A photonic integrated continuous-travelling-wave parametric amplifier.

The ability to amplify optical signals is of pivotal importance across science and technology typically using rare-earth-doped fibres or gain media based on III-V semiconductors. A different physical process to amplify optical signals is to use the Kerr nonlinearity of optical fibres through parametric interactions1,2. Pioneering work demonstrated continuous-wave net-gain travelling-wave parametric amplification in fibres3, enabling, for example, phase-sensitive (that is, noiseless) amplification4, link span increase5, signal regeneration and nonlinear phase noise mitigation6. Despite great progress7-15, all photonic integrated circuit-based demonstrations of net parametric gain have necessitated pulsed lasers, limiting their practical use. Until now, only bulk micromachined periodically poled lithium niobate (PPLN) waveguide chips have achieved continuous-wave gain16,17, yet their integration with silicon-wafer-based photonic circuits has not been shown. Here we demonstrate a photonic-integrated-circuit-based travelling-wave optical parametric amplifier with net signal gain in the continuous-wave regime. Using ultralow-loss, dispersion-engineered, metre-long, Si3N4 photonic integrated circuits18 on a silicon chip of dimensions 5 × 5 mm2, we achieve a continuous parametric gain of 12 dB that exceeds both the on-chip optical propagation loss and fibre-chip-fibre coupling losses in the telecommunication C band. Our work demonstrates the potential of photonic-integrated-circuit-based parametric amplifiers that have lithographically controlled gain spectrum, compact footprint, resilience to optical feedback and quantum-limited performance, and can operate in the wavelength ranges from visible to mid-infrared and outside conventional rare-earth amplification bands.

Single-cell profiling of African swine fever virus disease in the pig spleen reveals viral and host dynamics.

African swine fever, one of the major viral diseases of swine, poses an imminent threat to the global pig industry. The high-efficient replication of the causative agent African swine fever virus (ASFV) in various organs in pigs greatly contributes to the disease. However, how ASFV manipulates the cell population to drive high-efficient replication of the virus in vivo remains unclear. Here, we found that the spleen reveals the most severe pathological manifestation with the highest viral loads among various organs in pigs during ASFV infection. By using single-cell-RNA-sequencing technology and multiple methods, we determined that macrophages and monocytes are the major cell types infected by ASFV in the spleen, showing high viral-load heterogeneity. A rare subpopulation of immature monocytes represents the major population infected at late infection stage. ASFV causes massive death of macrophages, but shifts its infection into these monocytes which significantly arise after the infection. The apoptosis, interferon response, and antigen-presentation capacity are inhibited in these monocytes which benefits prolonged infection of ASFV in vivo. Until now, the role of immature monocytes as an important target by ASFV has been overlooked due to that they do not express classical monocyte marker CD14. The present study indicates that the shift of viral infection from macrophages to the immature monocytes is critical for maintaining prolonged ASFV infection in vivo. This study sheds light on ASFV tropism, replication, and infection dynamics, and elicited immune response, which may instruct future research on antiviral strategies.

Monolithic piezoelectric control of soliton microcombs.

High-speed actuation of laser frequency1 is critical in applications using lasers and frequency combs2,3, and is a prerequisite for phase locking, frequency stabilization and stability transfer among optical carriers. For example, high-bandwidth feedback control of frequency combs is used in optical-frequency synthesis4, frequency division5 and optical clocks6. Soliton microcombs7,8 have emerged as chip-scale frequency comb sources, and have been used in system-level demonstrations9,10. Yet integrated microcombs using thermal heaters have limited actuation bandwidths11,12 of up to 10 kilohertz. Consequently, megahertz-bandwidth actuation and locking of microcombs have only been achieved with off-chip bulk component modulators. Here we demonstrate high-speed soliton microcomb actuation using integrated piezoelectric components13. By monolithically integrating AlN actuators14 on ultralow-loss Si3N4 photonic circuits15, we demonstrate voltage-controlled soliton initiation, tuning and stabilization with megahertz bandwidth. The AlN actuators use 300 nanowatts of power and feature bidirectional tuning, high linearity and low hysteresis. They exhibit a flat actuation response up to 1 megahertz-substantially exceeding bulk piezo tuning bandwidth-that is extendable to higher frequencies by overcoming coupling to acoustic contour modes of the chip. Via synchronous tuning of the laser and the microresonator, we exploit this ability to frequency-shift the optical comb spectrum (that is, to change the comb's carrier-envelope offset frequency) and make excursions beyond the soliton existence range. This enables a massively parallel frequency-modulated engine16,17 for lidar (light detection and ranging), with increased frequency excursion, lower power and elimination of channel distortions resulting from the soliton Raman self-frequency shift. Moreover, by modulating at a rate matching the frequency of high-overtone bulk acoustic resonances18, resonant build-up of bulk acoustic energy allows a 14-fold reduction of the required driving voltage, making it compatible with CMOS (complementary metal-oxide-semiconductor) electronics. Our approach endows soliton microcombs with integrated, ultralow-power and fast actuation, expanding the repertoire of technological applications of microcombs.

