30+ year evolution of Cu in the surface sediment of Lake Poyang, China.

Poyang Lake, the largest freshwater lake in China, is increasingly experiencing Cu crises. Combining field data, laboratory experiments, and long-term simulations, we retrieved 30 + year evolution of Cu in surface sediments (SCu). SCu evolution between 1983 and 2015 may be separated into two distinguishable periods. During the first period (1983-2003), SCu underwent a continuous increase at a mean rate of 1.80 mg/kg/yr; however, since 2003 it displayed a stepwise reduction tendency. The average SCu concentration of the entire lake in 2015 fell to 54.26 mg/kg, which is approximately 30.01% lower than that in 2003. The operation of Three Gorges Dam (TGD) markedly altered the river-lake relationship, pulled more deposited Cu along with sediment out toward the Yangtze River, and made the regions of high SCu emanate from the southeastern lake extend northwestward between 2003 and 2015. SCu in the reserves showed significant inter-annual variations, with the exception of the Jiangxi Whitebait Spawning Reserve (JWSR), where SCu generally has not been significantly impacted and has displayed no departure from the 30 + year mean of 30.57 mg/kg. The National Germplasm Reserve (NGR) and Nanjishan National Nature Reserve (NNNR) were detected with the highest SCu, with the peak concentrations, respectively, of 123.15 mg/kg and 103.1 mg/kg

Targeting p53 via JNK Pathway: A Novel Role of RITA for Apoptotic Signaling in Multiple Myeloma

The low frequency of p53 alterations e.g., mutations/deletions (∼10%) in multiple myeloma (MM) makes this tumor type an ideal candidate for p53-targeted therapies. RITA is a small molecule which can induce apoptosis in tumor cells by activating the p53 pathway. We previously showed that RITA strongly activates p53 while selectively inhibiting growth of MM cells without inducing genotoxicity, indicating its potential as a drug lead for p53-targeted therapy in MM. However, the molecular mechanisms underlying the pro-apoptotic effect of RITA are largely undefined. Gene expression analysis by microarray identified a significant number of differentially expressed genes associated with stress response including c-Jun N-terminal kinase (JNK) signaling pathway. By Western blot analysis we further confirmed that RITA induced activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. These results suggest that RITA induced the activation of JNK signaling. Chromatin immunoprecipitation (ChIP) analysis showed that activated c-Jun binds to the activator protein-1 (AP-1) binding site of the p53 promoter region. Disruption of the JNK signal pathway by small interfering RNA (siRNA) against JNK or JNK specific inhibitor, SP-600125 inhibited the activation of p53 and attenuated apoptosis induced by RITA in myeloma cells carrying wild type p53. On the other hand, p53 transcriptional inhibitor, PFT-α or p53 siRNA not only inhibited the activation of p53 transcriptional targets but also blocked the activation of c-Jun suggesting the presence of a positive feedback loop between p53 and JNK. In addition, RITA in combination with dexamethasone, known as a JNK activator, displays synergistic cytotoxic responses in MM cell lines and patient samples. Our study unveils a previously undescribed mechanism of RITA-induced p53-mediated apoptosis through JNK signaling pathway and provides the rationale for combination of p53 activating drugs with JNK activators in the treatment of MM

COVID-19 vaccination and the risk of autoimmune diseases: a Mendelian randomization study

BackgroundIn recent times, reports have emerged suggesting that a variety of autoimmune disorders may arise after the coronavirus disease 2019 (COVID-19) vaccination. However, causality and underlying mechanisms remain unclear.MethodsWe collected summary statistics of COVID-19 vaccination and 31 autoimmune diseases from genome-wide association studies (GWAS) as exposure and outcome, respectively. Random-effects inverse variance weighting (IVW), MR Egger, weighted median, simple mode, and weighted mode were used as analytical methods through Mendelian randomization (MR), and heterogeneity and sensitivity analysis were performed.ResultsWe selected 72 instrumental variables for exposure (p < 5 × 10−6; r2 < 0.001, genetic distance = 10,000 kb), and MR analyses showed that COVID-19 vaccination was causally associated with an increased risk of multiple sclerosis (MS) (IVW, OR: 1.53, 95% CI: 1.065–2.197, p = 0.026) and ulcerative colitis (UC) (IVW, OR: 1.00, 95% CI: 1.000–1.003, p = 0.039). If exposure was refined (p < 5 × 10−8; r2 < 0.001, genetic distance = 10,000 kb), the associations became negative. No causality was found for the remaining outcomes. These results were robust to sensitivity and heterogeneity analyses.ConclusionOur study provided potential evidence for the impact of COVID-19 vaccination on the risk of MS and UC occurrence, but it lacks sufficient robustness, which could provide a new idea for public health policy

Plant Root Exudates Are Involved in Bacillus cereus AR156 Mediated Biocontrol Against Ralstonia solanacearum

The biological control process mediated by microbes relies on multiple interactions among plants, pathogens and biocontrol agents (BCAs). One such efficient BCA is Bacillus cereus AR156, a bacterial strain that controls a broad spectrum of plant diseases and potentially works as a microbe elicitor of plant immune reactions. It remains unclear, however, whether the interaction between plants and B. cereus AR156 may facilitate composition changes of plant root exudates and whether these changes directly affect the growth of both plant pathogens and B. cereus AR156 itself. Here, we addressed these questions by analyzing the influences of root exudate changes mediated by B. cereus AR156 during biocontrol against tomato bacterial wilt caused by Ralstonia solanacearum. Indeed, some upregulated metabolites in tomato root exudates induced by B. cereus AR156 (REB), such as lactic acid and hexanoic acid, induced the growth and motile ability of in vitro B. cereus AR156 cells. Exogenously applying hexanoic acid and lactic acid to tomato plants showed positive biocontrol efficacy (46.6 and 39.36%) against tomato bacterial wilt, compared with 51.02% by B. cereus AR156 itself. Furthermore, fructose, lactic acid, sucrose and threonine at specific concentrations stimulated the biofilm formation of B. cereus AR156 in Luria-Bertan- Glycerol- Magnesium medium (LBGM), and we also detected more colonized cells of B. cereus AR156 on the tomato root surface after adding these four compounds to the system. These observations suggest that the ability of B. cereus AR156 to induce some specific components in plant root exudates was probably involved in further biocontrol processes

