Search

The incidence of gout arthritis in patients with thalassemia and the association between them was indefinite. We aimed to give epidemiological evidence regarding the association between thalassemia and gout arthritis. This retrospective cohort study extracted data relating to the risk of gout arthritis from patients diagnosed with thalassemia between 2000 and 2013. We selected the control group at a ratio of 1:4 by propensity score matching (PSM). Univariable and multivariable Cox proportional hazard regression models were performed to analyze the association between thalassemia and gout arthritis and to evaluate the hazard ratio (HR) of gout arthritis after exposure with thalassemia. The sensitivity analysis was performed to avoid the mislabeled thalassemia disease, the transfusion-dependent thalassemia was classified to compare the risk of gout arthritis. The secondary outcome for the risk of gout arthritis with antigout drugs treatment was also evaluated between study groups. In the age and sex matched cohort, the majority of thalassemia patients were women (62.03%) and aged younger than 30 years old (44.79%). There were 138 (4.2%) and 500 (3.8%) incident cases of gout arthritis in the thalassemia and non-thalassemia group. After PSM, the incidence rate, per 100 person-years, of gout arthritis was 0.48 (95% CI 0.42 to 0.56) and 0.60 (95% CI 0.51 to 0.72) in non-thalassemia individuals and patients with thalassemia, respectively. In the Cox proportional hazard regression, patients with thalassemia had no significant increase in the risk of gout arthritis (adjusted HR, 1.00; 95%CI: 0.80 to 1.25) after adjusting demographic variables and comorbidities. The Kaplan–Meier curve showed that the cumulative incidence of gout arthritis was not a significant difference in the thalassemia group than in the comparison group (p > 0.05). The sensitivity analysis showed the consistent results about the risk of gout arthritis in patients with thalassemia. Our study indicated that there was no significant increase in the risk of gout arthritis in subjects with thalassemia.Future research needs to clarify the biological mechanisms behind this connection.

Management of vancomycin administration for intensive care units (ICU) patients remains a challenge. The aim of this study was to describe a population pharmacokinetic model of vancomycin for optimizing the dose regimen for ICU patients. We prospectively enrolled 466 vancomycin-treated patients hospitalized in the ICU, collected trough or approach peak blood samples of vancomycin and recorded corresponding clinical information from July 2015 to December 2017 at Tai Zhou Hospital of Zhejiang Province. The pharmacokinetics of vancomycin was analyzed by nonlinear mixed effects modeling with Kinetica software. Internal and external validation was evaluated by the maximum likelihood method. Then, the individual dosing regimens of the 92 patients hospitalized in the ICU whose steady state trough concentrations exceeded the target range (10–20 μg/ml) were adjusted by the Bayes feedback method. The final population pharmacokinetic model show that clearance rate (CL) of vancomycin will be raised under the conditions of dopamine combined treatment, severe burn status (Burn-S) and increased total body weight (TBW), but reduced under the conditions of increased serum creatinine (Cr) and continuous renal replacement therapy status; Meanwhile, the apparent distribution volume (V) of vancomycin will be enhanced under the terms of increased TBW, however decreased under the terms of increased age and Cr. The population pharmacokinetic parameters (CL and V) according to the final model were 3.16 (95%CI 2.83, 3.40) L/h and 60.71 (95%CI 53.15, 67.46). The mean absolute prediction error for external validation by the final model was 12.61% (95CI 8.77%, 16.45%). Finally, the prediction accuracy of 90.21% of the patients’ detected trough concentrations that were distributed in the target range of 10–20 μg/ml after dosing adjustment was found to be adequate. There is significant heterogeneity in the CL and V of vancomycin in ICU patients. The constructed model is sufficiently precise for the Bayesian dose prediction of vancomycin concentrations for the population of ICU Chinese patients.

