The International Commission on Stratigraphy (ICS) utilises benchmark chronostratigraphies to divide geologic time. The reliability of these records is fundamental to understand past global change. ...Here we use the most detailed luminescence dating age model yet published to show that the ICS chronology for the Quaternary terrestrial type section at Jingbian, desert marginal Chinese Loess Plateau, is inaccurate. There are large hiatuses and depositional changes expressed across a dynamic gully landform at the site, which demonstrates rapid environmental shifts at the East Asian desert margin. We propose a new independent age model and reconstruct monsoon climate and desert expansion/contraction for the last ~250 ka. Our record demonstrates the dominant influence of ice volume on desert expansion, dust dynamics and sediment preservation, and further shows that East Asian Summer Monsoon (EASM) variation closely matches that of ice volume, but lags insolation by ~5 ka. These observations show that the EASM at the monsoon margin does not respond directly to precessional forcing.
Background & Aims
Genetic defects causing dysfunction in bile salt export pump (BSEP/ABCB11) lead to liver diseases. ABCB11 mutations alter the bile acid metabolome. We asked whether profiling plasma ...bile acids could reveal compensatory mechanisms and track genetic and clinical status.
Methods
We compared plasma bile acids in 17 ABCB11‐mutated patients, 35 healthy controls and 12 genetically undiagnosed cholestasis patients by ultra‐high‐performance liquid chromatography/multiple‐reaction monitoring‐mass spectrometry (UPLC/MRM‐MS). We developed an index to rank bile acid hydrophobicity, and thus toxicity, based on LC retention times. We recruited 42 genetically diagnosed hereditary cholestasis patients, of whom 12 were presumed to have impaired BSEP function but carried mutations in genes other than ABCB11, and 8 healthy controls, for further verification.
Results
The overall hydrophobicity indices of total bile acids in both the ABCB11‐mutated group (11.89 ± 1.07 min) and the undiagnosed cholestasis group (11.46 ± 1.07 min) were lower than those of healthy controls (13.69 ± 0.77 min) (both p < 0.005). This was owing to increased bile acid modifications. Secondary bile acids were detected in patients without BSEP expression, suggesting biliary bile acid secretion through alternative routes. A diagnostic panel comprising lithocholic acid (LCA), tauro‐LCA, glyco‐LCA and hyocholic acid was identified that could differentiate the ABCB11‐mutated cohort from healthy controls and undiagnosed cholestasis patients (AUC=0.946, p < 0.0001) and, in non‐ABCB11‐mutated cholestasis patients, could distinguish BSEP dysfunction from normal BSEP function (9/12 vs 0/38, p < 0.0000001).
Conclusions
Profiling of plasma bile acids has provided insights into cholestasis alleviation and may be useful for the clinical management of cholestatic diseases.
Raman spectroscopy is a powerful technique for the study of materials chemistry and nanostructure. This nondestructive technique is highly sensitive to molecular and crystal lattice vibrations, which ...allow for a comprehensive study of the vibrational modes of molecules incorporated in photovoltaic perovskite materials. In this study, we apply Raman spectroscopy to study FAPbX3 (X = Cl, Br, I) and FA x MA1–x PbI3 (FA stands for formamidinium; MA for methylammonium) metal halide perovskite single crystals and discuss the necessary conditions to obtain reliable data. We establish a correlation between perovskite composition and their unique Raman intensities/spectral shapes. In particular, we show that tuning of the halide content results in a spectral shift of the organic features of the Raman spectrum due to changes in the strength of hydrogen bonding, while tuning of the organic cation is related more to changes in peak intensity. Moreover, the effect of temperature on the vibrational modes corresponding to NCN bending, NH2 torsion, and NH2 wagging were studied. This enables the impact of the organic composition in FA x MA1–x PbI3 on the phase transition temperature of the material to be determined. Furthermore, we establish links between Raman spectroscopy and other conventional measurement techniques such as X-ray diffraction (XRD) and differential scanning calorimetry (DSC). This study provides insight into the interpretation of the Raman spectra of FA-based perovskites, which furthers understanding of the properties of these materials in relation to their full exploitation in solar cells.
(-)-Oleocanthal (oleocanthal) is a phenolic compound found in varying concentrations in extra virgin olive oil oleocanthal has been shown to be active physiologically, benefiting several diseased ...states by conferring anti-inflammatory and neuroprotective benefits. Recently, we and other groups have demonstrated its specific and selective toxicity toward cancer cells; however, the mechanism leading to cancer cell death is still disputed. The current study demonstrates that oleocanthal, as well as naturally oleocanthal-rich extra virgin olive oils, induced damage to cancer cells' lysosomes leading to cellular toxicity in vitro and in vivo. Lysosomal membrane permeabilization following oleocanthal treatment in various cell lines was assayed via three complementary methods. Additionally, we found oleocanthal treatment reduced tumor burden and extended lifespan of mice engineered to develop pancreatic neuroendocrine tumors. Finally, following-up on numerous correlative studies demonstrating consumption of olive oil reduces cancer incidence and morbidity, we observed that extra virgin olive oils naturally rich in oleocanthal sharply reduced cancer cell viability and induced lysosomal membrane permeabilization while oleocanthal-poor oils did not. Our results are especially encouraging since tumor cells often have larger and more numerous lysosomes, making them especially vulnerable to lysosomotropic agents such as oleocanthal.
New methods for preparation of tailor-made fluorine-containing compounds are in extremely high demand in nearly every sector of chemical industry. The asymmetric construction of quaternary C–F ...stereogenic centers is the most synthetically challenging and, consequently, the least developed area of research. As a reflection of this apparent methodological deficit, pharmaceutical drugs featuring C–F stereogenic centers constitute less than 1% of all fluorine-containing medicines currently on the market or in clinical development. Here we provide a comprehensive review of current research activity in this area, including such general directions as asymmetric electrophilic fluorination via organocatalytic and transition-metal catalyzed reactions, asymmetric elaboration of fluorine-containing substrates via alkylations, Mannich, Michael, and aldol additions, cross-coupling reactions, and biocatalytic approaches.
The reprogramming of human somatic cells to primed or naive induced pluripotent stem cells recapitulates the stages of early embryonic development
. The molecular mechanism that underpins these ...reprogramming processes remains largely unexplored, which impedes our understanding and limits rational improvements to reprogramming protocols. Here, to address these issues, we reconstruct molecular reprogramming trajectories of human dermal fibroblasts using single-cell transcriptomics. This revealed that reprogramming into primed and naive pluripotency follows diverging and distinct trajectories. Moreover, genome-wide analyses of accessible chromatin showed key changes in the regulatory elements of core pluripotency genes, and orchestrated global changes in chromatin accessibility over time. Integrated analysis of these datasets revealed a role for transcription factors associated with the trophectoderm lineage, and the existence of a subpopulation of cells that enter a trophectoderm-like state during reprogramming. Furthermore, this trophectoderm-like state could be captured, which enabled the derivation of induced trophoblast stem cells. Induced trophoblast stem cells are molecularly and functionally similar to trophoblast stem cells derived from human blastocysts or first-trimester placentas
. Our results provide a high-resolution roadmap for the transcription-factor-mediated reprogramming of human somatic cells, indicate a role for the trophectoderm-lineage-specific regulatory program during this process, and facilitate the direct reprogramming of somatic cells into induced trophoblast stem cells.
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