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Abstract Background Mean perfusion pressure (MPP) has recently emerged as a potential biomarker for personalized management of tissue perfusion in critically ill patients. However, its association with the occurrence of acute kidney injury (AKI) in septic patients and the optimal MPP range remain uncertain. Therefore, this study aims to investigate the relationship between MPP and AKI in critically ill patients with sepsis. Methods We identified 5867 patients with sepsis from the MIMIC-IV database who met the inclusion and exclusion criteria. The exposure variable was the first set of MPP measured within 24 h after ICU admission with invasive hemodynamic monitoring. The primary outcome was the incidence of AKI at 7 days following ICU admission according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Secondary outcomes included in-hospital mortality, lengths of ICU, and hospital stay. Optimal cut-off point for MPP were determined using the Youden index, and multivariable logistic regression was employed to examine the association between MPP and AKI. Subgroup analyses were conducted to enhance result robustness. Kaplan-Meier survival analysis was utilized to evaluate in-hospital mortality rates categorized by MPP. Results A total of 5,867 patients with sepsis were included in this study, and the overall incidence of AKI was 82.3%(4828/5867). Patients were categorized into low MPP ( 0.05). Kaplan-Meier curve analysis demonstrated a higher survival rate during hospitalization in the high MPP group compared to the low MPP group (Log-rank test, P

Abstract Background The insulin/insulin-like signalling (IIS) pathway is common in mammals and invertebrates, and the IIS pathway is unknown in Fasciola gigantica. In the present study, the IIS pathway was reconstructed in F. gigantica. We defined the components involved in the IIS pathway and investigated the transcription profiles of these genes for all developmental stages of F. gigantica. In addition, the presence of these components in excretory and secretory products (ESPs) was predicted via signal peptide annotation. Results The core components of the IIS pathway were detected in F. gigantica. Among these proteins, one ligand (FgILP) and one insulin-like molecule binding protein (FgIGFBP) were analysed. Interestingly, three receptors (FgIR-1/FgIR-2/FgIR-3) were detected, and a novel receptor, FgIR-3, was screened, suggesting novel functions. Fg14-3-3ζ, Fgirs, and Fgpp2a exhibited increased transcription in 42-day-old juveniles and 70-day-old juveniles, while Fgilp, Fgigfb, Fgsgk-1, Fgakt-1, Fgir-3, Fgpten, and Fgaap-1 exhibited increased transcription in metacercariae. FgILP, FgIGFBP, FgIR-2, FgIR-3, and two transcription factors (FgHSF-1 and FgSKN-1) were predicted to be present in FgESPs, indicating their exogenous roles. Conclusions This study helps to elucidate the signal transduction pathway of IIS in F. gigantica, which will aid in understanding the interaction between flukes and hosts, as well as in understanding fluke developmental regulation, and will also lay a foundation for further characterisation of the IIS pathways of trematodes.

Microbial contamination has profoundly impacted human health, and the effective eradication of widespread microbial issues is essential for addressing serious hygiene concerns. Taking polystyrene (PS) membrane as an example, we herein developed report a robust strategy for the in situ preparation of chlorine-regenerable antimicrobial polymer molecular sieve membranes through combining post-crosslinking and nucleophilic substitution reaction. The cross-linking PS membranes underwent a reaction with 5,5-dimethylhydantoin (DMH), leading to the formation of polymeric N-halamine precursors (PS-DMH). These hydantoinyl groups within PS-DMH were then efficiently converted into biocidal N-halamine structures (PS-DMH-Cl) via a simple chlorination process. ATR-FTIR and XPS spectra were recorded to confirm the chemical composition of the as-prepared PS-DMH-Cl membranes. SEM analyses revealed that the chlorinated PS-DMH-Cl membranes displayed a rough surface with a multitude of humps. The effect of chlorination temperature and time on the oxidative chlorine content in the PS-DMH-Cl membranes was systematically studied. The antimicrobial assays demonstrated that the PS-DMH-Cl membranes could achieve a 6-log inactivation of E. coli and S. aureus within just 4 min of contact time. Additionally, the resulting PS-DMH-Cl membranes exhibited excellent stability and regenerability of the oxidative chlorine content.

