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Bile acids (BAs) play a crucial role in lipid metabolism of children. However, the association between per- and polyfluoroalkyl substance (PFAS) exposure and BAs in children is scarce. To address this need, we selected 252 children from the Maoming Birth Cohort and measured 32 PFAS, encompassing short- and long-chain perfluorocarboxylic acids (PFCAs) and perfluorosulfonic acids (PFSAs) in the cord blood. Additionally, we analyzed nine primary and eight secondary BAs in the serum of three-year-old children. Generalized linear models with FDR-adjusted and Bayesian kernel machine regression (BKMR) were used to explore the associations of individual and mixture effects of PFAS and BAs. We found negative associations between cord blood long-chain PFCAs exposure and serum primary BAs in three-year-old children. For example, one ln-unit (ng/mL) increase of perfluoro-n-tridecanoic acid (PFTrDA), perfluoro-n-undecanoic acid (PFUnDA) and perfluoro-n-decanoic acid (PFDA) were associated with decreased taurochenodeoxycholic acid, with estimated percentage change of -24.28% [95% confidence interval (CI): -36.75%, -9.35%], -25.84% (95% CI: -39.67%, -8.83%), and -22.97% (95% CI: -34.45%, -9.47%) respectively. Notably, the observed associations were more pronounced in children with lower vegetable intake. Additionally, the BKMR model also demonstrated a monotonical decline in primary BAs as the PFAS mixture increased. We provided the first evidence of the association between intrauterine exposure to PFAS and its mixture with BAs in children. Further large-sample-size studies are needed to verify this finding.
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Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a growing health concern due to its increasing prevalence worldwide. Metabolic homeostasis encompasses the stable internal conditions vital for efficient metabolism. This equilibrium extends to the intestinal microbiota, whose metabolic activities profoundly influence overall metabolic balance and organ health. The metabolites derived from the gut microbiota metabolism can be defined as microbiota-related co-metabolites. They serve as mediators between the gut microbiota and the host, influencing various physiological processes. The recent redefinition of the term MASLD has highlighted the metabolic dysfunction that characterize the disease. Metabolic dysfunction encompasses a spectrum of abnormalities, including impaired glucose regulation, dyslipidemia, mitochondrial dysfunction, inflammation, and accumulation of toxic byproducts. In addition, MASLD progression has been linked to dysregulation in the gut microbiota and associated co-metabolites. Short-chain fatty acids (SCFAs), hippurate, indole derivatives, branched-chain amino acids (BCAAs), and bile acids (BAs) are among the key co-metabolites implicated in MASLD progression. In this review, we will unravel the relationship between the microbiota-related metabolites which have been associated with MASLD and that could play an important role for developing effective therapeutic interventions for MASLD and related metabolic disorders.
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Background: Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and is a complex heritable trait with both genetic and environmental risk factors, including sex and smoking. Methods: We performed genome-wide association (GWA) analyses for CAC among all participants and stratified by sex in the COPDGene study (n = 6144 participants of European ancestry and n = 2589 participants of African ancestry) with replication in the Diabetes Heart Study (DHS). We adjusted for age, sex, current smoking status, BMI, diabetes, self-reported high blood pressure, self-reported high cholesterol, and genetic ancestry (as summarized by principal components computed within each racial group). For the significant signals from the GWA analyses, we examined the single nucleotide polymorphism (SNP) by sex interactions, stratified by smoking status (current vs. former), and tested for a SNP by smoking status interaction on CAC. Results: We identified genome-wide significant associations for CAC in the chromosome 9p21 region [CDKN2B-AS1] among all COPDGene participants (p = 7.1 × 10-14) and among males (p = 1.0 × 10-9), but the signal was not genome-wide significant among females (p = 6.4 × 10-6). For the sex stratified GWA analyses among females, the chromosome 6p24 region [PHACTR1] had a genome-wide significant association (p = 4.4 × 10-8) with CAC, but this signal was not genome-wide significant among all COPDGene participants (p = 1.7 × 10-7) or males (p = 0.03). There was a significant interaction for the SNP rs9349379 in PHACTR1 with sex (p = 0.02), but the interaction was not significant for the SNP rs10757272 in CDKN2B-AS1 with sex (p = 0.21). In addition, PHACTR1 had a stronger association with CAC among current smokers (p = 6.2 × 10-7) than former smokers (p = 7.5 × 10-3) and the SNP by smoking status interaction was marginally significant (p = 0.03). CDKN2B-AS1 had a strong association with CAC among both former (p = 7.7 × 10-8) and current smokers (p = 1.7 × 10-7) and the SNP by smoking status interaction was not significant (p = 0.40). Conclusions: Among current and former smokers of European ancestry in the COPDGene study, we identified a genome-wide significant association in the chromosome 6p24 region [PHACTR1] with CAC among females, but not among males. This region had a significant SNP by sex and SNP by smoking interaction on CAC.
