Does levodopa affect endogenous and exogenous dopaminergic neuron survival?

Parkinson’s disease is a progressive neurodegenerative disease that has no cure to date. Fortunately, stem cell replacement therapy has now become a promising option that has the potential to greatly restore patient’s motor function. However, efforts have to be paid to understand if current golden standard L-DOPA treatment will have negative impact on the novel therapy. Therefore, this study aims to evaluate the effects of L-DOPA on endogenous and exogenous dopaminergic cells. To evaluate endogenous dopaminergic cells, the classical 6-OHDA rat model was used. The L-DOPA treatment plan was adjusted to more closely represent the clinical experiences of PD patients. Behavior and immunohistochemistry analysis were conducted for the evaluation of the results. Overall, L-DOPA treatment showed no negative influences on endogenous dopaminergic neuron survival. Next, the 6-OHDA model was used to observe if long-term L-DOPA treatment influences the survival of exogenous human grafts. Again, the treatment plan attempted to more closely represent the real situation, which includes the proper use of immunosuppressant and its withdrawal. The results reflected that L-DOPA did not negatively influence exogenous dopaminergic neurons in the absence of immunosuppression. Lastly, an improved α-synuclein overexpression plus preformed α-synuclein fibril model was used, allowing the progressive features of PD to be reproduced. This model still aimed to evaluate the impact of L-DOPA on the endogenous dopaminergic neurons, but it provides more information about the interplay between L-DOPA and the neurodegenerative feature of PD. Overall, the results still indicated that L-DOPA has no negative impact on the dopaminergic neuron survival. In conclusion, L-DOPA showed no detrimental effects to endogenous and exogenous dopaminergic neuron survival in any of these rat models mentioned above and this provides valuable information for further studies in this aspect

Design of a Novel Drug Delivery Nanosystem that Simultaneously Realizes Real‐Time Tracing and Drug Delivery Across the Blood–Brain Barrier

Abstract Acute encephalitis is a brain infection that can harm the nervous system if not recognized and treated promptly. However, the presence of the blood–brain barrier restricts therapeutic agent distribution from the bloodstream to the brain parenchyma, severely restricting effective therapy for this disease. Herein, a novel drug delivery system based on a macrophage (RAW 264.7 cells) artifactual diagnostic and therapeutic nanoparticles (IPD@RAW) drug‐loading approach is presented, which exploits RAW cells' ability to cross the blood–brain barrier and go toward inflammation, and efficiently realizes the targeted enrichment of diagnostic and therapeutic nanoparticles at the site of inflammation in the brain. This nano‐drug‐carrying technology can accurately depict the degree of inflammation in real time for an extended period due to the significant penetration depth and high signal‐to‐noise ratio of near‐infrared (NIR) imaging. Meanwhile, the modified polydopamine can trigger the controlled release of anti‐inflammatory drugs through photothermal conversion under NIR irradiation to reduce the expression of cellular inflammatory factors, such as TNF‐α, IL‐6, and IL‐1β, and alleviate the brain damage due to secretion of this inflammatory factor. As a result, this drug delivery system provides a reliable tool for overcoming the blood–brain barrier to achieve early diagnosis and treatment of acute encephalitis

Gesture Recognition Based on a Convolutional Neural Network–Bidirectional Long Short-Term Memory Network for a Wearable Wrist Sensor with Multi-Walled Carbon Nanotube/Cotton Fabric Material

Flexible pressure sensors play a crucial role in detecting human motion and facilitating human–computer interaction. In this paper, a type of flexible pressure sensor unit with high sensitivity (2.242 kPa−1), fast response time (80 ms), and remarkable stability (1000 cycles) is proposed and fabricated by the multi-walled carbon nanotube (MWCNT)/cotton fabric (CF) material based on a dip-coating method. Six flexible pressure sensor units are integrated into a flexible wristband and made into a wearable and portable wrist sensor with favorable stability. Then, seven wrist gestures (Gesture Group #1), five letter gestures (Gesture Group #2), and eight sign language gestures (Gesture Group #3) are performed by wearing the wrist sensor, and the corresponding time sequence signals of the three gesture groups (#1, #2, and #3) from the wrist sensor are collected, respectively. To efficiently recognize different gestures from the three groups detected by the wrist sensor, a fusion network model combined with a convolutional neural network (CNN) and the bidirectional long short-term memory (BiLSTM) neural network, named CNN-BiLSTM, which has strong robustness and generalization ability, is constructed. The three types of Gesture Groups were recognized based on the CNN-BiLSTM model with accuracies of 99.40%, 95.00%, and 98.44%. Twenty gestures (merged by Group #1, #2, and #3) were recognized with an accuracy of 96.88% to validate the applicability of the wrist sensor based on this model for gesture recognition. The experimental results denote that the CNN-BiLSTM model has very efficient performance in recognizing different gestures collected from the flexible wrist sensor

