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

Probiotics' effects on gut microbiota in jaundiced neonates: a randomized controlled trial protocol

IntroductionRecent evidence suggests that blue-light phototherapy impacts gut microbiota composition in jaundiced newborns, leading to disturbances closely related to the therapy's side effects. As a result, gut microbiota may serve as a potential intervention target to mitigate these side effects. In this study, we aim to examine the effects of AB-GG (Lactobacillus rhamnosus LGG), Bb-12 (Bifidobacterium animalis Bb-12) and M-16V (Bifidobacterium breve M-16V) and their combination on the intestinal microbiota, metabolomics and phototherapy-related side effects in neonates with jaundice.Methods and analysisA total of 100 jaundiced newborns aged two weeks or younger will be included in this randomized, single-blind (the parents knew, but the neonatologists did not know), single-center controlled trial to receive either 109 colony-forming units of AB-GG, Bb-12, M-16V, a combination of the three probiotics with blue-light phototherapy, or blue-light phototherapy alone. The experimental group will be treated with oral probiotics once daily for 30 days, while the control group will receive only blue-light phototherapy. The follow-up duration will last 30 days. The primary outcomes include changes in gut microbiota, metabolomics, and the incidence of phototherapy side effects, assessed after each phototherapy session, as well as on days 10, 20, and 30.Ethics and disseminationThe study protocol has been approved by the Ethics Committee of our institution. The findings of this trial will be submitted to a peer-reviewed pediatric journal. Its abstracts will be submitted to relevant national and international conferences.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifer (ChiCTR2000036013)

The bZIP Transcription Factor MoAP1 Mediates the Oxidative Stress Response and Is Critical for Pathogenicity of the Rice Blast Fungus Magnaporthe oryzae

Saccharomyces cerevisiae Yap1 protein is an AP1-like transcription factor involved in the regulation of the oxidative stress response. An ortholog of Yap1, MoAP1, was recently identified from the rice blast fungus Magnaporthe oryzae genome. We found that MoAP1 is highly expressed in conidia and during invasive hyphal growth. The Moap1 mutant was sensitive to H2O2, similar to S. cerevisiae yap1 mutants, and MoAP1 complemented Yap1 function in resistance to H2O2, albeit partially. The Moap1 mutant also exhibited various defects in aerial hyphal growth, mycelial branching, conidia formation, the production of extracellular peroxidases and laccases, and melanin pigmentation. Consequently, the Moap1 mutant was unable to infect the host plant. The MoAP1-eGFP fusion protein is localized inside the nucleus upon exposure to H2O2, suggesting that MoAP1 also functions as a redox sensor. Moreover, through RNA sequence analysis, many MoAP1-regulated genes were identified, including several novel ones that were also involved in pathogenicity. Disruption of respective MGG_01662 (MoAAT) and MGG_02531 (encoding hypothetical protein) genes did not result in any detectable changes in conidial germination and appressorium formation but reduced pathogenicity, whereas the mutant strains of MGG_01230 (MoSSADH) and MGG_15157 (MoACT) showed marketed reductions in aerial hyphal growth, mycelial branching, and loss of conidiation as well as pathogenicity, similar to the Moap1 mutant. Taken together, our studies identify MoAP1 as a positive transcription factor that regulates transcriptions of MGG_01662, MGG_02531, MGG_01230, and MGG_15157 that are important in the growth, development, and pathogenicity of M. oryzae

The mPEG-PCL Copolymer for Selective Fermentation of Staphylococcus lugdunensis Against Candida parapsilosis in the Human Microbiome.

Many human skin diseases, such as seborrheic dermatitis, potentially occur due to the over-growth of fungi. It remains a challenge to develop fungicides with a lower risk of generating resistant fungi and non-specifically killing commensal microbes. Our probiotic approaches using a selective fermentation initiator of skin commensal bacteria, fermentation metabolites or their derivatives provide novel therapeutics to rein in the over-growth of fungi. Staphylococcus lugdunensis (S. lugdunensis) bacteria and Candida parapsilosis (C. parapsilosis) fungi coexist in the scalp microbiome. S. lugdunensis interfered with the growth of C. parapsilosis via fermentation. A methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymer functioned as a selective fermentation initiator of S. lugdunensis, selectively triggering the S. lugdunensis fermentation to produce acetic and isovaleric acids. The acetic acid and its pro-drug diethyleneglycol diacetate (Ac-DEG-Ac) effectively suppressed the growth of C. parapsilosis in vitro and impeded the fungal expansion in the human dandruff. We demonstrate for the first time that S. lugdunensis is a skin probiotic bacterium that can exploit mPEG-PCL to yield fungicidal short-chain fatty acids (SCFAs). The concept of bacterial fermentation as a part of skin immunity to re-balance the dysbiotic microbiome warrants a novel avenue for studying the probiotic function of the skin microbiome in promoting health

A 672-nW, 670-n<italic>Vrms</italic> ECG Acquisition AFE With Noise-Tolerant Heartbeat Detector

This paper presents an electrocardiogram acquisition analog front-end (AFE) with a noise tolerant heartbeat (HB) detector. Source degradation and transconductance bootstrap techniques are incorporated into the AFE to reduce the 1/f noise of the amplifier. Furthermore, the chopper modulation, DC-servo loop (DSL) and pre-charge technology are combined to reduce interference from the environment. A mixed-signal implementation of HB detector with the symmetric-comparison loop is proposed to reduce the power consumption and area, which also suppresses motion artifact interference by adaptive thresholds. Implemented in $0.18 ~\mu \text{m}$ CMOS process, the circuit only occupies an area of $0.122 mm^{2}$ and consumes $0.62 ~\mu \text{W}$ at a 1.2-V supply, of which AFE and HB detector consume 507 nW and 110 nW, respectively. Simulation results show that the gain and the CMRR of AFE range from 30&#x2013;45 dB and 65&#x2013;105 dB, respectively. The input-referred noise is 670 nVrms with a mid-band gain of 42 dB and a bandwidth ranging from 0.5 Hz to 1 kHz

