Prediction of Late Hospital Arrival in Patients with Mild and Rapidly Improving Acute Ischemic Stroke in a Rural Area of China.

Purpose: Among all ischemic stroke patients, more than half are mild and rapidly improving acute ischemic stroke (MaRAIS) patients. However, many MaRAIS patients do not recognize the disease early on, and thus they delay access to the treatment that would be most effective if provided earlier. This is especially true in rural areas. The aim of this study was to develop and validate a late hospital arrival risk nomogram in a rural Chinese population of patients with MaRAIS. Methods: We developed a prediction model based on a training dataset of 173 MaRAIS patients collected from September 9, 2019 to May 13, 2020. Data analyzed included demographics and disease characteristics. A least absolute shrinkage and selection operator (LASSO) regression model was used to optimize feature selection for the late hospital arrival risk model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the features selected in the LASSO regression models. The discrimination, calibration, and clinical usefulness of the prediction model were assessed using the C-index, calibration plot, and decision curve analysis, respectively. Internal validation was then assessed using bootstrapping validation. Results: Variables contained in the prediction nomogram included transportation mode, history of diabetes, knowledge of stroke symptoms, and thrombolytic therapy. The model had moderate predictive power with a C-index of 0.709 (95% confidence interval: 0.636-0.783) and good calibration. In the internal validation, the C-index reached 0.692. The risk threshold was 30-97% according to the analysis of the decision curve, and the nomogram could be applied in clinical practice. Conclusion: This novel nomogram, which incorporates transportation mode, history of diabetes, knowledge of stroke symptoms, and thrombolytic therapy, was conveniently applied to facilitate individual late hospital arrival risk prediction among MaRAIS patients in a rural area of Shanghai, China.

In situ self-assembly of polydopamine inside injectable hydrogels: antibacterial activity and photothermal therapy for superbug-infected wound healing.

Inspired by the mussel foot proteins, polydopamine nanoparticles (PDA NPs) are often used to design hydrogel wound dressings due to their strong wet adhesion. However, additional antibiotics or nanometal bactericides are always required to enhance their poor antibacterial activity, which will cause drug resistance and toxic side effects. Herein, self-assembly confined PDA NPs (SC-PDA NPs, <50 nm) are employed as a freestanding antibacterial ingredient for constructing an ideal hydrogel wound dressing, which maintains relatively strong reducibility and size effect. Through a rapid gelation (within 10 s) strategy triggered by electrostatic complexation, an antibacterial hydrogel system is obtained, in which the in situ self-assembly of the SC-PDA NPs continues, endowing the gel with outstanding antibacterial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA, >99.9%). With the continuous in situ self-assembly, the size of the PDA NPs increases (>200 nm), eventually giving the gel an efficient photothermal therapy effect. Moreover, the gel presents a relatively strong wet adhesion (63 kPa), superior biocompatibility and non-immunogenicity. This work offers innovative insights into the antibacterial mechanism of SC-PDA NPs and provides a novel design for constructing safe antibacterial hydrogel wound dressings, demonstrating great potential applications in superbug-infected wound healing.

HDAC6-mediated Hsp90 deacetylation reduces aggregation and toxicity of the protein alpha-synuclein by regulating chaperone-mediated autophagy.