Integrated turnkey soliton microcombs.

Optical frequency combs have a wide range of applications in science and technology1. An important development for miniature and integrated comb systems is the formation of dissipative Kerr solitons in coherently pumped high-quality-factor optical microresonators2-9. Such soliton microcombs10 have been applied to spectroscopy11-13, the search for exoplanets14,15, optical frequency synthesis16, time keeping17 and other areas10. In addition, the recent integration of microresonators with lasers has revealed the viability of fully chip-based soliton microcombs18,19. However, the operation of microcombs requires complex startup and feedback protocols that necessitate difficult-to-integrate optical and electrical components, and microcombs operating at rates that are compatible with electronic circuits-as is required in nearly all comb systems-have not yet been integrated with pump lasers because of their high power requirements. Here we experimentally demonstrate and theoretically describe a turnkey operation regime for soliton microcombs co-integrated with a pump laser. We show the appearance of an operating point at which solitons are immediately generated by turning the pump laser on, thereby eliminating the need for photonic and electronic control circuitry. These features are combined with high-quality-factor Si3N4 resonators to provide microcombs with repetition frequencies as low as 15 gigahertz that are fully integrated into an industry standard (butterfly) package, thereby offering compelling advantages for high-volume production.

Plasminogen activator urokinase interacts with the fusion protein and antagonizes the growth of Peste des petits ruminants virus.

Peste des petits ruminants is an acute and highly contagious disease caused by the Peste des petits ruminants virus (PPRV). Host proteins play a crucial role in viral replication. However, the effect of fusion (F) protein-interacting partners on PPRV infection is poorly understood. In this study, we found that the expression of goat plasminogen activator urokinase (PLAU) gradually decreased in a time- and dose-dependent manner in PPRV-infected goat alveolar macrophages (GAMs). Goat PLAU was subsequently identified using co-immunoprecipitation and confocal microscopy as an F protein binding partner. The overexpression of goat PLAU inhibited PPRV growth and replication, whereas silencing goat PLAU promoted viral growth and replication. Additionally, we confirmed that goat PLAU interacted with a virus-induced signaling adapter (VISA) to antagonize F-mediated VISA degradation, increasing the production of type I interferon. We also found that goat PLAU reduced the inhibition of PPRV replication in VISA-knockdown GAMs. Our results show that the host protein PLAU inhibits the growth and replication of PPRV by VISA-triggering RIG-I-like receptors and provides insight into the host protein that antagonizes PPRV immunosuppression.IMPORTANCEThe role of host proteins that interact with Peste des petits ruminants virus (PPRV) fusion (F) protein in PPRV replication is poorly understood. This study confirmed that goat plasminogen activator urokinase (PLAU) interacts with the PPRV F protein. We further discovered that goat PLAU inhibited PPRV replication by enhancing virus-induced signaling adapter (VISA) expression and reducing the ability of the F protein to degrade VISA. These findings offer insights into host resistance to viral invasion and suggest new strategies and directions for developing PPR vaccines.

Impaired interferon response in senecavirus A infection and identification of 3Cpro as an antagonist.

