The spread of SARS-CoV-2 virus in the ongoing global pandemic has led to infections of millions of people and losses of many lives. The rapid, accurate and convenient SARS-CoV-2 virus detection is ...crucial for controlling and stopping the pandemic. Diagnosis of patients in the early stage infection are so far limited to viral nucleic acid or antigen detection in human nasopharyngeal swab or saliva samples. Here we developed a method for rapid and direct optical measurement of SARS-CoV-2 virus particles in one step nearly without any sample preparation using a spike protein specific nanoplasmonic resonance sensor. As low as 370 vp/mL were detected in one step within 15 min and the virus concentration can be quantified linearly in the range of 0 to 107 vp/mL. Measurements shown on both generic microplate reader and a handheld smartphone connected device suggest that our low-cost and rapid detection method may be adopted quickly under both regular clinical environment and resource-limited settings.
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•15min one step SARS-CoV-2 viral particles detection.•No sample processing and low-cost equipment and biosensor chip.•Sensitive for asymptomatic carriers diagnosis potentially.
Coronavirus disease 2019 (COVID-19) has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than 1,000 memory B cells specific to ...SARS-CoV-2 S1 or its RBD (receptor binding domain) and obtain 729 paired heavy- and light-chain fragments. Among these, 178 antibodies test positive for antigen binding, and the majority of the top 17 binders with EC50 below 1 nM are RBD binders. Furthermore, we identify 11 neutralizing antibodies, eight of which show IC50 within 10 nM, and the best one, 414-1, with IC50 of 1.75 nM. Through epitope mapping, we find three main epitopes in RBD recognized by these antibodies, and epitope-B antibody 553-15 could substantially enhance the neutralizing abilities of most of the other antibodies. We also find that 515-5 could cross neutralize the SARS-CoV pseudovirus. Altogether, our study provides 11 potent human neutralizing antibodies for COVID-19 as therapeutic candidates.
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•11 neutralizing antibodies against SARS-CoV-2 target three main epitopes on RBD•Epitope-A antibody 414-1 shows neutralizing IC50 at 1.75 nM•Epitope-B antibody 553-15 can enhance the neutralizing abilities of other antibodies•One neutralizing antibody, 515-5, can cross neutralize SARS-CoV pseudovirus
Wan et al. identify 11 potent neutralizing antibodies against COVID-19 from 11 convalescent patients. These human neutralizing antibodies target three separate epitopes on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, and epitope-B antibody (553-15) can enhance the neutralizing abilities of most other antibodies.
Induction of antigen-specific immune activation by the maturation of dendritic cells (DCs) is a strategy used for cancer immunotherapy. In this study, we find that FimH, which is an Escherichia coli ...adhesion portion, induces toll-like receptor 4-dependent and myeloid differentiation protein 2-independent DC maturation in mice in vivo. A combined treatment regimen with FimH and antigen promotes antigen-specific immune activation, including proliferation of T cells, production of IFN-γ and TNF-α, and infiltration of effector T cells into tumors, which consequently inhibits tumor growth in mice in vivo against melanoma and carcinoma. In addition, combined therapeutic treatment of anti-PD-L1 antibodies and FimH treatment efficiently inhibits CT26 tumor growth in BALB/c mice. Finally, FimH promotes human peripheral blood DC activation and syngeneic T-cell proliferation and activation. Taken together, these findings demonstrate that FimH can be a useful adjuvant for cancer immunotherapy.
In light of the pressing environmental and health issues stemming from electromagnetic pollution, advanced electromagnetic wave absorbing materials are urgently sought to solve these problems. The ...present study delved into the fabrication of the resorcinol formaldehyde (RF)/SiO
ceramic particles using the sol-gel route. From SEM images and XRD and XPS analysis, it can be seen that the RF/SiO
ceramic particles are successfully generated after heat treatment at 1500 °C. At room temperature, the sample treated at 1500 °C exhibited a minimum reflection loss of -47.6 dB in the range of 2-18 GHz when the matching thickness was 5.5 mm, showcasing strong attenuation capabilities. Moreover, these particles demonstrated a considerable effective electromagnetic wave absorption bandwidth of 3.14 GHz, evidencing their potential for wideband electromagnetic wave absorption. The temperature adjustment played a pivotal role in achieving optimal impedance matching. When the heat treatment temperature is increased from 800 °C to 1500 °C, the dielectric properties of the material are improved, thus achieving the best impedance matching, thereby optimizing the material's absorption properties for specific frequency ranges, which makes it possible to customize the electromagnetic wave-absorbing characteristics to meet specific requirements across a range of applications.
