Integrated Transcriptomic and Metabolomics Analyses Reveal Molecular Responses to Cold Stress in Coconut (Cocos nucifera L.) Seedlings.

Coconut is an important tropical and subtropical fruit and oil crop severely affected by cold temperature, limiting its distribution and application. Thus, studying its low-temperature reaction mechanism is required to expand its cultivation range. We used growth morphology and physiological analyses to characterize the response of coconuts to 10, 20, and 30 d of low temperatures, combined with transcriptome and metabolome analysis. Low-temperature treatment significantly reduced the plant height and dry weight of coconut seedlings. The contents of soil and plant analyzer development (SPAD), soluble sugar (SS), soluble protein (SP), proline (Pro), and malondialdehyde (MDA) in leaves were significantly increased, along with the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the endogenous hormones abscisic acid (ABA), auxin (IAA), zeatin (ZR), and gibberellin (GA) contents. A large number of differentially expressed genes (DEGs) (9968) were detected under low-temperature conditions. Most DEGs were involved in mitogen-activated protein kinase (MAPK) signaling pathway-plant, plant hormone signal transduction, plant-pathogen interaction, biosynthesis of amino acids, amino sugar and nucleotide sugar metabolism, carbon metabolism, starch and sucrose metabolism, purine metabolism, and phenylpropanoid biosynthesis pathways. Transcription factors (TFs), including WRKY, AP2/ERF, HSF, bZIP, MYB, and bHLH families, were induced to significantly differentially express under cold stress. In addition, most genes associated with major cold-tolerance pathways, such as the ICE-CBF-COR, MAPK signaling, and endogenous hormones and their signaling pathways, were significantly up-regulated. Under low temperatures, a total of 205 differentially accumulated metabolites (DAMs) were enriched; 206 DAMs were in positive-ion mode and 97 in negative-ion mode, mainly including phenylpropanoids and polyketides, lipids and lipid-like molecules, benzenoids, organoheterocyclic compounds, organic oxygen compounds, organic acids and derivatives, nucleosides, nucleotides, and analogues. Comprehensive metabolome and transcriptome analysis revealed that the related genes and metabolites were mainly enriched in amino acid, flavonoid, carbohydrate, lipid, and nucleotide metabolism pathways under cold stress. Together, the results of this study provide important insights into the response of coconuts to cold stress, which will reveal the underlying molecular mechanisms and help in coconut screening and breeding.

Quantitative prediction of potential areas likely to yield Se-rich and Cd-low rice using fuzzy weights-of-evidence method.

The research of high-quality agricultural products rich in selenium and low in cadmium (Se-rich and Cd-low, respectively) is related directly to the value of agricultural products and people's food safety. Now it is still challenging to carry out development planning for Se-rich rice. By fuzzy weights-of-evidence method, the geochemical soil survey data of Se and Cd from 27,833 surface soil samples and 804 rice samples was used to predict the probability of areas, in Hubei Province, China, that will likely yield (a) Se-rich and Cd-low rice, (b) Se-rich and Cd-normal rice and (c) Se-rich and Cd-high rice. The areas predicted to likely yield Se-rich and Cd-high rice, Se-rich and Cd-normal rice, and high quality (i.e., Se-rich and Cd-low) rice cover 6542.3 km2 (5.9 %), 35,845.9 km2 (32.6 %), 12,379.7 km2 (11.3 %), respectively, of the surveyed region. According to the predictive distribution probability mapping of Se and Cd, this paper gives preliminary suggestions on the use of endogenous and exogenous Se, and Cd-reduction measures in planting Se-rich rice in different regions of Hubei Province. This study provides a new perspective for rational rice planting of Se-rich agricultural products, and it lays a foundation for the effective implementation of a geochemical soil investigation engineering project, which is of great significance for improving the economic value of Se-rich agricultural products and sustainable utilization of Se land resources.

Factors Associated with PCV13 Vaccine Hesitancy in Parents under an Innovative Immunization Strategy: a Cross-Sectional Study - Weifang City, Shandong Province, China, 2021.

