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According to the Species Catalogue of China, Tibet, China, has more than 1,000 species of bryophytes, showing its remarkably high biodiversity. Amongst them, the Polytrichaceae is one of the largest family, with six genera and 25 species, one subspecies and two varieties reported previously.Based on a field survey and specimen identification, the following species have been newly recorded in the bryoflora of Tibet, namely Oligotrichum obtusatum Broth., Pogonatum contortum (Menzies ex Brid.) Lesq. and Polytrichum sphaerothecium (Besch.) Müll. Hal.

In response to the problems of unclear distribution of deep-water pre-salt carbonate reservoirs and formation conditions of large oil fields in the Santos passive continental margin basin, based on comprehensive utilization of geological, seismic, and core data, and reconstruction of Early Cretaceous prototype basin and lithofacies paleogeography, it is proposed for the first time that the construction of pre-salt carbonate build-ups was controlled by two types of isolated platforms: inter-depression fault-uplift and intra-depression fault-high. The inter-depression fault-uplift isolated platforms are distributed on the present-day pre-salt uplifted zones between depressions, and are built on half- and fault-horst blocks that were inherited and developed in the early intra-continental and inter-continental rift stages. The late intra-continental rift coquinas of the ITP Formation and the early inter-continental rift microbial limestones of the BVE Formation are continuously constructed; intra-depression fault-high isolated platforms are distributed in the current pre-salt depression zones, built on the uplifted zones formed by volcanic rock build-ups in the early prototype stage of intra-continental rifts, and only the BVE microbial limestones are developed. Both types of limestones formed into mound-shoal bodies, that have the characteristics of large reservoir thickness and good physical properties. Based on the dissection of large pre-salt oil fields discovered in the Santos Basin, it has been found that both types of platforms could form large-scale combined structural-stratigraphic traps, surrounded by high-quality lacustrine and lagoon source rocks at the periphery, and efficiently sealed by thick high-quality evaporite rocks above, forming the optimal combination of source, reservoir and cap in the form of “lower generation, middle storage, and upper cap”, with a high degree of oil and gas enrichment. It has been found that the large oil fields are all bottom water massive oil fields with a unified pressure system, and they are all filled to the spill-point. The future exploration is recommended to focus on the inter-depression fault-uplift isolated platforms in the western uplift zone and the southern section of eastern uplift zones, as well as intra-depression fault-high isolated platforms in the central depression zone. The result not only provides an important basis for the advanced selection of potential play fairways, bidding of new blocks, and deployment of awarded exploration blocks in the Santos Basin, but also provides a reference for the global selection of deep-water exploration blocks in passive continental margin basins.

Abstract Sequence-based genetic testing identifies causative variants in ~ 50% of individuals with developmental and epileptic encephalopathies (DEEs). Aberrant changes in DNA methylation are implicated in various neurodevelopmental disorders but remain unstudied in DEEs. We interrogate the diagnostic utility of genome-wide DNA methylation array analysis on peripheral blood samples from 582 individuals with genetically unsolved DEEs. We identify rare differentially methylated regions (DMRs) and explanatory episignatures to uncover causative and candidate genetic etiologies in 12 individuals. Using long-read sequencing, we identify DNA variants underlying rare DMRs, including one balanced translocation, three CG-rich repeat expansions, and four copy number variants. We also identify pathogenic variants associated with episignatures. Finally, we refine the CHD2 episignature using an 850 K methylation array and bisulfite sequencing to investigate potential insights into CHD2 pathophysiology. Our study demonstrates the diagnostic yield of genome-wide DNA methylation analysis to identify causal and candidate variants as 2% (12/582) for unsolved DEE cases.

Alfalfa (Medicago sativa. L.) is a globally significant autotetraploid legume forage crop. However, despite its importance, establishing efficient gene editing systems for cultivated alfalfa remains a formidable challenge. In this study, we pioneered the development of a highly effective ultrasonic-assisted leaf disc transformation system for Gongnong 1 alfalfa, a variety widely cultivated in Northeast China. Subsequently, we created a single transcript CRISPR/Cas9 (CRISPR_2.0) toolkit, incorporating multiplex gRNAs, designed for gene editing in Gongnong 1. Both Cas9 and gRNA scaffolds were under the control of the Arabidopsis ubiquitin-10 promoter, a widely employed polymerase II constitutive promoter known for strong transgene expression in dicots. To assess the toolkit’s efficiency, we targeted PALM1, a gene associated with a recognizable multifoliate phenotype. Utilizing the CRISPR_2.0 toolkit, we directed PALM1 editing at two sites in the wild-type Gongnong 1. Results indicated a 35.1% occurrence of editing events all in target 2 alleles, while no mutations were detected at target 1 in the transgenic-positive lines. To explore more efficient sgRNAs, we developed a rapid, reliable screening system based on Agrobacterium rhizogenes-mediated hairy root transformation, incorporating the visible reporter MtLAP1. This screening system demonstrated that most purple visible hairy roots underwent gene editing. Notably, sgRNA3, with an 83.0% editing efficiency, was selected using the visible hairy root system. As anticipated, tetra-allelic homozygous palm1 mutations exhibited a clear multifoliate phenotype. These palm1 lines demonstrated an average crude protein yield increase of 21.5% compared to trifoliolate alfalfa. Our findings highlight the modified CRISPR_2.0 system as a highly efficient and robust gene editing tool for autotetraploid alfalfa.

Drought stress inhibits oat growth and yield. The application of fulvic acid (FA) can improve the drought resistance of oats, but the corresponding molecular mechanism of FA-mediated drought resistance remains unclear. Here, we studied the effects of FA on the drought tolerance of oat leaves through physiological, transcriptomic, and metabolomics analyses, and identified FA-induced genes and metabolites related to drought tolerance. Physiological analysis showed that under drought stress, FA increased the relative water and chlorophyll contents of oat leaves, enhanced the activity of antioxidant enzymes (SOD, POD, PAL, CAT and 4CL), inhibited the accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2) and dehydroascorbic acid (DHA), reduced the degree of oxidative damage in oat leaves, improved the drought resistance of oats, and promoted the growth of oat plants. Transcriptome and metabolite analyses revealed 652 differentially expressed genes (DEGs) and 571 differentially expressed metabolites (DEMs) in FA-treated oat leaves under drought stress. These DEGs and DEMs are involved in a variety of biological processes, such as phenylspropanoid biosynthesis and glutathione metabolism pathways. Additionally, FA may be involved in regulating the role of DEGs and DEMs in phenylpropanoid biosynthesis and glutathione metabolism under drought stress. In conclusion, our results suggest that FA promotes oat growth under drought stress by attenuating membrane lipid peroxidation and regulating the antioxidant system, phenylpropanoid biosynthesis, and glutathione metabolism pathways in oat leaves. This study provides new insights into the complex mechanisms by which FA improves drought tolerance in crops.