BackgroundThere is a significant controversy surrounding the impact of the geriatric nutritional risk index (GNRI) on mortality among elderly septic patients. This retrospective cohort study aimed to investigate the association between GNRI at admission and 28 days mortality in elderly septic patients.MethodsWe retrospectively analyzed data collected from the MIMIC IV database between 2009 and 2019, which included 2,834 septic patients aged 65 years and above. The exposure variable was the GNRI, determined according to albumin levels, height, and weight. The primary outcome was 28 days mortality. We employed multivariable Cox regression analyses and Kaplan–Meier survival curves to examine the association between GNRI and 28 days mortality. We used restricted cubic splines to determine if there was a non-linear relationship between 28 days mortality and GNRI in elderly patients with sepsis and to examine the presence of a threshold saturation effect. In addition, interaction tests were conducted to identify subgroups that exhibited significant differences.ResultsA total of 2,834 elderly patients with sepsis participated in the study. Following adjustment, multivariable Cox regression analyses demonstrated that the GNRI was related to 28 days mortality (HR = 0.97, p

Abstract Hypoxia is considered as a key microenvironmental feature of solid tumors. Luminescent transition metal complexes particularly those based on iridium and ruthenium have shown remarkable potentials for constructing sensitive oxygen‐sensing probes due to their unique oxygen quenching pathway. However, the low aqueous solubility of these complexes largely retards their sensing applications in biological media. Moreover, it remains difficult so far to use the existing complexes typically possessing only one luminescent domain to quantitatively detect the intratumoral hypoxia degree. Herein, an Ir(III) complex showing red emissions is designed and synthesized, and innovatively encapsulated within a hydrophobic pocket of Cyanine7‐modified cyclodextrin. The Ir(III) complex enables the oxygen detection, while the cyclodextrin is used not only for improving the water solubility and suppressing the luminescence quenching effect of the surrounding aqueous media, but also for carrying Cyanine7 to establish a ratiometric oxygen fluorescence probe. 2D nuclear magnetic resonance is carried out to confirm the host–guest structure. The oxygen‐responsive ability of the resulting ratiometric probe is evaluated through in vitro cell and multicellular experiments. Further animal studies about tumor oxygen level mapping demonstrate that the probe can be successfully used for quantitatively visualizing tumor hypoxia in vivo.

Background: Brain development and maturation in adolescence is a complex process with active changes of metabolic and neurotransmission pathways. Positron emission tomography (PET) is a useful imaging modality for tracking metabolic and functional changes in adolescent brain. In this study, changes of glucose metabolism, expression of vesicular monoamine transporter 2 and dopamine transporter during adolescent brain development in rats were investigated with PET/CT.Methods: A longitudinal PET/CT study of age-dependent changes of VMAT2, DAT and glucose metabolism in adolescent brain was conducted in a group of Wistar rats (n = 6) post sequential intravenous injection of 18F-PF-(+)-DTBZ, 11C-CFT, and 18F-FDG, respectively. PET acquisition was performed at 2, 4, 9, and 12 months of age. Radiotracer uptake in different brain regions, including the striatum, cerebellum, and hippocampus, were quantified and recorded as Standardized uptake value (SUV) and striatal specific uptake ratio (SUVR: SUV in brain regions/SUV in cerebellum).Results: Variable uptake of 18F-PF-(+)-DTBZ and 11C-CFT were detected, with highest level uptake in the striatum and accumbens. There was significant age-dependent increase of 18F-PF-(+)-DTBZ and 11C-CFT uptake in the striatum from 2 months of age (SUV: 1.36 ± 0.22, 1.37 ± 0.39, respectively), to 4 months (SUV: 2.22 ± 0.29, 2.04 ± 0.33), 9 months (1.98 ± 0.34, 2.09 ± 0.18), 12 months (SUV: 1.93 ± 0.19, 2.00 ± 0.17) of age, SUV of 18F-FDG also increased from 2 months of age to older ages (SUV in the striatum: 3.71 ± 0.78 at 2 month, 5.28 ± 0.81, 5.14 ± 0.73, 4.94 ± 0.50 at 4, 9, 12 month, respectively).Conclusion: Age-dependent increases of striatal of 18F-FDG, 18F-PF-(+)-DTBZ, and 11C-CFT uptake were detected in rats from 2 to 4 month of age, demonstrating striatal development presents over the first 4 months of age. Four months of age can be considered a safe threshold to launch brain disease studies for exclusion of confusion of continuing tissue development. These findings support further investigation of age-dependent changes in expression of DAT, VMAT2, and glucose metabolism for their potential use as a new imaging biomarker for study of brain development and functional maturation.

