After millions of years of coevolution, symbiotic microbiota has become an integral part of the host and plays an important role in host immunity, metabolism, and health. Vaccination, as an effective ...means of preventing infectious diseases, has been playing a vital role in the prevention and control of human and animal diseases for decades. However, so far, minimal is known about the effect of vaccination on fish symbiotic microbiota, especially mucosal microbiota, and its correlation with intestinal metabolism remains unclear.
Here we reported the effect of an inactivated bivalent Aeromonas hydrophila/Aeromonas veronii vaccine on the symbiotic microbiota and its correlation with the intestinal metabolism of farmed adult Nile tilapia (Oreochromis niloticus) by 16S rRNA gene high-throughput sequencing and gas chromatography-mass spectrometry metabolomics.
Results showed that vaccination significantly changed the structure, composition, and predictive function of intestinal mucosal microbiota but did not significantly affect the symbiotic microbiota of other sites including gill mucosae, stomach contents, and stomach mucosae. Moreover, vaccination significantly reduced the relative abundance values of potential opportunistic pathogens such as Aeromonas, Escherichia-Shigella, and Acinetobacter in intestinal mucosae. Combined with the enhancement of immune function after vaccination, inactivated bivalent Aeromonas vaccination had a protective effect against the intestinal pathogen infection of tilapia. In addition, the metabolite differential analysis showed that vaccination significantly increased the concentrations of carbohydrate-related metabolites such as lactic acid, succinic acid, and gluconic acid but significantly decreased the concentrations of multiple lipid-related metabolites in tilapia intestines. Vaccination affected the intestinal metabolism of tilapia, which was further verified by the predictive function of intestinal microbiota. Furthermore, the correlation analyses showed that most of the intestinal differential microorganisms were significantly correlated with intestinal differential metabolites after vaccination, confirming that the effect of vaccination on intestinal metabolism was closely related to the intestinal microbiota.
In conclusion, this paper revealed the microbial and metabolic responses induced by inactivated vaccination, suggesting that intestinal microbiota might mediate the effect of vaccination on the intestinal metabolism of tilapia. It expanded the novel understanding of vaccine protective mechanisms from microbial and metabolic perspectives, providing important implications for the potential influence of vaccination on human intestinal microbiota and metabolism. Video Abstract.
•The mPEG-TK-PCL in NQNPs responded to ROS, enhancing controlled release of quercetin;•Neutrophil membrane conferred NQNPs with targeted delivery capability to lesion area;•NQNPs have synergistic ...effects of their compositions on repolarizing microglia in SCI.
Secondary neuroinflammation caused by proinflammatory microglia exacerbates the disability of patients with spinal cord injury (SCI), while low drug delivery efficiency reduces the therapeutic effect of conventional drugs on promoting functional recovery. Nowadays, resorting to nanocomposites has been regarded as a promising approach to overcome such an obstacle. Herein, neutrophil membrane-coated quercetin-loaded nanoparticles (denoted NQNPs) were developed to improve drug delivery efficiency and repolarize microglia thereby inhibiting secondary neuroinflammation in SCI. Quercetin-loaded nanoparticles (QNPs), which have the capacity to reprogram proinflammatory microglia toward anti-inflammatory microglia, act as the inner core of NQNPs. The neutrophil membrane was further coated onto the inner core for targeted drug delivery and co-neutralizing inflammatory factors. In vitro and in vivo studies demonstrated that NQNPs could controllably release quercetin under the reactive oxygen species (ROS) abundant environment, reprogram microglia polarization toward M2 phenotype via nuclear factor kappa-B (NK-κB) pathway, thereby inhibiting excessive neuroinflammation, increasing the density and functional status of neurons, and finally promoting motor recovery of SCI with outstanding biocompatibility. We believe that the current research brings a novel strategy and sheds new light on the treatment of SCI.
Somatic embryogenesis (SE) is an efficient tool for the propagation of plant species and also, a useful model for studying the regulatory networks in embryo development. However, the regulatory ...networks underlying the transition from nonembryogenic callus to somatic embryos during SE remain poorly understood. Here, we describe an upland cotton (Gossypium hirsutum)CASEIN KINASE Igene,GhCKI, which is a unique key regulatory factor that strongly affects SE. OverexpressingGhCKIhalted the formation of embryoids and plant regeneration because of a block in the transition from nonembryogenic callus to somatic embryos. In contrast, defectiveGhCKIin plants facilitated SE. To better understand the mechanism by whichGhCKIregulates SE, the regulatory network was analyzed. A direct upstream negative regulator protein, cotton LEAFY COTYLEDON1, was identified to be targeted to a cis-element, CTTTTC, in the promoter ofGhCKI. Moreover, GhCKI interacted with and phosphorylated cotton CINCINNATA like TEOSINTE BRANCHED1-CYCLOIDEA-PCF transcription factor15 by coordinately regulating the expression of cottonPHYTOCHROME INTERACTING FACTOR4, finally disrupting auxin homeostasis, which led to increased cell proliferation and aborted somatic embryo formation inGhCKI-overexpressing somatic cells. Our results show a complex process of SE that is negatively regulated byGhCKIthrough a complex regulatory network.
