Protocol for the safety and efficacy of fecal microbiota transplantation liquid in children with autism spectrum disorder: a randomized controlled study

BackgroundAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, repetitive behavior and language impairment, and its worldwide prevalence has been found to be increasing annually in recent years. Till now, ASD is uncurable as its pathogenesis remains unknown. However, studies on both animals and humans have demonstrated that fecal microbiota transplantation (FMT) may ameliorate the symptoms of ASD, as well as gastrointestinal symptoms. Nonetheless, there is still no agreement regarding the optimal dosage or duration of FMT treatment for individuals with ASD.MethodsThis clinical study is a double-blind, randomized, interventional trial conducted at a single center. The aim is to investigate the safety and efficacy of a pediatric formulation of FMT for ASD. A total of 42 children between the ages of 3–9 with ASD will be randomly assigned in a 2:1 ratio to either an FMT treatment group (n = 28) or a placebo group (n = 14), forming cohort 1. Additionally, 30 healthy children of similar age and gender will be recruited as the control group (cohort 2). Cohort 1 will be assessed using a variety of scales, including the Autism Behavior Checklist, Childhood Autism Rating Scale, Social Responsiveness Scale, Gastrointestinal Symptom Rating Scale, Children’s Sleep Habits Questionnaire, and Psychoeducational Profile (Third Edition). These assessments will evaluate the effectiveness of FMT in reducing core symptoms and comorbidities (such as gastrointestinal symptoms and sleep disturbances) in children with ASD. The study will use metagenomic and metabolomic sequencing to assess changes in the composition and structure of the intestinal flora and its metabolites in blood, urine, and feces following treatment. Furthermore, the study will evaluate the acceptability of the FMT formulation by participants’ legal guardians and investigate differences in the intestinal flora and metabolism in the FMT group before and after treatment compared to 30 healthy children.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2200058459

Hyperoside Protects Against Pressure Overload-Induced Cardiac Remodeling via the AKT Signaling Pathway

Background/Aims: Cardiac hypertrophy is a major predisposing factor for heart failure and sudden cardiac death. Hyperoside (Hyp), a flavonoid isolated from Rhododendron ponticum L., is a primary component of Chinese traditional patent medicines. Numerous studies have shown that Hyp exerts marked anti-viral, anti-inflammatory, anti-oxidant, anti-cancer, anti-ischemic, and particularly cardio-protective effects. However, the effects of Hyp on cardiac hypertrophy have not been explored. The aims of this study were to determine whether Hyp could protect against cardiac remodeling and to clarify the potential molecular mechanisms. Methods: Neonatal rat cardiac myocytes were isolated and treated with different concentrations of Hyp, then cultured with angiotensin II for 48 h. Mice were subjected to either aortic banding or sham surgery (control group). One week after surgery, the mice were treated with Hyp (20 mg/kg/day) or vehicle by oral gavage for 7 weeks. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histology, and biomarkers. Results: Hyp pretreatment suppressed angiotensin II-induced hypertrophy in cardiomyocytes. Hyp exerted no basal effects but attenuated cardiac hypertrophy and dysfunction, fibrosis, inflammation, and oxidative stress induced by pressure overload. Both in vivo and in vitro experiments demonstrated that the effect of Hyp on cardiac hypertrophy was mediated by blocking activation of the AKT signaling pathway. Conclusion: Hyp improves cardiac function and prevents the development of cardiac hypertrophy via AKT signaling. Our results suggest a protective effect of Hyp on pressure overload-induced cardiac remodeling. Taken together, Hyp may have a role in the pharmacological therapy of cardiac hypertrophy

Scaling of Berry-curvature monopole dominated large linear positive magnetoresistance

