Integration of anaerobic digestion and electrodialysis for methane yield promotion and in-situ ammonium recovery.

Ammonia inhibition is a common issue encountered in anaerobic digestion (AD) when treating nitrogen-rich substrates. This study proposed a novel approach, the electrodialysis-integrated AD (ADED) system, for in-situ recovery of ammonium (NH4+) while simultaneously enhancing AD performance. The ADED reactor was operated at two different NH4+-N concentrations (5,000 mg/L and 10,000 mg/L) to evaluate its performance against a conventional AD reactor. The results indicate that the ADED technology effectively reduced the NH4+-N concentration to below 2,000 mg/L, achieving this with a competitive energy consumption. Moreover, the ADED reactor demonstrated a 1.43-fold improvement in methane production when the influent NH4+-N was 5,000 mg/L, and it effectively prevented complete inhibition of methane production at the influent NH4+-N of 10,000 mg/L. The life cycle impact assessment reveals that ADED technology offers a more environmentally friendly alternative by recovering valuable fertilizer from the AD system.

Simultaneous removal of phenanthrene and Pb using novel PPG-CNTs-nZVI beads.

PPG-CNTs-nZVI bead was synthesized by polyvinyl alcohol, pumice, carbon nanotube, and guar gum-nanoscale zero-valent iron to be applied on simultaneously removal of polycyclic aromatic hydrocarbons (PAHs; phenanthrene) and heavy metals (Pb2+) via adsorption. The individual and simultaneous removal efficiency of phenanthrene and Pb2+ using the PPG-CNTs-nZVI beads was evaluated with a range of initial concentrations of these two pollutants. The kinetics and isotherms of phenanthrene and Pb2+ adsorption by the PPG-CNTs-nZVI beads were also determined. The PPG-CNTs-nZVI beads show reasonably high phenanthrene adsorption capacities (up to 0.16 mg/g), and they absorbed 85% of the phenanthrene (initial concentration 0.5 mg/L) in 30 min. High Pb2+ adsorption capabilities were also demonstrated by the PPG-CNTs-nZVI beads (up to 11.6 mg/g). The adsorption fits the Langmuir model better than the Freundlich model. The adsorption still remained stable with various ionic strength circumstances and a wide pH range (2-5). Additionally, the co-adsorption of phenanthrene and Pb2+ by the PPG-CNTs-nZVI beads resulted in synergistic effects. Particularly, phenanthrene-Pb2+ complex formation via π-cation interactions demonstrated a greater affinity than phenanthrene or Pb2+ alone. The present findings suggest that PPG-CNTs-nZVI beads may be effective sorbents for the simultaneous removal of PAHs and heavy metals from contaminated waters.

Occurrence and ecological risk of PAHs in urban road runoff in Beijing.

The occurrence and ecological risks of 16 polycyclic aromatic hydrocarbons (PAHs) in different types of urban road runoff in Beijing during two typical rainfall events were studied. The average concentration of PAHs in road runoff particulate was in the order of Guanyuanqiao Road (ring road, 15,175 ng/L) > Huayuanqiao Road (primary road, 4,792 ng/L) > Dongcheng Alley (alley, 4,774 ng/L) > Nansihuan Viaduct (viaduct, 770 ng/L), much higher than dissolved PAHs. The total concentration of ∑16PAHs decreased with runoff scouring. Rainfall conditions and the accumulation of PAHs in the early rainfall period show a significant impact on PAHs pollution. The event mean concentration range of PAHs is 674-21,596 ng/L, following in the order of ring road > primary road > alley > viaduct. The proportion of four-ring PAHs was the highest. The first flush effect of PAHs is found in both rainfall events, and the effect of different ring PAHs is relatively similar. The content of PAHs is positively correlated with the amount of total organic carbon and suspended substance in runoff (r2> 0.72). The ecological risk assessment indicated that PAHs in road runoff except viaduct road corresponded to high risk.

