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We previously found that the position of matrix attachment regions (MARs) within the vector significantly affects its ability to enhance transgenic expression in the recombinant protein production. This study aims to systematically investigate the position-dependent impacts of MAR on transgene expression. We observed a significant increase in enhanced green fluores-cent protein (eGFP) expression levels in stably transfected CHO-K1 cells with either MAR 1-68 or MAR X-29 when MARs located upstream of the promoter. This increase was especially evident with MAR flanked the expression cassette. Concurrently, a substantial increase was observed in the percentage of eGFP-expressing cells, with 97.8% and 96.0% in MAR-containing constructs versus 73.7% in MAR-absent constructs. Further analysis of erythropoietin (EPO) expression revealed that constructs with flanking MARs induced the highest EPO productivity. Bioinformatics analysis revealed that certain specific transcription factors are important in modulating the transcription process. In conclusion, vectors harboring both MARs around the expression cassette constitute an optimal construct for enhanced recom-binant protein production in CHO-K1 cells. This insight underscores the importance of strate-gic MAR incorporation in vector design for optimized recombinant protein expression.
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PURPOSE: We assessed the effects of tracheostomy timing (early vs. late) on outcomes among adult patients receiving mechanical ventilation. METHODS: PubMed, Embase, Web of Science and Cochrane Library were searched to identify relevant RCTs of tracheotomy timing on patients receiving mechanical ventilation. Two reviewers independently screened the literature, extracted data. Outcomes in patients with early tracheostomy and late tracheostomy groups were compared and analyzed. Meta-analysis was performed using Stata14.0 and RevMan 5.4 software. This study is registered with PROSPERO (CRD42022360319). RESULTS: Twenty-one RCTs were included in this Meta-analysis. The Meta-analysis indicated that early tracheotomy could significantly shorten the duration of mechanical ventilation (MD: -2.77; 95% CI -5.10~ -0.44; P = 0.02) and the length of ICU stay (MD: -6.36; 95% CI -9.84~ -2.88; P = 0.0003), but it did not significantly alter the all-cause mortality (RR 0.86; 95% CI 0.73~1.00; P = 0.06), the incidence of pneumonia (RR 0.86; 95% CI 0.74~1.01; P = 0.06), and length of hospital stay (MD: -3.24; 95% CI -7.99~ 1.52; P = 0.18). CONCLUSION: In patients requiring mechanical ventilation, the tracheostomy performed at an earlier stage may shorten the duration of mechanical ventilation and the length of ICU stay but cannot significantly decrease the all-cause mortality and incidence of pneumonia.
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Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , Traqueotomia , Humanos , Traqueotomia/efeitos adversos , Traqueotomia/métodos , Fatores de Tempo , Unidades de Terapia Intensiva , Traqueostomia/efeitos adversos , Traqueostomia/métodosRESUMO
Hydrogen-bonded organic frameworks (HOFs) are outstanding candidates for photocatalytic hydrogen evolution. However, most of reported HOFs suffer from poor stability and photocatalytic activity in the absence of Pt cocatalyst. Herein, a series of metal HOFs (Co2-HOF-X, X=COOMe, Br, tBu and OMe) have been rationally constructed based on dinuclear cobalt complexes, which exhibit exceptional stability in the presence of strong acid (12â M HCl) and strong base (5â M NaOH) for at least 10â days. More impressively, by varying the -X groups of the dinuclear cobalt complexes, the microenvironment of Co2-HOF-X can be modulated, giving rise to obviously different photocatalytic H2 production rates, following the -X group sequence of -COOMe>-Br>-tBu>-OMe. The optimized Co2-HOF-COOMe shows H2 generation rate up to 12.8â mmol g-1 h-1 in the absence of any additional noble-metal photosensitizers and cocatalysts, which is superior to most reported Pt-assisted photocatalytic systems. Experiments and theoretical calculations reveal that the -X groups grafted on Co2-HOF-X possess different electron-withdrawing ability, thus regulating the electronic structures of Co catalytic centres and proton activation barrier for H2 production, and leading to the distinctly different photocatalytic activity.
