3-Isopropyl-2-(4-methoxy­phen­oxy)-1-benzo­furo[3,2-d]pyrimidin-4(3H)-one

In the title compound, C20H18N2O4, all non-H atoms of the three fused rings of the benzofuro[3,2-d]pyrimidine system are almost coplanar (r.m.s. deviation 0.021 Å). The dihedral angle between the fused ring system and the benzene ring is 1.47 (12)°. Intra­molecular and inter­molecular C—H⋯O hydrogen bonds together with weak C—H⋯π inter­actions stabilize the structure

Icariin accelerates Bone Regeneration By inducing Osteogenesis-Angiogenesis Coupling in Rats With Type 1 Diabetes Mellitus

BACKGROUND: Icariin (ICA), a natural flavonoid compound monomer, has multiple pharmacological activities. However, its effect on bone defect in the context of type 1 diabetes mellitus (T1DM) has not yet been examined. AIM: to explore the role and potential mechanism of ICA on bone defect in the context of T1DM. METHODS: The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining, alizarin red S staining, quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis. A bone defect model was established in T1DM rats. The model rats were then treated with ICA or placebo and micron-scale computed tomography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area. RESULTS: ICA promoted bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation. The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers (alkaline phosphatase and osteocalcin) and angiogenesis-related markers (vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1) compared to the untreated group. ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs. In the bone defect model T1DM rats, ICA facilitated bone formation and CD31 CONCLUSION: ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs

Innovative modeling framework of chloride resistance of recycled aggregate concrete using ensemble-machine-learning methods

This study investigates the feasibility of introducing machine learning algorithms to predict the diffusion resistance to chloride penetration of recycled aggregate concrete (RAC). A total of 226 samples collated from published literature were used to train and test the developed machine learning framework, which integrated four standalone models and two ensemble models. The hyperparameters involved were fine-tuned by grid search and 10-fold cross-validation. Results showed that all the models had good performance in predicting the chloride penetration resistance of RAC and among them, the gradient boosting model outperformed the others. The water content was identified as the most critical factor affecting the chloride ion permeability of RAC based on the standardized regression coefficient analysis. The model’s interpretability was greatly improved through a two-way partial dependence analysis. Finally, based on the proposed machine learning models, a performance-based mixture design method and a service life prediction approach for RAC were developed, thereby offering novel and robust design tools for achieving more durable and resilient development goals in procuring sustainable concrete.This work was supported by the National Natural Science Foundation of China (52108123), Guangdong Basic and Applied Basic Research Foundation (2020A1515110101), and Guangdong Provincial Key Laboratory of Modern Civil Engineering Technology (2021B1212040003)

Experimental Study on the Feasibility of Using Water Glass and Aluminum Sulfate to Treat Complications in High Liquid Limit Soil Subgrade

The feasibility of using water glass and aluminum sulfate to treat high liquid limit soil subgrade diseases is studied through laboratory experiments, and the following results were observed. After improving the high liquid limit clay with water glass and aluminum sulfate, the liquid limit decreases, the plastic limit increases, and the plasticity index decreases. Compared with untreated soil, the clay content of the improved soil decreases, while the silt and coarse contents increase. The absolute and relative expansion rates of the improved soil are both lower than those of the untreated soil. With the same number of dry and wet cycles, the decreased degrees of cohesion and internal friction angle of the improved soil are, respectively, one-half and one-third of those of the untreated soil. After three dry and wet cycles, the California bearing ratio (CBR) of the untreated soil does not meet the requirements of specifications. However, after being cured for seven days and being subjected to three dry and wet cycles, the CBR of the improved soil, with 4% water glass solution and 0.4% aluminum sulfate, meets the requirements of specifications

Synergy of arsenic with smoking in causing cardiovascular disease mortality: A cohort study with 27 follow-up years in China