The lateral prefrontal cortex (LPFC) plays an important role in the neural networks involved in intertemporal choice. However, little is known about how the neural oscillation of LPFC functions during intertemporal choice, owing to the technical limitations of functional magnetic resonance imaging and event-related brain potential recordings. Electrocorticography (ECoG) is a novel neuroimaging technique that has high spatial and temporal resolution. In this study, we used ECoG and projected the ECoG data onto individual brain spaces to investigate human intracranial cortex activity and how neural oscillations of the LPFC impact intertemporal choice. We found that neural activity of theta oscillation was significantly higher during impulsive decisions, while beta oscillation activity was significantly higher during non-impulsive ones. Our findings suggest a functional dissociation between cortical theta and beta oscillations during decision-making processes involved in intertemporal choice, and that decision outcomes may be determined by LPFC modulation, which involves neural oscillations at different frequencies.

This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p

Hypoxia is a characteristic of locally advanced solid tumors, resulting from an imbalance between oxygen consumption and supply. In hypoxic solid tumors, an increased expression of nitroreductase (NTR) is detected, therefore, the development of NTR-targeted fluorescent probes to selectively and efficiently detect hypoxia in vivo is of utmost importance. In this study, a probe (1) has been designed and tested for effective optical detection of NTR in vitro and in vivo. The reduction of probe (1), catalyzed by NTR, resulted in changes of the electron-withdrawn nitrogen group into an electron-donation amino group. In addition, breakage of the O-C bond ensured selective fluorescence enhancement. The in vitro response towards exogenous NTR, from rat liver microsomes, resulted in the optical enhancement during the detection process. In vivo imaging of caerorhabditis elegans (C.elegan) further confirmed the detection of NTR by probe (1). Moreover, probe (1) was successfully used for the detection of hypoxia in both HI5 cells, and a murine tumor model, which demonstrates the potential of probe (1) for application in fluorescence bioimaging studies, and tumor hypoxia diagnosis.

The lateral prefrontal cortex (LPFC) plays an important role in the neural networks involved in intertemporal choice. However, little is known about how the neural oscillation of LPFC functions during intertemporal choice, owing to the technical limitations of functional magnetic resonance imaging and event-related brain potential recordings. Electrocorticography (ECoG) is a novel neuroimaging technique that has high spatial and temporal resolution. In this study, we used ECoG and projected the ECoG data onto individual brain spaces to investigate human intracranial cortex activity and how neural oscillations of the LPFC impact intertemporal choice. We found that neural activity of theta oscillation was significantly higher during impulsive decisions, while beta oscillation activity was significantly higher during non-impulsive ones. Our findings suggest a functional dissociation between cortical theta and beta oscillations during decision-making processes involved in intertemporal choice, and that decision outcomes may be determined by LPFC modulation, which involves neural oscillations at different frequencies.

What ideal w-LED phosphors always aim to do is to achieve a single phase near-sunlight emission phosphor simultaneously with both high luminescence efficiency and high thermal stability at operation temperature. And It is well known that apatite compound phosphors are one of the most promising optical materials to realize those above because of their unique structure enhanced luminescence properties and thermal stability. Here, we synthesized a co-doped single phase apatite phosphors Ca2La8(SiO4)6O2:Dy3+/Sm3+ (CLSO:Dy3+/Sm3+) for white light emission, which was provided with excellent thermal stability and of which luminescence intensity at 150 °C still was 92 percentage of that at room temperature. Moreover, X-ray diffraction technique, Fourier transform infrared spectroscopy, scanning electron microscope were employed to characterization of phase structure and morphology, and consequently pure apatite structure and gravel-like morphology of phosphors were proved. Analysis of photoluminescence spectra indicated that concentration quenching effect exist in single-doped CLSO:Dy3+ phosphors owing to dipole-dipole interaction between Dy3+ ions. It is revealed that maybe exist Dy3+ ↔ Sm3+ bilateral non-radiative energy transfer processes in Dy3+/Sm3+ co-doped CLSO system by PL spectra and decay curves. And variation of Sm3+ ion concentration can control color emission, namely CIE chromaticity coordinates and correlated color temperature, finally to achieve white light emission (0.309,0.309) with CCT 6848 K, able to be a potential candidate for commercial lighting applications.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cereal cyst nematode (Heterodera avenae) is attracted to and aggregated around wheat roots to initiate infection, but this interaction between wheat and the nematode is not fully understood. The transcriptional responses of both wheat and H. avenae were examined during their early contact stage by mRNA sequencing analysis; certain numbers of the differentially expressed genes (DEGs) were validated using quantitative real-time PCR. The immobile host wheat root only had 93 DEGs (27 up-regulated and 66 down-regulated), while the mobile plant parasitic nematode reacted much more actively with 879 DEGs (867 up-regulated and 12 down-regulated). Among them, a number of wheat DEGs (mostly down-regulated) were involved in biotic stress pathways, while several putative effector genes were up-regulated in the nematode DEGs. One putative chitinase-like effector gene of H. avenae was able to suppress BAX-triggered programmed cell death in Nicotiana benthamiana. Results of these experiments demonstrated that nematode responded more actively than wheat during the contact stage of parasitism. The parasite’s responses mainly involved up-regulation of genes including at least one anti-plant-defence effector gene, whereas the host responses mainly involved down-regulation of certain defence-related genes.