Senecavirus A (SVA), a picornavirus, causes vesicular diseases and epidemic transient neonatal losses in swine, resulting in a multifaceted economic impact on the swine industry. SVA counteracts host antiviral response through multiple strategies facilitatng viral infection and transmission. However, the mechanism of how SVA modulates interferon (IFN) response remains elusive. Here, we demonstrate that SVA 3C protease (3Cpro) blocks the transduction of Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway to antagonize type I IFN response. Mechanistically, 3Cpro selectively cleaves and degrades STAT1 and STAT2 while does not target JAK1, JAK2, and IRF9, through its protease activity. Notably, SVA 3Cpro cleaves human and porcine STAT1 on a Leucine (L)-Aspartic acid (D) motif, specifically L693/D694. In the case of STAT2, two cleavage sites were identified: glutamine (Q) 707 was identified in both human and porcine, while the second cleavage pattern differed, with residues 754-757 (Valine-Leucine-Glutamine-Serine motifs) in human STAT2 and Q758 in porcine STAT2. These cleavage patterns by SVA 3Cpro partially differ from previously reported classical motifs recognized by other picornaviral 3Cpro, highlighting the distinct characteristics of SVA 3Cpro. Together, these results reveal a mechanism by which SVA 3Cpro antagonizes IFN-induced antiviral response but also expands our knowledge about the substrate recognition patterns for picornaviral 3Cpro.IMPORTANCESenecavirus A (SVA), the only member in the Senecavirus genus within the Picornaviridae family, causes vesicular diseases in pigs that are clinically indistinguishable from foot-and-mouth disease (FMD), a highly contagious viral disease listed by the World Organization for Animal Health (WOAH). Interferon (IFN)-mediated antiviral response plays a pivotal role in restricting and controlling viral infection. Picornaviruses evolved numerous strategies to antagonize host antiviral response. However, how SVA modulates the JAK-STAT signaling pathway, influencing the type I IFN response, remains elusive. Here, we identify that 3Cpro, a protease of SVA, functions as an antagonist for the IFN response. 3Cpro utilizes its protease activity to cleave STAT1 and STAT2, thereby diminishing the host IFN response to promote SVA infection. Our findings underscore the significance of 3Cpro as a key virulence factor in the antagonism of the type I signaling pathway during SVA infection.

Innate sensing of picornavirus infection involves cGAS-STING-mediated antiviral responses triggered by mitochondrial DNA release.

Cyclic GMP-AMP synthase (cGAS) plays a key role in the innate immune responses to both DNA and RNA virus infection. Here, we found that enterovirus 71 (EV-A71), Seneca Valley virus (SVV), and foot-and-mouth disease virus (FMDV) infection triggered mitochondria damage and mitochondrial DNA (mtDNA) release in vitro and vivo. These responses were mediated by picornavirus 2B proteins which induced mtDNA release during viral replication. SVV infection caused the opening of mitochondrial permeability transition pore (mPTP) and led to voltage-dependent anion channel 1 (VDAC1)- and BCL2 antagonist/killer 1 (Bak) and Bak/BCL2-associated X (Bax)-dependent mtDNA leakage into the cytoplasm, while EV-A71 and FMDV infection induced mPTP opening and resulted in VDAC1-dependent mtDNA release. The released mtDNA bound to cGAS and activated cGAS-mediated antiviral immune response. cGAS was essential for inhibiting EV-A71, SVV, and FMDV replication by regulation of IFN-ß production. cGAS deficiency contributed to higher mortality of EV-A71- or FMDV-infected mice. In addition, we found that SVV 2C protein was responsible for decreasing cGAS expression through the autophagy pathway. The 9th and 153rd amino acid sites in 2C were critical for induction of cGAS degradation. Furthermore, we also show that EV-A71, CA16, and EMCV 2C antagonize the cGAS-stimulator of interferon genes (STING) pathway through interaction with STING, and highly conserved amino acids Y155 and S156 were critical for this inhibitory effect. In conclusion, these data reveal novel mechanisms of picornaviruses to block the antiviral effect mediated by the cGAS-STING signaling pathway, which will provide insights for developing antiviral strategies against picornaviruses.

The whole genomic analysis of the Orf virus strains ORFV-SC and ORFV-SC1 from the Sichuan province and their weak pathological response in rabbits.

