Identification of biomarkers for abdominal aortic aneurysm in Behçet's disease via mendelian randomization and integrated bioinformatics analyses.

Behçet's disease (BD) is a complex autoimmune disorder impacting several organ systems. Although the involvement of abdominal aortic aneurysm (AAA) in BD is rare, it can be associated with severe consequences. In the present study, we identified diagnostic biomarkers in patients with BD having AAA. Mendelian randomization (MR) analysis was initially used to explore the potential causal association between BD and AAA. The Limma package, WGCNA, PPI and machine learning algorithms were employed to identify potential diagnostic genes. A receiver operating characteristic curve (ROC) for the nomogram was constructed to ascertain the diagnostic value of AAA in patients with BD. Finally, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were conducted. The MR analysis indicated a suggestive association between BD and the risk of AAA (odds ratio [OR]: 1.0384, 95% confidence interval [CI]: 1.0081-1.0696, p = 0.0126). Three hub genes (CD247, CD2 and CCR7) were identified using the integrated bioinformatics analyses, which were subsequently utilised to construct a nomogram (area under the curve [AUC]: 0.982, 95% CI: 0.944-1.000). Finally, the immune cell infiltration assay revealed that dysregulation immune cells were positively correlated with the three hub genes. Our MR analyses revealed a higher susceptibility of patients with BD to AAA. We used a systematic approach to identify three potential hub genes (CD247, CD2 and CCR7) and developed a nomogram to assist in the diagnosis of AAA among patients with BD. In addition, immune cell infiltration analysis indicated the dysregulation in immune cell proportions.

Identification of key biomarkers for predicting CAD progression in inflammatory bowel disease via machine-learning and bioinformatics strategies.

The study aimed to identify the biomarkers for predicting coronary atherosclerotic lesions progression in patients with inflammatory bowel disease (IBD). Related transcriptome datasets were seized from Gene Expression Omnibus database. IBD-related modules were identified via Weighted Gene Co-expression Network Analysis. The 'Limma' was applied to screen differentially expressed genes between stable coronary artery disease (CAD) and acute myocardial infarction (AMI). Subsequently, we employed protein-protein interaction (PPI) network and three machine-learning strategies to further screen for candidate hub genes. Application of the receiver operating characteristics curve to quantitatively evaluate candidates to determine key diagnostic biomarkers, followed by a nomogram construction. Ultimately, we performed immune landscape analysis, single-gene GSEA and prediction of target-drugs. 3227 IBD-related module genes and 570 DEGs accounting for AMI were recognized. Intersection yielded 85 shared genes and mostly enriched in immune and inflammatory pathways. After filtering through PPI network and multi-machine learning algorithms, five candidate genes generated. Upon validation, CTSD, CEBPD, CYP27A1 were identified as key diagnostic biomarkers with a superior sensitivity and specificity (AUC > 0.8). Furthermore, all three genes were negatively correlated with CD4+ T cells and positively correlated with neutrophils. Single-gene GSEA highlighted the importance of pathogen invasion, metabolism, immune and inflammation responses during the pathogenesis of AMI. Ten target-drugs were predicted. The discovery of three peripheral blood biomarkers capable of predicting the risk of CAD proceeding into AMI in IBD patients. These identified biomarkers were negatively correlated with CD4+ T cells and positively correlated with neutrophils, indicating a latent therapeutic target.

QSIdb: quorum sensing interference molecules.

Quorum sensing interference (QSI), the disruption and manipulation of quorum sensing (QS) in the dynamic control of bacteria populations could be widely applied in synthetic biology to realize dynamic metabolic control and develop potential clinical therapies. Conventionally, limited QSI molecules (QSIMs) were developed based on molecular structures or for specific QS receptors, which are in short supply for various interferences and manipulations of QS systems. In this study, we developed QSIdb (http://qsidb.lbci.net/), a specialized repository of 633 reported QSIMs and 73 073 expanded QSIMs including both QS agonists and antagonists. We have collected all reported QSIMs in literatures focused on the modifications of N-acyl homoserine lactones, natural QSIMs and synthetic QS analogues. Moreover, we developed a pipeline with SMILES-based similarity assessment algorithms and docking-based validations to mine potential QSIMs from existing 138 805 608 compounds in the PubChem database. In addition, we proposed a new measure, pocketedit, for assessing the similarities of active protein pockets or QSIMs crosstalk, and obtained 273 possible potential broad-spectrum QSIMs. We provided user-friendly browsing and searching facilities for easy data retrieval and comparison. QSIdb could assist the scientific community in understanding QS-related therapeutics, manipulating QS-based genetic circuits in metabolic engineering, developing potential broad-spectrum QSIMs and expanding new ligands for other receptors.

