Transposon molecular domestication and the evolution of the RAG recombinase.

Domestication of a transposon (a DNA sequence that can change its position in a genome) to give rise to the RAG1-RAG2 recombinase (RAG) and V(D)J recombination, which produces the diverse repertoire of antibodies and T cell receptors, was a pivotal event in the evolution of the adaptive immune system of jawed vertebrates. The evolutionary adaptations that transformed the ancestral RAG transposase into a RAG recombinase with appropriately regulated DNA cleavage and transposition activities are not understood. Here, beginning with cryo-electron microscopy structures of the amphioxus ProtoRAG transposase (an evolutionary relative of RAG), we identify amino acid residues and domains the acquisition or loss of which underpins the propensity of RAG for coupled cleavage, its preference for asymmetric DNA substrates and its inability to perform transposition in cells. In particular, we identify two adaptations specific to jawed-vertebrates-arginine 848 in RAG1 and an acidic region in RAG2-that together suppress RAG-mediated transposition more than 1,000-fold. Our findings reveal a two-tiered mechanism for the suppression of RAG-mediated transposition, illuminate the evolution of V(D)J recombination and provide insight into the principles that govern the molecular domestication of transposons.

Self-Sustained-Release Strategy Realizes Colloid Oriented Assembly to Fabricate Prussian Blue with Hierarchical Structure.

The controlled self-assembly of nanomaterials has been a great challenge in nanosynthesis, especially for hierarchical architectures with high complexity. Particularly, the structural design of Prussian blue (PB) series materials with robustness and fast nucleation is even more difficult. Herein, a self-sustained-release strategy based on the slow release of metal ions from coordination ions is proposed to guide the assembly of PB crystals. The key to this strategy is the slow release by ligand, which can create ultra-low concentrations of metal ions so as to provide the possibility to realize the surface charge manipulation of PB primary colloids. By adding electrolyte or changing the polarity of the solution, the surface charge regulation of PB colloid is realized, and the PB hierarchical structures with branch fractal structure (PB-BS), octahedral fractal structure, and spherical fractal structure are effectively constructed. This work not only achieves the designability of the PB structure, but also synchronizes the functionalization during the PB assembly growth process by in situ encapsulation of the effective catalytic active component L-Ascorbic acid. As a result, the assembled PB-BS exhibits greatly enhanced catalytic activity and selectivity in styrene oxidation with the selectivity of oxidized styrene increasing from 35.6% (PB) to 80.5% (PB-BS).

Crystal Face Dominated Fabrication of Prussian Blue Analogue with Oriented Growth and Naturally Nonpreferred Unsaturated Coordination Center.

Defects, such as unsaturated coordination centers and vacancies, can fundamentally change materials' inherent properties and growth habits. The development of defect engineering has promoted the application of many technologies, but it is still a great challenge to selectively manufacture defect sites in existing material systems. It is shown here that in situ site-directed tailoring of metal sites in Prussian blue analogs (PBA) can be achieved according to the reducibility differences of different metal atoms, forming naturally nonpreferred unsaturated coordination centers. Meanwhile, the in situ capture of small reducing molecule can realize site-directed tailoring of crystal facets during crystal growth and results in oriented 1D growth. As an oxygen evolution reaction catalyst, the resulted PBA with the nonpreferred unsaturated coordination centers shows a low overpotential of 239 mV at 10 mA cm-2 in alkali, superior to the original PBAs and the previously reported defective PBA derivatives, which can be ascribed to the unsaturated coordination active center and the unique 1D structure. This work opens up opportunities for producing naturally nonpreferred unsaturated coordination center in nanomaterials for broad applications.

One-Step Phase Separation for Core-Shell Carbon@Indium Oxide@Bismuth Microspheres with Enhanced Activity for CO2 Electroreduction to Formate.

