Targeted nanoprobe for magnetic resonance imaging-guided enhanced antitumor via synergetic photothermal/immunotherapy.

Synergistic photothermal/immunotherapy has garnered significant attention for its potential to enhance tumor therapeutic outcomes. However, the fabrication of an intelligent system with a simple composition that simultaneously exerts photothermal/immunotherapy effect and imaging guidance function still remains a challenge. Herein, a glutathione (GSH)-responsive theranostic nanoprobe, named HA-MnO2/ICG, was elaborately constructed by loading photothermal agent (PTA) indocyanine green (ICG) onto the surface of hyaluronic acid (HA)-modified manganese dioxide nanosheets (HA-MnO2) for magnetic resonance (MR) imaging-guided synergetic photothermal/immuno-enhanced therapy. In this strategy, HA-MnO2 nanosheets were triggered by the endogenous GSH in tumor microenvironment to generate Mn2+ for MR imaging, where the longitudinal relaxation rate of HA-MnO2/ICG was up to 14.97 mM-1s-1 (∼24 times than that found in a natural environment), demonstrating excellent intratumoral MR imaging. Moreover, the HA-MnO2/ICG nanoprobe demonstrates remarkable photothermal therapy (PTT) efficacy, generating sufficient heat to induce immunogenic cell death (ICD) within tumor cells. Meanwhile the released Mn2+ ions from the nanosheets function as potent immune adjuvants, amplifying the immune response against cancer. In vivo experiments validated that HA-MnO2/ICG-mediated PTT was highly effective in eradicating primary tumors, while simultaneously enhancing immunogenicity to prevent the growth of distal metastasis. This hybrid HA-MnO2/ICG nanoprobe opened new avenues in the design of MR imaging-monitored PTT/immuno-enhanced synergistic therapy for advanced cancer.

Toward the Integration of Machine Learning and Molecular Modeling for Designing Drug Delivery Nanocarriers.

The pioneering work on liposomes in the 1960s and subsequent research in controlled drug release systems significantly advances the development of nanocarriers (NCs) for drug delivery. This field is evolved to include a diverse array of nanocarriers such as liposomes, polymeric nanoparticles, dendrimers, and more, each tailored to specific therapeutic applications. Despite significant achievements, the clinical translation of nanocarriers is limited, primarily due to the low efficiency of drug delivery and an incomplete understanding of nanocarrier interactions with biological systems. Addressing these challenges requires interdisciplinary collaboration and a deep understanding of the nano-bio interface. To enhance nanocarrier design, scientists employ both physics-based and data-driven models. Physics-based models provide detailed insights into chemical reactions and interactions at atomic and molecular scales, while data-driven models leverage machine learning to analyze large datasets and uncover hidden mechanisms. The integration of these models presents challenges such as harmonizing different modeling approaches and ensuring model validation and generalization across biological systems. However, this integration is crucial for developing effective and targeted nanocarrier systems. By integrating these approaches with enhanced data infrastructure, explainable AI, computational advances, and machine learning potentials, researchers can develop innovative nanomedicine solutions, ultimately improving therapeutic outcomes.

Biocompatible Electrical and Optical Interfaces for Implantable Sensors and Devices.

Implantable bioelectronics hold tremendous potential in the field of healthcare, yet the performance of these systems heavily relies on the interfaces between artificial machines and living tissues. In this paper, we discuss the recent developments of tethered interfaces, as well as those of non-tethered interfaces. Among them, systems that study neural activity receive significant attention due to their innovative developments and high relevance in contemporary research, but other functional types of interface systems are also explored to provide a comprehensive overview of the field. We also analyze the key considerations, including perforation site selection, fixing strategies, long-term retention, and wireless communication, highlighting the challenges and opportunities with stable, effective, and biocompatible interfaces. Furthermore, we propose a primitive model of biocompatible electrical and optical interfaces for implantable systems, which simultaneously possesses biocompatibility, stability, and convenience. Finally, we point out the future directions of interfacing strategies.

pH/glutathione-responsive theranostic nanoprobes for chemoimmunotherapy and magnetic resonance imaging of ovarian cancer cells.