We sought to quantify the effectiveness of a gifted and talented (GT) program, as was provided to university students who demonstrated a talent for learning English as a foreign language (EFL) in China. To do so, we used propensity score matching (PSM) techniques to analyze data collected from a tier-1 university where an English talent (ET) program was provided. Specifically, we provided (a) a step-by-step guide of PSM analysis using the R analytical package, (b) the codes for PSM analysis and visualization, and (c) the final analysis of baseline equivalence and treatment effect based on the matching sample. Collectively, the results of descriptive statistics, visualization, and baseline equivalence indicate that PSM is an effective matching technique for generating an unbiased counterfactual analysis. Moreover, the ET program yields a statistically significant, positive effect on ET students’ English language proficiency.

The quantification of neurofibrillary tangles (NFTs) using specific PET tracers can facilitate the diagnosis of Alzheimer’s disease (AD) and allow monitoring of disease progression and treatment efficacy. [18F]-THK523 has shown high affinity and selectivity for tau pathology. However, its high retention in white matter, which makes simple visual inspection difficult, may limit its use in research or clinical settings. In this paper, we optimized the automated radiosynthesis of [11C]-TKF and evaluated its biodistribution and toxicity in C57 mice. [11C]-TKF can be made by reaction precursor with [11C]MeOTf or 11CH3I, but [11C]MeOTf will give us higher labeling yields and specific activity. [11C]-TKF presented better brain uptake in normal mouse than [18F]-THK523 (3.23% ± 1.25% ID·g−1 vs. 2.62% ± 0.39% ID·g−1 at 2 min post-injection). The acute toxicity studies of [11C]-TKF were unremarkable.

The quantification of neurofibrillary tangles (NFTs) using specific PET tracers can facilitate the diagnosis of Alzheimer's disease (AD) and allow monitoring of disease progression and treatment efficacy. [18F]-THK523 has shown high affinity and selectivity for tau pathology. However, its high retention in white matter, which makes simple visual inspection difficult, may limit its use in research or clinical settings. In this paper, we optimized the automated radiosynthesis of [11C]-TKF and evaluated its biodistribution and toxicity in C57 mice. [11C]-TKF can be made by reaction precursor with [11C]MeOTf or 11CH3I, but [11C]MeOTf will give us higher labeling yields and specific activity. [11C]-TKF presented better brain uptake in normal mouse than [18F]-THK523 (3.23% ± 1.25% ID.g-1 vs. 2.62% ± 0.39% ID.g-1 at 2 min post-injection). The acute toxicity studies of [11C]-TKF were unremarkable. [ABSTRACT FROM AUTHOR]

The influence of ambient current fields on the mild-slope approximation is reassessed using the Hamiltonian variational principle. Considering the slowly modulated non-uniform currents which may posses both vertical and horizonal variations, the extended mild-slope equation for surface waves propagating over slowly varying topography is derived. It is found that for large current velocities comparable to the wave celerity and the group velocity, the extended mild-slope equation is valid. For the validity of the geometric optics-approximation, additional conditions concerning current fields should be satisfied. [ABSTRACT FROM AUTHOR]