A systematic review and meta-analysis on sex disparities in the outcomes of fenestrated branched endovascular aortic aneurysm repair.

OBJECTIVE: To compare the risk of mortality and complications between male and female patients undergoing aortic aneurysm repair with fenestrated-branched endovascular aortic repair (FBEVAR). METHODS: The PubMed, Embase, and Scopus databases were searched systematically for observational studies in patients undergoing elective fenestrated branched endovascular repair for aortic aneurysm. The included studies compared outcomes of interest based on the sex of the patients. The pooled effect sizes were reported as odds ratio (OR) and weighted mean difference (WMD). STATA software was used for statistical analysis. RESULTS: The meta-analysis included nine studies. Compared with males, females had a higher risk of perioperative and in-hospital mortality (OR, 3.01; 95% confidence interval [CI], 2.01-4.53), mortality within 1 year postoperatively (OR, 1.79; 95% CI, 1.09-2.93) and mortality at more than 1 year postoperatively (OR, 1.31l 95% CI, 1.02-1.69). Female patients had significantly higher operative time (minutes) (WMD, 33.77; 95% CI, 12.01-55.52), length of hospital stay (days) (WMD, 2.29; 95% CI, 1.52-3.07), and the risk of major complications (OR, 2.93; 95% CI, 1.36-6.32) There was an increased risk of respiratory complications (OR, 1.70; 95% CI, 1.20-2.40), renal complications (OR, 2.68; 95% CI, 1.25-5.74), stroke (OR, 2.74; 95% CI, 1.44-5.22), sepsis (OR, 2.24; 95% CI, 1.23-4.09), and ischemic colitis (OR, 2.63; 95% CI, 1.48-4.68) in female patients, and they were less likely to be discharged home postoperatively (OR, 0.58; 95% CI, 0.43-0.77). CONCLUSIONS: In patients undergoing FBEVAR, female sex is associated with higher risk of mortality and complications. These findings suggest the need for careful supervision and management by multidisciplinary team in females undergoing FBEVAR.

In Vitro Hypoglycemic Diterpenoids from the Roots of Croton yunnanensis.

Fifteen compounds including nine new diterpenes were isolated from the roots of Croton yunnanensis. By HRESIMS, NMR, ECD data, and X-ray diffraction analysis, the new compounds were characterized as eight neo-clerodane diterpenes (compounds 1-8) and one 15,16-dinor-ent-pimarane diterpene (9). All diterpenes were assayed for their hypoglycemic activities. Compounds 1-4, 6, 7, and 10 promoted glucose uptake activity in insulin-resistant 3T3-L1 adipocytes. Compounds 1 and 6 showed insulin sensitizing activity, potentiating conspicuously their glucose uptake activity at a concentration of 20 µM when treated synergistically with low-concentration insulin at 1 nM.

Tigliane Diterpenoids with Larvicidal, Antifungal, and α-Glucosidase Inhibitory Activities from Croton damayeshu.

Thirty-five tigliane diterpenoids and two ent-kaurane diterpenoids were isolated from the leaves of Croton damayeshu, and, among them, compounds 1-10 were characterized as new tigliane diterpenoids. The structures of compounds 1-10 were determined by analysis of their HRESIMS, NMR, and ECD data and by chemical methods. The isolates were assayed for their larvicidal, antifungal, and α-glucosidase inhibitory activities, and compounds 8-10 were found to possess larvicidal activities against Plutella xylostella with LC50 values of 0.19, 0.16, and 0.26 µM, respectively, comparable to the LC50 of 0.14 µM for the positive control, flubendiamide.

The role of biodiversity in mitigating the effects of nutrient limitation and short-term rotations in plantations of subtropical China.

