Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron.

The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population1. Although recent reports reveal that the Omicron variant robustly escapes vaccine-associated and therapeutic neutralization antibodies2-10, the pathogenicity of the virus remains unknown. Here we show that the replication of Omicron is substantially attenuated in human Calu3 and Caco2 cells. Further mechanistic investigations reveal that Omicron is inefficient in its use of transmembrane serine protease 2 (TMPRSS2) compared with wild-type SARS-CoV-2 (HKU-001a) and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. The replication of Omicron is markedly attenuated in both the upper and lower respiratory tracts of infected K18-hACE2 mice compared with that of the wild-type strain and Delta (B.1.617.2) variant, resulting in its substantially ameliorated lung pathology. Compared with wild-type SARS-CoV-2 and the Alpha (B.1.1.7), Beta (1.351) and Delta variants, infection by Omicron causes the lowest reduction in body weight and the lowest mortality rate. Overall, our study demonstrates that the replication and pathogenicity of the Omicron variant of SARS-CoV-2 in mice is attenuated compared with the wild-type strain and other variants.

Circulation pattern and genetic variation of rhinovirus infection among hospitalized children on Hainan Island, before and after the dynamic zero-COVID policy, from 2021 to 2023.

Throughout the COVID-19 pandemic, rhinovirus (RV) remained notable persistence, maintaining its presence while other seasonal respiratory viruses were largely suppressed by pandemic restrictions during national lockdowns. This research explores the epidemiological dynamics of RV infections among pediatric populations on Hainan Island, China, specifically focusing on the impact before and after the zero-COVID policy was lifted. From January 2021 to December 2023, 19 680 samples were collected from pediatric patients hospitalized with acute lower respiratory tract infections (ARTIs) at the Hainan Maternal and Child Health Hospital. The infection of RV was detected by tNGS. RV species and subtypes were identified in 32 RV-positive samples representing diverse time points by analyzing the VP4/VP2 partial regions. Among the 19 680 pediatric inpatients with ARTIs analyzed, 21.55% were found to be positive for RV infection, with notable peaks observed in April 2021 and November 2022. A gradual annual decline in RV infections was observed, alongside a seasonal pattern of higher prevalence during the colder months. The highest proportion of RV infections was observed in the 0-1-year age group. Phylogenetic analysis on 32 samples indicated a trend from RV-A to RV-C in 2022. This observation suggests potential evolving dynamics within the RV species although further studies are needed due to the limited sample size. The research emphasizes the necessity for ongoing surveillance and targeted management, particularly for populations highly susceptible to severe illnesses caused by RV infections.

Reconfigurable multi-channel microwave photonic receiver for a multi-band signal based on cascaded microring resonator banks.

What we believe to be a novel reconfigurable multi-channel microwave photonic (MWP) receiver for multi-band RF signal is demonstrated for the first time, to the best of our knowledge. A reconfigurable MWP signal processing chip based on two cascaded microring filter banks is employed in the proposed receiver, which slices the multi-band RF input into several narrow band signals and selects optical frequency comb lines for frequency converting of each channel. Due to the significant reconfigurability of the signal processing chip, the proposed receiver can flexibly choose the output frequency band of each channel, and thus different frequency components of the multi-band RF input can be down converted to the intermediate frequency (IF) band for receiving or converted to other frequency band for forwarding. A multi-band RF signal composed of a linear frequency modulation (LFM) signal with 2 GHz bandwidth and a quad-phase shift keyed (QPSK) signal with 100 Mbit/s rate is experimentally received and reconstructed by the proposed receiver, where the reconstructed LFM component exhibits a signal to noise ratio (SNR) of 10.2 dB, and the reconstructed QPSK component reaches a high SNR of 26.1 dB and a great error vector magnitude (EVM) of 11.73%. On the other hand, the QPSK component of the multi-band RF signal centered at 13.5 GHz is successfully converted to 3.1 GHz.

Dual-polarization RF channelizer based on microcombs.

