Lin Zhu

This study proposes a health-aware energy management strategy based on the twin delayed deep deterministic policy gradient (TD3) algorithm for hybrid fuel cell/battery-powered ships. Unlike traditional approaches that treat multiple fuel cell stacks as homogeneous units, this strategy innovatively implements differentiated power allocation based on the real-time state of health of each stack. The research first validates the superiority of the TD3 framework over the deep Q-learning framework at the algorithmic level. Further comparative experiments conducted across three scenarios with varying degrees of state of health differences show that, compared to the TD3 baseline strategy employing average power allocation, the health-aware differentiated TD3 strategy significantly reduces the total voyage cost of the system, with the cost-saving effect becoming more pronounced as the state of health disparity between stacks increases. Additionally, by incorporating rule-based constraints, the convergence speed of the TD3 algorithm is effectively enhanced, improving its feasibility for real-time control. Tests under dynamic and fluctuating load conditions further confirm the strategy’s effectiveness and applicability. In summary, the health-aware TD3 strategy proposed in this study not only provides an efficient and reliable energy management solution for hybrid-powered ships but also promotes the application of machine learning in the field of ship energy management.

The percentage of low response and adaptive resistance to current antibody‐based immune checkpoint blockade (ICB) therapy requires the development of novel immunotherapy strategies. Here, we developed an aptamer‐assisted immune checkpoint blockade (Ap‐ICB) against sialic acid‐binding immunoglobulin‐like lectin‐15 (Siglec‐15), a novel immune suppressor broadly upregulated on cancer cells and tumor infiltrating myeloid cells, which is mutually exclusive of programmed cell death ligand 1 (PD‐L1). Using protein aptamer selection, we identified WXY3 aptamer with high affinity against Siglec‐15 protein/Siglec‐15 positive cells. We demonstrated that WXY3 aptamer rescued antigen‐specific T cell responses in vitro and in vivo. Importantly, the WXY3 Ap‐ICB against Siglec‐15 amplified anti‐tumor immunity in the tumor microenvironment and inhibited tumor growth/metastasis in syngeneic mouse model, which may result from enhanced macrophage and T cell functionality. In addition, by using aptamer‐based spherical nucleic acids, we developed a synergetic ICB strategy of multivalent binding and steric hindrance, which further improves the in vivo anti‐tumor effect. Taken together, our results support Ap‐ICB targeted Siglec‐15 as a potential strategy for normalization cancer immunotherapy.

Extracellular vesicles (EVs) are cell-released vesicles in sub-micrometer size. EVs contain a tissue-specific signature wherein a variety of proteins and nucleic acids are selectively packaged. Incontestably, growing evidence has shown important biological roles and clinical relevance of EVs in cancers. They can promote cancer metastasis and therapeutic resistance. In particular, recent studies validate EV can be used for cancer diagnostics, staging, and treatment monitoring. While still in its infancy, the field of EV-based liquid biopsy has been exploding. To further thrive the EV-related clinical translation, EV isolation is a prerequisite. However, lengthy procedure, low yield, low throughput, and high contaminants disqualify the existing isolation approaches for large-scale clinical use. Hence, new approaches for rapid, efficient, and low-cost isolation of adequate EVs in high purity for flexible analyses of the diverse contents in real world clinical settings are currently unavailable yet highly desirable. Here, we report the heparin/polymer-coated microspheres (HPM) for EV isolation and retrieval. Approximately 81% of EVs can be isolated from plasma in 1 hour with depletion of ~99.5% plasma protein and nucleic acid contaminants, and 72% of isolated EVs can retrieved with saline in 5 minutes for various cargo analyses. This approach was further validated with clinical samples derived from patients with malignant ground-glass opacity (GGO). In 8 patients, the mutation concordance between EV DNA and tissue DNA is 39.8%. The prevalence and mutation count of EGFR, TP53, and NF1 are higher than other oncogenes and antioncogenes that are intensely associated with in lung adenocarcinoma. Moreover, different mutation prevalence and patterns between smokers and non-smokers can be observed. Our findings suggest that the HPM assay can rapidly and efficiently isolate pure EVs, and targeted sequencing of EV DNA could be used for differential diagnosis of malignant GGO with a short turnaround time.

Hypermethylation of TFAP2E (AP-2E) is associated with the chemotherapy-resistant in patients with colorectal cancer (CRC), but its implications on prognosis directly remain unknown. This study was aimed to investigate the role of AP-2E methylation status and other clinicopathologic parameters as predictors of prognosis.