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.

Smart Stimuli-Responsive Spherical Nucleic Acids: Cutting-Edge Platforms for Biosensing, Bioimaging, and Therapeutics.

Spherical nucleic acids (SNAs) with exceptional colloidal stability, multiple modularity, and programmability are excellent candidates to address common molecular delivery-related issues. Based on this, the higher targeting accuracy and enhanced controllability of stimuli-responsive SNAs render them precise nanoplatforms with inestimable prospects for diverse biomedical applications. Therefore, tailored diagnosis and treatment with stimuli-responsive SNAs may be a robust strategy to break through the bottlenecks associated with traditional nanocarriers. Various stimuli-responsive SNAs are engineered through the incorporation of multifunctional modifications to meet biomedical demands with the development of nucleic acid functionalization. This review provides a comprehensive overview of prominent research in this area and recent advancements in the utilization of stimuli-responsive SNAs in biosensing, bioimaging, and therapeutics. For each aspect, SNA nanoplatforms that exhibit responsive behavior to both internal stimuli (including sequence, enzyme, redox reactions, and pH) and external stimuli (such as light and temperature) are highlighted. This review is expected to offer inspiration and guidance strategies for the rational design and development of stimuli-responsive SNAs in the field of biomedicine.

Pathogenicity and inactivated vaccine treatment of Aeromonas veronii JW-4 on crucian carp.

Aeromonas veronii is a common bacterium found in a variety of aquatic environments, capable of causing a diverse array of diseases in both aquatic animals and humans. Therefore, evaluating the pathogenicity of A. veronii and implementing measures to control its spread are essential. In this study, a strain JW-4, identified as A. veronii, was isolated from diseased Scaphesthes macrolepis, a grade Ⅱ protected animal in China. To investigate the pathogenicity of the strain, fish were fed with serial levels JW-4 supplemented diet or basal diet (control group 1, CG1) for 28 days (d). Results showed that JW-4 stimulated an immune response, evidenced by an increase in immune-related enzyme activities (GOT and GPT) of serum and liver and an upregulation of genes expression levels (TNF-α and IFN-γ) of liver and spleen, and these effects gradually decreased over time. Histopathological examination revealed that JW-4 could alter the tissue structure of immune organs, such as liver and kidney. These changes were accompanied by vacuolar degeneration, nuclear dissolution, and an increased lymphocyte count. To assess protective effects of a vaccine against this strain, fish were injected with an inactivated vaccine (immunization group, IG) or 0.85% sterile saline (control group 2, CG2) for 28-day observation period, then challenged with JW-4 on the 28th day. The inactivated vaccine enhanced total and specific IgM to A. veronii levels of the fish, resulting in a relative percentage survival of 75% in IG. These findings provide a foundation for identifying pathogenic bacteria and developing more effective prophylactic strategies in aquaculture.

Ce4+/Ce3+ Redox Effect-Promoted CdS/CeO2 Heterojunction Photocatalyst for the Atom Economic Synthesis of Imines under Visible Light.

The employment of stoichiometric alcohols and amines for imine synthesis under mild and green reaction conditions is still a challenge in the field. In this work, based on our research foundation in the thermocatalytic synthesis of imines over ceria, a CdS/CeO2 heterojunction photocatalyst was constructed and successfully realized the atom-economic synthesis of imines under visible light without additives at room temperature. Mechanistic experiments and corresponding characterizations indicated that the CdS/CeO2 heterojunction can improve the separation efficiency of photogenerated carriers, which can be further enhanced by the Ce4+/Ce3+ redox pair by rapidly combining photogenerated e-. The in situ-reduced Ce3+ can better activate O2 to form Ce-O-O·, which, together with h+, efficiently accelerates alcohol oxidation, which is the rate-determined step for the synthesis of imines via oxidative coupling reaction of alcohol and amine. In addition, our photocatalyst exhibited fairly decent reusability and substrate universality. This work solves problems of using base additives and excess amine or alcohol in the reported photocatalytic systems and provides new insight for designing CeO2-based photocatalytic oxidation catalysts.