What is already known on this topic?: Pneumococcal diseases (PDs) are serious threats to child health. Although vaccination is one of the most effective ways to prevent these diseases, the pneumococcal vaccination coverage rate is still relatively low in China. What is added by this report?: This study investigated the factors associated with 13-valent pneumococcal conjugate vaccine (PCV13) vaccine hesitancy in parents under an innovative immunization strategy. This study found that 29.7% of the participants hesitated to vaccinate their children against PCV13 and the main reasons for vaccine hesitancy were individual and group influences. What are the implications for public health practice?: This study can provide scientific evidence for further improving children's PCV13 vaccination rate and improving the prevention and control strategy for PDs.

Driving more WHO-recommended vaccines in the National Immunization Program: Issues and challenges in China.

WHO-recommended vaccines substantially prevent and control vaccine-preventable diseases (VPDs), but their inclusion differs among countries and regions. We reviewed the application for WHO-recommended vaccines in China and described the concerns and obstacles in driving the inclusion of more vaccines into China's NIP, including immunization strategies, financial barriers, vaccination services, and behavioral and social supply-side and demand-side factors. China has made significant efforts, however, they may not be sufficient until the inclusion of more WHO-recommended vaccines in the National Immunization Program (NIP), ensuring that the vaccination encompasses the whole life course of individuals, establishment of more trustworthy vaccination finance and procurement, increasing vaccine development, optimizing vaccine demand forecasts, improving the accessibility and equity of vaccination services, capturing the key points of behavioral and social drivers of vaccination on the demand side, and establishing holistic prevention and control from a public health perspective.

Selenium Species and Fractions in the Rock-Soil-Plant Interface of Maize (Zea mays L.) Grown in a Natural Ultra-Rich Se Environment.

Selenium (Se) enrichments or deficiency in maize (Zea mays L.), one of the world's most important staple foods and livestock feeds, can significantly affect many people's diets, as Se is essential though harmful in excess. In particular, Se-rich maize seems to have been one of the factors that led to an outbreak of selenosis in the 1980s in Naore Valley in Ziyang County, China. Thus, this region's geological and pedological enrichment offers some insight into the behavior of Se in naturally Se-rich crops. This study examined total Se and Se species in the grains, leaves, stalks, and roots of 11 maize plant samples, Se fractions of soils around the rhizosphere, and representative parent rock materials from Naore Valley. The results showed that total Se concentrations in the collected samples were observed in descending order of soil > leaf > root > grain > stalk. The predominant Se species detected in maize plants was SeMet. Inorganic Se forms, mainly Se(VI), decreased from root to grain, and were possibly assimilated into organic forms. Se(IV) was barely present. The natural increases of Se concentration in soils mainly affected leaf and root dry-weight biomasses of maize. In addition, Se distribution in soils markedly correlated with the weathered Se-rich bedrocks. The analyzed soils had lower Se bioavailability than rocks, with Se accumulated predominantly as recalcitrant residual Se. Thus, the maize plants grown in these natural Se-rich soils may uptake Se mainly from the oxidation and leaching of the remaining organic-sulfide-bound Se fractions. A viewpoint shift from natural Se-rich soils as menaces to possibilities for growing Se-rich agricultural products is also discussed in this study.

Iron plaque effects on selenium and cadmium stabilization in Cd-contaminated seleniferous rice seedlings.

Dietary intake of selenium (Se)-enriched rice has benefit for avoiding Se-deficient disease, but there is a risk of excessive cadmium (Cd) intake. Through hydroponic culture and adsorption-desorption experiments, this paper focused on Se and Cd uptake in rice seedlings associated with the interactive effects of Se (Se4+ or Se6+), Cd, and iron (Fe) plaque. The formation of Fe plaque was promoted by Fe2+ and inhibited by Cd but not related with Se species. Shoot Se (Se4+ or Se6+) uptake was not affected by Fe plaque in most treatments, except that shoot Se concentrations were decreased by Fe plaque when Se4+ and Cd co-exposure. Shoot Cd concentrations were always inhibited by Fe plaque, regardless of Se species. Inhibiting Cd adsorption onto root surface (Se4+  + Cd) or increased Cd retention in Fe plaque (Se6+  + Cd) is an important mechanism for Fe plaque to reduce Cd uptake by rice. However, we found that DCB Cd concentrations (Cd adsorbed by Fe plaque) were not always positively correlated with Fe plaque amounts and always negatively correlated with the distribution ratios of Cd mass in root to that in Fe plaque (abbreviated as DRCMRF; r = - 0.942**); meanwhile, with the increase of DCB Fe concentration, the directions of variations of DCB Cd concentration and DRCMRF were affected by Se species. It indicated that the root system is also an important factor to affect DCB Cd concentration and inhibit Cd uptake, which is mediated by Se species. This paper provides a new understanding of Fe plaque-mediated interactive effect of Se and Cd uptakes in rice, which is beneficial for the remediation of Cd-contaminated and Cd-contaminated seleniferous areas.