The Orf virus (ORFV) is a member of the Parapoxvirus genus of the Poxviridae family and can cause contagious diseases in sheep, goats, and wild ungulates. In the present study, two ORFV isolates (ORFV-SC isolated from Sichuan province and ORFV-SC1 produced by 60 passages of ORFV-SC in cells) were sequenced and compared to multiple ORFVs. The two ORFV sequences had entire genome sizes of 14,0707 bp and 141,154 bp, respectively, containing 130 and 131 genes, with a G + C content of 63% for the ORFV-SC sequence and 63.9% for the ORFV-SC1 sequence. Alignment of ORFV-SC and ORFV-SC1 with five other ORFV isolates revealed that ORFV-SC, ORFV-SC1, and NA1/11 shared > 95% nucleotide identity with 109 genes. Five genes (ORF007, ORF20, ORF080, ORF112, ORF116) have low amino acids identity between ORFV-SC and ORFV-SC1. Mutations in amino acids result in changes in the secondary and tertiary structure of ORF007, ORF020, and ORF112 proteins. The phylogenetic tree based on the complete genome sequence and 37 single genes revealed that the two ORFV isolates originated from sheep. Finally, animal experiments demonstrated that ORFV-SC1 is less harmful to rabbits than ORFV-SC. The exploration of two full-length viral genome sequences provides valuable information in ORFV biology and epidemiology research. Furthermore, ORFV-SC1 demonstrated an acceptable safety profile following animal vaccination, indicating its potential as a live ORFV vaccine.

Peste Des Petits Ruminants Virus N Protein Is a Critical Proinflammation Factor That Promotes MyD88 and NLRP3 Complex Assembly.

Inflammatory responses play a central role in host defense against invading pathogens. Peste des petits ruminants virus (PPRV) causes highly contagious acute or subacute disease of small ruminants. However, the precise mechanism by which PPRV regulates inflammatory responses remains unknown. Here, we revealed a novel mechanism by which PPRV induces inflammation. Our study showed that PPRV induced the secretion of interleukin 1ß (IL-1ß) by activating the NF-κB signaling pathway and the NLRP3 inflammasome. Moreover, PPRV replication and protein synthesis were essential for NLRP3 inflammasome activation. Importantly, PPRV N protein promoted NF-κB signaling pathway and NLRP3 inflammasome via direct binding of MyD88 and NLPR3, respectively, and induced caspase-1 cleavage and IL-1ß maturation. Biochemically, N protein interacted with MyD88 to potentiate the assembly of MyD88 complex and interacted with NLPR3 to facilitate NLRP3 inflammasome complex assembly by forming an N-NLRP3-ASC ring-like structure, leading to IL-1ß secretion. These findings demonstrate a new function of PPRV N protein as an important proinflammation factor and identify a novel underlying mechanism modulating inflammasome assembly and function induced by PPRV. IMPORTANCE An important part of the innate immune response is the activation of NF-κB signaling pathway and NLPR3 inflammasome, which is induced upon exposure to pathogens. Peste des petits ruminants virus (PPRV) is a highly contagious virus causing fever, stomatitis, and pneumoenteritis in goats by inducing many proinflammatory cytokines. Although the NF-κB signaling pathway and NLRP3 inflammasome play an important role in regulating host immunity and viral infection, the precise mechanism by which PPRV regulates inflammatory responses remains unknown. This study demonstrates that PPRV induces inflammatory responses. Mechanistically, PPRV N protein facilitates the MyD88 complex assembly by directly binding to MyD88 and promotes the NLRP3 inflammasome complex assembly by directly binding to NLRP3 to form ring-like structures of N-NLRP3-ASC. These findings provide insights into the prevention and treatment of PPRV infection.

Third-harmonic-assisted four-wave mixing in a chip-based microresonator frequency comb generation.

