Ileal collision tumor associated with gastrointestinal bleeding: A case report and review of literature.

BACKGROUND: Collision tumors involving the small intestine, specifically the combination of a hamartomatous tumor and a lipoma, are extremely rare. To our knowledge, no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine. CASE SUMMARY: Here, we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm × 32 mm × 30 mm in the terminal ileum. Based on computed tomography scan findings, the mass was initially suspected to be a lipoma. A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line. A biopsy of the upper portion suggested a juvenile polyp (JP). Owing to the patient's advanced age, multiple comorbidities, and poor surgical tolerance, a modified endoscopic submucosal dissection was performed. Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top, demonstrating evidence of rupture and associated bleeding. The patient's overall health remained satisfactory, with no recurrence of hematochezia during the six-month follow-up period. CONCLUSION: This case report provides new evidence for the understanding of gastrointestinal collision tumors, emphasizing their diverse clinical presentations and histopathological characteristics. It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.

Identification and functional analysis of rare HECTD1 missense variants in human neural tube defects.

Neural tube defects (NTDs) are severe malformations of the central nervous system that arise from failure of neural tube closure. HECTD1 is an E3 ubiquitin ligase required for cranial neural tube closure in mouse models. NTDs in the Hectd1 mutant mouse model are due to the failure of cranial mesenchyme morphogenesis during neural fold elevation. Our earlier research has linked increased extracellular heat shock protein 90 (eHSP90) secretion to aberrant cranial mesenchyme morphogenesis in the Hectd1 model. Furthermore, overexpression of HECTD1 suppresses stress-induced eHSP90 secretion in cell lines. In this study, we report the identification of five rare HECTD1 missense sequence variants in NTD cases. The variants were found through targeted next-generation sequencing in a Chinese cohort of 352 NTD cases and 224 ethnically matched controls. We present data showing that HECTD1 is a highly conserved gene, extremely intolerant to loss-of-function mutations and missense changes. To evaluate the functional consequences of NTD-associated missense variants, functional assays in HEK293T cells were performed to examine protein expression and the ability of HECTD1 sequence variants to suppress eHSP90 secretion. One NTD-associated variant (A1084T) had significantly reduced expression in HEK293T cells. All five NTD-associated variants (p.M392V, p.T801I, p.I906V, p.A1084T, and p.P1835L) reduced regulation of eHSP90 secretion by HECTD1, while a putative benign variant (p.P2474L) did not. These findings are the first association of HECTD1 sequence variation with NTDs in humans.

Barriers and facilitators to older adult participation in intergenerational physical activity program: a systematic review.

BACKGROUND: The intergenerational physical activity program aims to promote the health, social engagement, and well-being of older adults. It is essential to comprehend the barriers and facilitators that affect their involvement to develop successful intervention strategies. This systematic review critically examines available research to identify the factors that impact the participation of older adults in intergenerational physical activity programs. METHODS: This study retrieved 13 electronic databases (from January 2000 to March 2023) and used a social-ecological model to classify and analyze the identified facilitators and barriers. RESULTS: A total of 12 articles were included, which identified 73 facilitators and 37 barriers. These factors were condensed into 7 primary themes and 14 sub-themes in total. CONCLUSIONS: The factors influencing the participation of older adults in intergenerational physical activities are multifaceted. These factors guide project developers, policymakers, and practitioners in developing and implementing intergenerational physical activity programs to help address global aging issues and promote intergenerational connections. TRIAL REGISTRY: PROSPERO ID: CRD42023420758.

Single-cell transcriptome landscape of zebrafish liver reveals hepatocytes and immune cell interactions in understanding nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease in the world. Immunity is the major contributing factor in NAFLD; however, the interaction of immune cells and hepatocytes in disease progression has not been fully elucidated. As a popular species for studying NAFLD, zebrafish, whose liver is a complex immune system mediated by immune cells and non-immune cells in maintaining immune tolerance and homeostasis. Understanding the cellular composition and immune environment of zebrafish liver is of great significance for its application in NAFLD. Here, we established a liver atlas that consists of 10 cell types using single-cell RNA sequencing (scRNA-seq). By examining the heterogeneity of hepatocytes and analyzing the expression of NAFLD-associated genes in the specific cluster, we provide a potential target cell model to study NAFLD. Additionally, our analysis identified two subtypes of distinct resident macrophages with inflammatory and non-inflammatory functions and characterized the successive stepwise development of T cell subclusters in the liver. Importantly, we uncovered the possible regulation of macrophages and T cells on target cells of fatty liver by analyzing the cellular interaction between hepatocytes and immune cells. Our data provide valuable information for an in-depth study of immune cells targeting hepatocytes to regulate the immune balance in NAFLD.

