Pharmacological effects of denervated muscle atrophy due to metabolic imbalance in different periods

Denervation-induced skeletal muscle atrophy can potentially cause the decline in the quality of life of patients and an increased risk of mortality.Complex pathophysiological mechanisms with dynamic alterations have been documented in skeletal muscle atrophy resulting from innervation loss.Hence,an in-depth comprehension of the key mechanisms and molecules governing skeletal muscle atrophy at varying stages,along with targeted treatment and protection,becomes essential for effective atrophy management.Our preliminary research categorizes the skeletal muscle atrophy process into four stages using microarray analysis.This review extensively discusses the pathways and molecules potentially implicated in regulating the four stages of denervation and muscle atrophy.Notably,drugs targeting the reactivare oxygen species stage and the inflammation stage assume critical roles.Timely intervention during the initial atrophy stages can expedite protection against skeletal muscle atrophy.Additionally,pharmaceutical intervention in the ubiquitin-proteasome pathway associated with atrophy and autophagy lysosomes can effectively slow down skeletal muscle atrophy.Key molecules within this stage encompass MuRF1,MAFbx,LC3II,p62/SQSTM1,etc.This review also compiles a profile of drugs with protective effects against skeletal muscle atrophy at distinct postdenervation stages,thereby augmenting the evidence base for denervation-induced skeletal muscle atrophy treatment.

Single-cell atlas of domestic pig cerebral cortex and hypothalamus

The brain of the domestic pig(Sus scrofa domesticus)has drawn considerable attention due to its high similarities to that of humans.However,the cellular compositions of the pig brain(PB)remain elusive.Here we investigated the single-nucleus transcriptomic profiles of five regions of the PB(frontal lobe,parietal lobe,temporal lobe,occipital lobe,and hypothalamus)and identified 21 cell subpopulations.The cross-species comparison of mouse and pig hypothalamus revealed the shared and specific gene expression patterns at the single-cell resolution.Furthermore,we identified cell types and molecular pathways closely associated with neurological disorders,bridging the gap between gene mutations and pathogenesis.We reported,to our knowledge,the first single-cell atlas of domestic pig cerebral cortex and hypothalamus combined with a comprehensive analysis across species,providing extensive resources for future research regarding neural science,evolutionary developmental biology,and regenerative medicine.

A single-cell atlas of mouse olfactory bulb chromatin accessibility

Olfaction,the sense of smell,is a fundamental trait crucial to many species.The olfactory bulb(OB)plays pivotal roles in processing and transmitting odor information from the environment to the brain.The cellular heterogeneity of the mouse OB has been studied using single-cell RNA sequencing.However,the epigenetic landscape of the m OB remains mostly unexplored.Herein,we apply single-cell assay for transposaseaccessible chromatin sequencing to profile the genome-wide chromatin accessibility of 9,549 single cells from the m OB.Based on single-cell epigenetic signatures,m OB cells are classified into 21 clusters corresponding to 11 cell types.We identify distinct sets of putative regulatory elements specific to each cell cluster from which putative target genes and enriched potential functions are inferred.In addition,the transcription factor motifs enriched in each cell cluster are determined to indicate the developmental fate of each cell lineage.Our study provides a valuable epigenetic data set for the m OB at single-cell resolution,and the results can enhance our understanding of regulatory circuits and the therapeutic capacity of the OB at the single-cell level.

CDCP:a visualization and analyzing platform for single-cell datasets

Recently,the rapid advances of single-cell sequencing technologies,including sequencing of single-cell genomics,transcriptomes,epigenetics,and spatial transcriptomes,have empowered researchers to scrutinize cellular heterogeneity,gene expression,epigenetic modifications.