The development of new technologies enables learners to learn more effectively, efficiently, flexibly and comfortably. Learners utilize smart devices to access digital resources through wireless network and to immerse in both personalized and seamless learning. Smart education, a concept that describes learning in digital age, has gained increased attention. This paper discusses the definition of smart education and presents a conceptual framework. A four-tier framework of smart pedagogies and ten key features of smart learning environments are proposed for foster smart learners who need master knowledge and skills of the 21 st century learning. The smart pedagogy framework includes class-based differentiated instruction, group-based collaborative learning, individual-based personalized learning and mass-based generative learning. Furthermore, a technological architecture of smart education, which emphasizes the role of smart computing, is proposed. The tri-tier architecture and key functions are all presented. Finally, challenges of smart education are discussed.

Head and neck squamous cell carcinomas (HNSCCs) are highly aggressive, multi-factorial tumors in the upper aerodigestive tract affecting more than half a million patients worldwide each year. Alcohol, tobacco, and human papillomavirus (HPV) infection are well known causative factors for HNSCCs. Current treatment options for HNSCCs are surgery, radiotherapy, chemotherapy, or combinatorial remedies. Over the past decade, despite the marked improvement in clinical outcome of many tumor types, the overall 5-year survival rate of HNSCCs remained ∼40–50% largely due to poor availability of effective therapeutic options for HNSCC patients with recurrent disease. Therefore, there is an urgent and unmet need for the identification of specific molecular signatures that better predict the clinical outcomes and markers that serve as better therapeutic targets. With recent technological advances in genomic and epigenetic analyses, our knowledge of HNSCC molecular characteristics and classification has been greatly enriched. Clinical and genomic meta-analysis of multicohort HNSCC gene expression profile has clearly demonstrated that HPV + and HPV - HNSCCs are not only derived from tissues of different anatomical regions, but also present with different mutation profiles, molecular characteristics, immune landscapes, and clinical prognosis. Here, we briefly review our current understanding of the biology, molecular profile, and immunological landscape of the HPV + and HPV - HNSCCs with an emphasis on the diversity and heterogeneity of HNSCC clinicopathology and therapeutic responses. After a review of recent advances and specific challenges for effective immunotherapy of HNSCCs, we then conclude with a discussion on the need to further enhance our understanding of the unique characteristics of HNSCC heterogeneity and the plasticity of immune landscape. Increased knowledge regarding the immunological characteristics of HPV + and HPV - HNSCCs would improve therapeutic targeting and immunotherapy strategies for different subtypes of HNSCCs.

This is a case example on the concept of personalized precision medicine in a surgical setting and demonstrates how 3D-printed, patient-specific implants may bring individualized solutions to rare problems wherein restoration of the specific anatomy of each patient is a key prognostic factor.

Metabolic reprogramming is reported to be one of the hallmarks of cancer, which is an adaptive mechanism by which fast-growing cancer cells adapt to their increasing energy demands. Recently, extracellular vesicles (EVs) known as exosomes have been recognized as crucial signaling mediators in regulating the tumor microenvironment (TME). Meanwhile, the TME is a highly heterogeneous ecosystem incorporating cancer cells, fibroblasts, adipocytes, endothelial cells, mesenchymal stem cells, and extracellular matrix. Accumulated evidence indicates that exosomes may transfer biologically functional molecules to the recipient cells, which facilitate cancer progression, angiogenesis, metastasis, drug resistance, and immunosuppression by reprogramming the metabolism of cancer cells and their surrounding stromal cells. In this review, we present the role of exosomes in the TME and the underlying mechanism of how exosomes exacerbate tumor development through metabolic reprogramming. In addition, we will also discuss the potential role of exosomes targeting metabolic process as biomarkers for tumor diagnosis and prognosis, and exosomes-mediated metabolic reprogramming as potential targets for cancer therapy. Furthermore, a better understanding of the link between exosomes and metabolic reprogramming, and their impact on cancer progression, would provide novel insights for cancer prevention and treatment in the future.

BackgroundMicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. A previous report has shown that let-7 family members can act as tumor suppressors in many cancers. Through miRNA array, we found that let-7f was downregulated in the highly metastatic potential gastric cancer cell lines GC9811-P and SGC7901-M, when compared with their parental cell lines, GC9811 and SGC7901-NM; however, the mechanism was not clear. In this study, we investigate whether let-7f acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers.Methodology/PrincipalReal-time PCR showed decreased levels of let-7f expression in metastatic gastric cancer tissues and cell lines that are potentially highly metastatic. Cell invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell lines after transfection with let-7f-mimics. Nude mice with xenograft models of gastric cancer confirmed that let-7f could inhibit gastric cancer metastasis in vivo after transfection by the lentivirus pGCsil-GFP- let-7f. Luciferase reporter assays demonstrated that let-7f directly binds to the 3′UTR of MYH9, which codes for myosin IIA, and real-time PCR and Western blotting further indicated that let-7f downregulated the expression of myosin IIA at the mRNA and protein levels.Conclusions/SignificanceOur study demonstrated that overexpression of let-7f in gastric cancer could inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene MYH9. These data suggest that let-7f may be a novel therapeutic candidate for gastric cancer, given its ability to reduce cell invasion and metastasis.