Identification and Functional Analysis of Rare HECTD1 Missense Variants in Human Neural Tube Defects.

Neural tube defects (NTDs) are severe malformations of the central nervous system that arise from failure of neural tube closure. HECTD1 is an E3 ubiquitin ligase required for cranial neural tube closure in mouse models. NTDs in the Hectd1 mutant mouse model are due to the failure of cranial mesenchyme morphogenesis during neural fold elevation. Our earlier research has linked increased secretion of extracellular heat shock protein 90 (eHSP90) to aberrant cranial mesenchyme morphogenesis in the Hectd1 model. Furthermore, overexpression of HECTD1 suppresses stress-induced eHSP90 secretion in cell lines. In this study, we report the identification of five rare HECTD1 missense sequence variants in NTD cases. The variants were found through targeted next-generation sequencing in a Chinese cohort of 352 NTD cases and 224 ethnically matched controls. We present data showing that HECTD1 is a highly conserved gene, extremely intolerant to loss-of-function mutations and missense changes. To evaluate the functional consequences of NTD-associated missense variants, functional assays in HEK293T cells were performed to examine protein expression and the ability of HECTD1 sequence variants to suppress eHSP90 secretion. One NTD-associated variant (A1084T) had significantly reduced expression in HEK293T cells. All five NTD-associated variants (p.M392V, p.T801I, p.I906V, p.A1084T, and p.P1835L) reduced regulation of eHSP90 secretion by HECTD1, while a putative benign variant (p.P2474L) did not. These findings are the first association of HECTD1 sequence variation with human disease and suggest that sequence variation in HECTD1 may play a role in the etiology of human NTDs.

Molecular Insights into the Specific Targeting of c-MYC G-Quadruplex by Thiazole Peptides.

Stabilization of a G-quadruplex (G4) in the promotor of the c-MYC proto-oncogene leads to inhibition of gene expression, and it thus represents a potentially attractive new strategy for cancer treatment. However, most G4 stabilizers show little selectivity among the many G4s present in the cellular complement of DNA and RNA. Intriguingly, a crescent-shaped cell-penetrating thiazole peptide, TH3, preferentially stabilizes the c-MYC G4 over other promotor G4s, but the mechanisms leading to this selective binding remain obscure. To investigate these mechanisms at the atomic level, we performed an in silico comparative investigation of the binding of TH3 and its analogue TH1 to the G4s from the promotors of c-MYC, c-KIT1, c-KIT2, and BCL2. Molecular docking and molecular dynamics simulations, combined with in-depth analyses of non-covalent interactions and bulk and per-nucleotide binding free energies, revealed that both TH3 and TH1 can induce the formation of a sandwich-like framework through stacking with both the top and bottom G-tetrads of the c-MYC G4 and the adjacent terminal capping nucleotides. This framework produces enhanced binding affinities for c-MYC G4 relative to other promotor G4s, with TH3 exhibiting an outstanding binding priority. Van der Waals interactions were identified to be the key factor in complex formation in all cases. Collectively, our findings fully agree with available experimental data. Therefore, the identified mechanisms leading to specific binding of TH3 towards c-MYC G4 provide valuable information to guide the development of new selective G4 stabilizers.

Molecular functional characterization of the setdb1 and its potential target gene sox5 illuminate the histone modification-mediated orchestration of gonadal development in Chinese tongue sole (Cynoglossus semilaevis).

