Parkinson’s disease (PD) is a chronic neurodegenerative disease with unclear pathogenesis that involves neuroinflammation and intestinal microbial dysbiosis. Intercellular adhesion molecule-1 ...(ICAM-1), an inflammatory marker, participates in neuroinflammation during dopaminergic neuronal damage. However, the explicit mechanisms of action of ICAM-1 in PD have not been elucidated. We established a subacute PD mouse model by the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and observed motor symptoms and gastrointestinal dysfunction in mice. Immunofluorescence was used to examine the survival of dopaminergic neurons, expression of microglial and astrocyte markers, and intestinal tight junction-associated proteins. Then, we use 16 S rRNA sequencing to identify alterations in the microbiota. Our findings revealed that ICAM-1-specific antibody (Ab) treatment relieved behavioural defects, gastrointestinal dysfunction, and dopaminergic neuronal death in MPTP-induced PD mice. Further mechanistic investigations indicated that ICAM-1Ab might suppress neuroinflammation by inhibiting the activation of astrocytes and microglia in the substantia nigra and relieving colon barrier impairment and intestinal inflammation. Furthermore, 16 S rRNA sequencing revealed that the relative abundances of bacterial Firmicutes, Clostridia, and Lachnospiraceae were elevated in the PD mice. However, ICAM-1Ab treatment ameliorated the MPTP-induced disorders in the intestinal microbiota. Collectively, we concluded that the suppressing ICAM-1 might lead to the a significant decrease of inflammation and restore the gut microbial community, thus ameliorating the damage of DA neurons.
•sICAM-1 expression is upregulated in the PD mouse model and patients with PD.•ICAM-1 may promote the loss of dopaminergic neurons in the SN by regulating inflammation in both the brain and gut.•ICAM-1 is involved in the dysbiosis of Firmicutes, Clostridia, and Lachnospiraceae in the PD mouse models.
Fluoxetine (FLX) is one of the selective serotonin reuptake inhibitors (SSRIs) antidepressants, which could be used to relieve depression and anxiety among AD patients. This study was designed to ...search for new mechanisms by which fluoxetine could activate Wnt/β-catenin signaling pathway and reduce amyloidosis in AD brain. Fluoxetine was administered via intragastric injection to APP/tau/PS1 mouse model of Alzheimer's disease (3×Tg-AD) mice for 4 months. In the hippocampus of AD mouse model, there could be observed neuronal apoptosis, as well as an increase in Aβ (amyloid-β) production. Moreover, there is a strong association between down-regulation of Wnt/β-catenin signaling and the alteration of AD pathology. The activity of protein phosphatases of type 2A (PP2A) could be significantly enhanced by the treatment of fluoxetine. The activation of PP2A, caused by fluoxetine, could then play a positive role in raising the level of active β-catenin, and deliver a negative impact in GSK3β activity in the hippocampal tissue. Both the changes mentioned above would lead to the activation of Wnt/β-catenin signaling. Meanwhile, fluoxetine treatment would reduce APP cleavage and Aβ generation. It could also prevent apoptosis in 3×Tg-AD primary neuronal cell, and have protective effects on neuron synapse. These findings imply that Wnt/β-catenin signaling could be a potential target outcome for AD prevention, and fluoxetine has the potential to be a promising drug in both AD prevention and treatment.
A simple prognostic model is needed for ICU patients. This study aimed to construct a modified prognostic model using easy-to-use indexes for prediction of the 28-day mortality of critically ill ...patients. Clinical information of ICU patients included in the Medical Information Mart for Intensive Care III (MIMIC-III) database were collected. After identifying independent risk factors for 28-day mortality, an improved mortality prediction model (mionl-MEWS) was constructed with multivariate logistic regression. We evaluated the predictive performance of mionl-MEWS using area under the receiver operating characteristic curve (AUROC), internal validation and fivefold cross validation. A nomogram was used for rapid calculation of predicted risks. A total of 51,121 patients were included with 34,081 patients in the development cohort and 17,040 patients in the validation cohort (17,040 patients). Six predictors, including Modified Early Warning Score, neutrophil-to-lymphocyte ratio, lactate, international normalized ratio, osmolarity level and metastatic cancer were integrated to construct the mionl-MEWS model with AUROC of 0.717 and 0.908 for the development and validation cohorts respectively. The mionl-MEWS model showed good validation capacities with clinical utility. The developed mionl-MEWS model yielded good predictive value for prediction of 28-day mortality in critically ill patients for assisting decision-making in ICU patients.
