Network meta-analysis of the risk of dyspepsia and anorexia in patients with type 2 diabetes mellitus induced by glucagon-like peptide 1 receptor agonist hypoglycemic drugs.

OBJECTIVE: The aim of this study was to investigate and evaluate the risk of dyspepsia and anorexia in patients with type 2 diabetes mellitus (T2DM) induced by glucagon-like peptide 1 receptor agonist (GLP-1 RA) hypoglycemic drugs. MATERIALS AND METHODS: We searched papers in PubMed, Web of Science, Cochrane Library, Google Scholar, CNKI, Wanfang, Embase, and VIP databases, and the retrieval time limit was set from the establishment of the database to May 2023. Randomized Controlled Trials (RCTs) were collected in which the subjects were T2DM patients, the intervention was GLP-1RA compared with placebo or traditional hypoglycemic drugs, and the outcome indicators included dyspepsia and anorexia. A meta-analysis and a network meta-analysis were performed. RESULTS: The results of the traditional meta-analysis showed that the risk of dyspepsia and anorexia of total GLP-1 RA was 3.01 and 2.56 times that of placebo, respectively. All types of GLP-1RA were compared with placebo and the results also showed a trend towards increased risk of digestive system adverse events (DSAEs). Among all interventions included, liraglutide was the one with the highest risk of dyspepsia in patients with T2DM, and dulaglutide was the one with the highest risk of anorexia. CONCLUSIONS: The results of the two meta-analyses are consistent, and both clearly show that GLP-1RA can increase the risk of dyspepsia and anorexia in T2DM patients.

MicroRNA-221 regulates proliferation of bovine mammary gland epithelial cells by targeting the STAT5a and IRS1 genes.

MicroRNAs (miRNA) play an essential role in mammary gland development and lactation. Previous studies in cattle have shown that miR-221 is highly expressed in peak compared with early lactation. However, the functions of miR-221 in bovine mammary gland epithelial cells and the mechanisms by which this miRNA affects cell proliferation and milk synthesis remain unclear. We hypothesized that miR-221 targets and modulates the expression of specific genes in the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and phosphatidylinositol 3-kinase-proteinkinase B/mammalian target of rapamycin (PI3K-Akt/mTOR) signaling pathways, which have crucial roles in lactation in cattle. Following transfection of miR-221 into cultured bovine mammary gland epithelial cells, inhibition of cell proliferation and reduced viability of these cells were observed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis. To elucidate the molecular mechanisms of the effects of miR-221 on cell proliferation, we selected potential candidate genes that can be targeted by miR-221 using bioinformatics prediction tools. The dual luciferase assay revealed that STAT5a, STAT3, and IRS1 interact with miR-221 by its direct binding to the 3'-untranslated regions (UTR) of these genes. Subsequent analysis showed that transfection of a miR-221 mimic resulted in significantly decreased expression of STAT5a and IRS1 at both the RNA and protein levels using quantitative real-time PCR and Western blot analyses. Furthermore, expression levels of the downstream genes SOCS3, AKT3, and mTOR that are regulated by STAT5a and IRS1 in the JAK-STAT and PI3K-Akt/mTOR signaling pathways, were also altered after miR-221 transfection. This is the first study to reveal the mechanisms by which miR-221 inhibits mammary gland epithelial cell proliferation by targeting STAT5a and IRS1, key genes in the PI3K-Akt/mTOR and JAK-STAT signaling pathways.

High sensitivity and high capacitance of the cylindrically shaped w-membrane hydrophone.

In hydrophone designs, intelligent use of structural effects is the key to obtaining high sensitivity. The uses of the moonie and spring structures are good examples of this approach. These transducers can be regarded as mechanical stress converters and amplifiers by which the hydropressure is transferred into a desired stress mode and amplified in magnitude for elastoelectric conversion. In this paper, a structure referred to as the w-membrane is introduced for hydrophone construction. By combining a cylindrical design with the w membrane structure, a hydrophone with very high sensitivity is designed. In addition, high capacitance is another advantage of this configuration. The analysis is carried out based on the concepts of stress conversion and amplification, and numerical results are presented.

Torsional modes in piezo helical springs.

Piezo springs have been studied for their advantages in receiver applications at low frequencies. In this paper, piezo helical springs shaped from curved unimorphs are proposed for actuator designs in which the torsional modes are used to obtain electroelastic conversion. In comparison with the use of bimorphs as low frequency actuators, the helices show advantages of large strain capabilities and high compliance. These advantages are confirmed by numerical calculations.

Investigation on piezoelectric helix for use as a hydrophone.

The piezoelectric helical spring is analyzed for use as a hydrophone. Because the polarity in the helix is arranged parallel to the electrode planes, the shear mode, g(15) can perform the elastoelectric conversion without any undesired couplings under hydrostatic condition. In this paper, the structural effects are modeled using the concept of stress amplifier. The gain factor, G, is defined as the ratio of the average stress in the piezoceramic to the detected pressure and, therefore, provides a G-fold increase in voltage responsivity. In addition, a solution for increasing the capacitance while maintaining the sensitivity is proposed. Numerical results showing high hydrostatic responsivities are given.