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Lili Hou,* Shuang Hou,* Lei Yin, Shuai Zhao, Xiaohua Li Department of Breast and Thyroid Surgery, Wuzhong People’s Hospital of Suzhou City, Suzhou, 215128, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuai Zhao; Xiaohua Li, Tel/Fax +86-18896587005 ; +86-13771721641, Email 1012889675@qq.com; xq810@163.comPurpose: Regulation of inducers and transcription factor families influence epithelial–mesenchymal transition (EMT), a contributing factor to breast cancer invasion and progression.Methods: Molecular subtypes were classified based on EMT-related mRNAs using ConsensusClusterPlus package. Differences in tumor immune microenvironment and prognosis were assessed among subtypes. Based on EMT genes, a gene signature for prognosis was built using TCGA training set by performing multivariate and univariate Cox regression analyses. Prediction accuracy of the signature was validated by receiver operating characteristic (ROC) curves and overall survival analysis on internal and external datasets. By conducting univariate and multivariate Cox regression analyses, the risk signature as an independent prognostic indicator was assessed. A nomogram was constructed and validated by calibration analysis and decision curve analysis (DCA).Results: Five molecular subtypes were characterized based on EMT genes. Patients in Cluster 2 exhibited an activated immune state and a better prognosis. An 11-EMT gene-signature was built to predict breast cancer prognosis. After validation, the signature showed independence and robustness in predicting clinical outcomes of patients. A nomogram combining the RiskScore and pTNM_stage accurately predicted 1-, 2-, 3-, and 5-year survival chance. In comparison with published model, the current model showed a higher area under the curve (AUC).Conclusion: We characterized five breast cancer subtypes with distinct clinical outcomes and immune status. The study developed an 11-EMT gene

Steady state en time resolved spectroscopie zijn twee fundamentele methodes voor het bestuderen van fotochemische processen. In dit proefschrift zijn drie zelf-opgezette spectroscopische systemen beschreven, waarmee samen met andere spectroscopische methoden verscheidende met licht schakelbare systemen zijn bestudeerd. Met het eerste moleculaire systeem kan de magnetische interacties aan- en uitgeschakeld worden door het bestralen met licht van verschillende golflengte. Twee porfyrine gemodificeerde systemen zijn beschreven: In het eerste systeem zijn porfyrines covalent gebonden aan grafeen om zodoende de eigenschappen van grafeen te modificeren. In het tweede systeem zijn porfyrines gebruikt om moleculaire motoren met zichtbaar licht aan te drijven. Een ander met licht schakelbaar moleculair systeem bestaat uit diaryletheen schakelaars gemixt met fotosensitizers om het genereren van singlet zuurstof te reguleren door middel van licht. In het laatste deel van dit proefschrift zijn verscheidene moleculaire motoren gekarakteriseerd om nauwkeurig de totatiesnelheden en energiebarrières te bepalen.

Azobenzenes have been used as photoresponsive units for the control of numerous biological processes. Primary prerequisites for such applications are site-selective incorporation of photoswitchable units into biomolecules and the possibility of using non-destructive and deep-tissue-penetrating visible light for the photoisomerization. Here we report a push-pull azobenzene that readily undergoes a Staudinger-Bertozzi ligation with azide groups, that can be addressed with visible light (>440nm) and exhibits the solvato- and acidochromism typical for push-pull systems. The thermal relaxation in aqueous environment proceeds on the low-millisecond timescale, thus enabling control over biological processes on similar timescales. The approach is demonstrated in the modification of a quartz surface and in the incorporation of an azobenzene unit into a functional peptide, the third zinc finger in the mammalian factor Sp1.

