Results The epithelial cell-laden collagen/SIS villi showed significant cell proliferation (1.2-fold) and demonstrated meaningful results for the various cellular activities, such as the expression of tight-junction proteins (ZO-1 and E-cadherin), ALP and ANPEP activities, MUC17 expression, and the permeability coefficient and the glucose uptake ability, compared with the pure 3D collagen villus structure. Conclusion In vitro cellular activities demonstrated that the proposed cell-laden collagen/dECM villus structure generates a more meaningful epithelium layer mimicking the intestinal structure, compared with the pure cell-laden collagen villus structure having a similar villus geometry. Based on the results, we believe that this dECM-based 3D villus model will be helpful in obtaining a more realistic physiological small-intestine model. © The author(s).Rationale “Active targeting” based on the ligand-target affinity is a common strategy to precisely deliver nanoparticle (NP) imaging probes or drug carriers to the diseased tissue. GSK-3 activation However, such ligand-mediated active targeting inevitably takes place with prerequisite “passive targeting”, driven by the enhanced permeability and retention (EPR) effect. Thus, the efficiency of active targeting in relation to off-targeted unbound NPs is of great importance in quantitative imaging of tumor biomarkers and delivery. With the notion that easy clearance of off-targeted uIONPs may lead to enhanced active targeting and tumor accumulation, we examined the NP size effect on “active targeting” of the transferrin receptor (TfR) using transferrin (Tf)-conjugated sub-5 nm (3 nm core) ultrafine iron oxide NPs (uIONPs) and larger IONPs (30 nm core). Methods Green fluorescent dye (FITC)-labeled active targeting uIONPs (FITC-Tf-uIONPs) and red fluorescent dye (TRITC)-labeled passive targeting uIONPs (TRITC-uIONPs) were prepared.rstitial pressure, even though they are not favorable for macrophage uptake. Conclusion Ligand-mediated active targeting improves the delivery and accumulation of the sub-5 nm NPs. The improvement on active targeting is size-dependent and facilitated by NPs with sub-5 nm core sizes. Thus, sub-5 nm NPs may serve as favorable platforms for development of NP-based molecular imaging probes and targeted drug carriers. © The author(s).There is an urgent and unmet need to develop effective therapies for triple negative breast cancers (TNBCs) which are much more aggressive and have poor prognosis due to lack of receptor targets for Her2-targeted and endocrine therapy. In this study we systematically evaluated the effect of Vorinostat (SAHA, a pan-HDAC inhibitor) in reactivating the expression of functional estrogen receptor α (ERα) and synergizing with tamoxifen (TAM, a selective estrogen-receptor modulator) in antitumor activity. In addition, a SAHA prodrug-based dual functional nanocarrier was developed for codelivery of SAHA and TAM for effective combination therapy. Methods A SAHA-containing polymeric nanocarrier, POEG-co-PVDSAHA was developed via reversible addition-fragmentation transfer (RAFT) polymerization with SAHA incorporated into the polymer through a redox-responsive disulfide linkage. The effect of both free SAHA and POEG-co-PVDSAHA on reactivating the expression of functional ERα was investigated in several human and murine Tombination of free SAHA and TAM and TAM-loaded POEG-co-PVMA micelles. Conclusion Our prodrug-based co-delivery system may provide an effective and simple strategy to re-sensitize TNBCs to TAM-based hormone therapy. © The author(s).Manganese-based nanomaterials have piqued great interest in cancer nanotheranostics, owing to their excellent physicochemical properties. Here we report a facile wet-chemical synthesis of size-controllable, biodegradable, and metastable γ-phase manganese sulfide nanotheranostics, which is employed for tumor pH-responsive traceable gas therapy primed chemodynamic therapy (CDT), using bovine serum albumin (BSA) as a biological template (The final product was denoted as MnS@BSA). The as-prepared MnS@BSA can be degraded in response to the mildly acidic tumor microenvironment, releasing hydrogen sulfide (H2S) for gas therapy and manganese ions for magnetic resonance imaging (MRI) and CDT. In vitro experiments validated the pH-responsiveness of MnS@BSA at pH 6.8 and both H2S gas and •OH radicals were detected during its degradation. In vivo experiments showed efficiently tumor turn-on T 1-weighted MRI, significantly suppressed tumor growth and greatly prolonged survival of tumor-bearing mice following intravenous administration of MnS@BSA. Our findings indicated that MnS@BSA nanotheranostics hold great potential for traceable H2S gas therapy primed CDT of cancer. © The author(s).Background Preoperative weight loss has been shown to be a prognostic factor for many cancers. However, whether preoperative weight loss has clinical significance in patients with esophageal cancer is still controversial. Methods A total of 2,174 Chinese patients underwent radical resection of esophageal cancer from 2000 to 2008 were included in our study. Patients were divided into two group no weight loss (-) and weight loss (+), according to whether they had weight loss compared with their usual weight at diagnosis. The influence of preoperative weight loss on disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazard models. Results weight loss (+) was significantly associated with age (P=0.001), alcoholism (P less then 0.001), tumor location (P=0.003), pT category (P=0.003), pN category (P=0.001). Patients of group weight loss (+) had significantly poorer DFS (Mean 63.3 months (m) vs 76.8 m, P less then 0.001) and OS (67.4 m vs 83.3 m, P less then 0.001) than the no weight loss (-) group. In the final multivariate survival analysis with adjustment for covariates, we found that the weight loss (+) group had a 19% higher risk of death (HR=1.19, 95%CI 1.07-1.33, P=0.002) and had a 13% higher risk of disease progression (HR=1.13, 95%CI 1.01-1.25, P=0.027), respectively, than the no weight loss (-) group. Subgroup analysis indicated that the association with preoperative weight loss and better DFS or OS was observed in patients with esophageal squamous cell carcinoma (ESCC) and early pathological stage (I-II). Conclusion Preoperative weight loss is associated with shorter OS and DFS, which means poor postoperative prognosis in esophageal cancer patients. © The author(s).