Causal effect analysis of estrogen receptor associated breast cancer and clear cell ovarian cancer.

BACKGROUND: Evidence indicates that the risk of developing a secondary ovarian cancer (OC) is correlated with estrogen receptor (ER) status. However, the clinical significance of the relationship between ER-associated breast cancer (BC) and clear cell ovarian cancer (CCOC) remains elusive. METHODS: Independent single nucleotide polymorphisms (SNPs) strongly correlated with exposure were extracted, and those associated with confounders and outcomes were removed using the PhenoScanner database. SNP effects were extracted from the outcome datasets with minor allele frequency > 0.01 as the filtration criterion. Next, valid instrumental variables (IVs) were obtained by harmonizing exposure and outcome effects and further filtered based on F-statistics (> 10). Mendelian randomization (MR) assessment of valid IVs was carried out using inverse variance weighted (IVW), MR Egger (ME), weighted median (WM), and multiplicative random effects-inverse variance weighted (MRE-IVW) methods. For sensitivity analysis and visualization of MR findings, a heterogeneity test, a pleiotropy test, a leave-one-out test, scatter plots, forest plots, and funnel plots were employed. RESULTS: MR analyses with all four methods revealed that CCOC was not causally associated with ER-negative BC (IVW results: odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.66-1.20, P = 0.431) or ER-positive BC (IVW results: OR = 0.99, 95% CI = 0.88-1.12, P = 0.901). F-statistics were computed for each valid IV, all of which exceeded 10. The stability and reliability of the results were confirmed by sensitivity analysis. CONCLUSIONS: Our findings indicated that CCOC dids not have a causal association with ER-associated BC. The absence of a definitive causal link between ER-associated BC and CCOC suggested a minimal true causal influence of ER-associated BC exposure factors on CCOC. These results indicated that individuals afflicted by ER-associated BC could alleviate concerns regarding the developing of CCOC, thereby aiding in preserving their mental well-being stability and optimizing the efficacy of primary disease treatment.

Reduced miR-99a-3p levels in systemic lupus erythematosus may promote B cell proliferation via NCAPG and the PI3K/AKT signaling pathway.

BACKGROUND: Systemic lupus erythematosus is an immunologically dysregulated disease characterized by the presence of multiple autoantibodies. In SLE, B lymphocytes contribute to the dysregulated production of autoantibodies and cytokines. Recently, we discovered that miR-99a-3p binds to both EIF4EBP1 and NCAPG mRNA and that lowering miR-99a-3p can promote B cell autophagy in SLE by increasing EIF4EBP1 expression. However, the functions of miR-99a-3p and NCAPG in SLE have not been extensively investigated. OBJECTIVE: This work aims to evaluate the levels of miR-99a-3p and NCAPG expression in SLE B cells and to determine whether the aberrant expression of miR-99a-3p and NCAPG contributes to the pathological mechanisms in SLE. METHODS: B lymphocytes were obtained through immunomagnetic negative selection. Using RT-qPCR, miR-99a-3p and NCAPG mRNA expressions in B lymphocytes and in the BALL-1 cell line were measured. To determine the relative abundance of NCAPG, PI3K, p-PI3K, AKT, and p-AKT, we normalize them to the level of ß-actin using Western blotting. Evaluation of miR-99a-3p and NCAPG's impact on cell proliferation was done utilizing CCK-8 assay. Using flow cytometry, the cell cycle and apoptosis were both measured. RESULTS: Comparing SLE B cells to healthy controls, miR-99a-3p expression was significantly downregulated. Additionally, it was observed that SLE B cells had significantly higher NCAPG mRNA expression. Blocking miR-99a-3p expression in BALL-1 cells with an antagomir elevated NCAPG expression, facilitated PI3K/AKT pathway activation, improved cell proliferation, raised the fraction of S-phase cells, and prevented cell apoptosis. The opposite effects of upregulated miR-99a-3p levels on BALL-1 cells were observed by using an agomir. Furthermore, the effect of decreased miR-99a-3p expression on cell proliferation was partially mediated by elevating NCAPG levels and activating the PI3K/AKT pathway. CONCLUSION: Our research indicates that lower miR-99a-3p expression in SLE B cells appears to boost B cell number via the NCAPG and PI3K/AKT pathways.

Bipolar Polymeric Protective Layer for Dendrite-Free and Corrosion-Resistant Lithium Metal Anode in Ethylene Carbonate Electrolyte.

The unstable interface between Li metal and ethylene carbonate (EC)-based electrolytes triggers continuous side reactions and uncontrolled dendrite growth, significantly impacting the lifespan of Li metal batteries (LMBs). Herein, a bipolar polymeric protective layer (BPPL) is developed using cyanoethyl (-CH2CH2C≡N) and hydroxyl (-OH) polar groups, aiming to prevent EC-induced corrosion and facilitating rapid, uniform Li+ ion transport. Hydrogen-bonding interactions between -OH and EC facilitates the Li+ desolvation process and effectively traps free EC molecules, thereby eliminating parasitic reactions. Meanwhile, the -CH2CH2C≡N group anchors TFSI- anions through ion-dipole interactions, enhancing Li+ transport and eliminating concentration polarization, ultimately suppressing the growth of Li dendrite. This BPPL enabling Li|Li cell stable cycling over 750 cycles at 10 mA cm-2 for 2 mAh cm-2. The Li|LiNi0.8Mn0.1Co0.1O2 and Li|LiFePO4 full cells display superior electrochemical performance. The BPPL provides a practical strategy to enhanced stability and performance in LMBs application.

The correlation between dermoscopy and clinical and pathological tests in the evaluation of skin photoaging.

BACKGROUND: There are no standards for evaluating skin photoaging. Dermoscopy is a non-invasive detection method that might be useful for evaluating photoaging. OBJECTIVE: To assess the correlation between the dermoscopic evaluation of photoaging and clinical and pathological evaluations. METHODS: The age, clinical evaluation (Fitzpatrick classification, Glogau Photoaging Classification, and Chung's standardized image ruler), histopathology (Masson staining and MMP-1 immunohistochemistry), and dermoscopy (Hu's and Isik's) of 40 donor skin samples were analyzed statistically, and Spearman rank correlation analysis was performed. RESULTS: There was a robust correlation between the total Hu scores and Isik dermoscopy. The correlation of dermoscopy with histopathology was higher than that of clinical evaluation methods. There is a strong correlation between telangiectases and lentigo. Xerosis, superficial wrinkle, diffuse erythema, telangiectases, and reticular pigmentation were significantly correlated with the three clinical evaluation methods. Superficial wrinkles were correlated with Masson, MMP-1, various clinical indicators, and other dermoscopic items. CONCLUSION: There is a good correlation between dermoscopy and clinical and histopathological examination. Dermoscopy might help evaluate skin photoaging.