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BACKGROUND: The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. METHODS: Liquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RTâPCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments. RESULTS: Our findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry. CONCLUSION: Our findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.
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Proteínas de Transporte , Ácidos Graxos , Proteínas de Membrana , Proteínas de Neoplasias , Neoplasias Ovarianas , Proteínas de Ligação a Hormônio da Tireoide , Hormônios Tireóideos , Microambiente Tumoral , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Animais , Hormônios Tireóideos/metabolismo , Camundongos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Linhagem Celular Tumoral , Ácidos Graxos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Efeito Warburg em Oncologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Regulação Neoplásica da Expressão Gênica , Neovascularização Patológica/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de Células , ProteoglicanasRESUMO
BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).
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Anti-Hipertensivos/administração & dosagem , Hipertensão/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Hipertensão/complicações , Hipotensão/induzido quimicamente , Incidência , Masculino , Pessoa de Meia-Idade , Padrão de Cuidado , SístoleRESUMO
Objective: To examine the impact of moderate alcohol consumption on the progression of chronic kidney disease (CKD) in individuals diagnosed with non-alcoholic fatty liver disease (NAFLD), as NAFLD has been identified as an autonomous risk factor for CKD and previous research has demonstrated a reduction in overall mortality in NAFLD patients who consume alcohol in moderation.Methods: This study included participants from ten consecutive rounds of the National Health and Nutrition Examination Survey (NHANES:1998-2018). Multivariate logistic regression models were employed to assess the impact of moderate alcohol consumption on chronic kidney disease (CKD) in both male and female populations. Subgroup analysis was conducted by categorizing patients with non-alcoholic fatty liver disease (NAFLD) based on the Fibrosis-4 (FIB-4) index.Results: 17040 participants were eligible to be included in the study. The logistic regression analysis model showed that moderate alcohol consumption was a protective factor for CKD in male NAFLD patients, with an unadjusted OR: 0.37 (0.22,0.65), and p < 0.001. After further adjustment, the association persisted. However, the association was not significant in female patients with NAFLD. Among men with low risk of liver fibrosis group, moderate alcohol consumption remained a protective factor for CKD (OR = 0.32, 95% CI 0.12-0.84, p = 0.02), but the association was not significant in the high risk of liver fibrosis group. In female patients, both moderate alcohol consumption and excessive alcohol consumption were not significantly associated with CKD in either the low-risk group or the high-risk group.Conclusion: Moderate alcohol consumption is associated with a lower prevalence of CKD in men with NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Inquéritos Nutricionais , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Cirrose Hepática/complicaçõesRESUMO
This study aimed to investigate the role of Sirt6 and inflammatory cytokines in blood samples of patients with ACS. This is a retrospective randomized controlled clinical trial, a total of 30 patients from our hospital are included and divided into following two groups: control group and experimental group, and experimental group consists of 15 patients with ACS and control group consists of 15 patients with non-acute coronary syndrome. Sirt6 protein is detected by western blotting and Sirt6 mRNA is detected by real-time PCR, then inflammatory cytokines such as IL-1ß, IL-18, TnI, and CK-MB are measured by ELISA and cytokines NT-proBNP are monitored by immunofluorescence. Our outcomes show that Sirt6 protein and Sirt6 mRNA in experimental group are remarkably lower than those in control group, and IL-1ß, IL-18, TnI, CK-MB, and NT-proBNP in the experimental group are remarkably higher than those in control group. We can conclude that Sirt6 can prevent or inhibit the development of ACS and IL-1ß, IL-18, TnI, CK-MB, and NT-proBNP can accelerate the development of ACS.
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Síndrome Coronariana Aguda , Sirtuínas , Humanos , Biomarcadores , Citocinas , Interleucina-18/genética , Estudos Retrospectivos , RNA Mensageiro , Sirtuínas/sangue , Sirtuínas/metabolismoRESUMO
Alzheimer's disease (AD) is a serious brain disorder characterized by the presence of beta-amyloid plaques, tau pathology, inflammation, neurodegeneration, and cerebrovascular dysfunction. The presence of chronic neuroinflammation, breaches in the blood-brain barrier (BBB), and increased levels of inflammatory mediators are central to the pathogenesis of AD. These factors promote the penetration of immune cells into the brain, potentially exacerbating clinical symptoms and neuronal death in AD patients. While microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in AD, recent evidence suggests the infiltration of cerebral vessels and parenchyma by peripheral immune cells, including neutrophils, T lymphocytes, B lymphocytes, NK cells, and monocytes in AD. These cells participate in the regulation of immunity and inflammation, which is expected to play a huge role in future immunotherapy. Given the crucial role of peripheral immune cells in AD, this article seeks to offer a comprehensive overview of their contributions to neuroinflammation in the disease. Understanding the role of these cells in the neuroinflammatory response is vital for developing new diagnostic markers and therapeutic targets to enhance the diagnosis and treatment of AD patients.
