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Delivery of RNA using nanomaterials has emerged as a new modality to expand therapeutic applications in biomedical research. However, the delivery of RNA presents unique challenges due to its susceptibility to degradation and the requirement for efficient intracellular delivery. The integration of nanotechnologies with RNA delivery has addressed many of these challenges. In this review, we discuss different strategies employed in the design and development of nanomaterials for RNA delivery. We also highlight recent advances in the pharmaceutical applications of RNA delivered via nanomaterials. Various nanomaterials, such as lipids, polymers, peptides, nucleic acids, and inorganic nanomaterials, have been utilized for delivering functional RNAs, including messenger RNA (mRNA), small interfering RNA, single guide RNA, and microRNA. Furthermore, the utilization of nanomaterials has expanded the applications of functional RNA as active pharmaceutical ingredients. For instance, the delivery of antigen-encoding mRNA using nanomaterials enables the transient expression of vaccine antigens, leading to immunogenicity and prevention against infectious diseases. Additionally, nanomaterial-mediated RNA delivery has been investigated for engineering cells to express exogenous functional proteins. Nanomaterials have also been employed for co-delivering single guide RNA and mRNA to facilitate gene editing of genetic diseases. Apart from the progress made in RNA medicine, we discuss the current challenges and future directions in this field. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most frequently occurring cancer among women. Baicalin has been shown to inhibit breast cancer proliferation, but poor aqueous solubility and unknown mechanism of action limit its application. This study aimed to investigate the antiproliferative effects of baicalin-loaded folic acid-modified albumin nanoparticles (FA-BSANPs/BA) in breast cancer MCF-7 cells and its relationship with autophagy and ROS-mediated p38 MAPK and Akt/mTOR signaling pathways. Cell viability was detected by MTT assay. Flow cytometry and fluorescence microscopy were used to detect cell cycle, apoptosis and autophagy. Western blot was used to detect protein expression. Results: Compared with the control and free baicalin groups, FA-BSANPs/BA inhibited viability of MCF-7 cells and increased cells in S phase, apoptotic bodies, pro-apoptotic proteins, autophagy markers and autophagosomes. These effects could be reversed when combined with the autophagy inhibitor 3-methyladenine. FA-BSANPs/BA increased the levels of phosphorylated p38 MAPK, inhibited the levels of phosphorylated Akt and mTOR, and increased the level of ROS in MCF-7 cells. The effects of FA-BSANPs/BA could be reversed or enhanced using inhibitors of Akt, mTOR, p38 MAPK and ROS scavengers. Conclusions: Encapsulation in folate albumin nanoparticles improved the antiproliferative activity of baicalin. FA-BSANPs/BA induced autophagy and apoptosis via ROS-mediated p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells. [ABSTRACT FROM AUTHOR]

Background: The role of epithelial–mesenchymal transition (EMT) involved in breast cancer metastasis and chemoresistance has been increasingly recognized. However, it is necessary to search for more effective strategies to inhibit EMT thereby increase the sensitivity of breast cancer cells to chemotherapy drugs. Emodin has a potential in overcoming tumor drug resistance and restraining the development of EMT, but the poor internalization into breast cancer cells limited the application. Results: MCF-7/ADR cells have more EMT characteristics than MCF-7 cell. EMT in MCF-7/ADR cells promotes the development of drug resistance via apoptosis resistance and facilitating the expression of P-gp. The anti-cancer effect of DOX enhanced by the decreasing of drug resistance protein P-gp and apoptosis-related proteins after EMT inhibited in MCF-7/ADR cells. E-PLNs increase the cellular uptake of EMO and restore DOX sensitivity in MCF-7/ADR cells by inhibiting EMT. Conclusion: E-PLNs inhibit EMT to enhance the sensitivity of breast cancer to DOX. The combination of E-PLNs and DOX can improve the efficacy of DOX in the treatment of breast cancer, which provides a new method to prevent or delay clinical drug resistance. [ABSTRACT FROM AUTHOR]

Tumor cells, inflammatory cells and chemical factors work together to mediate complex signaling networks, which forms inflammatory tumor microenvironment (TME). The development of breast cancer is closely related to the functional activities of TME. This review introduces the origins of cancer-related chronic inflammation and the main constituents of inflammatory microenvironment. Inflammatory microenvironment plays an important role in breast cancer growth, metastasis, drug resistance and angiogenesis through multifactorial mechanisms. It is suggested that inflammatory microenvironment contributes to providing possible mechanisms of drug action and modes of drug transport for anti-cancer treatment. Nano-drug delivery system (NDDS) becomes a popular topic for optimizing the design of tumor targeting drugs. It is seen that with the development of therapeutic approaches, NDDS can be used to achieve drug-targeted delivery well across the biological barriers and into cells, resulting in superior bioavailability, drug dose reduction as well as off-target side effect elimination. This paper focuses on the review of modulation mechanisms of inflammatory microenvironment and combination with nano-targeted therapeutic strategies, providing a comprehensive basis for further research on breast cancer prevention and control. [ABSTRACT FROM AUTHOR]

