Ping Lin

Stem cell-independent reprogramming of differentiated cells has recently been identified as an important paradigm for repairing injured tissues. Following periportal injury, mature hepatocytes re-activate reprogramming/progenitor-related genes (RRGs) and dedifferentiate into liver progenitor-like cells (LPLCs) in both mice and humans, which contribute remarkably to regeneration. However, it remains unknown which and how external factors trigger hepatocyte reprogramming. Here, by employing single-cell transcriptional profiling and lineage-specific deletion tools, we uncovered that periportal-specific LPLC formation was initiated by regionally activated Kupffer cells but not peripheral monocyte-derived macrophages. Unexpectedly, using in vivo screening, the proinflammatory factor IL-6 was identified as the niche signal repurposed for RRG induction via STAT3 activation, which drove RRG expression through binding to their pre-accessible enhancers. Notably, RRGs were activated through injury-specific rather than liver embryogenesis-related enhancers. Collectively, these findings depict an injury-specific niche signal and the inflammation-mediated transcription in driving the conversion of hepatocytes into a progenitor phenotype.

New luminescent lanthanide-carboxylate frameworks, formulated as [Ln4(m-BDC)6(H2O)4(DMF)]·(H2O)2·(DMF) (Ln = Eu 1; Gd 2; Tb 3) (m-H2BDC = 1,3-benzenedicarboxylic acid) have been solvo(hydro)thermally synthesized. Single-crystal X-ray diffraction studies reveal that compounds 1–3 are isomorphous and each displays a layered structure constructed by helical lanthanide-carboxylate chains. DFT and TD-DFT calculations were conducted in detail to discuss the energy levels, including the HOMO, LUMO, singlet and triplet energies of the m-H2BDC ligand. The results indicate that the m-BDC2− dianion acts as an antenna chromophore that is able to efficiently absorb and transfer energy to the lanthanide ions. Compounds 1–3 all exhibit high thermostability and are stable up to 450 °C, as confirmed by the TGA and temperature-dependent PXRD experiments. Compounds 1 and 3 are strong luminescent materials. Compound 3 is among some of the best examples of luminescent lanthanide compounds, with highly efficient emission quantum yields of 81.40% at 77 K, 75.37% at room temperature and 56.64% after calcination at 450 °C, respectively. In addition, the energy transfer processes for compounds 1 and 3 have also been studied and illustrated in detail.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers due to its high metastasis rate in the liver. However, little is known about the molecular features of hepatic metastases due to difficulty in obtaining fresh tissues and low tumor cellularity. RESULTS: We conduct exome sequencing and RNA sequencing for synchronous surgically resected primary tumors and the paired hepatic metastases from 17 hepatic oligometastatic pancreatic ductal adenocarcinoma and validate our findings in specimens from 35 of such cases. The comprehensive analysis of somatic mutations, copy number alterations, and gene expressions show high similarity between primary tumors and hepatic metastases. However, hepatic metastases also show unique characteristics, such as a higher degree of 3p21.1 loss, stronger abilities of proliferation, downregulation of epithelial to mesenchymal transition activity, and metabolic rewiring. More interesting, altered tumor microenvironments are observed in hepatic metastases, especially a higher proportion of tumor infiltrating M2 macrophage and upregulation of complement cascade. Further experiments demonstrate that expression of C1q increases in primary tumors and hepatic metastases, C1q is mainly produced by M2 macrophage, and C1q promotes migration and invasion of PDAC cells. CONCLUSION: Taken together, we find potential factors that contribute to different stages of PDAC metastasis. Our study broadens the understanding of molecular mechanisms driving PDAC metastasis.

OBJECTIVES: Sox2 is a major transcription factor and the transforming growth factor-α (TGF-α)/EGFR autocrine loop is a hallmark of prostate cancer progression. In this study, we have evaluated the effects and potential mechanisms of Sox2 on cell proliferation and apoptosis, and investigated effects of TGF-α on expression of Sox2 on androgen-independent human prostate cancer cells. MATERIALS AND METHODS: Expression of Sox2 has been determined by RT-PCR, western blot analysis and immunocytochemistry, using RNAi and over-expression strategy to study functions of Sox2 in DU145 and PC-3 cells. Changes in level of proliferation, cell cycle and apoptosis profiles were measured by MTT, colony-forming, bromodeoxyuridine incorporation assays, cell cycle and annexin V analysis. RESULTS: Sox2 was expressed in six human prostate cancer cell lines, and its inhibition reduced cell proliferation and induced apoptosis in DU145 cells. We have shown that knock-down of Sox2 inhibited G(1) to S phase transition concomitantly with down-regulation of cyclin E and up-regulation of p27 proteins. Conversely, over-expression of Sox2 led to the opposite effect in PC-3 cells but its inhibition induced apoptosis by down-regulation of survivin in DU145 cells. We also found that TGF-α up-regulated Sox2 and survivin protein expression via the EGFR/PI3K/AKT pathway. CONCLUSIONS: Sox2 expression is necessary for cell proliferation and evasion of apoptosis in prostate cancer cells and TGF-α could regulate Sox2 and survivin expression by activating the EGFR/PI3K/AKT pathway.

Personality traits are associated with major adverse coronary events (MACE) in patients with coronary artery disease (CAD). However, the link between personality traits and intravascular morphology in CAD patients is poorly understood. This study investigated the relationship between personality traits, specifically Type A behavior pattern and Type D personality, and plaque vulnerability. After adjustment for demographic and clinical factors, multivariable regression analysis showed no association between Type A and optical coherence tomography indices. However, Type D personality was independently associated with lipid plaque, thin cap fibroatheroma (TCFA), and fibrous cap thickness. More specifically, negative affectivity of Type D was related to lipid plaque, TCFA and fibrous cap thickness, and social inhibition was associated with plaque rupture. Our results show that Type D personality was associated with plaque vulnerability, independent of clinical factors. Measurement of negative affectivity and social inhibition will increase our understanding of the progressive phase of the plaque vulnerability, which can contribute to the early identification of high risk patients and reduce the incidence of MACE.