MCM6 is a Poor Prognostic Biomarker and Promotes Progression in Breast Cancer.

BACKGROUND: Breast cancer is the commonest global malignancy and the primary cause of carcinoma death. MCM6 is vital to carcinogenesis, but the pathogenesis of MCM6 remains unclear. METHODS: MCM6 expression in patients with breast cancer was examined through The Cancer Genome Atlas (TCGA) database, immunohistochemistry, Quantitative Real-Time PCR (qRT‒PCR) and Western blotting. The prognostic factors were assessed by the Kaplan‒Meier method and Cox regression. On the basis of the key factors selected by multivariable Cox regression analysis, a nomogram risk prediction model was adopted for clinical risk assessment. The TCGA database was utilized to determine how MCM6 is correlated with chemotherapy sensitivity, immune checkpoint-related genes (ICGs), tumor-infiltrating immune cells, along with tumor mutation burden (TMB) and methylation. The impact of MCM6 on carcinoma cells was investigated in terms of proliferation, cell cycle as well as migrating and invasive behavior through CCK assays, flow cytometry, wound healing assays, Transwell assays and xenotransplantation experiments. RESULTS: MCM6 expression was upregulated, which is closely associated with the size of the tumor (p = 0.001) and lymph node metastasis (p = 0.012) in patients with breast cancer. Multivariate analysis revealed MCM6 to be an independent risk factor for prognosis in patients with breast carcinoma. The nomograph prediction model included MCM6, age, ER, M and N stage, which displayed good discrimination with a C index of 0.817 and good calibration. Overexpression of MCM6 correlated with chemotherapy sensitivity, immune checkpoint-related genes (ICGs), tumor-infiltrating immune cells, tumor mutation burden (TMB), and methylation. Silencing MCM6 significantly inhibited proliferation, prolonged the G1 phase of the cell cycle, and restrained the proliferation, migration and invasive behavior of cancerous cells and inhibited tumor growth in vivo. CONCLUSIONS: Our research shows that MCM6 is highly expressed in breast cancer and can be used as an independent prognostic factor, which is expected to become a new target for the treatment of breast cancer in the future.

Cosmic Coincidences of Primordial-Black-Hole Dark Matter.

If primordial black holes (PBHs) contribute more than 10% of the dark matter (DM) density, their energy density today is of the same order as that of the baryons. Such a cosmic coincidence might hint at a mutual origin for the formation scenario of PBHs and the baryon asymmetry of the Universe. Baryogenesis can be triggered by a sharp transition of the rolling rate of inflaton from slow-roll to (nearly) ultraslow-roll phases that produce large curvature perturbations for PBH formation in single-field inflationary models. We show that the baryogenesis requirement drives the PBH contribution to DM, along with the inferred PBH mass range, the resulting stochastic gravitational wave background frequency window, and the associated cosmic microwave background tensor-to-scalar ratio amplitude, into potentially observable regimes.

[Analysis of Clinical Characteristics of JAK2 V617F and BCR-ABL Double-Mutant Myeloproliferative Neoplasms].

OBJECTIVE: To analyze the disease types, clinical manifestations, efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant myeloproliferative neoplasms (MPN), and provide a reference for the diagnosis, treatment and prognosis of MPN. METHODS: The clinical characteristics, diagnosis, therapeutic efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant MPN were analyzed comprehensitively by combining a clinical case diagnosed and treated in our hospital with literature cases from CNKI and PubMed databases. RESULTS: A total of 38 related literatures were retrieved from the two databases by searching "JAK2 V617F" and "BCR-ABL" as key words from 1990 to 2019, and 59 cases were involved. Among all the 60 cases, 41 were males (68.3%) with a median age of 61 (32-77) years old, while 19 were females (31.7%) with a median age of 58 (21-82) years old. The BCR-ABL fusion gene and JAK2 V617F mutation were found simultaneously in 21 cases (35%), 19 cases (31.7%) with JAK2 V617F mutation were found during the treatment of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Ph+CML was detectable in 20 cases (33.3%) during the treatment of JAK2 V617F mutation positive MPN. Polycythemia vera (PV) was the most common MPN coexisting with CML (30%), followed by essential thrombocythemia (ET) (26.7%) and primary myelofibrosis (PMF) (21.7%). In addition, there were 13 cases (21.7%) not classified in the literature. Among the 60 cases, 35 CML patients were clearly staged, including 31 in the chronic phase, 3 in the accelerated phase, and 1 in the blast crisis phase. As for the subtypes of BCR-ABL fusion gene, there were 30 cases with clear classification, including 28 cases of p210, 1 case of p190 and 1 case of p230. CONCLUSION: As cases of BCR-ABL and JAK2 V617F double-mutant MPN are reported, simultaneous detection of JAK2 V617F mutation and BCR-ABL fusion gene in MPN patients is necessary to avoid misdiagnosis and missed diagnosis.

Postmodification of a supramolecular organic framework: visible-light-induced recyclable heterogeneous photocatalysis for the reduction of azides to amines.

We present the postmodification of a diamondoid 3D supramolecular organic framework (SOF) to append [Ru(BPY)3]2+ groups through the formation of a hydrazone bond. The resulting SOF works as an efficient recyclable heterogeneous catalyst for visible-light-induced reduction of aromatic azides to amines.