High-Performance Dual-Ion Battery Based on Silicon-Graphene Composite Anode and Expanded Graphite Cathode.

Dual-ion batteries (DIBs) are a new kind of energy storage device that store energy involving the intercalation of both anions and cations on the cathode and anode simultaneously. They feature high output voltage, low cost, and good safety. Graphite was usually used as the cathode electrode because it could accommodate the intercalation of anions (i.e., PF6-, BF4-, ClO4-) at high cut-off voltages (up to 5.2 V vs. Li+/Li). The alloying-type anode of Si can react with cations and boost an extreme theoretic storage capacity of 4200 mAh g-1. Therefore, it is an efficient method to improve the energy density of DIBs by combining graphite cathodes with high-capacity silicon anodes. However, the huge volume expansion and poor electrical conductivity of Si hinders its practical application. Up to now, there have been only a few reports about exploring Si as an anode in DIBs. Herein, we prepared a strongly coupled silicon and graphene composite (Si@G) anode through in-situ electrostatic self-assembly and a post-annealing reduction process and investigated it as an anode in full DIBs together with home-made expanded graphite (EG) as a fast kinetic cathode. Half-cell tests showed that the as-prepared Si@G anode could retain a maximum specific capacity of 1182.4 mAh g-1 after 100 cycles, whereas the bare Si anode only maintained 435.8 mAh g-1. Moreover, the full Si@G//EG DIBs achieved a high energy density of 367.84 Wh kg-1 at a power density of 855.43 W kg-1. The impressed electrochemical performances could be ascribed to the controlled volume expansion and improved conductivity as well as matched kinetics between the anode and cathode. Thus, this work offers a promising exploration for high energy DIBs.

Solvent-Controlled Morphology of Zinc-Cobalt Bimetallic Sulfides for Supercapacitors.

Bimetallic sulfides offer high theoretical specific capacitance and good stability as electrode materials due to their diverse redox reactions, larger specific surface areas, and better conductivity. The morphology of the electrode material is an important influencing factor for the electrochemical properties. Herein, a series of ZnCoS electrode materials with different morphologies were prepared by varying the solvent in the solvothermal reaction, and the effects of different microstructures on the electrochemical properties of ZnCoS were investigated. The ratio of water and ethanol in the solvent was controlled to modulate the microstructure of the as-prepared ZnCoS materials. XRD and XPS revealed the physical and chemical structure of the ZnCoS materials. SEM and TEM observations showed that the microstructure of ZnCoS transformed from one-dimensional wires to two-dimensional sheets with increasing amounts of ethanol. The maximum specific capacitance of the as-prepared ZnCoS materials is 6.22 F cm-2 at a current density of 5 mA cm-2, which is superior to that of most previously reported bimetallic sulfides. The enhanced electrochemical performance could be ascribed to its sheet-assembled spherical structure, which not only shortens the path of ion diffusion but also increases the contact between surface active sites and the electrolyte. Moreover, the spherical structure provides numerous void spaces for buffering the volume expansion and penetration of the electrolyte, which would be favorable for electrochemical reactions. Furthermore, the ZnCoS electrodes were coupled with activated carbon (AC) electrodes to build asymmetric supercapacitors (ASCs). The ASC device exhibits a maximum energy density of 0.124 mWh cm-2 under a power density of 2.1 mW cm-2. Moreover, even under a high-power density of 21 mW cm-2, the energy density can still reach 0.055 mWh cm-2.

Switching Adaptive Control with Applications on Robot Manipulators.

