The Association of Systemic Inflammatory Response Index and Neutrophil-to-High-Density Lipoprotein Ratio Mediated by Fasting Blood Glucose with 90-Day Prognosis in Acute Ischemic Stroke Patients.

INTRODUCTION: The contribution of individual and combined inflammatory markers for the prognosis of acute ischemic stroke (AIS) remains elusive. This study investigated the effect of systemic inflammatory response index (SIRI), and neutrophil to high-density lipoprotein ratio (NHR), which is mediated by fasting blood glucose (FBG), on 90-day prognosis of patients with AIS. METHODS: In this pre-specified substudy of an observational cohort study, 2,828 patients with AIS were enrolled from the Nanjing Stroke Registry between January 2017 and July 2021. Peripheral venous blood was collected from patients fasting for at least 8 h within 24 h of admission to gather information on the following parameters: neutrophil count, lymphocyte count, monocyte count, HDL level, and fasting blood glucose level. Then, the SIRI and NHR values were calculated. Following this, the correlation among SIRI, NHR, and modified Rankin Scale (mRS) scores 90 days after onset was examined via univariate and multivariate logistic analyses. Lastly, mediation analysis was performed to examine the relationship between systematic inflammatory response and study outcomes mediated by FBG. RESULTS: SIRI and NHR were both negatively correlated with clinical outcomes (p < 0.05). Logistic regression analysis revealed that SIRI and NHR were independently associated with poor outcomes after adjusting for potential confounders. Subgroup analyses further validated these correlations. Meanwhile, mediation analysis corroborated that FBG partially mediated the associations between SIRI and a poor prognosis at 90 days (indirect effect estimate = 0.0038, bootstrap 95% CI 0.001-0.008; direct effect estimate = 0.1719, bootstrap 95% CI 0.1258-0.2179). Besides, FBG also played a mediating role between NHR and poor outcomes (indirect effect estimate = 0.0066, bootstrap 95% CI 0.002-0.120; direct effect estimate = 0.1308, bootstrap 95% CI 0.0934-0.1681). CONCLUSION: Our study demonstrated that SIRI and NHR are positively associated with poor clinical and mortality outcomes at 90 days in AIS patients, which was partially mediated by FBG.

The relationship between systemic inflammation index, systemic immune-inflammatory index, and inflammatory prognostic index and 90-day outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: To explore the association of systemic inflammatory index (SIRI), systemic immune-inflammatory index (SII) and inflammatory prognosis index (IPI) with 90d outcomes in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. METHODS: The patients who underwent intravenous thrombolysis were enrolled in the present study from September 2019 to December 2022. According to the relevant blood indexes obtained in 24 h after admission, the corresponding values of SIRI, SII and IPI were calculated. The correlation among SIRI, SII, IPI, and admission NIHSS scores was examined by Spearman correlation analysis. ROC curve analysis was conducted to determine the optimal cut-off value of SIRI, SII, IPI, and their corresponding sensitivity and specificity to evaluate their predictive value on admission for poor prognosis. To investigate whether high SIRI, SII, and IPI were independent predictors of poor outcomes within 90 days, variables with P-value < 0.05 during univariate analysis were included in multivariate analysis. RESULTS: Compared with the good outcome group, the poor outcome group had higher SIRI, IPI, and SII. Spearman correlation analysis showed that the SIRI, IPI, and SII levels significantly correlated with the admission NIHSS score (r = 0.338, 0.356, 0.427, respectively; Ps < 0.001). Univariate analysis and Multivariate logistic regression analysis revealed high SIRI, SII, and IPI values as independent risk factors for poor 90-day prognosis (OR = 1.09, 1.003 and 7.109, respectively). CONCLUSIONS: High SIRI, IPI, and SII values are correlated with poor 90d outcomes in AIS patients undergoing intravenous thrombolysis.

In-situ growth of electrically conductive MOFs in wood cellulose scaffold for flexible, robust and hydrophobic membranes with improved electrochemical performance.

