Kinetic Evaluation on Lithium Polysulfide in Weakly Solvating Electrolyte toward Practical Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are highly considered as next-generation energy storage techniques. Weakly solvating electrolyte with low lithium polysulfide (LiPS) solvating power promises Li anode protection and improved cycling stability. However, the cathodic LiPS kinetics is inevitably deteriorated, resulting in severe cathodic polarization and limited energy density. Herein, the LiPS kinetic degradation mechanism in weakly solvating electrolytes is disclosed to construct high-energy-density Li-S batteries. Activation polarization instead of concentration or ohmic polarization is identified as the dominant kinetic limitation, which originates from higher charge-transfer activation energy and a changed rate-determining step. To solve the kinetic issue, a titanium nitride (TiN) electrocatalyst is introduced and corresponding Li-S batteries exhibit reduced polarization, prolonged cycling lifespan, and high actual energy density of 381 Wh kg-1 in 2.5 Ah-level pouch cells. This work clarifies the LiPS reaction mechanism in protective weakly solvating electrolytes and highlights the electrocatalytic regulation strategy toward high-energy-density and long-cycling Li-S batteries.

Anion-Involved Solvation Structure of Lithium Polysulfides in Lithium-Sulfur Batteries.

Lithium polysulfides (LiPSs) are pivotal intermediates involved in all the cathodic reactions in lithium-sulfur (Li-S) batteries. Elucidating the solvation structure of LiPSs is the first step for rational design of electrolyte and improving Li-S battery performances. Herein, we investigate the solvation structure of LiPSs and find that Li salt anions tend to enter the first solvation sheath of LiPSs and form contact ion pairs in electrolyte. The anion-involved solvation structure of LiPSs significantly influences the intrinsic kinetics of the sulfur redox reactions. In particular, the LiPS solvation structure modified by lithium bis(fluorosulfonyl)imide endows Li-S batteries with reduced polarization and enhanced rate performances under high sulfur areal loading and lean electrolyte volume conditions. This work updates the fundamental understanding of the solvation chemistry of LiPSs and highlights electrolyte engineering for promoting the performances of Li-S batteries.

Cathode Kinetics Evaluation in Lean-Electrolyte Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries afford great promise on achieving practical high energy density beyond lithium-ion batteries. Lean-electrolyte conditions constitute the prerequisite for achieving high-energy-density Li-S batteries but inevitably deteriorates battery performances, especially the sulfur cathode kinetics. Herein, the polarizations of the sulfur cathode are systematically decoupled to identify the key kinetic limiting factor in lean-electrolyte Li-S batteries. Concretely, an electrochemical impedance spectroscopy combined galvanostatic intermittent titration technique method is developed to decouple the cathodic polarizations into activation, concentration, and ohmic parts. Therein, activation polarization during lithium sulfide nucleation emerges as the dominant polarization as the electrolyte-to-sulfur ratio (E/S ratio) decreases, and the sluggish interfacial charge transfer kinetics is identified as the main reason for degraded cell performances under lean-electrolyte conditions. Accordingly, a lithium bis(fluorosulfonyl)imide electrolyte is proposed to decrease activation polarization, and Li-S batteries adopting this electrolyte provide a discharge capacity of 985 mAh g-1 under a low E/S ratio of 4 µL mg-1 at 0.2 C. This work identifies the key kinetic limiting factor of lean-electrolyte Li-S batteries and provides guidance on designing rational promotion strategies to achieve advanced Li-S batteries.

Morphological characteristics influence the spatial mixing patterns of shorebirds at Shengjin Lake.