The integration of immunotherapy and standard chemotherapy holds great promise for enhanced anticancer effects. In this study, we prepared a pH- and glutathione (GSH)-sensitive manganese-doped mesoporous silicon (MMSNs) based drug delivery system by integrating paclitaxel (PTX) and anti-programmed cell death-ligand 1 antibody (aPD-L1), and encapsulating with polydopamine (PDA) for chemoimmunosynergic treatment of ovarian cancer cells. The nanosystem was degraded in response to the tumor weakly acidic and reductive microenvironment. The Mn2+ produced by degradation can be used as a contrast agent for magnetic resonance (MR) imaging to provide visual exposure to tumor tissue. The released PTX can not only kill tumor cells directly, but also induce immunogenic death (ICD) of tumor cells, which can play a synergistic therapeutic effect with aPD-L1. Therefore, our study is expected to provide a promising strategy for improving the efficacy of cancer immunotherapy and the detection rate of cancer.

O2-Generating Fluorescent Carbon Dot-Decorated MnO2 Nanosheets for "Off/On" MR/Fluorescence Imaging and Enhanced Photodynamic Therapy.

Imaging-guided photodynamic therapy (PDT) has emerged as a promising protocol for cancer theragnostic. However, facile preparation of such a theranostic system for simultaneously achieving tumor location, real-time monitoring, and high-performance reactive oxygen species generation is highly desirable but remains challenging. Herein, we developed a reasonable tumor-targeting strategy based on carbon dots (CDs)-decorated MnO2 nanosheets (HA-MnO2-CDs) with an active magnetic resonance (MR)/fluorescence imaging and enhanced PDT effect. Under light irradiation, the addition of HA-MnO2-CDs increased the production of 1O2 by 2.5 times compared with CDs, providing favorable conditions for the PDT treatment effect on breast cancer. Moreover, HA-MnO2-CDs exhibited excellent performance in producing O2 in the presence of endogenous H2O2, which alleviated hypoxia in tumors and improved the therapeutic effect of PDT. In the presence of glutathione (GSH), the degraded MnO2 nanosheets released CDs and Mn2+ from HA-MnO2-CDs, restoring their fluorescence imaging function and increasing T1 relaxivity (r1) by 23 times. In vivo fluorescence and MR imaging suggested the excellent tumor-targeting property of HA-MnO2-CDs. By combining the complementary properties of nanoprobes and tumor microenvironments, the in vivo PDT therapeutic effect was significantly improved under the action of HA-MnO2-CDs. Overall, our reasonably designed HA-MnO2-CDs may inspire the future development of the next generation of high-performance tumor-responsive diagnostic and therapeutic agents to further enhance the targeted therapy effect of tumors.

Hierarchically Structured Hydroxyapatite Particles Facilitate the Enhanced Integration and Selective Anti-Tumor Effects of Amphiphilic Prodrug for Osteosarcoma Therapy.

Efficient delivery of cargo into target cells is a formidable challenge in modern medicine. Despite the great promise of biomimetic hydroxyapatite (HA) particles in tissue engineering, their potential applications in bone tumor therapy, particularly their structure-function relationships in cargo delivery to target cells, have not yet been well explored. In this study, biomimetic multifunctional composite microparticles (Bm-cMPs) are developed by integrating an amphiphilic prodrug of curcumin with hierarchically structured HA microspheres (Hs-hMPs). Then, the effects of the hierarchical structure of vehicles on the integration and delivery of cargo as well as the anti-osteosarcoma (OS) effect of the composite are determined. Different hierarchical structures of the vehicles strongly influence the self-assembly behavior of the prodrug. The flake-like crystals of Hs-hMPs enable the highest loading capacity and enhance the stability of the cargo. Compared to the normal cells, OS cells exhibit 3.56-times better uptake of flake-like Hs-hMPs, facilitating the selective anti-tumor effect of the prodrug. Moreover, Bm-cMPs suppress tumor growth and metastasis by promoting apoptosis and inhibiting cell proliferation and tumor vascularization. The findings shed light on the potential application of Bm-cMPs and suggest a feasible strategy for developing an effective targeted therapy platform using hierarchically structured minerals for OS treatment.

Tailorable hierarchical structures of biomimetic hydroxyapatite micro/nano particles promoting endocytosis and osteogenic differentiation of stem cells.

