invest ; : 1-12, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900045

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis (RA) and is associated with a poor prognosis. However, the role of blood biomarkers in RA-associated interstitial lung disease (RA-ILD) is ill-defined. We aim to evaluate the role of YKL-40 and Krebs von den Lungen-6 (KL-6) in the diagnosis and severity evaluation of RA-ILD. METHODS: 45 RA-non-ILD patients and 38 RA-ILD patients were included. The clinical data and the levels of YKL-40 and KL-6 were measured and collected for all patients. The risk factors for RA-ILD were analyzed and their correlation with relevant indicators and predictive value for RA-ILD was explored. RESULTS: The levels of YKL-40 and KL-6 in RA-ILD patients were higher than RA-non-ILD patients (p < .001). Both YKL-40 and KL-6 were correlated with the incidence of RA-ILD. The predictive power of combined KL-6 and YKL-40 for the presence of ILD was 0.789, with a sensitivity and specificity at 73.7% and 73.3%, respectively. In RA-ILD patients, both YKL-40 and KL-6 were positively correlated with the Scleroderma Lung Study (SLS) I score and negatively correlated with pulmonary function. CONCLUSIONS: KL-6 and YKL-40 might be a useful biomarker in the diagnosis and severity evaluation of RA-ILD.

6.
BMC Vet Res ; 20(1): 2, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172782

RESUMO

BACKGROUND: Pregnancy toxemia is a common disease, which occurs in older does that are pregnant with multiple lambs in the third trimester. Most of the sick goats die within a few days, which can seriously impact the economic benefits of goat breeding enterprises. The disease is believed to be caused by malnutrition, stress, and other factors, that lead to the disorder of lipid metabolism, resulting in increased ketone content, ketosis, ketonuria, and neurological symptoms. However, the changes in gut microbes and their metabolism in this disease are still unclear. The objective of this experiment was to evaluate the effect of toxemia of pregnancy on the fecal microbiome and metabolomics of does. RESULTS: Eight pregnant does suspected of having toxemia of pregnancy (PT group) and eight healthy does during the same pregnancy (NC group) were selected. Clinical symptoms and pathological changes at necropsy were observed, and liver tissue samples were collected for pathological sections. Jugular venous blood was collected before morning feeding to detect biochemical indexes. Autopsy revealed that the liver of the pregnancy toxemia goat was enlarged and earthy yellow, and the biochemical results showed that the serum levels of aspartate aminotransferase (AST) and ß-hydroxybutyric acid (B-HB) in the PT group were significantly increased, while calcium (Ca) levels were significantly reduced. Sections showed extensive vacuoles in liver tissue sections. The microbiome analysis found that the richness and diversity of the PT microbiota were significantly reduced. Metabolomic analysis showed that 125 differential metabolites were screened in positive ion mode and enriched in 12 metabolic pathways. In negative ion mode, 100 differential metabolites were screened and enriched in 7 metabolic pathways. CONCLUSIONS: Evidence has shown that the occurrence of pregnancy toxemia is related to gut microbiota, and further studies are needed to investigate its pathogenesis and provide research basis for future preventive measures of this disease.


Assuntos
Doenças das Cabras , Microbiota , Pré-Eclâmpsia , Doenças dos Ovinos , Toxemia , Feminino , Gravidez , Ovinos , Animais , Pré-Eclâmpsia/veterinária , Cabras/metabolismo , Toxemia/veterinária , Metaboloma , Metabolômica , Carneiro Doméstico/metabolismo , RNA Ribossômico 16S
7.
Biochem Genet ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316654

