GLP-1 in the Hypothalamic Paraventricular Nucleus Promotes Sympathetic Activation and Hypertension.

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for diabetes treatment. The paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expressions were present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist exendin 9-39 (EX9-39) or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor apocynin, adenylyl cyclase (AC) inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, AC, and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in the PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contributes to sympathetic overactivity and hypertension.

Parental cadmium exposure during the spawning period reduces cadmium sensitivity through the antioxidant system in rare minnow (Gobiocypris rarus) larvae.

Cadmium (Cd) is a noxious heavy metal widely dispersed in aquatic systems. Parental Cd exposure of fish species at environmental concentrations has been shown to cause deformities and stunted growth in their offspring. However, the long-term effects and the mechanisms underlying parental Cd exposure in fish species on Cd sensitivity in their offspring remain unclear. To explore the impacts of parental Cd exposures on Cd sensitivity, rare minnow (Gobiocypris rarus) larvae whose parents were exposed to Cd at 0, 5 or 10 µg/L for 28 days were established. Results showed that parental Cd exposure in rare minnow increased the Cd content of its larvae. In terms of malformation rate, mortality rate and total length at 7 days of rare minnow larvae, parental Cd exposure at 5 or 10 µg/L reduced Cd sensitivity. Further mechanistic investigation demonstrated that parental Cd exposure significantly upregulated the expression of antioxidant gene regulated by nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-кB) in rare minnow larvae. In addition, parental Cd exposure significantly elevated the level of reactive oxygen species (ROS) and malondialdehyde (MDA), but markedly decreased catalase (CAT), superoxide dismutase (SOD) and oxidized glutathione (GST) activity. The impact of parental Cd exposure to metallothionein (MT) content and the expression of MT mRNA, a detoxifying metallothionein, showed that parental Cd exposure of rare minnow induced oxidative stress in the larvae. Meanwhile, these results indicated that parental Cd exposure in rare minnow reduced the Cd sensitivity of the larvae via activating the Nrf2-mediated antioxidant system. This project helps us to further understand the toxicological mechanism of Cd in fish species and properly assess its potential ecological risk.

Asprosin in the Paraventricular Nucleus Induces Sympathetic Activation and Pressor Responses via cAMP-Dependent ROS Production.

Asprosin is a newly discovered adipokine that is involved in regulating metabolism. Sympathetic overactivity contributes to the pathogenesis of several cardiovascular diseases. The paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the regulation of sympathetic outflow and blood pressure. This study was designed to determine the roles and underlying mechanisms of asprosin in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male adult SD rats under anesthesia. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) were recorded, and PVN microinjections were performed bilaterally. Asprosin mRNA and protein expressions were high in the PVN. The high asprosin expression in the PVN was involved in both the parvocellular and magnocellular regions according to immunohistochemical analysis. Microinjection of asprosin into the PVN produced dose-related increases in RSNA, MAP, and HR, which were abolished by superoxide scavenger tempol, antioxidant N-acetylcysteine (NAC), and NADPH oxidase inhibitor apocynin. The asprosin promoted superoxide production and increased NADPH oxidase activity in the PVN. Furthermore, it increased the cAMP level, adenylyl cyclase (AC) activity, and protein kinase A (PKA) activity in the PVN. The roles of asprosin in increasing RSNA, MAP, and HR were prevented by pretreatment with AC inhibitor SQ22536 or PKA inhibitor H89 in the PVN. Microinjection of cAMP analog db-cAMP into the PVN played similar roles with asprosin in increasing the RSNA, MAP, and HR, but failed to further augment the effects of asprosin. Pretreatment with PVN microinjection of SQ22536 or H89 abolished the roles of asprosin in increasing superoxide production and NADPH oxidase activity in the PVN. These results indicated that asprosin in the PVN increased the sympathetic outflow, blood pressure, and heart rate via cAMP-PKA signaling-mediated NADPH oxidase activation and the subsequent superoxide production.

Determination of components in Radix paeoniae rubra based on QAMS.