Electrically conductive metal-organic frameworks (EC-MOFs) have attracted great attentions in electrochemical fields, but their practical application is limited by their hard-to-shape powder form. The aims was to integrate continuously nucleated EC-MOFs on natural wood cellulose scaffold to develop biobased EC-MOFs membrane with robust flexibility and improved electrochemical performance for wearable supercapacitors. EC-MOF materials (NiCAT or CuCAT) were successfully incorporated onto porous tempo-oxidized wood (TOW) scaffold to create ultrathin membranes through electrostatic force-mediated interfacial growth and simple room-temperature densification. The studies demonstrated the uniform and continuous EC-MOFs nanolayer on TOW scaffold and the interfacial bonding between EC-MOF and TOW. The densification of EC-MOF@TOW bulk yielded highly flexible ultrathin membranes (about 0.3 mm) with high tensile stress exceeding 180 MPa. Moreover, the 50 %-NiCAT@TOW membrane demonstrated high electrical conductivity (4.227 S·m-1) and hydrophobicity (contact angle exceeding 130°). Notably, these properties remained stable even after twisting or bending deformation. Furthermore, the electrochemical performance of EC-MOF@TOW membrane with hierarchical pores outperformed the EC-MOF powder electrode. This study innovatively anchored EC-MOFs onto wood through facile process, yielding highly flexible membranes with exceptional performance that outperforms most of reported conductive wood-based membranes. These findings would provide some references for flexible and functional EC-MOF/wood membranes for wearable devices.

Variation in the response to antibiotics and life-history across the major Pseudomonas aeruginosa clone type (mPact) panel.

Pseudomonas aeruginosa is a ubiquitous, opportunistic human pathogen. Since it often expresses multidrug resistance, new treatment options are urgently required. Such new treatments are usually assessed with one of the canonical laboratory strains, PAO1 or PA14. However, these two strains are unlikely representative of the strains infecting patients, because they have adapted to laboratory conditions and do not capture the enormous genomic diversity of the species. Here, we characterized the major P. aeruginosa clone type (mPact) panel. This panel consists of 20 strains, which reflect the species' genomic diversity, cover all major clone types, and have both patient and environmental origins. We found significant strain variation in distinct responses toward antibiotics and general growth characteristics. Only few of the measured traits are related, suggesting independent trait optimization across strains. High resistance levels were only identified for clinical mPact isolates and could be linked to known antimicrobial resistance (AMR) genes. One strain, H01, produced highly unstable AMR combined with reduced growth under drug-free conditions, indicating an evolutionary cost to resistance. The expression of microcolonies was common among strains, especially for strain H15, which also showed reduced growth, possibly indicating another type of evolutionary trade-off. By linking isolation source, growth, and virulence to life history traits, we further identified specific adaptive strategies for individual mPact strains toward either host processes or degradation pathways. Overall, the mPact panel provides a reasonably sized set of distinct strains, enabling in-depth analysis of new treatment designs or evolutionary dynamics in consideration of the species' genomic diversity. IMPORTANCE: New treatment strategies are urgently needed for high-risk pathogens such as the opportunistic and often multidrug-resistant pathogen Pseudomonas aeruginosa. Here, we characterize the major P. aeruginosa clone type (mPact) panel. It consists of 20 strains with different origins that cover the major clone types of the species as well as its genomic diversity. This mPact panel shows significant variation in (i) resistance against distinct antibiotics, including several last resort antibiotics; (ii) related traits associated with the response to antibiotics; and (iii) general growth characteristics. We further developed a novel approach that integrates information on resistance, growth, virulence, and life-history characteristics, allowing us to demonstrate the presence of distinct adaptive strategies of the strains that focus either on host interaction or resource processing. In conclusion, the mPact panel provides a manageable number of representative strains for this important pathogen for further in-depth analyses of treatment options and evolutionary dynamics.

Effects of CO2 on the transformation of antibiotic resistance genes via increasing cell membrane channels.