It is a substantial challenge to construct electrocatalysts with high activity, good selectivity, and long-term stability for electrocatalytic reduction of carbon dioxide to formic acid. Herein, bismuth and indium species are innovatively integrated into a uniform heterogeneous spherical structure by a neoteric quasi-microemulsion method, and a novel C@In2 O3 @Bi50 core-shell structure is constructed through a subsequent one-step phase separation strategy due to melting point difference and Kirkendall effect with the nano-limiting effect of the carbon structure. This core-shell C@In2 O3 @Bi50 catalyst can selectively reduce CO2 to formate with high selectivity (≈90% faradaic efficiency), large partial current density (24.53 mA cm-2 at -1.36 V), and long-term stability (up to 14.5 h), superior to most of the Bi-based catalysts. The hybrid Bi/In2 O3 interfaces of core-shell C@In2 O3 @Bi will stabilize the key intermediate HCOO* and suppress CO poisoning, benefiting the CO2 RR selectivity and stability, while the internal cavity of core-shell structure will improve the reaction kinetics because of the large specific surface area and the enhancement of ion shuttle and electron transfer. Furthermore, the nano-limited domain effect of outmost carbon prevent active components from oxidation and agglomeration, helpful for stabilizing the catalyst. This work offers valuable insights into core-shell structure engineering to promote practical CO2 conversion technology.

Artificial Intelligence-Driven Morphology-Based Enrichment of Malignant Cells from Body Fluid.

Cell morphology is a fundamental feature used to evaluate patient specimens in pathologic analysis. However, traditional cytopathology analysis of patient effusion samples is limited by low tumor cell abundance coupled with the high background of nonmalignant cells, restricting the ability of downstream molecular and functional analyses to identify actionable therapeutic targets. We applied the Deepcell platform that combines microfluidic sorting, brightfield imaging, and real-time deep learning interpretations based on multidimensional morphology to enrich carcinoma cells from malignant effusions without cell staining or labels. Carcinoma cell enrichment was validated with whole genome sequencing and targeted mutation analysis, which showed a higher sensitivity for detection of tumor fractions and critical somatic variant mutations that were initially at low levels or undetectable in presort patient samples. Our study demonstrates the feasibility and added value of supplementing traditional morphology-based cytology with deep learning, multidimensional morphology analysis, and microfluidic sorting.

Andrographolide Ameliorates Rheumatoid Arthritis by Regulating the Apoptosis-NETosis Balance of Neutrophils.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis with swelling and pain at synovial joints. In RA patients, delayed neutrophil apoptosis amplifies the inflammatory response and massively released neutrophil extracellular traps (NETs) induce tissue damage and provide self-antigens. Andrographolide (AD) is the major active labdane diterpenoid derived from Andrographis paniculata, which has multiple pharmacological effects, including hepatoprotection, anti-angiogenesis, anti-thrombosis, and anti-inflammation. In the present study, we investigated the effect of AD on an adjuvant-induced arthritis (AA) murine model of RA and found that AD alleviated murine arthritis by reducing neutrophil infiltration and NETosis in the ankle joints and relieved the systematic inflammation. In vitro experiments showed that AD accelerated the apoptosis of lipopolysaccharide-activated neutrophils and inhibited autophagy-dependent extracellular traps formation of neutrophils. These findings suggest that AD has considerable potential for RA therapy.

In Situ Antisolvent Approach to Hydrangea-like HCo3 O4 -NC@CoNi-LDH Core@Shell Superstructures for Highly Efficient Water Electrolysis.

Highly active, durable, and cost-effective electrocatalysts for water oxidation are at the center of renewable energy technologies. However, the development of water oxidation catalysts with high activity at low cost remains a great challenge. Herein, an in situ antisolvent approach is reported for synthesizing ultrathin Co-Ni layered double hydroxide (CoNi-LDH) nanosheets wrapped on hollow Co3 O4 nanoparticle-embedded nitrogen-doped carbon (HCo3 O4 -NC) as a high-performance catalyst for the oxygen evolution reaction (OER). Although HCo3 O4 -NC or NiCo-LDH alone has little OER activity, their hybrid exhibits low overpotential and Tafel slope as well as high stability, due to the synergistic effect of Co3 O4 and LDH. Furthermore, the hydrangea-like HCo3 O4 -NC@NiCo-LDH core@shell composite exhibits higher catalytic activity and stability than commercial IrO2 , which makes it a high-performance nonprecious-metal-based catalyst for OER.

Quantum Effects Allow the Construction of Two-Dimensional Co3 O4 -Embedded Nitrogen-Doped Porous Carbon Nanosheet Arrays from Bimetallic MOFs as Bifunctional Oxygen Electrocatalysts.

