Recombination of rapidly evolving RNA-viruses provides an important mechanism for diversification, spread, and emergence of new variants with enhanced fitness. Foot-and-mouth disease virus (FMDV) causes an important transboundary disease of livestock that is endemic to most countries in Asia and Africa. Maintenance and spread of FMDV are driven by periods of dominance of specific viral lineages. Current understanding of the molecular epidemiology of FMDV lineages is generally based on the phylogenetic relationship of the capsid-encoding genes, with less attention to the process of recombination and evolution of non-structural proteins. In this study, the putative recombination breakpoints of FMDVs endemic to Southeast Asia were determined using full-open reading frame sequences. Subsequently, the lineages' divergence times of recombination-free genome regions were estimated. These analyses revealed a close relationship between two of the earliest endemic viral lineages that appear unrelated when only considering the phylogeny of their capsid proteins. Contrastingly, one lineage, named O/CATHAY, known for having a particular host predilection (pigs) has evolved independently. Additionally, intra-lineage recombination occurred at different breakpoints compared to the inter-lineage process. These results provide new insights about FMDV recombination patterns and the evolutionary interdependence of FMDV serotypes and lineages. Foot-and-mouth disease (FMD) is one of the most important diseases of livestock worldwide 1,2. Many countries with endemic FMD have rural populations that are highly reliant on their livestock as critical assets. The causal agent, FMD virus (FMDV), affects cloven-hoofed animals and is endemic in all countries in mainland Southeast Asia, where clinical cases are regularly observed in livestock, including pigs, cattle, Asian buffalo and small ruminants. FMDV belongs to the genus Aphthovirus of the family Picornaviridae and has a single-stranded, positive-sense, non-segmented RNA genome consisting of an open reading frame (ORF) region of ~7000 nucleotides (nt). The genome encodes for a single polyprotein that is post-translationally processed into 4 capsid proteins (VP1-4) and 10 non-structural proteins (NSP; leader proteinase (L pro), 2A, 2B, 2C, 3A, 3B1 VPg1 , 3B2 VPg2 , 3B3 VPg3 , 3C pro and 3D pol), bounded by 5′and 3′untranslated regions (UTRs) 3. FMDV has been classified into seven distinct serotypes, namely A, O, C, Asia-1, Southern African Territories (SAT) 1, SAT 2 and SAT 3 4 , many of which exist as multiple strains or lineages circulating in endemic regions 5 .
Thermally responsive fluorescent nanoparticles can be constructed to allow robust, rapid, and noninvasive temperature measurements. Furthermore, due to their tiny size, they can be used to detect temperature changes at the nanoscale. In this way, such sensors are ideally suited to emerging applications including intracellular temperature sensing and microelectronics failure diagnostics. Despite their potential, current nanothermometers still suffer from limited sensitivity, dynamic range, and stability. By introducing thermal enhanced anti-Stokes emission from a pair of lanthanide ions, ytterbium and neodymium, we show an increase of more than 1 order of magnitude in both the sensitivity and the dynamic range when compared to conventional ytterbium and erbium-codoped nanothermometers. Here, we report heterogeneous temperature-responsive nanoparticles with a new record of sensitivity (9.6%/K at room temperature and above 2.3%/K at elevated temperatures up to 413 K) that can be used for ratiometric thermometry. The heterogeneous nanostructure design shows that the thermal responses can be fine-tuned by the controlled growth of nanoparticles. The stability of the ultrasensitive nanothermometers has enabled long-term noncontact monitoring of local heat dissipation of a microelectronic device.
Video-rate super-resolution imaging through biological tissue can visualize and track biomolecule interplays and transportations inside cellular organisms. Structured illumination microscopy allows for wide-field super resolution observation of biological samples but is limited by the strong absorption and scattering of light by biological tissues, which degrades its imaging resolution. Here we report a photon upconversion scheme using lanthanide-doped nanoparticles for wide-field super-resolution imaging through the biological transparent window, featured by near-infrared and low-irradiance nonlinear structured illumination. We demonstrate that the 976 nm excitation and 800 nm up-converted emission can mitigate the aberration. We found that the nonlinear response of upconversion emissions from single nanoparticles can effectively generate the required high spatial frequency components in Fourier domain. These strategies lead to a new modality in microscopy with a resolution of 130 nm, 1/7 th of the excitation wavelength, and a frame rate of 1 fps.
Nanoparticles with anti-Stokes emissions enable many sensing applications, but their efficiencies are considerably low. The key to enable the process of anti-Stokes emissions is to create phonons and assist the excited photons to be pumped from a lower energy state onto a higher one. Increasing the temperature will generate more phonons, but it unavoidably quenches the luminescence. Here by quantifying the number of phonons being generated from the host crystal and at the surface of Yb 3+ /Nd 3+ co-doped nanoparticles, we systematically investigated mechanisms towards the large enhancements of the phononassisted anti-Stokes emissions from 980 nm to 750 nm and 803 nm. Moreover, we provided direct evidence that moisture release from the nanoparticle surface at high temperature was not a main reason. We further demonstrated that the brightness of 10 nm nanoparticles were enhanced by more than two orders of magnitude, standing in stark contrast to the thermal quenching effect.
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