Stability of Sampled-Data Systems With Packet Losses: A Nonuniform Sampling Interval Approach.

In this article, inspired by the Halanay inequality, we study stability of sampled-data systems with packet losses by proposing a nonuniform sampling interval approach. First, a sampled-data controller with an exponential gain is put forward to reduce conservatism. We obtain the sufficient condition for linear sampled-data systems to be exponentially stable by extending the famous Halanay inequality to sampled-data systems. The obtained sufficient conditions indicate that the maximal-allowable bound of sampling intervals is determined by the constant terms in the Halanay inequality, and the decay rate is presented in the form of a Lambert function. Compared with some existing results on the stability of sampled-data systems by using the Gronwall-Bellman Lemma, the conservatism induced by the exponential term via the Gronwall-Bellman Lemma can be reduced to some extent. Considering the phenomenon of packet losses, a new lemma is further proposed to generalize the proposed Halanay-like inequality. The results derived by the new lemma permit that there exist some sampling intervals with the upper bound violating the desired condition of the Halanay-like inequality. This permits us to establish exponential stability in significant cases that do not satisfy the Halanay-like inequality needed in the previous results. Finally, the sampled-data local exponential stability is investigated for nonlinear systems with strong nonlinearity.

Targeted Nanobubbles of PD-L1 mAb Combined with Doxorubicin as a Synergistic Tumor Repressor in Hepatocarcinoma.

Purpose: Ultrasound nanobubbles (NBs) can kill tumor cells, mediated by their effects of cavitation and acoustic perforation through ultrasound, while as novel drug carriers, biomaterial-modified NBs release drugs at a target region. In this work, the ultrasound NBs bridged by biotin-streptavidin were prepared simultaneously to be loaded with both programmed death ligand 1 monoclonal antibody (PD-L1 mAb) and doxorubicin (DOX), which are immune checkpoint inhibitors (ICIs) and chemotherapeutic agents, to synergize immunotherapy and chemotherapy combined with sonodynamic therapy (SDT). Methods: The PD-L1 mAb/DOX NBs, using bridging affinity biotin (BRAB) technology as a bridge, were prepared by thin-film hydration and mechanical oscillation for the targeted delivery of biotinylated PD-L1 mAb and DOX. Characterization and pharmacokinetic studies of PD-L1 mAb/DOX NBs were performed in vitro and in vivo. The antitumor effect of ultrasound-mediated PD-L1 mAb/DOX-NBs was studied in the subcutaneously transplanted tumor of the H22 hepatoma model, and the mechanism of synergistic tumor repression was investigated. Results: The data of in vitro targeting experiments, contrast-enhanced ultrasound imaging (CEUS), in vivo imaging of the small animals imaging system (IVIS), and frozen sections showed that PD-L1 mAb/DOX-NBs have well-targeted aggregation in the tumor. By observing tumor inhibition rate, tissue cell apoptosis, and apoptosis-related gene and protein expression, the PD-L1 mAb/DOX-NBs group showed the best immunotherapy effects, and its tumor volume and mass inhibition rates were about 69.64% and 75.97%, respectively (P < 0.01). Therefore, blocking the PD-1/PD-L1 pathway could improve immune cells' tumor-killing ability. Antitumor immune cytokines were further enhanced when combined with DOX-induced tumor cell apoptosis and immunogenic cell death (ICD). Conclusion: In summary, ultrasound-mediated PD-L1 mAb/DOX-NBs showed significant synergistic antitumor effects, providing a potential combined immunotherapy strategy for HCC.