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Cotton is highly sensitive to potassium, and Xinjiang, China's leading cotton-producing region, faces a severe challenge due to reduced soil potassium availability. Biofertilizers, particularly potassium-solubilizing rhizobacteria (KSR), convert insoluble potassium into plant-usable forms, offering a sustainable solution for evergreen agriculture. This study isolated and characterized KSR from cotton, elucidated their potassium solubilization mechanisms, and evaluated the effects of inoculating KSR strains on cotton seedlings. Twenty-three KSR strains were isolated from cotton rhizosphere soil using modified Aleksandrov medium. Their solubilizing capacities were assessed in a liquid medium. Strain A10 exhibited the highest potassium solubilization capacity (21.8 ppm) by secreting organic acids such as lactic, citric, acetic, and succinic acid, lowering the pH and facilitating potassium release. A growth curve analysis and potassium solubilization tests of A10 under alkali stress showed its vigorous growth and maintained solubilization ability at pH 8-9, with significant inhibition at pH 10. Furthermore, 16S rRNA sequencing identified strain A10 as Pseudomonas aeruginosa. Greenhouse pot experiments showed that inoculating cotton plants with strain A10 significantly increased plant height and promoted root growth. This inoculation also enhanced dry biomass accumulation in both the aerial parts and root systems of the plants, while reducing the root-shoot ratio. These results suggest that Pseudomonas aeruginosa A10 has potential as a biofertilizer, offering a new strategy for sustainable agriculture.
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Mixed-format tests, which typically include dichotomous items and polytomously scored tasks, are employed to assess a wider range of knowledge and skills. Recent behavioral and educational studies have highlighted their practical importance and methodological developments, particularly within the context of multivariate generalizability theory. However, the diverse response types and complex designs of these tests pose significant analytical challenges when modeling data simultaneously. Current methods often struggle to yield reliable results, either due to the inappropriate treatment of different types of response data separately or the imposition of identical covariates across various response types. Moreover, there are few software packages or programs that offer customized solutions for modeling mixed-format tests, addressing these limitations. This tutorial provides a detailed example of using a Bayesian approach to model data collected from a mixed-format test, comprising multiple-choice questions and free-response tasks. The modeling was conducted using the Stan software within the R programming system, with Stan codes tailored to the structure of the test design, following the principles of multivariate generalizability theory. By further examining the effects of prior distributions in this example, this study demonstrates how the adaptability of Bayesian models to diverse test formats, coupled with their potential for nuanced analysis, can significantly advance the field of psychometric modeling.
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Rice blast, a prevalent and highly destructive rice disease that significantly impacts rice yield, is caused by the rice blast fungus. In the present study, a strain named MTC-8, identified as Bacillus mojavensis, was demonstrated has strong antagonistic activity against the rice blast fungus, Rhizoctonia solani, Ustilaginoidea virens, and Bipolaria maydis. The potential biocontrol agents were identified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis and chromatography. Further investigations elucidated the inhibitory mechanism of the isolated compound and demonstrated its ability to suppress spore germination, alter hyphal morphology, disrupt cell membrane integrity, and induce defense-related gene expression in rice. MTC-8 promoted plant growth and may lead to the development of a biocontrol agent that meets agricultural standards. Overall, the Bacillus mojavensis MTC-8 strain exerted beneficial effects on plant growth, immunity and disease resistance against rice blast fungus. In this study, we isolated and purified a bioactive substance from fermentation broth, and the results provide a foundation for the development and application of biopesticides. Elucidation of the inhibitory mechanism against rice blast fungus provides theoretical support for the identification of molecular targets. The successful development of a biocontrol agent lays the groundwork for its practical application in agriculture.
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In recent years, the importance of long non-coding RNA (lncRNA) in acute myeloid leukemia (AML) has attracted wide attention. Among them, lncRNAs that play a role in promoting cancer mainly include HOTAIR, UCA1, H19, ITGB2-AS1 and some genes of SNHG family, while in tumor suppression mainly include H22954, NEAT1, SNHG4, LINC01128 , etc. This article reviews the role of lncRNAs in the occurrence and development of AML, as well as those related to AML resistance and prognosis assessment, so as to provide a theoretical basis for the diagnosis and prognosis analysis of AML.
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Leucemia Mieloide Aguda , RNA Longo não Codificante , RNA Longo não Codificante/genética , Humanos , Leucemia Mieloide Aguda/genética , PrognósticoRESUMO
PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.