With growing interest in cancer therapeutics, anti-angiogenic therapy has received considerable attention and is widely administered in several types of human cancers. Nonetheless, this type of therapy may induce multiple signaling pathways compared with cytotoxics and lead to worse outcomes in terms of resistance, invasion, metastasis, and overall survival (OS). Moreover, there are important challenges that limit the translation of promising biomarkers into clinical practice to monitor the efficiency of anti-angiogenic therapy. These pitfalls emphasize the urgent need for discovering alternative angiogenic inhibitors that target multiple angiogenic factors or developing a new drug delivery system for the current inhibitors. The great advantages of nanoparticles are their ability to offer effective routes that target the biological system and regulate different vital processes based on their unique features. Limited studies so far have addressed the effectiveness of nanoparticles in the normalization of the delicate balance between stimulating (pro-angiogenic) and inhibiting (anti-angiogenic) factors. In this review, we shed light on tumor vessels and their microenvironment and consider the current directions of anti-angiogenic and nanotherapeutic treatments. To the best of our knowledge, we consider an important effort in the understanding of anti-angiogenic agents (often a small volume of metals, nonmetallic molecules, or polymers) that can control the growth of new vessels.

SUMMARYArabinogalactan proteins are widely distributed in plant tissues and cells, and may function in the growth and development of higher plants. To our knowledge, there is currently no direct evidence concerning the involvement of fasciclin-like arabinogalactan proteins (FLA) in sexual reproduction in Arabidopsis. In this study, Arabidopsis FLA3 was found to be specifically expressed in pollen grains and tubes. Subcellular localization showed that FLA3 anchors tightly to the plasma membrane, and its glycosylphosphatidylinositol anchor may affect its localization. FLA3-RNA interference transgenic plants had approximately 50% abnormal pollen grains (including shrunken and wrinkled phenotypes) which lacked viability. Cytological observations revealed that pollen abortion occurred during the transition from uninucleate microspores to bicellular pollens, with abnormal cellulose distribution seen by calcofluor white staining. Transmission electron microscopy showed that the basic structure of the exine layer in aberrant pollen was normal, but the intine layer appeared to have some abnormalities. Taken together, these results suggest that FLA3 is involved in microspore development and may affect pollen intine formation, possibly by participating in cellulose deposition. In FLA3-overexpressing transgenic plants, defective elongation of the stamen filament and reduced female fertility led to short siliques with low seed set, which suggested that ectopic expression of FLA3 in tissues may reduce or disrupt cell growth and then result in defects throughout the plant.

Preoperative localization of insulinoma is a clinical dilemma. We aimed to investigate whether glucagon-like peptide-1 receptor (GLP-1R) PET/CT with 68Ga-NOTA-MAL-cys40-exendin-4 (68Ga-NOTA-exendin-4) is efficient in detecting insulinoma. Methods In our prospective cohort study, patients with endogenous hyperinsulinemic hypoglycemia were enrolled. CT, MRI, endoscopic ultrasound, and 99mTc-hydrazinonicotinamide-TOC SPECT/CT were done according to standard protocols. GLP-1R PET/CT was performed 30–60 min after the injection of 68Ga-NOTA-exendin-4. The gold standard for diagnosis was the histopathologic results after surgery. Results Of 52 recruited patients, 43 patients with histopathologically proven insulinomas were included for the imaging studies. Nine patients did not undergo surgical intervention. 68Ga-NOTA-exendin-4 PET/CT correctly detected insulinomas in 42 of 43 patients with high tumor uptake (mean SUVavg ± SD, 10.2 ± 4.9; mean SUVmax ± SD, 23.6 ± 11.7), resulting in sensitivity of 97.7%. In contrast, 99mTc-hydrazinonicotinamide-TOC SPECT/CT showed a low sensitivity of 19.5% (8/41) in this group of patients; however, it successfully localized the tumor that was false-negative with GLP-1R PET/CT. The sensitivities of CT, MR, and endoscopic ultrasonography were 74.4% (32/43), 56.0% (14/25), and 84.0% (21/25), respectively. Conclusion 68Ga-NOTA-exendin-4 PET/CT is a highly sensitive imaging technique for the localization of insulinoma.