The size and function of the left atrium (LA) and right atrium (RA) are related closely with the prognosis of cardiovascular diseases. However, their normal reference values, as measured by cardiac magnetic resonance (CMR), are not well established in Chinese populations. Healthy Chinese subjects (n = 135, 66 males, age 23–83 years) without cardiovascular risk factors were recruited. We imaged the LA and RA of all subjects using short axis and long axis slices by steady-state free precession (SSFP) sequences using a 3.0T scanner. The size and functional parameters were measured. Age and gender differences in LA were further explored. The normal reference values of atrial dimensions, volumes, and empty fractions (EFs) were provided by short axis (SAX) and area-length methods. Volumes and EFs derived by the area-length method showed correlated well with those derived by the by SAX method, but significantly underestimated the volumes (all P

The cine magnetic resonance imaging based technique feature tracking-cardiac magnetic resonance (FT-CMR) is emerging as a novel, simple and robust method to evaluate myocardial strain. We investigated the distribution characteristics of left-ventricular myocardial strain using a novel cine MRI based deformation registration algorithm (DRA) in a cohort of healthy Chinese subjects. A total of 130 healthy Chinese subjects were enrolled. Three components of orthogonal strain (radial, circumferential, longitudinal) of the left ventricle were analyzed using DRA on steady-state free precession cine sequence images. A distinct transmural circumferential strain gradient was observed in the left ventricle that showed universal increment from the epicardial to endocardial myocardial wall (epiwall: −15.4 ± 1.9%; midwall: −18.8 ± 2.0%; endowall: −22.3 ± 2.3%, P

Rivaroxaban is an oral direct factor Xa inhibitor approved for the treatment of stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation. Despite its efficacy, rivaroxaban therapy results in adverse effects and complications, such as bleeding. Angiotensin II (AngII) is implicated in many cardiovascular conditions, such as hypertension and heart failure. In this study, we investigate whether AngII influences anticoagulant effects of rivaroxaban by using an experimental mouse model with type 2 diabetes mellitus and advanced glycation end product (AGE)-exposed human umbilical vein endothelial cells (HUVECs). We found that AngII promoted the anticoagulant effects of rivaroxaban in KKAy mice. The combination of rivaroxaban and AngII enhanced in vivo tissue factor pathway inhibitor (TFPI) activity and induced TFPI expression and activity in AGE-exposed HUVECs. Angiotensin type 2 receptor (AT2R) and Mas antagonists attenuated the AngII-enhanced anticoagulant action of rivaroxaban in vivo, and abolished the increased endothelial TFPI expression and activity. However, angiotensin type 1 receptor (AT1R) antagonist exerted no effects. Additionally, combination of rivaroxaban and AngII induced aortic AT2R and Mas expression. Our data suggest that the anticoagulant effects of rivaroxaban are promoted by AngII via AT2R and Mas signaling. These findings are significant for the clinical administration of rivaroxaban.

