Background. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV) with an average fatality rate of 12%. The clinical factors for death ...in SFTS patients remain unclear. Methods. Clinical features and laboratory parameters were dynamically collected for 11 fatal and 48 non-fatal SFTS cases. Univariate logistic regression was used to evaluate the risk factors associated with death. Results. Dynamic tracking of laboratory parameters revealed that during the initial fever stage, the viral load was comparable for the patients who survived as well as the ones that died. Then in the second stage when multi-organ dysfunction occurred, from 7-13 days after disease onset, the viral load decreased in survivors but it remained high in the patients that died. The key risk factors that contributed to patient death were elevated serum aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase fraction, as well as the appearance of CNS (central nervous system) symptoms, hemorrhagic manifestation, disseminated intravascular coagulation, and multi-organ failure. All clinical markers reverted to normal in the convalescent stage for SFTS patients who survived. Conclusions. We identified a period of 7-13 days after the onset of illness as the critical stage in SFTS progression. A sustained serum viral load may indicate that disease conditions will worsen and lead to death.
Select laser melting (SLM) is one of the practical metal additive manufacturing processes to fabricate complex structures. The inhomogeneous microstructure and high residual stress are typically ...resulted from a non-uniform melting and rapid solidification during a SLM process, which has the significant impact on part dimensional instability, corrosion resistance, and mechanical properties. The bulk of current research is limited to the general characterization of grain size, texture, and mechanical properties. However, grain boundary character distribution (GBCD) and its relationship with texture are yet to be understood. This study has shown that the preferred 〈110〉 along building direction and 〈100〉 along laser scanning direction were produced. The high density of low angle grain boundary (LAGB) can be an indicator of residual stress levels in the as-SLMed samples. The newly-developed ∑3, ∑9 and ∑27 grain boundaries were heavily populated, and the cluster of grains interfaced by ∑3n (n = 0, 1, 2…) was introduced at the expense of LAGB only at high recrystallization annealing (1150°C or over). The research results suggest that GBCD optimization be possible in the SLMed Inconel 625 alloy via suitable post annealing, which allows improving intergranular corrosion resistance and enhancing mechanical properties.
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•⟨110⟩ texture along layer build direction was generated in as-SLMed Inconel 625.•The stress relief process dominates texture and GBCD evolution.•SLMed IN 625 alloy can be GBEed via suitable post annealing.
Abstract Background Little is known regarding the association between clonal hematopoiesis of indeterminate potential (CHIP) and risk of neurodegenerative diseases. Objective To estimate the risk of ...neurodegenerative diseases among individuals with CHIP. Methods We conducted a community‐based cohort study based on UK Biobank and used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of any neurodegenerative disease, subtypes of neurodegenerative diseases (including primary neurodegenerative diseases, vascular neurodegenerative diseases, and other neurodegenerative diseases), and specific diagnoses of neurodegenerative diseases (i.e., amyotrophic lateral sclerosis ALS, Alzheimer's disease AD, and Parkinson's disease PD) associated with CHIP. Results We identified 14,440 individuals with CHIP and 450,907 individuals without CHIP. Individuals with CHIP had an increased risk of any neurodegenerative disease (HR 1.10, 95% CI: 1.01–1.19). We also observed a statistically significantly increased risk for vascular neurodegenerative diseases (HR 1.31, 95% CI 1.05–1.63) and ALS (HR 1.50, 95% CI 1.05–2.15). An increased risk was also noted for other neurodegenerative diseases (HR 1.13, 95% CI 0.97–1.32), although not statistically significant. Null association was noted for primary neurodegenerative diseases (HR 1.06, 95% CI 0.96–1.17), AD (HR 1.04, 95% CI 0.88–1.23), and PD (HR 1.02, 95% CI 0.86–1.21). The risk increase in any neurodegenerative disease was mainly observed for DNMT3A ‐mutant CHIP, ASXL1 ‐mutant CHIP, or SRSF2 ‐mutant CHIP. Conclusion Individuals with CHIP were at an increased risk of neurodegenerative diseases, primarily vascular neurodegenerative diseases and ALS, but potentially also other neurodegenerative diseases. These findings suggest potential shared mechanisms between CHIP and neurodegenerative diseases.
The accuracy of preoperative blood oxygen level-dependent fMRI remains controversial. This study assessed the association between the anatomic location of a tumor and the accuracy of fMRI-based motor ...function mapping in diffuse lower-grade gliomas.
