Aims
Purification of porcine circovirus type 2 (PCV2) using Gram‐positive enhancer matrix (GEM) surface display technology and immunogenicity evaluation of the purified antigen.
Methods and Results
A ...recombinant bifunctional protein containing a protein anchor domain and a ‘virus anchor’ domain was designed as a protein linker (PL) between PCV2 and GEM particles. By incubating with PL and GEM particles sequentially, PCV2 could be purified and enriched through a simple centrifugation process with GEM surface display technology. Our data showed that one unit (2·5 × 109 particles) of GEM particles with 80 μg PL could purify 100 ml of PCV2‐containing culture supernatant (viral titre: 106·5 TCID50 per ml−1) with a recovery rate up to 99·6%. The impurity removal efficiency of this method, calculated according to decreased total protein content during purification, was approximately 98%. Furthermore, in vivo experimentation showed that piglets immunized with purified PCV2 could elicit strong immune responses to prevent against PCV2 infection.
Conclusion
Porcine circovirus type 2 could be efficiently purified and enriched with GEM display technology via a crucial PL, and the purified PCV2 could elicit effective immune responses against PCV2 infection.
Significance and Impact of the Study
The GEM‐based purification method established here is cost‐efficient and high‐throughput, and may represent a promising large‐scale purification method for PCV2 vaccine production.
To construct a novel nomogram by integrating computed tomography perfusion (CTP) and clinical parameters for individualised prediction of haemorrhagic transformation (HT) in intravenous thrombolysis ...(IVT)-treated acute ischaemic stroke (AIS) patients.
Anterior circulation AIS patients who underwent IVT at a single centre from January 2018 to June 2020 were reviewed retrospectively. The CTP parameters of two regions of interest (ROI), the entire perfusion lesion areas, and the infract core areas, were assessed. HT was documented by follow-up CT 24 ± 2 h after IVT. Multivariable logistic regression was conducted by including clinical variables and CTP parameters to identify the independent predictors of HT. A nomogram was developed based on the independent predictors. The discriminative value and calibration of the nomogram were tested by concordance indexes (C-indexes) and calibration plots. Internal validation was performed using fivefold cross-validation.
The nomogram was generated using the complete data from 341 patients. Seven variables were included in the final nomogram, including: the relative cerebral blood volume (rCBV), permeability surface (PS), and relative PS (rPS) in infract core areas, the relative time to maximum (rTmax) and rPS in entire perfusion lesion areas, the National Institutes of Health Stroke Scale (NIHSS), and atrial fibrillation (AF). The C-indexes were 0.815 and 0.817 for the nomogram and internal validation. The calibration plots showed excellent agreement.
This is the first study establishing a nomogram based on CTP and clinical parameters to predict HT after stroke thrombolysis.
•CTP could predict the risk of cerebral hemorrhage after stroke thrombolysis.•The first attempt to develop a nomogram combines CTP and clinical risk factors.•The model can quantify the risk of hemorrhagic transformation after thrombolysis.
The aim of this study was to characterize the genetic diversity of domestic goat in China. For this purpose, we determined the sequence of the mitochondrial DNA (mtDNA) control region in 72 ...individuals of the Yangtze River delta white goat, and reanalysed 723 published samples from 31 breeds/populations across China. All goat haplotypes were classified into four haplogroups (A-D) previously described. The phylogenetic pattern that emerged from the mtDNA control region sequence was confirmed by the analysis of the entire cytochrome b sequence of eight goats representative of the four haplogroups. It appeared that in Chinese domestic goat, haplogroups A and B were dominant and distributed in nearly all breeds/populations, while haplogroups C and D were only found in seven breeds/populations. Four breeds/populations contained all four haplogroups. When grouping the breeds/populations into five geographic groups based on their geographic distributions and ecological conditions, the southern pasturing area had the highest diversity whereas the northern farming area had the lowest diversity. 84.29% and 11.37% of the genetic variation were distributed within breeds and among breeds within the ecologically geographical areas, respectively; only 4% of genetic variation was observed among the five geographic areas. We speculate that the traditional seasonal pastoralism, the annual long-distance migrations that occurred in the past, and the commercial trade would account for the observed pattern by having favoured gene flows.
