RESUMO
A multi-stage oxic biofilm system based on hydrophilic polyurethane foam was established and operated for advanced treatment of coking wastewater, in which distinct gradient variations of pollutants removal, biofilm properties and microbial community in the 5 stages were evaluated. The system rapidly achieved NH+4-N removal efficiency of 97.51⯱â¯2.29â¯% within 8â¯days. The biofilm growing attached on the carriers exhibited high biomass (≥10.29â¯g/L), which ensured sufficient microbial population. Additionally, the rising extracellular polymeric substance and declining proteins/polysaccharides ratios across stages suggested a dense-to-loose transition in the biofilm's structure, in response to the varying pollutant concentrations. The dominance of Nitrosomonas cluster in the first 3 stages and Nitrospira lineage in the following 2 stages facilitated the complete depletion of high NH+4-N concentration without NO- 2-N accumulation. Overall, the distinct biofilm property and community at each stage, shaped by the multi-stage configuration, maximized the pollutants removal efficiency.
RESUMO
Recent advancements in natural language processing, computational linguistics, and Artificial Intelligence (AI) have propelled the use of Large Language Models (LLMs) in Automated Essay Scoring (AES), offering efficient and unbiased writing assessment. This study assesses the reliability of LLMs in AES tasks, focusing on scoring consistency and alignment with human raters. We explore the impact of prompt engineering, temperature settings, and multi-level rating dimensions on the scoring performance of LLMs. Results indicate that prompt engineering significantly affects the reliability of LLMs, with GPT-4 showing marked improvement over GPT-3.5 and Claude 2, achieving 112% and 114% increase in scoring accuracy under the criteria and sample-referenced justification prompt. Temperature settings also influence the output consistency of LLMs, with lower temperatures producing scores more in line with human evaluations, which is essential for maintaining fairness in large-scale assessment. Regarding multi-dimensional writing assessment, results indicate that GPT-4 performs well in dimensions regarding Ideas (QWK=0.551) and Organization (QWK=0.584) under well-crafted prompt engineering. These findings pave the way for a comprehensive exploration of LLMs' broader educational implications, offering insights into their capability to refine and potentially transform writing instruction, assessment, and the delivery of diagnostic and personalized feedback in the AI-powered educational age. While this study attached importance to the reliability and alignment of LLM-powered multi-dimensional AES, future research should broaden its scope to encompass diverse writing genres and a more extensive sample from varied backgrounds.
RESUMO
OBJECTIVE: To investigate the role of curcumin in the treatment of lupus nephritis (LN) by inhibiting the migration of neutrophils and the underlying mechanism involved. METHODS: Two lupus mouse models, MRL/lpr mice and R848-treated mice, were treated with 50 mg/kg curcumin by intraperitoneal injection. H&E and Masson staining were used to estimate histopathological changes in the kidney. Immunofluorescence was used to assess the deposition of immune complexes. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription polymerase reaction (RT-PCR), and the protein expression was detected by western blotting. RESULTS: We revealed the remarkable potential of curcumin in improving inflammatory conditions in both MRL/lpr mice and R848-induced lupus mice. Curcumin effectively decelerates the progression of inflammation and diminishes the infiltration of neutrophils and their release of pivotal inflammatory factors, thereby reducing inflammation in renal tissues. Mechanistically, curcumin significantly inhibits the expression of p-PI3K, p-AKT and p-NF-κB, which are upregulated by interleukin-8 to induce neutrophil migration and renal inflammation, thereby reducing neutrophil migration and the release of inflammatory factors. CONCLUSION: Curcumin significantly inhibits the recruitment of neutrophils and the release of proinflammatory factors in the kidney by inhibiting the PI3K/AKT/NF-κB signalling pathway, providing new therapeutic targets and medication strategies for the treatment of LN.