Hydroxyapatite (HA) micro/nano particles show great promise as artificial bone and dental substitutes, or drug carrier systems. However, the precise regulation of hydroxyapatite micro/nano particles with controllable physicochemical properties (such as hierarchical structure, particle size, potential and crystallinity) is still a challenge. Furthermore, the effects of different hierarchical structures on biological responses have been rarely reported. Herein, the HA particles with a precisely tailored micro/nano hierarchical structure have been developed using an elaborate biomimetic synthesis technology. Three representative particles, namely, micro/nano needle-like HA particles, micro/nano rod-like HA particles, and micro/nano flake-like HA particles, were featured to evaluate their biological responses to stem cells. The pore structure facilitated the adsorption of serum adhesive proteins, which together with the unique hierarchical architecture of micro/nano flake-like HA particles remarkably promoted the endocytosis efficiency in a concentration-dependent manner. The qRT-PCR together with RNA-seq and western blot analyses showed that micro/nano flake-like HA particles more significantly up-regulated the expression of genes and production of proteins related to osteogenic differentiation among the three particles through the activated ERK/MAPK signalling pathway. RNA-seq further revealed a complex mechanism of cell interface events, suggesting that the hierarchical architecture of HA particles is of crucial importance for the regulation of actin cytoskeleton involved in the modulation of cell adhesion which positively stimulated osteogenic differentiation of stem cells. Moreover, the endocytosis of particles into lysosomes resulted in an increase in the intracellular Ca2+ levels, which activated possible intracellular Ca2+-mediated signaling cascades (Ras/cAMP/Rap1/MAPK signaling pathways) related to osteogenic differentiation of stem cells. Our findings shed light on the effects of different hierarchical structures of HA particles on stem cell differentiation and contribute to the optimal design of implant materials.

Tunable luminescence evolution and energy transfer behavior of Na3Sc2(PO4)3:Ce3+/Tb3+/Eu3+ phosphors.

A series of color-tunable emitting Na3Sc2(PO4)3:Ce3+/Tb3+/Eu3+ (NSPO) phosphors were prepared by a combination of hydrothermal synthesis and low temperature calcination. The phase structure, photoluminescence and energy transfer properties of the samples were studied in detail. The tunable colors were obtained by co-doping the Tb3+ ions into the NSPO:Ce3+ or NSPO:Eu3+ phosphors with varying concentrations. Under UV excitation, the energy transfers from Tb3+ to Eu3+ in the NSPO host occurred mainly via a dipole-dipole mechanism, and the critical distances of the ion pairs (R c) was calculated to be 17.94 Å by the quenching concentration method. And that, the emission colors of the NSPO:Tb3+,Eu3+ phosphors could be adjusted from green through yellow to red because of the energy transfer from Tb3+ to Eu3+. Based on its good photoluminescence properties and abundant emission colors, the NSPO:Ce3+/Tb3+/Eu3+ phosphors might be promising as potential candidates for solid-state lighting and display fields.

Delay Analysis for End-to-End Synchronous Communication in Monitoring Systems.

With the rapid development of smart grid technologies, communication systems are further integrated in the existing power grids. The real-time capability and reliability of the power applications are receiving increasing concerns. Thus, it is important to measure the end-to-end delay in communication systems. The network calculus theory has been widely applied in the communication delay measuring tasks. However, for better operation performance of power systems, most power applications require synchronous data communication, in which the network calculus theory cannot be directly applied. In this paper, we expand the network calculus theory such that it can be used to analyze the communication delay for power applications in smart grids. The problem of communication delay calculation for the synchronization system is converted into a maximum path problem in graph theory. Finally, our theoretical results are compared with the experimental ones obtained with the network simulation software EstiNet. The simulation results verify the feasibility and effectiveness of the proposed method.

[A Maternal Health Care System Based on Mobile Health Care].

Wearable devices are used in the new design of the maternal health care system to detect electrocardiogram and oxygen saturation signal while smart terminals are used to achieve assessments and input maternal clinical information. All the results combined with biochemical analysis from hospital are uploaded to cloud server by mobile Internet. Machine learning algorithms are used for data mining of all information of subjects. This system can achieve the assessment and care of maternal physical health as well as mental health. Moreover, the system can send the results and health guidance to smart terminals.