A simple and highly sensitive flexible sensor with extended-gate field-effect transistor for epinephrine detection utilizing InZnSnO sensing films.

This study introduces a straightforward method for depositing InZnSnO films onto flexible polyimide substrates at room temperature, enabling their application in electrochemical pH sensing and the detection of epinephrine. A comprehensive analysis of these sensing films, spanning structural, morphological, compositional, and profiling characteristics, was conducted using diverse techniques, including X-ray diffraction, atomic force microscopy, X-ray photoelectron spectroscopy, and secondary ion mass spectroscopy. The investigation into the influence of oxygen flow rates on the performance of InZnSnO sensitive films revealed a significant correlation between their structural properties and sensing capabilities. Notably, exposure to an oxygen flow rate of 30/2 (Ar/O2) the ratio of resulted in the InZnSnO sensitive film demonstrating outstanding pH sensitivity at 59.58 mV/pH within a broad pH range of 2-12, surpassing the performance observed with other oxygen flow rates. Moreover, under this specific condition, the film exhibited excellent stability, with a minimal drift rate of 0.14 mV/h at pH 7 and a low hysteresis voltage of 1.8 mV during a pH cycle of 7 â†’ 4→7 â†’ 10→7. Given the critical role of epinephrine in mammalian central nervous and hormone systems, monitoring its levels is essential for assessing human health. To facilitate the detection of epinephrine, we utilized the carboxyl group of 4-formylphenylboronic acid to enable a reaction with the amino group of the 3-aminopropyltriethoxysilane-coated InZnSnO film. Through optimization, the resulting InZnSnO-based flexible sensor displayed a broad and well-defined linear relationship within the concentration range of 10-7 to 0.1 µM. In practical applications, this sensor proved effective in analyzing epinephrine in human serum, showcasing notable selectivity, stability, and reproducibility. The promising outcomes of this study underscore the potential for future applications, leveraging the advantages of electrochemical sensors, including affordability, rapid response, and user-friendly operation.

Population pharmacokinetic and pharmacodynamic analysis of rivaroxaban in Chinese patients with non-valvular atrial fibrillation.

Rivaroxaban, a direct factor Xa inhibitor, is widely used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to conduct a population pharmacokinetic-pharmacodynamic (PK-PD) analysis of rivaroxaban in Chinese patients with NVAF to assess ethnic differences and provide model-based precision dosing. A total of 256 rivaroxaban plasma concentrations and 244 prothrombin time (PT) measurements were obtained from 195 Chinese NVAF patients from a prospective clinical trial. The population PK-PD model was developed using nonlinear mixed effects modeling (NONMEM) software. The PK of rivaroxaban was adequately described using a one-compartment model with first-order adsorption and elimination. Estimated glomerular filtration rate (eGFR) was identified as a major covariate for apparent clearance. No single nucleotide polymorphism was identified as a significant covariate. PT exhibited a linear relationship with rivaroxaban concentration. Total bilirubin (TBIL) and eGFR were identified as significant covariates for baseline PT. According to the Monte Carlo simulation, 15 mg for Chinese patients with eGFR ≥50 mL/min and normal liver function yielded an exposure comparable to 20 mg for Caucasian patients. Patients with moderately impaired renal function may require a lower dose of rivaroxaban to avoid overexposure. Moreover, there was an approximate 26% increase in PT levels in patients with TBIL of 34 µmol/L and eGFR of 30 mL/min, which could increase the risk of major bleeding. The established population PK-PD model could inform individualized dosing for Chinese NVAF patients who are administered rivaroxaban.

Rationale and design of a prospective study evaluating population pharmacokinetics and pharmacodynamics of rivaroxaban in Chinese patients with non-valvular atrial fibrillation.

INTRODUCTION: Rivaroxaban is one of the most commonly used non-vitamin K antagonists for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Different individual exposures exist for Asian and non-Asian populations, and dose selection is different for Japanese and non-Japanese subjects. Few studies have investigated the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in Chinese patients and provided a solid reference for dose selection and individualised therapy. METHODS AND ANALYSIS: This is a single-centre prospective study. Rivaroxaban-treated Chinese NVAF patients will be recruited according to predetermined inclusion criteria. Blood samples will be collected from both outpatients and inpatients with different sampling strategies at steady state. Rivaroxaban plasma concentration, factor Xa activity, prothrombin time and single-nucleotide polymorphisms of candidate genes will be evaluated. Follow-up will be conducted following 3 and 6 months after enrolment to collect information about the safety and efficacy outcomes. A nonlinear mixed-effects modelling strategy will be used to develop a population PK-PD model of rivaroxaban. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of Huashan Hospital, Fudan University (KY2020-016). The study findings will be submitted to peer-reviewed journals and shared with public health authorities. TRIAL REGISTRATION NUMBER: ChiCTR2100046685.

