Proteomic Mendelian randomization to identify protein biomarkers of telomere length.

Shortening of telomere length (TL) is correlated with many age-related disorders and is a hallmark of biological aging. This study used proteome-wide Mendelian randomization to identify the protein biomarkers associated with telomere length. Protein quantitative trait loci (pQTL) were derived from two studies, the deCODE Health study (4907 plasma proteins) and the UK Biobank Pharma Proteomics Project (2923 plasma proteins). Summary data from genome-wide association studies (GWAS) for TL were obtained from the UK Biobank (472,174 cases) and GWAS Catalog (418,401 cases). The association between proteins and TL was further assessed using colocalization and summary data-based Mendelian randomization (SMR) analyses. The protein-protein network, druggability assessment, and phenome-wide MR were used to further evaluate the potential biological effects, druggability, and safety of the target proteins. Proteome-wide MR analysis identified 22 plasma proteins that were causally associated with telomere length. Five of these proteins (APOE, SPRED2, MAX, RALY, and PSMB1) had the highest evidence of association with TL and should be prioritized. This study revealed telomere length-related protein biomarkers, providing new insights into the development of new treatment targets for chronic diseases and anti-aging intervention strategies.

Removal of sulfonamide antibiotics by non-free radical dominated peroxymonosulfate oxidation catalyzed by cobalt-doped sulfur-containing biochar from sludge.

The reuse of activated sludge as a solid waste is severely underutilized due to the limitations of traditional treatment and disposal methods. Given that, the sulfur-containing activated sludge catalyst doped with cobalt (SK-Co(1.0)) was successfully prepared by one-step pyrolysis and calcinated at 850 â„ƒ. The generation of CoSx was successfully characterized by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), indicating that the sulfur inside the sludge was the anchoring site for the externally doped cobalt. Cobalt (Ⅱ) (Co2+), as the main adsorption site for peroxymonosulfate(PMS), formed a complex (SK-Co(1.0)-PMS* ) and created the conditions for the generation of surface radicals. The SK-Co(1.0)/PMS system showed high degradation efficiency and apparent rate constants for Sulfamethoxazole (SMX) (91.56% and 0.187 min-1) and Sulfadiazine (SDZ) (90.73% and 0.047 min-1) within 10 min and 30 min, respectively. Three sites of generation of 1O2, which played a dominant role in the degradation of SMX and SDZ in the SK-Co(1.0)/PMS system, were summarized as：sulfur vacancies (SVs), the Co3+/Co2+ cycles promoted by sulfur(S) species, oxygen-containing functional groups (C-O). The degradation mechanisms and pathways had been thoroughly investigated using DFT calculations. In view of this, a new idea for the resource utilization of activated sludge solid waste was provided and a new strategy for wastewater remediation was proposed.

Covalent organic frameworks@ZIF-67 derived novel nanocomposite catalyst effectively activated peroxymonosulfate to degrade organic pollutants.

Metal organic frameworks-Covalent organic frameworks (MOFs-COFs) nanocomposites could improve the catalytic performance. Herein, a novel nanocomposite catalyst (CC@Co3O4) derived from MOFs-COFs (COF@ZIF-67) was prepared on peroxymonosulfate (PMS) activation for bisphenol A (BPA) and rhodamine B (RhB) degradation. Owing to the Co species, oxygen vacancy (OV), surface hydroxyl (-OH), graphite N and ketone groups (C=O), the CC@Co3O4 exhibited higher catalytic degradation performance and total organic carbon (TOC) for BPA (93.8% and 22.3%) and RhB (98.2% and 82.5%) with a small quantity of catalyst (0.10 g/L) and low concentration of PMS (0.20 g/L) even without pH adjustment. Sulfate radicals (•SO4-), hydroxyl radicals (•OH), single oxygen (1O2), superoxide radicals (•O2-) and electron transfer process were all involved in the degradation of BPA and RhB. Among them, the degradation of BPA and RhB mainly depended on •O2- and 1O2, respectively. Meanwhile, the degradation pathways of BPA and RhB were proposed, and the biotoxicity of the degradation products was evaluated by freshwater chlorella. The results illustrated that the degradation products were environmentally friendly to organisms. In addition, the role of COF in the nanocomposites was also studied. The addition of COF remarkably improved the catalytic performance of CC@Co3O4 due to the faster electron transfer, more graphite N and C=O. Overall, this work may open the door to the development of COF-based catalysts in the field of water pollutant remediation.

Cancer cell-oriented migration of mesenchymal stem cells engineered with an anticancer gene (PTEN): an imaging demonstration.

BACKGROUND: Mesenchymal stem cells (MSCs) have been considered to hold great potential as ideal carriers for the delivery of anticancer agents since the discovery of their tumor tropism. This study was performed to demonstrate the effects of phosphatase and tensin homolog (PTEN) engineering on MSCs' capacity for cancer cell-oriented migration. METHODS: MSCs were engineered with a PTEN-bearing plasmid and the expression was confirmed with Western blotting. A human glioma cell line (DBTRG) was used as the target cell; DBTRG cell-oriented migration of MSCs was monitored with a micro speed photographic system. RESULTS: The expression of transfected PTEN in MSCs was identified by immunoblotting analysis and confirmed with cell viability assessment of target cells. The DBTRG cell-oriented migration of PTEN-engineered MSCs was demonstrated by a real-time dynamic monitoring system, and a phagocytosis-like action of MSCs was also observed. CONCLUSION: MSCs maintained their capacity for cancer cell-directed migration after they were engineered with anticancer genes. This study provides the first direct evidence of MSCs' tropism post-anticancer gene engineering.

Noggin and bFGF cooperate to maintain the pluripotency of human embryonic stem cells in the absence of feeder layers.

Human embryonic stem (hES) cells are typically maintained on mouse embryonic fibroblast (MEF) feeders or with MEF-conditioned medium. However, these xenosupport systems greatly limit the therapeutic applications of hES cells because of the risk of cross-transfer of animal pathogens. Here we showed that the bone morphogenetic protein antagonist noggin is critical in preventing differentiation of hES cells in culture. Furthermore, we found that the combination of noggin and basic fibroblast growth factor (bFGF) was sufficient to maintain the prolonged growth of hES cells while retaining all hES cell features. Since both noggin and bFGF are expressed in MEF, our findings suggest that they may be important factors secreted by MEF for maintaining undifferentiated pluripotent hES cells. Our data provide new insight into the mechanism how hES cell self-renewal is regulated. The newly developed feeder-free culture system will provide a more reliable alternative for future therapeutic applications of hES cells.