Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

Aim To observe the effects of microRNA-204/-211 deficiency on osteoarthritis(OA) induced by medial meniscus amputation (DMM) in mice. Methods 12 C57BL/6J wild-type (WT) mice were randomly divided into sham operation groups and DMM groups, namely WT-control group and WT + DMM group. And twelve microRNA-204/-211 gene knockout (miR-204/-211-dKO) mice were randomly divided into sham operation groups and DMM groups, namely dKO group, and dKO + DMM group. The pain sensitivity of mice was measured by the von Frey test before sacrificing. Three months after the operation, the mice were sacrificed. The knee joints and dorsal root ganglion (DRG) were taken for detection. The subchondral bone structure was detected by micro-CT. Sections of knee joint tissue were stained with toluidine blue, PCNA, type Ⅱ collagen and immunohistochemistry. DRG tissues were detected for related pain factors and inflammatory factors by RT-qPCR. Results Compared with the mice in the WT-Control group, mice in the WT + DMM group showed typical OA symptoms such as osteophyte formation, subchondral osteosclerosis, and decreased pain thresholds. The expression of collagen Ⅱ in cartilage significantly decreased, while the expression of MMP13 significantly increased. The expression of inflammatory and pain-related factors in DRG significantly increased. At the same time, the OA phenotypes of mice in dKO + DMM were more obvious than that of mice in the WT + DMM group, indicating that miR-204/-211 deficiency aggravated the OA induced by DMM in mice. In particular, DMM did not cause synovial hyperplasia and synovial inflammation in WT mice, which could not completely represent the pathological characteristics of OA patients in clinical practice. However, miR-204/-211 deficiency significantly promoted synovial hyperplasia and synovial inflammation of knee joints in DMM mice. Conclusions After DMM operation, miR-204/-211 deficient mice showed not only typical OA phenotypes such as osteophyte formation, subchondral osteosclerosis, cartilage destruction and lower pain threshold, but also synovial hyperplasia and synovitis, which could better represent the pathological characteristics of clinical OA patients. MiR-204/-211 deficient mice with DMM can be used as a new OA model and an ideal animal model for screening anti-OA drugs.