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OBJECTIVE: Current guidelines are debated when it comes to starting anticoagulant therapy in patients with non-valvular atrial fibrillation (NVAF) and low CHA2DS2-VASc scores (1-2 in women and 0-1 in men). However, these individuals still have a high likelihood of developing left atrial thrombus/spontaneous echo contrast (LAT/SEC) and experiencing subsequent thromboembolism. Recent research has demonstrated that lipoprotein(a) [Lp(a)] may increase the risk of thrombosis, but the relationship between Lp(a) and LAT/SEC in NVAF patients is not clearly established. Therefore, this study sought to evaluate the predictive ability of Lp(a) for LAT/SEC among NVAF patients with low CHA2DS2-VASc scores. METHODS: NVAF patients with available transesophageal echocardiography (TEE) data were evaluated. Based on the TEE results, the subjects were classified into non-LAT/SEC and LAT/SEC groups. The risk factors for LAT/SEC were examined using binary logistic regression analyses and were validated by using 1:1 propensity score matching (PSM). Subsequently, novel predictive models for LAT/SEC were developed by integrating the CHA2DS2-VASc score with the identified factors, and the accuracy of these models was tested using receiver operating characteristic (ROC) analysis. RESULTS: In total, 481 NVAF patients were enrolled. The LAT/SEC group displayed higher Lp(a) concentrations. It was found that enlarged left atrial diameter (LAD), high concentrations of Lp(a), and a history of coronary heart disease (CHD) were independent predictors of LAT/SEC. Lp(a) and LAD still had predictive values for LAT/SEC after adjusting for PSM. In both the highest quartile groups of Lp(a) (>266 mg/L) and LAD (>39.5 mm), the occurrence of LAT/SEC was higher than that in the corresponding lowest quartile. By incorporating Lp(a) and the LAD, the predictive value of the CHA2DS2-VASc score for LAT/SEC was significantly improved. CONCLUSION: Elevated Lp(a) and enlarged LAD were independent risk factors for LAT/SEC among NVAF patients with low CHA2DS2-VASc scores. The prediction accuracy of the CHA2DS2-VASc score for LAT/SEC was significantly improved by the addition of Lp(a) and LAD. When evaluating the stroke risk in patients with NVAF, Lp(a) and LAD should be taken into account together with the CHA2DS2-VASc score. TRIAL REGISTRATION: Retrospectively registered.
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Fibrilação Atrial , Lipoproteína(a) , Trombose , Feminino , Humanos , Masculino , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico por imagem , Estudos Transversais , Pontuação de Propensão , Trombose/diagnóstico por imagem , Trombose/etiologiaRESUMO
We described a case of a double aortic arch (DAA) with a subaortic left brachiocephalic vein (LBCV) and right-side ductus arteriosus using high-definition (HD) flow render mode and spatiotemporal image correlation (STIC). We experienced uncertainty regarding this interesting case despite the diagnosis of right-sided ductus arteriosus. The ductus arteriosus originates from the right pulmonary artery (PA) and converges into the descending aorta (DAO), whereas the vessel originated from the PA and converged into the ascending aorta (AAO). Therefore, we assumed that the vessel connecting the PA to AAO may be a type-C persistent fifth aortic arch (PFAA).
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Permeabilidade do Canal Arterial , Canal Arterial , Anel Vascular , Gravidez , Feminino , Humanos , Canal Arterial/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Permeabilidade do Canal Arterial/diagnóstico por imagem , AortaRESUMO
OBJECTIVES: To evaluate the clinical utility of two dimensional (2D) ultrasound combined with spatiotemporal image correlation (STIC) in diagnosing interrupted aortic arch (IAA) in fetal life. METHODS: A total of 53 cases of fetal IAA were diagnosed using 2D ultrasound combined with STIC, and 53 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to assess the utility of employing 2D ultrasound combined with STIC in the diagnosis of IAA. RESULTS: 2D ultrasound combined with STIC detected 22 cases of type A IAA, 24 cases of type B IAA, and seven cases of type C IAA. Furthermore, combining 2D ultrasound with STIC enabled dynamic visualization of the IAA, aiding in prenatal diagnosis. The diagnostic coincidence rate of IAA was found to be higher in the HD-flow combined with STIC than that in the 2D combined with HD-flow. CONCLUSION: HD-flow combined with STIC can assist in diagnosing fetal IAA, and this technique has important clinical value.