Willingness of Caregivers to Have Their Children Vaccinated with Pneumococcal Vaccines in the Context of an Innovative Immunization Strategy - Weifang City, Shandong Province, 2021.

What is already known about this topic?: Pneumococcal diseases (PDs) pose a serious health threat to children. Vaccination is the most cost-effective intervention to prevent PDs, but pneumococcal vaccines coverage among children is low in China. What is added by this report?: This study investigated the willingness of children's caregivers to have their children vaccinated with pneumococcal vaccines under an innovative policy to offer 1-dose of the 13-valent pneumococcal conjugate vaccines at no charge to families. The research found that 70.51% of caregivers were willing to have their infants receive pneumococcal vaccines and that reducing the cost of vaccines may increase caregivers' willingness. What are the implications for public health practice?: This is the first evaluation in China of acceptance of pneumococcal vaccines among children under a 1-dose, cost-free policy. The results provide scientific evidence for updating local and national pneumococcal immunization strategies to promote the use of the pneumococcal vaccine.

Synergistic inhibitory effect of selenium, iron, and humic acid on cadmium uptake in rice (Oryza sativa L.) seedlings in hydroponic culture.

Selenium (Se), iron (Fe), and humic acid (HA) are beneficial fertilizers that inhibit cadmium (Cd) uptake in crops and are crucial for agricultural yields as well as human health. However, the joined effect of Se, Fe, and HA on Cd uptake in rice are still poorly understood. Therefore, a hydroponic culture experiment was established to evaluate the combined effect of Se (Se4+ or Se6+), Fe, and HA on the biomass, Cd uptake, and Cd translocation of/in rice seedlings. Compared to Se6+ application, Se4+ application in most treatments resulted in lower Cd translocations from roots to shoots, leading to a significant decrease in shoot Cd concentrations. Compared to the treatments with Se4+ or Fe2+ application, joined application of Se4+ and Fe2+ inhibited Cd uptake in shoots by decreasing Cd adsorption onto (iron plaque) and uptake by roots, and alleviating Cd translocation from root to shoot. Compared to the treatments with Se6+ or Fe2+ application, joined application of Se6+ and Fe2+ inhibited Cd uptake in shoots by sequestering (retaining) Cd onto root surface (iron plaque). HA inhibited Cd uptake in all treatments by decreasing the bioavailability of Cd in the nutrient solution through complexation. The simultaneous application of Se, Fe, and HA decreased the shoot Cd concentrations the most, followed by the combined application of two fertilizers and their individual application; the mean shoot Cd concentration in the Fe-SeIV-HA2 treatment was the lowest among all the treatments, at only 11.39 % of those in the control treatments. The 3-way ANOVA results indicated that the Cd concentrations in shoots were significantly affected by Se, Fe, HA, and certain of their interactions (Fe×Se and Se×HA) (p< 0.05). The above findings suggest that the joined application of Se, Fe, and HA ameliorated Cd uptake mainly by inhibiting Cd adsorption onto (iron plaque) and uptake by roots and the translocation from roots to shoots (Fe×Se4+), retaining (sequestering) Cd in iron plaque (Fe×Se6+), and decreasing Cd availability in nutrient solution (HA).

Heavy metal pollution caused by cyanide gold leaching: a case study of gold tailings in central China.