This paper concentrates on the study of logic-based switching adaptive control. Two different cases will be considered. In the first case, the finite time stabilization problem for a class of nonlinear system is studied. Based on the recently developed adding a barrier power integrator technique, a new logic-based switching adaptive control method is proposed. In contrast with the existing results, finite time stability can be achieved when the considered systems contain both fully unknown nonlinearties and unknown control direction. Moreover, the proposed controller has a very simple structure and no approximation methods, e.g., neural networks/fuzzy logic, are needed. In the second case, the sampled-data control for a class of nonlinear system is investigated. New sampled-data logic-based switching mechanism is proposed. Compared with previous works, the considered nonlinear system has an uncertain linear growth rate. The control parameters and the sampling time can be adjusted adaptively to render the exponential stability of the closed loop system. Applications in robot manipulators are conducted to verify the proposed results.

Asynchronous Stabilization for Two Classes of Stochastic Switching Systems with Applications on Servo Motors.

This paper addresses the asynchronous stabilization problem of two typical stochastic switching systems, i.e., dual switching systems and semi-Markov jump systems. By dual switching, it means that the systems contain both deterministic and stochastic switching dynamics. New stability criteria are firstly proposed for these two switched systems, which can well handle the asynchronous phenomenon. The conditional expectation of Lyapunov functions is allowed to increase during some unmatched interval to reduce the conservatism. Next, we present numerically testable asynchronous controller design methods for the dual switching systems. The proposed method is suitable for the situation where the asynchronous modes come from both inaccurate mode detection and time varying delay. Meanwhile, the transition probabilities are both uncertain and partly accessible. Finally, novel asynchronous controller design methods are proposed for the semi-Markov jump systems. The sojourn time of the semi-Markov jump systems can have both lower and upper bounds, which could be more practical than previous scenarios. Examples are utilized to demonstrate the effectiveness of the proposed methods.

Comparative proteomic and transcriptomic analysis reveals high pH-induced expression signatures of Chinese shrimp Fenneropenaeus chinensis.

pH has a great impact on the distribution, growth, behavior, and physiology in many aquatic animals. The comparison of proteomics between normal and high pH stress samples was successfully achieved using iTRAQ proteomic analysis to screen key response proteins and pathways. After high pH stress, 124 upregulated and 41 downregulated proteins were identified. The higher expression levels of proteins like citrate synthase, glutathione S-transferase, glutathione peroxidase, and cytochrome c oxidase are associated with oxidative stress and mitochondrial dysfunction. The upregulation of glucose-regulated protein 78 indicated that the endoplasmic reticulum stress is induced by high pH stress. There were significant upregulation expressions of V-type H+-ATPase, Na+, K+-ATPase, 14-3-3 protein, as well as ATP-binding cassette transmembrane transporters after high pH exposure, which indicating their important roles in response to high pH stress. The abundance of proteins involved in protein glycosylation, oxidative pentose phosphate pathway, protein export, and glutathione metabolism were found enriched in high pH group than in control group. Quantitative proteomic profiling and integrated analysis with transcriptomic data provide new insights into the mechanisms underlying the molecular response to high pH stress in Fenneropenaeus chinensis.

Target-triggered "signal-off" electrochemical aptasensor assisted by Au nanoparticle-modified sensing platform for high-sensitivity determination of circulating tumor cells.

In this study, we fabricated a high-sensitivity "signal-off" electrochemical aptasensing platform for quantifying circulating tumor cells (CTCs) based on target-triggered signal readout of methylene blue (MB). Au nanoparticles (AuNPs) were introduced to enlarge the specific surface area of the gold electrode (GE), which would immobilize homogeneous and more MB-aptamers. MB-modified and stem-loop-like aptamers were assigned as a recognition element with K562 cells. Thiolated complementary strands hybridized with MB-aptamers to form double-stranded DNA (dsDNA) conformation which were further self-assembled on the surface of AuNP-modified GE, leading to a marked current peak of MB signal. In the presence of K562 cells, the MB-aptamers preferred to recognize and bind with the cells, causing the disassembly of MB-aptamers from the GE surface. Therefore, the reduced value of MB signal was related to the number of K562 cells. With the proposed aptasensor, a dynamic linear range from 1 × 102 to 1 × 106 cells mL-1 was obtained with a detection limit of 23 cells mL-1. Moreover, the aptasensor showed good selectivity, stability, and reproducibility as well as potential use in the clinical setting. Meanwhile, characterization techniques such as field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy were performed to analyze the evolution of the morphology and each fabricated step of the constructed aptasensor. Our proposed aptasensor could be designed as a universal platform for CTC determination by replacing tumor cell-specific aptamers, which is a promising strategy for basic research and clinical applications. Graphical abstract.