We report a dual-polarization radio frequency (RF) channelizer based on microcombs. Two high-Q micro-ring resonators (MRRs) with slightly different free spectral ranges (FSRs) are used: one MRR is pumped to yield soliton crystal microcombs ("active"), and the other MRR is used as a "passive" periodic optical filter supporting dual-polarization operation to slice the RF spectrum. With the tailored mismatch between the FSRs of the active and passive MRRs, wideband RF spectra can be channelized into multiple segments featuring digital-compatible bandwidths via the Vernier effect. Due to the use of dual-polarization states, the number of channelized spectral segments, and thus the RF instantaneous bandwidth (with a certain spectral resolution), can be doubled. In our experiments, we used 20 microcomb lines with ∼ 49 GHz FSR to achieve 20 channels for each polarization, with high RF spectra slicing resolutions at 144 MHz (TE) and 163 MHz (TM), respectively; achieving an instantaneous RF operation bandwidth of 3.1 GHz (TE) and 2.2 GHz (TM). Our approach paves the path towards monolithically integrated photonic RF receivers (the key components - active and passive MRRs are all fabricated on the same platform) with reduced complexity, size, and unprecedented performance, which is important for wide RF applications with digital-compatible signal detection.

Comparison of common human respiratory pathogens among hospitalized children aged ≤ 6 years in Hainan Island, China, during spring and early summer in 2019-2021.

The coronavirus disease 2019 (COVID-19) pandemic and related public health intervention measures have been reported to have resulted in the reduction of infections caused by influenza viruses and other common respiratory viruses. However, the influence may be varied in areas that have different ecological, economic, and social conditions. This study investigated the changing epidemiology of 8 common respiratory pathogens, including Influenza A (IFVA), Influenza B (IFVB), Respiratory syncytial virus (HRSV), rhinovirus (RV), Human metapneumovirus Adenovirus, Human bocavirus, and Mycoplasma pneumoniae, among hospitalized children during spring and early summer in 2019-2021 in two hospitals in Hainan Island, China, in the COVID-19 pandemic era. The results revealed a significant reduction in the prevalence of IFVA and IFVB in 2020 and 2021 than in 2019, whereas the prevalence of HRSV increased, and it became the dominant viral pathogen in 2021. RV was one of the leading pathogens in the 3 year period, where no significant difference was observed. Phylogenetic analysis revealed close relationships among the circulating respiratory viruses. Large scale studies are needed to study the changing epidemiology of seasonal respiratory viruses to inform responses to future respiratory virus pandemics.

High-resolution reconfigurable RF signal spectral processor.

Recent developments in microwave photonic filters (MPFs) offer superior properties for radio frequency (RF) signal processing, such as large instantaneous bandwidth, high resolution and multifunctional shapes. However, it is quite challenging to realize two or more characteristics simultaneously to meet the diverse needs in complex electromagnetic environment. In this paper, we propose a reconfigurable RF signal spectral processor with both large instantaneous bandwidth and high resolution. In the proposed spectral processor, sufficient taps supplied by an optical frequency comb (OFC) offer a large instantaneous bandwidth to process broadband RF signals. Flexible tap coefficients can be obtained by manipulating an optical spectral shaper (OSS), which provides excellent reconfigurability. This tap-by-tap manipulation is realized with a high resolution of hundreds of megahertz, allowing precise shape configuration of the response. In the experiment, we demonstrate a flat-top response with a wide bandwidth of 7.1 GHz. Reconfigurable features such as tunable bandwidth, adjustable center frequency and diverse shapes are also shown. In particular, the measured frequency resolution of 96.5 MHz demonstrates the ability for precise configuration.

Laser frequency noise correction in LFM-based interferometric fiber-optic hydrophone array.

In this paper, we propose a novel time-division multiplexed (TDM) array for a large-scale interferometric fiber-optic hydrophone system, in which we introduce a power-optimized reference probe and effectively reduce the additional white noise while correcting for light source frequency noise. Laser frequency noise usually introduces appreciable phase noise during demodulation of interferometric fiber-optic hydrophones. In the previous means, one would introduce an additional probe isolated from the environment in sensor array, and use it as a reference to calibrate the demodulation results of the other actual sensors. However, while correcting, the reference probe also introduces a large white noise. In our array, the echo of the reference probe is higher than the other sensors, thus solving this problem. The novel array design is applied to our previously proposed fiber-optic hydrophone based on a linear frequency modulated (LFM) light source. Experiments show that the deterioration of phase noise floor caused by additional white noise is improved from at least 3 dB originally to within 1 dB. This paper analyzes the factors that need to be concerned for the successful implementation of correction algorithms in hydrophone systems based on LFM sources. Particular focus is given to the impact of the power optimization of reference probe on the white noise and the corrected phase noise. Our proposal allows a significant relaxation of the demanding linewidth requirement for interferometric hydrophone. It is shown that laser with linewidth of 338.06 MHz can replace that with 1.417 kHz in our new system, while achieves the same demodulation noise floor.

