Despite decades of rigorous research and numerous clinical trials, Alzheimer’s disease (AD) stands as a notable healthcare challenge of this century, with effective therapeutic solutions remaining elusive. Recently, the endocannabinoid system (ECS) has emerged as an essential therapeutic target due to its regulatory role in different physiological processes, such as neuroprotection, modulation of inflammation, and synaptic plasticity. This aligns with previous research showing that cannabinoid receptor ligands have the potential to trigger the functional structure of neuronal and brain networks, potentially impacting memory processing. Therefore, our study aims to assess the effects of prolonged, intermittent exposure (over 90 days) to JWH-133 (0.2 mg/kg) and an EU-GMP certified Cannabis sativa L. (Cannabixir^® Medium Flos, 2.5 mg/kg) on recognition memory, as well as their influence on brain metabolism and modulation of the expanded endocannabinoid system in APP/PS1 mice. Chronic therapy with cannabinoid receptor ligands resulted in reduced anxiety-like behavior and partially reversed the cognitive deficits. Additionally, a reduction was observed in both the number and size of Aβ plaque deposits, along with decreased cerebral glucose metabolism, as well as a decline in the expression of mTOR and CB2 receptors. Furthermore, the study revealed enlarged astrocytes and enhanced expression of M1 mAChR in mice subjected to cannabinoid treatment. Our findings highlight the pivotal involvement of the extended endocannabinoid system in cognitive decline and pathological aspects associated with AD, presenting essential preclinical evidence to support the continued exploration and assessment of cannabinoid receptor ligands for AD treatment.

Malware attacks are a significant part of the new software security threats detected each year. Intel Software Guard Extensions (SGX) are a set of hardware instructions introduced by Intel in their recent lines of processors that are intended to provide a secure execution environment for user-developed applications. To our knowledge, there was no serious attempt yet to overcome the SGX protection by exploiting the weaknesses in the software supply chain infrastructure, namely at the level of the development, build or signing servers. While SGX protection does not specifically take into consideration such threats, we show in the current paper that a simple malware attack exploiting a separation between the build and signing processes can have a serious damaging impact, practically nullifying SGX integrity protection measures. We also explore two possible mitigations against the attack, one centralized leveraging SGX itself, and one distributed that relies on a smart contract deployed on a blockchain infrastructure. Our evaluation shows that both methods are feasible in practice and their added costs are acceptable for the offered protection.

Malware attacks represent a significant part of today's security threats. Software guard extensions (SGX) are a set of hardware instructions introduced by Intel in their recent lines of processors that are intended to provide a secure execution environment for user-developed applications. To our knowledge, there was no serious attempt yet to overcome the SGX protection by leveraging the software supply chain infrastructure, such as weaknesses in the development, build or signing servers. While SGX protection does not specifically take into consideration such threats, we show in the current paper that a simple malware attack exploiting a separation between the build and signing processes can have a serious damaging impact, practically nullifying the SGX integrity protection measures. Finally, we also suggest some possible mitigations against the attack.