A porous hybrid g-C3N4/RGO (CNRG) material has been fabricated through a facile hydrothermal process with the help of glucose molecules, and serves as an efficient immobilization substrate to support ultrathin Ni(OH)2 nanosheets under an easy precipitation process. It was found that the g-C3N4 flakes can uniformly coat on both sides of the RGO, forming sandwich-type composites with a hierarchical structure. It is worth noting that the introduction of the g-C3N4 can effectively achieve the high dispersion and avoid the agglomeration of the nickel hydroxide, and significantly enhance the synthetically capacitive performance. Owning to this unique combination and structure, the CNRG/Ni(OH)2 composite possesses large surface area with suitable pore size distribution, which can effectively accommodate the electrolyte ions migration and accelerate efficient electron transport. When used as electrode for supercapacitor, the hybrid material exhibits high supercapacitive performance, such as an admirable specific capacitance (1785 F/g at a current density of 2 A/g), desirable rate stability (retain 910 F/g at 20 A/g) and favorable cycling durability (maintaining 71.3% capacity after 5000 cycles at 3 A/g). Such desirable properties signify that the CNRG/Ni(OH)2 composites can be a promising electrode material in the application of the supercapacitor.

A facile strategy has been adopted for the preparation of ZnFe2O4/NRG composite by anchoring ultrasmall ZnFe2O4 nanoparticles on nitrogen-doped reduced graphene (denoted as NRG) for high-performance supercapacitor electrode. Remarkably, the growth of ZnFe2O4 nanocrystals, the reduction of graphitic oxide and the doping of nitrogen to graphene have been simultaneously achieved in one process. It is found that the NRG employed as substrate can not only control the formation of nano-sized ZnFe2O4, but also guarantee the high dispersion without any agglomeration. Benefiting from this novel combination and construction, the hybrid material has large surface area which can provide high exposure of active sites for easy access of electrolyte and fast electron transport. When served as supercapacitor electrode, the ZnFe2O4/NRG composite exhibits a favorable specific capacitance of 244 F/g at 0.5 A/g within the potential range from −1 to 0 V, desirable rate stability (retain 131.5 F/g at 10 A/g) and an admirable cycling durability of 83.8% at a scan rate of 100 mV/s after 5000 cycles. When employed as symmetric supercapacitor, the device demonstrates favorable performance. These satisfactory properties of the ZnFe2O4/NRG composite can make it be of great promise in the supercapacitor application.

A facile strategy has been adopted for the preparation of ZnFe2O4/NRG composite by anchoring ultrasmall ZnFe2O4 nanoparticles on nitrogen-doped reduced graphene (denoted as NRG) for high-performance supercapacitor electrode. Remarkably, the growth of ZnFe2O4 nanocrystals, the reduction of graphitic oxide and the doping of nitrogen to graphene have been simultaneously achieved in one process. It is found that the NRG employed as substrate can not only control the formation of nano-sized ZnFe2O4, but also guarantee the high dispersion without any agglomeration. Benefiting from this novel combination and construction, the hybrid material has large surface area which can provide high exposure of active sites for easy access of electrolyte and fast electron transport. When served as supercapacitor electrode, the ZnFe2O4/NRG composite exhibits a favorable specific capacitance of 244 F/g at 0.5 A/g within the potential range from −1 to 0 V, desirable rate stability (retain 131.5 F/g at 10 A/g) and an admirable cycling durability of 83.8% at a scan rate of 100 mV/s after 5000 cycles. When employed as symmetric supercapacitor, the device demonstrates favorable performance. These satisfactory properties of the ZnFe2O4/NRG composite can make it be of great promise in the supercapacitor application.

Alzheimer’s disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-β (Aβ) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Aβ15-THc-C immunogen was formulated with alum adjuvant as a novel Aβ B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3 × Tg-AD mice. Using a toxin-derived carrier protein, the rCV02 vaccine elicited robust Aβ-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3 × Tg-AD mice. Along with the behavioral improvement in aged 3 × Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble Aβ or oligomeric forms of Aβ, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing Aβ levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong Aβ-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine.