Time reversal of broadband microwave signal based on frequency conversion of multiple subbands.

Time reversal of broadband microwave signals based on frequency conversion of multiple subbands is proposed and experimentally demonstrated. The broadband input spectrum is cut into a number of narrowband subbands, and the center frequency of each subband is reassigned by multi-heterodyne measurement. The input spectrum is inversed, while the time reversal of the temporal waveform is also realized. The equivalence between time reversal and the spectral inversion of the proposed system is verified by mathematical derivation and numerical simulation. Meanwhile, spectral inversion and time reversal of a broadband signal with instantaneous bandwidth larger than 2 GHz are experimentally demonstrated. Our solution shows good potential for integration where no dispersion element is employed in the system. Moreover, this solution for an instantaneous bandwidth larger than 2 GHz is competitive in the processing of broadband microwave signals.

Digital radio-over-fiber system based on differential pulse code modulation and space division multiplexing.

In this paper, we present and experimentally demonstrate a digital-radio-over-fiber (D-RoF) architecture based on differential pulse code modulation (DPCM) and space division multiplexing (SDM). At low quantization resolution, DPCM can effectively reduce quantization noise and obtain significant signal-to-quantization noise ratio (SQNR) gain. We experimentally study the 7-core and 8-core multicore fiber transmission of 64-ary quadrature amplitude modulation (64QAM) orthogonal frequency division multiplexing (OFDM) signals with a bandwidth of 100 MHz in a fiber-wireless hybrid transmission link. Compared to PCM-based D-RoF, the error vector magnitude (EVM) performance in the DPCM-based D-RoF is effectively improved when the quantization bits (QBs) are 3-5 bits. In particular, when the QB is 3 bits, the EVM of the DPCM-based D-RoF is 6.5% and 7% lower than that of the PCM-based system in 7-core- and 8-core-multicore fiber-wireless hybrid transmission links, respectively.

Low latency microwave photonic RTFT processing based on bandwidth slicing and equivalent dispersion.

Microwave photonic real-time Fourier transformation (RTFT) processing based on optical dispersion is a promising solution for microwave spectrum analysis. However, it usually brings the drawbacks of limited frequency resolution and large processing latency. Here, we demonstrate a low-latency microwave photonic RTFT processing based on bandwidth slicing and equivalent dispersion. The input RF signal is first divided into different channels with the help of bandwidth slicing technique, and then finely analyzed by the fiber-loop based frequency-to-time mapping. In the proof-of-concept experiment, a 0.44-m fiber-loop offers an equivalent dispersion as high as 6 × 105 ps/nm with a small transmission latency of 50 ns. As a result, we can realize a wide instantaneous bandwidth of 1.35 GHz, a high frequency resolution of approximately 20 MHz, and a high acquisition frame rate of approximately 450 MHz, together with a total latency of less than 200 ns.

Genome Sequencing and Organization of Three Geographically Different Isolates of Nucleopolyhedrovirus from the Gypsy Moth Reveal Significant Genomic Differences.

