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The human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor and tumor-associated antigen abnormally expressed in various types of cancer, including breast, ovarian, and gastric cancer. HER2 overexpression is highly correlated with increased tumor aggressiveness, poorer prognosis, and shorter overall survival. Consequently, multiple HER2-targeted therapies have been developed and approved; however, only a subset of patients benefit from these treatments, and relapses are common. More potent and durable HER2-targeted therapies are desperately needed for patients with HER2-positive cancers. In this study, we developed a lipid nanoparticle (LNP)-based therapy formulated with mRNA encoding a novel HER2-CD3-Fc bispecific antibody (bsAb) for HER2-positive cancers. The LNPs efficiently transfected various types of cells, such as HEK293S, SKOV-3, and A1847, leading to robust and sustained secretion of the HER2-CD3-Fc bsAb with high binding affinity to both HER2 and CD3. The bsAb induced potent T-cell-directed cytotoxicity, along with secretion of IFN-λ, TNF-α, and granzyme B, against various types of HER2-positive tumor cells in vitro, including A549, NCI-H460, SKOV-3, A1847, SKBR3, and MDA-MB-231. The bsAb-mediated antitumor effect is highly specific and strictly dependent on its binding to HER2, as evidenced by the gained resistance of A549 and A1847 her2 knockout cells and the acquired sensitivity of mouse 4T1 cells overexpressing the human HER2 extracellular domain (ECD) or epitope-containing subdomain IV to the bsAb-induced T cell cytotoxicity. The bsAb also relies on its binding to CD3 for T-cell recruitment, as ablation of CD3 binding abolished the bsAb's ability to elicit antitumor activity. Importantly, intratumoral injection of the HER2-CD3-Fc mRNA-LNPs triggers a strong antitumor response and completely blocks HER2-positive tumor growth in a mouse xenograft model of human ovarian cancer. These results indicate that the novel HER2-CD3-Fc mRNA-LNP-based therapy has the potential to effectively treat HER2-positive cancer. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) challenges us to assess the disease due to the lack of definitive biomarkers. Currently, PD patients have been found to contract several gastrointestinal comorbidities such as constipation and intestinal inflammation that precede its symptomatic manifestations. These conditions are intricately linked to proliferative metabolisms of the gut microbiota, which are manifested to be some primary changes in the gut microbiota or other changes involved in medication during treatment. In this paper we review the recent research on gut microbiota biomarkers in PD, arguing for the clinical relevance of gut microbiota as a marker in the progression of PD and prospecting the potential efficacy of fecal microbiota transplantation as an intervention in managing PD. [ABSTRACT FROM AUTHOR]

Pressure-induced phase transformation and fluorescent properties of ErF3 were investigated here using in-situ synchrotron X-ray diffraction and photoluminescence up to 32.1 GPa at room temperature. Results showed that ErF3 underwent a reversible pressure-induced phase transition from the β-YF3-type to the fluocerite LaF3-type at 9.8 GPa. The bulk moduli B0 for low- and high-pressure phases were determined to be 130 and 208 GPa, respectively. Photoluminescencent studies showed that new emission lines belonging to the transition of 2H11/2→4I15/2, 4S3/2→4I15/2, and 4F9/2→4I15/2 appeared during phase transition, suggesting pressure-induced electronic band splitting. Remarkably, significant pressure-induced enhancement of photoluminescence was observed, which was attributed to lattice distortion of the material under high pressure.