Histone deacetylase 6 (HDAC6) has been shown to control major cell response pathways to the cytotoxic ubiquitinated aggregates in some protein aggregation diseases. However, it is not well known whether HDAC6 affects the aggregation process of α-synuclein (α-syn) in Parkinson's disease (PD). Previously, we demonstrated that HDAC6 inhibition exacerbated the nigrostriatal dopamine neurodegeneration and up-regulated α-syn oligomers in a heat shock protein 90 (Hsp90)-dependent manner in PD mouse model. Here, we further showed that HDAC6 overexpression partly improved the behavior deficits of the PD model and alleviated the nigrostriatal dopamine (DA) neurons injury. Furthermore, HDAC6 was found to regulate α-syn oligomers levels through activation of chaperone-mediated autophagy (CMA). During this process, Hsp90 deacetylation mediated the crosstalk between HDAC6 and lysosome-associated membrane protein type 2A. Liquid chromatography-tandem mass spectrometry and mutational analysis showed that acetylation status Hsp90 at the K489 site was a strong determinant for HDAC6-induced CMA activation, α-syn oligomers levels, and cell survival in the cell model of PD. Therefore, our findings uncovered the mechanism of HDAC6 in the PD model that HDAC6 regulated α-syn oligomers levels and DA neurons survival partly through modulating CMA, and Hsp90 deacetylation at the K489 site mediated the crosstalk between HDAC6 and CMA. HDAC6 and its downstream effectors appear as key modulators of the cytotoxic α-syn aggregates, which deserve further investigations to evaluate their values as potential therapeutic targets in PD.

Peptidyl arginine deiminase 4 and its potential role in Alzheimer's disease.

Alzheimer's disease (AD) is the main cause of dementia, and its pathogenesis is still not clear. Peptidyl arginine deiminases 4(PAD4) as one of the important members of PAD family, is the only protein with nuclear transfer function, it can regulate the expression of many proteins through citrullinating histone. PAD4 can also interact with many transcription factors, involved in regulating gene expression. PAD4 expression is closely related to the inflammatory factors secreted, cell autophagy, tumorigenesis and other neurodegenerative diseases. More importantly, PAD4 and its citrullinated protein were found in cortical and hippocampal neurons of AD patients. To study the expression and regulatory pathway of PAD4 in vivo and in vitro experiments on AD may be of helpful to elucidate the pathogenesis of AD. Meanwhile, detection of anti-citrullinated antibody will have potential value as novel biomarkers of AD.

Extreme Temperature-Tolerant Conductive Gel with Antibacterial Activity for Flexible Dual-Response Sensors.

Flexible sensors based on conductive hydrogel show great potential in electronic skin and human-machine interface. However, pure water in hydrogel inevitably freezes or rapidly evaporates under extreme temperatures, leading to inadequate fulfillment of sensor performances. Herein, a well-designed strategy is reported for fabricating extreme temperature-tolerant gel-based sensors. By immersing a gelatin/polyacrylamide (PAAm)-clay composite (GC) hydrogel into a ZnCl2/water/glycerol system, a phase-transition-tunable gel (PTTGC gel) is obtained with outstanding antifreezing (-82 °C) and long-lasting moisture (70 °C, more than 40 days) properties. Meanwhile, the gel also presents good antibacterial activity and biocompatibility attributing to Zn2+ and gelatin, respectively. Then, a dual-response sensor with a wide operating temperature (-60 to 60 °C) is proposed, presenting high stress and temperature sensitivities and long-term stability. The sensor will meet the needs of the human-machine interface for scientific investigation and data monitoring in polar, desert, etc.

Chitosan-Gated Fluorescent Mesoporous Silica Nanocarriers for the Real-Time Monitoring of Drug Release.

We have constructed a novel gated nanocarrier for the real-time monitoring of drug release, consisting of three parts: (i) mesoporous silica nanoparticles (MSNs) as the drug carrier, (ii) chitosan as the nanovalve to block and unlock the pores, and (iii) 1,8-naphthalimide fluorophore as a connecting arm and fluorescent signal source. In the absence of glutathione (GSH), the integrity of the system results in the formation of pores in a closed state and the sulfone would block the intramolecular charge transfer (ICT) process, leading to no fluorescence emission. However, the nucleophilic attack of GSH can cause the removal of the chitosan and recovery of ICT property, thus triggering drug release and green fluorescence emission. The results demonstrate that the change of GSH concentration in vivo or vitro would lead to a change in drug release as well as a concurrent change in fluorescence signal, which can expand the application of our gated nanocarrier for monitoring different drug release in real time.

A self-healing, robust adhesion, multiple stimuli-response hydrogel for flexible sensors.