SET (SuVar3-9, Enhancer of Zeste, Trithorax) domain bifurcated histone lysine methyltransferase 1, setdb1, is the predominant histone lysine methyltransferase catalyzing H3K9me3. Prior studies have illustrated that setdb1 and H3K9me3 critically regulate sex differentiation and gametogenesis. However, the molecular details by which setdb1 is involved in these processes in fish have been poorly reported. Here, we cloned and characterized the setdb1 ORF (open reading frame) sequence from Chinese tongue sole (Cynoglossus semilaevis). The setdb1 ORF sequence was 3,669 bp, encoding a 1,222-amino-acid protein. Phylogenetic analysis showed that setdb1 was structurally conserved. qRT-PCR revealed that setdb1 had a high expression level in the testes at 12 mpf (months post fertilization). Single-cell RNA-seq data at 24 mpf indicated that setdb1 was generally expressed in spermatogenic cells at each stage except for sperm and was centrally expressed in oogonia. H3K9me3 modification was observed in gonads with the immunofluorescence technique. Furthermore, the overexpression experiment suggested that sox5 was a candidate target of setdb1. sox5 was abundantly expressed in male and pseudomale gonads at 24 mpf. Single-cell RNA-seq data showed that sox5 was mainly expressed in spermatogonia and its expression gradually declined with differentiation. Taken together, our findings imply that setdb1 regulates sox5 transcription in gonads, which provides molecular clues into histone modification-mediated orchestration of sex differentiation and gametogenesis.

Bi-ligand-fabricated CdS quantum dots to photo-induce aqueous-phase aldol condensation for biomass-derived carbonyl compounds.

CdS QDs were fabricated using bi-ligands 11-sulfanylundecanoic acid and proline for photo-induced aqueous-phase aldol condensation of biomass-derived furfural compounds and ketones, and they displayed acceptable selectivity, activity and recycling properties for generation of a wide range of products with diverse applications. This work facilitates understanding the molecular-level design concepts of semiconductor photocatalysts.

[Anti-endothelial cell antibodies in predicting early miscarriage].

OBJECTIVE: To explore the clinical significance of anti-endothelial cell antibodies (AECA) in predicting early miscarriage. METHODS: A total of 122 pregnant women with no history of autoimmune diseases who underwent prenatal examination at Peking University People's Hospital from January 2020 to December 2022 were selected, and they were tested for AECA. Based on the history of early miscarriage (gestational age at miscarriage < 12 weeks), the participants were divided into an early miscarriage group and a control group. t-tests, non-parametric Wilcoxon tests, Chi-square tests, and Fisher's exact probability method were used to compare general information and laboratory indicators between the two groups. A multivariate Logistic regression model was used to analyze the factors associated with early miscarriage. The natural miscarriage rates were assessed through follow-up with pregnant women, and Kaplan-Meier survival analysis was employed to compare the natural miscarriage rates between AECA-positive and AECA-negative pregnant women. RESULTS: (1) A total of 122 pregnant women were enrolled, comprising 35 cases (28.7%) in the early miscarriage group, with an average age of (32.1±6.1) years, and 87 cases (71.3%) in the control group, with an average age of (30.7±5.1) years. The early miscarriage group had higher gravidity [3 (2, 4) vs. 1 (1, 2), Z=-6.402, P < 0.001] and a higher prevalence of hypertension (11.4% vs.1.1%, P=0.024). The positive rate of AECA in the early miscarriage group (34.3% vs. 8.0%, χ2=13.070, P < 0.001) and the proportion of elevated immunoglobulin G (17.1% vs. 4.6%, P=0.032) were significantly higher than that in the control group. (2) Multivariate logistic regression analysis showed that higher gravidity (OR=4.149, 95%CI: 2.287-7.529, P < 0.001), AECA positivity (OR= 4.288, 95% CI: 1.157-15.893, P=0.029), and elevated immunoglobulin G levels (OR =6.177, 95%CI: 1.156-33.015, P=0.033) were risk factors for early miscarriage. (3) The 122 pregnant women were categorized into two groups: the AECA-positive group (19 cases) and the AECA-negative group (103 cases). Survival analysis demonstrated that at the end of 12 weeks of gestation, the fetal survival rate in the AECA-positive group was significantly lower than that in the AECA-negative group (84.2% vs. 96.1%, P= 0.035). CONCLUSION: Higher gravidity, AECA positivity, and elevated immunoglobulin G levels are significant risk factors for early miscarriage. The results demonstrate that AECA is a novel predicting test in early miscarriage.