Roles of hyaluronan in cardiovascular and nervous system disorders.

Hyaluronan is a widely occurring extracellular matrix molecule, which is not only a supporting structural component, but also an active regulator of cellular functions. The chemophysical and biological properties of hyaluronan are greatly affected by its molecular size and several hyaluronan-binding proteins, making hyaluronan a fascinating molecule with great functional diversity. This review summarizes our current understanding of the roles of hyaluronan in cardiovascular and nervous system disorders, such as atherosclerosis, myocardial infarction, and stroke, with the aim to provide a foundation for future research and clinical trials.

Use of an Artificial Neural Network to Construct a Model of Predicting Deep Fungal Infection in Lung Cancer Patients.

BACKGROUND: The statistical methods to analyze and predict the related dangerous factors of deep fungal infection in lung cancer patients were several, such as logic regression analysis, meta-analysis, multivariate Cox proportional hazards model analysis, retrospective analysis, and so on, but the results are inconsistent. MATERIALS AND METHODS: A total of 696 patients with lung cancer were enrolled. The factors were compared employing Student's t-test or the Mann-Whitney test or the Chi-square test and variables that were significantly related to the presence of deep fungal infection selected as candidates for input into the final artificial neural network analysis (ANN) model. The receiver operating characteristic (ROC) and area under curve (AUC) were used to evaluate the performance of the artificial neural network (ANN) model and logistic regression (LR) model. RESULTS: The prevalence of deep fungal infection from lung cancer in this entire study population was 32.04%(223/696), deep fungal infections occur in sputum specimens 44.05% (200/454). The ratio of candida albicans was 86.99% (194/223) in the total fungi. It was demonstrated that older (≥65 years), use of antibiotics, low serum albumin concentrations (≤37.18 g /L), radiotherapy, surgery, low hemoglobin hyperlipidemia (≤93.67 g /L), long time of hospitalization (≥14 days) were apt to deep fungal infection and the ANN model consisted of the seven factors. The AUC of ANN model (0.829±0.019) was higher than that of LR model (0.756±0.021). CONCLUSIONS: The artificial neural network model with variables consisting of age, use of antibiotics, serum albumin concentrations, received radiotherapy, received surgery, hemoglobin, time of hospitalization should be useful for predicting the deep fungal infection in lung cancer.

Blood compatibility and interaction with endothelial cells of titanium modified by sequential immobilization of poly (ethylene glycol) and heparin.

In this study, poly(ethylene glycol) (PEG) and heparin were sequentially immobilized on a titanium surface by the carbodiimide covalent coupling method with the aim to improve the blood compatibility of titanium and enhance endothelial cell adhesion and proliferation. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) confirmed that PEG and heparin were successfully immobilized on the titanium surface. Compared to the pristine titanium, a highly hydrophilic layer was achieved after the immobilization, and the resulting heparin-PEG layer can significantly prevent human plasma fibrinogen adsorption. Analysis of platelet attachment to the modified surfaces, via scanning electron microscopy (SEM), showed strikingly fewer platelets attached to the PEG and heparin modified surfaces, compared to the control. The immobilized PEG and heparin effectively prolonged the activated partial thromboplastin time (APTT) and inhibit platelet activation significantly. Furthermore, the modified samples showed good cytocompatibility. Endothelial cells exhibited improved proliferative profiles in terms of a CCK-8 assay, as compared to those on the pristine titanium. The modified samples showed a better endothelial cell adhesion and spreading, than the pristine titanium. Therefore, the blood compatibility and cytocompatibility of the titanium surface can be enhanced by PEG immobilization and further, by subsequent heparin grafting. It could be concluded that the negatively charged heparin-PEG layer with excellent hydrophilicity could obviously improve the blood compatibility and enhance the endothelial cell adhesion and proliferation, and the approach of the present study is considered as an effective method to improve the hemocompatibility and cytocompatibility of biomaterials.

Improved anticoagulation of titanium by sequential immobilization of oligo(ethylene glycol) and 2-methacryloyloxyethyl phosphorylcholine.

Titanium and its alloys have been widely used for blood-contacting biomedical devices; however, their blood compatibility needs to be improved. In this study, titanium surface was modified by sequential immobilization of oligo(ethylene glycol) (OEG) and 2-methacryloyloxyethyl phosphorylcholine (MPC) to improve its anticoagulation. Water contact angle results showed an excellent hydrophilic surface after the immobilization. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) confirmed that OEG and MPC were successfully immobilized on titanium surface. Static platelet adhesion and APTT (activated partial thromboplastin time) experiments suggested that the anticoagulation of titanium was significantly enhanced by the immobilization of OEG and further by subsequent MPC grafting. The approach in the present study opens up a window of promising an effective and efficient method to improve the anticoagulation of blood-contact biomedical devices such as coronary stents.