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INTRODUCTION: Although there are several psychological theories on bipolar disorders (BD), the empirical evidence on these theories through experimental studies is still limited. The current study systematically reviews experimental methods used in studies on the main theories of BD: Reward Hypersensitivity Theory (RST) or Behavioral Activation System (BAS), Integrative Cognitive Model (ICM), Positive Emotion Persistence (PEP), Manic Defense theory (MD), and Mental Imagery (MI). The primary aim is to provide an overview of the used methods and to identify limitations and suggest areas of improvement. METHODS: A systematic search of six databases until October 2023 was conducted. Study selection involved two independent reviewers extracting data on experimental study design and methodology. RESULTS: A total of 84 experimental studies were reviewed. BAS and RST were the most frequently studied theories. The majority of these experimental studies focus on mechanisms of reward sensitivity. Other important elements of the reviewed theories, such as goal setting and-attainment, situation selection (avoidance or approach), activation, affective/emotional reactivity, and regulatory strategies, are understudied. Self-report and neuropsychological tasks are most often used, while mood induction and physiological measures are rarely used. CONCLUSION: There is a need for more consensus on the operationalization of psychological theories of mania. Standardization of test batteries could improve comparability among studies and foster a more systematic approach to experimental research. Research on affective (activated) states is still underrepresented in comparison with studies on trait vulnerabilities.
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Tibroviruses are novel rhabdoviruses detected in humans, cattle, and arthropods. Four tibroviruses are known to infect humans: Bas-Congo virus (BASV), Ekpoma virus 1 (EKV-1), Ekpoma virus 2, and Mundri virus. However, since none of them has been isolated, their biological properties are largely unknown. We aimed to characterize the human tibrovirus glycoprotein (G), which likely plays a pivotal role in viral tropism and pathogenicity. Human tibrovirus Gs were found to share some primary structures and display 14 conserved cysteine residues, although their overall amino acid homology was low (29%-48%). Multiple potential glycosylation sites were found on the G molecules, and endoglycosidase H- and peptide-N-glycosidase F-sensitive glycosylation was confirmed. AlphaFold-predicted three-dimensional (3D) structures of human tibrovirus Gs were overall similar. Membrane fusion mediated by these tibrovirus Gs was induced by acidic pH. The low pH-induced conformational change that triggers fusion was reversible. Virus-like particles (VLPs) were produced by transient expression of Gs in cultured cells and used to produce mouse antisera. Using vesicular stomatitis Indiana virus pseudotyped with Gs, we found that the antisera to the respective tibrovirus VLPs showed limited cross-neutralizing activity. It was also found that human C-type lectins and T-cell immunoglobulin mucin 1 acted as attachment factors for G-mediated entry into cells. Interestingly, BASV-G showed the highest ability to utilize these molecules. The viruses infected a wide range of cell lines with preferential tropism for human-derived cells whereas the preference of EKV-1 was unique compared with the other human tibroviruses. These findings provide fundamental information to understand the biological properties of the human tibroviruses. IMPORTANCE: Human tibroviruses are poorly characterized emerging rhabdoviruses associated with either asymptomatic infection or severe disease with a case fatality rate as high as 60% in humans. However, the extent and burden of human infection as well as factors behind differences in infection outcomes are largely unknown. In this study, we characterized human tibrovirus glycoproteins, which play a key role in virus-host interactions, mainly focusing on their structural and antigenic differences and cellular tropism. Our results provide critical information for understanding the biological properties of these novel viruses and for developing appropriate preparedness interventions such as diagnostic tools, vaccines, and effective therapies.
