Foxg1 is one of the forkhead box genes that are involved in morphogenesis, cell fate determination, and proliferation, and Foxg1 was previously reported to be required for morphogenesis of the mammalian inner ear. However, Foxg1 knock-out mice die at birth, and thus the role of Foxg1 in regulating hair cell (HC) regeneration after birth remains unclear. Here we used Sox2 CreER/+ Foxg1 loxp/loxp mice and Lgr5-EGFP CreER/+ Foxg1 loxp/loxp mice to conditionally knock down Foxg1 specifically in Sox2+ SCs and Lgr5+ progenitors, respectively, in neonatal mice. We found that Foxg1 conditional knockdown (cKD) in Sox2+ SCs and Lgr5+ progenitors at postnatal day (P)1 both led to large numbers of extra HCs, especially extra inner HCs (IHCs) at P7, and these extra IHCs with normal hair bundles and synapses could survive at least to P30. The EdU assay failed to detect any EdU+ SCs, while the SC number was significantly decreased in Foxg1 cKD mice, and lineage tracing data showed that much more tdTomato+ HCs originated from Sox2+ SCs in Foxg1 cKD mice compared to the control mice. Moreover, the sphere-forming assay showed that Foxg1 cKD in Lgr5+ progenitors did not significantly change their sphereforming ability. All these results suggest that Foxg1 cKD promotes HC regeneration and leads to large numbers of extra HCs probably by inducing direct trans-differentiation of SCs and progenitors to HCs. Real-time qPCR showed that cell cycle and Notch signaling pathways were significantly down-regulated in Foxg1 cKD mice cochlear SCs. Together, this study provides new evidence for the role of Foxg1 in regulating HC regeneration from SCs and progenitors in the neonatal mouse cochlea.

Edited by Tamas DalmayKeywords: MicroRNAs Glioma Eph tyrosine kinase receptor A8 Migration Invasion Epithelial-mesenchymal transition a b s t r a c t MicroRNAs (miRNAs) play a critical role in the development of cancers. However, the role of miRNAs in glioma is still poorly understood. In this study, we demonstrate that microRNA-10a (miR-10a) promotes cell migration and invasion by negatively regulating the expression of Eph tyrosine kinase receptor A8 (EphA8). Ectopic expression of EphA8 counteracts the promotion of migration and invasion induced by miR-10a. We further demonstrate that miR-10a and EphA8 regulate epithelial-mesenchymal transition (EMT) to affect cell migration and invasion. Collectively, we unveil a branch of the miR-10a/EphA8 pathway that regulates the progression of glioma.

ARHGEF6 belongs to the family of guanine nucleotide exchange factors (GEFs) for Rho GTPases, and it specifically activates Rho GTPases CDC42 and RAC1. Arhgef6 is the X-linked intellectual disability gene also known as XLID46, and clinical features of patients carrying Arhgef6 mutations include intellectual disability and, in some cases, sensorineural hearing loss. Rho GTPases act as molecular switches in many cellular processes. Their activities are regulated by binding or hydrolysis of GTP, which is facilitated by GEFs and GTPase-activating proteins, respectively. RAC1 and CDC42 have been shown to play important roles in hair cell (HC) stereocilia development. However, the role of ARHGEF6 in inner ear development and hearing function has not yet been investigated. Here, we found that ARHGEF6 is expressed in mouse cochlear HCs, including the HC stereocilia. We established Arhgef6 knockdown mice using the clustered regularly interspaced short palindromic repeat-associated Cas9 nuclease (CRISPR-Cas9) genome editing technique. We showed that ARHGEF6 was indispensable for the maintenance of outer hair cell (OHC) stereocilia, and loss of ARHGEF6 in mice caused HC stereocilia deficits that eventually led to progressive HC loss and hearing loss. However, the loss of ARHGEF6 did not affect the synapse density and did not affect the mechanoelectrical transduction currents in OHCs at postnatal day 3. At the molecular level, the levels of active CDC42 and RAC1 were dramatically decreased in the Arhgef6 knockdown mice, suggesting that ARHGEF6 regulates stereocilia maintenance through RAC1/CDC42.

