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In 2018, to help undergraduate medical students strengthen their self-learning and scientific research skills, we introduced an instructional model that combined literature-based learning with experimental design. We tested this model on the molecular biology class at Tongji University. In the first step of the model, a topic is chosen, and students find, read, and evaluate scientific papers in groups and deliver presentations. In the second step, they design scientific experiments in groups and discuss their proposed experiments in class, which is to be followed by further experimental verification in the lab course. This entire activity was given 20% weightage in the final score. The model led to better student-centered teaching and self-directed learning according to quantitative and qualitative assessment. Students showed great interest in literature and research. They enjoyed group work and gained experience in organization and presentation. Apart from a significant increase in final score, assessment data from students indicated that they were satisfied with this teaching model and considered it a positive experience. Looking at the positive impact of the literature-based learning and experiment design model, we support its continued use for teaching molecular biology to undergraduate medical students.

Background and Aims Anti-hypertensive agents are one of the most frequently used drugs worldwide. However, no blood pressure–lowering strategy is superior to placebo with respect to survival in diabetic hypertensive patients. Previous findings show that Wnt co-receptors LDL receptor–related proteins 5 and 6 (LRP5/6) can directly bind to several G protein–coupled receptors (GPCRs). Because angiotensin II type 1 receptor (AT1R) is the most important GPCR in regulating hypertension, this study examines the possible mechanistic association between LRP5/6 and their binding protein Dickkopf-1 (DKK1) and activation of the AT1R and further hypothesizes that the LRP5/6-GPCR interaction may affect hypertension and potentiate cardiac impairment in the setting of diabetes. Methods The roles of serum DKK1 and DKK1-LRP5/6 signalling in diabetic injuries were investigated in human and diabetic mice. Results Blood pressure up-regulation positively correlated with serum DKK1 elevations in humans. Notably, LRP5/6 physically and functionally interacted with AT1R. The loss of membrane LRP5/6 caused by injection of a recombinant DKK1 protein or conditional LRP5/6 deletions resulted in AT1R activation and hypertension, as well as β-arrestin1 activation and cardiac impairment, possibly because of multiple GPCR alterations. Importantly, unlike commonly used anti-hypertensive agents, administration of the anti-DKK1 neutralizing antibody effectively prevented diabetic cardiac impairment in mice. Conclusions These findings establish a novel DKK1-LRP5/6-GPCR pathway in inducing diabetic injuries and may resolve the long-standing conundrum as to why elevated blood DKK1 has deleterious effects. Thus, monitoring and therapeutic elimination of blood DKK1 may be a promising strategy to attenuate diabetic injuries. [ABSTRACT FROM AUTHOR]

BackgroundNeural crest defects lead to congenital heart disease involving outflow tract malformation. Integrin-linked-kinase (ILK) plays important roles in multiple cellular processes and embryogenesis. ILK is expressed in the neural crest, but its role in neural crest and outflow tract morphogenesis remains unknown.ResultsWe ablated ILK specifically in the neural crest using the Wnt1-Cre transgene. ILK ablation resulted in abnormal migration and overpopulation of neural crest cells in the pharyngeal arches and outflow tract and a significant reduction in the expression of neural cell adhesion molecule (NCAM) and extracellular matrix components. ILK mutant embryos exhibited an enlarged common arterial trunk and ventricular septal defect. Reduced smooth muscle differentiation, but increased ossification and neurogenesis/innervation were observed in ILK mutant outflow tract that may partly be due to reduced transforming growth factor β2 (TGFβ2) but increased bone morphogenetic protein (BMP) signaling. Consistent with these observations, microarray analysis of fluorescence-activated cell sorting (FACS)-sorted neural crest cells revealed reduced expression of genes associated with muscle differentiation, but increased expression of genes of neurogenesis and osteogenesis.ConclusionsOur results demonstrate that ILK plays essential roles in neural crest and outflow tract development by mediating complex crosstalk between cell matrix and multiple signaling pathways. Changes in these pathways may collectively result in the unique neural crest and outflow tract phenotypes observed in ILK mutants.

The Jurassic is one of the most important periods generating hydrocarbon source rocks and coals in Northwest China, and the Qaidam Basin is an important petroliferous and coal-forming basin. However, a series of explorations in the Qaidam Basin targeting Jurassic source rocks have failed over the past several years. These failures were mainly caused by missing the targeted Jurassic strata, suggesting that the current understanding of the Jurassic distribution in the Qaidam Basin is still limited. Therefore, this study conducts detailed analyses of the drilling wells and seismic data in the middle segment of the northern Qaidam Basin. The seismic profiles and borehole data indicate a rifting tectonic setting with discontinuous deposition and rapid facies transition during the Jurassic. A well-preserved buried rift valley proved in the Hongnan region reveals that the Jurassic deposits are mainly restricted in the narrow rift system. Therefore, further exploration targeting the Jurassic source rocks should focus on delineating the distribution of the Jurassic rift system in the Qaidam Basin, combined with the recovery of the complex Cenozoic tectonic overprinting. [ABSTRACT FROM AUTHOR]

Butyrate, one of the SCFA, promotes the development of the intestinal barrier. However, the molecular mechanisms underlying the butyrate regulation of the intestinal barrier are unknown. To test the hypothesis that the effect of butyrate on the intestinal barrier is mediated by the regulation of the assembly of tight junctions involving the activation of the AMP-activated protein kinase (AMPK), we determined the effect of butyrate on the intestinal barrier by measuring the transepithelial electrical resistance (TER) and inulin permeability in a Caco-2 cell monolayer model. We further used a calcium switch assay to study the assembly of epithelial tight junctions and determined the effect of butyrate on the assembly of epithelial tight junctions and AMPK activity. We demonstrated that the butyrate treatment increased AMPK activity and accelerated the assembly of tight junctions as shown by the reorganization of tight junction proteins, as well as the development of TER. AMPK activity was also upregulated by butyrate during calcium switch-induced tight junction assembly. Compound C, a specific AMPK inhibitor, inhibited the butyrate-induced activation of AMPK. The facilitating effect of butyrate on the increases in TER in standard culture media, as well as after calcium switch, was abolished by compound C. We conclude that butyrate enhances the intestinal barrier by regulating the assembly of tight junctions. This dynamic process is mediated by the activation of AMPK. These results suggest an intriguing link between SCFA and the intracellular energy sensor for the development of the intestinal barrier.