Subject(s)
Viral Envelope Proteins , Humans , Animals , Viral Envelope Proteins/metabolism , Viral Envelope Proteins/genetics , Mice , Glycosylation , Virus Internalization , Viral Tropism , Cell Line , Mucin-1/metabolism , HEK293 Cells , Antibodies, Viral/immunology , Amino Acid SequenceABSTRACT
BACKGROUND: This study aims to investigate the predictive value of the circulating blood cell count, including neutro-philto-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), and thesystemic inflammation index (SII) for the development of severe oral mucositis (SOM) induced by radiation in patients undergoing radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, 142 NPC patients were screened, and based on mucositis toxicity grade, they were categorized into two groups: SOM and nonSOM. Peripheral blood cell counts were conducted prior to Intensity-Modulated Radiation Therapy (IMRT). Associations between blood cell count, NLR, PLR, SII, and SOM occurrence were examined. RESULTS: Revealed elevated NLR and SII levels, along with reduced lymphocyte (LYM), eosinophil (EOS), and basophil (BAS) in patients with SOM. LYM, EOS, BAS, NLR, and SII were effective predictors of the severity of radiation-induced oral mucositis (RIOM) in NPC patients. CONCLUSIONS: The occurrence of SOM was strongly linked to the hematological status at the start of Radiation Therapy (RT). Integrating BAS count and NLR into comprehensive risk prediction models could prove valuable for predicting SOM in NPC patients.
Subject(s)
Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Radiotherapy, Intensity-Modulated , Stomatitis , Humans , Retrospective Studies , Male , Female , Radiotherapy, Intensity-Modulated/adverse effects , Middle Aged , Stomatitis/etiology , Stomatitis/blood , Stomatitis/pathology , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/blood , Nasopharyngeal Carcinoma/pathology , Adult , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/blood , Aged , Prognosis , Radiation Injuries/blood , Radiation Injuries/etiology , Radiation Injuries/pathology , Radiation Injuries/diagnosis , Biomarkers/blood , Inflammation/etiology , Inflammation/blood , Follow-Up Studies , Predictive Value of TestsABSTRACT
Deciphering the lncRNA-associated competitive endogenous RNA (ceRNA) network is essential in decoding glioblastoma multiforme (GBM) pathogenesis by regulating miRNA availability and controlling mRNA stability. This study aimed to explore novel biomarkers for GBM by constructing a lncRNA-miRNA-mRNA network. A ceRNA network in GBM was constructed using lncRNA, mRNA and miRNA expression profiles from the TCGA and GEO datasets. Seed nodes were identified by protein-protein interaction (PPI) network analysis of deregulated-mRNAs (DEmRNAs) in the ceRNA network. A lncRNA-miRNA-seed network was constructed by mapping the seed nodes into the preliminary ceRNA network. The impact of the seed nodes on the overall survival (OS) of patients was assessed by the GSCA database. Functional enrichment analysis of the deregulated-lncRNAs (DElncRNA) in the ceRNA network and genes interacting with OS-related genes in the PPI network were performed. Finally, the positive correlation between seed nodes and their associated lncRNAs and the expression level of these molecules in GBM tissue compared with normal samples was validated using the GEPIA database. Our analyzes revealed that three novel regulatory axes AL161785.1/miR-139-5p/MS4A6A, LINC02611/miR-139-5p/MS4A6A and PCED1B-AS1/miR-433-3p/MS4A6A may play essential roles in GBM pathogenesis. MS4A6A is upregulated in GBM and closely associated with shorter survival time of patients. We also identified that MS4A6A expression positively correlates with genes related to tumour-associated macrophages, which induce macrophage infiltration and immune suppression. The functional enrichment analysis demonstrated that DElncRNAs are mainly involved in neuroactive ligand-receptor interaction, calcium/MAPK signalling pathway, ribosome, GABAergic/Serotonergic/Glutamatergic synapse and immune system process. In addition, genes related to MS4A6A contribute to immune and inflammatory-related biological processes. Our findings provide novel insights to understand the ceRNA regulation in GBM and identify novel prognostic biomarkers or therapeutic targets.
