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Alzheimer’s disease (AD) is a pathological disorder defined by the symptoms of memory loss and deterioration of cognitive abilities over time. Although the etiology is complex, it is mainly associated with the accumulation of toxic amyloid-β peptide (Aβ) aggregates and tau protein-induced neurofibrillary tangles (NFTs). Even now, creating non-invasive, sensitive, specific, and cost-effective diagnostic methods for AD remains challenging. Over the past few decades, polymers, and nanomaterials (e.g., nanodiamonds, nanogold, quantum dots) have become attractive and practical tools in nanomedicine for diagnosis and treatment. This review focuses on current developments in sensing methods such as enzyme-linked immunosorbent assay (ELISA) and surface-enhanced Raman scattering (SERS) to boost the sensitivity in detecting related biomarkers for AD. In addition, optical analysis platforms such as ELISA and SERS have found increasing popularity among researchers due to their excellent sensitivity and specificity, which may go as low as the femtomolar range. While ELISA offers easy technological usage and high throughput, SERS has the advantages of improved mobility, simple electrical equipment integration, and lower cost. Both portable optical sensing techniques are highly superior in terms of sensitivity, specificity, human application, and practicality, enabling the early identification of AD biomarkers.

This paper presents a resource-saving system to extract a few important features of electrocardiogram (ECG) signals. In addition, real-time classifiers are proposed as well to classify different types of arrhythmias via these features. The proposed feature extraction system is based on two delta-sigma modulators adopting 250 Hz sampling rate and three wave detection algorithms to analyze outputs of the modulators. It extracts essential details of each heartbeat, and the details are encoded into 68 bits data that is only 1.48% of the other comparable methods. To evaluate our classification, we use a novel patient-specific training protocol in conjunction with the MIT-BIH database and the recommendation of the AAMI to train the classifiers. The classifiers are random forests that are designed to recognize two major types of arrhythmias. They are supraventricular ectopic beats (SVEB) and ventricular ectopic beats (VEB). The performance of the arrhythmia classification reaches to the F1 scores of 81.05% for SVEB and 97.07% for VEB, which are also comparable to the state-of-the-art methods. The method provides a reliable and accurate approach to analyze ECG signals. Additionally, it also possesses time-efficient, low-complexity, and low-memory-usage advantages. Benefiting from these advantages, the method can be applied to practical ECG applications, especially wearable healthcare devices and implanted medical devices, for wave detection and arrhythmia classification.

Bromelain, an enzyme extracted from the stems of pineapples, exerts anticoagulant effects; however, the regulatory mechanisms are not fully understood. Here, we aimed to investigate the effects of bromelain on non-alcoholic fatty liver disease (NAFLD)-induced deregulation of blood coagulation and the underlying molecular mechanisms. C57BL/6 mice were fed a high-fat diet (HFD), with or without bromelain (20 mg/kg/day) administration, for 12 weeks. Treatment with bromelain decreased thrombus formation in the liver and prolonged HFD-induced shortened prothrombin, activated partial thromboplastin, and fibrinogen times. Moreover, liquid chromatography-mass spectrometry/mass spectrometry and Western blot analysis showed that bromelain inhibited NAFLD-induced activation of the intrinsic, extrinsic, and common pathways by upregulating the protein expression of antithrombin III, serpin family G member 1, and α1-antitrypsin, and downregulating the protein expression of fibrinogen in the liver and plasma. Bromelain also upregulated the level of plasminogen and downregulating factor XIII expression in the liver and plasma. Collectively, these findings suggest that bromelain exerts anticoagulant effects on NAFLD-induced deregulation of coagulation by inhibiting the activation of the coagulation cascade, decreasing the stability of clots, and promoting fibrinolytic activity. The present study provides new insights into the potential therapeutic value of bromelain for the prevention and treatment of thrombosis-related diseases.