RESUMO

Despite many studies on papillary thyroid carcinoma (PTC) in the past few decades, some critical and significant genes remain undiscovered. To explore genes that may play crucial roles in PTC, a detailed analysis of the expression levels, mutations, and clinical significance of Kallikrein-related peptidases (KLKs) family genes in PTC was undertaken to provide new targets for the precise treatment of the disease. A comprehensive analysis of KLK family genes was performed using various online tools, such as GEPIA, Kaplan-Meier Plotter, LinkedOmics, GSCA, TIMER, and Cluego. KLK7, KLK10, and KLK11 were critical factors of KLK family genes. Then, functional assays were carried out on KLK7/10/11 to determine their proliferation, migration, and invasion capabilities in PTC. The mRNA expression levels of KLK7, KLK10, KLK11, and KLK13 were significantly elevated in thyroid carcinoma, while KLK1, KLK2, KLK3 and KLK4 mRNA levels were decreased compared to normal tissues. Correlations between KLK2/7-12/15 expression levels and tumor stage were also observed in thyroid carcinoma. Survival analysis demonstrated that KLK4/5/7/9-12/14 was associated with overall survival in patients with thyroid cancer. Not only were KLK genes strongly associated with cancer-related pathways, but also KLK7/10/11 was associated with immune-cell infiltration. Finally, silencing KLK7/10/11 impaired human papillary thyroid carcinoma cells' growth, migration ability, and invasiveness. The increased expression of KLK7, KLK10, and KLK11 may serve as molecular markers to identify PTC patients. KLK7, KLK10, and KLK11 could be potential prognostic indicators and targets for precision therapy against PTC.

8.
J Virol ; 96(20): e0131822, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36173190

RESUMO

Pseudorabies virus (PRV), which is extremely infectious and can infect numerous mammals, has a risk of spillover into humans. Virus-host interactions determine viral entry and spreading. Here, we showed that neuropilin-1 (NRP1) significantly potentiates PRV infection. Mechanistically, NRP1 promoted PRV attachment and entry, and enhanced cell-to-cell fusion mediated by viral glycoprotein B (gB), gD, gH, and gL. Furthermore, through in vitro coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays, NRP1 was found to physically interact with gB, gD, and gH, and these interactions were C-end Rule (CendR) motif independent, in contrast to currently known viruses. Remarkably, we illustrated that the viral protein gB promotes NRP1 degradation via a lysosome-dependent pathway. We further demonstrate that gB promotes NRP1 degradation in a furin-cleavage-dependent manner. Interestingly, in this study, we generated gB furin cleavage site (FCS)-knockout PRV (Δfurin PRV) and evaluated its pathogenesis; in vivo, we found that Δfurin PRV virulence was significantly attenuated in mice. Together, our findings demonstrated that NRP1 is an important host factor for PRV and that NRP1 may be a potential target for antiviral intervention. IMPORTANCE Recent studies have shown accelerated PRV cross-species spillover and that PRV poses a potential threat to humans. PRV infection in humans always manifests as a high fever, tonic-clonic seizures, and encephalitis. Therefore, understanding the interaction between PRV and host factors may contribute to the development of new antiviral strategies against PRV. NRP1 has been demonstrated to be a receptor for several viruses that harbor CendR, including SARS-CoV-2. However, the relationships between NRP1 and PRV are poorly understood. Here, we found that NRP1 significantly potentiated PRV infection by promoting PRV attachment and enhanced cell-to-cell fusion. For the first time, we demonstrated that gB promotes NRP1 degradation via a lysosome-dependent pathway. Last, in vivo, Δfurin PRV virulence was significantly attenuated in mice. Therefore, NRP1 is an important host factor for PRV, and NRP1 may be a potential target for antiviral drug development.


Assuntos
COVID-19 , Herpesvirus Suídeo 1 , Pseudorraiva , Camundongos , Humanos , Animais , Herpesvirus Suídeo 1/metabolismo , Neuropilina-1/genética , Neuropilina-1/metabolismo , Furina/metabolismo , SARS-CoV-2 , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Replicação Viral , Proteínas Virais/metabolismo , Antivirais/metabolismo , Mamíferos
9.
J Pathol ; 258(2): 121-135, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35723032

