Lipid and Transcriptional Regulation in a Parkinson's Disease Mouse Model by Intranasal Vesicular and Hexosomal Plasmalogen-Based Nanomedicines.

Plasmalogens (vinyl-ether phospholipids) are an emergent class of lipid drugs against various diseases involving neuro-inflammation, oxidative stress, mitochondrial dysfunction, and altered lipid metabolism. They can activate neurotrophic and neuroprotective signaling pathways but low bioavailabilities limit their efficiency in curing neurodegeneration. Here, liquid crystalline lipid nanoparticles (LNPs) are created for the protection and non-invasive intranasal delivery of purified scallop-derived plasmalogens. The in vivo results with a transgenic mouse Parkinson's disease (PD) model (characterized by motor impairments and α-synuclein deposition) demonstrate the crucial importance of LNP composition, which determines the self-assembled nanostructure type. Vesicle and hexosome nanostructures (characterized by small-angle X-ray scattering) display different efficacy of the nanomedicine-mediated recovery of motor function, lipid balance, and transcriptional regulation (e.g., reduced neuro-inflammation and PD pathogenic gene expression). Intranasal vesicular and hexosomal plasmalogen-based LNP treatment leads to improvement of the behavioral PD symptoms and downregulation of the Il6, Il33, and Tnfa genes. Moreover, RNA-sequencing and lipidomic analyses establish a dramatic effect of hexosomal nanomedicines on PD amelioration, lipid metabolism, and the type and number of responsive transcripts that may be implicated in neuroregeneration.

Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassemblies.

Cyclic-AMP-response element-binding protein (CREB) is a leucine zipper class transcription factor that is activated through phosphorylation. Ample CREB phosphorylation is required for neurotrophin expression, which is of key importance for preventing and regenerating neurological disorders, including the sequelae of long COVID syndrome. Here we created lipid-peptide nanoassemblies with different liquid crystalline structural organizations (cubosomes, hexosomes, and vesicles) as innovative nanomedicine delivery systems of bioactive PUFA-plasmalogens (vinyl ether phospholipids with polyunsaturated fatty acid chains) and a neurotrophic pituitary adenylate cyclase-activating polypeptide (PACAP). Considering that plasmalogen deficiency is a potentially causative factor for neurodegeneration, we examined the impact of nanoassemblies type and incubation time in an in vitro Parkinson's disease (PD) model as critical parameters for the induction of CREB phosphorylation. The determined kinetic changes in CREB, AKT, and ERK-protein phosphorylation reveal that non-lamellar PUFA-plasmalogen-loaded liquid crystalline lipid nanoparticles significantly prolong CREB activation in the neurodegeneration model, an effect unattainable with free drugs, and this effect can be further enhanced by the cell-penetrating peptide PACAP. Understanding the sustained CREB activation response to neurotrophic nanoassemblies might lead to more efficient use of nanomedicines in neuroregeneration.

Poly(3,4-ethylenedioxythiophene):Polystyrene Sulfonate-Modified Electrode for the Detection of Furosemide in Pharmaceutical Products.

Furosemide (4-chloro-2-(furan-2-ylmethylamino)-5-sulfamoyl benzoic acid) is a widely used, FDA-approved drug prescribed for several symptoms associated with heart, kidney, liver failure, or chronic high blood pressure. In this work, a glassy carbon working electrode modified with poly(3,4-ethylenedioxythiophene):polystyrene sulfonate is developed to detect furosemide (FURO) with high sensitivity and precise selectivity. The modified electrode was also characterized using field emission scanning electron microscopy, attenuated total reflectance-Fourier transform infrared, and cyclic voltammetry. Here, an efficient and cost- and time-efficient technique to study the furosemide mechanism of reaction in an acidic liquid medium is presented. An electrochemical oxidation of loop diuretic furosemide was investigated in a supporting electrolyte, 0.01 M of phosphate buffer (at a pH level of 4.0) at 25 ± 0.1 °C using a differential pulse voltammetric (DPV) technique. Under optimized parameters, the developed sensor displays a wide detection range of furosemide concentrations of 6.0 × 10-6 to 1.0 × 10-4 M with a detection limit of 2.0 × 10-6 M using DPV. The presented sensor offers a robust and high-precision technique with an excellent reproducibility to detect furosemide in as a real sample such as urine and pharmaceutical products.

MonkeyNet: A robust deep convolutional neural network for monkeypox disease detection and classification.