Corrigendum: Diseases of the musculoskeletal system and connective tissue and risk of breast cancer: mendelian randomization study in European and East Asian populations.

[This corrects the article DOI: 10.3389/fonc.2023.1170119.].

Single­nucleotide polymorphism rs6592645 confers asthma risk through regulating LRRC32 expression.

Asthma is a complex disease, often with evident genetic predisposition; for example, the single-nucleotide polymorphism (SNP) rs7130588 was significantly associated with asthma by genome-wide association study (GWAS). Analysis of 1000 Genomes Project data suggests that there is another SNP, rs6592645, in complete linkage disequilibrium with rs7130588 and should present the same signal in GWAS. However, the causal SNP and the mechanism for the association between rs7130588 and asthma remain to be elucidated. In the presents study, results from dual-luciferase assays indicated that the A/G alleles of rs7130588 failed to present significantly different reporter gene expression. By contrast, A allele of rs6592645 presented a significant increase in relative luciferase activity than G allele, thus suggesting that rs6592645 may be a causal SNP. Using chromosome conformation capture, the enhancer region containing rs6592645 was observed to interact with promoter region of leucine-rich repeat-containing 32 (LRRC32). Gene expression quantification suggested that LRRC32 expression is significantly increased in lung tissue of patients with asthma and is dependent on the genotype of this locus, thus verifying that LRRC32 may be involved in asthma onset and that rs6592645 can regulate LRRC32 expression. Through chromatin immunoprecipitation, transcription factor 3 (TCF3) was identified to bind to rs6592645 surrounding region and the interaction between TCF3 and rs6592645 surrounding region was investigated. Results from the present study may improve our understanding of the mechanism by which the genetic variation in this locus might influence asthma susceptibility.

Multiplex modification of Yarrowia lipolytica for enhanced erythritol biosynthesis from glycerol through modularized metabolic engineering.

Erythritol is a novelty 4-carbon sugar polyol and has great potential to be used as the precursor of some platform chemicals. The increasing cost of glucose poses researchers shifting insights to the cheaper biodiesel raw materials. Herein, we engineered a non-degradation, non-byproducts Yarrowia lipolytica for the erythritol production with high-titer from glycerol. Initially, the degradation and competition modules were blocked by URA3 counter-selection marker. Subsequently, a shortened biosynthetic pathway was explored to elevate its synthetic flux by multi-modules combination expression of functional genes. Furthermore, a screened glycerol transporter ScFPS1 was integrated into ERY6 genome to promote the glycerol uptake. The constructed strain ERY8 produced 176.66 g/L erythritol in the 5-L bioreactor with a yield and productivity of 0.631 g/g and 1.23 g/L/h, respectively, which achieved the highest fermentation production efficiency till date. This study proposed a novel multi-modules combination strategy for effectively engineering Y. lipolytica to produce erythritol using glycerol.

[Effects of stereoscopic traction on photosynthetic characteristics, yield, and quality of Codonopsis pilosula under organic cultivation].

To solve the serious problem of stem and leaf shading in the middle and late stage of traditional flat planting of Codonopsis pilosula, this study analyzed the effects of different stereoscopic traction heights on the photosynthetic characteristics and growth of C. pilosula and explored the optimal traction height to improve the yield and quality of C. pilosula. The experiment designed three stereo-scopic traction heights [H1(60 cm), H2(90 cm), and H3(120 cm)] with natural growth without traction as the control(CK). The results showed that the increase in stereoscopic traction heights broadened the growth space of stems and leaves of C. pilosula, enhanced the ventilation effect, significantly increased the average daily net photosynthetic rate of C. pilosula, promoted the absorption of intercellular CO_2, decreased the transpiration rate, and reduced the evaporation of water. Moreover, it effectively avoided the problem of weakened photosynthesis, maintained the carbon balance of individual plants, and promoted the growth and development of the C. pilosula roots. In terms of the seed yield of C. pilosula, it was ranked as H2>H1>H3>CK. To be specific, H1 increased by 213.41% compared with CK, H2 increased by 282.43% compared with CK, and H3 increased by 133.95% compared with CK. The yield and quality of C. pilosula were the highest in the H3 treatment group, with the fresh yield of 6 858.33 kg·hm~(-2), 50.59% higher than CK, dry yield of 2 398.33 kg·hm~(-2), 76.54% higher than CK, and lobetyolin content of 0.56 mg·g~(-1), 45.22% higher than CK. Therefore, the stereoscopic traction height has a great influence on the photosynthetic characteristics, yield, and quality of C. pilosula. Particularly, the yield and quality of C. pilosula can be optimized and improved in the traction height treatment of H3(120 cm). This planting method is worth popularizing and applying in the cultivated management of C. pilosula.

