The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.
Animals ; Mice ; Humans ; Ependymoglial Cells/metabolism* ; Hedgehog Proteins/metabolism* ; Ferrets/metabolism* ; Cerebral Cortex ; Neurogenesis ; Mammals/metabolism* ; Neuroglia/metabolism* ; Bone Morphogenetic Protein 7/metabolism*

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Mice ; Animals ; Transcriptome ; Aging/metabolism* ; Cochlea ; Stria Vascularis ; Presbycusis

Cell Differentiation ; Humans ; Hyperthermia, Induced ; Stem Cells

Objective:To compare the clinical outcome of navigation-assisted percutaneous cannulated screw fixation and posterior percutaneous plate fixation for Day type II crescent fracture dislocation of pelvis (CFDP).Methods:A retrospective cohort analysis was performed on clinical data of 40 patients with Day type II CFDP treated in General Hospital of Central Theater Command of PLA from January 2012 to June 2021. There were 23 males and 17 females, with age range of 42-73 years [(54.2±7.8)years]. A total of 19 patients were treated with navigation-assisted percutaneous cannulated screw fixation (navigation group) and 21 with posterior percutaneous plate fixation (plate group). The incision length, operation time, intraoperative blood loss and in-hospital time were compared between the two groups. The reduction quality was evaluated by Matta radiographic standard at day 2 after surgery. The functional recovery was assessed by Majeed functional score at 3 and 6 months after surgery. The postoperative complications were observed.Results:All patients were followed up for 10-24 months [(13.6±2.9)months]. The incision length, operation time, intraoperative blood loss and in-hospital time was (2.4±0.3)cm, (43.1±5.2)minutes, (48.4±18.4)ml and (14.4±1.9)days in navigation group, showing significant difference compared with plate group [(8.8±0.4)cm, (132.2±19.4)minutes, (302.9±57.5)ml, (18.9±3.7)days] (all P<0.01). According to Matta radiographic standard at day 2 after surgery, the excellent and good rate was 89% in navigation group (excellent in 13 patients, satisfactory in 4 and poor in 2) and 95% in plate group (excellent in 15 patients, satisfactory in 5 and poor in 1) ( P>0.05). According to Majeed criteria at 3 months after surgery, the excellent and good rate was 89% in navigation group (excellent in 12 patients, good in 5 and poor in 2) and 95% in plate group (excellent in 15 patients, good in 5 and poor in 1) ( P>0.05). According to Majeed criteria at 6 months after surgery, the excellent and good rate was 95% in navigation group (excellent in 14 patients, good in 4 and poor in 1) and 95% in plate group (excellent in 17 patients, good in 3 and poor in 1) ( P>0.05). There was no iatrogenic neurovascular injury. The incidence of complications was 11% (2/19) in navigation group, including one patients with sacroiliac screw loosening and one with posterior iliac screw penetrating the medial cortex of the bone, while that was 29% (6/21) in plate group, including two patients with skin tenderness, two with deep vein thrombosis in the lower extremity and two with incision infection ( P<0.05). Conclusions:For Day type II CFDP, both navigation-assisted percutaneous cannulated screw fixation and posterior percutaneous plate fixation can attain satisfactory efficacy, but the former has advantages of shorter operation time, less surgical trauma, less bleeding, shorter in-hospital time and lower incidence of complications.

Animals ; Antlers ; Exosomes ; Mesenchymal Stem Cells ; Osteoarthritis/therapy*

Gallic Acid/pharmacology* ; Humans ; Senotherapeutics ; Stem Cells

Animals ; Chloroquine/pharmacology* ; Longevity ; Rats

Medium spiny neurons (MSNs) in the striatum, which can be divided into D1 and D2 MSNs, originate from the lateral ganglionic eminence (LGE). Previously, we reported that Six3 is a downstream target of Sp8/Sp9 in the transcriptional regulatory cascade of D2 MSN development and that conditionally knocking out Six3 leads to a severe loss of D2 MSNs. Here, we showed that Six3 mainly functions in D2 MSN precursor cells and gradually loses its function as D2 MSNs mature. Conditional deletion of Six3 had little effect on cell proliferation but blocked the differentiation of D2 MSN precursor cells. In addition, conditional overexpression of Six3 promoted the differentiation of precursor cells in the LGE. We measured an increase of apoptosis in the postnatal striatum of conditional Six3-knockout mice. This suggests that, in the absence of Six3, abnormally differentiated D2 MSNs are eliminated by programmed cell death. These results further identify Six3 as an important regulatory element during D2 MSN differentiation.

Mouse cortical radial glial cells (RGCs) are primary neural stem cells that give rise to cortical oligodendrocytes, astrocytes, and olfactory bulb (OB) GABAergic interneurons in late embryogenesis. There are fundamental gaps in understanding how these diverse cell subtypes are generated. Here, by combining single-cell RNA-Seq with intersectional lineage analyses, we show that beginning at around E16.5, neocortical RGCs start to generate ASCL1

Objective: To investigate the therapeutic effects and pharmacological mechanisms of Yishen Xingyang capsule (YXC) in oligoasthenospermia (OA) rats.Methods: Forty-eight male Sprague-Dawley rats were randomly divided into eight groups of six rats each:normal control (NC);model control (MC);three different positive drug (PD);and low-, medium-, and high-dose YXC groups. A rat model of OA was established by administering glucosides of Triptery-gium wilfordii Hook. F (GTW). After YXC administration, penile erectile function was observed. The epididymis, blood, and testes of the rats were harvested for analysis of sperm quality, sex hormone levels, mitochondrial membrane potential, and the transforming growth factor (TGF)-β1/Smad signaling pathway. Results: Compared with that in the MC group, penile erectile function in the YXC groups and three PD groups increased (all P<.01). Moreover, sperm quality in the YXC groups and three PD groups improved (all P < .001). The levels of testosterone, follicle stimulating hormone, and luteinizing hormone in the three PD and YXC groups increased (all P<.05). The mitochondrial membrane potential in the three PD and YXC groups significantly improved (all P<.001). Furthermore, the YXC and three PD groups showed decreased TGF-β1 expression (all P< .05) compared with the MC group. The high-dose YXC group and three PD groups improved Smad2 and Smad4 expression (all P<.05). Conclusion: YXC improved penile erectile function and sperm quality in OA rats, and the underlying mechanism included increase in sex hormones, inhibition of sperm apoptosis, and regulation of the TGF-β1/Smad signaling pathway. Meanwhile, this study provides a new effective drug option for the treat-ment of OA, which is beneficial to male reproductive health and social harmony.