In terms of promising candidates for high-performance fuel cells and water splitting electrocatalysts, two-dimensional (2D) materials refer to a class of materials with high electrical conductivity along 2D conducting channels and possessing abundant active sites in the form of surface atoms and edge sites. Herein, we report an ammonia-modulated method for the synthesis of nanosized bimetallic ZnCo-ZIF, and owing to quantum effects, the nanosized ZnCo-ZIF can be transformed into novel 2D nanosheet arrays, which can be used as a bifunctional electrocatalyst. The size of the ZnCo-ZIF crystals can be controlled to less than 10 nm by increasing the ammonia amount. The products from the nanosized particles through calcination have a distinct structure from the microsized nanoparticles owing to quantum effects and appear to be well-aligned 2D mono-crystalline Co3 O4 -embedded nitrogen-doped porous carbon nanosheet arrays (2D-MCo3 O4 -NCNAs). These novel 2D nanosheet arrays lead to large active surface areas, enhanced mass/charge transport capability, numerous active sites, and strong structure stability. When used as bifunctional catalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), the 2D-MCo3 O4 -NCNAs exhibit superior ORR activity as well as efficient OER activity in alkaline electrolyte, in comparison to the state-of-the-art precious metal catalysts.

Delicate Control of Multishelled Zn-Mn-O Hollow Microspheres as a High-Performance Anode for Lithium-Ion Batteries.

Mixed/composite oxides of transition metals with hollow structures, especially multishelled hollow architecture, have promising potential for different applications, but their syntheses still remain a big challenge. Herein, a facile coordination polymer precursor method was developed to construct various multishelled Zn-Mn-O hollow microspheres, including ZnMnO3, ZnMn2O4, and ZnMn2O4/Mn2O3. The composition of the hollow structures can be adjusted by controlling the composition of the coordination polymer precursors, which are easily obtained with Zn2+, Mn2+, and salicylic acid under solvothermal conditions. With a simple programmable heating process, the shell of the hollow structures can be adjusted and double-/triple-shelled ZnMnO3, ZnMn2O4, and ZnMn2O4/Mn2O3 hollow microspheres have been controllably obtained. When the triple-shelled ZnMn2O4 hollow microspheres are used as anode materials for lithium-ion batteries, excellent activity and enhanced stability can be achieved. The triple-shelled hollow ZnMn2O4 exhibits a reversible capacity of 537 mA·h·g-1 at 400 mA·g-1 and a nearly 100% capacity retention after 150 cycles. This strategy is facile and scalable for the production of high-quality complex hollow nanostructures, with the possibility of extension to the preparation of other mixed metal oxides with complex structures.

[Effects of Tengmei Decoction on the PPAR-y/NF-KB Signaling Pathway in Synovium of Collagen-in- duced Arthritis Rats].

Objective To observe the effects of Tengmei Decoction (TMD) on the expressions of peroxisome proliferator activated receptor gamma (PPARγ) , nuclear factor kappa B (NF-κB) , and IL- 17 in synovium of collagen-induced arthritis (CIA) rats, and to study its molecular mechanismpf. inhibi- ting synovial immune inflammatory injuries. Methods CIA model was established in Sprague-Dawley rats. Successfully modeled rats were randomly divided into the model group, the positive drug ,oup, high and low dose TMD groups, 6 in each group. Besides, a normal group was set up (n =6). Deionized water (10 mL . kg⁻¹ . d⁻¹) was administrated to rats in the normal group and the model group by gastro- gavage. Leflunomide (1. 87 mg . kg ⁻¹ . d ⁻¹) was administrated to rats in the positive drug group by gastro- gavage. TMD (31. 8 g crude drugs . kg ⁻¹ . d ⁻¹ and 15. 9 g crude drugs . kg ⁻¹ . d ⁻¹) was administrated to rats in high and low dose TMD groups respectively by gastrogavage. The intervention lasted for 12 suc- cessive weeks. Protein and mRNA levels of PPARy, P65, and IL-17 were detected at the end of intervention. Results Compared with the normal group, mRNA and protein expression levels of PPARγ, P65, and IL-17 were up-regulated in the model group (P <0. 01). Compared with the model group, PPARγ pro- tein expression level was up-regulated, mRNA and protein expression levels of P65 and IL-17 were down-regulated in high dose TMD group (P <0. 01). mRNA and protein expression levels of PPARγ were up-regulated, mRNA and protein expression levels of P65 and IL-17 were down-regulated in the positive drug group and low dose TMD group (P <0. 01). Conclusions TMD could ameliorate pathological damage of joint synovium , and inhibit expressions of immune inflammatory factors.