The current study aimed to establish simple and quick quality evaluation method of Chishao based on QAMS. Oxypaeoniflorin is used as a marker in the Chishao root. Based on it, the content of other components could be obtained by establishing the mathematical relationship. UPLC method was used to collect data, and the detection wavelengths were 230nm (benzoic acid, paeoniflorin), 263nm (hydroxy paeoniflorin) 274nm (gallic acid, paeoniflorin, catechin), respectively. The stationary phase was an Agilent ZORBAX SB-C18 and the mobile phase was acetonitrile -0.1% formic acid-water. The gradient elution method was adopted at the certain flow rate (0.3 mL/min). The column temperature set 40oC, and the injection volume was 1µL. Multiple reaction monitoring mode was selected for data collection. The linear ranges of benzoic acid, paeoniflorin, hydroxy-paeoniflorin, gallic acid, catechin and paeoniflorinhad good linearity (r ≥0.9995). The UPLC method was established to determine the content of paeoniflorin, benzoic acid, catechin, gallic acid, paeoniflorin, andhydroxy-paeoniflorin in Radix Paeoniae Rubra. In the current study, the method for the chemical components in Radix Paeoniae Rubra to provide the evaluation basis of medicinal effects.

Enhancing Effect of Fe3O4/Nanolignocelluloses in Magnetorheological Fluid.

Magnetorheological fluid (MRF) is an intelligent material, which can be controlled by an external magnetic field. It is widely used in damping, finishing, mechanical transmission, sealing, and other engineering fields due to its magnetorheological (MR) effect. However, despite decades of research and experimental development, the wide application of MRF is still restricted by its serious settlement problem owing to the density difference between the magnetic particles and carrier liquid. Here, using the coprecipitation method, a kind of Fe3O4-modified nanolignocellulose (Fe3O4/NLC) composite fiber was characterized by its unique advantages such as low density, soft magnetism property, and high specific surface. These Fe3O4/NLCs were used as a kind of reinforcing particle with carbonyl iron powder in the new bidisperse MRF system. The performances of MRF samples were enhanced by these superior properties. We found that all MRF samples with composite fibers exhibited excellent antisettlement and dynamic mechanical characteristics and cooperativity between Fe3O4 and NLCs. Furthermore, redispersibility of MRF is qualitatively evaluated by a shearing test in this paper, explaining the high property of antihardening. This composite fiber improves the comprehensive performance of MRF and has the potential to be repeatedly used in engineering applications.

Is unilateral transverse process-pedicle percutaneous kyphoplasty a better choice for osteoporotic thoracolumbar fractures in the old patients?

BACKGROUND: A few reports have shown that unilateral transverse process-pedicle percutaneous kyphoplasty is a good choice for patients with osteoporotic vertebral compression fracture (OVCF). However, this issue remains controversial and the related comprehensive research was lacked. METHODS: A retrospective study was conducted on patients receiving PKP surgery for OVCF. Patients were divided into three groups according to surgical approach. Symptom and radiographical evaluation were performed preoperatively, 1-month postoperatively, 1-year postoperatively and follow-ups. And follow-ups were repeated every year. Visual Analogue Scale Score (VAS), Oswestry Disability Index (ODI) scores, anterior vertebral height, coronal Cobb angle and sagittal Cobb angle was determined and compared among three groups. RESULTS: Totally 447 patients were included with an average age of 76.6 ± 7.2 years old. UTP showed significantly shorter surgical duration (p < 0.001), lower cement volume (p < 0.001) but higher cement leakage proportion (p = 0.044). No significant statistical difference was found in terms of improvement rates among three groups. Besides, it was notable that the a significantly higher coronal Cobb angle was observed in UTP group, and a about 4°coronal correction was found after UTP PKP. CONCLUSION: UTTP PKP could achieve similar symptoms relief and kyphosis correction as UTP and BTP PKP. However, it had shorter surgical time and less radio exposure than BTP PKP, lower risk of cement leakage and higher proportion of bilaterally cement distribution than UTP PKP. It seemed to be a better choice for patients with OVCF. In addition, we found that UTP PKP was especially fit for OVCF patients with asymmetrical vertebral compression.

Protein acetylation in mitochondria plays critical functions in the pathogenesis of fatty liver disease.