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Terapia Neoadjuvante , Neoplasias Retais , Microambiente Tumoral , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Quimiorradioterapia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the body. Periploca forrestii was a miao ethnic drug in China that was used to treat arthritis for hundreds of years. But, the therapeutic mechanism is so far unknown. Therefore, the chemical component and effect of Periploca forrestii on arthritis in rats were studied using HPLC-QTOF MS, micro-CT, and other experiments in this paper. Method: Male Sprague-Dawley rats were used to assess the in vivo activity. HPLC QTOF-MS was used to analyze the chemical profile of the P. forrestii (PF). Bovine type II collagen and Complete Freund's Adjuvant were used to stimulate and construct the collagen-induced arthritis (CIA) model. Three dosages of PF (100 mg/kg, 200 mg/kg, 400 mg/kg) were used to evaluate in vivo activity. Methotrexate was used as the positive drug. H/E staining and micro-CT methods were used to monitor the pathological changes of CIA rats. ELISA method was used to assess the serum level of immune- and inflammation-related cytokines. Immunohistochemical experiments were used to test the gene expression in JAK and Nf-κB pathways. Results: 42 compounds were identified from PF. PF administration lowered the increased spleen index compared with that of control and MTX groups, and partially restored body weight, reduced paw swelling, and arthritis score compared with the model group. Macroscopic assessment indicated inflamed paw with significant swelling in the model group, while the extent of inflammation and swelling was attenuated by both MTX and PF. H/E staining experiments demonstrated that pathological changes of synovial cells and infiltration of inflammatory cells were observed in the model group. In contrast, the MTX and PF treatment partially reversed these pathological changes. Micro-CT examination showed severe injuries and scars caused by inflammation for the model group, and in the high-dosage group (400 mg/kg) the inflammation-caused injuries and scars were dramatically ameliorated. Mechanism study showed that PF restored Nf-κB phosphorylation and JAK2 expression compared with the model group. Conclusion: P. forrestii possesses a potent effect on CIA rats. Nf-κB and JAK2 pathways are involved in its protective effect on CIA.
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This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1ß), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1ß, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1ß, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1ß, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.
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Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Ciclo-Oxigenase 2 , Fígado , NF-kappa B , Panax , Saponinas , Transdução de Sinais , Animais , Acetaminofen/efeitos adversos , Acetaminofen/toxicidade , Camundongos , Panax/química , Masculino , Saponinas/farmacologia , Saponinas/administração & dosagem , NF-kappa B/genética , NF-kappa B/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Transdução de Sinais/efeitos dos fármacos , Humanos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
Balanophora harlandii Hook (B. harlandii), a folk medicine, has been traditionally employed to treat traumatic bleeding, gastroenteritis, icteric hepatitis, hemorrhoids, and other conditions. In this work, polysaccharides with anti-inflammatory effects were extracted from B. harlandii and purified. The extraction conditions were optimized, and the properties of one purified neutral fraction, denoted as BHPs-W-S3, were analyzed. BHPs-W-S3 has a molecular weight of 14.1â¯kDa, and its three main monosaccharides are glucose, galactose, and xylose, with a molar ratio of 6.4:1.7:1.1. Its main chain consists of â6)-α-D-Glcp-(1â, â4,6)-α-D-Glcp-(1â, â6)-ß-D-Galp-(1â, â3,6)-ß-D-Galp-(1â, and it has branch chains at the O-4 and/or O-3 positions. In addition, in vitro experiments showed that the polysaccharides from B. harlandi can decrease the phosphorylation level of p65 and IκBα in LPS-induced RAW264.7 cells to reduce the expression of the pro-inflammatory genes such as TNF-α, IL-6, and IL-1ß.