Abstract Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of multiple tissue types for diagnosis. Of 99 total tumor specimens, 16 (16.1%) have 11p15.5 normal retention of imprinting, 25 (25.2%) have 11p15.5 copy neutral loss of heterozygosity, and 58 (58.6%) have 11p15.5 H19/ICR1 epigenetic hypermethylation (loss of imprinting). Here, we ascertain the epigenetic and genetic modes of bilateral Wilms tumor predisposition.

The East African Rift System (EARS) is the youngest rift with the eastern and western branches, consisting of multiple secondary rifts. It is generally characterized by low extent of exploration and great exploration potential. Identifying the differences in hydrocarbon accumulation conditions in various rifts is very important in providing guidance for hydrocarbon exploration and selecting favorable exploration targets in this area. Based on the interpretation of first-hand seismic-geological data, and combining other materials such as commercial databases and open access literature, the structural characteristics of the main rifts in the eastern and western branches of the EARS are comparatively analyzed; based on the anatomy of the discovered hydrocarbon reservoirs, the rifts of the EARS are classified into four types depending on their structural styles, including double-fault type, simple single-fault type, single-fault transfer type, and single-fault terrace type, and the control of structural style over hydrocarbon accumulation in the EARS is discussed. In the Western Branch of the EARS, large rifts such as the Albertine Rift and the Tanganyika Rift are mainly of double-fault type and single-fault transfer type, and only some small rifts are of the simple single-fault type. The rifts in the Eastern Branch of the EARS are generally small; the rifts in the northern section of the Western Branch are mainly of the simple single-fault type, and those in the southern section are mainly of the single-fault terrace type. The hydrocarbon potential of double-fault rifts is the greatest, followed by that of simple single-fault rifts and single-fault transfer rifts, and the hydrocarbon potential of single-fault terrace rifts is relatively limited. The results obtained from a comparative analysis of the structures, sediment fills, and reservoir elements of various rifts show that the west side of the Albertine Rift, the southeast of the Tanganyika Rift, the Kerio Rift, and the land in the northwest of the Turkana Rift have great exploration potential.

The global trends in deepwater oil and gas exploration, characteristics of deepwater oil and gas discovery, and layout of deepwater oil and gas exploration business by seven major international oil companies are systematically analyzed using commercial databases (e.g. S&P Global and Rystad) and public information of oil companies. The deepwater area is currently the most important domain for global oil and gas exploration and discovery, with the most discoveries and reserves in passive continental margin basins. The deepwater discoveries have the greatest contribution to the total newly discovered oil and gas reserves in the sea areas, with an increasing number of lithological reservoirs discovered, and oil and gas discoveries mainly distributed in the Mesozoic–Cenozoic. The seven major international oil companies are widely active in various aspects of deepwater oil and gas exploration and development, and play a leading role. Based on years of theoretical understanding of global oil and gas geology and resource evaluation, it is proposed that favorable deepwater exploration areas in the future will mainly focus on three major areas: the Atlantic coast, the Indian Ocean periphery, and the Arctic Ocean periphery. Six suggestions are put forward for expanding overseas deepwater oil and gas exploration business: first, expand the sources for obtaining multi-user seismic data and improve the scientific selection of deepwater exploration areas; second, increase efforts to obtain deepwater exploration projects in key areas; third, adopt various methods to access into/exit from resource licenses flexibly; fourth, acquire licenses with large equity and operate in “dual-exploration” model; fifth, strengthen cooperation with leading international oil companies in deepwater technology; and sixth, improve business operation capabilities and gradually transform from “non-operators” to “operators”.

Abstract Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Abstract Background DNA methylation (DNAm) plays an important role in lipid metabolism, however, no epigenome-wide association study (EWAS) of lipid levels has been conducted among childhood cancer survivors. Here, we performed EWAS analysis with longitudinally collected blood lipid data from survivors in the St. Jude lifetime cohort study. Methods Among 2052 childhood cancer survivors of European ancestry (EA) and 370 survivors of African ancestry (AA), four types of blood lipids, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG), were measured during follow-up beyond 5-years from childhood cancer diagnosis. For the exposure EWAS (i.e., lipids measured before blood draw for DNAm), the DNAm level was an outcome variable and each of the blood lipid level was an exposure variable; vice versa for the outcome EWAS (i.e., lipids measured after blood draw for DNAm). Results Among EA survivors, we identified 43 lipid-associated CpGs in the HDL (n = 7), TC (n = 3), and TG (n = 33) exposure EWAS, and 106 lipid-associated CpGs in the HDL (n = 5), LDL (n = 3), TC (n = 4), and TG (n = 94) outcome EWAS. Among AA survivors, we identified 15 lipid-associated CpGs in TG exposure (n = 6), HDL (n = 1), LDL (n = 1), TG (n = 5) and TC (n = 2) outcome EWAS with epigenome-wide significance (P 70%) between EA and AA survivors, highlighting differences in DNAm markers of blood lipids between populations with diverse genetic ancestry. Ten lipid-associated CpGs were cis-expression quantitative trait methylation with their DNAm levels associated with the expression of corresponding genes, out of which seven were negatively associated. Conclusions We identified distinct signatures of DNAm for blood lipids as exposures or outcomes and between EA and AA survivors, revealing additional genes involved in lipid metabolism and potential novel targets for controlling blood lipids in childhood cancer survivors.

