Due to the difficulty in early diagnosis and the lack of treatment for advanced disease, the mortality rate of hepatocellular carcinoma (HCC) is high, and the 5-year overall survival rate is low at present. SLC1A4 is a neutral amino acid transporter, but its regulatory role and mechanism in HCC are still unclear. Through analyzing the TCGA database and clinical tissue specimens, this study uncovered the high expression of SLC1A4 in tumor tissues of HCC. Worse more, a high level of SLC1A4 may lead to a poor prognosis of HCC. Mechanically, silencing SLC1A4 inhibited the phosphorylation activation of AKT by suppressing the ubiquitin modification of AKT at lysine 63 and amino acid influx represented by D-serine, decreasing the protein level of β-catenin in the cell nucleus and suppressing the transcriptional activity of c-Myc and EpCAM promoters. As a result, silencing SLC1A4 inhibited the proliferation, migration, and stemness of hepatic cancer cells, which was successfully reversed by the introduction of exogenous AKT. Moreover, epithelial–mesenchymal transition (EMT) in vitro and metastasis potential in vivo of hepatic cancer cells was suppressed by the downregulated SLC1A4 level. In conclusion, SLC1A4 promotes the malignant transformation of HCC through activating signal transduction mediated by AKT. The findings in this study suggested that SLC1A4 may be a diagnostic indicator for the early HCC and a therapeutic target for the advanced HCC.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cytology
The opening of the Qiongzhou Strait during the Holocene was a significant geological event in the Beibu Gulf, profoundly influencing sediment provenance and ocean circulation systems. Due to the scarcity of geological records documenting this event, the understanding of regional Holocene sedimentary evolution has been constrained. To investigate the impact of this event on sediment provenance and ocean currents in the Beibu Gulf, geochemical analyses were conducted on sediment core SO-31 retrieved from the South China Sea. The sediments in core SO-31 were stratigraphically divided into three units based on vertical geochemical profiles, reflecting changes in sea level and shifts in sediment provenance within the study area. The Th/Cr vs. Th/Sc scatter plot for core SO-31 indicate that sedimentary materials primarily originated from the Red River during 11,400–7700 a BP, and a significant change in provenance occurred in the study region around 7700 a BP, characterized by increased contributions from the Qiongzhou Strait and decreased contributions from the Red River. This suggests that the opening of the Qiongzhou Strait significantly influenced the sediment supply to the central Beibu Gulf around 7700 a BP. These findings provide critical geochemical evidence for studying the Qiongzhou Strait opening event and enhance our understanding of Holocene sedimentary evolution and “source–sink” transitions in the Beibu Gulf.
The southern Mediterranean region, particularly North Africa, is a crucial area for biodiversity conservation. However, the impacts of climate change on plant species in this region are not well understood. Dendroecology, the study of tree rings, is a valuable technique for analyzing the effects of environmental changes on woody plants over time. In this study, we intend to assess the state of the art in dendrochronological research in North Africa and identify knowledge gaps and limitations in the field. The period of analysis spans from 1979 to 2023. We used all the available literature in Dendrobox and Google Scholar during this period. Our study revealed several research gaps in the region, including the need for more studies on the history of forest fires and their relationship to climate conditions in Morocco, Algeria, and Tunisia, the impact of climate on the anatomical characteristics of growth rings, and the effects of climate change on tree species diversity and forest health. Applying this technique in the future would allow for detailed insights into the effect of climate on the internal structure and growth of forest trees. The findings of this study will help guide future research and contribute to a better understanding of the climate-growth relationship of woody plants in North Africa.
The Subtropical Front (STF) plays a key role in the ecology of Chilean jack mackerel <i>Trachurus murphyi</i>. Nonetheless, there are few remote sensing studies of the STF in the open Southeast Pacific, and almost all of them have been conducted by satellite oceanographers in Russia and Ukraine to support respective large-scale fisheries of jack mackerel in this region. We reviewed these studies that documented long-term seasonal and interannual variability of the STF from sea surface temperature (SST) and sea surface height (SSH) data. We also mapped the STF from satellite sea surface salinity (SSS) data of the SMOS mission (2012–2019). The Subtropical Front consists of two fronts–North and South STF about 500 km apart–that border the Subtropical Frontal Zone (STFZ) in-between. The STF is density-compensated, with spatially divergent manifestations in temperature and salinity. In the temperature field, the STF extends in the WNW to ESE direction in the Southeast Pacific. In the salinity field, the STFZ appears as a broad frontal zone, extending zonally across the entire South Pacific. Three major types of satellite data-SST, SSH, and SSS-can be used to locate the STF. The SSH data is most advantageous with regard to the jack mackerel fisheries, owing to the all-weather capability of satellite altimetry and the radical improvement of the spatial resolution of SSH data in the near future. Despite the dearth of dedicated in situ studies of the South Pacific STFZ, there is a broad consensus regarding the STFZ being the principal spawning and nursing ground of <i>T. murphyi</i> and a migration corridor between Chile and New Zealand. Major data/knowledge gaps are identified, and key next steps are proposed to mitigate the data/knowledge gaps and inform fisheries management.
