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Epithelial-mesenchymal transition (EMT) has been implicated in various aspects of tumor development, including tumor invasion and metastasis, cancer stemness, and therapy resistance. Diverse stroma cell types along with biochemical and biophysical factors in the tumor microenvironment impinge on the EMT program to impact tumor progression. Here we provide an in-depth review of various tumor microenvironmental signals that regulate EMT in cancer. We discuss the molecular mechanisms underlying the role of EMT in therapy resistance and highlight new therapeutic approaches targeting the tumor microenvironment to impact EMT and tumor progression.

Novel research and development (R&D) institutions are an important organizational form of scientific and technological innovation in China. Novel R&D institutions in life sciences and medicine are oriented toward people’s life and health and play an important role in promoting the development of life sciences and medicine, forming multiple innovation subjects, and building an innovation ecology with active elements. However, their construction is still in an exploration stage, and it is urgent to optimize the construction strategy and form a stable and sustainable development capability. This study used the methods of policy research, on-site research, case study, and expert consultation to summarize the progress of policy promotion and exploration practices of novel R&D institutions in China, analyzed the construction modes and operation mechanisms of similar R&D institutions abroad, and presented challenges in the development of novel R&D institutions in the field of life sciences and medicine in China. On this basis, we proposed the following strategies for optimizing the construction of novel R&D institutions in life sciences and medicine in China: (1) building up a diversified and stable funding mechanism, (2) establishing a differentiated development path, (3) improving the recruiting and cultivating mechanism of outstanding professionals, (4) continuously innovating the organizational form of scientific research, (5) exploiting the advantages of the flexible mechanism for scientific achievement transformation, and (6) enhancing the academic influence of these institutions, thereby promoting the high-quality development of these institutions and the self-reliance and strength of China in science and technology.

Chronic adipose tissue inflammation accompanied by macrophage accumulation and activation is implicated in the pathogenesis of insulin resistance and type 2 diabetes in humans. The transcriptional coregulator CREBZF is a key factor in hepatic metabolism, yet its role in modulating adipose tissue inflammation and type 2 diabetes remains elusive. The present study demonstrates that overnutrition‐induced CREBZF links adipose tissue macrophage (ATM) proinflammatory activation to insulin resistance. CREBZF deficiency in macrophages, not in neutrophils, attenuates macrophage infiltration in adipose, proinflammatory activation, and hyperglycemia in diet‐induced insulin‐resistant mice. The coculture assays show that macrophage CREBZF deficiency improves insulin sensitivity in primary adipocytes and adipose tissue. Mechanistically, CREBZF competitively inhibits the binding of IκBα to p65, resulting in enhanced NF‐κB activity. In addition, bromocriptine is identified as a small molecule inhibitor of CREBZF in macrophages, which suppresses the proinflammatory phenotype and improves metabolic dysfunction. Furthermore, CREBZF is highly expressed in ATM of obese humans and mice, which is positively correlated with proinflammatory genes and insulin resistance in humans. This study identifies a previously unknown role of CREBZF coupling ATM activation to systemic insulin resistance and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Radiogenic skin injury (RSI) is a common complication during cancer radiotherapy or accidental exposure to radiation. The aim of this study is to investigate the metabolism of bile acids (BAs) and their derivatives during RSI. Rat skin tissues were irradiated by an X-ray linear accelerator. The quantification of BAs and their derivatives were performed by liquid chromatography–mass spectrometry (LC–MS)-based quantitative analysis. Key enzymes in BA biosynthesis were analyzed from single-cell RNA sequencing (scRNA-Seq) data of RSI in the human patient and animal models. The in vivo radioprotective effect of deoxycholic acid (DCA) was detected in irradiated SD rats. Twelve BA metabolites showed significant differences during the progression of RSI. Among them, the levels of cholic acid (CA), DCA, muricholic acid (MCA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA), glycohyodeoxycholic acid (GHCA), 12-ketolithocholic acid (12-ketoLCA) and ursodeoxycholic acid (UDCA) were significantly elevated in irradiated skin, whereas lithocholic acid (LCA), tauro-β-muricholic acid (Tβ-MCA) and taurocholic acid (TCA) were significantly decreased. Additionally, the results of scRNA-Seq indicated that genes involved in 7a-hydroxylation process, the first step in BA synthesis, showed pronounced alterations in skin fibroblasts or keratinocytes. The alternative pathway of BA synthesis is more actively altered than the classical pathway after ionizing radiation. In the model of rat radiogenic skin damage, DCA promoted wound healing and attenuated epidermal hyperplasia. Ionizing radiation modulates the metabolism of BAs. DCA is a prospective therapeutic agent for the treatment of RSI. [ABSTRACT FROM AUTHOR]

We present the calculated equations of state (EOSs) for deuterium-xenon mixtures using mixing rules. Three mixing rules, which are the ideal rule, volume rule, and pressure rule, were used for the calculations, and the thermodynamic self-consistency was evaluated. The volume rule predicts the pressures of mixtures rather accurately, but it fails in the predictions of energies. The pressure ionization has an impact on energy and pressure. Furthermore, the calculated results of the mixing rules were compared with average-atom molecular dynamics (AAMD) simulations, and the pressure rule performs better than the ideal and volume rules over the investigated range.Key words: equation of state, mixing rule, average-atom molecular dynamics, mixing, deuterium-xenon.Nous presentons les equations d'etat (EdE) calculees pour des melanges deuterium-xenon en utilisant les regles de melange. Trois regles de melange, qui sont la regle ideale, la regle de volume et celle de pression, sont utilisees ici pour les calculs et nous verifions l'auto-coherence thermodynamique. La regle de volume predit la pression des melanges de facon assez precise, mais echoue a predire les energies. L'ionisation par pression a un impact surl'energie et la pression. De plus, les resultats calcules des regles de melange sont compares avec des simulations de dynamique moleculaire atomiste (moyenne) (DMAM) et la regle de pression donne de meilleurs resultats que la regle ideale et la regle de volume sur le domaine etudie des parametres physiques. [Traduit par la Redaction.]Mots-cles: equation d'etat, regle de melange, dynamique moleculaire atomiste (moyenne), melange, deuterium-xenon., 1. IntroductionIn the field of inertial confinement fusion (ICF) research [1], high-Z elements could mix into the fusion fuel (i.e., hydrogen isotopes), because of hydrodynamics instabilities. The performance of the [...]