ObjectivesThe study aimed to explore the underlying mechanisms of OSA-related cognitive impairment by investigating the altered topology of brain white matter networks in children with OSA.MethodsGraph theory was used to examine white matter networks' network topological properties in 46 OSA and 31 non-OSA children. All participants underwent MRI, polysomnography, and cognitive testing. The effects of the obstructive apnea-hypopnea index (OAHI) on topological properties of white matter networks and network properties on cognition were studied using hierarchical linear regression. Mediation analyses were used to explore whether white matter network properties mediated the effects of OAHI on cognition.ResultsChildren with OSA had significantly higher assortativity than non-OSA children. Furthermore, OAHI was associated with the nodal properties of several brain regions, primarily in the frontal and temporal lobes. The relationship between OAHI and verbal comprehension index was mediated through clustering coefficients in the right temporal pole of the superior temporal gyrus.ConclusionsOSA affects the development of white matter networks in children's brains. Besides, the mediating role of white matter network properties between the OAHI and the verbal comprehension index provided neuroimaging evidence of impaired cognitive function in children with OSA.

This study aimed to investigate sex differences in cerebral blood flow (CBF) and serum inflammatory cytokines, as well as their correlations in patients with acute-stage mild traumatic brain injury (mTBI). Forty-one patients with mTBI and 23 matched healthy controls underwent 3D-pseudo-continuous arterial spin labeling imaging on 3T magnetic resonance imaging. The patients underwent cognitive evaluations and measurement of a panel of ten serum cytokines: interleukin (IL)-1I, IL-4, IL-6, IL-8, IL-10, IL-12, C–C motif chemokine ligand 2, interferon-gamma, nerve growth factor-beta (β-NGF), and tumor necrosis factor-alpha (TNF-α). Spearman rank correlation analysis was performed to evaluate the relationship between inflammation levels and CBF. We found that both male and female patients showed increased IL-1L and IL-6 levels. Female patients also demonstrated overexpression of IL-8 and low expression of IL-4. As for CBF levels, three brain regions [the right superior frontal gyrus (SFG_R), left putamen, and right precuneus] increased in male patients while three brain regions [the right superior temporal gyrus (STG_R), left middle occipital gyrus, and right postcentral (PoCG_R)] decreased in female patients. Furthermore, the STG_R in female controls was positively correlated with β-NGF while the right PoCG_R in female patients was negatively correlated with IL-8. In addition, compared with male patients, female patients showed decreased CBF in the right pallidum, which was negatively correlated with IL-8. These findings revealed abnormal expression of serum inflammatory cytokines and CBF levels post-mTBI. Females may be more sensitive to inflammatory and CBF changes and thus more likely to get cognitive impairment. This may suggest the need to pay closer attention to the female mTBI group.

Inflammation-based scores have been increasingly used for prognosis prediction in neurological diseases. This study aimed to investigate the predictive value of inflammation-based scores combined with radiological characteristics in children with moderate or severe traumatic brain injury (MS-TBI). A total of 104 pediatric patients with MS-TBI were retrospectively enrolled and randomly divided into training and validation cohorts at a 7:3 ratio. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of prognosis in pediatric patients with MS-TBI. A prognostic nomogram was constructed, and its predictive performance was validated in both the training and validation cohorts. Sex, admission platelet-to-lymphocyte ratio, and basal cistern status from initial CT findings were identified as independent prognostic predictors for children with MS-TBI in multivariate logistic analysis. Based on these findings, a nomogram was then developed and its concordance index values were 0.918 [95% confidence interval (CI): 0.837-0.999] in the training cohort and 0.86 (95% CI: 0.70-1.00) in the validation cohort, which significantly outperformed those of the Rotterdam, Marshall, and Helsinki CT scores. The proposed nomogram, based on routine complete blood count and initial CT scan findings, can contribute to individualized prognosis prediction and clinical decision-making in children with MS-TBI.