Subject(s)
Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Glioblastoma , MicroRNAs , RNA, Long Noncoding , RNA, Messenger , Humans , Glioblastoma/genetics , Glioblastoma/pathology , Glioblastoma/mortality , Glioblastoma/metabolism , RNA, Long Noncoding/genetics , Prognosis , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Protein Interaction Maps/genetics , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/mortality , Brain Neoplasms/metabolism , Gene Expression Profiling , Computational Biology/methods , Databases, Genetic , RNA, Competitive EndogenousABSTRACT
Phubbing is a common sight, but it is not merely a technological faux pas. The present study aims to explore phubbing (phubbing others and getting phubbed) through the lens of two types of personalities (grandiose and vulnerable narcissism). Moreover, the study also aimed to evaluate the indirect role of motivational systems (BAS/BIS) between these two sets of variables. The sample of the study comprised 525 Indian college students. Data were analyzed through Hayes Process Macro (Hayes) in SPSS (Version 26). Vulnerable narcissism was found to be positively related to phubbing others and getting phubbed. Grandiose narcissism was found to be related to phubbing others but not to getting phubbed. BAS and BIS were significantly and positively related to phubbing and getting phubbed. BAS indirectly affected the relationship between two kinds of narcissism (vulnerable and grandiose) and phubbing (phubbing others and getting phubbed); however, BIS failed to influence the relationship between narcissism and phubbing. The results of the present study challenge the notion that all phubbing behaviors are truly deviant as narcissistic personality played an important role in phubbing behavior. The study also highlighted the importance of rewards and punishment on phubbing behaviors, and therefore there is a need to focus on BAS and BIS while dealing with phubbing behaviors.
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OBJECTIVE: This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1 (PCED1B-AS1) in the development of hepatocellular carcinoma (HCC). METHODS: A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients. The interactions of PCED1B-AS1 and microRNA-34a (miR-34a) were detected by dual luciferase activity assay and RNA pull-down assay. The RNA expression levels of PCED1B-AS1, miR-34a and CD44 were detected by RT-qPCR, and the protein expression level of CD44 was determined by Western blotting. The cell proliferation was detected by cell proliferation assay, and the cell invasion and migration by transwell invasion assay. The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study. RESULTS: PCED1B-AS1 was highly expressed in HCC tissues, which was associated with poor survival of HCC patients. Furthermore, PCED1B-AS1 interacted with miR-34a in HCC cells, but they did not regulate the expression of each other. Additionally, PCED1B-AS1 increased the expression level of CD44, which was targeted by miR-34a. The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro, while CD44 exhibited the opposite effects. Furthermore, PCED1B-AS1 suppressed the role of miR-34a. Moreover, the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo. CONCLUSION: PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.