Association of sugary beverages with survival among patients with cancers of the upper aerodigestive tract.

PURPOSE: The role of consumption of added sugars in cancers of the upper aerodigestive tract (UADT) is unclear. We examined associations between sugary beverages and susceptibility to UADT cancer as well as overall survival among UADT cancer patients. METHODS: The association between dietary added sugar and susceptibility to UADT cancers or overall survival among 601 UADT cancer cases was evaluated using data from a population-based case-control study conducted in Los Angeles County. Unconditional logistic regression was used to estimate odds ratios and 95 % confidence intervals (CI) for cancer susceptibility, and Cox regression was used to estimate hazards ratios (HRs) with 95 % CIs for survival, adjusting for relevant confounders. RESULTS: A total of 248 deaths were observed during follow-up (median 12.1 years). A positive association was observed with consumption of grams of sugar from beverages, including soft drinks and fruit juices, and poorer survival among UADT cancer cases (aHR, Q4 vs. Q1:1.88; 95 % CI 1.29, 2.72; p for trend = 0.002), as well as servings of sugary beverages (aHR, Q4 vs. Q1: 95 % CI 1.97, 95 % CI 1.32-2.93). This was due largely to consumption of sugars from soft drinks. Particularly, high consumption of sugary beverages was associated with poorer survival among esophageal cancer cases, driven by squamous cancers. No association was observed between sugary beverages and cancer susceptibility. CONCLUSION: These findings suggest that consumption of sugary beverages may decrease survival associated with UADT cancers. Additional studies should be conducted to examine survival among cancer patients consuming high amounts of added or refined sugars. Such studies may highlight prognostic factors for UADT cancers.

Two-Dimensional Hollow TiO2 Nanoplates with Enhanced Photocatalytic Activity.

Two-dimensional anatase TiO2 hollow nanoplates were firstly synthesized through a facile synthesis route by using α-Fe2 O3 nanoplates as removable templates. Two-dimensional hollow TiO2 nanoplates with different ratios of anatase and rutile phases were obtained by adjusting the calcining temperature. The average diameters were around 600 nm, and the shell thickness was approximately 30 nm. The photocatalytic performance of TiO2 was investigated by decomposing rhodamine B under simulated sunlight. Among the TiO2 samples, the anatase TiO2 hollow nanoplates manifested a significant enhancement in the photocatalytic performances. The excellent catalytic performance can be attributed to the unique structure of the two-dimensional anatase TiO2 hollow nanoplates, including a large surface area and increased dye-photocatalyst contact areas as well as more active sites for photodegradation.

Template-Free Synthesis of Nanorod-Assembled Hierarchical Zn1-x Mnx S Hollow Nanostructures with Enhanced Pseudocapacitive Properties.

Mixed-metal sulfide Zn1-x Mnx S nanorod-assembled hierarchical hollow spheres were synthesized by a template-free solvothermal process based on Ostwald ripening. In the reaction system, glycerol plays a key role in the formation of Znx Mn1-x S hierarchical hollow structures by a quasi-microemulsion-template mechanism. When applied as capacitor electrode material, the hierarchical Zn1-x Mnx S hollow spheres show excellent electrochemical performance. Specifically, Zn0.25 Mn0.75 S hollow spheres can deliver a high specific capacitance of 664 F g-1 at a current rate of 1 A g-1 , which is almost five times of that of MnS under the same conditions and higher than those of previously reported single Mn-based compounds.

Generalized Low-Temperature Fabrication of Scalable Multi-Type Two-Dimensional Nanosheets with a Green Soft Template.

Two-dimensional nanosheets with high specific surface areas and fascinating physical and chemical properties have attracted tremendous interests because of their promising potentials in both fundamental research and practical applications. However, the problem of developing a universal strategy with a facile and cost-effective synthesis process for multi-type ultrathin 2 D nanostructures remains unresolved. Herein, we report a generalized low-temperature fabrication of scalable multi-type 2 D nanosheets including metal hydroxides (such as Ni(OH)2, Co(OH)2, Cd(OH)2, and Mg(OH)2), metal oxides (such as ZnO and Mn3O4), and layered mixed transition-metal hydroxides (Ni-Co LDH, Ni-Fe LDH, Co-Fe LDH, and Ni-Co-Fe layered ternary hydroxides) through the rational employment of a green soft-template. The synthesized crystalline inorganic nanosheets possess confined thickness, resulting in ultrahigh surface atom ratios and chemically reactive facets. Upon evaluation as electrode materials for pseudocapacitors, the Ni-Co LDH nanosheets exhibit a high specific capacitance of 1087 F g(-1) at a current density of 1 A g(-1), and excellent stability, with 103% retention after 500 cycles. This strategy is facile and scalable for the production of high-quality ultrathin crystalline inorganic nanosheets, with the possibility of extension to the preparation of other complex nanosheets.