Catherine A. Brownstein, Elise Douard, Robin L. Haynes
et al.
Abstract In sudden unexplained death in pediatrics (SUDP) the cause of death is unknown despite an autopsy and investigation. The role of copy number variations (CNVs) in SUDP has not been well‐studied. Chromosomal microarray (CMA) data are generated for 116 SUDP cases with age at death between 1 and 28 months. CNVs are classified using the American College of Medical Genetics and Genomics guidelines and CNVs in our cohort are compared to an autism spectrum disorder (ASD) cohort, and to a control cohort. Pathogenic CNVs are identified in 5 of 116 cases (4.3%). Variants of uncertain significance (VUS) favoring pathogenic CNVs are identified in 9 cases (7.8%). Several CNVs are associated with neurodevelopmental phenotypes including seizures, ASD, developmental delay, and schizophrenia. The structural variant 47,XXY is identified in two cases (2/69 boys, 2.9%) not previously diagnosed with Klinefelter syndrome. Pathogenicity scores for deletions are significantly elevated in the SUDP cohort versus controls (p = 0.007) and are not significantly different from the ASD cohort. The finding of pathogenic or VUS favoring pathogenic CNVs, or structural variants, in 12.1% of cases, combined with the observation of higher pathogenicity scores for deletions in SUDP versus controls, suggests that CMA should be included in the genetic evaluation of SUDP.
Davide Slaghenaufi, Giovanni Luzzini, Matteo Borgato
et al.
In this work, the aromatic characterization of commercially available Prosecco wines with a price range between EUR 7 and 13 was carried out. These wines came from three different areas of origin: Valdobbiadene, Asolo and Treviso. Seventy volatile compounds were identified and quantified in the wines. Quantitatively, the wines were mainly characterized by compounds of fermentation origin (alcohols, acids, esters), and C<sub>6</sub>-alcohols, and to a lesser extent, terpenes, low molecular weight volatile sulfur compounds (VSC), and benzenoids. To determine their impact on the aroma of Prosecco wine, the respective OAVs were calculated. The molecules with higher OAV were ethyl hexanoate, isoamyl acetate, and β-damascenone. More generally, esters, responsible for fruity notes, seemed to play a major role in the aroma of Prosecco wine. Investigation into the possible effect of different production zones indicated 16 significantly different compounds accounting for differences between the various areas of origin of the wines, being mostly VSC, esters and C<sub>6</sub>-alcohols. A sensory evaluation through a sorting task highlighted the formation of clusters; wine samples were divided into two main groups partially attributable to the areas of origin. From a chemical point of view, cluster A was richer in esters, while cluster B had, on average, higher concentrations of compounds associated with wine aging such as cyclic terpenes, norisoprenoids (TDN and vitispirane), and VSC.
Fluvalinate is a widely used and relatively safe acaricide for honeybees, but it still has a negative impact on honeybee colonies. Such negative effects may be related to fluvalinate-induced brain nerve tissue damage, but the detailed molecular regulatory mechanism of this phenomenon is still poorly understood. In this study, we analyzed the miRNA expression profile changes in the brain tissue of Apis mellifera ligustica by miRNA sequencing after fluvalinate treatment. A total of 1,350 miRNAs were expressed in Apis mellifera ligustica brain tissue, of which only 180 were previously known miRNAs in honeybees. Among all known and novel miRNAs, 15 were differentially expressed between at least two of the four time periods before and after fluvalinate administration. Further analysis revealed five significantly enriched KEGG pathways of the differentially expressed miRNA (DEM) potential target genes, namely, “Hippo signaling pathway-fly,” “Phototransduction-fly,” “Apoptosis-fly,” “Wnt signaling pathway,” and “Dorso-ventral axis formation,” which indicates that differentially expressed miRNA function may be related to cell apoptosis and memory impairment in the fluvalinate-treated Apis mellifera ligustica brain. Ame-miR-3477-5p, ame-miR-375-3p, and miR-281-x were identified as key miRNAs. Overall, our research provides new insights into the roles of miRNAs in brain tissue during the process of fluvalinate-induced Apis mellifera ligustica poisoning.
E. Lundberg, Linn Fagerberg, Daniel Klevebring
et al.