The monkeypox virus poses a new pandemic threat while we are still recovering from COVID-19. Despite the fact that monkeypox is not as lethal and contagious as COVID-19, new patient cases are recorded every day. If preparations are not made, a global pandemic is likely. Deep learning (DL) techniques are now showing promise in medical imaging for figuring out what diseases a person has. The monkeypox virus-infected human skin and the region of the skin can be used to diagnose the monkeypox early because an image has been used to learn more about the disease. But there is still no reliable Monkeypox database that is available to the public that can be used to train and test DL models. As a result, it is essential to collect images of monkeypox patients. The "MSID" dataset, short form of "Monkeypox Skin Images Dataset", which was developed for this research, is free to use and can be downloaded from the Mendeley Data database by anyone who wants to use it. DL models can be built and used with more confidence using the images in this dataset. These images come from a variety of open-source and online sources and can be used for research purposes without any restrictions. Furthermore, we proposed and evaluated a modified DenseNet-201 deep learning-based CNN model named MonkeyNet. Using the original and augmented datasets, this study suggested a deep convolutional neural network that was able to correctly identify monkeypox disease with an accuracy of 93.19% and 98.91% respectively. This implementation also shows the Grad-CAM which indicates the level of the model's effectiveness and identifies the infected regions in each class image, which will help the clinicians. The proposed model will also help doctors make accurate early diagnoses of monkeypox disease and protect against the spread of the disease.

Plasmalogens inhibit neuroinflammation and promote cognitive function.

Neuroinflammation (NF) is defined as the activation of brain glial cells that are found in neurodegenerative diseases including Alzheimer's disease (AD). It has been known that an increase in NF could reduce the memory process in the brain but the key factors, associated with NF, behind the dysregulation of memory remained elusive. We previously reported that the NF and aging processes reduced the special phospholipids, plasmalogens (Pls), in the murine brain by a mechanism dependent on the activation of transcription factors, NF-kB and c-MYC. A similar mechanism has also been found in postmortem human brain tissues with AD pathologies and in the AD model mice. Recent evidence showed that these phospholipids enhanced memory and reduced neuro-inflammation in the murine brain. Pls can stimulate the cellular signaling molecules, ERK and Akt, by activating the membrane-bound G protein-coupled receptors (GPCRs). Therefore, recent findings suggest that plasmalogens could be one of the key phospholipids in the brain to enhance memory and inhibit NF.

Volatile compounds of Bacillus pseudomycoides induce growth and drought tolerance in wheat (Triticum aestivum L.).

The plant growth-boosting biofilm-forming bacteria Bacillus pseudomycoides is able to promote growth and drought stress tolerance in wheat by suppressing the MYB gene, which synthesizes Myb protein (TaMpc1-D4) through secreted volatile compounds. In the present study, Triticum aestivum seeds were inoculated with five distinct bacterial strains. The growth, germination rate, root-shoot length, RWC, and chlorophyll content of seedlings were investigated. Furthermore, the levels of soluble sugars, proteins, H2O2, NO, cell death, and antioxidant enzymes (CAT, SOD, POD, and APX) were observed throughout the growth stage. All of the results showed that B. pseudomycoides had a substantially higher ability to form biofilm and promote these traits than the other strains. In terms of molecular gene expression, B. pseudomycoides inoculation strongly expressed the Dreb1 gene by silencing the expression of MYB gene through secreted volatile compounds. For identifying the specific volatile compound that silenced the MYB gene, molecular docking with Myb protein was performed. Out of 45 volatile compounds found, 2,6-ditert-butylcyclohexa-2,5-diene-1,4-dione and 3,5-ditert-butylphenol had a binding free energy of - 6.2 and - 6.5, Kcal/mol, respectively, which predicted that these compounds could suppress this protein's expression. In molecular dynamics simulations, the RMSD, SASA, Rg, RMSF, and hydrogen bonding values found assured the docked complexes' binding stability. These findings suggest that these targeted compounds may be suppressing Myb protein expression as well as the expression of Dreb1 and other drought response genes in wheat. More research (field trial) into plant growth and drought stress is needed to support the findings of this study.

Plasmalogen-Mediated Activation of GPCR21 Regulates Cytolytic Activity of NK Cells against the Target Cells.

It is widely known that the immune system becomes slower to respond among elderly people, making them more susceptible to viral infection and cancer. The mechanism of aging-related immune deficiency remained mostly elusive. In this article, we report that plasmalogens (Pls), special phospholipids found to be reduced among the elderly population, critically control cytolytic activity of human NK cells, which is associated with activation of a cell surface receptor, G protein-coupled receptor 21 (GPCR21). We found the extracellular glycosylation site of GPCR21, which is conserved among the mammalian species, to be critically important for the activation of NK cells by Pls. The Pls-GPCR21 signaling cascade induces the expression of Perforin-1, a cytolytic pore-forming protein, via activation of STAT5 transcription factor. Inhibition of STAT5 abrogates GPCR21-mediated cytolytic activation of NK cells against the target cancer cells. In addition, oral ingestion of Pls inhibited cancer growth in SCID mice and inhibited the systemic spread of murine CMV in adult C57BL/6J mice. These findings advocate that Pls-GPCR21 signaling could be critical in maintaining NK cell function, and that the age-related reduction of this signaling cascade could be one of the factors behind immune deficiency in mammals, including humans.

