A clustered regularly interspaced short palindromic repeats (CRISPR)-like "mimivirus virophage resistance element" (MIMIVIRE) system, which contains specific cascade genes and a CRISPR array against virophages, was reported in mimiviruses. An essential component of the MIMIVIRE system is R354, encoding a nuclease and a likely functional homolog of Cas4. Here we show that R354 is a dual nuclease with both exonuclease and endonuclease activities. Structural analysis revealed that the catalytic core domain of R354 is similar to those of Cas4 and ? exonuclease despite their low sequence identity. R354 forms a homodimer that is important for its exonuclease but not endonuclease activity. Structural comparisons between the active and semi-active states of R354 demonstrated that an activation loop adjacent to the catalytic site is critical for enzymatic activity. Overall, the results suggest that R354 belongs to a novel MIMIVIRE system involved in innate virus immunity and provides a template for the identification of new CRISPR systems in other species.
Developing a sensitive, low-cost, and easy-to-use point-of-care testing system for genotyping is important for informing treatment decisions and predicting the risk of underlying diseases. Conventional methods normally require complex operational procedures as well as expensive and sophisticated instruments. Here, we report a general approach that enables us to detect the genotype of multiple sample types directly without DNA purification. Moreover, the PCR results can be further quantitatively analyzed based on a magnetic lateral flow assay (MLFA) system, which avoids multiple steps needed for conventional nucleic acid biosensors. As a demonstration, we show that three genotypes of aldehyde dehydrogenase 2 (ALDH2) can be identified using a small volume of sample with an accuracy of 100% and a sensitivity of 1.0 × 10 2 cells/μL, which are better than those of the gold standard methods. We believe that the direct PCR-MLFA system represents a significant advance toward the development of portable, sensitive biomedical platforms.
The design of blue fluorescent materials combining both deep-blue emission (CIE y <0.06) and high-efficiency climbing over the typically limited exciton production efficiency of 25% is a challenge for organic light-emitting diodes (OLEDs). In this work, we have synthesized two blue luminogens, trans-9,10-bis(2-butoxyphenyl)anthracene (BBPA) and trans-9,10-bis (2,4-dimethoxyphenyl)anthracene with high photoluminescence quantum yields (PLQYs) of 89.5% and 87.0%, respectively. Intriguingly, we have proposed a strategy to avoid aggregation-caused quenching, which can effectively reduce the undesirable excimeric emission by introducing two host matrices with twisted molecular structure, 9,10-di(naphth-2-yl) anthracene and 10,10'-bis-(4-fluorophenyl)-3,3'-dimethyl-9,9'-bianthracene (MBAn-(4)-F), in the BBPA emission layer. The device containing the EML of BBPA-doped MBAn-(4)-F exhibited a high external quantum efficiency of 10.27% for deep-blue emission with the Commission International de L'Eclairage CIE coordinates of (0.15, 0.05) via the steric effect. Importantly, this represents an advance in deep-blue-emitting fluorescent OLED architectures and materials that meet the requirements of high-definition display.
By a combination of microstructure analysis techniques, we reveal the structural origin of the extremely high supercurrent (up to the practical level of 0.1 MA/cm2 at 10 T, 4.2 K) in Sr0.6K0.4Fe2As2 (122) tape. Transmission Kikuchi diffraction analysis reveals that hot pressing promotes a very high fraction of low-angle grain boundaries and texturing of the crystals, which is beneficial for the intergrain physical properties. Moreover, the unique characteristics of low-angle grain boundaries favor both long-range dislocations and short-range dislocations that totally change the pinning mechanism of the bulk 122 system. These defects combined with the grain texturing are not only effective for pinning vortices in the superconducting state, but also improve inter-granular supercurrent degradation, leading to substantially enhanced supercurrent over a wide range of magnetic fields.
for elevated amyloid: 1.32 DVR) and tau pathology was extracted from the entorhinal cortex (FreeSurfer-defined). Generalized additive (GAM) and (curvi-)linear regression models were performed to investigate LC intensity associations with age, APOE status, amyloid and tau. Results: A nonlinear agerelationship with LC signal was observed (p1⁄40.02 polynomial, p1⁄40.05 GAM, Figure 2). The peak in LC signal intensity occurred at w45 years, comparable to the age of 50 reported in autopsy studies. Individuals with elevated amyloid burden (n1⁄49) showed a lower LC signal compared to individuals with lower amyloid levels (n1⁄418; p1⁄40.03, age-corrected) and a borderline difference between APOE-E4 carriers (n1⁄47) and non-carriers (n1⁄49) was observed (p1⁄40.07). We observed an interaction between LC intensity and amyloid burden on entorhinal tau pathology (n1⁄416; p1⁄40.03, corrected for age), suggesting that lower LC intensity was associated with higher entorhinal tau when amyloid burden increases (Figure 3). Conclusions: These preliminary findings suggest that LC changes can reflect early Alzheimer’s disease pathology that is not entirely attributable to age. Further inclusion of participants across the entire lifespan is ongoing.
Over the past decade, there has been increasing interest in the use of multifunctional nanoparticles (NPs) for cancer treatment. Of importance are systems that can deliver drugs at a sustained rate to target cancer cells, which can result in higher efficiency and reduced systemic toxicity. In this study, we present the route for the synthesis of tantalum pentoxide (Ta 2 O 5 ) NPs with a particle size of 27 nm that were individually coated with poly(acrylic acid) (PAA) with a different layer thickness of 2-8 nm by in-situ polymerization of the acrylic acid monomer. The capability of Ta 2 O 5 -PAA to provide anatomical contrast-enhancing features has been demonstrated via computed tomography. The Ta 2 O 5 -PAA conjugate was further loaded with methotrexate, and the drug release was observed for a total of 72 h at a pH of 3.6, 5.4, 7.4, and 9.4. While the different layer thicknesses did not influence the drug release kinetics, a decrease in pH of the release medium resulted in a slower drug release. The developed nanocomposite particles present a great potential as a theranostic system for biomedical applications.
Cities, the core of the global climate change mitigation and strategic low-carbon development, are shelters to more than half of the world population and responsible for three quarters of global energy consumption and greenhouse gas (GHG). This special volume (SV) provides a platform that promotes multi- and inter- disciplinary analyses and discussions on the climate change mitigation for cities. All papers are divided into four themes, including GHG emission inventory and accounting, climate change and urban sectors, climate change and sustainable development, and strategies and mitigation action plans. First, this SV provides methods for constructing emission inventory from both production and consumption perspectives. These methods are useful to improve the comprehensiveness and accuracy of carbon accounting for international cities. Second, the climate change affects urban sectors from various aspects; simultaneously, GHG emissions caused by activities in urban sectors affect the climate system. This SV focuses on mitigation policies and assessment of energy, transport, construction, and service sectors. Third, climate change mitigation of cities is closely connected to urban sustainable development. This SV explores the relationships between climate change mitigation with urbanization, ecosystems, air pollution, and extreme events. Fourth, climate change mitigation policies can be divided into two categories: quantity-based mechanism (e.g., carbon emission trading) and price-based mechanism (e.g., carbon tax). This SV provides experiences of local climate change mitigation all over the world and proposes the city-to-city cooperation on climate change mitigation.