Impact of apolipoprotein A1 on tumor immune microenvironment, clinical prognosis and genomic landscape in hepatocellular carcinoma

Background: Current knowledge on apolipoprotein A1 (APOA1) in hepatocellular carcinoma (HCC) is fragmented and even contradictory. Multi-dimensional analyses are required to comprehensively elucidate its value and underlying mechanism. Methods: We collected 49 RNA-seq datasets, 40 cell line types data and 70 scRNA pan-cancer datasets public available, including 17 HCC datasets (1754 tumor samples), and enrolled 73 pairs of HCC tissue and 516 blood samples independently from our clinics. APOA1 impacting on the HCC tumor microenvironment (TME) was analyzed using intensive data mining. Methylation sequencing, flow cytometry, quantitative PCR, western blot, immunohistochemistry and clinical chemistry assays were conducted for wet experimental investigation. Results: The APOA1 ontology fingerprint indicated that it played various crucial biological roles in HCC, primarily involved in cholesterol efflux. Consistent findings at histology, serology, and clinical follow-up revealed that high APOA1 was a good prognosis indicator of HCC. Hypermethylation in the APOA1 promoter region was found in clinical samples which is in accordance with the reduction of APOA1 in HCC. The cell cycle, DNA replication, mismatch repair pathways, and tumor cell proliferation were less observed in the HCC APOA1high subgroup. The favorable immunoregulatory abilities of APOA1 showed interesting findings: A positive correlation between APOA1 and anti-Tumor immune cells (NK, CD8+ T cells) and a negative association with immune cells exerting immunosuppressive effects, including M2 macrophages. Conclusion: This is an integrative multidimensional exploration of APOA1 using bioinformatics and experiments. Both the prognostic value and anti-Tumor effects based on APOA1 panoramic exploration in the HCC TME demonstrate a new potential clinical target for HCC assessment and intervention in the future.</p

MSH2/MSH6 Complex Promotes Error-Free Repair of AID-Induced dU:G Mispairs as well as Error-Prone Hypermutation of A:T Sites

Mismatch repair of AID-generated dU:G mispairs is critical for class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The generation of a previously unavailable Msh2−/−Msh6−/− mouse has for the first time allowed us to examine the impact of the complete loss of MutSα on lymphomagenesis, CSR and SHM. The onset of T cell lymphomas and the survival of Msh2−/−Msh6−/− and Msh2−/−Msh6−/−Msh3−/− mice are indistinguishable from Msh2−/− mice, suggesting that MSH2 plays the critical role in protecting T cells from malignant transformation, presumably because it is essential for the formation of stable MutSα heterodimers that maintain genomic stability. The similar defects on switching in Msh2−/−, Msh2−/−Msh6−/− and Msh2−/−Msh6−/−Msh3−/− mice confirm that MutSα but not MutSβ plays an important role in CSR. Analysis of SHM in Msh2−/−Msh6−/− mice not only confirmed the error-prone role of MutSα in the generation of strand biased mutations at A:T bases, but also revealed an error-free role of MutSα when repairing some of the dU:G mispairs generated by AID on both DNA strands. We propose a model for the role of MutSα at the immunoglobulin locus where the local balance of error-free and error-prone repair has an impact in the spectrum of mutations introduced during Phase 2 of SHM

The oyster genome reveals stress adaptation and complexity of shell formation

The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa. © 2012 Macmillan Publishers Limited. All rights reserved

Quantitative evaluation of the diagenesis and porosity evolution of tight sandstone reservoirs: A case study of the Yanchang Formation in the southern Ordos basin, China

