Subicular Caspase-1 Contributes to Pharmacoresistance in Temporal Lobe Epilepsy.

OBJECTIVE: Unidentified mechanisms largely restrict the viability of effective therapies in pharmacoresistant epilepsy. Our previous study revealed that hyperactivity of the subiculum is crucial for the genesis of pharmacoresistance in temporal lobe epilepsy (TLE), but the underlying molecular mechanism is not clear. METHODS: Here, we examined the role of subicular caspase-1, a key neural pro-inflammatory enzyme, in pharmacoresistant TLE. RESULTS: We found that the expression of activated caspase-1 in the subiculum, but not the CA1, was upregulated in pharmacoresistant amygdaloid-kindled rats. Early overexpression of caspase-1 in the subiculum was sufficient to induce pharmacoresistant TLE in rats, whereas genetic ablation of caspase-1 interfered with the genesis of pharmacoresistant TLE in both kindled rats and kainic acid-treated mice. The pro-pharmacoresistance effect of subicular caspase-1 was mediated by its downstream inflammasome-dependent interleukin-1ß. Further electrophysiological results showed that inhibiting caspase-1 decreased the excitability of subicular pyramidal neurons through influencing the excitation/inhibition balance of presynaptic input. Importantly, a small molecular caspase-1 inhibitor CZL80 attenuated seizures in pharmacoresistant TLE models, and decreased the neuronal excitability in the brain slices obtained from patients with pharmacoresistant TLE. INTERPRETATION: These results support the subicular caspase-1-interleukin-1ß inflammatory pathway as a novel alternative mechanism hypothesis for pharmacoresistant TLE, and present caspase-1 as a potential target. ANN NEUROL 2021;90:377-390.

Thermal transport properties of gas-filled silica aerogels.

Silica aerogel (SA), recognized as an efficient insulating material, is characterized by its extremely low thermal conductivity (TC) and high porosity, presenting extensive application potential in aerospace and building energy conservation. In this study, the thermal transport properties of gas-filled SA are explored using molecular dynamics (MD) methods. It is found that an increase in porosity leads to a significant decrease in TC, primarily due to enhanced phonon scattering and reduced material stiffness. Additionally, the TC of SA influenced by gas exhibits a pattern of initial decrease, followed by an increase, and then a decrease again, driven by complex interactions between gas molecules and pore walls, phonon localization, and scattering mechanisms. At a gas concentration of 80%, the TC in confined spaces is significantly increased by nitrogen, attributed to enhanced intermolecular interactions and increased collision frequency. The impact of gases on the TC of gas-solid coupled composite materials is also investigated, revealing that gas molecules serve as a "bridge" for phonons, playing a crucial role in reducing interfacial scattering and enhancing low-frequency vibrational modes, thus further enhancing heat transfer efficiency. The TC of these composite materials is primarily regulated by the gas-phase TC in response to temperature, while the response to strain is predominantly governed by variations in the solid-phase TC. These results provide essential theoretical support and design guidelines for the development and design of new high-efficiency insulating materials.

An Integrated Building Block for Cascade Diels-Alder and Hetero-Diels-Alder Reactions.

The Diels-Alder (DA) reaction and hetero-Diels-Alder (HDA) reaction are among the most powerful methods for the construction of carbocycles and heterocycles. Herein, an integrated building block of DA and HDA reactions is described. The triazenyl dienes could undergo a DA reaction, while the newly released alkene moiety and the triazene were able to engage in a HDA reaction. In these processes, the triazene group could facilitate the electron-demand DA reaction and also act as a fragment of diazadiene.

Power Intelligent Terminal Intrusion Detection Based on Deep Learning and Cloud Computing.

Numerous internal and external intrusion attacks have appeared one after another, which has become a major problem affecting the normal operation of the power system. The power system is the infrastructure of the national economy, ensuring that the information security of its network not only is an aspect of computer information security but also must consider high-standard security requirements. This paper analyzes the intrusion threat brought by the power information network and conducts in-depth research and investigation combined with the intrusion detection technology of the power information network. It analyzes the structure of the power knowledge network and cloud computing through deep learning-based methods and provides a network interference detection model. The model combines the methods of abuse detection and anomaly detection, which solves the problem that the abuse analysis model does not detect new attack variants. At the same time, for big data network data retrieval, it retrieves and analyzes data flow quickly and accurately with the help of deep learning of data components. It uses a fuzzy integral method to optimize the accuracy of power information network intrusion prediction, and the accuracy reaches 98.11%, with an increase of 0.6%.

SuFExable Isocyanides for Ugi Reaction: Synthesis of Sulfonyl Fluoro Peptides.

Herein, the sulfonyl fluoro isocyanides were first developed as a new type of SuFExable synthon, and they are used as building blocks in the Ugi reaction (U-4CR). The Ugi reaction was established and the substrate scope was investigated, and various sulfonyl fluoro α-amino amides and peptides could be reached in a one-step synthesis. Therefore, this protocol opens a new vision for SuFExable building blocks and click chemistry, and it also provides a distinct approach to sulfonyl fluoro peptides.