The substantial heterogeneity and hierarchical organization in liver cancer support the theory of liver cancer stem cells (LCSCs). However, the relationship between chronic hepatic inflammation and ...LCSC generation remains obscure. Here, we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in nonobese diabetic/severe combined immunodeficient mice, suggesting the malignant transformation of LPCs toward LCSCs. Interestingly, depletion of Kupffer cells in vivo attenuated the LCSC properties of transformed LPCs and suppressed cytokeratin 19/Oval cell 6–positive tumor occurrence. Conversely, LPCs cocultured with macrophages exhibited enhanced LCSC properties. We further demonstrated that macrophage‐secreted tumor necrosis factor‐α triggered chromosomal instability in LPCs through the deregulation of ubiquitin D and checkpoint kinase 2 and enhanced the self‐renewal of LPCs through the tumor necrosis factor receptor 1/Src/signal transducer and activator of transcription 3 pathway, which synergistically contributed to the conversion of LPCs to LCSCs. Clinical investigation revealed that cytokeratin 19/Oval cell 6–positive liver cancer patients displayed a worse prognosis and exhibited superior response to sorafenib treatment. Conclusion: Our results not only clarify the cellular and molecular mechanisms underlying the inflammation‐mediated LCSC generation but also provide a molecular classification for the individualized treatment of liver cancer. (Hepatology 2017;66:1934–1951)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The archaeal phylum Woesearchaeota, within the DPANN superphylum, includes phylogenetically diverse microorganisms that inhabit various environments. Their biology is poorly understood due to the ...lack of cultured isolates. Here, we analyze datasets of Woesearchaeota 16S rRNA gene sequences and metagenome-assembled genomes to infer global distribution patterns, ecological preferences and metabolic capabilities. Phylogenomic analyses indicate that the phylum can be classified into ten subgroups, termed A-J. While a symbiotic lifestyle is predicted for most, some members of subgroup J might be host-independent. The genomes of several Woesearchaeota, including subgroup J, encode putative FeFe hydrogenases (known to be important for fermentation in other organisms), suggesting that these archaea might be anaerobic fermentative heterotrophs.
Background
Intrahepatic cholangiocarcinoma (ICC) is the second most common tumor in primary liver cancer, but the prognostic factors associated with long-term outcomes after surgical resection remain ...poorly defined. This study aimed to develop a novel prognostic classifier for patients with ICC after surgery.
Methods
Using a proteomics approach, we screened tumor markers that up-regulated in ICC tissues, and narrowed down by bioinformatics analysis, western blot and immunohistochemistry. Prognostic markers were identified using Cox regression analyses in primary training cohort and the predictive models for time to recurrence (TTR) were established. The predictive accuracy of predictive model was validated in external validation cohort and prospective validation cohort. MTT assay, clonal formation assay and trans-well assays were used to verify the effect on the proliferation and migration in ICC cell line.
Results
Triosephosphate isomerise (TPI1) was significantly up-regulated in ICC tissues and Kaplan–Meier analysis reveals that higher TPI1 expression was strongly correlated with higher recurrence rate of ICC patients. In the primary training cohort, mean TTR was significantly longer (
p
< 0.0001) than in the low-risk group (26.9 months for TTR, 95% CI 22.4–31.5) than in the high-risk group (14.5 months for TTR, 95% CI 10.6–18.4). Similar results were observed in two validation cohorts. In addition, a nomogram to predict recurrence was developed. Moreover, Knockdown of TPI1 by shRNA inhibited ICC cell growth, colony information, migration, invasion in vitro.
Conclusions
Current prognostic models were accurate in predicting recurrence for ICC patients after surgical resection.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Lignocellulosic biomass is a geographically abundant source of renewable energy, showing enormous potential to contribute to escalating energy demands. Improving the industrial economics of cellulase ...production remains a significant hurdle, thus enhancing the yield of cellulase production and the catalytic efficiency of cellulases would be the key targets for research and development. The isolation of Trichoderma reesei in the 1940s marked the beginning of cellulase research. Subsequently, fungal cellulases have been extensively studied to understand the mechanisms of cellulose degradation. Over the years, continuous efforts have been devoted to discovering novel cellulases with diverse physiochemical properties. The attention has been gradually shifted to bacterial sources due to its high specific activity and heterologous production efficiency. Recently, cellulases identified from archaea are considered promising candidates for industrial applications under harsh conditions. As sequencing technology develops, the approaches to discover cellulases have gone through rapid changes. In this review, we show the sequence and structural diversity of non-homologous cellulases and summarize cellulolytic enzyme systems used by cellulose degrading microorganisms. We also discuss recent progress in culture-independent metagenomic approaches as a powerful tool for the bioprospecting of novel cellulases, as well as the advantages and limitations of these methods.