The linear positive magnetoresistance (LPMR) is a widely observed phenomenon in topological materials, which is promising for potential applications on topological spintronics. However, its mechanism remains ambiguous yet and the effect is thus uncontrollable. Here, we report a quantitative scaling model that correlates the LPMR with the Berry curvature, based on a ferromagnetic Weyl semimetal CoS2 that bears the largest LPMR of over 500% at 2 Kelvin and 9 Tesla, among known magnetic topological semimetals. In this system, masses of Weyl nodes existing near the Fermi level, revealed by theoretical calculations, serve as Berry-curvature monopoles and low-effective-mass carriers. Based on the Weyl picture, we propose a relation $$\text{MR}=\frac{e}{\hbar }B{{\Omega }_{\text{F}}}$$, with B being the applied magnetic field and $${{\Omega }_{\text{F}}}$$ the average Berry curvature near the Fermi surface, and further introduce temperature factor to both MR/B slope (MR per unit field) and anomalous Hall conductivity, which establishes the connection between the model and experimental measurements. A clear picture of the linearly slowing down of carriers, i.e., the LPMR effect, is demonstrated under the cooperation of the k-space Berry curvature and real-space magnetic field. Our study not only provides an experimental evidence of Berry curvature induced LPMR for the first time, but also promotes the common understanding and functional designing of the large Berry-curvature MR in topological Dirac/Weyl systems for magnetic sensing or information storage

The GALAH survey: Properties of the Galactic disc(s) in the solar neighbourhood

Using data from the GALAH pilot survey, we determine properties of the Galactic thin and thick discs near the solar neighbourhood. The data cover a small range of Galactocentric radius (7.9 RGC 9.5 kpc), but extend up to 4 kpc in height from the Galactic plane, and several kpc in the direction of Galactic anti-rotation (at longitude 260◦ ≤ ≤ 280◦). This allows us to reliably measure the vertical density and abundance profiles of the chemically and kinematically defined ‘thick’ and ‘thin’ discs of the Galaxy. The thin disc (low-α population) exhibits a steep negative vertical metallicity gradient, at d[M/H]/dz = −0.18 ± 0.01 dex kpc−1, which is broadly consistent with previous studies. In contrast, its vertical α-abundance profile is almost flat, with a gradient of d[α/M]/dz = 0.008 ± 0.002 dex kpc−1. The steep vertical metallicity gradient of the low-α population is in agreement with models where radial migration has a major role in the evolution of the thin disc. The thick disc (high-α population) has a weaker vertical metallicity gradient d[M/H]/dz = −0.058 ± 0.003 dex kpc−1. The αabundance of the thick disc is nearly constant with height, d[α/M]/dz = 0.007 ± 0.002 dex kpc−1. The negative gradient in metallicity and the small gradient in [α/M] indicate that the high-α population experienced a settling phase, but also formed prior to the onset of major Type Ia supernova enrichment. We explore the implications of the distinct α-enrichments and narrow [α/M] range of the sub-populations in the context of thick disc formation.LD and MA acknowledge funding from the Australian Government through ARC Laureate Fellowship FL110100012. LD, KCF, and RFGW acknowledge support from ARC grant DP160103747. LC gratefully acknowledges support from the Australian Research Council (grants DP150100250, FT160100402). DMN was supported by the Allan C. and Dorothy H. Davis Fellowship. DS is the recipient of an Australian Research Council Future Fellowship (project number FT1400147). TZ acknowledges financial support from the Slovenian Research Agency (research core funding No. P1-0188). Part of this research was supported by the Munich Institute for Astro- and Particle Physics (MIAPP) of the DFG cluster of excellence ‘Origin and Structure of the Universe’