Green synthesis of silver nanoparticles using Cinnamomum tamala (Tejpata) leaf and their potential application to control multidrug resistant Pseudomonas aeruginosa isolated from hospital drainage water.

Green Synthesis of Metal Nanoparticles is becoming a more common method for producing nanoparticles with a diameter of 1-100 nm that may be employed in a variety of medical applications. The antibacterial efficacy of silver nanoparticles (AgNPs) derived from Cinnamomum tamala (Tejpata) leaf extract against antibiotic-resistant Pseudomonas aeruginosa is investigated in this study. Green AgNP synthesis is safe, cost-effective, and ecologically friendly. The biosynthesized AgNPs were studied using UV-Visible spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), Dynamic Light Scattering (DLS), X-ray Diffraction (XRD), and Transmission Electron Microscopy (TEM). The AgNPs were virtually spherical, with an average size of 25-30 nm, according to TEM observations. Biochemical and molecular identification were used to isolate multidrug-resistant P. aeruginosa from the hospital's drainage water. The antibacterial potential of AgNPs against P. aeruginosa is determined using the agar diffusion method. Silver nanoparticles produced from Cinnamomum tamala (Tejpata) leaf extract were shown to be effective in inhibiting four strains of P. aeruginosa. According to the agar disc diffusion method, AgNPs had the largest inhibition zone of 17.67 ± 0.577 mm, while aqueous extract had 5.67 ± 0.5777 mm, indicating that AgNPs had antibacterial activity. This study on AgNPs might assist with managing multidrug resistant pathogenic bacteria and be a possible source of medicinal application due to its potential antibacterial effect.

A Novel Hybrid Deep Learning Approach for Skin Lesion Segmentation and Classification.

Skin cancer is one of the most common diseases that can be initially detected by visual observation and further with the help of dermoscopic analysis and other tests. As at an initial stage, visual observation gives the opportunity of utilizing artificial intelligence to intercept the different skin images, so several skin lesion classification methods using deep learning based on convolution neural network (CNN) and annotated skin photos exhibit improved results. In this respect, the paper presents a reliable approach for diagnosing skin cancer utilizing dermoscopy images in order to improve health care professionals' visual perception and diagnostic abilities to discriminate benign from malignant lesions. The swarm intelligence (SI) algorithms were used for skin lesion region of interest (RoI) segmentation from dermoscopy images, and the speeded-up robust features (SURF) was used for feature extraction of the RoI marked as the best segmentation result obtained using the Grasshopper Optimization Algorithm (GOA). The skin lesions are classified into two groups using CNN against three data sets, namely, ISIC-2017, ISIC-2018, and PH-2 data sets. The proposed segmentation and classification techniques' results are assessed in terms of classification accuracy, sensitivity, specificity, F-measure, precision, MCC, dice coefficient, and Jaccard index, with an average classification accuracy of 98.42 percent, precision of 97.73 percent, and MCC of 0.9704 percent. In every performance measure, our suggested strategy exceeds previous work.

Plasmalogens, the Vinyl Ether-Linked Glycerophospholipids, Enhance Learning and Memory by Regulating Brain-Derived Neurotrophic Factor.

Plasmalogens (Pls), a kind of glycerophospholipids, have shown potent biological effects but their role in hippocampus-dependent memory remained mostly elusive. Here, we first report Pls can enhance endogenous expression of brain-derived neurotrophic factor (Bdnf) in the hippocampus and promotes neurogenesis associated with improvement of learning and memory in mice. Genomic and proteomic studies revealed that Pls enhanced recruitment of CREB transcription factor onto the murine Bdnf promoter region via upregulating ERK-Akt signaling pathways in neuronal cells. Reduction of endogenous Pls in murine hippocampus significantly reduced learning and memory associated with the reduction of memory-related protein expression, suggesting that Pls can regulate memory-related gene expression in the hippocampus.

Plasmalogens ensure the stability of non-neuronal (microglial) cells during long-term cytotoxicity.