Ionic hydrogels have great application potential in human index monitoring and wound treatment, such as in wearable sensors, wound dressings, and ionic skin. However, the design of a hydrogel achieving the synergistic characteristics of excellent mechanical properties, robust adhesion, and multiple stimuli-responses remains a critical challenge. Herein, by introducing negatively charged clay nanosheets, we report a smart ionic Gelatin/PAAm/Clay hydrogel (GPNs gel) with a high conductivity of 10.87 mS cm-1. The as-prepared gel exhibits excellent self-healing properties, robust adhesion (interfacial toughness of up to 485 J m-2 with pigskin), and multiple stimuli-responses driven by salt ions, pH, and stress. Based on this hydrogel, a capacitive sensor has also been designed, which provides linear responses over a wide range (applied pressure up to 2 kPa) and sensitively monitors human motion. In addition, the gel also displays good biocompatibility with human lung embryonic (MRC-5) cells. These characteristics demonstrate that the GPNs gel is an ideal candidate for developing flexible sensor devices.

Electrospun Gelatin Fibers Surface Loaded ZnO Particles as a Potential Biodegradable Antibacterial Wound Dressing.

Traditional wound dressings require frequent replacement, are prone to bacterial growth and cause a lot of environmental pollution. Therefore, biodegradable and antibacterial dressings are eagerly desired. In this paper, gelatin/ZnO fibers were first prepared by side-by-side electrospinning for potential wound dressing materials. The morphology, composition, cytotoxicity and antibacterial activity were characterized by using Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), particle size analyzer (DLS), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), thermogravimetry (TGA) and Incucyte™ Zoom system. The results show that ZnO particles are uniformly dispersed on the surface of gelatin fibers and have no cytotoxicity. In addition, the gelatin/ZnO fibers exhibit excellent antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with a significant reduction of bacteria to more than 90%. Therefore, such a biodegradable, nontoxic and antibacterial fiber has excellent application prospects in wound dressing.

Environmentally Friendly Gelatin/ß-Cyclodextrin Composite Fiber Adsorbents for the Efficient Removal of Dyes from Wastewater.

In this paper, environmentally friendly gelatin/ß-cyclodextrin (ß-CD) composite fiber adsorbents prepared by electrospinning were used for the removal of dyes from wastewater. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and a universal materials tester were employed to characterize the internal structures, surface morphologies and mechanical strength of the composite fiber adsorbents. Additionally, the fiber was evaluated as an adsorbent for the removal of methylene blue (MB) from aqueous solution. The effects of the raw material ratio, pH, temperature, concentration and adsorption time were studied. The results show that the gelatin/ß-CD composite fiber adsorbents possess excellent mechanical strength and high adsorption efficiency for MB. The adsorption equilibrium and adsorption kinetics are well-described by the Langmuir isotherm model and the pseudo-second-order kinetic model, respectively. The theoretical maximum adsorption capacity is 47.4 mg·g-1. Additionally, after nine successive desorption-adsorption cycles, the removal rate is still over 70%. Moreover, the gelatin/ß-CD composite fiber adsorbents exhibit excellent adsorption capability for basic fuchsin, gentian violet, brilliant blue R and malachite green dyes. Therefore, owing to the characteristics of degradability, low cost and high-efficiency, the gelatin/ß-CD composite fiber can be used as an efficient adsorbent for the removal of dyes from wastewater.

Early Use of Statin in Patients Treated with Alteplase for Acute Ischemic Stroke.