Subject(s)
Carcinoma, Hepatocellular , Cell Proliferation , Gene Expression Regulation, Neoplastic , Hyaluronan Receptors , Liver Neoplasms , MicroRNAs , Neoplasm Invasiveness , RNA, Long Noncoding , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Humans , Hyaluronan Receptors/genetics , Hyaluronan Receptors/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Cell Proliferation/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Animals , Mice , Neoplasm Invasiveness/genetics , Male , Cell Line, Tumor , Female , Cell Movement/genetics , Middle Aged , Mice, Nude , RNA, Antisense/geneticsABSTRACT
BACKGROUND: Making timely moral decisions can save a life. However, literature on how moral decisions are made under time pressure reports conflicting results. Moreover, it is unclear whether and how moral choices under time pressure may be influenced by personality traits like impulsivity and sensitivity to reward and punishment. METHODS: To address these gaps, in this study we employed a moral dilemma task, manipulating decision time between participants: one group (N = 25) was subjected to time pressure (TP), with 8 s maximum time for response (including the reading time), the other (N = 28) was left free to take all the time to respond (noTP). We measured type of choice (utilitarian vs. non-utilitarian), decision times, self-reported unpleasantness and arousal during decision-making, and participants' impulsivity and BIS-BAS sensitivity. RESULTS: We found no group effect on the type of choice, suggesting that time pressure per se did not influence moral decisions. However, impulsivity affected the impact of time pressure, in that individuals with higher cognitive instability showed slower response times under no time constraint. In addition, higher sensitivity to reward predicted a higher proportion of utilitarian choices regardless of the time available for decision. CONCLUSIONS: Results are discussed within the dual-process theory of moral judgement, revealing that the impact of time pressure on moral decision-making might be more complex and multifaceted than expected, potentially interacting with a specific facet of attentional impulsivity.
Subject(s)
Decision Making , Impulsive Behavior , Morals , Reward , Humans , Male , Female , Adult , Young Adult , Time Factors , Reaction Time , Choice BehaviorABSTRACT
BACKGROUND: LncRNA PCED1B-AS1 is abnormally expressed in multiple cancers and has been confirmed as an oncogene. Our study aimed to investigate the regulatory mechanism of lncRNA PCED1B-AS1 in gastric cancer. METHODS: TCGA database was used to analyze the abnormal expression of lncRNA PCED1B-AS1 in gastric cancer. By database prediction and mass spectrometric analysis, miR-3681-3p and MAP2K7 are potential downstream target molecules of lncRNA PCED1B-AS1 and verified by dual-luciferase report assay. RT-qPCR analysis and western blot were performed to detect the expressions of PCED1B-AS1 and MAP2K7 in gastric cancer cell lines and tissues. CCK-8 kit was applied to measure the cell viability. Wound healing and Transwell experiment were used to detect the migration and invasion. Western blot and immunohistochemical staining were performed to detect the expressions of EMT-related proteins in tissues. The changes of tumor proliferation were detected by xenograft experiment in nude mice. RESULTS: PCED1B-AS1 expression was higher but miR-3681-3 expression was lower in gastric cancer cell lines or tissues, compared to normal group. Function analysis verified PCED1B-AS1 promoted cell proliferation and inhibited cell apoptosis in gastric cancer cells in vitro and in vivo. LncRNA PCED1B-AS1 could bind directly to miR-3681-3p, and MAP2K7 was found to be a downstream target of miR-3681-3p. MiR-3681-3p mimics or si-MAP2K7 could partly reverse the effect of PCED1B-AS1 on gastric cancer cells. CONCLUSION: PCED1B-AS1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-3681-3p to upregulate MAP2K7 expression in gastric cancer, which indicated PCED1B-AS1/miR-3681-3p/MAP2K7 axis may serve as a potential therapeutic target for gastric cancer.