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Aorta Torácica , Ultrassonografia Pré-Natal , Humanos , Feminino , Ultrassonografia Pré-Natal/métodos , Gravidez , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/anormalidades , Aorta Torácica/embriologia , Estudos Retrospectivos , Adulto , Reprodutibilidade dos Testes , Coração Fetal/diagnóstico por imagemRESUMO
OBJECTIVE: This study aimed to assess the use of two-dimensional (2D) ultrasound combined with high-definition flow (HD-flow) render mode and spatiotemporal image correlation (STIC) in diagnosing and classifying fetal persistent left superior vena cava (PLSVC). METHODS: Overall, 114 cases of fetal PLSVC were diagnosed using 2D ultrasound combined with STIC, and 114 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to evaluate the effectiveness of the diagnostic approach. RESULTS: All 114 PLSVC cases were diagnosed using 2D ultrasound combined with STIC. Although the diagnostic coincidence rate of PLSVC in the HD-flow combined with STIC was similar to that in the 2D ultrasound combined with HD-flow (96.8 vs 96.2%), 2D ultrasound with STIC enabled dynamic visualization of the PLSVC, furthering prenatal diagnosis. These cases were classified as type I PLSVC: 80 cases of type Ia, 29 cases of type Ib, and 5 cases of type Ic. Seventy isolated PLSVC cases (61.4%) were noted, whereas 44 cases (35.6%) were associated with concomitant structural abnormalities. Intracardiac structural malformations accounted for the highest proportion (n = 53, 58.89%), followed by single umbilical artery and facial/bodily abnormalities (n = 10, 11.11%). CONCLUSION: Combining HD-flow and STIC complements 2D ultrasound in diagnosing and classifying fetal PLSVC, demonstrating significant clinical relevance.
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Diabetes mellitus (DM) and osteoporosis are two major health care problems worldwide. Emerging evidence suggests that DM poses a risk for osteoporosis and can contribute to the development of diabetes-induced osteoporosis (DOP). Interestingly, some epidemiological studies suggest that DOP may be at least partially distinct from those skeletal abnormalities associated with old age or postmenopausal osteoporosis. The increasing number of DM patients who also have DOP calls for a discussion of the pathogenesis of DOP and the investigation of drugs to treat DOP. Recently, non-coding RNAs (ncRNAs) have received more attention due to their significant role in cellular functions and bone formation. It is worth noting that ncRNAs have also been demonstrated to participate in the progression of DOP. Meanwhile, nano-delivery systems are considered a promising strategy to treat DOP because of their cellular targeting, sustained release, and controlled release characteristics. Additionally, the utilization of novel technologies such as the CRISPR system has expanded the scope of available options for treating DOP. Hence, this paper explores the functions and regulatory mechanisms of ncRNAs in DOP and highlights the advantages of employing nanoparticle-based drug delivery techniques to treat DOP. Finally, this paper also explores the potential of ncRNAs as diagnostic DOP biomarkers.
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Diabetes Mellitus , MicroRNAs , Osteoporose , RNA Longo não Codificante , Humanos , RNA não Traduzido/genética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Osteoporose/etiologia , Osteoporose/genéticaRESUMO
A novel ternary heterojunction material In2O3/In2S3/ZnIn2S4 was synthesized, and a photoelectrochemical sensor was fabricated for the non-invasive test of dopamine (DA) in sweat. In2O3 multihollow microtubules were synthesized and then In2S3 was formed on their surface to construct a type-I heterojunction between In2S3 and In2O3. ZnIn2S4 was further introduced to form a Z-scheme heterojunction between In2S3/ZnIn2S4. Under photoexcitation, the photogenerated holes of In2O3 transferred to the valence band of In2S3, superimposed with the holes produced by In2S3, leads to a significantly higher photocatalytic oxidation capacity of In2O3/In2S3/ZnIn2S4 ternary composites than that of In2O3/In2S3. The Z-scheme heterojunction accelerates the transfer of photogenerated electrons accumulated on the type-I heterojunction. In the presence of DA, it is rapidly oxidized into polydopamine (PDA) by In2O3/In2S3, and the benzoquinone groups of PDA compete for the photogenerated electrons to reduce the current in the external circuit, whereby DA determination is achieved. Owing to the combination of type-I and Z-scheme heterojunction, the sensor showed extremely high sensitivity, with a detection limit of 3.94 × 10-12 mol/L. It is one of the most sensitive methods for DA detection reported and has been applied to the determination of DA in human sweat.