Steady state en time resolved spectroscopie zijn twee fundamentele methodes voor het bestuderen van fotochemische processen. In dit proefschrift zijn drie zelf-opgezette spectroscopische systemen beschreven, waarmee samen met andere spectroscopische methoden verscheidende met licht schakelbare systemen zijn bestudeerd. Met het eerste moleculaire systeem kan de magnetische interacties aan- en uitgeschakeld worden door het bestralen met licht van verschillende golflengte. Twee porfyrine gemodificeerde systemen zijn beschreven: In het eerste systeem zijn porfyrines covalent gebonden aan grafeen om zodoende de eigenschappen van grafeen te modificeren. In het tweede systeem zijn porfyrines gebruikt om moleculaire motoren met zichtbaar licht aan te drijven. Een ander met licht schakelbaar moleculair systeem bestaat uit diaryletheen schakelaars gemixt met fotosensitizers om het genereren van singlet zuurstof te reguleren door middel van licht. In het laatste deel van dit proefschrift zijn verscheidene moleculaire motoren gekarakteriseerd om nauwkeurig de totatiesnelheden en energiebarrières te bepalen.

Peihao Yin,1,* Yan Wang,1,* YanYan Qiu,1 LiLi Hou,1 Xuan Liu,1 Jianmin Qin,1 Yourong Duan,2 Peifeng Liu,2 Ming Qiu,3 Qi Li11Department of Clinical Oncology, Putuo Hospital and Interventional Cancer Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2Shanghai Cancer Institute, Jiaotong University, Shanghai, China; 3Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China *These authors contributed equally to this workBackground: Recent studies have shown that bufalin has a good antitumor effect but has high toxicity, poor water solubility, a short half-life, a narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study aimed to determine the targeting efficacy of nanoparticles (NPs) made of methoxy polyethylene glycol (mPEG), polylactic-co-glycolic acid (PLGA), poly-L-lysine (PLL), and cyclic arginine-glycine-aspartic acid (cRGD) loaded with bufalin, ie, bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles (BNPs), in SW620 colon cancer-bearing mice.Methods: BNPs showed uniform size. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these nanoparticles were studied in vitro. The tumor targeting, cellular uptake, and growth-inhibitory effect of BNPs in vivo were tested.Results: BNPs were of uniform size with an average particle size of 164 ± 84 nm and zeta potential of 2.77 mV. The encapsulation efficiency was 81.7% ± 0.89%, and the drug load was 3.92% ± 0.16%. The results of in vitro cytotoxicity studies showed that although the blank NPs were nontoxic, they enhanced the cytotoxicity of bufalin in BNPs. Drug release experiments showed that the release of the drug was prolonged and sustained. The results of confocal laser scanning microscopy indicated that BNPs could effectively bind to human umbilical vein endothelial cells. In t

Peihao Yin,1,* Yan Wang,1,* YanYan Qiu,1 LiLi Hou,1 Xuan Liu,1 Jianmin Qin,1 Yourong Duan,2 Peifeng Liu,2 Ming Qiu,3 Qi Li11Department of Clinical Oncology, Putuo Hospital and Interventional Cancer Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2Shanghai Cancer Institute, Jiaotong University, Shanghai, China; 3Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China *These authors contributed equally to this workBackground: Recent studies have shown that bufalin has a good antitumor effect but has high toxicity, poor water solubility, a short half-life, a narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study aimed to determine the targeting efficacy of nanoparticles (NPs) made of methoxy polyethylene glycol (mPEG), polylactic-co-glycolic acid (PLGA), poly-L-lysine (PLL), and cyclic arginine-glycine-aspartic acid (cRGD) loaded with bufalin, ie, bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles (BNPs), in SW620 colon cancer-bearing mice.Methods: BNPs showed uniform size. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these nanoparticles were studied in vitro. The tumor targeting, cellular uptake, and growth-inhibitory effect of BNPs in vivo were tested.Results: BNPs were of uniform size with an average particle size of 164 ± 84 nm and zeta potential of 2.77 mV. The encapsulation efficiency was 81.7% ± 0.89%, and the drug load was 3.92% ± 0.16%. The results of in vitro cytotoxicity studies showed that although the blank NPs were nontoxic, they enhanced the cytotoxicity of bufalin in BNPs. Drug release experiments showed that the release of the drug was prolonged and sustained. The results of confocal laser scanning microscopy indicated that BNPs could effectively bind to human umbilical vein endothelial cells. In t