Strand displacement-triggered G-quadruplex/rolling circle amplification strategy for the ultra-sensitive electrochemical sensing of exosomal microRNAs.

Emerging evidence suggests that exosomal microRNAs are potential biomarkers for the early diagnosis and prognostic assessment of tumor. Here, we design a strand displacement-initiated G-quadruplex/rolling circle amplification (RCA) strategy for highly specific and sensitive electrochemical sensing of exosomal microRNAs. In the presence of exosomal miRNA-21, a locked nucleic acid (LNA)-labeled toehold mediated strand displacement reaction (TMSDR) is initiated, releasing output P2 to trigger the subsequent RCA reaction by hybridizing with the C-rich circular template. Then the obtained G-rich RCA products can bind to the probe anchored on the surface of gold electrode and generate G-quadruplex conformations. Based on the TMSDR-triggered G-quadruplex/RCA strategy, the detection limit of this electrochemical biosensor is down to 2.75 fM. Moreover, our biosensor exhibits excellent repeatability, stability, and high consistency compared to RT-PCR for clinical detection. In conclusion, this assay is expected to provide a hopeful strategy for the early non-invasive diagnosis and prognostic estimation of cancer. Graphical abstract Schematic illustration of electrochemical sensing of exosomal microRNAs based on strand displacement-initiated G-quadruplex/rolling circle amplification (RCA) strategy.

Measurement of Dead Space Fraction Upon ICU Admission Predicts Length of Stay and Clinical Outcomes Following Bidirectional Cavopulmonary Anastomosis.

OBJECTIVES: Increased alveolar dead space fraction has been associated with prolonged mechanical ventilation and increased mortality in pediatric patients with respiratory failure. The association of alveolar dead space fraction with clinical outcomes in patients undergoing bidirectional cavopulmonary anastomosis for single ventricle congenital heart disease has not been reported. We describe an association of alveolar dead space fraction with postoperative outcomes in patients undergoing bidirectional cavopulmonary anastomosis. DESIGN: In a retrospective case-control study, we examined for associations between alveolar dead space fraction ([PaCO2 - end-tidal CO2]/PaCO2), arterial oxyhemoglobin saturation, and transpulmonary gradient upon postoperative ICU admission with a composite primary outcome (requirement for surgical or catheter-based intervention, death, or transplant prior to hospital discharge, defining cases) and several secondary endpoints in infants following bidirectional cavopulmonary anastomosis. SETTINGS: Cardiac ICU in a tertiary care pediatric hospital. PATIENTS: Patients undergoing bidirectional cavopulmonary anastomosis at our institution between 2011 and 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 191 patients undergoing bidirectional cavopulmonary anastomosis, 28 patients were cases and 163 were controls. Alveolar dead space fraction was significantly higher in the case (0.26 ± 0.09) versus control group (0.17 ± 0.09; p < 0.001); alveolar dead space fraction at admission was less than 0.12 in 0% of cases and was greater than 0.28 in 35% of cases. Admission arterial oxyhemoglobin saturation was significantly lower in the case (77% ± 12%) versus control group (83% ± 9%; p < 0.05). Sensitivity and specificity for future case versus control assignment was best when prebidirectional cavopulmonary anastomosis risk factors, admission alveolar dead space fraction (AUC, 0.74), and arterial oxyhemoglobin saturation (AUC, 0.65) were combined in a summarial model (AUC, 0.83). For a given arterial oxyhemoglobin saturation, the odds of becoming a case increased on average by 181% for every 0.1 unit increase in alveolar dead space fraction. Admission alveolar dead space fraction and arterial oxyhemoglobin saturation were linearly associated with prolonged ICU length of stay, hospital length of stay, duration of mechanical ventilation, and duration of thoracic drainage (p < 0.001 for all). CONCLUSIONS: Following bidirectional cavopulmonary anastomosis, alveolar dead space fraction in excess of 0.28 or arterial oxyhemoglobin saturation less than 78% upon ICU admission indicates an increased likelihood of requiring intervention prior to hospital discharge. Increasing alveolar dead space fraction and decreasing arterial oxyhemoglobin saturation are associated with increased lengths of stay.