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Dopamina , Suor , Humanos , ElétronsRESUMO
INTRODUCTION: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a rare autosomal dominant disorder characterized by megalencephaly (i.e., overgrowth of the brain), polymicrogyria, focal hypoplasia of the cerebral cortex, and polydactyly. Persistent hyperplastic primary vitreous (PHPV) involves a spectrum of congenital ocular abnormalities that are characterized by the presence of a vascular membrane behind the lens. CASE PRESENTATION: Here, we present a case of foetal MPPH with PHPV that was diagnosed using prenatal ultrasound. Ultrasound revealed the presence of megalencephaly, multiple cerebellar gyri, and hydrocephalus. Whole-exome sequencing confirmed the mutation of the AKT3 gene, which led to the consideration of MPPH syndrome. Moreover, an echogenic band with an irregular surface was observed between the lens and the posterior wall of the left eye; therefore, MPPH with PHPV was suspected. CONCLUSION: MPPH syndrome with PHPV can be diagnosed prenatally.
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Hidrocefalia , Malformações do Desenvolvimento Cortical , Megalencefalia , Vítreo Primário Hiperplásico Persistente , Polidactilia , Polimicrogiria , Gravidez , Feminino , Humanos , Polimicrogiria/diagnóstico por imagem , Polimicrogiria/genética , Vítreo Primário Hiperplásico Persistente/diagnóstico por imagem , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/diagnóstico , Malformações do Desenvolvimento Cortical/genética , Hidrocefalia/diagnóstico por imagem , Megalencefalia/genética , Polidactilia/diagnóstico por imagem , Polidactilia/genética , Síndrome , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Distillers dried grains with solubles (DDGS) are rich in nutrition, and they are potential protein feed raw material. However, the existence of cellulose, hemicellulose and lignin hinders animals' digestion and absorption of DDGS. Making full use of unconventional feed resources such as DDGS can alleviate the shortage of feed resources to a certain extent. This research investigated the effects of twin-screw extrusion on the macromolecular composition, physical and chemical properties, surface structure and in vitro protein digestibility (IVPD) of DDGS. RESULTS: The findings showed that extrusion puffing significantly increased the protein solubility, bulk density, water holding capacity, and swelling capacity, while significantly decreased hemicellulose and crude protein content, particle size and zeta potential of DDGS. The structure damage of DDGS induced by the extrusion was characterized by scanning electron microscopy (SEM), Fourier-transform infrared (FITR) spectroscopy and X-ray diffraction (XRD) analysis. Interestingly, no random coil was observed in the analysis of the secondary structure, and extrusion promoted the transformation of α-helix and ß-turn to ß-sheet, which led to significant increases in protein solubility and IVPD of DDGS (P < 0.05). Additionally, correlation analysis revealed that IVPD and PS had a positive relationship. CONCLUSION: Extrusion puffing was an ideal pretreatment method for DDGS modification to improve in vitro protein digestibility. © 2023 Society of Chemical Industry.