Microcombs generated in photonic integrated circuits can provide broadband and coherent optical frequency combs with a high repetition rate from microwave to terahertz. Coherent microcombs formed in normal group velocity dispersion microresonators usually have a flat-top temporal profile, called platicon. Here, we propose a novel scheme to generate platicon in Si3N4 microresonator with the assistance of third-harmonic generation. The nonlinear coupling between the fundamental and the third-harmonic waves that draws support from third-order sum/difference frequency generation provides a new mechanism to achieve the phase matching of four-wave mixing in normal dispersion microresonators. We show that single or multiple platicons can be obtained by changing the third-harmonic nonlinear coupling strength and phase matching condition for third-order sum/difference frequency generation. Our work provides a promising solution to facilitate coherent and visible microcomb generation in a pure χ(3) microresonator, which is potential for self-referencing combs and optical clock stabilization.

Discrete metal nanoparticles with plasmonic chirality.

From a geometrical perspective, a chiral object does not have mirror planes or inversion symmetry. It exhibits the same physical properties as its mirror image (enantiomer), except for the chiroptical activity, which is often the opposite. Recent advancements have identified particularly interesting implications of chirality on the optical properties of metal nanoparticles, which are intimately related to localized surface plasmon resonance phenomena. Although such resonances are usually independent of the circular polarization of light, specific strategies have been applied to induce chirality, both in assemblies and at the single-particle level. In this tutorial review, we discuss the origin of plasmonic chirality, as well as theoretical models that have been proposed to explain it. We then summarise recent developments in the synthesis of discrete nanoparticles with plasmonic chirality by means of wet-chemistry methods. We conclude with a discussion of promising applications for discrete chiral nanoparticles. We expect this tutorial review to be of interest to researchers from a wide variety of disciplines where chiral plasmonics can be exploited at the nanoparticle level, such as chemical sensing, photocatalysis, photodynamic or photothermal therapies, etc.

Low-Loss Integrated Nanophotonic Circuits with Layered Semiconductor Materials.

Monolayer transition-metal dichalcogenides with direct bandgaps are emerging candidates for optoelectronic devices, such as photodetectors, light-emitting diodes, and electro-optic modulators. Here we report a low-loss integrated platform incorporating molybdenum ditelluride monolayers with silicon nitride photonic microresonators. We achieve microresonator quality factors >3 × 106 in the telecommunication O- to E-bands. This paves the way for low-loss, hybrid photonic integrated circuits with layered semiconductors, not requiring heterogeneous wafer bonding.

Genetic Determinants of Altered Virulence of Type O Foot-and-Mouth Disease Virus.

Under different circumstances, the alteration of several viral genes may give an evolutionary advantage to the virus to maintain its prevalence in nature. In this study, a 70-nucleotide deletion in the small fragment (S fragment) of the viral 5'-untranslated region (5'-UTR) together with one amino acid insertion in the leader protein (Lpro) that naturally occurred in several serotype O foot-and-mouth disease virus (FMDV) strains in China was identified. The properties of two field serotype O FMDV strains, with or without the 70-nucleotide deletion in the S fragment and the amino acid insertion in Lpro, were compared in vitro and in vivo Clinical manifestations of FMD were clearly observed in cattle and pigs infected by the virus without the mutations. However, the virus with the mentioned mutations caused FMD outcomes only in pigs, not in cattle. To determine the role of the 70-nucleotide deletion in the S fragment and the single amino acid insertion in Lpro in the pathogenicity and host range of FMDV, four recombinant viruses, with complete genomes and a 70-nucleotide deletion in the S fragment, a single amino acid insertion in Lpro, or both mutations, were constructed and rescued. It showed that deletion of 70 nucleotides in the S fragment or insertion of one amino acid (leucine) at position 10 of Lpro partly decreased the viral pathogenicity of Mya-98 lineage virus in cattle and pigs. However, the virus with dual mutations caused clinical disease only in pigs, not in cattle. This suggested that the S fragment and Lpro are significantly associated with the virulence and host specificity of FMDV. The naturally occurring dual mutation in the S fragment and Lpro is a novel determinant of viral pathogenicity and host range for serotype O FMDV.IMPORTANCE FMD is probably the most important livestock disease in the world due to the severe economic consequences caused. The alteration of several viral genes may give the virus selective advantage to maintain its prevalence in nature. Here, we identified that a 70-nucleotide deletion in the S fragment combined with a single leucine insertion in the leader protein (Lpro) is a novel determinant of restricted growth on bovine cells, which significantly contributes to the altered virulence of serotype O FMDV in cattle. A synergistic and additive effect of the 70-nucleotide deletion in the S fragment and the single leucine insertion in Lpro on the virulence and host specificity of the virus was determined. These results will benefit efforts to understand the vial pathogenicity mechanism and molecular characteristics of FMDV.

