A multicenter study of fetal chromosomal abnormalities in Chinese women of advanced maternal age

AbstractObjectiveThis study aimed to determine the rates of different fetal chromosomal abnormalities among women of advanced maternal age in China and to discuss the possible misdiagnosis risks of newer molecular techniques, for selection of appropriate prenatal screening and diagnostic technologies.Materials and MethodsSecond trimester amniocentesis and fetal karyotype results of 46,258 women were retrospectively reviewed. All women were ≥ 35 years old with singleton pregnancies. The rates of clinically significant chromosomal abnormalities (CSCAs), incidence of chromosomal abnormalities, and correlations with age were determined.ResultsFrom 2001 to 2010, the proportion of women of advanced maternal age undergoing prenatal diagnosis increased from 20% to 46%. The mean age was 37.4 years (range, 35–46 years). A total of 708 cases of CSCAs, with a rate of 1.53% were found. Trisomy 21 was the most common single chromosome abnormality and accounted for 55.9% of all CSCAs with an incidence of 0.86%. Trisomy 13, trisomy 18, and trisomy 21, the most common chromosome autosomal aneuploidies, accounted for 73.6% of all CSCAs, with a rate of 1.13%. As a group, the most common chromosomal aneuploidies (13/18/21/X/Y) accounted for 93.9% of all abnormalities, with a rate of 1.44%. The incidence of trisomy 21, trisomy 13/18/21 as a group, and 13/18/21/X/Y as a group was significantly greater in women aged 39 years and older (p < 0.001), but was not different between women aged 35 years, 36 years, 37 years, and 38 years.ConclusionThese findings may assist in genetic counseling of advanced maternal age pregnant women, and provide a basis for the selection of prenatal screening and diagnostic technologies

A multimechanistic antibody targeting receptor-binding sites potently cross-protects against influenza B viruses

流感病毒HA是研制流感药物和流感疫苗的重要靶标，但HA具有高度变异性，如何在高变异HA中找到不变之处，即高度保守表位，是研制流感特效药物和广谱疫苗的关键。近年来国外报道的流感HA广谱中和单抗的识别位点均在较为保守的HA茎部区，而针对流感病毒与细胞受体结合部位的HA头部区尤其是RBS区，一直未能发现广谱中和抗体。夏宁邵教授团队通过探索多种免疫策略和筛选策略，成功筛选出一株广谱中和单抗12G6，识别一个位于HA头部RBS上的全新保守性表位。体外实验显示12G6人源化改造的C12G6抗体能高效中和1940-2016年间世界各地历年流行的代表三个遗传变异亚系的18个乙型流感病毒代表株对细胞的感染，并能保护小鼠致死性感染，治疗效果显著优于已报道的代表性抗体以及抗流感药物；C12G6与“达菲”联合用药具有明显的协同效果。此外，雪貂感染模型的预防和治疗效果进一步证实了C12G6作为抗体药物的治疗潜能。研究还显示该表位是病毒感染复制的关键表位，该位点的突变会造成病毒毒力显著下降。最后，研究揭示了C12G6通过五种不同的抗病毒作用机制发挥作用，提示其高效的抗病毒活性得益于多机制协同效应，这也是目前国内外第一次发现一个流感抗体能通过如此全面的抗病毒机制发挥作用。 该发现为研制能抵抗各种变异株的乙型流感特效治疗药物和通用疫苗带来新希望。 该研究工作依托分子疫苗学和分子诊断学国家重点实验室（厦门大学）、国家传染病诊断试剂与疫苗工程技术研究中心、厦门大学养生堂生物药物联合实验室完成。陈毅歆副教授、夏宁邵教授为该研究论文的共同通讯作者。在读博士研究生沈晨光、陈俊煜、李睿、王国松和硕士研究生张梦娅等为共同第一作者。【Abstract】Influenza B virus causes considerable disease burden worldwide annually, highlighting the limitations of current influenza vaccines and antiviral drugs. In recent years, broadly neutralizing antibodies (bnAbs) against hemagglutinin (HA) have emerged as a new approach for combating influenza. We describe the generation and characterization of a chimeric monoclonal antibody, C12G6, that cross-neutralizes representative viruses spanning the 76 years of influenza B antigenic evolution since 1940, including viruses belonging to the Yamagata, Victoria, and earlier lineages. Notably, C12G6 exhibits broad cross-lineage hemagglutination inhibition activity against influenza B viruses and has higher potency and breadth of neutralization when compared to four previously reported influenza B bnAbs. In vivo, C12G6 confers stronger cross-protection against Yamagata and Victoria lineages of influenza B viruses in mice and ferrets than other bnAbs or the anti-influenza drug oseltamivir and has an additive antiviral effect when administered in combination with oseltamivir. Epitope mapping indicated that C12G6 targets a conserved epitope that overlaps with the receptor binding site in the HA region of influenza B virus, indicating why it neutralizes virus so potently. Mechanistic analyses revealed that C12G6 inhibits influenza B viruses via multiple mechanisms, including preventing viral entry, egress, and HA-mediated membrane fusion and triggering antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity responses. C12G6 is therefore a promising candidate for the development of prophylactics or therapeutics against influenza B infection and may inform the design of a truly universal influenza vaccine.This research was supported by grants from the National Natural Science Foundation of China (31670934 and 81371817), the Ministry of Science and Technology of the People’s Republic of China (2011ZX09102-009-12 and 2012DFH30020), the Research Grants Council of the Hong Kong Special Administrative Region (7629/13M, 17103214, and 17154516), and a sponsored research agreement from Sanofi Pasteur. 研究工作得到了香港大学新发传染病国家重点实验室和赛诺菲巴斯德公司的技术支持和帮助，获得国家自然科学基金、新药创制国家科技重大专项、科技部对港科技合作项目等课题资助

