Shepherdshort3067

Biologics manufacturers must continually monitor the attachment of carbohydrates, called glycans, to their products, because any variability can impact safety and efficacy. To help the industry meet this challenge, the United States Pharmacopeial Convention (USP) offers glycan reference standards and validated methods for glycoprofiling using high-performance liquid chromatography (HPLC). The industry has recently adopted more advanced technologies for glycan analysis, including ultra-high performance liquid chromatography (UHPLC) and mass spectrometry. In this study, we confirm that USP's glycan reference standards are compatible with UHPLC by demonstrating comparable peak separation and glycan identification to HPLC methods. The improved resolving power and shorter run-times of UHPLC also allowed us to identify many of the minor glycan components present in USP's glycan reference standards. These more comprehensively characterized glycan reference standards will enable manufacturers to assess the micro-heterogeneity that can negatively impact the safety and efficacy of biological products.We report an electrochemical biosensor based on gold platinum bimetallic nanoparticles (AuPtBNPs)/3-aminopropyltriethoxy silane (APTS) nanocomposite coated fluorine-doped tin oxide (FTO) as a biosensing platform for hybridization-based detection of miRNA-21. Field Emission-Scanning Electron Microscopy (FE-SEM), Fourier Transform Infrared Spectroscopy (FT-IR) and electrochemical measurements were carried out to ensure the successful construction of the biosensor. The amount of cDNA immobilized on electrode surface and hybridization time required for the miRNA-21 sensing were optimized. The biosensing platform showed detection limit of 0.63 fM with wide linear range i.e. 1 fM-100 nM for miRNA-21 detection. The biosensing strategy demonstrates a good recovery yield from 90.18% to 94.6% in serum samples. It offers good selectivity for its complementary miRNA compared to the non-complementary miRNAs. Other analytical features of the biosensor such as stability, reusability and reproducibility were also tested, providing appropriate results.Aconitase 2 (ACO2) belongs to the tricarboxylic acid (TCA) cycle, which represents a key metabolic hub for cellular metabolism that is frequently altered in cancer for satisfying bioenergetic and biosynthetic requirements of proliferating cells. The promotion of ACO2 activity in breast cancer cell lines was shown to slow down proliferation imposing a switch from aerobic glycolysis to oxidative metabolism. The alteration of metabolic pathways in cancer also impinges on the sensitivity to chemotherapeutic interventions. In this work, we evidence that the presence of ACO2 sensitizes cells to the treatment with the genotoxic agents cisplatin (CDDP) and doxorubicin activating the apoptotic cell death mechanism. This response was driven by the accumulation of reactive oxygen species (ROS) following both ACO2 overexpression and CDDP exposure that permit the stabilization/activation of p53 in nuclear and mitochondrial compartments. Semaxanib research buy Collectively, our results highlight that in ACO2 overexpressing cells the promotion of mitochondrial metabolism accounts for increased ROS production that was buffered by p53 mitochondrial recruitment and autophagy induction. However, these systems are not able to counteract the CDDP-mediated oxidative stress that becomes the Achilles heel for increasing susceptibility to apoptotic cell death.The signaling lymphocytic activation molecule family 3 (SLAMF3) is highly expressed on plasma cells from patients with multiple myeloma (MM) and induces high malignant potential by ERK signaling mediated via the interaction with adaptor proteins SHP2 and GRB2. This study focused on the single-nucleotide polymorphism (SNP) of the SLAMF3 gene (rs509749, 1804A>G, M602V) in MM. The SNP G allele was a major type, and the frequencies of the GG, GA, and AA genotypes were 61.8%, 29.4%, and 8.8%, respectively, in patients with MM, which was almost the same as in healthy the control group in the Japanese population. Interestingly, patients with GG genotypes had significantly shorter overall survival times than patients with GA/AA genotypes. Consistent with those results, SLAMF3-overexpressing KMS-34 cells with the G allele (V602) had higher cell proliferation potential and were more resistant to anti-MM agents than those with the A allele (M602). When those cells were subcutaneously inoculated into NOG mice, tumor sizes in mice receiving V602 cells rapidly increased, and survival was significantly shorter than in mice injected with M602 cells. Furthermore, SLAMF3 V602 molecules bound more tightly to SHP2 and GRB2, with increased SHP2 and ERK phosphorylation compared with M602 cells. The mRNA expression of cell cycle-related genes (CCND1 and CCNE1) and anti-apoptotic genes (BCL2L and p21) was increased in V602 cells compared with M602 cells. The results thus suggested that the G allele of SLAMF3 SNP rs509749 may be associated with MM disease progression.Environmental concern with emerging contaminants has increased in recent years, especially with regard to endocrine-disrupting compounds (EDCs), among them hormones. Conventional water treatment processes have been shown to be ineffective in removing these compounds from water and sewage, while heterogeneous photocatalysis has been demonstrated to be a promising technique. However, the catalytic efficiency is strongly related to the choice of the photocatalyst material. In order to obtain a fast and efficient degradation of these endocrine disruptors, nanotubes grown on Ti-0.5wt%W alloy (NT/Ti-0.5W) were used in photocatalytic (PC) and photoelectrocatalytic (PEC) processes for the degradation of estrone (E1) and 17α-ethinylestradiol (EE2) under irradiation with ultraviolet (UV) and visible light. The NT/Ti-0.5W catalysts were synthesized by an anodization process, followed by thermal treatment at 450 °C. Raman, X-ray diffraction and diffuse reflectance spectroscopic analyses indicated that the tungsten dopingwhen compared to a NT/TiO2 electrode.Metal-organic frameworks (MOFs) are emerging class of porous materials that attracted tremendous attention as eco-friendly photocatalysts. However, poor charge separation in most MOFs largely thwarts their photocatalytic performance. In this work, Materials of Institut Lavoisier-100(Fe) (MIL-100 (Fe)) based on iron mesh was successfully fabricated by in situ growth. MIL-100(Fe) doped with polyaniline, namely MIL-100(Fe)/PANI, were then fabricated by galvanostatic deposition followed by annealing. Compared to pure MIL-100(Fe), MIL-100(Fe)/PANI composites exhibited excellent photocatalytic performances towards Thiamphenicol (TAP) degradation and Escherichia coli (E. Coli.) inactivation. The apparent rate constant, k, for TAP elimination of the MIL-100(Fe)/PANI composites with H2O2 is approximately 3 times as high as that of pure MIL-100(Fe). The electrochemical studies showed enhanced photocatalytic performances, which can be attributed to the electronic conductivity of PANI polymers. Quenching experiments, fluorescent tests and electron paramagnetic resonance (EPR) all suggested ⋅O2-, e-, ⋅OH and h+ as reactive oxidizing species (ROSs) involved in the photocatalytic process, where ⋅OH played the predominant ROSs.