Background: The gypsy moth (Lymantria dispar L., Lepidoptera: Erebidae) is a worldwide pest of trees and forests. Lymantria dispar nucleopolyhedrovirus (LdMNPV) belongs to the Baculoviridae family and is an insect virus specific to gypsy moth larvae. In this study, we describe the complete genome sequences of three geographically diverse isolates, H2 (China), J2 (Japan), and T3 (Turkey), of Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV). Methods: The genomes of isolates H2, J2, and T3 were subjected to shotgun pyrosequencing using Roche 454 FLX and assembled using Roche GS De Novo Assembler. Comparative analysis of all isolates was performed using bioinformatics methods. Results: The genomes of LdMNPV-H2, J2, and T3 were 164,746, 162,249, and 162,614 bp in size, had GC content of 57.25%, 57.30%, and 57.46%, and contained 162, 165, and 164 putative open reading frames (ORFs ≥ 150 nt), respectively. Comparison between the reference genome LdMNPV-5/6 (AF081810) and the genomes of LdMNPV-H2, J2, and T3 revealed differences in gene content. Compared with LdMNPV-5/6, ORF5, 6, 8, 10, 31, and 67 were absent in LdMNPV-H2, ORF5, 13, and 66 were absent in LdMNPV-J2, and ORF10, 13, 31, and 67 were absent in LdMNPV-T3. In addition, the gene encoding the mucin-like protein (ORF4) was split into two parts in isolates H2 and T3 and designated ORF4a and ORF4b. Phylogenetic analysis grouped isolates H2 and J2 in a different cluster than isolate T3, which is more closely related to the Turkish and Polish isolates. In addition, H2 was found to be closely related to a South Korean LdMNPV isolate. Conclusion: This study provided a more detailed overview of the relationships between different geographic LdMNPV isolates. The results showed remarkable differences between groups at the genome level.

Low Environmental Temperature Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Golden Syrian Hamsters.

BACKGROUND: The effect of low environmental temperature on viral shedding and disease severity of Coronavirus Disease 2019 (COVID-19) is uncertain. METHODS: We investigated the virological, clinical, pathological, and immunological changes in hamsters housed at room (21°C), low (12-15°C), and high (30-33°C) temperature after challenge by 105 plaque-forming units of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: The nasal turbinate, trachea, and lung viral load and live virus titer were significantly higher (~0.5-log10 gene copies/ß-actin, P < .05) in the low-temperature group at 7 days postinfection (dpi). The low-temperature group also demonstrated significantly higher level of tumor necrosis factor-α, interferon-γ (IFN-γ), interleukin-1ß, and C-C motif chemokine ligand 3, and lower level of the antiviral IFN-α in lung tissues at 4 dpi than the other 2 groups. Their lungs were grossly and diffusely hemorrhagic, with more severe and diffuse alveolar and peribronchiolar inflammatory infiltration, bronchial epithelial cell death, and significantly higher mean total lung histology scores. By 7 dpi, the low-temperature group still showed persistent and severe alveolar inflammation and hemorrhage, and little alveolar cell proliferative changes of recovery. The viral loads in the oral swabs of the low-temperature group were significantly higher than those of the other two groups from 10 to 17 dpi by about 0.5-1.0 log10 gene copies/ß-actin. The mean neutralizing antibody titer of the low-temperature group was significantly (P < .05) lower than that of the room temperature group at 7 dpi and 30 dpi. CONCLUSIONS: This study provided in vivo evidence that low environmental temperature exacerbated the degree of virus shedding, disease severity, and tissue proinflammatory cytokines/chemokines expression, and suppressed the neutralizing antibody response of SARS-CoV-2-infected hamsters. Keeping warm in winter may reduce the severity of COVID-19.

Generation of a coherent distributed RF array with a strong positive correlation.

In this work, we present a coherent distributed radio frequency (RF) array, discover and quantitatively describe the strong positive correlation between reconstructed signals for the first time. Eight replicable parallel receivers are connected to the phase-locked common trunk link via eight optical couplers spaced 1 km apart. The forward and backward signals at each receiver, extracted from two ports of optical couplers, are recovered to RF signals separately and then mixed to achieve upward frequency conversion. The link delay jitter is counteracted by wavelength-tuning of the optical carrier. With the long-term stability of point-to-multipoint fiber-optic RF dissemination effectively improved, the coherent distributed array is generated, and further the relative frequency stability between signals at different receivers is studied. The proposed correlation coefficient at 103 s is ∼0.8 and shows a slight downward trend with the increase of averaging time based on our experimental results.

Optically magnified dispersion of microwave signals with a wide and flexible tunable range.