Subject(s)
Epithelial-Mesenchymal Transition , MAP Kinase Kinase Kinases , Mice, Nude , MicroRNAs , RNA, Long Noncoding , Stomach Neoplasms , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Epithelial-Mesenchymal Transition/genetics , Cell Line, Tumor , Animals , Mice , MAP Kinase Kinase Kinases/genetics , MAP Kinase Kinase Kinases/metabolism , Cell Proliferation , Gene Expression Regulation, Neoplastic , Neoplasm Invasiveness , Cell Movement , Neoplasm MetastasisABSTRACT
Endometriosis (EMs)-related infertility commonly has decreased endometrial receptivity and normal decidualization is the basis for establishing and maintaining endometrial receptivity. However, the potential molecular regulatory mechanisms of impaired endometrial decidualization in patients with EMs have not been fully clarified. We confirmed the existence of reduced endometrial receptivity in patients with EMs by scanning electron microscopy and quantitative real-time PCR. Here we identified an lncRNA, named BMPR1B-AS1, which is significantly downregulated in eutopic endometrium in EMs patients and plays an essential role in decidual formation. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and rescue analyses revealed that BMPR1B-AS1 positively regulates decidual formation through interaction with the RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Downregulation of IGF2BP2 led to a decreased stability of BMPR1B-AS1 and inhibition of activation of the SMAD1/5/9 pathway, an inhibitory effect which diminished decidualization in human endometrial stromal cells (hESCs) decidualization. In conclusion, our identified a novel regulatory mechanism in which the IGF2BP2-BMPR1B-AS1-SMAD1/5/9 axis plays a key role in the regulation of decidualization, providing insights into the potential link between abnormal decidualization and infertility in patients with EMs, which will be of clinical significance for the management and treatment of infertility in patients with EMs.
Subject(s)
Endometriosis , RNA, Long Noncoding , RNA-Binding Proteins , Adult , Female , Humans , Bone Morphogenetic Protein Receptors, Type I/metabolism , Bone Morphogenetic Protein Receptors, Type I/genetics , Decidua/metabolism , Decidua/pathology , Endometriosis/metabolism , Endometriosis/genetics , Endometriosis/pathology , Endometrium/metabolism , Endometrium/pathology , Infertility, Female/metabolism , Infertility, Female/genetics , Infertility, Female/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Signal Transduction , Stromal Cells/metabolism , Smad Proteins , Young AdultABSTRACT
BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary CNS tumor, characterized by high mortality and heterogeneity. However, the related lncRNA signatures and their target microRNA (miRNA) for GBM are still mostly unknown. Therefore, it is critical that we discover lncRNA markers in GBM and their biological activities. MATERIALS AND METHODS: GBM-related RNA-seq data were obtained from the Cancer Genome Atlas (TCGA) database. The "edger" R package was used for differently expressed lncRNAs (DELs) identification. Then, we forecasted prospective miRNAs that might bind to lncRNAs by Cytoscape software. Survival analysis of those miRNAs was examined by the starBase database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the miRNAs' target genes was conducted by the Gene Set Enrichment Analysis (GSEA) database and R software. Moreover, the proliferative ability of unc-5 netrin receptor B antisense RNA 1 (UNC5B-AS1) cells was evaluated by Cell Counting Kit-8 (CCK-8) analysis. Mechanistically, the regulatory interaction between UNC5B-AS1 and miRNA in GBM biological processes was studied using CCK-8 analysis. RESULTS: Our results indicated that overexpression of UNC5B-AS1 has been shown to suppress GBM cell growth. Mechanistically, miR-24-3p in GBM was able to alleviate the anti-oncogenic effects of UNC5B-AS1 on cell proliferation. CONCLUSION: The discovery of the novel UNC5B-AS1-miR-24-3p network suggests possible lncRNA and miRNA roles in the development of GBM, which may have significant ramifications for the analysis of clinical prognosis and the development of GBM medications.
