miR-221/222 promotes S-phase entry and cellular migration in control of basal-like breast cancer.

The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC

miR-17/20 sensitization of breast cancer cells to chemotherapy-induced apoptosis requires Akt1.

The serine threonine kinase Akt1 has been implicated in the control of cellular metabolism, survival and growth. Herein, disruption of the ubiquitously expressed member of the Akt family of genes, Akt1, in the mouse, demonstrates a requirement for Akt1 in miRNA-mediated cellular apoptosis. The miR-17/20 cluster is known to inhibit breast cancer cellular proliferation through G1/S cell cycle arrest via binding to the cyclin D1 3\u27UTR. Here we show that miR-17/20 overexpression sensitizes cells to apoptosis induced by either Doxorubicin or UV irradiation in MCF-7 cells via Akt1. miR-17/20 mediates apoptosis via increased p53 expression which promotes Akt degradation. Akt1-/- mammary epithelial cells which express Akt2 and Akt3 demonstrated increased apoptosis to DNA damaging agents. Akt1 deficiency abolished the miR-17/20-mediated apoptosis. These results demonstrated a novel pathway through which miR17/20 regulate p53 and Akt controlling breast cancer cell apoptosis

Who suffered most after deaths due to COVID-19? Prevalence and correlates of prolonged grief disorder in COVID-19 related bereaved adults

BACKGROUND: Deaths by COVID-19 have left behind nearly 12 million recent bereaved individuals worldwide and researchers have raised concerns that the circumstances of COVID-19 related deaths will lead to a rise prevalence of prolonged grief disorder (PGD) cases. However, to date, no studies have examined the prevalence of PGD among people bereaved due to COVID-19. This study aimed to estimate the prevalence of PGD and investigated demographic and loss-related factors associated with prolonged grief symptoms among Chinese individuals bereaved due to COVID-19. METHODS: This was a cross-sectional online survey conducted between September 1 and October 3, 2020. A total of 422 Chinese participants (55.5% males; 32.73 [9.31] years old) who lost a close person due to COVID-19 participated in the study. Demographic and loss-related information was collected, and self-reported prolonged grief symptoms were measured by a 13-item International Prolonged Grief Disorder Scale (IPGDS: 1–65) and a 17-item Traumatic Grief Inventory Self Report (TGI-SR: 1–85). Multiple linear regression analysis was used to determine the associated factors of levels of grief symptoms. RESULTS: Prevalence of PGD was 37.8% screened by IPGDS and 29.3% by TGI-SR. No difference was found in levels of grief symptoms between participants whose close one died more than 6 months ago and those who experienced the loss less than 6 months ago. More severe prolonged grief symptoms assessed by IPGDS was associated with losing a close person by COVID-19 rather than complications (B: 5.35; 95% CI: 0.54–10.05), losing a partner (B: 7.80; 95% CI: 3.24–12.37), child (B: 8.15; 95% CI: 1.03–15.26), and parent (B: 5.49; 95% CI: 1.49–9.48) rather than losing a relative or a person with other relationship, feeling more traumatic about the loss (B: 1.71; 95% CI: 0.52–2.90), being closer with the deceased (B: 1.60; 95% CI: 0.34–2.86). Moreover, Losing a grandparent (B: 6.62; 95% CI: 0.53–12.71) and having more conflicts with the deceased (B: 1.05; 95% CI: − 0.008–2.11) were related to higher levels of grief symptoms assessed by TGI-SR. CONCLUSIONS: Echoing researchers’ concerns, the prevalence of PGD is high among people bereaved due to COVID-19. Individuals with a higher risk of developing PGD should be identified and bereavement support should be offered as early as possible

Compressive Properties and Energy Absorption Characteristics of Extruded Mg-Al-Ca-Mn Alloy at Various High Strain Rates

This paper is focused on the mechanical properties and the energy absorption characteristics of the extruded Mg-Al-Ca-Mn alloy in different compression directions under high strain rate compression. Compressive characterization of the alloy was conducted from the high strain rate (HSR) test by using a Split Hopkinson Pressure Bar (SHPB). Results show that the investigated alloy exhibits a strong strain rate sensitivity. With the rise of strain rate, the compressive strength is increased significantly, and the deformation ability also improves. When compressed along the extrusion direction, as the strain rate increases, the total absorbed energy E, the crush force efficiency (CFE), and the specific energy absorption SEA of Mg-Al-Ca-Mn alloy are all greatly improved as compared with those obtained along other compression directions

CircRNA-UCK2 increased TET1 inhibits proliferation and invasion of prostate cancer cells via sponge miRNA-767-5p

