CD44ICD promotes breast cancer stemness via PFKFB4-mediated glucose metabolism.

CD44 is a single-pass cell surface glycoprotein that is distinguished as the first molecule used to identify cancer stem cells in solid tumors based on its expression. In this regard, the CD44high cell population demonstrates not only the ability to regenerate a heterogeneous tumor, but also the ability to self-regenerate when transplanted into immune-deficient mice. However, the exact role of CD44 in cancer stem cells remains unclear in part because CD44 exists in various isoforms due to alternative splicing. Methods: Gain- and loss-of-function methods in different models were used to investigate the effects of CD44 on breast cancer stemness. Cancer stemness was analyzed by detecting SOX2, OCT4 and NANOG expression, ALDH activity, side population (SP) and sphere formation. Glucose consumption, lactate secretion and reactive oxygen species (ROS) levels were detected to assess glycolysis. Western blot, immunohistochemical staining, ELISA and TCGA dataset analysis were performed to determine the association of CD44ICD and PFKFB4 with clinical cases. A PFKFB4 inhibitor, 5MPN, was used in a xenograft model to inhibit breast cancer development. Results: In this report, we found that the shortest CD44 isoform (CD44s) inhibits breast cancer stemness, whereas the cleaved product of CD44 (CD44ICD) promotes breast cancer stemness. Furthermore, CD44ICD interacts with CREB and binds to the promoter region of PFKFB4, thereby regulating PFKFB4 transcription and expression. The resultant PFKFB4 expression facilitates the glycolysis pathway (vis-à-vis oxidative phosphorylation) and promotes stemness of breast cancer. In addition, we found that CD44ICD and PFKFB4 expressions are generally up-regulated in the tumor portion of breast cancer patient samples. Most importantly, we found that 5MPN (a selective inhibitor of PFKFB4) suppresses CD44ICD-induced tumor development. Conclusion: CD44ICD promotes breast cancer stemness via PFKFB4-mediated glycolysis, and therapies that target PFKFB4 (e.g., 5MPN therapy) may lead to improved outcomes for cancer patients

Effects of Catastrophic Insect Outbreaks on the Harvesting Solutions of Dahurian Larch Plantations

Optimal harvesting under pest outbreak risk was studied on a set of even-aged Dahurian larch (Larix gmelinii) stands in northeastern Inner Mongolia, China. The effects of catastrophic pest outbreaks caused by the Siberian moth (Dendrolimus sibiricus) on the economic harvesting plan are compared through both deterministic and stochastic cases. Stand simulation is based on an individual-tree growth system. A scenario approach is applied when simulating the effects of catastrophic pest outbreaks. Insect damage is assumed to be a Poisson process with an average rate of 0.1 per year. One hundred scenarios of insect damage are created using the Poisson process to simulate the distribution of bare land value of each of the optimal regimes. Numerical results show that the optimal rotation is shortened with an increasing probability of a catastrophe. The average bare land values in the stochastic case are approximately 14.8% to 22.9% lower. Numbers of thinnings are decreased for most plots when seeking a highest bare land value, compared to the deterministic optima. If given a constant thinning rate, increasing risk-taking shortens the optimum rotation, as the model set used.Peer reviewe

2,3-Dichloro­pyridine

The complete mol­ecule of the title compound, C5H3Cl2N, is generated by crystallographic twofold symmetry, which forces the pyridine N atom and the opposite C—H group to be statistically disordered. In the crystal, weak aromatic π–π stacking [centroid–centroid separation = 3.805 (4) Å and slippage = 1.704 Å] leads to [100] stacks of mol­ecules. Short Cl⋯Cl contacts [3.334 (3) Å] are also observed

Molecular cloning and expression analysis of adiponectin and its receptors (AdipoR1 and AdipoR2) in the hypothalamus of the Huoyan goose during different stages of the egg-laying cycle

Multiple amino acid sequence alignment of the Huoyan goose adiponectin protein with other vertebrate species. The colour black denotes 100 % conserved sequences, and the colour grey indicates non-conservative sequences. Gaps (−) were introduced to maximize the alignment. Sequences for the alignment were obtained from GenBank (accession numbers are in brackets): Anas platyrhynchos (ADA68839.1); Ovis aries (AHV91023.1); Canis lupus familiaris (BAD15362.1); Felis catus (BAF52934.1); Gallus (AAX40986.1); Homo sapiens (NP_004788.1); Meleagris gallopavo (XP_010714799.1); Mus musculus (NP_033735.3); and Sus scrofa (ABQ95350.1). (TIFF 3483 kb

Enhancing the quality of open and distance learning in China through the identification and development of learning design skills and competencies

Purpose The purpose of this paper is to identify staff skills and competencies on which Chinese open universities should focus their professional development activities in order to enhance the quality of open and distance learning (ODL) in China. Design/methodology/approach Data were collected from surveys of 220 academic and academic-related Chinese staff, each of whom participated in one of seven 3-day Learning Design and Course Creation (LDCC) workshops at three large regional open universities in China between 2017 and 2019. The workshops were based on the UK Open University (UKOU) approach to learning design (LD) and course creation. Using content analysis methodology, textual responses were analysed and compared against the Instructional Design Competencies framework provided by the International Board of Standards for Training, Performance and Instruction (IBSTPI).Findings (1) Designing instructional interventions, (2) keeping up to date with design theories, (3) communicating in order to manage stakeholders, teams and projects were the main competencies identified from the participants responses. However, these three identified competencies differed in emphasis between the institutions that took part. Originality/value In Western higher education institutions (HEIs), LD has developed as an important approach to improving quality. A need has been identified for robust approaches to quality and professional development opportunities to enhance teaching and learning standards in open and distance learning (ODL) in China. This paper identifies and discusses specific LD skills and competencies that could be targeted to improve the quality of ODL in China

Glycyrrhizin for treatment of CRS caused by CAR T-cell therapy: A pharmacological perspective

Chimeric antigen receptor T (CAR T)-cell therapy promises to revolutionize the management of hematologic malignancies and possibly other tumors. However, the main side effect of cytokine release syndrome (CRS) is a great challenge for its clinical application. Currently, treatment of CRS caused by CAR T-cell therapy is limited to tocilizumab (TCZ) and corticosteroids in clinical guidelines. However, the theoretical risks of these two agents may curb clinicians’ enthusiasm for their application, and the optimal treatment is still debated. CAR T-cell therapy induced-CRS treatment is a current research focus. Glycyrrhizin, which has diverse pharmacological effects, good tolerance, and affordability, is an ideal therapeutic alternative for CRS. It can also overcome the shortcoming of TCZ and corticosteroids. In this brief article, we discuss the therapeutic potential of glycyrrhizin for treating CRS caused by CAR T-cell therapy from the perspective of its pharmacological action

2-[(3R,6R)-6-Methyl-2,5-dioxomorph­olin-3-yl]-N-(propan-2-yl)acetamide

The molecular conformation of the title compound, C10H16N2O4, is determined by an intra­molecular N—H⋯O hydrogen bond involving the morpholine NH group and the amide O atom. In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds into chains along the a-axis direction