Objective:
Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. Stroke-associated acute symptomatic seizures are an important risk factor: 20.8–34.3% of these patients ...will go on to develop PSE. Identifying these “high risk” individuals may result in earlier PSE diagnosis, treatment, and avoidance of seizure-related morbidity. This study was to identify predictors of PSE development in patients with stroke-associated acute symptomatic seizures.
Participants and Methods:
This was a retrospective cohort study of 167 patients with stroke-associated acute symptomatic seizures admitted to the Neurology Department of a tertiary Hospital of China, from 1 May 2006 to 30 January 2020. Both those with primary ischemic stroke and intracerebral hemorrhage were included in the study. Patient demographics, medical history, stroke-associated, and seizure-related variables were evaluated with univariable analysis and multivariable Cox regression analysis. PSE was defined as unprovoked seizures occurring > 7 days post-stroke. Data points were extracted from medical records and supplemented by tele-interview.
Results:
Of the 167 patients with stroke-associated acute symptomatic seizures, 49 (29.3%) developed PSE. NIHSS score > 14 hazard ratio (HR) 2.98, 95% CI 1.57–5.67, longer interval from stroke to acute symptomatic seizures (days 4–7 post-stroke) (HR 2.51, 95% CI 1.37–4.59) and multiple acute symptomatic seizures (HR 5.08, 95% CI 2.58–9.99) were independently associated with PSE development. This association remained in the sub-analysis within the ischemic stroke cohort. In the sub-analysis of the hemorrhagic stroke cohort, multilobar involvement (HR 4.80, 95% CI 1.49–15.39) was also independently associated with development of PSE. Further, we developed a nomogram to predict individual risk of developing PSE following stroke-associated acute symptomatic seizures. The nomogram showed a C-index of 0.73.
Conclusion:
More severe neurofunctional deficits (NIHSS score > 14), longer interval from stroke to acute symptomatic seizures (days 4–7 post-stroke), and multiple acute symptomatic seizures were independently associated with development of PSE in patients with stroke-associated acute symptomatic seizures. This knowledge may increase clinical vigilance for development of PSE, facilitating rapid diagnosis and treatment initiation, and subsequently reduce seizure-related morbidity.
To determine whether fibroblast growth factor receptor (FGFR)-targeting drug could impact human meibomian gland.
We followed up with three patients who were using pemigatinib for 4 to 10 weeks. The ...patients were evaluated for their ocular surface disease index, best-corrected visual acuity, Schirmer test, cornea staining, meibum expressibility score, tear meniscus height, noninvasive tear film breakup time, and meibomian gland area. The distribution of the FGFR family, FGF7, and FGF10 were evaluated by immunofluorescence staining and Western blot in fresh tarsal tissues from deidentified patients who underwent lid plastic surgeries.
All patients developed apparent meibomian gland atrophy, shortening and narrowing of ducts, and significantly increased meibum expressibility and decreased noninvasive tear film breakup time within 5 to 8 weeks. Laboratory evaluations confirmed that human meibomian gland expresses abundant fibroblast growth factor receptors.
These findings indicate that meibomian gland is a target tissue of FGFR inhibitors, and patients who use these drugs may develop meibomian gland dysfunction.
To determine whether contrast-enhanced CT radiomics features can preoperatively predict lymphovascular invasion (LVI) and perineural invasion (PNI) in gastric cancer (GC).
A total of 148 patients ...were included in the LVI group, and 143 patients were included in the PNI group. Three predictive models were constructed, including clinical, radiomics, and combined models. A nomogram was developed with clinical risk factors to predict LVI and PNI status. The predictive performance of the three models was mainly evaluated using the mean area under the curve (AUC). The performance of three predictive models was assessed concerning calibration and clinical usefulness.
In the LVI group, the predictive power of the combined model (AUC=0.871, 0.822) outperformed the clinical model (AUC=0.792, 0.728) and the radiomics model (AUC=0.792, 0.728) in both the training and testing cohorts. In the PNI group, the combined model (AUC=0.834, 0.828) also had better predictive power than the clinical model (AUC=0.764, 0.632) and the radiomics model (AUC=0.764, 0.632) in both the training and testing cohorts. The combined models also showed good calibration and clinical usefulness for LVI and PNI prediction.