BACKGROUND: Fatty liver is a high incidence of perinatal disease in dairy cows caused by negative energy balance, which seriously threatens the postpartum health and milk production. It has been reported that lysine acetylation plays an important role in substance and energy metabolism. Predictably, most metabolic processes in the liver, as a vital metabolic organ, are subjected to acetylation. Comparative acetylome study were used to quantify the hepatic tissues from the severe fatty liver group and normal group. Combined with bioinformatics analysis, this study provides new insights for the role of acetylation modification in fatty liver disease of dairy cows. RESULTS: We identified 1841 differential acetylation sites on 665 proteins. Among of them, 1072 sites on 393 proteins were quantified. Functional enrichment analysis shows that higher acetylated proteins are significantly enriched in energy metabolic pathways, while lower acetylated proteins are significantly enriched in pathways related to immune response, such as drug metabolism and cancer. Among significantly acetylated proteins, many mitochondrial proteins were identified to be interacting with multiple proteins and involving in lipid metabolism. Furthermore, this study identified potential important proteins, such as HADHA, ACAT1, and EHHADH, which may be important regulatory factors through modification of acetylation in the development of fatty liver disease in dairy cows and possible therapeutic targets for NAFLD in human beings. CONCLUSION: This study provided a comprehensive acetylome profile of fatty liver of dairy cows, and revealed important biological pathways associated with protein acetylation occurred in mitochondria, which were involved in the regulation of the pathogenesis of fatty liver disease. Furthermore, potential important proteins, such as HADHA, ACAT1, EHHADH, were predicted to be essential regulators during the pathogenesis of fatty liver disease. The work would contribute to the understanding the pathogenesis of NAFLD, and inspire in the development of new therapeutic strategies for NAFLD.

Sequential thermal dissolution of two low-rank coals and characterization of their structures by high-performance liquid chromatography/time-of-flight mass spectrometry and gas chromatography/mass spectrometry.

RATIONALE: Gas chromatography/mass spectrometry (GC/MS) and high-performance liquid chromatography/time-of-flight mass spectrometry (HPLC/TOF-MS) were used to separate and reveal the molecular characteristics of organic matter in low-rank coals. METHODS: Six soluble portions (SPs) were obtained by sequential thermal dissolution (TD) of two low-rank coals in the order of cyclohexane, acetone and methanol solvents at 300°C. Organic matter with different molecular characteristics were enriched in eachTD extract, which was further separated and analyzed by GC/MS and HPLC/TOF-MS using an electrospray ionization source in positive mode to obtain a comprehensive understanding of the structural composition of coals. RESULTS: Low polarity compounds like alkanes and arenes have a better solubility in cyclohexane. Phorone has the highest relative abundance in the acetone SPs, and the main compounds detected in the methanol SPs are alcohols and phenols. According to the data from HPLC/TOF-MS, most of the oxygen atoms are in the form of carbonyl and alkoxy groups. The nitrogen-containing compounds in SPs are mainly saturated aliphatic amines and pyridines. The sulfur-containing compounds mainly exist in the form of thioalkanes and thiophenes. CONCLUSIONS: Non-destructive methods were used to obtain soluble matter from coals, and different chromatographic and mass spectrometric techniques were used to separate and analyze the organic matter in coals. Detailed molecular structural information was obtained for the efficient and clean utilization of low-rank coals.

Effect of lychee biochar on the remediation of heavy metal-contaminated soil using sunflower: A field experiment.