Thirty-five patients with lower-grade gliomas involving motor areas underwent preoperative blood oxygen level-dependent fMRI scans with grasping tasks and received intraoperative direct cortical stimulation. Patients were classified into an overlapping group and a nonoverlapping group, depending on the extent to which blood oxygen level-dependent fMRI and direct cortical stimulation results concurred. Tumor location was quantitatively measured, including the shortest distance from the tumor to the hand knob and the deviation distance of the midpoint of the hand knob in the lesion hemisphere relative to the midline compared with the normal contralateral hemisphere.
A 4-mm shortest distance from the tumor to the hand knob value was identified as optimal for differentiating the overlapping and nonoverlapping group with the receiver operating characteristic curve (sensitivity, 84.6%; specificity, 77.8%). The shortest distances from the tumor to the hand knob of ≤4 mm were associated with inaccurate fMRI-based localizations of the hand motor cortex. The shortest distances from the tumor to the hand knob were larger (
= .002), and the deviation distances for the midpoint of the hand knob in the lesion hemisphere were smaller (
= .003) in the overlapping group than in the nonoverlapping group.
This study suggests that the shortest distance from the tumor to the hand knob and the deviation distance for the midpoint of the hand knob on the lesion hemisphere are predictive of the accuracy of blood oxygen level-dependent fMRI results. Smaller shortest distances from the tumor to the hand knob and larger deviation distances for the midpoint of hand knob on the lesion hemisphere are associated with less accuracy of motor cortex localization with blood oxygen level-dependent fMRI. Preoperative fMRI data for surgical planning should be used cautiously when the shortest distance from the tumor to the hand knob is ≤4 mm, especially for lower-grade gliomas anterior to the central sulcus.
In this paper, ZnO nanorods were grown on Si substrate with hydrothermal method, followed by Al(2)O(3) and ZnO thin layers deposited on ZnO nanorods by atomic layer deposition, a coated nanocomposite ...structure ZnO/Al(2)O(3)/ZnO nanorods were obtained. Based on Kirkendall effect, ZnO/ZnAl(2)O(4) core-shell nanostructure were fabricated by annealing treatment through an interfacial solid-state reaction between ZnO and Al(2)O(3), which were confirmed by X-ray diffraction spectra. In this process, due to that Zn ions diffused into Al(2)O(3) and formed ZnAl(2)O(4), Zn vacancies were introduced in ZnO. In PL spectra, the emission related to acceptor located at 3.355 eV and 3.315 eV can be observed, which were attributed to A(0)X and FA emission, respectively. The calculated acceptor binding energy is 118 meV.
We present an amplitude analysis of the decay D0→K−π+π+π− based on a data sample of 2.93 fb−1 acquired by the BESIII detector at the ψ(3770) resonance. With a nearly background free sample of about ...16000 events, we investigate the substructure of the decay and determine the relative fractions and the phases among the different intermediate processes. Our amplitude model includes the two-body decays D0→K¯*0ρ0, D0→K−a1+(1260) and D0→K1−(1270)π+, the three-body decays D0→K¯*0π+π− and D0→K−π+ρ0, as well as the four-body nonresonant decay D0→K−π+π+π−. The dominant intermediate process is D0→K−a1+(1260), accounting for a fit fraction of 54.6%.
Despite the rapid advance of neonatal care, bronchopulmonary dysplasia (BPD) remains a significant burden for the preterm population, and there is a lack of effective intervention. Stem cell ...depletion because of preterm birth is regarded as one of the underlying pathological mechanisms for the arrest of alveolar and vascular development. Preclinical and small-sample clinical studies have proven the efficacy and safety of stem cells in treating and preventing lung injury. However, there are currently no randomized clinical trials (RCTs) investigating the use of autologous cord blood mononuclear cells (ACBMNC) for the prevention of BPD in premature infants. The purpose of this study is to investigate the effects of infusion of ACBMNC for the prevention of BPD in preterm neonates <28 weeks.
In this prospective, randomized controlled double-blind multi-center clinical trial, 200 preterm neonates <28 weeks gestation will be randomly assigned to receive intravenous ACBMNC infusion (5 × 10
cells/kg) or placebo (normal saline) within 24 h after birth in a 1:1 ratio using a central randomization system. The primary outcome will be survival without BPD at 36 weeks of postmenstrual age or at discharge, whichever comes first. The secondary outcomes will include the mortality rate, other common preterm complication rates, respiratory support duration, length, and cost of hospitalization, and long-term outcomes after a 2-year follow-up.