Idiopathic pulmonary fibrosis (IPF) may present comorbid obstructive lung diseases with small airway dysfunction (SAD). Existing guidelines suggest that inhaled bronchodilators should be used if the ratio of forced expiratory volume in the 1st second and forced vital capacity (FEV1/FVC) 1/FVC > 0.7 even with coexisting emphysema. We retrospectively enrolled IPF patients who were registered at our outpatient clinic. At baseline, 63 patients completed computed tomography (CT) scans, lung function measurements, and symptom questionnaires. Among these patients, 54 (85.71%) underwent antifibrotic treatment and 38 (60.32%) underwent long-acting bronchodilator treatment. The median FEV1/FVC was 0.86. Not all patients treated with bronchodilators showed significant changes in lung function. IPF patients with SAD, determined by IOS parameters, showed significant improvement in FEV1, FEF25–75%, and symptom scores after bronchodilator treatment. Bronchodilator efficacy was not observed in patients without SAD. CT-confirmed emphysema was seen in 34.92% of patients. There were no changes in lung function or symptom scores after bronchodilator treatment in patients with emphysema. In conclusion, FEV1/FVC cannot reflect the airflow limitation in IPF. Emphysema in IPF is not a deciding factor in whether patients should receive bronchodilator treatment. IOS parameters may be useful to guide bronchodilator therapy in patients with IPF coexisting with SAD.

Ractopamine, a synthetic β-adrenoreceptor agonist, is used as an animal feed additive to increase food conversion efficiency and accelerate lean mass accretion in farmed animals. The U.S. Food and Drug Administration claimed that ingesting products containing ractopamine residues at legal dosages might not cause short-term harm to human health. However, the effect of ractopamine on chronic inflammatory diseases and atherosclerosis is unclear. Therefore, we investigated the effects of ractopamine on atherosclerosis and its action mechanism in apolipoprotein E-null (apoe

Nanoparticles (NPs) with feature sizes ranging between 1 nm and 100 nm have increasingly gained momentum for their versatile functionality as the pharmaceutical agents in many branches of biomedical research and clinical experiments. However, NPs' inherent material toxicity and the concomitant adverse effects of their function, such as photo-physical properties, often remain a major concern over the issues of environmental safety and human health, and require a thorough assessment before a wide-spread usage can be complied. This research herein investigates the intrinsic and photothermal toxicity of Cs

Understanding the formation process and the spatial distribution of nanoparticle (NP) clusters on amyloid fibrils is an essential step for the development of NP-based methods to inhibit aggregation of amyloidal proteins or reverse the assembling trend of the proto-fibrillary complexes that prompts pathogenesis of neuro degeneration. For this, a detailed structural determination of the diverse hybrid assemblies that are forming is needed, which can be achieved by advanced X-ray scattering techniques. Using a combined solution small angle X-ray scattering (SAXS) and atomic force microscopy (AFM) approach, this study investigates the intrinsic trends of the interaction between lysozyme amyloid fibrils (LAFs) and Fe3O4 NPs before and after fibrillization at nanometer resolution. AFM images reveal that the number of NP clusters interacting with the lysozyme fibers does not increase significantly with NP volume concentration, suggesting a saturation in NP aggregation on the fibrillary surface. The data indicate that the number of non-adsorbed Fe3O4 NPs is highly dependent on the timing of NP infusion within the synthesis process. SAXS data yield access to the spatial distribution, aggregation manner and density of NP clusters on the fibrillary surfaces. Employing modern data analysis approaches, the shape and internal structural morphology of the so formed nanocomposites are revealed. The combined experimental approach suggests that while Fe3O4 NPs infusion does not prevent the fibril-formation, the variation of NP concentration and size at different stages of the fibrillization process can impose a pronounced impact on the superficial and internal structural morphologies of these nanocomposites. These findings may be applicable in devising advanced therapeutic treatments for neurodegenerative diseases and designing novel bio-inorganic magnetic devices. Our results further demonstrate that modern X-ray methods give access to the structure of—and insight into the formation process of—biological–inorganic hybrid structures in solution.