Assuntos
Movimento Celular , Curcumina , Nefrite Lúpica , NF-kappa B , Neutrófilos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Curcumina/farmacologia , Curcumina/uso terapêutico , Animais , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/imunologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/imunologia , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos , Movimento Celular/efeitos dos fármacos , Feminino , Modelos Animais de Doenças , Camundongos Endogâmicos MRL lpr , Rim/efeitos dos fármacos , Rim/patologiaRESUMO
Moving computation units closer to sensors is becoming a promising approach to addressing bottlenecks in computing speed, power consumption, and data storage. Pre-sensor computing with optical neural networks (ONNs) allows extensive processing. However, the lack of nonlinear activation and dependence on laser input limits the computational capacity, practicality, and scalability. A compact and passive multilayer ONN (MONN) is proposed, which has two convolution layers and an inserted nonlinear layer, performing pre-sensor computations with designed passive masks and a quantum dot film for incoherent light. MONN has an optical length as short as 5 millimeters, two orders of magnitude smaller than state-of-the-art lens-based ONNs. MONN outperforms linear single-layer ONN across various vision tasks, off-loading up to 95% of computationally expensive operations into optics from electronics. Motivated by MONN, a paradigm is emerging for mobile vision, fulfilling the demands for practicality, miniaturization, and low power consumption.
RESUMO
To learn more about the nutritional composition and health benefits for human consumers of peas, we used a widely targeted metabolomics-based approach to reveal the metabolite components from three main varieties, and a total of 1095 metabolites were identified. A comparison of 487 differentially accumulated metabolites shared among three varieties of fresh and dried peas found most of the amino acids and derivatives were downregulated and most of the lipids and flavonoids were upregulated in dried peas. Furthermore, comparing the main nutrient profiles exclusively showed that there were few differences in free fatty acids, sugars, vitamins, and alkaloids between dried and fresh peas. Peas are especially enriched with B-group vitamins. Through detailed identification and classification, the flavonoid pathway of peas was revealed; a variety of glycosylated derivatives from kaempferol, quercetin, and luteolin were confirmed to be abundant in peas. It was also found that isoflavones are richer in peas than in many other plants, and putatively the isoflavone synthesis pathway originates from liquiritigenin and naringenin. Our study not only offers guidance for understanding the nutritional components of peas, but also provides the basis for healthy diet analysis of the edible value and health benefits of peas.
RESUMO
Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.
RESUMO
OBJECTIVE: The purpose of this study was to analyze the independent risk factors of malignant subpleural pulmonary lesions (SPLs) on B-mode ultrasound (US) images, to construct the combined predictive indicators, and to prospectively verify their predictive efficacy. METHODS: A total of 336 patients with SPLs were included in the prospective study, of whom the single-center included patients between September 2019 and December 2019 were the development cohort (DC) (n = 219); Patients who were concurrently enrolled in three centers between January and February 2020 were the validation cohort (VC) (n = 117). The clinical features and B-mode US parameters were collected. Based on the DC, a combined predictive indicators model was developed using binary logistic regression. Then the discrimination was verified externally in the VC. The reference criteria were from the comprehensive diagnosis of clinical-radiological-pathological made by two senior respiratory physicians. RESULTS: The combined predictive indicators model was finally constructed by five parameters: age, borderline, angle between the lesion border and thoracic wall, posterior echo of the lesion and invasion of the pleura. The fitting degree of the model was good (χ2 = 9.198, p = 0.326). The area under ROC curve of the model was 0.872 (DC) and 0.808 (VC), yielding a higher net benefit than individual risk factors. CONCLUSION: The combined predictive indicators are useful in the assessment of malignant SPLs and are a useful adjunct diagnostic tool, especially in primary healthcare settings in developing countries.
RESUMO
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile women. Currently, glucocorticoids and immunosuppressants are widely used to treat SLE patients. However, ovarian dysfunction occurs following the use of these drugs in women with SLE. Here, we summarize recent progress in terms of understanding ovarian injury, the effects of drug application and strategies to improve ovarian function in women with SLE. This review could be helpful to precisely cure SLE in women desiring to have offspring.