It is known that the tailings of gold mines have brought serious heavy metal pollution; however, the heavy metal pollution caused by gold tailings in specific geological environments and extraction processes still must be studied. This study investigated the distribution, speciation, bioaccumulation, and pollution of heavy metals in soils from the Yueliangbao gold tailings area in central China, where gold was extracted by cyanidation. The results show that the concentrations of Cu, Pb, Zn, Mn, Mo, and Cd in the soils of the tailings pond were higher than those in the local background. The concentrations of heavy metals related to mineralization activities, such as Cu, Pb, Zn, and Mo, varied with the distance to the tailings pond center. There was a decreasing trend of tailings pond center > tailings pond entrance > surrounding environment. This study's gold tailings pond differed from those of other regions because of its high content of unextracted Cu remaining in the pond. The proportion of non-residual Cu in the tailing pond soil was much higher than that of residual Cu, indicating it was likely to migrate to the surrounding environment. The pollution assessment indicated that the tailings pond soils were heavily polluted by Cu, and the level of heavy metal pollution in soils was positively correlated with the distance to the tailings pond center. Consequently, this tailings pond may become a source of Cu pollution in the surrounding environment, thus endangering environmental safety and human health. The study of heavy metal concentrations in the dominant plants showed that Chinese brake (Pteris vittata L.), Ramose scouring rush (Equisetum ramosissimum), and Manyflower silvergrass (Miscanthus floridulus) had the potential to be used for the phytostabilization of Cu.

MicroRNA-1246 regulates proliferation, invasion, and differentiation in human vascular smooth muscle cells by targeting cystic fibrosis transmembrane conductance regulator (CFTR).

MicroRNA (miRNA) plays a key role in the proliferation and invasion of vascular smooth muscle cells (VSMCs). However, the role and underlying mechanism of miRNAs in VSMCs are not fully understood. Therefore, this study was designed to investigate the role and mechanism of microRNA-1246 (miR-1246) in VSMCs. VSMCs were cultured, and the proliferation of VSMCs was stimulated by platelet-derived growth factor (PDGF-BB) or 15% fetal bovine serum (FBS). The quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression levels of miR-1246 and cystic fibrosis transmembrane conductance regulator (CFTR) in VSMCs. The CCK-8 assay and transwell assay were used to detect the proliferation and invasion of VSMCs. Target gene prediction and screening and luciferase reporter assays were used to verify downstream target genes of miR-1246. Western blotting was used to detect the protein expression levels of PCNA, α-SMA, SM-MHC, Collagen-1, and Cyclin D1 in VSMCs. PDGF-BB and FBS treatment induced VSMCs proliferation and the upregulation of miR-1246 expression. Overexpression of miR-1246 promoted VSMCs proliferation, invasion, and differentiation towards synthetic phenotype, while knockdown of miR-1246 had opposite effects. In addition, CFTR was found to be a direct target for miR-1246, and miR-1246 inhibited the expression of CFTR. Moreover, overexpression of CFTR inhibited VSMC proliferation and synthetic differentiation, while overexpression of miR-1246 partly abolished the effects of CFTR overexpression on VSMCs proliferation and differentiation. Our data suggest that MiR-1246 promotes VSMC proliferation, invasion, and differentiation to synthetic phenotype by regulating CFTR. MiR-1246 may be a potential therapeutic target for atherosclerosis.

Immunogenicity of three sequential schedules with Sabin inactivated poliovirus vaccine and bivalent oral poliovirus vaccine in Zhejiang, China: an open-label, randomised, controlled trial.