[Prognostic Value of Pre-treatment Albumin/Fibrinogen Ratio in Patients with Diffuse Large B-cell Lymphoma].

OBJECTIVE: To investigate the value of pre-treatment albumin/fibrinogen ratio (AFR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of DLBCL patients in the Affiliated Hospital of North Sichuan Medical College from April 2014 to March 2021 were retrieved, and 111 newly diagnosed patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with complete data were included in the study. The clinical, laboratory examination and follow-up data of the patients were collected, and the receiver operating characteristic curve (ROC) was drawn according to patients' AFR before treatment and the survival status at the end of the follow-up, which could be used to preliminarily evaluate the predictive value of AFR for disease progression and patients' survival outcome. Furthermore, the correlation of AFR with the clinical and laboratory characteristics, progression-free survival (PFS) and overall survival (OS) was analyzed, and finally, univariate and multivariate Cox proportional hazard regression models were used to analyze factors affecting PFS and OS of DLBCL patients. RESULTS: The ROC curve indicated that AFR level had a moderate predictive value for PFS and OS in DLBCL patients, with the area under the curve (AUC) of 0.616 (P =0.039) and 0.666 (P =0.004), respectively, and the optimal cut-off values were both 9.06 for PFS and OS. Compared with high-AFR (≥9.06) group, the low-AFR (<9.06) group had a higher proportion of patients with Lugano III-IV stage ( P <0.001), elevated lactate dehydrogenase (P =0.007) and B symptoms (P =0.038). The interim analysis of response showed that the overall response rate (ORR) in the high-AFR group was 89.7%, which was significantly higher than 62.8% in the low-AFR group (P =0.001). With a median follow-up of 18.5 (3-77) months, the median PFS of the high-AFR group was not reached, which was significantly superior to 17 months of the low-AFR group (P =0.009). Similarly, the median OS of high-AFR group was not reached, either, which was significantly superior to 48 months of the low-AFR group (P < 0.001). In multivariate Cox regression analysis, AFR <9.06 was an independent risk factor both for PFS and OS (HR PFS=2.047, P =0.039; HR OS=4.854, P =0.001). CONCLUSION: Pre-treatment AFR has a significant value for the prognosis evaluation in newly diagnosed DLBCL patients.

Nurses' and nursing students' knowledge and attitudes to pressure injury prevention: A meta-analysis based on APUP and PUKAT.

BACKGROUND: Morbidity and mortality among patients due to pressure injuries continue to rise. Nurses play a critical role in preventing pressure injuries. However, published results on nurses' knowledge and attitudes for pressure injury prevention are often contradictory. OBJECTIVES: To conduct a meta-analysis of nurses' and nursing students' knowledge and attitudes toward pressure injury prevention. DESIGN: A meta-analysis of cross-sectional studies. DATA SOURCES: Ten databases were queried for the meta-analysis. The search period was from the time of the databases' establishment to February 2023. REVIEW METHODS: This review followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The Agency for Healthcare Research and Quality (AHRQ) was used to assess the methodological quality of the included studies. Statistical analysis was conducted with the Stata 15.0 software, and the quantitative data of knowledge and attitude toward preventing PI in all studies were summarized. RESULTS: Thirteen studies from 9 countries were included. The meta-analysis showed that nurses and nursing students had low knowledge but positive attitudes toward pressure injury prevention. Subgroup analysis showed that the pooled proportion of both knowledge and attitudes was higher in Asia than in Europe. Nurses had higher knowledge than nursing students, however, the former had a more negative attitude than the latter. Sensitivity analyses were robust. Egger's test showed no significant publication bias. CONCLUSION: The knowledge of nurses and nursing students about pressure injury prevention is not promising and there is an urgent need for continuous learning. Attitudes are more positive but there is room for improvement. The relevant departments should strengthen nurses' and nursing students' knowledge of pressure injury prevention and further improve their attitudes toward pressure injury prevention.