RESUMO
MXene usually exhibits weak pseudo-capacitance behavior in aqueous zinc-ion batteries, which cannot provide sufficient reversible capacity, resulting in the decline of overall capacity when used as the cathode materials. Taking inspiration from polymer electrolyte engineering, we have conceptualized an in situ induced growth strategy based on MXene materials. Herein, 5.25 % MXene was introduced into the nucleation and growth process of vanadium oxide (HVO), providing the heterogeneous nucleation site and serving as an initiator to regulate the morphology and structural of vanadium oxide (T-HVO). The resulted materials can significantly improve the capacity and rate performance of zinc-ion batteries. The growth mechanism of T-HVO was demonstrated by both characterizations and DFT simulations, and the improved performance was systematically investigated through a series of in situ experiments related to dynamic analysis steps. Finally, the evaluation and comparison of various defect introduction strategies revealed the efficient, safety, and high production output characteristics of the in situ induced growth strategy. This work proposes the concept of in situ induced growth strategy and discloses the induced chemical mechanism of MXene materials, which will aid the understanding, development, and application of cathode in aqueous zinc-ion batteries.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia as a major health issue has attracted much public attention. As a geographical indication product of China, Liupao tea (LPT) is a typical representative of traditional Chinese dark tea that has shown good potential in regulating glucose and lipid metabolism. LPT has important medicinal value in hyperlipidemia prevention. However, the active ingredients and metabolic mechanisms by which LPT alleviates hyperlipidemia remain unclear. AIM OF THE STUDY: This study aimed to systematically investigate the metabolic mechanisms and active ingredients of LPT extract in alleviating hyperlipidemia. MATERIALS AND METHODS: Firstly, we developed a mouse model of hyperlipidemia to study the pharmacodynamics of LPT. Subsequently, network pharmacology and molecular docking were performed to predict the potential key active ingredients and core targets of LPT against hyperlipidemia. LC-MS/MS was used to validate the identity of key active ingredients in LPT with chemical standards. Finally, the effect and metabolic mechanisms of LPT extract in alleviating hyperlipidemia were investigated by integrating metabolomic, lipidomic, and gut microbiome analyses. RESULTS: Results showed that LPT extract effectively improved hyperlipidemia by suppressing weight gain, remedying dysregulation of glucose and lipid metabolism, and reducing hepatic damage. Network pharmacology analysis and molecular docking suggested that four potential active ingredients and seven potential core targets were closely associated with roles for hyperlipidemia treatment. Ellagic acid, catechin, and naringenin were considered to be the key active ingredients of LPT alleviating hyperlipidemia. Additionally, LPT extract modulated the mRNA expression levels of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 associated with bile acid (BA) metabolism, mitigated the disturbances of BA and glycerophospholipid (GP) metabolism in hyperlipidemia mice. Combining fecal microbiota transplantation and correlation analysis, LPT extract effectively improved species diversity and abundance of gut microbiota, particularly the BA and GP metabolism-related gut microbiota, in the hyperlipidemia mice. CONCLUSIONS: LPT extract ameliorated hyperlipidemia by modulating GP and BA metabolism by regulating Lactobacillus and Dubosiella, thereby alleviating hyperlipidemia. Three active ingredients of LPT served as the key factors in exerting an improvement on hyperlipidemia. These findings provide new insights into the active ingredients and metabolic mechanisms of LPT in improving hyperlipidemia, suggesting that LPT can be used to prevent and therapeutic hyperlipidemia.
