Hepatocellular carcinoma (HCC) is often associated with poor outcomes due to lung metastasis. ICAM-1+ circulating tumor cells, termed circulating cancer stem cells (CCSCs), possess stem cell–like ...characteristics. However, it is still unexplored how their presence indicates lung metastasis tendency, and particularly, what mechanism drives their lung metastasis. Here, we demonstrated that a preoperative CCSC count in 5 mL of blood (CCSC5) of >3 was a risk factor for lung metastasis in clinical HCC patients. The CSCs overexpressed with circ-CDYL entered the bloodstream and developed lung metastases in mice. Mechanistically, circ-CDYL promoted COL14A1 expression and thus ERK signaling to facilitate epithelial-mesenchymal transition. Furthermore, we uncovered that an RNA-binding protein, EEF1A2, acted as a novel transcriptional (co-) factor to cooperate with circ-CDYL and initiate COL14A1 transcription. A high circ-CDYL level is caused by HIF-1⍺-mediated transcriptional upregulation of its parental gene CDYL and splicing factor EIF4A3 under a hypoxia microenvironment. Hence, the hypoxia microenvironment enables the high-tendency lung metastasis of ICAM-1+ CCSCs through the HIF-1⍺/circ-CDYL-EEF1A2/COL14A1 axis, potentially allowing clinicians to preoperatively detect ICAM-1+ CCSCs as a real-time biomarker for precisely deciding HCC treatment strategies.
•Preoperative CCSC detection helps determine therapies for hepatocellular carcinoma.•An RNA-binding protein cooperates with a circular RNA to regulate transcription.•Hypoxia enables the high-tendency lung metastasis of liver cancer stem cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Previous studies have demonstrated that JMJD2A is a potential oncogene and is overexpressed in human tumors. However, its role in the endometrial carcinoma remains largely unknown. In this study, we ...discovered that JMJD2A was overexpressed in endometrial carcinoma, using immunohistochemistry, quantitative real- time polymerase chain reaction, and western blotting. Downregulation of JMJD2A led to reduced endometrial carcinoma RL95-2 and ISK cell proliferation, invasion and metastasis as asessed with cell counting kit-8, cell migration and invasive assays. Collectively, our results support that JMJD2A is a promoter of endometrial carcinoma cell proliferation and survival, and is a potential novel drug target.
Scope
Tryptophan (Trp) metabolites are closely related to neurological diseases, whereas, the underlying mechanism related to the alleviative effects of Trp metabolites on neurodegeneration in aging ...remains unclear. This study aims to evaluate the protective effects and mechanisms of Trp metabolites on neurodegeneration in aging process.
Methods and results
The neuroprotective properties of Trp metabolites are evaluated in vitro and in vivo experimental model. Trp metabolites such as indole, indole‐3‐acetic acid (IAA), indole‐3‐propionic acid (IPA), indole‐3‐lactic acid (ILA), and indole‐3‐carboxyaldehyde (Icld) could significantly reduce oxidative stress, inflammation, and neuronal apoptosis induced by H2O2 in HT‐22 cells. Meanwhile, indoles could upregulate the expressions of G protein‐coupled receptor 30 (GPR30)/5ʹ‐adenosine monophosphate (AMP)‐activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) pathway in vitro. Furthermore, the neuroprotective effects of IAA and IPA are unveiled through activation of GPR30/AMPK/SIRT1 pathway in d‐galactose induced aging mice. Finally, the regulatory effects of indoles on GPR30/AMPK/SIRT1 pathway are further confirmed by pretreating HT‐22 and Neuro‐2a with GPR30 antagonist of G15. In that case, indoles are furtherly proved with inhibitory effects on neurodegeneration by activating the GPR30/AMPK/SIRT1 pathway in aging process.
Conclusions
The findings reveal that Trp metabolites significantly improve neurodegeneration via GPR30/AMPK/SIRT1 pathway in aging process. This study provides the potential novel intervention strategy and target to prevent the neurodegeneration.
This study shows that indole and its derivatives can alleviate neuroinflammation and neurodegeneration induced by aging through activating the GPR30/AMPK/SIRT1 pathway in vitro and in vivo. Suggesting that indoles hold promise as a valuable therapeutic candidate for neurodegeneration in aging process.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Granular materials, composed of densely packed particles, are known to possess unique mechanical properties that are highly dependent on the surface structure of the particles. A microscopic ...understanding of the structure‐property relationship in these systems remains unclear. Here, supra‐nanoparticle clusters (SNPCs) with precise structures are developed as model systems to elucidate the unexpected elastic behaviors. SNPCs are prepared by coordination‐driven assembly of polyhedral oligomeric silsesquioxane (POSS) with metal‐organic polyhedron (MOP). Due to the disparity in sizes, the POSS‐MOP assemblies, like their classic nanoparticles counterparts, ordering is suppressed, and the POSS‐MOP mixtures will vitrify or jam as a function of decreasing temperature. An unexpected elasticity is observed for the SNPC assemblies with a high modulus that is maintained at temperatures far beyond the glass transition temperature. From studies on the dynamics of the hierarchical structures of SNPCs and molecular dynamic simulation, the elasticity has its origins in the interpenetration of POSS‐ended arms. The physical molecular interpenetration and inter‐locking phenomenon favors the convenient solution or pressing processing of the novel cluster‐based elastomers.