BACKGROUND: The globally synchronised introduction of inactivated poliovirus vaccine (IPV) and replacement of trivalent oral poliovirus vaccine (OPV) with bivalent OPV (bOPV) were successfully implemented in China's routine immunisation programme in May, 2016. In response to the global shortage of Salk-strain IPV, Sabin-strain IPV production was encouraged to develop and use in low-income and middle-income countries. We assessed the immunogenicity of the current routine poliovirus vaccination schedule in China and compared it with alternative schedules that use Sabin-strain IPV (sIPV) and bOPV. METHODS: This open-label, randomised, controlled trial recruited healthy infants aged 60-75 days from two centres in Zhejiang, China. Eligible infants were full-term, due for their first polio vaccination, weighed more than 2·5 kg at birth, were healthy on physical examination with no obvious medical conditions, and had no contraindications to vaccination. Infants were randomly assigned (1:1:1) using permuted block randomisation (block size of 12) to one of three polio vaccination schedules, with the first, second, and third doses given at ages 2 months, 3 months, and 4 months, respectively: sIPV-bOPV-bOPV (1sIPV+2bOPV group; current regimen), sIPV-sIPV-bOPV (2sIPV+1bOPV group), or sIPV-sIPV-sIPV (3sIPV group). The primary endpoint was the proportion of infants with seroconversion to each of the three poliovirus serotypes 1 month after the third dose. Serious and medically important adverse events were monitored for up to 30 days after each vaccination. We assessed immunity in the per-protocol population (all children who completed all three vaccinations and had pre-vaccination and post-vaccination laboratory data) and safety in all children who received at least one dose of study vaccine. This trial is registered with Clinicaltrials.gov, NCT03147560. RESULTS: Between May 1, 2016, and Dec 1, 2017, we enrolled and randomly assigned 528 eligible infants to one of the three treatment groups (176 in each group); 473 infants (158 in the 1sIPV+2bOPV group, 152 in the 2sIPV+1bOPV group, and 163 in the 3sIPV group) were included in the per-protocol population. 100% seroconversion against poliovirus types 1 and 3 was observed in all three groups. Infants who received an immunisation schedule containing bOPV had significantly higher antibody titres against poliovirus types 1 and 3 than did the sIPV-only group (2048 in all three treatment groups; p<0·0001). Seroconversion against type 2 poliovirus was observed in 98 (62%) infants in the 1sIPV+2bOPV group, 145 (95%) infants in the 2sIPV+1bOPV group, and 161 (99%) infants in the 3sIPV group. No serious adverse events occurred during the study; 14 minor, transient adverse events were observed, with no significant differences across study groups. INTERPRETATION: All three study schedules were well tolerated and highly immunogenic against poliovirus types 1 and 3. Schedules containing two or three sIPV doses had higher seroconversion rates against poliovirus type 2 than did the schedule with a single dose of sIPV. Our findings support inclusion of two sIPV doses in the routine poliovirus vaccination schedule in China to provide better protection against poliovirus type 2 than provided by the current regimen. FUNDING: Chinese Center for Disease Control and Prevention and China National Biotec Group Company.

Cost-effectiveness of augmenting universal hepatitis B vaccination with immunoglobulin treatment: a case study in Zhejiang Province, East China.

Objective: To evaluate the cost-effectiveness of the current strategy combining universal vaccination with hepatitis B immunoglobulin (HBIG) treatment for infants of hepatitis B surface antigen (HBsAg) positive mothers compared with universal vaccination with hepatitis B vaccine only.Methods: A decision tree model with a Markov process was constructed and used to simulate the lifetime of the birth cohort in Zhejiang Province during 2016. The current strategy was compared against universal vaccination with respect to costs and health effects. Costs were assessed from the health care system perspective. Health effects were measured by the number of hepatitis B virus (HBV) related diseases and deaths avoided and quality-adjusted life-years (QALYs) gained. The incremental cost­effectiveness ratio (ICER) is calculated and compared to standard willingness-to-pay thresholds. A one-way sensitivity analysis and a probabilistic sensitivity analysis (PSA) were performed to assess parameter uncertainties.Results: Over the cohort's lifetime, 182 acute symptomatic infections, 2215 chronic infections, 872 cases of cirrhosis, 595 cases of hepatocellular carcinoma (HCC) and 1,350 HBV-related deaths among the cohort of 624,000 infants would be further avoided by the current strategy compared to universal vaccination. Universal vaccination was dominated by the current strategy that produced not only higher total QALYs, but also had lower costs. The results remained robust over a wide range of assumptions.Conclusions: The current strategy was cost saving compared to universal vaccination, and continuing the current strategy is recommended to further decrease the burden of hepatitis B.

Quantitative Analysis of Iron and Silicon Concentrations in Iron Ore Concentrate Using Portable X-ray Fluorescence (XRF).