Because of the von Neumann bottleneck, neuromorphic networks aimed at in-memory computing, such as brains, are extensively studied. As artificial synapses are essential in neuromorphic networks, a ...photonic synapse based on slot-ridge waveguides with nonvolatile phase-change materials (PCMs) was proposed and demonstrated in an SOI platform with standard complementary metal-oxide-semiconductor (CMOS) process for a larger weight dynamic range. The change of the optical transmission spectrum of our photonic synapses was about 3.5dB higher than that of primitive synapses, which meant large weight dynamic range and more weight values. A 90.7% recognition accuracy based on our photonic synapses, which was 2.6% higher than that of primitive synapses, was realized for the MNIST handwritten digits recognition task performed by a three-layer perceptron. Besides, because of the nonvolatile nature of PCMs, the weights achieved by our photonic synapses can be stored in situ ensuring a lower consumption in in-memory computing. This framework can potentially achieve a more efficient in-memory computing neuromorphic network in silicon photonics.
Optical neural networks are expected to solve the problems of computational efficiency and energy consumption in neural networks. Herein, we experimentally implemented a 2 × 2 photonic convolutional ...kernel (PCK) using four on-chip micro-ring resonators (MRRs) and demonstrated feature extraction for images with different convolutional kernels. We trained a simple convolutional neural network model to recognize the MNIST dataset and used our PCK devices for processing in the first convolutional layer, achieving a recognition rate of 91%, which further verified the feasibility of MRRs for convolution operations. In addition to the source, all silicon photonic devices used can be monolithically integrated and feature good scalability, which is important for realizing large-scale, low-cost optical neural networks.
Inspired by the mechanism of visual attentional selection, a color feature selection unit consisting of photoreceptors and an attentional selection circuit (ASC) is presented. The detection and ...wavelength recognition of trichromatic light are accomplished by the photoreceptors with RGB filters. The ASC, fabricated in a standard CMOS technology, activates the competition among photoreceptors to select the principal color-component feature defined as the attentional focus. The number of focuses and resolution can be changed with a top-down stimulus. Electrical test results show that the ASC can select and interpret the most important color-component feature. In optical tests, the ASC chip-based unit can extract the principal color-component of single-color and dual-color light in real-time to complete color recognition. The percentage ratio between the intensity of stray light relative to the light with maximum intensity is up to 93.58%. And the maximum achievable recognition frame rate is 1 kHz, which is more than one order of magnitude higher than the frequency of the biological vision systems. Besides, the unit's outputs can be transformed into binary codes as labels for color recognition, and the color recognition process does not require the participation of ADC, CPU, and memory, consequently avoiding the von Neumann bottleneck.
This paper presents an easy and low-cost flame treatment method to improve the bonding performance of GF/EP (Glass Fiber-Reinforced Epoxy) pultrusion plates, which are using widely for large size ...wind blades. In order to explore the effect of flame treatment on the bonding performance of the precast GF/EP pultruded sheet vs. the infusion plate, the GF/EP pultruded sheets were treated with different flame treatment cycles and were embedded in the fiber fabrics during the vacuum-assisted resin infusion process (VARI). The bonding shear strengths were measured by tensile shear tests. It is found that after 1, 3, 5, and 7 flame treatments, the tensile shear strength between the GF/EP pultrusion plate and infusion plate increased by 8.0%, 13.3%, 22.44%, and -2.1%, respectively. This indicates that the maximum tensile shear strength can be obtained after five times of flame treatment. In addition, DCB and ENF tests were also adopted to characterize the fracture toughness of the bonding interface with the optimal flame treatment. It is found that the optimal treatment gives increments of 21.84% and 78.36% for G I C and G II C, respectively. Finally, the surficial topography of the flame-treated GF/EP pultruded sheets were characterized by optical microscopy, SEM, contact angle test, FTIR, and XPS. The results show that flame treatment plays an impact on the interfacial performance through the combination of physical meshing locking and chemical bonding mechanism. Proper flame treatment would remove the weak boundary layer and mold release agent on the surface of the GF/EP pultruded sheet, etch the bonding surface and improve the oxygen-containing polar groups, such as C-O and O-C=O, to improve the surface roughness and surface tension coefficient of pultruded sheet to enhance the bonding performance. Excessive flame treatment destroys the integrity of epoxy matrix on bonding surface which results into the exposure of the glass fiber, and the carbonization of release agent and resin on the surface loosen the surficial structure, which reduces the bonding properties.
