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1.
ACS Infect Dis ; 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703116

RESUMO

In this study, we designed and synthesized a series of pleuromutilin derivatives containing thiazole. The in vitro antimicrobial efficacy of these synthesized compounds was examined by using four strains. Compared with tiamulin (MIC = 0.25 µg/mL), compound 14 exhibited potency in inhibiting MRSA growth (MIC = 0.0625 µg/mL) in these derivatives. Meanwhile, the time-killing kinetics further demonstrated that compound 14 could efficiently inhibit the MRSA growth. After exposure at 4 × MIC, the postantibiotic effect (PAE) of compound 14 was 1.29 h. Additionally, in thigh-infected mice, compound 14 exhibited a more potent antibacterial efficacy (-1.78 ± 0.28 log10 CFU/g) in reducing MRSA load compared to tiamulin (-1.21 ± 0.23 log10 CFU/g). Moreover, the MTT assay on RAW 264.7 cells demonstrated that compound 14 (8 µg/mL) had no significant cytotoxicity. Docking studies indicated the strong affinity of compound 14 toward the 50S ribosomal subunit, with a binding free energy of -9.63 kcal/mol. Taken together, it could be deduced that compound 14 was a promising candidate for treating MRSA infections.

2.
Infect Dis Model ; 9(3): 728-743, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38689855

RESUMO

Background: The structure of age groups and social contacts of the total population influenced infection scales and hospital-bed requirements, especially influenced severe infections and deaths during the global prevalence of COVID-19. Before the end of the year 2022, Chinese government implemented the national vaccination and had built the herd immunity cross the country, and announced Twenty Measures (November 11) and Ten New Measures (December 7) for further modifications of dynamic zero-COVID polity on the Chinese mainland. With the nation-wide vaccination and modified measures background, Fuzhou COVID-19 large wave (November 19, 2022-February 9, 2023) led by Omicron BA.5.2 variant was recorded and prevailed for three months in Fujian Province. Methods: A multi-age groups susceptible-exposed-infected-hospitalized-recovered (SEIHR) COVID-19 model with social contacts was proposed in this study. The main object was to evaluate the impacts of age groups and social contacts of the total population. The idea of Least Squares method was governed to perform the data fittings of four age groups against the surveillance data from Fujian Provincial Center for Disease Control and Prevention (Fujian CDC). The next generation matrix method was used to compute basic reproduction number for the total population and for the specific age group. The tendencies of effective reproduction number of four age groups were plotted by using the Epiestim R package and the SEIHR model for in-depth discussions. The sensitivity analysis by using sensitivity index and partial rank correlation coefficients values (PRCC values) were operated to reveal the differences of age groups against the main parameters. Results: The main epidemiological features such as basic reproduction number, effective reproduction number and sensitivity analysis were extensively discussed for multi-age groups SEIHR model in this study. Firstly, by using of the next generation matrix method, basic reproduction number R0 of the total population was estimated as 1.57 using parameter values of four age groups of Fuzhou COVID-19 large wave. Given age group k, the values of R0k (age group k to age group k), the values of R0k (an infected of age group k to the total population) and the values of R^0k (an infected of the total population to age group k) were also estimated, in which the explorations of the impacts of age groups revealed that the relationship R0k>R0k>R^0k was valid. Then, the fluctuating tendencies of effective reproduction number Rt were demonstrated by using two approaches (the surveillance data and the SEIHR model) for Fuzhou COVID-19 large wave, during which high-risk group (G4 group) mainly contributed the infection scale due to high susceptibility to infection and high risks to basic diseases. Further, the sensitivity analysis using two approaches (the sensitivity index and the PRCC values) revealed that susceptibility to infection of age groups played the vital roles, while the numerical simulation showed that infection scale varied with the changes of social contacts of age groups. The results of this study claimed that the high-risk group out of the total population was concerned by the local government with the highest susceptibility to infection against COVID-19. Conclusions: This study verified that the partition structure of age groups of the total population, the susceptibility to infection of age groups, the social contacts among age groups were the important contributors of infection scale. The less social contacts and adequate hospital beds for high-risk group were profitable to control the spread of COVID-19. To avoid the emergence of medical runs against new variant in the future, the policymakers from local government were suggested to decline social contacts when hospital beds were limited.