Social epigenomics is an emerging field in which social scientist collaborate with computational biologists, especially epigeneticists, to address the underlying pathway for biological embedding of life experiences. This social epigenomics study included long-term childhood cancer survivors enrolled in the St. Jude Lifetime Cohort. DNA methylation (DNAm) data were generated using the Illumina EPIC BeadChip, and three social determinants of health (SDOH) factors were assessed: self-reported educational attainment, personal income, and an area deprivation index based on census track data. An epigenome-wide association study (EWAS) was performed to evaluate the relation between DNAm at each 5’-cytosine-phosphate-guanine-3’ (CpG) site and each SDOH factor based on multivariable linear regression models stratified by ancestry (European ancestry, n = 1,618; African ancestry, n = 258). EWAS among survivors of European ancestry identified 130 epigenome-wide significant SDOH–CpG associations (P

The global exploration investment, new oil and gas discoveries, exploration business adjustment strategies of oil companies in 2021, and future favorable exploration domains are systematically analyzed using commercial databases such as IHS and public information of oil companies. It has been found that the world oil and gas exploration situation in 2021 has continued the downturn since the outbreak of COVID-19. The investment and drilling workload decreased slightly, but the success rate of exploration wells, especially deepwater exploration wells, increased significantly, and the newly discovered reserves increased slightly compared with last year. Deep waters of the passive continental margin basins are still the leading sites for discovering conventional large and medium-sized oil and gas fields. The conventional oil and gas exploration in deep formations of onshore petroliferous basins has been keeping a good state, with tight/shale oil and gas discoveries made in Saudi Arabia, Russia, and other countries. While strengthening the exploration and development of local resources, national, international, and independent oil companies have been focusing on major overseas frontiers using their advantages, including risk exploration in deep waters and natural gas. Future favorable exploration directions in the three major frontiers, the global deep waters, deep onshore formations, and unconventional resources, have been clarified. Four suggestions are put forward for the global exploration business of Chinese oil companies: first, a farm in global deepwater frontier basins in advance through bidding at a low cost and adopt the “dual exploration model” after making large-scale discoveries; second, enter new blocks of emerging hot basins in the world through farm-in and other ways, to find large oil and gas fields quickly; third, cooperate with national oil companies of the resource host countries in the form of joint research and actively participate exploration of deep onshore formations of petroliferous basins; fourth, track tight/shale oil and gas cooperation opportunities in a few countries such as Saudi Arabia and Russia, and take advantage of mature domestic theories and technologies to farm in at an appropriate time.

Eosinophilia may result from three main causes: secondary (reactive), primary (clonal), and/or idiopathic. The diagnosis of idiopathic eosinophilia must be made based on excluding all reactive or clonal causes. However, some causes may be very rare so as to be misdiagnosed as idiopathic. We present the case of eosinophilia caused by aggressive systemic mastocytosis, originally recognized as idiopathic. Lymphadenopathy, dysmyelopoiesis, and hepatosplenomegaly gradually appeared and deteriorated with increasing eosinophils. This case carried KIT D816V mutation. The BCR::ABL fusion gene and the mutations in JAK2 V617F, PDGFRα , and PDGFRβ in bone marrow were all negative. PHF6, PPM1D , and TET2 mutations were demonstrable. The patient was prescribed to avapritinib. The condition was effectively controlled. However, the patient discontinued medication for economic reasons 5 months later. Disease progression happened and died 10 months after diagnosis. Our study indicates that gene mutation detection at diagnosis is helpful for patient accurate diagnosis and targeted therapy of such patients.

Grazing disturbance can change the structure of plant rhizosphere microbial communities and thereby alter the feedback to promote plant growth or induce plant defenses. However, little is known about how such changes occur and vary under different grazing pressures or the roles of root metabolites in altering the composition of rhizosphere microbial communities. In this study, the effects of different grazing pressures on the composition of microbial communities were investigated, and the mechanisms by which different grazing pressures changed rhizosphere microbiomes were explored with metabolomics. Grazing changed composition, functions, and co-expression networks of microbial communities. Under light grazing (LG), some saprophytic fungi, such as Lentinus sp., Ramichloridium sp., Ascobolus sp. and Hyphoderma sp., were significantly enriched, whereas under heavy grazing (HG), potentially beneficial rhizobacteria, such as Stenotrophomonas sp., Microbacterium sp., and Lysobacter sp., were significantly enriched. The beneficial mycorrhizal fungus Schizothecium sp. was significantly enriched in both LG and HG. Moreover, all enriched beneficial microorganisms were positively correlated with root metabolites, including amino acids (AAs), short-chain organic acids (SCOAs), and alkaloids. This suggests that these significantly enriched rhizosphere microbial changes may be caused by these differential root metabolites. Under LG, it is inferred that root metabolites, especially AAs such as L-Histidine, may regulate specific saprophytic fungi to participate in material transformations and the energy cycle and promote plant growth. Furthermore, to help alleviate the stress of HG and improve plant defenses, it is inferred that the root system actively regulates the synthesis of these root metabolites such as AAs, SCOAs, and alkaloids under grazing interference, and then secretes them to promote the growth of some specific plant growth-promoting rhizobacteria and fungi. To summarize, grasses can regulate beneficial microorganisms by changing root metabolites composition, and the response strategies vary under different grazing pressure in typical grassland ecosystems.

How to assess intercultural competence is the key to exploring intercultural effectiveness. Although various methods have been developed for assessing intercultural competence (e.g., interviews, self-report questionnaire, critical analysis, etc.), this study assesses intercultural competence using videotapes to observe participants’ performance in the multicultural interactions. A comparative study was conducted comparing home students who were interculturally trained and who did not. By examining their performance in group discussion, two specific aspects – eye gaze and amount of talk – were analysed by both quantitative and qualitative techniques. The results show that trained home students not only had more and longer eye gazes than the untrained students during group discussion, but they also used more other-oriented speech than the untrained. Such findings indicate that the trained home students were more interculturally competent than the untrained especially in the multicultural intra-group interaction setting. As there are many other variables to examine (e.g., non-verbal cues such as body gestures and facial expressions), this study demonstrates a way to assess intercultural competence using videotapes in both verbal and non-verbal cues for the future research.