Heart failure (HF) is a major global healthcare problem accounting for substantial deterioration of prognosis. As a complex clinical syndrome, HF often coexists with multi-comorbidities of which cognitive impairment (CI) is particularly important. CI is increasing in prevalence among patients with HF and is present in around 40%, even up to 60%, of elderly patients with HF. As a potent and independent prognostic factor, CI significantly increases the hospitalization and mortality and decreases quality of life in patients with HF. There has been a growing awareness of the complex bidirectional interaction between HF and CI as it shares a number of common pathophysiological pathways including reduced cerebral blood flow, inflammation, and neurohumoral activations. Research that focus on the precise mechanism for CI in HF is still ever insufficient. As the tremendous adverse consequences of CI in HF, effective early diagnosis of CI in HF and interventions for these patients may halt disease progression and improve prognosis. The current clinical guidelines in HF have begun to emphasize the importance of CI. However, nearly half of CI in HF is underdiagnosed, and few recommendations are available to guide clinicians about how to approach CI in patients with HF. This review aims to synthesize knowledge about the link between HF and cognitive dysfunction, issues pertaining to screening, diagnosis and management of CI in patients with HF, and emerging therapies for prevention. Based on data from current studies, critical gaps in knowledge of CI in HF are identified, and future research directions to guide the field forward are proposed.

PurposeTo investigate changes in local spontaneous brain activity in patients with active thyroid-associated ophthalmopathy (TAO) and explore the relationship between such alterations and microvascular indices.MethodsThirty-six active TAO patients with active phase and 39 healthy controls (HCs) were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI), neuropsychological tests, and ophthalmological examinations. The rs-fMRI-based fractional low-frequency fluctuation amplitude (fALFF) analysis methods were used to assess spontaneous brain activity in both groups. The structure (peripapillary retinal nerve fiber layer, pRNFL) and microvascular indices (the optic nerve head (ONH) whole image vessel density, ONH-wiVD, and peripapillary vessel density) were analyzed through optical coherence tomographic angiography imaging. The relationship between abnormal spontaneous brain activity and ophthalmological indices was analyzed using the Spearman’s rank correlation analysis.ResultsCompared with HCs, active TAO patients had increased fALFF in the right inferior temporal gyrus (R.ITG) and left posterior cingulate gyrus (L.PCC), but decreased fALFF in the right calcarine (R.CAL). The fALFF values in L.PCC were positively correlated with peripapillary vessel density, whereas fALFF values in R.CAL were negatively related to peripapillary vessel density.ConclusionsThis study demonstrates that changes in spontaneous brain activity of active TAO are accompanied by peripapillary microvascular variations. These results provide insights into the pathophysiological mechanisms of active TAO. In addition, the combination of fALFF values and peripapillary vessel density may be served as important references for better clinical decision making.

Background Parental migration has been associated with a higher risk of cognitive and behavioral abnormalities in left-behind children (LBC). This study aimed to explore the spontaneous brain activity in LBC and reveal the mechanisms underlying behavioral and cognitive abnormalities. Methods Involved LBC (n = 36) and non-LBC (n = 22) underwent resting-state functional MRI (fMRI) examination and cognitive and behavioral assessment. The fMRI-based amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were assessed to analyze the spontaneous brain activity pattern. The relationships among abnormal spontaneous brain activity, behavioral and cognitive deficits and altered family environment were assessed by partial correlation analysis. Results Compared with non-LBC, LBC exhibited increased amplitude of low-frequency fluctuations in the right lingual gyrus (LING), while a decreased ALFF was observed in the bilateral insula and right orbital part of the middle frontal gyrus (ORBmid) (two-tailed voxel-level p < 0.01 and cluster-level p <0.05, Gaussian Random Field (GRF) correction). The fALFF in LBC were significantly increased in the left cerebellum 9 (Cbe9) and right cerebellum Crus2 (CbeCru2), while it decreased in the right hippocampus and left superior temporal gyrus (STG) (two-tailed voxel-level p < 0.01 and cluster-level p < 0.05, GRF correction). The ALFF and fALFF values in abnormal brain regions were found to be correlated with the learning ability, except for the right insula, while the fALFF values of the left STG were positively correlated with the full-scale IQ scores (p < 0.05). Moreover, the ALFF and fALFF values in all abnormal brain regions correlated with the education level of caregivers (p < 0.05). Conclusions Our study provided empirical evidence that the lack of direct parental care during early childhood could affect brain function development involving cognition, behavior, and emotion. Our findings emphasized that intellectual and emotional cares are essential for LBC.

