Suchergebnisse

From the perspective of spatial geography, this paper verifies the spatial dependence of China&rsquo ; s provincial carbon emissions. The contribution of impact factors with different fields of view to carbon emissions&rsquo ; growth is estimated based on the spatial panel data model, t. The study found that during 2000&ndash ; 2015, China&rsquo ; s energy-related carbon emissions in the provinces were dependent on the spatial, and the spatial spillover effect of carbon emissions and its influencing factors in the neighboring provinces are obvious. It was also found that economic growth, industrial structure, financial development, and urbanization rates are positive, and the effect of the population and technological progress on reducing carbon emissions is significant. The effect of source price, export dependence, and fiscal decentralization on carbon emissions&rsquo ; growth did not pass a significance test. In the formulation of carbon emission-related policies and development plans, the government must consider the effect of the influencing factors affecting the carbon emissions in the adjacent area and combine the carbon emissions and spatial spillover effect of the related factors in order to reduce carbon emissions in the time dimension and the spatial dimension of China as a whole.

Abstract

Background
Nucleus pulposus cell (NPC) senescence in intervertebral disc (IVD) tissue is the major pathological cause of intervertebral disc degeneration (IDD). N6-methyladenosine (m6A) methylation and gut microbiota play important roles in the progression of IDD. This study investigated whether methyltransferase-like 3 (METTL3) regulates TLR2 m6A modification and gut microbiota to influence NPC senescence.


Methods
An IDD rat model was established by lumbar IVD puncture and NPCs were challenged with IL-1β to mimic IVD injury. IDD rats and IL-1β-exposed NPCs were treated with METTL3-interfering lentivirus and the TLR2 agonist Pam3CSK4. Compositional changes in the rat gut microbiota were analyzed and fecal microbiota transplantation procedures were used. NPC senescence, cell cycle, and the expression of senescence-associated secretory phenotype (SASP) factors were assessed. The m6A enrichment of TLR2 and the binding of IGF2BP1 to TLR2 mRNA were examined.


Results
METTL3 and TLR2 were highly expressed in IDD rats. METTL3 silencing attenuated senescent phenotypes and reduced secretion of SASP factors. Pam3CSK4 reversed the beneficial effects of METTL3 silencing on NPC senescence and IVD injury. METTL3 stabilized TLR2 mRNA in an IGF2BP1-dependent manner. METTL3 silencing restored specific gut microbiota levels in IDD rats, which was further reversed by administration of Pam3CSK4. Fecal microbiota from METTL3 silenced IDD rats altered the pathological phenotypes of IDD rats.


Conclusions
These results demonstrate the beneficial effects of METTL3 silencing on NPC senescence and amelioration of IVD injury, involving modulation of TLR2 m6A modification and gut microbiota. These findings support METTL3 silencing as a potential therapeutic target for IDD.