New idea to promote the clinical applications of stem cells or their extracellular vesicles in central nervous system disorders:Combining with intranasal delivery

The clinical translation of stem cells and their extracellular vesicles(EVs)-based therapy for central nervous system(CNS) diseases is booming. Nevertheless, the insufficient CNS delivery and retention together with the invasiveness of current administration routes prevent stem cells or EVs from fully exerting their clinical therapeutic potential. Intranasal(IN) delivery is a possible strategy to solve problems as IN route could circumvent the brain-blood barrier non-invasively and fit repeated dosage regimens. Herein, we gave an overview of studies and clinical trials involved with IN route and discussed the possibility of employing IN delivery to solve problems in stem cells or EVs-based therapy. We reviewed relevant researches that combining stem cells or EVs-based therapy with IN administration and analyzed benefits brought by IN route. Finally, we proposed possible suggestions to facilitate the development of IN delivery of stem cells or EVs.

Dissecting the brain with spatially resolved multi-omics

Recent studies have highlighted spatially resolved multi-omics technologies,including spatial genomics,transcriptomics,proteomics,and metabolomics,as powerful tools to decipher the spatial heterogeneity of the brain.Here,we focus on two major approaches in spatial transcriptomics(next-generation sequencing-based technologies and image-based technologies),and mass spectrometry imaging technologies used in spatial proteomics and spatial metabolomics.Furthermore,we discuss their applications in neuroscience,including building the brain atlas,uncovering gene expression patterns of neurons for special behaviors,deciphering the molecular basis of neuronal communication,and providing a more comprehensive explanation of the molecular mechanisms underlying central nervous system disorders.However,further efforts are still needed toward the integrative application of multi-omics technologies,including the real-time spatial multi-omics analysis in living cells,the detailed gene profile in a whole-brain view,and the combination of functional verification.

Progress in magnetic resonance imaging of the glymphatic system

The glymphatic system(GS)is a newly discovered brain anatomy.Its discovery improves our understanding of brain fluid flow and waste removal paths and provides an anatomical basis for the flow of cerebral interstitial fluid(ISF)and cerebrospinal fluid(CSF).GS occurs through a normal exchange within perivascular space(PVS),facilitating the elimination of metabolic wastes generated by nerve cells from the brain.Therefore,the GS is mainly responsible for the removal of metabolic waste.Reduced GS activity has been observed to be associated with central nervous system disorders such as cerebral small vessel disease(CSVD)and neurodegenerative diseases.Its activity is expected to be an indicator for diagnosing diseases and predicting their prognosis.This review introduces the magnetic resonance imaging(MRI)technology related to the GS suitable for clinical use and the difference in the system's activity in normal and abnormal states.Through a summary of previous research,imaging methods suitable for monitoring the activity of the GS in the clinic were proposed,and their diagnostic effect on different brain disorders was analyzed.This review aims to clarify ideas for the clinical translation of basic research focusing on GS and provide future clinical research directions and perspectives.