Immune Sensing of Synthetic, Bacterial, and Protozoan RNA by Toll-like Receptor 8 Requires Coordinated Processing by RNase T2 and RNase 2.

Human toll-like receptor 8 (TLR8) activation induces a potent T helper-1 (Th1) cell response critical for defense against intracellular pathogens, including protozoa. The receptor harbors two distinct binding sites, uridine and di- and/or trinucleotides, but the RNases upstream of TLR8 remain poorly characterized. We identified two endolysosomal endoribonucleases, RNase T2 and RNase 2, that act synergistically to release uridine from oligoribonucleotides. RNase T2 cleaves preferentially before, and RNase 2 after, uridines. Live bacteria, P. falciparum-infected red blood cells, purified pathogen RNA, and synthetic oligoribonucleotides all required RNase 2 and T2 processing to activate TLR8. Uridine supplementation restored RNA recognition in RNASE2-/- or RNASET2-/- but not RNASE2-/-RNASET2-/- cells. Primary immune cells from RNase T2-hypomorphic patients lacked a response to bacterial RNA but responded robustly to small-molecule TLR8 ligands. Our data identify an essential function of RNase T2 and RNase 2 upstream of TLR8 and provide insight into TLR8 activation.

Enhancing the Properties of Yttria-Stabilized Zirconia Composites with Zeolitic Imidazolate Framework-Derived Nanocarbons.

Ceramic matrix composites (CMCs) reinforced with nanocarbon have attracted significant interest due to their potential to enhance mechanical, thermal, and electrical properties. Although the investigation of carbon-based materials such as graphene and carbon nanotubes as additives for advanced ceramics has been widespread, the utilization of metal-organic framework (MOF)-derived nanocarbons in CMCs remains largely unexplored. We extended our previous proof-of-concept investigations by demonstrating the effectiveness of a different type of MOF-derived carbon as a reinforcing phase in an alternative ceramic matrix. We employed spark plasma sintering (SPS) to consolidate yttria-stabilized zirconia (YSZ) and zeolitic imidazolate framework (ZIF-67) powder blends at 1300 °C and a uniaxial pressure of 50 MPa. YSZ serves as the ceramic matrix, whereas ZIF-67 serves as the nanocarbon source. The composite exhibits a highly significant improvement in fracture toughness with an increase of up to 13% compared to that of the YSZ monolith. The formation of ZIF-derived nanocarbon interlayers is responsible for the observed enhancement in ductility, which can be attributed to their ability to facilitate energy dissipation during crack propagation and inhibit grain growth. Furthermore, the room-temperature electrical conductivity of the sintered samples demonstrates a substantial improvement, primarily due to the in situ formation of nanocarbon-based fillers, reaching an impressive 27 S/m with 10 wt % ZIF-67 content. Based on the results, it can be inferred that the incorporation of in situ MOF-derived nanocarbons into CMCs leads to a substantial improvement in both the mechanical and electrical properties.

Evaluation of the Nova StatSensor® Xpress(TM) Creatinine point-of-care handheld analyzer.

Creatinine is a parameter that is required to monitor renal function and is important to follow in patients under treatment with potentially toxic renal drugs, such as the anti-HIV drug Tenofovir. A point of care instrument to measure creatinine would be useful for patients monitoring in resource-limited settings, where more instruments that are sophisticated are not available. The StatSensor Xpress Creatinine (Nova Biomedical Cooperation, Waltham, MA, USA) point of care analyzer was evaluated for its diagnostic performance in indicating drug therapy change. Creatinine was measured in parallel using the Nova StatSensor Xpress Creatinine analyzer and the Vitros 5,1FS (Ortho Clinical Diagnostics, Inc, Rochester, USA), which served as reference standard. The precision (i.e., repeatability and reproducibility) and accuracy of the StatSensor Xpress Creatinine analyzer were calculated using a panel of specimens with normal, low pathological and high pathological values. Two different Nova StatSensor Xpress Creatinine analyzers were used for the assessment of accuracy using repeated measurements. The coefficient of variation of the StatSensor Xpress Creatinine analyzers ranged from 2.3 to 5.9% for repeatability and from 4.2 to 9.0% for between-run reproducibility. The concordance correlation agreement was good except for high values (>600 µmol/L). The Bland-Altman analysis in high pathological specimens suggests that the Nova StatSensor Xpress Creatinine test tends to underestimate high creatinine values (i.e., >600 µmol/L). The Nova StatSensor Xpress Creatinine analyzers showed acceptable to good results in terms of repeatability, inter-device reproducibility and between-run reproducibility over time using quality control reagents. The analyzer was found sufficiently accurate for detecting pathological values in patients (age >10 year) and can be used with a moderate risk of misclassification.