Yunfan Kong

SUMMARY: Understanding how cell types are organized across the central nervous system (CNS) is key to uncovering neural function. Here, we integrate single-nucleus Multiome (RNA+ATAC) sequencing, spatial transcriptomics, and computational analyses to map conserved cell type signatures in the adult mouse brainstem and spinal cord. We identify a shared core of neuronal and non-neuronal cell types, alongside region-specific specializations reflecting distinct functions. Spatial data reveal conserved cellular niches across the brainstem–spinal cord boundary, indicating a continuous organizational logic. Cross-region comparisons uncover recurrent gene expression modules and signaling programs that may support shared circuit features. Chromatin accessibility profiling highlights cell-type-specific regulatory programs and implicates Hox transcription factors in positional identity. Notably, cell-type and positional identities are largely orthogonal, with varying regional influence across neuronal classes: motor neurons show strong positional coupling, whereas glutamatergic and GABAergic interneurons show minimal entrainment. This work provides a reference for the shared molecular architecture of these CNS regions.

Peripheral nerve injury (PNI) is a common problem worldwide. PNI can lead to loss of sensory and motor functions, chronic neuropathic pain, and mental health issues, significantly impacting the patients' quality of life. Recent studies revealed that, beyond the topical injury site at peripheral nerves, PNIs can also induce dysfunctions in the central nervous system (CNS) by causing maladaptive plasticity, which will result in exaggeration and exacerbation of the pathological condition caused by the primary injuries. The typical therapy strategies for traumatic PNI treatment are using sutures, nerve autografts, or conduits in cases requiring surgical intervention as well as applying physical-based rehabilitation to facilitate functional recovery. However, the functional restoration is generally unsatisfactory due to insufficient regeneration and long-lasting maladaptive neuroplasticity in the nervous system. In this review, we summarized various neurotrophic factors and neuroprotective agents that have been extensively studied as adjuvant therapies to enhance recovery efficiency after PNIs in the last two decades. Particularly, with the rapid development of biomaterials and bioengineering, controllable drug delivery techniques have shown great potential to maintain the drug bioactivity and, consequently, prolonging the therapeutic effects. Additionally, we explored the virus-based gene delivery technique, which has been used to transduce neural cells for enhancing nerve regeneration. Finally, we discussed current challenges, including inadequate motor function restoration, poorly defined rehabilitation protocols, unresolved chronic inflammation, and limited understanding of macrophage dynamics. We also offered perspectives on integrating various approaches to develop effective and comprehensive treatment strategies for PNIs.

Psoriasis is a chronic inflammatory disease with a complex pathogenesis, influenced by various factors involving environment, genes, and immunity. The main symptoms of psoriasis include erythema, scales, itching, etc. At present, therapeutic drugs for psoriasis are continually evolving towards enhancing treatment efficacy and reducing side effects. Firstly, the pathogenesis and characteristics of psoriasis were summarized. Then, the types and benefits of topical therapy were introduced, such as the aspects of avoiding systemic toxic effects, first pass effect, and gastrointestinal reactions with accelerating the onset time of the drugs and improving its efficacy, and were compared to systemic drugs. In the case of methotrexate, cyclosporin A, Janus kinase (JAK) inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors, this review had a further discussion on the improvement and translation of these molecules from systemic therapy to topical therapy in clinical practice. To further augment the limitation of skin permeability, nanotechnology and novel topical drug delivery system including nanomedicines, hydrogels, ionic liquids, and microneedles were elaborated for psoriasis management. Also, exploration of topical targeting pathogenic genes through small interfering RNA (siRNA) using nanoparticles and ionic liquids (ILs) is of great significance for long-term treatment in psoriasis. Taken together, the development of numerous topical delivery platforms is expected to achieve enhanced penetration, and precise and efficient delivery of small molecule and RNA interference (RNAi) therapeutics in psoriasis with clinical translation prospects.