Background Type 2 diabetes is associated with a variety of complications, including micro- and macrovascular complications, neurological manifestations and poor wound healing. Adhering to a ...Mediterranean Diet (MED) is generally considered an effective intervention in individuals at risk for type 2 diabetes mellitus (T2DM). However, little is known about its effect with respect to the different specific manifestations of T2DM. This prompted us to explore the effect of MED on the three most significant microvascular complications of T2DM: diabetic retinopathy (DR), diabetic kidney disease (DKD), and vascular diabetic neuropathies (DN). Methods We examined the association between the MED and the incidence of these microvascular complications in a prospective cohort of 33,441 participants with hyperglycemia free of microvascular complications at baseline, identified in the UK Biobank. For each individual, we calculated the Alternate Mediterranean Diet (AMED) score, which yields a semi-continuous measure of the extent to which an individual's diet can be considered as MED. We used Cox proportional hazard models to analyze hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographics, lifestyle factors, medical histories and cardiovascular risk factors. Results Over a median of 12.3 years of follow-up, 3,392 cases of microvascular complications occurred, including 1,084 cases of diabetic retinopathy (DR), 2,184 cases of diabetic kidney disease (DKD), and 632 cases of diabetic neuropathies (DN), with some patients having 2 or 3 microvascular complications simultaneously. After adjusting for confounders, we observed that higher AMED scores offer protection against DKD among participants with hyperglycemia (comparing the highest AMED scores to the lowest yielded an HR of 0.79 95% CIs: 0.67, 0.94). Additionally, the protective effect of AMED against DKD was more evident in the hyperglycemic participants with T2DM (HR, 0.64; 95% CI: 0.50, 0.83). No such effect, however, was seen for DR or DN. Conclusions In this prospective cohort study, we have demonstrated that higher adherence to a MED is associated with a reduced risk of DKD among individuals with hyperglycemia. Our study emphasizes the necessity for continued research focusing on the benefits of the MED. Such efforts including the ongoing clinical trial will offer further insights into the role of MED in the clinical management of DKD. Keywords: Mediterranean diet, Microvascular complications, UK Biobank
► We propose parylene C coating serves as surface anti-adhesion layer in PDMS double casting technique. ► Microstructure copies with different aspect ratios and sharp angles can be fabricated from ...master by using this new method. ► This new method is environment friendly. ► A single coating of parylene C can keep anti-adhesive property on its substrate for long lifetime regardless of the number of replica molding cycles.
As a simple method to fabricate a high quality copy of master, PDMS double casting technique has been more and more popular in microfluidics chips and bioMEMS application. In this work, the method in which conformal coating of parylene C serves as a demolding anti-adhesion layer in PDMS double casting technique was proposed. First casting was carried out onto master mold to generate negative PDMS mold and second casting was done onto negative PDMS mold likewise to generate positive PDMS replica with the same structure as master mold. Microstructures with aspect ratio from 4:1 to 20:1 and sharp angle from 5° to 40° were successfully obtained by using this new method. Experiments show replicas remain high fidelity to their masters. This new method of surface anti-adhesive treatment is environment friendly. Moreover, a single coating of parylene C can make the treated mold keep its anti-adhesive property for long lifecycle regardless of the number of replica molding cycles.
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