Microglia (MG) are resident phagocytes in the brain responsible for neuronal maintenance. The regulation of MG necroptosis is required for protecting neurons during neurodegenerative diseases. Therefore, this study proposed to elucidate the molecular mechanisms underlying microglia necroptosis during long-time apoptotic stimuli (lipopolysaccharide, LPS). The protective role of plasmalogens (PLS) was also investigated against LPS insult in MG cells (including BV2 and MG6 cell lines). LPS produced time-dependent decreases in the survival of BV2 and MG6 cells mediated by the caspase signaling pathway. Interestingly, MG death was mediated by caspase-8 and 9 signaling pathways suggesting that MG necroptosis was actively attributed to long-time LPS treatment through intrinsic and extrinsic pathways. Notably, caspase signaling was markedly inhibited in the PLS-pretreated cells; thereby, PLS were capable of maintaining the MG cell population and inhibit the MG necroptosis against the longtime of LPS administration via its antioxidant and anti-inflammatory properties.

The relationship between exercise and Physical Fitness towards Economic Survival: A Comparative Study of Gender discrimination / La relación entre el ejercicio y la aptitud física para la supervivencia económica: un estudio comparativo de la discriminación de género

Everyone's health is critically important. Managing health problems is just as critical as surviving economically. Any country's economic survival is entirely contingent upon its economic strategy. The study of the relationship between exercise and fitness and its impact on economic survival has as its primary objective educating us about the significance and necessity of exercise and physical fitness in our lives. Exercise and physical activity have unquestionable health benefits. The comparative study of differences in physical fitness and activity between men and women. The study's independent variables include exercise and physical fitness, while the dependent variable is economic survival. The data analysis was performed using AMOS 26v. Because this study contained three hypothesis statements, the results suggested a positive and significant link between the variables.(AU)

Mycoremediation of reactive red HE7B dye by Aspergillus salinarus isolated from textile effluents.

Reactive dyes are widely utilized in the textile industry due to their advantageous properties of vivid color, water-fastness, and simple application procedures with minimal energy usage. The toxicity of most azo dyes is a significant environmental concern, as effluents from dye processing and manufacturing sectors are known to be carcinogenic and mutagenic to numerous species. These issues are more grievous in Bangladesh, one of the largest exporters of apparel. This study aimed to isolate and identify potential fungal strains from textile effluent that are capable of degrading Reactive Red HE7B dye (a sulphonated reactive azo dye), a widely used dye in local thread dyeing industries. Dye degradation assay was performed in potato dextrose broth supplemented with 50 mg/l Reactive Red HE7B and the degradation rate was measured by a UV spectrophotometer. DNA extraction, quantification, PCR, internal transcribed spacer (ITS) sequencing, and phylogenetic analysis were performed to identify the selected fungi. Among the isolates, the three best performing strains TEF -3, TEF -4, and TEF -5 showed 97.41%, 93.12%, and 82.89% dye degrading efficacy after 96 h of incubation, respectively. All three strains, TEF-3, TEF-4, and TEF-5 showed similarity with Aspergillus salinarus (accession no. NR_157473.1) and the similarity percentages were 97.02, 96.95, and 95.28 respectively. Interestingly, this study probably the very first indication of textile dye degradation by Aspergillus salinarus strains. Thus, these fungal strains possess the prospectiveness to be utilized in the textile wastewater treatment plants, since the isolates demonstrated the substantial capacity (>80%) to degrade Reactive Red dye after 96 h of incubation.

NLRR1 Is a Potential Therapeutic Target in Neuroblastoma and MYCN-Driven Malignant Cancers.

Receptor tyrosine kinases (RTKs) receive different modulation before transmitting proliferative signals. We previously identified neuronal leucine-rich repeat 1 (NLRR1) as a positive regulator of EGF and IGF-1 signals in high-risk neuroblastoma cells. Here, we show that NLRR1 is up-regulated in various adult cancers and acts as a key regulator of tumor cell proliferation. In the extracellular domains of NLRR1, fibronectin type III (FNIII) domain is responsible for its function to promote cell proliferation. We generated monoclonal antibodies against the extracellular domains of NLRR1 (N1mAb) and screened the positive N1mAbs for growth inhibitory effect. The treatment of N1mAbs reduces tumor cell proliferation in vitro and in vivo, and sensitizes the cells to EGFR inhibitor, suggesting that NLRR1 is a novel regulatory molecule of RTK function. Importantly, epitope mapping analysis has revealed that N1mAbs with growth inhibitory effect recognize immunoglobulin-like and FNIII domains of NLRR1, which also indicates the importance of FNIII domain in the function of NLRR1. Thus, the present study provides a new insight into the development of a cancer therapy by targeting NLRR1 as a modulator of proliferative signals on cellular membrane of tumor cells.

