Long-term effects of nitrogen and phosphorus fertilization on profile distribution and characteristics of dissolved organic matter in fluvo-aquic soil.

Dissolved organic matter (DOM) drives numerous biogeochemical processes (e.g. carbon cycling) in agro-ecosystems and is sensitive to fertilization management. Nevertheless, changes in the quantity and quality of DOM in the vertical soil profile following long-term continuous nitrogen (N) and phosphorus (P) inputs remain unclear. In this study, the contents and optical characteristics of DOM along a 2-m soil profile were investigated using a 40-year wheat/maize rotation combined with experiments using different N and P fertilization rates in the North China Plain. The results revealed that the dissolved organic carbon (DOC) content decreased with an increase in soil depths. Compared with that in the control (no fertilization), 40-year N, P, and N + P additions increased the soil DOC content by 26%-69%, except for 270-kg N, and 67.5-kg P treatments. N + P application resulted in higher DOC contents than N-alone and P-alone applications. N, P, and N + P inputs increased or did not affect the aromaticity and hydrophobicity of DOM at 0-40 cm but reduced them from 40 to 200 cm. Compared with that in the control, N, P, and N + P inputs enhanced the content of humic acid-like substances (C1+C2+C3+C4) and decreased the content of protein-like substance (C5). C1 was the dominant component among the five DOM, representing the microbial humic component. Optical indices also indicated that soil DOM primarily originated from microbial sources. Nutrient addition accelerated transformation between complex C1 and simple C5 via promoting microbial activities. These results imply that N and P fertilizers increased the DOM content and altered its composition, thereby potentially affecting the stability of soil organic matter in the agroe-cosystems.

Effects of Microplastics on Soil Carbon Mineralization: The Crucial Role of Oxygen Dynamics and Electron Transfer.

Although our understanding of the effects of microplastics on the dynamics of soil organic matter (SOM) has considerably advanced in recent years, the fundamental mechanisms remain unclear. In this study, we examine the effects of polyethylene and poly(lactic acid) microplastics on SOM processes via mineralization incubation. Accordingly, we evaluated the changes in carbon dioxide (CO2) and methane (CH4) production. An O2 planar optical sensor was used to detect the temporal behavior of dissolved O2 during incubation to determine the microscale oxygen heterogeneity caused by microplastics. Additionally, the changes in soil dissolved organic matter (DOM) were evaluated using a combination of spectroscopic approaches and ultrahigh-resolution mass spectrometry. Microplastics increased cumulative CO2 emissions by 160-613%, whereas CH4 emissions dropped by 45-503%, which may be attributed to the oxygenated porous habitats surrounding microplastics. Conventional and biodegradable microplastics changed the quantities of soil dissolved organic carbon. In the microplastic treatments, DOM with more polar groups was detected, suggesting a higher level of electron transport. In addition, there was a positive correlation between the carbon concentration, electron-donating ability, and CO2 emission. These findings suggest that microplastics may facilitate the mineralization of SOM by modifying O2 microenvironments, DOM concentration, and DOM electron transport capability. Accordingly, this study provides new insights into the impact of microplastics on soil carbon dynamics.

Microplastic presence significantly alters soil nitrogen transformation and decreases nitrogen bioavailability under contrasting temperatures.

Plastic mulch is frequently used to increase crop yield, resulting in large quantities of residues accumulating in soil due to low recovery rates. However, the effects of microplastic residues from traditional and biodegradable plastic films on soil nitrogen (N) transformation and bioavailability are not well understood. Here, the main objectives were to examine the effects of micro-sized residues (diameter <5 mm) of polyethylene (PE) and biodegradable plastic mulch films (PLA) on the soil N in two contrasting soils (clay soil and sandy loam soil) in different temperatures (15 °C vs. 25 °C). Results showed that the microplastic presence showed a little effect on soil N transformation and bioavailability at 15 °C, but both microplastics significantly decreased NO3-, mineral N (MN), total dissolved N (TDN), the net cumulative N nitrification (Nn), and the net cumulative N mineralization (Nm) at 25 °C, indicating that microplastics decreased soil N bioavailability at elevated temperature. Meanwhile, the microplastics significantly reduced the temperature sensitivity (Q10) of N mineralization. The presence of microplastics changed the composition of soil mineral N with lower relative NO3- and higher NH4+ compared to the control in clay soil. The sandy loam soil was more susceptible to microplastic pollution compared to clay soil in N transformation, due to different textures and biochemistry properties in the two soils, which showed that microplastics have a significant soil heterogeneity-dependent effect on soil N processes. Therefore, the results underline that the effects of microplastic residues on soil N cycling can be partly linked to soil properties, suggesting the urgent need for further studies examining their impacts on soil nutrient cycling in different soil systems.

