Given the intensive application of nanoscale zinc oxide (ZnO) materials in our life, growing concerns have arisen about its unintentional health and environmental impacts. In this study, the neurotoxicity of different sized ZnO nanoparticles in mouse neural stem cells (NSCs) was investigated. A cell viability assay indicated that ZnO nanoparticles manifested dose-dependent, but no size-dependent toxic effects on NSCs. Apoptotic cells were observed and analyzed by confocal microscopy, transmission electron microscopy examination, and flow cytometry. All the results support the viewpoint that the ZnO nanoparticle toxicity comes from the dissolved Zn(2+) in the culture medium or inside cells. Our results highlight the need for caution during the use and disposal of ZnO manufactured nanomaterials to prevent the unintended environmental and health impacts.

Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events.

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Choline acetyltransferase neurons in the vertical diagonal band of Broca (vChATs) degenerate in the early stage of Alzheimer’s disease (AD). Here, we report that vChATs directly innervate newly generated immature neurons (NGIs) in the dorsal hippocampus (dNGIs) of adult mice and regulate both the dNGIs survival and spatial pattern separation. In a mouse model that exhibits amyloid-β plaques similar to AD patients, cholinergic synaptic transmission, dNGI survival and spatial pattern separation are impaired. Activation of vChATs with theta burst stimulation (TBS) that alleviates the decay in cholinergic synaptic transmission effectively protects against spatial pattern separation impairments in the AD mice and this protection was completely abolished by inhibiting the dNGIs survival. Thus, the impairments of pattern separation-associated spatial memory in AD mice are in part caused by degeneration of cholinergic synaptic transmission that modulates the dNGIs survival.

The optimal systemic treatment for pulmonary largecell neuroendocrine carcinoma (LCNEC) is still under debate. Previous studies showed that LCNEC with different genomic characteristics might respond differently to different chemotherapy regimens. In this study, we sought to investigate genomic subtyping using cell-free DNA (cfDNA) analysis in advanced LCNEC and assess its potential prognostic and predictive value.Experimental Design: Tumor DNA and cfDNA from 63 patients with LCNEC were analyzed by target-captured sequencing. Survival and response analyses were applied to 54 patients with advanced stage incurable disease who received first-line chemotherapy.Results: The mutation landscape of frequently mutated cancer genes in LCNEC from cfDNA closely resembled that from tumor DNA, which led to a 90% concordance in genomic subtyping. The 63 patients with LCNEC were classified into small-cell lung cancer (SCLC)-like and non-small cell lung cancer (NSCLC)-like LCNEC based on corresponding genomic features derived from tumor DNA and/or cfDNA. Overall, patients with SCLC-like LCNEC had a shorter overall survival than those with NSCLC-like LCNEC despite higher response rate (RR) to chemotherapy. Furthermore, treatment with etoposide-platinum was associated with superior response and survival in SCLC-like LCNEC compared with pemetrexed-platinum and gemcitabine/taxane-platinum doublets, while treatment with gemcitabine/taxane-platinum led to a shorter survival compared with etoposide-platinum or pemetrexed-platinum in patients with NSCLC-like LCNEC.Conclusions: Genomic subtyping has potential in prognostication and therapeutic decision-making for patients with LCNEC and cfDNA analysis may be a reliable alternative for genomic profiling of LCNEC.

The blood brain barrier is the main obstacle to delivering diagnostic and therapeutic agents to the diseased sites of brain. It is still of great challenge for the combined use of focused ultrasound (FUS) and theranostic nanotechnology to achieve noninvasive and localized delivery of chemotherapeutic drugs into orthotopic brain tumor. In this work, a unique theranostic nanoplatform for highly efficient photoacoustic imaging‐guided chemotherapy of brain tumor both in vitro and in vivo, which is based on the utilization of hollow mesoporous organosilica nanoparticles (HMONs) to integrate ultrasmall Cu2− xSe particles on the surface and doxorubicin inside the hollow interior, is synthesized. The developed multifunctional theranostic nanosystems exhibit tumor‐triggered programmed destruction due to the reducing microenvironment‐responsive cleavage of disulfide bonds that are incorporated into the framework of HMONs and linked between HMONs and Cu2− xSe, resulting in tumor‐specific biodegradation and on‐demand drug‐releasing behavior. Such tumor microenvironment‐responsive biodegradable and biocompatible theranostic nanosystems in combination with FUS provide a promising delivery nanoplatform with high performance for orthotopic brain tumor imaging and therapy.

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BackgroundWe aimed to investigate the function of miR-1307 in chemoresistance and to explore its chemoresistance mechanism in ovarian cancer.MethodsIC50 determination was used to test the chemoresistance profling in ovarian cancer cells. QRT-PCR or western blot was used to validate the expression level of miR-1307 and candidate gene or protein. Colony formation assay and FITC-labeled enhanced Annexin V immunofluorescence were used to compare cell proliferation and apoptosis ability, respectively. The potential target gene and its biological function of miRNA-1307 were also analyzed. Bioinformatics and Luciferase Reporter Gene Assay were conducted to validate the regulation of miRNA-1307 on the ING5 expression. Xenografts assay was used to demonstrate the inhibiting effect of miR-1307 ASO and Taxol therapy against ovarian cancer in vivo.ResultsMiR-1307 was over-expressed in chemoresistant ovarian cancer cell line A2780/Taxol, and over-expression or loss of miR-1307 promoted or inhabited chemoresistance. And we also found that the over-expression of miR-1307 promoted proliferation and inhibited apoptosis in ovarian cancer cells. Besides, we demonstrated that ING5 was a direct target of miR-1307 and miR-1307 down-regulated the ING5 expression in ovarian cancer cells. Additionally, we showed that ING5 inhibited cell proliferation, promoted cell apoptosis and inhabited chemoresistance reversely. Furthermore, the up-regulated ability of cell apoptosis and down-regulated ability of chemoresistance following the loss of miR-1307 was reversed by adding ING5 siRNA in vitro. Finally, we proved the inhibiting effect of miR-1307 ASO and Taxol therapy by increasing the ING5 expression against ovarian cancer through xenografts assay in vivo.ConclusionOur results suggested that miR-1307 could promote ovarian cancer chemoresistance by targeting the ING5 expression and miR-1307 might serve as a therapeutic target for ovarian cancer.