BackgroundTo explore the patterns of the exposure-response relationship between arsenic exposure and cardiovascular disease (CVD) mortality and investigate the effect of cigarette smoking on the association.MethodsSeven thousand seven hundred thirty-five tin miners with at least 10 years of arsenic exposure were enrolled since 1992 and followed up for 27 years. Each individual's air arsenic exposure at workplace was calculated by time weighted average arsenic concentration × exposure months. Detailed information on smoking was collected at baseline, and information on smoking status was collected for five consecutive years from 1992 to 1996. Hazard ratio (HR) and 95% confidence interval (CI) for the risk of CVD were estimated using Cox proportional hazards models.ResultsA total of 1,046 CVD deaths occurred in this cohort over 142,287.7 person-years of follow up. We firstly reported that for equal cumulative exposure, participants exposed to higher concentrations over shorter duration had a higher risk of CVD mortality than those exposed to lower concentration over longer duration. The HR and 95% CI were 1.38 (95%CI: 1.03–1.85) in participants exposed to arsenic concentration (45.5–99.5 mg/m3), 1.29 (95%CI: 1.02–1.67) in 99.5–361.0 mg/m3. Further, participants with age at first exposure <18 years had a significantly higher risk of morality from CVD, cerebrovascular and heart diseases than those with ≥18 years. Finally, all synergy indices were greater than 1 (range, 1.11–2.39), indicating that the joint effect of arsenic exposure and cigarette smoking on CVD mortality was greater than the sum of their individual effect.ConclusionsExposure to air arsenic at workplace is adversely associated with mortality from CVD, especially among smokers younger than 18 years and smokers

The role of the transcription factor Rbpj in the development of dorsal root ganglia

<p>Abstract</p> <p>Background</p> <p>The dorsal root ganglion (DRG) is composed of well-characterized populations of sensory neurons and glia derived from a common pool of neural crest stem cells (NCCs), and is a good system to study the mechanisms of neurogenesis and gliogenesis. Notch signaling is known to play important roles in DRG development, but the full scope of Notch functions in mammalian DRG development remains poorly understood.</p> <p>Results</p> <p>In the present study, we used <it>Wnt1-Cre </it>to conditionally inactivate the transcription factor Rbpj, a critical integrator of activation signals from all Notch receptors, in NCCs and their derived cells. Deletion of <it>Rbpj </it>caused the up-regulation of <it>NeuroD1 </it>and precocious neurogenesis in DRG early development but led to an eventual deficit of sensory neurons at later stages, due to reduced cell proliferation and abnormal cell death. In addition, gliogenesis was delayed initially, but a near-complete loss of glia was observed finally in <it>Rbpj</it>-deficient DRG. Furthermore, we found P75 and Sox10, which are normally expressed exclusively in neuronal and glial progenitors of the DRG after the NCCs have completed their migration, were co-expressed in many cells of the DRG of <it>Rbpj </it>conditional knock-out mice.</p> <p>Conclusions</p> <p>Our data indicate that Rbpj-mediated canonical Notch signaling inhibits DRG neuronal differentiation, possibly by regulating <it>NeuroD1 </it>expression, and is required for DRG gliogenesis <it>in vivo</it>.</p

Deficiency of Mkrn2 causes abnormal spermiogenesis and spermiation, and impairs male fertility.

Although recent studies have shed insights on some of the potential causes of male infertility, new underlining molecular mechanisms still remain to be elucidated. Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. We developed an Mrkn2 knockout mouse model to study the role of this gene, and found that deletion of Mkrn2 in mice led to male infertility. Mkrn2 knockout mice produced abnormal sperms characterized by low number, poor motility, and aberrant morphology. Disruption of Mkrn2 also caused failure of sperm release (spermiation failure) and misarrangement of ectoplasmic specialization (ES) in testes, thus impairing spermiogenesis and spermiation. To understand the molecular mechanism, we found that expression of Odf2, a vital protein in spermatogenesis, was significantly decreased. In addition, we found that expression levels of Odf2 were decreased in Mkrn2 knockout mice. We also found that MKRN2 was prominently expressed in the sperm of normal men, but was significantly reduced in infertile men. This result indicates that our finding is clinically relevant. The results of our study provided insights into a new mechanism of male infertility caused by the MKRN2 downregulation