Interfacial Nanoprecipitation toward Stable and Responsive Microbubbles and Their Use as a Resuscitative Fluid.

A new approach has been developed to prepare stable microbubbles (MBs) by interfacial nanoprecipitation of bioabsorbable polymers at air/liquid interfaces. This facile method offers robust control over the morphology and chemophysical properties of MBs by simple chemical modifications. This approach is amenable to large-scale manufacturing, and is useful to develop functional MBs for advanced biomedical applications. To demonstrate this, a MB-based intravenous oxygen carrier was created that undergoes pH-triggered self-elimination. Intravenous injection of previous MBs increased the risk of pulmonary vascular obstruction. However, we show, for the first time, that our current design is superior, as they 1) yielded no evidence of acute risks in rodents, and 2) improved the survival in a disease model of asphyxial cardiac arrest (from 0 to 100 %), a condition that affects more than 100 000 in-hospital patients, and carries a mortality of about 90 %.

Hemodynamic Effects of Lipid-Based Oxygen Microbubbles via Rapid Intravenous Injection in Rodents.

PURPOSE: Low oxygen levels, or hypoxemia, is a common cause of morbidity and mortality in critically ill patients. Hypoxemia is typically addressed by increasing the fraction of inspired oxygen, the use of mechanical ventilation, or more invasive measures. Recently, the injection of oxygen gas directly into the bloodstream by packaging it within lipid-based oxygen microbubbles (LOMs) has been explored. The purpose of this work is to examine the acute hemodynamic effects of intravenous injections of LOMs. METHODS: LOMs composed of 1,2-distearoyl-sn-glycero-3-phosphocoline and cholesterol were manufactured using a process of shear homogenization under an oxygen headspace. A 5 mL aliquot of either PlasmaLyte A, or low (37%) or high (55%) concentration LOMs (n = 10 per group) was injected over a 1 min period into Sprague Dawley rats instrumented for measurement of cardiac index and pulmonary (PVR) and systemic (SVR) vascular resistance during a 60 min observation period. Hemodynamics were compared between groups by linear mixed modeling. RESULTS: Approximately 1011 LOMs with mean diameter 3.77 ± 1.19 µm were injected over the 1 min period. Relative to controls, rodents treated with high concentration LOMs exhibited a higher pulmonary artery pressure (20 ± 0.4 mmHg vs 18 ± 0.4 mmHg, P < 0.001) and higher PVR (0.31 ± 0.01 vs 0.23 ± 0.01 mmHg/mL*min*kg, P < 0.001. Despite a stable cardiac index (62.2 ± 3.5 vs 62.3 ± 3.4 mL/min*kg, P < 0.001), mean arterial blood pressure decreased significantly in LOM-treated animals (46 ± 2 vs 60 ± 2 mmHg, P < 0.001) due to a decrease in SVR. Injections with aged LOM emulsions (>48 h since manufacture) resulted in a higher incidence of hemodynamic collapse during the observation period (P = 0.02). CONCLUSIONS: LOMs may be injected in quantities sufficient to deliver clinically meaningful volumes of oxygen but cause significant decrements in blood pressure and elevations in PVR.