Background Generalized tonic–clonic seizures (GTCS) are associated with significant disability and sudden unexpected death when they cannot be controlled. We aimed to explore the underlying neural substrate of the different responses to antiseizure drugs between the seizure-free (SF) and non-seizure-free (NSF) patients with GTCS through the amplitude of low-frequency fluctuation (ALFF) method. Methods We calculated ALFF among the SF group, NSF group, and healthy controls (HCs) by collecting resting-state functional magnetic resonance imaging (rs-fMRI) data. One-way ANOVA was used to compare the ALFF of the three groups, and post-hoc analysis was done at the same time. Pearson's correlation analysis between ALFF in the discrepant brain areas and the clinical characteristics (disease course and age of onset of GTCS) was calculated after then. Results A significant group effect was found in the right fusiform gyrus (R.FG), left fusiform gyrus (L.FG), left middle occipital gyrus (L.MOG), right inferior frontal gyrus (R.IFG), right precentral gyrus (R.PreG), right postcentral gyrus (R.PostG), and left calcarine sulcus (L.CS). The SF and NSF groups both showed increased ALFF in all discrepant brain areas compared to HCs except the R.IFG in the NSF group. Significantly higher ALFF in the bilateral FG and lower ALFF in the R.IFG were found in the NSF group compared to the SF group. Conclusions Higher ALFF in the bilateral FG were found in the NSF group compared to the SF and HC groups. Our findings indicate that abnormal brain activity in the FG may be one potential neural substrate to interpret the failure of seizure control in patients with GTCS.

Objective: We aimed to evaluate the effect of vitamin D supplementation in post-stroke fatigue (PSF) patients with vitamin D deficiency on fatigue symptoms and outcomes.Methods: Patients with primary acute ischemic stroke (AIS) were recruited consecutively from July 2016 to June 2018. Post-stroke fatigue patients were screened out with the Fatigue Severity Scale (FSS) questionnaire, serum concentrations of 25-hydroxyvitamin D [25-(OH)-D] were assessed with enzyme-linked immunosorbent assay (ELISA), and neurological function was evaluated with FSS and modified Rankin Scale (mRS) scoring criteria. Post-stroke fatigue patients with vitamin D deficiency were divided into two groups: a study group in which patients received vitamin D supplementation (cholecalciferol, 600 IU/day) along with usual care, and a control group in which patients received usual care alone. At the end of 1 and 3 months after treatment, all PSE patients accepted re-measurement of serum vitamin D and re-evaluation of fatigue and neurological function.Results: A total of 532 AIS patients were consecutively recruited to participate in this study. Patients without PSF, non-vitamin D deficiency, pre-stroke fatigue, or vitamin D supplementation were excluded from the study. In addition, patients who were lost to follow-up were also excluded. Finally, 139 out of 532 (26.1%) patients with PSF and vitamin D deficiency received vitamin D supplementation treatment. Fatigue Severity Scale score was significantly lower in the study group than in the control group at 1 month (t = −4.731, p < 0.01) and 3 months (t = −7.937, p < 0.01) after treatment. One month after treatment, mRS score in the study group was lower than that in the control group without statistical difference (t = −0.660, p > 0.05), whereas mRS was significantly higher in the study group than in the control group at 3 months after treatment (t = −4.715, p < 0.01).Conclusions: Our results indicated that vitamin D supplementation could improve fatigue symptoms and neurological outcomes in PSF patients with vitamin D deficiency. Subject to replication in other settings, a randomized controlled trial (RCT) might be undertaken to validate the potential beneficial impact of vitamin D supplementation in post-stroke patients found to be vitamin D deficient.

PURPOSE:Marshall and Rotterdam are the most commonly used CT scoring systems to predict the outcome following traumatic brain injury (TBI). Although several studies have compared the performance of the two scoring systems in adult patients, none of these studies has evaluated the performance of the two scoring systems in pediatric patients. This study aimed to determine the predictive value of the Marshall and Rotterdam scoring systems in pediatric patients with TBI. METHODS:This retrospective study included 105 children with admission GCS < 12, with a mean age of 6.2 (±3.5) years. Their initial CT and status at hospital discharge (dead or alive) were reviewed, and both the Marshall and Rotterdam scores were calculated. We examined whether each score was related to the early death of pediatric patients. RESULTS:The pediatric patients with higher Marshall and Rotterdam scores had a higher mortality rate. There was a good correlation between the Marshall and Rotterdam scoring systems (Spearman's rho = 0.618, significant at the 0.05 level). Both systems demonstrated a high degree of discrimination when predicting early mortality. The Marshall scoring system had reasonable discrimination (AUC 0.782), and the Rotterdam scoring system had good discrimination (AUC 0.729). Comparing the two CT scoring systems, the Marshall scoring system provided a better positive predictive value (90%) for early mortality than the Rotterdam scoring system (78%). CONCLUSIONS:Both the Marshall and Rotterdam scoring systems have good predictability for assessing mortality in pediatric patients with TBI. The performance of the Marshall scoring system was equal to or slightly better than that of the Rotterdam scoring system.