Abstract Background Increased epigenetic age acceleration (EAA) in survivors of childhood cancer is associated with specific treatment exposures, unfavorable health behaviors, and presence of certain chronic health conditions. To better understand inter-individual variability, we investigated the genetic basis underlying EAA. Methods Genome-wide association studies of EAA based on multiple epigenetic clocks (Hannum, Horvath, PhenoAge, and GrimAge) were performed. MethylationEPIC BeadChip array and whole-genome sequencing data were generated with blood-derived DNA from participants in the St. Jude Lifetime Cohort Study (discovery: 2138 pre-existing and 502 newly generated data, all survivors; exploratory: 282 community controls). Linear regression models were fit for each epigenetic age against the allelic dose of each genetic variant, adjusting for age at sampling, sex, and cancer treatment exposures. Fixed-effects meta-analysis was used to combine summary statistics from two discovery data sets. LD (Linkage disequilibrium) score regression was used to estimate single-nucleotide polymorphism (SNP)-based heritability. Results For EAA-Horvath, a genome-wide significant association was mapped to the SELP gene with the strongest SNP rs732314 (meta-GWAS: β=0.57, P=3.30×10-11). Moreover, the stratified analysis of the association between rs732314 and EAA-Horvath showed a substantial heterogeneity between children and adults (meta-GWAS: β=0.97 vs. 0.51, I 2 =73.1%) as well as between survivors with and without chest/abdominal/pelvic-RT exposure (β=0.64 vs. 0.31, I 2 =66.3%). For EAA-Hannum, an association was mapped to the HLA locus with the strongest SNP rs28366133 (meta-GWAS: β=0.78, P=3.78×10-11). There was no genome-wide significant hit for EAA-PhenoAge or EAA-GrimAge. Interestingly, among community controls, rs732314 was associated with EAA-Horvath (β=1.09, P=5.43×10-5), whereas rs28366133 was not associated with EAA-Hannum (β=0.21, P=0.49). The estimated heritability was 0.33 (SE=0.20) for EAA-Horvath and 0.17 (SE=0.23) for EAA-Hannum, but close to zero for EAA-PhenoAge and EAA-GrimAge. Conclusions We identified novel genetic variants in the SELP gene and HLA region associated with EAA-Horvath and EAA-Hannum, respectively, among survivors of childhood cancer. The new genetic variants in combination with other replicated known variants can facilitate the identification of survivors at higher risk in developing accelerated aging and potentially inform drug targets for future intervention strategies among vulnerable survivors.

In this paper, we study the structural characteristics and sedimentary filling differences of the passive continental margin basins of East Africa and establish hydrocarbon accumulation models in different basins. In the research process, the research methods of prototype basin and lithofacies paleogeography restoration, oil and gas reservoir anatomy, two-dimensional seismic data interpretation, etc. The passive continental margin basins in East Africa are divided into four types of passive continental margin basins, namely “rifted type,” “depressed type,” “faulted depression type,” and “reformed delta type,” based on the three prototype stages of intracontinental aborted rift, intracontinental-intercontinental rift, and passive continental margin basin, and the difference in sedimentary filling thickness between rift and depression periods. Finally, the accumulation models of different types of basins are established, and the favorable accumulation combinations and future exploration directions are discussed.

To investigate the flavor changes of Fuliji roast chicken during processing and storage, the volatile organic compounds (VOCs) during processing (fresh, fried, stewed and sterilized) and storage (1 month, 2 months and 4 months) were determined by gas chromatography ion mobility spectrometry (GC-IMS). A total of 47 kinds of VOCs were identified across seven sampling stages, including aldehydes, hydrocarbons, alcohols, ketones, esters, ethers and heterocyclic compounds. More diverse range of aldehydes, alcohols, ketones and esters have been detected compared to acids, ethers and heterocyclic substances. Fingerprints directly reflect the pattern of VOCs at different stages of growth and decay, revealing that frying and stewing are key processes in flavor formation, and that sterilization and storage processes lead to flavor loss in Fuliji roast chicken. Hexanal, nonanal, octanal, 2-heptanone, 3-octanol, 1-octene-3-alcohol, 1-pentanol and ethyl acetate were mainly generated during the frying process. Benzaldehyde, nonanal, octanal, methyl-5-hepten-2-one, 2-methyl-3-heptanone, 1,8-Cineole, linalool, butyl acetate, ethyl propionate, ethyl acetate, coumarin, 2-furfuryl methyl disulfide and 2-pentyl furan were mainly generated during the stewing process. After sterilization, the content of octanal-D, 2-heptanone-D, 2-Methyl-3-heptanone, pentan-1-ol-D decreased, resulting in the reduction of aroma, lemon flavor and oil flavor of Fuliji roast chicken. Seven flavor markers, including hexanal-D, nonanal-M, octanal-M, heptanal-D, acetone, 3-octanol and ethyl acetate-D, were identified in the evolution of the aroma profile of Fuliji roast chicken.

Abstract Resistance to anti-cancer monoclonal antibody (mAb) therapy remains a clinical challenge. Previous work in our laboratory has shown that T cell help in the form of interleukin-2 maintains long-term NK cell viability and NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Lack of such T cell help may be a potential mechanism for resistance to mAb therapy. Here, we evaluate whether concomitant treatment with anti-CD3 × anti-cancer bispecific antibodies (bsAbs) can overcome this resistance by enhancing T cell help, and thereby maintaining long-term NK cell-mediated ADCC. Normal donor peripheral blood mononuclear cells were depleted of T cells, replenished with defined numbers of autologous T cells (from 0.75 to 50%) and co-cultured with mono-/bispecific antibody-treated target tumor cells for up to 7 days. At low T cell concentrations, bsAb-activated T cells (mainly CD4+ T cells) were more effective than resting T cells at maintaining NK cell viability and ADCC. Brief (4 h to 2 day) bsAb exposure was sufficient to enhance long-term ADCC by NK cells. These findings raise the hypothesis that local T cell activation mediated by systemic treatment with anti-CD3 X anti-cancer bsAb may enhance the anti-tumor efficacy of monospecific mAbs that mediate their primary therapeutic effect via NK-mediated ADCC.