RESUMO

Tumour-associated macrophages (TAMs) abundantly infiltrate high-grade gliomas and orchestrate immune response, but their diversity in isocitrate dehydrogenase (IDH)-differential grade 4 gliomas remains largely unknown. This study aimed to dissect the transcriptional states, spatial distribution, and clinicopathological significance of distinct monocyte-derived TAM (Mo-TAM) and microglia-derived TAM (Mg-TAM) clusters across glioblastoma-IDH-wild type and astrocytoma-IDH-mutant-grade 4 (Astro-IDH-mut-G4). Single-cell RNA sequencing was performed on four cases of human glioblastoma and three cases of Astro-IDH-mut-G4. Cell clustering, single-cell regulatory network inference, and gene set enrichment analysis were performed to characterize the functional states of myeloid clusters. The spatial distribution of TAM subsets was determined in human glioma tissues using multiplex immunostaining. The prognostic value of different TAM-cluster specific gene sets was evaluated in the TCGA glioma cohort. Profiling and unbiased clustering of 24,227 myeloid cells from glioblastoma and Astro-IDH-mut-G4 identified nine myeloid cell clusters including monocytes, six Mo/Mg-TAM subsets, dendritic cells, and proliferative myeloid clusters. Different Mo/Mg-TAM clusters manifest functional and transcriptional diversity controlled by specific regulons. Multiplex immunostaining of subset-specific markers identified spatial enrichment of distinct TAM clusters at peri-vascular/necrotic areas in tumour parenchyma or at the tumour-brain interface. Glioblastoma harboured a substantially higher number of monocytes and Mo-TAM-inflammatory clusters, whereas Astro-IDH-mut-G4 had a higher proportion of TAM subsets mediating antigen presentation. Glioblastomas with a higher proportion of monocytes exhibited a mesenchymal signature, increased angiogenesis, and worse patient outcome. Our findings provide insight into myeloid cell diversity and its clinical relevance in IDH-differential grade 4 gliomas, and may serve as a resource for immunotherapy development. © 2022 The Pathological Society of Great Britain and Ireland.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Glioma , Astrocitoma/genética , Astrocitoma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioblastoma/genética , Glioblastoma/patologia , Glioma/genética , Humanos , Isocitrato Desidrogenase/genética , Mutação , Macrófagos Associados a Tumor
10.
Environ Sci Technol ; 57(30): 11325-11335, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37395618

RESUMO

Simultaneous recovery of energy and carbon from recalcitrant wastewater has attracted ever-growing interest for water management. However, the existing technologies to break down recalcitrant pollutants are mainly energy and chemical intensive. Here, a novel hydrothermal reaction amended with activated carbon (AC) was demonstrated to enable an unprecedented 99.5% removal of an exemplar difficult-to-degrade contaminant, polyvinyl alcohol (PVA), from wastewater. Meanwhile, an easy-separated hydrochar (C6H7.08O0.99) with an abundance of unsaturated aromatic rings was produced, exhibiting 118.46% of energy yield with a high heating value of 32.9 MJ/kg, outperforming the hydrochar(s) reported to date. The retrieved energy from the hydrochar was able to entirely offset the energy needs for this hydrothermal process. Interestingly, the AC catalyst can sustain in situ reuse over 125 cycles with no evidence of irreversible deactivation. The adjacent carbonyl groups on AC were revealed to provide active sites for dehydrogenation from either the C-H (1.24 Å) or O-H (1.40 Å) bond in PVA, forming hydroxyl groups on AC and highly reactive intermediates (ΔG0 = -11.5 kcal/mol). It was further proved that the free oxygen in the headspace extracted H atoms from the newly formed hydroxyl groups on AC (ΔG0 = -4.7 kcal/mol), thus regenerating the carbonyl sites on AC for the next catalytic hydrothermal dehydrogenation cycles. The long-lasting catalyst reusability and energy self-sufficient approach offer a sustainable route to carbon neutrality in recalcitrant wastewater treatment.

11.
Environ Sci Technol ; 57(13): 5305-5316, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36952228

RESUMO

The potential ecological risks caused by entering radioactive wastewater containing tritium and carbon-14 into the sea require careful evaluation. This study simulated seawater's tritium and carbon-14 pollution and analyzed the effects on the seawater and sediment microenvironments. Tritium and carbon-14 pollution primarily altered nitrogen and phosphorus metabolism in the seawater environment. Analysis by 16S rRNA sequencing showed changes in the relative abundance of microorganisms involved in carbon, nitrogen, and phosphorus metabolism and organic matter degradation in response to tritium and carbon-14 exposure. Metabonomics and metagenomic analysis showed that tritium and carbon-14 exposure interfered with gene expression involving nucleotide and amino acid metabolites, in agreement with the results seen for microbial community structure. Tritium and carbon-14 exposure also modulated the abundance of functional genes involved in carbohydrate, phosphorus, sulfur, and nitrogen metabolic pathways in sediments. Tritium and carbon-14 pollution in seawater adversely affected microbial diversity, metabolic processes, and the abundance of nutrient-cycling genes. These results provide valuable information for further evaluating the risks of tritium and carbon-14 in marine environments.


