A novel high-throughput strategy was developed to determine the calcium precipitation activity (CPA) of mineralization bacteria used for self-healing of concrete cracks. A bacterial strain designated as H4 with the highest CPA of 94.8 % was screened and identified as a Bacillus species based on 16S rDNA sequence and phylogenetic tree analysis. Furthermore, the effects of certain influential factors on the microbial calcium precipitation process of H4 were evaluated. The results showed that lactate and nitrate are the best carbon and nitrogen sources, with optimal concentrations of approximately 25 and 18 mM, respectively. The H4 strain is able to maintain a high CPA in the pH range of 9.5-11.0, and a suitable initial spore concentration is 4.0 × 10(7) spores/ml. Moreover, an ambient Ca(2+) concentration greater than 60 mM resulted in a serious adverse impact not only on the CPA but also on the growth of H4, suggesting that the maintenance of the Ca(2+) concentration at a low level is necessary for microbial self-healing of concrete cracks.
Background Spinal cord injury (SCI) is a debilitating medical condition that can result in the irreversible loss of sensorimotor function. Current therapies fail to provide an effective recovery being crucial to develop more effective approaches. Mesenchymal stem cell (MSC) exosomes have been shown to be able to facilitate axonal growth and act as mediators to regulate neurogenesis and neuroprotection, holding great therapeutic potential in SCI conditions. This study aimed to assess the potential of human placental MSC (hpMSC)-derived exosomes on the functional recovery and reactivation of endogenous neurogenesis in an experimental animal model of SCI and to explore the possible mechanisms involved. Methods The hpMSC-derived exosomes were extracted and transplanted in an experimental animal model of SCI with complete transection of the thoracic segment. Functional recovery, the expression of neural stem/progenitor cell markers and the occurrence of neurogenesis, was assessed 60 days after the treatment. In vitro, neural stem cells (NSCs) were incubated with the isolated exosomes for 24 h, and the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinases (ERK), and cAMP response element binding (CREB) proteins were assessed by western blot. Results Exosomes were successfully isolated and purified from hpMSCs. Intravenous injections of these purified exosomes significantly improved the locomotor activity and bladder dysfunction of SCI animals. Further study of the exosomes’ therapeutic action revealed that hpMSC-derived exosomes promoted the activation of proliferating endogenous neural stem/progenitor cells as denoted by the significant increase of spinal SOX2+GFAP+, PAX6+Nestin+, and SOX1+KI67+ cells. Moreover, animals treated with exosomes exhibited a significative higher neurogenesis, as indicated by the higher percentage of DCX+MAP 2+ neurons. In vitro, hpMSC-derived exosomes promoted the proliferation of NSCs and the increase of the phosphorylated levels of MEK, ERK, and CREB. Conclusions This study provides evidence that the use of hpMSC-derived exosomes may constitute a promising therapeutic strategy for the treatment of SCI.
Major depressive disorder (MDD) is the most prevalent mental disorder that affects more than 200 million people worldwide. Recent large-scale genome-wide association studies (GWAS) have identified multiple risk variants that show robust association with MDD. Nevertheless, how the identified risk variants confer risk of MDD remains largely unknown. To identify risk variants that are associated with gene expression in human brain and to identify genes whose expression change may contribute to the susceptibility of MDD, we systematically integrated the genetic associations from a large-scale MDD GWAS (N = 480,359) and brain expression quantitative trait loci (eQTL) data (N = 494) using a Bayesian statistical framework (Sherlock). Sherlock integrative analysis showed that FLOT1 was significantly associated with MDD (P = 6.02 × 10 −6), suggesting that risk variants may contribute to MDD susceptibility through affecting FLOT1 expression. We further examined the expression level of FLOT1 in MDD cases and controls and found that FLOT1 was significantly upregulated in brains and peripheral blood of MDD cases compared with controls (European sample). Interestingly, we found that FLOT1 expression was also significantly upregulated in peripheral blood of first-episode drugnaive MDD cases compared with controls (P = 1.01 × 10 −7 , Chinese sample). Our study identified FLOT1 as a novel MDD risk gene whose expression level may play a role in MDD. In addition, our findings also suggest that risk variants may confer risk of MDD through affecting expression of FLOT1. Further functional investigation of FLOT1 may provide new insights for MDD pathogenesis.
Mindfulness is described as the non-judgmental awareness of experiences in the present moment. The sustained practice of mindfulness may also have beneficial effects on an individual’s well-being. For instance, mindfulness meditation is an effective approach for improving emotion regulation. Specifically, the early stage of mindfulness meditation training enhances emotional monitoring systems related to attention regulation and executive function. Reduced activity in the default mode network (DMN) would probably be observed corresponding to the attenuated mind wandering. In the present study, we hypothesized that alterations in functional activity in the frontal-parietal cortex and DMN may be induced by short-term mindfulness meditation. In this study, before and after 8 weeks of weekly Mindfulness-Based Stress Reduction (MBSR) training, healthy participants were evaluated using a mindfulness questionnaire and an affect schedule, as well as via resting-state functional magnetic resonance imaging. Sixteen right-handed non-meditators were enrolled. Another 16 demographically matched healthy adults without any meditation experience were recruited as controls. Pre- and post-MBSR assessments were compared. Increased regional homogeneity in the right superior parietal lobule and left postcentral gyrus (PoCG), as well as altered functional connectivity in PoCG-related networks, were observed post-MBSR. The mindfulness questionnaire scores also improved and negative affect was significantly decreased after MBSR. Together with reduced involvement of the posterior brain, our results suggest a tendency toward stronger involvement of the parietal cortex in mindfulness beginners. This study provides novel evidence regarding the optimization of emotional processing with short-term mindfulness meditation.
Major depressive disorder (MDD) is recognized as a primary cause of disability worldwide, and effective management of this illness has been a great challenge. While genetic component is supposed to play pivotal roles in MDD pathogenesis, the genetic and phenotypic heterogeneity of the illness has hampered the discovery of its genetic determinants. In this study, in an independent Han Chinese sample (1824 MDD cases and 3031 controls), we conducted replication analyses of two genetic loci highlighted in a previous Chinese MDD genome-wide association study (GWAS), and confirmed the significant association of a single nucleotide polymorphism (SNP) rs12415800 near SIRT1. Subsequently, using hypothesis-free whole-brain analysis in two independent Han Chinese imaging samples, we found that individuals carrying the MDD risk allele of rs12415800 exhibited aberrant gray matter volume in the left posterior cerebellar lobe compared with those carrying the non-risk allele. Besides, in independent Han Chinese postmortem brain and peripheral blood samples, the MDD risk allele of rs12415800 predicted lower SIRT1 mRNA levels, which was consistent with the reduced expression of this gene in MDD patients compared with healthy subjects. These results provide further evidence for the involvement of SIRT1 in MDD, and suggest that this gene might participate in the illness via affecting the development of cerebellum, a brain region that is potentially underestimated in previous MDD studies.
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