Search

Background: Observational studies have shown that changes in circulating cytokine/growth factor levels occur throughout the initiation and progression of ankylosing spondylitis (AS), yet whether they are etiologic or downstream effects remains unclear. In this study, we performed a summarized-level bidirectional Mendelian randomization (MR) analysis to shed light on the causal relationship between the two. Methods: Genetic instrumental-variables (IVs) associated with circulating cytokine/growth factor levels were derived from a genome-wide association study (GWAS) of 8,293 European individuals, whereas summary data for the AS were obtained from a FinnGen GWAS of 166,144 participants. We used the inverse-variance-weighted (IVW) method as the main analysis for causal inference. Furthermore, several sensitivity analyses (MR-Egger, weighted median, MR-PRESSO and Cochran's Q test) were utilized to examine the robustness of the results. Finally, reverse MR analysis was performed to assess reverse causality between AS and circulating cytokine/growth factor levels. Results: After Bonferroni correction, circulating levels of Cutaneous T-cell attracting (CTACK) and Monocyte specific chemokine 3 (MCP-3) were positively associated with a higher risk of AS (odds ratio [OR]: 1.224, 95% confidence interval [95% Cl]: 1.022 ~ 1.468, P = 0.028; OR: 1.250, 95% Cl: 1.016 ~ 1.539, P = 0.035). In addition, elevated circulating levels of Basic fibroblast growth factor (FGF-basic), Granulocyte colony-stimulating factor (G-CSF) and MCP-3 was considered a consequence of AS disease (β = 0.023, P = 0.017; β = 0.017, P = 0.025; β = 0.053, P = 0.025). The results of the sensitivity analysis were generally consistent. Conclusion: The present study supplies genetic evidence for the relationship between circulating cytokine levels and AS. Targeted interventions of specific cytokines may help to reduce the risk of AS initiation and progression. [ABSTRACT FROM AUTHOR]

Carbon footprint is emerging as an effective tool for carbon emission management, especially that from fossil energy consumption. In addition, decoupling analysis is important to keep a high pace of economic growth while reducing carbon emission and its carbon footprint. Taking the Yangtze River Delta (YRD) urban agglomeration in China as a case, this paper examined the changes in carbon footprint and carbon footprint pressure by incorporating land resource limits. On this basis, we further analyzed the decoupling relationships between carbon footprint, carbon footprint pressure and economic growth. The GeoDetector was also employed to detect the spatial heterogeneity of the carbon footprint pressure. The results showed that despite the decrease of carbon emissions from 2011 to 2019 in the YRD, carbon footprint pressure still revealed an increased trend in this period. As to the decoupling relationships between carbon footprint, carbon footprint pressure and economic growth, they were improved in most of the cities in the YRD, changing from expansive coupling to weak decoupling to strong decoupling. However, the descending trend of decoupling elasticity coefficient for carbon footprint pressure is smaller than that of the carbon footprint. This result could be explained by the fact that not only carbon emission but also carbon sequestration (by productive lands including forests and grasslands) pose large impacts on carbon footprint pressure. The findings indicate the necessity not only to reduce carbon emission, but also to protect productive lands to realize low carbon economy.

The study of the contribution of the plant defence hormones, salicylic acid (SA) and jasmonic acid (JA), in the resistance against pathogens of plants associated with Epichloë fungal endophytes has been scanty. We hypothesised that Epichloë spp., capable of inducing host plant SA-dependent defences, would increase the levels of plant resistance against biotrophic pathogens. Plants of Achnatherum inebrians, with and without the fungal endophyte Epichloë gansuensis, were inoculated with the biotrophic fungal pathogen Blumeria graminis. We measured the status of plant defences (associated with SA and JA signalling pathways) and the levels of resistance to the pathogen. Plants associated with the endophyte showed less disease symptoms caused by the biotrophic pathogen than plants without the endophyte. In agreement with our hypothesis, the Epichloë endophyte increased the plant production of SA and enhanced the expression levels of plant genes of synthesis and response to the SA hormone. The elevated expression of SA-related genes coding for putative plant enzymes with anti-fungal activities promoted by the endophyte may explain the enhanced resistance to the pathogen. The present study highlights that interaction between the plant immune system and Epichloë fungal endophytes can contribute significantly to the resistance of endophyte-symbiotic plants against pathogens.