3.
Zhongguo Zhong Yao Za Zhi ; 49(4): 912-923, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621898

RESUMO

With the promotion of chemical fertilizer and pesticide reduction and green production of traditional Chinese medicines, microbial fertilizers have become a hot way to achieve the zero-growth of chemical fertilizers and pesticides, improve the yield and qua-lity of medicinal plants, maintain soil health, and promote the sustainable development of the planting industry of Chinese herbal medicines. Soil conditions and microenvironments are crucial to the growth, development, and quality formation of medicinal plants. Microbial fertilizers, as environmentally friendly fertilizers acting on the soil, can improve soil quality by replenishing organic matter and promoting the metabolism of beneficial microorganisms to improve the yield and quality of medicinal plants. In this regard, understanding the mechanism of microbial fertilizer in regulating the quality formation of medicinal plants is crucial for the development of herbal eco-agriculture. This study introduces the processes of microbial fertilizers in improving soil properties, participating in soil nutrient cycling, enhancing the resistance of medicinal plants, and promoting the accumulation of medicinal components to summarize the mechanisms and roles of bacterial fertilizers in regulating the quality formation of medicinal plants. Furthermore, this paper introduces the application of bacterial fertilizers in medicinal plants and makes an outlook on their development, with a view to providing a scientific basis for using microbial fertilizers to improve the quality of Chinese herbal medicines, improve the soil environment, promote the sustainable development of eco-agriculture of traditional Chinese medicine, and popularize the application of microbial fertilizers.


Assuntos
Praguicidas , Plantas Medicinais , Fertilizantes , Agricultura , Solo/química , Bactérias/genética , Extratos Vegetais , Microbiologia do Solo
4.
Biosens Bioelectron ; 257: 116268, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636316

RESUMO

The recent global upsurge in Monkeypox virus (MPXV) outbreaks underscores the critical need for rapid and precise diagnostic solutions, particularly in resource-constrained settings. The gold standard diagnostic method, qRT-PCR, is hindered by its time-consuming nature, requirement for nucleic acid purification, expensive equipment, and the need for highly trained personnel. Traditional CRISPR/Cas fluorescence assays, relying on trans-cleavage of ssDNA/RNA reporters labeled with costly fluorophores and quenchers, pose challenges that limit their widespread application, especially for point-of-care testing (POCT). In this study, we utilized a cost-effective and stable fluorogenic RNA aptamer (Mango III), specifically binding and illuminating the fluorophore TO3-3 PEG-Biotin Fluorophore (TO3), as a reporter for Cas13a trans-cleavage activity. We propose a comprehensive strategy integrating RNA aptamer, recombinase-aided amplification (RAA), and CRISPR-Cas13a systems for the molecular detection of MPXV target. Leveraging the inherent collateral cleavage properties of the Cas13a system, we established high-sensitivity and specificity assays to distinguish MPXV from other Orthopoxviruses (OPVs). A streamlined one-pot protocol was developed to mitigate aerosol contamination risks. Our aptamer-coupled RAA-Cas13a one-pot detection method achieved a Limit of Detection (LoD) of 4 copies of target MPXV DNA in just 40 min. Validation using clinical MPX specimens confirmed the rapid and reliable application of our RAA-Cas13a-Apt assays without nucleic acid purification procedure, highlighting its potential as a point-of-care testing solution. These results underscore the user-friendliness and effectiveness of our one-pot RAA-Cas13a-Apt diagnostic platform, poised to revolutionize disease detection and management.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Sistemas CRISPR-Cas , Corantes Fluorescentes , Monkeypox virus , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Monkeypox virus/isolamento & purificação , Monkeypox virus/genética , Humanos , Limite de Detecção
5.
Colloids Surf B Biointerfaces ; 238: 113921, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38631280