Species diversity plays an essential role in enhancing ecosystem functions (EF) in both natural and plantation forests. However, we do not fully understand whether species diversity could maintain the sustainability of EFs in multiple-rotation plantations. Here, we hypothesized that tree species mixtures could mitigate declines in EFs along successive rotations, but could not maintain ecosystem multifunctionality. To test our hypothesis, we examined the effects of species diversity on four EFs, i.e., aboveground biomass (AGB), soil available nitrogen (SAN) and phosphorus (SAP), and soil organic matter (SOM), based on pure model simulation in plantations of subtropical China. The model fusion framework was set up by the integration of the process-based FORECAST and Multivariate Diversity-Interactions models. In the simulation, four local typical plantation tree species (two conifers, one evergreen broadleaf, and one deciduous N-fixing broadleaf) were selected and combined to form four monoculture and 11 mixture stands, and for each stand, the simulation was made for four 25-year rotations. The results showed that all the four EFs declined with the progress of rotations in both monoculture and mixtures, and the declining range was larger in monoculture than in mixtures in each rotation. Particularly, SAP significantly decreased while AGB, SAN, and SOM increased with diversity evenness from 0 (monoculture) to 1 (four species being equal abundant in the mixture). Overall, SAP and AGB displayed higher sensitivity to the disturbance of successive rotations compared with SAN and SOM. These results suggest that mixing species could not maintain EFs along with successive rotations because it could not alleviate SAP deficiencies in the soils resulted from the disturbances of silvicultural measures.

In Situ Reactor-Integrated Electrospray Ionization Mass Spectrometry for Heterogeneous Catalytic Reactions and Its Application in the Process Analysis of High-Pressure Liquid-Phase Lignin Depolymerization.

Process analysis of heterogeneous catalytic reactions such as lignin depolymerization is essential to understand the reaction mechanism at the molecular level, but it is always challenging due to harsh conditions. Herein, we report an operando process analysis strategy by combining a microbatch reactor with high-resolution mass spectrometry (MS) via a reactor-integrated electrospray ionization (R-ESI) technique. R-ESI-MS expands the applications of traditional in situ MS to a heterogeneous and high-pressure liquid-phase system. With this strategy, we present the evolution of a series of monomers, dimers, and oligomers during lignin depolymerization under operando conditions (methanol solvent, 260 °C, ∼8 MPa), which is the first experimental elucidation of a progressive depolymerization pathway and evidence of repolymerization of active monomers. The proposed R-ESI-MS is crucial in probing depolymerization intermediates of lignin; it also provides a flexible strategy for process analysis of heterogeneous catalytic reactions under operando conditions.

Combinational quorum sensing devices for dynamic control in cross-feeding cocultivation.

Quorum sensing (QS) offers cell density dependent dynamic regulations in cell culture through devices such as synchronized lysis circuit (SLC) and metabolic toggle switch (MTS). However, there is still a lack of studies on cocultivation with a combination of different QS-based devices. Taking the production of isopropanol and salidroside as case studies, we have mathematically modeled a comprehensive set of QS-regulated cocultivation schemes and constructed experimental combinations of QS devices, respectively, to evaluate their feasibility and optimality for regulating growth competition and corporative production. Glucose split ratio is proposed for the analysis of competition between cell growth and targeted production. Results show that the combination of different QS devices across multiple members offers a new tool with the potential to effectively coordinate synthetic microbial consortia for achieving high product titer in cross-feeding cocultivation. It is also evident that the performance of such systems is significantly affected by dynamic characteristics of chosen QS devices, carbon source control and the operational settings. This study offers insights for future applications of combinational QS devices in synthetic microbial consortia.

Quorum sensing for population-level control of bacteria and potential therapeutic applications.

Quorum sensing (QS), a microbial cell-to-cell communication process, dynamically regulates a variety of metabolism and physiological activities. In this review, we provide an update on QS applications based on autoinducer molecules including acyl-homoserine lactones (AHLs), auto-inducing peptides (AIPs), autoinducer 2 (AI-2) and indole in population-level control of bacteria, and highlight the potential in developing novel clinical therapies. We summarize the development in the combination of various genetic circuits such as genetic oscillators, toggle switches and logic gates with AHL-based QS devices in Gram-negative bacteria. An overview is then offered to the state-of-the-art of much less researched applications of AIP-based QS devices with Gram-positive bacteria, followed by a review of the applications of AI-2 and indole based QS for interspecies communication among microbial communities. Building on these general-purpose QS applications, we highlight the disruptions and manipulations of QS devices as potential clinical therapies for diseases caused by biofilm formation, antibiotic resistance and the phage invasion. The last part of reviewed literature is dedicated to mathematical modelling for QS applications. Finally, the key challenges and future perspectives of QS applications in monoclonal synthetic biology and synthetic ecology are discussed.