An essential question in human biology is how cells and tissues differ in gene and protein expression and how these differences delineate specific biological function. Here, we have performed a global analysis of both mRNA and protein levels based on sequence‐based transcriptome analysis (RNA‐seq), SILAC‐based mass spectrometry analysis and antibody‐based confocal microscopy. The study was performed in three functionally different human cell lines and based on the global analysis, we estimated the fractions of mRNA and protein that are cell specific or expressed at similar/different levels in the cell lines. A highly ubiquitous RNA expression was found with >60% of the gene products detected in all cells. The changes of mRNA and protein levels in the cell lines using SILAC and RNA ratios show high correlations, even though the genome‐wide dynamic range is substantially higher for the proteins as compared with the transcripts. Large general differences in abundance for proteins from various functional classes are observed and, in general, the cell‐type specific proteins are low abundant and highly enriched for cell‐surface proteins. Thus, this study shows a path to characterize the transcriptome and proteome in human cells from different origins.
Abstract More than half of the total population in China are living in cities. Especially, the people in highly developed and spatially integrated city clusters, i.e., urban agglomerations (UAs), are facing increasing human‐perceived heat stress that describes the combined effects of hot temperature, high humidity, and lowered surface wind speed. By analyzing multiple indicators over 20 major UAs across China, we demonstrate that summer heat stress has been significantly intensifying in nearly all UAs during 1971–2014. This intensification is more profound in northern than southern regions and is especially stronger in more urbanized and densely populated areas (e.g., Beijing‐Tianjin‐Hebei and the Yangtze River Delta). Based on a dynamic classification of weather stations using time‐varying land use/land cover maps, we find that urban core areas exhibit distinctly stronger increasing heat stress trends than their surrounding rural areas. On average, urbanization contributes to approximately one‐quarter of the total increase in mean heat stress over urban core areas of UAs and nearly half of the total increase in extreme heat stress events. The urbanization effect is also dependent on the geographical region within China. Urbanization tends to have stronger intensifying effects on heat stress in UAs with higher population density in low‐altitude areas, while it has a relatively weaker intensifying and even weakening effect in some arid and high‐altitude regions. Moreover, as various heat stress metrics may yield different estimations of long‐term trend and urbanization contribution, the particular choice of heat stress indicator is of critical importance for investigations on this subject matter.
To date, no reports have linked the multifunctional protein, staphylococcal nuclease domain-containing protein 1 (SND1), to host defense against intracellular infections. In this study, we investigated the role and mechanisms of SND1, by using SND1 knockout (SND1-/-) mice, in host defense against the lung infection of Chlamydia muridarum, an obligate intracellular bacterium. Our data showed that SND1-/- mice exhibited significantly greater body weight loss, higher organism growth, and more severe pathological changes compared with wild-type mice following the infection. Further analysis showed significantly reduced Chlamydia-specific Th1/17 immune responses in SND1-/- mice after infection. Interestingly, the dendritic cells (DCs) isolated from SND1-/- mice showed lower costimulatory molecules expression and IL-12 production, but higher IL-10 production compared with those from wild-type control mice. In the DC-T cell co-culture system, DCs isolated from SND1-/- infected mice showed significantly reduced ability to promote Chlamydia-specific IFN-γ producing Th1 cells but enhanced capacity to induce CD4+T cells into Foxp3+ Treg cells. Adoptive transfer of DCs isolated from SND1-/- mice, unlike those from wild-type control mice, failed to protect the recipients against challenge infection. These findings provide in vivo evidence that SND1 plays an important role in host defense against intracellular bacterial infection, and suggest that SND1 can promote Th1/17 immunity and inhibit the expansion of Treg cells through modulation of the function of DCs.
Ioannis G. Lempesis, Gijs H. Goossens, Konstantinos N. Manolopoulos
Adipose tissue blood flow (ATBF) is an important determinant of adipose tissue (AT) function. 133Xenon wash-out technique is considered the gold-standard for human ATBF measurements. However, decreasing 133Xenon clinical use and costly production and preservation, make alternative (non-invasive) methods necessary. Here, we explored percutaneous Doppler ultrasound as a proxy method to quantify intravascular subcutaneous abdominal and femoral ATBF in humans (n= 17). Both fasting ATBF and the postprandial increase in ATBF were significantly higher in abdominal compared to femoral AT. Although anatomical variations in vein location and depot thickness may impact feasibility, we demonstrate that Doppler ultrasound detects the expected depot-differences and postprandial increase in ATBF in healthy individuals. This method warrants further investigation in other populations and metabolic conditions.