RESUMO

Tumor microenvironment (TME)-responsive size-changeable and biodegradable nanoplatforms for multimodal therapy possess huge advantages in anti-tumor therapy. Hence, we developed a hyaluronic acid (HA) modified CuS/MnO2 nanosheets (HCMNs) as a multifunctional nanoplatform for synergistic chemodynamic therapy (CDT)/photothermal therapy (PTT)/photodynamic therapy (PDT). The prepared HCMNs exhibited significant NIR light absorption and photothermal conversion efficiency because of the densely deposited ultra-small sized CuS nanoparticles on the surface of MnO2 nanosheet. They could precisely target the tumor cells and rapidly decomposed into small sized nanostructures in the TME, and then efficiently promote intracellular ROS generation through a series of cascade reactions. Moreover, the local temperature elevation induced by photothermal effect also promote the PDT based on CuS nanoparticles and the Fenton-like reaction of Mn2+, thereby enhancing the therapeutic efficiency. Furthermore, the T1-weighted magnetic resonance (MR) imaging was significantly enhanced by the abundant Mn2+ ions from the decomposition process of HCMNs. In addition, the CDT/PTT/PDT synergistic therapy using a single NIR light source exhibited considerable anti-tumor effect via in vitro cell test. Therefore, the developed HCMNs will provide great potential for MR imaging and multimodal synergistic cancer therapy.


Assuntos
Cobre , Ácido Hialurônico , Imageamento por Ressonância Magnética , Compostos de Manganês , Óxidos , Fotoquimioterapia , Microambiente Tumoral , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Óxidos/química , Óxidos/farmacologia , Humanos , Cobre/química , Cobre/farmacologia , Tamanho da Partícula , Nanoestruturas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Fototerapia , Nanopartículas/química , Sobrevivência Celular/efeitos dos fármacos , Propriedades de Superfície , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Animais
6.
PLoS One ; 19(4): e0300884, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38603698

RESUMO

Human-to-human contact plays a leading role in the transmission of infectious diseases, and the contact pattern between individuals has an important influence on the intensity and trend of disease transmission. In this paper, we define regular contacts and random contacts. Then, taking the COVID-19 outbreak in Yangzhou City, China as an example, we consider age heterogeneity, household structure and two contact patterns to establish discrete dynamic models with switching between daytime and nighttime to depict the transmission mechanism of COVID-19 in population. We studied the changes in the reproduction number with different age groups and household sizes at different stages. The effects of the proportion of two contacts patterns on reproduction number were also studied. Furthermore, taking the final size, the peak value of infected individuals in community and the peak value of quarantine infected individuals and nucleic acid test positive individuals as indicators, we evaluate the impact of the number of random contacts, the duration of the free transmission stage and summer vacation on the spread of the disease. The results show that a series of prevention and control measures taken by the Chinese government in response to the epidemic situation are reasonable and effective, and the young and middle-aged adults (aged 18-59) with household size of 6 have the strongest transmission ability. In addition, the results also indicate that increasing the proportion of random contact is beneficial to the control of the infectious disease in the phase with interventions. This work enriches the content of infectious disease modeling and provides theoretical guidance for the prevention and control of follow-up major infectious diseases.


Assuntos
COVID-19 , Doenças Transmissíveis , Adulto , Pessoa de Meia-Idade , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Quarentena , Surtos de Doenças
7.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1564-1569, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621940

RESUMO

Various separation methods in combination with spectral data analysis, X-ray single crystal diffraction analysis, and litera-ture data comparison were employed to clarify the chemical constituents of Itea yunnanensis. Seven compounds were obtained from I. yunnanensis, which were identified as(S)-3-[1-(4-hydroxyphenyl)propane-2-yl]-4-methoxybenzoate methyl ester(1), iteafuranal B(2), syringaresinol(3), dihydrokaempferol(4), trimethoxybenzene(5), eicosane(6), and nonacosane(7), respectively. Among them, compound 1 was a new nor-neolignan compound named iteanorneoligan A, and the rest of the compounds were identified from I. yunnanensis for the first time. The anti-hepatocellular carcinoma effect of the compound was evaluated based on Sk-hep-1 cells model via MTT assay, and compound 2 showed a significant inhibitory effect on the proliferation of Sk-hep-1 cells with an IC_(50) of 9.4 µmol·L~(-1). The antioxidant capacity was determined via DPPH, ABTS~(·+), and O■ radical scavenging ability, and compound 1 exhibited a significant ABTS~(·+) radical scavenging effect with an IC_(50) of 0.178 mg·mL~(-1).