BackgroundOver 50% of childhood cancer survivors are exercise intolerant, with maximal aerobic capacities comparable to individuals decades older, suggesting early physiologic ageing. In addition, 36% of survivors are obese. Optimal exercise capacity provides a foundation to support daily function and healthy body habitus and is associated with benefits to cognition, cardiovascular health, and longevity. Cellular senescence and inflammation are key mechanisms that drive age-related disease, quantifiable as biomarkers in peripheral blood.AimsThis study aimed to evaluate associations between p16INKa, a biomarker of cellular senescence, and inflammation and exercise capacity among adult survivors of childhood cancer.Materials and methodsEligible survivors were recruited from the St. Jude Lifetime (SJLIFE) Cohort Study. Exercise capacity was assessed by maximal oxygen uptake (VO2, ml/kg/min) obtained via cardiopulmonary exercise testing using a modified Bruce protocol. Body fat (%) was determined from dual energy x-ray absorptiometry (DEXA). Peripheral blood samples were used to evaluate log2 p16INK4a mRNA expression, a biomarker of cellular senescence, and inflammation with high sensitivity C-reactive protein (hs-CRP) levels. Multivariable regression evaluated associations between p16INK4a, hs-CRP, body fat, and exercise capacity.ResultsParticipants included 185 five-year childhood cancer survivors (mean age 36.6 [range 20.1 - 55.7] years, 44% male, 77% non-Hispanic white, 53% leukemia/lymphoma). Compared to males, females had lower peak VO2 (mean ± SD, 22.5 ± 8.2 vs. 28.8 ± 7.7 ml/kg/min, p

Abstract Myelodysplastic syndrome with myelofibrosis (MDS-MF) has been associated with an inferior prognosis compared with MDS without MF. However, MDS-MF is not listed independently as a subtype of MDS, and its clinical and genetic characteristics remain poorly understood. We retrospectively compared 53 patients with MDS-MF (44 MF grade 1/MF1; 9 MF grade 2–3/MF2 − 3) and 31 with de novo MDS without MF (MDS). The leukemic transformation risks of both MDS-MF2 − 3 and MDS-MF1 were increased compared with the MDS group. To identify the potential mechanisms responsible for the leukemic transformation of MDS-MF, we performed single-cell sequencing for one MDS-MF2 − 3 patient before and after leukemic transformation to explore the variations in gene expression levels. In addition to upgraded expression levels of acute myeloid leukemia-related genes during leukemic transformation, expression levels of some inflammation-related genes (such as S100s, RNASE3, and CYBB) were also increased, and inflammation-related pathways were up-regulated. These results suggest that inflammation-related genes and pathways may play an important role in the leukemic transformation of MDS-MF.

Abstract Background It is well-established that cancer treatment substantially increases the risk of long-term adverse health outcomes among childhood cancer survivors. However, there is limited research on the underlying mechanisms. To elucidate the pathophysiology and a possible causal pathway from treatment exposures to cardiometabolic conditions, we conducted epigenome-wide association studies (EWAS) to identify the DNA methylation (DNAm) sites associated with cancer treatment exposures and examined whether treatment-associated DNAm sites mediate associations between specific treatments and cardiometabolic conditions. Methods We included 2052 survivors (median age 33.7 years) of European ancestry from the St. Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Cumulative doses of chemotherapy and region-specific radiation were abstracted from medical records. Seven cardiometabolic conditions were clinically assessed. DNAm profile was measured using MethylationEPIC BeadChip with blood-derived DNA. Results By performing multiple treatment-specific EWAS, we identified 935 5′-cytosine-phosphate-guanine-3′ (CpG) sites mapped to 538 genes/regions associated with one or more cancer treatments at the epigenome-wide significance level (p

Based on regional geology, 2D seismic and ocean drilling data, the formation of the Eratosthenes Seamount (ESM) and its surrounding isolated platforms, types of organic reefs and hydrocarbon accumulation conditions in the eastern Mediterranean were analyzed through fine tectonic interpretation and seismic facies study, and the future exploration targets were pointed out. The formation and evolution of the ESM and its peripheral isolated platforms are highly related to the open and close of the Neotethyan ocean. The precursors of the ESM and its peripheral isolated platforms are both horst-type fault blocks formed in the Middle Triassic–Early Jurassic intracontinental rift stage. The ESM and its peripheral isolated platforms underwent continued and inherited carbonate build-ups during the Middle Jurassic intercontinental rift stage, the Late Jurassic–Late Cretaceous Turonian passive drift stage, and Late Cretaceous Senonian–Miocene subduction stage, as well as medium-slight inversion transformation beginning in the Late Miocene Messinian caused by the closure of the Neotethyan ocean. Three types of isolated platforms formed controlled by variant paleo-tectonic settings: the first type is composed of a single patch-like reef controlled by a small-scale and narrow horst-type fault block, the second type consists of a single atoll controlled by a middle-scale and wide horst-type fault block, and the third type is comprised of multiple reef-beach complexes controlled by a large-scale and broad paleo-high. The first two types universally developed in the highs of the alternate sag-uplift structural zones on the south and west of Eratosthenes, and the third type only developed in the ESM. As a result of fluctuation of sea level, two sequences of reef build-ups, i.e. the Middle Jurassic Bajocian–Upper Cretaceous Turonian and the Miocene, developed in the ESM as well as the highs in the alternate sag-uplift structural zones on the south and west of Eratosthenes. Drillings have confirmed that the first two types of isolated platforms with a single patch-like reef and a single circle-like reef have good conditions for natural gas accumulations. The isolated platform of reef-beach complexes in the ESM also has accumulation potentials of natural gas and is worth prospecting.

Abstract Background There is currently no method to precisely measure the errors that occur in the sequencing instrument/sequencer, which is critical for next-generation sequencing applications aimed at discovering the genetic makeup of heterogeneous cellular populations. Results We propose a novel computational method, SequencErr, to address this challenge by measuring the base correspondence between overlapping regions in forward and reverse reads. An analysis of 3777 public datasets from 75 research institutions in 18 countries revealed the sequencer error rate to be ~ 10 per million (pm) and 1.4% of sequencers and 2.7% of flow cells have error rates > 100 pm. At the flow cell level, error rates are elevated in the bottom surfaces and > 90% of HiSeq and NovaSeq flow cells have at least one outlier error-prone tile. By sequencing a common DNA library on different sequencers, we demonstrate that sequencers with high error rates have reduced overall sequencing accuracy, and removal of outlier error-prone tiles improves sequencing accuracy. We demonstrate that SequencErr can reveal novel insights relative to the popular quality control method FastQC and achieve a 10-fold lower error rate than popular error correction methods including Lighter and Musket. Conclusions Our study reveals novel insights into the nature of DNA sequencing errors incurred on DNA sequencers. Our method can be used to assess, calibrate, and monitor sequencer accuracy, and to computationally suppress sequencer errors in existing datasets.