Assuntos
Microbioma Gastrointestinal , Hiperlipidemias , Simulação de Acoplamento Molecular , Chá , Animais , Hiperlipidemias/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos , Chá/química , Biologia Computacional , Farmacologia em Rede , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Camundongos Endogâmicos C57BL , Metabolismo dos Lipídeos/efeitos dos fármacos , Hipolipemiantes/farmacologia , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/uso terapêutico , Modelos Animais de Doenças , Metabolômica , MultiômicaRESUMO
Objective: There is no study on the relationship between triglyceride-glucose index (TyG index) and skeletal muscle mass in middle-aged and elderly C population. Therefore, the aim of the study is to investigate the relationship between the TyG index and weight-adjusted relative skeletal muscle index (RSMI) in middle-aged and elderly C population. Methods: We retrospectively studied 947 aged ⩾40 years subjects who got a routine medical examination in the Department of Geriatrics of R Hospital from May 2021 to March 2023. The RSMI was designed to evaluate skeletal muscle mass and calculated based on lean mass of the limbs(kg)/body weight(kg) × 100%. Skeletal muscle mass reduction was defined as a RSMI of 1-2 standard deviations (SD) below of healthy adults aged 30-49 years old. Considering the quartile groups of the TyG index, the subjects were assigned to 4 groups: Q1 (less than or equal to 8.171), Q2 (from 8.172 to 8.569), Q3 (from 8.570 to 8.992), and Q4 (greater than or equal to 8.993). Results: With TyG index increased, RSMI levels significantly reduced(P < .001). Spearman's correlation analysis showed that the TyG index was negatively correlated with RSMI in males (r = -0.320) and females (r = -0.240). The TyG index was positively correlated with body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) (P < .05). Besides, binary logistic regression analysis showed that the risk of developing reduced skeletal muscle mass in the group Q4 was 2.131 (95%CI:1.118-4.064) in males; and was 2.472 (95%CI:1.581-3.867) in females compared to the Q1 group. Conclusion: TyG index was negatively correlated with relative skeletal muscle index, and a higher TyG index was associated with the development of reduced skeletal muscle mass independently of other influencing factors. Therefore, the TyG index promises to be a predictor of skeletal muscle mass loss.
RESUMO
What we believe to be a novel reconfigurable multi-channel microwave photonic (MWP) receiver for multi-band RF signal is demonstrated for the first time, to the best of our knowledge. A reconfigurable MWP signal processing chip based on two cascaded microring filter banks is employed in the proposed receiver, which slices the multi-band RF input into several narrow band signals and selects optical frequency comb lines for frequency converting of each channel. Due to the significant reconfigurability of the signal processing chip, the proposed receiver can flexibly choose the output frequency band of each channel, and thus different frequency components of the multi-band RF input can be down converted to the intermediate frequency (IF) band for receiving or converted to other frequency band for forwarding. A multi-band RF signal composed of a linear frequency modulation (LFM) signal with 2 GHz bandwidth and a quad-phase shift keyed (QPSK) signal with 100 Mbit/s rate is experimentally received and reconstructed by the proposed receiver, where the reconstructed LFM component exhibits a signal to noise ratio (SNR) of 10.2 dB, and the reconstructed QPSK component reaches a high SNR of 26.1 dB and a great error vector magnitude (EVM) of 11.73%. On the other hand, the QPSK component of the multi-band RF signal centered at 13.5 GHz is successfully converted to 3.1 GHz.
RESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) poses a significant global public health concern. Liupao tea (LPT) is a Chinese national geographical indication product renowned for its lipid-lowering properties. However, the precise mechanisms and active constituents contributing to the efficacy of LPT against NAFLD remain unclear. PURPOSE: This study aims to comprehensively explore the therapeutic potential of Liupao tea extract (LPTE) in alleviating NAFLD through an integrated strategy. METHODS: Initially, network pharmacology analysis was conducted based on LPTE chemical ingredient analysis, identifying core targets and key components. Potential active ingredients were validated through chemical standards based on LC-MS/MS. To confirm the pharmacological efficacy of LPTE in NAFLD, NAFLD mice models were employed. Alterations in hepatic lipid metabolism were comprehensively elucidated through integration of metabolomics, lipidomics, network pharmacology analysis, and real-time PCR analysis. To further explore the binding interactions between key components and core targets, molecular docking and microscale thermophoresis (MST) analysis were employed. Furthermore, to investigate LPTE administration effectiveness on gut microbiota in NAFLD mice, a comprehensive approach was employed. This included Metorigin analysis, 16S rRNA sequencing, molecular docking, and fecal microbiome transplantation (FMT). RESULTS: Study identified naringenin, quercetin, luteolin, and kaempferol as the potential active ingredients of LPTE. These compounds exhibited therapeutic potential for NAFLD by targeting key proteins such as PTGS2, CYP3A4, and ACHE, which are involved in the metabolic pathways of hepatic linoleic acid (LA) and glycerophospholipid (GP) metabolism. The therapeutic effectiveness of LPTE was observed to be comparable to that of simvastatin. Furthermore, LPTE exhibited notable efficacy in alleviating NAFLD by influencing alterations in gut microbiota composition (Proteobacteria phylum, Lactobacillus and Dubosiella genus) that perhaps impact LA and GP metabolic pathways. CONCLUSION: LPTE could be effective in preventing high-fat diet (HFD)-induced NAFLD by modulating hepatic lipid metabolism and gut microbiota. This study firstly integrated bioinformatics and multi-omics technologies to identify the potential active components and key microbiota associated with LPTE's effects, while also primally elucidating the action mechanisms of LPTE in alleviating NAFLD. The findings offer a conceptual basis for LPTE's potential transformation into an innovative pharmaceutical agent for NAFLD prevention.