•Cellulases are highly diverse in sequence, structure and function.•Distribution of microbial cellulases is widespread but dispersed in specific lineages.•Metagenomics has been and will remain a powerful tool to discover novel cellulases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Glycogen metabolism commonly altered in cancer is just beginning to be understood. Phosphoglucomutase 1 (PGM1), the first enzyme in glycogenesis that catalyzes the reversible conversion between ...glucose 1-phosphate (G-1-P) and glucose 6-phosphate (G-6-P), participates in both the breakdown and synthesis of glycogen. Here, we show that PGM1 is down-regulated in hepatocellular carcinoma (HCC), which is associated with the malignancy and poor prognosis of HCC. Decreased PGM1 expression obstructed glycogenesis pathway, which leads to the increased flow of glucose into glycolysis, thereby promoting tumor cell proliferation and HCC development. The loss of forkhead box protein J2 (FOXJ2), at least partly due to low genomic copy number in HCC, releases cellular nucleic acid-binding protein (CNBP), a nucleic acid chaperon, to bind to and promote G-quadruplex formation in PGM1 promoter and therefore decreases PGM1 expression. In addition, integrated analyses of PGM1 and FOXJ2 expression provide a better prediction for the malignance and prognosis of HCC. This study establishes a tumor-suppressive role of PGM1 by regulating glucose trafficking and uncovers a novel regulatory mechanism of PGM1 expression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived ...from marigold flowers, exhibits a spectrum of biological activities including anti‐inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC‐derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)‐induced lipid accumulation and the upregulation of adipose differentiation‐associated protein Plin2 in a dose‐ and time‐responsive manner. We elucidated that Scu effectively diminishes OA‐provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B‐II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA‐induced decrement of LC3B‐II levels in the presence of bafilomycin‐a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross‐sectional area, wall‐to‐lumen ratio and serum total cholesterol levels in comparison to the high‐fat diet model group. Collectively, our findings suggest that Scu attenuates OA‐induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract The fallback disk model is widely accepted to explain long-period neutron stars (NSs) that cannot be simulated by magnetic dipole radiation. However, there was no confirmed detection of ...disks from the newly discovered long-period pulsars GLEAM-X 162759.5-523504.3 and GPM J1839-10 and the slowest known isolated NS 1E 161348-5055. This might be because the disks have either been in a noninteracting/inactive state where their emission is too weak to be detected or have been disrupted. In this work, we conduct simulations to examine the lifetime of supernova fallback disks around isolated NSs. We assume that the disks' mass varies in a self-similar way, and their interaction with the NS occurs only in an interacting/active state. Our results reveal that nearly all the interacting lifetimes for the disks are shorter than 10 5 yr, while the existence lifetimes are considerably longer.
Zika Virus (ZIKV) infection is a global threat. Other than the congenital neurological disorders it causes, ZIKV infection has been reported to induce cardiac complications. However, the precise ...treatment plans are unclear. Thus, illustrating the pathogenic mechanism of ZIKV in the heart is critical to providing effective prevention and treatment of ZIKV infection. The mechanism of autophagy has been reported recently in Dengue virus infection. Whether or not autophagy participates in ZIKV infection and its role remains unrevealed. This study successfully established the in vitro cardiomyocytes and in vivo mouse models of ZIKV infection to investigate the involvement of autophagy in ZIKV infection. The results showed that ZIKV infection is both time and gradient‐dependent. The key autophagy protein, LC3B, increased remarkably after ZIKV infection. Meanwhile, autophagic flux was detected by immunofluorescence. Applying autophagy inhibitors decreased the LC3B levels. Furthermore, the number of viral copies was quantified to evaluate the influence of autophagy during infection. We found that autophagy was actively involved in the ZIKV infection and the inhibition of autophagy could effectively reduce the viral copies, suggesting a potential intervention strategy for reducing ZIKV infection and the undesired complications caused by ZIKV.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
It has been found that the topology effect and the possible emergent hidden scale and hidden local flavor symmetries at high density reveal a novel structure of compact star matter. When Nf≥2, ...baryons can be described by skyrmions when the number of color Nc is regarded as a large parameter and there is a robust topology change—the transition from skyrmion to half-skyrmion—in the skyrmion matter approach to dense nuclear matter. The hidden scale and local flavor symmetries, which are sources introducing the scalar meson and vector mesons, are significant elements for understanding the nuclear force in nonlinear chiral effective theories. We review in this paper how the robust conclusions from the topology approach to dense matter and emergent hidden scale and hidden local flavor symmetries figure in generalized nuclear effective field theory (GnEFT), which is applicable to nuclear matter from low density to compact star density. The topology change encoded in the parameters of the effective field theory is interpreted as the hadron-quark continuity in the sense of the Cheshire Cat Principle. A novel feature predicted in this theory that has not been found before is the precocious appearance of the conformal sound velocity in the cores of massive stars, although the trace of the energy-momentum tensor of the system is not zero. That is, there is a pseudoconformal structure in the compact star matter and, in contrast to the usual picture, the matter is made of colorless quasiparticles of fractional baryon charges. A possible resolution of the longstanding gA quench problem in nuclei transition and the compatibility of the predictions of the GnEFT with the global properties of neutron star and the data from gravitational wave detections are also discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A new depsidone derivative (
), aspergillusidone G, was isolated from a marine fungus
, together with eight known depsidones (
‒
) and a cyclic peptide (
): agonodepside A (
), nornidulin (
), ...nidulin (
), aspergillusidone F (
), unguinol (
), aspergillusidone C (
), 2-chlorounguinol (
), aspergillusidone A (
), and unguisin A (
). Compounds
‒
and
‒
were obtained from the plasma induced mutant of this fungus, while
,
, and
were isolated from the original strain under chemical induction. Their structures were identified using spectroscopic analysis, as well as by comparison with literature data. The HPLC fingerprint analysis indicates that chemical induction and plasma mutagenesis effectively influenced the secondary metabolism, which may be due to their regulation in the key steps in depsidone biosynthesis. In bioassays, compound
inhibited acetylcholinesterase (AChE) with IC
in 56.75 μM. Compounds
,
,
,
, and
showed moderate to strong activity towards different microbes. Compounds
,
, and
exhibited potent larvicidality against brine shrimp. In docking studies, higher negative CDOCKER interaction energy and richer strong interactions between AChE and
explained the greater activity of
compared to
. Chemical induction and plasma mutagenesis can be used as tools to expand the chemodiversity of fungi and obtain useful natural products.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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