Immunogenicity and Safety of One versus Two Doses of Quadrivalent Inactivated Influenza Vaccine (IIV4) in Vaccine-Unprimed Children and One Dose of IIV4 in Vaccine-Primed Children Aged 3-8 Years.

Two doses of the inactivated influenza vaccine (IIV) are generally recommended for children under 9 years old. This study assessed the necessity for a second dose of quadrivalent IIV (IIV4) in children aged 3-8 years. In this randomized, open-label, paralleled-controlled study, 400 children aged 3-8 years who were vaccine-unprimed were randomly assigned at a 1:1 ratio to receive a two-dose (Group 1) or one-dose (Group 2) regimen of IIV4, and 200 who were vaccine-primed received one dose of IIV4 (Group 3). A serum sample was collected before and 28 days after the last dose to determine the hemagglutination inhibition (HI) antibody level. Adverse events were collected within 28 days after each dose. One-dose or two-doses of IIV4 were well tolerated and safe in children aged 3-8 years, and no serious adverse events related to the vaccine were reported. The seroconversion rates (SCRs) of HI antibody ranged from 61.86% to 95.86%, and the post-vaccination seroprotection rates (SPRs) were all >70% in three groups against the four virus strains. The two-dose regimen in vaccine-unprimed participants (Group 1) achieved similar SPRs in comparison with the one-dose in the vaccine-primed group (Group 3), and the SPRs in Group 1 and Group 3 were higher in vaccine-unprimed participants of the one-dose regimen (Group 2). The present study supports the recommendations of a two-dose regimen for IIV4 use in children aged 3-8 years.

Immunogenicity persistence of hepatitis A vaccines Healive® and Havrix® among children:15 years follow-up and long-term prediction.

Healive® was the only Chinese WHO-prequalified inactivated vaccine for the hepatitis A virus, which has been widely used in national immunization programs in China. Long-term follow-up studies are needed to estimate the persistence of vaccine-induced antibody levels and the necessity for booster vaccines. During the trial, geometric mean concentrations (GMCs) and seroconversion rates (SRs) of anti-HAV antibodies were compared based on two different inactivated hepatitis A vaccines, Healive® and Havrix®. Four hundred children were randomly assigned to receive two doses of Healive® or Havrix® at 0 and 6 months. The current study assessed antibody persistence for both vaccines 15 years post-immunization. A mixed linear model was used to predict long-term antibody persistence. The GMCs were significantly higher for Healive® compared to Havrix® at 1, 6, 7, 66, 138 months (P < .001) and 186 months (P = .004 < .05) post-vaccination. Healive® and Havrix® reached a GMC of 164.8 mIU/ml and 105.7 mIU/ml post-15 years of vaccination, respectively. The seroconversion rates of both vaccines showed no statistically significant differences (97.9% for Healive® and 94.7% for Havrix®, P = .20). The prediction showed that Healive® would provide protection for a minimum of 30 years following immunization, with a lower limit of the 95% confidence intervals for GMCs greater than 20mIU/mL. Compared to Havrix®, the vaccine Healive® showed a stronger protective effect and better persistence among children at 15 years post-full immunization. Prediction indicated at least 30 years of antibody persistence for Healive® and at least 25 years for Havrix®.

Occurrence and risk assessment of PAHs from athletic fields under typical rainfall events.

