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Directed fuzzing aims to find program inputs that lead to specified target program states. It has broad applications, such as debugging system crashes, confirming reported bugs, and generating exploits for potential vulnerabilities. This task is inherently challenging because target states are often deeply nested in the program, while the search space manifested by numerous possible program inputs is prohibitively large. Existing approaches rely on branch distances or manually-specified constraints to guide the search; however, the branches alone are often insufficient to precisely characterize progress toward reaching the target states, while the manually specified constraints are often tailored for specific bug types and thus difficult to generalize to diverse target states and programs. We present Locus, a novel framework to improve the efficiency of directed fuzzing. Our key insight is to synthesize predicates to capture fuzzing progress as semantically meaningful intermediate states, serving as milestones towards reaching the target states. When used to instrument the program under fuzzing, they can reject executions unlikely to reach the target states, while providing additional coverage guidance. To automate this task and generalize to diverse programs, Locus features an agentic framework with program analysis tools to synthesize and iteratively refine the candidate predicates, while ensuring the predicates strictly relax the target states to prevent false rejections via symbolic execution. Our evaluation shows that Locus substantially improves the efficiency of eight state-of-the-art fuzzers in discovering real-world vulnerabilities, achieving an average speedup of 41.6 ×. So far, Locus has found nine previously unpatched bugs, with three already acknowledged with draft patches. 

Understanding the intimate interactions between plants and their microbiota at the cellular level is essential for unlocking the full potential of plant holobionts in agricultural systems. Traditional bulk and microbial community-level sequencing approaches reveal broad community patterns but fail to resolve how distinct plant cell types interact with or regulate microbial colonization, as well as the diverse antagonistic and synergistic interactions and responses existing between various microbial populations. Recent advances in single-cell and spatial multi-omics have transformed our understanding of plant cell identities as well as gene regulatory programs and their dynamic regulation in response to environmental stresses and plant development. In this review, we highlight the single-cell discoveries that uncover the plant cell-type-specific microbial perception, immune activation, and symbiotic differentiation, particularly in roots, nodules, and leaves. We further discuss how integrating transcriptomic, epigenomic, and spatial data can reconstruct multilayered interaction networks that connect plant cell-type-specific regulatory states with microbial spatial niches and inter-kingdom signaling (e.g., ligand–receptor and metabolite exchange), providing a foundation for developing new strategies to engineer crop–microbiome interactions to support sustainable agriculture. We conclude by outlining key methodological challenges and future research priorities that point toward building a fully integrated cellular interactome of the plant holobiont. 

Nucleoside triphosphate (NTP)-dependent protein assemblies such as microtubules and actin filaments have inspired the development of diverse chemically fueled molecular machines and active materials but their functional sophistication has yet to be matched by design. Given this challenge, we asked whether it is possible to transform a natural adenosine 5′-triphosphate (ATP)-dependent enzyme into a dissipative self-assembling system, thereby altering the structural and functional mode in which chemical energy is used. Here we report that FtsH (filamentous temperature-sensitive protease H), a hexameric ATPase involved in membrane protein degradation, can be readily engineered to form one-dimensional helical nanotubes. FtsH nanotubes require constant energy input to maintain their integrity and degrade over time with the concomitant hydrolysis of ATP, analogous to natural NTP-dependent cytoskeletal assemblies. Yet, in contrast to natural dissipative systems, ATP hydrolysis is catalyzed by free FtsH protomers and FtsH nanotubes serve to conserve ATP, leading to transient assemblies whose lifetimes can be tuned from days to minutes through the inclusion of external ATPases in solution. 

Despite significant progress in video question answering (VideoQA), existing methods fall short of questions that require causal/temporal reasoning across frames. This can be attributed to imprecise motion representations. We introduce Action Temporality Modeling (ATM) for temporality reasoning via three-fold uniqueness: (1) rethinking the optical flow and realizing that optical flow is effective in capturing the long horizon temporality reasoning; (2) training the visual-text embedding by contrastive learning in an action-centric manner, leading to better action representations in both vision and text modalities; and (3) preventing the model from answering the question given the shuffled video in the fine-tuning stage, to avoid spurious correlation between appearance and motion and hence ensure faithful temporality reasoning. In the experiments, we show that ATM outperforms existing approaches in terms of the accuracy on multiple VideoQAs and exhibits better true temporality reasoning ability.