Transcriptome analysis of Brassica juncea var. tumida Tsen responses to Plasmodiophora brassicae primed by the biocontrol strain Zhihengliuella aestuarii.

Mustard clubroot, caused by Plasmodiophora brassicae, is a serious disease that affects Brassica juncea var. tumida Tsen, a mustard plant that is the raw material for a traditional fermented food manufactured in Chongqing, China. In our laboratory, we screened the antagonistic bacteria Zhihengliuella aestuarii against P. brassicae. To better understand the biocontrol mechanism, three transcriptome analyses of B. juncea var. tumida Tsen were conducted using Illumina HiSeq 4000, one from B. juncea only inoculated with P. brassicae (P), one inoculated with P. brassica and the biocontrol agent Z. aestuarii at the same time (P + B), and the other was the control (H), in which P. brassicae was replaced by sterile water. A total of 19.94 Gb was generated by Illumina HiSeq sequencing. The sequence data were de novo assembled, and 107,617 unigenes were obtained. In total, 5629 differentially expressed genes between biocontrol-treated (P + B) and infected (P) samples were assigned to 126 KEGG pathways. Using multiple testing corrections, 20 pathways were significantly enriched with Qvalue ≤ 0.05. The resistance-related genes, involved in the production of pathogenesis-related proteins, pathogen-associated molecular pattern-triggered immunity, and effector-triggered immunity signaling pathways, calcium influx, salicylic acid pathway, reactive oxygen intermediates, and mitogen-activated protein kinase cascades, and cell wall modification, were obtained. The various defense responses induced by the biocontrol strain combatted the P. brassicae infection. The genes and pathways involved in plant resistance were induced by a biocontrol strain. The transcriptome data explained the molecular mechanism of the potential biocontrol strain against P. brassicae. The data will also serve as an important public information platform to study B. juncea var. tumida Tsen and will be useful for breeding mustard plants resistant to P. brassicae.

Highly selective coextraction of rhodamine B and dibenzyl phthalate based on high-density dual-template imprinted shells on silica microparticles.

A simple one-pot approach based on molecularly imprinted polymer shells dispersed on the surface of silica for simultaneous determination of rhodamine B and dibenzyl phthalate (DBzP) has been developed. Highly dense molecularly imprinted polymer shells were formed in the mixture of acetonitrile and toluene by the copolymerization of methacrylic acid and ethylene glycol dimethacrylate, as well as two templates, rhodamine B and dibenzyl phthalate, directed by the vinyl end groups functional monolayer at surface silica microspheres after 3-methacryloxypropyl trimethoxysilane modification. The obtained imprinted polymer shells showed large average pore diameter (102.5 nm) and about 100 nm shell thickness. The imprinted particles also showed high imprinting factor (αRhB = 3.52 and αDBzP = 3.94), rapid binding kinetics, and excellent selective affinity capacity for rhodamine B and dibenzyl phthalate containing another three competitors in mixed solution. Moreover, the imprinted particles coupled with ultra high performance liquid chromatography was successfully applied to simultaneous analysis of rhodamine B and dibenzyl phthalate in two spiked beverage samples with average recoveries in the range of 88.0-93.0% for rhodamine B and 84.0-92.0% for dibenzyl phthalate with the relative standard deviation lower than 5.1%.

Microbes drive metabolism, community diversity, and interactions in response to microplastic-induced nutrient imbalance.