The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a ...growing number of non-natural polymers. Despite its free availability to academic users and improving documentation, use of Rosetta has largely remained confined to developers and their immediate collaborators due to the code's difficulty of use, the requirement for large computational resources, and the unavailability of servers for most of the Rosetta applications. Here, we present a unified web framework for Rosetta applications called ROSIE (Rosetta Online Server that Includes Everyone). ROSIE provides (a) a common user interface for Rosetta protocols, (b) a stable application programming interface for developers to add additional protocols, (c) a flexible back-end to allow leveraging of computer cluster resources shared by RosettaCommons member institutions, and (d) centralized administration by the RosettaCommons to ensure continuous maintenance. This paper describes the ROSIE server infrastructure, a step-by-step 'serverification' protocol for use by Rosetta developers, and the deployment of the first nine ROSIE applications by six separate developer teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance, Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated by the number and diversity of these applications, ROSIE offers a general and speedy paradigm for serverification of Rosetta applications that incurs negligible cost to developers and lowers barriers to Rosetta use for the broader biological community. ROSIE is available at http://rosie.rosettacommons.org.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A unique avian-origin A/H7N9 influenza virus has so far caused 134 cases with 44 deaths. Probing the host factors contributing to disease severity, we found that lower levels of plasma inflammatory ...cytokines on hospital admission correlated with faster recovery in 18 patients with A/H7N9 influenza virus, whereas high concentrations of (in particular) IL-6, IL-8, and macrophage inflammatory protein-1β were predictive of a less favorable or fatal outcome. Analysis of bronchoalveolar lavage samples showed up to 1,000-fold greater cytokine/chemokine levels relative to plasma. Furthermore, patients with the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype had more rapid disease progression and were less likely to survive. Compared with patients with the rs12252-T/T or rs12252-T/C genotype of IFITM3, patients with the C/C genotype had a shorter time from disease onset to the time point when they sought medical aid (hospital admission or antiviral therapy) and a shorter interval to development of the acute respiratory distress syndrome stage (reflected by shorter intervals between clinical onset and methylprednisolone treatments and higher rates of mechanical ventilator use), as well as experiencing elevated/prolonged lung virus titers and cytokine production and higher mortality. The present analysis provides reported data on the H7N9 influenza-induced “cytokine storm” at the site of infection in humans and identifies the rs12252-C genotype that compromises IFITM3 function as a primary genetic correlate of severe H7N9 pneumonia. Together with rs12252 sequencing, early monitoring of plasma cytokines is thus of prognostic value for the treatment and management of severe influenza pneumonia.
Background
Macrophages are key effector cells of innate immunity and play a critical role in the immune balance of disease pathogenesis, especially in the tumor microenvironment. In previous studies, ...we showed that FimH, an Escherichia coli adhesion portion, promoted dendritic cell activation. However, the effect of FimH in macrophage polarization has yet to be fully examined. In this study, we investigated the potential effect of FimH on macrophages, as well as the polarization from M2 to M1 macrophages, contributing to the overall antitumor effect
Methods
Mouse bone marrow derived macrophages and peritoneal macrophages were generated to test the effect of FimH in vitro. The expression of costimulatory molecules and production of cytokines were analyzed. The effect of FimH in the tumor-associated macrophages was examine in the B16F10-tumor bearing C57BL/6.
Results
FimH was found to promote M1 macrophage activation. In addition, FimH polarized M2 macrophages, which were induced by interleukin (IL)-4 and IL-13 into M1 macrophages were dependent on toll-like receptor 4 and myeloid differentiation factor 2. Moreover, FimH reprogramed the tumor-associated macrophage (TAM) into M1 macrophages in B16 melanoma tumor-bearing mice and promoted an inflammatory reaction in the tumor microenvironment (TME). Furthermore, FimH promoted M1 macrophage activation, as well as the reversion of M2 macrophages into M1 macrophages in humans. Finally, FimH treatment was found to enhance the anti-cancer immunity of anti-PD-L1 antibody by the induction of M1 polarization from TAM.
Conclusion
This study demonstrated the potential effect of FimH on the activation of macrophages, responsible for the repolarization of M2 macrophages into the M1 phenotype via the TLR4 signaling pathway. Moreover, FimH could also reprogram TAM polarization to the M1 status in the TME, as well as enhance the anti-tumor activity of immune checkpoint blockade.
The outbreak of Zika virus (ZIKV) in 2016 created worldwide health emergency which demand urgent research efforts on understanding the virus biology and developing therapeutic strategies. Here, we ...present a time-resolved chemical proteomic strategy to track the early-stage entry of ZIKV into host cells. ZIKV was labeled on its surface with a chemical probe, which carries a photocrosslinker to covalently link virus-interacting proteins in living cells on UV exposure at different time points, and a biotin tag for subsequent enrichment and mass spectrometric identification of the receptor or other host proteins critical for virus internalization. We identified Neural Cell Adhesion Molecule (NCAM1) as a potential ZIKV receptor and further validated it through overexpression, knockout, and inhibition of NCAM1 in Vero cells and human glioblastoma cells U-251 MG. Collectively, the strategy can serve as a universal tool to map virus entry pathways and uncover key interacting proteins.
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