Studies have reported that statin usage before stroke can increase the incidence of intracerebral hemorrhage after thrombolytic treatment. However, whether the administration of statin at an early stage of ischemic stroke increases hemorrhage occurrence is unknown. The aim of this study was to assess the effect of statin on neurological imaging and functional outcomes after intravenous alteplase treatment, within 24 h of acute ischemic stroke attack. A total of 119 consecutive acute ischemic stroke patients treated by intravenous alteplase were recruited, of which 71 patients (59.7 %) were given statin therapy within 24 h of stroke onset. The physiological parameters, including demography, vascular risk factors, and clinical characteristics were recorded. The occurrence of intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day functional outcomes, and mortality in the patients were further analyzed. There were 24 occurrences of ICH after alteplase treatment (20.2 %) and there was no difference when patients were treated with statin (p = 0.280). Multivariate logistic regression analysis showed no significant correlation between the administration of statin and the occurrence of ICH (p = 0.230) or sICH (p = 0.949). There was a trend toward better neurological function with higher statin dose. The use of statin in the early stage of ischemic stroke is safe and does not increase the risk of intracerebral hemorrhage after alteplase treatment, suggesting that a clinical trial of early statin treatment on a large scale following thrombolysis is needed for further evaluation.

[Determination of prometryne residue in shellfish by gas chromatography].

OBJECTIVE: To develop a method of gas chromatography (GC) for determining residues of promtryne in shellfish. METHODS: The sample was extracted with ethyl acetate, and cleaned-up with Envi-Carb SPE cartridge, alumina-N SPE cartridge, and determined by GC-FPD with DB - 1701 capillary chromatographic column (30 m x0.53 .mm x 0.5µm). RESULTS: Good linear was obtained in the concentration range of 0.10-0.96µg/ml with a correlation coefficient of 0. 999. The limit of detection (LOD) was 0.0037 mg/kg and limit of quantity (LOQ) was 0.010 mg/kg. The average recoveries was 83. 7% - 102. 0% and relative standard deviations (RSD) was 0. 54% - 8.14% CONCLUSION: The method is simple, fast and credible, so it can be applied to determination of prometryne in shellfish.

Thrombelastography maximal clot strength could predict one-year functional outcome in patients with ischemic stroke.

BACKGROUND: Elevated maximal clot strength, measured by thrombelastography (TEG) maximum amplitude (MA) has been associated with a higher risk for ischemic events in patients with coronary artery diseases. However, it has not been investigated in patients with cerebrovascular diseases. In the current study, we aimed to evaluate the predictive ability of TEG-MA in assessing the risk for ischemic event recurrence and the functional outcome after index ischemic stroke. METHODS: This was a prospective observational study. Consecutive eligible patients with acute ischemic stroke were included and followed up for one year. Patients were stratified into tertile groups based on MA levels. TEG-hypercoagulability was defined as an MA of ≥ 69 mm. Ischemic events were defined as a composite of ischemic stroke, myocardial infarction, or vascular death (excluding hemorrhagic death). The functional outcome was evaluated by modified Rankin Scale (mRS). Unfavorable functional outcome was defined as mRS ≥ 2. RESULTS: Two hundred and eleven patients were enrolled with 27 lost to follow-up at one year contact. At baseline, 38 (18.0%) patients were TEG-hypercoagulopathy after the treatment of antiplatelets. Patients with higher tertile of MA were more likely to be females, and had lower hemoglobin levels, higher platelet counts, higher fibrinogen levels, higher white blood cell counts, as well as higher ESR and hsCRP levels. Patients in the third tertile group were more likely to have intracranial artery stenosis and large-vessel subtype stroke than those in the other two groups. Higher tertile of MA was also related to stroke severity in acute phase (higher NIHSS scores on admission and longer in-hospital stay). At one year of follow-up, a higher percentage of unfavorable functional outcome and a non-significant trend of higher ischemic event rate were observed in higher MA tertile groups. Multivariate logistic analysis revealed that higher MA level (OR = 1.192, p = 0.022) was an independent predictor for unfavorable one-year functional outcome. Other independent predictors included old age (OR = 1.119, p = 0.001), diabetes mellitus (DM) (OR = 4.280, p = 0.014), previous ischemic stroke/TIA history (OR = 4.953, p = 0.008), and higher NIHSS scores on admission (OR = 1.437, p = 0.001). CONCLUSIONS: We found that higher TEG-MA levels could predict an unfavorable functional outcome after index ischemic stroke. Further, large-scale studies are required to investigate the relationship between MA levels and risk of recurrent ischemic events in ischemic stroke patients.