Heavy metal contamination of soils is a serious issue with various consequences in Hunan Province. Here, we aimed to determine the effect and action mechanisms of lychee biochar on the remediation of Pb, Cd, As, and Zn from soil using sunflower (Helianthus annuus). Different amounts of lychee biochar (2.5, 5, and 10%) were added to heavy metal-contaminated soil in the Shuikoushan mining area, Hunan Province. The effects of biochar on the biomass of sunflower plants, and the accumulation and distribution of Pb, Cd, As, and Zn in sunflower plants, and changes in Pb, Cd, As, and Zn concentrations in the rhizosphere soil were studied. The application of biochar stimulated the growth of the sunflower plants, with the maximum biomass recorded in the 5% biochar treatment; however, above this level, biochar inhibited plant growth. Pb, Cd, As, and Zn in sunflower plants were redistributed with biochar addition. The concentration of Pb, Cd, As, and Zn in the leaves and receptacles of sunflower plants increased with biochar application, but their concentration in the roots, stems, and seeds significantly decreased compared with the control. The total amount of accumulated Pb, Cd, and As in sunflower plants increased by 22.9-58.9%, 15.8-42.3%, and 67.9-110%, respectively, compared with that in the control. In the biochar treatments, the total amount of accumulated Zn in sunflowers decreased by 13.8-37.2%, compared with that in the control. The accumulated Pb, Cd, and As in sunflower plants have an antagonistic effect on Zn required by sunflowers. The sunflower plants significantly reduced the concentration of Pb, Cd, As, and Zn in contaminated soil (P < 0.05), which decreased by 12.4, 11.0, 4.35, and 8.17%, respectively, compared with that before planting sunflower. The addition of biochar in heavy metal-contaminated soil significantly enhanced the heavy metal-remediation effect of sunflower. Compared with the control (0% biochar), 10% biochar application decreased the Pb, Cd, As, and Zn concentrations in the rhizosphere of sunflower plants, by 40.6, 31.6, 35.4, and 30.8%, respectively. In conclusion, lychee biochar enhanced the remediation of heavy metals in contaminated soil.

[Improvement of compliance of Pudilan Xiaoyan Oral Liquid based on comprehensive analysis of bad taste of traditional Chinese medicine oral liquid preparation].

From "good efficacy with a bad taste" to "good efficacy with no bitterness" and then to "good efficacy with a good taste" is the only way to develop oral liquid preparations of traditional Chinese medicine, and "good medicine is beneficial to disease" is the only way for the development of oral liquid preparations of traditional Chinese medicine. Based on the analysis of the causes, the sources of bitterness, the formation principles and their solutions of traditional Chinese medicine oral liquid preparations, we explored the causes of the bad taste and the material basis of bitterness of Pudilan Xiaoyan Oral Liquid, and applied the solutions in improving the taste of Pudilan products. The overall taste of Pudilan Xiaoyan Oral Liquid was improved by modifying the original product taste, enhancing the process and changing the dosage form, which improves the compliance of the patients who take the medicine, and better serve the clinical medication.

[Product improvement and secondary development of Pudilan Xiaoyan Oral Liquid based on clinical medication].

Pudilan Xiaoyan Oral Liquid is widely used in clinical applications, with safe and effective results. Its coverage rate in the national first, second and third grade hospitals is as high as 71%. In this study, we analyzed and summarized the research progress on the material basis, quality control, production process and clinical medication of Pudilan Xiaoyan Oral Liquid based on the clinical diseases(parotitis, tonsillitis, pharyngitis), and deeply explored the intrinsic quality improvement and secondary development of Pudilan product. Pharmacodynamic material basis of Pudilan Xiaoyan Oral Liquid was explored through the network pharmacology technology and quality control indicators of the production process were optimized by cell anti-inflammatory experiments. Through these techno-logies, it would be more specific, scientific and effective to carry out process optimization of each link and multidimensional quality control of the whole process. The dosage and oral compliance for special patients(children) were explored, providing a reference for clinical pediatric medication of Pudilan Xiaoyan Oral Liquid. Simultaneously, it is helpful to expand the application market by developing Pudilan daily chemical products, and promote the traditional Chinese medicine products in terms of curative effect and daily life.

An efficient simulated annealing algorithm for the RNA secondary structure prediction with Pseudoknots.

BACKGROUND: RNA pseudoknot structures play an important role in biological processes. However, existing RNA secondary structure prediction algorithms cannot predict the pseudoknot structure efficiently. Although random matching can improve the number of base pairs, these non-consecutive base pairs cannot make contributions to reduce the free energy. RESULT: In order to improve the efficiency of searching procedure, our algorithm take consecutive base pairs as the basic components. Firstly, our algorithm calculates and archive all the consecutive base pairs in triplet data structure, if the number of consecutive base pairs is greater than given minimum stem length. Secondly, the annealing schedule is adapted to select the optimal solution that has minimum free energy. Finally, the proposed algorithm is evaluated with the real instances in PseudoBase. CONCLUSION: The experimental results have been demonstrated to provide a competitive and oftentimes better performance when compared against some chosen state-of-the-art RNA structure prediction algorithms.

All-optical coaxial framing photography using parallel coherence shutters.