The present study was designed to explore the effects of the endophyte Epichloë gansuensis on gene expression related to plant hormone biosynthesis and response pathways and the content of salicylic acid (SA) and jasmonic acid (JA) hormones of Achnatherum inebrians, under different moisture conditions. Through a pot experiment and transcriptome analysis, we found a total of 51 differentially expressed genes (DEGs) related to hormone biosynthesis and response pathways, including 12 auxin related genes, 8 cytokinin (CTK) related genes, 3 gibberellin (GA) related genes, 7 abscisic acid (ABA) related genes, 7 ethylene (ET) related genes, 12 JA related genes and 4 SA related genes. Furthermore, key genes of JA and SA biosynthesis and response pathways, such as LOX2S, AOS, OPR, ACX, JMT, JAZ, PAL, NPR1, TGA and PR-1, showed different degrees of upregulation or downregulation. Under 60% soil moisture content, the JA content of endophyte-free (EF) A. inebrians was significantly (p < 0.05) higher than that of endophyte-infected (EI) A. inebrians. Under 30% and 60% soil moisture content, the SA content of EF A. inebrians was significantly (p < 0.05) higher than that of EI A. inebrians. SA content of EI A. inebrians under 30% and 60% soil moisture content was significantly (p < 0.05) higher than that under 15% soil moisture content. With both EI and EF plants, the SA and JA levels, respectively, are very similar at 15% soil moisture content. This study has revealed that E. gansuensis differentially activated plant hormone synthesis and signal transduction pathways of A. inebrians plants under different soil moisture availability.

Aiming at protecting the confidentiality of data for cloud storage users,a scheme that encrypt data in cloud service providers was presented.The scheme constructed a closed-box computing environment by virtual machine isolation technique,improved algorithm of RSA to change keys without having to produce large prime numbers,transfer data and keys through SSL and encrypted data in the closed computing environment before storing to the distributed file system.Closed-box computing environment can prevent attacks from cloud administrators and malicious applications in the operating system.It also can guard against data leakage effectively.The result of experiment shows that the confidentiality of data improved and the performance loss is decreased considering to other cloud storage scheme that encrypt data in cloud.

Although non-small cell lung cancer (NSCLC) patients benefit from standard taxane-platin chemotherapy, many relapse, developing drug resistance. We established preclinical taxane-platin-chemoresistance models and identified a 35-gene resistance signature, which was associated with poor recurrence-free survival in neoadjuvant-treated NSCLC patients and included upregulation of the JumonjiC lysine demethylase KDM3B. In fact, multi-drug-resistant cells progressively increased the expression of many JumonjiC demethylases, had altered histone methylation, and, importantly, showed hypersensitivity to JumonjiC inhibitors in vitro and in vivo. Increasing taxane-platin resistance in progressive cell line series was accompanied by progressive sensitization to JIB-04 and GSK-J4. These JumonjiC inhibitors partly reversed deregulated transcriptional programs, prevented the emergence of drug-tolerant colonies from chemo-naive cells, and synergized with standard chemotherapy in vitro and in vivo. Our findings reveal JumonjiC inhibitors as promising therapies for targeting taxane-platin-chemoresistant NSCLCs.