RESUMO
Probiotic biofilms have been beneficial in the fight against infections, restoring the equilibrium of the host's gut microbiota, and enhancing host health. They are considered a novel strategy for probiotic gut colonization. In this case, we evaluated the effects of various active substances from traditional Chinese medicine on Escherichia coli Nissle 1917 (EcN) to determine if they promote biofilm formation. It was shown that 8-64 µg/mL of oleanolic acid increased the development of EcN biofilm. Additionally, we observed that oleanolic acid can effectively suppress biofilm formation in pathogenic bacteria such as Salmonella and Staphylococcus aureus. Next, we assessed the amount of EcN extracellular polysaccharides, the number of live bacteria, their metabolic activity, the hydrophobicity of their surface, and the shape of their biofilms using laser confocal microscopy. Through transcriptome analysis, a total of 349 differentially expressed genes were identified, comprising 134 upregulated and 215 downregulated genes. GO functional enrichment analysis and KEGG pathway enrichment analysis revealed that oleanolic acid functions are through the regulation of bacterial motility, the iron absorption system, the two-component system, and adhesion pathways. These findings suggest that the main effects of oleanolic acid are to prevent bacterial motility, increase initial adhesion, and encourage the development of EcN biofilms. In addition, oleanolic acid interacts with iron absorption to cooperatively control the production of EcN biofilms within an optimal concentration range. Taking these results together, this study suggests that oleanolic acid may enhance probiotic biofilm formation in the intestines, presenting new avenues for probiotic product development.
RESUMO
Cytosolic Glycerol-3-phosphate dehydrogenase 1 (GPD1, EC 1.1.1.8) plays a pivotal role in regulating the Embden-Meyerhof glucose glycolysis pathway (E-M pathway), as well as in conditions such as Huntington's disease, cancer, and its potential role as a specific marker for Dormant Glioma Stem Cells. In this study, we conducted virtual screening using the ZINC database ( http://zinc.docking.org/ ) and the GPD1 structure to identify potential GPD1 modulators. The investigation involved screening active candidate ligands using ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters, combined with molecular docking, pose analysis, and interaction analysis based on Lipinski and Veber criteria. Subsequently, the top 10 ligands were subjected to 200 ns all-atom molecular dynamics (M.D.) simulations, and binding free energies were calculated. The findings revealed that specific residues, namely TRP14, PRO94, LYS120, ASN151, THR264, ASP260, and GLN298, played a crucial role in ensuring system stability. Furthermore, through a comprehensive analysis involving molecular docking, molecular M.D., and DeLA-Drug, we identified 10 promising small molecules. These molecules represent potential lead compounds for developing effective therapeutics targeting GPD1-associated diseases, thereby contributing to a deeper understanding of GPD1-associated mechanisms. This study's significance lies in identifying key residues associated with GPD1 and discovering valuable small molecules, providing a foundation for further research and development.