Efficient access to cis-decalinol frameworks: copper(i)-catalyzed borylative cyclization of allene cyclohexanediones.

Cu-catalyzed borylative cyclization of allene cyclohexanediones has been described through a tandem ß-borylation and intramolecular allylic addition process, affording borylated cis-decalinols with excellent yields and diastereoselectivities. A good enantioselectivity is also achieved in the asymmetric version. The hemiboronate group in the cyclization products could be subjected to several useful transformations.

Development and validation of the Chinese-language version of the eating pathology symptoms inventory.

OBJECTIVE: Eating disorders are becoming increasingly prevalent among individuals from non-Western countries, yet few non-English-language measures of eating pathology exist. The current study sought to develop and validate a Chinese version of the Eating Pathology Symptoms Inventory(1) with cross-cultural equivalence. METHOD: The Chinese version of the Eating Pathology Symptoms Inventory (CEPSI) was translated and back-translated by native Chinese speakers, and administered to a pilot sample of native Chinese speaking students (N = 45) from a Midwestern university in the United States. The measure was revised based on participant's feedback, and administrated to a large sample of native Chinese speakers recruited from a Midwestern community (N = 195; 49.2% women) to test the factor structure and convergent and discriminant validity of the measure. RESULTS: As hypothesized, the CEPSI had a robust eight-factor structure, and demonstrated evidence for acceptable internal consistency (median coefficient alphas were 0.80 for men and 0.79 for women, and alpha values ranged from 0.36 to 0.85 in men and 0.70 to 0.89 in women), and good convergent validity (correlations with relevant translated scales from the Eating Disorder Examination-Questionnaire and the Eating Attitudes Test-26 ranged from 0.22 to 0.58) and discriminate validity (correlations with a translated version of the Center for Epidemiological Studies - Depression Scale ranged from .12 to .30). DISCUSSION: Results indicate that the CEPSI has high potential value as a new self-report measure of eating pathology that can be used in future research and clinical settings to assess eating disorder-related psychopathology among Chinese speaking individuals.

Efficient Access to Bicyclo[4.3.0]nonanes: Copper-Catalyzed Asymmetric Silylative Cyclization of Cyclohexadienone-Tethered Allenes.

The creation of three consecutive chiral carbon centers in one step is achieved using Cu-catalyzed asymmetric silylative cyclization of cyclohexadienone-tethered allenes. Through regioselective ß-silylation of the allene and subsequent enantioselective 1,4-addition to cyclohexadienone, this tandem reaction could afford cis-hydrobenzofuran, cis-hydroindole, and cis-hydroindene frameworks with excellent yields (80-98%) and enantioselectivities (94-98% ee) bearing vinylsilane and enone substructures. Meanwhile, this mild transformation is generally compatible with a wide range of functional groups, which allows further conversion of the bicyclic products to bridged and tricyclic ring structures.

Comparative transcriptome reveals importance of export apparatus subunit (ascR) in type III secretion system and its roles on biological properties, gene expression profiles, virulence and colonization of Aeromonas veronii.

Aeromonas veronii, an opportunistic pathogen, is known to cause serious infections across various species. In our previous study, we discovered that A. veronii GL2 exhibited a virulence up to ten times greater than that of FO1. To ascertain the factors contributing to the disparity in virulence between the two strains, we conducted a comparative transcriptome analysis. This analysis reveals a significant upregulation (P < 0.05) of the ascR gene in GL2 compared with FO1. Additionally, six differentially expressed genes (DEGs) were identified within the "Bacterial secretion system" pathway (map03070), with ascR being an essential component of type III secretion system (T3SS). AscR, considered as SctR family export apparatus subunit within the T3SS, has ambiguous roles in the biological properties, gene expression profiles, virulence and colonization of A. veronii. Therefore, we constructed a mutant strain (ΔascR) by homologous recombination. Comparative analysis with the wide-type GL2 reveals no significant differences in terms of colony morphology, growth curve, hemolytic activity and protease activity. However, significant reductions (P < 0.01) were observed in the abilities of biofilm formation and swimming mobility. No remarkable difference was noted in the lengths of flagella. The LD50 value of ΔascR was to be 5.15 times higher than that of GL2. Interestingly, the mRNA expression of ascC, ascD, ascJ and ascI genes in the T3SS, and mshB, mshE, mshK and mshP genes in the MSHA type pili were significantly upregulated (P < 0.05) in ΔascR, potentially due to transcriptional compensation. Further analysis of enzymatic biomarkers revealed that ΔascR might not destruct the recognition of innate immune response in host remarkably, but the colonization levels of A.veronii were significantly suppressed (P < 0.01) in ΔascR group. In conclusion, the ascR gene may be a key determinant in regulating the virulence of A. veronii, and the destruction of the T3SS caused by ascR deficiency results in these notable changes.