As a technique capable of rapid, nondestructive, and multi-elemental analysis, portable X-ray fluorescence (pXRF) has applications to mineral exploration, environmental evaluation, and archaeological analysis. However, few applications have been conducted in the smelting industry especially when analyzing the metal concentration in ore concentrate samples. This research analyzed the effectiveness of using pXRF in determining the metal concentration in Fe concentrate. For this proof of concept study, Fe ore samples dominated by Fe and Si were collected from the Northeastern University Mineral Processing Laboratory (Shenyang, China) and directly analyzed using pXRF, laboratory-based XRF, and titration methods. The compactness (density) of the ore concentrate was found to have very little effect on pXRF readings. The pXRF readings for Fe and Si were comparative to laboratory-based XRF results. Based on the strong correlations between the pXRF and XRF results (Fe: R2 > 0.99, Si: R2 > 0.96), linear calibrations were adopted to improve the accuracy of pXRF readings. Linear regression equations derived from the relations between XRF results and pXRF results of 21 Fe ore concentrate samples were used to calibrate the pXRF, and then validation was performed on five additional samples. Results from this preliminary study suggest that ordinary least squares (OLS) regression improves the accuracy dramatically, especially for Fe with relative errors (REs) decreasing to 0.03%-3.27% from 4.26%-8.32%. Consequently, pXRF shows strong promise for rapid, quantitative analysis of Fe concentration in Fe ore concentrate. Based on the results obtained in this study, a larger, more comprehensive study is warranted to confirm the results obtained.

Study on factors associated with seroprotection after measles vaccination in children of 6-14 years in Eastern China.

Measles cases have occurred in individuals with histories of vaccination against the disease in Zhejiang Province, China. The purposes of this study were to determine the seroprevalence of immunoglobulin G (IgG) measles antibodies in vaccinated individuals, to explore the waning kinetics of measles antibody among children after receipt of a measles-containing vaccine, and to define high-risk groups in the population. A seroprevalence survey of measles antibody was conducted with 1900 randomly selected and age-stratified participants aged 6-14 years in Zhejiang province. In our study, seronegative persons accounted for 7.17% of study participants. A case-control study of participants who had received at least one dose of measles-containing vaccine was conducted, with 123 cases of immune failure and 1593 controls with immune success. Multivariate logistic regression analysis showed that age, and number of doses were the influencing factors for measles immunization failure. The older a participant (odds ratio [OR] = 1.164), the more likely that measles vaccine immunity failed. In addition, immune failure was more likely to occur after one dose of MCV than two doses (OR = 0.008) or three doses and more (OR = 0.047). In a univariate logistic regression analysis, we found that immune failure was more likely to occur with MCV vaccination beginning at 8 months than at 9-11 months (OR = 0.562) and the subjects whose registration residence was in other cities in Zhejiang province (OR = 3.527). However, these differences in seropositivity were not significant in the multivariate logistic regression analysis. The exponential regression equation of the attenuation model after measles immunization was y = 884.64e-0.057x (R2 = 0.0521, p < 0.001), and results showed that the measles geometric mean concentration of IgG antibodies was approximately 884.64 mIU/ml after the last MCV vaccination and decreased with time since last vaccination.

Eight Elements in Soils from a Typical Light Industrial City, China: Spatial Distribution, Ecological Assessment, and the Source Apportionment.

Contamination with the eight elements, Hg, As, Cr, Cu, Ni, Pb, Zn, and Cd, is a serious concern in Zhongshan, which is a typical light industrial city, China. 60 surface soil samples were collected to investigate the concentrations, spatial distribution, human health risk, and sources of these elements in the soils in Zhongshan. The concentrations of the eight elements were analyzed while using ordinary kriging analysis, pollution load index (PLI), potential ecological risk index (RI), human health risk, correlation analysis, and factor analysis. The mean concentrations of the tested elements, excluding Pb and As, were higher than the soil background values in the Pearl River Delta. The spatial distribution of the tested elements revealed a zonal distribution pattern and high values in several areas. The mean PLI and RI indicated slight and moderate risk levels. Health risk assessment demonstrates that both children and adults were more exposed to Cu than to Cr, As, and Cd. However, the associated carcinogenic risk is acceptable. Hg that originated from human activities; As, Cr, Cu, Ni, and Cd originated from industrial activities; and, Pb and Zn originated from transportation activities. Cd was the main pollutant in the study area and it was present at higher concentrations when compared with those of the other elements. Therefore, Zhongshan should encourage enterprises to conduct industrial transformation to control the ecological risk.

Iron-dependent histone 3 lysine 9 demethylation controls B cell proliferation and humoral immune responses.

