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The recent development and mass administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines allowed for disease control, reducing hospitalizations and mortality. Most of these vaccines target the SARS-CoV-2 Spike (S) protein antigens, culminating with the production of neutralizing antibodies (NAbs) that disrupt the attachment of the virus to ACE2 receptors on the host cells. However, several studies demonstrated that the NAbs typically rise within a few weeks after vaccination but quickly reduce months later. Thus, multiple booster administration is recommended, leading to vaccination hesitancy in many populations. Detecting serum anti-SARS-CoV-2 NAbs can instruct patients and healthcare providers on correct booster strategies. Several in vitro diagnostics kits are available; however, their high cost impairs the mass NAbs diagnostic testing. Recently, we engineered an ACE2 mimetic that interacts with the Receptor Binding Domain (RBD) of the SARS-2 S protein. Here we present the use of this engineered mini-protein (p-deface2 mut) to develop a detection assay to measure NAbs in patient sera using a competitive ELISA assay. Serum samples from twenty-one patients were tested. Nine samples (42.8%) tested positive, and twelve (57.1%) tested negative for neutralizing sera. The data correlated with the result from the standard commercial assay that uses human ACE2 protein. This confirmed that p-deface2 mut could replace human ACE2 in ELISA assays. Using bacterially expressed p-deface2 mut protein is cost-effective and may allow mass SARS-CoV-2 NAbs detection, especially in low-income countries where economical diagnostic testing is crucial. Such information will help providers decide when a booster is required, reducing risks of reinfection and preventing the administration before it is medically necessary. [ABSTRACT FROM AUTHOR]

We study the distributed output‐feedback tracking control problem by linear sampled‐data control for nonlinear multi‐agent systems with unmeasurable states in this paper. Noting that sampled‐data control can effectively reduce implementation cost and time, we develop a novel linear sampled‐data high‐gain homogeneous domination control strategy by integrating backstepping method and high‐gain homogeneous domination method into sampled‐data control. A series of linear sampled‐data output‐feedback controllers and reduced‐order observers are designed to ensure that the output tracking errors can be tuned arbitrarily small while all states of the closed‐loop system are globally bounded. A numerical example is given to verify the effectiveness of the sampled‐data strategy. [ABSTRACT FROM AUTHOR]

This paper considers the global stabilization for a class of uncertain nonlinear systems with unknown powers, unknown control directions, and unknown nonlinearities. Mainly due to the presence of the unknown powers which have not known upper bound, no existing methods are applicable to the control problem to be solved. In this paper, to compensate the serious system uncertainties and particularly to overcome the major obstruction from unknown powers, we appeal to the mechanism of switching adaptive feedback. By flexibly combining the domination and the method of adding a power integrator, we propose a new adaptive controller design, whose design parameters are tuned online based on a switching logic. The designed controller will become operative as long as finite switchings happen and will not lead to Zeno phenomenon, and can guarantee the global boundedness as well as ultimate convergence of the resulting closed-loop system. Two numerical examples are given to demonstrate the effectiveness of the developed design scheme. [ABSTRACT FROM AUTHOR]

Asarinin is one of the main active chemical components isolated from Xixin, a Chinese medicine. To investigate the role of asarinin in rheumatoid arthritis (RA), the present study investigated the effect of an asarinin-medicated serum on human fibroblast-like synoviocytes in vitro. An asarinin-medicated serum was generated and analyzed by high-performance liquid chromatography. Fibroblast-like synoviocytes were isolated from patients with osteoarthritis and RA. The third generation of the rheumatoid synoviocytes was used in the experimental research and the third generation of osteoarthritic synoviocytes was used as control cells. Trypan blue staining was performed to detect the viability of RA synovial fibroblasts (RASFs). ELISA, reverse transcription-quantitative (RT-q) PCR and western blotting were also performed to detect the expression of various cytokines. Additionally, RT-qPCR was employed to detect Toll-like receptor (TLR) 2 and TLR4. The results revealed that medicated asarinin serum inhibited the viability of RASFs in a dose- and time-dependent manner. The serum also suppressed the expression of interleukin (IL)-17A, tumor necrosis factor-α, interferon-γ, IL-6, TLR2 and TLR4. The inhibitory effect of asarinin drug serum on RASFs may be achieved by inhibition of T helper cell (Th)1/Th17 cytokines through suppression of TLR2 and TLR4. [ABSTRACT FROM AUTHOR]

This paper considers the global output-feedback stabilisation for power integrator systems with unknown control direction. The presence of uncontrollable and unobservable linearisation renders the strategy based on Nussbaum function rather difficult (even impossible) to compensate the unknown control direction. In this paper, to dominate the inherent nonlinearities and unknowns, a powerful switching strategy is proposed by combining an output-feedback scheme and a switching mechanism. First, a special case with known control direction is considered to provide a basic structure and selection rules of design parameters for the expected controller, and then, the essential case with unknown control direction is investigated to build a suitable switching logic to online tune the design parameters. The proposed switching-type output-feedback controller guarantees that all the system signals are globally bounded and ultimately converge to zero. A numerical example is given to illustrate the effectiveness of the proposed methods. [ABSTRACT FROM AUTHOR]