The impact of conventional and biodegradable microplastics on soil nutrients (carbon and nitrogen) has been widely examined, and the alteration of nutrient conditions further influences microbial biosynthesis processes. Nonetheless, the influence of microplastic-induced nutrient imbalances on soil microorganisms (from metabolism to community interactions) is still not well understood. We hypothesized that conventional and biodegradable microplastic could alter soil nutrients and microbial processes. To fill this knowledge gap, we conducted soil microcosms with polyethylene (PE, new and aged) and polylactic acid (PLA, new and aged) microplastics to evaluate their effects on the soil enzymatic stoichiometry, co-occurrence interactions, and success patterns of soil bacterial communities. New and aged PLA induced soil N immobilization, which decreased soil mineral N by 91-141 %. The biodegradation of PLA led to a higher bioavailable C and wider bioavailable C:N ratio, which further filtered out specific microbial species. Both new and aged PLA had a higher abundance of copiotrophic members (Proteobacteria, 35-51 % in PLA, 26-34 % in CK/PE treatments) and rrn copy number. The addition of PLA resulted in a lower alpha diversity and reduced network complexity. Conversely, because of the chemically stable hydrocarbon structure of PE polymers, the new and aged PE microplastics had a minor effect on soil mineral N, bacterial community composition, and network complexity, but led to microbial C limitation. Collectively, all microplastics increased soil C-, N-, and P -acquiring enzyme activities and reduced the number of keystone species and the robustness of the co-occurrence network. The PLA treatment enhanced nitrogen fixation and ureolysis, whereas the PE treatment increased the degradation of recalcitrant carbon. Overall, the alteration of soil nutrient conditions by microplastics affected the microbial metabolism and community interactions, although the effects of PE and PLA microplastics were distinct.

Alkaline ultrasonic irradiation-mediated boosted H2 production over O/N-rich porous carbon anchored Ru nanoclusters.

Developing efficient catalytic systems to boost hydrogen evolution from hydrolytic dehydrogenation of ammonia borane (AB) is of broad interest but remains a formidable challenge since the widespread usages of hydrogen have been considered as sustainable solutions to ensure future energy security. Herein, we developed an alkaline ultrasonic irradiation-mediated catalytic system with O/N-rich porous carbon supported Ru nanoclusters (NCs) (Ru/ONPC) to considerably boost the catalytic activity for hydrogen production from the hydrolytic dehydrogenation of AB. The uniformly distributed sub-2.0 nm Ru NCs on the ONPC were demonstrated to be efficient catalysts to boost hydrogen generation from the hydrolytic dehydrogenation of AB with the synergistic effect between ultrasonic irradiation and alkaline additive without any additional heating. An ultrahigh turnover frequency (TOF) of 4004 min-1 was achieved in the developed catalytic system, which was significantly higher than that of ultrasound-mediated AB hydrolysis without alkali (TOF: 485 min-1) and alkaline AB hydrolysis (TOF: 1747 min-1) without ultrasound mixing. The alkaline ultrasonic irradiation was beneficial for the cleavage of the OH bonds in the attacked H2O molecules catalyzed by the Ru/ONPC and thus considerably boost the catalytic hydrogen generation from AB. This study provides a tractable and ecofriendly pathway to promote the activity toward AB hydrolysis to release hydrogen.

Diatomasinensis: a new diatom species (Bacillariophyta) found in the brackish Lake Qinghai, China.

Lake Qinghai is an ancient brackish water lake in which several endemic diatom species have been discovered. In this study, a species of Diatoma is observed under light and scanning electron microscopy and described as new, Diatomasinensis sp. nov. The living cells of D.sinensis always lie in girdle view due to the cell depth being much larger than valve width (3.3-8.8 vs. 2.0-3.0 µm). The valves of D.sinensis are characterized by their narrow, linear-lanceolate outline, with capitate to subcapitate apices, the presence of two rimoportulae, one at each apex, embedded in the last rib or located among striae and a 4:2 configuration of girdle bands in normal vegetative cells, with four bands assigned to the epivalve and two to the hypovalve. The new taxon is compared with similar species from the genera Diatoma and Distrionella.

Microplastic additions alter soil organic matter stability and bacterial community under varying temperature in two contrasting soils.