Assuntos
Bactérias , Microbiota , Radioisótopos de Carbono/metabolismo , Trítio/metabolismo , Bactérias/genética , Bactérias/metabolismo , RNA Ribossômico 16S/genética , Microbiota/genética , Água do Mar , Redes e Vias Metabólicas , Carbono/metabolismo , Nitrogênio/metabolismo , Fósforo/metabolismo , Sedimentos Geológicos/química
12.
Acta Pharmacol Sin ; 44(7): 1350-1365, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36737635

RESUMO

Sympathetic stress is prevalent in cardiovascular diseases. Sympathetic overactivation under strong acute stresses triggers acute cardiovascular events including myocardial infarction (MI), sudden cardiac death, and stress cardiomyopathy. α1-ARs and ß-ARs, two dominant subtypes of adrenergic receptors in the heart, play a significant role in the physiological and pathologic regulation of these processes. However, little is known about the functional similarities and differences between α1- and ß-ARs activated temporal responses in stress-induced cardiac pathology. In this work, we systematically compared the cardiac temporal genome-wide profiles of acute α1-AR and ß-AR activation in the mice model by integrating transcriptome and proteome. We found that α1- and ß-AR activations induced sustained and transient inflammatory gene expression, respectively. Particularly, the overactivation of α1-AR but not ß-AR led to neutrophil infiltration at one day, which was closely associated with the up-regulation of chemokines, activation of NF-κB pathway, and sustained inflammatory response. Furthermore, there are more metabolic disorders under α1-AR overactivation compared with ß-AR overactivation. These findings provide a new therapeutic strategy that, besides using ß-blocker as soon as possible, blocking α1-AR within one day should also be considered in the treatment of acute stress-associated cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Receptores Adrenérgicos beta , Animais , Camundongos , Receptores Adrenérgicos beta/genética , Receptores Adrenérgicos beta/metabolismo , Coração , Arritmias Cardíacas , Inflamação/metabolismo , Receptores Adrenérgicos alfa 1/genética , Receptores Adrenérgicos alfa 1/metabolismo
13.
Environ Res ; 234: 116491, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37394168

RESUMO

The soil microbial diversity in the gangue accumulation area is severely stressed by a variety of heavy metals, while the influence of long-term recovery of herbaceous plants on the ecological structure of gangue-contaminated soil is to be explored. Therefore, we analysed the differences in physicochemical properties, elemental changes, microbial community structure, metabolites and expression of related pathways in soils in the 10- and 20-year herbaceous remediation areas of coal gangue. Our results showed that phosphatase, soil urease, and sucrase activities of gangue soils significantly increased in the shallow layer after herbaceous remediation. However, in zone T1 (10-year remediation zone), the contents of harmful elements, such as Thorium (Th; 1.08-fold), Arsenic (As; 0.78-fold), lead (Pb; 0.99-fold), and uranium (U; 0.77-fold), increased significantly, whereas the soil microbial abundance and diversity also showed a significant decreasing trend. Conversely, in zone T2 (20-year restoration zone), the soil pH significantly increased by 1.03- to 1.06-fold and soil acidity significantly improved. Moreover, the abundance and diversity of soil microorganisms increased significantly, the expression of carbohydrates in soil was significantly downregulated, and sucrose content was significantly negatively correlated with the abundance of microorganisms, such as Streptomyces. A significant decrease in heavy metals was observed in the soil, such as U (1.01- to 1.09-fold) and Pb (1.13- to 1.25-fold). Additionally, the thiamin synthesis pathway was inhibited in the soil of the T1 zone; the expression level of sulfur (S)-containing histidine derivatives (Ergothioneine) was significantly up-regulated by 0.56-fold in the shallow soil of the T2 zone; and the S content in the soil significantly reduced. Aromatic compounds were significantly up-regulated in the soil after 20 years of herbaceous plant remediation in coal gangue soil, and microorganisms (Sphingomonas) with significant positive correlations with benzene ring-containing metabolites, such as Sulfaphenazole, were identified.