Summary: Attempts to generate functional blood cells from human pluripotent stem cells (hPSCs) remain largely unsuccessful, mainly due to the lack of understanding of the regulatory network of human hematopoiesis. In this study, we identified leucine-rich-repeat-containing G-protein-coupled receptor 4 (LGR4) as an essential regulator of early hematopoietic differentiation of hPSCs. The deletion of LGR4 severely impairs mesoderm development, thereby limiting hematopoietic differentiation both in vitro and in vivo. In contrast, LGR5 is dispensable for hPSC hematopoiesis. The four R-spondin proteins show differential activities and dependencies on LGR4 in hematopoietic differentiation. The deletion of LGR4 almost entirely abolishes the enhancement induced by R-spondin1 and R-spondin3, but not R-spondin2. In addition, ZNRF3 is required for the response of R-spondin1–R-spondin3. At the mechanistic level, LGR4 regulates transforming growth factor beta (TGF-beta) signaling to control hematopoietic differentiation. Together, our results reveal vital roles of LGR4 in hematopoietic development and uncover distinct functions and underlying mechanisms for R-spondins.

Purpose To investigate the mechanisms underlying the gray matter volume (GMV) and functional connectivity (FC) changes in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD) patients. Methods This cross-sectional study consisted of 21 patients with aquaporin-4 antibody-positive NMOSD and 22 age- and sex-matched healthy controls. All participants underwent cerebral magnetic resonance imaging and testing each individual’s visual acuity was done. Results Neuromyelitis optica spectrum disorder patients showed significantly reduced GMV in the left calcarine, left thalamus and right lingual gyrus of the NMOSD patients when compared to HC (P < 0.05). NMOSD patients showed significantly decreased FC values (P < 0.05) in both the left and right calcarine, right lingual gyrus and left thalamus, respectively, when compared to HC. We also observed a positive correlation between the FC values of the left thalamus, bilateral calcarine gyrus and the visual acuity, respectively (P < 0.05). Furthermore, a negative association was seen between the duration of the disease, frequency of optic neuritis, and the FC values in the lingual gyrus, bilateral calcarine gyrus, and right lingual gyrus, respectively (P < 0.05). Conclusion Reduced visual acuity and frequency of optic neuritis are associated with alterations in the GMV and FC in NMOSD. Our current study, which provides imaging evidence on the impairment involved in NMOSD, sheds light on pathophysiological responses of optic neuritis attack on the brain especially on the visual network.

心力衰竭(HF)是由于任何心脏结构或功能异常导致心室充盈或射血功能受损的一组复杂的临床综合征,可通过不同机制影响到包括大脑在内的多种器官功能.近年来,在HF疾病的研究中"心-脑双向交互作用"逐渐受到重视,其中HF相关的认知障碍(CI)得到临床极大关注.尽管已有研究提示HF患者合并CI可明显增加再入院及死亡的风险,但在现有的临床实践中,并不常规对HF患者进行CI筛查,易出现漏诊,从而影响患者预后.因此,本文对近期HF相关CI病理生理机制的临床研究及筛选方法 、治疗等方面的新进展进行综述,以期提高临床工作者对该问题的认识.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, demyelinating disorder, accompanied by abnormal spontaneous activity of the brain and impairment of the retina and optic nerve. Functional connectivity density (FCD) map, a graph theory method, was applied to explore the functional connectivity alterations of brian in NMOSD patients and investigate the alterations of FCD to the structural and microvascular changes around the optic nerve head (ONH). Methods: Nineteen NMOSD patients and 22 healthy controls (HCs) were included in our study. All participants underwent resting-state functional magnetic resonance imaging (fMRI) scans of the brain, and ophthalmological examinations included optical coherence tomographic angiography (OCT-A) imaging, visual acuity (VA), and intraocular pressure (IOP). The long- and short-range FCD was calculated by the fMRI graph theory method and two-sample t-tests were performed to compare the discrepancy of FCD between NMOSD and HCs. OCT-A imaging was used to obtain the structure (peripapillary retinal nerve fiber layer, pRNFL) and microvessels (radial peripapillary capillary, RPC) details around the ONH. The association between the long- and short-range FCD values with the structural and microvascular variation around the ONH were evaluated using Spearman's correlation. Results: Significantly decreased (corrected p < 0.05) long-range FCD was seen in the right superior parietal gyrus (SPG) in patients with NMOSD when compared to HCs. Increased long-range FCD was seen in the right fusiform gyrus (FFG), left orbital part of superior frontal orbital gyrus (ORBsup) and left anterior cingulum and paracingulate gyri (ACG) in NMOSD patients (corrected p < 0.05). The regions with reduced short-range FCD in NMOSD were the left angular gyrus (ANG) and right SPG (corrected p < 0.05). Increased short-range FCD was shown (corrected p < 0.05) in the right FFG of NMOSD. The pRNFL thickness and RPC density in all participants were negatively correlated with the long-range FCD values in the right FFG, left ORBsup, and left ACG as well as short-range FCD values in the right FFG, besides, both were positively correlated with the long-range FCD values in the right SPG and short-range FCD values in the left ANG and right SPG (p < 0.05). Conclusion: Our study demonstrates that patients with NMOSD have widespread brain dysfunction after optic neuritis attacks which shows as impairment of widespread spatial distribution in long- and short-range FCD. Structural and microvascular changes around the ONH are associated with neural changes in the brain.