Summary: This paper is devoted to the global stabilization via output feedback for a class of nonlinear systems with unknown relative degree, dynamics uncertainties, unknown control direction, and nonparametric uncertain nonlinearities. In particular, the unknown relative degree is without known upper bound, which renders us to research for a filter with varying dimension rather than the ones with over dimensions in the existing literature. In comparison with more popular but a bit stronger input‐to‐state stable or input‐to‐state practically stable requirement, only bounded‐input bounded‐state stable requirement is imposed on the dynamics uncertainties, which affect the systems in a persistent intensity rather than in a decaying one. In this paper, to compensate multiple serious system uncertainties and realize global output‐feedback stabilization, a design scheme via switching logic together with varying dimensional filter is developed. In this scheme, 2 switching sequences, which separately generate the gains of the controller and act as the varying dimensions of the filter, are designed to overcome unknown control direction, dynamics uncertainties and nonparametric uncertain nonlinearities, and unknown relative degree, respectively. A 2‐mass lumped‐parameter structure is provided to show the effectiveness of the proposed method in this paper. [ABSTRACT FROM AUTHOR]

This paper considers the distributed tracking control problem for a class of nonlinear multi-agent systems with nonlinearly parameterized control coefficients and inherent nonlinearities. The essential of multi-agent systems makes it difficult to directly generalize the existing works for single nonlinearly parameterized systems with uncontrollable unstable linearization to the case in this paper. To dominate the inherent nonlinearities and nonlinear parametric uncertainties, a powerful distributed adaptive tracking control is presented by combing the algebra graph theory with the distributed backstepping method, which guarantees that all the closed-loop system signals are global bounded while the range of the tracking error between the follower's output and the leader's output can be tuned arbitrarily small. Finally, a numerical example is provided to verify the validity of the developed methods.

Asarinin is one of the main active chemical components isolated from Xixin, a Chinese medicine. To investigate the role of asarinin in rheumatoid arthritis (RA), the present study investigated the effect of an asarinin-medicated serum on human fibroblast-like synoviocytes in vitro . An asarinin-medicated serum was generated and analyzed by high-performance liquid chromatography. Fibroblast-like synoviocytes were isolated from patients with osteoarthritis and RA. The third generation of the rheumatoid synoviocytes was used in the experimental research and the third generation of osteoarthritic synoviocytes was used as control cells. Trypan blue staining was performed to detect the viability of RA synovial fibroblasts (RASFs). ELISA, reverse transcription-quantitative (RT-q) PCR and western blotting were also performed to detect the expression of various cytokines. Additionally, RT-qPCR was employed to detect Toll-like receptor (TLR) 2 and TLR4. The results revealed that medicated asarinin serum inhibited the viability of RASFs in a dose- and time-dependent manner. The serum also suppressed the expression of interleukin (IL)-17A, tumor necrosis factor-α, interferon-γ, IL-6, TLR2 and TLR4. The inhibitory effect of asarinin drug serum on RASFs may be achieved by inhibition of T helper cell (T h )1/T h 17 cytokines through suppression of TLR2 and TLR4., (Copyright: © Dai et al.)

To study the role of asarinin on collagen-induced arthritis (CIA) and its treatment mechanism on dendritic cells (DCs) and T cells. Before the onset of arthritis, asarinin were given orally to CIA mouse. Macroscopic scoring and micrometer caliper measurement were used to assess arthritis. The occurrence of cartilage destruction and bone erosion were assessed by histology of knee. Sandwich enzyme-linked immunosorbent assay (ELISA) and PCR were used to assess the level of cytokines in hindpaw and arthritic joint. The CD11c MicroBeads were employed to isolate CD11c+ cells from the spleen. Quantitative PCR was used to determine DCs surface molecules of spleen. Macroscopic score and the frequency of arthritis were inhibited by asarinin. Swelling of hindpaws, inflammatory cell infiltration in the synovium, cartilage destruction, and bone erosion were delayed with asarinin. Asarinin treatment suppressed the expression of T helper type 1 (Th1) cytokines and increased the levels of Th2 cytokines (interleukin (IL)-10), transforming growth factor (TGF)-β and Foxp3 in the synovium and hindpaw, however T-bet mRNA levels in synovium decreased. Lower expression of toll-like receptor 9 (TLR9) and nuclear factor-kappaB (NF-κB) were found in DCs after asarinin treatment. There was no difference in the expression of intercellular cell adhesion molecule-1(ICAM-1), OX40-L, and 4-1BBL in spleen DCs between the asarinin group and model control group. Asarinin can treat CIA. TLR9/NF-κB pathway may be involved in the asarinin treatment of CIA by skewing the balance of Th1/Th2/regulatory T (Treg) to a Th2 type.