Assuntos
Lignanas , Estrutura Molecular , Benzotiazóis , Ácidos Sulfônicos , Antioxidantes/farmacologia , Antioxidantes/química
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 325-330, 2024 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-38660894

RESUMO

Medicine is a continuously advancing science, characterized by the integration of multiple disciplines, ultimately focusing on the "human" aspect. Over the past half-century, there has been a global surge in efforts to reshape the humanistic spirit of medicine. Narrative medicine, a field that highly integrates medical professionalism with universal humanistic values, has developed rapidly in China from scratch over the past decade or so. This article introduces the development of narrative medicine both domestically and internationally, explains how to correctly understand the connotation of China's narrative medicine system and the significance of practicing narrative medicine. It analyzes current challenges in clinical practice, education and teaching, scientific research, doctor-patient consensus, and social recognition. Furthermore, it proposes directions for effort, namely, in the context of "greater health" and "new medical science", narrative medicine is empowered to help construct a harmonious medical narrative ecosystem, promote high-quality development in pediatrics, contribute to the innovation in medical education and talent training with humanistic strength and wisdom.


Assuntos
Medicina Narrativa , Pediatria , Pediatria/educação , Humanos
10.
Nat Commun ; 15(1): 2340, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491013

RESUMO

Protein synthesis is frequently deregulated during tumorigenesis. However, the precise contexts of selective translational control and the regulators of such mechanisms in cancer is poorly understood. Here, we uncovered CNOT3, a subunit of the CCR4-NOT complex, as an essential modulator of translation in myeloid leukemia. Elevated CNOT3 expression correlates with unfavorable outcomes in patients with acute myeloid leukemia (AML). CNOT3 depletion induces differentiation and apoptosis and delayed leukemogenesis. Transcriptomic and proteomic profiling uncovers c-MYC as a critical downstream target which is translationally regulated by CNOT3. Global analysis of mRNA features demonstrates that CNOT3 selectively influences expression of target genes in a codon usage dependent manner. Furthermore, CNOT3 associates with the protein network largely consisting of ribosomal proteins and translation elongation factors in leukemia cells. Overall, our work elicits the direct requirement for translation efficiency in tumorigenesis and propose targeting the post-transcriptional circuitry via CNOT3 as a therapeutic vulnerability in AML.


Assuntos
Leucemia Mieloide Aguda , Proteômica , Fatores de Transcrição , Humanos , Carcinogênese/genética , Diferenciação Celular , Leucemia Mieloide Aguda/genética , Receptores CCR4 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
11.
Jpn J Radiol ; 42(5): 536-545, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38316724

RESUMO

AIMS: To investigate the clinical value and performance of [18F]AlF-NOTA-FAPI-04 PET/CT in assessing early-stage liver fibrosis in liver transplantation (LT) recipients. METHODS: A prospective study including 17 LT recipients and 12 chronic Hepatitis B (CHB) patients was conducted. All patients received liver biopsy, transient elastography (TE), and [18F]AlF-NOTA-FAPI-04 PET/CT. On [18F]AlF-NOTA-FAPI-04 PET/CT scans, the liver parenchyma's maximum standardized uptake values (SUVmax) were measured. The receiver operating characteristic (ROC) curve analysis was applied to determine the diagnostic efficacy of [18F]AlF-NOTA-FAPI-04 PET/CT in early-stage liver fibrosis (S1-S2) compared with the diagnostic performance of TE. RESULTS: Among those 29 patients enrolled in this study, 15(51.7%) had fibrosis S0, 10(34.5%) had S1, and 4(13.8%) had S2, respectively. The SUVmax of patients with early-stage liver fibrosis was significantly higher than those without liver fibrosis in LT recipients and CHB patients (P = 0.004, P = 0.02). In LT recipients, a SUVmax cut-off value of 2.0 detected early-stage liver fibrosis with an AUROC of 0.92 (P = 0.006), and a liver stiffness measurements (LSM) score cut-off value of 8.2 kPa diagnosed early-stage liver fibrosis with an AUROC of 0.80 (P = 0.012). In CHB patients, a SUVmax cut-off value of 2.7 detected early-stage liver fibrosis with an AUROC of 0.94 (P < 0.001) and an LSM scores cut-off value of 8.4 kPa diagnosed early-stage liver fibrosis with an AUROC of 0.91 (P < 0.001). CONCLUSION: [18F]AlF-NOTA-FAPI-04 PET/CT could be applied to evaluate early-stage liver fibrosis in LT recipients and CHB patients properly, with the potential additional advantages in monitoring and predicting complications after LT.