The coexistence of species with similar ecological niches is one of the core interests of community ecology research. However, how functional feeding traits, including bill size and leg length, determine the niche of mixed flocks of shorebird species has seldomly been studied, as well as, microhabitat variables affect the spatial patterns of availability and the quality of patches for wintering. From October 2016 to March 2017 at Shengjin Lake, Anhui Province, China, we recorded 226 scan samples from the different microhabitats and 93 focal animal videos of four common shorebird species: common greenshank, spotted redshank, Kentish plover, and little ringed plover. We found that the species participating in the mixed groups were different in each microhabitat. The results of the overlap index for microhabitats and foraging techniques between the species were consistent with the morphological characteristics of these species. Kentish and little ringed plovers had the highest Pianka's niche overlap index values of 0.95 and 0.98 for microhabitats and foraging techniques, respectively, whereas common greenshank and spotted redshank had values of 0.78 and 0.89, respectively. Common greenshank and spotted redshank used four foraging techniques: a single probe (PR), multiple probes (MPR), a single peck (PE), and multiple pecks (MPE). Kentish and little ringed plovers only used PE and MPE. The mean bill size, mean leg length, and mean foraging frequency were significantly associated with water depth. The mean bill size and mean leg length were both significantly correlated with the mean foraging frequency of shorebirds. The vegetated area was the most important variable for grouping among shorebirds. We concluded that the four species showed differences in their preferred microhabitats and foraging patterns. Interspecific morphological differences, including bill and leg lengths, resulted in niche differentiation. Thus, effective resource allocation by regional species was realized, and a dynamic balance was achieved by the mixed foraging species. The information on foraging behavior and habitat requirements could be useful in the management of water levels in natural areas and conservation of a diversity of wintering shorebirds.

Semi-Immobilized Molecular Electrocatalysts for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries constitute promising next-generation energy storage devices due to the ultrahigh theoretical energy density of 2600 Wh kg-1. However, the multiphase sulfur redox reactions with sophisticated homogeneous and heterogeneous electrochemical processes are sluggish in kinetics, thus requiring targeted and high-efficient electrocatalysts. Herein, a semi-immobilized molecular electrocatalyst is designed to tailor the characters of the sulfur redox reactions in working Li-S batteries. Specifically, porphyrin active sites are covalently grafted onto conductive and flexible polypyrrole linkers on graphene current collectors. The electrocatalyst with the semi-immobilized active sites exhibits homogeneous and heterogeneous functions simultaneously, performing enhanced redox kinetics and a regulated phase transition mode. The efficiency of the semi-immobilizing strategy is further verified in practical Li-S batteries that realize superior rate performances and long lifespan as well as a 343 Wh kg-1 high-energy-density Li-S pouch cell. This contribution not only proposes an efficient semi-immobilizing electrocatalyst design strategy to promote the Li-S battery performances but also inspires electrocatalyst development facing analogous multiphase electrochemical energy processes.

Direct Intermediate Regulation Enabled by Sulfur Containers in Working Lithium-Sulfur Batteries.

Polysulfide intermediates (PSs), the liquid-phase species of active materials in lithium-sulfur (Li-S) batteries, connect the electrochemical reactions between insulative solid sulfur and lithium sulfide and are key to full exertion of the high-energy-density Li-S system. Herein, the concept of sulfur container additives is proposed for the direct modification on the PSs species. By reversible storage and release of the sulfur species, the container molecule converts small PSs into large organosulfur species. The prototype di(tri)sulfide-polyethylene glycol sulfur container is highly efficient in the reversible PS transformation to multiply affect electrochemical behaviors of sulfur cathodes in terms of liquid-species clustering, reaction kinetics, and solid deposition. The stability and capacity of Li-S cells was thereby enhanced. The sulfur container is a strategy to directly modify PSs, enlightening the precise regulation on Li-S batteries and multi-phase electrochemical systems.

Spatial and Kinetic Regulation of Sulfur Electrochemistry on Semi-Immobilized Redox Mediators in Working Batteries.

Use of redox mediators (RMs) is an effective strategy to enhance reaction kinetics of multi-electron sulfur electrochemistry. However, the soluble small-molecule RMs usually aggravate the internal shuttle and thus further reduce the battery efficiency and cyclability. A semi-immobilization strategy is now proposed for RM design to effectively regulate the sulfur electrochemistry while circumvent the inherent shuttle issue in a working battery. Small imide molecules as the model RMs were co-polymerized with moderate-chained polyether, rendering a semi-immobilized RM (PIPE) that is spatially restrained yet kinetically active. A small amount of PIPE (5 % in cathode) extended the cyclability of sulfur cathode from 37 to 190 cycles with 80 % capacity retention at 0.5 C. The semi-immobilization strategy helps to understand RM-assisted sulfur electrochemistry in alkali metal batteries and enlightens the chemical design of active additives for advanced electrochemical energy storage devices.