After insemination, a large number of leukocytes migrate into the uterus, which is accompanied by intense inflammation. However, the details of how seminal plasma interacts with the uterus are still not very clear. Here, we present that neutrophils migrate and accumulate around the uterine epithelium following insemination, which is accompanied by an increase in interleukin (IL) 17A levels. Additionally, we find that γδ T cells are the major source of IL-17A, and the seminal plasma could induce the γδ T cells to secret IL-17A. Blocking IL-17A could reduce the number of neutrophils in the uterus and prevent them from migrating to the epithelium by decreasing the chemokines CXCL1, CXCL2 and CXCL5. Blocking IL-17A did not affect the Th1/Th2 balance but actually diminished the inflammation in the uterus by reducing the expression of IL-1β and TNF-α. In summary, we found a new mechanism by which seminal plasma could influence the inflammation in the uterus through the γδ T/IL-17 pathway to regulate the expression of various chemokines and cytokines.

Astragalus membranaceus is an important medicinal plant in Asia. Several of its varieties have been used interchangeably as raw materials for commercial production. High resolution genetic markers are in urgent need to distinguish these varieties. Here, we sequenced and analyzed the chloroplast genome of A. membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P.K. Hsiao using the next generation DNA sequencing technology. The genome was assembled using Abyss and then subjected to gene prediction using CPGAVAS and repeat analysis using MISA, Tandem Repeats Finder, and REPuter. Finally, the genome was subjected phylogenetic and comparative genomic analyses. The complete genome is 123,582 bp long, containing only one copy of the inverted repeat. Gene prediction revealed 110 genes encoding 76 proteins, 30 tRNAs, and four rRNAs. Five intra-specific hypermutation loci were identified, three of which are heteroplasmic. Furthermore, three gene losses and two large inversions were identified. Comparative genomic analyses demonstrated the dynamic nature of the Papilionoideae chloroplast genomes, which showed occurrence of numerous hypermutation loci, frequent gene losses, and fragment inversions. Results obtained herein elucidate the complex evolutionary history of chloroplast genomes and have laid the foundation for the identification of genetic markers to distinguish A. membranaceus varieties.

Active immunotherapy targeting β-amyloid (Aβ) is the most promising strategy to prevent or treat Alzheimer's disease (AD). Based on pre-clinical studies and clinical trials, a safe and effective AD vaccine requires a delicate balance between providing therapeutically adequate anti-Aβ antibodies and eliminating or suppressing unwanted adverse T cell-mediated inflammatory reactions. We describe here the immunological characterization and protective efficacy of co-immunization with a 6Aβ15-T DNA and protein mixture without adjuvant as an AD immunotherapeutic strategy. Impressively, this co-immunization induced robust Th2-polarized Aβ-specific antibodies while simultaneously suppressed unwanted inflammatory T cell reactions and avoiding Aβ42-specific T cell-mediated autoimmune responses in immunized mice. Co-immunization with the DNA + protein vaccine could overcome Aβ42-associated hypo-responsiveness and elicit long-term Aβ-specific antibody responses, which helped to maintain antibody-mediated clearance of amyloid and accordingly alleviated AD symptoms in co-immunized PDAPP mice. Our DNA and protein combined vaccine, which could induce an anti-inflammatory Th2 immune response with high level Aβ-specific antibodies and low level IFN-γ production, also demonstrated the capacity to inhibit amyloid accumulation and prevent cognitive dysfunction. Hence, co-immunization with antigen-matched DNA and protein may represent a novel and efficacious strategy for AD immunotherapy to eliminate T cell inflammatory reactions while retaining high level antibody responses.

The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are exclusively produced by intracellular heterologous expression in Pichia pastoris for use in subunit vaccines; the same Hc proteins produced by secreted heterologous expression are hyper-glycosylated and immunologically inert. Here, several different recombinant secreted Hc proteins of botulinum neurotoxin serotype B (BHc) were expressed in yeast and we characterized and assessed their immunological activity in detail. Recombinant low-glycosylated secreted BHc products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc products (BSG), although deglycosylation restored their immunological activities. Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an α-factor signal and fortuitous N-linked glycosylation sites in the non-cleaved pro-peptide sequences, but not in the BHc sequences. Notably, a non-glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully prepared after deleting the pro-peptide and removing its single potential glycosylation site, was immunologically active and could confer effective protective immunity, similarly to non-glycosylated rBHc. In summary, we conclude that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting the pro-peptide of the α-factor signal and mutating its single potential glycosylation site. This approach provides a rational and feasible strategy for the secretory expression of botulism or other toxin antigens.