Objective:Puberty is a sensitive period of brain development accompany with pubertal hormones fluctuation. However, the underlying mechanisms of the impact of hypothalamus-pituitary-gonadal (HPG) axis reactivation and associated elevated pubertal hormones on brain structure are still unclear. Here, we investigated the brain structure differences between girls with and without HPG axis reactivation and the influence of pubertal hormones on these brain regions. Methods:126 girls aged 8-9.5 years underwent a gonadotropin-releasing hormone (GnRH) stimulation test to identify the HPG axis status and categorized into HPG+ group (n = 80) and HPG- group (n = 46). T1-weighted gradient echo three dimensional MRI was performed using a 3.0-Tesla scanner to assess the difference in GMV between the two groups. Correlation analyses were conducted to explore the relations between the brain regions showing significant GMV differences and serum hormone concentrations. Result:The HPG+ group showed significantly higher GMV in the bilateral lingual gyrus and lower GMV within the right orbital inferior frontal gyrus compare to the HPG - group. Furthermore, GMV in the right orbital inferior frontal gyrus was positively associated with plasma concentrations of follicle stimulating hormone (FSH) in HPG+ group. Conclusion:The present study suggests that the reactivated HPG axis could affects regional structural brain changes in early pubertal girls. FSH production play an important role in bilateral lingual gyrus, which are involved in vision processing, semantic processing and emotional expression.

BACKGROUND:Whether ischemic stroke per se, rather than older age or additional comorbidities, accounts for the adverse prognosis of heart failure (HF) is uncertain. The present study examineed the intrinsic association of ischemic stroke with outcomes in a propensity-matched cohort. METHODS AND RESULTS:Of 1,351 patients hospitalized with HF, 388 (28.7%) had prior ischemic stroke. Using propensity score for prior ischemic stroke, estimated for each patient, a matched cohort of 379 pairs of HF patients with and without prior ischemic stroke, balanced on 32 baseline characteristics was assembled. At 30 days, prior ischemic stroke was associated with significantly higher risks of the combined endpoint of all-cause death or readmission (hazard ratio [HR]: 1.91; 95% confidence interval [CI]: 1.38 to 2.65; P<0.001), all-cause death (HR: 2.08; 95% CI: 1.28 to 3.38; P=0.003), all-cause readmission (HR: 2.67; 95% CI: 1.78 to 4.01; P<0.001), and HF readmission (HR: 2.11; 95% CI: 1.19 to 3.72; P=0.010). Prior ischemic stroke was associated with a significantly higher risk of all 4 outcomes at both 6 months and 1 year. CONCLUSIONS:Prior ischemic stroke was a potent and persistent risk predictor of death and readmission among patients with HF after accounting for clinical characteristics.