Microplastics can accumulate in soils and strongly affect the biogeochemical cycle. Biodegradable plastic films show potential as sustainable alternatives that could reduce microplastic soil contamination and accumulation. However, the effects of traditional and biodegradable microplastics on soil organic matter (SOM) stability are not sufficiently understood, particularly under varying temperatures. The objective of this study was to examine the effects of polyethylene (PE) and biodegradable polylactic acid (PLA) microplastics on SOM stability and bacterial community in two contrasting soils (Black soil vs. Loess soil) under varying temperature conditions (15 °C vs. 25 °C). Results showed that microplastics addition significantly enhanced cumulative CO2 emissions and DOC contents, particularly 1 % PLA treatment accelerated CO2 emissions by 19 % - 74 %, DOC content by 3 % - 23 % at 25 °C. A higher temperature sensitivity (Q10) at the PLA treatment indicated that PLA is more susceptible to elevated temperature compared to PE. The presence of both PE and PLA microplastics significantly changed the DOC spectral characteristics, i.e., high temperature increased the value of the specific UV absorbance (SUVA) in soil without microplastics, while decreased it in soil with microplastics. In comparison to soil without microplastics, soil exposed to 1 % microplastics had lower MBC concentrations and greater metabolic quotient. 16S rRNA gene sequencing showed that the presence of PLA microplastic significantly alters soil bacterial community. PE and CK had similar Bray-Curtis distances between two temperatures, while PLA increased the dissimilarity between CK compared to PE. Compared to the two soils, loess soil is more sensitive to microplastics addition. Microplastics have a non-ignorable effect on soil organic matter stability, the interaction between microplastics and soil environment should be considered.

Clinical outcome, long-term survival and tolerability of sequential therapy of first-line crizotinib followed by alectinib in advanced ALK+NSCLC: A multicenter retrospective analysis in China.

BACKGROUND: There is limited data on the clinical outcome, long-term survival and tolerability of sequential therapy of first-line crizotinib followed by alectinib in a real-world setting for Chinese patients with advanced ALK+ NSCLC. METHODS: The medical records of patients who received sequential therapy with first-line crizotinib followed by alectinib (no intermittent systemic therapy was allowed between the two ALK-TKIs) were collected from six centers in China. Combined time treatment to failure (C-TTF) was defined as the period from the start of crizotinib to the complete discontinuation of alectinib due to any cause. RESULTS: A total of 61 patients were included in our study. Fifty-two patients were switched to alectinib due to disease progression, seven as a result of toxicity, and two due to patient preference. At the time of data cutoff, alectinib treatment was discontinued in 31 patients on account of disease progression while severe adverse events resulted in cessation of alectinib in another two patients. Rebiopsy was conducted in 21 patients following disease progression on alectinib in whom ALK secondary mutation was found in 13 patients. Patients with ALK secondary mutation demonstrated better PFS during treatment with subsequent ALK-TKIs compared with those without (10.4 vs. 3.1 m, p = 0.0018, HR = 0.08). With a median follow-up of 34.3 months, C-TTF was 39.2 months and estimated 5-year OS was 68.6% in the overall population. CONCLUSION: Sequential therapy with first-line crizotinib followed by alectinib demonstrated long-term benefits. Different efficacy in subsequent ALK-TKI between patients with or without ALK secondary mutation further emphasized the importance of rebiopsy to guide targeted therapy more precisely.

Alectinib as first-line treatment for advanced ALK-positive non-small cell lung cancer in the real-world setting: preliminary analysis in a Chinese cohort.