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Anti-Inflamatórios , Polissacarídeos , Camundongos , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Células RAW 264.7 , Peso Molecular , Balanophoraceae/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Inflamação/tratamento farmacológicoRESUMO
The coastal aquaculture areas have been subject to a variety of anthropogenic pressures in recent studies, and reasonable environmental quality assessment is essential for both ecological conservation and production practices. However, there are significant differences between the results produced from various environmental quality assessment regarding the focus of the evaluation and the fundamental methodology. Furthermore, many of these methods are very specific and difficult to adapt to general applications. Here, we utilized the Modelling-Ongrowing fish farms-Monitoring B investigation system (MOM-B), we assessed the benthic habitat quality of benthic bivalve aquaculture areas in the Xiaoqing River estuary located in Laizhou Bay, China. The aim was to validate the accuracy and practicality of this system. The biological, chemical, and sensory parameters of the MOM-B system, temperature, chlorophyll a (Chl-a), food availability, and planktonic larvae were evaluated throughout the investigation area during the summer of 2021. The MOM-B results indicated that the benthic habitat quality in the survey area was good and lightly disturbed, but the quality in the middle tide area began to deteriorate in August, the hottest month of the summer. Environmental factors indicated that the combined effects of high temperatures and fine sedimentation had led to increased environmental stress in the middle tide area. Food availability and population recruitment also suggested that the benthic habitat quality was better in the high tide and low tide areas than in the middle tide area, and more favorable for the survival of Manila clams. The accuracy, sensitivity, and discriminatory ability of the MOM-B system were demonstrated by environmental and biological indicators. This work showed that the MOM-B system is a practical, simple, and sensitive environmental assessment tool that is easy to implement in estuarine and benthic bivalve aquaculture areas. It can be used for long-term continuous monitoring and as an early warning tool for benthic habitat quality.
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Aquicultura , Bivalves , Ecossistema , Monitoramento Ambiental , Animais , Bivalves/fisiologia , Monitoramento Ambiental/métodos , China , EstuáriosRESUMO
Screening for eating disorders (EDs) is an essential part of the prevention and intervention of EDs. Traditional screening methods mostly rely on predefined cutoff scores which have limitations of generalizability and may produce biased results when the cutoff scores are used in populations where the instruments or cutoff scores have not been validated. Compared to the traditional cutoff score approach, the diagnostic classification modeling (DCM) approach can provide psychometric and classification information simultaneously and has been used for diagnosing mental disorders. In the present study, we introduce DCM as an innovative and alternative approach to screening individuals at risk of EDs. To illustrate the practical utility of DCM, we provide two examples: one involving the application of DCM to examine probable ED status from the 12-item Short form of the Eating Disorder Examination-Questionnaire (EDE-QS) to screen probable thinness-oriented EDs and the Muscularity-Oriented Eating Test (MOET) to screen probable muscularity-oriented EDs.
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Seed germination is an important development process in plant growth. The phytohormone abscisic acid (ABA) plays a critical role during seed germination. However, the mechanism of rapeseed in response to ABA is still elusive. In order to understand changes of rapeseed under exogenous ABA treatment, we explored differentially expressed metabolites (DEMs) and the differentially expressed genes (DEGs) between mock- and ABA-treated seedlings. A widely targeted LC-MS/MS based metabolomics were used to identify and quantify metabolic changes in response to ABA during seed germination, and a total of 186 significantly DEMs were identified. There are many compounds which are involved in ABA stimuli, especially some specific ABA transportation-related metabolites such as starches and lipids were screened out. Meanwhile, a total of 4440 significantly DEGs were identified by transcriptomic analyses. There was a significant enrichment of DEGs related to phenylpropanoid and cell wall organization. It suggests that exogenous ABA mainly affects seed germination by regulating cell wall loosening. Finally, the correlation analysis of the key DEMs and DEGs indicates that many DEGs play a direct or indirect regulatory role in DEMs metabolism. The integrative analysis between DEGs and DEMs suggests that the starch and sucrose pathways were the key pathway in ABA responses. The two metabolites from starch and sucrose pathways, levan and cellobiose, both were found significantly down-regulated in ABA-treated seedlings. These comprehensive metabolic and transcript analyses provide useful information for the subsequent post-transcriptional modification and post germination growth of rapeseed in response to ABA signals and stresses.