Evaluation of the pore evolution is key to gaining a better understanding of oil migration and accumulation in tight oil exploration for tight sandstone; to study the diagenesis and porosity evolution of tight sandstone reservoirs, we analysed the 8th member of the Yanchang Formation by core observation, thin section observation, cathodoluminescence, scanning electron microscopy, and logging data analysis. The following conclusions can be drawn (1) In the typical tight sandstone reservoir, numerous secondary pores developed at burial depths in the range of 1300 m to 1400 m, and approximately 1500 m to 1600 m. (2) Compaction was the most influential factor of reservoir density and decreased the average pore size by 24.8%. Carbonate cementation decreased the porosity by 8.2%. The most important diagenetic process for increasing the reservoir porosity was dissolution, which increased the pore size by 5.1%. In addition, chlorite played an active role in inhibiting secondary quartz growth and preserving primary pores. (3) The early gas invasion can inhibit diagenesis, and the organic acids produced by the later oil can increase dissolution, so that the high oil saturation phenomenon becomes more obvious.La evaluación de la evolución de los poros es clave para obtener una mejor comprensión de la migración y acumulación de petróleo en la exploración de petróleo para arenas compactas; Para estudiar la diagénesis y la evolución de la porosidad de los reservorios de arenas compactas, se anlizó el octavo componente de la Formación Yanchang a través de la observación de núcleos, la observación de secciones delgadas, análisis de catodoluminiscencia, microscopía electrónica de barrido y análisis de registro de datos. Del presente studio se pueden extraer las siguientes conclusiones (1) En los reservorios característicos de arenas compactas, se desarrollaron numerosos poros secundarios a profundidades de enterriamiento en el rango de 1300 a 1400 m, y de aproximadamente 1500 m a 1600 m. (2) La compactación fue el factor más influyente en la densidad del yacimiento y disminuyó el tamaño promedio de los poros en un 24.8%. La cementación por carbonato disminuyó la porosidad en un 8,2%. Mientras que el proceso diagenético más importante para aumentar la porosidad del yacimiento fue la disolución, que aumentó el tamaño de los poros en un 5,1%. Además, la clorita desempeñó un papel activo en la inhibición del crecimiento secundario del cuarzo y en la conservación de los poros primarios. (3) La invasión temprana de gas puede inhibir la diagénesis, y los ácidos orgánicos producidos posteriormente por el petróleo pueden aumentar la disolución, por lo que el fenómeno de alta saturación de petróleo se hace más significativo

Topological basis realization associated with Hermitian and non-Hermitian Heisenberg XXZ model

We investigate the topological basis realization associated with the Hermitian and non-Hermitian Heisenberg XXZ model based on the matrix representation of the Temperley-Lieb algebra. The results show that the topological space is spanned by the topological basis associated with the Temperley-Lieb algebra. When the q-deformed parameter q is a complex number and $|q|=1$ , the corresponding model is the non-Hermitian XXZ model. The real q corresponds to the Hermitan case. The topological basis realization for these two cases is constructed by means of matrix representation of the Temperley-Lieb algebra. Then the properties of the topological basis and ground state are studied. Particularly, the four-qubit Heisenberg XXZ model is investigated in detail. We also give some discussions on the case in which q is a root of unity

Characterization of the complete chloroplast genome sequence of Vicia costata (Fabaceae) and its phylogenetic implications

Vicia costata Ledeb. is a fine leguminous pasture which has advantages of drought resistance and barren tolerance. In this study, the complete chloroplast (cp) genome of V. costata was assembled and annotated. The total genome size of V. costata was 134,184 bp in length with IR loss. The cp genome encoded a set of 112 genes, containing 74 protein-coding genes, 34 tRNA genes, and 4 rRNA genes. The overall GC content was 34.82%. Phylogenetic analysis showed that V. costata got together with the same genus species V. ramuliflora, V. bungei, V. faba, V. sativa and V. sepium with high support value, and V. costata had a close relationship with V. ramuliflora. The whole cp genome of V. costata will be a useful resource for future studies on phylogeny and conservation in Vicia

Association of dyslipidemia with renal cell carcinoma: a 1∶2 matched case-control study.

Abnormal serum lipid profiles are associated with the risk of some cancers, but the direction and magnitude of the association with renal cell carcinoma is unclear. We explore the relationship between serum lipids and renal cell carcinoma via a matched case-control study. A 1∶2-matched case-control study design was applied, where one renal cell carcinoma patient was matched to two non-renal-cell-carcinoma residents with respect to age (±0 year) and gender. Cases (n = 248) were inpatients with a primary diagnosis of renal cell carcinoma, confirmed by pathology after operations. Controls were sampled from a community survey database matched on age and gender with cases, 2 controls for each case. Stratified Cox proportional hazard regression analysis was used to obtain hazard ratios and corresponding 95% confidence intervals of lipids level and dyslipidemia for the risk of renal cell carcinoma. Elevated serum cholesterol (p<0.001), LDL cholesterol (p<0.001), and HDL cholesterol (p = 0.003) are associated with decreased hazard of renal cell carcinoma, adjusting for obesity, smoke, hypertension and diabetes. However, risk caused by hTG showed no statistical significance (p = 0.263). This study indicates that abnormal lipid profile influences the risk of renal cell carcinoma