Background: Tyrosine kinase inhibitors (TKIs) have been a major advance in the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) which have been substantiated in clinical trials. However, real-world data on first-line alectinib in a Chinese patient population are limited. Methods: We enrolled patients diagnosed with advanced ALK-positive NSCLC treated with first-line alectinib at 8 centers in China, including cases with symptomatic or active CNS metastases. Continuation of alectinib was permitted after local or gradual progression at the treating clinician's discretion. Time-to-treatment failure (TTF) was defined as the period from the start of alectinib to discontinuation for any cause including disease progression, death, adverse events and patient's preference. We defined longer EML4-ALK variants as containing EML4 fusions to at least exon 13 and shorter variants had EML4 fusions up to exon 6. Results: Of the 110 patients included, 26.4% had Eastern Cooperative Oncology Group Performance Status (ECOG) ≥2 points. The objective response rate (ORR) was 88.5% [95% confidence interval (CI): 79.9-94.3%] and median tumor shrinkage rate was 60% (range, 0-100%) in patients with target lesions. For patients with measurable central nervous system (CNS) metastases, the CNS-ORR was 92.9% (95% CI: 66.1-99.8%), additionally, 80% (8/10) of patients experienced significant improvement in CNS-related symptoms following alectinib treatment. With a median follow-up of 18.3 months, the estimated 2-year progression-free survival (PFS) rate and 2-year treatment failure-free rate were 81.1% (95% CI: 71.5-87.7%) and 81.0% (95% CI: 70.6-88.0%) respectively. Grade 3-4 adverse events occurred in 6.4% and only 2 patients (1.8%) permanently discontinued alectinib due to adverse events. Multivariate analysis indicated that patients with metastases in ≥3 distant organs and a tumor reduction rate ≤50% demonstrated more unfavorable mPFS than their counterparts. Furthermore, patients carrying longer variants showed superior mPFS to those with shorter variants (not reached vs. 24.2 months, hazard ratio =0.17, 95% CI: 0.04-0.68, P=0.004). Conclusions: Alectinib showed substantial efficacy and an excellent safety profile in a real-world setting of Chinese patients. Clinical outcomes and long-term survival still require longer follow-up. Tumors with shorter EML4 fusion variants, more extensive metastases and less reduction in tumor lesions may require more aggressive strategies.

Sustainable one-pot construction of oxygen-rich nitrogen-doped carbon nanosheets stabilized ultrafine Rh nanoparticles for efficient ammonia borane hydrolysis.

Heteroatom-doped porous carbons that possess large surface areas and well-defined porosity show great promise in heterogeneous catalysis, whereas their syntheses inevitably require complicated steps, hazardous activation and functional reagents, and an inert gas atmosphere. Herein, a one-pot synthetic strategy to oxygen-rich porous nitrogen-doped carbon (OPNC) is developed through pyrolysis of ethylenediamine tetra-acetic acid tetra-sodium in air without any activation and functionalization agents. The as-prepared OPNC with more surface oxygenated groups and mesopores not only benefits synthesis of well-dispersed ultrafine Rh nanoparticles (NPs) with abundant accessible active sites, but also facilitates the diffusion of reactants and avoids mass transfer limitations, thereby considerably contributes to a high performance toward AB hydrolysis. Specifically, the optimal Rh/OPNC exhibits a high activity toward AB hydrolysis with a turnover frequency (TOF) of 433 min-1. The kinetic isotope studies indicate that the cleavage of OH bond in H2O molecules is the rate-determining step (RDS). The Rh/OPNC can be reused for five repetitive cycles with approximately 62% remained activity of the first cycle. The catalytic activity of Rh/OPNC can be further improved with a very high TOF of 1201 min-1 in alkaline solution. This study proposes a simple and sustainable pathway to synthesize efficient catalyst support for depositing metal NPs toward AB hydrolysis.

Sichuan paocai fermented by mixed-starter culture of lactic acid bacteria.

To satisfy the demand of industrial production, selecting strains suitable for fermentation initiation is necessary. In this study, the effects of mixed-starter culture including Leuconostoc, Lactobacillus, and Weissella on the quality of Sichuan pickle were discussed. Results showed that mixed-starter culture can accelerate fermentation and had the highest efficiency for nitrite degradation, that is, the maximum nitrite concentration was 8.97 g/kg on day 1 and decreased to 1.88 mg/kg after 3 days. The mixed-starter culture improved the sensory properties of pickles, which easily produced acids but had reduced amounts of total acids. The pickle products fermented by the mixed-starter culture contained increased lactic acid (17.52 g/kg), mannitol (0.62%), umami (35.85), and sweet (11.36) amino acids on day 4. The strains Weissella paramesenteroides C2-2 and Lactobacillus brevis ZP11-2 grew well in the mixed-starter culture fermentation.