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Brassica napus , Brassica rapa , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Plântula/metabolismo , Brassica napus/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Perfilação da Expressão Gênica , Germinação/genética , Brassica rapa/metabolismo , Metaboloma , Amido/metabolismo , Sacarose/metabolismo , Sementes , Regulação da Expressão Gênica de Plantas , TranscriptomaRESUMO
BACKGROUND: In recent years, Raoultella ornithinolytica (R. ornithinolytica) have attracted clinical attention as a new type of pathogen. A wide range of infections with these germs is reported, and commonly found in urinary tract infections, respiratory infections, and bacteremia. CASE PRESENTATION: We report the case of an elderly woman with liver abscess, choledocholithiasis and cholangitis, who developed gastric fistula and abdominal abscess after underwent choledocholithotomy, and R. ornithinolytica were isolated from the abdominal drainage fluid. The patient was treated with meropenem and levofloxacin and had a good outcome. CONCLUSIONS: To the best of our knowledge, case of isolating R. ornithinolytica from a patient with non-viscerally abdominal abscess was extremely rare. We share a case of a woman with non-viscerally abdominal abscess secondary to postoperative gastric fistula, R. ornithinolytica was isolated from the patient's pus, and the pathogenic bacteria may originate from the gastrointestinal tract. Based on this case, We should be cautious that invasive treatment may greatly increase the probability of infection with this pathogenic bacterium.
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Infecções por Enterobacteriaceae , Fístula Gástrica , Abscesso Hepático , Feminino , Humanos , Idoso , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/complicações , Fístula Gástrica/complicações , Enterobacteriaceae , Complicações Pós-Operatórias/tratamento farmacológico , Abscesso Hepático/complicaçõesRESUMO
BACKGROUND: Tumor metastasis and recurrence are major causes of mortality in patients with hepatocellular carcinoma (HCC) that is still lack of effective therapeutic targets and drugs. Previous reports implied that ras homolog family member C (RhoC) plays a toxic role on metastasis and proliferation of cancer. METHODS: In this research, the correlation between RhoC and metastasis ability was confirmed by in vitro experiments and TCGA database. We explored whether quercetin could inhibit cell migration or invasion by transwell assay. Real-time PCR, overexpression and ubiquitination assay, etc. were applied in mechanism study. Primary HCC cells and animal models including patient-derived xenografts (PDXs) were employed to evaluate the anti-metastasis effects of quercetin. RESULTS: Clinical relevance and in vitro experiments further confirmed the level of RhoC was positively correlated with invasion and metastasis ability of HCC. Then we uncovered that quercetin could attenuate invasion and metastasis of HCC by downregulating RhoC's level in vitro, in vivo and PDXs. Furthermore, mechanistic investigations displayed quercetin hindered the E3 ligase expression of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) leading to enhancement of RhoC's ubiquitination and proteasomal degradation. CONCLUSIONS: Our research has revealed the novel mechanisms quercetin regulates degradation of RhoC level by targeting SMURF2 and identified quercetin may be a potential compound for HCC therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Quercetina/farmacologia , Invasividade Neoplásica/genética , Proteína de Ligação a GTP rhoC/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Mercury (Hg) pollution not only poses a threat to the environment but also adversely affects the growth and development of plants, with potential repercussions for animals and humans through bioaccumulation in the food chain. Maize, a crucial source of food, industrial materials, and livestock feed, requires special attention in understanding the genetic factors influencing mercury accumulation. Developing maize varieties with low mercury accumulation is vital for both maize production and human health. In this study, a comprehensive genome-wide association study (GWAS) was conducted using an enlarged SNP panel comprising 1.25 million single nucleotide polymorphisms (SNPs) in 230 maize inbred lines across three environments. The analysis identified 111 significant SNPs within 78 quantitative trait loci (QTL), involving 169 candidate genes under the Q model. Compared to the previous study, the increased marker density and optimized statistical model led to the discovery of 74 additional QTL, demonstrating improved statistical power. Gene ontology (GO) enrichment analysis revealed that most genes participate in arsenate reduction and stress responses. Notably, GRMZM2G440968, which has been reported in previous studies, is associated with the significant SNP chr6.S_155668107 in axis tissue. It encodes a cysteine proteinase inhibitor, implying its potential role in mitigating mercury toxicity by inhibiting cysteine. Haplotype analyses provided further insights, indicating that lines carrying hap3 exhibited the lowest mercury content compared to other haplotypes. In summary, our study significantly enhances the statistical power of GWAS, identifying additional genes related to mercury accumulation and metabolism. These findings offer valuable insights into unraveling the genetic basis of mercury content in maize and contribute to the development of maize varieties with low mercury accumulation.
