Early Emerging SARS-CoV-2 Spike Mutants Are Diversified in Virologic Properties but Elicit Compromised Antibody Responses.

Despite the effective antivirals and vaccines, COVID-19 remains a public health concern. The mutations that occurred during the early stage of the pandemic can be valuable in assessing the viral fitness and evolutionary trajectory. In this study, we analyzed a panel of 2969 spike sequences deposited in GISAID before April 2020 and characterized nine representative spike single-point mutants in detail. Compared with the WA01/2020, most (8 out of 9) mutants demonstrated an equivalent or diminished protein expression or processing, pseudovirus infectivity, and cell-cell fusion. Interestingly, most of the mutants in native form elicited minimum antibody responses in mice despite unaltered CD4+ and CD8+ T cell responses. The mutants remained sensitive to the antisera and the type I interferon. Taken together, these data suggest that the early emerging mutants are virologically divergent, and some of which showed transmission fitness. Our findings have important implications for the retrospective tracing of the early SARS-CoV-2 transmission and future pandemic preparedness.

Response of partial nitritation and denitrification processes to high levels of free ammonia in a pilot mature landfill leachate treatment system: Stability and microbial community dynamics.

The high levels of free ammonia (FA) challenge the application of partial nitritation (PN) and denitrification (DN) in the treatment of ammonia-rich wastewater. This study explored the impact of high levels of FA on the PN and DN stability and microbial community dynamics. By reducing reflux and increasing influent load, the concentrations of FA in PN and DN reactors increased from 28.9 mg/L and 140.0 mg/L to 1099.8 mg/L and 868.4 mg/L, respectively. During this process, the performance of PN and DN remained stable. The microbial analysis revealed that the Nitrosomonas exhibited strong tolerance to high levels of FA, and its relative abundance was positively correlated with amoABC (R2 0.984) and hao (R2 0.999) genes. The increase in microbial diversity could enhance the resistance ability of PN against the FA impact. In contrast, high levels of FA had scant influence on the microbial community and performance of DN.

Improving stability and nitrogen removal performance of pilot-scale autotrophic process for mature landfill leachate treatment utilizing in-situ organics.

This study established a stable and efficient pilot-scale denitrification (DN) and partial nitritation (PN) combined with autotrophic nitrogen removal process for mature landfill leachate treatment. A total inorganic nitrogen removal efficiency (TINRE) of 95.3% was achieved without any external carbon source input, including 17.1%, 1.0% and 77.2% of nitrogen removal contributed by the DN, PN and autotrophic processes, respectively. ANAMMOX genus, Ca_Anammoxoglobus (19.4%) was dominant in autotrophic reactor. Moreover, denitrifying bacteria could utilize in-situ organics, including poorly degradable organics, to enhance the nitrogen removal performance of autotrophic process, contributing 3.4% of TINRE. This study provides new insights for the economical, low-carbon, and efficient treatment of mature landfill leachate.

Large-scale (500 kg N/day) two-stage partial nitritation/anammox (PN/A) process for liquid-ammonia mercerization wastewater treatment: Rapid start-up and long-term operational performance.

The nitrogen pollution control of liquid-ammonia mercerization wastewater (LMWW) is one of the typical obstacle restricting the sustainability of textile industry. In this study, a 500 kg N/day two-stage partial nitritation/anammox (PN/A) process containing PN reactor filled with zeolite and biofilm anammox reactors was successfully started up in 45 days and operated stably with high shock resistance over one year for LMWW treatment. The large-scale process achieved an average ammonium removal efficiency (94.3 ± 2.3%), total nitrogen removal efficiency (89.4 ± 2.7%) and nitrogen removal rate (1.003 ± 0.386 kg N/m3/day) during one year engineering operation. Simultaneous denitrification was revealed by the contribution of 5.2% total nitrogen removed. High-throughput sequencing results showed that Nitrosomonas was the most dominant genus in PN reactor, and Ca. Anammoxoglobus and Ca. Kuenenia were the functional bacteria for nitrogen removal in anammox reactors. Compared to traditional nitrification-denitrification process, the large-scale process reduced a total operational cost of 46.03 CNY/kg N for LMWW. This study revealed the proposed process was quite reliable with fast start-up and high impact resistance to overcome the obstacle of nitrogen pollution control for LMWW economically and conducive to the sustainable development for textile industry.

Highly sensitive curvature sensor based on a sandwich multimode fiber Mach-Zehnder interferometer.