Genome-Wide Identification and Expression Analysis of <i>HSP70</i> Gene Family in <i>Chrysanthemum lavandulifolium</i> under Heat Stress

As a molecular chaperone, HSP70 is widely involved in complex activities in plants. Under high temperature, drought, high salt, low temperature, heavy metals, and other stresses, HSP70 is rapidly synthesizes, stabilizes protein and biological macromolecular structures, and improves the stress resistance of plants. In this study, 83 ClHSP70 genes in Chrysanthemum lavandulifolium were identified based on the published Chrysanthemum lavandulifolium genome database. The genes were divided into six clusters based on a phylogenetic analysis, and the gene structures, conserved motifs, and functional domains were relatively conserved. Only two collinear genes were observed, and they formed a pair of duplicating genes. Multiple abiotic stress and phytohormone response elements were observed on the ClHSP70 promoter, such as temperature, drought, methyl jasmonate, abscisic acid, and other stress-related elements, and CpG islands were found on some ClHSP70 promoters, suggesting that they may be related to methylation modifications. Tissue expression analysis showed that the ClHSP70 genes were highly expressed in the roots. In addition, the gene expression changed significantly after 1 h of heat treatment and plays an important role in plant responses to temperature stress. The results of this study provide insights on the ClHSP70 gene family members and a theoretical basis for further research on functional analyses of the ClHSP70 gene family

The Roles of Periodontal Bacteria in Atherosclerosis

Atherosclerosis (AS) is an inflammatory vascular disease that constitutes a major underlying cause of cardiovascular diseases (CVD) and stroke. Infection is a contributing risk factor for AS. Epidemiological evidence has implicated individuals afflicted by periodontitis displaying an increased susceptibility to AS and CVD. This review concisely outlines several prevalent periodontal pathogens identified within atherosclerotic plaques, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum. We review the existing epidemiological evidence elucidating the association between these pathogens and AS-related diseases, and the diverse mechanisms for which these pathogens may engage in AS, such as endothelial barrier disruption, immune system activation, facilitation of monocyte adhesion and aggregation, and promotion of foam cell formation, all of which contribute to the progression and destabilization of atherosclerotic plaques. Notably, the intricate interplay among bacteria underscores the complex impact of periodontitis on AS. In conclusion, advancing our understanding of the relationship between periodontal pathogens and AS will undoubtedly offer invaluable insights and potential therapeutic avenues for the prevention and management of AS

Epidemiology and evolution of Norovirus in China

Norovirus (NoV) has been recognized as a leading cause of gastroenteritis worldwide. This review estimates the prevalence and genotype distribution of NoV in China to provide a sound reference for vaccine development. Studies were searched up to October 2020 from CNKI database and inclusion criteria were study duration of at least one calendar year and population size of >100. The mean overall NoV prevalence in individuals with sporadic diarrhea/gastroenteritis was 16.68% (20796/124649, 95% CI 16.63–16.72), and the detection rate of NoV was the highest among children. Non-GII.4 strains have replaced GII.4 as the predominant caused multiple outbreaks since 2014. Especially the recombinant GII.P16-GII.2 increased sharply, and virologic data show that the polymerase GII.P16 rather than VP1 triggers pandemic. Due to genetic diversity and rapid evolution, predominant genotypes might change unexpectedly, which has become major obstacle for the development of effective NoV vaccines

Theoretical Investigation of the ESIPT Mechanism for the 1-Hydroxy-9H-fluoren-9-one and 1-Hydroxy-11H-benzo[b]fluoren-11-one Chromophores

The excited state intramolecular proton transfer (ESIPT) dynamics of the 1-hydroxy-9H-fluoren-9-one (HHF) and 1-hydroxy-11H-benzo[b]fluoren-11-one (HHBF) chromophores were investigated theoretically. The calculated bond lengths and angles, hydrogen bond energies and infrared vibrational spectra involved in the hydrogen bonding of O-H center dot center dot center dot O indicated that the intramolecular hydrogen bond was strengthened in the S-1 state. Our calculated results accurately reproduced the experimental absorbance and fluorescence emission spectra, demonstrating that the adopted time-dependent density functional theory (TDDFT) method is reasonable and effective. In addition, qualitative and quantitative intramolecular charge transfer based on the frontier molecular orbitals provided the possibility of the ESIPT reaction. The potential energy curves of the ground and first excited states have been constructed to illustrate the ESIPT mechanism. Based on our calculations, we explain the equilibrium ESIPT processes observed in previous experiments

