Leaf-Encapsulated Vaccines: Agroinfiltration and Transient Expression of the Antigen Staphylococcal Endotoxin B in Radish Leaves.

Transgene introgression is a major concern associated with transgenic plant-based vaccines. Agroinfiltration can be used to selectively transform nonreproductive organs and avoid introgression. Here, we introduce a new vaccine modality in which Staphylococcal enterotoxin B (SEB) genes are agroinfiltrated into radishes (Raphanw sativus L.), resulting in transient expression and accumulation of SEB in planta. This approach can simultaneously express multiple antigens in a single leaf. Furthermore, the potential of high-throughput vaccine production was demonstrated by simultaneously agroinfiltrating multiple radish leaves using a multichannel pipette. The expression of SEB was detectable in two leaf cell types (epidermal and guard cells) in agroinfiltrated leaves. ICR mice intranasally immunized with homogenized leaves agroinfiltrated with SEB elicited detectable antibody to SEB and displayed protection against SEB-induced interferon-gamma (IFN-γ) production. The concept of encapsulating antigens in leaves rather than purifying them for immunization may facilitate rapid vaccine production during an epidemic disease

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)

A comprehensive review of circRNA: from purification and identification to disease marker potential

Circular RNA (circRNA) is an endogenous noncoding RNA with a covalently closed cyclic structure. Based on their components, circRNAs are divided into exonic circRNAs, intronic circRNAs, and exon-intron circRNAs. CircRNAs have well-conserved sequences and often have high stability due to their resistance to exonucleases. Depending on their sequence, circRNAs are involved in different biological functions, including microRNA sponge activity, modulation of alternative splicing or transcription, interaction with RNA-binding proteins, and rolling translation, and are a derivative of pseudogenes. CircRNAs are involved in the development of a variety of pathological conditions, such as cardiovascular diseases, diabetes, neurological diseases, and cancer. Emerging evidence has shown that circRNAs are likely to be new potential clinical diagnostic markers or treatments for many diseases. Here we describe circRNA research methods and biological functions, and discuss the potential relationship between circRNAs and disease progression

Clinical characteristics and lateralization of the horizontal semicircular canal light cupula

IntroductionPositional vertigo and nystagmus are the main symptoms and signs of dizziness, respectively. Despite the clinical utility of the supine roll test (SRT) and null point (NP) in diagnosing light cupula, a type of positional vertigo, there exists a notable gap in the literature concerning the comprehensive evaluation of lateralization values based on various nystagmus characteristics and the intensity of direction-changing positional nystagmus (DCPN) in the SRT, particularly in comparison to the NP. Additionally, limited data on abnormal canal paresis (CP) in light cupula patients underscores the need for further research with a larger patient population to elucidate this mechanism. This study aims to investigate the characteristics of positional nystagmus and lateralization of the horizontal semicircular canal (HSCC) light cupula, which is a type of positional vertigo and nystagmus that is poorly understood.MethodsEighty-five patients (17 males, 68 females; mean age, 60.9 years) with light cupula were reviewed. We summarized the characteristics of spontaneous nystagmus and positional nystagmus, including supine positioning nystagmus, bow nystagmus, and lean nystagmus. Then, the side of the NP was identified as the affected side, and the values of the fast phase direction of the spontaneous nystagmus, supine positioning nystagmus, bow nystagmus, and lean nystagmus, as well as the intensity of the DCPN in the SRT, were used to diagnose the affected sides. Caloric testing was also performed for some patients.ResultsLight cupula was observed in 5.7% of the patients with positional nystagmus. The frequencies of supine positioning nystagmus (88.2%), bow nystagmus (90.6%), and lean nystagmus (83.5%) were higher than spontaneous nystagmus (61.2%) (p < 0.001). The second NP (NP2) (92.9%) and third NP (NP3) (83.5%) were readily detected, affecting the left and right sides in 38 and 47 patients, respectively. Lateralization through the fast phase directions of bow nystagmus and lean nystagmus did not significantly differ from that of NP (all p > 0.05). However, the accuracy rate of lateralization through the sides with more vigorous DCPN in the SRT was 63.5%, significantly lower than through NP (p < 0.001). Particularly in patients with supine positioning nystagmus (n = 75), the rate was only 58.7% (p < 0.001). However, the rate was 100% in patients without supine positioning nystagmus (n = 10). Among the 70 patients who underwent caloric testing, 37 had abnormal CP, and the sides of the reduced caloric reaction were ipsilateral to the affected sides of the light cupula in 83.8% of the patients.ConclusionBesides utilizing the NP to determine the affected side, the fast phase direction of the bow nystagmus or lean nystagmus can also aid in identification. However, a simple comparison of the intensity of DCPN in SRT cannot provide accurate lateralization, especially in patients with supine positioning nystagmus. There is a high incidence of CP on the affected side of the light cupula

Leaf-Encapsulated Vaccines: Agroinfiltration and Transient Expression of the Antigen Staphylococcal Endotoxin