Diseases of the endocrine glands. Clinical endocrinology, Cytology
Simple nucleotide matching identification methods are not as accurate as once thought at identifying environmental fungal sequences. This is largely because of incorrect naming and the underrepresentation of various fungal groups in reference datasets. Here, we explore these issues by examining an environmental metabarcoding dataset of partial large subunit rRNA sequences of Basidiomycota and basal fungi. We employed the simple matching method using the QIIME 2 classifier and the RDP Classifier in conjunction with the latest releases of the SILVA (138.1, 2020) and RDP (11, 2014) reference datasets and then compared the results with a manual phylogenetic binning approach. Of the 71 query sequences tested, 21 and 42% were misidentified using QIIME 2 and the RDP Classifier, respectively. Of these simple matching misidentifications, more than half resulted from the underrepresentation of various groups of fungi in the SILVA and RDP reference datasets. More comprehensive reference datasets with fewer misidentified sequences will increase the accuracy of simple matching identifications. However, we argue that the phylogenetic binning approach is a better alternative to simple matching since, in addition to better accuracy, it provides evolutionary information about query sequences.
Fecal transplants are increasingly utilized for treatment of recurrent infections (i.e., Clostridium difficile) in the human gut and as a general research tool for gain-of-function experiments (i.e., gavage of fecal pellets) in animal models. Changes observed in the recipient's biology are routinely attributed to bacterial cells in the donor feces (~1011 per gram of human wet stool). Here, we examine the literature and summarize findings on the composition of fecal matter in order to raise cautiously the profile of its multipart nature. In addition to viable bacteria, which may make up a small fraction of total fecal matter, other components in unprocessed human feces include colonocytes (~107 per gram of wet stool), archaea (~108 per gram of wet stool), viruses (~108 per gram of wet stool), fungi (~106 per gram of wet stool), protists, and metabolites. Thus, while speculative at this point and contingent on the transplant procedure and study system, nonbacterial matter could contribute to changes in the recipient's biology. There is a cautious need for continued reductionism to separate out the effects and interactions of each component.
Marco Villani, Salvatore Magrì, Andrea Roli
et al.
Living beings share several common features at the molecular level, but there are very few large-scale “operating principles” which hold for all (or almost all) organisms. However, biology is subject to a deluge of data, and as such, general concepts such as this would be extremely valuable. One interesting candidate is the “criticality” principle, which claims that biological evolution favors those dynamical regimes that are intermediaries between ordered and disordered states (i.e., “at the edge of chaos”). The reasons why this should be the case and experimental evidence are briefly discussed, observing that gene regulatory networks are indeed often found on, or close to, the critical boundaries. Therefore, assuming that criticality provides an edge, it is important to ascertain whether systems that are critical can further evolve while remaining critical. In order to explore the possibility of achieving such “always-critical” evolution, we resort to simulated evolution, by suitably modifying a genetic algorithm in such a way that the newly-generated individuals are constrained to be critical. It is then shown that these modified genetic algorithms can actually develop critical gene regulatory networks with two interesting (and quite different) features of biological significance, involving, in one case, the average gene activation values and, in the other case, the response to perturbations. These two cases suggest that it is often possible to evolve networks with interesting properties without losing the advantages of criticality. The evolved networks also show some interesting features which are discussed.
The first complete chloroplast genome (cpDNA) sequence of Michelia floribunda was determined from Illumina HiSeq pair-end sequencing data in this study. The cpDNA is 160,049 bp in length, contains a large single-copy region (LSC) of 88,140 bp and a small single-copy region (SSC) of 18,773 bp, which were separated by a pair of inverted repeats (IR) regions of 26,568 bp. The genome contains 132 genes, including 87 protein-coding genes, 8 ribosomal RNA genes, and 37 transfer RNA genes. Further phylogenomic analysis showed that M. floribunda was closely related to Michelia yunnanensis in Michelieae tribe.
The goal of this research was to analyze the fungal community responsible for the biodeterioration of a pirogue in the National Maritime Museum of China and to make recommendations for the protection of this artifact. Molecular identification of fungal strains isolated from the surface of the pirogue and the air of the storage room that were most closely related to <i>Cladosporium</i>, <i>Penicillium</i>, <i>Talaromyces</i> and <i>Trichoderma</i> spp. DNA extracted from the samples was sequenced on the Illumina MiSeq platform. The results showed that the predominant fungal genera present were <i>Penicillium</i> sp., <i>Cladosporium</i> sp. and <i>Exophiala</i> sp. Thereafter, cellulose degradation experiments were carried out on the predominant fungi screened by pure culturing. Finally, we tested the sensitivity of the predominant fungal isolates to four biocides. This work suggests that we should pay more attention to <i>Penicillium</i> sp. and <i>Cladosporium</i> sp. in the protection of wooden artifacts, and environmental control is recommended as the main means of protecting the pirogue.