Plasma folate, vitamin B12, and homocysteine and cancers of the esophagus, stomach, and liver in a Chinese population.

Evidence is accumulating regarding a role of micronutrients in folate metabolism in cancer risk. We investigated the associations of plasma folate, vitamin B12, and homocysteine with upper gastrointestinal (GI) cancers in a population-based case-control study in Taixing City, China. With informed consent, we recruited cases with cancers of esophagus (n = 218), stomach (n = 206), and liver (n = 204), and one common healthy control group (n = 405). A standardized epidemiologic questionnaire was used in face-to-face interviews, and blood samples were collected during interviews. We observed an inverse association between plasma folate levels and liver cancer. The adjusted odds ratio (aOR) was 0.46 [95% confidence interval (CI) = 0.24-0.88] comparing individuals in the highest quartile to those in the lowest. We found a positive association between plasma vitamin B12 levels and all three cancers. The aORs for those in the highest quartile were 2.80 (95% CI = 1.51-5.18) for esophageal cancer, 2.17 (1.21-3.89) for stomach cancer, and 9.97 (4.82-20.60) for liver cancer, comparing to those in the lowest quartile. We further observed interaction between plasma folate and vitamin B12 on these cancers. Our data indicated associations between plasma folate and vitamin B12 with upper GI cancers in Chinese population. Further research is warranted considering the debate over the necessity of food fortification.

Multi-layered heterogeneous interfaces created in Co0.85Se@Ni3S4/NF to enhance supercapacitor performances by multi-step alternating electrodeposition.

Heterogeneous interface construction is of far-reaching significance to optimize the electrochemical performance of electrodes. Herein, a multi-step alternating electrochemical deposition (MAED) method is proposed to alternately deposit Co0.85Se and Ni3S4 nanosheets on a nickel foam (NF), forming a special alternate layer-by-layer structure with multi-layered heterogeneous interfaces. The creation of the multi-layered heterogeneous interfaces provides a large interfacial area for redox reactions with optimum interstitials facilitating ion diffusion, thus greatly improving the electrochemical energy storage efficiency. With the increase in the layer number, the material exhibits increasingly better energy storage performance, and 8L-Co0.85Se@Ni3S4/NF exhibits the highest specific capacitances of 2508 F g-1 and 1558 F g-1 at a scan rate of 2 mV s-1 and a current density of 1 A g-1. The 8L-Co0.85Se@Ni3S4/NF//polypyrrole (PPy)/NF asymmetric supercapacitor provides a maximum operation potential window of 1.55 V and energy densities of 76.98 and 35.74 W h kg-1 when the power densities are 775.0 and 15 500 W kg-1, respectively, superior to most of the related materials reported. Through MAED, the deposited phase and the layer number can be accurately controlled, thus providing an efficient strategy for interface construction so as to increase the electrochemical activity of the energy storage materials.

Evidence for activation of mutated p53 by apigenin in human pancreatic cancer.

Pancreatic cancer is an exceedingly lethal disease with a five-year survival that ranks among the lowest of gastrointestinal malignancies. Part of its lethality is attributable to a generally poor response to existing chemotherapeutic regimens. New therapeutic approaches are urgently needed. We aimed to elucidate the anti-neoplastic mechanisms of apigenin-an abundant, naturally-occurring plant flavonoid-with a particular focus on p53 function. Pancreatic cancer cells (BxPC-3, MiaPaCa-2) experienced dose and time-dependent growth inhibition and increased apoptosis with apigenin treatment. p53 post-translational modification, nuclear translocation, DNA binding, and upregulation of p21 and PUMA were all enhanced by apigenin treatment despite mutated p53 in both cell lines. Transcription-dependent p53 activity was reversed by pifithrin-α, a specific DNA binding inhibitor of p53, but not growth inhibition or apoptosis suggesting transcription-independent p53 activity. This was supported by immunoprecipitation assays which demonstrated disassociation of p53/BclXL and PUMA/BclXL and formation of complexes with Bak followed by cytochrome c release. Treated animals grew smaller tumors with increased cellular apoptosis than those fed control diet. These results suggest that despite deactivating mutation, p53 retains some of its function which is augmented following treatment with apigenin. Cell cycle arrest and apoptosis induction may be mediated by transcription-independent p53 function via interactions with BclXL and PUMA. Further study of flavonoids as chemotherapeutics is warranted.