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Mercúrio , Locos de Características Quantitativas , Humanos , Mapeamento Cromossômico , Zea mays/genética , Zea mays/metabolismo , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla , Mercúrio/toxicidade , Mercúrio/metabolismo , FenótipoRESUMO
The Intuitive Eating Scale-2 (IES-2) is a measure of intuitive eating behaviors that has been extensively validated, with traditional latent variable modeling approaches, in youth and adults from many different populations, including college students in China. However, there is still a lack of research on the psychometric properties of the IES-2 in adults from the Chinese general population. Moreover, psychometric network analysis, as a complement to traditional latent variable modeling approaches, has not been used for examining the psychometric properties of the IES-2. Thus, the present study used a psychometric network approach to evaluate the psychometric properties of the IES-2 in Chinese adults from the general population. A sample of 700 Chinese general adults (50% women; Mage = 31.13 years, SD = 9.19) recruited online were included in the present study. Psychometric network analysis was performed. Exploratory graph analysis (EGA) identified four dimensions, which were well separated in the estimated network. The network structure showed excellent stability and metric measurement invariance (i.e., network loadings) across men and women. Furthermore, several items on the IES-2 were identified as key nodes in the network of the IES-2 that may be important for the development and maintenance of intuitive eating. For example, two items (i.e., "I trust my body to tell me when to eat," and "I trust my body to tell me when to stop eating") related to reliance on body cues were the most impactful nodes in the complete network. The findings of our study provide a greater understanding of the IES-2 from the perspective of network analysis and have implications for applications of intuitive eating interventions for general populations.
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Comportamento Alimentar , Intuição , Psicometria , Adulto , Feminino , Humanos , Masculino , Inquéritos e Questionários , População do Leste Asiático , Adulto JovemRESUMO
Hypotonia, Ataxia, Developmental Delay, and Tooth Enamel Defect Syndrome (HADDTS) is an exceptionally rare disorder resulting from a heterozygous variant in the C-terminal binding protein 1 (CTBP1) gene. To date, a mere two variants (14 patients) have been documented on a global scale. The aim of this study was to identify a causative CTBP1 variant in a Chinese patient, and to determine the potential pathogenicity of the identified variant. Here, Whole-exome sequencing (WES) was conducted on the proband to pinpoint the candidate variant. Following this, Sanger sequencing was employed to validate the identified candidate variant and examine its co-segregation within the available family members. Employing both in silico prediction and three-dimensional protein modeling, we conducted an analysis to assess the potential functional implications of the variant on the encoded protein. Our investigation led to the identification of a novel heterozygous variant in the CTBP1 gene, namely, c.371 C>T (p.Ser124Phe), in a Chinese patient. This case represents the first confirmed instance of such a variant in a Chinese patient. When comparing the patient's clinical symptoms with those reported in the literature, notable distinctions were observed between her primary symptoms and those associated with HADDTS. She showed other signs such as microcephaly, coarse facial features, single transverse palmar crease, visible beard, myopia, coarse toenail and skeletal anomalies. This study enriching the spectrum of genetic variants observed in different ethnic populations and expanding the phenotypic profile associated with this gene. These findings are expected to contribute to the enhancement of future variant-based screening and genetic diagnosis, while also providing further insights into the pathogenic mechanisms underlying CTBP1-related conditions.
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Our prophase studies have manifested that the sweet triterpenoid glycoside from the leaves of Cyclocarya paliurus (CPST) effectively improved the disorders of glucolipid metabolism in vitro and in patients. The current purpose was to further detect its mechanisms involved. The results demonstrated that CPST could ameliorate high-fat diet (HFD)-induced insulin resistance (IR), which was linked to reducing HFD-induced mice's body weight, serum glucose (GLUO), triglyceride (TG), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C), lowering the area under the oral glucose tolerance curve and insulin tolerance, elevating the percentage of brown adipose, high-density lipoprotein cholesterol (HDL-C), reducing fat droplets of adipocytes in interscapular brown adipose tissue (iBAT) and cross-sectional area of adipocytes. Further studies manifested that CPST obviously downregulated TLR4, MyD88, NLRP3, ASC, caspase-1, cleased-caspase-1, IL-18, IL-1ß, TXNIP, and GSDMD protein expressions and p-NF-кB/NF-кB ratio in iBAT. These aforementioned findings demonstrated that CPST ameliorated HFD induced IR by regulating TLR4/NF-κB/NLRP3 signaling pathway, which in turn enhancing insulin sensitivity and glucose metabolism.