Six polycyclic aromatic hydrocarbons (PAHs) including naphthalene (Nap), fluorene (Flu), phenanthrene (Phe), fluoranthene (Fla), pyrene (Pyr), and chrysene (Chr) were detected in runoff from five athletic fields during three rainfall events. The event mean concentration (EMC) of ∑6PAHs ranged from 3.96 to 23.23 µg/L, which was much higher than the EMC in urban traffic area runoff. Except for Nap, the PAH concentrations followed in the order of artificial turf > badminton court > basketball court > plastic runway > optennis court. The surface characteristics of the athletic fields, such as the composition of materials and roughness, played an essential role in the release of PAHs. ∑6PAHs concentration during the 2nd rainfall event (July 22nd) was the highest among the three rainfall events, indicating that high rainfall intensity facilitated the PAHs release. PAHs during three rainfall events showed little first flush effect except for the artificial turf during the 2nd (22nd July) and 3rd (29th July) rainfall events. The first flush effect could be affected by rainfall characters, PAH properties, and surface characteristics of athletic fields. Ecological risk assessment showed that PAHs in runoff corresponded to moderate-to-high risk, while health risk assessment showed that PAHs could pose a potential carcinogenic danger to human health via dermal contact.

Ageing characteristics and microplastic release behavior from rainwater facilities under ROS oxidation.

Reactive oxygen species (ROS) are ubiquitous in the natural environment that are generated by chemical or biochemical processes. Plastic rainwater facilities, as an important part of modern rainwater systems, are inevitably deteriorated by ROS. As a consequence, microplastics will be released. However, information on how ROS affect the ageing characteristics of plastic rainwater facilities and the subsequent microplastic release behavior is still insufficient. To address this knowledge gap, Fenton reagents were used to simulate the reactive oxygen species (ROS) induced ageing process of three typical plastic rainwater components (rainwater pipe, made of polyvinyl chloride; modular storage tank, made of polypropylene; inspection well, made of high-density polyethylene) and the subsequent microplastic release behavior. After 6 days of Fenton ageing, an increase in sharpness, holes, and fractures on the rainwater facilities' surface was observed by scanning electron microscope (SEM). The functional group changes on the rainwater facilities' surface were analyzed by Fourier transform infrared spectrometer (FTIR) and two-dimensional correlation spectroscopy (2D-COS) and compared with the results of X-ray photoelectron spectroscopy (XPS). During the ageing process, oxygen-containing functional groups were generated and the carbon chains were broken, which promoted peeling and the release of microplastics. The amount of released microplastics (ranging from 158 to 6617 items/g facility) varied with the type of rainwater facilities, and the order was modular storage tank > inspection well > rainwater pipe. The release amount increased with ageing time, and a significant linear relationship was observed (r2 > 0.91). The particle size of the released microplastics ranged from 2 to 1362 µm, among which 10-30 µm particles accounted for the largest proportion (62.7 %). The release amount increased exponentially with decreasing particle size (r2 > 0.71). This study indicates that large amounts of microplastics could be released from plastic rainwater components during ROS-induced ageing.

Safety and immunogenicity following a homologous booster dose of CoronaVac in children and adolescents.

Data on safety and immunity elicited by a third booster dose of inactivated COVID-19 vaccine in children and adolescents are scarce. Here we conducted a study based on a double-blind, randomised, placebo-controlled phase 2 clinical trial (NCT04551547) to assess the safety and immunogenicity of a third dose of CoronaVac. In this study, 384 participants in the vaccine group were assigned to two cohorts. One received the third dose at a 10-months interval (cohort 1) and the other one at a 12-months interval (cohort 2). The primary endpoint is safety and immunogenicity following a third dose of CoronaVac. The secondary endpoint is antibody persistence following the primary two-dose schedule. Severities of local and systemic adverse reactions reported within 28 days after dose 3 were mild and moderate in both cohorts. A third dose of CoronaVac increased GMTs to 681.0 (95%CI: 545.2-850.7) in cohort 1 and 745.2 (95%CI: 577.0-962.3) in cohort 2. Seropositivity rates against the prototype were 100% on day 28 after dose 3. Seropositivity rates against the Omicron variant were 90.6% (cohort 1) and 91.5% (cohort 2). A homologous booster dose of CoronaVac is safe and induces a significant neutralising antibody levels increase in children and adolescents.

Lot-to-lot consistency, immunogenicity, and safety of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults: A randomized, double-blind, phase IV trial.