Nutrient Status of Vitamin D among Chinese Children

Background: Vitamin D deficiency is considered to be a public health problem. However, the nutrient status of vitamin D in Chinese children is unclear. The aim of this study was to describe the vitamin D status among children aged under 18 years in southeast China. Methods: Children who visited the Huzhou Maternal and Child Care Hospital from January 2012 to August 2015 were included in this large cross-sectional study. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured by electrochemiluminescence immunoassay. Vitamin D status was defined as deficiency (25(OH)D &lt; 20 ng/mL), insufficiency (25(OH)D: 20–29 ng/mL) and sufficiency (25(OH)D ≥ 30 ng/mL). The association between relevant variables and vitamin D status was analyzed by a using generalized estimated equation model and a multivariate regression model. Results: 13,997 children aged under 18 years were included. Of these, 23.3% children suffered from low vitamin D status (deficiency and insufficiency), while 76.7% had a sufficient vitamin D status. The prevalence of low vitamin D status was 29.7% in winter and 23.4% in spring, which was higher than that in summer (21.4%) and autumn (19.9%). Clinical visiting children (32.1%) suffered more from low vitamin D than health examination children (17.6%). Additionally, age and season were independently and significantly associated with 25(OH)D concentrations, respectively. Conclusions: The deficiency and insufficiency status of vitamin D was very common among newborns and children aged one to 17 years. This indicates that more sunshine and vitamin D–fortified foods are necessary among Chinese children

Are there sufficient Landsat observations for retrospective and continuous monitoring of land cover changes in China?

Unprecedented human-induced land cover changes happened in China after the Reform and Opening-up in 1978, matching with the era of Landsat satellite series. However, it is still unknown whether Landsat data can effectively support retrospective analysis of land cover changes in China over the past four decades. Here, for the first time, we conduct a systematic investigation on the availability of Landsat data in China, targeting its application for retrospective and continuous monitoring of land cover changes. The latter is significant to assess impact of land cover changes, and consequences of past land policy and management interventions. The total and valid observations (excluding clouds, cloud shadows, and terrain shadows) from Landsat 5/7/8 from 1984 to 2017 were quantified at pixel scale, based on the cloud computing platform Google Earth Engine (GEE). The results show higher intensity of Landsat observation in the northern part of China as compared to the southern part. The study provides an overall picture of Landsat observations suitable for satellite-based annual land cover monitoring over the entire country. We uncover that two sub-regions of China (i.e., Northeast China-Inner Mongolia-Northwest China, and North China Plain) have sufficient valid observations for retrospective analysis of land cover over 30 years (1987-2017) at an annual interval; whereas the Middle-Lower Yangtze Plain (MLYP) and Xinjiang (XJ) have sufficient observations for annual analyses for the periods 1989-2017 and 2004-2017, respectively. Retrospective analysis of land cover is possible only at a two-year time interval in South China (SC) for the years 1988-2017, Xinjiang (XJ) for the period 1992-2003, and the Tibetan Plateau (TP) during 2004-2017. For the latter geographic regions, land cover dynamics can be analyzed only at a three-year interval prior to 2004. Our retrospective analysis suggest that Landsat-based analysis of land cover dynamics at an annual interval for the whole country is not feasible; instead, national monitoring at two- or three-year intervals could be achievable. This study provides a preliminary assessment of data availability, targeting future continuous land cover monitoring in China; and the code is released to the public to facilitate similar data inventory in other regions of the world

