SoK: Training Machine Learning Models over Multiple Sources with Privacy Preservation

Nowadays, gathering high-quality training data from multiple data controllers with privacy preservation is a key challenge to train high-quality machine learning models. The potential solutions could dramatically break the barriers among isolated data corpus, and consequently enlarge the range of data available for processing. To this end, both academia researchers and industrial vendors are recently strongly motivated to propose two main-stream folders of solutions: 1) Secure Multi-party Learning (MPL for short); and 2) Federated Learning (FL for short). These two solutions have their advantages and limitations when we evaluate them from privacy preservation, ways of communication, communication overhead, format of data, the accuracy of trained models, and application scenarios. Motivated to demonstrate the research progress and discuss the insights on the future directions, we thoroughly investigate these protocols and frameworks of both MPL and FL. At first, we define the problem of training machine learning models over multiple data sources with privacy-preserving (TMMPP for short). Then, we compare the recent studies of TMMPP from the aspects of the technical routes, parties supported, data partitioning, threat model, and supported machine learning models, to show the advantages and limitations. Next, we introduce the state-of-the-art platforms which support online training over multiple data sources. Finally, we discuss the potential directions to resolve the problem of TMMPP.Comment: 17 pages, 4 figure

Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain

Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro

Blockade LAT1 Mediates Methionine Metabolism to Overcome Oxaliplatin Resistance under Hypoxia in Renal Cell Carcinoma

Hypoxic microenvironment and metabolic dysregulation of tumor impairs the therapeutic efficacy of chemotherapeutic drugs, resulting in drug resistance and tumor metastasis, which has always been a challenge for the treatment of solid tumors, including renal cell carcinoma (RCC). Herein, starting from the evaluation of methionine metabolism in RCC cells, we demonstrated that the increased methionine accumulation in RCC cells was mediated by L-type amino acid transporter 1 (LAT1) under hypoxia. Glutathione (GSH), as a methionine metabolite, would attenuate the therapeutic efficacy of oxaliplatin through chemical chelation. Reducing methionine uptake by LAT1 inhibitor JPH203 significantly enhanced the sensitivity of RCC cells to oxaliplatin by reducing GSH production in vitro and in vivo. Therefore, we proposed an effective and stable therapeutic strategy based on the combination of oxaliplatin and LAT1 inhibitor, which is expected to solve the resistance of RCC to platinum-based drugs under hypoxia to a certain extent, providing a meaningful insight into the development of new therapeutic strategies and RCC treatmen