Variation of microbial necromass carbon and its potential relationship with humification during composting of chicken manure with and without biochar addition.

Microbial necromass carbon (MNC) is an important stable organic C component. However, the variation of MNC and its potential relationship with humus components in composting remains uncertain. During a 45-day chicken manure composting study with and without biochar, MNC ranged from 24.9 to 77.9 g/kg and increased significantly by 80.9 % to 133 %. MNC constituted 5.77 % to 21.3 % of total organic C, with bacterial/fungal necromass C ratio ranging from 0.82 to 1.78. The MNC/humus C ratio ranged from 0.15 to 0.55, and humic acid C showed significant positive associations with bacterial necromass C (R2 = 0.72) and fungal necromass C (R2 = 0.51). Biochar addition reduced electrical conductivity and moisture content, increased pH, and induced microbial phosphorus limitation, thereby enhancing MNC content by 29.2 % and promoting humification. Our study is the first to elucidate the relationship between microbial necromass and humus substances, providing fundamental data for advancing the microbial carbon pump theory in composting.

Restoring the Function of Thalamocortical Circuit Through Correcting Thalamic Kv3.2 Channelopathy Normalizes Fear Extinction Impairments in a PTSD Mouse Model.

Impaired extinction of fear memory is one of the most common symptoms in post-traumatic stress disorder (PTSD), with limited therapeutic strategies due to the poor understanding of its underlying neural substrates. In this study, functional screening is performed and identified hyperactivity in the mediodorsal thalamic nucleus (MD) during fear extinction. Furthermore, the encoding patterns of the hyperactivated MD is investigated during persistent fear responses using multiple machine learning algorithms. The anterior cingulate cortex (ACC) is also identified as a functional downstream region of the MD that mediates the extinction of fear memory. The thalamocortical circuit is comprehensively analyzed and found that the MD-ACC parvalbumin interneurons circuit is preferentially enhanced in PTSD mice, disrupting the local excitatory and inhibitory balance. It is found that decreased phosphorylation of the Kv3.2 channel contributed to the hyperactivated MD, primarily to the malfunctioning thalamocortical circuit. Using a lipid nanoparticle-based RNA therapy strategy, channelopathy is corrected via a methoxylated siRNA targeting the protein phosphatase 6 catalytic subunit and restored fear memory extinction in PTSD mice. These findings highlight the function of the thalamocortical circuit in PTSD-related impaired extinction of fear memory and provide therapeutic insights into Kv3.2-targeted RNA therapy for PTSD.

Targeting Mitochondrial Sirtuins in Age-Related Neurodegenerative Diseases and Fibrosis.

Aging is a natural and complex biological process that is associated with widespread functional declines in numerous physiological processes, terminally affecting multiple organs and tissues. Fibrosis and neurodegenerative diseases (NDs) often occur with aging, imposing large burdens on public health worldwide, and there are currently no effective treatment strategies for these diseases. Mitochondrial sirtuins (SIRT3-5), which are members of the sirtuin family of NAD+-dependent deacylases and ADP-ribosyltransferases, are capable of regulating mitochondrial function by modifying mitochondrial proteins that participate in the regulation of cell survival under various physiological and pathological conditions. A growing body of evidence has revealed that SIRT3-5 exert protective effects against fibrosis in multiple organs and tissues, including the heart, liver, and kidney. SIRT3-5 are also involved in multiple age-related NDs, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Furthermore, SIRT3-5 have been noted as promising targets for antifibrotic therapies and the treatment of NDs. This review systematically highlights recent advances in knowledge regarding the role of SIRT3-5 in fibrosis and NDs and discusses SIRT3-5 as therapeutic targets for NDs and fibrosis.