Tenofovir alters the immune microenvironment of pregnant women with hepatitis B virus infection: Evidence from single-cell RNA sequencing.

BACKGROUND: Mother-to-child is the main route of the transmission of hepatitis B virus (HBV) infection. Tenofovir fumarate (TDF) antiviral treatment has become the most extensive choice worldwide. However, the effects of TDF treatment on the immune function of pregnant women remains unclear. Here we investigate the effect of TDF treatment on the immune microenvironment of pregnant women with HBV infection using single-cell RNA sequencing (scRNA-seq). METHODS: Three HBV-infected pregnant women were treated with TDF and six samples were collected before and after the treatment. In total, 68,200 peripheral blood mononuclear cells (PBMCs) were extracted for 10 × scRNA-seq. The cells were clustered using t-distributed stochastic neighbor embedding (t-SNE) and unbiased computational informatics analysis. RESULTS: The analysis identified four-cell subtypes, including T cells, monocytes, natural killer (NK) cells, and B cells, and unraveled the developmental trajectory and maturation of CD4+ T and CD8+ T cell subtypes. The cellular state and molecular features of the effector/memory T cells revealed a significant increase in the inflammatory state of CD4+ T cells and the cytotoxic characteristics of CD8+ T cells. Additionally, after TDF treatment, the monocytes showed a tendency for M1 polarization, and the cytotoxicity of NK cells was enhanced. Furthermore, the analysis of intercellular communication revealed the interaction of various subtypes of cells and the heterogeneous expression of key signal pathways. CONCLUSIONS: The findings of this study reveal significant differences in cellular subtypes and molecular characteristics of PBMCs of pregnant women with HBV infection before and after TDF treatment and demonstrate the recovery of immune response after treatment. These findings could help develop immune intervention measures to control HBV during pregnancy and the puerperium period.

Diseases of the musculoskeletal system and connective tissue and risk of breast cancer: Mendelian randomization study in European and East Asian populations.

Objective: Associations between diseases of the musculoskeletal system and connective tissue (MSCTD) and breast cancer (BC) have not been elucidated completely. The purpose of this study was to investigate the associations of MSCTD, rheumatoid arthritis (RA), Sjogren syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), polymyositis (PM), osteoarthritis (OA) of hip or knee, and ankylosing spondylitis (AS) with BC in European populations and East Asian populations using Mendelian randomized (MR) analysis. Methods: The genetic instruments linked to MSCTD, RA, SS, SLE, SSc, DM, PM, OA, and AS were chosen from the EBI database of complete genome-wide association studies (GWAS) summary data and the FinnGen consortium. The associations of genetic variants with BC were extracted from the Breast Cancer Association Consortium (BCAC). Two Sample MR was performed using summary data from GWAS, principally using the inverse variant weighted (IVW) method. Heterogeneity, pleiotropy, and sensitivity analyses were performed to evaluate the robustness of the results by weighted median, MR Egger, simple mode, weighted mode, and leave-one-out analysis. Results: In the European population, causal relationships between RA and BC (OR=1.04, 95%CI: 1.01-1.07, P=0.023), AS and BC (OR=1.21, 95%CI: 1.06-1.36, P=0.013) were confirmed. IVW analysis showed DM (OR=0.98, 95%CI: 0.96-0.99, P=0.026) and PM (OR=0.98, 95%CI: 0.97-0.99, P=0.002) were associated with slightly decreased risks of estrogen receptor (ER)+ BC, and MSCTD was associated with an increased risk of ER- BC (OR=1.85, 95%CI: 1.27-2.44, P=0.039). There was no causal relationship between SLE, SS, SSc, OA, and BC, neither ER+ BC nor ER- BC. However, in the East Asian population, IVW analysis showed that RA (OR=0.94, 95%CI: 0.89-0.99, P=0.0096) and SLE (OR=0.95, 95%CI: 0.92-0.99, P=0.0058) was associated with decreased risks of BC. Conclusions: This study suggests that causal relationships between patients with MSCTD and BC in the European population are different from those in the East Asian population, patients with RA and AS in the European population have an increased risk of BC, patients with MSCTD have increased risk of ER- BC in the European population, while patients with RA and SLE in the East Asian population have decreased risk of BC.