Supra‐nanoparticle clusters (SNPCs) were synthesized by convergence of metal–organic polyhedron scaffolds with precise giant building blocks. The mechanical properties and structural dynamics can be regulated by fine‐tuning the surface functionalization of the terminal POSS moieties. Unexpected elasticity with high Young's modulus of the OPOSS‐ended SNPCs was found to be highly correlated with the interpenetration of the neighboring GLs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective To investigate the effect of exosome in cultured in vitro H9C2 myocardial cells injury of diabetic mice and its mechanism. Methods The mouse model of diabetic myocardial injury was ...established by using db/db mice (n=10) and their mate mice db/+ (n=5). Serum exosomes were isolated and quantitated using the exosome isolation reagent and EXOCET Quantitation kit. The serum exosomes were labeled with PKH26 (red fluorescent cell linker) to detect the endocytosis in H9C2 cells. The expressions of exocrine associated protein and inflammatory cytokines in H9C2 cells with or without exosome stimulation were detected by Western blotting. TUNEL was used to detect apoptosis. A neutralizing antibody of Rab1a was used for blocking experiment. Results Db/db mice produced more exosomes than db/+ mice (30.95×10 9 /ml vs. 10.45×10 9 /ml, P<0.01). Moreover, H9C2 cells cultured in vitro could swallow more serum-exosomes derived from db/db mice. Meanwhile, serum exosome from db/ db mice, as used to interfere H9C2 cell
To identify efficient predictors of clinical outcomes of in vitro fertilization (IVF).
Two hundred and one women undergoing their first IVF cycle were measured for antral follicle count (AFC) and ...endometrial thickness via ultrasound. On day 2 or 3 of the menstrual cycle and the day of human chorionic gonadotropin administration, serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone were determined. The difference of ovarian response and clinical pregnancy rates were measured.
Basal FSH was the single best predictor of ovarian response in women <35 years old before the initiation of treatment, with an area under the receiver operating characteristic curve (AUC) of 0.752. For women ≥35 years old, none of parameters was a single good predictor of IVF pregnancy. For women older than 35 years, adding body mass index (BMI) with AFC and basal FSH improved prediction of ovarian response (AUC=0.859). Prediction of clinical pregnancy for women ≥ 35 years was improved either by combining only AFC and basal FSH (AUC=0.757) or adding BMI to the combined AFC and FSH (AUC=0.722).
Combining AFC, basal FSH, and BMI was the best predictor of ovarian response and clinical pregnancy after IVF in women ≥ 35 years.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The ancient city of Dai Xian in Shanxi, a frontier town which arose from the ancient military defense in China , has the complete city pattern, which is the first and the main problem in the process ...of the historical and cultural city protection. In this paper,the pattern system,the evolution process and the present situation of the ancient city of DaiXian is carried on the concrete analysis, and it illustrates the "one city three close" city pattern, points out the necessity of the protection of the city pattern, and finally comes up with some general ideas about the protection of the city pattern to realize the sustainable development of the ancient city.
The evolutionary transition from self-incompatible distyly to self-compatible homostyly frequently occurs in heterostylous taxa. Although the inheritance of distyly and homostyly has been deeply ...studied, our understanding on modifications of the classical simple Mendelian model is still lacking. Primula forbesii, a biennial herb native to southwest China, is a typical distylous species, but after about 20 years of cultivation with open pollination, self-compatible homostyly appeared, providing ideal material for the study of the inheritance of distyly and homostyly. In this study, exogenous homobrassinolide was used to break the heteromorphic incompatibility of P. forbesii. Furthermore, we performed artificial pollination and open-pollination experiments to observe the distribution of floral morphs in progeny produced by different crosses. The viability of seeds from self-pollination was always the lowest among all crosses, and the homozygous S-morph plants (S/S) occurred in artificial pollination experiments but may experience viability selection. The distyly of P. forbesii is governed by a single S-locus, with S-morph dominant hemizygotes (S/-) and L-morph recessive homozygotes (-/-). Homostylous plants have a genotype similar to L-morph plants, and homostyly may be caused by one or more unlinked modifier genes outside the S-locus. Open pollinations confirm that autonomous self-pollination occurs frequently in L-morphs and homostylous plants. This study deepens the understanding of the inheritance of distyly and details a case of homostyly that likely originated from one or more modifier genes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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