Construction and validation of an aging-related gene signature for prognosis prediction of patients with breast cancer.

BACKGROUND: Breast cancer (BC) is an aging-related disease. Aging-related genes (ARGs) participate in the initiation and development of lung and colon cancer, but the prognosis signature of ARGs in BC has not been clearly studied. AIMS: This study aimed to construct an ARGs signature to predict the prognosis of patients with breast cancer. METHOD: Firstly, the expression data of ARGs from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were collected. Then COX and least absolulute shrinkage and selection operator(LASSO) were performed to construct the ARGs prognostic signature. The correlation between the signature and immune cell infiltration, immunotherapeutic response and drug sensitivity were subsequently analysed. The TCGA nomogram was constructed by combining the signature with other clinical features, and was validated by using GEO database. RESULTS: After LASSO and COX regression analyses, a prognostic signature based on nine ARGs, namely, HSP90AA1, NFKB2, PLAU, PTK2, RECQL4, CLU, JAK2, MAP3K5, and S100B, was built by using the TCGA dataset. Moreover, this risk signature is closely related to immune cell infiltration, immunotherapeutic response, and responses to chemotherapy and targeted therapy. Subsequently, The calibration curve demonstrates that the nomogram agrees well with practical prediction results. The receiver operating characteristic curve and decision-making curve analysis demonstrate that ARG signature has the better prognosis diagnosis ability and clinical net benefits. CONCLUSIONS: Therefore, the proposed ARG prognosis signature is a new prognosis molecular marker of patients with BC, and it can provide good references to individual clinical therapy.

Characterization and Genomic Analysis of a Novel Drexlervirial Bacteriophage IME268 with Lytic Activity Against Klebsiella pneumoniae.

Introduction: Klebsiella pneumoniae, a multidrug resistant bacterium, that causes nosocomial infections including septicemia, pneumonia etc. Bacteriophages are potential antimicrobial agents for the treatment of antibiotic resistant bacteria. Methods and Results: In this study, a novel bacteriophage IME268 was isolated from hospital sewage against clinical multi-drug resistant Klebsiella pneumoniae. Transmission electron microscopy and genomic characterization of this phage exhibited it belongs to the Webervirus genus, Drexlerviridae family. Phage IME268 possessed a double-stranded DNA genome composed of 49,552bp with a GC content of 50.5%. The phage genome encodes 77 open reading frames, out of 44 are hypothetical proteins while 33 had assigned putative functions. No tRNA, virulence related or antibiotic resistance genes were found in phage genome. Comparative genomic analysis showed that phage IME268 has 95% identity with 87% query cover with other phages in NCBI database. Multiplicity of infection, one step growth curve and host range of phage were also measured. Conclusion: According to findings, Phage IME268 is a promising biological agent that infects Klebsiella pneumoniae and can be used in future phage therapies.

Hereditary protein C deficiency caused by novel compound heterozygous mutants in a Chinese pedigree: A case report.

Purpura fulminans (PF) is a neonatal presentation of homozygous or compound heterozygous protein C (PC) deficiency; infants who are diagnosed with it are determined to have a major defect in coagulation regulation which is associated with undetectable levels of PC. We report a pedigree who suffered from the hereditary PC deficiency with compound heterozygous mutants; genetic analysis revealed compound heterozygous mutations of 262 G > T(Asp88Tyr) and 400 + 5G > A that were identified in the proband; moreover, Asp88Tyr and 400 + 5G > A were also detected in the father and the mother, respectively. A bioinformatics analysis revealed 262 G > T is probably damaging, and structural analysis indicated a possible mechanism for the functional impairment of PC in this pedigree.

A sensitive photoelectrochemical immunoassay of N6-methyladenosine based on dual-signal amplification strategy: Ru doped in SiO2 nanosphere and carboxylated g-C3N4.

A novel, simple and sensitive photoelectrochemical (PEC) immunosensing platform was constructed for detecting N6-methyladenosine (m6A) based on the carboxylated CN and avidin functionalized Ru@SiO2 (ARS) nanocomposite. Herein, the N6-methyladenosine-5'-triphosphate (m6ATP) was selected as the detection target molecule, m6A antibody was used as recognition unit for m6A, the carboxylated g-C3N4 (CN) was not only used as the photoactive substance, but the substrate for the m6A antibody immobilization, ARS was synthesized and used as signal amplification unit to improve the photocurrent of CN, Phos-tag-biotin was employed as bridge of m6ATP and Ru@SiO2 through the specific interaction between phosphate group of m6ATP and Phos-tag, biotin and avidin, respectively. Under the optimal condition, the fabricated PEC biosensor showed a linear range of 0.01-10nM and high detection sensitivity with low detection limit of 3.23pM for m6ATP. Besides, the developed strategy was also successfully applied to evaluate the content of m6A in human serum samples.

Screening specific polypeptides of breast cancer stem cells from a phage display random peptide library.

The present study aimed to identify polypeptides that specifically bond to breast cancer stem cells from a phage display random 12 peptide library, in addition to the affinity and specificity of polypeptides. A phage display random 12 peptide library was screened using breast cancer stem cells as targets isolated from the MDA-MB-231 cell line using the serum-free culture technique with hs578bst and MDA-MB-231 cells as subtract-screening cells. Positive and specific binding clones were amplified and sent for sequencing. The affinity and specificity of the positive clones were subsequently identified by ELISA and 3,3'-diaminobenzidine staining. The results demonstrated that phages were gathered ~500 times following three rounds of biopanning. ELISA identified that the affinity to breast cancer stem cells of the no. 6 phage was 6.14 times higher than that in the control group. In addition, immunohistochemistry observed that the no. 6 phage exhibited high-specificity bonding to breast cancer stem cells, and the peptide sequence of the positive phage was GYSASRSTIPGK following DNA sequencing and translation. Thus, the present study isolated a specific peptide that bonds to breast cancer stem cells from a phage display random peptide library, which may facilitate further studies regarding the stem cell-targeted therapy of breast cancer.