Trace elements play important roles in human health, but little is known about their functions in humoral immunity. Here, we show an important role for iron in inducing cyclin E and B cell proliferation. We find that iron-deficient individuals exhibit a significantly reduced antibody response to the measles vaccine when compared to iron-normal controls. Mice with iron deficiency also exhibit attenuated T-dependent or T-independent antigen-specific antibody responses. We show that iron is essential for B cell proliferation; both iron deficiency and α-ketoglutarate inhibition could suppress cyclin E1 induction and S phase entry of B cells upon activation. Finally, we demonstrate that three demethylases, KDM2B, KDM3B and KDM4C, are responsible for histone 3 lysine 9 (H3K9) demethylation at the cyclin E1 promoter, cyclin E1 induction and B cell proliferation. Thus, our data reveal a crucial role of H3K9 demethylation in B cell proliferation, and the importance of iron in humoral immunity.

An economic evaluation of the current measles vaccination program: A case study in Zhejiang Province, east China.

OBJECTIVE: To evaluate the economic impact of the current measles vaccination program in Zhejiang Province, east China. METHODS: A decision tree-Markov model with parameters from published literatures, government documents and surveys was developed and used to simulate over 40 years of a birth cohort in Zhejiang Province during the year 2014. The expected cost and effectiveness of the current measles vaccination program was compared against no vaccination. Costs were assessed from the payer's perspective. Benefits were defined as savings on the direct cost of measles treatment, and the effectiveness was measured according to the number of measles cases and deaths averted. The net present value (NPV), benefit-cost ratio (BCR) and incremental cost-effectiveness ratio (ICER) were also calculated. A threshold for cost-effectiveness of less than 3 times the Gross Domestic Product (GDP) per capita was used. One-way sensitivity analysis was performed to assess parameter uncertainties. RESULTS: The total vaccination cost was estimated to be $2.52 million. The BCR of the current measles program was found to be 6.06 with a NPV of $73.38 million. It was also calculated that a total of 195,165 measles cases and 191 measles-related deaths would be prevented by vaccination. The ICER was approximately $12.91 per case averted and $13,213.43 per death averted, respectively, which was cost-effective. The models were proven to be robust. CONCLUSIONS: The current measles vaccination program appeared to be cost-effective and to offer substantial benefits. The results of this analysis sought to contribute to the justification of future investments to achieve the goal of measles elimination.

Economic burden and associated factors of measles patients in Zhejiang Province, China.

This study aimed to figure out the economic burden of measles patients and explore the associated factors for total cost in measles cases that occurred in the year 2015 from Jiaxing, Jinhua, and Taizhou cities in Zhejiang Province, China. Direct interviews were conducted to collect information on patient expenses during treatment, including outpatient expenses, hospitalization expenses, self-treatment fees, productivity loss, and transportation fees. Descriptive epidemiological methods and chi-square tests were used to assess the direct and indirect cost of measles patients. Ordinal logistic regression was applied to explore the possible factors contributing to cost. A total of 136 measles cases were investigated and the average direct cost, indirect cost, and total cost were #747.14, #520.12, and #1,267.26, respectively. Direct cost accounted for 58.96% of the total cost, which was significantly higher than the indirect cost (P < 0.001). In 2015, 1,386 confirmed cases were reported in the Zhejiang Province, and the overall direct, indirect, and total economic burden reached #1.04 million, #0.72 million, and #1.76 million, respectively. Quality-adjusted life years for measles patient were calculated to be 76.06 in Zhejiang, 2015. Hospitalization, occupation, complication, disease duration, age, and site had a significant influence on the total cost according to ordinal logistic regression, with the maximum contribution from hospitalization. Measles resulted in heavy economic burdens, and local public health departments or community health service centers should spare no effort to maintain a high rate of vaccination coverage and protect susceptible populations.

Immunogenicity and safety of measles-rubella vaccine co-administered with attenuated Japanese encephalitis SA 14-14-2 vaccine in infants aged 8 months in China: a non-inferiority randomised controlled trial.