The Pseudoknot Region of the 5' Untranslated Region Is a Determinant of Viral Tropism and Virulence of Foot-and-Mouth Disease Virus.

Foot-and-mouth disease virus (FMDV) is the causative agent of foot-and-mouth disease. It is characterized by genetic instability and different antigenic properties. The nonstructural protein 3A is a primary determinant of the tropism and virulence of Cathay topotype FMDVs. However, several other determinants are also speculated to be involved in viral tropism and virulence. Deletion of 43 nucleotides (nt) in the pseudoknot (PK) region of the 5' untranslated region (UTR) has been found to coexist with the identified 3A deletion in Cathay topotype FMDV genomes. In this study, we isolated an O/ME-SA/PanAsia lineage FMDV strain, O/GD/CHA/2015, that includes an 86-nt deletion in the PK region and shows a porcinophilic phenotype. To investigate the potential role of the PK region in viral pathogenicity, we generated a recombinant FMDV strain with an incomplete PK region and compared its virulence and pathogenesis to the intact FMDV strain in swine and bovines. Deletion of the 86 nt in the PKs had no major effects on the pathogenicity of the virus in swine but significantly attenuated its ability to infect bovine cells and cattle, indicating that the PK region is a newly discovered determinant of viral tropism and virulence. The role of the 43-nt deletion existing in the Cathay topotype FMDV was also investigated by evaluating the infection properties of genetically engineered viruses. Consistently, the 43-nt deletion in the PK region significantly decreased the pathogenicity of the virus in bovines. Overall, our findings suggest that the PK region deletion occurred naturally in the FMDV genome and that the PK region is highly associated with viral host range and functions as a novel determinant for FMDV pathogenesis.IMPORTANCE This study demonstrates that the deletion in the PK region occurred naturally in the FMDV genome. The isolated O/ME-SA/PanAsia lineage FMDV with an 86-nt deletion in the PK region showed a pig-adapted characteristic that could cause clinical signs in swine but not bovines. Compared to the wild-type FMDV strain, which possesses full infection capacity in both swine and bovines, the recombinant virus with the 86-nt deletion in the PK region is deficient in causing disease in bovines. Deletion of the previously reported 43 nt in the PK region also led to significantly decreased pathogenicity of FMDV in bovines. This study indicates that the PK region is a novel determinant of the tropism and virulence of FMDV.

Chip-based soliton microcomb module using a hybrid semiconductor laser.

Photonic chip-based soliton microcombs have shown rapid progress and have already been used in many system-level applications. There has been substantial progress in realizing soliton microcombs that rely on compact laser sources, culminating in devices that only utilize a semiconductor gain chip or a self-injection-locked laser diode as the pump source. However, generating single solitons with electronically detectable repetition rates from a compact laser module has remained challenging. Here we demonstrate a current-initiated, Si3N4 chip-based, 99-GHz soliton microcomb driven directly by a compact, semiconductor-based laser. This approach does not require any complex soliton tuning techniques, and single solitons can be accessed by tuning the laser current. Further, we demonstrate a generic, simple, yet reliable, packaging technique to facilitate the fiber-chip interface, which allows building a compact soliton microcomb package that can benefit from the fiber systems operating at high power (> 100 mW). Both techniques can exert immediate impact on chip-based nonlinear photonic applications that require high input power, high output power, and interfacing chip-based devices to mature fiber systems.

Observation of Stimulated Brillouin Scattering in Silicon Nitride Integrated Waveguides.