A majority of the patients with advanced prostate cancer initially respond to androgen deprivation therapy and enzalutamide therapy, but eventually enter the castration-resistant prostate cancer (CRPC) phase. Some studies have shown that the activation of other signalling pathways in CRPC cells replaces the function of the androgen receptor, as well as promotes cell metastasis and progression. However, the mechanisms underlying this side effect remain unclear. The present study aims to explore the continued progression of cells after enzalutamide resistance. Low expression of circRNA-UCK2 (circUCK2) was detected in enzalutamide-resistant (EnzR) cells. Moreover, miR-767-5p was found to be resistant to EnzR cells when the level of circUCK2 is increased. The decrease in free miR-767-5p increases the expression of TET1 protein through the post-transcriptional regulation of mRNA, thereby inhibiting cell invasion and proliferation. Knocking down circUCK2 in enzalutamide-sensitive cells reduces the concentration of TET1, thereby increasing cell invasion and proliferation. A preclinical study using in vivo mouse models also showed that a high expression of circUCK2 inhibited the EnzR cell growth. Thus, this study might aid in developing a novel therapy to better suppress the CRPC progression

Fabrication of Ultra-Fine Micro-Vias in Non-Photosensitive Polyimide for High-Density Vertical Interconnects

With the growing demands for transferring large amounts of data between components in a package, it is required for advanced packaging technologies to form smaller vertical vias in the insulators. Plasma etching is one of the most widely used micro-vias formation processes. This paper has developed a fabrication process for 5–10 µm residue-free micro-vias with 70° tapered angle in polyimide film based on O2/CHF3 inductively coupled plasma (ICP). The etch rate would monotonically increase with the ICP power, RF power, and gas flow rate. As for the gas ratio, there is an optimum range of CHF3 ratio, which could obtain the highest etch rate. The results have clearly shown that the enhancement of ion bombardment and prolongation of etching time would be beneficial to grass-like residue removal. In addition, during the etching of partially cured polyimide, the lateral etch rate would significantly increase in the region near the metal hard mask

Additively Manufactured Dual-functional Metamaterials with Customizable Mechanical and Sound-absorbing Properties

Virtual and Physical Prototyping174864-88

Disease Resistance and Molecular Variations in Irradiation Induced Mutants of Two Pea Cultivars

Induced mutation is useful for improving the disease resistance of various crops. Fusarium wilt and powdery mildew are two important diseases which severely influence pea production worldwide. In this study, we first evaluated Fusarium wilt and powdery mildew resistance of mutants derived from two elite vegetable pea cultivars, Shijiadacaiwan 1 (SJ1) and Chengwan 8 (CW8), respectively. Nine SJ1 and five CW8 M3 mutants showed resistant variations in Fusarium wilt, and the same five CW8 mutants in powdery mildew. These resistant variations were confirmed in M4 and M5 mutants as well. Then, we investigated the genetic variations and relationships of mutant lines using simple sequence repeat (SSR) markers. Among the nine effective SSR markers, the genetic diversity index and polymorphism information content (PIC) values were averaged at 0.55 and 0.46, which revealed considerable genetic variations in the mutants. The phylogenetic tree and population structure analyses divided the M3 mutants into two major groups at 0.62 genetic similarity (K = 2), which clearly separated the mutants of the two cultivars and indicated that a great genetic difference existed between the two mutant populations. Further, the two genetic groups were divided into five subgroups at 0.86 genetic similarity (K = 5) and each subgroup associated with resistant phenotypes of the mutants. Finally, the homologous PsMLO1 cDNA of five CW8 mutants that gained resistance to powdery mildew was amplified and cloned. A 129 bp fragment deletion was found in the PsMLO1 gene, which was in accord with er1-2. The findings provide important information on disease resistant and molecular variations of pea mutants, which is useful for pea production, new cultivar breeding, and the identification of resistance genes

Transient model of unsteady creep of sliding zone soil under cyclic dynamic load based on fractional derivative

The shear mechanical behavior of soils in the slip zone under cyclic loading is of great importance for the stability analysis of landslides. In this paper, an experimental device is developed to study the nonlinear deformation mechanism of soil in sliding zone under cyclic load. Based on field tests and model tests, the change of shear strength parameters of the soil in the slip zone with cyclic loading parameters was investigated. Based on the deformation characteristics of slip zone soils under cyclic dynamic loading, the unsteady creep transient model based on fractional derivative is established, and three deformation types of sliding zone soil are described: stable, critical and destructive. The Levenberg-Marquardt (LM) algorithm is used to fit the nonlinear curves, and the applicability of the model is also verified. This research method provides a test apparatus and a method for studying the deformation characteristics of slip zone soils under cumulative loading