A Novel Platinum Resistance-Related Immune Gene Signature for Overall Survival Prediction in Patients with Ovarian Cancer.

Ovarian cancer (OV) is a highly heterogeneous gynecological tumor that makes the prognostic prediction challenging. Resistance to platinum-based chemotherapy is associated with a poor prognosis in OV. There seems to be an overlap between molecular mechanisms responsible for platinum resistance and immunogenicity in OV. However, the predictive role of platinum resistance-related immune genes for OV prognosis needs to be further explored. In our study, the mRNA expression data of OV patients with corresponding clinical information were collected from The Cancer Genome Atlas (TCGA) cohort and International Cancer Genome Consortium (ICGC) cohort. A multigene signature was constructed for OV patients in the TCGA cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model according to the optimal value of λ and was validated in the ICGC cohort. Furthermore, we performed functional analysis to explore the immune status between low- and high-risk groups based on the median value of the risk score for the multigene signature. Our data showed that there were 41.1% of the platinum resistance-related genes which differentially expressed between immune score low- and high-OV patients in the TCGA cohort. Univariate Cox regression analysis identified 30 differentially expressed genes (DEGs) associated with overall survival (OS) (P < 0.05). 14 genes were identified to construct a novel platinum resistance-related immune model for classifying OV patients into the low- and high- risk groups. Patients in the low-risk group showed significantly higher OS than those in the high-risk group (P < 0.0001 in the both TCGA and ICGC cohort), which was associated with different immune status for the two risk groups. A novel platinum resistance-related immune model can be used for prognostic prediction in OV. Targeting tumor immunity may be a therapeutic alternative for OV with platinum resistance.

STAT3 inhibitor BBI608 reduces patient-specific primary cell viability of cervical and endometrial cancer at a clinical-relevant concentration

Aberrant activation of STAT3 signal pathway promotes tumor progression in many solid tumor types, including cervical cancer and endometrial cancer. BBI608, the STAT3 inhibitor had been reported in previous studies for restraining cancer stem cells. However, whether BBI608 is available for inhibiting the proliferation of cervical cancer or endometrial cancer remains poorly understood. This study investigated the anti-tumor effect and molecular mechanism of BBI608 on the patient-specific primary cells (PSPC) generated from cervical and endometrial cancer in vitro. Methods PSPCs were obtained from four patients via biopsy. The cell viability was analyzed by the CCK8 assay. The PSPCs were treated with various concentrations of BBI608 or/and paclitaxel; and then, western blot was applied to investigate the expression of phosphorylated STAT3 (pSTAT3). Results The PSPCs cell viability was reduced after treated with BBI608 at a lower concentration. Western blot results showed a reduction trend of pSTAT3 after PSPCs treated with BBI608. Our results demonstrated that BBI608 at the certain concentrations worked well in reducing the cell viability of PSPC from the patients who suffered from cervical cancer and endometrial cancer. Conclusions In this study, the patient-specific primary cell (PSPC) was used as the pre-clinical model for investigating the efficiency of BBI608 in reducing cancer cells viability. BBI608, at a clinical-relevant concentration, had valid efficiency in PSPCs from the patients. The dose of drugs treatment and the measured results were more valuable for further guiding clinical trials (AU)

STAT3 inhibitor BBI608 reduces patient-specific primary cell viability of cervical and endometrial cancer at a clinical-relevant concentration.

PURPOSE: Aberrant activation of STAT3 signal pathway promotes tumor progression in many solid tumor types, including cervical cancer and endometrial cancer. BBI608, the STAT3 inhibitor had been reported in previous studies for restraining cancer stem cells. However, whether BBI608 is available for inhibiting the proliferation of cervical cancer or endometrial cancer remains poorly understood. This study investigated the anti-tumor effect and molecular mechanism of BBI608 on the patient-specific primary cells (PSPC) generated from cervical and endometrial cancer in vitro. METHODS: PSPCs were obtained from four patients via biopsy. The cell viability was analyzed by the CCK8 assay. The PSPCs were treated with various concentrations of BBI608 or/and paclitaxel; and then, western blot was applied to investigate the expression of phosphorylated STAT3 (pSTAT3). RESULTS: The PSPCs cell viability was reduced after treated with BBI608 at a lower concentration. Western blot results showed a reduction trend of pSTAT3 after PSPCs treated with BBI608. Our results demonstrated that BBI608 at the certain concentrations worked well in reducing the cell viability of PSPC from the patients who suffered from cervical cancer and endometrial cancer. CONCLUSIONS: In this study, the patient-specific primary cell (PSPC) was used as the pre-clinical model for investigating the efficiency of BBI608 in reducing cancer cells viability. BBI608, at a clinical-relevant concentration, had valid efficiency in PSPCs from the patients. The dose of drugs treatment and the measured results were more valuable for further guiding clinical trials.