Significant Differences in the Gut Bacterial Communities of Hooded Crane (Grus monacha) in Different Seasons at a Stopover Site on the Flyway.

Intestinal bacterial communities form an integral component of the organism. Many factors influence gut bacterial community composition and diversity, including diet, environment and seasonality. During seasonal migration, birds use many habitats and food resources, which may influence their intestinal bacterial community structure. Hooded crane (Grus monacha) is a migrant waterbird that traverses long distances and occupies varied habitats. In this study, we investigated the diversity and differences in intestinal bacterial communities of hooded cranes over the migratory seasons. Fecal samples from hooded cranes were collected at a stopover site in two seasons (spring and fall) in Lindian, China, and at a wintering ground in Shengjin Lake, China. We analyzed bacterial communities from the fecal samples using high throughput sequencing (Illumina Mi-seq). Firmicutes, Proteobacteria, Tenericutes, Cyanobacteria, and Actinobacteria were the dominant phyla across all samples. The intestinal bacterial alpha-diversity of hooded cranes in winter was significantly higher than in fall and spring. The bacterial community composition significantly differed across the three seasons (ANOSIM, P = 0.001), suggesting that seasonal fluctuations may regulate the gut bacterial community composition of migratory birds. This study provides baseline information on the seasonal dynamics of intestinal bacterial community structure in migratory hooded cranes.

Microhabitat variables explain patch switching by wintering Bewick's swans through giving-up net energy intake rates.

Microhabitat variables are determinants for animals to select forage patches and evaluate the cost/benefit tradeoffs of habitat switching. Optimal foragers would weigh habitat quality by giving-up net energy intake rate (GUN), which includes the energy intake rate and cost rate. The GUNs, energy intake rate, and cost rate can be influenced by variations in different microhabitat factors and interactive effects. In this study, we assessed the GUN patterns of wintering Bewick's swans and the effects of microhabitat factors on their foraging strategy in three different habitats: foxnut ponds, paddy fields, and shallow lake. The foraging behaviors and microhabitat variables of the swans were investigated during the winters of 2016-2018 and 2017/2018 at Huangpi and Shengjin Lakes in Anhui Province, southeastern China. The results showed that the percentage of disturbance time and the giving-up food density in shallow water had significant negative effects on GUNs. In contrast, water depth and the giving-up food density in deep water showed positive effects on GUNs. GUNs were significantly different among the three habitats. GUNs also decreased as winter progressed. Swans would decrease their GUNs under unfavorable foraging conditions such as more disturbances; however, GUNs would increase with water depth and food availability in patches with deep water. The swans demonstrated diverse GUN patterns in different foraging habitats, driven by the tradeoffs between energy intake rates and energy cost rates that were influenced by microhabitat variables. It implies that waterbirds exposed to decreasing GUNs may mitigate energy demand and environmental stress by switching foraging habitat while in subprime foraging habitat if alternative habitats that offered higher net rates of energy gain were available.

The Influence of Food Density, Flock Size, and Disturbance on the Functional Response of Bewick's Swans (Cygnus columbianus bewickii) in Wintering Habitats.