Control of osteoblast cells adhesion and spreading by microcontact printing of extracellular matrix protein patterns.

In this study, we report a simple method for creating extracellular matrix (ECM) protein patterns to control osteoblast cell adhesion and spreading. The fibronectin patterns are directly produced on polystyrene (PS) surfaces by microcontact printing (µCP). Confocal laser scanning microscopy (CLSM) images show that protein patterns are successfully fabricated on PS surfaces. Newborn rat osteoblast cells are then seeded on these protein patterns and cultured for 4 days. The results demonstrate that osteoblast cells preferentially adhere and grow on the protein areas. The pattern dimensions have significant influences on cell behaviors, including cell adhesion, spreading, distribution, and growth direction. Therefore, it is possible to control the cell morphology and even cell function by carefully designing the pattern shapes and sizes. The present study suggests that the ECM protein patterns can be used to modify biomaterials' surfaces and spatially control the morphologies of osteoblast cells. We believe that our work could find applications for creating patterned bioactive surfaces to control cell adhesion, spreading and cell function. It may be helpful for the development of novel implantable biomaterials, such as artificial bone implants, where control of interfacial biological interactions between implants and cells would be preferable.

Extracellular matrix protein patterns guide human chondrocytes adhesion and alignment characterized by vimentin and matrilin-3.

The main purpose of the present study is to investigate the influences of collagen VI (col-VI) patterns on human chondrocytes behaviors. To this end, col-VI stripes with varying width and interstripe spacing are created on polystyrene (PS) surfaces by microcontact printing (µCP). Human chondrocytes are then seeded on these protein patterns and the cell adhesion and alignment are investigated by staining the vimentin and matrilin-3 secreted by seeded chondrocytes. The results indicate that the cells preferentially attach onto the protein areas, rendering cell patterns and the elongated cell shapes. The pattern dimensions can significantly influence cell adhesion, spreading and orientation. The stripe protein patterns can guide cell adhesion and alignment. The cell morphologies can be controlled by carefully designing the pattern shapes and sizes. Our results suggest that the protein patterns can be used to modify biomaterials' surfaces for selective cell-binding and cell alignment. It could provide some cues for the development of novel implantable biomaterials, such as tissue-engineered scaffolds for cartilage replacement, where specific cell alignment is needed.

[Study of regional cerebral blood flow around hematoma in acute intracerebral hemorrhage by xenon-CT].

OBJECTIVE: To study the change of regional cerebral blood flow (rCBF) around hematoma in acute intracerebral hemorrhage. METHODS: Xenon-CT was performed on 5 patients of basal ganglia hemorrhage with the hematoma volume less than 30 ml, 3 males and 2 females, aged 56.8 +/- 5.6. within 36 hours of the onset and 13 days after to measure the rCBF was measured by 27 pixel rings respectively in the core of hematoma, edema region around the hematoma and compared with rCBF in the uninvolved hemisphere. RESULTS: (1) all the 5 patients had a history of hypertension, the mean intracerebral hemorrhage volume was 13 ml +/- 7 ml (6.4 approximately 23.7 ml). The first examination was conducted 23 h +/- 6 h (19 approximately 34 h) after the onset and the second examination was conducted 13.0 d +/- 0.7 d (12 approximately 14 d) after the onset. (2) Within 36 hours of the onset, the mean rCBF in the core of hematoma was 15 ml.100 g(-1).min(-1) +/- 8 ml.100 g(-1).min(-1), and the mean rCBF in edema region around the hematoma was 30 ml.100 g(-1).min(-1) +/- 8 ml.100 g(-1).min(-1). Thirteen days after the onset the mean rCBF in the core of hematoma was 9 ml.100 g(-1).min(-1) +/- 4 ml.100 g(-1).min(-1), significantly reduced in comparison with that measured in the first examination (P = 0.014), and the mean rCBF in the edema region around the hematoma was 23 ml.100 g(-1).min(-1) +/- 13 ml.100 g(-1).min(-1), reduced in comparison with those measured in the first examination too, however, not significantly (P = 0.055). The rCBF reduction was more significant in the edema region adjacent to the hematoma (P = 0.004), but not in the distant edema region. During the first examination the rCBF in the edema region around the hematoma was lower than the enantiomorph rCBF by 20.9%. Thirteen days after, the rCBF in the edema region around the hematoma was lower than the enantiomorph rCBF by 46.3%, significantly greater than the reduction during the first examination (P = 0.324). There was no difference between the values of enantiomorph rCBF during the first and second examinations (P = 0.038). CONCLUSION: There exists reduced perihematoma rCBF after intracerebral hemorrhage by xenon-CT examination, this phenomenon lasts 14 days and have the tendency of further reduced.