Tunable microwave dispersion is highly desired for a wide field of microwave signal processing. However, a conventional microwave dispersive delay line usually suffers from either a small dispersion value or a narrow operation bandwidth. Here, we experimentally demonstrate the optically magnified dispersion of a microwave signal with a wide and flexible tunable range, based on a bandwidth-scaling microwave photonic system. The obtained microwave dispersion can therefore be magnified from the corresponding optical dispersion with a magnification factor that can be continuously tuned from 10,000 to 85,000. Meanwhile, a proof-of-concept experiment that includes both compression and stretching of chirped microwave pulses is reported. Microwave dispersion from 1.34 ns/GHz to 10.92 ns/GHz can be secured by the corresponding magnification of an optical dispersion value of 16 ps/nm.

Mixed genotypes of Orientia tsutsugamushi in conserved genes and a single immune-dominant tsa56 genotype discovered from a patient with scrub typhus in Hainan Island, China: a case report.

BACKGROUND: Orientia tsutsugamushi (O. tsutsugamushi), an obligate intracellular bacterium, is transmitted to humans through infected larval trombiculid mite bites, causing scrub typhus. Mixed genotypes of O. tsutsugamushi in canonical conserved genes were reported in 8-25% of blood samples from patients. Yet, there are few clinical descriptions of these mixed O. tsutsugamushi-infected patients. CASE PRESENTATION: We report a patient with scrub typhus complicated with pulmonary involvement and hepatic dysfunction, who carried mixed genotypes of the conserved genes but had a single immune-dominant 56-kDa type-specific antigen (tsa56) genotype. The patient was successfully recovered by doxycycline treatment. CONCLUSIONS: In this reported case, both patient's eschar and blood samples have repeatedly shown the same results, i.e., no variants were discovered in tsa56 gene that bears multiple hypervariable regions. Whereas the selected highly conserved genes were identified with up to 32 variants in a 2700 base-pair concatenated sequence. The prevalence, disease severity and mechanism of these single-tsa56-genotype mixed infections remain to be investigated on a large scale with more cases.

Monocytes subtypes from pleural effusion reveal biomarker candidates for the diagnosis of tuberculosis and malignancy.

BACKGROUND: Pleural effusion is a common clinical condition caused by several respiratory diseases, including tuberculosis and malignancy. However, rapid and accurate diagnoses of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remain challenging. Although monocytes have been confirmed as an important immune cell in tuberculosis and malignancy, little is known about the role of monocytes subpopulations in the diagnosis of pleural effusion. METHODS: Pleural effusion samples and peripheral blood samples were collected from 40 TPE patients, 40 MPE patients, and 24 transudate pleural effusion patients, respectively. Chemokines (CCL2, CCL7, and CX3CL1) and cytokines (IL-1ß, IL-17, IL-27, and IFN-γ) were measured by ELISA. The monocytes phenotypes were analyzed by flow cytometry. The chemokines receptors (CCR2 and CX3CR1) and cytokines above in different monocytes subsets were analyzed by real-time PCR. Receiver operating characteristic curve analysis was performed for displaying differentiating power of intermediate and nonclassical subsets between tuberculous and malignant pleural effusions. RESULTS: CCL7 and CX3CL1 levels in TPE were significantly elevated in TPE compared with MPE and transudate pleural effusion. Cytokines, such as IL-1ß, IL-17, IL-27, and IFN-γ, in TPE were much higher than in other pleural effusions. Moreover, CD14+ CD16++ nonclassical subset frequency in TPE was remarkably higher than that in MPE, while CD14++ CD16+ intermediate subset proportion in MPE was found elevated. Furthermore, CX3CL1-CX3CR1 axis-mediated infiltration of nonclassical monocytes in TPE was related to CX3CL1 and IFN-γ expression in TPE. Higher expression of cytokines (IL-1ß, IL-17, IL-27, and IFN-γ) were found in nonclassical monocytes compared with other subsets. Additionally, the proportions of intermediate and nonclassical monocytes in pleural effusion have the power in discriminating tuberculosis from malignant pleural effusion. CONCLUSIONS: CD14 and CD16 markers on monocytes could be potentially used as novel diagnostic markers for diagnosing TPE and MPE.