Assuntos
Glicerolfosfato Desidrogenase , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Humanos , Ligantes , Glicerolfosfato Desidrogenase/metabolismo , Glicerolfosfato Desidrogenase/química , Ligação Proteica , Termodinâmica , Sítios de LigaçãoRESUMO
Tungsten (W) film is increasingly utilized in various microheater applications due to its numerous advantages. These advantages include a high melting point, positive constant temperature coefficient of resistance (TCR), good mechanical stability, and compatibility with semiconductor processes. In this paper, deposition parameters for enhancing the properties of W film were investigated, and an optimized microheater was fabricated. It was found that the deposition temperature and pressure can modify the TCR to be negative or positive and the crystalline phase of W films to be alpha phases or mixed with beta phases. A W film deposited under 650 °C with a pressure of 1 pa has a positive TCR and pure alpha phase crystalline structure. We applied this optimized W film as a microheater in an RF phase-change switch (RFPCS), and the maximum voltage of the optimized W microheater increased by at least 48% in this work. By optimizing the microheater, the phase-change switch can be successfully actuated in both on and off states, demonstrated by the Raman results of the phase-change material. A voltage pulse of 20 V/200 ns was enough to turn the switch off with MΩ, and 11 V/3 µs could turn the switch on with 138 Ω. The optimized microheater and device can cycle 500 times without failure. The insertion loss and isolation of the device at 20 GHz was 1.0 dB and 22 dB.
RESUMO
BACKGROUND: Understanding the metabolic changes in colorectal cancer (CRC) and exploring potential diagnostic biomarkers is crucial for elucidating its pathogenesis and reducing mortality. Cancer cells are typically derived from cancer tissues and can be easily obtained and cultured. Systematic studies on CRC cells at different stages are still lacking. Additionally, there is a need to validate our previous findings from human serum. METHODS: Ultrahigh-performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics were employed to comprehensively measure metabolites and lipids in CRC cells at four different stages and serum samples from normal control (NR) and CRC subjects. Univariate and multivariate statistical analyses were applied to select the differential metabolites and lipids between groups. Biomarkers with good diagnostic efficacy for CRC that existed in both cells and serum were screened by the receiver operating characteristic curve (ROC) analysis. Furthermore, potential biomarkers were validated using metabolite standards. RESULTS: Metabolite and lipid profiles differed significantly among CRC cells at stages A, B, C, and D. Dysregulation of glycerophospholipid (GPL), fatty acid (FA), and amino acid (AA) metabolism played a crucial role in the CRC progression, particularly GPL metabolism dominated by phosphatidylcholine (PC). A total of 46 differential metabolites and 29 differential lipids common to the four stages of CRC cells were discovered. Eight metabolites showed the same trends in CRC cells and serum from CRC patients compared to the control groups. Among them, palmitoylcarnitine and sphingosine could serve as potential biomarkers with the values of area under the curve (AUC) more than 0.80 in the serum and cells. Their panel exhibited excellent performance in discriminating CRC cells at different stages from normal cells (AUC = 1.00). CONCLUSIONS: To our knowledge, this is the first research to attempt to validate the results of metabolism studies of serum from CRC patients using cell models. The metabolic disorders of PC, FA, and AA were closely related to the tumorigenesis of CRC, with PC being the more critical factor. The panel composed of palmitoylcarnitine and sphingosine may act as a potential biomarker for the diagnosis of CRC, aiding in its prevention.
Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Metabolômica , Humanos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Metabolômica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Lipidômica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Curva ROC , Metaboloma , Espectrometria de Massas em Tandem/métodos , Estadiamento de Neoplasias , Idoso , Ácidos Graxos/metabolismo , Ácidos Graxos/sangue , MultiômicaRESUMO
Biofilms often engender persistent infections, heightened antibiotic resistance, and the recurrence of infections. Therefor, infections related to bacterial biofilms are often chronic and pose challenges in terms of treatment. The main transcription regulatory factor, CsgD, activates csgABC-encoded curli to participate in the composition of extracellular matrix, which is an important skeleton for biofilm development in enterobacteriaceae. In our previous study, a wide range of natural bioactive compounds that exhibit strong affinity to CsgD were screened and identified via molecular docking. Tannic acid (TA) was subsequently chosen, based on its potent biofilm inhibition effect as observed in crystal violet staining. Therefore, the aim of this study was to investigate the specific effects of TA on the biofilm formation of clinically isolated Escherichia coli (E. coli). Results demonstrated a significant inhibition of E. coli Ec032 biofilm formation by TA, while not substantially affecting the biofilm of the ΔcsgD strain. Moreover, deletion of the csgD gene led to a reduction in Ec032 biofilm formation, alongside diminished bacterial motility and curli synthesis inhibition. Transcriptomic analysis and RT-qPCR revealed that TA repressed genes associated with the csg operon and other biofilm-related genes. In conclusion, our results suggest that CsgD is one of the key targets for TA to inhibit E. coli biofilm formation. This work preliminarily elucidates the molecular mechanisms of TA inhibiting E. coli biofilm formation, which could provide a lead structure for the development of future antibiofilm drugs.