Assuntos
Metais Pesados , Microbiota , Poluentes do Solo , Urânio , Carvão Mineral , Chumbo/toxicidade , Chumbo/análise , Metais Pesados/análise , Plantas , Solo/química , Metaboloma , Poluentes do Solo/toxicidade , Poluentes do Solo/análise
14.
Blood Purif ; 52(7-8): 609-620, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37591223

RESUMO

BACKGROUND: Hyperphosphatemia is associated with cardiovascular morbidity and mortality in adults with chronic kidney disease (CKD). Drug therapy has an irreplaceable role in the management of hyperphosphatemia. OBJECTIVES: We aimed to compare and rank phosphorus-lowering drugs, including phosphate binder and nonphosphate binder, in hyperphosphatemia adults with CKD. METHODS: We did a systematic review and frequentist random-effect network meta-analysis. We searched in PubMed, Cochrane Library, Web of Science, and Embase from inception to February 1, 2023, for randomized controlled trials of 12 phosphorus-lowering drugs in adults with hyperphosphatemia and CKD. Primary outcomes were efficacy (changes in serum phosphorus) and acceptability (treatment withdrawals due to any cause). We ranked each drug according to the value of surface under the cumulative ranking curve. We applied the Confidence in Network Meta-Analysis frameworks to rate the certainty of evidence. This study was registered with PROSPERO, number CRD42022322270. RESULTS: We identified 2,174 citations, and of these, we included 94 trials comprising 14,459 participants and comparing 13 drugs or placebo. In terms of efficacy, except for niacinamide, all drugs lowered the level of serum phosphorus compared with placebo, with mean difference ranging between -1.61 (95% credible interval [CrI], -2.60 to -0.62) mg/dL for magnesium carbonate and -0.85 (-1.66 to -0.05) mg/dL for bixalomer. Only ferric citrate with odds ratios 0.56 (95% CrI: 0.36-0.89) was significantly associated with fewer dropouts for acceptability. Of the 94 trials, 43 (46%), 7 (7%), and 44 (47%) trials were rated as high, moderate, and low risk of bias, respectively, the certainty of the evidence was moderate to very low. CONCLUSIONS: Magnesium carbonate has the best phosphorus-lowering effect in hyperphosphatemia adults with CKD; considering efficacy and acceptability, ferric citrate shows evidence to be the most appropriate drug with or without dialysis.


Assuntos
Hiperfosfatemia , Insuficiência Renal Crônica , Humanos , Adulto , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Metanálise em Rede , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico
15.
Proc Natl Acad Sci U S A ; 117(36): 22281-22292, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32843340

RESUMO

Seawater Mg:Ca and Sr:Ca ratios are biogeochemical parameters reflecting the Earth-ocean-atmosphere dynamic exchange of elements. The ratios' dependence on the environment and organisms' biology facilitates their application in marine sciences. Here, we present a measured single-laboratory dataset, combined with previous data, to test the assumption of limited seawater Mg:Ca and Sr:Ca variability across marine environments globally. High variability was found in open-ocean upwelling and polar regions, shelves/neritic and river-influenced areas, where seawater Mg:Ca and Sr:Ca ratios range from ∼4.40 to 6.40 mmol:mol and ∼6.95 to 9.80 mmol:mol, respectively. Open-ocean seawater Mg:Ca is semiconservative (∼4.90 to 5.30 mol:mol), while Sr:Ca is more variable and nonconservative (∼7.70 to 8.80 mmol:mol); both ratios are nonconservative in coastal seas. Further, the Ca, Mg, and Sr elemental fluxes are connected to large total alkalinity deviations from International Association for the Physical Sciences of the Oceans (IAPSO) standard values. Because there is significant modern seawater Mg:Ca and Sr:Ca ratios variability across marine environments we cannot absolutely assume that fossil archives using taxa-specific proxies reflect true global seawater chemistry but rather taxa- and process-specific ecosystem variations, reflecting regional conditions. This variability could reconcile secular seawater Mg:Ca and Sr:Ca ratio reconstructions using different taxa and techniques by assuming an error of 1 to 1.50 mol:mol, and 1 to 1.90 mmol:mol, respectively. The modern ratios' variability is similar to the reconstructed rise over 20 Ma (Neogene Period), nurturing the question of seminonconservative behavior of Ca, Mg, and Sr over modern Earth geological history with an overlooked environmental effect.