Genome-wide association scan for stature in Chinese: evidence for ethnic specific loci.

In Caucasian, several studies have identified some common variants associated with human stature variation. However, no such study was performed in Chinese, which is the largest population in the world and evidently differs from Caucasian in genetic background. To identify common or ethnic specific genes for stature in Chinese, an initial GWAS and follow-up replication study were performed. Our initial GWAS study found that a group of 13 contiguous SNPs, which span a region of approximately 150 kb containing two neighboring genes, zinc finger protein (ZNP) 510 and ZNP782, achieved strong signals for association with stature, with P values ranging from 9.71 x 10(-5) to 3.11 x 10(-6). After false discovery rate correction for multiple testing, 9 of the 13 SNPs remain significant (FDR q=0.036-0.046). The follow-up replication study in an independent 2,953 unrelated southern Chinese confirmed the association of rs10816533 with stature (P=0.029). All the 13 SNPs were in consistently strong linkage disequilibrium (D'>0.99) and formed a single perfect haplotype block. The minor allele frequencies for the 13 contiguous SNPs have evidently ethnic difference, which range from 0.21 to 0.33 in Chinese but have as low as approximately 0.017 reported in dbSNP database in Caucasian. The present results suggest that the genomic region containing the ZNP510 and ZNP782 genes is an ethnic specific locus associated with stature variation in Chinese.

A novel AuNPs-based nanosensors for smart detection of NO with low concentration.

A novel method for detection of nitric oxide (NO) was developed by the structural transition of oxidized cytochrome c (Cyt c III) on gold nanoparticles (AuNPs)/glycine (Gly)/graphene quantum dots (GQDs) composite using surface-enhanced Raman scattering (SERS) spectroscopy. Importantly, the composite can be used as a good SERS substrate for the selective detection of trace NO based on the interaction of the Cyt c (III) and NO, and the structural transition of oxidized Cyt c III on AuNPs/Gly/GQDs composite. The NO concentration in real seawater sample was determined to be 7.28 × 10-8 M. Combined with the interaction of the Cyt c (III) and NO, and the structural transition of oxidized Cyt c (III) on AuNPs/Gly/GQDs composite, a novel AuNPs-based SERS probe for the selective detection of trace NO was constructed, and the detection limit for NO can reach about ~10-8 M.

Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites.

UNLABELLED: In this study, the associations of novel LRP5 variants with BMD variation were detected and some replicated in the two ethnic groups of Chinese and white origins, respectively. These data support the concept that LRP5 variation can contribute to minor and major variation in bone structure. INTRODUCTION: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been shown to cause both high and low bone mass. However, it is still controversial whether LRP5 is associated with normal BMD variation. This study explored the association of LRP5 with BMD phenotypes at three clinically important skeletal sites-the spine, hip, and ultradistal radius (UD)-in two independent populations of Chinese and white ethnicities, respectively. MATERIALS AND METHODS: The Chinese sample consisted of 733 unrelated subjects. The white sample was made up of 1873 subjects from 405 nuclear families. High-density single nucleotide polymorphisms (SNPs) across the whole LRP5 gene were genotyped and analyzed in both samples. RESULTS: Linkage disequilibrium (LD) analyses showed that the haplotype structures of LRP5 between Chinese and whites were in good agreement. Association tests showed that polymorphisms in block 5 spanning intron 7 to intron 19 of LRP5 significantly associated with spine BMD variation in both samples. Particularly, the significant association of SNP rs491347 in intron 7 with spine BMD in the Chinese sample (p=0.002) was replicated in whites, even after adjusting for multiple testing (p=0.005). Its strongly associated SNP rs1784235 could cause the loss of an estrogen receptor alpha (ERalpha) binding site in LRP5, which could partially explain the above replicated association. However, we did not observe any significant replication with BMD variation at the hip and UD. After accounting for multiple testing, associations with BMD variation at these two sites were mainly found in Chinese. Sex-stratified analyses further revealed that the LRP5 associations with BMD in Chinese and whites were driven by male and female subjects, respectively. CONCLUSIONS: Our work supported LRP5 genetic variants as possible susceptibility factors for osteoporosis and fractures in humans. Especially, the SNP rs491347 and its strongly associated SNPs (e.g., rs1784235) could be important to human osteoporosis phenotypes.