BACKGROUND: In China, measles-rubella vaccine and live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) are recommended for simultaneous administration at 8 months of age, which is the youngest recommended age for these vaccines worldwide. We aimed to assess the effect of the co-administration of these vaccines at 8 months of age on the immunogenicity of measles-rubella vaccine. METHODS: We did a multicentre, open-label, non-inferiority, two-group randomised controlled trial in eight counties or districts in China. We recruited healthy infants aged 8 months who had received all scheduled vaccinations according to the national immunisation recommendations and who lived in the county of the study site. Enrolled infants were randomly assigned (1:1) to receive either measles-rubella vaccine and LJEV simultaneously (measles-rubella plus LJEV group) or measles-rubella vaccine alone (measles-rubella group). The primary outcome was the proportion of infants with IgG antibody seroconversion for measles 6 weeks after vaccination, and a secondary outcome was the proportion of infants with IgG antibody seroconversion for rubella 6 weeks after vaccination. Analyses included all infants who completed the study. We used a 5% margin to establish non-inferiority. This trial was registered at ClinicalTrials.gov (NCT02643433). FINDINGS: 1173 infants were assessed for eligibility between Aug 13, 2015, and June 10, 2016. Of 1093 (93%) enrolled infants, 545 were randomly assigned to the measles-rubella plus LJEV group and 548 to the measles-rubella group. Of the infants assigned to each group, 507 in the measles-rubella plus LJEV group and 506 in the measles-rubella group completed the study. Before vaccination, six (1%) of 507 infants in the measles-rubella plus LJEV group and one (<1%) of 506 in the measles-rubella group were seropositive for measles; eight (2%) infants in the measles-rubella plus LJEV group and two (<1%) in the measles-rubella group were seropositive for rubella. 6 weeks after vaccination, measles seroconversion in the measles-rubella plus LJEV group (496 [98%] of 507) was non-inferior to that in the measles-rubella group (499 [99%] of 506; difference -0·8% [90% CI -2·6 to 1·1]) and rubella seroconversion in the measles-rubella plus LJEV group (478 [94%] of 507) was non-inferior to that in the measles-rubella group (473 [94%] of 506 infants; difference 0·8% [90% CI -1·8 to 3·4]). There were no serious adverse events in either group and no evidence of a difference between the two groups in the prevalence of any local adverse event (redness, rashes, and pain) or systemic adverse event (fever, allergy, respiratory infections, diarrhoea, and vomiting). Fever was the most common adverse event (97 [19%] of 507 infants in the measles-rubella plus LJEV group; 108 [21%] of 506 infants in the measles-rubella group). INTERPRETATION: The evidence of similar seroconversion and safety with co-administered LJEV and measles-rubella vaccines supports the co-administration of these vaccines to infants aged 8 months. These results will be important for measles and rubella elimination and the expansion of Japanese encephalitis vaccination in countries where it is endemic. FUNDING: US Centers for Disease Control and Prevention, US Department of Health and Human Services; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases.

Kriging methods with auxiliary nighttime lights data to detect potentially toxic metals concentrations in soil.

The spatial distribution of potentially toxic metals (PTMs) has been shown to be related to anthropogenic activities. Several auxiliary variables, such as those related to remote sensing data (e.g. digital elevation models, land use, and enhanced vegetation index) and soil properties (e.g. pH, soil type and cation exchange capacity), have been used to predict the spatial distribution of soil PTMs. However, these variables are mostly focused on natural processes or a single aspect of anthropogenic activities and cannot reflect the effects of integrated anthropogenic activities. Nighttime lights (NTL) images, a representative variable of integrated anthropogenic activities, may have the potential to reflect PTMs distribution. To uncover this relationship and determine the effects on evaluation precision, the NTL was employed as an auxiliary variable to map the distribution of PTMs in the United Kingdom. In this study, areas with a digital number (DN) ≥ 50 and an area > 30 km2 were extracted from NTL images to represent regions of high-frequency anthropogenic activities. Subsequently, the distance between the sampling points and the nearest extracted area was calculated. Barium, lead, zinc, copper, and nickel concentrations exhibited the highest correlation with this distance. Their concentrations were mapped using distance as an auxiliary variable through three different kriging methods, i.e., ordinary kriging (OK), cokriging (CK), and regression kriging (RK). The accuracy of the predictions was evaluated using the leave-one-out cross validation method. Regardless of the elements, CK and RK always exhibited lower mean absolute error and root mean square error, in contrast to OK. This indicates that using the NTL as the auxiliary variable indeed enhanced the prediction accuracy for the relevant PTMs. Additionally, RK showed superior results in most cases. Hence, we recommend RK for prediction of PTMs when using the NTL as the auxiliary variable.