Quasi-Solid-State Polymer Electrolyte Based on Electrospun Polyacrylonitrile/Polysilsesquioxane Composite Nanofiber Membrane for High-Performance Lithium Batteries.

Considering the safety problem that is caused by liquid electrolytes and Li dendrites for lithium batteries, a new quasi-solid-state polymer electrolyte technology is presented in this work. A layer of 1,4-phenylene bridged polysilsesquioxane (PSiO) is synthesized by a sol-gel way and coated on the electrospun polyacrylonitrile (PAN) nanofiber to prepare a PAN@PSiO nanofiber composite membrane, which is then used as a quasi-solid-state electrolyte scaffold as well as separator for lithium batteries (LBs). This composite membrane, consisting of the three-dimensional network architecture of the PAN nanofiber matrix and a mesoporous PSiO coating layer, exhibited a high electrolyte intake level (297 wt%) and excellent mechanical properties. The electrochemical analysis results indicate that the ionic conductivity of the PAN@PSiO-based quasi-solid-state electrolyte membrane is 1.58 × 10-3 S cm-1 at room temperature and the electrochemical stability window reaches 4.8 V. The optimization of the electrode and the composite membrane interface leads the LiFePO4|PAN@PSiO|Li full cell to show superior cycling (capacity of 137.6 mAh g-1 at 0.2 C after 160 cycles) and excellent rate performances.

Association between periodontal disease and osteoporosis in postmenopausal women: a protocol for systematic review and meta-analysis.

INTRODUCTION: Periodontal disease and osteoporosis are common chronic diseases, especially for the postmenopausal women. Several original studies explore the association, but there still controversial. Therefore, we will conduct this systematic review and meta-analysis to assess the association between periodontal disease and osteoporosis in postmenopausal women. METHODS AND ANALYSIS: This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Protocols. We will systematically search Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and Scopus from inception to August 2021 to collect all relevant publications, with no restrictions on publication date or languages. Study selection, data extraction and risk of bias assessment will be conducted independently by two trained reviewers independently. The Cochrane's tool for assessing risk of bias, Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality will be used for the risk of bias assessment. OR, HR and risk ratio with 95% CI were considered as the effect size for dichotomous outcomes, weighted mean difference with 95% CI were calculated as the effect size for continuous outcomes. Random-effects models will be used. Heterogeneity between studies will be assessed via the forest plot and I². Publication bias will detected by funnel plots, Begg's test and Egger's test. The subgroup analyses and sensitivity ananlyses will also be used to explore and interpret the heterogeneity. ETHICS AND DISSEMINATION: This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021225746.

A highly conductive quasi-solid-state electrolyte based on helical silica nanofibers for lithium batteries.

The replacement of flammable liquid electrolytes by inorganic solid ones is considered the most effective approach to enhancing the safety of Li batteries. However, solid electrolytes usually suffer from low ionic conductivity and poor rate capability. Here we report a unique quasi-solid-state electrolyte based on an inorganic matrix composed of helical tubular silica nanofibers (HSNFs) derived from the self-assembly of chiral low-molecular-weight amphiphiles. The HSNFs/ionic liquid quasi-solid-state electrolyte has high thermal stability (up to ∼370 °C) and good ionic conductivity (∼3.0 mS cm-1 at room temperature). When tested as the electrolyte in a LiFePO4/Li cell, excellent rate capability and good cycling stability are demonstrated, suggesting that it has potential be the electrolyte for a new generation of safer Li batteries.

Elevated MYO10 Predicts Poor Prognosis and its Deletion Hampers Proliferation and Migration Potentials of Cells Through Rewiring PI3K/Akt Signaling in Cervical Cancer.