Accuracy Assessment and Inter-Comparison of Eight Medium Resolution Forest Products on the Loess Plateau, China

Forests play an important role in maintaining ecosystem services, especially in ecologically fragile areas such as the Loess Plateau (LP) in China. However, there is still great uncertainty in the spatial extent and distribution of forests in such a fragmented region. In order to examine the advantages and disadvantages of existing forest mapping products, we conducted a thorough accuracy assessment on the eight recent, medium resolution (30–50 m) products by using the LP in 2010 as the region of interest. These mapping products include Landsat and/or PALSAR images (including the forest products from GlobeLand30), FROM-GLC, Hansen, ChinaCover, NLCD-China, GLCF VCF, OU-FDL, and JAXA. The same validation data were used to assess and rank the accuracy of each product. Additionally, the spatial consistency of the different forest products and their dependence on the terrain were analyzed. The results showed that the overall accuracies of the eight forest products on the LP in 2010 were between 0.93 ± 0.003 and 0.97 ± 0.002 with a 95% confidence interval, and GlobeLand30 presented the highest overall accuracy (0.97 ± 0.002). Among them, the PALSAR-based products (OU-FDL and JAXA) indicated relatively high accuracies, while the six Landsat-based products showed a large diversity in the accuracy. According to the eight products, the total estimated forest area of the LP varied from 7.627 ± 0.077 to 10.196 ± 0.1 million ha with a 95% confidence interval. We also found that the consistency in the spatial distribution of forests between these maps: 1) increased substantially with increasing elevation until 2000m, but then decreased at higher elevations, and 2) showed mild variation along increasing slope, but had a slight rate of increase. Our findings implied that future forest mapping studies should consider topographical attributes such as elevation and slope in their final products. Our results are fundamental in guiding future applications of these existing forest maps

Vaccination with Deglycosylated Modified Hemagglutinin Broadly Protects against Influenza Virus Infection in Mice and Ferrets

Recent efforts have been directed toward the development of universal influenza vaccines inducing broadly neutralizing antibodies to conserved antigenic supersites of Hemagglutinin (HA). Although several studies raise the importance of glycosylation in HA antigen design, whether this theory can be widely confirmed remains unclear; which influenza HA with an altered glycosylation profile could impact the amplitude and focus of the host immune response. Here, we evaluated the characteristics and efficacy of deglycosylated modified HA proteins, including monoglycosylated HA (HAmg), unglycosylated HA (HAug), and fully glycosylated HA (HAfg), without treatment with H3N2 Wisconsin/67/2005. Our results showed that HAug could induce a cross-strain protective immune response in mice against both H3N2 and H7N9 subtypes with better antibody-dependent cellular cytotoxicity (ADCC) than the HAmg- and HAfg-immunized groups, which suggested that highly conserved epitopes that were masked by surface glycosylation may be exposed and thus promote the induction of broad antibodies that recognize the hidden epitopes. This strategy may also supplement the direction of deglycosylated modified HA for universal influenza vaccines

Reduced graphene oxide encapsulated Cu2O with controlled crystallographic facets for enhanced visible-light photocatalytic degradation

The Cu2O/reduced graphene oxide (Cu2O/rGO) composites with effective crystallographic facet controlling of Cu2O crystals were fabricated through a simple one-step wet chemistry method. The crystallographic facet-dependent photocatalytic performance of Cu2O was confirmed, favoring the cuboctahedral Cu2O with {100} and {111} facets and a better photocatalytic activity when compared to cubic and octahedral ones. This was attributed to the slight difference of surface energy between {100} and {111} facets which served as a driving force to promote the separation of photogenerated electron-hole pairs. Moreover, the introduction of two-dimensional rGO sheets could accelerate the transfer of photogenerated electrons from Cu2O to rGO, which further promoted the separation of photogenerated electron-hole pairs and the degradation of methyl orange (MO) under visible-light irradiation. The cuboctahedral Cu2O/rGO composite exhibited a superb photocatalytic performance with the degradation percentage of MO about 97.6% after one periodic photocatalysis due to the synergistic effect of cuboctahedral Cu2O and rGO sheets, foreboding its potential application as photocatalyst