Dobson Lockhart (lacecase17)
Artificial metalloenzymes as catalysts are promising candidates for their use in different technologies, such as bioremediation, biomass transformation, or biosensing. Despite this, their practical exploitation is still at an early stage. Immobilized natural enzymes have been proposed to enhance their applicability. Immobilization may offer several advantages (i) catalyst reuse; (ii) easy separation of the enzyme from the reaction medium; (iii) better tolerance to harsh temperature and pH conditions. Here, we report an easy immobilization procedure of an artificial peroxidase on different surfaces, by means of click chemistry. FeMC6*a, a recently developed peroxidase mimic, has been functionalized with a pegylated aza-dibenzocyclooctyne to afford a "clickable" biocatalyst, namely FeMC6*a-PEG4@DBCO, which easily reacts with azide-functionalized molecules and/or nanomaterials to afford functional bioconjugates. The clicked biocatalyst retains its structural and, to some extent, its functional behaviors, thus housing high potential for biotechnological applications. Non-small-cell lung cancer (NSCLC) is a significant public health issue worldwide. The aim of our study was to develop a serum miRNA-based molecular signature for the early detection and prognosis prediction of NSCLC. The significantly altered circulating miRNAs were profiled in GSE24709. The top ten upregulated miRNAs were miR-432, miR-942, miR-29c-5p, miR-601, miR-613, miR-520d-3p, miR-1261, miR-132-5p, miR-302b, and miR-154-5p, while the top ten downregulated miRNAs were miR-562, miR-18b, miR-9-3p, miR-154-3p, miR-20b, miR-18a, miR-487a, miR-20a, miR-103, and miR-144. Then, the top four upregulated serum miRNAs (miR-432, miR-942, miR-29c-5p, and miR-601) were validated by real-time quantitative PCR. The clinical significance of two candidate serum miRNAs, miR-942 and miR-601, was further explored. Our results showed that the expression levels of serum miR-942 and serum miR-601 were significantly upregulated in NSCLC. In addition, serum miR-942 and serum miR-601 showed better performance than CEA, CYFRA21-1, and SCCA for early diagnosis of NSCLC. Combining serum miR-942 and serum miR-601 enhanced the efficacy of detecting early-stage NSCLC. Moreover, high serum miR-942 and serum miR-601 were both associated with adverse clinical variables and poor survival. The NSCLC patients with simultaneously high serum miR-942 and serum miR-601 suffered worst clinical outcome, while those with simultaneously low serum miR-942 and serum miR-601 had most favorable outcome. The multivariate analysis showed that serum miR-942 and serum miR-601 were independent prognostic factors for NSCLC. Taken together, serum miR-942 and serum miR-601 might serve as a promising molecular signature for the early detection and prognosis prediction of NSCLC. Taken together, serum miR-942 and serum miR-601 might serve as a promising molecular signature for the early detection and prognosis prediction of NSCLC.Craniometaphyseal dysplasia (CMD), a rare genetic bone disorder, is characterized by lifelong progressive thickening of craniofacial bones and metaphyseal flaring of long bones. The autosomal dominant form of CMD is caused by mutations in the progressive ankylosis gene ANKH (mouse ortholog Ank), encoding a pyrophosphate (PPi) transporter. We previously reported reduced formation and function of osteoblasts and osteoclasts in a knockin (KI) mouse model for CMD (AnkKI/KI) and in CMD patients. We also showed rapid protein degradation of mutant ANK/ANKH. Mutant ANK protein displays reduced PPi transport, which may alter the inorganic phosphate (Pi) and PPi ratio, an important regulatory mechanism for bone mineralization. Here we investigate whether reducing dietary Pi intake can ameliorate the CMD-like skeletal phenotype by comparing male and female Ank+/+ and AnkKI/KI mice exposed to a low (0.3%) and normal (0.7%) Pi diet for 13 weeks from birth. Seru