Fibroblast growth factor (FGF) signaling has been implicated in the regulation of osteogenesis in both intramembranous and endochondral ossifications. In the developing palate, the anterior bony ...palate forms by direct differentiation of cranial neural crest (CNC)–derived mesenchymal cells, but the signals that regulate the osteogenic cell fate in the developing palate remain unclear. In the present study, we investigated the potential role of FGF signaling in osteogenic fate determination of the palatal mesenchymal cells. We showed that locally activated FGF8 signaling in the anterior palate using a Shox2Cre knock-in allele and an R26RFgf8 allele leads to a unique palatal defect: a complete loss of the palatine process of the maxilla as well as formation of ectopic cartilaginous tissues in the anterior palate. This aberrant developmental process was accompanied by a significantly elevated level of cell proliferation, which contributes to an abnormally thickened palatal tissue, where the palatine process of the maxilla would normally form, and by a complete inhibition of Osterix expression, which accounts for the lack of bone formation. The coexpression of Runx2 initially with Sox9 and subsequently with Col II in the ectopic cartilaginous tissues indicates a conversion of osteogenic fate to a chondrogenic one. Consistent with the unique palatal phenotype, RNA-Sequencing analysis revealed that the augmented FGF8 signaling downregulated genes involved in ossification, biomineral tissue development, and bone mineralization but upregulated genes involved in cell proliferation, cartilage development, and cell fate commitment, which was further supported by quantitative real-time reverse transcription polymerase chain reaction validation of selected genes. Our results demonstrate that FGF8 signaling functions as a negative regulator of osteogenic fate and is sufficient to convert a subset of CNC cell-derived mesenchymal cells into cartilage in the anterior hard palate, which will have implications in future directed differentiation of CNC-derived precursor cells for clinical application.
Based on Dorfmann and Ogden's nonlinear theory of electroelasticity and the associated linear incremental theory, the non-axisymmetric wave propagation in an infinite incompressible soft ...electroactive hollow cylinder under biasing fields is investigated. The biasing fields are uniform, including an axial pre-stretch and a radial stretch in the plane perpendicular to the axis of the cylinder as well as an axial electric displacement. Such biasing fields make the originally isotropic electroactive material behave during its incremental motion like a conventional transversely isotropic piezoelectric material, hence greatly facilitating the following analysis. The three-dimensional equations of wave motion in cylindrical coordinates are derived and exactly solved by introducing three displacement functions. The exact solution is expressed in terms of Bessel functions, and explicit frequency equations are presented in different cases. For a prototype nonlinear model of electroactive material, numerical results are given and discussed. It is found that the initial biasing fields as well as the geometrical parameters of the hollow cylinder have significant influences on the wave propagation characteristics.
To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.
The clinical data of children with septic ...shock in children's PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by
-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed b
The inter-regional power trade inevitably leads to transmissions of carbon and air pollutant emissions (CAEs), which is unfair for energy-dependent regions. Therefore, this study develops an ...indeterministic fractional two-stage inter-regional energy system (IFTS-IRES) optimization model for planning the energy system in Shanxi Province. The developed model can deal with uncertain parameters expressed as interval values and modify the pre-made policies, which could be an effective method to solve multi-objective optimization problems. Multiple mitigation-policy scenarios are analyzed based on imposing CAEs compensation taxes on electricity consumption regions (ECRs), adjusting renewable energy power targets, and upgrading traditional power plants with carbon capture and storage technology (CCS). The comparison results show that IFTS-IRES is able to detailly reflect the tradeoff between economic development and environmental protection, and the maximal amount of CO2 mitigation will be 1.80, 3.34 K tonne/million RMB. By 2040, wind and biomass would account for 24.55%, 29.02% and 33.38%, 35.48% of the power generation capacity, and renewable energy will gradually substitute traditional fossil fuels. Therefore, Shanxi's power system should develop renewable energy rather than upgrade with CCS to realize the goal of carbon peak and carbon neutrality. In addition, the future electricity export will keep increasing, among which the share of wind and biomass power will be 50.86%, 51.69% and 21.25%, 21.78%. It is suggested that the mitigation responsibility of inter-regional CAEs should be shouldered by ECRs through paying for compensation taxes. These findings could help decision makers analyze economic and environmental effects with multiple objectives under uncertainties. It provides new insight into regulating the mitigation responsibility existing in inter-regional power transmission grid. The developed model is expected to be applied to other regions heavily dependent on energy resources.
•An indeterministic fractional two-stage energy system optimization model is developed.•Inter-regional energy trades features are reflected.•Dual objectives and multiple uncertainties are examined.•Carbon/air pollutant emissions compensation taxes and related policies are investigated.•The tradeoff between system sustainability and economic benefit is analyzed.