Objective: Data on changes in bone mineral density (BMD) from valproate (VPA) therapy are ambiguous and conflicting. Thus, the aim of this study was to systematically review the existing data and carry out a meta-analysis to investigate the effect of VPA as a monotherapy on BMD in people with epilepsy (PWE).Methods: We systematically searched PubMed, EMBASE, and MEDLINE for eligible studies. We calculated the standardized mean difference (SMD) with 95% confidence interval (CI) to investigate the statistical power of the association between VPA treatment and BMD.Results: Nineteen studies were included in this systematic review and meta-analysis. We found that BMD was lower in the VPA group than in the control group (SMD: −0.44; 95% CI: −0.65 to −0.22). A significant association was found in adult patients (SMD: −0.57; 95% CI: −0.88 to −0.26; I2 = 69.8%) and pediatric patients (SMD: −0.32; 95% CI: −0.60 to −0.03; I2 = 67.8%) by subgroup analysis. This study indicated that BMD was significantly lower in patients treated for more than 36 months than in controls (SMD: −0.52; 95% CI: −0.76 to −0.27; I2 = 61.8%). However, a significant difference was not found between patients who were treated for less than 36 months and controls (SMD: −0.36; 95% CI: −0.72 to 0.01; I2 = 74.8%).Conclusion and significance: The present study provided evidence that VPA treatment was significantly associated with BMD loss in PWE. Thus, for patients at a high risk of osteoporosis and fracture, especially for patients who need long-term treatment, VPA may not be a good choice.

Here, we describe the first case of familial hemiplegic migraine type 1 (FHM1) resulting from a T666M mutation in the CACNA1A gene of a Chinese individual. A 54-year-old female patient demonstrated extensive clinical manifestations, including transient paropsia, hemianesthesia, logaphasia, hemiplegia, migraine, fever, impaired consciousness, and progressive cerebellar ataxia. At admission, neurological examination showed a fever of 38.6°C, coma, bilateral pupillary constriction, left-sided deviation of both eyes, meningeal irritation, and bilateral positive Chaddock's sign. Brain magnetic resonance imaging (MRI) displayed only cerebellar atrophy. The pressure and white blood cells of the cerebrospinal fluid (CSF) were elevated. Her nine relatives also had similar clinical spectra. To further clarify the diagnosis, we conducted a genetic analysis on the family. The results of genetic testing showed that all seven living affected members carried the T666M mutation in the CACNA1A gene. This case report indicates that the diagnosis of FHM should be taken into account when a patient manifests migraine accompanied with hemiplegia, acute encephalopathy, and abnormal CSF. In addition, genetic testing is indispensable for the identification of some atypical attacks of hemiplegic migraine.

Background: In recent years, increasing attention has been paid to the association between C-reactive protein (CRP) levels and epilepsy. However, studies concerning CRP levels in epilepsy have also yielded conflicting results. Thus, the objective of the present study is to systematically review the evidence and conduct a meta-analysis to investigate CRP levels in epileptic patients compared with healthy controls.Methods: A systematic search of PubMed, EMBASE, and the Cochrane Library was performed for eligible studies. Standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were used as a measure to assess the association between CRP and epilepsy.Results: In total, 16 case–control studies were included in the present meta-analysis, which comprised 1918 individuals. Combined results indicated that epileptic patients had significantly increased CRP levels in peripheral blood compared with healthy controls (SMD = 0.43; 95% CI: 0.19–0.67). In addition, subgroup analyses by age demonstrated that significant differences in blood CRP levels between epileptic patients and healthy controls could be found in adults (SMD = 0.47; 95% CI: 0.21–0.73) but not children (SMD = 0.26; 95% CI: −0.48–0.99).Conclusion: The present meta-analysis shows that the CRP levels in peripheral blood were significantly increased in epileptic patients compared to healthy controls, indicating a significant association between inflammation and epilepsy. Epileptic seizures may be associated with the inflammatory response.

Background: Epilepsy is one of the most prevalent chronic brain diseases worldwide and is often accompanied by cognitive impairment. Event-related potentials (ERPs) are an objectively non-invasive approach for studying information processing and cognitive functions in the brain. The P300 is an important and extensively explored late component of ERPs that has been widely applied to assess cognitive function in epilepsy in previous studies. However, consistent conclusions have not yet been reached for various reasons.Objective: We conducted a comprehensive systematic review and meta-analysis of P300-related studies to assess the latency and amplitude of the P300 in epileptic patients.Methods: PubMed, EMBASE, and Cochrane Library databases were systematically searched for eligible studies. The standard mean difference (SMD) and the 95% confidence interval (CI) were calculated as the effect size of the P300 component.Results: The main results of the present meta-analysis indicated that epileptic patients have a longer P300 latency and a lower P300 amplitude than controls. Subgroup analysis based on age group demonstrated that these differences can be observed in both children and adult patients compared with healthy controls. In addition, the P300 latency was longer in patients with the five main types of epileptic seizures than in controls.Conclusion: This study revealed that epileptic patients have abnormalities in the P300 component, which may reflect deficits in cognitive function. Thus, the P300 may be a potential objective approach for evaluating cognitive function in epileptic patients.