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Digestão , Zea mays , Animais , Zea mays/química , Ração Animal/análise , Dieta , Estrutura Secundária de Proteína , Fenômenos Fisiológicos da Nutrição Animal , Grão Comestível/químicaRESUMO
Given the escalating global crisis in feed protein availability, Jatropha curcas L. cake has attracted significant interest as a viable alternative protein source in animal feed. This experiment was conducted to investigate the effects of fermented Jatropha curcas L. cake (FJCC) as a protein feed in the diet of pigs. A total of 96 growing pigs with an average weight of 27.60 ± 1.59 kg were divided into three dietary groups with varying FJCC inclusion levels (0, 2.5, and 5%) for a 28 d trial. Results showed that the diet with 5% FJCC (FJCC5) demonstrated significant improvements in average daily gain (p = 0.009), feed-to-gain ratio (p = 0.036), nutrient digestibility, and intestinal morphology. Furthermore, the FJCC5 diet resulted in a decrease in pH values in different gut sections (jejunum p = 0.045, cecum p = 0.001, colon p = 0.012), and favorably altered the profile of short-chain fatty acids (SCFAs) with increased butyric acid content (p = 0.005) and total SCFAs (p = 0.019). Additionally, this diet notably decreased IL-6 levels in the jejunum (p = 0.008) and colon (=0.047), significantly reduced IL-1 levels in the hypothalamus (p < 0.001), and lowered IL-1, IL-6, and IL-10 levels in plasma (p < 0.05). Microbiota and metabolite profile analysis revealed an elevated abundance of beneficial microbes (p < 0.05) and key metabolites such as 4-aminobutyric acid (GABA) (p = 0.003) and serotonin (5-HT) (p = 0.022), linked to neuroactive ligand-receptor interaction. Moreover, FJCC5 significantly boosted circulating neurotransmitter levels of 5-HT (p = 0.006) and GABA (p = 0.002) in plasma and hypothalamus, with corresponding increases in precursor amino acids (p < 0.05). These findings suggest that FJCC, particularly at a 5% inclusion rate, can be an effective substitute for traditional protein sources like soybean meal, offering benefits beyond growth enhancement to gut health and potentially impacting the gut-brain axis. This research underscores FJCC's potential as a valuable component in sustainable animal nutrition strategies.
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Phosphomonoesters are important biosynthetic and energy metabolism intermediates in microorganisms. A comprehensive analysis of phosphomonoester metabolites is of great significance for the understanding of their metabolic phosphorylation process and inner mechanism. In this study, we established a pair of isotope reagent d0/d5-2-diazomethyl-N-methyl-phenyl benzamide-labeling-based LC-MS method for the comprehensive analysis of phosphomonoester metabolites. By this method, the labeled phosphomonoester metabolites specifically produced characteristic isotope paired peaks with an m/z difference of 5.0314 in the MS1 spectra and a pair of diagnostic ions (m/z 320.0693/325.1077) in the MS2 spectra. Based on this, a diagnostic ion-based strategy was established for the rapid screening, identification, and relative quantification of phosphomonoester metabolites. Using this strategy, 42 phosphomonoester metabolites were highly accurately identified fromSaccharomyces cerevisiae (S. cerevisiae). Notably, two phosphomonoesters were first detected fromS. cerevisiae. The relative quantification results indicated that the contents of nine phosphomonoester metabolites including two intermediates (Ru5P and S7P) in the pentose phosphate pathway (PPP) were significantly different between lycopene-producible and wild-type S. cerevisiae. A further enzyme assay indicated that the activity of the PPP was closely related to the production of lycopene. Our findings provide new perspectives for the related mechanism study and valuable references for making informed microbial engineering decisions.
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Saccharomyces cerevisiae , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Marcação por Isótopo , Licopeno , Espectrometria de Massas em Tandem/métodosRESUMO
FeNC catalysts demonstrate remarkable activity and stability for the oxygen reduction reaction (ORR) in polymer electrolyte membrane fuel cells and Zn-air batteries (ZABs). The local coordination of Fe single atoms in FeNC catalysts strongly impacts ORR activity. Herein, FeNC catalysts containing Fe single atoms sites with FeN3 , FeN4 , and FeN5 coordinations are synthesized by carbonization of Fe-rich polypyrrole precursors. The FeN5 sites possess a higher Fe oxidation state (+2.62) than the FeN3 (+2.23) and FeN4 (+2.47) sites, and higher ORR activity. Density functional theory calculations verify that the FeN5 coordination optimizes the adsorption and desorption of ORR intermediates, dramatically lowering the energy barrier for OH- desorption in the rate-limiting ORR step. A primary ZAB constructed using the FeNC catalyst with FeN5 sites demonstrates state-of-the-art performance (an open circuit potential of 1.629 V, power density of 159 mW cm-2 ). Results confirm an intimate structure-activity relationship between Fe coordination, Fe oxidation state, and ORR activity in FeNC catalysts.