In quiescent cells, mitochondria are the primary source of reactive oxygen species (ROS), which are generated by leakiness of the electron transport chain (ETC). High levels of ROS can trigger cell ...death, whereas lower levels drive diverse and important cellular functions. We show here by employing a newly developed mitochondrial matrix-targeted superoxide indicator, that individual mitochondria undergo spontaneous bursts of superoxide generation, termed “superoxide flashes.” Superoxide flashes occur randomly in space and time, exhibit all-or-none properties, and provide a vital source of superoxide production across many different cell types. Individual flashes are triggered by transient openings of the mitochondrial permeability transition pore stimulating superoxide production by the ETC. Furthermore, we observe a flurry of superoxide flash activity during reoxygenation of cardiomyocytes after hypoxia, which is inhibited by the cardioprotective compound adenosine. We propose that superoxide flashes could serve as a valuable biomarker for a wide variety of oxidative stress-related diseases.
We investigated phase constitutions, ferroelectric, magnetic, and nanomechanical characteristics of BiFeO3 films with Dy substitution. Bi1−xDyxFeO3 (x = 0.00–0.15) thin film were prepared on the Pt ...buffered glass substrates by pulsed laser deposition. BDFO films with x = 0.00–0.15 were confirmed to mainly consist of the perovskite phase. The structure is transformed from rhombohedral for x = 0.00 to pseudo-cubic for x = 0.05, and an additional phase, orthorhombic, is coexisted for x = 0.10 and 0.15. The studied BDFO polycrystalline films exhibit the desired ferroelectric and ferromagnetic properties at the same time. The remanent polarization (2Pr) of 165.7 μC/cm2 and electrical coercive field (Ec) of 337.5 kV/cm are obtained for BDFO films at x = 0.05. Leakage mechanisms in BDFO films with various contents x are also discussed. Besides, the saturation magnetization (Ms) of 2.1–26.8 emu/cm3 and coercivity (Hc) of 133–522 Oe are found. The increased Ms with Dy content x is related to the magnetic moment of the doped Dy3+ ion in addition to the suppressed spiral spin configuration. Furthermore, the hardness of 5.3–8.0 GPa for the BDFO films is found. The relationship between the hardness and grain size well agrees with the impeded propagation of dislocation by grain boundary mainly dominates the hardness. The result of this work indicates that the radius and magnetic moment of the Dy3+ ions plays a critical role in the structural evolution, refined microstructure, and therefore enhanced multiferroic and nanomechanical properties for Dy substituted BiFeO3 polycrystalline films.
•Simultaneous improvement in ferroelectric and ferromagnetic properties is found in Bi1−xDyxFeO3 films.•Good (110) texture, promoted crystallinity, and modified microstructure make BDFO have high ferroelectric properties.•Leakage mechanisms in BDFO films with x are also discussed.•The enhanced magnetic properties relates to the suppression of the spiral spin configuration and large magnetic moment of Dy3+ ion.•BDFO polycrystalline film is a high potential multiferroic material for advanced applications.
The inflammasome activates caspase-1 and the release of interleukin-1β (IL-1β) and IL-18, and several inflammasomes protect against intestinal inflammation and colitis-associated colon cancer (CAC) ...in animal models. The absent in melanoma 2 (AIM2) inflammasome is activated by double-stranded DNA, and AIM2 expression is reduced in several types of cancer, but the mechanism by which AIM2 restricts tumor growth remains unclear. We found that Aim2-deficient mice had greater tumor load than Asc-deficient mice in the azoxymethane/dextran sodium sulfate (AOM/DSS) model of colorectal cancer. Tumor burden was also higher in Aim2(-/-)/Apc(Min/+) than in APC(Min/+) mice. The effects of AIM2 on CAC were independent of inflammasome activation and IL-1β and were primarily mediated by a non-bone marrow source of AIM2. In resting cells, AIM2 physically interacted with and limited activation of DNA-dependent protein kinase (DNA-PK), a PI3K-related family member that promotes Akt phosphorylation, whereas loss of AIM2 promoted DNA-PK-mediated Akt activation. AIM2 reduced Akt activation and tumor burden in colorectal cancer models, while an Akt inhibitor reduced tumor load in Aim2(-/-) mice. These findings suggest that Akt inhibitors could be used to treat AIM2-deficient human cancers.
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