Biomolecule-assisted construction of cadmium sulfide hollow spheres with structure-dependent photocatalytic activity.

In this study, we report the synthesis of monodispersive solid and hollow CdS spheres with structure-dependent photocatalytic abilities for dye photodegradation. The monodispersive CdS nanospheres were constructed with the assistance of the soulcarboxymthyi chitosan biopolymer under hydrothermal conditions. The solid CdS spheres were corroded by ammonia to form hollow CdS nanospheres through a dissolution-reprecipitation mechanism. Their visible-light photocatalytic activities were investigated, and the results show that both the solid and the hollow CdS spheres have visible-light photocatalytic abilities for the photodegradation of dyes. The photocatalytic properties of the CdS spheres were demonstrated to be structure dependent. Although the nanoparticles comprising the hollow spheres have larger sizes than those comprising the solid spheres, the hollow CdS spheres have better photocatalytic performances than the solid CdS spheres, which can be attributed to the special hollow structure.

Ellagic acid and embelin affect key cellular components of pancreatic adenocarcinoma, cancer, and stellate cells.

Ellagic acid is a polyphenolic phytochemical present in many fruits and nuts with anticancer properties demonstrated in experimental tumor studies. Embelin is a benzoquinone phytochemical isolated from the Japanese herb Ardisiae Japonicae and has been shown to induce apoptosis in cancer cells. We found that ellagic acid and embelin each dose-dependently increased apoptosis and inhibited proliferation in human pancreatic cancer cells, MIA PaCa-2 and HPAF-II cells, and in pancreatic stellate cells, which are progenitors of pancreatic cancer desmoplasia. In each of these cell types, combinations of ellagic acid and embelin at low micromolar concentrations (0.5-3 µM) induced synergistic increases in apoptosis and decreases in proliferation. Ellagic acid decreased NF-κB transcriptional activity, whereas embelin decreased STAT-3 phosphorylation and protein expression of its downstream target survivin in cancer cells. In vivo dietary ellagic acid alone or in combination with embelin decreased tumor size and tumor cellularity in a subcutaneous xenograft mouse model of pancreatic cancer. These results show that ellagic acid and embelin interact with divergent intracellular signaling pathways resulting in augmentation of apoptosis and inhibition of proliferation at low micromolar concentrations for the key cellular components of pancreatic adenocarcinoma.

Genetic variants of peroxisome proliferator-activated receptor δ are associated with gastric cancer.

BACKGROUND: Peroxisome proliferator-activated receptors (PPAR) are implicated in pathogenesis of insulin resistance and cancers of the digestive system. AIM: We investigated the associations of single nucleotide polymorphisms (SNPs) of PPAR δ and γ with gastric cancer and explored interactions with risk factors of gastric cancer. METHODS: We conducted our analysis in a case-control study of 196 gastric cancer patients and 397 controls residing in the Taixing region of Jiangsu, China. Six SNPs in the PPARδ (rs2076167, rs3734254) and PPARγ genes (rs10865710, rs1801282, rs3856806, rs13306747) were genotyped. We employed logistic regression to evaluate the association between each genotype and gastric cancer and tested for gene-environment interaction with Helicobacter pylori (H. pylori) infection, smoking status, and meat and salt intake. RESULTS: We found that the G/G variant rs2076167, in tight linkage disequilibrium with rs3734254 (R (2) = 0.97), was associated with increased risk of gastric cancer in a recessive model (OR 2.20, 95 % CI 1.12, 4.32). The association between G/G variant of rs2016167 and gastric cancer was particularly strong among those with higher salt intake (OR 5.11, 95 % CI 1.11, 23.5), but did not vary by H. pylori infection or smoking status. CONCLUSION: We found that genetic variants of PPARδ were associated with gastric cancer. If the association is confirmed in larger studies, it may implicate a role for PPARδ activators, such as insulin-sensitizing agents, in prevention of gastric cancer.