Minjuan Wang is an associate professor of Educational Technology at San Diego State University. Her research specialties focus on the sociocultural facets of online learning, mobile learning and technological interventions in language education. She has published peer-reviewed articles in Educational Technology Research and Development, Computers and Education, Educational Media International, TechTrends, and the British Journal of Educational Technology. She has also published book chapters on engaged learning in online problem solving, Cybergogy for interactive learning online, informal learning via the Internet, and effective learning in multicultural and multilingual classrooms. AbstractChinese classrooms, whether on school grounds or online, have long suffered from a lack of interactivity. Many online classes simply provide recorded instructor lectures, which only reinforces the negative effects of passive nonparticipatory learning. At Shanghai Jiaotong University, researchers and developers actively seek technologic interventions that can greatly increase interactivity in large blended classes. They developed a cutting-edge mobile learning system that can deliver live broadcasts of real-time classroom teaching to students with mobile devices. Their system allows students to customise means of content-reception based on when and where they tune into the broadcast. The system also supports short text messaging and instant polls. Through these venues, students can ask questions and make suggestions in real time, and the instructor can address them immediately. This article describes this system in detail, and also reports results from a formal implementation of the system in a blended English classroom of 1000 students (with about 800 being online). As the data reveal, m-learning activities can much better engage students in the learning process. Students in this class changed from passive learners to truly engaged learners who are behaviourally, intellectually and emotionally involved in their learning tasks.

Background & Aim: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism is associated with NAFLD severity and the PNPLA3 gene is expressed in the kidneys,but whether PNPLA3 rs738409 polymorphism is also associated with renal tubular injury is uncertain. We assessed the effect of PNPLA3 genotypes on biomarkers of renal tubular injury (RTI) and glomerular function in subjects with NAFLD who had either normal (nALT) or abnormal (abnALT) alanine aminotransaminase levels. Methods: 217 patients with histologically-proven NAFLD, of which 75 had persistently nALT (below upper limit of normal for 3 months) were included. Multivariable regression analyses were undertaken to test associations between PNPLA3 genotype and biomarkers of kidney dysfunction. Results: The nALT patient group had higher urinary neutrophil gelatinase-associated lipocalin levels (u-NGAL, a biomarker of RTI) (P <0.001), higher albuminuria (P =0.039) and greater prevalence of chronic kidney disease (CKD) (P =0.046) than the abnALT group. The association between PNPLA3 GG genotype and risk of CKD and abnormal albuminuria remained significant after adjustment for kidney risk factors and severity of NAFLD histology, mostly in the nALT group. Similarly, PNPLA3 GG 6 genotype was associated with higher u-NGAL levels in the nALT group, even after adjustment for the aforementioned risk factors and glomerular filtration-based markers (β-coefficient: 22.29, 95% CI: 0.99-43.60, P =0.041). Conclusion: Patients with NAFLD and persistently nALT, who carry the PNPLA3 rs738409 G allele, are at higher risk of early glomerular and tubular damage. We suggest PNPLA3 genotyping may help identify patients with NAFLD at higher risk of RTI.

ObjectivesThe rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches.MethodsThis was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or ‘no immunosuppressant’. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival.ResultsOf 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: −4.0 (−5.2 to −2.7) units for methotrexate, −4.1 (−5.3 to −2.9) for MMF, −3.3 (−4.9 to −1.7) for cyclophosphamide and −2.2 (−4.0 to −0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months.ConclusionsThese findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.Trial registration numberNCT02339441.

Stapled peptides recapitulate the binding affinity and specificity of α-helices in proteins, resist proteolytic degradation, and may provide a novel modality against challenging drug targets such as protein–protein interactions. However, most of the stapled peptides have limited cell permeability or are impermeable to the cell membrane. We show herein that stapled peptides can be rendered highly cell-permeable by conjugating a cyclic cell-penetrating peptide to their N-terminus, C-terminus, or stapling unit. Application of this strategy to two previously reported membrane-impermeable peptidyl inhibitors against the MDM2/p53 and β-catenin/TCF interactions resulted in the generation of potent proof-of-concept antiproliferative agents against key therapeutic targets.