Many aerial applications require unmanned aerial systems operate in safe zones because of the presence of obstacles or security regulations. It is a non-trivial task to generate a smooth trajectory satisfying both dynamic constraints and motion limits of the unmanned vehicles while being inside the safe zones. Then the task becomes even more challenging for real-time applications, for which computational efficiency is crucial. In this study, we present a safe flying corridor navigation method, which combines jerk limited trajectories with an efficient testing method to update the position setpoints in real time. Trajectories are generated online and incrementally with a cycle time smaller than 10 μs, which is exceptionally suitable for vehicles with limited onboard computational capability. Safe zones are represented with multiple interconnected bounding boxes which can be arbitrarily oriented. The jerk limited trajectory generation algorithm has been extended to cover the cases with asymmetrical motion limits. The proposed method has been successfully tested and verified in flight simulations and actual experiments. [ABSTRACT FROM AUTHOR]

The study described here focuses on the microstructure and mechanical properties of a novel hot-rolled medium-Mn steel (Fe-0.25C-4Mn-1.88Al-0.6Si-0.04Nb-0.08V, wt%) that contained only 4 wt% Mn and modest Al content of 1.88 wt%. It was found that a relatively high content (25-53 vol%) of retained austenite was obtained by intercritical annealing process. With increase in intercritical annealing temperature from 700 to 740 and to 760 °C, retained austenite fraction increased from 25.1 to 53.2% and then decreased to 46.1%. Besides, mechanical stability of retained austenite in 700-760 °C intercritically annealed steels decreased with increase in intercritical annealing temperature. The 720 °C intercritically annealed steel yielded excellent mechanical properties with yield strength of 766 MPa, tensile strength of 951 MPa, total elongation of 48.6% and PSE of 46.22 GPa·%, achieved by a high volume fraction of retained austenite (46%) with relatively high mechanical stability. Thus, the 4% Mn steel present in this study indicated excellent mechanical properties of medium-Mn steels can be achieved using low alloy content. [ABSTRACT FROM AUTHOR]

Desynchronization attack is known as one of the most difficult attacks to resist, which can desynchronize the location of the watermark and hence causes incorrect watermark detection. Based on multi-scale SIFT (Scale Invariant Feature Transform) detector and local image histogram shape invariance, we propose a new content based image watermarking algorithm with good visual quality and reasonable resistance toward desynchronization attacks in this paper. Firstly, the stable image feature points are extracted from the original host by using multi-scale SIFT detector, and the local feature regions (LFRs) are constructed adaptively according to the feature scale theory. Then, the discrete Fourier transform (DFT) is performed on the LFR, and the local image histogram is extracted from a selected DFT amplitude range. Finally, the bins of the histogram are divided into many groups, and the digital watermark is embedded into LFR by reassigning the number of DFT amplitudes in bin groups. By binding the watermark with the geometrically invariant image features, the watermark detection can be done without synchronization error. Experimental results show that the proposed image watermarking is not only invisible and robust against common image processing operations such as sharpening, noise adding, and JPEG compression, but also robust against the desynchronization attacks such as rotation, translation, scaling, row or column removal, and cropping. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a neurodegenerative disorder frequently accompanied by neuroinflammation and oxidative stress. The medicine and food homology (MFH) has shown potential for treating neuroinflammation and oxidative stress. This study aimed to provide a safe and efficient therapy for AD based on MFH. In this study, we develop a MFH formula consisting of egg yolk oil, perilla seed oil, raphani seed oil, cinnamon oil, and noni puree (EPRCN). To evaluate the ameliorative effects of EPRCN on AD-related symptoms, a mouse model of AD was constructed using intraperitoneal injection of scopolamine in ICR mice. Experimental results demonstrated that EPRCN supplement restored behavioral deficits and suppressed neuroinflammation and oxidative stress in the hippocampus of scopolamine-induced mice. An in vitro study was then performed using induction of Aβ(25–35) in glial (BV–2 and SW–1783) and neuron (SH–SY5Y) cell lines to examine the improvement mechanism of EPRCN on cognitive deficits. Multi-omics and in vitro studies demonstrated that these changes were driven by the anandamide (AEA)-Trpv1-Nrf2 pathway, which was inhibited by AM404 (an AEA inhibitor), AMG9810 (a Trpv1 inhibitor), and BT (an Nrf2 inhibitor). Consequently, EPRCN is an effective therapy on preventing cognitive deficits in mouse models of AD. In contrast to donepezil, EPRCN exhibits a novel modes action for ameliorating neuroinflammation. The mechanism of EPRCN on preventing cognitive deficits is mediated by improving neuroinflammation and oxidative stress via activating the AEA–Trpv1–Nrf2 pathway. [ABSTRACT FROM AUTHOR]