Combination of MHI148 Targeted Photodynamic Therapy and STING Activation Inhibits Tumor Metastasis and Recurrence.

Metastasis and recurrence are notable contributors to mortality associated with breast cancer. Although immunotherapy has shown promise in mitigating these risks after conventional treatments, its effectiveness remains constrained by significant challenges, such as impaired antigen presentation by dendritic cells (DCs) and inadequate T cell infiltration into tumor tissues. To address these limitations, we developed a multifunctional nanoparticle platform, termed GM@P, which consisted of a hydrophobic shell encapsulating the photosensitizer MHI148 and a hydrophilic core containing the STING agonist 2'3'-cGAMP. This design elicited robust type I interferon responses to activate antitumor immunity. The GM@P nanoparticles loaded with MHI148 specifically targeted breast cancer cells. Upon exposure to 808 nm laser irradiation, the MHI148-loaded nanoparticles produced toxic reactive oxygen species (ROS) to eradicate tumor cells through photodynamic therapy (PDT). Notably, PDT stimulated immunogenic cell death (ICD) to foster the potency of antitumor immune responses. Furthermore, the superior photoacoustic imaging (PAI) capabilities of MHI148 enabled the simultaneous visualization of diagnostic and therapeutic procedures. Collectively, our findings uncovered that the combination of PDT and STING activation facilitated a more conducive immune microenvironment, characterized by enhanced DC maturation, infiltration of CD8+ T cells, and proinflammatory cytokine release. This strategy stimulated local immune responses to augment systemic antitumor effects, offering a promising approach to suppress tumor growth, inhibit metastasis, and prevent recurrence.

Distributed Sequential Detection for Cooperative Spectrum Sensing in Cognitive Internet of Things.

The rapid development of wireless communication technology has led to an increasing number of internet of thing (IoT) devices, and the demand for spectrum for these devices and their related applications is also increasing. However, spectrum scarcity has become an increasingly serious problem. Therefore, we introduce a collaborative spectrum sensing (CSS) framework in this paper to identify available spectrum resources so that IoT devices can access them and, meanwhile, avoid causing harmful interference to the normal communication of the primary user (PU). However, in the process of sensing the PUs signal in IoT devices, the issue of sensing time and decision cost (the cost of determining whether the signal state of the PU is correct or incorrect) arises. To this end, we propose a distributed cognitive IoT model, which includes two IoT devices independently using sequential decision rules to detect the PU. On this basis, we define the sensing time and cost functions for IoT devices and formulate an average cost optimization problem in CSS. To solve this problem, we further regard the optimal sensing time problem as a finite horizon problem and solve the threshold of the optimal decision rule by person-by-person optimization (PBPO) methodology and dynamic programming. At last, numerical simulation results demonstrate the correctness of our proposal in terms of the global false alarm and miss detection probability, and it always achieves minimal average cost under various costs of each observation taken and thresholds.

Potential roles of gut microbiota and microbial metabolites in Parkinson's disease.

Parkinson's disease (PD) is a complicated neurodegenerative disease attributed to multifactorial changes. However, its pathological mechanism remains undetermined. Accumulating evidence has revealed the emerging functions of gut microbiota and microbial metabolites, which can affect both the enteric nervous system and the central nervous system via the microbiota-gut-brain axis. Accordingly, intestinal dysbiosis might be closely associated with PD. This review explores alterations to gut microbiota, correlations with clinical manifestations of PD, and briefly probes the underlying mechanisms. Next, the highly controversial roles of microbial metabolites including short-chain fatty acids (SCFAs), H2 and H2S are discussed. Finally, the pros and cons of the current treatments for PD, including those targeting microbiota, are assessed. Advancements in research techniques, further studies on levels of specific strains and longitudinal prospective clinical trials are urgently needed for the identification of early diagnostic markers and the development of novel therapeutic approaches for PD.