Genetically engineered pre-microRNA-34a prodrug suppresses orthotopic osteosarcoma xenograft tumor growth via the induction of apoptosis and cell cycle arrest.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children, and microRNA-34a (miR-34a) replacement therapy represents a new treatment strategy. This study was to define the effectiveness and safety profiles of a novel bioengineered miR-34a prodrug in orthotopic OS xenograft tumor mouse model. Highly purified pre-miR-34a prodrug significantly inhibited the proliferation of human 143B and MG-63 cells in a dose dependent manner and to much greater degrees than controls, which was attributed to induction of apoptosis and G2 cell cycle arrest. Inhibition of OS cell growth and invasion were associated with release of high levels of mature miR-34a from pre-miR-34a prodrug and consequently reduction of protein levels of many miR-34a target genes including SIRT1, BCL2, c-MET, and CDK6. Furthermore, intravenous administration of in vivo-jetPEI formulated miR-34a prodrug significantly reduced OS tumor growth in orthotopic xenograft mouse models. In addition, mouse blood chemistry profiles indicated that therapeutic doses of bioengineered miR-34a prodrug were well tolerated in these animals. The results demonstrated that bioengineered miR-34a prodrug was effective to control OS tumor growth which involved the induction of apoptosis and cell cycle arrest, supporting the development of bioengineered RNAs as a novel class of large molecule therapeutic agents

Correlated Photons from Collective Excitations of Three-Level Atomic Ensemble

We systematically study the interaction between two quantized optical fields and a cyclic atomic ensemble driven by a classic optical field. This so-called atomic cyclic ensemble consists of three-level atoms with Delta-type transitions due to the symmetry breaking, which can also be implemented in the superconducting quantum circuit by Yu-xi Liu et al. [Phys. Rev. Lett. 95, 087001 (2005)]. We explore the dynamic mechanisms to creating the quantum entanglements among photon states, and between photons and atomic collective excitations by the coherent manipulation of the atom-photon system. It is shown that the quantum information can be completely transferred from one quantized optical mode to another, and the quantum information carried by the two quantized optical fields can be stored in the collective modes of this atomic ensemble by adiabatically controlling the classic field Rabi frequencies.Comment: 10 pages, 2 figure

Genos: General In-Network Unsupervised Intrusion Detection by Rule Extraction

Anomaly-based network intrusion detection systems (A-NIDS) use unsupervised models to detect unforeseen attacks. However, existing A-NIDS solutions suffer from low throughput, lack of interpretability, and high maintenance costs. Recent in-network intelligence (INI) exploits programmable switches to offer line-rate deployment of NIDS. Nevertheless, current in-network NIDS are either model-specific or only apply to supervised models. In this paper, we propose Genos, a general in-network framework for unsupervised A-NIDS by rule extraction, which consists of a Model Compiler, a Model Interpreter, and a Model Debugger. Specifically, observing benign data are multimodal and usually located in multiple subspaces in the feature space, we utilize a divide-and-conquer approach for model-agnostic rule extraction. In the Model Compiler, we first propose a tree-based clustering algorithm to partition the feature space into subspaces, then design a decision boundary estimation mechanism to approximate the source model in each subspace. The Model Interpreter interprets predictions by important attributes to aid network operators in understanding the predictions. The Model Debugger conducts incremental updating to rectify errors by only fine-tuning rules on affected subspaces, thus reducing maintenance costs. We implement a prototype using physical hardware, and experiments demonstrate its superior performance of 100 Gbps throughput, great interpretability, and trivial updating overhead.Comment: accepted by IEEE International Conference on Computer Communications (INFOCOM 2024