Previous phase I to III clinical trials have shown that the inactivated SARS-CoV-2 vaccine namely CoronaVac has good efficacy, safety, and immunogenicity. This phase IV trial aims to evaluate the lot-to-lot consistency, immunogenicity, and safety on a commercial scale in healthy adults, which could provide data to support stable manufacturing. In this single-center, randomized, double-blind study, 1,080 healthy adults aged 26-45 years were randomly assigned into three groups to receive one of three lots of vaccines. All subjects received two doses of CoronaVac with an interval of 28 days. Serum samples were collected before the first dose and 28 days after the second dose to assess the immunogenicity. Solicited local and systemic adverse events (AEs) within 7 days and unsolicited AEs within 28 days after each dose of vaccination were recorded. A total of 1,039 participants completed the study and were included in the per-protocol set (PPS). The GMTs were 75.2 (68.5,82.6), 65.0 (59.0,71.7), and 65.3 (59.4,71.8), respectively, and the seroconversion rates of neutralizing antibody were all higher than 98%. The GMT ratios of each pair of lots were 1.16 (1.01,1.32), 1.15 (1.01, 1.32), and 0.99 (0.87, 1.14), respectively, meeting the immunological equivalence criteria. The incidence rates of adverse reactions (ARs) were 19.17%, 13.89%, and 18.33%, with no statistical difference. The ARs were all in grade 1 and grade 2, with incidences of 15.46% and 2.50%. Non-vaccine-related serious adverse events (SAEs) were reported. These results showed robust lot-to-lot consistency, immunogenicity, and safety. The stable production indicated that CoronaVac is suitable for large-scale use.Trial registration number: NCT04894227 (ClinicalTrials.gov).

Distinguishing responses of acetoclastic and hydrogenotrophic methanogens to ammonia stress in mesophilic mixed cultures.

A shift from the acetoclastic to the hydrogenotrophic pathway in methanogenesis under ammonia inhibition is a common observation in anaerobic digestion. However, there are still considerable knowledge gaps concerning the differential ammonia tolerance of acetoclastic and hydrogenotrophic methanogens (AMs and HMs), their responses to different ammonia species (NH4+, NH3), and their recoverability after ammonia inhibition. With the successful enrichment of mesophilic AMs and HMs cultures, this study aimed at addressing the above knowledge gaps through batch inhibition/recovery tests and kinetic modeling under varying total ammonia (TAN, 0.2-10 g N/L) and pH (7.0-8.5) conditions. The results showed that the tolerance level of HMs to free ammonia (FAN, IC50=1345 mg N/L) and NH4+ (IC50=6050 mg N/L) was nearly 11 times and 3 times those of AMs (NH3, IC50=123 mg N/L; NH4+, IC50=2133 mg N/L), respectively. Consistent with general belief, the AMs were more impacted by FAN. However, the HMs were more adversely affected by NH4+ when the pH was ≤8.0. A low TAN (1.0-4.0 g N/L) could cause irreversible inhibition of the AMs due to significant cell death, whereas the activity of HMs could be fully or even over recovered from severe ammonia stress (FAN≤ 0.9 g N/L or TAN≤10 g N/L; pH ≤8.0). The different tolerance responses of AMs and HMs might be associated with the cell morphology, multiple energy-converting systems, and Gibbs free energy from substrate-level phosphorylation.

Low energy harvesting of hydrophobic microalgae (Tribonema sp.) by electro-flotation without coagulation.

