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*

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Objective     To compare the clinical effects of coronary artery bypass grafting (CABG) via the left anterior small thoracotomy (LAST) versus lower-end sternal splitting (LESS) approach in the treatment of coronary heart disease. Methods     The patients who underwent LAST CABG in Tianjin Chest Hospital from October 2015 to December 2020 were allocated to an observation group (LAST group), and the patients who underwent LESS CABG at the same period were allocated to a LESS group. Propensity score matching method was applied with a ratio of 1∶1. The baseline data, perioperative data and grafts data were compared between the two groups after matching. Results     Before matching, there were 110 patients in the LAST group, and 206 patients in the LESS group. After matching, there were 110 patients in each group. In the LAST group, there were 83 males and 27 females with an average age of 60.6±8.3 years. In the LESS group, there were 80 males and 30 females with an average age of 61.0±9.6 years. There was no statistical difference in baseline data between the two groups after matching (P>0.05). The hospital stay time (t=2.255, P=0.025) and ventilator using time (t=−2.229, P=0.027) in the LAST group were significantly shorter than those in the LESS group. There were no statistical differences between the two groups in the postoperative hospital stay time, ICU stay time, postoperative left ventricular ejection fraction, postoperative left ventricular end-diastolic diameter, average number of grafts, secondary intubation, secondary thoracotomy, postoperative wound infection, sternal complications, postoperative atrial fibrillation, postoperative pulmonary infection or main adverse cardiovascular and cerebrovascular events (P>0.05). There was no statistical difference in the distribution of target vessels in the anterior descending branch, diagonal branch or posterior descending branch between the two groups (P>0.05). The grafts of the LAST group were significantly more than those of the LESS group in the area of obtuse marginal branch and posterior ventricular branch, and the grafts of the LESS group were significantly more than those of the LAST group in the area of right coronary artery (P<0.05). Post-operative computerized tomography angiography indicated that 1 patient in the LAST group had obtuse marginal branch vein bridge vessel occlusion, and the bridge vessels in the other patients were unobstructed. Conclusion     Minimally invasive CABG via both LAST and LESS approaches is safe and effective. LAST approach can achieve complete revascularization for multi-vessel lesions, and it is safe and reliable, with the advantages of less trauma and aesthetic appearance. However, it requires a certain learning curve of surgical techniques and certain surgical indications.

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

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

Animals ; Chloroquine/pharmacology* ; Longevity ; Rats

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

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