Enhanced dye-sensitized solar cells performance using anatase TiO2 mesocrystals with the Wulff construction of nearly 100% exposed {101} facets as effective light scattering layer.

Anatase TiO2 mesocrystals with a Wulff construction of nearly 100% exposed {101} facets were successfully synthesized by a facile, green solvothermal method. Their morphology, and crystal structure are characterized by powder X-ray diffraction (XRD), Field emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HRTEM). Accordingly, a possible growth mechanism of anatase TiO2 mesocrystals is elucidated in this work. The as-prepared single anatase TiO2 mesocrystal's mean center diameter is about 500 nm, and the length is about 1 µm. They exhibit high light adsorbance, high reflectance and low transmittance in the visible region due to the unique nearly 100% exposed {101} facets. When utilized as the scattering layer in dye-sensitized solar cells (DSSCs), such mesocrystals effectively enhanced light harvesting and led to an increase of the photocurrent of the DSSCs. As a result, by using an anatase TiO2 mesocrystal film as a scattering overlayer of a compact commercial P25 TiO2 nanoparticle film, the double layered DSSCs show a power conversion efficiency of 7.23%, indicating a great improvement compared to the DSSCs based on a P25 film (5.39%) and anatase TiO2 mesocrystal films, respectively. The synergetic effect of P25 and the mesocrystals as well as the latters unique feature of a Wulff construction of nearly 100% exposed (101) facets are probably responsible for the enhanced photoelectrical performance. In particular, we explore the possibility of the low surface area and exposed {101} facets as an efficient light scattering layer of DSSCs. Our work suggests that anatase TiO2 mesocrystals with the Wulff construction is a promising candidate as a superior scattering material for high-performance DSSCs.

[Identification of irradiated abalone by ESR spectroscopy].

OBJECTIVE: To establish an analytical method for the detection and identification of irradiated abalone by electron spin resonance spectroscopy. METHODS: Electron spin resonance (ESR) was used to study the spectral characteristics of abalone and the characteristic peak for quantitation. RESULTS: There were obvious different ESR spectra between unirradiated and irradiated abalone. The g factor for unirradiated abalone was 2.0055-2.0060, the g1 and g2 factor for irradiated abalone were (2.0027 +/- 0.0001) and (1.9994 +/- 0.0001), respectively. The ESR signal intensity of characteristic peak was positively correlated with absorbed dose in the range of 0.5 - 10 kGy, left peak was the characteristic peak for quantitation and the detection limit was < or = 0.5 kGy. It was difficult to quantitate when the absorbed dose was over 10 kGy. ESR characteristic peak and g factor were able to qualitatively determine the irradiation of abalone. CONCLUSION: ESR spectroscopy is an effective method to determine whether the abalone being irradiated or not.

[The factors predicting early efficacy of intravenous thrombolysis with alteplase in acute ischemic stroke].

OBJECTIVE: To analyze the factors affecting on early efficacy of intravenous thrombolysis with alteplase. METHODS: The clinical data of 100 acute cerebral infarction patients treated by intravenous thrombolysis with alteplase were retrospectively analyzed. The patients were divided into early effective group and ineffective group, which assessed by National Institute of Health Stroke Scale (NIHSS) with criteria of whether there were > 3 or not at 24 hours after therapy. Univariate analysis and multivariate logistic regression analysis were used to determine the differences of clinical data between the two groups. RESULTS: Univariate analysis revealed that the early improvement was significantly associated with favorable outcome at 3 month (P = 0.000). Multivariate logistic analysis revealed that the systolic pressure at baseline was moderately positively associated with early improvement (OR 1.031, 95%CI 1.008 - 1.056, P = 0.009). CONCLUSION: Moderately lower baseline systolic pressure is associated with early improvement after thrombolytic therapy which is associated with favorable outcome at 3 month.