Perceiving how animals adjust their feeding rate under a variety of environmental conditions and understanding the tradeoffs in their foraging strategies are necessary for conservation. The Holling functional response, which describes the relationship of feeding rate and food density to searching rate and handling time, has been applied to a range of waterbirds, especially with regard to Type II functional responses that describe an increasing feeding rate with food density but at a decelerating rate as the curve approaches the asymptote. However, feeding behavior components (feeding rate, searching rate, and handling time) are influenced by factors besides prey density, such as vigilance and flock size. In this study, we aim to elucidate how Bewick's swans (Cygnus columbianus bewickii) adopt flexible foraging strategies and vary their feeding behavior components in response to disturbance, flock size, and food density. We collected focal sampling data on the foraging behavior of swans that foraged rice grains, foxnut seeds, and tubers in paddy field, foxnut pond, and lake habitats, respectively, in Shengjin and Huangpi lakes during winter from 2016 to 2018. The observed feeding rate was not correlated with food density and displayed a positive relationship with searching rate but negative relationships with handling time, flock size, overall vigilance time, and disturbance time. Handling time was negatively correlated with food density and flock size, yet it increased with disturbance, overall vigilance time, and normal vigilance time. Searching rate was negatively correlated with food density, flock size, and disturbance time. Feeding rate was affected by the combined effects of handling time and searching rate, as well as food density and searching rate. The shape of the observed functional response could not be fitted to Holling's disc equation. However, the disc equation of the predicted feeding rate of wintering swans was found to be driven by food density. This provides insight into how wintering waterbirds adopt appropriate foraging strategies in response to complicated environmental factors, which has implications for wildlife conservation and habitat management.

Implanting Atomic Cobalt within Mesoporous Carbon toward Highly Stable Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries hold great promise to serve as next-generation energy storage devices. However, the practical performances of Li-S batteries are severely limited by the sulfur cathode regarding its low conductivity, huge volume change, and the polysulfide shuttle effect. The first two issues have been well addressed by introducing mesoporous carbon hosts to the sulfur cathode. Unfortunately, the nonpolar nature of carbon materials renders poor affinity to polar polysulfides, leaving the shuttling issue unaddressed. In this contribution, atomic cobalt is implanted within the skeleton of mesoporous carbon via a supramolecular self-templating strategy, which simultaneously improves the interaction with polysulfides and maintains the mesoporous structure. Moreover, the atomic cobalt dopants serve as active sites to improve the kinetics of the sulfur redox reactions. With the atomic-cobalt-decorated mesoporous carbon host, a high capacity of 1130 mAh gS -1 at 0.5 C and a high stability with a retention of 74.1% after 300 cycles are realized. Implanting atomic metal in mesoporous carbon demonstrates a feasible strategy to endow nanomaterials with targeted functions for Li-S batteries and broad applications.

Variations in gut bacterial communities of hooded crane (Grus monacha) over spatial-temporal scales.

BACKGROUND: Microbes have been recognized as important symbionts to regulate host life. The animal gut harbors abundance and diverse bacteria. Numerous internal and external factors influence intestinal bacterial communities, including diet, seasonal fluctuations and habitat sites. However, the factors that influence the gut bacterial communities of wild bird is poorly characterized. METHODS: By high-throughput sequencing and statistical analysis, we investigated the variations in gut bacterial communities of the hooded cranes at three wintering stages in Caizi (CZL) and Shengjin Lake (SJL), which are two shallow lakes in the middle and lower Yangtze River floodplain. RESULTS: Our results revealed significant differences in gut bacterial community structure and diversity among different sampling sites and wintering stages. Seasonal changes have a significant impact on the gut microbe composition of hooded cranes in the two lakes. ANOSIM analysis demonstrated that the samples in CZL had greater differences in the gut bacterial composition than that in SJL. Our data showed strong evidence that the host's gut filtering might be an important factor in shaping bacterial community according to mean nearest taxon distance (MNTD). The PICRUSt analysis showed that the predicted metagenomes associated with the gut microbiome were carbohydrate metabolism, amino acid metabolism and energy metabolism over the entire wintering period at the two lakes. CONCLUSIONS: The results demonstrated that both seasonal changes and habitat sites have significant impact on the gut bacterial communities of hooded cranes. In addition, predictive function of gut microbes in hooded cranes varied over time. These results provide new insights into the gut microbial community of the cranes, which serves as a foundation for future studies.

From Supramolecular Species to Self-Templated Porous Carbon and Metal-Doped Carbon for Oxygen Reduction Reaction Catalysts.