Microalgae have great potential for biofuel production and wastewater treatment, but the high cost of harvesting hinders their practical application. In this study, economical harvesting of hydrophobic microalgae by electro-flotation without coagulation was assessed. The harvesting performance of this method for selected species of freshwater microalgae with different degrees of hydrophobicity (Tribonema sp., highly hydrophobic; Scenedesmus sp., moderately hydrophobic; and Pandorina sp., hydrophilic) were compared. It was found that microalgal hydrophobicity played a critical role in electro-flotation. Under the same condition (current 0.3 A, velocity gradient 200 s-1, biomass concentration 1 g/L), Tribonema sp. could be effectively harvested (96.2 ± 0.4%) after 20 min of electro-flotation, while the harvesting efficiency decreased significantly with Scenedesmus sp. (70.1 ± 5.2%, 20 min) and Pandorina sp. (<10%, 1 h). The influences of current, electrolysis time, mixing intensity (velocity gradient) and biomass concentration on Tribonema sp. (hydrophobic) harvesting were further investigated. Increasing the current within a certain range (0.1 A-0.4 A) was beneficial to harvesting, while it's further increase decreased floating velocity, which was similar to the effect of the velocity gradient. Under the optimal condition, the harvesting efficiency of Tribonema sp. was 96.3% and the energy consumption (0.19 kWh/kg biomass) was much lower than other harvesting techniques, indicating that electro-flotation is a time-saving and economical approach for hydrophobic microalgae harvesting.

Immunogenicity and Safety of a Booster Dose of Live Attenuated Varicella Vaccine, and Immune Persistence of a Primary Dose for Children Aged 2 to 6 Years.

AIM: To evaluate the immunogenicity and safety of a booster dose of live attenuated varicella vaccine (VarV) manufactured by Sinovac (Dalian) Vaccine Technology Co. Ltd., and the immune persistence of a primary dose in 2- to 6-year-old children. METHODS: A phase IV, open-label study was conducted in China. Children previously vaccinated with a single dose of VarV at 1~3 years old received one dose of homologous VarV in the first year, the second year, or the third year after the primary immunization as booster immunization. Immune persistence was evaluated in an immune persistence analysis set, while immunogenicity was evaluated in a per-protocol analysis set, and safety was evaluated in a safety analysis set. The primary endpoint was the seropositive rate and the seroconversion rate of VarV antibody. The trial was registered at ClinicalTrials.gov (NCT02981836). RESULTS: From July 2018 to August 2020, a total of 849 vaccinated children received the booster vaccination of VarV, one booster dose for each child (301 vaccinated in the first year after primary immunization (Group 1), 276 vaccinated in the second year after primary immunization (Group 2), 272 vaccinated in the third year after primary immunization (Group 3)). The seropositive rates were 99.34%, 97.83%, and 98.16% in Groups 1-3, with GMTs of 1:22.56, 1:18.49, and 1:18.45, respectively. Thirty days after the vaccine booster dose, the seropositive rates of the three groups were all 100% and the seroconversion rates were 52.54%, 67.46%, and 66.67%, with GMTs of 1:68.49, 1:76.32 and 1:78.34, respectively. The seroconversion rates in Groups 2 and 3 were both higher than that in Group 1 (p = 0.0005 and p = 0.0008). The overall incidence of adverse reactions was 7.77%, with 7.64%, 8.33%, and 7.35% in Groups 1, 2, and 3, respectively. The main symptom among adverse reactions was fever, the incidence of which ranged from 5.07% to 6.64% in each group, and no vaccine-related serious adverse events occurred. CONCLUSIONS: VarV had good immune persistence in 1~3 years after primary immunization. A vaccine booster dose for children aged 1~3 years after primary immunization recalled specific immune response to varicella-zoster virus, with no safety concerns increased.

Stimulatory effects of biochar addition on dry anaerobic co-digestion of pig manure and food waste under mesophilic conditions.