In this work, we experimentally achieved a real-time video optical wireless transmission which can broadcast two users in different positions, simultaneously. Firstly, a single-pixel 50-μm micro-LED is designed and fabricated on a GaN-based wafer and then two micro-LED chips are connected as parallel form in a single bulb. The transceiver based on two FPGA boards is used to generate quadrature amplitude modulation-orthogonal frequency division multiplexed (QAM-OFDM) signals and measure the communication performance of the VLC system. The low-power micro-LEDs bulb emits 0.8 mW optical power through two optical paths at 20 mA driving current, and the modulation bandwidths for two users’ access are 90 MHz and 73 MHz, respectively. In this two-user real-time video transmission system, the total data rate exceeds 105.54 Mbps without naked eye discernable distortion over 2-m free-space distance. Different from traditional point-to-point links, this work demonstrates the possibility of flexible high-speed multi-user real-time video optical wireless transmission based on a parallel micro-LEDs bulb.

The five-year survival rate of childhood cancer has increased substantially over the past 50 yr; however, racial/ethnic disparities in health outcomes of survival have not been systematically reviewed. This scoping review summarized health disparities between racial/ethnic minorities (specifically non-Hispanic Black and Hispanic) and non-Hispanic White childhood cancer survivors, and elucidated factors that may explain disparities in health outcomes. We used the terms “race”, “ethnicity”, “childhood cancer”, “pediatric cancer”, and “survivor” to search the title and abstract for the articles published in PubMed and Scopus from inception to February 2021. After removing duplicates, 189 articles were screened, and 23 empirical articles were included in this review study. All study populations were from North America, and the mean distribution of race/ethnicity was 6.9% for non-Hispanic Black and 4.5% for Hispanic. Health outcomes were categorized as healthcare utilization, patient-reported outcomes, chronic health conditions, and survival status. We found robust evidence of racial/ethnic disparities over four domains of health outcomes. However, health disparities were explained by clinical factors (e.g., diagnosis, treatment), demographic (e.g., age, sex), individual-level socioeconomic status (SES; e.g., educational attainment, personal income, health insurance coverage), family-level SES (e.g., family income, parent educational attainment), neighborhood-level SES (e.g., geographic location), and lifestyle health risk (e.g., cardiovascular risk) in some but not all articles. We discuss the importance of collecting comprehensive social determinants of racial/ethnic disparities inclusive of individual-level, family-level, and neighborhood-level SES. We suggest integrating these variables into healthcare systems (e.g., electronic health records), and utilizing information technology and analytics to better understand the disparity gap for racial/ethnic minorities of childhood cancer survivors. Furthermore, we suggest national and local efforts to close the gap through improving health insurance access, education and transportation aid, racial-culture-specific social learning interventions, and diversity informed training.

Based on the compilation and analysis of the lithofacies and paleogeography distribution maps at present and paleoplate locations during six key geological periods of the Mesozoic and Cenozoic, the lithofacies and paleogeography features and their development laws were expounded. Based on our previous research results on lithofacies and paleogeography from Precambrian to Paleozoic, we systematically studied the features and evolution laws of global lithofacies and paleogeography from the Precambrian and their effects on the formation of source rocks, reservoirs, cap rocks and the distribution of oil and gas worldwide. The results show that since Precambrian, the distribution areas of uplift erosion and terrestrial clastic deposition tended to increase gradually, and increased significantly during the period of continental growth. The scale of coastal and shallow marine facies area had three distinct cycles, namely, from Precambrian to Devonian, from Carboniferous to Triassic, and from Jurassic to Neogene. Correspondingly, the development of shallow carbonate platform also showed three cycles; the lacustrine facies onshore was relatively developed in Mesozoic and Cenozoic; the sabkha was mainly developed in the Devonian, Permian and Triassic. The Cretaceous is the most important source rock layers in the world, followed by the Jurassic and Paleogene source rocks; the clastic reservoirs have more oil and gas than the carbonate reservoirs; the basins with shale caprocks have the widest distribution, the most abundant reserves of oil and gas, and the evaporite caprocks have the strongest sealing capacity, which can seal some huge oil and gas fields. Key words: global, lithofacies and paleogeography, plate tectonics, tectonic evolution, source rocks, reservoir, caprock, oil and gas distribution

Abstract Background Sequencing errors are key confounding factors for detecting low-frequency genetic variants that are important for cancer molecular diagnosis, treatment, and surveillance using deep next-generation sequencing (NGS). However, there is a lack of comprehensive understanding of errors introduced at various steps of a conventional NGS workflow, such as sample handling, library preparation, PCR enrichment, and sequencing. In this study, we use current NGS technology to systematically investigate these questions. Results By evaluating read-specific error distributions, we discover that the substitution error rate can be computationally suppressed to 10−5 to 10−4, which is 10- to 100-fold lower than generally considered achievable (10−3) in the current literature. We then quantify substitution errors attributable to sample handling, library preparation, enrichment PCR, and sequencing by using multiple deep sequencing datasets. We find that error rates differ by nucleotide substitution types, ranging from 10−5 for A>C/T>G, C>A/G>T, and C>G/G>C changes to 10−4 for A>G/T>C changes. Furthermore, C>T/G>A errors exhibit strong sequence context dependency, sample-specific effects dominate elevated C>A/G>T errors, and target-enrichment PCR led to ~ 6-fold increase of overall error rate. We also find that more than 70% of hotspot variants can be detected at 0.1 ~ 0.01% frequency with the current NGS technology by applying in silico error suppression. Conclusions We present the first comprehensive analysis of sequencing error sources in conventional NGS workflows. The error profiles revealed by our study highlight new directions for further improving NGS analysis accuracy both experimentally and computationally, ultimately enhancing the precision of deep sequencing.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10−26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10−3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