The preparation of carbon materials usually involves the decomposition of precursors and the reorganization of the as-generated fragments. However, the cleavage of bonds and the simultaneous formation of new bonds at nearly the same positions prevents effective yet precise fabrication. Herein, a supramolecular precursor, cucurbit[6]uril, that contains multiple bonds with distinct bond strengths is proposed to decouple the twin problem of simultaneous bond cleavage and formation, allowing multistage transformations to hierarchical porous carbon and metal-doped carbon in a single yet effective pyrolysis step without the need of a template or additional purification. As a proof-of-concept, the Fe-doped carbon electrocatalysts realized a Pt/C-like half-wave potential of 0.869 V vs. RHE and small Tafel slope of 51.3 mV dec-1 in oxygen reduction reaction.

Complete mitochondrial genome of Accipiter trivirgatus.

Crested goshawk (Accipiter trivirgatus) is a diurnal raptor tropical Asia which is a bird species in family Accipitridae. In the present study, we determined its complete mitochondrial genome by PCR-based method. The complete mitochondrial genome was 18,454 bp in length which overall base composition was 31.2% A, 24.4% T, 31.0% C, and 13.4% G. It consisted of the typical structure of 13 PCGs, 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 2 control regions. All of the PCGs started with ATG codon, except for ND3 which was started with ATC. Most of the genes terminate with codons TAA. The non-coding regions include pseudo-control regions.

Downregulated PITX1 Modulated by MiR-19a-3p Promotes Cell Malignancy and Predicts a Poor Prognosis of Gastric Cancer by Affecting Transcriptionally Activated PDCD5.

BACKGROUND/AIMS: PITX1 has been identified as a potential tumor-suppressor gene in several malignant tumors. The molecular mechanism underlying PITX1, particularly its function as a transcription factor regulating gene expression during tumorigenesis, is still poorly understood. METHODS: The expression level and location of PITX1 were determined by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemical staining in gastric cancer (GC). The effect of PITX1 on the GC cell proliferation and tumorigenesis was analyzed in vitro and in vivo. To explore how PITX1 suppresses cell proliferation, we used PITX1-ChIP-sequencing to measure genome-wide binding sites of PITX1 and assessed global function associations based on its putative target genes. ChIP-PCR, electrophoretic mobility shift assay, and promoter reporter assays examined whether PITX1 bound to PDCD5 and regulated its expression. The function of PDCD5 in GC cell apoptosis was further examined in vitro and in vivo. The relationship between the PITX1 protein level and GC patient prognosis was evaluated by the Kaplan-Meier estimator. Meanwhile, the expression level of miR-19a-3p, which is related to PITX1, was also detected by luciferase reporter assay, qRT-PCR, and western blotting. RESULTS: The expression level of PITX1 was decreased in GC tissues and cell lines. Elevated PITX1 expression significantly suppressed the cell proliferation of GC cells and tumorigenesis in vitro and in vivo. PITX1 knockdown blocked its inhibition of GC cell proliferation. PITX1 bound to whole genome-wide sites, with these targets enriched on genes with functions mainly related to cell growth and apoptosis. PITX1 bound to PDCD5, an apoptosis-related gene, during tumorigenesis, and cis-regulated PDCD5 expression. Increased PDCD5 expression in GC cells not only induced GC cell apoptosis, but also suppressed GC cell growth in vitro and in vivo. Moreover, PITX1 expression was regulated by miR-19a-3p. More importantly, a decreased level of PITX1 protein was correlated with poor GC patient prognosis. CONCLUSION: Decreased expression of PITX1 predicts shorter overall survival in GC patients. As a transcriptional activator, PITX1 regulates apoptosis-related genes, including PDCD5, during gastric carcinogenesis. These data indicate PDCD5 to be a novel and feasible therapeutic target for GC.

The gut microbiome of hooded cranes (Grus monacha) wintering at Shengjin Lake, China.

