Attenuation of PITPNM1 signaling cascade can inhibit breast cancer progression

Phosphatidylinositol transfer protein membrane-associated 1 (PITPNM1) contains a highly conserved phosphatidylinositol transfer domain which is involved in phosphoinositide trafficking and signaling transduction under physiological conditions. However, the functional role of PITPNM1 in cancer progression remains unknown. Here, by integrating datasets of The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer (METABRIC), we found that the expression of PITPNM1 is much higher in breast cancer tissues than in normal breast tissues, and a high expression of PITPNM1 predicts a poor prognosis for breast cancer patients. Through gene set variation analysis (GSEA) and gene ontology (GO) analysis, we found PITPNM1 is mainly associated with carcinogenesis and cell-to-cell signaling ontology. Silencing of PITPNM1, in vitro, significantly abrogates proliferation and colony formation of breast cancer cells. Collectively, PITPNM1 is an important prognostic indicator and a potential therapeutic target for breast cancer

Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway

Background: Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents. Methods: The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysfunction was determined by reactive oxygen species accumulation, mitochondrial membrane potential and ATP levels. Results: Our results determined that ivermectin significantly inhibited the proliferation of ESCC cells in vitro and in vivo. Furthermore, we found that ivermectin markedly mediated mitochondrial dysfunction and induced apoptosis of ESCC cells, which indicated the anti-proliferative effect of ivermectin on ESCC cells was implicated in mitochondrial apoptotic pathway. Mechanistically, ivermectin significantly triggered ROS accumulation and inhibited the activation of NF-κB signaling pathway and increased the ratio of Bax/Bcl-2. Conclusions: These finding indicated that ivermectin has significant anti-tumour potential for ESSC and may be a potential therapeutic candidate against ESCC

Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone

Bone metastasis from triple-negative breast cancer (TNBC) frequently results in poorer prognosis than other types of breast cancer due to the delay in diagnosis and intervention, lack of effective treatments and more skeletal-related complications. In the present study, we identified CTNND1 as a most reduced molecule in metastatic bone lesion from TNBC by way of high throughput sequencing of TNBC samples. In vivo experiments revealed that knockdown of CTNND1 enhanced tumor cells metastasis to bones and also increased neutrophils infiltration in bones. In vitro, we demonstrated that knockdown of CTNND1 accelerated epithelial–mesenchymal transformation (EMT) of tumor cells and their recruitment to bones. The involvement by CTNND1 in EMT and bone homing was achieved by upregulating CXCR4 via activating the PI3K/AKT/HIF-1αpathway. Moreover, TNBC cells with reduced expression of CTNND1 elicited cytotoxic T-cells responses through accelerating neutrophils infiltration by secreting more GM-CSF and IL-8. Clinically, patients with triple-negative breast cancer and lower level of CTNND1 had shorter overall survival (OS) and distant metastasis-free survival (DMFS). It was concluded that downregulation of CTNND1 played a critical role in facilitating bone metastasis of TNBC and that CTNND1 might be a potential biomarker for predicting the risk of bone metastases in TNBC

Developmental and Functional Hair Cell-Like Cells Induced by Atoh1 Overexpression in the Adult Mammalian Cochlea In Vitro

Hair cells (HCs) in the mammalian cochleae cannot spontaneously regenerate once damaged, resulting in permanent hearing loss. It has been shown that Atoh1 overexpression induces hair cell-like cells (HCLCs) in the cochlea of newborn rodents, but this is hard to achieve in adult mammals. In this study, we used a three-dimensional cochlear culture system and an adenoviral-mediated delivery vector to overexpress Atoh1 in adult mouse cochleae. HCLCs were successfully induced from 3 days after virus infection (3 DVI) in vitro, and the number increased with time. HCLCs were myosin7a positive and distinguishable from remnant HCs in a culture environment. Meanwhile, patch-clamp results showed that noninactive outward potassium currents (sustained outward potassium currents) could be recorded in HCLCs and that their magnitude increased with time, similar to normal HCs. Furthermore, transient HCN currents were recorded in some HCLCs, indicating that the HCLCs experienced a developmental stage similar to normal HCs. We also compared the electrophysiological features of HCLCs from adult mice with native HCs and found the HCLCs gradually matured, similar to the normal HCs. Meanwhile, HCLCs from adult mice possessed the same bundles as developmental HCs. However, these HCLCs did not express prestin, which is a special marker for outer hair cells (OHCs), even at 13 DVI. These results demonstrate that Atoh1 overexpression induces HCLC formation in the adult mammalian cochlea and that these HCLCs were functional and experienced a developmental process similar to that of normal HCs