[This corrects the article DOI: 10.1371/journal.pone.0212951.].

The present work is concerned with dynamic characteristics of beam-stiffened rectangular plate by an improved Fourier series method (IFSM), including mobility characteristics, structural intensity, and transient response. The artificial coupling spring technology is introduced to establish the clamped or elastic connections at the interface between the plate and beams. According to IFSM, the displacement field of the plate and the stiffening beams are expressed as a combination of the Fourier cosine series and its auxiliary functions. Then, the Rayleigh–Ritz method is applied to solve the unknown Fourier coefficients, which determines the dynamic characteristics of the coupled structure. The Newmark method is adopted to obtain the transient response of the coupled structure, where the Rayleigh damping is taken into consideration. The rapid convergence of the current method is shown, and good agreement between the predicted results and FEM results is also revealed. On this basis, the effects of the factors related to the stiffening beam (including the length, orientations, and arrangement spacing of beams) and elastic parameters, as well as damping coefficients on the dynamic characteristics of the stiffened plate are investigated.

Chitosan oligosaccharide (COS) is known for its unique biological activities such as anti-tumor, anti-inflammatory, anti-oxidant, anti-bacterial activity, biological recognition, and immune enhancing effects, and thus continuous attracting many research interests in drug, food, cosmetics, biomaterials and tissue engineering fields. In comparison to its corresponding polymer, COS has much higher absorption profiles at the intestinal level, which results in permitting its quick access to the blood flow and potential contacting with blood components. However, the effects of COS on blood components remain unclear to date. Herein, two COS with different molecular weight (MW) were characterized by FTIR and 1H NMR, and then their effects on human blood components, including red blood cells (RBCs) (hemolysis, deformability, and aggregation), coagulation system [activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and the concentration of fibrinogen (Fib)], complement (C3a and C5a activation), and platelet (activation and aggregation), were comprehensively studied. In the case of RBCs, COS exhibited a low risk of hemolysis in a dose and molecular weight dependent manner and the irreversible aggregation was observed in their high concentration. For coagulation system, COS has a mild anticoagulation activity through blocking the intrinsic coagulation pathway. In addition, COS showed no effect on complement activation in C3a and C5a and on platelet activation while inhibition of platelet aggregation was evident. Finally, the mechanism that effects of COS on blood components was discussed and proposed.

Covalent coupling with cell-penetrating peptides (CPPs) has been a common strategy to facilitate the cell entry of nanomaterial and other macromolecules. Though efficient, this strategy requires chemical modifications on nanomaterials, which is not always desired for their applications. Recent studies on a few cationic CPPs have revealed that they can stimulate the cellular uptake of nanoparticles (NPs) simply via co-administration (bystander manner), which bypasses the requirement of chemical modification. In this study, we investigated the other classes of CPPs and discovered that transportan (TP) peptide, an amphiphilic CPP, also exhibited such bystander activities. When simply co-administered, TP peptide enabled the cells to engulf a variety of NPs, as well as common solute tracers, while these payloads had little or no ability to enter the cells by themselves. This result was validated in vitro and ex vivo, and TP peptide showed no physical interaction with co-administered NPs (bystander cargo). We further explored the cell entry mechanism for TP peptide and its bystander cargo, and showed that it was mediated by a receptor-dependent macropinocytosis process. Together, our findings improve the understanding of TP-assisted cell entry, and open up a new avenue to apply this peptide for nanomaterial delivery.