Subject(s)
Glioblastoma , MicroRNAs , RNA, Long Noncoding , Humans , Glioblastoma/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Prospective Studies , Cell Line, Tumor , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Proliferation/genetics , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Netrin Receptors/genetics , Netrin Receptors/metabolismABSTRACT
The inadequate electrical conductivity of metal sulfides, along with their tendency to agglomerate, has hindered their use in energy storage and catalysis. The construction of a heterojunction can ameliorate these deficiencies to some extent. In this paper, MnS-BaS heterojunction catalysts were prepared by a hydrothermal method, which is a simple and inexpensive process. The MnS-BaS heterojunction catalysts exhibited superior performance owing to the strong synergistic interaction between MnS and BaS. Density functional theory (DFT) calculations reveal strong interactions at the heterojunction interface and significant electron transfer between MnS and BaS, which further modulates the electronic structure of Mn. The elevation of the center of the d-band enhances the adsorption of oxygen and oxygen-containing intermediates on the catalyst, thus promoting the oxygen reduction reaction (ORR). The practical application of MnS-BaS catalysts was tested by assembling zinc-air batteries. This study provides a rational strategy for designing transition metal catalysts that are efficient and low cost.
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Three adaptive trait-based personality types have been replicated across ages, cultures, clinical problems and clustering methods: Resilient, Undercontrolled and Overcontrolled type (RUO). Recently there is growing interest in and importance of biopsychosocial transdiagnostic factors underlying personality types, such as temperamental reactivity and self-regulation. Latter can be understood in terms of Behavioural Inhibition (BIS), Behavioural Activation Systems (BAS) and Effortful Control (EC). The occurrence of temperament based RUO types has not yet been confirmed in older adults with or without a mental disorder. Therefore, based on a person-centered approach, the current study investigates whether RUO types can be corroborated in older adults based on the aforementioned temperamental factors. Latent profile analysis yielded two distinct personality profiles in community-dwelling over-60s, which we tentatively labeled a resilient (n = 167) and overcontrolled/inhibited type (n = 241). Compared to the resilient type, the overcontrolled/inhibited type scored lower on EC and higher on BIS. We could not corroborate an undercontrolled type (profiles scored equally on BAS). Group comparisons revealed that overcontrolled/inhibited older adults demonstrated significantly more clinical symptoms, higher emotional instability, lower scores on adaptive traits, less resilience and were significantly more likely to use passive and avoidant coping styles, compared to resilient older adults.
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Dietary methionine restriction (MetR) offers an integrated set of beneficial health effects, including delaying aging, extending health span, preventing fat accumulation, and reducing oxidative stress. This study aimed to investigate whether MetR exerts entero-protective effects by modulating intestinal flora, and the effect of MetR on plasma metabolites in rats. Rats were fed diets containing 0.86% methionine (CON group) and 0.17% methionine (MetR group) for 6 weeks. Several indicators of inflammation, gut microbiota, plasma metabolites, and intestinal barrier function were measured. 16S rRNA gene sequencing was used to analyze the cecal microbiota. The MetR diet reduced the plasma and colonic inflammatory factor levels. The MetR diet significantly improved intestinal barrier function by increasing the mRNA expression of tight junction proteins, such as zonula occludens (ZO)-1, claudin-3, and claudin-5. In addition, MetR significantly increased the levels of short-chain fatty acids (SCFAs) by increasing the abundance of SCFAs-producing Erysipclotxichaceae and Clostridium_sensu_stricto_1 and decreasing the abundance of pro-inflammatory bacteria Proteobacteria and Escherichia-Shigella. Furthermore, MetR reduced the plasma levels of taurochenodeoxycholate-7-sulfate, taurocholic acid, and tauro-ursodeoxycholic acid. Correlation analysis identified that colonic acetate, total colonic SCFAs, 8-acetylegelolide, collettiside I, 6-methyladenine, and cholic acid glucuronide showed a significant positive correlation with Clostridium_sensu_stricto_1 abundance but a significant negative correlation with Escherichia-Shigella and Enterococcus abundance. MetR improved gut health and altered the plasma metabolic profile by regulating the gut microbiota in rats.