Improved short-circuit current density of a-Si:H thin film solar cells with n-type silicon carbide layer

In this work, the performance of p-i-n hydrogenated amorphous silicon thin film solar cells by adopting n-type silicon carbide (n-SiCx:H) layer was investigated. By varying CH4/SiH4 gas flow ratio, refractive index and electrical conductivity of n-SiCx:H thin films were changed in the range of 3.4 to 3.8 and 1.48E-5 to 1.24 S/cm, respectively. Compared with solar cells with n-Si:H/Ag configuration, short-circuit current density (J (sc) ) of solar cells with n-SiCx:H/Ag configuration was improved up to 8.4%, which was comparable with that of solar cells with n-Si:H/ZnO/Ag configuration. Improved J (sc) was related with enhanced spectral response at long wavelength of 500-800 nm. It was supposed that the decreased refractive index of n-SiCx:H layer resulted in the increased back reflectance, which contributed to the improved J (sc). Our experiments demonstrated that n-SiCx:H thin films were attractive choice because they functioned both as n-layer and interlayer in back reflector, and their deposition method was compatible with preparation process of solar cells

Additional file 1. of Diagnostic performance analysis for diabetic cardiovascular autonomic neuropathy based on short-term heart rate variability using Bayesian methods: preliminary analysis

Supplementary appendix for diagnostic performance analysis for diabetic cardiovascular autonomic neuropathy based on short-term heart rate variability using Bayesian methods: preliminary analysi

A study of superstrate amorphous silicon thin film solar cells and modules on flexible BZO glass

Flexible thin film silicon solar modules on heat-resistant transparent flexible substrates are promising to achieve high efficiency by a combination of high-quality silicon thin films and fully monolithic series integration. In this work, performance of superstrate hydrogenated amorphous silicon (a-Si:H) thin film solar cells and modules on flexible glass using boron-doped zinc oxide (BZO) front electrode have been investigated. Compared with conventional glass, BZO thin films on flexible glass exhibited mixed structure of large-sized pyramid and small-sized grain, preferential crystalline orientations of (100) and (110), relatively lower surface roughness and scattering ability. Accordingly, compared with conventional BZO glass, a-Si:H thin film solar cells on flexible BZO glass exhibited a relative increase in open-circuit voltage, fill factor, and efficiency of 2.0, 5.5, and 3.4%, respectively. Finally, similar to 50cm(2) flexible a-Si:H thin film solar modules were prepared by fully monolithic series integration using laser scribing, and relatively higher efficiency was achieved by improving thin films uniformity

Mental health status of medical students during postgraduate entrance examination

Abstract Background The postgraduate entrance examination can be a milestone for many medical students to advance their careers. An increasing number of students are competing for limited postgraduate offers available, and failure to enter postgraduate studies can have adverse mental health consequences. In this paper, we aim to investigate the mental health status of medical students during the postgraduate application entrance examination and to provide a targeted basis for mental health education and psychological counselling. Methods Using the Symptom Checklist-90 scale (SCL-90) questionnaire, the mental health status of 613 students who passed two rounds of the Postgraduate Entrance Examination in 2019 to enroll in Guangzhou Medical University in China was evaluated and followed up for retesting 6 months later. We used SPSS 20.0 statistical software for comparative analysis, including One-Sample T-Test, Independent-Samples T-Test, Paired Samples T-Test and Chi-square Test. Results Our data showed that 12.10% of students had mental health problems during the postgraduate entrance examination, and it decreased significantly to 4.40% at the 6-month follow-up after the examination period finished (P < 0.01). Somatization was the most significant symptom of the students both during and after the postgraduate entrance examination stages. All SCL-90 factors were scored significantly lower both in and after the postgraduate entrance examination stages than the 2008 national college student norm score (P < 0.01). Excluding psychiatric factors, all other SCL-90 factors in the postgraduate entrance examination stage scored higher than the graduate stage (P < 0.05), and the total score of SCL-90 in female medical students was higher compared to male students (P < 0.05). Conclusion The postgraduate entrance examination event has a significant negative influence on students’ mental health. The mental health of college and graduate students as an important part of their higher education experience should be systematically studied, and psychological counselling or help should be provided to them throughout their studies, specifically during the examination period. Educating applicants about mental health should be implemented during the postgraduate entrance examination curriculum