The stimulatory effect of biochar addition on dry anaerobic digestion (AD) has been rarely investigated. In this study, the effects of commonly used biochars (bamboo, rice husk, and pecan shell) on dry co-AD were investigated using mesophilic batch digesters fed with pig manure and food waste as substrates. The results show that the specific methane yield was mildly elevated with the addition of biochars by 7.9%, 9.4%, and 12.0% for bamboo, rice husk, and pecan shell-derived biochar additions, respectively. Biochar did facilitate the degradation of poorly biodegradable organics. In comparison, there was no significant effect on the peak methane production rate by the supplementation of the selected biochars. Among the three mechanisms of enhancing methanogenesis by biochar (buffering, providing supporting surface, and enhancing electron transfer), the first two mechanisms did not function significantly in dry co-AD, while the third mechanism (i.e., enhancing electron transfer) might play an important part in dry AD process. It is recommended that the utilization of biochar for the enhancement of biomethanation in dry AD should be more focused on mono digestion in future studies.

Translating daily COVID-19 screening into a simple glucose test: a proof of concept study.

Home testing is an attractive emerging strategy to combat the COVID-19 pandemic and prevent overloading of healthcare resources through at-home isolation, screening and monitoring of symptoms. However, current diagnostic technologies of SARS-CoV-2 still suffer from some drawbacks because of the tradeoffs between sensitivity, usability and costs, making the test unaffordable to most users at home. To address these limitations, taking advantage of clustered regularly interspaced short palindromic repeats (CRISPRs) and a portable glucose meter (PGM), we present a proof-of-concept demonstration of a target-responsive CRISPR-PGM system for translating SARS-CoV-2 detection into a glucose test. Using this system, a specific N gene, N protein, and pseudo-viruses of SARS-CoV-2 have been detected quantitatively with a PGM. Given the facile integration of various bioreceptors into the CRISPR-PGM system, the proposed method provides a starting point to provide patients with a single-device solution that can quantitatively monitor multiple COVID-19 biomarkers at home.

Improved reduction of antibiotic resistance genes and mobile genetic elements from biowastes in dry anaerobic co-digestion.

This study investigated the performance of anaerobic co-digestion (AcoD) of pig manure and food waste on the reduction of antibiotic resistomes under wet and dry AcoD conditions. High-throughput quantitative PCR technology was utilized for a comprehensive assessment of the performances of the two processes. The results show that dry AcoD with a total solids (TS) content of 20% effectively reduced total antibiotic resistance genes (ARGs) by 1.24 log copies/g wet sample, while only 0.54 log copies/g wet sample was reduced in wet AcoD with a TS content of 5%. Dry AcoD was more efficient in reduction of aminoglycosides, multidrug and sulfonamide resistance genes compared with the reduction of other classes of ARGs. Dry AcoD caused a significant reduction of ARGs with resistance mechanisms of efflux pump and antibiotic deactivation. In contrast, there was no obvious difference in reductions of ARGs with different resistance mechanisms in wet AcoD. Network analysis showed that ARGs were significantly correlated with mobile genetic elements (MGEs) (Spearman's r > 0.8, P < 0.05), as well as microbial communities. Enrichment of ARGs and MGEs was found at the early period of AcoD processes, indicating some ARGs and MGEs increased during the hydrolysis and acidogenesis stages. But after a long retention time, their abundances were effectively reduced by dry AcoD in the subsequent stages.

Application of magnetic fields to wastewater treatment and its mechanisms: A review.

Magnetic field (MF) has been applied widely and successfully as an efficient, low-cost and easy-to-use technique to enhance wastewater treatment (WWT) performance. Although the effects of MF on WWT were revealed and summarized by some works, they are still mysterious and complex. This review summarizes the application of MF in magnetic adsorption-separation of heavy metals and dyes, treatment of domestic wastewater and photo-magnetic coupling technology. Furthermore, the mechanisms of MF-enhanced WWT are critically elaborated from the perspective of magnetic physicochemical and biological effects, such as magnetoresistance, Lorentz force, and intracellular radical pair mechanism. At last, the challenges and opportunities for MF application in WWT are discussed. For overcoming the limitations and taking advantages of MFs in WWT, fundamental research of the mechanisms of the application of MFs should be carried out in the future.

Effects of C/N ratio and dissolved oxygen on aerobic denitrification process: A mathematical modeling study.