This will be the first randomized, controlled, blinded trial to evaluate the efficacy of ACBMNC infusion as a prevention therapy for BPD. The results of this trial will provide valuable clinical evidence for recommendations on the management of BPD in extremely preterm infants.
ClinicalTrials.gov, NCT03053076, registered 02/14/2017, retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0006WN4&selectaction=Edit&uid=U0002PLA&ts=2&cx=9y23d4 (Additional File 2).
Dendritic cell (DC) targeted antigen delivery is a promising strategy to enhance vaccine efficacy and delivery of therapeutics. Self-assembling peptide-based nanoparticles and virus-like particles ...(VLPs) have attracted extensive interest as non-replicating vectors for nanovaccine design, based on their unique properties, including molecular specificity, biodegradability and biocompatibility. DCs are specialized antigen-presenting cells involved in antigen capture, processing, and presentation to initiate adaptive immune responses. Using DC-specific ligands for targeted delivery of antigens to DCs may be utilized as a promising strategy to drive efficient and strong immune responses.
In this study, several candidates for DC-binding peptides (DCbps) were individually integrated into C-terminal of porcine circovirus type 2 (PCV2) Cap, a viral protein that could self-assemble into icosahedral VLPs with 60 subunits. The immunostimulatory adjuvant activity of DC-targeted VLPs was further evaluated in a vaccine model of PCV2 Cap.
With transmission electron microscopy (TEM),
expressed Cap-DCbp fusion proteins were observed self-assembled into highly ordered VLPs. Further, in dynamic light scattering (DLS) analysis, chimeric VLPs exhibited similar particle size uniformity and narrow size distribution as compared to wild type Cap VLPs. With a distinctly higher targeting efficiency, DCbp3 integrated Cap VLPs (Cap-DCbp3) displayed enhanced antigen uptake and increased elicitation of antigen presentation-related factors in BM-DCs. Mice subcutaneously immunized with Cap-DCbp3 VLPs exhibited significantly higher levels of Cap-specific antibodies, neutralizing antibodies and intracellular cytokines than those with other DCbp integrated or wild type Cap VLPs without any DCbp. Interestingly, Cap-DCbp3 VLPs vaccine induces robust cellular immune response profile, including the efficient production of IFN-γ, IL-2 and IL-10. Meanwhile, the improved proliferation index in lymphocytes with Cap-DCbp3 was also detected as compared to other VLPs.
This study described the potential of DC-binding peptides for further improved antigen delivery and vaccine efficacy, explainning nanovaccine optimization in relation to a range of emerging and circulating infectious pathogens.
Medical nitroglycerin (glyceryl trinitrate, GTN) use is limited principally by tolerance typified by a decrease in nitric oxide (NO) produced by biotransformation. Such tolerance may lead to ...endothelial dysfunction by inducing oxidative stress. In vivo studies have demonstrated that aldehyde dehydrogenase 2 (ALDH2) plays important roles in GTN biotransformation and tolerance. Thus, modification of ALDH2 expression represents a potentially effective strategy to prevent and reverse GTN tolerance and endothelial dysfunction. In this study, a eukaryotic expression vector containing the ALDH2 gene was introduced into human umbilical vein endothelial cells (HUVECs) by liposome-mediated transfection. An indirect immunofluorescence assay showed that ALDH2 expression increased 24 h after transfection. Moreover, real-time polymerase chain reaction and western blotting revealed significantly higher ALDH2 mRNA and protein expression in the gene-transfected group than in the two control groups. GTN tolerance was induced by treating HUVECs with 10 mM GTN for 16 h + 10 min, which significantly decreased NO levels in control cells, but not in those transfected with ALDH2. Overexpression of ALDH2 increased cell survival against GTN-induced cytotoxicity and conferred protection from oxidative damage resulting from nitrate tolerance, accompanied by decreased production of intracellular reactive oxygen species and reduced expression of heme oxygenase 1. Furthermore, ALDH2 overexpression promoted Akt phosphorylation under GTN tolerance conditions. ALDH2 gene transfection can reverse and prevent tolerance to GTN through its bioactivation and protect against oxidative damage, preventing the development of endothelial dysfunction.
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