A genome wide association study between copy number variation (CNV) and human height in Chinese population.

Copy number variation (CNV) is a type of genetic variation which may have important roles in phenotypic variability and disease susceptibility. To hunt for genetic variants underlying human height variation, we performed a genome wide CNV association study for human height in 618 Chinese unrelated subjects using Affymetrix 500K array set. After adjusting for age and sex, we found that four CNVs at 6p21.3, 8p23.3-23.2, 9p23 and 16p12.1 were associated with human height (with borderline significant p value: 0.013, 0.011, 0.024, 0.049; respectively). However, after multiple tests correction, none of them was associated with human height. We observed that the gain of copy number (more than 2 copies) at 8p23.3-23.2 was associated with lower height (normal copy number vs. gain of copy number: 161.2 cm vs. 153.7 cm, p = 0.011), which accounted for 0.9% of height variation. Loss of copy number (less than 2 copies) at 6p21.3 was associated with 0.8% lower height (loss of copy number vs. normal copy number: 154.5 cm vs. 161.1 cm, p = 0.013). Since no important genes influencing height located in CNVs at loci of 8p23.3-23.2 and 6p21.3, the two CNVs may cause the structural rearrangements of neighbored important candidate genes, thus regulates the variation of height. Our results expand our knowledge of the genetic factors underlying height variation and the biological regulation of human height.

Whole genome distribution and ethnic differentiation of copy number variation in Caucasian and Asian populations.

Although copy number variation (CNV) has recently received much attention as a form of structure variation within the human genome, knowledge is still inadequate on fundamental CNV characteristics such as occurrence rate, genomic distribution and ethnic differentiation. In the present study, we used the Affymetrix GeneChip(R) Mapping 500K Array to discover and characterize CNVs in the human genome and to study ethnic differences of CNVs between Caucasians and Asians. Three thousand and nineteen CNVs, including 2381 CNVs in autosomes and 638 CNVs in X chromosome, from 985 Caucasian and 692 Asian individuals were identified, with a mean length of 296 kb. Among these CNVs, 190 had frequencies greater than 1% in at least one ethnic group, and 109 showed significant ethnic differences in frequencies (p<0.01). After merging overlapping CNVs, 1135 copy number variation regions (CNVRs), covering approximately 439 Mb (14.3%) of the human genome, were obtained. Our findings of ethnic differentiation of CNVs, along with the newly constructed CNV genomic map, extend our knowledge on the structural variation in the human genome and may furnish a basis for understanding the genomic differentiation of complex traits across ethnic groups.

Sex-specific association of the glucocorticoid receptor gene with extreme BMD.

UNLABELLED: To study the role of the GR gene on BMD regulation in the Chinese, a sex-specific association study was performed. The results indicated that GR variation contributed to the extreme BMD variation in the Chinese. INTRODUCTION: The glucocorticoid (GC) receptor (GR) gene is an important candidate gene for BMD regulation in GC-induced osteoporosis (GIO). However, no study has explored the genetic effects of the GR gene on BMD variation in the Chinese population. MATERIALS AND METHODS: Our sample consisted of 800 unrelated subjects (400 women and 400 men) with extreme age-adjusted hip BMD Z-scores selected from a population composed of 1988 normal adult Chinese Han. Four single nucleotide polymorphisms (SNPs) in the GR gene were genotyped. Both single SNP and haplotype association analyses were conducted. RESULTS: SNP rs1866388 (p(c) = 0.028) was found to be significantly associated with extreme BMD only in men. In both sexes, haplotypes involving rs1866388 and rs2918419 were found to have different frequency distributions in extremely low and high BMD groups (p(p) = 0.024, 0.001, and 0.002 in women and 0.002, 0.003, and 0.003 in men for window sizes of two, three, and four SNPs, respectively). Most shared haplotypes showed opposite effects between women and men. CONCLUSIONS: For the first time, our study suggested the possible role of the GR gene on BMD regulation and sex specificity in the association of GR with extreme BMD in the Chinese.