Gut microbes of animals play critical roles in processes such as digestion and immunity. Therefore, identifying gut microbes will shed light on understanding the annual life of animal species, particularly those that are threatened or endangered. In the present study, we conducted nucleotide sequence analyses of the 16S rRNA genes of gut microbiome of the hooded cranes (Grus monacha) wintering at Shengjin Lake, China, by Illumina high-throughput sequencing technology. We acquired 503,398 high-quality sequences and 785 operational taxonomic units (OTUs) from 15 fecal samples from different cranes, representing 22 phyla that were dominated by Firmicutes, Proteobacteria, and Actinobacteria. A total of 305 genera were identified that were dominated by Clostridium, Lysinibacillus, and Enterobacter. The core gut microbiome comprised 26 genera, including many probiotic species such as Clostridium, Bacillus, Cellulosilyticum, and Cellulomonas that could catabolize cellulose. The findings reported here contribute to our knowledge of the microbiology of hooded cranes and will likely advance efforts to protect waterbirds that inhabit Shengjin Lake Reserve during winter.

Upregulation of DNMT1 mediated by HBx suppresses RASSF1A expression independent of DNA methylation.

The hepatitis B virus (HBV) X protein (HBx) plays a key role in the molecular pathogenesis of HBV-related hepatocellular carcinoma (HCC). However, its critical gene targets remain largely unknown. RASSF1A gene (Ras-association domain family 1A, RASSF1A), a tumor-suppressor gene, is frequently found to be hypermethylated and downregulated in HCC. In the present study, we investigated whether HBx is involved in the hypermethylation and downregulation of RASSF1A and we examined the potential regulation mechanisms. RT-PCR analysis was used to determine RASSF1A and HBx expression in 9 liver cell lines and the results showed that RASSF1A expression was relatively low in HBx-positive cells. Notably, RASSF1A was downregulated in HepG2.2.15 cells, as compared to HepG2 cells. Further analysis revealed that HBx transfection suppressed RASSF1A expression and HBx knockdown induced its expression. Enforced HBx suppressed RASSF1A and meanwhile induced DNMT1 and DNMT3B expression. In addition, RASSF1A is negatively regulated by DNMT1. ChIP analysis using an antibody against DNMT1 revealed that HBx enhanced the binding of DNMT1 to the RASSF1A promoter but the inhibition of RASSF1A by HBx is DNA methylation-independent as detected by methylation-specific PCR (MSP). Further studies using MSP and bisulfite genomic sequencing (BGS) revealed that no significant methylation changes were observed for regional methylation levels of RASSF1A in DNMT1 knockdown cells, although methylation levels of specific CpG sites at the predicted binding sites for the Sp1 and USF transcription factors were reduced. Additionally, RASSF1A was downregulated in HBV-associated HCC (HBV-HCC) as detected by RT-PCR and immunohistochemistry suggesting RASSF1A expression may be related to HBx in HCC and the clinical relevance of our observations. Collectively, our data showed that HBx suppressed RASSF1A expression via DNMT1 and offered a new mechanism of RASSF1A inactive in HCC in addition to the widely known DNA methylation, enriching the epigenetic mechanism by which HBx contributes to the pathogenesis of HBV-HCC.

DNMT3A rs36012910 A>G polymorphism and gastric cancer susceptibility in a Chinese population.

DNA-methyltransferase (DNMT)-3A plays a crucial role in embryonic development and aberrant DNA methylation in carcinogenesis. Polymorphisms of the DNMT3A gene may influence its enzymatic activity and its contribution to susceptibility to cancer. This study evaluated the association of DNMT3A rs36012910 A>G with susceptibility to gastric cancer (GC) in a Chinese population. Genomic DNA was extracted from samples taken from 340 patients with GC and 251 healthy control subjects. The genotype frequency of DNMT3A rs36012910 A>G in all subjects was detected by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. Stratification analyses were used to study subgroups by age and gender and to evaluate the association of rs36012910 A>G polymorphism with genetic susceptibility to GC. All patients and control individuals were successfully genotyped for the DNMT3A rs36012910 A>G polymorphism. The frequency of DNMT3A rs36012910 allele G is 3.39 % in healthy individuals and 7.78 % in GC patients, respectively. The rs36012910 AG genotype was significantly more common in the GC group than in the controls, although the rs36012910 GG genotype was only one case in GC patients. Further stratification indicated that AG+GG genotypes were associated with susceptibility to GC in males older than 60, but this polymorphism has no significant association with GC susceptibility in females. Male individuals who carried AG+GG genotypes had a 2.362-fold increased risk of GC compared to those who carried the AA genotype. The rs36012910 allele G was associated with an increased risk of GC compared to the rs36012910 allele A. This is the first report to investigate the distribution and evaluate the association of a rare SNP in DNMT3A with genetic susceptibility to GC. DNMT3A rs36012910 A>G might become a potential biomarker for use in GC prediction, although further studies in larger groups and different populations are needed for confirmation.