Subject(s)
Gastrointestinal Microbiome , Methionine , Animals , Rats , RNA, Ribosomal, 16S/genetics , Racemethionine , MetabolomicsABSTRACT
OBJECTIVE: To assess the short-term functional outcomes and morbidity of robotic-assisted cystectomy (RAC) and intracorporeal urinary diversion (ICUD) in patients with lower urinary tract dysfunction (LUTD). METHODS: All consecutive patients who underwent RAC+ICUD for LUTD in a tertiary hospital center, between July 2018 and May 2021 were retrospectively included. Medical records were systematically reviewed and patient, perioperative and postoperative data were collected. A good short-term functional outcome was defined by the combination of a satisfying urostomy equipment (absence of urine leakage and easy appliance of the urostomy bag), the absence of pelvicaliceal system dilatation on sonography, and the absence of renal function decrease at the 2months post-operative consultation. Intraoperative parameters and post-operative complications were collected to assess morbidity. RESULTS: Thirty-five patients were included. Eight (22.8%) patients needed intraoperative conversion to laparotomy. Twenty-five patients (92,5%) met criteria for a good functional outcome 2months post-operatively. The median operative time was 346min (86.5-407.5). The median blood loss was 100mL (100-290) and 5 patients (18.5%) required blood transfusion. The median times to return of bowel function was 3 days (2-4) and the median length of hospital stay was 10 days (10-18). Peri-operative complications were reported in 16 patients (59.2%): 6 (22.2%) minor complications Clavien ≤ II and 10 (37%) major complications Clavien ≥ III. There was no significative decrease of the renal function (mean preoperative creatininemia of 61.2µmol/L (50.5-74.5) vs 64.5µmol/L (47-85.25) postoperatively) CONCLUSION: RAC+ICUD in LUTD can provide good short-term functional outcomes while limiting blood transfusion, time to return of bowel function and the length of hospital stay. These results should be confirmed by larger prospective study.
Subject(s)
Cystectomy , Laparoscopy , Robotic Surgical Procedures , Urinary Diversion , Humans , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/methods , Cystectomy/methods , Cystectomy/adverse effects , Retrospective Studies , Male , Urinary Diversion/methods , Urinary Diversion/adverse effects , Female , Middle Aged , Laparoscopy/methods , Laparoscopy/adverse effects , Aged , Treatment Outcome , Time Factors , Lower Urinary Tract Symptoms/surgery , Lower Urinary Tract Symptoms/etiology , Recovery of Function , Postoperative Complications/epidemiology , Postoperative Complications/etiologyABSTRACT
The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.
Subject(s)
Akkermansia , Bacteroides , Bile Acids and Salts , Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Symbiosis , Animals , Humans , Male , Mice , Akkermansia/metabolism , Bacteroides/metabolism , beta-Lactamases/metabolism , Bile Acids and Salts/metabolism , Biosynthetic Pathways/genetics , Fatty Liver/metabolism , Liver/metabolism , Mice, Inbred C57BL , Verrucomicrobia/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/microbiologyABSTRACT
The geometric structure of the BAs/WTe2heterojunction was scrutinized by employingab initiocalculations grounded on density functional theory. Multiple configurations are constructed to determine the equilibrium state of the heterojunction with optimal stability. The results show that the H1-type heterojunction with interlayer distance of 3.92 Å exhibits exceptional stability and showcases a conventional Type-II band alignment, accompanied by a direct band gap measuring 0.33 eV. By applying external electric field and introducing strain, one can efficaciously modulate both the band gap and the quantity of charge transfer in the heterojunction, accompanied by the transition of band alignment from Type-II to Type-I, which makes it expected to achieve broader applications in light-emitting diodes, laser detectors and other fields. Ultimately, the heterojunction undergoes a transformation from a semiconducting to a metallic state. Furthermore, the outstanding optical characteristics inherent to each of the two monolayers are preserved, the BAs/WTe2heterojunction also serves to enhance the absorption coefficient and spectral range of the material, particularly within the ultraviolet spectrum. It merits emphasis that the optical properties of the BAs/WTe2heterojunction are capable of modification through the imposition of external electric fields and mechanical strains, which will expand its applicability and potential for future progression within the domains of nanodevices and optoelectronic apparatus.