Assuntos
Hepatite B Crônica , Cirrose Hepática , Transplante de Fígado , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Masculino , Feminino , Cirrose Hepática/diagnóstico por imagem , Estudos Prospectivos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Hepatite B Crônica/diagnóstico por imagem , Hepatite B Crônica/complicações , Adulto , Técnicas de Imagem por Elasticidade/métodos , Idoso , Fígado/diagnóstico por imagem , Fígado/patologia
12.
Infect Dis Model ; 9(2): 354-372, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38385019

RESUMO

To effectively combat emerging infectious diseases like COVID-19, it is crucial to adopt strict prevention and control measures promptly to effectively contain the spread of the epidemic. In this paper, we propose a transmission model to investigate the influence of two control strategies: reducing contact numbers and improving medical resources. We examine these strategies in terms of constant control and time-varying control. Through sensitivity analysis on two reproduction numbers of the model with constant control, we demonstrate that reducing contact numbers is more effective than improving medical resources. Furthermore, these two constant controls significantly influence the peak values and timing of infections. Specifically, intensifying control measures can reduce peak values, albeit at the expense of delaying the peak time. In the model with time-varying control, we initially explore the corresponding optimal control problem and derive the characteristic expression of optimal control. Subsequently, we utilize real data from January 10th to April 12th, 2020, in Wuhan city as a case study to perform parameter estimation by using our proposed improved algorithm. Our findings illustrate that implementing optimal control measures can effectively reduce infections and deaths, and shorten the duration of the epidemic. Then, we numerically explore that implementing control measures promptly and increasing intensity to reduce contact numbers can make actual control be more closer to optimized control. Finally, we utilize the real data from October 31st to November 18th, 2021, in Hebei province as a second case study to validate the feasibility of our proposed suggestions.

13.
Infect Dis Model ; 9(2): 437-457, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38385020

RESUMO

In this paper, we analyze the global asymptotic behaviors of a mathematical susceptible-infected(SI) age-infection-structured human immunodeficiency virus(HIV) model with heterogeneous transmission. Mathematical analysis shows that the local and global dynamics are completely determined by the basic reproductive number R0. If R0<1, disease-free equilibrium is globally asymptotically stable. If R0>1, it shows that disease-free equilibrium is unstable and the unique endemic equilibrium is globally asymptotically stable. The proofs of global stability utilize Lyapunov functions. Besides, the numerical simulations are illustrated to support these theoretical results and sensitivity analysis of each parameter for R0 is performed by the method of partial rank correlation coefficient(PRCC).

14.
Cancer Res ; 84(10): 1583-1596, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38417135

RESUMO

Patients with primary refractory acute myeloid leukemia (AML) have a dismal long-term prognosis. Elucidating the resistance mechanisms to induction chemotherapy could help identify strategies to improve AML patient outcomes. Herein, we retrospectively analyzed the multiomics data of more than 1,500 AML cases and found that patients with spliceosome mutations had a higher risk of developing refractory disease. RNA splicing analysis revealed that the mis-spliced genes in refractory patients converged on translation-associated pathways, promoted mainly by U2AF1 mutations. Integrative analyses of binding and splicing in AML cell lines substantiated that the splicing perturbations of mRNA translation genes originated from both the loss and gain of mutant U2AF1 binding. In particular, the U2AF1S34F and U2AF1Q157R mutants orchestrated the inclusion of exon 11 (encoding a premature termination codon) in the eukaryotic translation initiation factor 4A2 (EIF4A2). This aberrant inclusion led to reduced eIF4A2 protein expression via nonsense-mediated mRNA decay. Consequently, U2AF1 mutations caused a net decrease in global mRNA translation that induced the integrated stress response (ISR) in AML cells, which was confirmed by single-cell RNA sequencing. The induction of ISR enhanced the ability of AML cells to respond and adapt to stress, contributing to chemoresistance. A pharmacologic inhibitor of ISR, ISRIB, sensitized U2AF1 mutant cells to chemotherapy. These findings highlight a resistance mechanism by which U2AF1 mutations drive chemoresistance and provide a therapeutic approach for AML through targeting the ISR pathway. SIGNIFICANCE: U2AF1 mutations induce the integrated stress response by disrupting splicing of mRNA translation genes that improves AML cell fitness to enable resistance to chemotherapy, which can be targeted to improve AML treatment.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda , Mutação , Fator de Processamento U2AF , Humanos , Fator de Processamento U2AF/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/genética , Splicing de RNA/genética , Animais , Estudos Retrospectivos , Camundongos , Linhagem Celular Tumoral , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo
15.
Birth Defects Res ; 116(3): e2282, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38192201

