Multiomics analysis of metabolic heterogeneity in cervical cancer cell lines with or without HPV.

Metabolomics analysis revealed the metabolic heterogeneity of cervical cancer (CC) cell lines C33A and CaSki, and their molecular mechanisms were explored. Using the modified Bligh-Dyer method, the endogenous metabolites of C33A and CaSki cells were divided into polar and nonpolar fractions. The metabolites were analysed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Then, the differential metabolites were screened by combining multivariate statistical analysis and volcano maps, and functional enrichment and pathway analysis of the differential metabolites were performed. Finally, association analysis was carried out in combination with transcriptomics, and the important differential metabolisms were experimentally verified by real-time PCR (RT-qPCR) and oil red staining. The results showed that between the C33A and CaSki cell lines, there were significant differences in amino acids, nucleotides and lipids, such as in threonine, arachidonic acid and hypoxanthine, in the metabolic pathways. These compounds could be used as markers of differences in cellular metabolism. The heterogeneity of lipid metabolism accounted for 87.8%, among which C33A cells exhibited higher contents of fatty acid polar derivatives, while CaSki cells showed higher contents of free fatty acids and glycerides. Based on correlation analysis of the above metabolic differences in HPV pathways as well as lipid metabolism-related genes, p53 and the genes involved in lipid metabolism pathways, such as Peroxisome Proliferator Activated Receptor Gamma(PPARG) and stearoyl-CoA desaturase (SCD), are relevant to the metabolic heterogeneity of the cells. The differential expression of some genes was validated by RT-qPCR. CaSki cells showed significantly higher glyceride levels than that of C33A cells, as verified by oil red O staining and glyceride assays. The above results showed that the metabolomic differences between C33A and CaSki cells were relatively obvious, especially in lipid metabolism, which might be related to the decreased expression of PPARG and p53 caused by HPV E6. Further studies on the molecular mechanism of lipid metabolism heterogeneity in cervical cancer cell lines with or without HPV could provide a new reference for the development of CC and individualized treatments of tumour patients.

Role of exosomes in the development of the immune microenvironment in hepatocellular carcinoma.

Despite numerous improved treatment methods used in recent years, hepatocellular carcinoma (HCC) is still a disease with a high mortality rate. Many recent studies have shown that immunotherapy has great potential for cancer treatment. Exosomes play a significant role in negatively regulating the immune system in HCC. Understanding how these exosomes play a role in innate and adaptive immunity in HCC can significantly improve the immunotherapeutic effects on HCC. Further, engineered exosomes can deliver different drugs and RNA molecules to regulate the immune microenvironment of HCC by regulating the aforementioned immune pathway, thereby significantly improving the mortality rate of HCC. This study aimed to declare the role of exosomes in the development of the immune microenvironment in HCC and list engineered exosomes that could be used for clinical transformation therapy. These findings might be beneficial for clinical patients.

Prehistoric human migration between Sundaland and South Asia was driven by sea-level rise.

Rapid sea-level rise between the Last Glacial Maximum (LGM) and the mid-Holocene transformed the Southeast Asian coastal landscape, but the impact on human demography remains unclear. Here, we create a paleogeographic map, focusing on sea-level changes during the period spanning the LGM to the present-day and infer the human population history in Southeast and South Asia using 763 high-coverage whole-genome sequencing datasets from 59 ethnic groups. We show that sea-level rise, in particular meltwater pulses 1 A (MWP1A, ~14,500-14,000 years ago) and 1B (MWP1B, ~11,500-11,000 years ago), reduced land area by over 50% since the LGM, resulting in segregation of local human populations. Following periods of rapid sea-level rises, population pressure drove the migration of Malaysian Negritos into South Asia. Integrated paleogeographic and population genomic analysis demonstrates the earliest documented instance of forced human migration driven by sea-level rise.

Glacial isostatic adjustment: physical models and observational constraints.

By far the most prescient insights into the interior structure of the planet have been provided on the basis of elastic wave seismology. Analysis of the travel times of shear or compression wave phases excited by individual earthquakes, or through analysis of the elastic gravitational free oscillations that individual earthquakes of sufficiently large magnitude may excite, has been the central focus of Earth physics research for more than a century. Unfortunately, data provide no information that is directly relevant to understanding the solid state 'flow' of the polycrystalline outer 'mantle' shell of the planet that is involved in the thermally driven convective circulation that is responsible for powering the 'drift' of the continents and which controls the rate of planetary cooling on long timescales. For this reason, there has been an increasing focus on the understanding of physical phenomenology that is unambiguously associated with mantle flow processes that are distinct from those directly associated with the convective circulation itself. This paper reviews the past many decades of work that has been invested in understanding the most important of such processes, namely that which has come to be referred to as 'glacial isostatic adjustment' (GIA). This process concerns the response of the planet to the loading and unloading of the high latitude continents by the massive accumulations of glacial ice that have occurred with almost metronomic regularity over the most recent million years of Earth history. Forced by the impact of gravitationaln-body effects on the geometry of Earth's orbit around the Sun through the impact upon the terrestrial regime of received solar insolation, these surface mass loads on the continents have left indelible records of their occurrence in the 'Earth system' consisting of the oceans, continents, and the great polar ice sheets on Greenland and Antarctica themselves. Although this ice-age phenomenology has been clearly recognized since early in the last century, it was for over 50 years considered to be no more than an interesting curiosity, the understanding of which remained on the periphery of the theoretical physics of the Earth. This was the case in part because no globally applicable theory was available that could be applied to rigorously interpret the observations. Equally important to understanding the scientific lethargy that held back the understanding of this phenomenon involving mantle flow processes was the lack of appreciation of the wide range of observations that were in fact related to GIA physics. This paper is devoted to a review of the global theories of the GIA process that have since been developed as a means of interpreting the extensive variety of observations that are now recognized as being involved in the response of the planet to the loading and unloading of its surface by glacial ice. The paper will also provide examples of the further analyses of Earth physics and climate related processes that applications of the modern theoretical structures have enabled.