Effect of Parental Migration on the Intellectual and Physical Development of Early School-Aged Children in Rural China

Abstract OBJECTIVE: The purpose of this study is to estimate the effect of parent migration on intellectual and physical development of early school-aged children in rural China. DESIGN: setting and participants: The present cross-sectional study participants were a subset from a controlled, cluster-randomized, double-blind trial. From October 2012 to September 2013, the offspring of women who participated in a large trial were examined in the present study. Wechsler intelligence scale for children (WISC-IV) in which validity and reliability were shown to be satisfactory was used to measure the intellectual function and trained anthropometrists measured weight and height of children using standard procedures. RESULTS: The mean difference of FSIQ scores between non-migration and both-parent migration groups was -3.68 (95%CI: -5.49, -1.87). After adjusting for the confounders, the mean difference of full-scale IQ between non-migration and both-parent migration group was -1.97 (95%CI: -3.92, -0.01), the mean differences of perceptual reasoning index and processing speed index were -2.41 (95%CI: -4.50, -0.31) and -2.39 (95%CI: -4.42, -0.35) between two groups respectively. CONCLUSION: Our results emphasized the impairment of both-parental migration in intellectual function (FSIQ, PRI, PSI) of children. These findings have important policy implications for the Chinese government to prevent the impairment of left-behind children. Further research is required to clarify the mechanisms by which both-parental migration influence the impairment in intellectual function of children

Performance of Detecting IgM Antibodies against Enterovirus 71 for Early Diagnosis

Enterovirus 71 (EV71) infection is more likely to induce severe complications and mortality than other enteroviruses. Methods for detection of IgM antibody against EV71 had been established for years, however, the performance of the methods in the very early diagnosis of EV71 infection had not been fully evaluated, which is especially meaningful because of the short incubation period of EV71 infection. In this report, the performance of an IgM anti-EV71 assay was evaluated using acute sera collected from 165 EV71 infected patients, 165 patients infected with other enteroviruses, and more than 2,000 sera from healthy children or children with other infected diseases. The results showed a 90% sensitivity in 20 patients who were in their first illness day, and similar sensitivity remained till 4 days after onset. After then the sensitivity increased to 95% to 100% for more than one month. The specificity of the assay in non-HFMD children is 99.1% (95% CI: 98.6–99.4), similar as the 99.9% specificity in healthy adults. The cross-reaction rate in patients infected with other non-EV71 enteroviruses was 11.4%. In conclusion, the data here presented show that the detection of IgM anti-EV71 by ELISA affords a reliable, convenient, and prompt diagnosis of EV71 infection

EUD-MARS: End-User Development of Model-Driven Adaptive Robotics Software Systems

Empowering end-users to program robots is becoming more significant. Introducing software engineering principles into end-user programming could improve the quality of the developed software applications. For example, model-driven development improves technology independence and adaptive systems act upon changes in their context of use. However, end-users need to apply such principles in a non-daunting manner and without incurring a steep learning curve. This paper presents EUD-MARS that aims to provide end-users with a simple approach for developing model-driven adaptive robotics software. End-users include people like hobbyists and students who are not professional programmers but are interested in programming robots. EUD-MARS supports robots like hobby drones and educational humanoids that are available for end-users. It offers a tool for software developers and another one for end-users. We evaluated EUD-MARS from three perspectives. First, we used EUD-MARS to program different types of robots and assessed its visual programming language against existing design principles. Second, we asked software developers to use EUD-MARS to configure robots and obtained their feedback on strengths and points for improvement. Third, we observed how end-users explain and develop EUD-MARS programs, and obtained their feedback mainly on understandability, ease of programming, and desirability. These evaluations yielded positive indications of EUD-MARS

Hypersurfaces with Null Higher Order Anisotropic Mean Curvature

Given a positive function on which satisfies a convexity condition, for , we define for hypersurfaces in the th anisotropic mean curvature function , a generalization of the usual th mean curvature function. We call a hypersurface anisotropic minimal if , and anisotropic -minimal if . Let be the set of points which are omitted by the hyperplanes tangent to . We will prove that if an oriented hypersurface is anisotropic minimal, and the set is open and nonempty, then is a part of a hyperplane of . We also prove that if an oriented hypersurface is anisotropic -minimal and its th anisotropic mean curvature is nonzero everywhere, and the set is open and nonempty, then has anisotropic relative nullity

Existence of solutions to a normalized F-infinity Laplacian equation

In this article, for a continuous function F that is twice differentiable at a point $x_0$, we define the normalized F-infinity Laplacian $\Delta_{F; \infty}^N$ which is a generalization of the usual normalized infinity Laplacian. Then for a bounded domain $\Omega\subset\mathbb{R}^n$, $f\in C(\Omega)$ with $\inf_\Omega f(x)>0$ and $g\in C(\partial\Omega)$, we obtain existence and uniqueness of viscosity solutions to the Dirichlet boundary-value problem $$\displaylines{ \Delta_{F; \infty}^N u=f, \quad \text{in }\Omega,\cr u=g, \quad \text{on }\partial\Omega. }$