Axonal degeneration is a common pathological feature in many acute and chronic neurological diseases such as spinal cord injury (SCI). SARM1 (sterile alpha and TIR motif-containing 1), the fifth TLR (Toll-like receptor) adaptor, has diverse functions in the immune and nervous systems, and recently has been identified as a key mediator of Wallerian degeneration (WD). However, the detailed functions of SARM1 after SCI still remain unclear.

Yes-associated protein (YAP) transcriptional coactivator is negatively regulated by the Hippo pathway and functions in controlling the size of multiple organs, such as liver during development. However, it is not clear whether YAP signaling participates in the process of the formation of glia scars after spinal cord injury (SCI). In this study, we found that YAP was upregulated and activated in astrocytes of C57BL/6 male mice after SCI in a Hippo pathway-dependent manner. Conditional knockout (KO) ofyapin astrocytes significantly inhibited astrocytic proliferation, impaired the formation of glial scars, inhibited the axonal regeneration, and impaired the behavioral recovery of C57BL/6 male mice after SCI. Mechanistically, the bFGF was upregulated after SCI and induced the activation of YAP through RhoA pathways, thereby promoting the formation of glial scars. Additionally, YAP promoted bFGF-induced proliferation by negatively controlling nuclear distribution of p27^Kip1mediated by CRM1. Finally, bFGF or XMU-MP-1 (an inhibitor of Hippo kinase MST1/2 to activate YAP) injection indeed activated YAP signaling and promoted the formation of glial scars and the functional recovery of mice after SCI. These findings suggest that YAP promotes the formation of glial scars and neural regeneration of mice after SCI, and that the bFGF-RhoA-YAP-p27^Kip1pathway positively regulates astrocytic proliferation after SCI.SIGNIFICANCE STATEMENTGlial scars play critical roles in neuronal regeneration of CNS injury diseases, such as spinal cord injury (SCI). Here, we provide evidence for the function of Yes-associated protein (YAP) in the formation of glial scars after SCI through regulation of astrocyte proliferation. As a downstream of bFGF (which is upregulated after SCI), YAP promotes the proliferation of astrocytes through negatively controlling nuclear distribution of p27^Kip1mediated by CRM1. Activation of YAP by bFGF or XMU-MP-1 injection promotes the formation of glial scar and the functional recovery of mice after SCI. These results suggest that the bFGF-RhoA-YAP-p27^Kip1axis for the formation of glial scars may be a potential therapeutic strategy for SCI patients.

Background: Multiple myeloma (MM) is a growing global public health challenge. Known epidemiological data suggest that MM accounts for approximately 10% of all hematologic malignancies and remains the second most common hematologic cancer worldwide. This study utilized data from the 2021 Global Burden of Diseases (GBD) study to evaluate the prevalence, incidence, mortality, disability-adjusted life years (DALYs), and attributable risk factors of MM from 1990 to 2021, and to project future trends for the next 15 years.Methods: GBD 2021 data were analyzed to assess MM’s global burden using four key epidemiological measures: prevalence, incidence, mortality, and DALYs. Estimates are reported per 100,000 population with uncertainty intervals (UI). Temporal trends were assessed through estimated annual percentage change (EAPC) and 95% confidence intervals (CI). All analyses were conducted using R version 4.2.1.Results: From 1990 to 2021, global MM prevalence, incidence, mortality, and DALYs more than doubled, particularly among males. All Social-Demographic Index (SDI) regions showed increases in ASPR, ASIR, ASMR, and ASDR (all EAPCs >0), with the middle SDI regions exhibiting the most rapid growth. ARIMA model predictions suggest that the MM burden will continue rising over the next 15 years. The proportion of MM cases attributable to high BMI also increased globally, from 6.40% in 1990 to 7.96% in 2021. MM primarily affects older adults, with the highest incidence observed in the 70–74 age group and the highest mortality rate recorded in the same age range.Conclusion: MM presents an escalating global health challenge. Targeted preventive interventions and improvements in diagnosis, treatment, and care are critical, especially in underdeveloped regions, to address the growing global burden of MM.