A significant challenge of visible-light communication systems (VLC) is to overcome their limited converge area in non-line-of-sight (NLOS) transmission. To tackle this problem, for the first time, a real-time high-speed dual-hop VLC system based on blue micro-light-emitting diodes (micro-LED) is proposed and experimentally demonstrated. Benefiting from the advantage of high electrical-to-optical (E-O) bandwidth of the micro-LED, the frequency-response measurements show that the 3-dB modulation bandwidth of 2 m free-space single-hop link is 880 MHz, and the dual-hop system can reach to 715 MHz over a 4 m communication distance. We then investigated the communication performance of our proposed single-hop and dual-hop systems. The real-time waveforms are analyzed at different positions of the dual-hop link and eye diagrams at the receiving terminal are captured for evaluation. Furthermore, the bit error rate (BER) at the target node is measured. The results demonstrate that a 1.1 Gbps on-off keying (OOK) signal with a BER less than the forward-error-correction (FEC) limit could be achieved over a 4 m NLOS free-space link. This work shows that the proposed dual-hop system based on a micro-LED can meet the requirements for most indoor NLOS-transmission scenarios.

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00–1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01–1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a non-Hodgkin-type B cell lymphoma. Here, the authors identify two risk loci for WM/LPL in a two-stage GWAS involving a family-oversampling approach and provide evidence for a functional role of the non-coding SNP rs116446171.

Zagros Basin is one of the essential basins in the Middle East with the giant oil and gas reserves. It is indicated by regional tectonic and sedimentary evolution, basin structural division, petroleum distribution characteristics and main controlling factors of petroleum accumulation. It has experienced four significant phases which are early Paleozoic intra-Cratonic pull apart basin and platform margin basin, late Paleozoic platform margin basin, Mesozoic passive continental margin basin, and Cenozoic foreland basin. The Zagros Mountain Front Fault and High Zagros Fault divided the basin into foredeep zone, simply folded zone, and Zagros thrust fault zone from southwest to northeast. The oil fields are mainly located in the foredeep zone, while the gas fields are mostly in the simply folded zone and few fields are in the Zagros thrust fault zone. The Lower Cretaceous Kazhdumi Formation mudstone is the main source rock for the Mesozoic, and Cenozoic reservoirs and the Silurian Gahkum Formation mudstone is the main source rock for the Paleozoic reservoirs. The Cenozoic carbonate is main reservoir followed by the Cretaceous Sarvak and upper Permian Dalan carbonate. The evaporite and mudstone are the main seal in the foredeep zone, while the mudstone in the simple anticline zone. The anticline structure and the seal type is the main controlling factor for the petroleum accumulation. Keywords: Zagros Basin, Structure division, Zagros Mountain Front Fault, High Zagros Fault, Evaporite

Using conventional and unconventional oil and gas resource evaluation methods with play as a unit, this study evaluates the oil and gas geology and resource potential of conventional oil and gas resources and seven types of unconventional resources in the global major oil and gas basins (excluding China). For the first time, resource evaluation data with independent intellectual property rights has been obtained. According to evaluation and calculation, the global recoverable conventional oil resources are 5 350.0×108 t, the recoverable condensate oil resources are 496.2×108 t, and the recoverable natural gas resources are 588.4×1012 m3. The remaining oil and gas 2P recoverable reserves are 4 212.6×108 t, the reserve growth of oil and gas fields are 1 531.7×108 t. The undiscovered oil and gas recoverable resources are 3 065.5×108 t. The global unconventional oil recoverable resources are 4 209.4×108 t and the unconventional natural gas recoverable resources are 195.4×1012 m3. The evaluation results show that the global conventional and unconventional oil and gas resources are still abundant. Key words: global oil and gas bearing basins, resource evaluation, conventional oil and gas resources, oil and gas reserve growth, unconventional oil and gas resources

Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.

We investigated the effect of repeated freeze-thaw cycles on the quality of rabbit meat. Twenty-five Hyla rabbits were slaughtered using standard commercial procedures. A freeze-thaw procedure—i.e., seven days frozen at –18°C followed by thawing at 4°C for 12h— was repeated 5 times, and 9 Longissimus thoracis et lumborum muscles were randomly selected at pre-set cycles (0, 1, 2, 3, and 5). The Longissimus lumborum muscles were used to determine meat quality parameters, while the Longissimus thoracis muscles were used for chemical analysis. During the repeated freeze-thaw process, muscle pH, redness, hardness, and water holding capacity gradually decreased, whereas meat lightness and yellowness gradually increased. The amount of total volatile basic nitrogen significantly increased (P

Abstract Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.

Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

In this paper, dual-branch pre-distorted enhanced asymmetrically clipped direct current (DC) biased optical orthogonal frequency division multiplexing (PEADO-OFDM) for underwater optical wireless communication (UOWC) is firstly proposed and simulated. The performances of PEADO-OFDM on the underwater optical channel model (UOCM) are analyzed and further compared with the typical ADO-OFDM. Using the Monte Carlo method for the modeling of UOCM, we adopt a double-gamma function to represent three different water qualities including clear, coastal and harbor waters. The full-duplex architecture enables the removal of Hermitian symmetry (HS) from conventional optical OFDM and can increase the spectral efficiency at the cost of hardware complexity. A new PEADO-OFDM transmitter is also proposed to reduce the complexity of the transmitter. The simulation results exhibit that our proposed dual-branch PEADO-OFDM scheme outperforms the typical ADO-OFDM scheme in spectral efficiency, bit error rate (BER) and stability over the underwater channels of three different water qualities.