Genome-Wide Identification and Analysis of <i>NF-Y</i> Gene Family Reveal Its Potential Roles in Stress-Resistance in <i>Chrysanthemum</i>

Nuclear factor Y (NF-Y) is a class of transcription factors (TFs) with various biological functions that exist in almost all eukaryotes. In plants, heterotrimers composed of different NF-Y subunits are numerous and have different functions that can participate in the regulation of plant growth at various stages. However, NF-Y genes have not been systematically analyzed in chrysanthemum, only involving several NF-Y members. In this study, forty-six NF-Y members were identified from the diploid species Chrysanthemum seticuspe, including eight NF-YA members, twenty-one NF-YB members, and seventeen NF-YC members. These NF-Y genes were analyzed for their physicochemical characteristics, multiple alignments, conserved motifs, gene structure, promoter elements, and chromosomal location. Phylogenetic analysis revealed that only two gene pairs in C. seticuspe underwent gene duplication events. The Ka/Ks ratios were both less than one, indicating that the two pairs underwent purifying selection. Promoter element analysis showed that multiple abiotic stress and hormone response elements were present in the CsNF-Y genes, suggesting that these genes play an important role in the response to stress, growth, and development in plants. Further validation of candidate genes in response to drought regulation using RT-qPCR demonstrated that CsNF-Y genes in C. seticuspe play an important role in drought regulation

A SNP Mutation in Homeodomain-DDT (HD-DDT) Transcription Factor Results in Multiple Trichomes (mt) in Cucumber (Cucumis sativus L.)

Trichome is a natural physical barrier protecting plants against environmental stresses, natural infestations, ultraviolet rays and pathogenicity. Trichome also helps plants in maintaining appropriate water content by reducing transpiration rate. The molecular mechanism regulating unicellular trichome development in Arabidopsis has been extensively elucidated, but the molecular mechanism regulating multicellular trichome development remains unclear. In this study, we identified a multiple trichomes (mt) mutant from a cucumber EMS (Ethylmethylsulfone) mutagenesis population. Genetic analysis indicated that an incomplete dominant gene controls the mt trait. Using a combination of map-based cloning and BSA-seq (Bulked Segregant Analysis -Sequencing), we identified the candidate gene, CsaV3_6G050410, responsible for the mt mutation. Sequence alignment revealed one base substitution in gene CsaV3_6G050410, resulting in an amino acid substitution. The deduced amino acid sequence of CsaV3_6G050410 encodes a HD-DDT (homeodomain-DDT) transcriptional regulatory protein containing a conserved homeobox domain and a DDT domain. Gene expression analysis revealed that the expression level of CsaV3_6G050410 in the mt mutant was similar to that in the WT (wild type). Transcriptome analysis indicated that the mt gene may regulate the development of the epidermis by influencing plant hormone signaling pathways or participating in several transcription factor pathways. The results of this study are fundamental for a better understanding of the function of the HD-DDT transcription factor in the trichome development of cucumber

Functional identification of MdMYB5 involved in secondary cell wall formation in apple

Being the principal elements of secondary cell wall, cellulose and lignin both play a strengthening role in plant structures and stress resistance. However, little research has been done regarding the molecular mechanisms involved in the formation of cellulose and lignin in apple. In this study, in order to better understand the regulatory network in the formation of secondary cell wall, an R2R3 MYB transcriptional factor MdMYB5 was identified and explored. The subcellular localization experiments showed that MdMYB5 could function in the nucleus. Even though lignin and cellulose content, and the expression of their biosynthesis related genes decreased in the MdMYB5-RNAi apple, the ectopic overexpression of MdMYB5 promotes lignin and cellulose content in Arabidopsis, which contributes to the dwarf phenotype. At the same time, salt and osmotic stress affect MdMYB5-RNAi apple tissue cultures. Further transcriptional activation assays carried out demonstrated that MdMYB5 could be activated by MdMYB46 and MdSND1. In conclusion, MdMYB5 was required for the normal formation of secondary cell wall in apple and could be activated by the key regulatory factors MdMYB46 and MdSND1