The increase of CO2 concentration in the atmosphere, water and soil environment can lead to the changes in microbial activities. However, the transformation of antibiotic resistance genes has not been investigated in the presence of higher levels of CO2. This study demonstrated that CO2 facilitated the transformation of pUC19 plasmid, carrying ampicillin resistance genes, into Escherichia coli. Mechanism studies revealed that the type Ⅱ secretion system, type Ⅳ pilus and some other secretion systems were enhanced by CO2, leading to DNA capture by pilus, larger cell pore sizes and more cell membrane channels. CO2 also increased reactive oxygen species production, leading to SOS response and cell membrane damage. Besides, changes in intracellular Fe2+ and Mg2+ concentrations induced by CO2 caused greater damage to the cell membrane and enhanced secretion systems, respectively. Overall, increased CO2 provided more cell membrane channels for plasmid uptake and led to higher transformation efficiencies. The potential risk of a natural factor on the transformation of ARGs was first studied in this study, which helps us understand the fate of ARGs in ecosystems. As the carbon emission will continue to grow and enhance the enrichment of CO2 in water and soil, the findings revealed a more severe public health issue under the background of carbon emission and CO2 leakage.

CO2 promotes the conjugative transfer of multiresistance genes by facilitating cellular contact and plasmid transfer.

The dissemination of antibiotic resistance genes (ARGs), especially via the plasmid-mediated conjugation, is becoming a pervasive global health threat. This study reported that this issue can be worse by CO2, as increased CO2 was found to facilitate the conjugative transfer of ARGs carried on plasmid RP4 by 2.4-9.0 and 1.3-3.8 fold within and across genera, respectively. Mechanistic studies revealed that CO2 benefitted the cell-to-cell contact by increasing cell surface hydrophobicity and decreasing cell surface charge, both of which resulted in the reduced intercellular repulsion. Besides, the transcriptional expression of genes responsible for global regulator (korA, korB and trbA), plasmid transfer and replication system (trfAp), and mating pair formation system (traF and traG) were all influenced by CO2, facilitating the mobilization and channel transfer of plasmid. Furthermore, the presence of CO2 induced the release of intracellular Ca2+ and increased the transmembrane potential of recipients, which contributed to the increased proton motive force (PMF), providing more power for DNA uptake. This is the first study addressing the potential risks of increased CO2 on the propagation of ARGs, which provides a new insight into the concerns of anthropogenic CO2 emissions and CO2 storage.

Low-level free nitrous acid efficiently inhibits the conjugative transfer of antibiotic resistance by altering intracellular ions and disabling transfer apparatus.

Recently, the dissemination of antibiotic resistance genes (ARGs) via plasmid-mediated conjugation has been reported to be facilitated by a series of contaminants. This has highlighted potential challenges to the effective control of this principal mode of horizontal transfer. In the present study, we found that low levels (<0.02 mgN/L) of free nitrous acid (FNA) remarkably inhibited (over 90%) the conjugative transfer of plasmid RP4, a model broad-host-range plasmid, between Escherichia coli. The antimicrobial role of FNA at the applied dosages was firstly ruled out, since no dramatic reductions in viabilities of donor or recipient were observed. Instead, FNA appeared to reduce the available intracellular free Mg2+, which was confirmed to be triggered by the liberation of intracellular Fe2+. These alterations in intracellular Mg2+ and Fe2+ concentrations were found to significantly limit the available energy for conjugative transfer through suppression of glycolysis by decreasing the activities of glycogen phosphorylase and glyceraldehyde-3-phosphate dehydrogenase and also by diverting the glycolytic flux into the pentose phosphate pathway via activation of glucose-6-phosphate dehydrogenase towards the generation of NADPH rather than ATP. Moreover, RP4-encoding genes responsible for DNA transfer and replication (traI, traJ and trfAp), coupling (traG) and mating pair formation (traF and trbBp) were all significantly down-regulated after FNA treatment, indicating that the transfer apparatus required for plasmid processing and delivery was deactivated. By validating the inhibitory effects of FNA on conjugation in real wastewater, this study highlights a promising method for controlling the dissemination of ARGs in systems such as wastewater treatment plants.