An all-optical framing camera has been developed to obtain serial images of high temporal and spatial resolution with identical spatial benchmark, identical temporal benchmark, and identical chromatic benchmark in a single shot. A train of laser probe pulses with identical wavelength coaxially illuminate the target and form sequentially timed images by means of parallel coherence shutters. A coherence shutter only selects one of the probe pulses to form a nonmultiplexing hologram. The other probe pulses superpose incoherently on the hologram as the background. By this method, each hologram is entirely separated from the others both in spatial and temporal domains. Two kinds of ultrafast physical process experiments, including laser driving air and laser driving aluminum foil, were performed to verify the feasibility of the parallel coherence shutters.

Analysis of soluble components in coals and interpretations for the complex mass spectra.

RATIONALE: The deduction of useful information from the mass spectra of a complex mixture like coals remains difficult, which limits the clean and efficient utilization of coals. It is necessary to explore the data interpretation methods for mass spectra and visualize the analytical data of coals for industrial utilization such as feedstock selection. METHODS: Coal sample and methanol were mixed and heated to 310 °C and kept at that temperature for 2 h. The solvent was under supercritical state at 310 °C and the solubility for the solid mixture increased. Soluble products from thermal dissolution of two Chinese coals were analyzed by high-performance liquid chromatography/atmospheric pressure chemical ionization orbitrap mass spectrometry. RESULTS: The iso-abundance plot for molecules in coals was upgraded to display the distributions of isomers which are indicated as concentric circles or triangles with the same carbon number and value of double-bond equivalent. The concentration ratio was introduced from economics to describe the content inequality of organic species within the same class of coal molecules. CONCLUSIONS: Interpretation methods for mass spectra visualize and simplify the understanding of complex components in coals for industrial utilization. Coals with a high concentration ratio for a specific class should take priority as a feedstock for chemicals and receive more attention. Copyright © 2016 John Wiley & Sons, Ltd.

Sequential ultrasonic extraction of a Chinese coal and characterization of nitrogen-containing compounds in the extracts using high-performance liquid chromatography with mass spectrometry.

Dongming lignite was sequentially extracted with petroleum ether, carbon disulfide, methanol, acetone, and isometric carbon disulfide/acetone mixed solvent at room temperature to afford extracts 1-5, respectively. High-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry was used to separate and characterize heteroatomic species in the extracts at molecular level. Molecular mass of compounds in the extracts is mainly distributed from 300 to 800 u, and the relative abundance of compounds with molecular mass over 800 u in the carbon disulfide extract is 135 times of that in the petroleum ether extract. The acetone extract has the highest relative abundance for organonitrogen compounds. Double bond equivalence numbers of detected species indicate that most of the organonitrogen compounds contain N-heterocyclic aromatic rings, including pyridine, quinoline and pyrrole. Some organonitrogen isomers in Dongming lignite were separated and identified by high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry, and the corresponding structural information was proposed.

Multiple folded resonator for LD pulse end pumped Q-switched Yb:YAG slab laser.

In this paper, a multiple folded resonator is presented which consists of a multiple optical folding setup, a flat total reflector, a flat output coupler, a Q-switch crystal and a polarizer. By this technique, the output energy of 32.6mJ and pulse width of 13.4ns with a repetition rate of 5Hz was obtained, which is three times higher than that reported in the past publications by the use of the currently existing technique of the Q-switched slab gain lasers with the unstable resonator. The output beam with a quality of M² = 1.55 in the slow axis and M² = 1.40 in the fast axis was also obtained.

Incident-angle dependent color tuning from a single plasmonic chip.

We report on a broad color tuning effect covering the visible range from a single plasmonic chip. By simply tilting the orientation of the designed plasmonic chip within a certain range, the photon-plasmon coupling interactions between the incident light and the plasmonic nanostructures on the chip can be finely tuned, resulting in an angle-dependent continuous color filtering effect. The physical mechanism of the device is investigated through the full-wave calculations, which provide important guidance for the design and optimization of the proposed devices. The broad color tuning from the demonstrated single chip will potentially benefit visualization and display technologies, and is particularly useful for the construction of reflection-based spatial light modulators.

High gain differentiator based neuro-adaptive arbitrary order sliding mode control design for MPE of standalone wind power system.