Association of the DNMT3A -448A>G polymorphism with genetic susceptibility to colorectal cancer.

The DNA methyltransferase 3A (DNMT3A) -448A>G polymorphism is a novel functional single nucleotide polymorphism (SNP) that contributes to the genetic susceptibility to gastric cancer. In this study, we aimed to assess the genotype frequencies of DNMT3A -448A>G in colorectal cancer (CRC) patients and healthy control subjects, and to explore the association of the DNMT3A functional SNP, -448A>G, with genetic susceptibility to CRC. Genomic DNA was extracted from samples of 258 patients with CRC and 280 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was employed to assess the genotype frequencies of DNMT3A -448A>G in all of the subjects. Stratification analyses were used to study subgroups of subjects by age and gender, and to evaluate the association between the DNMT3A -448A>G polymorphism and the genetic susceptibility to CRC. The allele frequency of -448A among CRC patients and the controls was 26.4 versus 19.8%, respectively. Overall, we found that compared with GG carriers, the DNMT3A -448AA homozygotes had a 3.692-fold increased risk of CRC. Stratification analysis showed a significant difference in this SNP between the CRC patients and the control subjects of different genders. AA homozygotes carried an increased risk in the subgroup of individuals aged ≥50 years in male CRC. Compared with GG homozygotes in females aged ≥50 years, the AG and AA genotypes carried a 0.355-fold decreased risk in this subgroup. These data imply that the DNMT3A SNP -448A>G contributes to genetic susceptibility to CRC. -448A>G may be used as a stratification marker to predict the susceptibility of certain individuals to CRC, particularly in male individuals aged ≥50 years.

A functional polymorphism in the DNA methyltransferase-3A promoter modifies the susceptibility in gastric cancer but not in esophageal carcinoma.

BACKGROUND: DNA-methyltransferase (DNMT)-3A plays an important role in the development of embryogenesis and the generation of aberrant methylation in carcinogenesis. The aim of this study was to investigate the role of a DNMT3A promoter genetic variant on its transcriptional activity and to evaluate the association between DNMT3A gene polymorphism and the susceptibility to gastric cancer (GC) and oesophagus carcinoma (EC) in the Chinese population. METHODS: We selected one of the single nucleotide polymorphisms (SNPs) -448A>G in the DNMT3A promoter region and evaluated its effect on activity using a luciferase assay. -448A>G polymorphisms of DNMT3A were determined by polymerase chain reaction/restriction fragment length polymorphism and confirmed by sequencing. The distribution of -448A>G polymorphisms was detected in 208 GC patients and 346 healthy controls matched for age and gender. The distribution of -448A>G polymorphisms was also detected in 96 EC patients and matched 241 healthy controls. The association of -448A>G polymorphisms of DNMT3A and the risk of GC and EC was evaluated by stratified analysis according to the patient's age and gender. RESULTS: In a promoter assay, carriage of the -448 A allele showed a significantly higher promoter activity (> two fold) compared with the -448G allele (P < 0.001). The allele frequency of -448A among GC patients and controls was 32.9% versus 19.9%, respectively. Overall, we found that, compared with GG carriers, the DNMT3A -448AA homozygotes has a > six fold increased risk of GC. Stratification analysis showed that AA homozygotes have a more profound risk in the subgroups of individuals at the age range G polymorphism is a novel functional SNP and contributes to its genetic susceptibility to GC. -448A>G can be used as a stratification marker to predict an individual's susceptibility to GC, especially in the subgroups of individuals at the age range G in EC can not be used as a prediction marker in order to evaluate an individual's susceptibility to EC.