rs66651343 and rs12909095 confer lung cancer risk by regulating CCNDBP1 expression.

Lung cancer is a malignant tumor with high rates of mortality and shows significant hereditary predisposition. Previous genome-wide association studies suggest that rs748404, located at promoter of TGM5 (transglutaminase 5), is associated with lung carcinoma. By analysis of 1000 genomes project data for three representative populations in the world, another five SNPs are identified to be in strong linkage disequilibrium with rs748404, thus suggesting that they may also be associated with lung carcinoma risk. However, it is ambiguous about the actually causal SNP(s) and the mechanism for the association. Dual-luciferase assay indicates that the functional SNPs are not rs748404, rs12911132 or rs35535629 but another three SNPs (rs66651343, rs12909095 and rs17779494) in lung cell. By chromosome conformation capture, it is disclosed that the enhancer encompassing the two SNPs, rs66651343 and rs12909095, can interact with the promoter of CCNDBP1 (cyclin D1 binding protein 1). RNA-seq data analysis indicates that CCNDBP1 expression is dependent on the genotype of these two SNPs. Chromatin immunoprecipitation assay suggests that the fragments spanning rs66651343 and rs12909095 can bind with the transcription factors, cut like homeobox 1 and SRY-box transcription factor 9, respectively. Our results establish the connection between genetic variations at this locus and lung cancer susceptibility.

The enormous repetitive Antarctic krill genome reveals environmental adaptations and population insights.

Antarctic krill (Euphausia superba) is Earth's most abundant wild animal, and its enormous biomass is vital to the Southern Ocean ecosystem. Here, we report a 48.01-Gb chromosome-level Antarctic krill genome, whose large genome size appears to have resulted from inter-genic transposable element expansions. Our assembly reveals the molecular architecture of the Antarctic krill circadian clock and uncovers expanded gene families associated with molting and energy metabolism, providing insights into adaptations to the cold and highly seasonal Antarctic environment. Population-level genome re-sequencing from four geographical sites around the Antarctic continent reveals no clear population structure but highlights natural selection associated with environmental variables. An apparent drastic reduction in krill population size 10 mya and a subsequent rebound 100 thousand years ago coincides with climate change events. Our findings uncover the genomic basis of Antarctic krill adaptations to the Southern Ocean and provide valuable resources for future Antarctic research.

Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan.

Our previous work identified one region upstream human UGT2B4 (UDP glucuronosyltransferase family 2 member B4) which is associated with breast cancer and under balancing selection. However, the distribution, functional variation and molecular mechanism underlying breast cancer and balancing selection remain unclear. In current study, the two haplotypes with deep divergence are described by analyzing 1000 genomes project data and observed to be with high frequencies in all human populations. Through population genetics analysis and genome annotation, the potential functional region is identified and verified by reporter gene assay. Further mutagenesis indicates that the functional mutations are rs66862535 and rs68096061. Both SNPs can alter the interaction efficiency of transcription factor POU2F1 (POU class 2 homeobox 1). Through chromosome conformation capture, it is identified that the enhancer containing these two SNPs can interact with UGT2B4 promoter. Expression quantitative trait loci analysis indicates that UGT2B4 expression is dependent on the genotype of this locus. The common haplotype in human is lost in four genomes of archaic hominins, which suggests that Neanderthal and Denisovan should present relatively lower UGT2B4 expression and further higher steroid hormone level. This study provides new insight into the contribution of ancient population structure to human phenotypes.