A highly sensitive optical fiber Mach-Zehnder interference curvature sensor based on MMF-GIMMF-MMF, which was made by sandwiching the graded-index multimode fiber (GIMMF) between two pieces of very short stepped-index multimode fibers (SIMMFs) spliced with input-single-mode fiber (SMF) and output-SMF, respectively, was proposed. The core diameter of the SIMMFs and GIMMF was 105 µm and 50 µm, respectively, and cladding diameter of them were both 125 µm. The sensing principle of the MMF-GIMMF- MMF sensors and the influences of structure parameters on the interference spectrum characteristics were theoretically analyzed in detail. Experimental results showed that when the length of the GIMMF was short enough (usually ≤ 10 mm), interference spectrum was induced by the interaction between the core modes and the low-order cladding modes due to the special structure of the designed Mach-Zehnder interferometer. Intensity of the interference valleys was highly sensitive to the applied bending but nearly independent of the surrounding temperature, on the contrary, the dip wavelength showed negligible sensitivity to the applied bending but relatively high temperature sensitivity. Thus, a temperature- independent curvature sensor could be realized by tracing the intensity variation of interference valley. In addition, different interference valley exhibited different intensity-based curvature sensitivity, providing more options for curvature sensing applications. Especially, total length of the sensor could be as short as 3 mm with length of GIMMF and SIMMFs only 1mm, the maximum curvature sensitivity could reach up to -78.75 dB/m-1 in the small curvature range of 0-2.36 m-1. Owing to its compact size, easy fabrication, good reproducibility and low cost, the proposed sensor is promising for bending-related high-precision engineering applications.

Engineering His-Tagged Senecavirus A for One-Step Purification of Viral Antigens.

Senecavirus A (SVA) is a picornavirus that causes vesicular disease in swine, and the inactivated vaccine is used to prevent and control SVA infection. To develop a new chromatography strategy for the purification and concentration of SVA vaccine antigens, we inserted a 6×His-tag at the VP1 C-terminal of the SVA/HLJ/CHA/2016 in an infectious clone to rescue a His-tagged SVA. The constructed and rescued recombinant virus, named as rSVA-His, exhibited similar growth kinetics to that of its parental virus. In addition, the expression of a 6×His-tag on the surface of SVA showed genetic stability in cell passages in vitro, which allowed one-step purification of SVA antigens by Ni2+ affinity columns. Furthermore, the immunogenicity of the inactivated rSVA-His was evaluated by inoculating rabbits and detecting neutralizing antibodies. The animals receiving two doses of the inactivated rSVA-His emulsified with oil adjuvant developed a high titer of neutralizing antibodies, indicating that SVA VP1 is tolerant to His-tag insertion without detriment to its antigenicity. In summary, the constructed 6×His-tagged SVA may offer a feasible approach to the affinity purification and concentration of antigens in the process of SVA inactivated vaccine production.

The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery.

Senecavirus A (SVA) is a picornavirus that causes vesicular disease in swine and the only member of the Senecavirus genus. Like in all members of Picornaviridae, the 5' untranslated region (5'UTR) of SVA contains an internal ribosome entry site (IRES) that initiates cap-independent translation. For example, the replacement of the IRES of foot-and-mouth disease virus (FMDV) with its relative bovine rhinitis B virus (BRBV) affects the viral translation efficiency and virulence. Structurally, the IRES from SVA resembles that of hepatitis C virus (HCV), a flavivirus. Given the roles of the IRES in cap-independent translation for picornaviruses, we sought to functionally characterize the IRES of this genus by studying chimeric viruses generated by exchanging the native SVA IRES with that of HCV either entirely or individual domains. First, the results showed that a chimeric SVA virus harboring the IRES from HCV, H-SVA, is viable and replicated normally in rodent-derived BHK-21 cells but displays replication defects in porcine-derived ST cells. In the generation of chimeric viruses in which domain-specific elements from SVA were replaced with those of HCV, we identified an essential role for the stem-loop I element for IRES activity and recombinant virus recovery. Furthermore, a series of stem-loop I mutants allowed us to functionally characterize discrete IRES regions and correlate impaired IRES activities, using reporter systems with our inability to recover recombinant viruses in two different cell types. Interestingly, mutant viruses harboring partially defective IRES were viable. However, no discernable replication differences were observed, relative to the wild-type virus, suggesting the cooperation of additional factors, such as intermolecular viral RNA interactions, act in concert in regulating IRES-dependent translation during infection. Altogether, we found that the stem-loop I of SVA is an essential element for IRES-dependent translation activity and viral replication.

