Background: Autism spectrum disorder (ASD) is a developmental disorder, and the effective pharmacological treatments for the core autistic symptoms are currently limited. Increasing evidence, particularly that from clinical studies on ASD patients, suggests a functional link between the gut microbiota and the development of ASD. However, the mechanisms linking the gut microbiota with brain dysfunctions (gut-brain axis) in ASD have not yet been full elucidated. Due to its genetic mutations and downregulated expression in patients with ASD, EPHB6, which also plays important roles in gut homeostasis, is generally considered a candidate gene for ASD. Nonetheless, the role and mechanism of EPHB6 in regulating the gut microbiota and the development of ASD are unclear. Results: Here, we found that the deletion of EphB6 induced autism-like behavior and disturbed the gut microbiota in mice. More importantly, transplantation of the fecal microbiota from EphB6-deficient mice resulted in autism-like behavior in antibiotic-treated C57BL/6J mice, and transplantation of the fecal microbiota from wild-type mice ameliorated the autism-like behavior in EphB6-deficient mice. At the metabolic level, the disturbed gut microbiota in EphB6-deficient mice led to vitamin B 6 and dopamine defects. At the cellular level, the excitation/inhibition (E/I) balance in the medial prefrontal cortex was regulated by gut microbiota-mediated vitamin B 6 in EphB6-deficient mice. Conclusions: Our study uncovers a key role for the gut microbiota in the regulation of autism-like social behavior by vitamin B 6 , dopamine, and the E/I balance in EphB6-deficient mice, and these findings suggest new strategies for understanding and treating ASD.

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Hybrid cache architectures have been proposed to mitigate the increasing on-chip power dissipation through the exploitation of the emerging non-volatile memories (NVMs). To overcome the high energy and long latency associated with write operations of NVMs, a small SRAM is typically incorporated into the hybrid cache for accommodating write-intensive cache blocks. How to efficiently manage this SRAM and manipulate the write operations are crucial to the performance of the hybrid cache. In this paper, we first present our observation that the intensity of write operations on different cache sets is usually non-uniform for real applications, such as multimedia, multi-programmed, multithreaded applications. The previously proposed hybrid cache schemes can not efficiently and symmetrically utilize the small SRAM to accommodate such widely-existing non-uniform writes on cache sets.Based on this observation, we propose a novel hybrid cache design, Dual Associative Hybrid Cache (denoted as DAHYC), as well as the corresponding cache management policy. By organizing the SRAM blocks in the hybrid cache as a semi-independent set-associative cache, several hybrid cache sets can efficiently share and cooperatively utilize their SRAM blocks, instead of exclusively utilizing the SRAM blocks in each cache set in previous hybrid cache schemes, to boost power-efficiency. Through prudently manipulating the locality information of SRAM blocks in both the NVM sets and the SRAM sets, the proposed cache management policy also delivers high-performance. Experimental results show that, compared with previous works, the DAHYC can reduce the dynamic power of the hybrid cache by 24.8% on average and up to 54% for SPEC2000 INT benchmarks, while at the same time improving the performance of the hybrid cache by 1.16% on average.

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