Background: Mobile health interventions may support risk factor management and are readily scalable in healthcare systems. We aim to evaluate the efficacy of a text messaging–based intervention to improve glycemic control in patients with coronary heart disease and diabetes mellitus in China. Methods and Results: The CHAT-DM study (Cardiovascular Health and Texting-Diabetes Mellitus) was a parallel-group, single-blind, randomized clinical trial that included 502 patients with both coronary heart disease and diabetes mellitus from 34 hospitals in China. The intervention group (n=251) received 6 text messages per week for 6 months in addition to usual care. Messages were theory driven and culturally tailored to provide educational and motivational information on glucose monitoring, blood pressure control, medication adherence, physical activity, and lifestyle. The control group (n=251) received usual care and 2 thank you messages per month. The primary outcome was change in glycated hemoglobin (HbA 1C [hemoglobin A 1C ]) from baseline to 6 months. Secondary outcomes were change in proportion of patients achieving HbA 1C <7%, fasting blood glucose, systolic blood pressure, LDL (low-density lipoprotein) cholesterol, body mass index, and physical activity from baseline to 6 months. The end points were assessed using analyses of covariance. The follow-up rate was 99%. When compared with control group at 6 months, the intervention group had a greater reduction in HbA 1C (−0.2% versus 0.1%; P =0.003) and a greater proportion of participants who achieved HbA 1C <7% (69.3% versus 52.6%; P =0.004). Change in fasting blood glucose was larger in the intervention group (between-group difference: −0.6 mmol/L; 95% CI, −1.1 to −0.2; P =0.011), but no other outcome differences were observed. Nearly all participants reported that messages were easy to understand (97.1%) and useful (94.1%). Conclusions: A text message intervention resulted in better glycemic control in patients with diabetes mellitus and coronary heart disease. While the mechanism of this benefit remains to be determined, the results suggest that a simple, culturally sensitive mobile text messaging program may provide an effective and feasible way to improve disease self-management. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02883842.

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Background: Mobile health technologies are low cost, scalable interventions with the potential to promote patient engagement and behavior change. We aimed to test whether a culturally sensitive text messaging intervention supporting secondary prevention improves the control of risk factors in patients with coronary heart disease in China. Methods and Results: In this multicenter, single-blinded randomized controlled trial, 822 patients (mean age, 56.4 [SD, 9.5] years; 14.1% women) with coronary heart disease and without diabetes mellitus from 37 hospitals in China were enrolled between August 2016 and March 2017. In addition to usual care, the control group (n=411) received 2 thank you messages/month; the intervention group (n=411) received 6 text messages/week for 6 months delivered by an automated computerized system. The messages provided educational and motivational information related to disease-specific knowledge, risk factor control, physical activity, and medication adherence. The primary end point was change in systolic blood pressure from baseline to 6 months. Secondary end points included the proportion with systolic blood pressure <140 mm Hg, smoking status, and change in body mass index, LDL-C (low-density lipoprotein cholesterol), and physical activity (assessed using the International Physical Activity Questionnaire). The end points were assessed using analyses of covariance. Follow-up was 99.6%. At 6 months, systolic blood pressure was not significantly lower in the intervention group compared with the control group, with a mean change (SD) of 3.2 (14.3) mm Hg and 2.0 (15.0) mm Hg ( P >0.05) from baseline, respectively (mean net change, −1.3 mm Hg [95% CI, −3.3 to 0.8]; P =0.221). There were no significant differences in the change in LDL-C level, physical activity, body mass index, or smoking status between the 2 groups. Nearly all patients in the intervention group reported the text messages to be useful (96.1%), easy to understand (98.8%), appropriate in frequency (93.8%), and reported being willing to receive future text messages (94.8%). Conclusions: Text messages supporting secondary prevention among patients with coronary heart disease did not lead to a greater reduction in blood pressure at 6 months. Mobile phone text messaging for secondary prevention was feasible and highly acceptable to patients. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT02888769.

Abstract. the HiWi gene is one of the members of the PiWi gene family that is important for stem cell self-renewal and expressed highly in certain human tumors. Some studies have demonstrated that HiWi plays a key role in the development of tumors in cervical, colon and liver cancer. Previous studies have demonstrated that HiWi is associated with prognosis of patients with glioma. However, there is no report on the analysis of HiWi in the biological characteristics of glioma cells. the aim of the study was to investigate whether HiWi plays an important role in the progress of glioma. Silencing HiWi inhibited cell proliferation by promoting apoptosis and increased cell cycle arrest. the expression of proteins related to apoptosis and the cell cycle, including p21, cyclin D1, Bcl-2, and Bax was significantly altered. Moreover, knockdown of HiWi inhibited the migration and invasion of glioma cells by reducing the expression of MMP-2 and MMP-9. furthermore, we found that reduction of HiWi inhibited tumor growth in vivo. These findings suggest that HIWI is an oncogene involved in the progression of glioma.

Mutations of telomerase reverse transcriptase (TERT) and the α thalassemia/mental retardation syndrome X-linked (ATRX) genes have been the subject of numerous studies on the classification and prognosis of glioma. However, the association between TERT and ATRX in World Health Organization (WHO) grade II to IV glioma remains unclear. The present study utilized Sanger sequencing and immunohistochemical methods to detect the expression of the TERT promoter region, ATRX mutations and proliferation marker protein Ki-67 (Ki-67) protein expression in 179 cases of glioma. The current study analyzed these variables and their association with clinicopathological characteristics to further basic research and provide a theoretical basis for the clinical diagnosis and treatment of this type of tumor (1). The results demonstrated that TERT promoter mutations were negatively associated with ATRX. Additionally, Ki-67 protein expression in TERT wild-type samples was higher compared with samples with ATRX deletion. Overall, the results demonstrated, for the first time to the best of the authors' knowledge, that TERT promoter mutations are negatively associated with ATRX expression in WHO grade II to IV gliomas. These findings provide a theoretical basis for further basic research and may improve clinical diagnosis and treatment of glioma in the future.