Scientometric Research on Trend Analysis of Nano-Based Sustained Drug Release Systems for Wound Healing

Nanomaterials, such as the nanoparticle (NP), nanomicelle, nanoscaffold, and nano-hydrogel, have been researched as nanocarriers for drug delivery more and more recently. Nano-based drug sustained release systems (NDSRSs) have been used in many medical fields, especially wound healing. However, as we know, no scientometric analysis has been seen on applying NDSRSs in wound healing, which could be of great importance to the relevant researchers. This study collected publications from 1999 to 2022 related to NDSRSs in wound healing from the Web of Science Core Collection (WOSCC) database. We employed scientometric methods to comprehensively analyze the dataset from different perspectives using CiteSpace, VOSviewer, and Bibliometrix. The results indicated that China published the most significant number of documents in the last two decades, Islamic Azad Univ was the most productive institution, and Jayakumar, R was the most influential author. Regarding the analysis of keywords, trend topics indicate that “antibacterial”, “chitosan (CS)”, “scaffold”, “hydrogel”, “silver nanoparticle”, and “growth factors (GFs)” are the hot topics in recent years. We anticipate that our work will provide a comprehensive overview of research in this field and help scholars better understand the research hotspots and frontiers in this area, thus inspiring further explorations in the future

Deviant Peer Affiliation and Non-Suicidal Self-Injury among Chinese Adolescents: Depression as a Mediator and Sensation Seeking as a Moderator

Non-suicidal self-injury (NSSI) is an emerging health problem among adolescents. Although previous studies have shown that deviant peer affiliation is an important risk factor for this behavior, the reasons for this relationship are unclear. Based on the integrated theoretical model of the development and maintenance of NSSI and the social development model of delinquency prevention, this study tested whether depression mediated the relationship between deviant peer affiliation and NSSI and whether this mediating effect was moderated by sensation seeking. A sample of 854 Chinese adolescents (31.50% male; Mage = 16.35; SD = 1.15) anonymously completed questionnaires on the study variables. Results of regression-based analyses showed that depression mediated the association between deviant peer affiliation and NSSI, and this effect was stronger among adolescents who reported high sensation seeking. The results demonstrate the role of individual differences in the link between affiliation with deviant peers and NSSI, and have implications for preventing and treating this risky behavior

Does Self-Control Promote Prosocial Behavior? Evidence from a Longitudinal Tracking Study

Although numerous researches have shown that self-control is a significant promoter of prosocial behavior, the mechanism behind this relationship is still unclear. According to the organism–environment interaction model and self-control model, this study researched whether life satisfaction played a mediating role between self-control and adolescents’ prosocial behavior and if friendship quality played a moderating role between self-control and prosocial behavior. This study used a longitudinal tracking research (T1&T2; and the interval between T1&T2 is 6 months). A total of 1182 Chinese middle school students participated the survey. They were between 12 and 15 years old (average age: 14.16 years old, SD = 1.29). Results indicated that life satisfaction played a mediating role between self-control and adolescents’ prosocial behavior. Furthermore, this direct relationship in the link between self-control and prosocial behavior was significant when adolescents had a good-quality friendship. These results highlight that life satisfaction plays an important role in the relationship between self-control and prosocial behavior. The present study further determined that a high-quality friendship was an important factor that amplified this direct effect

Bioinspired Anti-digestive Hydrogels Selected by a Simulated Gut Microfluidic Chip for Closing Gastrointestinal Fistula

Summary: The anti-digestive features given to hydrogels can prolong their action time in gut environment; however, these types of hydrogels have rarely been reported. Inspired by indigestibility of dietary fibers, we introduced an injectable covalent hydrogel through photopolymerization of glycidyl methacrylate-modified xanthan. This newly synthesized hydrogel exhibited a specific concentration-dependent porosity, swelling ratio, and stiffness. The intestinal epithelial cells-6 could grow on the surface of the stiffer hydrogel, and achieved their gut barrier functions. A simulated gut microfluidic chip was manufactured to demonstrate the hydrogel's good performance of anti-digestion compared with the current product, fibrin sealant. Furthermore, calcium ions could induce the swelling-shrinking behavior of the hydrogel, which assisted in removing the hydrogels at the proper time so as to avoid the mismatch of hydrogel degradation and tissue regeneration. Therefore, this hydrogel is expected to be an outstanding gut repair material, especially for closing gastrointestinal fistula. : Surgery; Polymers; Biomaterials; Biomedical Materials Subject Areas: Surgery, Polymers, Biomaterials, Biomedical Material

Palladium(II)-Catalyzed Sequential C–H Arylation/Aerobic Oxidative C–H Amination: One-Pot Synthesis of Benzimidazole-Fused Phenanthridines from 2‑Arylbenzimidazoles and Aryl Halides

Starting from 2-arylbenzimidazoles and aryl halides, an efficient palladium-based catalytic method for the synthesis of benzimidazole-fused phenanthridines has been developed. This reaction sequence comprises intermolecular C–H arylation and intramolecular aerobic oxidative C–H amination, involving the rupture of two C–H bonds, one C–X bond, and one N–H bond in one pot. The Pd^II–Pd^IV–Pd^II and Pd^II–Pd⁰–Pd^II catalytic cycles work together under the reported conditions to generate phenanthridines with diverse substituents