MYO10, recognized as an important regulator of cytoskeleton remodeling, has been reported to be associated with tumorigenesis. However, its functional implication in cervical cancer and potential mechanism still remain to be undetermined currently. MYO10 level in cervical cancer tissues was analyzed by using data retrieved from The Cancer Genome Atlas and ONCOMINE databases. Messenger RNA and protein expression levels were determined by quantitative real-time polymerase chain reaction and Western blotting. Small-interfering RNA and overexpressing plasmid were used for MYO10 silencing and overexpression, and cell proliferation was analyzed by CCK-8. Transwell assays were performed to investigate the ability of cell migration and invasion. MYO10 was upregulated in cervical cancer tissues and cells when compared to normal controls, and survival analysis showed patients with high MYO10 expression had worse overall survival. Moreover, knockdown/overexpression of MYO10 significantly inhibited/enhanced the proliferation, invasion, and migration capabilities of cervical cells transfected with siRNAs/overexpressing plasmid. Additionally, MYO10 silencing inhibited PI3K/Akt signaling pathway by decreasing the phosphorylation status of PI3K and AKT. Data from the present study indicated that MYO10 were overexpressed in patients with cervical cancer and positively linked with poor prognosis. Experimental results suggested that MYO10 induced a significant encouraging effect in cervical cancer cell proliferation, invasion, and migration, linked with involvement of PI3K/Akt signaling. Collectively, these results emphasize a novel role for MYO10 overexpression in cervical cancer and provide a potent therapeutic strategy against cervical cancer.

Vasoactive intestinal peptide expression in the vaginal anterior wall of patients with pelvic organ prolapse.

OBJECTIVE: Perimenopausal women are at high risk for pelvic organ prolapse (POP) and stress urinary incontinence (SUI) diseases. In the present study, the expression of VIP in the vaginal epithelium of 70 perimenopausal women was correlated with the severity of POP with or without SUI. MATERIALS AND METHODS: Seventy biopsy specimens from the anterior vaginal epithelium were obtained from postmenopausal patients. Immunohistochemical labeling for vasoactive intestinal peptide (VIP) and hematoxylin and eosin staining were performed. The VIP innervation was then compared between eight patient groups. Semiquantitative analysis of VIP protein by Western blotting was performed and compared between the eight patient groups. RESULTS: The results of the immunohistochemical study showed that the intensity of VIP-immunoreactivity (VIP-ir) in the eight groups was as follows (in decreasing order): Control; POPI; POP II; POP II + SUI; POP III; POP IV and POP III + SUI; and POP IV + SUI. The intensity of VIP-ir was obviously weak and similar among the POP IV, POP III + SUI, and POP IV + SUI groups. This result was validated by the Western blotting analysis. The level of the VIP peptide also deceased in POP patients and was as follows (in decreasing order): Control; POPI; POP II and POP II + SUI; POP III and POP III + SUI; and POP IV and POP IV + SUI. CONCLUSION: The present study found that reduced VIP innervation in the vaginal epithelium of the perimenopausal women was correlated with the severity of POP with or without SUI.

Neuropeptide Y innervation in the vaginal mucosa among patients with pelvic organ prolapse.

The purpose of this study was to explore the innervation of neuropeptide Y (NPY) in the anterior vaginal mucosa of menopausal patients suffering from pelvic organ prolapse (POP). To do this, we analyzed the distribution and expression of NPY and its correlation with the occurrence and development of POP. Changes in NPY abundance in the anterior vaginal mucosa were assessed by immunohistochemistry in tissue samples collected from 41 POP patients and 9 control subjects. We divided patients into 4 populations, designated POP IV-POP I, exhibiting decreasing levels of NPY innervation. Through multivariate regression analysis, the level of reduction in NPY innervation was shown to be associated with an increasing severity of POP disease in a statistically significant manner. In conclusion, our data reveal that as the symptoms of POP intensify, the expression of NPY in anterior vaginal mucosa decreases progressively. Menopause, in combination with stress urinary incontinence (SUI), results in a stronger effect on both nerve damage to the pelvic floor and NPY alteration, compared to other risk factors, such as parity and weight.