RESUMO

BACKGROUND: Congenital heart defects (CHDs) are the most common congenital malformation in the world. Recent studies have found that essential and toxic trace element levels may play a crucial role in the risk of neonatal malformation. However, the relationships between element levels in early pregnancy and CHD risk among humans remain unclear. This study investigates the association between maternal essential element (copper [Cu], zinc [Zn], calcium [Ca], manganese [Mg] and iron [Fe]) and toxic element (lead [Pb] and cadmium [Cd]) levels during early pregnancy and CHDs. METHODS: A hospital-based case-control study was conducted, including 181 cases and 218 controls. Eligible participants underwent antenatal examination during gestational weeks 11-14 and trace element levels were detected by the atomic absorption method. Multi-variable logistic regression was used to examine the associations between the level of maternal trace elements and CHD risks. RESULTS: Higher levels of Ca in early pregnancy were associated with lower risk of ASD/VSD risks. Moreover, higher Fe, Pb, and Cd levels in the first trimester were associated with higher risks of all CHD and the subtypes risks, and the tests for trend were significant (all p < .05). The restricted cubic spline analysis showed that there was a nonlinear inverted u-shaped dose-response relationship between levels of Zn, Pb, and Cd in the first trimester and risk of CHDs (non-linearity test p < .05). CONCLUSIONS: A moderate increase in Zn and Ca levels and a decrease in Pb and Cd levels during early pregnancy are needed to reduce the incidence of CHDs in the Chinese population.


Assuntos
Permeabilidade do Canal Arterial , Cardiopatias Congênitas , Comunicação Interatrial , Comunicação Interventricular , Oligoelementos , Recém-Nascido , Gravidez , Feminino , Humanos , Oligoelementos/análise , Cádmio , Permeabilidade do Canal Arterial/complicações , Estudos de Casos e Controles , Chumbo , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/etiologia , Cardiopatias Congênitas/diagnóstico , Comunicação Interventricular/complicações , Comunicação Interatrial/complicações , Zinco
16.
J Gene Med ; 26(1): e3657, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38282150

RESUMO

BACKGROUND: Natural killer (NK) cells are crucial to cancer development and prognosis. However, the role of NK cell-related genes in immunotherapy and the tumor immune microenvironment (TIME) is not well understood. This study aimed to develop reliable risk signatures associated with NK cell-related genes for predicting thyroid cancer (THCA). METHODS: The single-cell RNA sequencing (scRNA-seq) data from seven THCA samples (GSE184362) and bulk-RNA-seq data of 502 THCA patients (TCGA-THCA) were included. The scRNA-seq data was analyzed using the "Seurat" R package to identify differentially expressed genes in NK cells. The clustering analysis was carried out using the R package "ConsensusClusterPlus". The gene set variation analysis (GSVA) algorithm was applied to assess the variations in biological pathways among subtypes. The ESTIMATE algorithm was utilized to calculate the scores for stromal, immune and estimate variables. In addition, we used the single sample Gene Set Enrichment Analysis and CIBERSORT algorithms to assess the degree to which immune cells and pathways related to immunity were enriched based on the meta-cohort. In the TCGA-THCA cohort, the "glmnet" R package was used for the gene selection, and LASSO Cox analysis was used to construct prognostic features. The "maftools" R package was used to examine the somatic mutation landscape of THCA in both low- and high-risk groups. RESULTS: One-hundred and eighty-five NK cell marker genes were screened, and nine genes were associated with the THCA prognosis. KLF2, OSTF1 and TAPBP were finally identified and constructed a risk signature with significant prognostic value. KLF2 and OSTF1 were protective genes, and TAPBP was a risk gene. Patients at high risk had a considerably lower overall survival compared with those at low risk. Mutations in the TCGA-THCA cohort were predominantly C > T. Increased tumor mutation burden (TMB) levels were linked to overall survival. The low-risk H-TMB+ group had a better prognosis, while the high-risk L-TMB+ group had the worst prognosis. CONCLUSION: Natural killer cell-related genes KLF2, OSTF1 and TAPBP were used to develop a novel prognostic risk signature, offering a new perspective on the prognosis and treatment of THCA.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/terapia , Imunoterapia , Células Matadoras Naturais , Algoritmos , Análise por Conglomerados , Microambiente Tumoral/genética
17.
Eur J Med Chem ; 266: 116148, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38237344