Assuntos
Biofilmes , Proteínas de Escherichia coli , Escherichia coli , Regulação Bacteriana da Expressão Gênica , Taninos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Taninos/farmacologia , Escherichia coli/efeitos dos fármacos , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Antibacterianos/farmacologia , TransativadoresRESUMO
BACKGROUND: Acinetobacter lwoffii (A.lwoffii) is a serious zoonotic pathogen that has been identified as a cause of infections such as meningitis, bacteremia and pneumonia. In recent years, the infection rate and detection rate of A.lwoffii is increasing, especially in the breeding industry. Due to the presence of biofilms, it is difficult to eradicate and has become a potential super drug-resistant bacteria. Therefore, eradication of preformed biofilm is an alternative therapeutic action to control A.lwoffii infection. The present study aimed to clarify that baicalin could eradicate A.lwoffii biofilm in dairy cows, and to explore the mechanism of baicalin eradicating A.lwoffii. RESULTS: The results showed that compared to the control group, the 4 MIC of baicalin significantly eradicated the preformed biofilm, and the effect was stable at this concentration, the number of viable bacteria in the biofilm was decreased by 0.67 Log10CFU/mL. The total fluorescence intensity of biofilm bacteria decreased significantly, with a reduction rate of 67.0%. There were 833 differentially expressed genes (367 up-regulated and 466 down-regulated), whose functions mainly focused on oxidative phosphorylation, biofilm regulation system and trehalose synthesis. Molecular docking analysis predicted 11 groups of target proteins that were well combined with baicalin, and the content of trehalose decreased significantly after the biofilm of A.lwoffii was treated with baicalin. CONCLUSIONS: The present study evaluated the antibiofilm potential of baicalin against A.lwoffii. Baicalin revealed strong antibiofilm potential against A.lwoffii. Baicalin induced biofilm eradication may be related to oxidative phosphorylation and TCSs. Moreover, the decrease of trehalose content may be related to biofilm eradication.
Assuntos
Acinetobacter , Antibacterianos , Biofilmes , Flavonoides , Leite , Biofilmes/efeitos dos fármacos , Animais , Flavonoides/farmacologia , Acinetobacter/efeitos dos fármacos , Bovinos , Leite/microbiologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Feminino , Infecções por Acinetobacter/veterinária , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologiaRESUMO
OBJECTIVES: The study aims to identify the outcome and the related factors of unvaccinated patients with end-stage kidney disease during the Omicron pandemic. DESIGN: A multicentre retrospective study of patients with end-stage kidney disease undergone maintenance haemodialysis (HD) in China. SETTING: 6 HD centres in China. PARTICIPANTS: A total of 654 HD patients who tested positive for SARS-CoV-2 were ultimately included in the study. OUTCOME MEASURES: The primary outcomes of interest were adverse outcomes, including hospitalisation due to COVID-19 and all-cause mortality. RESULTS: The average age of the patients was 57 years, with 33.6% of them being over 65 years. Among the patients, 57.5% were male. During the follow-up period, 158 patients (24.2%) experienced adverse outcomes, and 93 patients (14.2%) died. The majority of patients (88/158) developed adverse outcomes within 30 days, and most deaths (77/93) occurred within 1 month. An advanced multivariable Cox regression analysis identified that adverse outcomes were associated with various factors while all-cause mortality was related to advanced age, male gender, high levels of C reactive protein (CRP) and low levels of prealbumin. The Kaplan-Meier curves demonstrated significantly higher all-cause mortality rates in the older, male, high CRP and low prealbumin subgroups. CONCLUSIONS: Among unvaccinated HD patients with confirmed Omicron infections, various factors were found to be linked to adverse outcomes. Notably, age, sex, CRP and prealbumin had a substantial impact on the risk of all-cause mortality.