Apigenin, a flavonoid isolated from plants, provides protection against non-alcoholic fatty liver disease. However, the mechanism by which apigenin decreases lipid accumulation in the liver is unclear. In this study, we investigated the molecular mechanism underlying the beneficial effect of apigenin on the hepatic deregulation of lipid metabolism. Oleic acid (OA)-induced lipid accumulation in human hepatoma cells (Huh7 cells) was used as an in vitro model. Western blot analysis was used for evaluating protein expression. Oil red O staining, Nile red staining, and conventional assay kits were used to assess the level of lipids. Immunocytochemistry was performed to observe mitochondrial morphology. Seahorse XF analyzer was used to measure mitochondrial bioenergetics. Treatment with OA induced lipid accumulation in Huh7 cells, which was attenuated by apigenin. Mechanistically, treatment with apigenin increased the expression of autophagy-related proteins including Beclin1, autophagy related gene 5 (ATG5), ATG7, and LC3II, and the formation of autophagolysosomes, leading to an increase in intracellular levels of fatty acids. Inhibition of autophagy by bafilomycin A1 or chloroquine abolished the protection of apigenin in OA-induced lipid accumulation. Apigenin up-regulated the protein expression related to the β-oxidation pathway including acyl-CoA synthetase long chain family member 1, carnitine palmitoyltransferase 1α, acyl-CoA oxidase 1, peroxisome proliferator activated receptor (PPAR) α, and PPARγ coactivator 1-α. Moreover, apigenin increased the mitochondrial network structure and mitochondrial function by increasing the protein expression related to the process of mitochondria fusion and mitochondrial function. Collectively, our findings suggest that apigenin ameliorates hepatic lipid accumulation by activating the autophagy-mitochondrial pathway.

Psoriasis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration, as well as hyperproliferation of keratinocytes in skin lesions, and is considered a metabolic syndrome. We found that the expression of galectin-7 is reduced in skin lesions of patients with psoriasis. IL-17A and TNF-α, 2 cytokines intimately involved in the development of psoriatic lesions, suppressed galectin-7 expression in human primary keratinocytes (HEKn cells) and the immortalized human keratinocyte cell line HaCaT. A galectin-7 knockdown in these cells elevated the production of IL-6 and IL-8 and enhanced ERK signaling when the cells were stimulated with IL-17A. Galectin-7 attenuated IL-17A-induced production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway. Moreover, galectin-7-deficient mice showed enhanced epidermal hyperplasia and skin inflammation in response to intradermal IL-23 injection. We identified fluvastatin as an inducer of galectin-7 expression by connectivity map analysis, confirmed this effect in keratinocytes, and demonstrated that fluvastatin attenuated IL-6 and IL-8 production induced by IL-17A. Thus, we validate a role of galectin-7 in the pathogenesis of psoriasis, in both epidermal hyperplasia and keratinocyte-mediated inflammatory responses, and formulate a rationale for the use of statins in the treatment of psoriasis.

Molecules 26(16), 4864 (1-17) (2021). doi:10.3390/molecules26164864, Understanding the formation process and the spatial distribution of nanoparticle (NP) clusters on amyloid fibrils is an essential step for the development of NP-based methods to inhibit aggregation of amyloidal proteins or reverse the assembling trend of the proto-fibrillary complexes that prompts pathogenesis of neuro degeneration. For this, a detailed structural determination of the diverse hybrid assemblies that are forming is needed, which can be achieved by advanced X-ray scattering techniques. Using a combined solution small angle X-ray scattering (SAXS) and atomic force microscopy (AFM) approach, this study investigates the intrinsic trends of the interaction between lysozyme amyloid fibrils (LAFs) and Fe$_3$O$_4$ NPs before and after fibrillization at nanometer resolution. AFM images reveal that the number of NP clusters interacting with the lysozyme fibers does not increase significantly with NP volume concentration, suggesting a saturation in NP aggregation on the fibrillary surface. The data indicate that the number of non-adsorbed Fe$_3$O$_4$ NPs is highly dependent on the timing of NP infusion within the synthesis process. SAXS data yield access to the spatial distribution, aggregation manner and density of NP clusters on the fibrillary surfaces. Employing modern data analysis approaches, the shape and internal structural morphology of the so formed nanocomposites are revealed. The combined experimental approach suggests that while Fe$_3$O$_4$ NPs infusion does not prevent the fibril-formation, the variation of NP concentration and size at different stages of the fibrillization process can impose a pronounced impact on the superficial and internal structural morphologies of these nanocomposites. These findings may be applicable in devising advanced therapeutic treatments for neurodegenerative diseases and designing novel bio-inorganic magnetic devices. Our results further demonstrate that modern X-ray methods give access to the structure of—and insight into the formation process of—biological–inorganic hybrid structures in solution., Published by MDPI, Basel