CECT-based radiomics analysis might serve as a non-invasive method to predict LVI and PNI status in GC.
Abstract The pathogenesis of systemic sclerosis (SSc) is still unclear. CD70, a B cell costimulatory molecule that interacts with CD27 during B–T cell contact, is overexpressed due to demethylation ...of its promoter regulatory elements in CD4+ T cells from patients with the following autoimmune diseases, namely systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE) and primary Sjögren's syndrome (pSS). However, as an autoimmune disease, it is unknown whether aberrant expression and methylation of CD70 occur in SSc CD4+ T cells. We aimed to investigate whether the aberrant expression and methylation status of CD70 occur in CD4+ T cells from patients with SSc. We found that the CD70 is overexpressed and the CD70 promoter region is demethylated in SSc CD4+ T cells. These findings suggest that demethylation of CD70 promoter region contributes to the overexpression of CD70 in CD4+ T cells and may contribute to autoimmune response in SSc.
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•A triangle-structure triple-frequency transducer which can work at three different frequencies was developed.•Static and transient FEM models were established to assist the design ...procedure. Simulation results measurement results suggested that the three different frequency elements have excellent directivity, and the acoustic field interference between elements is small.•The ultrasound imaging results proved that the fused image can maintain the imaging depth and image resolution at the same time.
In endoscopic ultrasound imaging, it is still challenging to acquire images with high resolution and deep imaging depth at the same time, this contradiction limits the performance of the endoscopic ultrasonic imaging system. Multi-frequency imaging and corresponding image fusion technique have the potential to reduce this contradiction. In this work, a triangle-structure triple-frequency transducer that can work at three different frequencies is presented, its outer diameter is less than 1.5mm. Static and transient models are built to assist its design. Simulation results and sound field measurement results suggest that the three different frequency elements have excellent directivity, and the acoustic field interference between elements is small. Pulse-echo results show that the center frequencies of the elements are 13.17MHz, 20.3MHz, and 30.85MHz, respectively. The ultrasound imaging results of phantom prove that the triple-frequency fusing image is better than single-frequency imaging, and the fused image can maintain the imaging depth and image resolution at the same time. The results certify the feasibility of triple-Frequency transducer in endoscopic imaging and show great potential in the diagnosis of gastrointestinal diseases.
The scientific issues of the instable decomposition and manufacturing size limitation of zirconium tungstate ceramic (ZrW2O8) fabricated by the conventional high-temperature sintering process ...(usually T ≥ 1105 °C) are desiderated to be solved. Here, an energy-efficient cold sintering process (CSP, 190 °C, 1–240 min, and 350 MPa) was employed to achieve the dense fabrication of ZrW2O8 (∼94.3% relative density and with up to 95.9% relative density after annealing treatment) with negative thermal expansion (NTE). Utilizing the CSP, the Vickers hardness is increased to 2.62 GPa; the phase composition is determined as the ZrW2O8 phase without any decomposition. The as-fabricated ZrW2O8 ceramic reveals an excellent NTE performance over the temperature range of 0–500 °C. In order to demonstrate the feasibility of the low energy consumption CSP in the fabrication of the ZrW2O8 ceramic, the evolution of densification, phase composition, and microstructure are systematically analyzed, and the fundamental densification mechanism of the CSP approach is elucidated by the theory of powder sintering. This research not only effectively solves the decomposition and resultant size limitation difficulties but also establishes an energy-efficient pathway and sustainable prospects for the fabrication of more metastable-material systems.
To improve the antimicrobial properties of chitosan films, cinnamon essential oil (CEO) nanoemulsion (1% and 3% v/v CEO) stabilized by ethyl-Nα-lauroyl-l-arginate hydrochloride (LAE) alone or ...co-stabilized by LAE and hydroxypropyl-β-cyclodextrin (HPCD) were incorporated into chitosan matrix. The micromorphology, physical and antimicrobial properties of the composite films were compared. The dense structure of the CEO nanoemulsion co-stabilized by LAE and HPCD reduced the water vapor permeability and water content. The incorporation of the CEO nanoemulsion co-stabilized by LAE and HPCD, reduced the adverse effects of CEO on the mechanical properties and microstructure of the film, and even slightly increased the tensile strength. In addition, the antimicrobial properties of chitosan films were enhanced due to the encapsulation and emulsification effect of HPCD and LAE on CEO. This work indicated that the prepared chitosan based edible films had the potential to be used in the field of food packaging to improve food safety.
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