BACKGROUND:There has been a myriad of neuroimaging studies that have suggested that pubertal stages and sex steroid fluctuations contribute to pubertal brain maturation. Investigations on the influence of hypothalamus-pituitary-gonadal (HPG) axis reactivation and the correlated elevated sex hormones on brain maturation have not unraveled these interactions to date. Here, we aimed to explore the impact of the reactivated HPG axis on spontaneous brain activity changes, by analyzing the amplitude of low-frequency fluctuation (ALFF) in developing girls aged 8-11 years old.METHODS:The gonadotropin-releasing hormone (GnRH) stimulation test was used to determine the HPG axis status and categorize subjects into two groups (HPG+ or HPG- group). Intelligence quotient (IQ) and the parent-rated Child Behavior Checklist (CBCL) were used to evaluate cognitive and behavioral performance. Two-sample t-tests were used to compare intergroup differences, the relations between brain areas' activities, age and hormonal levels were conducted by Pearson or Spearman correlation analyses.RESULTS:Compared with the HPG- group, the HPG+ group showed decreased ALFF values in the left superior temporal gyrus (STG) but increased ALFF values in the right superior frontal gyrus (SFG). In addition, in the HPG+ group, prolactin (PRL) levels were positively correlated with ALFF values in the right SFG, and there was significant negative correlation between ALFF values in the left STG and CBCL activities scores.LIMITATIONS:Due to the cross-sectional design of the present study, further study is needed to determine the relationships between age, reawakening of the HPG axis and related sex hormones and spontaneous brain activity change.CONCLUSIONS:These findings suggested that the reactivated HPG axis and elevated PRL level could affect changes in brain activity and this effect may be the neuroendocrine basis of mood, cognition, and social behavior changes in early pubertal girls.

Pubertal hormones play an important role in brain and psychosocial development. However, the role of abnormal HPG axis states in altering brain function and structure remains unclear. The present study is aimed at determining whether there were significant differences in gray matter volume (GMV) and resting state (RS) functional connectivity (FC) patterns in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). We further explored the correlation between these differences and serum pubertal hormone levels. To assess this, we recruited 29 idiopathic CPP girls and 38 age-matched PPP girls. A gonadotropin-releasing hormone (GnRH) stimulation test was performed, and pubertal hormone levels (including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin, and cortisol) were assessed. All subjects underwent multimodal magnetic resonance imaging of brain structure and function. Voxel-based morphometry (VBM) analysis was paired with seed-to-voxel whole-brain RS-FC analysis to calculate the GMV and RS-FC in idiopathic CPP and PPP girls. Correlation analyses were used to assess the effects of pubertal hormones on brain regions with structural and functional differences between the groups. We found that girls with CPP exhibited decreased GMV in the left insula and left fusiform gyrus, while connectivity between the left and right insula and the right middle frontal gyrus (MFG), as well as the left fusiform gyrus and right amygdala, was reduced in girls with CPP. Furthermore, the GMV of the left insula and peak FSH levels were negatively correlated while higher basal and peak E2 levels were associated with increased bilateral insula RS-FC. These findings suggest that premature activation of the HPG axis and pubertal hormone fluctuations alter brain structure and function involved in the cognitive and emotional process in early childhood. These findings provide vital insights into the early pathophysiology of idiopathic CPP.

Extracellular regulated protein kinase (ERK) pathway has been reported to play a critical role in hematopoiesis in zebrafish and mouse.However,the role of ERK pathway in hematopoietic differentiation from human embryonic stem cells (hESCs) remains unclear.In this study,we investigated the role of ERK pathway in hematopoietic specification from hESCs by taking the advantage of a chemical defined hematopoietic differentiation model and PD98059,a specific inhibitor of ERK pathway.The results of immtnofluorescence and flow cytometry analysis revealed that PD98059 treatment significantly inhibited the generation of CD43 positive hematopoietic stem and progenitor cells (HSPCs).Further studies demonstrate that PD98059 suppresses hematopoietic differentiation through inhibiting the generation of APLNR positive lateral plate mesoderm cells.The addition of PD98059 in the stage of lateral plate mesoderm cell generation and the whole process of hematopoietic differentiation shows similar inhibitory effect on the generation of HSPCs.Taken together,our findings indicate that the inhibition of ERK pathway suppresses hematopoietic differentiation from hESCs through repressing the generation of lateral plate mesoderm cells.This study provides a theoretical foundation for the establishment of a highly efficient hematopoietic differentiation system of hESCs and the large-scale production of functional blood cells in vitro.

In this study, fluorescent/magnetic dual-functional hollow nanospheres conducted by ternary CdMnS nanoparticles were synthesized via a facile Ostwald-ripening process. The as-prepared hollow nanospheres exhibited bright and tunable emission under excitation with a 365 nm UV light coupled with a strong MR signal, suggesting their promising applications in bioimaging.