In this paper, we introduce a novel Maximum Power Point Tracking (MPPT) controller for standalone Wind Energy Conversion Systems (WECS) with Permanent Magnet Synchronous Generators (PMSG). The primary novelty of our controller lies in its implementation of an Arbitrary Order Sliding Mode Control (AOSMC) to effectively overcome the challenges caused by the measurement noise in the system. The considered model is transformed into a control-convenient input-output form. Additionally, we enhance the control methodology by simultaneously incorporating Feedforward Neural Networks (FFNN) and a high-gain differentiator (HGO), further improving the system performance. The FFNN estimates critical nonlinear functions, such as the drift term and input channel, whereas the HGO estimates higher derivatives of the system outputs, which are subsequently fed back to the control inputs. HGO reduces sensor noise sensitivity, rendering the control law more practical. To validate the proposed novel control technique, we conduct comprehensive simulation experiments compared against established literature results in a MATLAB environment, confirming its exceptional effectiveness in maximizing power extraction in standalone wind energy applications.

Identifying Qingkailing ingredients-dependent mesenchymal-epithelial transition factor-axiation "π" structuring module with angiogenesis and neurogenesis effects.

OBJECTIVE: To explore the functional role of the drug-dependent mesenchymal-epithelial transition (Met)-axiation "π" structural module of neurogenesis after processing by three components of Qingkailing injection in neurogenesis and angiogenesis in cerebral ischemia. METHODS: We used a Glutathione S-transferase (GST)-pull down assay, isothermal titration calorimetry assay, and other related methods to identify the relationships among Met, inositol polyphosphate phosphatase like 1 (Inppl1), and death associated protein kinase 3 (Dapk3) in this allosteric module. The biological effects of the modules of neurons generation composed of Met, Inppl1, and Dapk3 were measured through Western blot, apoptosis analysis, and double immunofluorescence labeling. RESULTS: The GST-pull down assay revealed that proline-serine-threonine rich domain of Met binds to the Src homology domain of Inppl1 to form a protein-protein complex; Dapk3 with a C-terminal domain interacts weakly with the protein kinase C domain of Met in the intracellular region. Thus, we obtained a "π" structuring module considered a neural regeneration module. The biological effects of angiogenesis and neurogenesis modules composed of Met, Inppl1, and Dapk3 were also verified. CONCLUSION: The study suggested that understanding the functional modules that contribute to pharmaceutics might provide novel signatures that can be used as endpoints to define disease processes under stroke or cerebral ischemia conditions.

Relationships Between Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease: Indication from Gut Microbiota Alterations.

Rapid eye movement sleep behavior disorder (RBD) has a close relationship with Parkinson's disease (PD) and was even regarded as the most reliable hallmark of prodromal PD. RBD might have similar changes in gut dysbiosis to PD, but the relationship between RBD and PD in gut microbial alterations is rarely studied. In this study, we aim to investigate whether there were consistent changes between RBD and PD in gut microbiota, and found some specific biomarkers in RBD that might indicate phenoconversion to PD. Alpha-diversity showed no remarkable difference and beta-diversity showed significant differences based on the unweighted (R = 0.035, P = 0.037) and weighted (R = 0.0045, P = 0.008) UniFrac analysis among idiopathic RBD (iRBD), PD with RBD, PD without RBD and normal controls (NC). Enterotype distribution indicated iRBD, PD with RBD and PD without RBD were Ruminococcus-dominant while NC were Bacteroides-dominant. 7 genera (4 increased: Aerococcus, Eubacterium, Gordonibacter and Stenotrophomonas, 3 decreased: Butyricicoccus, Faecalibacterium and Haemophilus) were consistently changed in iRBD and PD with RBD. Among them, 4 genera (Aerococcus, Eubacterium, Butyricicoccus, Faecalibacterium) remained distinctive in the comparison between PD with RBD and PD without RBD. Through clinical correlation analysis, Butyricicoccus and Faecalibacterium were found negatively correlated with the severity of RBD (RBD-HK). Functional analysis showed iRBD had similarly increased staurosporine biosynthesis to PD with RBD. Our study indicates that RBD had similar gut microbial changes to PD. Decreased Butyricicoccus and Faecalibacterium might be potential hallmarks of phenoconversion of RBD to PD.