Broadband radio-frequency signal synthesis by photonic-assisted channelization.

A channelized radio-frequency (RF) signal synthesis scheme is proposed to generate broadband RF signals with reconfigurable waveform, center frequency and instantaneous bandwidth. Based on dual optical frequency combs (OFCs) with different free spectrum ranges (FSRs), multiple narrowband signals are up-converted and synthesized into a broadband signal. Reconfigurable waveforms are generated in the simulation, including a symmetrical triangular linear frequency modulation continuous wave (STLFMCW) signal and a binary phase shift keying (BPSK) signal. In addition, to realize phase stability among channels, dual OFCs are differently modulated through polarization-multiplexing electro-optical modulators (EOMs). An RF signal synthesis experiment shows the relative phase fluctuation among channels is only 1.8°.

Polar Solvents Induce Sum Frequency Generation Activity for Multiwalled Carbon Nanotubes.

Regarding methods of process and use of carbon nanotubes (CNTs), solvents are generally employed to disperse or dissolve CNTs as a pretreatment or intermediate process step. This naturally imposes an essential issue on how CNTs and solvents interact with each other, which seems trivial, comparatively inconsequential, and might often be overlooked from the perspective of engineering scenarios. However, as a matter of fact, it is indeed a fascinating and significant topic. In this article, to investigate the interfacial properties of multiwalled CNTs (MWCNTs) exposed to widely utilized solvents, we applied sum frequency generation vibrational spectroscopy (SFG-VS) to probe solvent-wetted MWCNTs and proved that polar solvents can substantially alter the interfacial optical property of MWCNTs. First, the interfacial optical phonon vibrational modes were detected when MWCNTs were wetted by polar solvents, i.e., water and dimethylformamide (DMF), while such modes were inactive when the solvents were nonpolar, i.e., decalin and air. Second, the interfacial optical phonon vibration frequency displayed distinct dependence on surface defects of MWCNTs. Combining theoretical analysis with experimental verification, a valid conjecture with respect to surface phonon vibration activity for MWCNTs was proposed. This phenomenon of polar solvent-induced SFG activity may have the potential to find applications in optical detection and environmental sensing in the near future.

Low spurious optoelectronic oscillator achieved by frequency conversion filtering without deteriorating phase noise.

In order to obtain microwave signals with low spurs and low phase noise, we studied the residual phase noise of the frequency-conversion filtering oscillator and methods to improve its phase noise performance. We first analyze the influence of the dispersion of the intermediate frequency (IF) filter on the residual phase noise in the frequency conversion filtering process. Then, we use an electro-optic modulator to achieve up-conversion in the frequency conversion filtering and extend the intra-cavity delay with an optical fiber after the modulator. This allows the optoelectronic oscillator (OEO) to improve the phase noise performance while having a good suppression of spurs. The spurs suppression ratio of the proposed OEO is 80 dB with a fiber of about 1.6 km in the cavity. The phase noise of the proposed OEO is -130 dBc/Hz at 10 kHz offset from 10 GHz, which is 10 dB lower than our previous work.

Stable downlink frequency transmission from arbitrary injection point with endless and quick phase error correction.

A stable frequency downlink transmission scheme, which delivers the frequency signal back to the central station from an arbitrary injection point along a radio-over-fiber (RoF) loop link, is proposed and demonstrated. The frequency signal at the arbitrary remote point is injected into the RoF loop link in both clockwise and counter-clockwise directions, simultaneously. The phase variation induced by the fiber loop link is obtained in real time with the help of a round-trip assistant frequency signal. The phase error can be exactly cancelled by a series of frequency mixing (i.e., up-conversion and down-conversion) among the signals. In the experiment, a 1.21-GHz frequency signal at an arbitrary remote point is downlink transferred to the central station in a 45-km fiber loop link. The result shows the overlapping Allan deviation (ADEV) of 1.04×10-12 at 0.1 s, 1.3×10-13 at 1 s and 1.1×10-15 at 104 s, respectively. The phase error correction operates entirely at the central station, leaving a simple and robust configuration of the remote site. No active adjusting part is integrated, and the all-passive compensation achieves an endless phase error correction range, as well as quick response to fiber delay changes.