We aimed to investigate the effect of bromelain, the extract from stems of pineapples on the high-fat diet (HFD)-induced deregulation of hepatic lipid metabolism and non-alcoholic fatty liver disease (NAFLD), and its underlying mechanism in mice. Mice were daily administrated with HFD with or without bromelain (20 mg/kg) for 12 weeks, and we found that bromelain decreased the HFD-induced increase in body weight by ~30%, organ weight by ~20% in liver weight and ~40% in white adipose tissue weight. Additionally, bromelain attenuated HFD-induced hyperlipidemia by decreasing the serum level of total cholesterol by ~15% and triglycerides level by ~25% in mice. Moreover, hepatic lipid accumulation, particularly that of total cholesterol, free cholesterol, triglycerides, fatty acids, and glycerol, was decreased by 15&ndash, 30% with bromelain treatment. Mechanistically, these beneficial effects of bromelain on HFD-induced hyperlipidemia and hepatic lipid accumulation may be attributed to the decreased fatty acid uptake and cholesteryl ester synthesis and the increased lipoprotein internalization, bile acid metabolism, cholesterol clearance, the assembly and secretion of very low-density lipoprotein, and the &beta, oxidation of fatty acids by regulating the protein expression involved in the above mentioned hepatic metabolic pathways. Collectively, these findings suggest that bromelain has therapeutic value for treating NAFLD and metabolic diseases.

Cs0.33WO3 nanomaterial absorbs a range of near-infrared (NIR) wavelength spanning 900–2400 nm, of which the main contributor of heat energy may be utilized for electrical generation. In this research, the capability of Cs0.33WO3 nanomaterial in enhancing the output of a thermoelectric (TE) device by trapping the absorbed heat at the hot-side surface of the device is investigated. The material is synthesized through a combination of the processes of co-precipitation and wet nano-grinding, and the characterization of its structural and optical properties was carried out using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and visible-near-infrared absorption spectroscopy. Likewise, the photothermal property of Cs0.33WO3 nanomaterial, in the form of solution or solid film, is assessed to gain better insight into its effects on the electrical output of the TE device, utilizing a laser with wavelength of 808 nm, a solar simulator, and sunlight in ambient environment. Moreover, the photoelectric property of the Cs0.33WO3 nanomaterial-incorporated TE device was evaluated in four different types of weather condition, sunny, sunny with partly cloudy, cloudy, and rainy; and our results indicate that Cs0.33WO3 nanomaterial is capable of enhancing the output of thermoelectric conversion in an ambient environment. In a complete sunny day, when compared with a bare thermoelectric device, the coating of Cs0.33WO3 nanomaterial with concentration of 0.66 wt% demonstrated a rise of 13.1% in the maximal attainable temperature and a corresponding increase of 291% in maximal output voltage.

HLJ1 (also called DNAJB4) is a member of the DNAJ/Hsp40 family and plays an important role in regulating protein folding and activity. However, there is little information about the role of HLJ1 in the regulation of physiological function. In this study, we investigated the role of HLJ1 in blood coagulation using wild-type C57BL/6 mice and HLJ1-null (HLJ1-/-) mice. Western blot analysis and immunohistochemistry were used to assess the expression and distribution of HLJ1 protein, respectively. The tail bleeding assay was applied to assess the bleeding time and blood loss. A coagulation test was used for measuring the activity of extrinsic, intrinsic and common coagulation pathways. Thromboelastography was used to measure the coagulation parameters in the progression of blood clot formation. The results showed that HLJ1 was detectable in plasma and bone marrow. The distribution of HLJ1 was co-localized with CD41, the marker of platelets and megakaryocytes. However, genetic deletion of HLJ1 did not alter blood loss and the activity of extrinsic and intrinsic coagulation pathways, as well as blood clot formation, compared to wild-type mice. Collectively, these findings suggest that, although HLJ1 appears in megakaryocytes and platelets, it may not play a role in the function of blood coagulation under normal physiological conditions.

A practical deep residual CNN model for the improvement of Raman spectral analysis is proposed in this work. Through the feature transformation in the deep residual blocks, it successfully denoises and precisely corrects the baseline.

We present colloidal nanocomposites formed by incorporating magnetite Fe3 O4 nanoparticles (MNPs) with lysozyme amyloid fibrils (LAFs). Preparation of two types of solutions, with and without addition of salt, was carried out to elucidate the structure of MNPs-incorporated fibrillary nanocomposites and to study the effect of the presence of salt on the stability of the nanocomposites. The structural morphology of the LAFs and their interaction with MNPs were analyzed by atomic force microscopy and small-angle x-ray scattering measurements. The results indicate that conformational properties of the fibrils are dependent on the concentration of protein, and the precise ratio of the concentration of the protein and MNPs is crucially important for the stability of the fibrillary nanocomposites. Our results confirm that despite the change in fibrillary morphology induced by the varying concentration of the protein, the adsorption of MNPs on the surface of LAF is morphologically independent. Moreover, most importantly, the samples containing salt have excellent stability for up to 1 year of shelf-life.