By using geologic and seismic data, this study restored the proto-type basins and lithofacies paleogeography of the Levant basin in Eastern Mediterranean during main geological periods, carried out comparison analysis on the basin architecture characteristics, and based on careful examination of the characteristics of discovered gas reservoirs, established the reservoir forming pattern and discussed the favorable reservoir forming combinations and future exploration direction in this region. Three structural architectures can be identified in the basin, the early-stage faults, the mid-stage faults and the late-stage faults. The early-stage faults are mainly controlled by intercontinental depression, which were less influenced by later compression stress in the southern deep water area of the basin. Controlled by the lateral structural stress and the Syrian Arc Fold Belt, the mid-stage faults became less active from north to south and from east to west. Influenced by the collision and/or Dead Sea strike-slip Fault Zone, the late-stage faults were active but did not pierce the thick Upper Miocene evaporites. Combined with the discovered reservoirs and outcrops, the Mesozoic sandstones and carbonates in deep water area near Eratosthenes seamount of Israel offshore and the Cenozoic carbonates and Tamar sands of Lebanon offshore are the main petroleum exploration targets in the next step. Key words: Eastern Mediterranean, lithofacies paleogeography, basin architecture, Levant Basin, deep water sedimentation, petroleum exploration direction

Abstract Based on our initial genome-wide association study (GWAS) on esophageal squamous cell carcinoma (ESCC) in Han Chinese, we conducted a follow-up study to examine the single nucleotide polymorphisms (SNPs) associated with family history (FH) of upper gastrointestinal cancer (UGI) cancer in cases with ESCC. We evaluated the association between SNPs and FH of UGI cancer among ESCC cases in a stage-1 case-only analysis of the National Cancer Institute (NCI, 541 cases with FH and 1399 without FH) and Henan GWAS (493 cases with FH and 869 without FH) data (discovery phase). The top SNPs (or their surrogates) from discovery were advanced to a stage-2 evaluation in additional Henan subjects (2801 cases with FH and 3136 without FH, replication phase). A total of 19 SNPs were associated with FH of UGI cancer in ESCC cases with P

Risk for renal cell carcinoma (RCC) is higher when there are first-degree family members with the disease. Here, Scelo and colleagues perform a genome-wide association meta-analysis and new genome-wide scan to identify seven new loci with significant RCC association.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

The origin and differential accumulation of hydrocarbons in the Cambrian sub-salt dolomite reservoirs in Zhongshen Area were studied based on comprehensive geochemical analysis of core samples, crude oil samples and natural gas samples. Mass spectrometric detection shows the core samples and crude oil samples are characterized by high C28 sterane content, low diasterane content, high gammacerane content and abundant aryl-Isoprenoids, and the associated gas has a low nitrogen content of 0.24%−4.02%, so it is inferred that the oil and gas are derived from Cambrian – Lower Ordovician source rock. The natural gas in the Middle Cambrian has a methane carbon isotope value of −51.4‰ − −44.7‰ and dryness coefficient of 0.65−0.78, representing associated gas, and the natural gas in the Lower Cambrian has a methane carbon isotope value of −41.4‰ − −40.6‰, and dryness coefficient of 0.99, representing cracking gas. The deep formations in the Tarim Basin contain cracking gas with high H2S content produced by thermo-chemical sulfate reduction (TSR). Due to the poorer reservoir properties and undeveloped fracture network system, the Middle Cambrian reservoirs have low charging degree of this kind of gas, so low H2S content (0.003 8%−0.200 0%); in contrast, with good reservoir properties and developed fracture network system, the Lower Cambrian reservoirs have a higher charging degree of this kind of gas, and thus high H2S content of 3.25%−8.20%. In summary, the oil and gas of Cambrian sub-salt dolomite reservoirs in Zhongshen Area are derived from Cambrian – Lower Ordovician source rock, and the differential accumulation of gas is the joint effect of reservoir physical property and development degree of fracture network system. Key words: Tarim Basin, Zhongshen Area, sub-salt dolomite, hydrocarbon origin, hydrocarbon differential accumulation

Chronic lymphocytic leukaemia has a hereditary component, much of which remains to be identified. Here, the authors perform a genome-wide association study and find new risk loci for the disease, which are associated with genes involved in immune function.

Prostate-specific antigen is used as a biomarker of prostate cancer, but levels can be affected by other factors not related to cancer. Here, the authors find genes associated with prostate specific antigen levels in healthy men, which could be used to reduce over-diagnosis and over-treatment.

Background/Aims: Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related gastrointestinal diseases. Recently, some studies have reported that PPIs can alter the gastric mucosal architecture; however, the relationship remains controversial. This meta-analysis study was designed to quantify the association between long-term PPI administration and gastric atrophy. Materials and Methods: A PubMed search was conducted to identify studies using the keywords proton pump inhibitors or PPI and gastric atrophy or atrophic gastritis; the timeframe of publication searched was up to May 2016. Heterogeneity among studies was tested with the Q test; odds ratios (OR) and 95% confidence intervals (CI) were calculated. P values were calculated by I2 tests and regarded as statistically significant when

The basins of the South Atlantic passive margins are filled with early rifting stage lacustrine sediments (Barremian, 129–125 Ma), transitional lacustrine and marine sediments (Aptian, 125–113 Ma), and drift stage marine sediments since early Cretaceous (Albian, 113 Ma). The South Atlantic margins can be divided into three segments by the Rio Grande Fracture Zone and the Ascension Fracture Zone according to variations in the basin evolution history and configuration style. The lacustrine shale and marine shale source rocks are developed in the rift stage and drift (post-rift) stage in the South Atlantic passive margins, respectively. The southern segment of the margins is dominated by the lacustrine sedimentary filling in the rifted stage overlain by a thin marine sag system as a regional seal, where the hydrocarbons are mainly accumulated in the structural-stratigraphic lacustrine reservoirs formed in the rift stage. The middle segment developed salty rift-sag-type basins with rift and sag systems and with salt deposited in the transitional intercontinental rift stage, where the lacustrine shale in the lower part of the rifted lacustrine sequence and the marine shale in the lower part of the sag sequence formed in the marine post-rift stage are high-quality source rocks. This segment in the middle is mainly dominated by pre-salt lacustrine carbonate and post-salt marine turbidite plays. The northern segment is characterized by sag-type basins with a narrowly and locally distributed rifted lacustrine system and its overlying widely distributed thick marine sag systems. Gravity-flow (mostly turbidite) marine sandstones as good reservoirs were extensively developed in the sag stage due to the narrow shelf and steep slope. The post-rift marine shales in the lower part of the sag sequence are the main source rocks in the northern segment and the hydrocarbons generated from these source rocks directly migrated to and accumulated in the deep marine turbidite sandstones in the same sag sequence formed in the drift stage. From southern segment to northern segment, source rocks and hydrocarbon accumulations tend to occur in the stratigraphically higher formations. The hydrocarbon accumulations in the southern segment are mainly distributed in the rifted lacustrine sequence while that in the northern segment primarily occur in the post-rift marine sequence.

BackgroundSeveral obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findingsGenetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.ConclusionsThis study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.