Transgene introgression is a major concern associated with transgenic plant-based vaccines. Agroinfiltration can be used to selectively transform nonreproductive organs and avoid introgression. Here, we introduce a new vaccine modality in which Staphylococcal enterotoxin B (SEB) genes are agroinfiltrated into radishes (Raphanw sativus L.), resulting in transient expression and accumulation of SEB in planta. This approach can simultaneously express multiple antigens in a single leaf. Furthermore, the potential of high-throughput vaccine production was demonstrated by simultaneously agroinfiltrating multiple radish leaves using a multichannel pipette. The expression of SEB was detectable in two leaf cell types (epidermal and guard cells) in agroinfiltrated leaves. ICR mice intranasally immunized with homogenized leaves agroinfiltrated with SEB elicited detectable antibody to SEB and displayed protection against SEB-induced interferon-gamma (IFN-γ) production. The concept of encapsulating antigens in leaves rather than purifying them for immunization may facilitate rapid vaccine production during an epidemic disease

piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity

Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has recently been recognized, studies on the role and functional mechanism of piRNAs in lung adenocarcinoma (LUAD) development and progression are limited. In this study, we identified 10 differently expressed piRNAs in LUAD tissues compared to normal tissues, among which, piR-hsa-211106 expression levels were downregulated in LUAD tissues and cell lines. Furthermore, the effects of piR-hsa-211106 on the malignant phenotypes and chemosensitivity of LUAD cells were detected by gain- and loss-of-function analyses in vitro and in vivo, which showed that piR-hsa-211106 inhibited LUAD cell proliferation, tumor growth, and migration, but promoted apoptosis. Moreover, our finding indicated that piR-hsa-211106 is a potential therapeutic target that synergistically imparts anticancer effects with a chemotherapeutic agent for LUAD-cisplatin. Further mechanistic investigation indicated that piR-hsa-211106 could bind to pyruvate carboxylase (PC) by RNA pull down and RNA immunoprecipitation assays and inhibited PC mRNA and protein expression. Our study demonstrates that piR-hsa-211106 inhibits LUAD progression by hindering the expression and function of PC and enhances chemotherapy sensitivity, suggesting that piR-hsa-211106 is a novel diagnostic and therapeutic target for LUAD

CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease

Complement receptor of immunoglobulin superfamily (CRIg) is expressed on liver macrophages and directly binds complement component C3b or Gram-positive bacteria to mediate phagocytosis. CRIg plays important roles in several immune-mediated diseases, but it is not clear how its pathogen recognition and phagocytic functions maintain homeostasis and prevent disease. We previously associated cytolysin-positive Enterococcus faecalis with severity of alcohol-related liver disease. Here, we demonstrate that CRIg is reduced in liver tissues from patients with alcohol-related liver disease. CRIg-deficient mice developed more severe ethanol-induced liver disease than wild-type mice; disease severity was reduced with loss of toll-like receptor 2. CRIg-deficient mice were less efficient than wild-type mice at clearing Gram-positive bacteria such as Enterococcus faecalis that had translocated from gut to liver. Administration of the soluble extracellular domain CRIg–Ig protein protected mice from ethanol-induced steatohepatitis. Our findings indicate that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of liver disease

The Internal and External Competition and System Changes Under the Background of Modern Chinese Party Politics

Since modern times, Chinese intellectual Liang Qichao and others have imitated the Western political system and vigorously advocated and implemented party politics in order to promote the historical process of political democratization and diplomacy in modern China. As China was in the current situation of internal and external troubles, various political parties have advocated national diplomacy, and have written national diplomacy policies into the party constitution or political program as a guideline for the fierce competition on the domestic and foreign affairs arena. Due to the frequent divisions and reorganizations between political parties, the political programs and political ideas of the political parties were confused with each other, and the responsibilities and obligations of party members were blurred, resulting in the increasingly complex internal and external competition of modern Chinese political parties, which reflected the modern Chinese political system Major changes

mm Wave Near Field Spot Focus Technique in Free Space Dielectric Properties Evaluation Method

Radomes were invented to protect sensitive antenna systems from the disturbing environment. Estimation of their permittivity is a vital step for their design. This project studies the free- space method to measure the permittivity of radome materials. The free space method has the advantages of non-contacting and free-of-reshaping, which are suitable for sheet-shape samples. In this method, the sample is placed between two antennas, and the permitivity of the material is determined based on the S-parameters between the two antennas. To avoid the influence of energy diffraction at the edges of samples, a near field focus(NFF) antenna is used. NFF antennas have their focal point in the near field. Consequently, the energy diffraction at the edges is reduced if the sample is placed at the focal point of the NFF antenna. The measurement results are processed with the genetic algorithm. This method starts from a group of assumption values of permittivity. An optimal value is obtained after multiple iterations. Compared with the results from a cavity resonant method provided in the datasheet of the materials, the free space setup in this thesis measurement provides an average 2.80% error in permittivity, and an average 34.14% error in loss tangent. Therefore, the genetic algorithm is suitable for this free space setup. The error of this thesis measurement is affected by several factors, such as thickness value error and inaccurate operation. Radom används för att skydda känsliga antennsystem från omgivningen. Det är viktigt att estimera permittiviteten av radom innan de designas. Med korrekt permittivitet kan radomets inverkan på systemet räknas ut. I det här projektet används en fri-rymdsmetod för att mäta permittivitet. Fri-rymdsmetoden har fördelarna av att vara kontaktfri och icke-invasiv, vilket gör den lämplig för permittivitetmätning av materialskivor. Med den här metoden placeras en materialskiva mellan två antenner. Permittiviteten kan beräknas från S-parametrarna mellan antennerna. För att undvika diffraktion från kanten av materialskivan används närfältsfokuserade (NFF) antenner i fri-rymdsmetoden. NFF antenner har en fokalpunkt i närfältet. Kantdiffraktionen minskas om materialskivan placeras i fokalpunkten av NFF antennen. Mätningarna efterbehandlas med en genetisk algoritm (GA). Denna metod gissar värden på permittiviteten. Ett optimalt värde räknas fram iterativt. Jämfört med specificerad permittivitet från tillverkaren skiljer sig fri-rymdsmätningarna i denna avhandling i medeltal 2.8% i realdelen för den relativa permittiviteten och 34.14% i förlusttangent. Felet i mätningen påverkas av flera faktorer, som fel i mätningen av materialskivans tjocklek och fel i mätuppställningen