RESUMO

Oxidative stress and inflammation responses are closely related to the occurrence and development of many diseases. Therefore, anti-oxidation and anti-inflammation have become hot spots in the treatment of diseases. A series of novel resveratrol derivatives which hybrid with benzoylhydrazines were designed, synthesized and assessed for their in vitro antioxidant and anti-inflammatory activity. Initially, the antioxidant abilities of resveratrol derivatives were investigated by DPPH, ABTS radical scavenging and FRAP assays. RAW 264.7 macrophages are routinely used to evaluate the antioxidant and anti-inflammatory activities of drugs, so we used it to construct cell models of oxidative stress and inflammation. Among all the derivatives, compound 5 exhibited superior ROS- and NO-inhibitory activities. The molecular mechanism detected by Western blotting showed that compound 5 could significantly activate the Nrf2 signaling pathway and up-regulate the expression of HO-1 to resist oxidative stress stimulated by H2O2. At the same time, it could down-regulate the expression of apoptosis-related proteins Caspase3 and PARP, alleviating cells damage and apoptosis. In addition, compound 5 dose-dependently inhibited the activation of NF-κB p65/iNOS and MAPKs signaling pathway.


Assuntos
Antioxidantes , Peróxido de Hidrogênio , Camundongos , Animais , Humanos , Antioxidantes/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Peróxido de Hidrogênio/farmacologia , NF-kappa B/metabolismo , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Estresse Oxidativo , Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo
18.
Environ Res ; 241: 117639, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37972811

RESUMO

In this study, CuFe2O4/CuS composite photocatalysts were successfully synthesized for the activation of peroxynomosulfate to remove ciprofloxacin from wastewater. The structural composition and morphology of the materials were analyzed by XRD, SEM, TEM, and Raman spectroscopy. The electrochemical properties of the samples were tested by an electrochemical workstation. The band gap of the samples was calculated by DFT and compared with the experimental values. The effects of different catalysts, oxidant PMS concentrations, and coexisting ions on the experiments were investigated. The reusability and stability of the photocatalysts were also investigated. The mechanism of the photocatalytic degradation process was proposed based on the free radical trapping experiment. The results show that the p-p heterojunction formed between the two contact surfaces of the CuFe2O4 nanoparticle and CuS promoted the charge transfer between the interfaces and inhibited the recombination of electrons and holes. CuFe2O4-5/CuS photocatalyst has the best catalytic activity, and the removal rate of ciprofloxacin is 93.7%. The intermediates in the degradation process were tested by liquid chromatography-mass spectrometry (LC-MS), and the molecular structure characteristics of ciprofloxacin were analyzed by combining with DFT calculations. The possible degradation pathways of pollutants were proposed. This study reveals the great potential of the photocatalyst CuFe2O4/CuS in the activation of PMS for the degradation of ciprofloxacin wastewater.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Peróxidos/química , Ciprofloxacina , Poluentes Químicos da Água/química , Oxidantes
19.
J Vasc Surg Venous Lymphat Disord ; 12(2): 101678, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37708938