16.
Tech Coloproctol ; 27(10): 799-811, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37634164

RESUMO

PURPOSE: This study used a network meta-analysis to evaluate the efficacy and safety of different surgical approaches in patients with hemorrhoids. METHODS: PubMed, Embase, Web of science, and Cochrane Library were searched for randomized controlled trials on patients with hemorrhoids treated by different surgical procedures. The search was conducted until January 15, 2023. Two investigators independently screened the resulting literature, extracted information, evaluated the risk of bias of the included studies, and performed a network meta-analysis. RESULT: A total of 23 randomized controlled studies were included and involved 3573 patients and 10 interventions, namely L (Ligasure), M-M (Milligan-Morgan), F (Ferguson), H (Harmonic), OH (open Harmonic), CH (closed Harmonic), PPH (procedure for prolapse and hemorrhoids), TST (tissue selecting technique), T-S (TST STARE+; tissue selection therapy stapled transanal rectal resection plus), and STARR (stapled transanal rectal resection). Network meta-analysis results showed that L has the shortest mean operating time and STARR has the longest mean operating time, F and H have the longest length of hospitalization and T-S has the shortest length of hospitalization, PPH has the most intraoperative blood loss and L has the least intraoperative blood loss, TST has the shortest time to first defecation and M-M has the longest time to first defecation, STARR had the least recurrence and PPH had the most recurrence, PPH had the least anal stenosis and L had the most anal stenosis, and F had the least postoperative pain after 24 h and PPH had the most postoperative pain after 24 h. CONCLUSION: Current evidence suggests that L is best at reducing mean operative time and intraoperative bleeding, T-S is best at reducing mean length of stay, TST has the shortest time to first defecation, STARR is best at reducing recurrence rates, PPH is best at reducing postoperative anal stricture, and F is best at reducing postoperative pain after 24 h.


Assuntos
Malformações Anorretais , Hemorroidas , Humanos , Hemorroidas/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Constrição Patológica , Metanálise em Rede , Dor Pós-Operatória/etiologia
17.
Water Sci Technol ; 88(8): 1927-1943, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37906450

RESUMO

In this paper, molybdenum disulfide was grown on the surface of iron-containing tailings by hydrothermal method, and a series of highly efficient activated persulfate (PMS) iron-based catalysts were successfully prepared. The results show that in the CTM 1-200/PMS system, the additional ratio of tailings and the hydrothermal temperature have important effects on the catalyst. The catalyst prepared under the conditions of CT:MoS2 (molar ratio 1:1) and hydrothermal temperature of 200 °C (CTM 1-200) had the best degradation effect on BPA, and the degradation effect was increased by four times. The reason for the improvement of degradation efficiency is that the introduction of MoS2 accelerates the REDOX cycle between Fe(II)/Fe(III), and the reduction of Fe(III) is mainly related to Mo(IV), while the reduction capacity of S is relatively weak. Molybdenum disulfide/iron tailing composite material provides a way for tailings to solve the problem of water pollution.


Assuntos
Ferro , Molibdênio , Compostos Férricos , Peróxidos
18.
BMC Bioinformatics ; 23(Suppl 7): 518, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457083