Silicon nitride (Si_{3}N_{4}) has emerged as a promising material for integrated nonlinear photonics and has been used for broadband soliton microcombs and low-pulse-energy supercontinuum generation. Therefore, understanding all nonlinear optical properties of Si_{3}N_{4} is important. So far, only stimulated Brillouin scattering (SBS) has not yet been reported. Here we observe, for the first time, backward SBS in fully cladded Si_{3}N_{4} waveguides. The Brillouin gain spectrum exhibits an unusual multipeak structure resulting from hybridization with high-overtone bulk acoustic resonances of the silica cladding. The reported intrinsic Si_{3}N_{4} Brillouin gain at 25 GHz is estimated as 4×10^{-13} m/W. Moreover, the magnitude of the Si_{3}N_{4} photoelastic constant is estimated as |p_{12}|=0.047±0.004, which is nearly 6 times smaller than for silica. Since SBS imposes an optical power limitation for waveguides, our results explain the capability of Si_{3}N_{4} to handle high optical power, central for integrated nonlinear photonics.

Interband Absorption Enhanced Optical Activity in Discrete Au@Ag Core-Shell Nanocuboids: Probing Extended Helical Conformation of Chemisorbed Cysteine Molecules.

Detailed understanding of the interaction between a chiral molecule and a noble metal surface is essential to rationalize and advance interfacial self-assembly of amino acids and metal-mediated anchoring of proteins. Here we demonstrate that individual Au@Ag core-shell nanocuboids can serve as a plasmonic reporter of an extended helical network formed among chemisorbed cysteine molecules, through generating an interband absorption enhanced, Ag-surface-exclusive circular dichroism (CD) band in the UV region. The observed unusual, strong CD response in the hybrid Au@Ag-cysteine system can be used to probe in real time conformational evolution and structural rearrangement of biomolecules in general and also monitor the interfacial interaction between a metal surface and an adsorbed molecule, opening up the possibility of using Ag nanostructures as promising stereochemically attuned nanosensors.

Specific detection of foot-and-mouth disease serotype Asia 1 virus by carboxyl-magnetic beads conjugated with single-domain antibody.

BACKGROUND: Immunomagnetic nanobead (IMNB) labeled with specific antibody, has been demonstrated to be useful for the capturing and detection of viruses. RESULTS: In this study, we developed an imunomagnetic bead based on carboxyl-magnetic beads (MNB) labeled with a single-domain antibody (sdAb) for capturing foot-and-mouth disease (FMD) Asia 1 virus. After magnetic separation, complexes of MNB-sdAb-virus were detected with either a sandwich ELISA or QDs-C5 probe under a fluorescence microscope, and the complexes were used as templates for extraction of total RNA for amplification of the VP1 or 3D gene fragments using RT-PCR and real-time RT-PCR. The Asia 1 VLPs were efficiently captured through IMNB with a high binding rate of 5.09 µg of antigen/µl of bead suspension. Moreover, this method has been successfully used to capture Asia 1 antigen in synthetic samples. CONCLUSION: Ultimately, a specific and highly sensitive capture FMDV Asia 1 tool has been established that has the potential to enhance the sensitivity and reliability when diagnosing FMDV Asia 1.

Characterization of single-domain antibodies against Foot and Mouth Disease Virus (FMDV) serotype O from a camelid and imaging of FMDV in baby hamster kidney-21 cells with single-domain antibody-quantum dots probes.

BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious disease that affects cloven-hoofed animals and causes significant economic losses to husbandry worldwide. The variable domain of heavy-chain antibodies (VHHs or single domain antibodies, sdAbs) are single-domain antigen-binding fragments derived from camelid heavy-chain antibodies. RESULTS: In this work, two sdAbs against FMD virus (FMDV) serotype O were selected from a camelid phage display immune library and expressed in Escherichia coli. The serotype specificity and affinity of the sdAbs were identified through enzyme-linked immunosorbent assay and surface plasmon resonance assay. Moreover, the sdAbs were conjugated with quantum dots to constitute probes for imaging FMD virions. Results demonstrated that the two sdAbs were specific for serotype O and shared no cross-reactivity with serotypes A and Asia 1. The equilibrium dissociation constant (KD) values of the two sdAbs ranged from 6.23 nM to 8.24 nM, which indicated high affinity to FMDV antigens. Co-localization with the sdAb-AF488 and sdAb-QD probes indicated the same location of FMDV virions in baby hamster kidney-21 (BHK-21) cells. CONCLUSIONS: sdAb-QD probes are powerful tools to detect and image FMDV in BHK-21 cells.