A remarkable microleafhopper genus emKoreoneura/em gen. nov. and newly recorded genus of the tribe Dikraneurini from Korea (Homoptera: Cicadellidae: Typhlocybinae).

Koreoneura eunyeopae Hossain et J. Kwon gen. et sp. nov., the biggest microleafhopper from East Asia, dwelling on Cornus coreana, along with a newly recorded genus, Igutettix Matsumura, 1932 based on I. oculatus (Lindberg), 1928, are described and illustrated from Korea. A key to the genera and checklist of Korean dikraneurine species are provided.

Taxonomic revision of the microleafhopper subgenus Alnetoidia Dlabola from Korea (Homoptera: Cicadellidae: Typhlocybinae).

Four species of Alnetoidia Dlabola, 1958 s. str. are described and illustrated. Among them, Alnetoidia (Alnetoidia) jejudoensis sp. nov. is new to science and Alnetoidia (Alnetoidia) straminea Anufriev, 1972 is newly recorded for the Korean fauna. A key to the Korean species is provided.

Glucose signaling in the brain and periphery to memory.

Glucose has many diverse physiological roles such as energy metabolism, appetite control and memory consolidation. We recently reported that memory-related gene expression is epigenetically controlled in murine brain cells and that glucose can regulate gene expression in a cell-specific manner. However, the literature reviews have indicated that glucose can also regulate gut cells to release incretins which might play a role in memory processes directly or indirectly by vagus nerve stimulation. In this review, we discussed the effects of glucose on the gut and brain, aiming to understand more in-depth the role of glucose in memory function. In addition, we also discussed the alteration of glucose-signaling in type-2 diabetes mellitus (T2DM) and a possible link to Alzheimer's disease (AD) pathologies.

Biological Functions of Plasmalogens.

Plasmalogens (Pls) are one kind of phospholipids enriched in the brain and other organs. These lipids were thought to be involved in the membrane bilayer formation and anti-oxidant function. However, extensive studies revealed that Pls exhibit various beneficial biological activities including prevention of neuroinflammation, improvement of cognitive function, and inhibition of neuronal cell death. The biological activities of Pls were associated with the changes in cellular signaling and gene expression. Membrane-bound GPCRs were identified as possible receptors of Pls, suggesting that Pls might function as ligands or hormones. Aging, stress, and inflammatory stimuli reduced the Pls contents in cells, and addition of Pls inhibited inflammatory processes, which could suggest that reduction of Pls might be one of the risk factors for the diseases associated with inflammation. Oral ingestion of Pls showed promising health benefits among Alzheimer's disease (AD) patients, suggesting that Pls might have therapeutic potential in other neurodegenerative diseases.

Therapeutic Efficacy of Plasmalogens for Alzheimer's Disease, Mild Cognitive Impairment, and Parkinson's Disease in Conjunction with a New Hypothesis for the Etiology of Alzheimer's Disease.

It has been reported in recent years that blood levels of plasmalogens (Pls) are decreased in various diseases. None of those reports, however, conducted any clinical trials to examine the effect of Pls on those diseases. This article describes our recent report on a therapeutic efficacy of orally administered Pls in mild cognitive impairment (MCI), mild to severe Alzheimer's disease (AD), and Parkinson's disease (PD). A 24-week, multicenter, randomized, double-blind, placebo-controlled trial was performed in patients with MCI (n = 178) and mild AD (n = 98). The study design for moderate AD (n = 57) and severe AD (n = 18) was 12-week open-labeled, and the design for patients with PD (n = 10) was 24-week open-labeled. They showed a significant improvement in cognitive function and other clinical symptoms with elevation of the blood Pls levels. No adverse events were reported. The baseline levels of plasma ethanolamine plasmalogen and erythrocyte ethanolamine plasmalogen in MCI, AD, and PD were significantly lower than those of normal aged. The degree of reduction in the blood Pls levels was in the order of MCI â‰º mild AD ≺ moderate AD ≺ severe AD ≺ PD. The findings suggest that the blood levels of Pls may be a beneficial biomarker for assessing AD severity. Based on these results, we have proposed a new hypothesis for the etiology of AD and other neuropsychiatric disorders.

Taxonomic revision of the microleafhopper genus Ziczacella Anufriev 1970 from Korea (Hemiptera: Cicadellidae: Typhlocybinae).

Four species of erythroneurine genus Ziczacella Anufriev, 1970 are revised. Among them, Ziczacella spinosa sp. nov. is new to science. Descriptions and illustrations of Korean species as well as a key and checklist of all known species are provided.