Highly sensitive vibration sensor based on the dispersion turning point microfiber Mach-Zehnder interferometer.

In the present work, we introduced a highly sensitive vibration sensor, which is based on the dispersion turning point (DTP) microfiber Mach-Zehnder interferometer. The axial strain and vibration sensing characteristics of the microfiber Mach-Zehnder interferometer were investigated. First, we theoretically analyzed the spectrum evolution characteristics of the microfiber Mach-Zehnder interferometer caused by axial strain. Second, the microfiber with different diameters was fabricated using the electrode discharge and fused taper method, and the axial strain experiments were conducted; the maximum sensitivity of the DTP microfiber with a diameter of ∼2.2 µm reached -45.55 pm/µÉ› at ∼1550 nm. Finally, based on the axial strain principle of the microfiber, we designed a highly sensitive vibration sensor using a DTP microfiber integrated into a rectangular through-hole cantilever beam. The 30-3500 Hz vibration signal monitoring could be realized, the maximum signal-to-noise ratio (SNR) was ∼75 dB at 52 Hz, and the acceleration sensitivity reached as high as 0.764 V/g at 45Hz. These results suggested the high performance of the microfiber in axial strain and micro-vibration sensing fields.

Optic-fiber vibration sensor based on a reflected 81° tilted fiber grating integrated with a symmetrical flexible hinge.

An optic-fiber vibration sensor based on the reflected 81° tilted fiber grating (81° TFG) integrated with a symmetrical flexible hinge is proposed and experimentally demonstrated in this paper. The vibration sensor is composed of a symmetrical flexible hinge and a reflected 81° TFG, the ends of which are simply fixed on the upper surface of the mass. The theoretical model of the proposed vibration sensor is analyzed, by which the important parameters related to the resonant frequency of the sensor are simulated and discussed; then, the vibration sensing experiments are conducted. Experiment results show that TE/TM mode of the 81° TFG can provide the maximal acceleration sensitivity of 338.28 and 299.94 mV/g at 400 Hz in the flat area of the amplitude-frequency response (50-400 Hz), which is increased by 9.95 and 11.5 times as compared with the optical fiber cantilever beam structure, respectively. Further, the signal-to-noise ratio in the flat area (50-400 Hz) is about ∼66.275dB under the acceleration of 2 g, which is increased by ∼20dB. Furthermore, it can be used for detecting mechanical vibration of medium-high frequency ranging from 50 to 3500 Hz. The proposed 81° TFG vibration sensor has the characteristics of small volume, simple package, high acceleration sensitivity, and wide vibration signal response range, which will ensure it has broad application prospects in the field of mechanical vibration.

Can systemic inflammatory response syndrome score at admission predict clinical outcome in patients with severe burns?

INTRODUCTION: The use of SIRS score as a predictor of outcomes in patients with severe burns has not been fully evaluated. Here, we aimed to test that whether admission SIRS score, combining with other predictors, could be used in predicting outcomes in patients with severe burns. Additionally, we compared the prognostic accuracy of admission SIRS score with other score systems and newly developed models. METHODS: We performed a retrospective study of adult patients with ≥40% total body surface area burns admitted to a burn center from 2005 to 2017. The primary outcome was in-hospital mortality, and the secondary outcomes were hospital and intensive care unit length of stay. SIRS score, rBaux score, ABSI and newly developed models were compared using area under the receiver operating characteristic curve analysis. RESULTS: Out of the total 144 patients, 128 (88.9%) met SIRS criteria on admission; with a predominant SIRS scores of 3. Patients with admission SIRS were more likely to have larger burns and have higher rBaux and ABSI scores when compared with non-SIRS patients. With the each increment of admission SIRS score, total and full-thickness burn areas, proportion of inhalation injury, tracheostomy and mortality increased significantly. However, SIRS score at admission was not increasingly predictive of deleterious outcomes when analyzed by multivariable regression analysis. Although the combination of SIRS score, age, and burn-specific variables showed better or equal prognostication of outcomes than that of other score systems, the contribution of the variable SIRS score was negligible. CONCLUSIONS: The model with the variables age, percentage full-thickness burns, and inhalation injury provided excellent prediction of poor outcomes in patients with severe burns, while SIRS score has limited use for prognostic determinations.