Exploration of effective biomarkers for venous thrombosis embolism in Behçet's disease based on comprehensive bioinformatics analysis.

Behçet's disease (BD) is a multifaceted autoimmune disorder affecting multiple organ systems. Vascular complications, such as venous thromboembolism (VTE), are highly prevalent, affecting around 50% of individuals diagnosed with BD. This study aimed to identify potential biomarkers for VTE in BD patients. Three microarray datasets (GSE209567, GSE48000, GSE19151) were retrieved for analysis. Differentially expressed genes (DEGs) associated with VTE in BD were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). Subsequently, potential diagnostic genes were explored through protein-protein interaction (PPI) network analysis and machine learning algorithms. A receiver operating characteristic (ROC) curve and a nomogram were constructed to evaluate the diagnostic performance for VTE in BD patients. Furthermore, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate potential underlying mechanisms. Finally, the efficacy of listed drugs was assessed based on the identified signature genes. The limma package and WGCNA identified 117 DEGs related to VTE in BD. A PPI network analysis then selected 23 candidate hub genes. Four DEGs (E2F1, GATA3, HDAC5, and MSH2) were identified by intersecting gene sets from three machine learning algorithms. ROC analysis and nomogram construction demonstrated high diagnostic accuracy for these four genes (AUC: 0.816, 95% CI: 0.723-0.909). Immune cell infiltration analysis revealed a positive correlation between dysregulated immune cells and the four hub genes. ssGSEA provided insights into potential mechanisms underlying VTE development and progression in BD patients. Additionally, therapeutic agent screening identified potential drugs targeting the four hub genes. This study employed a systematic approach to identify four potential hub genes (E2F1, GATA3, HDAC5, and MSH2) and construct a nomogram for VTE diagnosis in BD. Immune cell infiltration analysis revealed dysregulation, suggesting potential macrophage involvement in VTE development. ssGSEA provided insights into potential mechanisms underlying BD-induced VTE, and potential therapeutic agents were identified.

Aeromonas veronii tolC modulates its virulence and the immune response of freshwater pearl mussels, Hyriopsis cumingii.

Aeromonas veronii is an opportunistic pathogen that causes diseases in aquatic animals, but its key virulence factors remain unclear. We screened the gene tolC with significantly different expression levels in the two isolates, A. veronii GL2 (higher virulence) and A. veronii FO1 (lower virulence). Therefore, we constructed mutant strain ΔtolC and analyzed its immunological properties. ΔtolC exhibited the reduced ability of biofilms formation, inhibited envelope stress response mediated by several antibiotics except cefuroxime, implying the ability to evade host immunity might be restrained. Challenge tests showed that the LD50 of ΔtolC was 10.89-fold than that of GL2. Enzymatic activities of ΔtolC group were significantly lower and peak time was delayed to 12 h, as demonstrated by qRT-PCR results. Histopathological examination displayed that the degree of tissue damage in ΔtolC group was alleviated. The results show that tolC is an important virulence factor of A. veronii, which provides references for live-attenuated vaccine.