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With the rapid increase in the incidence of cervical cancer, anal cancer and other cancers, human papillomavirus (HPV) infection has become a growing concern. Persistent infection with high-risk HPV is a major cause of malignant tumors. In addition, microbiota and viruses such as human immunodeficiency virus, herpes simplex virus, and Epstein-Barr virus are closely associated with HPV infection. The limited effectiveness of existing treatments for HPV-associated tumors and the high rates of recurrence and metastasis in patients create an urgent need for novel and effective approaches. In recent years, HPV vaccine coverage has increased and can reduce the incidence of serious adverse events. Overall, this article provides a comprehensive overview of HPV biology, microbiome, and other viral interactions in cancer development, highlighting the need for a more comprehensive approach to cancer prevention and treatment. Current and emerging HPV-related cancer control and treatment strategies are also further explored.
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Infecções por Vírus Epstein-Barr , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/epidemiologia , HIV , Vacinas contra Papillomavirus/uso terapêutico , PapillomaviridaeRESUMO
BACKGROUND AND AIMS: Modern tropical rainforests house the highest biodiversity of Earth's terrestrial biomes and are distributed in three low-latitude areas. However, the biogeographical patterns and processes underlying the distribution of biodiversity among these three areas are still poorly known. Here, we used Tiliacoreae, a tribe of pantropical lianas with a high level of regional endemism, to provide new insights into the biogeographical relationships of tropical rainforests among different continents. METHODS: Based on seven plastid and two nuclear DNA regions, we reconstructed a phylogeny for Tiliacoreae with the most comprehensive sampling ever. Within the phylogenetic framework, we then estimated divergence times and investigated the spatiotemporal evolution of the tribe. KEY RESULTS: The monophyletic Tiliacoreae contain three major clades, which correspond to Neotropical, Afrotropical and Indo-Malesian/Australasian areas, respectively. Both Albertisia and Anisocycla are not monophyletic. The most recent common ancestor of Tiliacoreae occurred in Indo-Malesia, the Afrotropics and Neotropics in the early Eocene, then rapidly diverged into three major clades between 48 and 46 Ma. Three dispersals from Indo-Malesia to Australasia were inferred, one in the middle Eocene and two in the late Oligocene-late Miocene, and two dispersals from the Afrotropics to Indo-Malesia occurred in the late Eocene-Oligocene. CONCLUSIONS: The three main clades of Anisocycla correspond to three distinct genera [i.e. Anisocycla sensu stricto and two new genera (Georgesia and Macrophragma)]. Epinetrum is a member of Albertisia. Our findings highlight that sea-level fluctuations and climate changes in the Cenozoic have played important roles in shaping the current distribution and endemism of Tiliacoreae, hence contributing to the knowledge on the historical biogeography of tropical rainforests on a global scale.
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Menispermaceae , Floresta Úmida , Filogenia , Filogeografia , Menispermaceae/genética , Plastídeos/genéticaRESUMO
BACKGROUND: Coronary artery disease (CAD) tends to progress more rapidly in the type 2 diabetes mellitus (T2DM) population and may be associated with dyslipidemia. This study explored the relationship of the atherogenic index of plasma (AIP) to coronary artery lesions in the T2DM population of different sexes. METHODS: The research included 737 individuals who underwent coronary angiography from 2018 to 2019. The included clinical data and coronary angiographic findings were analyzed in the study. RESULTS: Among the included male patients, those with coronary artery disease had a higher adjusted AIP (aAIP). In correlation analysis, the Gensini score was positively and linearly correlated with the aAIP in male T2DM patients. An aAIP cutoff value of 1.17 was determined from the receiver operating characteristic (ROC) curve of aAIP versus CAD risk in the study population. After dividing the aAIP into two groups by the cutoff value of aAIP, the group with the lower value was used as the control for logistic regression analysis. The results showed that the risk of CAD and multivessel lesions was higher when the aAIP was higher in men with T2DM, and this positive association was not affected by HbA1c, age, or the presence of glucose-lowering therapy. The ROC curve suggested that the aAIP can predict CAD risk in male T2DM patients. However, no relationship was found in the included female patients. CONCLUSION: In male T2DM patients, AIP may serve as a reliable marker for coronary artery lesions.
Assuntos
Aterosclerose , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Feminino , Estudos Transversais , Fatores de Risco , Caracteres Sexuais , Angiografia Coronária/métodosRESUMO
Double aortic arch (DAA) with subaortic left brachiocephalic vein (LBCV) and right-side ductus arteriosus (RDA) was not reported before delivery, only in adults with anatomy course findings. We present a case of fetal DAA with subaortic LBCV and RDA using high-definition (HD) flow render mode and spatiotemporal image correlation (STIC).