OsteoporosAtlas: a human osteoporosis-related gene database

Background Osteoporosis is a common, complex disease of bone with a strong heritable component, characterized by low bone mineral density, microarchitectural deterioration of bone tissue and an increased risk of fracture. Due to limited drug selection for osteoporosis and increasing morbidity, mortality of osteoporotic fractures, osteoporosis has become a major health burden in aging societies. Current researches for identifying specific loci or genes involved in osteoporosis contribute to a greater understanding of the pathogenesis of osteoporosis and the development of better diagnosis, prevention and treatment strategies. However, little is known about how most causal genes work and interact to influence osteoporosis. Therefore, it is greatly significant to collect and analyze the studies involved in osteoporosis-related genes. Unfortunately, the information about all these osteoporosis-related genes is scattered in a large amount of extensive literature. Currently, there is no specialized database for easily accessing relevant information about osteoporosis-related genes and miRNAs. Methods We extracted data from literature abstracts in PubMed by text-mining and manual curation. Moreover, a local MySQL database containing all the data was developed with PHP on a Windows server. Results OsteoporosAtlas (http://biokb.ncpsb.org/osteoporosis/), the first specialized database for easily accessing relevant information such as osteoporosis-related genes and miRNAs, was constructed and served for researchers. OsteoporosAtlas enables users to retrieve, browse and download osteoporosis-related genes and miRNAs. Gene ontology and pathway analyses were integrated into OsteoporosAtlas. It currently includes 617 human encoding genes, 131 human non-coding miRNAs, and 128 functional roles. We think that OsteoporosAtlas will be an important bioinformatics resource to facilitate a better understanding of the pathogenesis of osteoporosis and developing better diagnosis, prevention and treatment strategies

Th1/Th2 Functional Imbalance After Acute Myocardial Infarction: Coronary Arterial Inflammation or Myocardial Inflammation

Objectives: The study clarified whether the T-helper (Th)1/Th2 imbalance existed only in coronary arterial inflammation or in both coronary arterial inflammation and myocardial inflammation and explored the significance of the imbalance of Th1/Th2 function after acute myocardial infarction (AMI). Background: There are two different inflammatory processes in patients with AMI: the coronary arterial inflammation that leads to the pathogenesis of AMI and the myocardial inflammation after AMI that leads to ventricular remodeling, which are positively and negatively regulated by Th1 and Th2 lymphocytes, respectively. Methods : Peripheral blood mononuclear cells from 33 AMI patients, 22 unstable angina (UA) patients and splenocytes from 35 AMI Wistar rats were collected. Cytokine-producing Th cells were ambulatorily monitored by 3-color flow cytometry. Interferon (IFN)-γ and interleukin (IL)-4 mRNA in the rat myocardium and chemokine receptors CCR3,CCR5 and CXCR3 mRNA on the surface of rat T-lymphocytes after AMI were measured by RT-PCR. Results: IFN-γ-producing T-cells significantly increased in patients with AMI and UA within 24 hours after the onset of symptom. The high ratio of IFN-γ-producing T-cells recovered 1 week after the onset in UA patients, while it could be examined 1 week and even 1 month after the onset in AMI patients. The up-regulation of Th1 cell function is consistent with bad heart function. There was no significant difference on the frequencies of IL-4-producing T-cells between each group. 1 week, 2 weeks and 1 month after AMI, IFN-γ mRNA increased in the myocardium of rats, but there was no significant change on global Th cell functions. Conclusions: Th1/Th2 functional imbalance exists in both coronary arterial inflammation and myocardial inflammation processes. The up-regulation of Th1 cell-functions may participate in the immune-mediated ventricular remodeling after AMI.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44845/1/10875_2005_Article_4088.pd

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Finite-state control of a robotic transtibial prosthesis with motor-driven nonlinear damping behaviors for level ground walking

This paper presents a finite-state control strategy for a robotic transtibial prosthesis to realize level ground walking with controlled damping behaviors in the ankle joint. We use a motor-driven method to generate braking torque to realize nonlinear damping behaviors. The controller performs damper control for the stance phase and angle control for the swing phase. We design and construct a robotic transtibial prosthesis prototype to evaluate the effectiveness of the proposed control strategy. One transtibial amputee subject participated in the experiments. By using the proposed finite-state control method, the robotic prosthesis can successfully mimick the behaviors of normal limb. The damping control strategy enabled the ankle to dorsiflex smoothly. ? 2014 IEEE.EICPCI-S(ISTP)