RESUMO

BACKGROUND: Self-interacting proteins (SIPs), two or more copies of the protein that can interact with each other expressed by one gene, play a central role in the regulation of most living cells and cellular functions. Although numerous SIPs data can be provided by using high-throughput experimental techniques, there are still several shortcomings such as in time-consuming, costly, inefficient, and inherently high in false-positive rates, for the experimental identification of SIPs even nowadays. Therefore, it is more and more significant how to develop efficient and accurate automatic approaches as a supplement of experimental methods for assisting and accelerating the study of predicting SIPs from protein sequence information. RESULTS: In this paper, we present a novel framework, termed GLCM-WSRC (gray level co-occurrence matrix-weighted sparse representation based classification), for predicting SIPs automatically based on protein evolutionary information from protein primary sequences. More specifically, we firstly convert the protein sequence into Position Specific Scoring Matrix (PSSM) containing protein sequence evolutionary information, exploiting the Position Specific Iterated BLAST (PSI-BLAST) tool. Secondly, using an efficient feature extraction approach, i.e., GLCM, we extract abstract salient and invariant feature vectors from the PSSM, and then perform a pre-processing operation, the adaptive synthetic (ADASYN) technique, to balance the SIPs dataset to generate new feature vectors for classification. Finally, we employ an efficient and reliable WSRC model to identify SIPs according to the known information of self-interacting and non-interacting proteins. CONCLUSIONS: Extensive experimental results show that the proposed approach exhibits high prediction performance with 98.10% accuracy on the yeast dataset, and 91.51% accuracy on the human dataset, which further reveals that the proposed model could be a useful tool for large-scale self-interacting protein prediction and other bioinformatics tasks detection in the future.


Assuntos
Evolução Biológica , Biologia Computacional , Humanos , Sequência de Aminoácidos , Matrizes de Pontuação de Posição Específica , Leucócitos , Saccharomyces cerevisiae/genética
19.
Cancer Invest ; 40(6): 494-504, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35404178

RESUMO

PURPOSE: To determine the predictive value of preoperative inflammatory markers in hepatocellular carcinoma (HCC) prognosis after transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA). MATERIALS AND METHODS: A total of 161 patients with HCC who underwent TACE combined with RFA were enrolled in this retrospective study. Receiver operating characteristic (ROC) curve analysis was used to decide the cutoff value of the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), the platelet-to-lymphocyte ratio (PLR), and the prognostic nutritional index (PNI). The relationship between preoperative NLR, LMR, PLR, PNI, and survival outcomes was analyzed using Kaplan-Meier curves and multivariate Cox regression analyses. RESULTS: The cutoff value of NLR for the best discrimination of HCC prognosis was 2.95. The median recurrence-free survival (RFS) of the low NLR (≤2.95) group was longer than that of the high NLR (>2.95) group (29 months vs. 20 months, p = 0.013). The median overall survival (OS) of the low NLR group was longer than that of the high NLR group (60 months vs. 38 months, p = 0.006). Multivariate analysis showed that the tumor size (≤3 cm vs. >3cm), tumor number (single vs. multiple), and NLR (≤2.95 vs. >2.95) were independent predictors of the PFS and OS. LMR, PLR, and PNI did not have any prognostic significance. CONCLUSION: NLR was confirmed as an independent predictive biomarker for hepatocellular carcinoma prognosis after TACE combined with RFA.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Ablação por Radiofrequência , Biomarcadores , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Linfócitos , Neutrófilos , Prognóstico , Estudos Retrospectivos
20.
Microb Ecol ; 84(2): 439-450, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34554284

RESUMO

This research provides a complete degradation scheme for acrylic copolymer/cellulose acetate butyrate peelable decontamination films. This study analyzed the removal efficiency of uranium by peelable decontamination film. More importantly, the degradability of the films was evaluated by a combined treatment with UV radiation and microbial biodegradation. The results showed that UV radiation would rupture the surface of the decontamination films, which leaded the weight-average molecular weight decreased by 55.3% and number-average molecular weight decreased by 75.83%. Additionally, the microbial flora induced light-degradable decontamination film weight-average molecular weight and number-average molecular weight decreased by 9.3% and 30.73%, respectively. 16S rRNA microbial diversity analysis indicated that Pantoea, Xylella, Cronobacter, and Olivibacter were the major degrading bacteria genera. Among them, 4 key strains that can be stripped of decontamination films have been isolated and identified from the dominant degrading bacteria group. The results show that UV radiation combined with microbial flora can achieve rapid degradation of the decontamination films.


Assuntos
Urânio , Bactérias , Biodegradação Ambiental , Descontaminação , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Raios Ultravioleta , Urânio/metabolismo
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