This study uses the edge computing system for fast quality screening in the metal processing industry, and the Internet of Things technology is responsible for delivering data to the cloud for visualization and analysis. First, the system consists of optical components and embedded systems. Further, a fast Fourier transform is used to make the image have frequency characteristics. However, the convolution operation between the random kernel model and the image is the main means of feature extraction. In order to evaluate the performance and convergence of the proposed method, a rapid screening mechanism for good/bad products is defined. Finally, the data is passed to the cloud (ThingSpeak) platform for visualization through the MQTT protocol, and the content is subscribed to the content by the background host to perform the quality decision of the fuzzy inference system. The result is released back to the cloud. The experimental results in the industrial example show that the proposed method can accurately and quickly complete the quality inspection of surface roughness, and the feature distribution is easy to understand. At the same time, the edge computing system has the advantages of instant response and low cost, while the Internet of Things technology brings more management and analysis convenience. In future research, the unsupervised learning algorithm based on convolutional neural networks is a potential application, which can learn the quality of good or bad through a large amount of data.

Sorbic acid (SA) is one of the most commonly used food preservatives worldwide. Despite SA having no hepatotoxicity at legal dosages, its effect on hepatic lipid metabolism is still unclear. We investigated the effect of SA on hepatic lipid metabolism and its mechanism of action in C57BL/6 mice. Daily treatment with SA (1 g/kg in diet) for 4 weeks did not alter the body weight, organ weight, and blood lipids in mice. However, hepatic lipid accumulation, particularly that of triglycerides, fatty acids, and glycerol, but not cholesteryl ester and free cholesterol, was increased with SA treatment. Mechanistically, SA decreased the expression of proteins related to de novo fatty acid lipogenesis, fatty acid internalization, and very low-density lipoprotein (VLDL) secretion-related pathways, including sterol regulatory element-binding proteins, acetyl-coA carboxylase, fatty acid synthase, liver fatty acid-binding protein, CD36, and apolipoprotein E. In contrast, SA increased the expression of diacylglycerol O-acyltransferase 2, the key enzyme for triacylglycerol synthesis. Moreover, SA downregulated the protein expression of autophagy-related and β-oxidation-related pathways, the two major metabolic pathways for lipid metabolism, including LC-3, beclin-1, autophagy related protein 5 (ATG-5) and ATG-7, acyl-CoA synthetase long chain family member 1, carnitine palmitoyltransferase Iα, peroxisome proliferator-activated receptor α (PPARα), PPARγ, and PPARγ coactivator-1. Collectively, SA deregulates de novo lipogenesis and fatty acid internalization, VLDL secretion, autophagy, and β-oxidation in the liver, leading to impaired lipid clearance and ultimately, resulting in lipid accumulation in the liver.

This article focuses on embedded vision systems and their automation and intelligent technology research, such as illumination, focal length, and surface roughness analysis. In illuminance, YCbCr color space conversion is used to obtain the contrast of brightness, and it becomes the basis for judging the illuminance state. In the focal length, the frequency domain space conversion is used to perform the spectral convolution operation, and it becomes the basis for judging the focal length state. In the surface roughness, the result of the spectral convolution operation becomes the input of the fuzzy C-means clustering algorithm and helps the fuzzy inference system (2 input -1 output) to establish the membership function and rule base. From the inference results of the fuzzy inference system, it is known that the surface roughness can be divided into three categories to obtain an accuracy of 91.67 %, and only five data are misjudged. At the same time, we hope that the low-cost embedded vision system can help the industry upgrade.

Atrioventricular (AV) valve is a cardiac component of zebrafish that regulates the rhythm of blood flow, and may be utilized to assay unknown cardiac drug compounds. This research herein presents the construction of a near-infrared optical reflectance microspectroscopy (NIRORM), examining the rhythm of AV valve of wildtype zebrafish larvae in vivo as a preliminary drug toxicity assay, of which the experimental results indicate that NIRORM is effective in discriminating types of cardiac drugs based upon the stimulating or tranquilizing effects on AV valve, and such effects are highly dependent on the concentration of solution and duration of sample immersion. ©2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement