The extracellular cyclophilin A-integrin ß2 complex as a therapeutic target of viral pneumonia.

The acute respiratory virus infection can induce uncontrolled inflammatory responses, such as cytokine storm and viral pneumonia, which are the major causes of death in clinical cases. Cyclophilin A (CypA) is mainly distributed in the cytoplasm of resting cells and released into the extracellular space in response to inflammatory stimuli. Extracellular CypA (eCypA) is upregulated and promotes inflammatory response in severe COVID-19 patients. However, how eCypA promotes virus-induced inflammatory response remains elusive. Here, we observe that eCypA is induced by influenza A and B viruses and SARS-CoV-2 in cells, mice, or patients. Anti-CypA mAb reduces pro-inflammatory cytokines production, leukocytes infiltration, and lung injury in virus-infected mice. Mechanistically, eCypA binding to integrin ß2 triggers integrin activation, thereby facilitating leukocyte trafficking and cytokines production via the focal adhesion kinase (FAK)/GTPase and FAK/ERK/P65 pathways, respectively. These functions are suppressed by the anti-CypA mAb that specifically blocks eCypA-integrin ß2 interaction. Overall, our findings reveal that eCypA-integrin ß2 signaling mediates virus-induced inflammatory response, indicating that eCypA is a potential target for antibody therapy against viral pneumonia.

Antisymmetric Lamb Wave Simulation Study Based on Electromagnetic Acoustic Transducer with Periodic Permanent Magnets.

Due to its multi-mode and dispersion characteristics, Lamb waves cause interference to signal processing, which profoundly limits their application in nondestructive testing. To resolve this issue, firstly, based on the traditional EMAT, a horizontal polarization periodic permanent magnet electromagnetic acoustic transducer (HP-PPM-EMAT) was proposed. A 2-D finite element model was then developed to compare magnetic flux density, Lorentz force, and signal strength between the traditional EMAT and the HP-PPM-EMAT. The simulation results show that the HP-PPM-EMAT enhances the A0 mode Lamb wave (A0 wave) and suppresses the S0 mode Lamb wave (S0 wave). Finally, the influence of structural parameters of the HP-PPM-EMAT on the total displacement amplitude ratio of A0 and S0 was investigated using orthogonal test theory, and the width of magnet units was improved based on the orthogonal test. The results show that the total displacement amplitude ratio of A0 to S0 of the improved HP-PPM-EMAT can be improved by a factor of 7.74 compared with that of the traditional Lamb wave EMAT, which can produce higher-purity A0 mode Lamb waves.

Ponicidin attenuates streptozotocin-induced diabetic nephropathy in rats via modulating hyperlipidemia, oxidative stress, and inflammatory markers.

The present research work was proposed to discover the beneficial roles of ponicidin against the streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats via modulating the oxidative stress and inflammation. The DN was initiated to the Wistar rats via administering 45 mg/kg of STZ and then diabetic animals were supplemented with 50 mg/kg of ponicidin and 150 mg/kg of metformin (standard drug) for 8 weeks. The body weight and food intake of animals were checked every week. The glucose, insulin, and homeostasis model assessment- insulin resistance  (HOMA-IR) levels in the serum were assessed using kits. The levels of reactive oxygen species (ROS) accumulation, oxidative stress and antioxidant markers, and pro-inflammatory cytokines were examined using assay kits. The levels of lipid profiles and renal function markers were investigated using respective kits. The renal tissues were analyzed microscopically to detect the histological alterations. The ponicidin treatment effectively decreased the body weight, food intake, HOMA-IR, and HbAlc levels in the DN animals. The levels of ROS and MDA were decreased and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities were improved by the ponicidin. The ponicidin also reduced the blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), and kidney injury molecule (KIM-1) levels. The levels of low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), free fatty acid (FFA), and total cholesterol (TC) were decreased and the high-density lipoprotein (HDL) level was improved by the ponicidin treatment to the DN rats. The tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), nuclear factor-kappa B (NF-κB), and IL-6 levels were appreciably attenuated by the ponicidin. The ponicidin also ameliorated the DM-provoked histological alterations in the renal tissues. In conclusion, this study work evidenced that ponicidin has the therapeutic action in ameliorating the development of DN via averting oxidative stress, inflammation, and renal injury. It could be a promising therapeutic agent to treat DN in the future.

Numerical Study and Optimal Design of the Butterfly Coil EMAT for Signal Amplitude Enhancement.

The low energy conversion efficiency of electromagnetic acoustic transducers (EMATs) is a critical issue in nondestructive testing applications. To overcome this shortcoming, a butterfly coil EMAT was developed and optimized by numerical simulation based on a 2-D finite element model. First, the effect of the structural parameters of the butterfly coil EMAT was investigated by orthogonal test theory. Then, a modified butterfly coil EMAT was designed that consists of three-square permanent magnets with opposite polarity (TSPM-OP) to enhance the signal amplitude. Finally, the signal amplitude obtained from the three types of EMATs, that is, the traditional EMAT, the EMAT optimized by orthogonal test theory, and the modified EMAT with TSPM-OP, were analyzed and compared. The results show that the signal amplitude achieved by the modified butterfly coil EMAT with TSPM-OP can be increased by 4.97 times compared to the traditional butterfly coil EMAT.

Optimization Design of Surface Wave Electromagnetic Acoustic Transducers Based on Simulation Analysis and Orthogonal Test Method.

The energy conversion of electromagnetic acoustic transducers (EMATs) is typically lower, which seriously restricts the application of EMATs in the field of non-destructive testing and evaluation. In this work, parameters of surface wave EMATs, including structural parameters and electrical parameters, are investigated using the orthogonal test method to improve the transducer's energy conversion efficiency. Based on the established finite element 2-D model of EMATs, the amplitude of the displacement components at the observation point of a plate is the optimization objective to be maximized with five parameters pertaining to the magnets, meander-line coils, and excitation signal as design variables. Results show that the signal amplitude of EMATs is 3.48 times on in-plane and 3.49 times on out-of-plane, respectively, compared with the original model. Furthermore, a new material (amorphous nanocrystalline material of type 1K107) is applied to optimize the magnetic circuit of EMATs and enhance the eddy current in an aluminum plate to increase the signal amplitude. Finally, the signal amplitudes obtained from the three types of models, that is, the original one, the optimization one after an orthogonal test, and the optimization one with the addition of magnetic concentrators, are analyzed and compared, indicating that the signal amplitude, compared with the original one, is 6.02 times on in-plane and 6.20 times on out-of-plane, respectively.

Long Noncoding RNA Lnc-MxA Inhibits Beta Interferon Transcription by Forming RNA-DNA Triplexes at Its Promoter.

Previously, we identified a set of long noncoding RNAs (lncRNAs) that were differentially expressed in influenza A virus (IAV)-infected cells. In this study, we focused on lnc-MxA, which is upregulated during IAV infection. We found that the overexpression of lnc-MxA facilitates the replication of IAV, while the knockdown of lnc-MxA inhibits viral replication. Further studies demonstrated that lnc-MxA is an interferon-stimulated gene. However, lnc-MxA inhibits the Sendai virus (SeV)- and IAV-induced activation of beta interferon (IFN-ß). A luciferase assay indicated that lnc-MxA inhibits the activation of the IFN-ß reporter upon stimulation with RIG-I, MAVS, TBK1, or active IRF3 (IRF3-5D). These data indicated that lnc-MxA negatively regulates the RIG-I-mediated antiviral immune response. A chromatin immunoprecipitation (ChIP) assay showed that the enrichment of IRF3 and p65 at the IFN-ß promoter in lnc-MxA-overexpressing cells was significantly lower than that in control cells, indicating that lnc-MxA interfered with the binding of IRF3 and p65 to the IFN-ß promoter. Chromatin isolation by RNA purification (ChIRP), triplex pulldown, and biolayer interferometry assays indicated that lnc-MxA can bind to the IFN-ß promoter. Furthermore, an electrophoretic mobility shift assay (EMSA) showed that lnc-MxA can form complexes with the IFN-ß promoter fragment. These results demonstrated that lnc-MxA can form a triplex with the IFN-ß promoter to interfere with the activation of IFN-ß transcription. Using a vesicular stomatitis virus (VSV) infection assay, we confirmed that lnc-MxA can repress the RIG-I-like receptor (RLR)-mediated antiviral immune response and influence the antiviral status of cells. In conclusion, we revealed that lnc-MxA is an interferon-stimulated gene (ISG) that negatively regulates the transcription of IFN-ß by forming an RNA-DNA triplex.IMPORTANCE IAV can be recognized as a nonself molecular pattern by host immune systems and can cause immune responses. However, the intense immune response induced by influenza virus, known as a "cytokine storm," can also cause widespread tissue damage (X. Z. J. Guo and P. G. Thomas, Semin Immunopathol 39:541-550, 2017, https://doi.org/10.1007/s00281-017-0636-y; S. Yokota, Nihon Rinsho 61:1953-1958, 2003; I. A. Clark, Immunol Cell Biol 85:271-273, 2007). Meanwhile, the detailed mechanisms involved in the balancing of immune responses in host cells are not well understood. Our studies reveal that, as an IFN-inducible gene, lnc-MxA functions as a negative regulator of the antiviral immune response. We uncovered the mechanism by which lnc-MxA inhibits the activation of IFN-ß transcription. Our findings demonstrate that, as an ISG, lnc-MxA plays an important role in the negative-feedback loop involved in maintaining immune homeostasis.

Influence of aperture angles and design focal depths on the performance of point-focusing shear vertical wave electromagnetic acoustic transducers.

Electromagnetic acoustic transducers (EMATs) with concentric meander-line (CML) coils possess the capability of producing point-focusing shear vertical (PFSV) waves. For the CML coil, an intercepted circular arc of the concentric circle with a continuously changing spacing, the aperture angle is a key factor effecting the point-focusing performance. Thus, the influence of aperture angles of CML coils on the point-focusing behavior of PFSV-EMATs is analyzed using the established finite element modeling in detail, which also considers the effect of lift-off distance on the signal amplitude. The beam directional pattern is characterized quantitatively by the half-power beam width, indicating the relationship between the aperture angle and beam width. In addition, since the focus offset is sensitive in depth direction, the effect of design focal depths on focal offset is also carefully studied. Three CML coils with an aperture angle of 30°, 90°, and 150° are fabricated by printed circuit board technique and experimentally analyzed; the experimental results are well consistent with the simulation results. These findings can be used to design optimized PFSV-EMATs with good point-focusing performance.

An Improved Design of the Spiral-Coil EMAT for Enhancing the Signal Amplitude.

The low energy transition efficiency of electromagnetic ultrasonic transducer (EMAT) is a common problem in practical application. For the purpose of enhancing the amplitude of the received signal, an improved double-coil bulk wave EMAT is proposed for the thickness measurement of metallic block. This new configuration of magnets consists of a solid cylindrical magnet and a ring-shaped magnet encircling the outer side of the solid cylindrical one. A double-coil was applied instead of a single spiral-coil. Numerical simulations were performed to analyze and optimize the proposed configuration of the EMAT by the 2-D axisymmetric finite element model (FEM). The experiment effectively verifies the rationality of the new configuration and the feasibility of improving the signal strength.

Assessment of the internal genes of influenza A (H7N9) virus contributing to high pathogenicity in mice.

UNLABELLED: The recently identified H7N9 influenza A virus has caused severe economic losses and worldwide public concern. Genetic analysis indicates that its six internal genes all originated from H9N2 viruses. However, the H7N9 virus is more highly pathogenic in humans than H9N2, which suggests that the internal genes of H7N9 have mutated. To analyze which H7N9 virus internal genes contribute to its high pathogenicity, a series of reassortants was generated by reverse genetics, with each virus containing a single internal gene of the typical A/Anhui/1/2013 (H7N9) (AH-H7N9) virus in the genetic background of the A/chicken/Shandong/lx1023/2007 (H9N2) virus. The replication ability, polymerase activity, and pathogenicity of these viruses were then evaluated in vitro and in vivo. These recombinants displayed high genetic compatibility, and the H7N9-derived PB2, M, and NP genes were identified as the virulence genes for the reassortants in mice. Further investigation confirmed that the PB2 K627 residue is critical for the high pathogenicity of the H7N9 virus and the reassortant containing the H7N9-derived PB2 segment (H9N2-AH/PB2). Notably, the H7N9-derived PB2 gene displayed greater compatibility with the H9N2 genome than that of H7N9, endowing the H9N2-AH/PB2 reassortant with greater viability and virulence than the parental H7N9 virus. In addition, the H7N9 virus, with the exception of the H9N2 reassortants, could effectively replicate in human A549 cells. Our results indicate that PB2, M, and NP are the key virulence genes, together with the surface hemagglutinin (HA) and neuraminidase (NA) proteins, contributing to the high infectivity of the H7N9 virus in humans. IMPORTANCE: To date, the novel H7N9 influenza A virus has caused 437 human infections, with approximately 30% mortality. Previous work has primarily focused on the two viral surface proteins, HA and NA, but the contribution of the six internal genes to the high pathogenicity of H7N9 has not been systematically studied. Here, the H9N2 virus was used as a genetic backbone to evaluate the virulence genes of H7N9 virus in vitro and in vivo. Our data indicate that the PB2, M, and NP genes play important roles in viral infection in mice and, together with HA and NA, contribute to the high infectivity of the H7N9 virus in humans.

The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity.

The Orthopoxvirus (OPXV) genus of the Poxviridae includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the P2L gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.

A nuclear export signal in the matrix protein of Influenza A virus is required for efficient virus replication.

The influenza A virus matrix 1 protein (M1) shuttles between the cytoplasm and the nucleus during the viral life cycle and plays an important role in the replication, assembly, and budding of viruses. Here, a leucine-rich nuclear export signal (NES) was identified specifically for the nuclear export of the M1 protein. The predicted NES, designated the Flu-A-M1 NES, is highly conserved among all sequences from the influenza A virus subtype, but no similar NES motifs are found in the M1 sequences of influenza B or C viruses. The biological function of the Flu-A-M1 NES was demonstrated by its ability to translocate an enhanced green fluorescent protein (EGFP)-NES fusion protein from the nucleus to the cytoplasm in transfected cells, compared to the even nuclear and cytoplasmic distribution of EGFP. The translocation of EGFP-NES from the nucleus to the cytoplasm was not inhibited by leptomycin B. NES mutations in M1 caused a nuclear retention of the protein and an increased nuclear accumulation of NEP during transfection. Indeed, as shown by rescued recombinant viruses, the mutation of the NES impaired the nuclear export of M1 and significantly reduced the virus titer compared to titers of wild-type viruses. The NES-defective M1 protein was retained in the nucleus during infection, accompanied by a lowered efficiency of the nuclear export of viral RNPs (vRNPs). In conclusion, M1 nuclear export was specifically dependent on the Flu-A-M1 NES and critical for influenza A virus replication.

Targeting androgen receptor degradation with PROTACs from bench to bedside.

Inhibition of androgen receptor (AR) has been extensively investigated to treat prostate cancer. Resistance mechanisms such as increased levels of androgen production, increased AR gene, enhancer expression and AR point mutations always reduce the clinical efficacy. Design and discovery of small-molecule PROTAC AR degraders have been pursued as a new therapeutic strategy to overcome common resistance mechanisms developed during prostate cancer treatment. In the last two decades, potent and efficacious PROTAC AR degraders have been gotten rapid development and several such compounds have been advanced into preclinical phase and phase I/II trials for the treatment of human prostate cancers. Especially, the first PROTAC to enter the clinic, ARV-110, has shown good clinical effects in patients with mCRPC. This fully demonstrates the high clinical value of PROTAC strategy in treatment of human diseases. Here, we summarized the recent advances in the development of these potential clinical-stage PROTAC AR degraders.

Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins.

Influenza B circulates annually and causes substantial disease burden in humans. However, little is known about the infection mechanisms of influenza B virus (IBV). Here, we find that the host factor cyclophilin A (CypA) facilitates IBV replication by targeting IBV non-structural protein 1 (BNS1) and nucleoprotein (BNP). CypA promotes OTUD4-mediated K48-linked BNS1 deubiquitination to stabilize BNS1 by upregulating OTUD4 expression. Meanwhile, CypA and the E3 ligase MIB1 competitively interact with BNP to inhibit its proteasomal degradation. Moreover, cyclosporine A treatment or CypA R55A mutation results in an impaired function of CypA in IBV replication. Notably, BNP hijacks CypA into the nucleus to enhance the activity of viral ribonucleoprotein complexes by enhancing the interaction between BNP and IBV polymerase basic protein 1. Taken together, this study unveils the critical role of CypA in facilitating IBV replication, suggesting that CypA is a promising target for anti-IBV drug.

SARS-CoV-2 nonstructural protein 6 triggers endoplasmic reticulum stress-induced autophagy to degrade STING1.

ABBREVIATIONS: aa: amino acid; ATF6: activating transcription factor 6; ATG5: autophagy related 5; CCPG1: cell cycle progression 1; CFTR: CF transmembrane conductance regulator; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; CHX: cycloheximide; Co-IP: co-immunoprecipitation; CQ: chloroquine; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum to nucleus signaling 1; GFP: green fluorescent protein; HSPA5/GRP78: heat shock protein family A (Hsp70) member 5; HSV-1: herpes simplex virus type 1; IFIT1: interferon induced protein with tetratricopeptide repeats 1; IFNB1/IFN-ß: interferon beta 1; IRF3: interferon regulatory factor 3; ISG15: ISG15 ubiquitin like modifier; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MAVS: mitochondrial antiviral signaling protein; MOI: multiplicity of infection; NFKB/NF-κB: nuclear factor kappa B; NSP6: non-structural protein 6; Δ106-108: deletion of amino acids 106-108 in NSP6 of SARS-CoV-2; Δ105-107: deletion of amino acids 105-107 in NSP6 of SARS-CoV-2; RETREG1/FAM134B: reticulophagy regulator 1; RIGI/DDX58: RNA sensor RIG-I; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1.

Effects of a 'learn to think' intervention programme on primary school students.

BACKGROUND: Methods for teaching thinking may be described as out-of-context or infusion. Both approaches have potential to raise students' general cognitive processing ability and so raise academic achievement, but each has disadvantages. AIMS: To describe and evaluate a theory-based learn to think (LTT) curriculum for primary school students, which draws on the strengths of both out-of-context and infusion approaches. SAMPLE: One-hundred and sixty-six students in three classes of Grade 1 (6+ years old), Grade 2 (7+ years old), and Grade 3 (8+ years old) in a primary school in Shanxi province, China, randomly ascribed to experimental (90) and control (76) groups. METHODS: All students were pre-tested for non-verbal intelligence and academic achievement. Experimental students followed the LTT curriculum (one activity every 2 weeks) for 4 school years. All were post-tested on three occasions for thinking ability and four times for academic achievement. RESULTS: Grade 1 and Grade 2 students showed effects of LTT from 1 year after their start and increasing: on thinking ability d= .78-1.45; on Chinese d= .68-1.07; on maths .58-.87. Grade 3 students showed effects from 6 months after their start: on thinking ability .90-1.37; Chinese .77-1.32; maths .65-1.29. The effects were concentrated in students in the middle band of initial ability. CONCLUSIONS: A curriculum for teaching thinking based on a structured theoretical model that combines elements of out-of-context and infusion methods has been shown to have long-term far transfer effects on students' thinking ability and academic achievement. More work is needed to meet the needs of a wider range of abilities.

[Methodological study on eliminating nucleic acid contamination in molecular diagnostic laboratory].

Nucleic acid detection technique has good sensitivity and specificity and is widely used in in vitro diagnosis, animal and plant commodity quarantine, forensic identification, and other fields. However, it is susceptible to carryover contamination during the operation and leads to false-positive results, which seriously affects the detection accuracy. Therefore, finding an effective solution to prevent and eliminate nucleic acid carryover contamination has become particularly urgent. This study compared several different methods for removing nucleic acid contamination and confirmed that sodium hypochlorite solution and PCRguard reagent could effectively eliminate nucleic acid carryover in the liquid and on surfaces of different materials. Besides, the combination of sodium hypochlorite solution and PCRguard can solve the nucleic acid aerosol contamination. This study proposes solutions for the routine prevention of carryover contamination and removal of aerosol that has occurred in molecular diagnostic laboratories.

IgY antibodies against Ebola virus possess post-exposure protection in a murine pseudovirus challenge model and excellent thermostability.

Ebola virus (EBOV) is one of the most virulent pathogens that causes hemorrhagic fever and displays high mortality rates and low prognosis rates in both humans and nonhuman primates. The post-exposure antibody therapies to prevent EBOV infection are considered effective as of yet. However, owing to the poor thermal stability of mammalian antibodies, their application in the tropics has remained limited. Therefore, a thermostable therapeutic antibody against EBOV was developed modelled on the poultry(chicken) immunoglobulin Y (IgY). The IgY antibodies retaining their neutralising activity at 25°C for one year, displayed excellent thermal stability, opposed to conventional polyclonal antibodies (pAbs) or monoclonal antibodies (mAbs). Laying hens were immunised with a variety of EBOV vaccine candidates and it was confirmed that VSVΔG/EBOVGP encoding the EBOV glycoprotein could induce high titer neutralising antibodies against EBOV. The therapeutic efficacy of immune IgY antibodies in vivo was evaluated in the newborn Balb/c mice who have been challenged with the VSVΔG/EBOVGP model. Mice that have been challenged with a lethal dose of the pseudovirus were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. The group receiving a high dose of 106 NAU/kg (neutralising antibody units/kilogram) showed complete protection with no symptoms of a disease, while the low-dose group was only partially protected. Conversely, all mice receiving naive IgY died within 10 days. In conclusion, the anti-EBOV IgY exhibits excellent thermostability and protective efficacy. Anti-EBOV IgY shows a lot of promise in entering the realm of efficient Ebola virus treatment regimens.

The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice.

As COVID-19 continues to spread rapidly worldwide and variants continue to emerge, the development and deployment of safe and effective vaccines are urgently needed. Here, we developed an mRNA vaccine based on the trimeric receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein fused to ferritin-formed nanoparticles (TF-RBD). Compared to the trimeric form of the RBD mRNA vaccine (T-RBD), TF-RBD delivered intramuscularly elicited robust and durable humoral immunity as well as a Th1-biased cellular response. After further challenge with live SARS-CoV-2, immunization with a two-shot low-dose regimen of TF-RBD provided adequate protection in hACE2-transduced mice. In addition, the mRNA template of TF-RBD was easily and quickly engineered into a variant vaccine to address SARS-CoV-2 mutations. The TF-RBD multivalent vaccine produced broad-spectrum neutralizing antibodies against Alpha (B.1.1.7) and Beta (B.1.351) variants. This mRNA vaccine based on the encoded self-assembled nanoparticle-based trimer RBD provides a reference for the design of mRNA vaccines targeting SARS-CoV-2.

Insight into the improvement of dewatering performance of waste activated sludge and the corresponding mechanism by biochar-activated persulfate oxidation.

A novel activator, corn biochar, was produced to activate persulfate to dewater waste activated sludge (WAS). Results demonstrated that the biochar-activated persulfate oxidation can effectively improve the dewatering performance of WAS. After treating WAS by biochar-activated persulfate oxidation (biochar dosage: 2.1 g/L, persulfate concentration: 7.5 mM) at the original WAS pH, standardized-capillary suction time (SCST) increased to 4.21 times and moisture content (MC) decreased to 43.4%, indicating an excellent performance of WAS dewatering. The decrease of residual persulfate with the increasing biochar dosage during WAS dewatering process illustrated that the role of persulfate in improving WAS dewatering was because of the biochar activation. The behaviors of extracellular polymers (EPS) proved that the protein in tightly bound EPS (TB-EPS) linked to WAS dewatering, and its content significantly reduced to 10.5 mg/g-volatile solids (VS) after WAS treatment. Three-dimensional fluorescence spectroscopy for EPS once again proved that the disintegration of tryptophan protein and humic acid (hydrophobic organic substances in EPS) was responsible for the improvement of WAS dewatering. To sum up, the biochar-activated persulfate oxidation was a feasible application in improving WAS dewatering.

Effect of biosurfactant on ammonia removal from anaerobically digested swine wastewater by multi soil layering treatment bioreactors.

A biosurfactant was harvested from anaerobically digested swine wastewater (ADSW) and employed to enhance ammonia removal in a comparative study using two multiple soil layer bioreactors (MSLs). Results showed that toxicity of the biosurfactant to microorganisms was negligible within the experimental concentration range. Optimal dose of the biosurfactant in MSLs to remove ammonia from ADSW was 0.1 CMC (Critical Micelle Concentration) under different hydraulic loading rate (HLR). For instance, when the HLR was adjusted as 80, 120, 160, and 200 L/(m2·d), the average ammonia removal efficiency in MSL without biosurfactant addition was appeared as 85.6%, 89.2%, 85.2% and 84.1%, respectively, after enhanced by 0.1 CMC of the biosurfactant under the same condition, the average ammonia removal efficiency was improved to 90.1%, 92.6%, 90.3%, and 87.4%, respectively. Inlet ammonia concentration obviously affected ammonia removal, the average ammonia removal efficiency increased rapidly to 93.0% and 89.1% in MSLs (with and without biosurfactant) along with the increasing inlet ammonia concentration from 800 mg/L to 1000 mg/L, and subsequently dropped to 78.9% and 79.7% with a further increase in the inlet ammonia concentration to 1400 mg/L. These results showed that the biosurfactant effectively enhanced ammonia removal by using MSL. Thus, the construction of MSL represented an effective means of reducing ammonia pollution caused by swine wastewater, and the use of biosurfactant was assuredly a promising and feasible option for enhancing the biological activity in MSL bioreactor.