For the nonlinear parameter‐varying (NPV) model of unmanned surface vehicle with the consideration of the velocities on yaw and surge as well as wave disturbances, a robust H∞$$ {H}_{\infty } $$ control method is proposed based on extended homogeneous polynomial Lyapunov function (EHPLF) to regulate heading for the superior performance on the rapidity, accuracy, and robustness. First, a NPV model of heading error is established to design a general form of a state feedback controller with a robust H∞$$ {H}_{\infty } $$ performance. Second, a Lyapunov matrix with full states and varying parameter is constructed to derive the robust H∞$$ {H}_{\infty } $$ global exponential stability conditions by Euler's homogeneity relation for the NPV system, known as the EHPLF stability conditions. Third, since the EHPLF stability conditions consist of a set of nonlinear coupled inequalities that cannot be directly solved by sum of squares (SOS) toolboxes, they are decoupled with matrix transformations to obtain the EHPLF‐SOS stability conditions, which is solved for the parameters of the state feedback controller. Finally, the simulation results indicate that EHPLF method exhibits a superior performance on dynamic, steady‐state, and robustness. [ABSTRACT FROM AUTHOR]

A series of Mg2−xCoxTiO4 (x = 0.0, 0.5, 1.0, 1.5, 2.0) ceramics were synthesized by a conventional solid-state reaction route. The crystal structure, Raman vibrational characteristics, sintering behavior, microstructure, and microwave dielectric properties were systematically investigated. X-ray diffraction patterns and Raman spectroscopy indicated that the Mg2−xCoxTiO4 ceramics all exhibited a single-phase structure with cubic spinel (space group: Fd 3 ¯ m). The lattice parameters gradually increased with the continuous doping of Co2+ ions according to the Rietveld refinement results. Structure–property relationships were established based on Clausius–Mossotti equations, Raman spectroscopy, and bond valence theory. The εr values of Mg2−xCoxTiO4 ceramics were significantly affected by the ionic polarizability and the [Mg1/Co1O4] stretching vibration. The variation tendency of the Q × f values was closely related to the densification, and packing fraction. Moreover, the “rattling” effect at the A-site, the bond valence of the B-site, and the oxygen bond valence played an important role in controlling the τf values of Mg2−xCoxTiO4 single-phase ceramics. An excellent microwave dielectric property of εr = 15.88, Q × f = 38,157 GHz, and τf = − 32.21 ppm/°C can be obtained for Mg2−xCoxTiO4 ceramics with x = 1.0 sintered at 1350 °C for 4 h. [ABSTRACT FROM AUTHOR]

The leader–following consensus of linear heterogeneous multiagent systems is investigated in this paper. To comply with the most practical scenario, the communicating topologies among agents are assumed to switch stochastically and driven by a continuous‐time discrete‐state Markov process, whose state space corresponds to all the possible topologies. A novel distributed adaptive compensator is designed for the followers to reconstruct the exogenous signals without knowing the Laplacian matrix who is regarded as a global information, and sufficient conditions are given to ensure the compensator converges to the dynamic of the leader asymptotically in the mean square sense. Then, based on the compensator, we solved the consensus problem both by distributed state and measurement output feedback control schemes under output regulation framework, which allow followers to have nonidentical state dimensions. Finally, the theoretical results are demonstrated by a numerical example. [ABSTRACT FROM AUTHOR]

The ground conductor is prone to corrosion, which affects its ability to diverge current and the normal operation of the power system. The traditional detection method can’t detect its corrosion degree intuitively. This paper proposes a novel method based on Electromechanical impedance (EMI) technique to evaluate the corrosion degree of the grounding conductor. Firstly, based on the analysis of corrosion of metals. The change of ground conductor radius Δr is used as the corrosion parameter. A linear model of peak frequency Δfm and corrosion parameter Δr in asymmetric layout is established by analysing EMI and conductor mechanical admittance. Secondly, the EMI coupling models with different sensor layouts were built on the finite element software. It is verified that the asymmetric sensor layout effectively improves the sensitivity to corrosion. The linear model greatly improves the assessment accuracy compared with the Mean Absolute Percentage Deviation (MAPD) and Root Mean Square Deviation (RMSD) damage index. Thirdly, the proposed method is verified in a real grounding conductor corrosion experiment. The method based on the EMI technique with asymmetric sensor layout can evaluate the corrosion of the grounding conductor well. [ABSTRACT FROM AUTHOR]