COD to ammonium nitrogen (C/N) ratio and dissolved oxygen (DO) concentration are the most important factors affecting aerobic denitrification process, however, the effects of those on the mix-cultured aerobic denitrification process are still ambiguous. A mathematical model based on the framework of activated sludge model No. 3 (ASM3) was proposed for simulating nitrogen removal in an aerobic denitrification SBR process via anoxic/aerobic denitrification. AQUASIM 2.1G was employed for parameter estimation, sensitivity analysis and model calibration, as well as model validation. Ultimately, the impacts of the C/N ratio and the DO concentration on the aerobic denitrification process were revealed by the validated model. The model proposed well described nitrogen removal in an aerobic denitrification SBR process. The total nitrogen (TN) removal efficiency of the process increased with the increasing of C/N ratio and the decreasing of DO concentration. C/N ratio impacted the synthesis of cell internal storage products (XSTO), and the effects of DO concentration on the process resulted from the competition with substrate between heterotrophs and aerobic denitrifiers. High C/N ratio was preferred, however, the DO concentration should be maintained at a relatively lower level under the premise of ensuring the aerobic condition.

Quadrivalent influenza vaccine (Sinovac Biotech) for seasonal influenza prophylaxis.

INTRODUCTION: Quadrivalent Influenza Vaccine (Sinovac Biotech) is a quadrivalent split-virion-inactivated influenza vaccine approved in China in June 2020 for individuals ≥3 years of age. It contains 15 µg hemagglutinin per strain including A/H1N1, A/H3N2, B/Victoria, and B/Yamagata, which could potentially improve protection against influenza B viruses. AREAS COVERED: In this review, we summarize the development of quadrivalent influenza vaccines in China and foreign countries, and assess the immunogenicity and safety from the phase I and III clinical trials of Quadrivalent Influenza Vaccine in individuals ≥3 years of age. We also discuss the potential application of Quadrivalent Influenza Vaccine in young children 6-35 months of age according to the results of the phase III trial. EXPERT COMMENTARY: The immunogenicity and safety profiles of Quadrivalent Influenza Vaccine containing two A and two B strains were comparable to the trivalent vaccines for the shared strains. The addition of a second B strain to the trivalent vaccine could induce superior immune responses for the alternate B strain. Since the two B strains co-circulated worldwide, the introduction of quadrivalent influenza vaccines has been expected to be a cost-effective strategy.

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.