RESUMO

OBJECTIVE: This study aimed to compare the efficacy of customized graduated elastic compression stockings (c-GECSs) based on lower leg parameter models with standard GECSs (s-GECSs) in patients with chronic venous disease (CVD). METHODS: In this randomized, single-blind, controlled trial, 79 patients with stage C2 or C3 CVD were assigned to one of two groups: c-GECSs or s-GECSs. The primary outcome was change to Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) scores at months 1, 3, and 6 as compared with baseline. Secondary outcomes included compliance with wearing ECSs, interface pressure at the smallest circumference of the ankle (point B) and the largest circumference of the calf (point C), and calf volume (CV). RESULTS: There were 13 pairs of s-GECS and 2 pairs of c-GECS that showed pressure values higher than the standard at either point B or C. The c-GECSs were significantly superior to s-GECSs in terms of score improvement at all three time points (month 1, 8.47 [95% confidence interval (CI), 7.47-9.45] vs 5.89 [95% CI, 5.00-6.78]; month 3, 9.60 [95% CI, 8.47-10.72] vs 6.72 [95% CI, 5.62-7.83]; month 6, 7.09 [95% CI, 5.93-8.24] vs 3.92 [95% CI, 2.67-5.18]; P < .0001). Besides, at month 1, the mean daily use time of the c-GECS and s-GECS groups was 10.7 and 9.5 hours, respectively (P < .05). Correlation analysis indicated a negative relationship between local high pressure and daily duration in the s-GECS group (rpb = -0.388; n = 38; P < .05). Variances in pressure were greater in the s-GECSs group. The c-GECSs showed advantage in maintaining pressure. Both c-GECSs and s-GECSs effectively reduced CV (mL), with no significant differences between groups (month 1, 90.0 [95% CI, 71.4-108.5] vs 85.0 [95% CI, 65.6-104.2]; month 3, 93.8 [95% CI, 69.7-117.8] vs 85.9 [95% CI, 65.5-106.2]; month 6, 70.8 [95% CI, 46.5-95.2]) vs 60.8 [95% CI, 44.1-77.5]). CONCLUSIONS: The c-GECSs based on individual leg parameter models significantly improved VEINES-QOL scores and provided stable and enduring pressure as compared with s-GECSs for patients with stage C2 or C3 CVD. Although both c-GECSs and s-GECSs effectively reduced CV, the superior fit and comfort of c-GECSs improved patient compliance. Hence, c-GECSs are a viable alternative for patients who have difficulty tolerating s-GECSs.


Assuntos
Meias de Compressão , Insuficiência Venosa , Humanos , Qualidade de Vida , Método Simples-Cego , Veias , Insuficiência Venosa/terapia , Doença Crônica
20.
Int J Gynaecol Obstet ; 164(1): 324-333, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37597155

RESUMO

OBJECTIVE: To investigate the incidence of isolated distal deep venous thrombosis (IDDVT) concurrent with pulmonary embolism (PE) in gynecologic inpatients, analyze the risk factors for IDDVT with PE, and establish a nomogram model for IDDVT patients with PE. METHODS: A total of 260 patients were diagnosed with IDDVT between December 2017 and November 2020. The incidence of PE in these patients was determined using computed tomography pulmonary angiography. Logistic regression analysis was used to identify the related risk factors. On this basis, nomogram risk prediction models were established. RESULTS: Among 260 patients with IDDVT, 106 (40.8%) had concurrent PE, of whom 74 (28.5%) experienced silent PE. Univariate logistic analysis demonstrated statistical significance for body mass index (BMI; P = 0.044), glucocorticoid therapy (P = 0.009), hypertension (P < 0.001), and diabetes (P < 0.001). Multivariate logistic analysis revealed that these were independent risk factors for IDDVT with PE that retained statistical significance. A nomogram based on these factors was constructed to predict PE in patients with IDDVT. Its receiver operating characteristic (ROC) showed an area under the curve of 0.710 (95% confidence interval 0.642-0.779), with prediction sensitivity of 64.2% and prediction specificity of 76.6%. CONCLUSIONS: In the present study, a high prevalence of PE was found in gynecologic inpatients with IDDVT. Glucocorticoid therapy, hypertension, diabetes, and BMI were independent risk factors for IDDVT patients with PE. Taking these risk factors into account, a nomogram risk prediction model was developed to help facilitate early detection of concurrent PE.


Assuntos
Diabetes Mellitus , Hipertensão , Embolia Pulmonar , Trombose Venosa , Humanos , Feminino , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/epidemiologia , Pacientes Internados , Nomogramas , Glucocorticoides , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/complicações , Fatores de Risco , Hipertensão/complicações
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