BACKGROUND: With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, a vaccine against COVID-19 is urgently needed. We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity. METHODS: In this randomised, double-blind, placebo-controlled, phase 1/2 clinical trial, healthy adults aged 18-59 years were recruited from the community in Suining County of Jiangsu province, China. Adults with SARS-CoV-2 exposure or infection history, with axillary temperature above 37·0°C, or an allergic reaction to any vaccine component were excluded. The experimental vaccine for the phase 1 trial was manufactured using a cell factory process (CellSTACK Cell Culture Chamber 10, Corning, Wujiang, China), whereas those for the phase 2 trial were produced through a bioreactor process (ReadyToProcess WAVE 25, GE, Umea, Sweden). The phase 1 trial was done in a dose-escalating manner. At screening, participants were initially separated (1:1), with no specific randomisation, into two vaccination schedule cohorts, the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and within each cohort the first 36 participants were assigned to block 1 (low dose CoronaVac [3 µg per 0·5 mL of aluminium hydroxide diluent per dose) then another 36 were assigned to block 2 (high-dose Coronavc [6 µg per 0·5 mL of aluminium hydroxide diluent per dse]). Within each block, participants were randomly assigned (2:1), using block randomisation with a block size of six, to either two doses of CoronaVac or two doses of placebo. In the phase 2 trial, at screening, participants were initially separated (1:1), with no specific randomisation, into the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and participants were randomly assigned (2:2:1), using block randomisation with a block size of five, to receive two doses of either low-dose CoronaVac, high-dose CoronaVac, or placebo. Participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after injection in all participants who were given at least one dose of study drug (safety population). The primary immunogenic outcome was seroconversion rates of neutralising antibodies to live SARS-CoV-2 at day 14 after the last dose in the days 0 and 14 cohort, and at day 28 after the last dose in the days 0 and 28 cohort in participants who completed their allocated two-dose vaccination schedule (per-protocol population). This trial is registered with ClinicalTrials.gov, NCT04352608, and is closed to accrual. FINDINGS: Between April 16 and April 25, 2020, 144 participants were enrolled in the phase 1 trial, and between May 3 and May 5, 2020, 600 participants were enrolled in the phase 2 trial. 743 participants received at least one dose of investigational product (n=143 for phase 1 and n=600 for phase 2; safety population). In the phase 1 trial, the incidence of adverse reactions for the days 0 and 14 cohort was seven (29%) of 24 participants in the 3 ug group, nine (38%) of 24 in the 6 µg group, and two (8%) of 24 in the placebo group, and for the days 0 and 28 cohort was three (13%) of 24 in the 3 µg group, four (17%) of 24 in the 6 µg group, and three (13%) of 23 in the placebo group. The seroconversion of neutralising antibodies on day 14 after the days 0 and 14 vaccination schedule was seen in 11 (46%) of 24 participants in the 3 µg group, 12 (50%) of 24 in the 6 µg group, and none (0%) of 24 in the placebo group; whereas at day 28 after the days 0 and 28 vaccination schedule, seroconversion was seen in 20 (83%) of 24 in the 3 µg group, 19 (79%) of 24 in the 6 µg group, and one (4%) of 24 in the placebo group. In the phase 2 trial, the incidence of adverse reactions for the days 0 and 14 cohort was 40 (33%) of 120 participants in the 3 µg group, 42 (35%) of 120 in the 6 µg group, and 13 (22%) of 60 in the placebo group, and for the days 0 and 28 cohort was 23 (19%) of 120 in the 3 µg group, 23 (19%) of 120 in the 6 µg group, and 11 (18%) of 60 for the placebo group. Seroconversion of neutralising antibodies was seen for 109 (92%) of 118 participants in the 3 µg group, 117 (98%) of 119 in the 6 µg group, and two (3%) of 60 in the placebo group at day 14 after the days 0 and 14 schedule; whereas at day 28 after the days 0 and 28 schedule, seroconversion was seen in 114 (97%) of 117 in the 3 µg group, 118 (100%) of 118 in the 6 µg group, and none (0%) of 59 in the placebo group. INTERPRETATION: Taking safety, immunogenicity, and production capacity into account, the 3 µg dose of CoronaVac is the suggested dose for efficacy assessment in future phase 3 trials. FUNDING: Chinese National Key Research and Development Program and Beijing Science and Technology Program.

Filamentous microalgae as an advantageous co-substrate for enhanced methane production and digestate dewaterability in anaerobic co-digestion of pig manure.

This study aimed at exploring filamentous microalgae (Tribonema sp.) as an advantageous co-substrate for anaerobic digestion (AD) of pig manure. Its impacts on the AD performance were assessed in terms of methane yield, energy conversion efficiency, digestion kinetics, and digestate dewaterability. The microalgae substantially improved methane yield, AD kinetics, and digestate dewaterability of the AD process. The enhancement in methane yield ranged from 2 to 27.4%, with the maximum enhancement (corresponding to an energy conversion efficiency of 81%) occurring at a mixing ratio of 1:1 (VS basis). The AD kinetics was improved as indicated by the increased hydrolysis rate constants and diminished lag time. The specific resistance to filtration (SRF) of the digestate decreased significantly with the increasing proportion of the microalgae in the co-substrates, which would facilitate digestate processing and valorisation. Subsequently, the high biomass productivity of the microalgae (441 mg/L/d) in liquid digestate would enable sustainable bioenergy production through nutrient recycling.